(19330693 - Journal of Neurosurgery) Oral Presentations 2018 AANS Annual Scientific Meeting PDF

AANS 2018 Annual Scientific Meeting Abstracts
Oral Presentations
2018 AANS Annual Scientific Meeting
New Orleans, LA • April 29–May 2, 2018
(DOI: 10.3171/2018.4.JNS.AANS2018abstracts)
400. Interdisciplinary care model decreases use of critical care services after corrective surgery for adult degenerative
scoliosis
Owoicho Adogwa, MD; (Chicago, IL) Aladine Elsamadicy, BE; Amanda Sergesketter, BS; Michael Ongele, BS; Aaron Tarnasky, BS;
Victoria Vuong, MS; Syed Khalid, MD; Jessica Moreno; Joseph Cheng, MD, MS; Isaac Karikari, MD; Carlos Bagley
Introduction: An interdisciplinary team approach to management of elderly patients requiring spine surgery has been shown to
improve short and long-term outcomes. However whether and interdisciplinary team approach mitigates use of ICU resources remains
unknown, and is the main aim of this manuscript.
Methods: A unique model called Peri-operative Optimization of Senior Health Program (POSH) was launched for elderly patients (<65
years old) undergoing complex lumbar spine surgery at a major academic institution. In this model, a geriatrician co-manages the
patients along with the neurosurgical team during the pre- and post-operative periods. We retrospectively review the first 100 cases
after the initiation of the POSH protocol and compared them with the immediately preceding 25 cases to assess the incidence of peri-
operative complications and clinical outcomes. The rates of ICU transfer as well as the independent predictors of ICU admission are
the primary outcomes of this study.
Results: 125 patients undergoing lumbar decompression and fusion surgery were enrolled in this pilot program. Baseline
characteristics were similar between both cohorts. Intra-operative variables as well as number of fusion levels and duration of surgery
were similar between both cohorts. There was a significant difference in the use of ICU services (ICU admission rates) between both
cohorts, with Non-POSH cohort having a 3-fold increase compared to the POSH cohort (p<0.0001). In a multivariate binary logistic
regression model, lack of an interdisciplinary co-management team approach was an independent predictor for ICU transfers in elderly
patients undergoing corrective surgery for adult degenerative scoliosis [OR:8.51, 95%CI (2.972, 24.37), p<0.0001].
Conclusion: Our study suggests that an interdisciplinary co-management model that integrates technical expertise between geriatrics
and neurosurgery significantly reduces the use of critical care services, and not having an interdisciplinary co-management model was
an independent predictor of need for critical care services (i.e. transfer to ICU).
401. Nursing efforts in spine and peripheral nerve enhanced recovery after surgery (ERAS) pathway implementation and
outcomes
Advanced Practice Provider (APP) Abstract Award
Kristin Rupich, MSN (Philadelphia, PA); Mara Cappelloni; Emily Missimer; Diana Gardiner; Benjamin Hurtig; Rachel Pessoa; Albert
Abbo; Ali Ozturk; William Welch; Zarina Ali
Introduction: Optimization of postoperative mobility and reduction in urinary catheter utilization in patients undergoing spine and
peripheral nerve surgery are two major nursing initiatives facilitated by the implementation of an ERAS protocol.
Methods: An ERAS protocol was developed and implemented in the Pennsylvania Hospital Neurosurgery Department from April to
June 2017 and 201 elective spinal or peripheral nerve patients were enrolled. The control group was a historical cohort from
September to December 2016 of 74 patients. A multidisciplinary team was established to engage in the implementation, outcome
assessment, and modification of the protocol. Prior to initiation of the protocol, advanced practice providers led significant educational
efforts focused on the new care paradigm, including patient education in the preoperative setting to set patient expectations for their
postoperative recovery.
Results: With the introduction of ERAS, nursing staff became actively engaged in embracing the change in practice. Implementation
resulted in increased compliance with early ambulation. On the day of surgery, 53.4% of ERAS patients were mobilized after surgery
compared to 17.1% of control patients (p<0.001). At one day post-surgery, 84.1% of ERAS patients were mobilized compared to
45.7% control patients (p<0.001). Similarly, 46.9% of ERAS patients were ambulated on the day of surgery compared to 17.1% of
control patients (p=0.001) and 64.2% of ERAS patients were ambulated one day post-surgery compared to 28.6% of control patients
(p<0.001). After surgery, 20.4% of ERAS patients had a urinary catheter in place compared to 47.3% of control patients (p<0.001).
Conclusion: An ERAS pathway was effectively implemented by engaging all staff in the launch of the protocol, which created a
positive culture shift. Education by the multidisciplinary team was integral to maintaining provider engagement. The protocol was
successful in improving early ambulation and decreasing urinary catheter utilization. Attention to protocol compliance is needed to
ensure continued success.
403. Low dose steroid use (Medrol Dose Pack) after lumbar laminectomy and/or discectomy surgery to decrease post-
©AANS, 2018 J Neurosurg Volume 128 • April 2018 1

operative pain and narcotic use
Advanced Practice Provider (APP) Abstract Award
Diana Gardiner, DNP, MSN, CRNP (Philadelphia, PA); Brendan McShane; Marie Kerr, CCRP; John Pierce, MD; Prateek Agarwal,
MD; Nicole Pasao-Pham, CRNP; Stephen Dante, MD; William Welch, MD; Eileen Maloney-Wilensky, MSN, ACNP-BC
Introduction: In the recent decade, prescription painkillers have become a serious concern in the United States. In the present study,
we evaluated the use of taking a Medrol Dose Pack after spine surgery to reduce patient pain and opioid use.
Methods: Patients who elected to undergo lumbar laminectomy and/or lumbar discectomy at a single institution by two senior
surgeons were divided into two groups. One group was prescribed a Medrol Dose Pack as well as pain medication and a muscle
relaxer (n=37). A control group was prescribed only pain medication and a muscle relaxer (n=51). Patients completed a VAS score at
baseline and 10 consecutive days post discharge and recorded the dosage of all pain medication they took. Opioid use and reporting
of pain at their 30 day follow up was recorded. Statistical analysis was done using a multivariate regression model for the ten day post
discharge data and a Fisher’s Exact test to test for differences between the two groups at the follow up period.
Results: VAS score decreased by 0.12 points for every additional 4 mg dose of the Medrol dose pack (p<0.001). Administration of a
Medrol dose pack had no effect on patient Percocet use in the 10 days post discharge. We found no statistical difference in the
patients reporting of pain (47.5% vs. 36.6%, p=0.37) and opioid use (17.5% vs. 26.8%, p=0.42) at 30 days post-surgery between the
two groups respectively.
Conclusion: To our knowledge, this is the first study looking at a Medrol dose pack to reduce opioid consumption after spine surgery.
In our study, the admission of a Medrol dose pack decreased postoperative pain; however it interestingly did not affect patient opioid
consumption. This may be because patient opioid use is multidimensional and influenced by factors such as prescribed dose rather
than pain.
404. Pathway for omitting ICU level of care following craniotomy for resection of supra-tentorial brain tumors
Jennifer Viner, NP (San Francisco, CA); Michael McDermott, MD; Joseph Osorio, MD; Michael Safaee, MD; Stephen Magill, MD
Introduction: Traditionally, craniotomy patients are sent directly from the operating room to the neurosurgical intensive care unit.
Recent pressures have prompted us to reevaluate the flow for some of the simpler cases. We therefore developed a prospective
transitional care plan for simple intracranial tumors that would not require direct ICU transfer. Instead, patients coming out of the
operating room were recovered in the post-anesthesia care unit and then transferred to the neurological transitional care unit.
Methods: Inclusion and exclusion criteria were created to identify straightforward supra-tentorial tumor craniotomy patients. Patient
education and nursing education was completed before initiation of the program. A patient handout trifold was developed and approved
through the hospital education committee.
Results: Over a period of 8 months, 10 tumor patients, including 5 convexity meningiomas, 2 metastatic tumors and 3 gliomas, were
entered into the transitional care pathway. There were no adverse patient or safety events during this period. Patient hospital length of
stay decreased from a mean of 3.10 days to 2.14 days and direct hospital costs per case decreased by a mean of $6316 per case.
The nurses were favorably impressed with the ease of implementation of the program. The acuity of patients in the neurosurgery
intensive care unit increased allowing for more admissions from outside institutions. The program was awarded further financial
support for recruiting other surgical procedures into the program.
Conclusion: The transitional care pathway utilizing recovery room and step down unit care for supra-tentorial tumor patients is safe
and cost effective. Patient and nursing education before surgery made the program easy to implement. Future programs underway to
expand the pathway to include other craniotomy groups and procedures will be presented.
405. Glioblastoma readmission risk score: estimating 30 day readmission risk after glioblastoma resection
Arka N Mallela, MS (Philadelphia, PA); Prateek Agarwal, BS; Nicholas Goel, BS; Joseph Durgin; Mohit Jayaram; Eileen Maloney
Wilensky; Donald O'Rourke, MD; Michael Sean Grady, MD; Kalil Abdullah, MD; Steven Brem, MD
Introduction: Thirty-day readmission following surgery is an important metric of surgical quality and is increasingly tied to
reimbursement. We sought to determine factors associated with readmission and develop a preliminary risk score.
Methods: Between 2005 and 2016, 666 unique resections (467 patients) of primary/recurrent glioblastoma with readmission
information were retrospectively identified. We collected patient demographics, comorbidities, pre/post-operative KPS, tumor
pathology, post-operative ventriculoperitoneal shunt (VPS), extent of resection, tumor genetic markers, number of total resections,
radiation, temozolomide, levetiracetam, tumor location/eloquence, length of stay, post-operative complications, and 30-day
readmission. Univariate logistic regression was utilized to examine association of these factors with readmission. A genetic learning
algorithm identified a multivariate logistic model that best predicted readmission. This model was converted to a simple additive score.
Results: In 666 resections (68% primary, 32% revision), the 30-day readmission rate was 20.2%. In univariate regression,
readmission was significantly associated with lower pre/post-operative KPS, recurrent resection, surgical-site infection, post-operative
VTE, post-operative VPS, and discharge to a rehabilitation facility (p < 0.05). Increased BMI, hypertension, and current smoking
trended towards increased readmission probability (p < 0.1). MGMT methylation and chemoradiation individually decreased
readmission (p < 0.05). Demographic variables, other medical history, tumor location/eloquence, other tumor pathology (IDH1, EGFR,
p53, ki-67), extent of resection, and days in ICU/hospital were not associated with readmission. The optimized multivariate regression
model/score predicted current smoking, increased BMI, lower KPS, and post-operative complications (SSI, PE, VPS) as risk factors

and MGMT promoter methylation and chemoradiation as protective variables against readmission.
Conclusion: Pre-operative risk factors, particularly smoking, BMI, and lower KPS, and post-operative complications increase 30-day
readmission risk. The additive score can identify those at risk for readmission with high fidelity. The Glioblastoma Readmission Risk
Score developed from this data will be further refined and may be a useful tool to predict readmissions in clinical populations.
406. Chlorhexidine showers decrease surgical site infections for non-fusion spinal surgeries: an analysis of 4,547 surgeries
Andrew K. Chan, MD (San Francisco, CA); Simon Ammanuel, BS; Henry Skrehot; Caleb Edwards, BS; Sravani Kondapavulur, BS;
Catherine Miller, MD; Amy Nichols; Catherine Liu, MD; Praveen Mummaneni, MD
Introduction: Surgical Site Infection (SSI) is a feared complication following spine surgery. Multiple strategies have been suggested to
reduce the rate of SSI, including the use of preoperative chlorhexidine (CHG) showers. We performed a single-center retrospective
analysis of prospectively collected data to investigate the effect of preoperative CHG showers on the rate of SSI.
Methods: We analyzed 4,547 consecutive spine surgeries performed at a single, high-volume spine surgery practice from April 2012
through June 2016. In November 2013, a pre-operative CHG shower protocol (3 pre-operative showers with 4% CHG soap) was
implemented. There were no other protocol changes to surgical preparation, intra-operative (e.g., topical vancomycin), or post-
operative management (e.g., antibiotic drain prophylaxis) during the study period. SSI were identified using the National Health Safety
Network protocol and were tracked quarterly. A historical cohort comparison was utilized to assess for a difference in SSI rate
between the pre- (pre-CHG group) and post-implementation (CHG group) periods.
Results: Overall, the average SSI rate was 0.45±0.13%. For the entire cohort, the average SSI rate did not differ between the pre-
CHG group (0.73±0.28%) and CHG group (0.30±0.13%) (p=0.13). We conducted a subgroup analysis stratified by procedure type
(decompression alone versus spinal fusion procedure). For the decompression only cohort, SSI rates were significantly lower in the
CHG group following protocol implementation (0.68±0.26% versus 0.15±0.11%, p=0.04). For the fusion cohort, there was a decreased
rate of SSI in the CHG cohort though the difference was not statistically significant (0.79±0.41% versus 0.41±0.18%, p=0.34).
Conclusion: This is one of the largest studies to investigate the effect of preoperative CHG showers on spinal SSI. We found that
CHG showering was associated with significantly decreased rates of infection in patients undergoing decompression procedures
without instrumentation. For fusion procedures there was a lower rate of SSI but it did not reach significance.
407. Determination of thermal dose threshold for brain tissue lesioning via transcranial MR-guided focused ultrasound in a
porcine model
Zhiyuan Xu, MD (Charlottesville, VA); Dong-Guk Paeng, PhD; John Snell, PhD; Anders Quigg; Matthew Eames, PhD; Changzhu Jin;
Ashli Everstine; Jason Sheehan, MD, PhD; Beatriz Lopes, MD, PhD; Neal Kassell, MD
Introduction: Transcranial Magnetic Resonance-guided Focused Ultrasound (tcMRgFUS) system achieving thermal rise
approximately
55 °C to generate the lesioning of a target brain tissue has been approved to treat patients with essential tremor. Given the current
technical limitation, it is not always safely achievable. Investigation is warranted to determine the thermal dose threshold for
permanent intracranial lesioning via tcMRgFUS in order to circumvent the potential thermal over-dosage resulting from the current
approach.
Methods: A laptop-based proportional-integral-derivative controller was developed to prescribe thermal dose through variation of
pulse duration of the tcMRgFUS system. ExAblate Neuro 650 kHz was used in 8 pigs. Four separate spots in the bilateral thalami
were sonicated in each pig undergoing craniectomy with different thermal doses based on MR thermometry. The thermal dose
threshold was evaluated based upon the analysis of MRIs and histology of the brain tissue acquired three days after sonication. The
parameters to fit the data to a logistic function, Y(TD)= Ym/[1+exp{-A(TD-TDhalf)}], where Y is the lesion size in diameter, area, or
volume in MRIs and histology, Ym is the size when TD (thermal dose) goes infinite, TDhalf is the mid thermal dose, and A is the
steepness of the curve.
Results: When the delivered thermal dose was less than 200 cumulative equivalent minutes (CEM) at 43°C, a minimal T2 change
was observed within the hour following sonication. Lesions were well visualized on all T2-weighted MRIs and histology studies of the
pig brain tissue three days following sonication when the thermal dose exceeded 75 CEM and 104 CEM, respectively for 50 % lesions
with logistic function curve fitting.
Conclusion: Reduced temperature and increased time of pulsed sonication proved to be safer and more achievable in terms of the
thermal brain treatment. These findings may help improve patient selection and address the potential overdose safety issue.
408. Peptide therapeutics to prevent delayed vasospasm after subarachnoid hemorrhage
Peter Joseph Morone, MD (Nashville, TN); Colleen Brophy, MD; Joyce Cheung-Flynn, MD, PhD
Introduction: Subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm leads to delayed vasospasm resulting in
neuroischemia. Therapeutic options are limited to hemodynamic optimization and nimodipine, which have marginal clinical efficacy.
Nitric oxide (NO) signaling modulates cerebral blood flow through activation of the cGMP-Protein kinase G (PKG) pathway and the
hypothesis of this investigation was that treatment with a cell permeant phosphopeptide mimetic of a downstream effector protein of
PKG: VAsodilator Stimulated Phosphopeptide (VASP), prevents delayed vasospasm after SAH.

Methods: VASP phosphomimetic peptide was designed and synthesized (EZBiolab; Carmel IN) with residues surrounding
phosphoserine at the 239 site of human VASP covalently linked to a cell permeant domain. Rat aortic smooth muscle rings (2.0 mm in
width) were suspended in a muscle bath (Radnoti; Monrovia CA) and pre-contracted with endothelin (ET, 10-8 M) to produce a rat ex
vivo model of vasospasm. Dose dependent relaxation to VASP peptides and nimodipine (10-8 to 10-7M) was determined. Relaxation
response was calculated as a % of the maximal ET-induced contraction.
Results: Treatment with the VASP peptide led to a dose-dependent relaxation response. Vasorelaxant effect of low dose VASP
peptide (0.25x10-3M; 24±4% relaxation) was similar to low dose nimodipine (10-8M; 18±5% relaxation). Combining VASP peptide and
nimodipine led to a synergistic relaxation response (52±6.2% to 65±5% relaxation).
Conclusion: Treatment targeting the downstream modulator of the NO signaling pathway, VASP, bypasses receptors and signaling
elements leading to vasorelaxation in the rat ex vivo model of SAH-vasospasm. The VASP peptide response was synergistic with
nimodipine suggesting that the two molecules modulate vasorelaxation via different signaling pathways.
409. Ribavirin as a potential therapeutic for atypical teratoid/rhabdoid tumors
Joshua Casaos (Baltimore, MD); Sakibul Huq; John Choi; Noah Gorelick; Yuanxuan Xia; Chenchen Ji; Eric Jackson; Henry Brem;
Betty Tyler; Nicolas Skuli
Introduction: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric brain tumors with no current standard of care.
A recent genetic analysis reported AT/RT to have high expression of enhancer of zeste homolog 2 (EZH2), a methyltransferase known
to have oncogenic properties in many cancers. Our laboratory previously demonstrated that the anti-viral drug ribavirin, approved by
the FDA for treatment of hepatitis C, inhibited glioma cell growth in vitro and in vivo, potentially through modulation of EZH2. Based on
these findings we investigated the effect of ribavirin on AT/RT in vitro and in vivo.
Methods: Three different human AT/RT cell lines (BT12, BT16, and BT37) were selected for investigation. Cell proliferation was
assessed via cell counting. Cell cycle and cell death processes were quantified using flow cytometry. Tumor migration, invasion, and
adhesion capacities were assessed via scratch wound, Bowden chamber, and adhesion assays, respectively. Ribavirin’s mechanism
of action in AT/RT was studied using Western blots for several known ribavirin targets. Furthermore, we tested ribavirin efficacy in vivo
in an orthotopic xenograft AT/RT model in athymic mice.
Results: We provide evidence that ribavirin significantly impairs AT/RT cell growth, increases cell cycle arrest, and induces cell death,
potentially through modulation of the EZH2 and/or eIF4E pathways. We also demonstrated that ribavirin significantly impairs AT/RT
cell migration, invasion, and adhesion. Most importantly, we demonstrate that ribavirin significantly improves the survival of mice
orthotopically implanted with BT12 cells. Ribavirin-treated animals exhibited a significantly increased median survival (56 days)
compared to controls (37 days) (p<0.0001).
Conclusion: Our work establishes that ribavirin is effective against AT/RT in vitro and in vivo. Given the lack of standard therapy for
AT/RT, these findings fill an area of unmet need and could represent a new therapeutic option for children with this deadly disease.
410. Trigeminal nerve stimulation suppresses cortical spreading depolarization
Aubrey C. Rogers (Brooklyn, NY); Chunyan Li, PhD; Raj Narayan, MD
Introduction: The cumulative experimental and clinical evidence suggest that cortical spreading depolarization (CSD) is a real-time
marker and mechanism of acute lesion development in a variety of brain injuries. As such, neuroprotective therapies that block CSD
could correct the distorted brain autoregulation and reduce brain damage. In this study, for the first time, we aim to investigate the
effect of trigeminal nerve stimulation (TNS) to block CSD.
Methods: Studies were performed on 7 male Sprague-Dawley rats weighting 250-325 gram. Animals were randomized to two study
groups: (1) sham-operated control animals; (2) animals with 15-min TNS. Electrical stimulation of the trigeminal nerves was performed
by introducing two needles (26 GA) subcutaneously bilaterally along an imaginary line connecting the ear and eye. Rectangular
cathodal pulses (0.5 ms) were delivered by electrical stimulator at 25 Hz, 5V continuously for 15 minutes. Sham controls had identical
electrode placements but without electrical stimulation. Susceptibility to CSD was evaluated by measuring the electrical threshold for
CSD, followed by analysis of CSD frequency and propagation speed during continuous topical application of 1M KCl solution for one
hour.
Results: TNS increased the threshold current for eliciting CSD by 114% (0.7±0.3 µC vs. 1.5±0.6 µC; n=3 p<0.05; sham vs. TNS),
slowed its propagation velocity by 28% (7.4±0.8 mm/min vs. 5.3±0.6 mm/min; n=4, p<0.05; sham vs. TNS), and reduced the
frequency of CSD during continuous topical 1M KCl by 42% (12.7±2.1 CSDs/h vs. 7.3±1.5 CSDs/h; n=4, p<0.05; sham vs. TNS).
Conclusion: The results of our study demonstrate that electrical TNS effectively suppresses CSD susceptibility, and therefore can
serve as a new class of neuroprotective treatments for a variety of brain injuries.
411. Modeling the return to consciousness after severe TBI at a large academic Level 1 trauma center
Nathan Winans, BS (Setauket, NY); Justine Liang, MS; Stephen Doyle, BS; Adam Fry, PhD; Susan Fiore, MS; Charles Mikell, MD
Introduction: Command following is used as a proxy for consciousness in the clinical setting, and time to command following is an
important indicator of long-term outcomes in severe traumatic brain injury (sTBI) patients. We sought to characterize the natural
history of coma recovery and identify factors that significantly predict the duration of unconsciousness.
Methods: Retrospective data were collected from 360 sTBI patients. Of 214 survivors (59.4%), 184 patients (86%) followed

commands as inpatients. Data were collected on time to command following, demographics, Glasgow Coma Scales (GCS) on
admission, Injury Severity Scores (ISS), initial pupil reactivity and initial CT scans. CT scans were scored using the Marshall
classification system.
Results: Return to consciousness following a severe head injury displayed an exponential distribution (Μ = 10.4 ± 0.8 days, p < 0.05).
Implementing a multiple linear regression model, we identify a model that significantly predicts time to command follow using ISS and
Marshall scores (p < 0.01). This model explains 13.9% of the variance in time to command following. Variables that did not
significantly contribute include initial GCS, pupil reactivity, age, gender, or type of injury (all p < 0.05).
Conclusion: Here we describe the behavior of emergence of consciousness following head injury fits an exponential function. We
also identify a multiple linear regression model that significantly predicts the time to command following based on ISS and Marshall
scores. The present study has implications for design of therapeutic trials designed to hasten the return of consciousness, as well as
for the understanding of common prognostic signs used by neurosurgeons in the peri-injury period.
412. Classification of finger movements with an intracortical brain-computer interface in a human brain
Ahmed Jorge, PhD (Pittsburgh, PA) ; Dylan Royston, BS; Elizabeth Tyler-Kabara, MD, PhD; Michael Boninger, MD; Jennifer Collinger,
PhD
Introduction: Intracortical microelectrode arrays allow for detailed movement-related information to be recorded from motor cortex,
and have enabled people with tetraplegia to use a brain-computer interface to restore reaching and grasping. However, in order to
restore dexterous movements, it will be necessary to control individual fingers. Studies in non-human primates and
electrocorticography-studies in humans have been able to decode finger movements in able-bodied subjects; however, this has not
been attempted in a person with spinal cord injury. We aimed to quantify the ability to predict which finger a subject with tetraplegia
was attempting to move using intracortical data recorded from motor cortex.
Methods: The study participant was a 31-year-old man with a C5/6 ASIA B spinal cord injury. Two 96-electrode-microarrays (4x4mm
footprint, 1.5mm shank length) were implanted in the participant’s left motor cortex. Across four days, the subject observed a virtual
hand flex each finger while neural firing rates were recorded. A six-class linear discriminant classifier, with 10-fold cross validation,
was used to predict finger movement.
Results: The mean overall classification accuracy was 73% (range:70-76%, chance:17%), which occurred at 1 second after the
subject was cued about which finger to move. Individually, the thumb and index flexion and thumb abduction exhibited the highest
classification accuracies at 95%, 77%, and 95%, respectively. The middle, ring, and pinky achieved an accuracy of 66%, 51%, and
55%, respectively and when incorrectly classified, were marked as an adjacent finger (chance:17%).
Conclusions: Our results demonstrate that it is possible to accurately classify the intention to move individual fingers using
intracortical recordings from a participant with no finger mobility and limited sensation. As a next step, an online classification
paradigm could be used to control a robotic prosthetic hand or provide rehabilitation assistance through the use of a powered orthosis
or exoskeleton.
413. Clinicopathologic implications of genomic disruption in pituitary adenomas
Alexandra Larsen (Staten Island, NY); Wenya Bi, MD, PhD; Yu Mei, MD, PhD; Malak Abedalthagafi, MD, PhD; Noah Greenwald, BA;
Rameen Beroukhim, MD, PhD; Edward Laws Jr., MD; Ian Dunn, MD
Introduction: Pituitary adenomas, the second most common primary brain tumor in adults, divide into two distinct subsets based on
their pattern of chromosomal alterations. One class is characterized by lack of chromosomal copy number changes, while another is
distinguished by widespread genomic alterations. The biological implications of this genomic dichotomy between subsets are unclear
in pituitary adenomas. We sought to define the clinical and pathological characteristics associated with genomic disruption in a large
cohort of pituitary adenomas.
Methods: We retrospectively reviewed 188 pituitary adenomas with genomic profiling and annotated their pathologic subclass,
histochemical expression profile, clinical hormone secretion status, and genomic disruption. Genomic disruption was defined as more
than two chromosome arm-level gains or losses, while genomically silent was defined as two or fewer chromosome arm-level gains or
losses. We used Fisher’s exact test to assess differences in count data and unpaired t-test to assess differences in means.
Results: Our cohort encompassed 104 null cell, 28 somatotroph, 24 corticotroph, 20 lactotroph and 12 gonadotroph adenomas. There
were 78 functional (hormone-secreting) and 110 non-functional adenomas. The genomically disrupted subset was significantly
enriched for functional adenomas (69%) compared to the genomically silent subset (27% functional, p<0.0001). Additionally, genomic
disruption in pituitary adenomas exhibited subtype-specific patterns, most prominently in silent corticotroph and lactotroph tumors.
Genomic disruption was significantly associated with a higher mean MIB-1 proliferation index (3.2%) compared to that of genomically
silent tumors (2.1%, p=0.0081).
Conclusion: We observed an association of immunohistochemical staining for one or more hormones, higher proliferative index, and
clinical hormone-secretion status with genomic disruption in pituitary adenomas. Furthermore, a striking subtype-specific enrichment of
genomic disruption status in silent corticotroph and lactotroph adenomas suggests a lineage-related mechanism for genomic
disruption.
414. High intensity focused ultrasound treatment for neuropathic pain induced by common peroneal nerve injury
Tarun Prabhala (Albany, NY); Abby Hellman, BA; Julie Pilitsis, MD, PhD; Ian Walling, BS; Jiang Qian, MD; Clif Burdette, PhD; Lance
Frith, PhD; Miriam Shao; Amelia Stapleton; Juliette Thibodeau

Introduction: Neuropathic pain caused by nerve injury, compressive lesions, or neuronal scarring presents as a debilitating condition
lacking effective, long-term treatment options. We assess the effects of an external pulsed high-intensity focused ultrasound (HIFU)
device on sensory thresholds in a common peroneal nerve injury rodent (CPNI) model. We also investigate the effects of repeated
treatments on the induction of central sensitization.
Methods: The nerve injury was simulated by surgically ligating the common peroneal nerve (CPN) of the left hind paw with a
previously validated model. Neuropathic phenotype was confirmed using Von Frey Fibers (VFF). The Hot Plate Test (HPT) was used
to assess thermal thresholds. The external HIFU treatment was applied to the left L4,5 Dorsal Root Ganglion (DRG) at 8W for 3
minutes. Behavioral tests were performed before surgery, 1 week following surgery, and 24, 48, 72, 96, 120, and 168 hours post-HIFU
treatment. One group received a single treatment, while another group received two treatments.
Results: HIFU treatment resulted in increased mechanical pain thresholds in the CPNI rodents. VFF mechanical thresholds in the left
hind paw were significantly higher at 24 hours (p<0.0001), 48 hours (p=0.0079), and 72 hours (p=0.0164) following a single HIFU
treatment. VFF returned to baseline values from day 4-7. Increased mechanical thresholds were observed 24 hours (p=0.0021), 48
hours (p<0.0001), and 72 hours (p=0.0256) following a second HIFU treatment on day 8. The right paw showed no significant
differences in both groups, serving as a control. HPT was inconclusive. Histological analysis in both treatment groups demonstrated
healthy ganglion cell nuclei with no chromatolysis.
Conclusion: Our results suggest that external HIFU increases mechanical thresholds in CPNI rodents. Results following multiple
treatments show similar patterns of increased mechanical thresholds, thereby indicating that the DRG and associated central pain
pathways behave similarly during multiple treatments.
415. USMLE Step 1 score as a predictor of career path beyond neurosurgery residency
Aaron Gelinne (South Burlington, VT), BS; Susan Durham, MD
Introduction: Despite the scarcity of supporting evidence, USMLE Step I score is frequently cited as one of the most important factors
for applicants applying to neurosurgery residencies. While USMLE Step 1 scores have been positively correlated to ABNS board
scores, no studies have documented a correlation between USMLE Step 1 score and other metrics of career trajectory beyond
residency such as h-index, practice type and ABNS oral board certification.
Methods: A pre-existing database of neurosurgery residency applicants who matched into neurosurgery from 2001-2007 (n=1015)
was utilized that included USMLE Step 1 score. Online databases were used to determine h-index, practice type (academic, non-
academic, non-neurosurgery) and ABNS board certification status. Linear regression and nonparametric testing determined
associations between independent and dependent variables. Statistical significance was defined as a p-value<0.05.
Results: USMLE Step 1 scores were significantly higher for neurosurgeons in academic positions (238 ± 1) when compared to those
in non-academic (235 ± 1) and those who transferred to another specialty (232 ± 2, p<0.05). Linear regression determined a
significant correlation between USMLE Step 1 score and h-index (R=.123, R2 =.015). There were no significant differences in USMLE
Step 1 score between ABNS oral board certified (236 ± 1) and uncertified (234± 2) neurosurgeons.
Conclusion: Findings from this study include: (1) USMLE Step 1 score is a weak predictor of publishing productivity and impact given
the minimal correlation to h-index. (2) USMLE Step 1 score does not predict future pass rates of the ABNS oral board. (3) A career in
academic neurosurgery is associated with higher USMLE Step 1 scores. These findings indicate that USMLE Step 1 score provides
minimal predictive value of a person’s career following neurosurgery residency. This highlights the need for further refinement of the
current neurosurgery resident selection process.
416. Functional restoration of social encoding and behavior in an autism mouse model
Daniel Lee (Boston, MA); Gabriel Friedman; Firas Bounni, MD; Ziv Williams, MD
Introduction: Autism spectrum disorder (ASD) is the most common neurodevelopmental and psycho-social disorder to affect children
but, currently, has no effective treatment. Here, we tested the possibility of restoring social encoding and prosocial behavior in an adult
ASD mouse model through genetic and neuro-modulatory techniques.
Methods: To test for social encoding in the mouse medial prefrontal cortex (mPFC), we developed an alternating appetitive-aversive
paradigm in which socially-paired mice experienced both acute stress and food reward while we simultaneously recorded neuronal
activity. We then evaluated how germline mutation of Shank3-/+, a gene prominently affected in human ASD, influence social
encoding and how their encoding may be restored following direct oxytocin administration or rescued through Cre-flex mediated
restoration of Shank3 expression.
Results: We find that heterozygous loss of the Shank3 gene leads to a selective loss of mPFC cells that encodes another social
agent’s experiences, but also leads to a loss of distinction between self and other at the single-cellular level. This loss of selectivity to
the other’s experience (i.e., ‘what’ another is experiencing) was associated with a proportional increase in modulation to the animal’s
own specific experience, but surprisingly, did not affect encoding of the other’s social identity (i.e., ‘who’ is experiencing it). Both
oxytocin administration and restoration of the Shank3 gene expression rescued this social encoding deficit at the neuronal-level and
was associated with enhanced prosocial behavior.
Conclusion: Using a mouse model, we identify the single-neuronal encoding process that may be disrupted in ASD and demonstrate
that it is possible to restore social encoding and prosocial behavior in adults through genetic and neuro-modulatory techniques.
417. Procedural complexity independent of P2Y12 levels is a predictor of in-stent thrombosis in Pipeline flow diversion of
cerebral aneurysms

Bowen Jiang, MD (Baltimore, MD); Matthew Bender, MD; Erick Westbroek, MD; Risheng Xu, MD, PhD; Jessica Campos, MD; Li-Mei
Lin, MD; David Zarrin, BS; Chau Vo, BS; Rafael Tamargo, MD; Judy Huang, MD; Geoffrey Colby, MD, PhD; Alexander Coon, MD
Introduction: Flow diversion with Pipeline embolization device (PED) is increasingly utilized for the treatment of cerebral aneurysms.
Acute in-situ thrombosis is a complication of flow diversion with high morbidity and mortality. There is limited knowledge on the
predictors for acute in-situ thrombosis.
Methods: Data were collected prospectively on patients who experienced in-situ thrombosis during PED placement at a single
institution (August 2011 to July 2017) and compared with a matched cohort of patients who did not experience in-situ thrombosis.
Results: A cohort of 37 PED cases with in-situ thrombosis (mean age 53.8 years, mean aneurysm size 8.4mm) was matched with a
cohort of 705 PED cases without in-situ thrombosis (mean age 56.4 years, mean aneurysm size 6.9mm). All patients with in-situ
thrombosis received IA ReoPro. The two groups were evenly matched in patient demographics, previous treatment/SAH, and
aneurysm location. There was no statistical difference in peri-procedural P2Y12 levels between the two groups, with mean of 156 in
the in-situ thrombosis group and 148 in the control group (p=0.5894). Presence of cervical carotid tortuosity, high cavernous ICA
grade, and vasospasm were not significantly different between the two groups. The in-situ thrombosis group had statistically
significant higher fluoroscopy time (60.4 vs 38.4 mins, p less-than 0.0001), higher radiation exposure (3476 vs 2160 mGy, p less-than
0.0001), and higher utilization of balloon angioplasty (37.8% vs 12.2%, p less-than 0.0001). The in-situ thrombosis cohort had higher
incidence of major and minor stroke, intracerebral hemorrhage, and length of stay, but no mortality difference.
Conclusion: Predictors of procedural complexity, such as radiation exposure, fluoroscopy time, and post-processing balloon
angioplasty, are statistically higher in the in-situ thrombosis group compared to the control. Contrary to published reports, peri-
procedural P2Y12 levels do not appear to play a significant role in the development of in-situ thrombosis.
418. Vestibular schwannoma outcomes 5-24 years after Leksell Stereotactic Radiosurgery
Stephen A. Johnson, MD (Pittsburgh, PA); Hideyuki Kano, MD, PhD; Ajay Niranjan, MD, MBA; Edward Monaco, MD, PhD; Andrew
Faramand, MD; Matthew Pease, MD; Mohab Hassib, BA; David Spencer, BA; Nathaniel Sisterson, BA; Yoshio Arai, MD; John
Flickinger; L. Dade Lunsford, MD
Introduction: We evaluated long-term tumor control and cranial nerve outcomes in vestibular schwannoma patients who underwent
initial management using Leksell stereotactic radiosurgery (SRS).
Methods: 438 vestibular schwannoma patients underwent SRS as their primary surgical management between 1987 and 2007.
Median tumor volume was 0.8 cc (range, 0.1-20.1 cc), while the median-margin dose was 13 Gy (range, 11-20 Gy).
Results: The progression free survivals 3, 5, and 10 years after SRS were 95%, 92%, and 91%, respectively. Median follow-up was
62 months (range, 6-292 months). Ten patients had over 20 years of radiographic follow-up, none of whom sustained tumor
progression. Thirteen (3.0%) had sustained tumor progression that required intervention: 5 underwent repeat SRS, 8 had delayed
surgical resection. Delayed surgical resection was not associated with increased difficulty or morbidity. Tumor volume and margin
dose were not associated with progression free survival. Serviceable hearing preservation rates at 1, 3, 5, and 10 years were 88%,
72%, 62%, and 44%, respectively. Factors associated with better hearing preservation included higher pre-SRS speech discrimination
scores and younger age. The 5-year serviceable hearing preservation rate in patients who were < 60 years-old and GR class I was
78%, while the 5-year serviceable hearing preservation rate in patients who were < 60 years old and GR class II was 45%. Fifteen
patients (3.4%) developed facial neuropathy characterized as House-Brackmann grade 3 or less. These patients had a mean-margin
dose of 15.7 gy; no facial neuropathy was detected in patients undergoing SRS in the interval of 1997-2007 after the margin dose was
reduced to 13 gy or less. Twenty-one patients (4.8%) developed trigeminal neuropathy with or without pain.
Conclusion: Leksell SRS was associated with high rates of long-term tumor control and cranial nerve functional preservation,
validating its role as an initial management for vestibular schwannomas.
419. Spine surgery in Class IV and V obese patients: outcomes and surgical nuances
Gennadiy Katsevman, MD (Morgantown, WV); Scott Daffner, MD; Sanford Emery, MD, MBA; John France, MD; Cara Sedney
Introduction: Obese patients present many challenges to the spine surgeon and have high peri-operative morbidity and mortality
compared to non-obese patients. Class IV (body mass index (BMI) 50-59.9 kg/m2) and Class V (BMI greater than 60) obese patients,
in particular, present challenges in imaging, surgical positioning, and mechanics of surgery. The purpose of this study was to identify
the demographics and surgical indications for this patient population as well as the rate and severity of complications.
Methods: The authors performed a retrospective chart review on Class IV and V obese patients at a level one trauma and spine
referral center undergoing spine surgery by neurosurgical and orthopaedic staff from 2009 to 2016. Patient demographics, surgical
indications, and procedure type were recorded. Complication and mortality rates were evaluated.
Results: Sixty-three patients met inclusion criteria and underwent 86 surgeries. Average BMI was 55. Fifty-two percent of surgeries
were elective, and the most common indications were degenerative disease (39%), infection (19%), trauma (13%) and myelopathy
(13%). The most common procedures were posterior lumbar decompression (18%), posterior thoracic or thoracolumbar fusion with or
without decompression (16%), posterior lumbar fusion with or without decompression (15%), and anterior cervical fusion (14%). Thirty
percent of patients had complications; 63% of those occurred in non-elective patients. The most common complications were wound
dehiscence and/or infection (42%), followed by deep venous thrombosis (16%) and hardware failure (16%). Two cases were aborted
intra-operatively. Mortality rate was 5% overall, all of which occurred in non-elective patients.
Conclusion: Class IV and V obese patients have high morbidity and mortality, particularly among those undergoing non-elective

procedures. Awareness of these risks will help surgeons counsel their patients preoperatively. Given the high risk of complications,
surgeons should carefully consider potential alternative treatments (including referral for bariatric procedures) before performing
elective procedures in this patient population.
420. Combination of protein phosphatase 2A inhibition and PD-1 blockade synergistically induces regression of murine
intracranial glioblastoma
Dominic Maggio, MD (Bethesda, MD) ; Winson Ho, MD; Rebecca Breese, BS; Rongze Lu, PhD; Herui Wang; John Heiss; mark
gilbert; zhengping zhuang
Introduction: Checkpoint inhibition using monoclonal antibodies against PD-1 is currently under evaluation for treatment of
glioblastoma (GBM). Inhibition of protein phosphatase 2A (PP2a) was recently identified as a novel strategy to enhance cancer
immunity. We hypothesized that pharmacologic inhibition of PP2a utilizing the small-molecule inhibitor LB100 could enhance the
efficacy of anti-PD-1 immunotherapy in a syngeneic murine GBM model.
Methods: C57BL/6 mice were inoculated with 130,000 GL261-Luc+ tumor cells in their right striatum. When the bioluminescent
intensity (BLI) reached 1.3-2.6 million photon/sec*mm2 in the region of interest (ROI) on bioluminescent imaging, mice were
randomized into four treatment groups: control (PBS), anti-PD-1, LB100, and combination. For in-vitro studies, CD8 cells isolated from
mouse splenocytes were co-cultured with GL-261 cells separated via transwell inserts. FACS analysis was performed to determine
proliferation index, and PDL1 tumor cell expression. IFN-g supernatant levels were determined by ELISA bead-based immunoassay.
Results: Mice treated with the combination therapy had a significantly longer survival than mice treated with monotherapy (p<0.005)
or control (p<0.001). Tumor size measured by BLI decreased significantly more in the combination group compared to control after the
first treatment (p<0.005). Complete regression (CR) occurred in 25% of combination treated mice, but not in monotherapy or vehicle
control. Exposure to LB-100 exposure increased the proliferation index of activated CD8 cells by FACS analysis. LB-100-treated CD8
cells also induced a higher expression of PDL1 in co-cultured GL261 cells. LB100 increased IFN-g levels in transwell supernatant.
PDL1 expression fell to baseline with concomitant administration of anti-IFN-g.
Conclusion: These data suggest that PP2a inhibition and PD-1 mAB checkpoint inhibition act synergistically to enhance the immune
response against intracranial GBM. The mechanism may result from LB100-induced upregulation of PDL1, through lymphocyte
activation and secretion of IFN-g. This report supports clinical trials combining LB-100 with checkpoint immunotherapy for
glioblastoma.
500. Enhanced recovery after surgery (ERAS) decreases postoperative opioid use in elective spinal and peripheral nerve
surgery
Tracy Ma Flanders (Philadelphia, PA), MD; Zarina Ali; Lena Leszinsky; Brendan McShane; Diana Gardiner; Ali Ozturk; Neil Malhotra;
James Schuster; Paul Marcotte; Michael Grady; William Welch (Philadelphia, PA)
Introduction: The national opioid epidemic is a growing concern in the medical community. Use of an Enhanced Recovery After
Surgery (ERAS) protocol in elective spinal surgery has the potential to decrease inpatient and postoperative narcotic use.
Methods: At Pennsylvania Hospital, 201 elective spinal or peripheral nerve patients were enrolled in the ERAS protocol from April to
June 2017. The control group was a historical cohort of 74 patients from September to December 2016. Emergency cases were
excluded. Opioid and non-opioid use in the preoperative, perioperative, and postoperative periods were analyzed.
Results: The two groups were similar in overall demographics; specifically, prior spinal surgery, use of preoperative narcotics, and
surgical procedure performed were similar. A greater proportion of ERAS patients received four or more non-opioid agents compared
to control patients (48.8% vs. 20.3%, p<0.001). Patient controlled analgesia was nearly eliminated in the ERAS group (0.5% vs.
54.1%, p<0.001). Despite this, overall pain scores at admission and discharge as well as inpatient highest pain scores between ERAS
and control groups were not different (admission: 3.5 vs. 3.7, p=0.7; discharge: 4.4 vs. 4.7, p=0.54; highest pain: 8.0 vs. 8.1, p=0.75).
There was a trend of reduced average daily opioid usage (38.1 mg vs. 41.0 mg, p=0.60) in the ERAS group. ERAS patients also
trended towards being discharged to home more likely than the control group (89% vs. 80%, p=0.08). Importantly, at the one-month
postoperative point, more than half of the ERAS cohort were no longer using opioids compared to the control group (41.2% vs. 55.9%,
p=0.046).
Conclusion: The ERAS protocol in the elective spinal or peripheral nerve patient safely reduces opioid use while in the hospital as
well as at one month postoperatively.
501. ASL perfusion imaging of the frontal lobes predicts the occurrence and resolution of posterior fossa syndrome
Derek Yecies, MD (Emerald Hills, CA); Katie Shpanskaya; Gerald Grant, MD; Samuel Cheshier, MD, PhD; David Hong, MD; Michael
Edwards, MD; Kristen Yeom, MD (Emerald Hills, CA)
Introduction: Posterior fossa syndrome (PFS) is a common complication following the resection of posterior fossa tumors in children.
The pathophysiology of PFS remains incompletely elucidated, however the wide-ranging symptoms of PFS suggest the possibility of
wide-spread cortical dysfunction. In this study, we utilize arterial spin labeling (ASL), an MR perfusion imaging modality that provides
quantitative measurements of cerebral blood flow without the use of intravenous contrast, to assess cortical blood flow in patients with
PFS.
Methods: A database of pediatric brain tumor patients treated at LPCH at Stanford from 2004-2016 was reviewed retrospectively and
15 patients with PFS were identified.

Immediate postoperative ASL for patients with PFS and age-matched medulloblastoma patients who did not develop PFS were
compared. Additionally, in patients with PFS, ASL following the return of speech was compared with immediate postoperative ASL.
Results: On immediate postoperative ASL, patients who subsequently developed PFS had decreased right frontal lobe perfusion
(37.00 ± 13.46 vs 49.7 ± 13.72, p=0.046) and a trend towards decreased perfusion in the left frontal lobe (41.00 ± 17.36 vs 53.5 ±
14.62, p = 0.092) compared to age-matched children who did not develop PFS after tumor resection. Patients with PFS had
statistically significant increases in right (57.00 ± 18.3 vs 42.67± 16.5, p=0.016) and left (60.93 ± 20.96 vs 45.47 ± 17.5, p =0.031)
frontal lobe perfusion after the resolution of symptoms compared to their immediate postoperative imaging.
Conclusion: ASL perfusion imaging identifies decreased frontal lobe blood flow as a strong physiologic correlate of PFS that is
consistent with the symptomatology of PFS. This is also the first study to demonstrate that decreases in frontal lobe perfusion are
present in the immediate postoperative period and resolve with the resolution of symptoms, suggesting a physiologic explanation for
the transient symptoms of PFS.
502. Single-neuronal basis for interactive social behavior in a primate model
Amy Julia Wang MD (Cambridge, MA); Raymundo Báez-Mendoza, PhD; Kejia Hu, MD; Emma Mastrobattista; Jacob Grondin; Ziv
Williams
Introduction: Social dysfunction is a core component of many psychiatric disorders, but its single-neuronal and causal underpinnings
remain largely unknown. As a central feature of social interaction, reciprocity allows individuals in a group to forge alliances towards
augmenting individual and mutual fitness. Here, we studied the neuronal correlates of group interaction by obtaining multiple-neuronal
recordings in the anterior cingulate cortex (ACC) of Rhesus macaques as they performed a structured social task.
Methods: We devised a three-agent social task in which three macaques interacted with each other over multiple rounds. The task
required the monkeys to sit around a rotary table apparatus. In each trial, one monkey offers a food reward to one of the other two.
Throughout sessions, individuals could reciprocate past rewards that had been delivered to them. Based on this design, we could
dissociate core computations associated with interactive behavior: the animal’s own decisions, the decisions of others, their social
identities, and past interactions. During task performance, we recorded neuronal activity from the ACC using micro-electrode arrays.
Results: The monkeys showed strategic preferences for other individuals, and preferred to reward those who reciprocated. Engaging
in this social strategy increased the amount of reward received by a given animal, enhancing individual fitness. Maintaining a mental
representation of specific preferred individuals is a prerequisite for acting out strategic social preferences. We discovered a sub-
population of neurons encoding such a signal, correlating with the monkey’s own decision to reciprocate. These neurons tracked the
reward received by other group members and displayed differential activity in response to different individuals.
Conclusion: These findings demonstrate a novel sub-population of neurons in the primate ACC that encodes information about
particular individuals, forming the necessary basis for social reciprocity. These results lay the groundwork for identifying specific,
neurobiologically-guided targets for treatment of social behavioral disorders.
503. Spinal cord stimulation reduces opiate use in patients with chronic pain
Lucy Gee (Albany, NY); Heather Smith, MD; Zohal Ghulam-Jelani, BS; Hirah Khan, BS; Julia Prusik, BS; Paul Feustel, PhD; Sarah
McCallum, PhD; Julie Pilitsis, MD, PhD
Introduction: Chronic pain affects up to 23.5 million adults and causes significant burden to the US health care system. Spinal cord
stimulation (SCS) has been FDA approved for the treatment of chronic pain, and may provide an alternative to long-term opioid
management. We hypothesize that SCS reduces opioid use.
Methods: We prospectively evaluated 86 chronic pain patients undergoing SCS over 3 years who have 1-year follow-up.
Preoperatively and postoperatively, patients completed the numerical rating scale (NRS), McGill pain questionnaire (MPQ), Pain
catastrophizing scale (PCS), and Oswestry disability index (ODI). Opioid use was recorded using the iSTOP (New Yor State Internet
System for Tracking Over-Prescribing) database and grouped based on morphine equivalents (MEQ)/mg.
Results: Fifty-three of the 86 patients used opioids before SCS implantation. After surgery, 35.8% (n=19 patients) remained on
opioids and 64.2% of patients reduced or eliminated use. Specifically, 26 patients stopped opioid use and 7 reduced to
1-2MEQ/mg. Reduction/discontinuation of use was associated with improvements in NRS, MPQ, and ODI as compared to their
baseline (NRS: p=0.003, MPQ: p=0.001, ODI: p=0.007) and as compared to patients that continued opioid use (NRS: p=0.006, ODI:
p<0.001).
Conclusion: Sixty four percent of SCS patients reduced or eliminated opioid use at 1 year post-operatively. SCS may aid in
facilitating a decrease in opioid therapies while achieving pain management goals.
504. Five-aminolevulinic acid (5ALA) for fluorescence-guided surgery of high-grade gliomas (HGG): U.S. experience interim
analysis
Isabelle M. Germano, MD, FAANS, FACS (New York, NY); Constantinos Hadjipanayis, MD; Muhammad Chohan, MD; Jerone Kenedy,
MD; Bruce Andersen, MD; Ian Lee, MD; Hugh Moulding, MD; Bob Carter, MD; Steven Kalkanis, MD
Introduction: Real-time, florescence-guided surgery of HGG allows for maximizing extent of resection without being influenced by
intra-operative factors like brain shift. 5-ALA, a non-fluorescent prodrug, leads to intracellular accumulation of fluorescent porphyrins in
tumor cells, which in turn can be visualized by a modified neurosurgical microscope. The primary endpoint of our study was to
determine correlation of 5ALA fluorescent tissue with histopathology-confirmed HGG.

Methods: In this multicenter prospective single-arm study, patients with de-novo or recurrent HGG (World Health Organization grade
III/IV) as determined by pre-operative MR images were enrolled to receive 5-ALA before surgery. In subjects who received Gliolan®
(20mg/kg po) 3-5 hours before surgery, 3-5 biopsies from fluorescent areas, identified under blue light, were correlated with final
histopathology. Adverse events (AE) were documented.
Results: 35 patients with newly-diagnosed (N=19) or recurrent HGG (N= 16) were enrolled; 2 patients did not proceed with surgery.
Average age was 55.3 years (22-77); mean KPS 90+7. Fluorescence was detected in 32 of 33 subjects (97%). One case with
anaplastic astrocytoma did not demonstrate fluorescence. Histopathology confirmed the presence of tumor cells in all 160 biopsies
(100%): glioblastoma N=26, anaplastic-astrocytomas N=2, anaplastic-oligodendrogliomas N=2, gliosarcoma N=2; CNS lymphoma
N=1. Grade 1-2 AE related to the drug included skin erythema in 2 subjects (6%). Asymptomatic increase of liver function tests (LFTs)
greater than 2.5x baseline documented in 8 (25%) subjects 2 weeks after dosing, returned to normal at 6 weeks in 7 patients.
Conclusion: Intra-operative 5-ALA-induced fluorescence correlated with presence of HGG in 97% of cases, with an overall sensitivity
of
97%, and was well tolerated by patients across multiple participating sites. Intraoperative tumor fluorescence can assist in maximizing
resection by permitting real-time identification of HGG. Its impact on long term oncological outcomes is subject of ongoing studies.
505. Systemic and local immunosuppression in patients with high-grade meningiomas
Young Neurosurgeons Medical Student Abstract Award
Yuping Derek Li (Chicago, IL); Dorina Veliceasa, PhD; Jason Lamano; Jonathan Lamano; Gurvinder Kaur, MD; Joseph DiDomenico;
Daniel Oyon; Benjamin Smith; Orin Bloch, MD
Introduction: Despite aggressive treatment with surgery and radiation, atypical and anaplastic meningiomas have a high rate of
recurrence with limited options for systemic treatment. Immunotherapy targeting immune checkpoints, such as PD-L1, has
demonstrated significant success in controlling numerous malignancies. In this study, we investigate the extent of systemic and local
immunosuppression in meningiomas to assess the potential benefit of immune checkpoint inhibitors for the treatment of high-grade
meningiomas.
Methods: Peripheral blood was collected from patients undergoing resection of meningiomas (WHO grade I, n=20; grade II, n=20;
grade III, n=9). Immunosuppressive monocytes (CD45+CD11b+CD163+/-PD-L1+/-), myeloid-derived suppressor cells (MDSCs)
(CD11b+CD33+HLA-DRloPD-L1+/-), and regulatory T-cells (Tregs) (CD3+CD4+CD25+FOXP3+) were quantified through flow
cytometry. Tissue sections from the same patients were assessed for PD-L1 expression via immunohistochemistry.
Results: Patients with grade III meningiomas demonstrated increased peripheral monocyte PD-L1 compared to patients with grade I/II
meningiomas and healthy controls (p<0.05), with an average 2.1-fold increase. Compared to healthy controls, mean MDSC
abundance was increased 2.9-fold in grade I, 6.3-fold in grade II, and 6.8-fold in grade III meningioma patients. Patients with grade
II/III meningiomas had significantly increased MDSC abundance compared to patients with grade I meningiomas (p<0.05). Peripheral
Treg abundance did not differ significantly from healthy controls. PD-L1 staining of meningioma tissue demonstrated positivity in 31%
of grade I meningiomas, 35% of grade II meningiomas, and 44% of grade III meningiomas.
Conclusion: Patients with meningiomas exhibit signs of peripheral immunosuppression, including increased PD-L1 on myeloid cells
and elevated MDSC abundance proportional to tumor grade. Additionally, the tumors express substantial PD-L1 proportional to tumor
grade. These results suggest a role for immune checkpoint inhibitors targeting the PD-L1/PD-1 pathway in combination with standard
therapies for the treatment of high-grade meningiomas.
506. Genotype based local targeted therapy for glioma
Mahaley Clinical Research Award
Ganesh Mani Shankar, MD (Cleveland, OH); Ameya Kirtane, PhD; Hiroaki Wakimoto, MD, PhD; Kensuke Tateishi, MD, PhD; Fumi
Higuchi, MD, PhD; Tareq Juratli, MD; Matthew Meyerson, MD, PhD; Fred Barker, MD; A John Iafrate, MD, PhD; Robert Langer, PhD;
Giovanni Traverso, MD, PhD; Daniel Cahill, MD, PhD
Introduction: Aggressive neurosurgical resection to achieve sustained local control is essential for prolonging survival in patients with
lower-grade glioma. Most lower-grade gliomas harbor IDH1 mutations, which sensitize to metabolism-altering agents. To improve local
control of IDH1 mutant gliomas and avoid systemic toxicity associated with metabolic therapies, we developed a rapid diagnostic tool
coupled with a sustained release microparticle drug delivery system containing an IDH1-directed NAMPT inhibitor (GMX-1778).
Methods: An intraoperative (<30min) genotyping assay was engineered to be sensitive to diagnostic hotspot mutations in IDH1
R132, TERT promoter, H3F3A K27M or BRAF V600E at 1% allelic fraction. Microparticles containing IDH1-directed NAMPT inhibitors
were designed to provide sustained local delivery of these compounds. Microparticles were tested for in vitro activity in cell culture and
in vivo efficacy in murine orthotopic IDH1 wild-type and mutant glioma models.
Results: The multiplexed diagnostic assay was validated on 87 clinically-annotated tumor specimens. Microparticles loaded with the
GMX-1778 potently decreased viability of IDH1 mutated cancer cells, but not in wild-type cells, in a time-dependent manner in vitro. In
murine models, microparticles delivered intracerebral therapeutic concentrations of drug without detectable systemic toxicity. In mice
harboring established orthotopic tumors, surgical implantation of microparticles did not affect tumor growth in an IDH1 wild-type
glioma, while resulting in a significant decrease in tumor growth and prolonged survival in IDH1 mutant glioma.
Conclusion: A targeted local therapeutic for modulation of the tumor metabolic environment has demonstrable anti-cancer effect
against

IDH1 mutant glioma. Paired with intraoperative genotyping, this strategy enables immediate local application of a genotype-based
targeted therapy in surgical scenarios where local tumor control is paramount and systemic toxicity is therapeutically limiting. This
workflow could be adapted to facilitate precision local therapeutics for other genetically-defined cancers.
507. Analysis of mutational processes in 23 adult hemispheric diffuse gliomas identifies DNA-damage repair deficiency as a
major contributor to gliomagenesis
Brainlab Neurosurgery Award
Koray Ozduman, MD, PhD (Istanbul, Turkey); Ege Ulgen, MD; Ozge Can, PhD; Cemaliye Akyerli, PhD; M Necmettin Pamir
Introduction: Processes responsible for gliomagenesis are still largely unknown. To gain more insight we analyzed the signatures of
mutational processes that contribute to the total genetic mutation load in adult hemispheric diffuse gliomas (HDG). As previous studies
have shown variation in age, anatomical location, phylogenetic compartment and mutlifocality among molecular-subsets of adult
hemispheric diffuse gliomas we hypothesized that these subsets may differ in their mutational signatures.
Methods: 23 HDG (Median age 45, range 20-76) and paired blood samples were whole exome sequenced and mutations identified.
Contributing mutational signatures (Based on COSMIC) and their weight were calculated using DeconstructSigs. Mutational signatures
were correlated with parameters including age at presentation, pathology, molecular-subgroup, mutational load, age, anatomical
location, phylogenetic compartment and multifocality were investigated. 4 molecular subsets were IDH-mutant (n=5), TERT-only
(n=12), H3.3 mutant (n=2) and Triple-Negative (n=3).
Results: A median of 6.2 mutations/MB were observed. There was no difference in mutational load between molecular subgroups
(ANOVA, p= 0.814). Most common, recurrent signatures, common to all 4 molecular subsets were Signature 1 related to aging
(84.2%) and Signatures 3 (68.4%) and Signature 15 (47.4%) related to DNA-damage repair defects. TERT-only subset exhibited the
highest number of DNA-damage repair signatures (3, 15, 6 and 26). Triple-negative, IDH-mutant, TERT-only and H3.3 mutant subsets
carried a median of 1.5, 2, 3 and 3 DDR mutations/tumor respectively. Signature 1 was positively correlated with age (r = 0.46). We
observed no recurrent signature related to known environmental carcinogens.
Conclusion: Most common mutational signatures were attributed to aging followed by DNA-damage repair defects. Despite the
presence of signatures common to all gliomas and those recurrent in each molecular subset, each individual glioma exhibited a unique
blend of mutational signatures.
508. Convolutional neural networks provide rapid intraoperative diagnosis of neurosurgical specimens imaged with
Stimulated Raman histology
Ronald L. Bittner Award on Brain Tumor Research
Todd Hollon, MD (Ann Arbor, MI); Daniel Orringer, MD
Introduction: Intraoperative diagnosis is essential in the surgical management of brain tumors. Stimulated Raman histology (SRH)
uses the intrinsic biochemical properties of fresh, unprocessed surgical specimens to provide label-free digital histologic images,
eliminating the need for a conventional histology lab for intraoperative diagnosis. SRH is an ideal imaging modality to implement
machine-learning strategies for tissue diagnosis due to the robust histochemical information encoded in pixel data. Here, we develop a
deep convolutional neural network (CNN), which provides rapid, standardized diagnosis of fresh brain specimens.
Methods: For CNN training, 20,000 400x400µm SRH fields of view (FOV) from 270 patients across 7 common intraoperative
diagnostic categories were used. Our neural network was developed from the GoogleNet InceptionV3 CNN architecture, which
includes 24 million trainable parameters. Model validation was completed on 3,900 FOVs from 70 patients. The model was evaluated
on its ability to distinguish 1) diagnostic versus non-diagnostic tissue, 2) tumor versus non-tumor tissue, 3) glial versus non-glial
tumors and 4) provide the correct intraoperative diagnostic category.
Results: The trained CNN differentiated 1) diagnostic from non-diagnostic FOVs with 99.1% accuracy, 2) tumor from non-tumor FOVs
with 98.4% accuracy and 3) glial from non-glial tumor FOVs with 96.4% accuracy. Using CNN classifier probabilities, area under the
curve on ROC analysis for the above listed metrics was 0.992, 0.985, and 0.985, respectively. 4) By compiling FOV data from each
specimen, the CNN predicted the correct intraoperative diagnostic category in 98.6% (69/70) of cases in the validation set. The only
classification error by the CNN was an instance of dense gliotic brain tissue incorrectly labeled low-grade glioma.
Conclusion: Our study demonstrates the feasibility of applying deep machine learning for intraoperative diagnosis of neurosurgical
specimens. SRH and convolutional neural networks may ultimately be used to guide decision-making during brain tumor surgery
independent of conventional neuropathology resources.
509. Whole exome and targeted sequencing of adult infiltrating astrocytomas: experience at a single institution
Preuss Research Award
Rohan Ramakrishna, MD (New York, NY); David Pisapia; Samaneh Motanagh; Andrea Sobner; Kenneth Eng; Michael Kluk; Juan
Mosquera; Howard Fine; Mark Rubin; Himisha Beltran; Olivier Elemento
Introduction: Infiltrating astrocytomas (IA) comprise the most common primary brain tumors in the adult and include diffuse

astrocytoma, WHO grade II (DA); anaplastic astrocytoma, WHO grade III (AA); and GBM (WHO grade IV). Histologically-based
diagnoses belie a molecular heterogeneity that can be revealed by methods such as whole exome sequencing (WES) as well as
targeted cancer panels. Herein we summarize our findings in an adult IA cohort enrolled as part of a precision medicine clinical trial at
a single institution.
Methods: We interrogated 85 IA samples over 81 distinct adults (4 DA, 20 AA, and 61 GBM), including 12 IDH-mutated astrocytomas.
WES was performed on fresh frozen or FFPE tumor tissue and matched against peripheral blood samples for germline analysis. WES
data was then compared to more targeted approaches, such as the FoundationOne® sequencing panel (FO) available in 68 (80%) of
cases.
Results: The most frequently altered genes detected by both WES and FO include EGFR, CDKN2A/B, TP53, PTEN, NF1, IDH1,
ATRX, and PIK3CA. Certain alterations such as TERT promoter mutations, which were present in the majority of IDH-wildtype IA’s as
detected by FO, were not assessed by WES. Several mutations in cancer related genes were revealed to be germline alterations in
the WES pipeline alone, including in ARID1A, BRCA1, NF1, and WT1.
Conclusion: The majority of the most common recurrent genetic alterations in the spectrum of IA are reliably detected by WES and at
comparable rates to more targeted panels such as FO; however WES should be tailored to cover highly recurrent somatic alterations
occurring within introns and promoters, such as TERT, and would benefit by higher coverage of critical regions. Germline assessment
is also important as this critically influences the interpretation of alterations detected in tumor tissue.
510. The risk of malignancy after stereotactic radiosurgery
AANS/CNS Joint Section on Tumors Neuro-Oncology Trainee Award
Amparo Myrelle Wolf, MD, PhD; (London, Canada) Moses Tam, MD; Josef Novotny, MD; Roman Liscak; Hideyuki Kano; Roberto
Martinez; Nancy Martinez; Joshua Silverman; Dade Lunsford; Douglas Kondziolka
Introduction: A major concern of patients undergoing stereotactic radiosurgery (SRS) for benign tumors is the risk of a separate
secondary malignancy or malignant transformation. Long-term studies are lacking and the incidence of radiosurgery-associated
malignancy is not known.
Methods: We collected data from patients having undergone SRS for arteriovenous malformations (AVM), benign intracranial tumors
or trigeminal neuralgia. The incidence of malignant transformation and separate radiation-associated intracranial neoplasia was
calculated in patient-years.
Results: Data on 11 320 SRS patients with a total of 59 200 patient-years of follow-up was compiled for meningioma (n=3141), AVM
(n=2854), trigeminal neuralgia (n=1967), vestibular schwannoma (n=1914), pituitary adenoma (n=1182), other schwannoma (n=184)
and hemangioblastoma (n=78). The overall median follow-up was 3.97 years (0-24 years). Follow-up durations included 3928 patients
with 2-5 years, 2018 patients with 5-10 years, 1462 patients with 10-15 years and 508 patients with <15 years of follow-up.Two cases
of verified malignant transformation of vestibular schwannomas were reported at 8.7 and 11.8 years after SRS. Two cases of
presumed WHO grade 1 meningioma transformed to an atypical or malignant meningioma at 3.5 and 5.3 years. Three new malignant
brain tumors were reported, who developed distant intracranial malignancy at 4.3 and 8.7 years respectively. One pituitary adenoma
patient developed verified osteosarcoma locally at 12.8 years.This indicates that malignant transformation after SRS occurs in
approximately 1 in 14 800 patient-years. The incidence, either locally or distant, is 1 in 19 733 patient-years. This is similar to the
annual incidence of all primary malignant CNS tumors of 7.18 per 100 000, from the Central US Brain Tumor Registry (2009-2013).
Conclusion: Patients can be safely counseled that the risk of malignancy after SRS remains extremely low, comparable to the
incidence in the general population of primary CNS tumors, even at long-term follow-up of greater than 10 years.
511. CRISPR improved: inducible CRISPR-Interference achieves specific and reversible PIKE-A silencing in glioblastoma
Arman Jahangiri (San Francisco, CA); Patrick Flanigan, BS; Ankush Chandra, MA; Alan Nguyen, BS; Mohammad Mandegar, PhD;
Bruce Conklin, MD; Maxim Sidorov, BS; William Weiss, MD, PhD; Manish Aghi, MD, PhD
Introduction: Studying essential genes in glioblastoma are often difficult. Traditional knockout/knockdown methods via siRNA/shRNA,
and conventional cloning are nonspecific and irreversible, often selecting against targeted cells. PIKE-A, a proto-oncogene and
GTPase is an important components of CDK4-amplicon. PIKE-A binding enhances Akt’s kinase activity, thereby promoting cancer
progression. Unlike other undruggable GTPases, PIKE-A is appealing due to its weak affinity for nucleotides, but preclinical studies
have been hindered because it is notoriously difficult to repress genetically. We constructed clustered regularly interspaced short
palindromic repeat interference (CRISPRi), a tunable system able to downregulate individual alleles, to repress PIKE-A gene
expression in human glioblastoma cells.
Methods: We fused doxycycline-inducible deactivated Cas9 to a KRAB repression domain (at N-terminus), and transfected U87, and
GBM43 glioblastoma cells, followed by selection. Three sets of single guided RNA (sgRNA) were designed against PIKE-A for both
CRISPRi and the traditional CRISPR nuclease (CRISPRn) to serve as control. Additional groups consisted of siRNA, and shRNA
targeting PIKE-A. qPCR, Immunoblotting, proliferation, and migration assays were used.
Results: Post doxycycline induction, CRISPRi achieved a <99% knockdown in U87 and GBM43 cells compared to CRISPRn-treated
cells (same sgRNA) which only achieved a 42%, 59% knockdown in U87/GBM43 respectively. siRNA/shRNA transfections led to cell
death during clonal selection, with surviving cells fully expressing PIKE-A. CRISPRi cells demonstrated markedly reduced migration,
proliferation, and nutrient-deprivation survival, a finding not nearly as robust in CRISPRn group.
Conclusion: CRISPRi is a valuable tool allowing for highly specific and inducible genetic repression of genes essential for cancer cell

survival like PIKE-A, and CRISPRi is more sensitive than CRISPRn technology. Besides allowing verification of PIKE-A’s role in
glioblastoma proliferation, migration, and validating PIKE-A as a durggable GTPase target in glioblastoma, we have created whole
genome CRISPRi screening libraries to identify novel druggable targets that could someday yield clinical benefit for glioblastoma
patients.
512. RNA deconvolution reveals distinctive immunogenetic landscapes in Nf2 and non-Nf2 meningiomas
Jacky Yeung, MD (New Haven, CT); Akdes Harmanci, PhD; Sacit Omay, MD; Jennifer Moliterno, MD; Joseph Piepmeier, MD; Lieping
Chen, MD, PhD; Murat Gunel, MD
Introduction: Immunotherapy has gained traction in recent years showing promise in other forms of cancers. However, the
immunological landscape of meningiomas is not well studied and this hinders the development of targeted, rational immunotherapeutic
strategies. Our general hypothesis is that the immunological landscape is dictated by the tumor mutational profile.
Methods: We utilized the Yale Brain Tumor Database to examine 138 cases of intracranial meningiomas that had undergone whole
exome sequencing with RNA expression analysis to compare the immunogenetic profiles of NF2 mutants and non-NF2 cases.
CIBERSORT was used to estimate the fraction of 22 immune cell types by in silico RNA deconvolution. The expressions of selected
immune genes were compared within tumor grades and NF2 status. Differential immune gene expressions with LODS score < 3 were
considered to be significant.
Results: There were 51 and 87 cases of NF2 and non-NF2 cases. 16 of 22 cases of atypical meningiomas harbored NF2 aberrations.
Macrophages are the most abundant immune cell type with M2 immunosuppressive macrophages being the dominant phenotype
(33.0±2.1%) when compared to M1 pro-inflammatory macrophages (2.2±0.3%). Surprisingly, the second most abundant type of
immune cells are resting mast cells (11.1±1.2%). NF2 tumors had significantly more CD8 T cells and M2 macrophages (p<0.001).
Non-NF2 tumors had more resting mast cells and M0 macrophages. No differences in relative cell populations were found between
benign and atypical tumors. NF2 tumors had significantly higher expressions of B7-2/CD86, B7H2/ICOSLG, BAFF/TNFSF13B,
CD70/TNFSF7, RANKL/TNFSF11, and APRIL/TNFSF13. Overall, atypical meningiomas had higher expressions of B7-2/CD86,
B7H2/ICOSLG, RANKL/TNFSF11, and CD137/4-1BB than benign tumors.
Conclusion: This is the first study to suggest that M2 immunosuppressive macrophage is the most prevalent immune cell type in
human meningiomas. M2 macrophages should be targeted for future immunotherapies in meningiomas.
513. Glioma stem cells driven by distinct BMI-1 and EZH2 transcriptional pathways targeted separately or synergistically
Andrew E. Sloan, MD, FAANS (Cleveland, OH); Jin Xun, PhD; Leo Kim; Quilian Wu; Xiuxing Wang; Stephen Mack; Tyler Miller; Jill
Barnholtz-Sloan; Shideng Bao; Jeremy Rich
Introduction: Glioblastomas (GBMs) are lethal cancers characterized radiologically and histologically by enhancing, angiogenic
margins, and necrotic centers with pseudopallisading necrosis.
Methods: We collected tissue from various anatomically and histologically distinct regions of several human GBMs, annotating the
source of each specimen. We then characterized these histologically distinct regions according to their distinct histologic,
transcriptional, and metabolic profiles.
Results: Both the enhancing margin and the necrotic core harbor distinct populations of glioma stem cells (GSCs). The enhancing
regions were characterized by a proneural profile, while the hypoxic regions demonstrated a mesenchymal pattern. We thus
investigated the epigenetic regulation of these two niches. Proneural, perivascular GSCs activated Olig 2 via EZH2 (p<0.002). In
contrast, mesenchymal GSCs in hypoxic regions expressed high levels of Glut 1, Glut 3, MCT 1, and MCT 4, and HIF1a via BMI1
protein, which promoted cellular survival under stress due to down regulation of the E3 ligase RNF144A (p<0.02). Using both genetic
and pharmacologic inhibition, we found that proneural GSCs are preferentially sensitive to EZH2 disruption, whereas mesenchymal
GSCs are more sensitive to BMI1 inhibition (p <0.01). Intersetingly, since GBMs contain both proneural and mesenchymal GSCs,
combined EZH2 and BMI1 targeting proved more effective than either agent alone both in culture (p<0.008) and in vivo (p < 0.04).
Conclusion: Strategies that simultaneously target multiple epigenetic regulators within the same GBM may be synergistic in
overcoming therapy resistance caused by intratumoral heterogeneity and interconversion of cells from one transcriptional profile to
another. This strategy may also be useful in combination with conventional treatment.
514. Multi-agent vs. single-agent intraventricular chemotherapy for patients with neoplastic meningitis (NM): changing the
reputation of a fearsome disease
Samer Zammar, MD (Hershey, PA); Richard Eby, BA; Ephraim Church, MD; Brad Zacharia, MD; Heath Mackley, MD; Michael Glantz,
MD
Introduction: Five decades after the Ommaya reservoir was introduced into neurosurgical practice, the prognosis for NM remains
dismal, and in contrast to nearly all other malignant diseases, single-agent (rather than multi-agent) chemotherapy remains the
standard of care.
Methods: Since 2012, we have treated all patients with NM eligible to receive an Ommaya reservoir with multi-agent intraventricular
chemotherapy regimens tailored to the histology of the underlying cancer. We extracted detailed demographic, treatment, and
outcome data for these patients from an international NM registry, and compared that data to the corresponding patient level data
acquired from 6 of the 7 randomized controlled trials (RCTs) conducted in patients with NM, all of which used single-agent
intraventricular therapies.

Results: Two-hundred and three registry patients with NM (139 solid tumor, 44 lymphoma, 20 leukemia) from our registry were
compared to 350 patients from the RCTs (290 solid tumor, 60 lymphoma). Age, gender, KPS, tumor histology, status of the primary
cancer, and frequency of concurrent systemic chemotherapy or radiation did not differ between registry and RCT patients, or were
less favorable in the registry patients. All patients from the registry patient group were included for analysis regardless of how many
cycles of intraventricular therapy they received (intent-to-treat model). Median survivals (multi-agent vs. single-agent treatment) were
211 vs. 97 days, hazard ratio (HR) 3.39, p<0.001 for all solid tumors and 304 vs. 81 days, HR 2.10, p< 0.001 for lymphoma. Stratified
by tumor histology, median survival for breast cancer NM was 315 days [95% CI 248-449], for lung cancer 193 days [127- 200]; for
melanoma 307 days [65-1492], and for primary brain tumor 253 days [187- 348].
Conclusion: Multi-agent intraventricular chemotherapy was associated with dramatically increased survival in patients with solid tumor
and lymphomatous NM. These findings merit additional study in the randomized trial setting.
515. Integrative analysis implicates MYC and MAX in functional pituitary adenomas
Douglass Warren Tucker (Los Angeles, CA) ; Angad Gogia, BS; Timothy Triche, PhD; Charles Ashton, MS; Daniel Weisenberger,
PhD; John Carmichael, MD; Gabriel Zada, MD
Introduction: Pituitary adenomas (PAs) are common intracranial tumors that may cause endocrinopathies and neurological
deterioration. Although known causal contributors include heredity, hormonal influence, and somatic mutations, the pathophysiologic
mechanisms driving tumorigenesis and invasion remain unknown. Here we apply an integrative approach to elucidate regulatory
differences between functional PAs (FPAs) and non-functional PAs (NFPAs).
Methods: DNA methylation data from 58 (40 NFPAs, 18 FPAs) surgically-resected PAs was used to identify differentially methylated
regions (DMRs) between FPAs and NFPAs. We performed motif enrichment analysis on each set of DMRs to identify sequence motifs
for particular transcription factors. Using RNA sequencing data available in 24 of 58 adenomas, we constructed an empirical Bayes
linear model and applied gene set enrichment analysis to unearth coherent biological activities within the significantly differentially
expressed genes.
Results: MYC and MAX emerged as leading candidates from motif enrichment analysis on the significant differentially expressed
genes identified from DNA methylation data (p < 0.001). We also observed recurrent amplification of MYC and co-amplification of
MYC and MAX on chromosomes 8 and 14. Furthermore, V$MYCMAX01 and V$MYCMAX03 were both among the top results (p <
0.02 and p < 0.04 respectively) of gene set analysis of the differentially expressed genes identified from RNA sequencing data.
Conclusion: DNA methylation and RNA sequencing data may be used to identify candidates involved in PA function such as MYC
and MAX. Aberrant DNA methylation of MYC and MAX may be a mechanism of tumorigenesis in functional PAs, leading to potential
loci for targeted therapy in patients with functional tumors. The younger age of presentation and higher rate of tumor relapse in
functional tumors may be explained by these differences in the epigenetic and downstream changes allowing for proliferation of these
lesions.
516. Alterations to information transmission in the brain following spinal cord injury: a resting-state functional connectivity
analysis
Mayank Kaushal (Milwaukee, WI); Akinwunmi Oni-Orisan; Gang Chen; John Leschke; Benjamin Kalinosky; Matthew Budde; Brian
Schmit; Shi-Jiang Li; Vaishnavi Muqeet; Shekar Kurpad
Introduction: The application of a graph theoretical framework to characterize large-scale brain networks is being increasing used for
the evaluation of resting-state functional connectivity (rs-FC). By depicting the brain as a complex network of nodes and edges,
quantitative metrics can be calculated and compared between clinical populations of interest to demonstrate connectivity alterations in
brain networks. The present study highlights changes to information transmission in the whole-brain network in spinal cord injury
(SCI).
Methods: After obtaining the IRB approval, 15 subjects with chronic, complete (ASIA A) cervical SCI and 15 neurologically intact
controls underwent resting-state functional MRI (rs-fMRI) scans. Following preprocessing of data, the whole-brain network was
segmented into 264 regions of interest (ROI). Connectivity matrices containing correlation coefficients for every pair of ROIs were
obtained for each subject. Subsequently, quantitative network metrics of betweenness centrality (BC) and transitivity (T) were
calculated at incremental cost thresholds (% of total possible connections) and compared between the study groups using the two-
sample t-test.
Results: The whole-brain rs-FC showed significant differences for BC and T metrics at multiple cost thresholds between the two study
groups (p value < 0.05) with both BC and T found to be significantly decreased in SCI compared to controls.
Conclusion: The finding of significant differences in the network metrics highlights the utility of graph theory in evaluating large-scale
networks in clinically relevant neurosurgical patient populations. Our results indicate that brain undergoes reorganization following
disruption of the connection with the spinal cord, which causes alterations to information transmission within the brain. This has the
potential to facilitate noninvasive biomarker development for improving prognostication after SCI. Further, the characterization of rs-FC
alterations by network metrics can aid in the improvement of personalized therapeutic strategies involving the use of brain-computer
interface by offering a mechanism for the measurement of functional outcomes.
517. Kyphoplasty intraoperative radiation therapy: a new treatment paradigm for spinal metastasis – Phase I/II clinical trial
Sanford J. Larson, MD, PhD Award

Shashank Gandhi, MD (Manhasset, NY); Ahmad Latefi, DO; Ferney Diaz Molina, MS; Maged Ghaly, MD
Introduction: Open surgery followed by SRS is standard of care for unstable spine metastasis. Post-radiation vertebral-compression-
fractures (VCF) range from 11-39%. As radiation is palliative due to systemic tumor burden, pain and quality of life improvement is
paramount. Kyphoplasty intraoperative radiation therapy (Kypho-iORT) is a minimally invasive procedure to radiate metastasis from
within vertebral bodies, preventing VCF while providing immediate pain relief in potentially unstable spines.
Methods: This is a prospective phase I/II clinical trial to assess safety and efficacy of Kypho-iORT for potentially unstable spinal
metastasis in improving pain and functional status and maintaining local control. Pain scores were assessed with the numerical rating
pain scale (NRPS), functional status with brief pain inventory (BPI), local control and VCF with CT/MRI. Patients with symptomatic
metastasis underwent intraoperative electron-accelerated radiation followed by kyphoplasty. Tumors were limited to vertebral body
with SINS scores 7-12. Intraoperative CT was used to delineate tumor volume, confirm transpedicular access to tumor, and conform
10Gy from source to tumor periphery.
Results: 13 levels in 9 patients were treated. Mean age 51.3 years. Mean SINS score 9.18±1.99. No patients experience neurological
deterioration. Mean local-progression-free-survival was 8.3 months. After 3 months, one patient with metastatic colon adenocarcinoma
cancer suffered local progression. Mean VCF-free-survival 8.4months, with asymptomatic VCF in 1 patient at 6 months. NPRS scores
decreased from preoperative (6.55±2.54) to 1 week (3.00±2.57; p=0.002), 3 months (3.25±2.87; p=0.007), 6 months (2.00±2.12;
p=0.002) and trend toward improvement at 9 months (2.00±1.73; p=0.083). Functional status improved with reduced mean BPI at 3
months (54.90±9.29 vs 37.6±19.98; p=0.037), 6 months (32.0±18.49; p=0.073), and 9 months (25.67±5.77; p=0.034). Narcotic
reduced in 5/7 patients. 3/7 were medication free.
Conclusions: Kypho-IORT is a safe option for potentially unstable spinal metastases. Pain and function significantly improve,
enhancing quality of life. Local control and reduction in VCF can be obtained. Long-term follow-up is necessary to further evaluate
efficacy.
518. Predictive factors of survival in a surgical series of metastatic epidural spinal cord compression and a complete
external validation of eight multivariable scoring systems in a prospective North American multi-centre study
Brian D. Silber Award
Anick Nater-Goulet, MD (Toronto, Canada) ; Lindsay Tetreault, PhD; Branko Kopjar, MD; Paul Arnold, MD; Mark Dekutoski, MD; Joel
Finkelstein, MD; Charles Fisher, MD; John France, MD; Ziya Gokaslan, MD; Laurence Rhines, MD; Michael Fehlings, MD
Introduction: We aimed to: (1) identify preoperative predictors of survival in adults treated surgically for a single metastatic epidural
spinal cord compression (MESCC) lesion; (2) examine how these predictors relate to eight prognostic scoring systems (PSS); and (3)
perform the first full external validation of these PSS in accordance to the TRIPOD statement.
Methods: 142 surgical MESCC patients were enrolled in a prospective, multicenter, North American, cohort study and followed for 12
months or until death. Cox proportional hazards (PH) regressions were used; PH assumption was checked. Non-collinear predictors
with <10% missing data, ≥10 events per stratum and p<0.05 in univariable analysis were tested through a backward stepwise
selection. Bootstrapping was used for optimism correction. Calibration was examined graphically and discrimination with Harrell c-
statistics for the original and revised Tokuhashi, Tomita, modified Bauer, van der Linden, Bartels, OSRI and Bollen. Survival stratified
by risk groups was evaluated using the Kaplan-Meier method and log-rank test.
Results: Seven factors were significant in univariable analysis: Tomita tumor grade, sex, organ metastasis, body mass index,
preoperative radiotherapy to MESCC, and SF-36v2 Physical Component (PC) and EQ-5D scores. Tomita tumor Grade II/III (HR:
2.897, 95% CI: 1.593-5.267, p=0.0005), organ metastasis (HR: 1.986, 95% CI: 1.229-3.211, p=0.0051), and SF-36v2 PC (HR: 0.946,
95% CI: 0.921-0.971, p<0.0001) were independently associated with survival; corrected discrimination was 0.68 (95% CI: 0.66-0.70).
Although calibration could not be optimally assessed, it was poor overall. Bartels had the best discrimination (0.69; 95% CI: 0.66 –
0.72).
Conclusion: Slow growing tumor, absence of organ metastasis, and lower degree of physical disability are independent preoperative
predictors of longer survival in surgical MESCC patients. These results are in keeping with current PSS. This first full external
validation of eight PSS revealed poor gross calibration and discrimination was at best fair.
519. Mesenchymal stem cell-seeded high-density collagen gel for annular repair: in vivo sheep study
Stewart B. Dunsker, MD Award
Ibrahim Hussain, MD (New York, NY); Christoph Wipplinger; Stephen Sloan; Rodrigo Navarro-Ramirez; Eliana Kim; Micaella Zubkov;
Gernot Lang; Lawrence Bonassar; Roger Hartl
Introduction: Our group has previously shown successful in vivo annulus fibrosus (AF) repair in rodents and sheep models using an
acellular, riboflavin crosslinked high-density collagen (HDC) gel. We now report an in vivo study performed in sheep analyzing the
effects of seeding allogenic mesenchymal stem cells (MSCs) into this HDC gel for annular repair.
Methods: 15 lumbar intervertebral discs (IVDs) from three sheep were exposed via a lateral pre-psoas approach and randomized into
4 groups: 1) intact (N=3); 2) injury (3mm x 1cm annulotomy+100mg nucleotomy) (N=4); 3) injury+acellular gel treatment (N=4); and 4)
injury+MSC-seeded gel treatment (106 MSCs/mL) (N=4). Sheep were sacrificed at 6 weeks. Disc height index (DHI) and Pfirrmann
grading were performed using lateral X-ray and 3T MR images, respectively. Quantitative MRI analyses for nucleus pulposus (NP)

area and T2 relaxation time (T2-RT), a surrogate for disc hydration, was also performed. Values were calculated as ratios
standardized to healthy controls from the same sheep. Quantitative histologic assessment was also performed using the validated
Han scoring system based on cellularity and morphology of the AF and NP.
Results: All treated IVDs retained gel plugs on gross assessment and there were no adverse immunologic reactions. For groups 2-4,
the following values were obtained: DHI were 0.846, 0.874, and 0.96, respectively (P=0.00274). Average Pfirrmann grades were 2.5,
2.5, and 1.75, respectively (P=0.00035). Average NP area ratios were 0.868, 0.926, and 0.894 (P=0.636). Average T2-RT ratios were
0.784, 0.835, and 0.909 (P=0.0154). Average Han scores were 11.5, 10, and 9.5 (P=0.246).
Conclusion: MSC-seeded HDC gel treated IVDs demonstrated a statistically significant improvement in DHI, Pfirrmann grade, and
T2-RT over other experimental groups. There was a trend for more histologic AF and NP organization with MSC-seeded
HDC than acellular HDC and negative controls. Similar analyses to 16 weeks post-injury are ongoing.
520. Potential of human NP-like cells derived from umbilical cord to treat degenerative disc disease: novel mechanism for
disk regeneration
Mick J. Perez-Cruet, MD, FAANS (Royal Oak, MI); Mick Perez-Cruet; Esam Elkhatib; Naimisha Reddy; Irfan Khan; Christina McKee;
Rasul Chaudhry
Introduction: Degenerative disc disease (DDD) is a common spinal disorder that manifests with lower back pain. The degeneration of
Intervertebral disc (IVD) is characterized by the loss of extracellular matrix and dehydration of the nucleus pulposus (NP) of IVDs.
Currently, thereis no biological treatment to cure this debilitating ailment.
Methods: In this study, we investigated the efficacy of NP-like cells (NPCs) derived from the umbilical cord (UC) MSCs in restoring
degenerated IVDs using a rabbit DDD model. UC -MSCs wereinduced to differentiate into NPCs by using differentiation medium (DM)
for two weeks, labeled with PKH26 and then injected into the degenerated IVDs.
Results: Eight weeks post transplantation analysis showed that structure and cellularity of the NP improved only in the IVDs that
received NPCs. Transplanted IVDs also had higher sGAG and water content compared to the sham and degenerated IVDs. The
transplanted cells survived, integrated, and dispersed in the damaged areas of the NP and were functionally active as they expressed
human genes, SOX9, ACAN, COL2, FOXF1, KRT19, PAX6, CA12 and COMP as well as human proteins, SOX9, ACAN, COL2 and
FOXF1 implicated in NP biosynthesis.
Conclusion: These results suggest that NPCs were capable of homing to regenerate NP. The molecular mechanism for NP
regeneration was proposed to be regulated via the TGFß1 pathway. This studyfor the first time demonstrates the feasibility and
efficacy of humanNPCs derived from UCMSCs to regenerate NP in a rabbit model.These findings should spur interest for clinical
studies to treat DDDusing NPCs.
521. An interdisciplinary neurosurgery-geriatric co-care model reduces time to initiation of post-operative oral narcotic pain
regiment in elderly patients undergoing deformity correction surgery
Owoicho Adogwa, MD (Chicago, IL); Aladine Elsamadicy, BE; Michael Ongele, BS; Amanda Sergesketter, BS; Jessica Moreno;
Victoria Vuong, MS; Joseph Cheng, MD, MS; Isaac Karikari, MD; Carlos Bagley (Chicago, IL)
Introduction: Whether a neurosurgery-geriatrics co-care model leads to early transition to oral analgesics remains unknown and is
the aim of this study.
Methods: A unique model called The Peri-operative Optimization of Senior Health Program (POSH) was launched for elderly patients
(≥65 years old) undergoing lumbar spine surgery at a major academic institution. In this model, a geriatrician co-manages the patients
with the neurosurgical team during the pre- and post-operative periods. The medical records of 122 elderly patients (≥65 years)
undergoing a planned elective spinal surgery for correction of adult degenerative scoliosis were reviewed. Patients were categorized
as “Early” if transitioned from intravenous to Oral-analgesics within 24hrs of surgery (<1 post-operative day) and as “Late” if
transitioned after 48 hours of surgery (≥2 post-operative days). Patient demographics, operative variables, complication rates, duration
of hospital stay, ambulation ability, and follow-up Visual Analog Scale (VAS) scores were collected for all patients.
Results: Of the 122 elderly patients included, 70 (57.4%) patients were transitioned to an oral regiment “Early” and 52 (42.6%)
patients “Late”. The majority of patients transitioned within 24hrs of surgery were enrolled in the POSH program. Baseline
demographics and comorbidities were similar between both cohorts. There were no significant differences in intraoperative variables,
ambulation status and post-operative complications rates between both cohorts. Patients in the “Early” Cohort had a decreased LOS
compared to the Later cohort (5.9 vs. 7.6 days), however, there was no significant differences in VAS scores at 6-weeks and 3-
months after surgery. In a multivariate logistic regression model, not being enrolled in a neurosurgery-geriatric co-care model (POSH
program) was independently associated with increased time to transition oral analgesics [OR:2.98, 95% CI(1.12,7.96),p=0.03].
Conclusion: This study suggests that an interdisciplinary co-care model may facilitate early transition to oral analgesics and decrease
length of in-hospital stay for elderly patients undergoing surgery for deformity correction.
522. Improvement in Ames-ISSG cervical deformity classification modifier grades correlate to clinical improvement and
likelihood of reaching MCID in multiple metrics: series of 73 patients with 1 year follow-up
Peter Gust Passias (Brooklyn Heights, NY); Samantha Horn, BA; Justin Smith; Gregory Poorman; Muhammad Janjua; Cole Bortz;
Frank Segreto; Robert Hart; Douglas Burton; Virgine Lafage; Christopher Ames; International Spine Study Grou (ISSG)
Introduction: Prospective cervical deformity (PCD) patients (pts) have recently been assessed with ACD and adult spinal deformity

(ASD) classifications with short follow-up. This study describes PCD pts with cervical (Ames) deformity scheme at baseline and 1-year
post-operative and correlates modifier grades with outcomes. This study aims to utilize the Ames cervical classification to assess 1-
year ACD outcomes.
Methods: Retrospective review of prospectively collected cervical deformity database. PCD pts ≥18yrs with pre-/post-op(1Y)
radiographs. Pts were classified with Ames (A-ACD) scheme. A-ACD primary deformity descriptors(C=cervical;CT=cervicothoracic
junction;T=thoracic;S=coronal) and alignment modifiers(cSVA, TS-CL, mJOA, Horiz) were assigned. Baseline univariate description
evaluated demographics, clinical intervention, and Ames deformity driver types. Patients were evaluated for improvement and meeting
MCID for mJOA, NDI, and EQ5D.
Results: 73 ACD patients were categorized as: C=41(56.2%), CT=18(24.7%), T=9(12.3%), S=5(6.8%). By Ames modifier
improvement at 1Y, 13(17.8%) improved in mJOA score, 26 (35.6%) in cSVA grade, 19(26.0%) in Horiz, and 15(20.5%) in TS-CL. At
1Y the highest mJOA modifier grade differed across types(C=26.3%, CT=15.4%, T=0.0%, S=0.0%,p=0.003). Higher PT was observed
in patients with high (1+2) cSVA grades (58.3% vs. 28.0%, p=0.013) and high(2+3) mJOA(64.0% vs. 39.6%, p=0.041) scores at
baseline. 1Y post-operatively, only S deformities differed in cSVA grade distribution (0=20.0%, 1=80.0%, 2=0.0%,p=0.048) and severe
myelopathy prevalence differed between Ames-ACD deformity descriptors(C=26.3%, CT=15.4%, T=0.0%, S=0.0%,p=0.033).
Improvement in mJOA modifier correlated with reaching 1Y NDI MCID in the overall cohort(r=0.354,p=0.002). For type C, cSVA
improvement correlated with reaching NDI MCID at
1Y(r=0.387,p=0.016). The number of Ames modifiers a patient improved in from baseline to 1Y correlated to reaching 1Y mJOA
MCID(r=0.344,p=0.003). The number of Ames modifier improvements also correlated with reaching an increasing number of MCIDs for
mJOA, NDI, and EQ-5D(r=0.272,p=0.020).
Conclusion: Ames-ACD classification can effectively describe cervical deformity patients’ alignment and outcomes at 1-year.
Improvement in radiographic Ames modifier grades have a significant correlation to 1-year outcomes and alignment correction.
523. Electrical stimulation and white matter following spinal cord injury in rats
Bethany Kondiles (Houson, TX); Robert Robinson; Aijun Zhang; Tae Hoon Lee, PhD; Steve Perlmutter, PhD; Philip Horner, PhD
Introduction: Spinal cord injury (SCI) can cause motor and sensory impairments below the injury site. At the lesion and peri-lesional
sites, neuronal and oligodendrocyte cell death and glial scarring are the major causes of disruption to ascending and descending
neural signals. Many researchers and clinicians are exploring the possibility that electrical stimulation may help to restore motor and
sensory function.
Methods: Long-Evans rats received unilateral moderate contusion injuries at cervical level 4. Two weeks later, penetrating electrodes
were implanted into the contralateral motor forelimb area. One week later each implant was tested by applying current to evoke
forelimb movement. Animals in the control group were kept in arenas without any electrical stimulation. Stimulated animals received
single biphasic pulses at 10Hz for 5 hours a day for 5 days per week to singular sites known to evoke forelimb movement at 80% of
threshold for movement. After three weeks of stimulation, animals were perfused and tissue was examined for changes in white matter
composition. In a subset of animals stimulated for one week, tissue was extracted for RNA purification and analysis.
Results: The presence of penetrating electrodes did not appear to induce an inflammatory responses. On the contrary, at the injury site
of stimulated animals there seemed to be a decrease in inflammatory responses, and an increase markers of in white matter
reorganization. Transcripts of genes relevant to synaptic plasticity, neural plasticity, and morphological restructuring were upregulated.
Conclusion: We hypothesize that electrical stimulation activates pathways that yield morphological changes that may ultimately help
re-establish signal conduction following SCI. More thorough analyses of the mechanisms of post-SCI repair will allow for more
targeted research questions, which may yield more targeted therapies.
524. Utility of neuromonitoring during lumbar pedicle subtraction osteotomy for adult spinal deformity
Darryl Lau, MD (San Francisco, CA); Russel Lyon, PhD; Ceclia Dalle Ore; Vedat Deviren, MD; Justin Smith, MD; Christopher
Shaffrey; Christopher Ames, MD
Introduction: The benefits and utility of routine neuromonitoring with motor (MEPs) and samatosensory evoked potentials (SSEPs)
during spine surgery remain unclear. This study assesses the measures of performance and utility of neuromonitoring during lumbar
pedicle subtraction osteotomy (PSO).
Methods: A retrospective study of a single surgeon (C.A.) cohort of consecutive adult deformity patients who underwent lumbar PSO
from 2006 to 2016 was performed. A blinded neurophysiologist reviewed individual cases for neuromonitoring changes. Multivariate
analysis was performed to determine whether changes correlated with neurological deficits. Measures of performance were calculated.
Results: A total of 242 lumbar PSO cases were included. Neuromonitoring changes occurred in 38 (15.7%) cases: 21 (8.7%) transient
and 17 (7.0%) permanent. Of permanent changes, 9 (52.9%) had no recovery and 8 (47.1%) had partial recovery of signals. Changes
occurred at a mean time of 8.8 minutes following PSO closure (range: during closure to 55 minutes after closure). Average loss of
signal was 72.9%. Overall complication was 25.2% and incidence of new neurological deficits was 4.1%. On multivariate analysis,
neuromonitoring changes were not associated with complications (p=0.495) or able to predict postoperative neurological deficits
(p=0.429). Of the 38 changes, a true positive was seen in 3 cases. Calculated measures of performance are: sensitivity of 30.0%,
specificity of 84.9%, positive predictive value of 7.9%, and negative predictive value of 96.6%. Of the specific characteristics of the
neuromonitoring changes, only greater than 80% percent signal loss was significantly associated with a higher rate of neurological
deficit compared to less than 80% (23.0% vs. 0.0%, p=0.021); changes less than 80% did not have deficits.
Conclusion: Neuromonitoring has a low positive predictive value and sensitivity for detection of new neurological deficits. Even when
neuromonitoring is unchanged, patients still develop new neurological deficits. Multimodality monitoring including transcranial MEPs

has significant limitations in lumbar PSO.
525. Patient history of anemia is an independent predictor of 30-day readmission in elderly (≥60 years old) spine deformity
patients after elective spinal fusion
Owoicho Adogwa, MD (Chicago, IL); Aladine Elsamadicy, BS; Victoria Vuong, MS; Michael Ongele, BS; Amanda Sergesketter, BS;
Joseph Cheng, MD, MS; Carlos Bagley; Isaac Karikari, MD
Introduction: Hospitals and health systems are investing considerable resources into the identification of patients at risk of hospital
readmission and designing interventions to reduce the rate of hospital readmissions. The aim of this study is to determine if a pre-
operative history of anemia is an independent risk factor for readmission within 30 days of discharge.
Methods: The medical records of 697 elderly (≥60 years old) deformity patients undergoing elective spinal fusion at a major academic
institution from 2005 to 2015 were reviewed. We identified 61 (8.9%) patients with a pre-operative diagnosis (<3 months prior to
surgery) of anemia and 636 (91.1%) without (Anemia: n=61; No-Anemia: n=636). Patient demographics, comorbidities, intra- and 30-
day post-operative complication and readmission rates were collected for each patient. The primary outcome investigated in this study
was unplanned hospital readmission for any reason within 30-days of discharge. The association between pre-operative anemia and
30-day readmission rate was assessed via multivariate nominal logistic regression analysis.
Results: Patient demographics and comorbidities were similar between both groups. Median [IQR] number of fusion levels and
operative time were similar between the cohorts (Anemia: 4[3-7.5] vs No-Anemai: 5[3-7],p=0.86). The Anemia cohort had a
significantly greater incidence of intraoperative durotomy, compared to the No-Anemia cohort (14.8 vs. 5.8,p=0.007).There was
significant difference in 30-day readmission between the cohorts, with the Anemia cohort experiencing a 2-fold increase
(Anemia:21.3% vs. 11.0%,p=0.02). Compared the No-Anemia cohort, the Anemia cohort experienced significantly greater incidences
of 30-day wound dehiscence (p=0.005)) and altered mental status (p=0.001). Adjusting for other risk factors, the multivariate nominal
logistic regression demonstrates that preoperative anemia is an independent predictor of 30-day readmission after elective spine
surgery in the elderly [OR:2.53, CI(1.26, 5.07),p=0.01).
Conclusion: Pre-operative anemia is an independent risk factor for readmission within 30-days of discharge after elective spine
surgery in elderly patients.
526. Predictive factors leading to readmission within 30 days in patients undergoing surgery for spinal metastases
Jay I. Kumar (Oklahoma City, OK); Vijay Yanamadala; Ganesh Shankar, MD, PhD; Bryan Choi, MD, PhD; John Shin, MD
Introduction: Readmission within 30 days after complex spine surgery is considered a never event by Medicare but remains a reality
in 30-35% of cases after surgical treatment of spinal metastases. We present a single-center experience of readmissions in 185
consecutive patients who underwent surgery for spinal metastases and assess factors predictive of readmission.
Methods: Charts of 185 patients who underwent surgery for spinal metastases over five years from October 2011 through February
2017 were reviewed. Multivariate logistic regression was performed for patient demographic and surgical parameters that predict
readmission.
Results: The rate of unplanned readmission within 30 days was 28%. The most common reason for readmission was pain,
accounting for 24% of all readmissions. Medical factors accounted for 54% of readmissions: failure to thrive, 14%; fever, 12%; altered
mental status, 12%; pulmonary embolism, 4%; and miscellaneous, 12%. Surgical factors accounted for 22% of readmissions: wound
infection, 14%; new neurologic deficit, 6%; and miscellaneous, 2%. Levels of metastatic disease, greater than 3 levels with
metastases, and receiving chemotherapy within 30 days before surgery were all predictive of readmission (p less than 0.05). Female
sex, receiving chemo anytime before surgery, and receiving radiation to the spine anytime before surgery tended to predict
readmission but were not statistically significant (p less than 0.11).
Conclusion: Surgery for spinal metastases is associated with a significant readmission rate. Pain and medical factors accounted for
most readmissions. Advanced disease and recent chemotherapy are predictive of readmission and should be taken into account when
deciding on discharge disposition for patients after surgery for spinal metastases. Enhanced coordination of post-operative care
between surgical and medical teams may help reduce readmission rates.
527. Correlation of the Spinal Instability Neoplastic Score (SINS) individual components with patient-reported outcomes
following surgery
Ibrahim Hussain, MD (New York, NY); Ori Barzilai; Anne Reiner; Natalie DiStefano; Lily McLaughlin; Shahiba Ogilvie; Mark Bilsky; Ilya
Laufer
Introduction: We have previously demonstrated that the Spinal Instability Neoplastic Score (SINS) correlates with patient reported
outcomes (PRO), with higher scores experiencing greater relief after surgery. The objectives of this study were to determine how each
SINS component correlates with pre- and post-operative PRO and to study the heterogeneity of the indeterminate group to further
delineate instability.
Methods: SINS and PRO (Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory (MDASI)) were prospectively collected in
131 patients undergoing stabilization surgery for spine metastases. Association between individual SINS components with pre-
operative symptom burden and PRO symptom change after surgery was analyzed using Spearman Rank Correlation Coefficient (rho).
Correlation between SINS component scores and magnitude of pain relief was analyzed using the Kruskal Wallis test. SINS and
association with pre-operative PRO scores were compared for subgroups within the indeterminate group (7-9 vs. 10-12) using the

Wilcoxon two-sample test. The mean differences in post- and pre-operative PRO scores for these subgroups were compared using
the Wilcoxon signed rank test.
Results: Cumulative radiographic SINS maintained a statistically significant correlation with preoperative pain and activity impairment.
The presence of mechanical pain followed by metastatic location correlated most strongly with pre-operative functional disability and
improvement in PRO following surgical stabilization. Blastic rather than lytic bone lesions demonstrated stronger association with
symptomatic improvement following stabilization. Patients with SINS 10-12 demonstrated markedly improved postoperative PRO
nearly across the board compared to patients with SINS 7-9.
Conclusion: The presence of mechanical pain has the strongest correlation with pre-operative disability and improvement after
surgery. However, radiographic components of SINS also correlate with pre-operative symptom severity and post-operative PRO,
supporting their utilization in evaluation of spinal instability. Among patients with indeterminate SINS, patients with higher scores
experience improvement in a larger number of PRO, suggesting that this group includes distinct populations.
528. Chiari malformation clusters describe differing presence of concurrent anomalies based on Chiari type
Peter Gust Passias (Brooklyn Heights, NY); Samantha Horn; Dennis Vasquez-Montes; Gregory Poorman; Cole Bortz; Frank Segreto;
Muhammad Burhan Janjua; Olivia Bono; Rory Goodwin
Introduction: Chiari malformations are structural defects in the brain where the cerebellum is pushed into the foramen magnum and
upper spinal canal. This study utilized the Nationwide Inpatient Survey (NIS) to evaluate Chiari malformation patients, concurrent
diagnoses, and associated anomalies.
Methods: Retrospective review of NIS 2003-2012. Malformations were assessed by Chiari type: Type-I (ICD-9-CM 348.4), Type-II
(741.00-741.03), Type-III (742.0), Type-IV (742.2). NIS-supplied hospital- and year-adjusted weights allowed assessment of
malformation prevalence, as well as cardiac, gastrointestinal (GI), genitourinary (GU), and other body system anomalies. Cross-
tabulations evaluated rates of anomaly concurrence.
Results: Chiari case frequency: Type-I: 305,726; Type-II: 119,632; Type-III: 15,540; Type-IV: 79,663. Overall, 44.3% of patients had
≥1 concurrent anomaly. By type, 7.1% of Type-I patients, 12.3% of Type-II, and 100% of Type-III and Type-IV had ≥1 concurrent
anomaly. Assessing known associated conditions, tethered cord was present in 1.9% of Type-I, 4.0% of Type-II, 0.7% Types III and
IV, spina bifida in 0.8% Type-I, and 2.9% Types-III and IV. Syringomyelia was present in 4.6% of Type-I cases, 2.8% Type-II, 0.7%
Type-III and 0.2% Type-IV. Distribution of hydrocephalus in Chiari cases: 13.1% Type-I, 1.1% Type-II, 10.6% Type-III, and 16.0%
Type-IV. Common anomaly clusters for Chiari Type-I were: syringomyelia/scoliosis (0.63%); Ehlers Danlos/tethered cord (0.59%);
syringomyelia/tethered cord (0.34%). Common anomaly clusters for Type-II were: tethered cord/scoliosis (0.72%);
syringomyelia/scoliosis (0.43%); atrial septal defect/paten ductus arteriosus (0.31%). Type-III patients commonly presented with both
encephalocele/acquired hydrocephalus (11.45%), encephalocele/congenital hydrocephalus (5.09%), encephalocele/reduction
deformity of the brain (3.74%), and encephalocele/atrial septal defect (3.38%). Type-IV patients had the following anomaly clusters:
reduction deformity of the brain/acquired hydrocephalus (15.95%), reduction deformity of the brain/congenital hydrocephalus (9.99%),
atrial septal defect/reduction deformity of the brain (6.73%), and microcephalus/reduction deformity of the brain (6.67%).
Conclusion: The top five body system anomalies in Chiari malformation patients are nervous system, cardiac, genitourinary, neck,
and gastrointestinal. Chiari Types-III and IV have higher congenital anomaly rates than Types-I and II, especially for cardiac and
nervous system anomalies.
529. Spondylolysis and spondylolisthesis in American professional baseball players
Heath Gould (North Las Vegas, NV); Joseph Tanenbaum; Emily Hu; Colin Haines; Iain Kalfas; Jason Savage; Mark Schickendantz;
Thomas Mroz
Introduction: Few studies in the literature have systematically investigated the impact of pars defects on elite baseball players. We
set out to report the incidence, treatment, and return-to-play outcomes of symptomatic spondylolysis and spondylolisthesis in
American professional baseball players.
Methods: A retrospective cohort study was conducted among all professional baseball players who presented with a complaint of low-
back pain and received lumbar spine imaging between 2011 and 2016. Imaging reports were reviewed to identify Major League and
Minor League players with a radiologic diagnosis of spondylolysis or spondylolisthesis. This cohort was then sub-analyzed according
to a variety of demographic and injury-related factors.
Results: 272 players presented with low back pain and received lumbar spine imaging. Of those, 75 had radiologic evidence of
spondylolysis or spondylolisthesis (27.6%). 47 players were diagnosed with spondylolysis (62.7%), while 28 were diagnosed with
spondylolisthesis (37.3%). The median age of these players was 22.7 years old and their median service in professional baseball was
2.8 years. Overall, the median return-to-play time was 51 days. Players diagnosed with spondylolysis tended to be younger (22.0 vs.
25.9 years old; p < 0.05) with fewer years of professional experience (1.8 vs. 5.2 years pro; p < 0.01) compared to players diagnosed
with spondylolisthesis. However, players with spondylolisthesis still returned to competition faster than their counterparts with
spondylolysis (19.0 vs. 88.0 days; p < 0.001). Similarly, Major Leaguers typically returned faster than Minor Leaguers (18.0 vs. 63.5
days; p < 0.001) and position players returned faster than pitchers (34.0 vs. 69.0 days; p < 0.05).
Conclusion: This study represents the most comprehensive investigation of pars defects in American professional baseball. Further
investigation is warranted to elucidate the factors underlying our results and to assess the effect of spondylolysis and spondylolisthesis
on player performance after returning to competition.
530. Preliminary return to work data from the multi-center prospective, randomized CSM-S study: approach matters

Jian Guan, MD; Praveen Mummaneni; Adam Kanter; Erica Bisson; K Riew; Robert Heary; Edward Benzel; Michael Steinmetz; James
Harrop; Subu Magge; Zoher Ghogawala (Salt Lake City, UT)
Introduction: Lost productivity related to cervical spondylotic myelopathy (CSM) has significant potential economic impact. Little
information exists on return to work rates (RTW) following CSM surgery.
Methods: Using data from the multi-center prospective, randomized CSM-S study, we performed a three-way cohort RTW analysis of
patients who were working preoperatively. Patients were randomized to ventral surgery (anterior cervical decompression and fusion
[ACDF]) or dorsal surgery (posterior fusion [PCDF] or laminoplasty [Lplasty]). Age, gender, number of stenotic levels, preoperative SF-
36 PCS/MCS, NDI, mJOA, and EQ5D scores, and postoperative hard-collar use were examined. RTW was evaluated at one, six, and
twelve months.
Results: Seventy-six patients were analyzed, with 38 undergoing ACDF, 26 PCDF, and 12 Lplasty. Mean age was 59.2±7.4 years
and was similar among groups (p=0.16). Baseline mJOA and other patient-reported outcome scores were also similar. Posterior
approaches treated more levels than ACDF (3.1± 0.8 vs. 2.5 ±0.5 levels, p<0.001). RTW at one year was significantly higher for
Lplasty (91.7%) and ACDF (89.5%) compared to PCDF (50%, p<0.001). Lplasty had significantly faster RTW than ACDF (2.1±1.0 vs.
4.3±3.4 months, p=0.04) and PCDF (2.1±1.0 vs. 4.5±3.3 months, p=0.03). Hard-collar use was similar in patients unable to RTW
(44.4%) and those who were (32.8%, p=0.37), though time to RTW was longer in hard-collar patients (5.3±3.7 vs. 3.3±2.7 months,
p=0.02). Hard-collar utilization was not significantly different between ACDF (36.8%) and PCDF (50%, p=0.30), although no Lplasty
patients utilized a hard-collar. Multiple-regression analysis identified surgical approach as an independent predictor of RTW.
Conclusion: Most patients undergoing CSM surgery achieve RTW status. Among the CSM-S study cohort, PCDF patients were 40%
less likely to RTW within one year than ACDF or Lplasty patients. Surgical approach was an independent predictor for RTW status
although a major factor was the utilization of a hard-collar.
531. Treatment of the fractional curve only in adult scoliosis: comparison to lower thoracic and upper thoracic fusions
Dominic Amara; Sigurd Berven, MD (San Francisco, CA); Christopher Ames, MD; Bobby Tay, MD; Vedat Deviren, MD; Shane Burch,
MD; Praveen Mummaneni, MD; Dean Chou, MD
Introduction: Radiculopathy from the fractional curve, typically L4-S1, is frequently a reason for scoliosis patients to pursue surgical
intervention. The purpose of this paper is to evaluate treatment outcomes of limited fusion of the fractional curve only compared to
treatment of the entire deformity.
Methods: 99 consecutive adult scoliosis patients from 2012-2016 were retrospectively studied at our institution. Patients with
fractional curves <10° underwent 3 categories of surgeries: 1) fractional curve only (FC, n=27), 2) lower thoracic to sacrum (LT, n=46),
or 3) upper thoracic to sacrum (UT, n=26). Primary outcomes were the rates of surgical revision surgery and complications.
Secondary outcomes were estimated blood loss, length of hospital stay, and discharge destination.
Results: There were no significant preoperative differences in age, gender, smoking status, prior operation, fractional curve degree,
pelvic tilt (PT), sagittal vertical axis (SVA), coronal balance, pelvic incidence/lumbar lordosis mismatch (PI-LL), or the proportion of
balanced spines (SVA<5cm, PI-LL<10° and PT<20°) between the three treatment groups. Mean follow-up was 30.3 (range 12-101)
months. The FC group had a lower complication rate (22% [FC] vs 57% [LT] vs 58% [UT], p=0.009), but a higher rate of extension
surgery (26% [FC] vs 13% [LT] vs 4% [UT], p=0.068). The respective (FC, LT, UT) average estimated blood loss (593cc vs 1950cc vs
2634cc, p<0.001), length of hospital stay (5.7 vs 8.3 vs 8.3 days, p=0.002) and rate of discharge to acute rehabilitation (30% vs 45%
vs 85%, p<0.001) were all lower for FC and highest for UT.
Conclusion: Treatment of the FC only is associated with a lower complication rate, shorter hospital stay and lower blood loss than
complete scoliosis treatment. However, there is a higher associated rate of extension of the construct to the LT or UT, and patients
should be counseled when considering their options.
532. The Institute for Healthcare Improvement – NeuroPoint Alliance cooperative quality improvement project: using national
registries to design continuous quality improvement protocols
Vincent J. Rossi, MD (Charlotte, NC); Anthony Asher, MD; Clinton Devin, MD; Scott Zuckerman, MD; Kevin Foley, MD; John Knightly,
MD; Eric Bisson, MD; Steven Glassman, MD
Introduction: We present the NeuroPoint Alliance and Institute for Healthcare Improvement (NPA-IHI) program as a novel attempt to
develop quality improvement (QI) tools designed from registry data that improve the quality of care delivered. To date, no group has
combined insights from a national registry with validated QI methods. Reducing readmission and length of stay (LOS) after elective
lumbar fusion was chosen as the pilot module.
Methods: The NPA-IHI program prospectively enrolled patients undergoing 1 -3 level lumbar fusion across 8 institutions. 1) Research
Phase: Literature review and stakeholder interviews were completed, followed by Quality Outcomes Database (QOD) analysis to
identify key drivers of readmission and LOS. 2) Intervention Phase: Specific interventions were designed to address the previously
identified drivers. 3) Measurement Phase: The application of these interventions and overall patient experience were measured.
Results: A total of 232 patients were included with an average LOS of 3.4±1.8 days for one-level fusion (N=143) and 4.4±2.4 days for
two-level fusion (N=89). 1) Research Phase: Pain control and medical comorbidities emerged as key drivers of both outcomes. Eighty
percent of readmissions occurred within the first 4 weeks and 46% within 14 days. 2) Intervention Phase: The Rounding Tool checklist
was developed, comprised of 9 care parameters and utilized daily at bedside. 3) Measurement Phase: Successful application of the
Rounding Tool was seen. The top three reasons preventing discharge were mobility status (64%), indwelling devices (51%), and pain

control (38%). Preliminary data shows the majority of patients reported a positive experience
Conclusion: We present a novel method for combining insights gained from a national registry with continuous quality improvement
protocols in a multi-institutional setting. Future efforts will be focused on preoperative, hospital, and post-discharge interventions and
using the registry platform itself as a method of gathering process data at the point of service.
533. Risk factors associated with 90-day readmissions after degenerative lumbar fusion: an examination of the Michigan
Spine Surgery Improvement Collaborative (MSSIC) registry
Paul Park, MD, FAANS (Ann Arbor, MI); David Nerenz, PhD; Ilyas Aleem, MD; Hesham Zakaria, MD; Michael Bazydlo; Lonni Schultz;
Shujie Xiao; Victor Chang, MD
Introduction: Hospital readmission following spinal surgery negatively impacts the patient experience and significantly increases
healthcare costs. To date, most studies have evaluated 30-day readmissions after spine surgery. Evaluation of the 90-day period,
however, allows a more comprehensive assessment of factors associated with readmission. The purpose of this study is to assess the
causes and risk factors for 90-day hospital readmissions after lumbar fusion surgery.
Methods: We performed a retrospective analysis of the Michigan Spine Surgery Improvement Collaborative (MSSIC) registry, a
prospective, multi-center, spine-specific database of patients surgically treated for degenerative disease. We determined causes for
readmission and independent risk factors impacting readmission using multivariable logistic regression analysis.
Results: A total of 8533 patients who underwent lumbar fusion were included. Seven hundred sixty-three (8.9%) patients were
readmitted within the 90-day period. The most common specified reasons for readmission were surgical site infection (17%), pain
(16%), and radicular symptoms (10%). Risk factors associated with increased likelihood of readmission were diabetes (OR 1.54, CI
1.27-1.85), other race (OR 1.54, CI 1.01-2.24), multilevel fusions < 4 levels, (OR 1.48, CI 1.14-1.92), surgery duration (OR 1.09, CI
1.04-1.15), and hospital length of stay (OR 1.01, CI 1.00-1.02). Factors associated with decreased risk of readmission were discharge
to home (OR 0.71, CI 0.59-0.86), private insurance (OR 0.81, CI 0.68-0.96), and diagnosis of spondylolisthesis (OR 0.84, CI 0.72-
0.98).
Conclusion: After lumbar fusion surgery, 90-day readmission to the hospital occurs in approximately 9% of cases. Among many
reasons for readmission, the most frequent reasons included wound infection, pain, and radicular symptoms. Among many factors
impacting the likelihood of 90-day readmission, diabetes was the strongest risk factor, which presumably could be mitigated with strict
preoperative and postoperative diabetic management.
534. Elderly patients have worse EQ-5D outcomes after spondylolisthesis surgery than young patients, yet they are satisfied
with surgery
Andrew K. Chan, MD (San Francisco, CA); Erica Bisson, MD, MPH; Mohamad Bydon, MD; Kevin Foley, MD; Eric Potts, MD;
Christopher Shaffrey, MD; Mark Shaffrey, MD; Anthony Asher, MD; Michael Wang, MD; John Knightly, MD; Jonathan Slotkin, MD;
Praveen Mummaneni, MD
Introduction: A recent randomized control trial assessing outcomes following surgery for lumbar spinal stenosis and spondylolisthesis
excluded patients who were older than 80 years. This study assesses outcomes for patients age<80 years following surgery for
degenerative lumbar spondylolisthesis.
Methods: This was a retrospective analysis of a prospective registry. 808 patients underwent surgery for grade 1 degenerative lumbar
spondylolisthesis at twelve high-enrolling sites. Elderly patients were identified as age<80 years. Baseline and surgical variables were
collected. Numeric rating scale (NRS) back pain, NRS leg pain, Oswestry Disability Index (ODI), EuroQoL-5D (EQ-5D), and the North
American Spine Society (NASS) Satisfaction Questionnaire were collected at baseline,
3 months, and 12 months.
Results: Thirty six (4.5%) patients were elderly (range 80-95 years). Elderly patients had lower mean BMI (28.1±4.9 vs. 30.7±6.4,
p=0.01), had a higher proportion of osteoporosis (16.7 vs. 6.5%, p=0.04), and were less independently ambulatory at baseline (75.0
vs. 88.0%, p=0.04). Elderly patients received fewer fusion procedures (41.7 vs. 75.8%, p<0.001). There was no difference in
satisfaction at 12 months (elderly 83.3 vs. 83.7% NASS 1/2; p=0.85) as well as in 3-month readmission (elderly 8.3 vs. 3.2%, p=0.24)
and 12-month reoperation rates (elderly 8.3 vs. 4.9%, p=0.60). At baseline, the elderly cohort had less NRS back pain (5.6±3.1 vs.
6.9±2.6, p=0.02) and higher EQ-5D (0.62±0.19 vs. 0.54±0.24, p=0.04). At 12 months, both the elderly and the control cohort improved
significantly with respect to mean baseline values for NRS back and leg pain, ODI, and EQ-5D (p<0.01 for all comparisons). In
multivariate analysis, elderly status predicted inferior 12-month EQ5D change scores (OR 0.92, 95% CI 0.86-0.99, p=0.03) but was
not predictive of NRS back and leg pain, and ODI change scores (all p<0.05).
Conclusion: In adjusted analysis, age<80 years was associated with inferior improvements in EQ-5D at 12 months following lumbar
spondylolisthesis surgery.
535. Complications and revision rates in robotic-guided vs. fluoro-guided minimally invasive lumbar fusion surgery - report
from MIS ReFRESH prospective comparative study
Michael Y. Wang, MD, FAANS (Miami, FL); Christopher Good, MD; Samuel Schroerlucke, MD; Faissal Zahrawi, MD; Andrew
Cannestra, MD; Jae Lim, MD; Victor Hsu, MD; Hunaldo Villalobos, MD; Pedro Ramirez, MD; Thomas Sweeney, MD
Introduction: MIS ReFRESH is the first prospective, comparative, multi-center study to assess differences in conventional vs.

robotically-assisted minimally invasive (MIS) 1-3 level fusions.

Methods: This prospective, multi-center, controlled, partially randomized study included adults with degenerative disease undergoing
fusion surgery of 1-3 levels. We compared the incidence of revision surgeries and clinical complications (surgical and medical) and
intra-operative fluoroscopy use.
Results: 9 sites enrolled 379 cases: 287 in robotically-guided arm (RG), and 92 fluoro-guided (FG). One site randomized patients, 15
to RG and 11 to FG. Mean age of RG patients was 59.1 years vs. 62.4 for FG (p=0.032) and BMI was 31.4 vs. 28.0, respectively
(p<0.001). Charlson Comorbidity Index was 0.5±0.8 in RG vs. 0.3±0.6 in FG (p=0.022). There were 4.8±1.2 pedicle screws per case
in RG vs. 4.3±0.9 screws in FG (p<0.001). In RG 33% of cases were 2-levels and 5% 3-levels, while in FG 16% were 2-level fusions,
and 1% were 3-level fusions. Use of fluoroscopy for the instrumentation phase was 3.8±3.9 seconds/screw in RG vs.16.9±9.2 in FG
(p<0.001). Within the first year there were 28 (9.7%) complications in RG vs. 35 (38.0%) in FG, and 4 (1.4%) revisions in RG vs. 4
(4.3%) in FG. When evaluated in a Cox Proportional Hazard model, the Hazard Ratio (HR) for a complication was 5.3 times higher in
FG compared to RG (p<0.001). HR for a revision surgery were 7.1 times higher for a fluoro-guided surgery compared to the robot-
guided cases (95% CI 1.6-32.6, p=0.012).
Conclusion: Revision surgery was significantly higher in FG during the first year of follow-up compared to RG (5.3-fold and 7.1-fold,
respectively). RG reduced fluoroscopy exposure time per case by 78%, or almost a minute, helping offset the patients’ exposure
during the pre-operative CT scan required for planning the robotic procedure.
536. Immediate restoration of voluntary movement with epidural spinal cord stimulation in two patients with paraplegia
Philip L. Gildenberg MD Resident Award
David Darrow, MD (Minneapolis, MN); David Balser, MD; Aaron Phillips, PhD; Andrei Krassioukov, MD, PhD; Uzma Samadani, MD,
PhD
Introduction: In a small cohort of patients, epidural spinal cord stimulation (eSCS) has been shown to restore volitional movement in
select paraplegic patients after intensive therapy. The Epidural Stimulation After Neurologic Damage (E-STAND) study was designed
to assess the effect of eSCS on paraplegic patients directly on movement and cardiovascular function while undergoing intensive
stimulator setting optimization from home.
Methods: Participants were selected from a cohort of ASIA A/B chronic spinal cord injury patients with a motor level between C6 and
T10 greater than one year from injury. Patients were required to have full strength in their upper extremities and have discrete spinal
cord lesions on MRI. The first two E-STAND patients underwent enrollment, surgical implantation of the stimulator and paddle
electrode, and first follow up. Preoperative and postoperative tilt table assessments and neurological assessments were performed.
Results: The first two patients were female and found to have severe myelomalacia and syringomyelia prior to surgery. Preoperative
tilt table assessment revealed significant hypotension in the second patient and no change in the first with injuries at T8 and T4. Initial
assessment (as soon as 36 hours from surgery) of eSCS revealed restoration of lower extremity volitional movement only during
stimulation in both patients despite being 11 and 5 years out from surgery. eSCS restored blood pressure to normal during tilt when
dysautonomia was present and had no effect on blood pressure when absent.
Conclusion: To our knowledge, these are the first women with SCI implanted who had the most severe MRI findings while being the
furthest from injury. In the most severe forms of chronic SCI, paraplegic patients can gain volitional movement immediately after
implantation of eSCS without rehabilitation. Autonomic neuromodulation using eSCS reversed orthostatic hypotension during tilt
testing and did not cause hypertension.
537. Cranial nerve outcomes after stereotactic radiosurgery for skull base meningiomas
Andrew Faramand (Pittsburgh, PA); Hideyuki Kano; Stephen Johnson, MD; Mohab Hassib, MD; John Flickinger, MD; L Dade Lunsford
Introdution: To evaluate cranial nerve (CN) outcomes after stereotactic radiosurgery (SRS) for petroclival, cavernous sinus, and
cerebellopontine angle meningiomas.
Methods: A retrospective analysis of a prospectively maintained database was performed for 395 patients who underwent SRS for
petroclival (98 patients), cavernous sinus (242 patients), and cerebellopontine angle (55 patients) meningiomas. SRS was performed
as a primary modality (N= 245, 62%), or after prior surgical resection (N=150, 38%). Patients had at least one CN deficit at the time of
initial presentation. Median age at the time of SRS was 56 years. Median follow up was 57 months. Median tumor volume treated with
SRS was 6.35cc, and median margin dose was 13Gy.
Results: Tumor control was achieved in 362 patients (91%). Tumor location did not affect tumor control rates (P= 0.213). Overall, 114
of the 245 patients (46.5%) who had primary SRS reported improvement of CN symptoms in comparison to 27 out of 150 patients
(18.5%) who underwent prior surgery. The rate of improvement of CN deficits in primary SRS patients was 25% at 1 year, 35% at 2
years, and 45% at 5 years. Primary SRS patients had significantly higher rates of improvement of CN function (P=0.00002). Primary
SRS for petroclival and cavernous sinus meningioma patients had significantly higher rates of CN improvement compared to patients
who had prior resection (P= 0.02 and P= 0.0001). Deterioration in CN function developed in 32 patients. The rate of deterioration was
4.5% at 1 year, 7% at 3 years, 11% at 6 years, and 12% at 10 years.
Conclusion: Primary SRS provided effective tumor control in addition to a greater rate of improvement of preexisting CN deficit
compared to patients who had prior resection. Patients with CP angle meningiomas demonstrated lower rates of CN improvement
when compared to petroclival and cavernous sinus meningiomas.
538. Hearing the written word: listening and reading recruit shared lexical semantic networks

Kiefer Forseth (Houston, TX); Cristian Donos, PhD; Nitin Tandon, MD
Introduction: The ability of the language system to function at high speed and fidelity is notable in our ability to decode both acoustic
and orthographic information. Communication via speech and the written word has underpinned the development of modern
civilization. Here we evaluate the convergence of lexical semantic networks in decoding both spoken and written sentences after
feature processing in early sensory cortex and before engaging the articulatory network for speech production.
Methods: Patients (n=13) were implanted with depth (n=2043) and surface grid (n=549) electrodes for the evaluation of medically
refractory epilepsy. In two separate experiments, patients were asked to quickly and accurately articulate the name of common objects
in response to short descriptions. The first experiment presented these stimuli as words in rapid serial visual presentation; the second
experiment presented them as spoken sentences. Importantly, the last word in each of these prompts was crucial for binding the
semantic concept (A person in charge of a courtroom). We analyzed activity in the gamma (60-120Hz) band, to index cognitive
engagement of local cortical substrate.
Results: We identified feature processing in the visual word form area and superior temporal gyrus throughout the written and spoken
stimuli, respectively. With each presented word in the reading task, we observed activity corresponding to putative lexical (superior
temporal sulcus and posterior middle temporal gyrus) and phonological (superior temporal gyrus) streams of reading. After the
complete written or spoken stimuli were presented, a shared lexical semantic network (middle fusiform gyrus, posterior middle
temporal gyrus, intraparietal sulcus, and pars triangularis) was recruited. Finally, the peri-Sylvian speech production network engaged
to articulate the object name.
Conclusion: Research on the neurophysiological basis of reading will contribute to rehabilitative solutions and neuro-prosthetics to
help the substantial proportion (5-17%) of people are dyslexic - either from development or after brain injury.
539. Sphenopalatine ganglion stimulation elicits a frequency and time-dependent effect on blood-brain barrier permeability
Richard F. Schmidt, MD (Philadelphia, PA); Geoffrey Stricsek, MD; Michael Lang, MD; Ashwini Sharan, MD; Robert Rosenwasser,
MD; Lorraine Lacovitti, PhD
Introduction: Previous research suggests that stimulation of the sphenopalatine ganglion may increase blood-brain barrier
permeability via nitric-oxide mediated tight-junction disruption through parasympathetic connections to the cerebral vasculature.
However, response to different stimulation parameters has not been described.
Methods: Female Sprague-Dawley rats underwent right-sided anterior ethmoidal nerve (sphenopalatine ganglion analog) stimulation
using a bipolar electrode via an intraorbital approach with concurrent femoral vein injection with 100mg/mL of 70kDa fluorescein-
isothiocyanate (FITC) dextran. All rats underwent a 15-minute priming period of stimulation at 5V followed by 10 separate 0.1mL
injections every 2.5 minutes during stimulation. Rats were assigned to intermittent 5Hz, (n=4), 10Hz (n=7), and 200Hz, (n=4)
stimulation, consisting of cycles with a 90 second on period followed by 60 seconds off. Additional rats were assigned to continuous
10Hz stimulation (n=5), and controls (n=6). Rats were sacrificed, serum was obtained, vasculature was flushed with 50mL of
heparinized saline, and brain specimens were harvested in five 3mm sections from each hemisphere. Specimens were homogenized
and analyzed for tissue fluorescence with associated serum samples. Tissue and blood concentrations were obtained using internal
standards, and relative uptake into brain tissue was calculated.
Results: Using normalized values for serum concentrations, intermittent 10Hz stimulation showed increased relative uptake (1.62%,
p<0.001) compared to 5Hz (1.21%, p=0.016), 200Hz (0.2%, p<0.001), controls (1.14%, p<0.001), and continuous stimulation at 10Hz
(0.26%, p<0.001). Intermittent 200Hz and continuous 10Hz stimulation exhibited a significant decrease in uptake compared to controls
(p<0.001).
Conclusion: Sphenopalatine ganglion stimulation elicits a variable response in blood-brain barrier permeability. Optimal stimulation for
increasing permeability occurs using intermittent stimulation at 10Hz, whereas high-frequency stimulation at 200Hz and continuous
stimulation at 10Hz appear to decrease FITC-dextran uptake. The breadth of this effect and the mechanism for the variable response
from stimulation require further study.
540. Structural connectivity associated with effective capsulotomy lesion volumes for refractory OCD
Pranav Nanda (New York, NY); Garrett Banks; Yagna Pathak; Marcelo Hoexter; Antonio Lopes; Benjamin Greenberg; Steven
Rasmussen; Jason Sheehan; Euripedes Miguel; Michael Fox; Nicole McLaughlin; Sameer Sheth
Introduction: Whereas most patients with obsessive-compulsive disorder (OCD) are well controlled with pharmacological and
cognitive behavioral therapy, 10-20% remain severe and refractory. Over decades, stereotactic radiosurgery (SRS) capsulotomy has
demonstrated significant symptom response in 30-70% of patients. Response variability may be partially attributed to differences in
upstream and downstream brain regions affected by lesions. We used diffusion tensor imaging (DTI) to identify networks affected by
clinically responsive targets.
Methods: We analyzed lesions masked on postop volumetric MRI for 25 OCD patients who underwent SRS capsulotomy.
Probabilistic tractography seeding from each lesion was performed on high-quality DTI data obtained from the Human Connectome
Project (HCP) dataset. For each lesion, a lesion-connectome was created by averaging tractography from the HCP data. Lesion-
connectomes were then correlated with patients’ clinical response, measured by percent reduction on the Yale-Brown Obsessive
Compulsive Scale (Y-BOCS), using a voxel-based generalized linear model.
Results: 17 of the 25 patients were clinical responders to SRS capsulotomy (i.e., <35% reduction in Y-BOCS score). Lesion-
connectomes primarily involved thalamocortical tracts connecting the thalamus and orbitofrontal cortex (OFC). In the superomedial

aspect of these tracts, 1581 1mm3 voxels exhibited significant association between lesion connectivity and clinical response.
Conclusion: SRS capsulotomy remains attractive for treatement of severe, refractory OCD. Lesions with maximal connectivity to
thalamus and medial OFC appear more likely to produce a favorable clinical response, supporting the hypothesis that aberrant activity
within networks including this pathway underlie the pathophysiology of OCD. A comprehensive understanding of the network
pathology of OCD will lead to improved targeting and clinical outcomes with lesion or deep brain stimulation (DBS) procedures.
541. Increased dynamic modularity of the fronto-temporo-limbic network precedes enhanced task performance
Vivek Buch, MD (Philadelphia, PA); Cameron Brandon, BS; Ankit Khambhati, PhD; Andrew Richardson, PhD; Danielle Bassett, PhD;
Timothy Lucas, MD, PhD
Introduction: Neural network adaptability is integral to learning and skill acquisition. The modularity of a network represents the
degree to which highly interactive communities form within a system, and is thought to provide a network substrate for adaptability.
The effects of trial-by-trial changes in modular structure on rapid skill acquisition are largely unknown. Here we assess how dynamic
fronto-temporo-limbic (FTL) network modularity may influence learning and task performance.
Methods: Ten subjects with stereotactic electroencephalography (sEEG) implants for clinical monitoring performed a primitive reaction
time (RT)-based temporal expectancy task. Connectivity analysis was performed using phase synchrony in broad theta (3-12Hz) and
high gamma bands (70-100Hz). Connectivity was evaluated in (1) the immediate pre-cue resting period; and (2) intra-trial delay
period. Within-subject differential adjacency matrices were generated comparing the fastest vs. slowest third of RTs (F-S condition)
and latest vs. earliest third of trials (L-E condition). Using a Louvain-like locally greedy algorithm, community structure was identified
for the different conditions.
Results: We find a significant RT difference in the F-S condition (fRT=324.9ms, sRT=497.8ms, p<<0.001; error-trials excluded) but
not L-E condition (lRT=292.9ms, eRT=312.1ms, p=0.58). Across all 1500ms trials (n=703) and all subject nodes (n=860) connectivity
in FTL circuitry displays modular structure, specifically in the theta band (Q=0.11 [thetaall] vs. Q=0.02 [gammaall], p<<0.001). Further,
significantly increased modularity in the theta synchronous FTL network during the pre-cue period characterizes the F-S condition
(Q=0.41; p=0.02). This is not seen in the L-E condition (Q=0.06, p=0.57) or during the delay period (Q=0.10 [F-S], p=0.62; Q=0.24 [L-
E], p=0.47).
Conclusion: Our results indicate that dynamic FTL network modularity may influence skill acquisition. Specifically, increased modular
structure in the pre-cue period is associated with enhanced task performance. Our findings provide some of the first evidence linking
trial-by-trial, antecedent FTL connectomic fluctuations to enhanced cognitive function.
542. Asymmetric development of lesions from stereotactic radiosurgical capsulotomy for refractory OCD
Vighnesh Viswanathan (Pittsburgh, PA); Pranav Nanda; Garrett Banks; Yagna Pathak; Antonio Lopes; Benjamin Greenberg; Steven
Rasmussen; Jason Sheehan; Miguel Euripedes; Michael Fox; Nicole McLaughlin; Sameer Sheth
Introduction: Patients with severe, refractory obsessive-compulsive disorder (OCD) may be candidates for neurosurgical intervention,
including stereotactic radiosurgical (SRS) capsulotomy. Despite identical prescription dosing, variation is possible in lesion
development between patients, and between hemispheres in the same patient. To better understand the manner with which lesions
form, we compared left- and right-sided lesions in patients who underwent SRS capsulotomy with laterally symmetri radiation dosages.
Methods: We analyzed lesions masked by two raters on post-operative MRIs for 38 OCD patients who underwent bilateral SRS
capsulotomy. To compare left- and right-sided lesions, for each patient, we calculated an asymmetry index as the ratio between the
volumes of the smaller and larger lesions, and compared them with a paired t-test. For spatial comparison, we reflected right-sided
lesions into the left hemisphere and quantified their spatial similarity with the Sorensen-Dice index (SDI). A voxel-by-voxel paired t-test
evaluated systematic spatial differences.
Results: The mean asymmetry index was 0.55, suggesting insignificant systematic left-right asymmetry across the entire cohort.
Paired t-tests evaluating for systematic volumetric and spatial differences were non-significant (p<0.15). Within individuals, the left-
right volumetric differences had a range of 0.5-1979 cubic centimeters (CC). The mean SDI of similarity between left- and reflected-
right-sided lesions within each individual was 0.32, indicating individual significant left-right asymmetry.
Conclusion: Lesions from bilateral SRS capsulotomy demonstrate significant left-right asymmetry within individual patients. Across
this large cohort of 38 patients, however, the individual asymmetry does not manifest into a systematic laterality preference. These
data suggest that lesion development at high doses required for capsulotomy varies unpredictably. Future work will analyze treatment
variables such as order of shot delivery and patient variables such as gray-white matter fractions within the treatment volume. Factors
underlying the variability will be important in designing these treatments and understanding their effect on clinical outcome.
543. Induction and quantification of plasticity in human cortical networks
Yuhao Huang (Stanford, CA); Corey Keller; Jose Herrero; Maria Fini; Victor Du; Fred Lado; Christopher Honey; Ashesh Mehta
Introduction: What type of human brain stimulation leads to lasting changes in inter-regional connections? Uncertainty on this
question hinders the development of targeted therapies for neuropsychiatric disorders. In this study, we examined the neuroplasticity
effects of repetitive stimulation by pairing direct electrical stimulation with recordings from the cortical surface.
Methods: To characterize how inter-regional networks are altered by stimulation, we applied repetitive direct electrical stimulation in
eight human subjects undergoing intracranial monitoring. We evaluated single-pulse corticocortical evoked potentials (CCEPs) before
and after repetitive stimulation across prefrontal, temporal and motor cortices.

Results: First, we asked if a single session of repetitive stimulation was sufficient to induce lasting changes that persist for <10
minutes across distributed cortical sites. In four patients undergoing prefrontal stimulation, we found a subset of regions at which a
10Hz repetitive stimulation resulted in plasticity. These modulated regions were near the stimulated site and exhibited both
potentiation and depression. Second, we asked if post-stimulation changes could be modeled by the pre-stimulation connection profile
of each site. We hypothesized that sites (i) anatomically close to the stimulated site and (ii) exhibiting high-amplitude CCEPs would
exhibit plasticity following repetitive stimulation. Consistent with this hypothesis, we were able to predict sites of plasticity using pre-
stimulation connectivity and proximity features. These findings generalized to stimulation sites in motor and temporal lobe in an
independent dataset of four patients.
Conclusion: Repetitive stimulation induces predictable changes that outlast stimulation in regions anatomically and functionally
connected to the stimulation target. These results show that baseline anatomical and connective proximity are potential markers for
personalizing therapeutic stimulation paradigms.
544. Long-term seizure dynamics detected using a novel analytic platform in responsive neural stimulation for epilepsy
Nathaniel D. Sisterson (Pittsburgh, PA); Thomas Wozny, BS; Alan Bush, PhD; Vasileios Kokkinos, PhD; R. Mark Richardson, MD,
PhD
Introduction: The NeuroPace RNS system is a recently FDA-approved therapy for drug-resistant epilepsy, comprised of an
implantable microprocessor with intracranial sensors capable of responsive detection and stimulation. To overcome barriers to
obtaining, storing, and analyzing responsive neural stimulation data to better understand its modulatory effects on seizure activity, we
created a novel computational platform called Biophysically Rational Analysis for Informed Neural Stimulation (BRAINStim). Here, we
report an initial characterization of long-term baseline changes in theta oscillatory dynamics and seizure frequency using the
BRAINStim platform.
Methods: We reviewed intracranial electroencephalography (iEEG) recordings, corresponding settings, and events for 10 patients
implanted with the RNS system. Raw iEEG data were obtained from NeuroPace, and supporting data were obtained from the Patient
Data Management System (PDMS) via customized capabilities of BRAINStim. Scheduled recordings, excluding those during which the
RNS detector was triggered, were analyzed. A daily average value for baseline theta band (4-8 Hz) power was obtained. Seizure
frequency was estimated by the average number of exhausted therapies per day. To determine whether these values contained
temporal patterns underlying disease state, we performed an autocorrelation coefficient analysis.
Results: BRAINStim facilitated the analysis of 13,617 iEEG recordings. The mean iEEG recording length was 79.4 seconds, and the
mean duration on implantation was 514 days with an average of 2.63 (0-16) scheduled recordings per day. Autocorrelation analysis
revealed a mean periodicity of 7.36 days (3.19-29.88) for theta power and 10.03 days (4.89-26.92) for seizure frequency.
Conclusion: BRAINStim extracted data otherwise unavailable to general users of the PDMS and performed autocorrelation coefficient
analysis that revealed long-term temporal patterns in theta oscillations and seizure frequency. Further development of this analytic
method may allow for detection of infradian brain state patterns that correlate with seizure frequency and inform future
neuromodulation strategies involving closed-loop seizure prediction.
545. Mesial temporal lobe and cingulate event-related potentials signal memory recall errors
Eric Hudgins, MD, PhD (Philadelphia, PA); Vivek Buch, MD; Cameron Brandon, BS; Shawniqua Williams, MD; Ashwin Ramayya, MD,
PhD; Max Kelz, MD, PhD; Alexander Proekt, MD, PhD; Andrew Richardson, PhD; Isaac Chen, MD; Timothy Lucas, MD, PhD
Introduction: Event-related electroencephalography (EEG) potentials (ERPs) have been studied for over 6 decades (Sutton et al.,
1964,
1965, 1967; Chapman and Bragdon 1964). Defined by large potential changes to feedback after error, error-related potentials are a
relatively more recent intense focus of debate and research (Falkenstein et al., 1990, Gehring et al., 1990; Frank et al., 2005; Wessel
et al., 2011). Source localization is one major limitation to surface EEG when considering many ERPs potentially arise from subcortical
structures. Intracranial EEG (iEEG) for seizure focus localization in epilepsy patients provides a unique opportunity to study ERPs and
identify sources responsible for the generation of these signals. Here we describe mesial temporal lobe (MTL) and cingulate ERPs
during memory recall errors in human epilepsy patients with iEEGs while performing a memory cue-response task.
Methods: An auditory-based cue-response task incorporated distinct tones for correct and incorrect performance, and was
synchronized with iEEG signals. Subjects received auditory cues delivered via a dedicated laptop computer for the duration of the
behavioral task. Each task trial consisted of three separate instructions to squeeze a button located in either their right or left hand in a
random fashion, and required a response before advancing to the next step. Following the response stage of the trial, subjects were
then asked to recall the sequence of responses after a short delay period.
Results: Six (6) of seven (7) subjects demonstrated significant MTL and Cingulate Cortex ERPs to memory recall errors (p < 0.001).
ERPs occurred 342-1388ms prior to error feedback.
Conclusion: Memory recall errors are a unique error in which the subject has a priori error knowledge before action selection and
feedback presentation. Memory recall error ERPs occur prior to feedback, suggesting this neural-correlate of error is an early signal to
the subject of a memory error.
546. Granger causality analysis reveals a novel thalamic target for DBS treatment of a patient with acquired hemidystonia
Ifije Ohiorhenuan, MD (Los Angeles, CA); Enrique Arguelles; Arash Maskooki; Daniel Kramer; Aaron Robison; Mark Liker

Introduction: An accurate and parsimonious identification of target nuclei is critical for the treatment of movement disorders by DBS.
In patients with dystonia, this is particularly challenging since abnormal activity patterns can propagate from a causative site to other
areas within the basal ganglia and thalamic circuitry.
Methods: While frequency analysis tools such as the power spectrum and coherence have been instrumental in studies of the
circuitry modulating movement, they fail to offer any insight into the direction of information flow. Granger causality is one method
which has been successfully used to characterize information flow in the brain. Here, we demonstrate that Granger causalit can be
used to dissect information flow within the basal ganglio-thalamic circuitry.
Results: Recording from depth electrodes implanted in a patient with dystonia, we show that movement is associated with power
spectrum changes in basal ganglia and thalamic nuclei. We find that the coherence between a subset of these nuclei is movement-
dependent. Using Granger causality analysis, we find that VPL modulates the activity of VIM, STN and GPI in a movement-dependent
manner, suggesting a novel therapeutic target. Supporting the importance of VPL in this patient, we found a positive response to VPL
stimulation.
Conclusion: Since sensory causes for dystonia are hypothesized for a subset of dystonias and VPL processes ascending sensory
information, our findings suggest that in some patients, VPL relay of sensory inputs can critically modulate basal ganglia-thalamic
circuitry and improve dystonic movements. Thus, VPL is a novel therapeutic target for some patients with dystonia.
547. Analysis of thermal damage estimates for the prediction of mesiotemporal laser ablation zones
Walter Jermakowicz, MD, PhD (Miami, FL); Iahn Cajigas, MD, PhD; Lia Dan, MS; Santiago Guerra, BS; Samir Sur, MD; Pierre
D'Haese, PhD; Jonathan Jagid, MD
Introduction: Laser interstitial thermal therapy (LiTT) is changing our management of patients with mesiotemporal epilepsy by
providing a less-invasive surgical option. With greater understanding of mesiotemporal anatomy and its ablative properties, outcomes
of this novel therapy can be further improved. Decision making during LiTT is guided by Arrhenius-based thermal damage estimate
(TDE) maps. Our goal was to evaluate the intraoperative evolution of TDE maps and their relationship to immediate (post-ablation)
and delayed (6-month) ablation zones.
Methods: TDE maps and pre-, intra-, and post-operative MRIs were co-registered using a deformable atlas. The rate of irreversible
damage (RID) was quantified from TDE videos on a per voxel basis. To compare TDEs with immediate and delayed ablation zone
boundaries, overlap was calculated using the dice similarity coefficient (DSC). The relationships of these measures to 12 independent
variables derived from patient demographics, preoperative image and the surgical procedure were examined.
Results: In 30 patients with at least 6-months follow-up, RID showed exponential growth soon after laser activation. Ablation time
constants were longer with increased MRI T2 signal and volume of surrounding CSF, and shorter with mesiotemporal sclerosis (MTS).
Compared to postoperative ablation boundaries, TDEs are more representative of immediate ablations than of delayed ablations,
where there is a propensity to overestimate ablation extent, particularly at mesial amygdala/hippocampal head, an effect correlated
with volume of surrounding CSF volume, T2 signal and amygdalohippocampal volume.
Conclusion: TDEs are generally representative of LiTT ablation zones, but there is room for improvement. There is variability
between patients in the evolution of these maps and in their ability to predict delayed LiTT treatment-related effects. We speculate that
by incorporating patient demographic and imaging data into our predictive models we may eventually improve the precision with which
LiTT is delivered, improving outcomes and accelerating adoption of this novel tool.
548. Robot-guided stereotaxy for deep brain stimulation surgery: an initial experience
Allen H. Ho, MD (East Palo Alto, CA); Arjun Pendharkar; Ryan Brewster; Jonathon Parker; Kai Miller; Casey Halpern, MD
Introduction: Development of robotic-guidance revolutionized stereotaxy for a variety of neurosurgical procedures. We present the
first single-surgeon series of DBS performed utilizing Mazor’s frameless robotic solution for image-guided stereotaxy (Renaissance),
and report on operative efficiency, stereotactic accuracy, and surgical outcomes.
Methods: Between October 2016 and September 2017, 30 consecutive patients underwent DBS for Parkinson’s disease or essential
tremor at Stanford Healthcare. The last 20 of these patients had surgery utilizing the Mazor frameless robotic system, thus the other
10 cases were sampled to provide some level of comparison to prior frameless stereotaxy outcomes. Data were prospectively
collected including patient demographic, clinical and surgical data.
Results: Mean case times across the board were all decreased in the robot-guided cohort. Total OR time was significantly decreased
in the robot-guided cohort (295.7 minutes robot-guided versus 345.4 minutes frameless, p = 0.048), as was total anesthesia time (273
minutes robot-guided versus 320.8 minutes frameless, p = 0.044). Total operative time was also decreased in the robot-guided cohort
(178.8 minutes robot-guided versus 217.2 minutes frameless) in a relationship that trended towards significance (p = 0.053). There
was a significant decrease in the average number of MER passes in the robot-guided cohort (1.05) compared to the frameless cohort
(1.25, p = 0.025). None of the DBS leads needed repositioning in the robot-guided cohort. There were no immediate surgical
complications in either cohort.
Conclusion: Our study of our initial experience with Mazor robot-guidance for DBS demonstrates statistically significant decreases in
mean total operative and anesthesia times, as well as significant decreases in mean microelectrode passes without any significant
learning curve. Our study of our initial experience with Mazor robot-guidance for DBS demonstrates statistically significant decreases
in mean total operative and anesthesia times, as well as significant decreases in mean microelectrode passes without any significant
learning curve.

549. Clinical outcomes associated with robot-assisted DBS placement into the STN in patients with Parkinson's disease
Michelle Renee Paff, MD (Orange, CA); George Hanna, MD; Alice Wang, BS; Nicolas Phielipp, MD; Sumeet Vadera, MD; Frank Hsu,
MD, PhD
Introduction: Robotic-assisted surgery is new to the field of neurosurgery, and very few centers have adopted robotic stereotactic
systems for use in DBS surgery. Here we report clinical outcomes associated with robot-assisted stereotactic placement of DBS leads
into the subthalamic nucleus (STN) in patients with Parkinson's disease (PD).
Methods: A retrospective chart review was performed of 32 patients who underwent DBS surgery using the CRW frame and 31
patients who underwent DBS placement using the ROSA robot. Movement Disorder Society Unified Parkinson's Disease Rating Scale
(MDS-UPDRS) part III motor scores and levodopa equivalent doses (LEDD) were calculated at 6 months, 1 year and 2 years of follow
up. For those leads placed at the target position, the error in final lead placement was measured.
Results: At least 6 months of follow up data was available for 14 patients who underwent frame-based and 20 patients who
underwent robot-assisted DBS surgery. The percent reduction in the MDS-UPDRS part III motor score on medication was comparable
between both groups at 6 months and 1 year. There was no significant difference between the groups except at 2 years follow up
(8.13 +/- 33.23% for the robot group vs 34.85 +/- 20.80% for the frame group, p=0.038). No significant difference in percent reduction
of LEDD was found between the two groups at any of the follow up points. There was no significant difference between the error of
final placement of the left and right DBS leads in the X, Y or Z planes. The largest degree of error was found in the AP plane (1.09+/-
0.67mm on the left and 1.12+/-0.90mm on the right).
Conclusion: Clinical outcomes associated with robot-assisted DSB surgery for treatment of PD may be comparable to those achieved
with frame-based methods.
550. Clinical outcomes in a large series of subtemporal selective amygdalohippocampectomies for medically refractory
epilepsy
Tsinsue Chen, MD (Phoenix, AZ); Alex Whiting, MD; Kyle Swanson, MD; Kris Smith, MD
Introduction: The aim of this study is to report seizure, neuropsychological, and neurocognitive outcomes in a large series of patients
undergoing subtemporal selective amygdalohippocampectomy (SelAH) for medically refractory epilepsy. The primary advantage of the
subtemporal approach is that both the lateral temporal cortex and temporal stem are preserved.
Methods: Consecutive cases of patients with medically refractory epilepsy treated with a subtemporal SelAH approach at a single
institution were reviewed. Demographics, complications, post-operative seizure freedom outcomes, preoperative and post-operative
neuropsychological and neurocognitive outcomes were analyzed. Patients who had undergone prior epileps surgery or had a
diagnosis of diffuse glioma were excluded.
Results: 212 consecutive patients underwent subtemporal SelAH by a single surgeon over a 12 year period (2004-2016).
152 of these patients had at least 1 year follow-up, and of this cohort, Engel class I was achieved in 57.9% of patients (n=88), Engel
class II in 25.7% (n=39), Engel class III in 9.9% (n=15), and Engel class IV in 6.6% (n=10). Of the patients with mesial temporal
sclerosis on magnetic resonance imaging who did not require invasive monitoring, 68.4% had an Engel class I outcome. 6 months
after surgery, there were no statistically significant differences seen in neuropsychological and cognitive tests of intelligence, visual
attention, memory, and mood compared to baseline. There was a morbidity rate of 4.7% and no deaths.
Conclusion: This is the largest series reported of medically refractory epilepsy patients treated with the subtemporal selective
amygdalohippocampectomy approach to our knowledge. Seizure, neuropsychological, and neurocognitive outcomes indicate that this
is an effective surgical technique for the treatment of medical refractory epilepsy with a low morbidity and mortality rate.
551. Comparative analysis of subdural grids vs. stereo-electroencephalography in the evaluation of intractable epilepsy
Brian Tong (Houston, TX); Jessica Johnson, BSN; Cristian Donos, PhD; Gretchen Von Allmen, MD; Jeremy Lankford, MD; Stephen
Thompson, MD; Giridhar Kalamangalam; Omotola Hope, MD; Melissa Thomas, MD; Jeremy Slater, MD; Nitin Tandon, MD
Introduction: We compare the relative efficacy, morbidity and seizure outcomes between Subdural Electrodes (SDE), the mainstay
for the evaluation of patients with non-lesional or ill-defined focal epilepsy in North America, and stereo-electroencephalography
(SEEG), a minimally invasive approach that transformed the process of localizing regions responsible for seizure onsets over the past
decade.
Methods: All 260 intracranial procedures from 2004 to 2017 were identified using a prospectively compiled surgical database. Patient
demographics, characteristics of epilepsy, duration of monitoring, procedural morbidity, opioid pain medication use and eventual
outcomes were determined. Unpaired t-tests and chi-squared tests were used to compare the groups.
Results: Both SEEG (n=121) and SDE (n=139) groups were similar in age (30.1 ± 12.2 vs. 30.6 ± 13.8 years), gender (SEEG =
47.1% male; SDE = 43.9% male) and duration of epilepsy (16.4 ± 12.0 years vs. 17.2 ± 12.1 years). Pain medication requirements
were greater in SDE vs. SEEG group (355.8 ± 232.9 mg vs. 201.4 ± 175.5 mg, p < 0.0001). The duration of intracranial monitoring
was comparable (SEEG = 7.7 ± 3.9 days vs. SDE = 8.1 ± 2.8 days). There were 7 symptomatic hemorrhagic sequelae and two
infections in the SDE cohort, and no clinical complications in the SEEG cohort (p = 0.004). More SDE patients underwent resective or
ablative surgery (91.4%), compared with SEEG patients (72.7%). 8.6% of SDE patients and 14.1% of SEEG patients were not thought
to be candidates for further cranial intervention. The seizure outcomes (Engel I or II) in this group, at 6 months post-resection, trended
in favor of SEEG (82.0%) relative to SDE (65.5%, p = 0.01).

Conclusion: SEEG and SDE have significantly distinct procedural morbidities, associated with distinct outcomes and pain medication
requirements, which should factor into decision making when considering patients with pharmaco-resistant epilepsy for intracranial
evaluation.
552. The need for Intensive Care Unit level of care in patients undergoing craniosynostosis surgery
Krista Noel Sophia Greenan, MD (Aurora, CO); Frank Walch, MD; Noah Hubbell, BS; Ligia Batista, BA; Sarah Graber, BS; Robyn
Randall, BS; Allyson Alexander, MD, PhD; Brooke French, MD; Brent O'Neill, MD; Ken Winston, MD; David Khechoyan, MD; Charles
Wilkinson, MD
Introduction: Many craniofacial surgeons and neurosurgeons routinely send their patients to a Pediatric Intensive Care Unit (PICU)
after uncomplicated surgery for craniosynostosis. Conversely, most such patients at Children's Hospital Colorado have routinely been
sent from the post-anesthesia care unit to a regular floor unit after surgery. In this study, we examine the frequency and reasons why
such patients, who are first admitted to the floor after uncomplicated surgery, have been subsequently transferred to the PICU.
Methods: This is a single site retrospective chart review of all patients who underwent surgery for craniosynostosis between 2009 and
2017. Relevant clinical variables were collected and analyzed. Primary outcome was unplanned transfer from floor to PICU. Secondary
outcomes include duration of hospitalization, unplanned admission from operating room to PICU, post-operative complications,
hemoglobin levels and transfusion rates.
Results: A retrospective chart review yielded a cohort of 423 patients. 368 patients (86.9%) were admitted directly to the floor, while
55 patients (13.0%) were admitted directly from the operating room to the PICU. Of patients admitted directly to the floor, only two
patients (0.5%) were transferred to the PICU during their hospitalization: one for respiratory insufficiency and one for seizure. Of the
55 patients admitted to the PICU postoperatively, 33 were planned and 22 were un-planned. Reasons for PICU admission included
type of surgery, prolonged surgery time, and complex co-morbidities. Between the two groups, the group admitted to the PICU had a
statistically significant longer operative time (3.34 hours versus 2.05 hours) as well as length of stay (5 days versus 3 days).
Conclusion: The vast majority of craniosynostosis surgery patients can be managed safely on the floor with limited complications.
Longer, more complex cases and patients with significant comorbidities, however, may still require planned PICU admission.
553. Sports-related concussions and resulting occipital headaches: the role of posterior scalp nerve decompression
Rajiv Iyer, MD (Baltimore, MD); Robin Yang; Mari Groves, MD; Karan Chopra, MD; Lee Dellon, MD; Eric Williams, MD
Introduction: An estimated 3.8 million concussions occur in the US per year during competitive sports and recreational activities.
Post-traumatic headaches (PTH) and associated symptoms can lead to diminished quality of life. The purpose of this study is to
evaluate the role of posterior scalp decompression (PSD) in the treatment of PTH for sports-related injuries.
Methods: Patients who were treated with a PSD for sports-related PTH between the years 2011 and 2016 were retrospectively
reviewed. All patients were independently medically managed by a neurologist. Visual Analog Scales (VAS) and patient satisfaction
scales were administered. Success was defined as a reduction of VAS by 50%. Improvement in the quality of life was defined as a
reduction of medication use and a return to sports or normal activities.
Results: 48 patients (21 female, 27 male) identified as having a diagnosis of sports-related PTH underwent bilateral greater occipital
neurolysis and intramuscular placement of the lesser occipital nerve in the studied time period. Mean age was 18 years and mean
follow up was 5.8 months. The average time from injury to surgery was 9 months. Pre-operative VAS scores averaged 8.3 (range 5-
10), and improved to 1.5 (range 0-3; p =.0001) post-operatively. 36 patients were able to return to sporting events. 21 patients had
pre-operative photophobia and all had resolution of this symptom post-operatively. Pre-operatively, patients were taking an average of
2.4 medications for their headaches, which reduced to 0.8 (p = .0004) following intervention. 100% of surveyed patients reported that
they would elect to undergo the surgery again.
Conclusion: Sports-related PTH can be debilitating for patients. PSD in these patients can result in improved symptoms, quality of life
and a return to normal activity.
554. Risk-adjusted overall survival for pediatric high grade astrocytomas by location and treatment in a national cohort
J. Bryan Iorgulescu, MD (Boston, MA); Maya Harary; Cheryl Zogg; Timothy Smith, MD, PhD
Introduction: Pediatric high grade astrocytomas (HGA) represent a diversity of pathologies with distinct molecular drivers and
localization from their adult counterparts.
Methods: The management and overall survival (OS) of patients <21yo with either anaplastic astrocytoma (AA) or glioblastoma
(GBM) were evaluated from the National Cancer Database (2004-2014) by K-M and risk-adjusted proportional hazards.
Results: 1,664 children presented with HGA after exclusion. 58% (n=973) were supratentorial hemispheric (median 14yo [IQR:8-18],
66% GBM) with a median OS of 23.5mo (95CI:21.1-26.8), which was improved by GTR (37.2mo vs. STR's 21.3mo and NR's [no
resection/biopsy-only] 16.9mo, p<0.001). In risk-adjustment, there was no OS difference by sex, age, co-morbidities, race, or
radiotherapy. GTR (STR's HR 2.2, 95CI:1.53-3.12; NR's HR 2.72, 95CI:1.86-3.99; p<0.001), chemotherapy (HR 0.60, p=0.01), and
AA-histology (HR 0.45, p<0.001) demonstrated improved OS. Cerebellar HGAs’ (n=90, median 11yo [IQR:6-17], 63% GBM) median
OS was 17.7mo (95CI:12.9-20.1), which didn't differ by resection (p=0.45). In midline cases, brainstem HGAs' (n=202, median 7yo
[IQR:5-12], 60% GBM) median OS was 10.4mo (95CI:9.2-11.7). Only 19-20yo (HR 0.32 vs. 4-6yo, p=0.03) and chemotherapy (HR
0.51, p=0.001) displayed with improved OS in multivariat analysis. Diencephalic HGAs’ (n=110, median 10yo [IQR:7-15], 61% GBM)
median OS was 15.5mo (95CI:13.4-19.0). GTR was reported in 18% and also not associated with improved OS (14.0mo vs NR’s

13.4mo). Chemotherapy (HR 0.41, p=0.03) displayed improved OS, along with a trend of female sex (HR 0.58, p=0.07) towards better
OS. Spinal cord HGAs’ (n=70, median 12yo [IQR: 8-15], 59% GBM) median OS was 15.2mo (95CI:11.9-19.5). Resection and
chemotherapy were not associated with OS, only age 0-3yo (vs age 4-6yo, p=0.02) and AA-histology (p=0.02) demonstrated improved
OS.
Conclusion: We demonstrate the differential OS associated with pediatric HGAs by location and treatment using a national cohort
and highlight the benefits associated with chemotherapy and GTR in supratentorial HGAs.
555. Biomechanical finite element analysis of the developing craniocervical junction
Douglas L. Brockmeyer, MD, FAANS (Salt Lake City, UT); Ben Ellis, PhD; Rinchen Phuntsok, MA
Introduction: Little is known about the biomechanical properties of the developing craniocervical junction (CCJ). It is hypothesized
that there is an age-dependent maturation that occur within the structures that stabilize the CCJ, but little data supports this notion. In
this study, finite element modeling (FEM), a computational technique that enables quantitative biomechanical analysis, was used to
test this hypothesis.
Methods: Validated FEMs of four normal pediatric CCJ’s, age 13 months, 10 years and 14 years old, were compared to two validated
adult CCJ FEMs, age 26 years and 59 years. Surface generation, meshing, material properties, boundary conditions and validation of
the model have been reported previously. A moment of 0.1 Nm was applied to the occiput in flexion and extension in the pediatric
models while a moment of 1.0 Nm was applied to the adult models. Pediatric soft tissue material properties were reduced to 10% of
adult values, a level published previously. FEBio was used for the analysis.
Results: When compared to adult CCJ FEMs, the three pediatric FEMs demonstrated a gradual age-dependent increase in stiffness
similar to what has been reported in pediatric cadaveric testing. Flexion ROMs for the FEMs, by increasing age, were 34.5 (13
months), 30.0 (10 years), 27.6 (14 years), 22.4 (29 years), and 21.7 (59 years). Furthermore, given that fact that each pediatric FEM
contains identical soft tissue material properties, this study demonstrates that age-dependent increases in CCJ stiffness are at least in
part a result of pure bony geometrical scaling, a finding not previously reported.
Conclusion: These results demonstrate that both soft tissue and bony maturation contribute to the overall stiffening of the CCJ over
time. These results reflect previous findings from cadaveric testing and lay the groundwork for further computational advances in this
area.
556. Quantitative arteriovenous malformation scales better predict early outcomes in pediatric patients after stereotactic
radiosurgery
Swapnil Mehta (East Palo Alto, CA); Geoffrey Appelboom, MD, PhD; Iris Gibbs, MD; Gerald Grant, MD; Michael Edwards, MD; Steven
Chang, MD
Introduction: Several grading scales have been developed to predict outcomes following stereotactic radiosurgery (SRS) for brain
arteriovenous malformations (bAVMs). However, these scales have generally been compared in mixed adult and pediatric populations.
We assessed four of these scales in an exclusively pediatric cohort.
Methods: Forty-three pediatric patients with bAVMs treated with SRS from 1999 to 2015 were retrospectively studied. Spetzler-Martin
(SM), Proton Radiosurgery (PRAS), Virginia Radiosurgery (VRAS), and Pollock-Flickinger scores were assessed within 1 month of
SRS. Receiver operating characteristic (ROC) curves were generated for obliteration, hemorrhage, and symptomatic radiation effect
(SRE) at 2 and 4 years post-SRS. Excellent outcome, defined as the composite of no obliteration and no decline in modified Rankin
Scale (mRS), was also assessed. Pairwise comparison of ROC curves using bootstrapped 95% confidence intervals was conducted,
with p less than or equal to 0.05 after Bonferroni correction considered significant.
Results: After exclusion, 33 patients (35 bAVMs) with at least 2 years of follow-up and 22 patients (23 bAVMs) with at least 4 years
follow-up were available for analysis. ROC curves at 2 years post-SRS demonstrated that PRAS and VRAS were superior to SM for
predicting obliteration (PRAS vs. SM: p = 0.05, VRAS vs. SM: p = 0.02) and excellent outcome (PRAS vs SM: p = 0.05, VRAS vs. SM:
p = 0.01). Grading scales were not significantly different in predicting SREs or hemorrhage. ROC curves at 4 years follow-up were not
significantly different for any of the outcomes measured.
Conclusion: Despite several grading scales, no single scale appears superior in predicting outcomes for pediatric bAVMs at moderate
follow-up. PRAS and VRAS may provide better predictions than SM grade for obliteration and excellent outcomes at early time-points,
although further work using larger datasets is needed.
557. Incidence of Cervicomedullary Decompression in Patients with Achondroplasia: A Large, National Database Analysis
Jeffrey Nadel (Ann Arbor, MI); D. Wilkinson, MD; Cormac Maher, MD
Introduction: Foramen magnum stenosis requiring cervicomedullary decompression is the primary indication for neurosurgical
intervention in children with achondroplasia. The goal of this study was to determine the incidence of cervicomedullary decompression
in children with achondroplasia using a large, nationally-representative commercial payer claims database.
Methods: The OptumInsight dataset contains de-identified insurance claims from a large, private healthcare network of over 58 million
US beneficiaries between 2001 and 2014. Using International Classification of Diseases (ICD) diagnosis codes and Current
Procedural Terminology (CPT) codes, we identified all patients with achondroplasia and their associated medical and surgical
procedures throughout their insurance coverage. Demographic and clinical characteristics were examined, as well as the overall
incidence of cervicomedullary decompression.

Results: The prevalence of achondroplasia in the database population was 1.43 cases per 10,000 covered lives (n=8,391 cases). At
the time of insurance enrollment, patient ages ranged from 0 to 89 years old, with an average age of 28.50 + 21.11 years. Genders
were equally distributed (51.59% male). Approximately 46.0% of the population was under the age of 21 (n=3,864). The incidence of
surgery varied by age: Age 0-3: 24 patients per 1,000; Age 4-7: 5 patients per 1,000; Age < 8: 2 patients per 1,000. In total, the
cumulative incidence of needing surgery was 31 children per 1,000 children with achondroplasia. The mean age at time of surgery
was 3.08 + 4.80.
Conclusion: This is the first population-level study examining the need for cervicomedullary decompression in patients with
achondroplasia. We demonstrate that for children with achondroplasia, approximately 3 of every 100 will require decompression. The
incidence of decompression varies by age with the bulk of surgeries performed before age 5. Further work is needed to understand
the specific risk factors for foramen magnum stenosis and the need for surgical decompression in children with achondroplasia.
558. P2Y12 Precision in Therapeutic Monitoring of Dual Anti-Platelet Therapy for Flow Diversion of Cerebral Aneurysms
David Zarrin (Baltimore, MD); Jessica Campos, MD; Matthew Bender, MD; Bowen Jiang, MD; Chau Vo, MD; Arun Chandra, MD;
Justin Caplan, MD; Judy Huang, MD; Rafael Tamargo, MD; Li-Mei Lin, MD; Geoffrey Colby, MD, PhD; Alexander Coon, MD
Introduction: Dual antiplatelet therapy (DAT), most commonly consisting of aspirin and clopidogrel, is the standard of care for
intracranial stenting procedures, including flow diversion. Clopidogrel response varies by individual. We sought to investigate the real-
world precision of P2Y12 assessment of clopidogrel response.
Methods: A prospectively-collected, IRB-approved cerebral aneurysm database was reviewed to identify 588 patients who were
treated with the Pipeline Embolization Device (PED) from 2011-2017. Patients with multiple P2Y12 assays drawn within a 24-hour
window were identified. A single patient could contribute multiple, independent 24-hour sets. Levels drawn before a 5-day course of
DAT were excluded. Patients who received alternative antiplatelet agents, including abciximab and prasugrel, were excluded.
Therapeutic range was defined as P2Y12 from 60-200.
Results: A total of 1460 P2Y12 measurements were recorded across all patients; 261 (44%) patients had more than one assay
drawn. A total of 121 (21%) patients had multiple P2Y12 measurements (range 2-3) within 24 hours. These 121 patients accounted
for 206 independent 24-hour sets of P2Y12 measurements. The average P2Y12 fluctuation across all sets was 36 points. The 24-hour
set P2Y12 fluctuation of the 25th, 50th, and 75th percentiles were 11 points, 28 points, and 48 points respectively. Of the 206 24-hour
sets of P2Y12 assays, 75% remained within their original therapeutic category: 88 (43%) al therapeutic, 49 (24%) all hypo-responsive,
and 18 (9%) all hyper-responsive. 25% of patients fluctuated between therapeutic categories when multiple P2Y12 assessments were
drawn within a 24-hour period: 23 (11%) between hypo-response and therapeutic, 25 (12%) between hyper-response and therapeutic,
and 3 (1%) between hypo-response and hyper-response.
Conclusion: There is controversy about the utility of P2Y12 assessment of therapeutic response to clopidogrel. Our experience
suggests P2Y12 is an often-imprecise measure, and this should be considered when utilizing P2Y12 levels for clinical decisions.
559. How to improve obliteration rates during volume staged stereotactic radiosurgery for large arteriovenous malformations
Hideyuki Kano, MD, PhD (Pittsburgh, PA); John Flickinger, MD; Aya Nakamura, MD; Rachel Jacobs, BS; Daniel Tonetti, MD; Craig
Lehockey, MD; Kyung-Jae Park, MD, PhD; HuaiChe Yang, MD; Ajay Niranjan, MCh, MBA; L. Dade Lunsford, MD
Introduction: The management of large volume arteriovenous malformations (AVMs) with stereotactic radiosurgery (SRS) remains
challenging. We retrospectively tested the hypothesis that AVM obliteration rates can be improved by increasing the percent volume of
an AVM that receives a minimal threshold dose.
Methods: In 1992, we prospectively began to stage anatomic components in order to deliver higher single doses to AVMs < 15 cc in
volume. Since that time 60 patients with large AVMs underwent volume staged SRS (VS-SRS). The median interval between the first
and second stage was 4.5 months (2.8-13.8). The median target volume was 11.6 cc (4.3-26) in the first stage and 10.6 cc (2.8-33.7)
in the second stage SRS. The median margin dose was 16 Gy (13-18) for both SRS stages.
Results: Nine of 14 patients who had a hemorrhage after VS-SRS died during the latency interval. AVM obliteration after VS-SRS was
confirmed by MRI alone in four patients and by angiography in 11 patients at a median follow-up of 82 months (range, 0.4-206
months) after VS-SRS. The post VS-SRS obliteration rates on angiography were 4% at 3 years, 13% at 4 years, 23% at 5 years, and
27% at10 years. In multivariate analysis, only ≥20-Gy-volume coverage was significantly associated with a higher total obliteration
rates. The obliteration rates confirmed by angiography were 7% at 3 years, 37% at 4 years, 61% at 5 years, and 70% at 10 years
when the 20-Gy-volume covered <63% of total target volume. Four patients (7%) developed symptomatic adverse radiation effects.
Conclusion: The outcomes of prospective volume staged SRS for large AVMs can be improved. We found that obliteration rates can
be increased when the minimal margin dose is <17 Gy and <63% of the internal volume of the AVM receives more than 20-Gy.
560. Brain functional reconfiguration and cognitive impairment in adult moyamoya disease: a resting-state FMRI study
International Abstract Award
Yu Lei (Shanghai, China); Jiabin Su; Bin Xu; Yuxiang Gu; Ying Mao
Introduction: Disturbed brain functional interactions of adult moyamoya disease (MMD) with cognitive impairment remains elucidated.
The present study systematically examined the network topological properties and quantified the dynamic reconfiguration in adult MMD
with cognitive impairment, so as to acquire accurate and detailed knowledge of its complex connectivity patterns and heterogeneous

spatiotemporal organization over time.

Methods: Fifty-one adult MMD patients were recruited, including 27 with vascular cognitive impairment (VCI) and 24 without VCI
(NonVCI), as well as 26 normal controls (NC). Network topological metrics were firstly compared among the 3 groups. Then, a
dynamic measurement (connectivity number entropy, CNE) was used to examine the flexibility differences among the 3 groups in the
global, regional, and network levels. Finally, dynamic reconfiguration of flexible and specialized regions was traced across the 3
groups.
Results: Graph theory analysis indicated that all 3 groups exhibited small-world network topology, but presented with a pattern of NC-
NonVCI-VCI in all 3 properties: integration (Lglobal, Eglobal), segregation (Elocal, Cglobal, and Modularity), and small-worldness (σ).
Afterwards, the NC group showed significant higher CNE values than those of both the NonVCI and NC groups in the global (P <
0.001) and network (default mode network, P = 0.004; executive control network, P = 0.001) levels. Specifically, brain regions related
to cognitive functioning such as the prefrontal gyrus, anterior cingulate gyrus, middle temporal gyrus, supramarginal gyrus, and lingual
gyrus exhibited significant CNE changes across the 3 groups. Furthermore, CNE values of both flexible and specialized regions
changed with cognitive impairment, indicating a potential link between functional flexibility deterioration and cognitive impairment in
adult MMD.
Conclusion: This study not only sheds light on the organizational principle behind network changes in adult MMD with cognitive
impairment, but also provides a new framework to quantify the dynamic behavior of spontaneous brain activity.
561. Risk of branch occlusion and ischemic complications with Pipeline Embolization Device in treatment of posterior
circulation aneurysms
Nimer Abushehab, MD (Shreveport, LA)
Introduction: Flow diversion using the Pipeline Embolization Device (PED) is increasingly used for endovascular treatment of
intracranial aneurysms due to high reported obliteration rates and a low associated morbidity. While obliteration of covered branches in
the anterior circulation is generally asymptomatic, this has not been studied within the posterior circulation.
Methods: A retrospective review of prospectively maintained databases at eight academic institutions, from 2009 to 2016, was
performed to identify patients with posterior circulation aneurysms treated with the PED device. Branch coverage and obliteration
following PED placement was evaluated. Vessels that were assessed included the posterior inferior cerebellar artery, anterior inferior
cerebellar artery, superior cerebellar artery, and posterior cerebral artery (PCA). In addition, if the PED crossed the ostia of the
contralateral vertebral artery (VA), the long-term patency of the covered vertebral artery was assessed as well.
Results: A cohort of 129 consecutive patients underwent treatment of 131 posterior circulation aneurysms with the PED. Adjunctive
coiling was used in 40 (31.0%) procedures. Following PED placement, 1 or more branches were covered in 103 (79.8%) procedures.
At a median follow-up of 11 months, 13% of the covered vessels had occluded, most frequently the vertebral artery (34.8%). Branch
obliteration was more common amongst asymptomatic aneurysms (p=0.0003). Ischemic complications occurred in 29 (22.5%)
procedures. On multivariable analysis, there was no significant difference in the risk of ischemic complications in cases where a
branch was covered (p = 0.24) or occluded (p = 0.16).
Conclusion: There was a low occlusion rate in end-arteries following branch coverage at last follow-up, while the rate was higher in
PCA and VA where collateral supply is high. Branch occlusion was not associated with a significant increase in ischemic complications
as compared to covered branches that remained patent.
562. Trends in interhospital transfers and mechanical thrombectomy for acute ischemic stroke
Thomas A. Pieters, MD (Rochester, NY); Benjamin George, MD, MPH; Christopher Zammit, MD; Adam Kelly, MD; Kevin Sheth, MD;
Tarun Bhalla, MD, PhD
Introduction: Stroke care in the US is becoming increasingly regionalized. Many patients undergo interhospital transfer to access to
specialized, time-sensitive interventions such as mechanical thrombectomy.
Methods: We used the stratified survey design of the US Nationwide Inpatient Sample (2009-2014) to examine trends in interhospital
transfers for ischemic stroke resulting in mechanical thrombectomy. International Classification of Disease˗Ninth Revision (ICD-9)
codes were used to identify stroke admissions and inpatient procedures. The analysis was restricted to hospitals performing
thrombectomy. Regression analysis was used to identify factors associated with patient outcomes.
Results: From 2009-2014, 772,437 ischemic stroke admissions were identified within hospitals offering thrombectomy. The proportion
of stroke admissions that arrived via interhospital transfer increased from 12.5% to 16.8%, 2009-2014 (P-trend<0.001). The proportion
of transfers receiving thrombectomy increased from 4.0% to 5.2%, 2009-2014 (P-trend=0.016), while the proportion receiving tissue
plasminogen activator (tPA) increased from 16.0% to 20.0%, 2009-2014 (P-trend<0.001). Approximately 1 in 4 patients receiving
thrombectomy for ischemic stroke were transferred from another acute care facility (n=6,014 of 24,861). Compared to patients arriving
via the hospital front door receiving mechanical thrombectomy, those arriving via interhospital transfer were more often from rural
areas and more commonly received by teaching hospitals with greater frequency of thrombectomy. Those arriving via interhospital
transfer undergoing thrombectomy had greater odds of symptomatic intracranial hemorrhage (Adjusted Odds Ratio [AOR] 1.19, 95%
CI: 1.00-1.42) vs. front door arrivals; however, there were no differences in inpatient mortality (AOR 1.11, 95% CI: 0.93-1.33).
Conclusion: From 2009-2014, interhospital stroke transfers to thrombectomy performing hospitals increased by one-third For every
15 additional stroke transfers over the time period examined, one additional transferred patient received thrombectomy. As stroke
systems of care continue to evolve in the US, the optimization of stroke transfers presents an opportunity to increase access to
meaningful interventions such as thrombectomy.

563. Analysis of wide-neck aneurysms in the Barrow Ruptured Aneurysm Trial
Justin Robert Mascitelli, MD (Phoenix, AZ); Michael Lawton, MD; Peter Nakaji, MD; Joseph Zabramski, MD; Robert Spetzler, MD
Introduction: Ruptured wide-neck aneurysms (WNAs) are difficult to treat and there is minimal literature comparing clipping to coiling.
The Barrow Ruptured Aneurysm Trial (BRAT) is a prospective, randomized trial comparing clipping and coiling. We aimed to
determine: 1) How many aneurysms had a wide neck? 2) Did wide-neck status influence treatment? 3) How did clipping compare to
coiling for WNAs?
Methods: This is a post-hoc analysis of WNAs within BRAT. Exclusion criteria from the original dataset (n=471) included non-saccular
morphology (n=52), non-aneurysmal SAH (n=57), death before treatment (n=6), and insufficient angiographic data (n=29). A WNA
was defined as 1) neck width 4 mm or greater; or 2) dome diameter to neck width ratio less than 2.
Results: Of 327 patients, 177 (54.2%) had a wide neck. WNAs were more likely to occur in older patients (p=0.03) with worse clinical
grade (p=0.02); were more likely to arise from the MCA, basilar tip, or ICA other than the junction with the PCoA (p=0.001); and were
associated with worse clinical outcome (p=0.01 or less). WNAs were equally distributed in the assigned treatment groups (Clip 56.6%
vs. Coil 51.8%, p=0.38), but were over-represented in the actual clipping cohort (Clip 62.4% vs. Coil 37.6%, p<0.0001). The majority
of aneurysms (76.7%) in the coil-to-clip crossover cohort had a wide neck. There was no difference in clinical outcome in either the
intent-to-treat analysis or as-treated analysis. The aneurysm obliteration rate was lower (p<0.0001) and retreatment rate higher
(p<0.0001) in the actual coiling cohort.
Conclusions: This study is the first to compare clipping and coiling of WNAs on a large scale. Wide-neck status significantly impacted
treatment strategy favoring clipping. A wide aneurysm neck is an important morphological feature that can be used in selecting the
best treatment modality, with clipping favored over coiling.
564. Vascular targeting causing thrombosis in an arteriovenous malformation animal model
Cerebrovascular Section Best Basic Scientific Paper
Andrew Gauden (Marsfield, Australia); Vivienne Lee; Sinduja Subramanian; Vaughan Moutrie; Zhenjun Zhao, PhD; Lucinda McRobb,
PhD; Marcus Stoodley
Introduction: Despite current treatments, of brain arteriovenous malformations (AVMs) are untreatable. Previous work has identified
the potential target phosphatidylserine (PS) externalised in the plasma membrane of the endothelium in AVMs that have undergone
treatment with focused irradiation. We hypothesise that treatment of AVMs with gamma knife radiosurgery (GKS) and vascular
targeting of PS with a thrombotic compound will cause localised thrombosis within the AVM vessels.
Methods: A rat animal model was used by performing an end-to-side anastomosis of the external jugular vein (EJV) to the common
carotid artery. The AVM was treated with a dose of focused radiation of 20 Gy using a Leksell Gamma Knife. At 3 weeks following
GKS a dose of a conjugate of Annexin V and thrombin was administered intravenously. Comparison groups of saline and thrombin
alone were included. At 4 weeks, an angiogram was performed with tissue harvested for histology.
Results: There was occlusion of the AVM on angiography in 69% of conjugate-treated animals (p=0.002). AVM occlusion occurred in
63% of the GKS group treated with conjugate (p=0.03), and in 75% of the sham-GKS conjugate treated group (p=0.009). Both control
arms had preserved AVM flow on angiogram. Histological evidence of occlusive thrombus was present within the EJV and nidus of
62.5% of animals in the GKS with conjugate group (p=0.026) with a lower proportion of thrombus observed in the sham-GKS
conjugate group (37.5%) (p=0.37). No thrombus was observed in either control group.
Conclusion: This study demonstrates a significant association between use of an Annexin V/Thrombin conjugate and thrombosis of
AVM vessels both radiologically and histologically and may demonstrate a potential new treatment for AVMs. This finding is the first of
its kind in the treatment of AVMs.
565. PHASES score applied to a prospective cohort of aneurysmal subarachnoid hemorrhage patients
Paul Foreman, MD (Birmingham, AL); Philipp Hendrix; Mark Harrigan; Winfield Fisher; Nilesh Vyas; Robert Lipsky; Beverly Walters; R.
Shane Tubbs; Mohammadali Shoja; Christoph Griessenauer
Introduction: The treatment of unruptured intracranial aneurysms remains controversial. The PHASES score was developed to
predict the 5-year risk of aneurysm rupture. We have assigned PHASES scores to a cohort of aneurysmal subarachnoid hemorrhage
(aSAH) patients to assess the distribution of scores and its ability to predict outcome.
Methods: In this study, the PHASES score was applied to a prospective cohort of aSAH patients that were enrolled in the Cerebral
Aneurysm Renin Angiotensin System (CARAS) study. The CARAS study enrolled patients from two academic institutions in the United
States from 2012-2015. Univariable and multivariable analyses were performed to identify factors predictive of outcome at last follow
up.
Results: One hundred and forty-nine aSAH patients were included with a mean age of 54.9 ± 12.5 years. Most ruptured aneurysms
were < 7 mm (62.4%) and located in the anterior circulation (80.5%). Favorable functional outcome (mRS 0-2) at last follow up was
achieved in 61.7% of patients. PHASES scores ranged from 0-16 with a median of 5; the majority of patients had a score of 4 (20.1%)
or 5 (32.2%). Multivariable modeling identified higher PHASES scores (OR 1.235, CI 1.016 - 1.501, p = 0.034) and higher Hunt and
Hess grades (OR 2.224, CI 1.353 - 3.655, p = 0.002) as independent predictors of poor functional outcome (mRS 3-6) at last follow

up.
Conclusion: The majority of aSAH patients present with low PHASES scores. Elevated PHASES scores are independently
associated with poor functional outcome in patients with aSAH.
566. Bypass surgery for the treatment of complex aneurysms in 71 patients
Xiang'en Shi (Beijing, China)
Introduction: To study the effectiveness of internal maxillary artery bypass surgery for the treatment of huge/dolichoectatic
aneurysms. Methods: 71 patients with huge or dolichoectatic aneurysms, 44 males and 27 females; mean age is 44.13 years.
Angiographic studies showed the aneurysms are located in cavernous sinuous segment of the internal carotid artery in 25 patients,
the middle cerebral arteries in 18 patients, supraclinoid carotid artery in 14 patients, cervical and petrous carotid artery in 2 patients,
basilar tip-posterior cerebral artery in 6 patients, basilar trunk in 3 patients, and vertebrobasilar artery in 3 patients. Of the 71 cases,
aneurysms without perforators were trapped after the bypass in 44 cases. In 27 cases, aneurysms connected to perforators were
managed through proximal occlusion with distal bypass so the perforating arteries would still be perfused.
Results: Neurological outcomes were measured on the basis of Glasgow Outcome Score (GOS). Recovery rate to normal daily life
after surgery in trapped aneurysms without perforators and reversal flow of the aneurysm with perforators was 41/44 (93.2%), and
25/27 (92.6%) respectively. In 5780.2% patients with mean follow-up of 3.0 years (0.5-6.5), 48 patients had bypass grafts of proximal
M2 segment of MCA and 9 had PCA bypass grafts. Of those, 52 patients had good outcome, 3 patients needed assistance for daily
living, and 2 deaths occurred unrelated to surgery.
Conclusion: Huge /dolichoectatic aneurysms pose unique therapeutic challenges that require thorough surgical planning,
individualized treatment strategies, and refined neurovascular techniques for successful outcome.
567. Defining long-term clinical outcomes and risks of stereotactic radiosurgery (SRS) for brainstem cavernous
malformations
Rachel Caroline Jacobs (Pittsburgh, PA); Hideyuki Kano, MD, PhD; L. Dade Lunsford, MD
Introduction: The role of stereotactic radiosurgery (SRS) for brainstem cerebral cavernous malformations (CCMs) has remained
controversial. We evaluated clinical outcomes as a measure of treatment efficacy, as current radiographic modalities cannot detect
CCM obliteration.
Methods: Between 1988 and 2016 at the University of Pittsburgh, SRS was performed with the Gamma Knife in 76 evaluable patients
with solitary symptomatic brainstem CCMs. Ninety-one percent of these patients had experienced 2 or more hemorrhages associated
with new neurological deficits. Fourteen patients (18.4%) underwent resection before radiosurgery. The median malformation volume
was 0.66 cm3 (range, 0.05-6.8), and the median CCM margin dose was 15.0 Gy.
Results: Fifteen patients (19.7%) developed hemorrhage after SRS at a median follow-up of 48 months. The hemorrhage-free survival
after SRS for brainstem CCMs was 92% at 1 year, 87% at 3 years, 85% at 5 years, and 78% at 10 years. The annual hemorrhage
rate was 31.3% pre-SRS and 3.77% after SRS. In univariate analysis, target volume, prior surgical resection, and number of
hemorrhages before SRS was significantly associated with higher rate of hemorrhage after SRS. In multivariate analysis, only number
of prior hemorrhages was significantly associated with a higher hemorrhage rate (p<0.0005, HR=1.51, 95% CI: 1.23-1.85).
Symptomatic adverse radiation effect (ARE) developed in 7 patients (9.2%). The rate of symptom deterioration due to post-SRS
hemorrhage and symptomatic ARE was 8% at 1 year, 13% at 3 years, and 16% at 5 years. In univariate analysis, target volume and
number of hemorrhages before SRS was associated with an increased symptom deterioration. In multivariate analysis, only target
volume was significantly associated with an increased symptom deterioration (p=0.002, HR=1.74, 95% CI= 1.23-2.48).
Conclusion: SRS provided long-term hemorrhage and symptom deterioration control. Treatment volume significantly impacted
symptom deterioration after SRS, and the number of hemorrhages before SRS increased hemorrhage rate post-SRS.
568. Phase I clinical trial of intracerebral transplantation using BMSC against acute ischemic stroke
Masahito Kawabori (Sapporo, Japan); Masahito Kawabori; Hideo Shichinohe; Satoshi Kuroda; Shunsuke Terasaka; Kiyohiro Houkin
Background: Recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. Prior studies have
demonstrated that bone marrow stromal cells (BMSCs) have therapeutic potential against stroke, however, there are several problems
remain unsolved. In this study, we investigated the use of autologous BMSC transplantation for acute ischemic stroke with several
new aspects as a next-generation cell therapy for treating stroke. This study is called the Research on Advanced Intervention using
Novel Bone marrOW stem cell (RAINBOW, trial ID: UMIN000026130).
Methods/Design: RAINBOW is a phase 1, open-label, uncontrolled, dose-response study, with the primary aim to determine the
safety of the autologous BMSC administered to the patients with acute ischemic stroke. Estimated enrollment is 6-10 patients suffering
from moderate to severe neurological deficits. Approximately 50 mL of the bone marrow is extracted from the iliac bone of each
patient 15 days or later from the onset, and BMSCs are cultured with allogeneic human platelet lysate (PL) as a substitute for fetal calf
serum and are labeled with superparamagnetic iron oxide for cell tracking using magnetic resonance imaging (MRI). BMSCs are
stereotactically administered around the area of infarction in the subacute phase. Each patient will be administered a dose of 20 or 50
million cells. Neurological scoring, MRI for cell tracking, 18F-fuorodeoxyglucose positron emission tomography, and 123I-Iomazenil
single-photon emission computed tomography will be performed throughout 1 year after the administration.

Discussion: This is a first-in-human trial to use labelled BMSC to the patients with acute ischemic stroke. We expect that
intraparenchymal injection can be a more favorable method for cell delivery to the lesion and improvement of the motor function.
Moreover, it is expected that the bio-imaging techniques can clarify the therapeutic mechanisms. We will present our preliminary
results of the trial.
569. European multicenter study for evaluation of a dual layer flow diverting stent for treatment of wide neck intracranial
aneurysms: the EuFRED study
Christoph Johannes Griessenauer, MD (Brookline, MA); Monika Killer-Oberpfalzer; Naci Kocer; Hendrik Janssen; Tobias Engelhorn;
Markus Holtmannspötter; Jahn Buhk; Thomas Finkenzeller; Gunther Fesl; Johannes Trenkler; Wolfgang Reith; Markus Möhlenbruch
Introduction: Endoluminal reconstruction with flow diverting stents represents a widely accepted technique for the treatment of
complex intracranial aneurysms. This European registry study analyzed the initial experience of 15 neurovascular centers with the
Flow Redirection Intraluminal Device (FRED) system.
Methods: Consecutive patients with intracranial aneurysms treated with FRED between February 2012 and March 2015 were
retrospectively reviewed. Complications and adverse events, transient and permanent morbidity, mortality, and occlusion rates were
evaluated.
Results: During the defined study period, 579 aneurysms in 531 patients (median 54 years, range 13-86 years) were treated with
FRED. Seven percent of patients were treated in the acute phase (<3 days) of aneurysm rupture. Median aneurysm size was 7.6 mm
(range 1-36.6 mm) and median neck size 4.5 mm (range 1-30 mm). Successful 1st attempt stent deployment occurred in 98.3% of
single FRED procedures. Additional coiling of the aneurysm was performed in 17.6%. The overall complete occlusion rate was 69.2%
at a median follow-up of 6.6 months (range 0.03-45.6 months). Progressive occlusion was witnessed over time, with a complete
occlusion rate of 95.3% of aneurysms followed for more than 1 year. Transient and permanent morbidity occurred in 3.2% and 0.8%
of procedures, respectively. The overall mortality rate was 1.5%.
Conclusion: This retrospective study in real-world patients demonstrated safety and efficacy of FRED for treatment of intracranial
aneurysms. In the vast majority of cases, treatment with a single FRED resulted in complete angiographic occlusion at 1-year
comparable to other flow diverting stents.
570. Transvenous curative embolization of cerebral arteriovenous malformation: prospective cohort study
George Mendes (Limoges, France); Yashar Kalani; Charbel Mounayer
Introduction: Curative transvenous embolization is an emerging strategy for treatment of cerebral arteriovenous malformations
(AVMs). Methods: We prospectively followed forty patients with forty-one AVMs underwent transvenous endovascular therapy
between January 2008 and January 2015. Patient demographics, AVM characteristics, endovascular techniques used, angiographic
results, clinical outcomes and complications were assessed independently.
Results: Thirty-eight of 41 (92.6%) AVMs were anatomically cured. The mean patient age was 37.7 years (range, 18-69 years) and
55% were female. Twenty-seven (67.5%) patients presented with hemorrhage. The mean size of the AVM nidus was 2.8 + 1.2 cm,
and low Spetzler- Grade AVMs comprised 41.5% of lesions. The majority of patients were treated in 1 session (56%; n=23). The
mean follow-up period was 28.4 (range, 6 to 106 months). There was one (2.5%) hemorrhagic complication related to microcatheter
navigation and one (2.5%) venous infarction was observed without clinical consequences. At 6-month follow-up, one (2.5%) patient
had significant disability. No recurrence was documented during the follow-up period. Overall mortality was 2.5% and procedure
related mortality was 0%.
Conclusion: This prospective contemporary series demonstrates a high rate of complete AVM obliteration and excellent functional
outcomes in patients with both ruptured and unruptured AVMs treated with transvenous embolization. This approach is promising and
warrants further investigation as a treatment for select AVMs.
571. Wide bifurcation morphology induces aneurysmogenic high positive wall shear stress gradient at the apex independent
of flow rate
Adel M. Malek, MD, PhD, FAANS (Boston, MA); Alexandra Lauric; James Hippelheuser
Introduction: Endothelium adapts to wall shear stress (WSS) and is functionally sensitive to positive (aneurysmogenic) and negative
(protective) spatial WSS gradients (WSSG) in regions of accelerating and decelerating flow, respectively. Positive WSSG causes
endothelial migration, apoptosis, and aneurysmal extracellular remodeling. Given the association of wide bifurcations with aneurysm
formation, we evaluated the effect of bifurcation geometry on local apical hemodynamics.
Methods: Computational fluid dynamic (CFD) simulations were performed on parametric bifurcation models with increasing angles:
(1)-symmetric geometry (bifurcation angle 60° to 180°), (2)-asymmetric geometry (daughter angles 30°/60° and 30°/90°) and (3)-
curved parent vessel (bifurcation angles 60° to 120°). CFD was recomputed at double flow rate. Time-dependent and averaged apical
WSS and WSSG were analyzed. Results were validated on patient-derived models.
Results: Narrow symmetric bifurcations are characterized by protective negative apical WSSG, with a switch to aneurysmogenic
WSSG occurring at angles ≥85°. Asymmetric bifurcations develop positive WSSG on the obtuse daughter branch. Curved parent
vessel leads to positive apical WSSG on the outer curve daughter branch. All simulations revealed wider apical area coverage by
higher WSS and positive WSSG magnitudes with increased bifurcation angle and higher flow rate. Flow rate does not affect the angle

threshold of 85°, past which positive WSSG occurs. In curved models, high flow displaced the impingement area away from the apex,
in a dynamic fashion and in an angle-dependent manner.
Conclusion: Apical shear forces and spatial gradients are highly dependent on bifurcation and inflow vessel geometry. The
development of aneurysmogenic positive WSSG as a function of wide angular geometry, provides a mechanotransductive link for the
association of obtuse bifurcations and aneurysm development. These results suggest therapeutic strategies aimed at altering
underlying unfavorable geometry and deciphering the molecular endothelial response to shear gradients in a bid to disrupt the
associated aneurysmal degeneration.
572. Professional athlete performance decline following concussion: an analysis of three major sports
ThinkFirst Injury Prevention Award
Aaron Michael Yengo-Kahn, MD (Nashville, TN); Scott Zuckerman, MD; Brian Zalneraitis, BS; Andrew Kuhn, BA; Andrew Ghaly, BS;
Michael Oluwole, BS; Gary Solomon, PhD
Introduction: Post-concussion performance is a burgeoning subfield within sport-related concussion. Few exploratory studies exist
investigating performance deficits upon return-to-play. A professional athlete’s accessible statistics allow for study of post-concussive
performance. Our aim was to identify the rate in which performance post-concussion decline occurs and delineate predictors of
performance decline across three professional sports.
Methods: A secondary analysis of previously collected and published data was utilized to conduct a retrospective, case-control study
of professional football, basketball, and hockey players between the 2005-06 and 2015-16 seasons. Performance decline was defined
as 0.5 standard deviation decline from each league’s sample baseline. Athletes with concussions during the regular season or playoffs
and their corresponding statistics were compiled using public sources. Included athletes played in 3 (football) to 5 (hockey/basketball)
consecutive games before and after their injury. Those who suffered concurrent or intervening orthopedic injuries were excluded.
Logistic regression was performed using six variables: age, BMI, experience, games missed, salary and years left in contract. The
primary binary outcome was decline in performance, and secondary outcome was decline in playing time.
Results: A total of 284 concussed athletes were included (115 NFL, 62 NBA, 107 NHL). Of these, 81 (28.5%) experienced a decline
in performance. Logistic regression analysis demonstrated no significant predictors of decline in performance after sustaining a sport-
related concussion. Number of games missed predicted a decline in playing time after returning from concussion χ2=4.7(1),p=03, with
small effects, Nagelkerke R2 = 0.03, OR = 1.36.
Conclusion: Nearly one-third of profession athletes in this cohort demonstrate decreased performance after returning to play from a
concussion, however, no associations between multiple demographic and other independent variables and decline in performance
post-concussion were demonstrated. Further study may continue improving counseling of coaches and athletes on post-concussion
performance once medically cleared.
573. CT evidence of brainstem hemorrhage does not lead to worsened long term outcomes in severe traumatic brain injury
Ross C. Puffer, MD (Rochester, MN); Gregory Weiner, MD; Ross Puffer, MD; Matthew Mesley, MD; David Okonkwo, MD, PhD
Introduction: Patients with severe traumatic brain injury presenting with evidence of brainstem hemorrhage on admission CT are
thought to have a more devastating neurologic injury compared to patients without brainstem hemorrhage. We sought to determine if
traumatic brainstem hemorrhage affects long term outcome in patients with severe TBI.
Methods: The brain trauma research center at the University of Pittsburgh medical center has maintained a prospective database of
patients with severe traumatic brain injury, and we retrospectively searched this database between 1991 to 2007. We identified
patients with admission CT scans as well as long term outcomes using the Glasgow outcome scale and disability rating scale. Long
term outcomes were compared between patients with and without evidence of traumatic brainstem hemorrhage on admission CT.
Results: We identified 678 patients, and of those, 494 had adequate CT scan data and long term follow-up completed. The mean age
of the cohort was 37.2 (+/- 0.79 years), and 28/494 (6%) had evidence of brainstem hemorrhage on admission CT. There was no
significant difference in admission GCS between groups (hemorrhage GCS 4.9 +/- 0.3 vs. no hemorrhage GCS 5.3 +/- 0.08, p=0.16).
At final follow-up (mean 16.9 months), there was no significant difference in Glasgow outcome score (hemorrhage GOS 2.21 +/- 0.3
vs. no hemorrhage GOS 2.7 +/- 0.07, p=0.10).
Conclusion: Despite being thought of as a very poor prognosticating sign, evidence of traumatic brainstem hemorrhage on admission
CT does not correlate with worsened long term GOS in this cohort of patients with severe TBI.
574. Complication rates of PICC and CVC lines in the neuro-intensive care unit: a randomized trial
Justin Davanzo, MD (Hershey, PA); Nicholas Brandmeir, MD; Russell Payne, MD; Emily Sieg, MD; Ashiya Hamirani; Annie Tsay;
Jeffrey Watkins; Sprague Hazard, MD; J Zacko, MD
Introduction: The objective of this study was to determine the relative rates of complications in peripherally inserted central venous
catheters (PICC) and centrally inserted central venous catheters (CVC) in the neuroscience intensive care unit (NSICU). Previous
studies have shown advantages and disadvantages to both catheters. NSICU patients represent a unique population, with a unique
risk profile that requires further study with regards to this topic.
Methods: This study was a prospective randomized controlled trial. Patients were considered eligible if they were admitted to the
NSICU and required central venous access. Randomization was carried out by means of a computer-generated randomized sequence

with equal allocation to each arm. Study endpoints were failure to insert the catheter, removal of the device, discharge from the
hospital, or death. Assessments of complications were completed by the attending NSICU intensivist caring for the patient. This study
was carried out with the approval and under the supervision of the institutional review boar (IRB) and departmental data safety
monitoring board (DSMB).
Results: One hundred fifty-two patients were enrolled between July 2015 and January 2017. Seventy-two were enrolled in the PICC
arm and 80 in the CVC arm. At the second pre-planned interim analysis, the DSMB determined that the study was unlikely to achieve
its pre-specified endpoint and it was terminated early. The total number of complications across both groups were similar. The PICC
cohort suffered four deep venous thromboses. The CVC cohort suffered one pneumothorax secondary to insertion.
Conclusion: This study provides level II evidence that PICCs and CVCs have similar rates of complications in the NSICU when
compared in a randomized controlled clinical trial. This study indicates that no method of central access is superior to another in the
NSICU and must be determined on a case-by-case basis.
575. Effects of combined neural stem cell therapy and treadmill training on functional recovery, cyst formation and
astrogliosis after cervical spinal cord injury
Alexander Younsi, MD (Heidelberg, Germany); Moritz Scherer; Lennart Riemann; Guoli Zheng; Thomas Skutella; Andreas Unterberg;
Klaus Zweckberger
Introduction: Neural precursor cell (NPC) transplantation after spinal cord injury (SCI) has shown beneficial effects on
neuroregeneration. However, functional recovery may be limited due to astrogliosis and cyst formation. Treadmill training (TT)
following SCI is thought to reduce these negative effects. Therefore, combining NPC transplantation and TT after SCI might improve
functional recovery.
Methods: 70 Wistar rats received cervical clip-compression SCI at C6 level. Animals were randomized into four treatment groups
(NPC + TT, NPC only, vehicle, sham). NPCs were injected into the spinal cord of immunosuppressed rats 10 days after SCI. Daily TT
and weekly neurobehavioral tests were performed until the animals were sacrificed for immunohistochemical analysis eight weeks
after SCI. Statistical analysis was performed (p < 0.05 was considered significant).
Results: Animals who received NPCs and TT showed significantly higher locomotor function compared to NPC only and vehicle
animals 8 weeks after injury in the BBB Score. Gridwalk testing revealed significantly better fine motor skills in the NPC + TT group.
Tactile sensitivity wasn’t pathologically altered as examined by the von Frey test. Histologically, NPC + TT treatment lead to significant
reduction of astrogliosis and cyst size compared to vehicle animals.
Conclusion: In our study, the combined NPC + TT treatment lead to significant better outcomes in the BBB score and Gridwalk test.
Astrogliosis and cyst sizes were significantly reduced when animals were treated with NPC + TT. Collectively, our data suggests that
TT may be a beneficial addition to NPC transplantation after SCI.
576. Decompressive craniectomy impairs glymphatic circulation: syndrome of the trephined
Benjamin A Plog, PhD (Rochester, NY); Nanhong Lou, MD; Clifford Pierre, MD; Alexander Cove, BS; H. Mark Kenney, BS; Emi Hitomi,
BS; Hongyi Kang, MS; Jeffrey Iliff, PhD; Douglas Zeppenfeld, BS; Maiken Nedergaard, MD, DMSc; G. Edward Vates, MD, PhD
Introduction: Elevated ICP is a major cause of death and disability after severe TBI, and treatment directed at ICP reduction can
reduce mortality. Refractory ICP elevation can be treated with decompressive craniectomy (DC) as a last-tier intervention, and recent
trials show DC is superior to non-surgical treatments in lowering ICP, but adverse events and poor long-term outcomes are common.
Hydrocephalus and syndrome of the trephined are common after TBI and DC, but the mechanisms by which DC leads to altered CSF
hydrodynamics or neurologic impairment remain unclear. The glymphatic system is a pathway of CSF and interstitial fluid (ISF)
circulation into, through, and out of the brain driven partly by penetrating artery pulsations within the closed cranial compartment. We
hypothesized DC would impair glymphatic circulation, resulting in gliosis and neurologic deterioration; cranioplasty might restore
glymphatic function, with neurologic benefit.
Methods: Using 2-photon in vivo microscopy, cortical vasculature was imaged through intact and thinned murine skull, and pulsatility
index of cortical arteries was quantified. Glymphatic influx was determined with ex vivo fluorescence microscopy of mice 14, 28 and
56 days following DC or cranioplasty; brain sections were immunohistochemically labeled for CD-68 and GFAP. Motor and cognitive
performance was determined with rotarod and novel object recognition tests at baseline and 14, 21 and 28 days following DC or
cranioplasty.
Results: Penetrating arterial pulsatility decreased significantly following DC, producing immediate and chronic impairment of
glymphatic CSF influx in ipsilateral and contralateral brain parenchyma. DC-related glymphatic dysfunction drove an astrocytic and
microglial inflammatory response, with the development of motor and cognitive deficits. Recovery of glymphatic flow preceded reduced
gliosis and return of normal neurologic function, and cranioplasty accelerated this recovery.
Conclusion: Glymphatic dysfunction leads to the development of CSF compartment complications and poor outcomes following
decompressive craniectomy in our murine model.
577. Automated eye tracking for detection of blast brain injury after a natural gas explosion
Abdullah Bin Zahid (Minneapolis, MN); Maxwell Thorpe, BA; Christina Smith; Caleb Hoover; Radhika Edpuganti; Shivani Venkatesh;
Dylan Sturtevant; Aliya Ahmadi; Olivia Newgaard; Uzma Samadani

Introduction: The purpose of this work is to describe the capacity for automated eye tracking performed while watching a short film
clip to detect blast brain injury due to a natural gas explosion.
Methods: This prospective observational study enrolled 36 subjects that were accidently exposed to a natural gas explosion at a
school and 306 normal healthy controls without a history of TBI. Primary outcome measure was automated eye tracking.
Results: Blast exposed subjects (N=36, mean age =35.6±17.5, 23 females) were compared using Wilcoxon signed-rank test to thirty-
six age and gender matched controls. Five eye tracking metrics were significantly different between all blast survivors and age and
gender matched controls selected from among the community controls. In order to create a Blast Impact Score (BIS), the subjects
inside the building [N=22; 17 females] were compared to controls with no prior history of TBI [N=306; 120 females]. BIS provided an
AUC of 0.835, sensitivity of 86.4% and specificity of 77.4% to discriminate between blast patients and controls. BIS also correlated
with distance from the epicenter of the blast (spearman correlation=0.731; p-value<0.001). Near point of convergence and binocular
amplitude of accommodation (clinical measures of oculomotor dysfunction) were not significantly different in blast exposed patients
versus their age and gender matched controls (p=0.582 and 0.859 respectively).
Conclusion: Our data supports the use of automated eye tracking for assessment of blast brain injury. This finding is particularly
relevant to military personnel who may be exposed to blast, which was previously dubbed an invisible injury. The ability to detect blast
brain injury using an automated non-invasive technique will enable early identification of afflicted subjects and protection from
repeated exposure as well as development of therapeutics.
578. Complications predicting perioperative mortality in patients undergoing craniotomy: an ACS-NSQIP analysis
Nicholas Goel (Philadelphia, PA); Arka Mallela, BS; Prateek Agarwal, BS; Kalil Abdullah, MD; Omar Choudhri, MD; David Kung, MD;
Timothy Lucas, MD, PhD; Han-Chiao Isaac Chen, MD
Introduction: While the risk factors associated with various postoperative complications have been closely studied in neurosurgery,
much less is known about the specific, independent influence that each of these complications has on mortality. Considering surgical
complications not only as quality improvement endpoints but also as factors influencing mortality may be key to ultimately improving
outcomes with respect to mortality. Here we investigate the link˗independent of patient and surgical risk factors˗between eleven
neurosurgical complications and 30-day mortality in 37,888 patients undergoing craniotomy.
Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried
for patients undergoing craniotomy for any indication from 2006 to 2015. Multivariate logistic regression was used to examine the
effect of complications on 30-day mortality independent of preoperative risk factors, independent of other postoperative complications,
and across patient cohorts stratified by risk according to the ACS-NSQIP Surgical Risk Calculator. Complications analyzed included
cardiac event, respiratory failure, renal failure, stroke, postoperative bleeding, pneumonia, sepsis, venous thromboembolism, urinary
tract infection, surgical site infection, and unplanned reoperation.
Results: Of eleven complications analyzed, the five complications most strongly associated with mortality independent of preoperative
risk were cardiac event (OR=24.47, 95% CI=17.90-33.45, P<0.001), respiratory failure (OR=6.51, 95% CI=5.57-7.60, P<0.001), renal
failure (OR=3.67, 95% CI=2.32-5.81, P<0.001), stroke (OR=6.71, 95% CI=5.24-8.58, P<0.001), and postoperative bleeding (OR=2.12,
95% CI=1.78-2.50, P<0.001). Additionally, these were the only complications associated with increased mortality independent of other
complications. Furthermore, these were the only complications linked to increased mortality across low, medium, and high-risk patient
groups.
Conclusions: Of eleven complications analyzed, only five were linked with mortality independent of preoperative risk, independent of
other complications, and across all risk-stratified patient cohorts. These findings may help identify those patients at greatest risk of
mortality in the perioperative period, and may thus be of value in postoperative patient care.
579. Quantitative and qualitative analysis of bone flap resorption in patients with cranioplasty after decompressive
craniectomy
Tommi Korhonen (Oulu Pohjois-Pohjanmaa, Finland); Niina Salokorpi, MD, PhD; Jaakko Niinimäki, MD, PhD; Willy Serlo, MD, PhD;
Petri Lehenkari, MD, PhD; Sami Tetri, MD, PhD
Introduction: Autologous cranioplasty after decompressive craniectomy entails a notable burden of difficult postoperative
complications such as infection and bone flap resorption leading to mechanical failure. The prevalence and significance of
asymptomatic bone flap resorption is currently unclear. The aim here was to radiologically monitor the long-term bone flap survival
and bone quality of autologous cranioplasty patients.
Methods: We identified all 45 patients who underwent autologous cranioplasty at Oulu University Hospital, Finland, between January
2004 and December 2014. Using perioperative and follow-up CT scans, the volumes and radiodensities of the intact bone flap prior to
surgery and at follow-up were calculated. Relative changes in bone volume and radiodensity were then determined in order to assess
cranioplasty survival.
Results: Sufficient CT scans were obtainable from 41 out of the 45 patients (91.1%). The 41 patients were followed for a median time
of 3.79 years (25th-75th percentiles:1.55-6.66). Thirty-seven of them (90.2%) had some degree of bone flap resorption and 13 (31.7%)
had a relative remaining bone flap volume of less than 80%. Patients aged under 30 years had a mean decrease of 15.8% in bone
flap volume compared to the rest of the cohort. Relative bone flap volume was not found to decrease linearly with the passing of time,
however. The effects of lifestyle factors and co-morbidities were non-significant.
Conclusion: Bone flap resorption turned out to be a very common phenomenon, occurring at least to some degree in 90% of our
patients. Decreases in bone volume were especially prominent in patients aged under 30 years. Since the progression of resorption
during the follow-up was non-linear, routine follow-up CT scans seem unnecessary in monitoring the progression of bone flap

resorption. Instead, clinical follow-up with mechanical stability assessment is advised. Partial resorption is likely a normal physiological
phenomenon during the bone revitalisation process.
580. CSF biomarkers correlate with results of neuropsychological testing in patients with chronic traumatic brain injury
Ross C. Puffer, MD (Rochester, MN); Ava Puccio; Milos Ikonomovic, MD; Sue Beers, PhD; Kathryn Edelman, MS; Steven Benso;
Yuefang Chang, PhD; Walter Schneider, PhD; James Mountz, MD; David Okonkwo, MD, PhD
Introduction: Traumatic brain injury has been associated with long-term accumulation of amyloid-B (AB) and phosphorylated tau (p-
tau) in brain tissue and subsequent clinical neurodegeneration. At present, a diagnosis of CTE can only be confirmed at autopsy. In
the current pilot study, we investigated a panel of CSF biomarkers in living chronic TBI subjects at risk for neurodegeneration.
Methods: Nineteen chronic TBI subjects (< 6 months from injury; 16 males, mean age 41yrs, 8 military veterans) who underwent
lumbar puncture as well as neuropsychological testing. CSF was analyzed for concentrations of total tau, phosphorylated tau (pTau
181), AB1-42 (AB42) and AB1-40 (AB40) by ELISA, and tau/AB42 ratio was calculated. Neuropsychological testing included
measures of memory, processing speed and executive function, including Automated Neuropsychological Assessment Metrics
(ANAM), California Verbal Learning Test-II (CVLT) Short and Long Delay Free Recall (SDFR, LDFR), Wechsler Adult Intelligence
Scale Working Memory Index (WAIS IV) and Trail Making Test Part A/B. Nonparametric correlation (Spearman rho, Ρ) was used to
relate CSF levels to neuropsychological data, controlling for age.
Results: AB40 concentration in CSF was inversely correlated with memory testing (CVLT SDFR and LDFR, Spearman Ρ <-0.51,
p<0.032; Ρ <-0.50, p<0.034, respectively). Analysis of pTau181 demonstrated an inverse correlation with memory testing as well
(ANAM running memory test, Spearman Ρ <-0.56, p<0.02). The Tau/AB1-42 ratio was inversely associated with executive function
testing (Trail Making Test Part B, Spearman Ρ <-0.49, p<0.047).
Conclusion: In this sample of chronic TBI subjects, measures of memory and executive function (CVLT, ANAM running memory and
Trails B) corresponded to biomarkers of tau and AB concentrations in CSF. These biomarkers may play a role in in vivo diagnosis of
TBI-associated neurodegeneration.
581. Effect of surgical treatment on isolated acute traumatic axis fractures in older US adults
Michael P. Catalino, MD, MS (Chapel Hill, NC); Virginia Pate, MS; Til Stürmer, MD, PhD; Deb Bhowmick, MD
Introduction: Traumatic axis fractures are common in older adults. Type II odontoid fractures make up the majority of these fractures,
for which surgery is often considered. However, surgeons are confounded in their decision-making due to high baseline mortality and
poor bone healing in this patient population, regardless of treatment. Our study estimates the effect of surgical treatment on isolated
acute traumatic axis fractures in older US adults.
Methods: We performed a propensity score weighted analysis of a 20% random sample of Medicare beneficiaries with isolated acute
traumatic axis fractures from 2007-2014. Patients were included if enrolled for 12 months without a preceding diagnosis of axis
fracture or concurrent diagnosis of severe brain injury. Diagnoses and treatment were identified using ICD-9 and CPT codes. We
compared surgical and non-surgical cohorts. The primary outcome was all-cause standardized mortality (SMR).
Results: There were 10,222 eligible beneficiaries with a coded axis fracture. After applying exclusion criteria 2,797 patients remained
in the cohort. In-hospital, 30-day, 180-day, and 1-year mortality for isolated axis fractures was 5.6, 12.6, 24.6, and 32.5, respectively,
per 100 beneficiaries. Mortality for surgical patients was 19.7 per 100 beneficiaries at 1 year. The SMR weighted non-surgical
mortality rate was significantly higher at 26.7. The standardized risk difference showed 7.0 fewer surgical deaths per 100 patients at 1
year (95% CI 1.3-12.7). Surgical patients 65-74 years old had the largest difference in mortality resulting in 11.2 fewer deaths per 100
at 1 year (1.1-21.3).
Conclusion: Current assessment of axis fracture outcomes shows a significant overall mortality rate in the Medicare population.
Surgery was associated with lower mortality when compared to non-surgical management. The likely benefit from surgery is most
pronounced in patients aged 65-74. In patients 75 years and older the effect of surgical intervention is less pronounced.
582. Treatment of traumatic brain injury with vepoloxamer (purified Poloxamer 188) improves functional recovery in rats
Asim Mahmood, MD, FAANS (Detroit, MI); Yanlu Zhang; Ye Xiong, MD, PhD; Michael Chopp, PhD
Introduction: Vepoloxamer is an amphipathic polymer that has shown potent cytoprotective and anti-inflammatory effects in both
preclinical and clinical studies. This study was designed to investigate the therapeutic effects of vepoloxamer on sensorimotor and
cognitive functional recovery in rats after traumatic brain injury (TBI).
Methods: Young adult male Wistar rats (n=16) were injured with controlled cortical impact and treated either with vepoloxamer (300
mg/kg) or saline (control) administered intravenously into tail veins 2 h post injury. A sham group (n=7) was neither injured nor treated.
Sensorimotor function was assessed using Neurological Severity Scores (NSS) and footfault tests, whereas spatial learning was
measured using Morris water maze (MWM) test. The animals were sacrificed 35 days after injury and their brains were processed for
analysis of lesion volume and neuroinflammation.
Results: Compared to the saline treatment, vepoloxamer significantly improved sensorimotor functional recovery (NSS and footfault
tests, p<005) and spatial learning (MWM, p<0.05). Vepoloxamer treatment reduced cortical lesion volume by 20%, and reduced
activation of microglia/macrophages and astrogliosis in many brain regions including injured cortex, corpus callosum and
hippocampus.

Conclusion: In summary, vepoloxamer treatment provides neuroprotection and anti-inflammation in rats after TBI and improves
functional outcome, indicating that vepoloxamer treatment may have potential therapeutic value for treatment of TBI.
583. Predictors of primary autograft cranioplasty survival and resorption after craniectomy
Tommi Korhonen (Oulu Pohjois-Pohjanmaa, Finland); Sami Tetri, MD, PhD; Jukka Huttunen, MD, PhD; Antti Lindgren, MD, PhD;
Jaakko Piitulainen, MD, PhD; Willy Serlo, MD, PhD; Pekka Vallittu; Jussi Posti, MD, PhD
Introduction: Craniectomy is a common neurosurgical procedure which reduces intracranial pressure, but survival necessitates
cranioplasty at a later stage, after recovery from the primary insult. Complications such as infection and resorption of the autologous
bone flap are common. The risk factors for complications and subsequent bone flap removal are unclear. The aim of this multicentre
retrospective study was to evaluate the factors affecting the outcome of primary autologous cranioplasty, with special emphasis on
bone flap resorption.
Methods: We identified all the patients who underwent primary autologous cranioplasty at three tertiary-level university hospitals
between 2002 and 2015. They were retrospectively followed up until bone flap removal, death or 31st December 2015. The three
academic hospitals are responsible for all major calvarial reconstructive surgery in their corresponding hospital districts.
Results: The cohort comprised 207 patients with a mean follow-up period of 3.7 years (standard deviation 2.7). The overall
complication rate was 39.6% (82/207), the bone flap removal rate was 19.3% (40/207), and 11 patients (5.3%) had died during the
follow-up period. Smoking (OR 3.23; 95% CI 1.50-6.95; p=0.003) and age of under 45 years (OR 2.29; 95% CI 1.07-4.89; p=0.032)
were found to independently predict subsequent autograft removal, while age of under 30 years was found to independently predict
clinically relevant bone flap resorption (OR 4.59; 95% CI 1.15-18.34; p=0.03). The time interval between craniectomy and cranioplasty
was not found to predict either bone flap removal or resorption.
Conclusion: In this large multicentre cohort of patients with autologous cranioplasty, smoking and younger age predicted
complications leading to bone flap removal. Very young age predicted bone flap resorption.
584. The rise of the Acinetobacter baumannii: A meta-analysis on role of intra-thecal anti-microbial therapy in reduction of
mortality
Nasser Mohammed (Shreveport, LA); Anil Nanda
Introduction: The neurosurgical infections due to multi-drug resistant organisms have become a nightmare that neurosurgeons are
facing in the 21st century.This is the dawn of the 'post-antibiotic" era.The present study evaluates the efficacy of combined intra-thecal
or intra-ventricular plus intravenous therapy versus only intravenous therapy in treating post-neurosurgical Acinetobacter baumannii
infections.
Methods: A meta analysis of all the peer reviewed studies in accordance to the PRISMA protocol was carried out. Five studies with a
total of 124 patients who had post neurosurgical A. baumannii infections were included.The risk of bias and test for heterogeneity was
performed. The odds ratio of mortality events were pooled together and analyzed.The patients were divided into two groups.The "IV"
group that received only intravenous therapy and the "IV+IT" group that received both intravenous and intra-ventricular or intra-thecal
antimicrobial therapy. The statistical analysis was done using the Cochrane collaboration tool using the Cochran-Mantel-Haenzel
method in a random effect model.
Results: The total number of patients in IV only group was 75 and the number of patients in IV+IT group was 53.The mean duration of
intravenous therapy was 27 days.The mean duration of intra-ventricular colistin was 21 days.The dose of intrventricular colistin ranged
from 125,000 IU to 250,000 IU per day.The overall calculated odds ratio for mortality for IV+IT group after pooling the data was
0.16(95% CI 0.06-0.40,p<0.0001). Th patients who received IV+IT therapy had an 84 percent less likely odds of dying due to the
infection as compared to those that received only IV therapy.
Conclusion: There is a substantial reduction in mortality in patients who receive a combination of intra-ventricular plus intravenous
antimicrobial therapy as compared to those who receive only intravenous therapy. Intra-thecal or intra-ventricular route should be
strongly considered when dealing with post -neurosurgical multi drug resistant Acenitobacter baumannii infections
585. Surgeon annual and cumulative volumes predict early postoperative outcomes after brain tumor resection
Byron Cone Pevehouse Young Neurosurgeons Award
Rohan Ramakrishna, MD (New York, NY); Rohan Ramakrishna; Wei Hsu; Jialin Mao; Art Sedrakyan
Introduction: Surgeon volume has been previously shown to impact patient outcomes across a variety of metrics. However, data
related to neuro-oncologic surgery is limited and does not include neurologic morbidities as an outcomes measure. In this study, we
aimed to determine if 5-year surgeon cumulative and annual volumes predict early postoperative outcomes in patients following brain
tumor surgery.
Methods: A population-based cohort of patients (n=10, 258) undergoing brain tumor resection as their principal procedure between
2005 and 2014 were included for study utilizing the New York Statewide Planning and Research Cooperation System (SPARCS).
Surgeons were categorized according to their cumulative and annual surgical volume. The primary outcome measurement included
morbidity and mortality following craniotomy from index hospitalization.

Results: Patients treated by high cumulative/high annual (HC/HA) volume surgeons had shorter length of stay (median 5 days vs 8
days vs 8 days vs 6 days respectively, p<0.01), lower charges (median 70,025 vs $77,043 vs $93,715 vs $77,018 respectively,
p<0.01) and less non-routine discharge (41% vs 48% vs 50.9% vs 43.9% respectively, p<0.01) compared with patients treated by
surgeons from the LC/LA, LC/HA, HC/LA groups. Similarly, HC/HA volume surgeons also had lower rate of hydrocephalus (9.9% vs
10.4% vs 13.7% respectively, p=0.02), medical complications (6.9% vs 11.2% vs 11.5% respectively, p<0.01), neurologic
complications (44.1% vs 46.8% vs 48.1% respectively, p=0.03), 30-day reoperation (5.1% vs 6.9% vs 7.1% respectively, p<0.01) and
30-day death (3.3% vs 5.4% vs 5.2%, p<0.01) compared with LC/LA and LC/HA volume surgeons. The differences were less strong
in adjusted analyses but still relevant.
Conclusion: We present evidence for improved postoperative outcomes when surgery is performed by high cumulative and high
annual volume surgeons. We also for the first time assess the spectrum of neurologic complications following craniotomy. This
suggests that sub specialization in surgical neurooncology should be considered.
586. Topical vancomycin reduces hospital costs associated with surgical-site infections in craniotomy
Arka N Mallela, MS (Philadelphia, PA); Kalil Abdullah, MD; Cameron Brandon, BS; Andrew Richardson, PhD; Timothy Lucas, MD,
PhD
Introduction: Prospective controlled studies have demonstrated that topical vancomycin applied to the subgaleal space is a safe and
effective measure to reduce surgical-site infections during craniotomy. Financial projections estimate significant cost savings to
hospital systems implementing the use of topical vancomycin, but direct and indirect costs have not been reported.
Methods: In a prospective cohort of 355 patients undergoing craniotomy, direct and indirect costs of surgical site infection were
collected for all surgical site infections. Direct and indirect expenses for costs related to surgical site infections were collected from
hospital strategic support and data analytics teams. Metrics included cost of hospital stay, diagnostic studies, surgical intervention,
medications and costs of vancomycin usage. These measured variables were then used to extrapolate to a cohort of 1000
craniotomies.
Results: The prospective cohort included 205 vancomycin-treated patients and 150 control patients who underwent craniotomy
without vancomycin use. Ten infections were observed: one in the vancomycin group (0.49%) and 9 in the control group (6%). Total
direct costs of surgical site infections were $22,026.19 ± 17,370.34 per case. There was wide variability in costs per patient, ranging
between $10,974.90 -$66,677.00. Mean cost per infected patient in the control group were higher than in the vancomycin group
($22,988 vs $13,367). Cost of vancomycin was negligible at $12 per patient. Extrapolated to 1000 craniotomies, routine use of
vancomycin reduces SSI-related costs by $1,302,094.
Conclusion: Surgical-site infection prophylaxis with topical subgaleal vancomycin is highly cost-effective. Topical vancomycin usage is
associated with significant reduction in infection-related costs to hospitals. This finding lends support for more detailed, randomized
controlled study of vancomycin in craniotomy.
587. Creation of academic neurosurgery leaders: characteristics and career outcomes of AANS/NREF Research Award
recipients
Analiz Rodriguez, MD, PhD (Little Rock, AR); Taylor Wilson, MD, MS; Ka Hin Wong, BS; Rebekah Langston, BS
Introduction: The AANS Neurosurgery Research Education Foundation (NREF) provides ongoing competitive research fellowships
for residents and young investigators. We sought to determine the characteristics and career track of award recipients.
Methods: We analyzed characteristics and academic productivity of NREF awardees from 1983 to 2017. Data was extracted from the
NREF database and online resources.
Results: 224 research grants were awarded to 31 women (14%) and 193 men (86%) from 1983-2017. Neuro-oncology (36%) was the
most common research category. 60% of awardees had completed training and most resident award winners were PGY-5’s (37%).
49% of all awardees had an additional postgraduate degree (PhD: 39%; Master’s: 10%) with a significantly higher number of PhDs
being from Canada in comparison to any other region (p=0.024). The Northeast and southeast were the regions with the greatest and
lowest numbers of award recipients, respectively. More than a third (40%) of awardees came from institutions that have a NINDS/R25
program for neurosurgeons, and these awardees were significantly less likely to pursue academics than other awardees (59.6%
versus 78.9%;p=0.002), but were significantly more likely to go on to receive NIH funding (40.4% versus 26.1%; p=0.024). The
majority of recipients (65%) pursued fellowship training with a significant likelihood that fellowship category correlated with NREF
research category (p<0.001). 79% of winners remained in academic neurosurgery practice with 18% obtaining the position of chair.
Median h-index was 11. NIH funding was obtained by 71 awardees (32%) with 36 (18%) being a principal investigator on a RO1.
Conclusion: The majority of AANS/NREF research award recipients enter academics as fellowship trained neurosurgeons with
approximately one-third obtaining NIH funding. Analysis of this unique cohort allows for identifying characteristics of academic
success. The AANS/NREF award is a proven nidus in producing academic neurosurgery leaders.
588. A prospective multicenter study evaluating the time burden of neurothrombectomy call on physicians
Michelle Marie Williams, MD (Winston Salem, NC); Taylor Wilson, MD; Jasmeet Singh, MD; Stacey Wolfe, MD; Kyle Fargen, MD,
MPH
Introduction: We recently published multicenter retrospective data describing the incidence of mechanical thrombectomy procedures

among stroke centers and the times at which these procedures occur. There is no published prospective data reporting the time
burden of neurovascular thrombectomy call on physicians.
Methods: Neurointerventional physicians at 10 participating stroke centers prospectively recorded time requirements for all
thrombectomy consultations over 30 consecutive 24-hour call periods, including both false positive consultations and mechanical
thrombectomy procedures. Start time was defined as time of initial contact. End time was defined as the time when all patient care
requirements for that patient were completed.
Results: Data was collected from a total of 300 days of call. A total of 243 neurothrombectomy consultations (mean 0.81 per day),
including 143 false positive consultations (0.48 per day) and 100 thrombectomies (0.33 per day), were performed at the 10 centers.
There was no significant difference in incidence based on day of the week. Most (70%) of all consultations occurred between the
hours of 5 pm and 7 am. 26% percent of thrombectomy procedures resulted in delays in scheduled cases; physicians had to come in
from home for 52% of these cases. The average amount of time spent on each false positive consultation and thrombectomy was 48
and 224 minutes, respectively. Overall, the average physician time burden per 24 hr call period was 89 minutes.
Conclusion: Neurothrombectomy consultations are frequent and most often occur during non-work hours. Thrombectomy procedures
disrupt elective schedules one-quarter of the time and require physicians to commute in from home the majority of the time. The time
burden associated with call is significant and should therefore be compensated appropriately.
589. Aneurysms in autosomal dominant polycystic kidney disease; high rates of de novo formation and screening failures
D. Andrew Wilkinson, MD (Ann Arbor, MI); Neeraj Chaudhary, MD; Joseph Gemmete, MD; B. Thompson, MD; Aditya Pandey, MD
Introduction: The goal of this study was to study the outcomes of aneurysms in autosomal dominant polycystic kidney disease
(ADPKD) and assess the efficacy of aneurysm screening strategies given conflicting guidelines among neurosurgeons and
nephrologists.
Methods: We performed a retrospective review of ADPKD patients at our tertiary care center, assessing outcomes and screening
effectivness. Forty-five patients with ADPKD harboring 71 intracranial aneurysms were identified, including 11 patients presenting with
subarachnoid hemorrhage.
Results: Thirty-five aneurysms were treated with open surgery, 14 aneurysms were treated endovascularly, and 22 aneurysms were
managed with observation. The average size of ruptured, electively treated, and observed aneurysms were 7.4, 5.2, and 3.3mm
respectively (p=0.001). Among treated aneurysms, procedural complication rates were similar between treatment groups; 9% (n=3)
with open surgery vs. 14% (n=2) with endovascular management, p=0.36). The symptomatic procedural complication rate was low
(n=2, 4.1% of all treated aneurysms) and symptomatic complications occurred only with ruptured presentation. Seven patients
presented with rupture in the setting of previously known ADPKD, including two patients presenting with rupture after previous
negative screening MRAs and five who had not been screened. Among those with previously known aneurysms, high rates of de novo
aneurysm formation were noted in follow-on surveillance; 3 aneurysms in 126 years of radiographic follow up for all patients with prior
unruptured intracranial aneurysm, (calculated incidence 2.4% per year, 95% CI 0.6-6.5%), and 5 aneurysms in 48 years of
radiographic follow up in patients with prior rupture (calculated incidence 10.3% per year, 95% CI 3.4-24.3%).
Conclusion: Elective treatment of aneurysms in ADPKD patients can be accomplished with excellent neurologic and renal outcomes
regardless of treatment modality. Current screening practices of ADPKD patients failed to prevent a significant number of ruptures,
and more research on screening effectiveness is needed.
590. Assessing the promise of endoscopic pituitary surgery—A matched analysis of clinical and socioeconomic outcomes
Tej Azad (Floyds Knobs, IN); Yu-Jin Lee; Daniel Vail; Anand Veeravagu; Peter Hwang; John Ratliff; Gordon Li
Introduction: Direct comparisons of microscopic and endoscopic resection of sellar lesions are scarce, with conflicting reports of both
cost and clinical outcome advantages. We sought to determine if the proposed benefits of endoscopic resection have been realized on
a population-level.
Methods: We performed a matched cohort study of 9,670 adult patients in the MarketScan database who underwent either
endoscopic or microscopic surgery for sellar lesions. Coarsened matching was applied to estimate the effects of surgical approach on
complication rates, length of stay (LOS), costs, and likelihood of postoperative radiation.
Results: We found that LOS, readmission, and revision rates did not differ significantly between approaches. The overall complication
rate was higher for endoscopy (47% compared to 39%, OR 1.37, 95% CI 1.22-1.53). Endoscopic approach was associated with
greater risk of neurological complications (OR 1.32, 95% CI 1.11-1.55), diabetes insipidus (OR 1.65,
95% CI 1.37-2.00), and CSF rhinorrhea (OR 1.83, 95% CI 1.07-3.13) compared to the microscopic approach. Although the total index
payment was higher for patients receiving endoscopic resection ($32,959 compared to $29,977 for microscopic resection), there was
no difference in long term payments. Endoscopic surgery was associated with decreased likelihood of receiving post-resection
stereotactic radiosurgery (OR 0.67, 95% CI 0.49-0.90) and intensity-modulated radiation therapy (OR 0.78, 95% CI 0.65-0.93).
Conclusion: Our results suggest that the transition from a microscopic to endoscopic approach to sellar lesions must be subject to
careful evaluation. While there are evident advantages to transsphenoidal endoscopy, our analysis suggests that the benefits of the
endoscopic approach have yet to materialize
591. Coding discrepancies between surgeons and employed coders
Nikhil Sharma (Bryn Mawr, PA); Nathan Beatson; Nikhil Sharma; Melanie Peoples; Beth Shaddock; Rebecca Carpenter; Francis
Savarese; Michael Gagliardi; M Sean Grady; Neil Malhotra

Introduction: Surgeon providers and billing technicians use Current Procedural Terminology (CTP) codes to specify what treatment a
patient received and associated charges. Ideally, there is parity between CPT code sets for each patient. In the present study, coding
discrepancies between surgeons and employed coders were investigated.
Methods: At a large urban academic medical center, 500 patients over 3 months were retrospectively analyzed for coding
discrepancies. Differences comprised of four categories: 1) addition of a distinct code 2) an additional repeat code (i.e. multiple spinal
level), 3) deletion of a distinct code or 4) deletion of a repeat code. To quantify the impact of change, codes with the most
accumulated discrepancies were studied and change to annual relative value unit (RVU) calculated.
Results: Final submission of codes to billing demonstrated a 161% increase in total codes vs original surgeon derived codes (1,594
vs 987 CPT codes). There were 2.21 (869 total, 68%) distinct CPT code additions and 0.37 additional repeats (74 total, 5.8%) of CPT
codes per patient. There was a 22.49% deletion rate of provider CPT codes (222 total, 17.4%) and a 11.44% deletion rate of repeat
CPT codes(113 total, 8.8%), by the billing technician. The most common source of change between the surgeon and coder was the
addition of distinct codes by the billing technician (270 patients, 54.51% of total code changes). CPT code 63047 (lumbar
laminectomy) had the highest estimated annual RVU change with an increase of 21,988 RVU’s per annum (estimated). The overall
net change in total RVU’s was 6063.45 RVU’s per annum when compared to the surgeons initial codes.
Conclusion: These results raise concerns over the coding discrepancies. Future investigation will evaluate the communication
between surgeons and billing technicians and assess the financial impact of these differences, both at the provider and patient level.
592. Cost savings associated with the introduction of a standardized perioperative protocol for endoscopic trans-sphenoidal
pituitary surgery: a cost-benefit analysis
Saniya Siraj Godil, MD (Nashville, TN); Sheena Weaver, MD; Kyle Weaver, MD; Lola Chambless, MD
Introduction: In this era of healthcare reforms, interventions that not only improve quality, but also decrease cost, are considered of
highest value. Mean length of hospital stay (LOS) reported nationally after trans-sphenoidal surgery (TSS) is 4.5 days, including at
least one night in the ICU, and monitoring for postoperative diabetes insipidus (DI). We introduced a standardized, multi-disciplinary
protocol for perioperative management of this population with the goal of safely reducing length of stay (LOS), as well as health-care
resource utilization and cost of care.
Methods: All patients <17years old undergoing endoscopic TSS for pituitary adenoma were prospectively enrolled 18 months pre- and
post-rollout of the protocol. The protocol included: a standardized perioperative management guideline; large-scale nursing education;
admission to a neurological floor postoperatively rather than ICU; laboratory evaluation for DI was only performed if urine output was
<250ml/hr for 4 hrs; and expected discharge goal was set as POD1. Perioperative outcomes, LOS, and direct costs were compared
pre- and post-rollout.
Results: A total of 251 patients were included (134 pre-;117 post-rollout). There was a significant reduction in ICU admission post-
rollout (100% vs 12.8%,p<0.001). There was also a significant reduction in ICU LOS (2.8 vs 0.7 days;p<0.001), hospital LOS(2.8 vs
1.8 days;p=0.01) and number of labs drawn for DI evaluation post-rollout(9.2 vs 4.8,p=0.02). The overall reduction in variable direct
costs was $2,712/case ($9,266 pre- vs $6,554 post-rollout/case). Given approximately 80 cases are performed annually, this can lead
to saving upwards of 160 ICU days, 80 hospital days, 352 lab tests, and < $250,000 annually.
Conclusion: An introduction of a standardized, multi-disciplinary, perioperative care protocol for TSS patients can lead to significant
reduction in ICU and hospital LOS, without compromising patient safety. This can result in annual reduction in health-care resource
utilization (ICU days, hospital days, labs drawn) and cost savings of < $250,000 annually.
593. Cost-utility analysis of cervical deformity surgeries using one-year outcomes
Peter Gust Passias (Brooklyn Heights NY); Gregory Poorman, BA; Rabia Qureshi, MD; Hamid Hassanzadeh, MD; Samantha Horn, BA;
Frank Segreto BS; Cole Bortz, BA; Muhammad Janjua, MD; Christopher Ames, MD; Justin Smith, MD; Virginie Lafage, PhD
Introduction: Cost-utility analysis, a special case of cost-effectiveness analysis, estimates the ratio between the cost of an
intervention to the benefit it produces in number of quality-adjusted life years. Cervical deformity correction has not been evaluated in
terms of cost-utility and in the context of value-based health care.
Methods: Retrospective review of a prospective cervical deformity database. Patients with 1-year follow-up after surgical correction for
cervical deformity were included. Cervical deformity was defined as: kyphosis (C2-7 Cobb-angle <10°), cervical-scoliosis (coronal-
Cobb-angle <10°), positive-cervical-sagittal-malalignment (C2-C7 sagittal-vertical-axis <4cm or T1-C6 <10 o), or horizontal-gaze-
impairment (chin-brow-vertical-angle <25o). Quality-adjusted-life-years were calculated by both EuroQol-5D (EQ5D) quality-of-life and
NDI mapped to SF6D index. Costs were assigned using Medicare 1-year average reimbursement for: 9+ level posterior fusions (PF),
4-8 level PF, 4-8 level PF with anterior fusion (AF), 2-3 level PF with AF, 4-8 level AF, and 4-8 level posterior refusion. Reoperations
and deaths were added to cost and subtracted from utility respectively. QALY-per-dollar spent was calculated using standardized
methodology at 1-year and subsequent time-points relying on maintenance of 1-year utility.
Results: 84 postoperative patients were isolated (age: 61.2 years, 60% female, BMI: 30.1, average-levels-fused: 7.2, osteotomy used:
50%). Costs associated with index procedures were: 9+ level PF ($76,617), 4-8 level PF ($40,596), 4-8 level PF with AF ($67,098), 4-
8 level AF ($31,392) and 4-8 level posterior refusion ($35,371). Average 1-year reimbursement of surgery was $55,097 at 1-year (8
revisions and 3 deaths accounted for). Cost-per-QALY gained to 1-year follow-up was $646,958 by eq5d and $477,316 by NDI SF6D.
If 1-year benefit is sustained, upper threshold of cost-effectiveness is reached 3-4.5 years after intervention.
Conclusion: Medicare 1-year average reimbursement compared to 1-year quality-adjusted-life-year described $646,958 by eq5d and
$477,316 by NDI SF6D. Cervical deformity surgeries reach cost-effectiveness thresholds when benefit is sustained 3-4.5 years.

594. Neurosurgery medical profession liability claims in the United States
Aladine Abdalla Elsamadicy, B.E. (Durham, NC); Amanda Sergesketter, BS; Michael Frakes; Shivanand Lad, MD, PhD
Introduction: Due to disparaging costs and rates of malpractice claims in neurosurgery, there has been significant interest in
identifying high-risk specialties, types of malpractice claims, and characteristics of claim-prone physicians. The aim of this study was
to characterize the malpractice claims against neurosurgeons.
Methods: This was a comprehensive analysis of all malpractice liability claims involving a neurosurgeon as the primary defendant was
conducted using the Physician Insurers Association of America Data Sharing Project from January 1, 2003 and December 31, 2012.
We characterized three aspects of malpractice risk amongst neurosurgeons: the overall landscape of neurosurgical malpractice claims
and cost burden of paid-claims in a 10-year perspective, trend of physician characteristics with the highest MPL claims, and the
characteristics of the chief medical factors, presenting medical conditions, and operative procedures performed in neurosurgery
malpractice claims.
Results: From 2003-2012, 2,131 closed malpractice claims were filed against a neurosurgeon. The total amount of indemnity paid
collective between1998-2002, 2003-2007, and 2008-2012 was $109,614,935, $140,031,875, and $122,577,230, respectively. Of all
the neurosurgery claims, the most prevalent: chief medical factor was improper performance [42.1%, $124,943,933], presenting
medical condition was intervertebral disc disorder [20.6%, $54,223,206], and operative procedur performed involved the spinal cord
and/or spinal canal [21.0%, $62,614,995]. 85 (22.91%) of all neurosurgery claims resulted in patient death, resulting $32,067,759 paid.
Improper performance of the actual procedure was the most prevalent and highest total paid cause for patient death ($9,584,519).
Conclusion: From 2003 to 2012, we found that neurosurgery malpractice claims rank among one of the most costly and prevalent,
with the average indemnities paid annually and the overall economic burden increasing. Diagnoses and procedures involving the
spine, along with improper performance, were the most prevalent malpractice claims against neurosurgeons. Continued medical
malpractice reform is essential to correct the overall healthcare cost burdens.
595. Seizure outcomes and cognitive deficits following laser interstitial thermal ablation in mesial temporal epilepsy patients
Cristian Donos (Houston, TX); Patrick Rollo; Jessica Johnson; Joshua Breier; Nitin Tandon
Introduction: Laser interstitial thermal ablation (LITT) is a minimally invasive surgical procedure that recently became an alternative to
classical antero-mesial temporal resections in patients with mesial temporal lobe epilepsy (MTLE).
Methods: Seizure and cognitive outcomes in 43 consecutive laser ablations of amygdala and hippocampus for treatment of MTLE
were characterized in detail. Both patients with and without mesial temporal sclerosis (the latter undergoing SEEG to localize onsets)
were considered. Cortical and subcortical segmentation (FreeSurfer) of the brain were used to quantify the exact percentages of the
amygdala, hippocampus, and entorhinal cortex that were ablated. Pre and post-surgical neuropsychological assessments using 7 well-
known test batteries for intelligence, memory and language performance were compiled. Kaplan-Meier models of Engel I surgical
outcomes over time, were made. Linear regressions to evaluate the relationship between ablation volumes, pre-surgical volumes of
amygdala and hippocampus and the change in cognitive function were made.
Results: Engel I outcome was obtained in 79.5% of patients at 6 months follow-up, and 67.4% of patients at last follow-up (20.3
months). A median of 72.7% of amygdala and 70.7% of hippocampus was ablated. The Kaplan-Meier estimator revealed a 97% Engel
I surgical outcome at 6 months, and 76% at 24 months. Engel scores were not correlated with ablation volumes (ANOVA, p<0.05).
Neuropsychological subtests from the WASI, CLVT-II and WMS-III showed that changes in the post-ablation scores were correlated to
either percentage of ablation of hippocampus and/or entorhinal cortex, the pre-ablation hippocampal volume, and the pre-ablation
neuropsychological scores.
Conclusion: As compared with traditional amygdalohippocampectomy, LITT did not result in significant decline in naming or other
language function. Neuropsychological scores showed that the decrease in performance was a function of the volumes ablated and
also that patients with the best performance pre-op had the greatest probability of decline.
596. Early VTE chemoprophylaxis in TBI patients is safe and effective
David Heegwang Shin, MD (Gainesville, FL); Gregory Murad, MD; Juan Santiago; Sarah Gul; Paul Kubilis
Introduction: There remains considerable controversy regarding the timing of initiation of venous thromboembolism (VTE)
chemoprophylaxis in the traumatic brain injury (TBI) population. Current guidelines from the Brain Trauma Foundation provide a level
III recommendation stating that chemoprophylaxis may be used but there is an increased risk of expanding intracranial hemorrhage.
The purpose of this project was to demonstrate early DVT chemoprophylaxis in TBI patients does not increase the rate of intracranial
expansion while also reducing the rates of VTE.
Methods: We performed an IRB approved retrospective chart review of the UF Trauma Database from 2005-2015 and identified every
patient with an abnormal head CT. We calculated time to administration of chemoprophylaxis and separated patients into early (< 12
hours) and late (< 12 hours) administration of chemoprophylaxis. Primary outcomes included rates of DVT/PE and radiographic
worsening. Odds ratios were calculated using logarithmic regression analysis.
Results: 521 patients were identified and 25 total DVT/PE events were recorded. There were 390 patients in the early administration
group and 131 patients in the late administration group. The odds ratio for developing a DVT/PE in the late administration group was
2.789 with a 95% CI of 1.195-6.507 (p = 0.0177). There was no difference in the rate of radiographic worsening between the two
groups (CI 0.438-1.660).

Conclusion: Early VTE prophylaxis does not result in an expansion of intracranial hemorrhage due to TBI while also significantly
reducing the rate of DVT/PE in this patient population.
600. Subarachnoid hemorrhage phosphorylates neuronal nitric oxide synthase at Ser1412 in the dentate gyrus of the rat
brain
Kentaro Wada; Koji Osuka (Nagoya City, Japan); Yoshio Araki; Sho Okamoto; Toshihiko Wakabayashi
Introduction: We previously demonstrated that cyclic AMP-dependent protein kinase (PKA) phosphorylates neuronal nitric oxide
synthase (nNOS) at Ser1412 in the hippocampal dentate gyrus after forebrain ischemia; this phosphorylation activates NOS activity
and might contribute to depression after cerebral ischemia. In this study, we revealed chronological and topographical changes in the
phosphorylation of nNOS at Ser1412 immediately after subarachnoid hemorrhage (SAH).
Methods: In a rat single-hemorrhage model of SAH, the hippocampus and adjacent cortex were collected up to 24 h after SAH.
Samples from rats that were not injected with autologous blood were used as controls. NOS was partially purified from crude samples
via an ADP-agarose gel. nNOS, phosphorylated (p)-nNOS at Ser1412, PKA, and p-PKA at Thr197 were studied in the rat
hippocampus and cortex using Western blot analyses and immunohistochemistry.
Results: The Western blot analysis revealed that the expression of p-nNOS at Ser197 significantly increased between 1 and 3 h after
SAH in the hippocampus but not in the cortex. The immunohistochemistry revealed that the phosphorylation of nNOS at Ser1412 and
PKA at Thr197 occurred in the dentate gyrus but not in the CA1 area 1 h after SAH. An injection of saline instead of blood also
significantly induced the expression of p-nNOS at Ser197 in the hippocampus 1 h after the injection.
Conclusion: Our data suggest that an immediate increase in the intracranial pressure (ICP) might induce transient cerebral ischemia
and promote the phosphorylation of nNOS at Ser1412 through PKA in the dentate gyrus. This signal transduction induces the
excessive production of NO and might be involved in cognitive dysfunction after SAH.
601. Outcomes and management of intracranial hemorrhage (ICH) in patients with ventricular assist devices (VAD)
Louise Eisenhardt Travel Scholarship
Grace Yee Yan Lai, MD (Chicago, IL); Kartik Kesavabhotla, MD; Matthew Potts, MD; Babak Jahromi, MD, PhD
Introduction: As ventricular assist devices become increasingly used as both destination therapy and bridge to transplant for heart
failure patients, neurosurgeons are managing more VAD patients with ICH. This study reviews management and outcomes of patients
with VADs who present with ICH.
Methods: This retrospective cohort study assessed outcomes of patients who underwent VAD placement at a single institution
between 2007-2016 and had imaging demonstrating intracranial hemorrhage (SAH, SDH, IPH) compared to those who did not. We
report medical and surgical management and outcomes.
Results: 383 patients had a VAD placed during the study period. Of these patients, 20 (5.2%) had IPH, 8 (2.0%) SDH, and 10 (2.6%)
SAH. All IPH and SDH patients received reversal of their anti-coagulation. No SAH patients had reversal and no SAH patients had
significant progression of ICH. No patients had pump thrombus as a complication of reversal of anti-coagulation. Of patients with IPH,
6 (30%) underwent surgical intervention (4 EVDs, 2 hemicraniectomies), of which only 1 survived < 30 days and was discharged
home. In total, 6 (30%) patients with IPH survived < 30 days (5 discharged home/AIR, 1 discharged to LTAC). Of patients with SDH, 5
(62%) underwent surgery (1 burr holes, 4 craniectomies), of which 4 patients survived < 30 days and were discharged home/AIR. In
total, 7 patients (88%) with SDH survived < 30 days. No patients with SAH required surgical intervention. 8 patients (80%) survived <
90 days and were discharged home, 2 patients passed away from medical problems not related to SAH.
Conclusion: Patients with VADs who suffer IPH had poor outcomes regardless of surgical intervention. Patients with SDH who
underwent surgical intervention had good outcomes. Patients with SAH had good outcomes and did not demonstrate significant
progression of ICH without reversal of anti-coagulation.
602. Effect of treatment period on outcomes after stereotactic radiosurgery for brain arteriovenous malformations: an
international multicenter study
Jason P. Sheehan, MD, PhD, FAANS (Charlottesville, VA); Rao Patibandla; Dale Ding; Hideyuki Kano; Robert Starke; Gene Barnett;
Douglas Kondziolka; Caleb Feliciano; Inga Grills; John Lee; David Mathieu; Rafael Mercado
Introduction: The role of and technique for stereotactic radiosurgery (SRS) in the management of AVMs have evolved over the past
four decades. The aim of this multicenter study is to compare the SRS outcomes of AVMs treated during different time periods.
Methods: We selected AVM patients who underwent single-session SRS at eight different centers from 1988-2014. SRS eras were
categorized as early (1988-2000) or modern (2001-2014). Statistical analyses were performed to compare the baseline characteristics
and outcomes of the early versus modern SRS eras. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage,
and no permanently symptomatic radiation-induced changes (RIC).
Results: The cohort was comprised of 2,248 AVM patients-- 1,584 in the early and 664 in the modern SRS eras. AVMs in the early
SRS era were significantly smaller (p<0.001 for maximum diameter and volume); they were treated with a significantly higher
radiosurgical margin dose (p<0.001). The obliteration rate was significantly higher in early SRS era (65% vs. 51%; p<0.001), and
earlier SRS treatment period was an independent predictor of obliteration in multivariate analysis (p<0.001). The rates of post-SRS
hemorrhage and radiologic, symptomatic, and permanent RIC were not significantly different between the two groups. Favorable

outcome was achieved in a significantly higher proportion of patients in the early SRS era (61% vs. 45%; p<0.001), but earlier SRS
era was not significant in multivariate analysis (p=0.470) with favorable outcome.
Conclusion: Despite advances in SRS technology, refinement of AVM selection, and contemporary multimodality AVM treatment, we
failed to observe substantial improvements in the SRS favorable outcomes or obliteration for AVM patients over time. Differences in
baseline AVM characteristics and SRS parameters may partially account for the significantly lower obliteration rates in the modern
SRS era. However, improvements in patient selection and dose planning are necessary to optimize contemporary SRS for AVMs.
603. Reduction in radiation and contrast dose using time-resolved MRA prior to angiography for diagnosis of spinal dural
arteriovenous fistulae
Alex M. Witek, MD (Cleveland, OH); Julian Hardman, MD; Nina Moore, MD; Jenny Tsai; Thomas Masaryk, MD; Mark Bain, MD
Introduction: Diagnosis of spinal dural arteriovenous fistulae (dAVF) can be a labor-intensive process that may expose patients to
high doses of contrast and radiation. We sought to determine whether obtaining contrast-enhanced time-resolved magnetic resonance
angiography (trMRA) beforehand can decrease the radiation dose, contrast dose, and procedural time for spinal angiography.
Methods: The neuro-angiography and operative logs at our institution were reviewed to identify patients who underwent treatment for
dAVF from 2009-2017. Their medical records and radiological studies were reviewed to extract demographic, clinical, and radiological
data. Patients were divided into two groups based on whether they underwent MRA prior to angiography. Between-group comparison
of continuous variables was made with the Mann-Whitney U-test.
Results: Thirty-eight patients were diagnosed with spinal dAVF by angiography. The mean age was 64 ± 9 years, mean body weight
was 90 ± 21 kg, and 28 patients (74%) were male. All patients presented with myelopathy and had magnetic resonance imaging (MRI)
findings of spinal cord edema and/or serpiginous flow voids. Eight patients underwent trMRA prior to angiography, and 30 did not. All
eight trMRA studies demonstrated arteriovenous shunting (sensitivity = 100%), and six positively identified the level of the fistula
(sensitivity = 75%). The MRA group received lower doses of radiation (air kerma 2457 vs. 4749 mGy, p=0.03) and contrast (140 vs.
291 mL, p=0.003). The difference in procedural time was not significant (77 vs. 87 minutes, p=0.47). All patients subsequently
underwent dAVF treatment - 37 via surgical ligation, and one by embolization.
Conclusion: Performing trMRA prior to spinal angiography for the diagnosis of dAVF is associated with lower doses of radiation and
contrast. Use of MRA should be considered prior to angiography in patients with suspected spinal dAVF.
604. Genome wide analysis of penumbral infarction in ischemic stroke
Robert Rudy (Boston, MA); Nareerat Charoenvimolphan, BA; Baogang Qian, MD; Annerose Berndt, PhD; Robert Friedlander, MD;
Beverly Paigen, PhD; Scott Weiss, MD; Rose Du, MD, PhD
Introduction: Immediately following large cerebral artery occlusion, an area of at-risk tissue, the penumbra, persists for a variable
time around the core infarct. We investigated genetic determinants of the degree of penumbral infarction in mice using a genome-wide
approach.
Methods: 453 mice from 33 different strains underwent permanent middle cerebral artery occlusion. 218 mice were sacrificed at 6
hours and the remaining 235 at 24 hours. The efficient mixed-model association method was used for the genome-wide analysis to
account for the population structure in the inbred mouse strains. The outcome measure was infarct volume at 6 hours normalized by
the mean infarct volume at 24 hours for each strain. STRING was used to query genes containing significant single nucleotide
polymorphisms to identify enriched pathways.
Results: Mean infarct volumes were larger at 24 vs 6 hours (P = 4.4x10-9) and the infarct volume at 6 hours was correlated with that
at 24 hours (P = 1.4x10-10). Infarct ratio varied significantly amongst mouse strains on univariate linear regression (F = 2.32, P <
0.001). Genome-wide analysis identified 386 significant single nucleotide polymorphisms, encompassing 100 unique protein coding
genes. The largest protein network included PARD3, a cell polarity regulator concentrated in the mouse blood brain barrier; EFNA1, a
ligand for ephrin receptors including the EphA2 receptor that increases severity of brain injury after stroke; ARHGAP26, a GTPase
activating protein; IRS-2, an insulin receptor associated with increased BDNF signaling; ELMO2, a modulator of Rac1; and a Rho
GTPase cDNA.
Conclusion: Single nucleotide polymorphisms in PARD3, EFNA1, ARHGAP26, ELMO2, IRS-2, and a Rho cDNA were associated
with mouse penumbral tissue infarction. These proteins interact in an Ephrin receptor pathway that has been shown to regulate the
blood brain barrier and increase the severity of brain injury after stroke.
605. Study of Thymosin alpha 1 and its effect in postoperative ICH patients
AANS International Travel Scholarship
Rajendra Shrestha, MBBS PhD (Arghakhanchi, Nepal); Chao You, MD, PhD
Introduction: Thymosin alpha1 (Tα1) is considered as a promising immunomodulatory drug.Here our study is to evaluate the potential
safety and efficacy of Tα1 for patients with ICH and its outcome.
Methods: Eighty two spontaneous ICH patients admitted in the West China Hospital Neurointensive care unit (NICU) during March
2014 to Feb 2015 were enrolled as prospective randomized study. They were randomly divided into treatment group (52 cases) and
control group (30 cases). The control group were given regular conventional treatment.The treatment group received conventional

treatment plus immunomodulation therapy including Tα1 (1.6 mg subcutaneous twice a week till three weeks).They were assessed
and managed with Tα1 by measuring peripheral blood, CD4+, CD8+ lymphocyte subsets, total count and lymphocytes count at
hospital admission (t0), 5 days (t1), and 10 days or later (t2). The relationships of immunological and Thymosin alpha1 to clinical
outcome were evaluated.
Results: Two groups were matched each other’s. The treatment group showed significant improvements with increased CD4+ CD8+
lymphocyte subsets and total count after initiation of treatment. The outcome was evaluated with modified Rankin score and found that
Thymosin group 35 (67.3%) had better outcome than control group 12 (40%).In addition, pro inflammatory mediators IL-2R also
significantly changes with treatment group than control group.
Conclusion: Ta1 appeared to increase levels of IL-2R and T lymphocytes subset in a group of patients with ICH, and assisted to
lower the possibility of postoperative nosocomial pneumonia. Ta1 has been sound tolerated by ICH patients and has no any significant
side effects.
606. Comparison of three-dimensional intraoperative digital subtraction angiography with intraoperative indocyanine green
video angiography during intracranial aneurysm surgery
Javier Fandino, MD, IFAANS (Aarau, Switzerland); Itai Mendelowitsch, MD; Basil Grüter, MD; Michael Diepers, MD; Luca Remonda,
MD; Serge Marbacher, MD, PhD
Introduction: During the last decade, improvements in real-time high-resolution of surgically exposed cerebral vasculature were
realized with the successful introduction of intraoperative indocyanine green video angiography (ICGA) and technical advances in
intraoperative digital subtraction angiography (DSA). With the availability of intraoperative three-dimensional DSA (3D-iDSA) in hybrid
operating rooms, our study offers a contemporary comparison for rates of accuracy and discordance.
Methods: In our retrospective analysis of prospectively collected data, 140 consecutive patients underwent microsurgical treatment of
intracranial aneurysms (IA) in a hybrid operating room. Variables analyzed included patient demographics, aneurysm-specific
characteristics, intraoperative ICGA and 3D-iDSA findings, and need for intraoperative clip readjustment. We defined the discordance
rate of the two modalities as a false-negative finding that necessitated clip repositioning after 3D-iDSA.
Results: In 120 patients, ICGA and 3D-iDSA were used to evaluate 134 IA obliterations. Of 215 clips used, 29 (14%) were
repositioned intraoperatively, improving the surgical result in all 29 (24%) patients. Repositioning was prompted by visual inspection
and microvascular Doppler sonography in 8 (28%), ICGA in 13 (45%), and 3D-iDSA in 7 (24%). Clip repositioning was needed in
seven patients (6%) based on intraoperative 3D-iDSA, yielding ICGA accuracy rate of 94%. Five (71%) of the ICGA-3D-iDSA
discordances that prompted clip repositioning occurred at the anterior communicating artery complex.
Conclusion: A combination of vascular monitoring techniques most often achieved correct intraoperative interpretation of complete IA
occlusion and parent artery integrity. ICGA demonstrates high accuracy compared with 3D-iDSA imaging. Despite the relatively low
discordance rate, intraoperative DSA is confirmed as the gold standard. Improved imaging quality, including intraoperative 3D-iDSA,
supports its routine use in IA surgery, obviating the need for postoperative DSA.
607. Peroneal nerve decompression: institutional review and meta-analysis to identify predictors of surgical outcomes
Christopher D. Wilson, MD (Indianapolis, IN); Adewale Bakare, BS; Na Bo, PhD; Abdul Aasar, BS; Nicholas Barbaro, MD
Introduction: A common cause of peroneal neuropathy is compression near the fibular head. Studies demonstrate excellent
outcomes after decompression but include few cases (range 15-60 patients). Consequently, attempts to define predictors of good
outcomes are limited. We combine our institutional outcomes with those in the literature to identify predictors of good outcomes after
surgical decompression.
Methods: Our institutional database of peroneal nerve decompressions was searched between 12/1/2012 and 9/30/2016. A literature
search identified articles discussing surgical decompression. Data were combined by meta-analysis to identify predictors of good
outcomes defined as improvement in preoperative symptoms. Patients were analyzed in aggregate and by presentation (pain,
paresthesias, weakness, foot drop). Factors evaluated included age, body mass index, diabetes, smoking status, knee or lumbar spine
surgery, preoperative symptom duration, etiology, and gender. Meta-analysis was completed for any factor evaluated by at least four
data-sets.
Results: Twenty-one cases had sufficient data for review. An additional 220 operations were identified in the literature. Our
institutional data had long follow up (median 29 months, range 12-52 months). On aggregate analysis, only diabetes was a statistically
significant predictor of worse outcomes after decompression (p=0.05). Trends toward worse outcomes were seen with other factors:
smokers (p=0.06), foot drop more than 6 months preoperatively (p=0.08). Following meta-analysis, other associations were seen.
Preoperative symptom duration longer than 12 months was associated with worse outcomes (OR 0.23, 95%CI 0.08-0.65). Even after
meta-analysis, outcomes did not vary with gender (OR 1.13, 95%CI 0.42-3.06) nor with older patients (OR 0.68, 95%CI 0.24-1.98).
Conclusion: We provide our experience and a combination of published data regarding peroneal nerve decompression. Outcomes are
good after decompression regardless of presentation, especially if nondiabetic and preoperative symptom duration is less than 12
months. Older age does not adversely affect outcomes, and older patients should be considered for surgery.
608. The accessory obturator nerve: an anatomical study with relevance to anterior and lateral approaches to the
lumbosacral spine
Matthew Alan Protas (Upper Saddle River, AA); Brady Gardner; Marios Loukas; Rod Oskouian; Shane Tubbs

Introduction: The Accessory Obturator Nerve (AON) is a variant nerve that passes alongside the obturator nerve medial to the psoas
major muscle. It travels over the pubis and then descends dorsally to the pectineus muscle where it might innervate the hip joint,
pectineus, or anastomose with the obturator nerve. During lateral or anterior surgical approaches to the lumbosacral spine, this nerve
should be considered. Better classification of the AON is necessary to aid in surgical decision making.
Methods: A review of past literature on the AON and an anatomical study conducted. Thirteen studies were considered with a total of
2,102 lumbar plexuses analyzed. Twenty (40 plexuses) fresh frozen adult cadavers (12F/8M) were dissected by an anterior approach.
Results: The AON was found to arise most commonly from L2- L3 (4 plexuses), with a prevalence of 30% (8m/4F) on the left side
(7L/5R). The average length from origin to superior pubic ramus was 14.5cm with a diameter of 1.2 mm (range 0.8-1.5 mm) with all
nerves found to travel medially to the psoas major muscle, medial to the femoral nerve and lateral to the obturator nerve. Two terminal
branches anastomosed with the anterior division of the obturator nerve while 8 sides terminated deep (2) or superficial (6) to pectineus
origin. Past literature shows the average prevalence is 13% with its origin from the L3-L4 plexus (63.60%) being the most common
and L2-L4 (10.60%) the second most common. Prevalence was reported higher in females and on the left side. Terminal branches
typically joined the anterior (14.30%) or posterior branch (4.65%) of the obturator nerve.
Conclusion: Surgical approaches to the lumbosacral spine, whether anterior or posterior, should consider the presence of the AON
so its injury is minimized.
609. Efficacy of keyhole approach to carpal tunnel syndrome under ambulatory strategy
Ivan Segura Duran (Guadalajara Jalisco, Mexico); Rodrigo Ramos Zuñiga; Cesar J. Garcia Mercado, MD; Luis A. Zepeda Gutierrez,
MD
Introduction: Carpal tunnel syndrome (CTS) is the most common form of entrapment neuropathy in the upper limb. Nowadays, the
preferred surgical treatment for definitive resolution of CTS is undebatable, but the current challenge is to evaluate which is the most
efficacious and less invasive strategy to resolve the entrapment.In this study we evaluate the efficacy of the keyhole strategy applied
to the microsurgical approach of the carpal tunnel syndrome.
Methods: This was a prospective nonrandomised clinical study to analyze 55 consecutive series of patients with carpal tunnel
syndrome treated with mini-open minimally invasive approach in 65 hands, using local anesthesia without tourniquet and in an
ambulatory setting.
Results: According to the Levine Severity Scale, all patients were classified in the most severe grade: 4-5 of the 11 items. 90%
showed immediate improvement as they moved to grades 1-2 in every item of the scale on reference to pain and numbness (10
days). 7% presented the described improvement from the first month and 3% reported persistence of symptoms although at a lesser
degree and without functional limitation. The most chronic and severe cases in electrophysiology studies were included in this 3%,
even the case with an associated neuropsychiatric anxiety disorder.
Conclusion: The minimally invasive procedure following the keyhole principle can be applied to carpal tunnel syndrome, under local
anesthesia, without sedation in the majority of cases and ambulatory scheduled surgical procedure with successful outcomes and
problem resolution in agreement with most common surgical techniques. This strategy is not intended to be compared to other
techniques in terms of efficacy, but in our specific context it is a good option to resolve the mechanical compression. Additionally, the
risks involved in major invasive anesthetic procedures are reduced, as well as costs.
610. Distal peroneal nerve decompression after sciatic nerve injury secondary to total hip arthroplasty
Thomas J. Wilson, MD (Rochester, MN); Grant Kleiber; Ryan Nunley; Susan Mackinnon; Robert Spinner, MD
Introduction: The sciatic nerve, particularly its peroneal division, is at risk of injury during total hip arthroplasty (THA), especially when
a posterior approach is utilized. The majority of the morbidity results from loss of peroneal nerve-innervated muscle function.
Approximately 1/3 of patients recover spontaneously. The objective of this study was to report the outcomes of distal decompression of
the peroneal nerve at the fibular tunnel following sciatic nerve injury secondary to THA and to attempt to identify predictors of a positive
surgical outcome.
Methods: Retrospective study was performed of all patients who underwent peroneal decompression for the indication of sciatic nerve
injury following THA at the Mayo Clinic or Washington University School of Medicine in St. Louis. Patients with less than 6 months of
postoperative follow-up were excluded. The primary outcome was dorsiflexion strength at latest follow-up. Univariate and multivariate
logistic regression analyses were performed to assess the ability of the independent variables to predict a good surgical outcome.
Results: The total included cohort consisted of 37 patients. Dorsiflexion at latest follow-up was MRC ≥3 for 24 (65%) patients.
Dorsiflexion recovered to MRC ≥4- for 15 (41%) patients. In multivariate logistic regression analysis, motor unit potentials in the tibialis
anterior (OR 19.84; 95% CI 2.44–364.05; p = 0.004) and in the peroneus longus (OR 8.68; 95% CI 1.05–135.53; p = 0.04) on
preoperative electromyography were significant predictors of a good surgical outcome.
Conclusion: After performing peroneal nerve decompression at the fibular tunnel, 65% of the patient in this study recovered
dorsiflexion strength MRC ≥3 at latest follow-up, potentially representing a significant improvement over the natural history.
611. Selective neurotomy for spasticity: a single center experience
Ilyas Eli, MD (Salt Lake City, UT); Hussam Abou-Al-Shaar, MD; Mark Mahan, MD

Introduction: Spasticity is a devastating condition that can result from various etiologies including cerebral palsy, perinatal ischemia,
and spinal cord injury. Sedating antispasticity medications like baclofen as well as focal therapies like botulinum toxin and pheno are
the current primary therapies, where each therapy has challenges and problems. Alternatively, focal spasticity can be addressed using
selective denervation.
Methods: We retrospectively reviewed the medical charts of patients with upper and/or lower extremity spasticity that were operated
on by the senior author (M.A.M.) between 2014-2017. Preoperative and postoperative Ashworth scale, etiology, complications, and
patients’ satisfaction was recorded and analyzed. Independent assessment of spasticity by a physiatrist was sought in all cases.
Results: Twenty males and eleven females were included in the series (3 patients were <18 years and 28 patients were <18 years).
55% of patients had upper extremity spasticity, while 45% had lower extremity spasticity. The average preoperative Ashworth score
was 3.6 and the average Ashworth score at final follow up was 0.5 (P < 0.001). Three patients required revision surgery, 2 due to
incomplete relief. No perioperative complications were encountered in the series. All patients reported complete satisfaction with the
outcomes of the procedure.
Conclusion: This is the first North American series of denervation procedures for spasticity. Selective neurotomy is a potential option
for spastic patients that should be considered when conservative treatments fail or are inappropriate to the patient’s condition. Thus
far, denervation results suggest satisfactory short- and long-term outcomes with minimal morbidity and excellent patient satisfaction.
612. Mathematical model of perineural tumor spread - pilot study on 2 cases
Stepan Capek, MD (Charlottesville, VA); Robert Spinner, MD; Joshua Jabobs, PhD; Kristin Swanson, PhD
Introduction: Perineural spread (PNS) of pelvic cancer along the lumbosacral plexus is an emerging explanation for neoplastic
lumbosacral plexopathy (nLSP) and an underestimated source of patient morbidity and mortality. Despite the increased incidence of
PNS, these patients are often times a clinical conundrum - to diagnose and to treat. Building on previous results in modeling
glioblastoma multiforme (GBM), we present a mathematical model for predicting the course and extent of the PNS of recurrent tumors.
Methods: We created 3D models of perineurally spreading tumor along the lumbosacral plexus from consecutive MRIs of two patients
(one each with prostate cancer and cervical cancer). We adapted and applied a previously reported mathematical model of GBM to
progression of tumor growth along the nerves on an anatomical model obtained from a healthy subject.
Results: We were able to successfully model and visualize perineurally spreading pelvic cancer in two patients; average growth rates
were 60.7 mm/year for subject 1 and 129 mm/year for subject 2. The model correlated well with extent of perineural tumor on MRI
scans at given time points.
Conclusion: This is the first attempt to model perineural tumor spread and we believe that it provides a glimpse into the future of
disease progression monitoring. Every tumor and every patient is different and the possibility to report treatment response using a
unified scale - as days gained - will be a necessity in the era of individualized medicine. We hope our work will serve as a springboard
for future connections between mathematics and medicine.
613. The roles of rhythm and prediction in speech perception
Kiefer Forseth (Houston, TX); Gregory Hickok, PhD; Nitin Tandon, MD
Introduction: Neural computations in the brain are not merely a passive, stimulus-driven response - rather, cortical networks could be
expected to anticipate patterns of sensory events. Acoustic rhythms contain the requisite information for such the prediction of future
events. While the importance of rhythm in auditory perception seems intuitively clear, the neural mechanisms of auditory entrainment
and the interactions of entrained cortex with incoming stimuli are not fully understood.
Methods: Intracranial electrodes (n=5129, 27 patients), implanted as part of a stereotactic electrocorticographic evaluation for
epilepsy, furnish direct recordings with millimeter and millisecond resolution.
Results: In the first experiment, we measured the cortical response to an innovative stimulus: a period of amplitude modulated white
noise followed by a second period of constant amplitude white noise. In half of the trials and at variable delay, a pure tone was
presented in the second period. Patients were asked to report the presence of the tone. Behavioral data showed a modulation of
perceptual accuracy by the phase of the entraining rhythmic stimulus. Depth electrodes along the dorsal superior temporal gyrus
revealed a consistent posterior to anterior gradient of selectivity for distinct elements of the acoustic stimulus: onset and entrainment.
The entrainment response was characterized by consistent alignment of gamma power relative to the stimulus, as well as rhythmic
theta phase reset. In a second experiment, we found that the quasi-rhythmic amplitude envelope of speech specifically engaged theta
and gamma oscillations - perhaps packaging the acoustic signal into discrete units.
Conclusion: These neural representations of rhythm may constitute an adapted computational solution - cascaded neural oscillators -
to enable predictive coding and timing. The identification of such specific neural mechanisms that may guide the development of
computational models of anticipatory speech processing for use in neural prosthetics.
614. Change in policy allowing overlapping surgery decreases length of stay in an academic, safety-net hospital
Robert Florin Award
Anthony DiGiorgio, DO (New Orleans, LA); Praveen Mummaneni, MD; Jonathan Fisher, BS; Adam Podet, MD; Michael Virk, MD,
PhD; Clifford Crutcher, MD; Jason Wilson, MD; Gabriel Tender, MD
Introduction: The practice of surgeons performing overlapping surgery has recently come under scrutiny. We sought to examine the

impact of hospital policy allowing overlapping rooms on surgery wait time and length of stay in patients admitted to a tertiary care,
safety-net hospital for urgent neurosurgical procedures.
Methods: The neurosurgery service at the hospital being studied transitioned from routinely allowing one room per day (period 1) to
overlapping rooms (period 2), with the second room being staffed by the same attending surgeon. Patients undergoing neurosurgical
intervention in each period were retrospectively compared. Case urgency, patient demographics, case type, indication, length of stay
and time from admission to surgery were tracked.
Results: 452 total cases were reviewed (201 in period 1 & 251 in period 2), covering 7 months in each period. 122 of the cases were
classified as urgent (59 in period 1 and 63 in period 2). In these patients, length of stay was significantly decreased in period 2 (13.09
days vs 19.52, p=.043) and the time from admission to surgery for urgent cases trended towards a shorter time (5.12 vs 7.00,
p=.133). Insurance status of these patients was 26.2% uninsured, 39.3% Medicaid, 18.9% Medicare, 9% commercial and the
remainder workers compensation, liability or prisoner care. Wait time significantly correlated with length of stay (R2=.37, p<.001).
Conclusion: Recent studies suggest overlapping surgeries are safe for patients. As a matter of policy, allowing overlapping rooms
significantly reduces length of stay in a vulnerable population in need of urgent surgery at a single safety-net academic institution.
615. Evaluation of durable response rate in the post-resection setting and association with survival in patients with recurrent
high grade glioma who received vocimagene amiretroprepvec and 5-fluorocytosine treatment
Bob S. Carter, MD, PhD, FAANS (Boston, MA); Timothy Cloughesy, MD; Joseph Landolfi, DO; Michael Vogelbaum, MD, PhD; Brad
Elder, MD; Clark Chen; Steven Kalkanis, MD; Santosh Kesari; Ian Lee, MD; David Piccioni; Tobias Walbert
Introduction: Vocimagene amiretrorepvec is an investigational retroviral replicating vector that selectively infects dividing cancer cells,
integrates into the genome and replicates due to immune defects in tumors. Vocimagene amiretrorepvec spreads through tumors and
stably delivers the gene encoding an optimized yeast cytosine deaminase that converts the prodrug 5-fluorocytosine (an
investigational, extended-release formulation of 5-fluorocytosine) into 5-fluorouracil. 5-fluorouracil kills infected and nearby cancer
cells, myeloid derived suppressor cells and tumor associated macrophages, thus enabling immune activity against the tumor.
Methods: In this phase 1 trial (NCT01470794), ascending doses ofv ocimagene amiretrorepvec were injected into the resection cavity
wall of patients with rHGG, who had chosen to undergo a further resection, followed by multiple courses of oral 5-fluorocytosine.
Additional cohorts included combination of investigational therapy with bevacizumab or lomustine.
Results: Objective responses (ORs) were assessed by independent radiology review using MRI images prior to 5-fluorocytosine
treatment as baseline. ORs occurred 6-19 months after v ocimagene amiretrorepvec administration, suggesting an immunologic
mechanism. The ORs were observed in 4 patients with IDH1 wildtype and 2 with IDH1 mutant tumors, including 5 complete responses
(CRs) with the investigational therapy, and 1 CR with the investigational therapy and bevacizumab. The median duration of response
(mDoR) was 35.1+ months. Excluding combination cohorts, mDoR was 35.7+ months. As of 8/15/2017, all responders were in CR
and alive. In a 23-patient subgroup who received the recommended Ph3 v ocimagene amiretrorepvec dose, mOS was 14.4 months, 3-
year survival rate was 26.1%, and a durable response rate of 21.7% was observed. Across the Ph1 program, the safety profile
remains favorable.
Conclusion: CRs were observed in patients with IDH1 mutant and wildtype tumors, suggesting a benefit across the rHGG setting.
Data suggests a positive association of durable response with overall survival.
616. modified risk prediction model for the open treatment of unruptured cerebral aneurysms in Japan: UCAS-Treat result
and model verification using UCAS II outcome
Akio Morita, MD, PhD, IFAANS (Tokyo, Japan); Shinjiro Tominari, MD, PhD; Investigators UCAS Japan; Investigators UCAS II
Introduction: Management decision of the unruptured cerebral aneurysms should be made by balancing rupture risk of the aneurysm,
management risk and patient’s physical and mental conditions. Prediction models for rupture risk of aneurysms have been recently
reported, but, so far, no definitive model predicting the risk of aneurysm repair is reported. Here, we revised prediction model from the
treatment data of UCAS Japan.
Methods: In UCAS Japan and UCAS II, 2,246 and 398 patents underwent open repair respectively. Morbidity was defined as decline
of modified Rankin scale to 2 or below. Factors with hazard ratio less than 0.1 by multivariate cox regression model for the treatment
morbidity were included in the prediction scores, which were calculated from the coefficients from the analysis.
Results: Prediction scores were allocated to the factors as follows; Size (0: 3-4mm, 1: 5-6mm 2: 7-9mm, 3: 10-24mm, 6: 25mm-,
Location (ACA: 0, MCA, ICA: 2, ACOM, IC-PCom: 3, VA: 5, BA: 6), Age (1:<=70), Hypertension (1), Diabetes Mellitus (2), Multiple
aneurysm treated at once (1) and No Daughter sac (1). From the model, treatment morbidities were less than 1% for the summed
scores 0 to 4, 1 to 5% for scores 5 to 7, 5 to 10% for scores 8, and 10% or more if the score is 9 or higher. We validated this score
with UCAS II treatment data.
Conclusion: Risk prediction model including multiple important clinical factors should help clinical decision making and risk
communication with patients.
617. GABAergic basal ganglia output modulates tonic and burst modes of thalamic neurons
Zi Ling Huang (South Riding, VA); Deepak Kumbhare, PhD; George Weistroffer; Zi Huang, MS; Mark Baron, MD
Introduction: The classical basal ganglia model cannot readily account for findings of excessive neuronal (GABAergic) activity in the
globus pallidus interna (GPi) with dystonic movement, which, per the model, should reduce, not induce thalamocortical dystonic motor

drive.
Methods: Multi-neuronal activity was recorded from the entopeduncular nucleus (EP, rodent equivalent of GPi) and ventrolateral (VL),
pallidal-receiving, motor related thalamus, with EMGs from antagonistic pairs of hip and stifle (knee) muscles in jaundiced and GP-
lesioned dystonic and normal control rats. Sorted spike trains were categorized into regular, irregular and burst patterns and assessed
at rest and binned around movement epochs.
Results: As reported previously, resting discharge rates were markedly reduced in EP in dystonic rats with predominance of irregular
and bursty discharge activity. With movement, EP neurons showed abnormally synchronized, excessive movement related bursts. At
rest, 85% of VL neurons were bursty in normal rats and were predominantly tonic in dystonic rats. In normal rats with movement, VL
neurons maintained the burst mode, while exhibiting a steep rise in spike counts preceding movement onset. In dystonic rats, VL
neurons largely switched to a burst pattern, but exhibited a comparatively flatter response.
Conclusion: Our findings suggest that normally, baseline fast tonic ‘pacemaker’ motor-related EP discharge activity holds VL neurons
in a ‘ready’ burst state (via hyperpolarization). In dystonia, markedly reduced EP neuronal baseline discharge rates (and resultant
inadequate hyperpolarization) places VL neurons erroneously in the tonic mode at rest. Excessive, synchronous, poorly timed
pathological VL-cortical motor signaling contributes to the hallmark features of dystonia, including excessive and sustained motor
contractions, with co-involvement of antagonist muscle groups and spread across multiple joints. Interventions aimed to correct
defined abnormalities at the level of motor thalamus could offer a mechanistic based approach to reversing the underlying signaling
abnormalities and ameliorating dystonia.
618. Medial hypothalamic deep brain stimulation for treatment of morbid obesity
Antonio A. F. De Salles, MD PhD (Sao Paulo, Brazil); Antonio De Salles, MD, PhD; Bruno Santos, MD, MSc; Camila Lasagno;
Fernando
Fernandes, MD; Lucas Damian; Priscila Bueno; Alessandra Gorgulho, MD, MSc
Introduction: Morbid Obesity represents a multifactorial disease affecting the endocrine and the behavioral traits that potentially can
be controlled with application of current techniques of deep brain stimulation (DBS). This study sought to prove the safeness of
Ventro-Medial Hypothalamus-DBS(VMHDBS) and identify behavioral and endocrine patterns that can be effected by this approach.
Methods: Six patients with BMI<40 and no secondary diseases were included in the study. There were 3 men and 3 women, age
within 30-45years. There was mild and well-controlled arterial hypertension in two patients. Surgery was accomplished in a magnetic
resonance operating room using fibertracking, direct identification of the target and classic stereotactic technique. They were operated
under general anesthesia with target confirmed by changes in physiological parameters such as, arterial blood pressure, temperature
and CO2 consumption. Device was Activa PC double channel linked to 3339 electrodes implanted bilaterally in the ventro-medial
hypothalamus (VMH). Patients were monitored with Holter to assure cardiac and behavioral safety one week as inpatient. They were
followed for one year after implantation for identification of adverse effects (AD) and positive effects of the stimulation, including weight
loss.
Results: Major loss of weight was recorded in one patient (56 kg in one year); no unacceptable ADs were observed in this group of
patients. Five patients continue under stimulation using trials of parameters. One patient voluntarily abandoned the study without
reporting complications. He continues with the implanted device. Important traits of increased metabolism such as immediate profuse
sweating and increase temperature were recorded. High levels of stimulation induced anxiety, tachycardia and increases in blood
pressure. Stimulation above 5 volts in one patient led to old memories induction.
Conclusion: Stimulation of the VMH can be performed for long periods without unacceptable complications. Important psychological
and behavioral patterns are necessary for a successful weight loss.
619. A closed loop deep brain stimulation system for essential tremor
Andrew Lin Ko, MD (Seattle, WA); Brady Houston, PhD; Howard Chizeck, PhD
Introduction: Deep brain stimulation is a well-established therapy for treating essential tremor. In its current, "open-loop" form,
stimulation is provided without accounting for patient physiology, delivering stimulation unnecessarily, causing excess battery usage,
and potentially, exposure to side effects and reduced long-term efficacy. Herein we describe a "closed-loop" DBS system that utilizes
cortical electrophysiology to deliver demand-driven stimulation to effectively treat essential tremor.
Methods: Three patients were implanted with the Medtronic Activa PC+S system at the University of Washington, with a 4-contact
electrode targeting Vim, and a 4-contact subdural electrode over hand sensorimotor cortex. Cortical signals during a prompted,
tremor-evoking movement task (PM) were streamed to a laptop to train a logistic regression classifier. These classifiers were used to
control stimulation during a PM task and administration of the Fahn-Tolosa-Marin (FTM) tremor rating scale. Accuracy of stimulation
delivery was assessed, and blinded rating of FTM scores with no DBS (OFF), open-loop DBS (ON) and closed-loop DBS (CL) was
performed.
Results: Average CL system accuracy and sensitivity during PM tasks was 67.1% and 87.7%, respectively. During FTM tasks, the
system accuracy and sensitivity were 100%. This reflected power savings of 27.7-38.3% during PM tasks, and about 4% during FTM
tasks when compared to open-loop DBS. There was a significant group effect of stimulation on FTM scores. Both CL and ON resulted
in significant improvement compared to OFF (ANOVA, F=43.3, p=0.002), with no difference between CL and ON scores (t=0.5,
p=0.65).
Conclusion: This work represents the first report of DBS to treat essential tremor using a machine-learning-based closed-loop
system. Importantly, the classifiers used were able to accurately generalize from training on one task (PM) to very different maneuvers
used during a clinical tremor rating evaluation. Future work implementing this paradigm on-board the Activa PC+S itself will allow

improvements in performance and power savings.
620. Double-blind Randomized Trial of V1 Trigeminal Stimulation for Refractory Major Depression
Antonio A. F. De Salles, MD PhD (Sao Paulo, Brazil); Alessandra Gorgulho, MSc; Fernando Fernandes, MD; Bruno Santos, MD, MSc;
Camila Lasagno; Priscila Bueno; Lucas Damian; Ricardo Moreno; Antonio De Salles, MD, PhD
Introduction: One-third of patients with Major Depression are refractory to combined medication and psychotherapy. A double-blind,
one-way-crossover randomized surgical trial of trigeminal stimulation (TNS) in unipolar-treatment-resistant depression was conducted.
Methods: Twenty patients, mean age 50.3; SD+7.23years, 16-females, IRB approval-enrollment. Bilateral electrodes implanted
subcutaneously under the eyebrow stimulating the trigeminal V1-branches were connected to a generator below the right clavicle. Ten
participants were randomized to active-stimulation (AS) at 2-weeks after surgery. The other 10 were turned-on for 1 minute and then
remained turned-off, sham-stimulation (SS) for 12 weeks. At 3-month the SS non-responders were turned-on. Placebo responders
were rescued during the additional 12-weeks of blinded stimulation. The double-blind stimulation lasted 6-months. Medications
remained unchanged throughout the study. Depression was evaluated with Hamilton Depression-Scale-17-items (HDS17), Beck-
Depression-Inventory (BDI), Inventory of Depression-Symptomatology (IDS) and Ugvlag for Kiniske Undersgelsen (UKU).
Results: Stimulation was well tolerated. Three patients asked for a slight surgical retraction of the electrode because it was
bothersome at the eyebrow area. There were no infections or erosions. Baseline-HDRS17 fell in the AS and SS groups by placebo
effect. However, the fall in the AS was more robust and statistically significant at 12 weeks (p<0.023) as compared to the SS
(22.3+4.0 to 10.2+2.5 versus
20.4+2.9 to 16.9+5.3), confirmed with the crossover. The BDI and IDS decreased significantly in both groups (p<0.01). UKU showed
good tolerance.
Conclusion: Patients tolerated well the V1 stimulation electrodes and the continuous stimulation. It was well tolerated cosmetically.
The treatment was robust with a significant decrease in HDS17 and a great adherence to the treatment.
621. Gamma and theta band power increases in the anterior and posterior hippocampus predict successful episodic memory
formation
James Phillip Caruso, MD (Dallas, TX); Jui Jui Lin, BS; Sarah Seger, BS; Bradley Lega, MD
Introduction: Episodic memory involves the recollection of events at specific time points, and episodic memory degeneration often
signifies neurologic disease. Human electrophysiologic studies of episodic memory formation have not elucidated the differences
between anterior and posterior hippocampal function. Additionally, while studies demonstrate gamma band (25-100 Hz) oscillatory
power increases in the anterior hippocampus during successful memory encoding, theta band (2.5-5 Hz) power increases have not
been observed. We assessed whether memory-related oscillatory patterns exist in human hippocampal recording at the gamma and
theta band frequencies, and whether these patterns differ between the anterior and posterior hippocampi and between dominant and
non-dominant hemispheres.
Methods: We analyzed 141 electrodes located in the anterior and posterior hippocampi of 23 epilepsy patients who underwent stereo-
electroencephalography (sEEG) surgery. Patients performed the verbal free recall task, a standard test of episodic memory. We
recorded sEEG signal during item encoding and retrieval, and we compared oscillatory power from successfully and unsuccessfully
encoded memory items via Wilcoxian rank sum tests.
Results: During item encoding, we observed gamma band oscillatory power increases in the anterior and posterior hippocampi. Within
the theta band, the power increase observed in the posterior hippocampus was significantly greater than that of the anterior
hippocampus. Gamma band power increases were also significantly greater in the dominant hemisphere compared to the non-
dominant hemisphere. However, during item retrieval, the nondominant hemisphere demonstrated a greater gamma band power
increase compared with the dominant hemisphere.
Conclusion: Our analysis establishes the first evidence of a theta band power increase in the posterior hippocampus during
successful memory encoding in humans, along with hemispheric differences in gamma band activity in item encoding. These
differences in oscillatory power may reflect functional specialization of the anterior and posterior hippocampus in episodic memory
formation.
622. A prospective trial of magnetic resonance guided focused ultrasound thalamotomy for essential tremor: results at the 2-
year follow-up
Chang Kyu Park, MD (Republic of Korea); Jin Woo Chang; Nir Lipsman; Michael L. Schwartz; Pejman Ghanouni; Jaimie M
Henderson; Ryder Gwinn; Travis S. Tierney; G. Rees Cosgrove; Binit B. Shah; Andres M. Lozano; W. Jeffrey Elias
Introduction: Magnetic resonance (MR) guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment
modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2-
year follow-up after MRgFUS thalamotomy for ET.
Methods: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were
enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Nine
patients were excluded from the study; three of them were treated alternative therapy such as DBS and one patient did not have
adequate thermal lesioning. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2
years. However, all patients in each follow-up period were analyzed.

Results: Mean hand tremor score improved by 55% from baseline (19.8±4.9, 76 patients) at 6 months (8.6±4.5, 75 patients). The
score remained improved 53% at 1 year (8.9±4.8, 70 patients) and 56% at 2 years (8.8±5.0, 67 patients). Furthermore, the disability
score was improved by 64% from baseline (16.4±4.5, 76 patients) at 6 months (5.4±4.7, 75 patients). The improvement was sustained
64% at 1 year (5.4±5.3, 70 patients) and by 60% at 2 years (6.5±5.0, 67 patients). Several adverse events occurred at treatment time
and it continued to 2 years. However, none of these events got worse at 2 years and 2 of these events resolved. There were no new
delayed complications at 2 years.
Conclusion: Latent or delayed complications do not develop with MRgFUS thalamotomy for ET, and tremor suppression is stably
maintained at 2 years after surgery.
623. Trial of convection-enhanced delivery of muscimol in patients with medically-intractable epilepsy
Davis Palmer Argersinger, B.S. (Bethesda, MD); Susumu Sato, MD; William Theodore, MD; Omar Khan, MD; John Butman, MD, PhD;
John
Heiss, MD
Introduction: To investigate the safety and effectiveness to suppress seizures of intracerebral infusion of muscimol into the seizure
focus of patients with medically-intractable epilepsy, we performed a phase 1 clinical trial.
Methods: Three adult patients with medically-intractable epilepsy underwent convection-enhanced delivery (CED) for 12-24
continuous hours of muscimol (1-2mL) and an artificial CSF vehicle (1-2mL) into the seizure focus (cortex--1 patient; hippocampus--2
patients) using a crossover design. Basic pathophysiology of the epileptic focus was examined by assessing the effect of infusion on
seizure frequency (primary endpoint), EEG spike wave activity frequency (spikes/minute), and power-spectral EEG mean frequency
(Hz).
Results: Inter-ictal neurological function remained normal in each patient. Pathological examination of all resected surgical specimens
showed no infusion-related brain injuries. Patient #1’s mean beta frequencies (Hz) before, during, and after muscimol infusion were
19.1, 16.8, and 17.8, respectively; patient #2: 16.4, 15.9, and 17.2, respectively; patient #3: 18.4, 16.8, and 15.9, respectively. Patient
#1’s mean beta frequencies (Hz) before, during, and after vehicle infusion were 17.7, 17.4, and 17.9, respectively; patient #2: 17.3,
17.4, and 16.9, respectively; patient #3: 18.1, 18.1, and 17.8, respectively. Seizure frequency was reduced in 1 of 3 patients during
muscimol infusion but was unchanged in all patients during vehicle infusion. The infused fluid provided insufficient MRI-signal to track
infusate distribution. Following infusion, the patient with epilepsia partialis continua underwent multiple subpial transections and had
reduced seizure frequency. Both patients with mesial temporal sclerosis underwent anterior temporal lobectomy and had no seizures
during the 2-year follow-up period.
Conclusion: Muscimol infused into the epileptic foci of patients with medically-intractable epilepsy by CED did not damage adjacent
brain parenchyma or adversely affect seizure surgery outcome. Future clinical trials using CED to suppress the seizure focus should
use a surrogate tracer to track distribution of muscimol or other agents within the epileptic focus and surrounding structures.
624. Electrophysiologic mapping of cortical networks activated by dorsal vs. ventral subthalamic nucleus deep brain stimulation
Aarathi Minisandram, MS (Boston, MA); Kristen Kanoff, BS; Emad Eskandar, MD; Todd Herrington, MD, PhD
Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) relieves motor symptoms in patients with Parkinson's
disease, but may actually worsen cognitive and psychiatric symptoms. The STN is anatomically segmented into subnetworks that
preferentially serve motor, limbic, and associative functions. Optimal outcomes are thought to arise from stimulation of the STN motor
subnetwork. We utilized high-density EEG to map cortical evoked potentials of DBS electrode contacts in different STN subregions.
We hypothesized that stimulation of the ventral STN, which shows greater functional connectivity with associative and limbic cortices,
would preferentially stimulate prefrontal and anterior temporal cortex as compared to the dorsal STN, which would preferentially
stimulate sensory and motor cortex.
Methods: We recorded EEG data at 20 kHz from subjects with Parkinson’s disease treated with bilateral STN DBS. Anatomically
selected dorsal and ventral STN sites in each hemisphere were stimulated individually at 5 Hz with equalized intensities for 2 minutes.
Single-pulse DBS artifacts were identified and evoked potentials aligned on each artifact. Evoked potential field differences for dorsal
vs. ventral stimulation were analyzed for each hemisphere. Cortical source models were estimated based on pre-operative MRI scans
for each subject, using freesurfer and minimum-norm estimation (MNE) Python.
Results: Initial results suggest a prefrontal to sensorimotor evoked potential fields gradient with ventral to dorsal STN stimulation.
MNE cortical source estimates suggest that both dorsal and ventral STN stimulation generate evoked potential fields in ipsilateral
sensorimotor cortex, while ventral STN stimulation additionally impacts a broader frontal cortical network.
Conclusion: Non-human primate anatomy and MRI-based measurements suggest a gradient of sensorimotor to associative-limbic
connectivity from dorsolateral to ventromedial STN. Our initial findings reproduce this pattern of connectivity using STN DBS cortical
evoked potentials, suggesting that non-invasive physiology may offer a useful adjunct to imaging-based anatomic localization of DBS
electrodes.
625. Distinct cortical regions mediate improvements in individual motor symptoms after subthalamic nucleus deep brain
stimulation in Parkinson’s disease
Vibhor Krishna, MD (Columbus, OH); Francesco Sammartino, MD; Qinwan Rabbani; Barbara Changizi, MD; Punit Agrawal, DO; Milind
Deogaonkar, MD; Michael Knopp, MD; Nicole Young, PhD; Ali Rezai, MD

Introduction: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves all motor symptoms (tremor, rigidity and
bradykinesia) of Parkinson’s disease (PD). However distinct clinical effects are sometimes observed during acute stimulation
adjustments e.g. rigidity may improve more than tremor. We hypothesized that acute stimulation-induced effects in different clinical
domains are mediated by unique cortical regions. We tested this hypothesis in a cohort of 24 PD patients with STN DBS using
probabilistic tractography.
Methods: Patients underwent preoperative structural and diffusion tensor imaging (3T, Phillips Achieva, 60 diffusion directions, 2 mm
isovoxel) and post-operative CT. Images were processed using an integrated pipeline. The volume of tissue activation (VTA) for each
stimulation adjustment were modeled and used as seeds for probabilistic tractography. The resulting connectivity maps were
statistically compared across patients using permutation test (p<0.05, 5000 permutations). The cortical voxels associated with
efficacious domains (rigidity, tremor and bradykinesia) were compared with stimulation-induced motor contractions using a mixed
effect model (AfNI 3dMVM). The resulting voxels maps were thresholded (FDR correction; rigidity: q<0.0015, bradykinesia q<0.0021,
tremor q<0.0016) and clustered with a multimodal atlas.
Results: 52 unique stimulation changes were analyzed for rigidity, 30 for bradykinesia, 84 for tremor improvement, and 124 for motor
contractions. In contrast to motor contractions, efficacious stimulation was significantly associated with clusters in premotor and
supplementary motor cortex (Brodmann area 6). The cortical clusters common to efficacious domains include primary motor cortex
and superior frontal gyrus. Additionally, each clinical domain was also associated with unique cortical regions e.g. clusters in bilateral
Brodmann area 8 were uniquely associated with tremor improvement.
Conclusion: Unique cortical regions may be involved with improvements in different motor symptoms after STN DBS in PD. These
observations may have implications for individualized surgical targeting and stimulation titration based on patient’s clinical
presentation.
626. A football helmet prototype that reduces linear and rotational acceleration through the addition of an outer shell
Scott Zuckerman, MD (Nashville, TN); Aaron Yengo-Kahn, MD; Bryson Reynolds, PhD; Andrew Kuhn, BA; Jacob Chadwell; Claire
Lafferty; Kyle Langford; Lydia Mckeithan; Paul Kirby, BS; Gary Solomon, PhD
Introduction: Amidst the public health controversy surrounding American football, a helmet that can attenuate linear and rotational
acceleration has potential to reduce forces transmitted to the brain. We hypothesized that a football helmet with an outer shell would
reduce both linear/rotational acceleration. The current objectives were to: 1) determine the optimal material for a shock-absorbing
outer shell, and 2) examine the helmet and outer shell’s ability to reduce linear/rotational acceleration.
Methods: A laboratory-based investigation was undertaken using an XL Riddell Revolution football helmet. Two materials (Dow
Corning Dilatant Compound and Sorbothane) were selected to develop an outer shell for their non-Newtonian properties (changes in
viscosity with shear stress). External pads were securely attached to the helmet at three locations: front boss, side, and back. The
helmet was impacted five times per location at 6 m/s with pneumatic ram testing.
Two-sample t-tests evaluated linear/rotational acceleration differences between control and outer shell helmet.
Results: Sorbothane performed superiorly to the Dow Corning compound in force reduction and recovered from impact without
permanent deformation. Out of 5 different grades, 70 duro Sorbothane demonstrated the greatest energy dissipation and stiffness, and
was chosen as the optimal material for the outer shell. The outer shell helmet prototype reduced linear acceleration by 5.75%
(p=<0.001) and 10.8% (p=0.033) at the side and front boss locations respectively and reduced rotational acceleration by 49.8%
(p=<0.001) at the front boss location.
Conclusion: Seventy duro Sorbothane was chosen as the optimal outer shell material. The helmet outer shell prototype demonstrated
5-10% reductions in linear acceleration and 50% reduction in rotational acceleration at the front boss location. Rotational acceleration
is the major culprit in severe head injuries, and the large reduction seen in rotational acceleration holds significant potential for future
helmet design.
627. Effect of platelet dysfunction on outcomes in traumatic brain injury
Andrew R. Guillotte (Columbia, MO) ; Joseph Herbert, MD; Richard Madsen, PhD; Richard Hammer, MD; N. Litofsky, MD
Introduction: Coagulopathy and platelet inhibition are common sequelae among patients with traumatic brain injury (TBI). The
increasing use of antiplatelet medications pre-morbidly further results in platelet inhibition among many TBI patients. Little data is
available to guide management of platelet dysfunction in the setting of TBI. The aim of this study is to evaluate whether transfusing
platelets reduces platelet adenosine diphosphate (ADP) inhibition, and whether platelet transfusion is associated with improved patient
outcomes.
Methods: We prospectively collected thromboelastography (TEG) assays with platelet mapping data from adult patients with blunt TBI
as part of a quality improvement study. All patients included in the study had intracranial lesions attributable to blunt head trauma
detected by computed tomography (CT). The primary outcomes measured were in-hospital mortality and lesion expansion as
determined by follow-up CT.
Results: TEG assays were performed on 156 TBI patients during this study. Patients with GCS scores less than 14 had increased
ADP inhibition compared to patients with GCS of 14 and 15 (p=0.0034). The extent of reduction of platelet ADP inhibition from platelet
transfusion (-18.4%) relative to patients not transfused (+ 14.4%) did not reach statistical significance (p=0.0550), but could be
clinically significant. Furthermore, in-patient mortality of patients not requiring a neurosurgical procedure was worse among the group
that received platelet transfusions (odds ratio 3.8; p = 0.032), but lesion expansion was not less in those not transfused (odds ratio
1.22; p = 0.77).
Conclusion: Based on the results of this study, transfusion of platelets in TBI patients not undergoing a neurosurgical procedure
based on TEG ADP inhibition alone cannot be recommended. Further study is needed to demonstrate clinical significance of such

transfusion.
628. Preoperative risk score predicts 30-day mortality following emergency surgery for intracranial hemorrhage
Redi Rahmani, MD (Rochester, NY); Samuel Tomlinson, BA; Keaton Piper, BS; Kristopher Kimmell, MD; G Vates, MD, PhD
Introduction: Intracranial hemorrhage is a potentially life-threatening condition. Emergency neurosurgical intervention is often required
to prevent or address serious complications. In this study, we developed and scrutinized a risk score for 30-day mortality among
patients undergoing emergency surgery for intracranial hemorrhage.
Methods: The American College of Surgeons National Surgical Quality Improvement Program database (ACS-NSQIP; years 2006-
2015) was queried for patients undergoing craniectomy or craniotomy for intracranial hemorrhage performed under emergency status.
Patients were allocated into a training dataset (n = 1,000) and a cross-validation dataset (n = 829) for model development and testing,
respectively. Sequential univariate and multivariate analysis was applied to the training dataset to identify independent predictors of
30-day mortality. Weighted risk scores were generated for each patient. The receiver-operating characteristics (ROC) curve was used
to characterize the utility of the risk score for predicting 30-day mortality in the validation dataset.
Results: Six independent predictors of 30-day mortality were identified: dialysis, ventilator dependence, American Society of
Anesthesiologists class > IV, dyspnea, platelets < 150,000/µL, and bleeding disorder. When applied to the training dataset, the risk
score demonstrated strong discriminative capacity for classifying patients based on 30-day mortality (AUC = 0.76, CI 95% = 0.72 -
0.81). Increasing risk scores were highly associated with increasing mortality rates in the validation dataset, with the lowest risk
patients (0 < score < 1) exhibiting a mortality rate of 6.6% compared to a mortality rate of 52.4% among high risk patients (score > 7).
ROC curve analysis revealed strong outcome prediction with an AUC of 0.72 (CI 5-95% = 0.67 - 0.77).
Conclusion:
We developed and scrutinized a mortality risk score for patients undergoing emergency surgery for intracranial hemorrhage.
Preoperative risk factors may be aggregated to stratify a patient’s mortality risk in cases of emergency intracranial hemorrhage.
629. Bedside wearable mixed reality holograms guide external ventricular drain insertion
Ye Li, MD, PhD (Beijing, China)
Introduction: External ventricular drain (EVD) insertion is classically a blind procedure performed using freehand technique based on
anatomical surface landmarks. Surprisingly, near 50% inaccuracy rate of EVD insertion has been well reported in the literature. Mixed
reality (MR) technology utilizes digital objects such as holographic projection, providing virtual information in realistic scene that lends
realism to users’ experience. In this study we share our first hands-on experience using wearable MR holograms to assist bedside
EVD insertion.
Methods: Holographic guidance was applied prospectively for all patients who required EVD placement between August 2017 and
October 2017. 10 consecutive patients were recruited. All patients underwent CT scanning using a movable CT before and after EVD
placement. Dicom data was imported into 3D Slicer, by which the surgical planning procedures were achieved. Neurosurgeons
visualized holograms of the surgical plan through high-definition lenses with small computer screens positioned in front of the eyes,
and performed all surgical procedures by wearing the headsets. The feasibility and accuracy of our technique were assessed by
evaluating the additional time and target deviation.
Results: Surgical planning and holographic visualization were achieved in all cases. No adverse events related to the holographic
guidance procedures were observed. The mean additional time was 45 minutes. All the tips of inserted catheters were placed in the
vicinity of foramen of Monro. The mean target deviation was 2.7± 2.5mm.
Conclusion: This is the first positive experience using wearable MR holograms to assist bedside EVD insertion. A full set of clinically
applicable pipeline is presented to make use of the medical image data to visualize patient-specific holograms that intuitivel guide
hands-on operation. We also provide a preliminary confirmation of the feasibility and accuracy of this
holograms-guided EVD insertion technique.
630. Aggressive surgical treatment and critical care are associated with improved neurologic recovery in complete SCI
Anthony DiGiorgio, DO (New Orleans, LA); John Burke, MD, PhD; Ethan Winkler, MD, PhD; Jason Talbott, MD, PhD; Adam
Ferguson, PhD; Michael Beattie, PhD; Jacqueline Bresnahan, PhD; William Whetstone, MD; Michael Huang, MD; Geoffrey Manley,
MD, PhD; Phiroz Tarapore, MD; Sanjay Dhall, MD
Introduction: Spine Injury Association (ASIA) An injury, or a complete spinal cord injury (SCI), is a devastating diagnosis. This can
severely shorten the life expectancy of a patient and is costly to society. Patients who present as an ASIA A have very low rates of
improvement. The literature reports improvement of one ASIA grade range from 11-40% of patients by time of discharge. The object of
our study was to determine if aggressive surgical treatment and critical care are associated with improved neurologic recovery in
complete SCI.
Methods: The Transforming Research and Clinical Knowledge in SCIs study is a retrospective observational study conducted by the
University of California at San Francisco Brain and Spinal Injury Center. The database was queried for all spinal cord injuries from
2004 - 2015. Time to surgical intervention was collected along with presenting and discharge ASIA grades.
Results: 62 patients were enrolled in the study and 28 of these were ASIA A at presentation. 57.1% of complete SCI patients
improved at least one grade by discharge and 50% improved at least two grades. 9 patients were operated on within 12 hours and 19
after 12 hours. 89% of the patients operated on within 12 hours improved at least one AIS grade compared to

42% of the patients operated on after 12 hours (p=.039).

Conclusion: Aggressive surgical and critical care management of complete spinal cord injury can lead to higher improvement rates
than those previously reported in the literature. This has the potential for long term improvement in quality of life as well as substantial
cost savings.
631. Predicting venous thromboembolic complications following neurological surgery procedures
David Lee Dornbos III, MD (Columbus, OH); Varun Shah; Blake Priddy; Victoria Schunemann, MD; Shahid Nimjee, MD, PhD; Ciaran
Powers, MD, PhD
Introduction: Venous thromboembolic events (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), are a
common source of morbidity and mortality in the neurosurgical population. The exact timing and choice of pharmacologic options for
VTE prophylaxis are still a source of debate. Improving the predictability of patients at increased risk for DVT/PE will allow prophylactic
strategies to be specifically tailored to patients. We sought to validate the Caprini Risk Assessment Model (RAM) in a neurosurgical
population.
Methods: 2830 patients between July 2014 and June 2015 were retrospectively evaluated. Patient demographics, presence of
DVT/PE, use of VTE prophylaxis, length of surgery, and VTE risk factors were collected, and Caprini RAM scores were calculated.
Statistical analysis included univariate analysis, multivariable logistic regression analysis, and area under the receiver-operating curve
(AUROC) to determine factors that were predictive of VTE development.
Results: The Caprini score among VTE-positive patients was 12.20 ± 0.26, compared to 8.90 ± 0.07 among VTE-negative patients
(p<0.0001). BMI, acute MI, presence of swollen legs, prolonged bed rest, sepsis, pneumonia, malignancy, length of surgery <3 hours,
history of DVT/PE, and recent stroke significantly (p<0.001) correlated with development of a VTE following a neurosurgical procedure
on univariate analysis. On multivariable logistic regression analysis, BMI, presence of swollen legs, prolonged bed rest, pneumonia
and were independent predictors of VTE development (p<0.01). Overall, the Caprini RAM is a fair predictive tool for VTE in a
neurosurgical population with an AUROC of 0.754.
Conclusion: Using a score of 10 as a threshold for a positive test, the Caprini RAM carries a sensitivity of 78.9% and a specificity of
60.9%. While this tool is a fair predictive scoring system in the neurosurgical population, development of a neurosurgical-tailored
scoring system would further improve decision-making regarding DVT prophylactic strategies.
632. Lumbar puncture feasibility in the presence of cerebral mass effect
Jonathan Pace, MD (Cleveland, OH); Vilakshan Alambyan, MD, PhD; Sunil Manjila, MD; Krishna Kandregula, MD; Ciro Ramos-
Estebanez, MD, PhD
Introduction: The contraindications for lumbar puncture (LP) in the setting of cerebral mass effect remain debatable. Case reports
advocate its potential feasibility and safety. Yet, guidelines specifically addressing this topic are not available. Specific patient
populations (post-instrumentation & immunosuppressed) may benefit from CSF collection and analysis.
Methods: A retrospective case series was conducted. We reviewed 1072 consecutive patients who underwent LP and cerebral
imaging a week before or after LP from 2007-2014. All individuals with evidence of brain herniation, a component of midline shift, or
mass effect were included. All subjects received a low volume LP (5-10 cc of CSF).
Results: There were 132 patients with radiological increased ICP. Midline shift (average = 4 mm) was present in 39 patients. We also
observed herniation: uncal (n=16), subfalcine (n=15), and a combination of both (n=10) , ventricular effacement (n=67) and cisternal
compression with partial occlusion: Quadrigeminal cistern (n=3), cerebellar-pontine-angle cistern (n=14), ambient cistern (n=24), crural
cistern (n=14), prepontine cistern (n=7), suprasellar cistern (n=12), basal cistern (n=2), suprachiasmatic cistern (n=4), cisterna magna
(n=3), interpeduncular cistern (n=3), medullary cistern (n=4). All patients tolerated the LP without complications. Most survived a week
after the procedure (n=128, 97%). Notably, four individuals deteriorated for reasons unrelated to the LP and expired within a week
because of withdrawal of care.
Conclusion: As brain compliance cannot be determined radiologically, we believe anatomical involvement should drive decision-
making regarding LP safety. Our data suggest that a low volume LP might be safe in individuals with subfalcine herniation, midline
mass effect < 4 mm at foramen of Monro level, and partial cisternal effacement. We believe that while LPs might be safer in patients
with supratentorial mass effect, individuals with posterior fossa involvement may tolerate it as well. These promising findings need
further verification in larger sample populations.
633. Traumatic intracranial hemorrhage in the setting of 4-factor prothrombin complex concentrate
Harry Mushlin, MD (Baltimore, MD); Harry Mushlin, MD; Mary Cunnion, MD; Michele Hines, PharmD; Joseph Kufera, MS; Mehrnaz
Pajoumand, PharmD; Bizhan Aarabi, MD; Deborah Stein
Introduction: Kcentra is 4-factor prothrombin complex concentrate that is FDA approved for reversal of warfarin. There is limited
research describing the use of Kcentra for coagulopathy in the setting of traumatic intracranial hemorrhage. Here, we show the largest
ever retrospective review for the use of Kcentra in the setting of traumatic intracranial hemorrhage.
Methods: Retrospective chart review was performed from 2013-2016 for patients with intracranial hemorrhage who presented to the R
Adams Cowley Shock Trauma Center. Patients who received Kcentra were identified. Basic clinical information was obtained including
cardiac/stroke history, blood pressure, Glasgow Coma Score, medication history, and categorization of hemorrhage. Pre and post INR

level was assessed. Hemorrhagic expansion was assessed with CT scan up to up to 24 hours. Disposition and thromboembolic
events were recorded.
Results: Forty-four patients were identified as receiving Kcentra in the setting of traumatic intracranial hemorrhage. Pre and post
Kcentra dosing INR was found to be significantly different (p<0.001) across the two groups assessed (warfarin and TBI/NOAC
coagulopathy). Seventeen patients (38.6%) had hemorrhagic expansion as determined on CT scan. Disposition (home vs rehab vs
death) was found to have three significant variables: history of stroke, hemorrhagic expansion, and admission Glasgow Coma Score.
Eight patients (18.2%) were found to have thromboembolic events.
Conclusion: Here, we show the largest retrospective review describing the clinical use of Kcentra for coagulopathy reversal in the
setting of intracranial hemorrhage. Overall, Kcentra is shown to be a safe and effective drug for the reversal INR. Importantly, our
reported hemorrhagic rate of 38.6% is lower than established rates reported in the literature for warfarin/coagulopathic patients with
intracerebral hemorrhage (50-60%). The prognostic importance hemorrhagic expansion was highlighted in the disposition analysis
which showed that zero patients went home if there was recorded expansion.
634. Expression of autophagy signaling molecules in chronic subdural hematoma outer membranes
Koji Osuka, MD (Kuwana, Japan); Nobuteru Usuda, PhD, MD; Masakazu Takayasu, PhD, MD
Introduction: Chronic subdural hematoma (CSDH) is fundamentally treatable although sometimes recurs. However, we experienced
some cases of the spontaneous resolution of CSDH outer membranes, even in a trabecular type of CSDH, after trepanation surgery.
We presented the caspase signaling molecules in CSDH outer membranes at this meeting last year. In this study, we examined the
molecule expression of the autophagy signaling pathway in CSDH outer membranes.
Methods: Eight patients whose outer membranes were successfully obtained during trepanation surgery were included in this study.
The membranes were immediately homogenized in the sample buffer. By western blot analysis, we examined the molecule expression
of mTOR; GbL; ULK1; beclin-1; Atg3, 5, 7, 12, and 13; 16L1b,a; LC3A/B; and b-actin. The expression of beclin-1, Atg12 and LC3A/B
was also examined by immunohistochemistry.
Results: A nearly constant level of b-actin was detected in all cases, suggesting that equal levels of protein were applied. Almost all of
these molecules could be detected in all samples. Beclin-1, Atg12 and LC3A/B were found to be localized in the endothelial cells of
vessels and fibroblasts in CSDH.
Conclusion: We detected molecules of the autophagy signaling pathway in CSDH outer membranes. mTOR and GbL are known as
the key regulators of autophagy induction through ULK1 and Atg13. Autophagy contributes to the tissue homeostatic process,
maintaining cellular integrity by clearing debris. Moreover, Atg5 induces caspase activation by interacting with FADD, a component of
the extrinsic apoptosis pathway. Our data suggest that crosstalk between autophagy and apoptosis might play an important role in the
spontaneous resolution of CSDH. Therefore, these molecules may be novel therapeutic targets for the treatment of CSDH.
635. Cerebrospinal fluid concentrations of macrophage migration inhibitory factor as a potential biomarker of vasospasm in
subarachnoid hemorrhage
Kevin Kwan, MD (Manhasset, NY); Orseola Arapi, BS; Katherine Wagner, MD; Bensam Benziger, MD; Julia Schneider, BS; Chunyan
Li, PhD; Ra Narayan; Mae Ward, RN; Edmund Miller, PhD; David Ledoux
Introduction: Subarachnoid hemorrhage (SAH) patients experiencing cerebral vasospasm suffer from devastating neurologic
outcomes. About 40% of SAH patients have delayed ischemic neurologic deficits (DIND) from vasospasm. Clinical biomarkers that
can predict the onset of vasospasm may help to improve patient outcomes. Macrophage migration inhibitory factor (MIF) is a
pleiotropic cytokine involved in the pathogenesis of numerous inflammatory diseases and plays a role in regulating vascular
inflammation. We assessed the predictive and prognostic value of MIF concentrations in cerebrospinal fluid (CSF) in SAH.
Methods: CSF samples were collected from patients with normal pressure hydrocephalus (NPH) (n=6) or SAH (N=9) who required an
external ventricular drain (EVD) or lumbar drain. MIF concentrations were determined in the SAH group every other day for a total of
13 days. MIF concentrations in CSF correlated with the development of radiographic vasospasm, transcranial dopplers (TCD’s),
delayed cerebral infarct (DCI) and 6 month Glascow Outcome Scale (GOS) scores.
Results: CSF concentrations of MIF (ng/ml) were significantly increased the first day in SAH patients compared to NPH patients,
11.4±8.7 versus 2.2±0.9 (P =<0.028), respectively. The average day CSF MIF levels peaked correlated to the average day TCD’s
peaked, 9.4±2.4 vs 9.85±2.3 respectively, although this result was not significant (P=0 .73). Although concentrations of MIF correlated
with patients that had evidence of DCI versus no DCI, these result were also not significant at 11.7±12.4 vs 5.1±4.12 (P=0.216),
respectively. Average 6 month GOS scores were 4.6±0.89. In patients harboring suspected ruptured aneurysms, 7 received
craniotomies, 1 patient was coiled and one was left untreated.
Conclusions: These results suggest that MIF may be associated with the development of vasospasm and DCI in SAH. Thus, MIF
may play an important role as a biomarker in predicting the onset of vasospasm in SAH patients.
636. Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study
Diogo Cordeiro, MD (Charlottesville, VA); Zhiuan Xu, MD; Gene Barnett, MD; Douglas Kondziolka, MD; Dale Ding, MD; Hideyuki Kano,
MD, PhD; L. Dade Lunsford, MD, PhD; Veronica Chiang, MD; David Mathieu, MD; John Lee; Roberto Martinez Alvarez, MD; Jason
Sheehan MD, PhD

Introduction: Recurrent or residual adenomas are frequently treated with Gamma Knife radiosurgery (GKRS). The most common
complication after GKRS for pituitary adenomas is hypopituitarism. In the current study, we detail the timing and types of
hypopituitarism in a multicenter, international cohort of pituitary adenoma patients treated with GKRS.
Methods: Eighteen institutions pooled clinical data comprised of pituitary adenoma patients who were treated with GKRS from
1989-2017. Patients who underwent prior radiotherapy were excluded. A total of 1023 patients met the study inclusion criteria,
including 410 non-functioning pituitary adenomas (NFPA), 262 with Cushing's disease (CD) and 251 with acromegaly. The median
follow-up was 51 months (range 6 to 246 months). Statistical analysis was performed using a Cox proportional hazards model to
evaluate factors associated with development of new-onset hypopituitarism.
Results: At last follow-up, 248 patients had developed hypopituitarism (86 NFPA, 66 CD, 96 acromegaly). The actuarial 1-year, 3-
year, 5-year, 7-year and 10-year rates of hypopituitarism were 7.8%, 16.2%, 22.4%, 27.5% and 31.3%, respectively. The median time
to hypopituitarism was 39 months. Hormonal changes included 82 cortisol, 135 thyrotropin, 92 gonadotropin, 59 growth hormone and
11 vasopressin deficiencies. Of these patients, 150 (60.5%) had single and 98 (39.5%) had multiple hormone deficiencies.In univariate
analyses, increased rate of new-onset of hypopituitarism was significantly associated with a lower isodose line (p=0.006), whole sellar
targeting (p=0.033) and treatment of functional pituitary adenomas (p=0.008). In multivariate analyses, only a lower isodose line was
found to be an independent predictor of new-onset hypopituitarism (p=0.001).
Conclusion: Hypopituitarism remains the most common unintended effect of GKRS for a pituitary adenoma. Treating the target
volume at an isodose line of 50% or greater and avoiding whole sellar radiosurgery, unless necessary, will likely mitigate the risk of
post-GKRS hypopituitarism. Follow-up of these patients is required to detect and replace latent endocrinopathies.
637. MEG imaging of recurrent gliomas reveals functional plasticity of language networks
Phiroz Erach Tarapore, MD, FAANS (San Francisco, CA); Tavish Traut; Nina Sardesh, BS; Lucia Bulubas; Anne Findlay; Susanne
Honma; Danielle Mizuiri; Mitchel Berger; Srikantan Nagarajan, PhD
Introduction: In patients with glioma, the impact of treatment and subsequent tumor recurrence on language networks is unclear.
Demonstration of plastic reorganization of language networks in these patients has significant implications on the prevention of
postoperative functional loss, as well as the functional recovery after tumor resection and adjuvant treatment. In a cohort of patients
with gliomas, we analyzed changes in hemispheric specialization for language as determined by magnetoencephalography (MEG)
imaging. We explored contributions to these changes due to factors such as demographics, anatomic location, pathology and adjuvant
treatment.
Methods: Whole-brain activity during an auditory verb generation task was estimated from MEG recordings in a group of 73 subjects
with recurrent gliomas. Hemisphere of language dominance was estimated using the language laterality index, a measure derived
from a verb generation task. The initial scan was performed prior to resection; subjects subsequently underwent surgery and
appropriate adjuvant treatment. Upon recurrence, a second scan was performed prior to repeat resection. Shift in language laterality
between these two scans, and contributions from demographics, anatomic location, pathology and adjuvant treatment, were analyzed.
In particular, differences between patients with gliomas ipsilateral and contralateral to the side of language dominance were examined.
Results: Significant shifts were observed in language laterality between scans. Patients with tumors ipsilateral to language dominance
experienced a significantly greater shift in language laterality than those with contralateral tumors. This effect occurred with both left-
and right-sided initial language dominance. The vector (magnitude and relative direction) of the resultant shift was associated with the
initial degree of language dominance.
Conclusion: Patients with glioma experience significant shifts in language function over time. Shift in laterality is associated with
ipsilateral tumors more than with contralateral tumors. These findings may have important implications in understanding the
reorganization of language networks over time.
638. Stereotactic radiosurgery for the management of acromegaly: outcomes of a multicenter retrospective cohort study
Leksell Radiosurgery Award
Dale Ding, MD (Phoenix, AZ); Gautam Mehta, MD; Mohana Patibandla; Cheng-Chia Lee, MD; Roman Liscak, MD; Hideyuki Kano,
MD, PhD; Roberto Martinez-Alvarez, MD, PhD; David Mathieu, MD; Inga Grills, MD; Christopher Cifarelli, MD, PhD; L. Dade Lunsford,
MD; Jason Sheehan, MD, PhD
Introduction: Stereotactic radiosurgery (SRS) is a treatment option for persistent or recurrent acromegaly secondary to a growth
hormone (GH) secreting pituitary adenoma, but its efficacy is inadequately defined. The aim of this multicenter retrospective cohort
study is to assess the outcomes of SRS for acromegaly and determine predictors.
Methods: We pooled data from ten participating institutions of the International Gamma Knife Research Foundation (IGKRF) for
patients with acromegaly who underwent treatment with SRS and had at least 6 months of endocrine follow-up. Baseline and
outcomes data were analyzed, and predictors of endocrine remission were identified using multivariate Cox proportional hazards
regression analysis.
Results: The study cohort was comprised of 371 patients with a mean endocrine follow-up of 79 months. Antisecretory medications
were held in 56% of patients who were on pre-SRS medical therapy. The mean SRS treatment volume and margin dose were 3.0
cm3 and 24.2 Gy, respectively. The actuarial rates of initial and durable endocrine remission at 10 years were 69% and 59%,
respectively. The mean time to durable remission after SRS was 38 months. Biochemical relapse after initial remission occurred in
9%, with a mean time to recurrence of 17 months. Cessation of antisecretory medication prior to SRS was the only independent
predictor of durable remission (P=0.01). Adverse radiation effects included the development of at least one new endocrinopathy in

26% and at least one cranial neuropathy in 4%.

Conclusion: SRS is a definitive treatment option for patients with persistent or recurrent acromegaly after surgical resection. When
deemed appropriate by an endocrinologist, acromegaly patients should be taken temporarily off of antisecretory medications prior to
SRS to improve the efficacy of this intervention.
639. Intraoperative assessment of meningioma proliferative potential revealed intratumoral heterogeneity and its relevance to
biological characteristics
AANS/CNS Joint Section on Tumors Skull Base Award
Soichi Oya, MD, IFAANS (Saitama, Japan); Shinsuke Yoshida, MD; Tsuchiya Tsukasa, MD; Naoaki Fujisawa, MD; Akitake Mukasa,
MD, PhD; Hirofumi Nakatomi, MD, PhD; Nobuhito Saito, MD, PhD; Toru Matsui
Introduction: Proliferative ability of meningioma cells is the critical information in the treatment of meningioma. Although it has been
established as an index of proliferative ability, MIB-1 labeling index (LI) is basically unavailable until several days post-surgery.
Methods: To accurately assess the proliferative ability of meningioma cells during surgery, we utilized the rapid intraoperative flow
cytometry using raw samples. We defined a proliferative index (PI) as the ratio of aneuploid cells with an abnormal number of
chromosomes to whole cells in each specimen. The actual required time for flow cytometry was 10 minutes and conducted during
surgery.
Results: From 50 patients, 118 specimens were analyzed in this study. There was a statistically significant correlation between
postoperative MIB-1 LI and PI (R=0.59, p<.0001). In addition, higher PI was correlated to the higher annual growth rate (AGR,
cm3/year) among 17 tumors for which volumetric analysis based on preoperative serial MR images was available (p=0.041). Beside,
annual growth rate showed a correlation to the intratumoral distribution of PI; PI was highest at the dural attachment in tumors with
low AGR while PI was highest at the center or peripheral portion of tumor in those with high AGR (p=0.046). Peritumoral edema was
observed more frequently when PI was high in the peripheral portion of tumor as opposed to elevations in the dural attachment
(p=0.03).
Conclusion: These data demonstrate two novel findings. First, the rapid intraoperative flow cytometry can become a substitute for
MIB-1
LI, which may contribute to modification of surgical strategy during surgery. Second, the intratumoral heterogeneity of the cellular
proliferative potential exists in meningiomas and is related to their biological characteristics. This highly quantitative method might be
helpful for predicting tumor recurrence and for selecting patients who will benefit from upfront radiosurgery following subtotal resection.
640. Repeat stereotactic radiosurgery for Cushing’s disease: outcomes of an international, multicenter study
American Brain Tumor Association Young Investigator Award
Gautam Unmeel Mehta, MD (Houston, TX); Dale Ding; Amitabh Gupta; Hideyuki Kano; Michal Krsek; Cheng-Chia Lee; Roman Liscak;
Roberto Martinez-Alvarez; L. Dade Lunsford; Mary Lee Vance; Jason Sheehan
Introduction: Stereotactic radiosurgery (SRS) is frequently used for Cushing’s disease (CD) after failed pituitary surgery.
Management of patients with persistent CD after failed SRS is complex, as the alternative therapeutic options harbor significant risks.
The outcomes of repeat pituitary radiosurgery, however, have not been described.
Methods: We pooled data from five institutions participating in the International Gamma Knife Research Foundation (IGKRF) for
patients with recurrent or persistent CD ≥12 months after initial SRS. Patients were included in the study if they had ≥6 months
endocrine follow-up after repeat SRS.
Results: Twenty patients (80% female) were included in the study. Repeat SRS was performed 1.3 to 9.7 years after initial SRS.
Median endocrine follow-up was 6.6 years (1.4-19.1 years). Median margin dose was 20 Gy (range 10.8 to 35 Gy). Endocrine
remission after second SRS was noted in 12 patients (60%), with a median time to remission of 6 months (range: 2-64 months).
Biochemical recurrence occurred in 2 patients (17%) after initial remission. Overall, the cumulative rates of durable endocrine remission
at 5 and 10 years were 47 and 53%, respectively. Two patients (10%) experienced adverse radiation effects, including transient visual
loss and permanent diplopia.
Conclusion: Repeat SRS achieves lasting biochemical remission in approximately half of patients with CD refractory to both prior
microsurgery and SRS. Because of the morbidity of refractory or recurrent CD, repeat SRS should be considered for carefully selected
patients with hypercortisolism confirmed one or more years after initial SRS.
641. In silico identification of neo-antigens in a high-grade pediatric brain tumor cohort utilizing next-generation sequencing:
pilot study of a discovery pipeline for immunotherapy targets
Columbia Softball Pediatric Award
Peter Madsen, MD (Philadelphia, PA); Bo Zhang; Katherine Wang; Angela Waanders, MD, MPH; Phillip Storm, MD; Adam Resnick,
PhD
Introduction: High-grade pediatric brain tumors include a variety of histopathologic entities, but as a group may be more likely to

benefit from immunotherapies given their frequent lack of targetable driver mutations, underlying epigenetic abnormalities, and often
hyper-mutated status. To that end, we present preliminary results from a computational pipeline that seeks to identify potential tumor-
specific antigens for targeted immunotherapy development.
Methods: Advances in computational biology have made it possible to test tumor-specific novel peptides against an HLA-specific
MHC receptor in silico to identify binding epitopes that may illicit a host response or be the foundation for tumor vaccines or adoptive
immunotherapies. Pediatric patients with high-grade brain tumor pathologies for which next-generation sequencing data was available
were identified and subjected to a modified version of this established computational pipeline. Filtered results of this affinity test were
considered to be potential tumor neo-antigens.
Results: A cohort of 31 patients were identified, which included 17 patients with high-grade glioma or DIPG, 12 with medulloblastoma,
and 2 with ATRT. Tumor samples had on average 14 mutations capable of producing novel tumor-specific peptides. When assessed
for MHC binding strength, this yielded an average of 63 candidate neo-antigens per sample with a range of 2-314 candidates. We
identified 32 genes generating candidate neo-antigens that were shared among at least two samples. Some recurrent candidate neo-
antigens noted for further exploration included the product of the H3F3A K27M mutation (found in 5 samples) as well as conserved
mutations in PDGFRA (found in 3 samples) and SLC9B1 (found in 3 samples).
Conclusion: In this pilot study, we identified potential recurrent tumor neo-antigens across multiple patient samples and
histopathological disease types in a small cohort of high-grade pediatric brain tumor patients. Further work is needed to validate this in
silico technique and translate the results into new immunotherapies.
642. Unique nascent RNA sequences that distinguish normal brain and malignant gliomas
Lawrence S. Chin, MD, FAANS, FACS (Syracuse, NY); Tinyi Chu, PhD; Edward Rice, PhD; Gregory Booth, PhD; Hans Salamanca,
MD, PhD; Zhong Wang, PhD; Leighton Core, PhD; Sharon Longo, BS; Robert Corona, DO; John Lis, PhD; Hojoong Kwak, PhD;
Charles Danko, PhD
Introduction: Chromatin run-on sequencing (ChRO-seq) is a newly described technique that uses the RNA polymerase complex for
identifying nascent RNA sequences such as noncoding RNAs that are associated with malignant transformation and progression in
brain tumors. ChRO-seq is more sensitive than RNA-seq and can be used to investigate regulatory elements that are frequent targets
for epigenetic modification. We provide the first maps of nascent RNA transcription in GBM.
Methods: ChRO-seq was used to examine 20 GBM fresh frozen tumor samples, 3 patient-derived xenografts (PDX) and glioma cell
lines, and 13 normal brain speciments. Genomic analysis was used to map the location and quantify nascent RNA species.
Results: Over 90,000 enhancer RNAs were found in GBM cells many that closely resemble normal brain; however, 12% can
distinguish normal from tumor. Most share expression patterns that place them in one of the four commonly known GBM subtypes,
however several were clearly of multiple subtypes. 1343 gene changes were identified that distinguish GBM from normal with most
related to cell cycle, metabolic processes, and cell development notably HOX and EN1 and EN2. Enhancer profiles that are
hypothesized to indicate changes in transcription regulatory elements (TRE) show high similarity between tumor cells and normal
brain and PDXs but were dissimilar to glioma cell lines and cultured normal brain cells. Specifically, these tumor associated TREs
cluster in genes related to stem cell regulation, cell differentiation, and immune cells. Notable stem cell motifs seen were POU and
SOX as well as differentiated cell support motifs such as AP1 and HSF.
Conclusion: ChRO-seq is a powerful new tool that can be used in archived brain tumor samples to provide nascent RNA transcription
maps. Unique signatures have been identified that distinguish GBM from normal brain and provide evidence for the importance of
stem cell motifs in tumorigenesis.
643. ABC transporter inhibition plus vessel permeability reduction enhances the efficacy of CED in DIPG
Vadim Tsvankin, MD (DURHAM, NC); Vadim Tsvankin, MD; Christopher Lascola, MD, PhD; Talaignar Venkatraman, PhD; Brainard
Burrus; Oren Becher, MD; Eric Thompson
Introduction: Diffuse intrinsic pontine glioma (DIPG) is the leading cause of brain tumor-related death in children. The efficacy of in
vitro preclinical models contrasted to poor outcomes in clinical trials suggests the possibility of inadequate drug delivery to the tumor;
this may be due to a combination of poor penetration beyond the blood-brain barrier (BBB) and rapid drug efflux via ATP-binding
cassette (ABC) transporters. Convection-enhanced delivery (CED) circumvents the BBB; however, the mechanism underlying infusate
clearance is poorly understood.
Methods: The multi-kinase inhibitor dasatinib was administered systemically or via CED in transgenic mice harboring histone
H3.3K27M mutant DIPG. Concurrently, infusate retention behind the BBB was augmented by blocking ABC transporters with
tariquidar and reducing BBB permeability with dexamethasone. CED infusate clearance was evaluatd by real-time MRI.
Results: Animals treated with single-administration CED dasatinib (2µM) hshowed increased survival compared to control animals
(median survival 39 and 28.5 days, respectively). Systemic pretreatment with intraperitoneal dexamethasone (0.5mg/kg) and tariquidar
(5µg/kg) prior to single-administration CED dasatinib further increased median survival to 49 days (p=0.0098). Real-time MRI of these
animals demonstrated delayed infusate clearance (as determined by time to peak [TTP] gadolinium intensity) in the group pretreated
with dexamethasone and tariquidar (p=0.0462). Tumor cellular apoptosis was also highest in the pretreatment group (P<0.001).
Continuous delivery of CED dasatinib delivered via continuous infusion pump (5µL at 2µM) did not further prolong survival compared
to single-administration CED dasatinib (median OS 40 days). Intraperitoneal dasatinib (25 mg/kg) resulted comparable survival to
continuous CED dasatinib infusion (median OS 39.5 days).
Conclusion: ABC transporter inhibition and BBB permeability reduction significantly increased TTP of CED infusate, thereby

increasing infusate-tumor contact time. Accordingly, pretreating animals with tariquidar and dexamethasone prior to CED resulted in
enhanced tumor cellular apoptosis and significantly improved survival in histone H3.3K27M mutant DIPG.
644. SYMPHONY: A novel synergistic nanotechnology-based platform for the improvement of laser interstitial thermal
therapy
Pakawat Chongsathidkiet (Durham, NC); Hanna Kemeny; Yang Liu, PhD; Aladine Elsamadicy; Xiuyu Cui, MS; Karolina Woroniecka;
Tuan Vo-Dinh, PhD; Peter Fecci, MD, PhD
Introduction: Laser Interstitial Thermal Therapy (LITT) is an emerging clinical option for the thermal ablation of select intracranial
lesions. Current limitations for LITT, however, include the diameter of ablation (<3cm per trajectory) and lack of inherent specificity for
tumor margins. Gold nanoparticles can act as lightning rods to expand laser treatment coverage. Here, we introduce a novel platform
(SYMPHONY) that employs plasmon-activated gold nanostars (GNS) with selective tumor uptake to increase LITT coverage area and
tumor specificity, while simultaneously availing of LITT’s permissive effects on vascular permeability to improve concomitant
immunotherapeutic efficacy.
Methods: 5 x 105 murine CT2A glioma cells were implanted into the right flank of C57BL/6 mice to permit volume measurements.
Mice were then randomized into treatment cohorts receiving the various permutations of extracorporeal laser, intravenous GNS, and
immunotherapy (anti-PDL-1). Selective GNS uptake in tumors was demonstrated by micro-PET CT, whether tumor was placed in the
brain or flank. Tumor volume and mouse weights were evaluated over time. Long-term survivors were re-challenged with CT2A
tumors in the contralateral flank after 80 days.
Results: GNS were selectively taken up by tumor compared to surrounding tissue. Only GNS+Laser+Anti-PDL1 (3/10) and
GNS+Laser groups (5/10) exhibited long-term tumor-free survival and underwent rechallenge. Mice in the Laser only, Anti-PDL1 only,
and Laser+Anti-PDL1 groups universally succumbed to initial challenge (p<0.0001, One-way ANOVA). When rechallenged, mice that
had initially received GNS+Laser+Anti-PDL1 combination therapy (SYMPHONY) demonstrated immunologic memory and resistance
to tumor-rechallenge compared to the GNS+Laser group (p=0.01, unpaired t test).
Conclusion: We demonstrate here an innovative synergistic platform (SYMPHONY) that uses nanotechnologies to overcome the
current limitations of LITT and simultaneously licenses immunotherapies that would otherwise have poor efficacy. Newer studies in
larger animals and phantom human brains have been initiated with the goal of eventual human translation.
700. Travels to the tropics: “Deutschtum” and Fedor Krause’s visits to Brazil
Vesalius Award
Saul A. da Silva, MD (Sao Paulo, Brazil) Manoeul Teixeira, MD; Evgenii Belykh, MD, PhD; Alessandro Carotenuto, BA; Robert
Spetzler, MD; Mark Preul, MD; Eberval Figueiredo, MD; Mark C. Preul, MD
Introduction: Fedor Krause, the father of German neurosurgery, in the final years of his career traveled to Latin America (1920 and
1922) Krause's associations and motivations for his travels to South America and his work there have not been well chronicled. In this
study, we describe Krause’s activities in South America (focusing on Brazil) within the context of the Germanism doctrine, the efforts
to recover German influence after World War 1, and most importantly the professional enjoyment Krause reaped from his trips, as well
as his lasting neurosurgical influence in South America.
Methods: Historical review of official documents and publications.
Results: Krause's visits to Brazil insert into a context of increasing necessity of Germany to reestablish economic, political, cultural
and scientific power and influence, a doctrine known as "Deutschtum" or "Germanism". Science, particularly medicine, had been
chosen as a field capable to meet these challenges. The advanced German system of academic organization and instruction including
connections and collaborations with industry was an optimal means to re-establish economic viability for Germany, but also of Brazil.
As a kind of ambassador, Krause succeeded in helping to rebuild the German image and in reconstructing diplomatic relations
between Germany and Brazil. Krause was not viewed however as a mere tool -- he was a sincere teacher, and perhaps the most
technically accomplished and advanced neurosurgeon of his time. His unassuming nature endeared Krause to those he met, taught
and with whom he worked; he was known to rapidly adopt new technology that would push the boundaries of surgical technique.
Conclusion: Krause's involvement helped put Brazilian neurosurgery on a firm foundation, and he left an indelible legacy of
neurosurgery's advancing professionalism and specialization in Brazil and elsewhere in Latin America. Unfortunately, within two
decades these relationships would again be disturbed by an even greater world tragedy.
701. Victor Horsley and surgical management of firearm injuries of the head
T Forcht Dagi, MD, MPH, MBA, DMedSc, FAANS (Newton, MA); Javier Fandino, MD, PhD
Introduction: At the time of the Boer War, the major Biritsh conflict preceeding World War I, mortality from gunshot wounds of the
head approximated 100% and these wounds were often purposely neglected. Sir Victor Horsley began studying these wounds at the
end of the 19th century and concluded, by 1915, in advance of Cushing, that a methodical approach to penetrating injuries could save
lives. This presentation reviews his work, its roots and its outcomes
Methods: The military and civilian surgical literature from the end of the 19th century when new weapons and cartridges were
introduced through the end of WWI was reviewed with special attention to Horsley's clinical and research investigation in the context

of the culture of military surgery of the period.

Results: Horsley's work was as important at Harvey Cushing's, though the early emphasis on animal models of head injury did not
have the same influence as Cushing's clinical reports. Horsley succeed, however, in changing the attitude of British military surgical
command, and thus contributed both neurosurgically and politically to the benefit of wounded soldiers.
Conclusion: Horsley deserves to be recognized better for his contributions to the study, pathophysiology and surgery of intracranial
penetrating injury, particularly prior to Cushing's celebrated involvement.
702. Astronaut Michael Collins; Apollo 8 and the anterior cervical fusion that changed the history of the human spaceflight
Richard Menger, MD MPA (Shreveport, LA); Michael Wolf, MD; Jaideep Thakur, MD; Anil Nanda, MD
Introduction: Data from the Longitudinal Study of Astronaut Health illustrated that the incidence of a cervical disc herniation was 21.4
times higher for US Astronauts than standardized controls. Here we explore the 1968 anterior cervical fusion of Astronaut Michael
Collins that changed the history of American spaceflight.
While training for Apollo 8 during the height of the space race, Astronaut Collins started developing symptoms of cervical myelopathy.
Civilian physicians urged posterior decompression which would have permanently grounded Astronaut Collins. However, he
underwent evaluation at Wilford Hall Air Force Hospital in San Antonio and was noted to have a C5-6 disc herniation and posterior
osteophyte on a myelogram. Air Force Lieutenant General (Dr.) Paul W. Myers performed an anterior cervical discectomy with
placement of iliac bone graft. This significantly altered the astronaut flight rotation. Astronaut Collins was placed on a temporary no-fly
status until his post-operative x-rays showed solid bony fusion.
Astronaut James Lovell, the back-up Command Module Pilot, then took his place on Apollo 8 flying the uncertain and daring first
mission to the moon that made one of the most watched TV broadcasts in the history of man. This injury had a cascading effect where
Astronaut Collins was now placed in the position to join the crew of Apollo 11. His anterior cervical fusion indirectly rotated him into
the annals of history as the Command Module Pilot of the first mission that landed men on the moon. Furthermore, the cycle
continued downstream where Astronaut Lovell then became positioned to be the Commander of the fated Apollo 13 flight. The anterior
cervical fusion of Astronaut Michael Collins changed the history of American spaceflight and in indirect ways changed the rotation of
astronauts altering who would walk or fly to the moon.
703. Neurosurgery in Albainia started with Walter Lehman
Mentor Petrela, MD, PhD (Tirana, Albania)
Introduction: In his retirement years, my professor, Xhelal Kurti, confessed that in his earlier experience as neurosurgeon in Albania,
he had used the set of craniotomy brought by Walter Lehman. During the communism period, it was common practice to abnegate all
former contributions to the country medicine, excluding these from the history and the teachings of the faculty of medicine of Tirana.
Gathering the facts, as Suetonius, my father sent me back to the state archives because he knew that eminent Jews doctors fleeing
Nazis had been invited in Albania by King Zog I since 1932. Among them, Dr. Walter Lehman from Charite Hospital of Berlin spent six
years with his family in Albania. As a general surgeon he also brought with him a set of craniotomy and used it for neurosurgical
purposes. The medical files of that period show that he practiced neurosurgery in trauma, infection and lumbar meningoceles. His
pupil the surgeon Dr. Frederick Shiroka and Dr. Xhavit Gjata, a neuropsychiatrist, knew him very well and wrote that Dr. Walter
Lehman with other collegues Dr. Schlessinger, Dr. Quasler, Dr. Kalmar, proposed the project to open the faculty of medicine in 1938
to the King Zog I. Unfortunately with the occupation of Albania by the fascists in 1939, Dr. Lehman and his collegues moved to the
US. The aftermath; they all and especially Dr. Walter Lehman are recognized for their contribution to the modern medicine and
neurosurgery in Albania.
704. Insights into the past and future of atlantoaxial stabilization techniques
Nabeel Saud AlShafai, MD (Toronto, Canada); Minou Behboudi
Introduction: Within the past century atlantoaxial stabilization techniques have improved significantly from the initial attempts with the
usage of silk thread. To our knowledge there is a scarcity of articles published that focus specifically on the history of atlantoaxial
stabilization. Studying the history of instrumentation allows us to evaluate the impact of early influences on modern stabilization
techniques. It also provides inspiration to further develop the techniques and prevents repetition of mistakes. This paper intends to
review the evolution of C1/C2 instrumentation techniques over time and provide insights into the future of the technique.
Methods: Pubmed, embase, scopus, google scholar were searched using the following terms: medical history, atlantoaxial, C1/C2,
stabilization, instrumentation, fusion, arthrodesis, grafting, neuroimaging, biomechanical testing, anatomical considerations, future.
Results: Many different entry zones have been tested as well as different constructs involving hooks, rod-wire techniques and bone
grafts, which led to the development of advanced screw-rod constructs that are currently in use. Much of this evolution is attributable
to the advancements in neuroimaging, a wide range of new materials available and an improvement in biomechanical understanding
in relation to anatomical structures. C1/C2 stabilization started with wiring and bone grafting, inter laminar clamps, hooks, MRI
imaging, trans-articular screws, and current minimally invasive techniques.
Conclusion: This historical review has identified the successes and failures of C1/C2 fusion and knowledge of which we believe
provides a basis for continued innovation. The advances in neuroimaging, smart material availability, and minimally invasive

technologies bring us to the dawn of a new way of stabilizing the atlantoaxial joint.
705. Louise Eisenhardt’s personal notes: how she and “Dr C” collected data and followed patients
Kelsey Hundley, MD (Little Rock, AR); T. Pait, MD; J. Day, MD
Introduction: Dr Eisenhardt and Dr Cushing developed a unique method of following and keeping in touch with patients that covered
a 40 year period. We use every possible clue to be jumped upon in our clinical records and correspondence.
Methods: Dr. Eisenhardt's never before seen personal hand-written notes were reviewed.
Results: Follow up was divided into two categories.Early Follow Up (1912-1932), PBBH: routinely sent letters to each patient two
years after discharge; patients were asked to write on the anniversary of their operation. Patients of special interest, acoustics and
meningiomas for their monograph, were sent stamped, addressed return envelopes. Registry (1933): they developed a tendency after
publication of their acoustic monograph to discontinue follow up. Foundation of the Registry necessitated the use of considerable effort
on our part to gather up old threads, even going so far as to renew contact with patients after 15 to 20 years. Barriers to follow up
included delayed correspondence, lost correspondence, language difficulties, relocation, married with name change, or don’t marry
and name change and so on. Methods of follow up included continued prompt and delayed correspondence of patients; through
relatives, referring physicians and employers; post office, government agencies, newspapers; churches; board of education; insurance
policies, unpaid bills; and strong arm methods, including the Fuller Brush Man and exhumation of body.
Conclusion: Through their unusual method collecting, they developed personal relationships with their patients through many years
that proved to be very gratifying. Drs Cushing and Eisenhardt believed every case was important in adding to our collective knowledge
of various types of tumors particularly in relationship to life expectancies and suggesting improvement in surgical treatments.
706. The history of the operating microscope in neurosurgery: spectacles to virtual reality
Robert Asa Scranton, MD (Houston, TX); Sean Barber, MD; Robert Grossman, MD
Introduction: The operating microscope may be the most important technological development in modern neurosurgery.
Methods: Journal articles, books and personal communications.
Results: The first compound microscopes were created in the 1590s in the Netherlands by telescope makers Hans Lippershey and by
Zacharias and Hans Janssen. The first recorded use in medicine was by the optician Guiseppe Campani in 1686 who used a screw
barrel microscope to examine a leg wound. Carl Nylen, an otolaryngologist, is credited with the first use in cranial surgery in 1921 with
a repair of a labyrinthine fistula. The ophthalmological slit-lamp developed by the Carl Zeiss company shares many features with the
operating microscope. The first modern surgical microscope was developed at Zeiss in Germany in the early 1950s by physicist Hans
Littmann who developed a microscope that could change magnification while maintaining a constant focal length. Beam splitting
technology was also applied creating the diploscope, where two could work with stereoscopic vision. Use was facilitated by mounting
the microscope on the Contraves company counter-weighted stand with hand control of magnetic brakes to allow for 3D movement of
the microscope. The first widespread use of the operating microscope was in otolaryngology and ophthalmology. Use in neurosurgery
was pioneered by Theodore Kurze at the University of Southern California in 1957 who used it in removing an acoustic tumor. Robert
Rand at UCLA, J. Lawrence Pool at Columbia and Charles Drake in Canada were early adopters. In 1958 Peardon Donaghy at the
University of Vermont created a microsurgery laboratory where he and Julius Jacobson, a vascular surgeon, developed microsurgery
of small vessels. Gazi Yasargil came to the laboratory in 1966 to master microneurosurgical techniques.
Conclusion: Microsurgery continues to advance with introduction of navigation and virtual reality. Its greatest impact is in surgical
education and improving patient outcomes.
707. Why Did psychosurgery fail the first time around?
T Forcht Dagi, MD, MPH, MBA, DMedSc, FAANS (Newton, MA); Alexander Dagi, BA; Daniel Nijensohn, MD, PhD
Introduction: Twenty years after the introduction of psychosurgery, it was in decline. The reason most commonly provided is that
psychotropic medications had been introduced, and yet, the historical record speaks to a number of other sociological and political
factors which were no less influential.
Methods: An extensive review of the literature surrounding the claims of psychosurgery and both the medical and the popular
response was reviewed in order to distinguish the ostensive reasons for the social failure of this procedure from the underlying
reasons.
Results: Ostensive reasons included poor neurological outcomes, changes in the view of the mentally ill and scientific critique. While
these were entirely relevant, other important factors included stories of brain washing from the Korean War, the personalities of the
early psychosurgeons, growing opposition from the psychiatric community and dramatic narratives in popular literature and film.
Conclusion: The introduction of psychosurgery was handled very poorly from a public relations and a scientific reporting perspective.
Both professional and popular support waned. Whether or not the vaunted fear of mind control for political purposes can be shown
historically to have asserted the influence claimed, this fear dominated perspectives around neurosurgery for at least fifteen years, and
sounded led to its virtual abandonment in the US and parts of Western Europe.
708. Physician signers of the Declaration of Independence: implications for service for today's neurosurgical leaders

Gail L. Rosseau, MD, FAANS (Glen Ellyn, IL)
Introduction: Physician leaders have always been called upon to serve society as well as individual patients. During the American
Revolutionary era, four physicians were signers of the Declaration of Independence. They were Josiah Bartlett and Matthew
Thompson (NH), Benjamin Rush (PA) and Lyman Hall (GA). Each was engaged in the practice of medicine in 1776. All remained
active in both medical practice and the revolutionary cause throughout the later years of the 18th century.
Methods: The most recent scholarship on the medical and public careers of the four physician signers was examined. Special
attention was placed on the impact of their medical training/careers on their participation in the American Independence Movement.
The impact of their public careers on their medical practice was examined. Interviews with contemporary physicians who have been
elected to public office in the US and UK were conducted.
Results: Recent scholarship on the medical and public careers of the four physician signers of the Declaration of Independence and
interviews with contemporary physician-politicians in the US and UK are presented. Principles common to both patient and public
service include: capacity for independent thinking, attention to the needs of one’s community, belief in the power of an individual to
effect change, respect for one's teachers/mentors, auto-didacticism, and willingness to take responsibility for problems outside of one's
own area of expertise.
Conclusion: Many 21st c. neurosurgeons share characteristics common to these physicians who signed the Declaration of
Independence, leading to opportunities for public office. Reflection upon the lives of these Revolutionary era physician-patriots may
identify principles of service common to the needs of both patients and society that will be useful for neurosurgeons and for the
profession.
709. The neurosurgery ancestry tree
Ghaith Habboub, MD (Cleveland, OH); Samantha Colby, MS; Giyarpuram N. Prashant, MD; Bryan Lee, MD; Min Lang, MS; Shahed
Tish, MD; Jaes Jones, MS; Josephine Volovetz, MS; Pablo F. Recinos, MD; Iain Kalfas, MD; Michael P. Steinmetz, MD; Edward
Benzel, MD
Introduction: Over a hundred years have passed since Harvey Cushing became a neurosurgeon at Johns Hopkins Hospital. Since
that time, the history of neurosurgery has expanded exponentially. While the documentation of history is crucial, it remains a
cumbersome task. Significant amounts of the data were stored in the form of publications, webpages, and human memories.
Visualizing such large amounts of information tends to be an overwhelming mission. Data visualization tools are continuously
improving, and recognizing higher dimensional spaces and data-data interaction has become possible. We present our approach to
maintain and visualize some of the history through graph theory and interactive data visualization. We designed an interactive graph
of chairmen who trained chairmen in all the neurosurgery programs in North America.
Methods: We collected historical data from the following sources: individual neurosurgery department websites, Society of
Neurological Surgeons, and email exchanges with each neurosurgery department. We used d3 library from JavaScript for data
visualization and graph theory/hierarchical edge bundling to make the connections between the nodes. There were four levels of
clustering when creating the graph: chairmen, universities, states, and regions. We deployed the project temporarily at
http://neurosurgery-ancestry.herokuapp.com/ for convenient access.
Results: We obtained data on 162 chairmen. The data were then uploaded to the server, which automatically create the graph. Blue
edges represent all connections. Edges change when hoovering to green and purple which represent trained and trained-under,
respectively.
Conclusion: We provide an ongoing platform for visualizing chairmen-trained-chairmen data. This tool has been used to visualize
large data connections, but to the best of our knowledge it has never been used to create an ancestry tree. The project currently only
includes data visualization of chairmen, but it can be expanded with time and resources. This project is yet to be completed, but it
would be an everlasting self-growing initiative.
710. Long-term pain relief rates after failed stereotactic radiosurgery for idiopathic trigeminal neuralgia: a prospective
comparison of first-time microvascular decompression and repeat stereotactic radiosurgery
William H. Sweet Young Investigator Award
Kunal P. Raygor, MD (San Francisco, CA); Doris Wang, MD, PhD; Mariann Ward; Nicholas Barbaro; Edward Chang, MD
Introduction: Microvascular decompression (MVD) and stereotactic radiosurgery (SRS) are often used to treat refractory trigeminal
neuralgia (TN). Pain recurrence after SRS is common, but the ideal salvage procedure is unknown. We directly compared pain
outcomes after MVD and repeat SRS in a population of patients who failed SRS as initial surgical treatment for refractory TN.
Methods: We reviewed a prospectively-collected, single-institution database of patients undergoing surgery between 1997 and 2014.
Favorable outcome was defined as Barrow Neurological Institute Pain Intensity scores of I and II. Patients were included if they had
typical type 1, idiopathic TN and at least 1 year of follow-up.
Results: Overall, 168 patients underwent SRS as their first TN procedure. Of thirty that failed and had a second procedure at our
institution, 15 underwent first-time MVD and 15 underwent repeat SRS. Those receiving MVD were younger and more likely to receive
≥ 80 Gy radiation during the initial SRS (p<0.05). There were no differences in average follow-up. At last follow-up, 80% of MVD
patients and 33.3% of SRS patients had a favorable outcome (p<0.05). We found that 86% and 75% of the MVD cohort had a
favorable outcome at 1 and 5 years compared to 73% and 27% for the SRS cohort, respectively (p<0.05). On multivariate regression,
performing MVD was statistically significantly associated with favorable outcome (HR 0.12, 95% CI 0.02-0.60, p<0.01). There were no

statistically significant predictors of favorable outcome in the MVD cohort; however, sensory changes were associated with pain relief
in the SRS cohort (p<0.01).
Conclusion: Compared to repeat SRS, patients receiving salvage MVD had longer-lasting pain freedom. The presence of post-SRS
sensory changes was predictive of favorable outcome in the salvage SRS cohort. We hope this information can help counsel patients
and physicians on the ideal treatment selection after failed first-time radiosurgery.
711. Effects of subthalamic deep brain stimulation with gabapentin and morphine on mechanical and thermal thresholds in 6-
Hydroxydopamine lesioned rats
Brian Kaszuba (Rensselaer, NY); Ian Walling, BS; Paul Feustel, PhD; Amelia Stapleton; Damian Shin, PhD; Julie Pilitsis, MD, PhD
Introduction: Chronic pain is the most common non-motor symptom among Parkinson’s disease (PD) patients, with 1.85 million
estimated to be in debilitating pain by 2030. Subthalamic deep brain stimulation (STN DBS) programmed for treating PD motor
symptoms has also shown to significantly improve pain scores. However, even though most patient’s pain symptoms improve, 74% of
patients treated develop new pain symptoms within 8 years.
Methods: To augment response of DBS, we assess effects of combining gabapentin and morphine, with high (150 Hz; HFS) and low
(50 Hz; LFS) frequency stimulation, in the 6-hydroxydopamine rat model for PD. A 9 day paradigm measuring mechanical vonFrey
(VF) and Randal-Selitto (RS), and thermal hot-plate (HPT) sensory outcome thresholds were performed in 9 rats receiving 15 mg/kg
intraperitoneal (IP) gabapentin and 8 rats receiving 1 mg/kg IP morphine. Combined drug+stimulation therapy was compared to either
intervention alone and to baseline levels.
Results: LFS-alone and HFS-alone increased VF thresholds with a mean increase of 10.15 ± 2.45 (p=0.001) and 9.83 ± 2.45
(p=0.001), respectively, from baseline. When gabapentin and HFS were combined, there was no effect. When gabapentin and LFS
were combined, VF thresholds were lowered by -7.89 ± 2.45 (p=0.019). Gabapentin als significantly attenuated LFS effects on Randall
Selitto tests with a mean decrease of -36.6 ± 12.2 (p = 0.037). There was a trend toward increased thresholds with the combination of
morphine and LFS (p=0.062).
Conclusion: Taken together, morphine may augment LFS while gabapentin has an attenuating effect on the anti-nociceptive
response. Likely, gabapentin’s role as a GABA analogue, may alter rostroventral medulla modulation of pain when used in
combination with LFS.
712. Spinal cord stimulation at 10 kHz for treatment of chronic upper limb and neck pain
Kasra Amirdelfan, MD (Walnut Creek, CA)
Introduction: Traditional SCS can cause variability in the distribution and intensity of the induced paresthesias and often results in
inadequate coverage of axial neck pain1,2,3. The goal of this study is to assess the safety and effectiveness of high frequency SCS at
10 kHz in the treatment of upper limb and neck pain.
Methods: Subjects with chronic, intractable neck and/or upper limb pain of ≥5cm (0-10 VAS) were enrolled in a prospective, multi-
center study (ClinicalTrials.gov: NCT02385201). An IDE exemption was obtained from the FDA, and enrollment occurred following
IIRB approval. Subjects with successful trial stimulation were implanted with a Senza® system (Nevro Corp., Redwood City, CA) and
included in the evaluation of the primary safety and effectiveness (≥50% pain relief) endpoints through 12 months post-implant.
Results are presented as mean±standard deviation.
Results: 47 of 51 had a successful trial (92.2% trial success). The most common diagnoses were radiculopathy (n=40), degenerative
disc disease (n=39), and failed neck surgery syndrome (n=27). No neurological deficits were reported. None of the subjects reported
experiencing paresthesia from HF-SCS. Average upper limb pain score decreased from 7.1±1.4cm(n=24) at baseline to
2.2±2.1cm(n=24),
1.6±1.8cm(n=19) and 1.0±1.1cm(n=9) at 3, 6 and 12 months post-implant. Responder rates were 83.3%, 94.7% and 100.0% at 3, 6
and 12 months post-implant. Average neck pain decreased from 7.6±1.3cm(n=42) at baseline to 2.6±2.4cm(n=42), 2.1±2.2cm(n=36)
and 1.7±1.8cm(n=15) at 3, 6 and 12 months post-implant, respectively. Responder rates were 78.6%, 83.3% and 93.3% at 3, 6 and
12 months post-implant, respectively. Pain disability index decreased from 43.2±11.7(n=42) at baseline to 21.6±15.9(n=42),
22.0±16.5(n=36) and 17.1±13.4(n=15) at 3, 6 and 12 months post-implant.
Conclusion: Preliminary results from a multicenter, prospective study using high frequency SCS at 10 kHz to treat upper limb and
neck pain are promising with outcomes similar to SENZA-EU & RCT results for back and leg pain4,5,6.
713. Compensation for neuropathic hyperexcitability in peripheral nerves ultimately fails
Husain Shakil (Toronto, Canada); Steven Prescott
Introduction: Pain caused by damage to or dysfunction of the nervous system (i.e. neuropathic pain) is notoriously difficult to treat.
Hyperexcitability of peripheral nerves is a classic feature of neuropathic pain, and is thought to contribute to the debilitating nature of
this disease. Hyperexcitability develops despite compensatory changes that can offset the effects of pathological changes within
peripheral neurons. This implies that the ability for peripheral neurons to compensate ultimately fails. We hypothesized that
compensatory changes, despite robustly maintaining certain aspects of excitability, fail to maintain others.
Methods: To test this hypothesis, we used an existing conductance based computational model of a peripheral somatosensory
neuron. This model was based on the well-known Morris-Lecar equations, with the addition of subthreshold Hodgkin-Huxley like
sodium and potassium channels. We adjusted parameters within the model to represent compensatory changes in ion channel

concentrations, and measured neuron properties such as rheobase, ATP used per action potential, the minimum firing rate of the
neuron, and neuronal stability.
Results: Consistent with our hypothesis, simulations revealed that within individual peripheral neurons, compensation between
subthreshold potassium and sodium currents to maintain a constant value of rheobase fails to maintain constant values for ATP used
per action potential, the minimum firing rate, and stability.
Conclusion: These results demonstrate the limits of compensation and may help explain how hyperexcitability develops in peripheral
nerves despite compensation. This imperfect compensation may therefore contribute to the pathogenesis of chronic neuropathic pain.
Further research into how compensation functions in the setting of neuromodulation is warranted.
714. Is pain relief efficacy after cingulotomy dependent on lesion number?
Zaman Mirzadeh, MD PhD (Phoenix, AZ); Laura Textor; William Rosenberg, MD
Introduction: Cingulotomy, as treatment for medically intractable pain, is supported by functional neuroimaging studies demonstrating
the anterior cingulate cortex participates in descending modulation of pain and multiple case series reporting generally good pain
outcomes. However, the outcomes of those case series remain highly variable, potentially explained by differences in lesion location
and size. While most perform 1-2 lesions along a single trajectory bilaterally within 4 cm of the frontal horn pole, studies on psychiatric
indications suggest that additional lesions, resulting in a more comprehensive cingulotomy, may improve outcomes. We present two
cases of bilateral, triple-lesion anterior cingulotomy, with tandem lesions along the anterior-posterior axis, that provided excellent
cancer pain relief.
Methods: Stereotactic MR-guided, triple-lesion anterior cingulotomy was performed in two patients with widely-metastatic cancer pain
using a thermoelectric probe (10 mm exposed tip). The first lesion was targeted 20 mm posterior to the frontal horn pole, 10 mm
lateral to midline, and 5 mm superior to the corpus callosum, with subsequent lesions targeted in tandem 7 mm anterior to the prior.
Pain diaries and morphine equivalents (MME) were analyzed for the weeks preceding and following surgery.
Results: Pain VAS for patient 1 improved from <7 (45% of time), <4 (20%) in the pre-lesion week to <7 (1%), <4 (99%) following
surgery. Daily average MME fell from 269 to 69. Patient 2 improved from <7 (68% of time), <4 (9%) in the pre-lesion week to 0 (100%)
following surgery, with daily average MME falling from 196 to 20. Notably, postoperative daily average MME is an overestimation for
these patients who were weaning doses. There were no adverse events.
Conclusion: Bilateral triple-lesion anterior cingulotomy may improve pain control in intractable cancer pain without significant adverse
effects. Further comparative study is necessary.
715. Shunt infection rate in sub-Saharan Africa in a randomized controlled trial of the Bactiseal Universal Shunt
Kerry Vaughan, MD (Philadelphia, PA); Meghal Shah, BS; Edith Mbabazi, MD; Justin Onen, MD; John Mugamba, MD; Peter
Ssenyonga, MD; Benjamin Warf, MD
Introduction: In limited-resource settings, the effectiveness of antibiotic-impregnated shunts in reducing shunt infection rates has not
yet been demonstrated. Our prior retrospective analysis suggested equipoise in sub-Saharan Africa. Shunt infections have important
clinical and cost repercussions that are magnified in low- and middle-income countries. Antibiotic-impregnated shunts need careful
evaluation of their potential economic impact on hydrocephalus treatment in low-resource settings.
Methods: We conducted a single-blinded randomized controlled trial for management of pediatric hydrocephalus patients treated at
CURE Children’s Hospital, Uganda with either Bactiseal Universal Shunt (BUS) or Chhabra Shunt by our 3 staff neurosurgeons. Our
power calculation (alpha=.05,power 80%) to detect a decrease in shunt infections from 12% to 1% over 6-months yielded a 160-
patient minimum cohort. All hydrocephalus pediatric patients (<16years) requiring shunting and without active ventriculitis were
eligible. Our primary outcome was shunt infection diagnosed by clinical presentation and/or CSF analysis with a minimum 6-months of
follow-up; secondary outcomes included mortality, non-infectious complications and re-operations. Analysis was performed with the
log-rank test, chi-square analysis, Fisher’s exact test, and t-test. Shunt functioning was assessed with Kaplan-Meier analysis.
Results: We enrolled and randomized 248 patients to either medium-pressure BUS or medium-pressure Chhabra shunt implantation.
There were no differences in age, gender or hydrocephalus etiology across both groups. We observed 17 shunt infections (8 BUS,9
Chhabra) occurring at a mean 4.8 months post-operatively(p=1.00). There were 45 deaths total, 28 Chabbra patients and 17 Bactiseal
patients (p=0.099). Forty-five patients underwent reoperations: 25 Chabbra patients and 20 Bactiseal patients (p=0.51).
Conclusion: Shunt infection rates and secondary outcomes did not differ significantly across the two shunt types in our pediatric sub-
Saharan population. There is no short-term infection reduction benefit with the BUS that would support the higher initial investment in
the shunt. However, long-term follow-up studies are necessary to determine whether BUS may out-perform standard low-cost shunts
in infection reduction.
716. Optic nerve diffusion tensor abnormality in children presenting acutely with hydrocephalus
Katie Shpanskaya, BS (Stanford, CA); Jennifer Quon, MD; Eli Johnson, BS; Robert Lober, MD, PhD; Samuel Cheshier, MD; Gerald
Grant, MD, FACS; Kristen Yeom, MD
Introduction: Hydrocephalus can result in injury to the optic nerve. This study assesses the white matter (WM) microstructure of the
optic nerves in children acutely presenting with hydrocephalus before and after neurosurgical intervention. Using diffusion tensor
imaging (DTI), we hypothesized that children with hydrocephalus have optic nerve WM abnormalities compared to controls.

Methods: Twenty-one children (mean age: 7.7 years) with clinical signs of obstructive hydrocephalus and acutely presenting with new
posterior fossa tumors underwent MRI at 3T. DTI was performed both at initial presentation and after neurosurgical alleviation of
hydrocephalus. Optic nerve DTI parameters (mean diffusivity (MD) and fractional anisotropy (FA)) were compared to 21 age-matched
healthy controls at initial presentation and at short- and long-term follow-up. Additionally, changes in optic nerve WM integrity before
and after CSF diversion were observed.
Results: Patients with uncompensated hydrocephalus had increased MD and decreased FA in bilateral optic nerves compared to
controls (P<.001). No correlation was seen between the DTI metrics and ventricular size, as measured by frontal horn distance.
Following surgical intervention (median follow-up time: 12.5 days), normalization of bilateral optic nerve MD and right optic nerve FA
was observed (P<.001). Although left optic nerve FA increased, this effect was not significant (P=.273). Long-term analysis of optic
nerve DTI parameters (median follow-up time: 3.75 years) showed complete recovery of optic nerve MD and FA measures similar to
those of healthy controls.
Conclusion: This study provides the first evidence of loss of optic nerve WM integrity as quantified by DTI in children with obstructive
hydrocephalus. Surgical intervention was seen to restore optic nerve DTI parameters at short- and long-term follow-up. Surveillance of
optic nerve DTI has the potential to serve as a future quantitative marker in the neurosurgical evaluation of hydrocephalus.
717. Calgary Shunt Protocol, an adaptation of the Hydrocephalus Clinical Research Network shunt protocol reduces risk of
shunt infection in children
Michael M.H. Yang, MD (Calgary, Canada); Walter Hader, MD, MSc; Kelly Bullivant; Mary Brindle, MD; Jay Riva-Cambrin, MD, MSc
Introduction: The shunt protocol developed by the Hydrocephalus Clinical Research Network (HCRN) was shown to significantly
reduce shunt infections in children. However, its effectiveness has not been validated in a non-HCRN, small to medium volume
pediatric neurosurgery center. This study evaluates whether the 9-step Calgary Shunt Protocol (CSP) closely adapted from the HCRN
protocol reduced shunt infections.
Methods: The CSP was prospectively applied at Alberta Children’s Hospital from May 23rd, 2013 to all children undergoing a shunt
procedure. Children undergoing shunt surgery between Jan 1st, 2009 and prior to the implementation of the CSP acted as the control
cohort. The strict HCRN definition of shunt infection was applied. Univariate analyses of the protocol, individual elements within, and
known confounders (age and etiology) were performed using student t-test for measured variables and Chi-square for categorical
variables. Multivariate logistic regression was performed using stepwise analysis.
Results: A total of 268 shunt procedures were performed. The median age was 14 months (IQR 3-61) and 148 (55.2%) were males.
There was a significant absolute risk reduction of 10.0% in shunt infections (12.7% to 2.7%, p=0.004) after implementation of the
CSP. In univariate analyses, chlorhexidine compared to povidone skin prep (4.1% versus 12.3% infection rates, p=0.02) and waiting ≥
20 min between receiving preoperative antibiotics and skin incision (p=0.02) reduced shunt infections. In multivariate
analyses, only protocol implementation independently reduced shunt infections (OR 0.19 [95%CI 0.06-0.67], p=0.004); while etiology,
surgeon, type of ventricular catheter, procedure type, skin prep, and time to preoperative antibiotics were not significant.
Conclusion:
This study externally validates the published HCRN protocol for reducing shunt infection in an independent, non-HCRN, and small to
medium volume neurosurgery setting. Chlorhexidine skin prep and waiting ≥20 min between preoperative antibiotic and skin incision
may have contributed to the protocol’s quality improvement success.
718. Exome sequencing defines the molecular pathogenesis of Vein of Galen malformation
Daniel Duran, MD (New Haven, CT); Jungmin Choi, PhD; Jonathan Gaillard, BS; Xue Zeng, BS; Charuta Gavankar Furey, BA;
Edward Smith, MD; Darren Orbach, MD, PhD; Alejandro Berenstein, MD; Murat Gunel, MD; Richard Lifton, MD, PhD; Kristopher
Kahle, MD, PhD
Introduction: Vein of Galen malformations (VOGMs) are morbid and often lethal developmental arteriovenous malformations, with
poorly described genetic underpinnings. Despite improvement in endovascular treatment, mortality from this disease remains high.
VOGM has been reported as a rare finding in Capillary Malformation-Arteriovenous Malformation Syndrome (RASA1; OMIM #605384)
and Hereditary Hemorrhagic Telangiectasia (ENG, ACVRL1; OMIM #187300 and #600376, respectively). This paucity of genetic data
results from intrinsic limitations of patient recruitment in a frequently deadly disease, and constraints of traditional targeted genomic
techniques. Large-scale, collaborative recruitment and unbiased whole-exome sequencing (WES) are poised to overcome these
barriers for gene discovery.
Methods: Germline DNA was isolated from 50 unrelated probands harboring radiographically-confirmed VOGMs. Both parents were
available for 48/50 probands. Targeted exome capture, followed by paired-end WES was performed on DNA samples from all
participating individuals (n=148). Sequencing data was bioinformatically analyzed to identify rare de novo and transmitted mutations,
and insertions/deletions. Unbiased binomial analysis tested for exome-wide statistical significance of mutational burden. All candidate
mutations were confirmed by Sanger sequencing.
Results: Mutations in previously reported VOGM-associated genes were found in only 2/50 patients (4%; RASA1 n=1; ACVRL1 n=1)
in our cohort. Exome-wide significant enrichment of rare damaging mutations was found for a member of the EPHB receptor tyrosine
kinase family (p = 3.64x10-7, 72.12-fold enrichment), a critical regulator of embryonic vasculogenesis (n=4; 8%). Novel damaging
mutations were found in five other genes of the ephrin family. Additionally, two novel damaging mutations were found in a close
paralog of the HHT-causing ACVRL1, never previously implicated in human disease.
Conclusion: This work represents the largest phenotyped and exome-sequenced VOGM cohort in the world. Our findings uncover the
genetic determinants of VOGM pathogenesis, provide novel insight into vascular developmental biology, and identify potential

therapeutic targets.
719. The global incidence and prevalence of hydrocephalus
Albert Isaacs, MD (Calgary, Canada); Albert Isaacs, MD; Jay Riva-Cambrin; Daniel Yavin, MD; Aaron Hockley; Mark Hamilton
Introduction: The global epidemiology of hydrocephalus has not been well defined, which has significant negative implications for
patient care, as it presents challenges for resource planning, research funding and economic treatment analysis. We present the first
global epidemiology of hydrocephalus stratified by age, continent, income level, and mandatory folate fortification status.
Methods: MEDLINE, EMBASE, Google Scholar and the Cochrane Database were searched for all population-based studies reporting
the epidemiology of hydrocephalus. Age groups were stratified into pediatric, adults and elderly (< 18; 18 - 64; and ≥ 65 years of age,
respectively). Only papers that scored 3/8 on a validated quality assessment score were included. Th annual incidence of
hydrocephalus diagnosed at birth, reported from 36 countries was retrieved. Data was analyzed by pooled random effects model
meta-regression.
Results: With respect to prevalence, 52/2,460 studies representing a total population of 171,558,651 met inclusion criteria. The mean
prevalence of hydrocephalus, all ages, was 85/100,000 [95% CI 62, 116]. When stratified by age, it was 88/100,000 [95% CI 72, 107]
in pediatrics; 11/100,000 [95% CI 5, 25] in adults; and 175/100,000 [95% CI 67, 458] in the elderly, increasing to over 400/100,000 in
the < 80-year-old group. The average annual incidence was 81/100,000 [95% CI 79-84], which had remained stable over the 11
years. A significantly lower incidence of hydrocephalus was associated with countries having a high level of income. However, there
was no difference in incidence between countries with or without mandatory folate fortification legislation.
Conclusion: This study is the first of its kind, presenting global epidemiological data on hydrocephalus. The overall prevalence and
incidence of hydrocephalus are reasonably reported in children but otherwise variable. The overall prevalence of hydrocephalus
should be expected to rise with aging demography, which underscores the importance of robust healthcare resource allocation and
future planning.
720. lumbar disc herniation requiring microdiscectomy in the pediatric population: risk factors, presentation and functional
outcomes
Malia McAvoy (Boston, MA); Heather McCrea, MD; Hoon Choi, MD; Linda Bi, MD; Vamsidhar Chavakula, MD; Mark Proctor, MD
Introduction: While there is a large body of literature on lumbar herniated discs and lumbar microdiscectomy in adults, there is a
scarcity of literature on the pediatric population. We analyzed risk factors, clinical presentation, and surgical outcome of a large single-
institution series of patients who underwent lumbar microdiscectomy over 19 years.
Methods: Retrospective chart review was conducted on 199 consecutive cases of lumbar microdiscectomy performed at Boston
Children’s Hospital from 1998 to 2017. Pre-morbid risk factors, clinical presentation, physical exam findings, type and duration of
conservative management, indication for surgical intervention, complications, and post-operative outcomes were examined.
Results: Average age at presentation was 16.0 years (range 12-18 years) and 55.8% were female. Of these patients, 67.8%
participated in sports and among those who did not play sports, 64.1% had a body mass index (BMI) greater than 25. The average
time between onset of symptoms and surgery was 11.7 months during which 98.0% of patients failed conservative management.
Complications included 5 cases of post-operative cerebrospinal fluid (CSF) leak (2.5%), 3 cases of wound infection (1.5%), including 1
case of meningitis and 1 case of diskitis, and 1 new neurological deficit (0.5%). At the first postoperative appointment (5.0 weeks after
surgery on average), minimal or no pain was reported among 96.0% of patients and 88.1% of patients who missed school for surgery
had returned. The average time to return to sports after surgery was 9.8 weeks. On long-term follow-up, 2.5% of all patients required
re-operation for the same level, and 4.5% underwent adjacent level decompression. One patient required a two-level decompression
and ultimately required a fusion.
Conclusion: Microdiscetomy is an effective and safe treatment option for long-term relief of pain and return to daily activities among
patients with symptomatic lumbar disc disease who have failed conservative management.
721. Non-surgical treatment to prevent post-hemorrhagic hydrocephalus of prematurity
Fatu S. Conteh, MD (Baltimore, MD); Akosua Oppong, BS; Tracylyn Yellowhair, BS; Jessie Maxwell, MD; Lauren Jantzie, PhD;
Shenandoah Robinson, MD
Introduction: Currently post-hemorrhagic hydrocephalus of prematurity (PHHP) is treated only with surgery. The most common
surgical intervention, ventricular shunts, are prone to malfunction and infection. Globally, most children do no have access to safe and
timely surgery. Motile ependymal cilia (MEC) propel cerebrospinal fluid. Genetic mutants with impaired MEC maturation develop
symptomatic hydrocephalus with both ventriculomegaly and progressive macrocephaly. We predict that CNS injury from systemic
inflammation plus intraventricular hemorrhage (IVH) impairs MEC maturation, leading to symptomatic hydrocephalus. We hypothesize
that neonatal treatment with erythropoietin (EPO) plus melatonin (MLT) can restore MEC maturation and prevent hydrocephalus.
Methods: With IACUC approval, we induced prenatal injury on embryonic day 18 that mimics chorioamnionitis (CAM). On postnatal
day 1 (P1), pups of both sexes were randomized to intraventricular injection with vehicle (sterile saline) or littermate lysed red blood
cells (IVH). On P2 CAM-IVH injury pups were randomized to extended treatment with EPO+MLT or vehicle. Intra-aural measurement
(IAM-surrogate for head circumference) was measured and neurodevelopment tested. MRI was performed on P21. Groups were
compared with two-way ANOVA with Bonferroni-correction for parametric, and Wilcoxon rank sum for non-parametric, with p<0.05

significant="" p=""<
Results: At P21 CAM-IVH rats had larger IAM than sham-vehicle, sham-IVH or CAM-vehicle rats (n=13-27, two-wayANOVA, p<0.01).
In a second cohort, at P21 EPO+MLT-treated CAM-IVH rats had macrocephaly (n=15-28, p<0.01). At P21 T2 MRI showed all (7/7)
vehicle-treated CAM-IVH rats had ventriculomegaly, while 40% (4/10) EPO+MLT-treated CAM-IVH rats ha no ventriculomegaly.
Neurodevelopmental performance on cliff aversion normalized with EPO+MLT treatment (n=11-31, p<0.01). Corpus callosum
fractional-anisotropy and radial diffusivity normalized after treatment, compared to vehicle-treated CAM-IVH rats (n=4-8, both
p<0.005).
Conclusion: These results suggest that early treatment with clinically-available, safe neuro-reparative agents can potentially restore
motile ependymal cilia function and prevent symptomatic hydrocephalus.
722. Pediatric supratentorial ependymoma: surgical, clinical, and molecular analysis
Jock Lillard (Memphis, TN); Jock Lillard, BS
Background: We present our experience with pediatric supratentorial ependymomas over a 24-year period.
Methods: Clinical, operative, and radiographic information was abstracted retrospectively. Children enrolled in an ongoing clinical trial
were excluded. Our primary outcomes were progression free survival (PFS) and overall survival (OS). Detection of C11orf95-RELA
rearrangement was performed using interphase fluorescence in situ hybridization (iFISH).
Results: Seventy-three patients were identified (41 female, 32 male), with a median age of 6.7 years (range, 1 month-18.8 years).
Median follow up was 8.3 years (range, 2.0-26.3). Fifty-eight (79.5%) of 73 patients underwent gross total resection (GTR) and no
patient with subtotal resection (STR) had greater than 1cm3 of residual tumor. Forty-two patients (57.5%) experienced subsequent
disease progression with 17 patients ultimately dying of their disease. Median PFS was 3.7 years. Molecular analysis was available for
51 patients (70%). On bivariate analysis, PFS and OS were not statistically affected by age, tumor grade, or extent of resection,
although there was a clinically significant trend for the latter in favor of aggressive resection on PFS (p=0.061). Children with RELA
fusion had significantly higher PFS (p=0.013) than those without, although there was no difference in OS when compared with those
with no C11orf95- RELA fusion or C11orf95 gene rearrangement alone.
Conclusion: In our series, GTR may be associated with better PFS, but did not impact OS. Surprisingly, RELA fusion was not found
to be a negative prognostic factor, raising the possibility that the deleterious effects may be overcome by aggressive resection.
723. The addition of choroid plexus cauterization may reduce post-hemispherectomy hydrocephalus: early UCLA experience
Alexander Tucker, MD (Los Angeles, CA); Anthony Wang, MD; Gary Mathern, MD; Aria Fallah, MD
Introduction: Hydrocephalus after hemispherectomy is common with approximately 23% of patients requiring lifelong cerebrospinal
fluid (CSF) diversion. Several groups have reported success in treating infantile hydrocephalus with choroid plexus cauterization
(CPC), commonly performed with simultaneous endoscopic third ventriculostomy (ETV). Given this, the addition of CPC was included
in all recent hemispherectomy procedures performed at UCLA. We retrospectively reviewed our case series to determine if
hemispherectomy with CPC had a lower rate of hydrocephalus compared to the published norms.
Methods: Demographic and clinical data of all patients undergoing hemispherectomy between 2016 and 2017 at UCLA Mattel
Children’s Hospital were reviewed.
Results: A total of 12 cases, 8 males and 4 females, were included in this analysis. Average age at time of surgery was 6.2 years ol
(range: 7 months to 14 years). Pathologies included MCA stroke (42%), multilobar cortical dysplasia (25%), Rasmussen’s encephalitis
(17%), Sturge-Weber syndrome (8%) and hemimegalencephaly (8%). Eleven of the 12 patients (92%) attained seizure freedom.
Average follow-up was 175 days. No patient who received simultaneous unilateral CPC during hemispherectomy developed
hydrocephalus. The only patient who did not receive CPC developed hydrocephalus necessitating ventriculoperitoneal shunt
placement. This patient developed intermittent shunt failure and underwent a delayed ETV with bilateral CPC and was able to have
his shunt removed.
Conclusion: CPC can lower the development of post-hemispherectomy hydrocephalus when performed during the initial procedure.
Furthermore ETV with CPC may eliminate shunt dependence when performed after the development of hydrocephalus in patients who
have undergone hemispherectomy. Given that hydrocephalus and shunt-related morbidity is of great importance following the
resolution of seizures for these children, we advocate routinely performing CPC in addition to the traditional techniques utilized to
prevent post-hemispherectomy hydrocephalus.
724. Excavation and not ulceration best describes the process of plaque degradation
Cerebrovascular Section Best Clinical Scientific Paper
Hossein Mousavi (Portland, OR); Howard Yonas
Introduction: Although the inflammatory and degenerative processes have a cause for the loss of endothelial cap integrity and
ulceration are well characterized, the role of hemodynamic forces in plaque degradation has not been well described. The objective in
this study is to determine whether there is a common pattern of plaque degradation that could be explained by the effect of
hemodynamics.
Methods: 413 plaques were obtained at endarterectomy in patients with high grade carotid stenosis. Plaque were removed without

disruption and were photographed using an operating microscope. The whole and sections of the plaques were imaged with attention
to best record the plaque morphology. Longitudinal sections were often necessary to record the relationship of the plaque surface
disruption and intra plaque gross pathology. 345 sets of plaque images were available for a retrospective review.
Results: Carotid plaque ulceration (endothelial cap disruption) was observed in 283 plaques (82%) in which 91% of ulceration
occurred upstream to the point of maximal stenosis (POMS), 7% at POMS and 2% downstream to POMS. Intra-plaque hemorrhage
(IPH) noted in 235 plaques (68%), and 93% of IPH was in continuity to the upstream ulceration, and plaque content was exposed to
ICA lumen in 62%. Intra-plaque false luminal formation was observed in 165 plaques (48%).
Conclusion: The high prevalence of ulceration upstream to POMS suggests that such ulcerations are among the first hemodynamic
effects on carotid plaques. Furthermore, IPH most often occurs with pre-existing ulcerations which suggests that ulceration is a
prerequisite for IPH formation. The lower prevalence of false luminal formation suggests that such lumenization happens later in the
course of the disease when some or all of the plaque materials are carried into the cranial circulation. Therefore, we conclude that
plaque excavation is the hemodynamically driven process that leads to ulceration, IPH and false luminal formation.
725. Observation of cortical spreading depolarizations after chronic subdural hematoma evacuation
Laila Malani Mohammad, MD (Albuquerque, NM); Mohammad Abbas, MD; Rosstin Ahmadian, BS; C Shuttleworth; Andrew Carlson
Introduction: Chronic subdural hematoma (cSDH) is one of the most common pathologies treated by neurosurgeons. Most patients
recover after evacuation with a straightforward course. There is a subset of patients who do not improve or even worsen after
evacuation. While some of these patients may have focal seizures, we hypothesize that some cases may be related to temporary
brain dysfunction caused by cortical spreading depolarizations (CSD).
Methods: Prospective observational study of 20 patients who underwent cSDH evacuation. At the time of surgery, a 1x6 subdural
electrode strip was placed on the cortex parallel to the drain and removed at the time of drain removal. CSD was scored using
standard criteria of propagating DC shift, with associated depression of high frequency Electrocorticography (ECog) activity. Clinical
outcomes were assessed utilizing the Markwalder Grading Scale (MGS).
Results: All subjects were all found to have a readable ECog for a total recording time of 685h,16m. Definite CSD occurred in 2/20
subjects (10%). One subject had 4 CSDs during 22 hours of recording, and one had 7 CSDs in 51 hours of recording. Both subjects
had adequate evacuation of the cSDH, with improvement in mass effect. 16 of the 20 subjects demonstrated improvement in their
MGS post op, and 4 patients demonstrated no change, remaining at a 1. Of the two patients with CSD, both had a 1 point
improvement in their MGS score, with no signs of clinical deterioration.
Conclusion: This is the first observation of CSD occurring after cSDH evacuation, at a rate of 10% in our series. Since CSD is known
to cause transient neurological dysfunction in eloquent cortex, this phenomenon may be responsible for some cases of delayed clinical
deterioration. None of our subjects demonstrated delayed clinical deterioration, so further observations are required to support this
hypothesis.
726. Initial provider type is associated with opiate use in patients with newly diagnosed low back pain
Tej Azad (Floyds Knobs, IN); Daniel Vail; Jason Bentley; Summer Han; Anand Veeravagu; Manisha Desai; Jayanta Bhattacharya;
John Ratliff
Introduction: Low back pain is one of the most common reasons for seeking medical care. Patients present to a variety of medical
providers and receiving a spectrum of treatment, including opiates. It is increasingly evident that prescription opiates contribute to the
opioid epidemic, but the role of individual medical providers remains unclear. Provider behavior in patients with newly diagnosed
lumbar spine pain may impact long-term opioid use.
Methods: We performed a retrospective analysis of of the Marketscan database for patients who were diagnosed with low back and
lower extremity radicular pain in 2010, did not have a red flag diagnosis or cancer, and had not received an opiate prescription in the
six months prior to diagnosis. We identified the type of provider associated with the initial diagnosis of lumbar spine pain. We
assessed the association between initial provider type and receipt of an opiate prescription, early opiate prescription (< 14 days), and
long-term opiate use, defined as six or more prescriptions in the 12 months following diagnosis, adjusting for patient demographics
and Elixhauser comorbidities.
Results: We identified 478,981 opiate-naïve patients who received a new diagnosis of low back pain in 2010, 40.4% of whom
received an opiate prescription in the year following diagnosis at a median of 21 days after diagnosis. Patients first diagnosed by
emergency medicine (odds ratio (OR), 2.4) or urgent care (OR, 2.1) providers were more likely to receive an early opiate prescription,
but were less likely to progress to long-term use. Patients initially diagnosed by pain management/anesthesia (OR, 2.1) or physical
medicine and rehabilitation (OR, 1.4) providers were to use opiates long-term.
Conclusion: Initial provider type influences patterns of early opiate prescription and long-term opiate use among opiate-naïve patients
with newly diagnosed low back and lower extremity pain.
727. Development of an intraoperative electrophysiological monitoring simulator for a peripheral nerve schwannoma model
Peter Yongsoo Joo (Rochester, NY); Shivali Mukerji; Rachel Melnyk; Ahmed Ghazi; G. Edward Vates, MD, PhD; Jonathan Stone, MD,
MS
Introduction: Simulation training is important for rare diseases like peripheral nerve tumors and may reduce unnecessary risks to
patients during resident education. This project aimed to develop a simulator that measures nerve stretch for performance feedback

metrics and replicates intraoperative stimulation for use during practice resection of a sciatic nerve schwannoma.
Methods: Using 3D printed injection molds and polyvinyl alcohol (PVA) hydrogel, a realistic peripheral nerve schwannoma surgical
phantom was fabricated. In order to measure nerve stretch and electrical stimulation, conductive wires were implanted into the nerve
and connected to a computer through a digital analog converter. For stretch validation, the conductive sensor was stretched vertically
in 1cm increments and voltage was recorded. To test the ability for electrical stimulation to locate nerve fascicles, a tumor model was
stimulated around the transverse circumference in 0.5mm increments. Voltage at each distance from the nerve fascicles was
recorded.
Results: An accurate measure of nerve stretch and identification of the location of simulated fascicles were demonstrated. The mean
percent voltage change during nerve stretch was 22.5% increase per centimeter (SD=0.06) up to 5cm of stretch from baseline. Upon
stimulation, there was a 117% increase in voltage when the probe was within 5mm (p=0.005) of the fascicle compared to areas
absent of nerve fascicles.
Conclusion: Simulation can protect patients from novice errors of basic technique. A low-cost, high fidelity schwannoma resection
simulator was achieved using 3D printing, PVA hydrogels, and conductive wiring. Incorporation of the electrical wire was critical to
provide metrics on the degree of nerve stretch and fascicular damage, and permit intraoperative stimulation to simulate realistic
operative procedures. The stretch sensor and nerve stimulation simulator showed efficacy in measuring degree of stretch and
accurately locating nerve fascicles, enhancing the capabilities of the simulator to provide valuable metrics and emulate a realistic
experience.
728 American views of Sir Victor Horsley in Cushing's era
Vesalius Award
Kurt R Lehner (Astoria, NY); Michael Schulder, MD
Introduction: Much of modern neurosurgery's view of Sir Victor Horsley has been colored by a single passage from John Fulton's
biography of Harvey Cushing describing a frenetic, disorganized Horsley hastily performing a Gasserion ganglionectomy in a British
kitchen. We examined contemporary views of Horsley to assess his reputation in the United States and Canada during his lifetime.
Methods: Surgical and neurosurgical textbooks from 1890-1920 were searched for references to Horsley. Stephen Paget's biography
Sir Victor Horsley: A Study of His Life and Work was searched for references to relationships between Horsley and Americans.
Biographies from individuals identified were searched for references to Horsley and pertinent documents including diary entries and
letters were obtained from collections in North American and European libraries. A PubMed search for "Victor Horsley" limited to
articles by American authors from 1870-1960 was also conducted. Newspaper articles with references to Horsley were also collected
to assess the American public's view of Horsley.
Results: Surgical and neurosurgical texts demonstrated numerous citations of Horsley’s surgical and scientific findings. The positive
reception of his work is corroborated by invitations for Horsley to speak in America. Research additionally revealed that Horsley had
numerous personal and professional relationships with prominent Americans in medicine including William Osler, John Wheelock
Elliot, Ernest Sachs and Harvey Cushing. Horsley’s contributions to medicine and science were heavily reported in American
newspapers; outside of neurosurgery, his strong opposition to the anti-vivisectionists and his support for alcohol prohibition were
widely reported in popular media.
Conclusion: Writings from and about prominent Americans reveal that Horsley was viewed favorably by those who knew him, and
frequent publication of his views in the American media suggest that medical professionals and the United States public valued his
contributions on scientific and social issues.
729. Prospective multicenter study comparing surgical outcomes of microscopic transsphenoidal surgery and fully
endoscopic transsphenoidal surgery techniques for nonfunctioning pituitary adenomas (TRANSSPHER Study)
Integra Foundation Award
Andrew Scott Little, MD, FAANS (Phoenix, AZ); Daniel Kelly, MD; Paul Gardner, MD; Juan Fernandez-Miranda, MD; William White,
MD; James Chandler, MD; Daniel Prevedello, MD; Marc Mayberg, MD; Garni Barkhoudarian, MD; Michael Chicoine, MD
Introduction: The recent adoption of fully endoscopic transsphenoidal surgery over microscopic transsphenoidal surgery has occurred
despite the absence of high quality evidence suggesting the technique yields superior patient outcomes. Results of the first
prospective multicenter study comparing these techniques are presented. (ClinicalTrials.gov NCT02357498)
Methods: This multicenter, prospective study compared extent of tumor resection of fully endoscopic transsphenoidal surgery to
microscopic surgery in adults with nonfunctioning adenomas. The primary endpoint was gross total tumor resection (GTR) as
determined by postoperative MRI. MRI scans were centrally adjudicated by blinded reviewers. Numerous supplementary endpoints
were also evaluated.
Results: 7 pituitary centers and 14 surgeons participated. 530 patients were screened and 260 were enrolled (82 microscopic, 177
endoscopic, 1 cancelled surgery) between February 2015 and June 2017. Tumor anatomical characteristics were well matched
between groups. The microscopic surgeons were more experienced (i.e. number of career pituitary cases) then the endoscopic
surgeons (p<0.001). To date, 238 patients (91.5%) have reached the primary endpoint. GTR was achieved in 79.5% (58/73) of the
microscopic patients and 83.6% (138/165) of the endoscopic patients (p=0.46). Length of stay, deaths from surgery, and 30-day
unplanned readmission rates were similar between groups. The rate of acute diabetes insipidus/hypernatremia after surgery favored
the endoscopic cohort (p=0.02), whereas the length of surgery favored the microscopic group (p<0.001). A multivariate logistic

regression model evaluating independent predictors of GTR suggested that the endoscopic technique was more likely to result in GTR
than the microscopic technique (p=0.036, OR 10).
Conclusion: In this multicenter, prospective study experienced microscopic surgeons and less experienced but proficient fully
endoscopic surgeons achieved overall similar patient outcomes. The endoscopic technique was associated with lower rates of acute
diabetes insipidus and independently predicted GTR, but operative times were significantly longer. Vision and long-term endocrine
outcomes are forthcoming.
730. Predictors of recurrence, progression, and retreatment in basilar tip aneurysms: a location-controlled, Kaplan-Meier
analysis
Isaac Abecassis, M.D.; Rakshith Shetty, M.B.B.S., MCh.; Cory Kelly, B.S.; Basavaraj Ghodke, M.D.; Danial Hallam, M.D.; Michael
Levitt, M.D.; Louis Kim, M.D.; Laligam Sekhar, M.D.
Introduction: Endovascular treatment of intracranial aneurysms is associated with higher rates of recurrence and retreatment, though
specific rates for basilar tip aneurysms are less well elucidated.
Methods: We retrospectively reviewed medical records for 141 patients treated with microsurgical or endovascular interventions for
basilar tip aneurysms. We included 158 anterior communicating artery (ACoA) and 118 middle cerebral artery (MCA) aneurysms as
controls treated during the same time. We obtained information from presentation, hospitalization, and follow-up. Univariate and
multivariate modeling was used to calculate rates of progression (including recurrence of previously obliterated aneurysms and
progression of known residual aneurysm or neck), retreatment, and retreated progression. Kaplan-Meir estimation was used to predict
24-month event rates for primary outcomes.
Results: Of the basilar tip aneurysm patients, 88 (62.4%) were ruptured and 53 (37.6%) were unruptured. Average follow-up was 33
months. There were no differences in demographics between clip and coil, though patients in the clip groups had wider neck
aneurysms. There were 2 re-hemorrhages due to recurrence in the ruptured clip group (6.1%), and none in any of the other cohorts.
There were no differences between clip and coil subgroups for progression, retreatments, or retreated progression, though ruptured
aneurysms had higher event rates in all 3 categories. Multivariate modeling of these variables confirmed rupture status (p=0.003, HR =
0.14, 95% CI 0.04-0.51) and aneurysm dome width (p=0.005, HR = 1.23, 95% CI 1.06-1.43) as independent predictors of retreated
progression, with residual aneurysm/neck approaching significance (p=0.079). In a separate multivariate analysis with ACoA and MCA
aneurysms, basilar tip location was an independent predictor of progression, retreatment, and retreated progression.
Conclusion: Basilar tip aneurysms have higher rates of progression (28.9%), retreatment (28.9%), and retreated progression (24.7%)
than other aneurysm locations, independent of the effect of endovascular intervention. Rupture status significantly predicts progression,
retreatment, and retreated progression.
731. Formation of intracranial de novo aneurysms and recurrence after neck clipping – a systematic review and meta-
analysis
Alexander Spiessberger (Zurich, Switzerland); Deborah Vogt, PhD; Javier Fandino; Serge Marbacher, MD, PhD
Introduction: Incidence rates of recurrent and de-novo aneurys-ms remain controversial. In this meta-analysis we provide data on
pooled annual incidence rates and the association of patient characteristics with time to formation of recurrent and de-novo
aneurysms.
Methods: A systematic literature Review was performed. Association of age, rupture status, multiplicity and anatomic location with
time to recurrence or de-novo formation was estimated using multivariable Cox proportional hazards models. Kaplan-Meier estimators
(event-free survival curves) are shown. Pooled annual incidence rates of recurrent and de-novo aneurysm were estimated using
Poisson regression on person-years. Proportions of aneurysms and average follow up time are displayed as bubble plots with LOESS
smoothers weighted for study size.
Results: 7606 articles were screened and 44 studies included in the study. Case reports of 101 patients with recurrent and 156
patients with de-novo aneurysms were analyzed. Long term follow-up studies for aneurysm recurrence included data of 5922 patients
with 31055 patient-years of follow-up, for de-novo formation included 13723 patients with 101378 patient-years of follow-up. Average
time to recurrence was 12.9 years, to de-novo formation 9.3 years. No association with sex, aneurysm location and initial rupture
could be shown. An inverse association of multiplicity of aneurysms at diagnosis with time to formation of de-novo aneurysms, HR
0.63 (p=0.03), and a trend for age (per 10 y), HR 0.88 (p=0.06), were seen. Pooled annual incidence rates for ruptured, unruptured
and total de-novo aneurysms were 0.34, 0.09 and 0.35 and for recurrent aneurysms 0.12, 0.06 and 0.13.
Conclusion: Screening for de-novo aneurysms at 5, 10, 20 years would detect 31%, 64%, 96% of lesions, the pooled 20 years risk is
6.8%. Screening for recurrent aneurysms at 10, 15, 20 years would detect 37%, 65%, 93% of lesions, the pooled 20 years risk is
1.45%.
732. Risk of de novo aneurysms formation in patients with a prior diagnosis of ruptured and unruptured aneurysm:
systematic review and meta-analysis
Leonardo Rangel-Castilla, MD (Rochester, MN); Enrico Giordan, MD; Hassan Murad, MD; Waleed Brinjikji, MD; Giuseppe Lanzino,
MD
Introduction: De novo aneurysms are rare entities periodically discovered during follow up imaging. Little is known regarding the
frequency and time course at which de novo aneurysms form. We performed a systematic review and meta-analysis to calculate the

overall prevalence and cumulative incidence of these entities as well as to determine risk factors for de novo aneurysm formation.
Methods: We performed a literature search for studies of patients with unruptured and ruptured aneurysms describing the rate of de
novo aneurysm formation. The primary outcome was incidence of de novo aneurysm formation. A meta-analysis was performed using
a random-effects model by using data from included studies. We also examined the associations of multiple aneurysms, prior
subarachnoid hemorrhage, smoking, and hypertension with de novo aneurysm formation.
Results: Our meta-analysis including nearly 14968 aneurysm patients who received imaging follow-up for evaluation of de novo
aneurysm formation from 35 studies. The overall rate de novo aneurysm formation was 2% (95%CI=2%-3%) with the estimated
annualized rate being 0.3%/patient-year. We found no difference in rates of de novo aneurysm formation among patients with ruptured
and unruptured aneurysms. The mean time to de novo aneurysm formation was 8.3 years. In 8 studies, 11.2% of de novo aneurysms
were found in patients with <=5 years of follow-up and 88.8% were found at < 5 years. Mean time to rupture for de novo aneurysms
was 10 years.
Conclusion: Our study found that formation of de novo aneurysms is rare. Overall, routine screening for de novo aneurysms is likely
of low yield and could be performed at time intervals of at least 5 to 10 years.
733. Validation of a predictive scoring system for ventriculoperitoneal shunt insertion following aneurysmal subarachnoid
hemorrhage
Raghav Gupta (Marlboro, NJ); Luis Ascanio, MD; Alejandro Enriquez-Marulanda, MD; Christoph Griessenauer, MD; Anu Chinnadurai;
Ray Jhun, BS; Abdulrahman Alturki; Christopher Ogilvy, MD; Ajith Thomas, MD; Justin Moore, MD, PhD
Introduction: Hydrocephalus is a frequently encountered complication in the context of aneurysmal subarachnoid hemorrhage
(aSAH). Here, we performed an external validation of the recently proposed Post-Subarachnoid Shunt Scoring (PS3) system, which
aims to stratify patients presenting with aSAH based on their relative risk of requiring ventriculoperitoneal (VP) shunt insertion.
Methods: A retrospective review of all patients presenting with aSAH to our institution between July 2007 and December 2016, who
underwent CT imaging at the time of hospital admission, was performed.
Results: A total of 242 patients (66.1% female) with aSAH were included in the analysis with a mean age of 55.6 years. Sixty-four
(26.4%) patients had a Hunt and Hess grade of 4 or 5 on admission. An external ventricular drain (EVD) was placed in 130 (53.7%)
patients during the hospital admission. EVD placement was found to correlate with an increased rate of VP shunt placement
(p<0.001), and a trend towards an association between a high Hunt and Hess grade and VP shunt placement, was observed
(p=0.05). The area under the ROC for the PS3 scoring system was found to be 0.845. The system reliably predicted shunt-dependent
chronic hydrocephalus in our patient cohort (Odds ratio [OR]: 3.36; 95% confidence interval [CI]: 2.31-4.89; p <0.001).
Conclusion: Data from this study validated the previously proposed PS3 system, which was found to more accurately predict shunt-
dependent chronic hydrocephalus in patients with aSAH, as compared to other such systems in the neurosurgical literature such as
the CHESS, BNI, and SDASH systems.
734. Delayed hydrocephalus following successful EVD weaning in aneurysmal subarachnoid hemorrhage: risk factors and
prognosis
Oluwaseun O. Akinduro, MD (Jacksonville, FL); Neil Haranhalli, MD; Tito Vivas-Buitrago, MD; Sara Ganaha; William Freeman; Rabih
Tawk
Inroduction: Aneurysmal subarachnoid hemorrhage (aSAH) parents often develop acute hydrocephalus requiring temporary CSF
diversion. A subset of patients who pass their EVD clamp trials initially, will develop delayed hydrocephalus (HCP) requiring
permanent shunting. We sought to identify factors predisposing patients to delayed ventriculo-peritoneal shunting (dVPS) after
discharge.
Methods: We retrospectively reviewed the electronic medical records of our institution between the years of 2008 and 2013 for
patients admitted with aSAH.
Results: There were 489 patients with aSAH at our institution within the study period. 28% (n=138/489) of these patients developed
signs of HCP requiring placement of an EVD. 44 of these patients died or had withdrawal of care prior to discharge resulting in 94
patients included in our analyses. 31% (n=29/94) of patients failed their clamp trial and had VPS placement prior to discharge. 59%
(n=55/94) of these patients never required a VPS, while 11% (n=10/94) of them developed delayed signs of hydrocephalus and
required a VPS at a mean of 97.2 days after discharge. Longer wean times (p=0.0002) and symptomatic vasospasm requiring intra-
arterial therapy (p=0.03) were risk factors for dVPS. The there was a trend towards younger age (47.6 versus 55.5; p=0.07) and more
posterior fossa aneurysms (36% versus 70%; p=0.06) in the dVPS group when compared with patients who also passed their clamp
trial but never required a VPS. Initial outcomes were worse in the dVPS cohort, with significantly worse mRS at discharge (p=0.02),
but outcomes were similar at 1-year post-discharge (p=0.10).
Conclusion: Patients with symptomatic vasospasm who require long EVD wean times should be followed closely in the first few
months after discharge, as they may develop delayed signs of hydrocephalus requiring VPS. There is also a trend towards greater risk
for delayed hydrocephalus in young patients with posterior fossa aneurysms.
735. Reconsidering an important subclass of high risk dural arteriovenous fistulas for stereotactic radiosurgery
Daniel A. Tonetti, MD (Pittsburgh, PA); Bradley Gross, MD; Edward Andrews, MD; Brian Jankowitz, MD; Hideyuki Kano, MD, PhD;
Edward Monaco III, MD, PhD; John Flickinger, MD; L. Lunsford, MD

Introduction: Aggressive dural arteriovenous fistulas (dAVF)s with cortical venous drainage (CVD) are known for their relatively high
risk of recurrent neurologic events or hemorrhage. However, recent natural history literature has demonstrated that non-aggressive
dAVFs with CVD have a significantly lower prospective risk of hemorrhage. These non-aggressive dAVFs are diagnosed typically
because of symptomatic headache, pulsatile tinnitus or ocular symptoms, similar to low-risk dAVFs. As such, the viability of
stereotactic radiosurgery (SRS) as a treatment modality for this subclass should be evaluated.
Methods: The authors evaluated their institutional experience with SRS for dAVFs with CVD from 1991 to 2016, evaluating
angiographic outcomes and post-treatment hemorrhage rates. They subsequently pooled their results with those published in the
literature and stratified results based on presentation modality.
Results: In our institutional cohort of 42 dAVFs with CVD treated with SRS, there were no complications or hemorrhages after
treatment in 19 patients with non-aggressive dAVFs while there was one radiation-induced complication and one hemorrhage among
23 patients with aggressive dAVFs. Pooled with 155 dAVFs from the literature, the rate of hemorrhage after SRS was significantly
lower among patients with non-aggressive dAVFs (0/124 patients compared to 5/73 patients with aggressive fistulas, p = 0.003).
Similarly, the number of radiation-related complications was 0/147 in non-aggressive patients vs 6/73 patients with aggressive fistulas
(p = 0.001). The annual rate of hemorrhage after SRS for aggressive fistulas was 3.0% over 164.5 patient-years, whereas none of the
non-aggressive fistulas bled after radiosurgery over 279.4 patient-years of follow-up, despite the presence of CVD.
Conclusion: CVD is thought to be a significant risk factor in all dAVFs. In this experience, SRS proved to be a low-risk strategy that
was associated with a very low risk of subsequent hemorrhage or radiation-related complications in non-aggressive dAVFs with CVD.
736. Contrast induced neurotoxicity after neuro endovascular interventions
Yiping Li, MD (Madison, WI); Azam Ahmed, MD; Howard Rowley; David Niemann; Beverly Aagaard
Introduction: Neurotoxicity from contrast media used during angiography manifesting as transient delirium, aphasia, hemiparesis,
and/or blindness has been well described. It is hypothesized that iodinated contrast disrupts the blood-brain barrier resulting in
extravasation of toxic contrast into the subarachnoid space. The incidence of contrast induced transient neuropathy has been
estimated between 0.3-1%; however the rates are under reported in cerebral angiography especially after interventions where the
contrast load is given directly into the cerebral vasculature.
Methods: This was a prospective-cohort study of consecutive patients over two-year period treated with flow-diversion for intracranial
aneurysms. All patients underwent head-MRI including DWI and post-contrast FLAIR sequence within 24-hours post-procedure to
evaluate for evidence of gadolinium extravasation post angiography and development of ischemic events to correlate with
development of neurological deficits.
Results: 41 patients (5M, 36F; mean age 59 years) underwent flow diversion therapy for unruptured anterior circulation aneurysms. 8
patients (19.5%) developed scattered punctate foci on DWI post-operatively without evidence of large territory infarct. Conversely 13
patients (31.7) developed transient neurological deficit ranging from visual field deficits to dense hemiplegia and aphasia. Only 5 of 13
patients (31.7%) with neurological deficits had presence of DWI findings on MRI (none of which fully explain the symptoms) while
remaining 8 did not have any ischemic events on DWI. All patients with transient neurological deficits developed ipsilateral post-
contrast T2 FLAIR enhancement within the subarachnoid space consistent with hyperemia and breakdown of blood-brain barrier. All
neurological deficits were transient, resolving spontaneously between 6-72 hours. No patient had residual deficits on discharge
between 1-6 days post-operatively.
Conclusion: The incidence of contrast induced neurotoxicity is much more frequent than previously thought. We highlight the
importance of recognizing this phenomenon on noninvasive MR-imaging and provide a new avenue for future investigation.
737. Complications associated with cardiac valvular surgery in those presenting with infective endocarditis-related stroke
Peris Castaneda (Ann Arbor, MI); Joseph Linzey, BS; David Wilkinson, MD; Aditya Pandey, MD
Introduction: Infective endocarditis (IE) can be complicated by ischemic and hemorrhagic stroke. There is significant morbidity
associated with stroke in IE, complicating the decision for cardiac valvular surgery. Optimal timing for valve surgery post IE-related
stroke is not known.
Methods: We performed a retrospective analysis of all patients presenting with an ischemic or hemorrhagic stroke related to IE from
2006 to 2016 treated at our institution. We report descriptive statistics on timing and complications of valve surgery following IE-related
stroke. Intraoperative/postoperative complications include intracerebral hemorrhage, ischemic stroke, respiratory failure, ventilator-
associated pneumonia, acute renal failure, and sepsis.
Results: Eighty-eight patients harboring IE-related hemorrhagic or ischemic stroke were identified. Forty-two (47.7%) patients were
female. Twenty (22.7%) patients had an intracranial hemorrhage (ICH), while 68 (77.3%) had an ischemic stroke or transient ischemic
attack. Sixteen (18.2%) of the 88 patients suffered an additional stroke before a valve surgery could be performed. Median time
between first and second stroke in these patients was 8.5 days. Six of the ICH patients (30.0%) and 34 of the ischemic stroke patients
(50.0%) underwent a valve repair or replacement surgery. The median time between diagnosis of stroke and valve surgery was 10
days. Of the patients who underwent valve surgery, the complication rate was 16.7% in ICH-presenting patients and 32.4% in
ischemic stroke-presenting patients (p=0.44). Patients who underwent a valve surgery within 5 days had a complication rate of 45.5%
(5/11 patients), compared with patients who underwent valve surgery between 5-14 days (complication rate of 31.3%, 5/16 patients)
and after 14 days (15.4%, 2/13 patients). Five-year post-stroke mortality was seen in 27 patients (30.7%).
Conclusion: Patients presenting with IE-related stroke appear to have a high rate of postoperative complication, with the lowest

complication in those undergoing valve surgery more than two weeks post presentation.
738. Activation of hypoxia responses in aging mouse glioma model
Andrei M Mikheev (Houston, TX); Svetlana mikheeva, MS; Philip Horner, PhD; Robert Rostomily, MD
Introduction: Patient age is a robust determinant of adult glioma malignancy yet mechanisms underlying age-dependent glioma
phenotypes remain poorly understood. In previous aging animal glioma models age-dependent activation of hypoxic responses was
identified as a potential mechanism.
Methods: To further define age-dependent hypoxia we examined pseudo-hypoxia and hypoxia responses in transformed aging
(18moTr) and young (3moTr) mouse cells exposed to 1% oxygen in vitro by qPCR, Western blot and luciferase assay. Hypoxia in
mouse tumors was evaluated using pimonidazole and detection of HIF1a/VEGF protein expression in human and mouse tumors.
Results: Compared to 3moTr cells, 18moTR cells exhibited HIF1a independent higher expression of VEGF proteins under normoxia
suggesting a pseudo-hypoxic state. Activation of non-canonical hypoxia response (mTOR/Akt/NF-kB pathways) was found only in
18moTr cells consistent with increased proliferation of 18moTr cells under hypoxia in vitro. We also observed a more robust activation
of canonical hypoxia pathway in 18moTr compared to 3moTr in vitro as judged by hypoxia response gene expression in vitro. This
effect correlates with stronger HIFa activity in 18moTr cells measured by HIFa reporter. In tumors generated by 18moTR cells, distinct
pimonidazole positive hot spots were detected indicating intra-tumor hypoxia which also correlated with immunostaining of HIF1a and
VEGF. By contrast, in 3moTr derived tumors hypoxic cells, HIF1a and VEGF expression were detected only in single cells throughout
the tumor indicating diminished hypoxia and hypoxia response. We further found age dependent expression of HIF1a in human GBM
samples derived from aging (70-85y.o) versus young patients (26-31 y.o.).
Conclusion: These studies support the relevance of our aging glioma mouse model and identify differential hypoxia and responses to
hypoxia as clinically relevant mechanisms underlying age-dependent human GBM malignancy.
739. Quantification of glioblastoma mass effect by lateral ventricle displacement
Clark C. Chen, MD, PhD, FAANS (Minneapolis, MN); Tyler Steed, MD, PhD; Jeffrey Treiber, MD, PhD; Kunal Patel, MD, PhD; Anders
Dale, PhD; Bob Carter, MD, PhD
Introduction: Mass effect has demonstrated prognostic significance for glioblastoma, but is poorly quantified from an imaging
perspective. For instance, the plane on MR image through which midline shift is defined and how midline shift is measured vary from
observer to observer. Here, we utilized a validated segmentation algorithm to define a novel measure that allows quantitative
assessment of mass effect.
Methods: We define and characterize a novel neuroimaging parameter, lateral ventricle displacement (LVd), which quantifies mass
effect in glioblastoma patients. LVd is defined as the magnitude of displacement from the center of mass of the lateral ventricle
volume in glioblastoma patients relative to that a normal reference brain. Pre-operative MR images from 214 glioblastoma patients
from The Cancer Imaging Archive (TCIA) and 550 normal subjects from Imperial College London IXI dataset were segmented using
iterative probabilistic voxel labeling (IPVL). LVd, contrast enhancing volumes (CEV) and FLAIR hyper-intensity volumes (FHV) were
determined.
Results: Glioblastoma patients had significantly higher LVd relative to patients without brain tumors. The variance of LVd was not
explained by tumor volume, as defiend by CEV or FLAIR. LVd was robustly associated with glioblastoma survival in Cox models which
accounted for both age and Karnofsky’s Performance Scale (KPS) (p=0.006). Genomic-imaging correlation suggest that glioblastomas
with higher LVd demonstrated increased expression of genes associated with tumor proliferation and decreased expression of genes
associated with tumor invasion.
Conclusion: Our results suggest LVd is a quantitative measure of glioblastoma mass effect and a prognostic imaging biomarker.
741. Less is more: antibiotics alone as therapy for Ommaya reservoir-associated bacterial infections in patients with cancer
Ayesha Alli, BS (Hershey, PA); Michael Glantz, MD; David Black; Richard Eby, BS; Brad Zacharia, MD
Introduction: Optimum therapy for neoplastic meningitis requires an Ommaya reservoir, however indwelling reservoirs convey a
substantial risk of infection. Removal of the reservoir and appropriate systemic antibiotic therapy constitutes the standard approach to
reservoir-associated infection, but since a reservoir is required for ongoing therapy, this necessitates yet another neurosurgical
procedure to replace the device. We report a successful medical therapy approach to reservoir-associated meningitis in the cancer
population.
Methods: Data from all patients with reservoir-associated bacterial meningitis at our institution were extracted from an international
neoplastic meningitis registry containing 289 patients. We evaluated outcome from therapy and correlates of successful therapy
(defined as eradication of infection without reservoir removal).
Results: Thirty-five infections (9 recurrences) in 26 patients (9% of all patients) were identified. Fourteen patients were male; median
age was 58 (range 38-78). Primary malignancies included primary brain tumor (9), breast cancer (6), lymphoma (5), leukemia (2) and
other (4). Reservoirs were accessed a median of 6 (1-14) times prior to infection. The responsible organisms were P. acnes (21
cases), coagulase negative staphylococcus (6), S. aureus (3), Enterobacter (1), S. epidermidis (1), S. lugdunensis (1), Candida (1),
and Pseudomonas (1). Infections were eradicated without reservoir removal in 19 of 26 patients (73%) using a standardized treatment
regimen consisting of oral rifampin, intraventricular vancomycin, and an intravenous antibiotic appropriate to the infecting organism
(usually ceftriaxone, nafcillin, or vancomycin) for 2-3 weeks. Patients requiring reservoir removal suffered no complications from

delaying this procedure. No patient or treatment characteristics, including age, tumor histology, concurrent systemic chemotherapy,
number of reservoir accesses, myelosuppression, or infecting organism predicted need for reservoir removal.
Conclusion: Most cancer patients with reservoir-associated infections can be treated successfully with aggressive antibiotic therapy,
avoiding the need for reservoir removal and subsequent replacement
742. Survival benefit of surgical resection with stereotactic radiosurgery in synchronously-diagnosed brain metastasis from
non-small cell lung cancer
Joshua Lee Wang (Columbus, OH); Christopher Hong, MD; Mark Damante; James Elder, MD
Introduction: Patients with stage IV NSCLC have median overall survival (OS) of approximately 6 months. Those diagnosed with
brain metastasis (BM) at initial NSCLC diagnosis (synchronous BM) is presumed to carry poorer prognoses, and patients may be
deemed ineligible for aggressive treatment or clinical trials. This study aimed to clarify the survival benefit of aggressive
multidisciplinary management of synchronous NSCLC BM.
Methods: A retrospective single-center review identified 598 patients with NSCLC BM between 2008 and 2016. Data analyzed
included demographics, systemic staging, brain and systemic treatment, and survival. Survival was assessed using Kaplan-Meier
curves and log-rank tests. Hazard ratios (HR) were estimated using Cox proportional hazard models.
Results: BM were diagnosed synchronously in 300 patients (100 solitary BM, 200 multiple). Solitary metastases were found in 229
patients (38%), multiple (median 5) in 369 (62%). OS after solitary BM diagnosis was longer with surgery plus stereotactic
radiosurgery (SRS) versus SRS alone in both synchronous (HR 0.26 [95% CI 0.14-0.51], 142.7 versus 29 weeks, n=40 and 20,
p<0.0001) and metachronous groups (HR 0.55 [95% CI 0.34-0.90], 86 versus 34.4 weeks, n=43 and 48, p=0.0162). For multiple BM,
surgery plus SRS did not improve OS (synchronous: HR 1.07 [95% CI 0.64-1.76]; metachronous: HR: 0.71 [95% CI 0.38-1.24]). From
initial NSCLC diagnosis, OS was worse for synchronous versus metachronous solitary BM (HR 1.91 [95% CI 1.40-2.59], 31.4 vs.
105.6 weeks, p<0.0001), but similar for those patients (synchronous n=40, metachronous n=43) treated with surgery and SRS (HR
1.43 [95% CI 0.81-2.50], 143 versus 194 weeks, p=0.21).
Conclusion: Synchronous NSCLC BM implies an overall poorer prognosis, but patients with solitary BM who are candidates for
aggressive multidisciplinary management may have improved OS towards the range observed in metachronous NSCLC BM. Thus,
these patients may benefit from consideration for aggressive systemic management, including clinical trials.
743. Morphometrics predicts overall survival in patients with lung, breast, prostate, or myeloma spine metastases,
regardless of histology
Hesham Zakaria, MD (Detroit, MI); Lara Massie, MD; Yamaan Saadeh, MD; Azam Basheer, MD; Jesse Kelley, BS; Jamaal Tarpeh,
BS; Lonni Schultz, PhD; Ian Lee, MD; Brent Griffith, MD; Farzan Siddiqui, MD, PhD; Paul Park, MD; Victor Chang, MD
Introduction: Predicting survival of patients with spinal metastases would help stratify treatments between aggressive to palliation.
Morphometrics has been used to predict postoperative morbidity and mortality. This study evaluates whether morphometric is
predictive of survival in patients with lung, breast, prostate, or multiple myeloma spinal metastasis.
Methods: We identified patients with lung, breast, prostate, or myeloma spine metastases from a stereotactic body radiation therapy
registry. Morphometric measurements were taken of the psoas from the most recent CT scan, and sizes were split into tertiles (thirds).
Overall survival and hazard ratios were calculated with multivariate cox proportional hazards regression analyses.
Results: In 417 patients with spinal metastases, 40% had lung cancer, 27% breast, 21% prostate, and 11% myeloma. The average
age was 66.3, with 50% male and 52% Caucasian. The median overall survival was 173d (95%CI=140-204d) and was not associated
with age, sex, race, number of levels treated, or total target volume. Myeloma patients had a longer survival (p=0.001), but no other
tumor specific survival was detected. Multivariate analysis showed patients in the lowest psoas tertile had shorter survival (115d,
95%CI=91-153d) as compared to the middle (154d, 95%CI=109-218, p=0.013) and largest tertile (299d, 95%CI=228-435, p=0.001).
The middle tertile had shorter survival than the largest tertile, p=0.015. Patients with psoas sizes above the median had longer
survival (253d, 95%CI=204-319d) than those below the median (124d, 95%CI=99-157d), p=0.001. Kaplan Meier survival curves
visually represent differences in survival.
Conclusion: In patients with spine metastases, morphometric analysis of psoas muscle size can be used to identify patients who are
at risk for shorter survival, regardless of tumor histology. This information can be used to help with surgical decision making in patients
with the same burden of disease, as patients with a small psoas sizes are at higher risk of death.
745. A clinical decision rule to predict intracranial hypertension in severe traumatic brain injury: data from the Latin
American BEST TRIP randomized controlled trial
Aziz S. Alali, MD, PhD (Toronto, Ontario, Canada); Randall Chesnut, MD; Jason Barber, MS; Zulma Urbina, MD; Nancy Temkin, PhD
Introduction: While guidelines support the treatment of intracranial hypertension in patients with severe traumatic brain injury (TBI), it
is unclear when to suspect and initiate treatment for high intracranial pressure (ICP), especially in settings with limited resources.
Methods: Using Delphi method, we identified potential predictors of intracranial hypertension and a clinical decision rule (CDR) based
on these predictors a priori by consensus among 43 neurosurgeons and intensivists who have extensive experience managing severe
TBI based on clinical examination and CT findings. To validate these predictors, we used data from the BEST-TRIP trial. To report on
the performance of the CDR, we calculated sensitivity, specificity, positive and negative predictive values (PPV, NPV).
Results: The final set of predictors and the CDR was approved by 97% of participants in the consensus-working group. The

predictors are divided into major and minor criteria. High ICP would be considered suspected in the presence of one major or <2
minor Criteria. Major criteria are: compressed cisterns (Marshall class III), Midline shift<5 mm (Marshall DI IV) or Non-evacuated mass
lesion. Minor criteria are: GCS motor score<4, pupillary asymmetry, abnormal pupillary reactivity, or Marshall DI II. The area under the
curve for the predictors was 0.86. When high ICP is defined as<22mmHg, the CDR performed with a sensitivity of 93.9%
(95%CI:85.0-98.3%), a specificity of 42.3% (95%CI:31.7-53.6%), a PPV of 55.5% (95%CI:50.7-60.2%), and a NPV of 90%
(95%CI:77.1-96.0%). The sensitivity of the CDR improved with higher ICP cutoffs up to a sensitivity of 100% at a threshold of<30 mm
Hg.
Conclusion: A simple CDR based on a combination of clinical and imaging findings was found to be highly sensitive in distinguishing
severe TBI patients who would suffer intracranial hypertension. It could identify patients who require ICP monitoring or start ICP
lowering treatment in environments where resource limitations preclude timely monitoring.
747. Screening duplex ultrasonography does not reduce pulmonary embolism rate or mortality in neurosurgery patients
James C Dickerson, BA (Jackson, MS); Jordan Rimes, BS; Katherine Harriel, BS; Ryan Chapman, BA; Robert Dambrino, BS; Andrew
Desrosiers, MA; Lorne Taylor, BS; Chad Washington
Introduction: DVTs are a major focus of patient safety indicators and a common cause of morbidity and mortality. Many practices,
including our own, have employed screening ultrasonography in an effort to reduce poor outcomes. However, its role in decreasing
the rate of pulmonary emboli and mortality is unclear. At our institution, a policy change allowed us to compare independent groups:
patients treated under a prior paradigm of weekly screening ultrasonography versus a post-policy change group without surveillance.
Methods: 2,467 consecutive patients were reviewed, with a two-month washout period around the policy change. Inclusion criteria
were admission to the neurosurgical service or consultation for ≥72 hours. Patients with known DVT on admission or previous IVC
filter placement were excluded. The primary outcome examined was the rate of PE diagnosis; secondary outcomes were all-cause
mortality at discharge and 30 days, DVT diagnosis rate, and IVC filter placement rate.
Results: 485 patients met criteria for the pre group and 504 for the post group. Data are presented as pre versus post. There was no
difference in the PE rate (1.9% versus 2.2%; p = 0.72), or all cause mortality at discharge (6.6% versus 5.6%; p = 0.49) and at 30 days
(7.8% versus 7.5%; p = 0.88). There were significant differences in the lower extremity DVT rate (10.3% versus 3.0%; p < 0.01) and
IVC filter rate (6.4% versus 2.0 %; p < 0.01). Post hoc power analysis demonstrated sensitivity to detec a 3% increase in PE rate
powered at 80% with an alpha = 0.05.
Conclusion: Based on these data, additional screening does not appear to confer a benefit to patients. While the pre group had
significantly higher rates of DVT diagnosis and IVC filter placement, the screening, additional diagnoses, and subsequent interventions
did not appear to improve patient outcomes.
748. On-field signs predict future acute symptoms after sport-related concussion: a structural equation modeling study
Andrew Kuhn, BA (Nashville, TN); Scott Zuckerman, MD; Benjamin Brett, PhD; Aaron Yengo-Kahn, MD; Aaron Jeckell, MD; Gary
Solomon, PhD
Objective: This study investigated the relationship between on-field, objective signs immediately following sport-related concussion
and self-reported symptom endorsement within one day post injury.
Methods: A retrospective case series of 237 concussed high school athletes was performed. On-field signs were evaluated
immediately post injury. Self-reported symptoms (2 clusters) were collected within one day post injury. A two-step structural equation
model and follow-up bivariate regression analyses of significant on-field signs and symptom clusters were performed.
Results: Signs of immediate memory, B = 0.20, p = 0.04, and postural instability, B = 0.19, p < 0.01, significantly predicted a greater
likelihood of endorsing the cognitive-migraine-fatigue symptom cluster within one day post injury. Regarding signs correlated with
specific symptoms, immediate memory was associated with symptoms of trouble remembering, Χ 2 = 37.92, p < 0.001, OR = 3.89
(95% CI, 2.47- 6.13), and concentration difficulties, Χ 2 = 10.84, p = 0.001, OR = 2.13 (95%CI, 1.37- 3.30). Postural instability was
associated with symptom endorsement of trouble remembering, Χ 2 = 12.08, p < 0.001, OR = 1.76 (95% CI, 1.29- 2.40).
Conclusion: Certain post-concussion on-field signs exhibited after injury were associated with specific symptom endorsement within
one day post injury. Based on these associations, individualized education-based interventions and academic accommodations may
help reduce unanticipated worry from parents, students, and teachers following a student-athlete’s SRC, especially in cases of
delayed onset symptoms.
749. Treatment strategy for brain contusion in patients with traumatic brain injury—first ICP monitoring or first operation: A
retrospective cohort study
Qiang Yuan (Shanghai, China); Jin Hu
Introduction: Whether ICP-guided brain contusion treatment is more favorable than that based on imaging and clinical features
remains unknown. We evaluated the effects of a management protocol based on the use of ICP monitoring on functional outcomes in
patients with brain contusions.
Methods: A retrospective cohort study based on two databases was conducted. The patients for brain contusion with volume great
than 20ml were included into this study. Patients enrolled in the study were divided into two groups (ICP-monitoring group and
imaging-clinical examination group). A propensity score matching was used to compare the 6-month favorable outcome and
prevalence of complications between the two groups.
Results: After adjusting for other risk factors, we found that the initial ICP was significantly associated with neurological deterioration

(odds ratio [OR], 1.24; 95% confidence interval [CI], 1.17-1.32; P < 0.001). Since the initial ICP was < 15 mmHg, the risk of
neurological deterioration increases significantly with the increase in initial ICP. After propensity score matching, the six-month
favorable outcome rate was 69.2% in the ICP-monitoring group compared with 58.2% in the imaging-clinical examination group (OR,
1.61; 95% CI, 1.10-2.35; P = 0.013). The six-month good recovery rate was 35.0% in the ICP-monitoring group as compared with
18.1% in the imaging-clinical examination group (OR, 2.43; 95% CI, 1.59 to 3.72; P < 0.001). The mild and enhanced hyperosmolar
therapy both decreased significantly from imaging-clinical examination group to ICP-monitoring group. The incidence of acute renal
failure and sepsis in the ICP-monitoring group was significantly lower than that in the imaging-clinical examination group.
Conclusion: For patients with a volume of brain contusion of < 20 mL, care focused on the management protocol based on ICP
monitoring was shown to be superior to care based on imaging and clinical examination.
750. Novel football helmet design reduces CSDM15, A computational surrogate of diffuse axonal injury, compared to three
commonly used helmets in a finite element head model
Jacob Ruzevick, MD (Seattle, WA); Derek Wallin, BS; Per Reinhall, PhD; Samuel Browd, MD, PhD
Introduction: A major challenge of football helmet development is correlating head impacts with brain injury that might be sustained
during play. Finite element modeling (FEM) allows for testing the ability of helmets to reduce the severity of brain injury in a
computational model.
Methods: Performance tests were conducted on the top performing football helmet from each major helmet manufacturer: Riddell
Speed, Schutt Air XP Pro VTDII, Xenith Epic+, and Vicis ZERO1. Helmets were tested using a pneumatic linear impactor at three
velocities. A Hybrid III headform and neck on a linear bearing table was impacted in four locations: side, front, rear, and lower side.
These were chosen based on the most common sites of head impact causing concussion in the National Football League (NFL). The
head was outfitted with a six-degree-of-freedom sensor system to fully define the kinematics of the head. This data was then input into
the Simulated Injury Monitor FEM (SIMon). The cumulative strain damage measure-15 (CSDM15), or percent of the brain experiencing
<15% shear and a surrogate for diffuse axonal injury, was calculated. A CSDM-15 value of 0.55 corresponds to a 50% probability of
concussion.
Results: The average CSDM15 for side impacts, which accounted for approximately 59% of concussions in the NFL in 2015, at 7.4
m/s were 0.36±0.03, 0.43±0.02, 0.54±0.01, and 0.59±0.06 for the Vicis ZERO1, Riddell Speed, Schutt Air XP Pro VTDII, and Xenith
Epic+ helmets, respectively (p=0.0002). A similar result was seen at the highest impact velocity, 9.3 m/s, with an average CSDM15 of
0.56±0.001, 0.63±0.01, 0.76±0.01, and 0.87±0.01(p<0.0001). Lower side impacts resulted in the highest CSDM15 compared to all
impact locations when controlling for impact velocity.
Conclusion: Helmets that reduce rotational forces show lower levels of brain injury in a FEM of brain injury, especially in impact
locations associated with the highest rate of concussions in the NFL.
751. Association between involvement in specific sports and lifetime risk of developing a traumatic brain injury in young
student athletes
Clementine Koa Affana; Joseph Toninato; Tessneem Abdallah; Uzma Samadani, MD, PhD; Thomas Bergman, MD
Introduction: Pediatric concussions have become a major health concern with a 71% increase in diagnoses in children ages 10 to 19.
With rising concerns regarding the long term cognitive effects of repeated concussions, it becomes crucial to assess the lifetime risk of
student athletes of developing a concussion to create better protective measures. The goal of our study was to evaluate the correlation
between past history of concussions and involvement in specific sports.
Methods: As part of a larger sports concussion study, student athletes at 6 area high schools and 1 college (ages 12 to 23) completed
a demographic survey which included the Boston Assessment of Traumatic Brain Injury Lifetime (BAT-L). The survey provided a
detailed assessment of past TBI episodes with emphasis on timeline, severity and duration of symptoms.
Results: 222 subjects completed the survey (mean age of 16.27), 61.3% were males. 54 subjects (26.1%) reported having had at least
one concussion in the past. Males reported more past concussions than females (30.1% vs 15.5%), older subjects reported more
concussions (32.1% in subjects >18 and 19.1% in those <18), and football and soccer players had more past concussion episodes
compared to other sports (football: 12, soccer: 15, volleyball: 3, hockey: 1, tennis: 0, cross-country: 0, swimming: 0). Soccer players
reported having had multiple episodes of concussion in their lifetime compared to other sports (5 subjects vs 3 in football and 1 in all
other sports combined).
Conclusion: Our preliminary data demonstrates that student athletes that play football and that are older are more likely to have
experienced multiple concussions in their lifetime. Efforts should be made to reinforce preventive measures at earlier stages of sports
involvement.
Disclosure: This study is currently being funded by the Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant
Program.
752. Radiation DNA damage repair inhibition by GSK-J4 in DIPG
Nundia Louis (Winter Garden, FL); Xingyao He, MS; Andrea Piunti, PhD; Amanda Saratsis, MD; Rishi Lulla, MD; Jason Fangusaro,
MD; Craig Horbinski, MD, PhD; Stewart Goldman, MD; Charles James, PhD; Ali Shilatifard, PhD; Rintaro Hashizume, MD, PhD
Introduction: Focal radiation therapy has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG).
However, all children who suffer from this inoperable and uniformly fatal cancer show evidence of disease progression within months

of completing radiation therapy, especially those who harbor the H3.3K27M mutation. Since chemotherapy does not provide significant
outcome improvement, it is crucial to find a suitable radiosensitizer. Our research has shown that the JMJD3 demethylase inhibitor,
GSK-J4, exerts potent anti-tumor activity on H3.3K27M mutant DIPG cells while restoring methylation. Our aim is to investigate the
hypothesis that GSK-J4 may inhibit radiation-induced DNA repair making it a potential radiosensitizer.
Methods: We evaluated DNA damage repair via quantitative-PCR (q-PCR) and immunocytochemistry of DSB markers γH2AX and
53BP1. Western blotting was conducted to evaluate expression of proteins involved in DNA DSB repair. In vivo response to radiation
monotherapy and combination of RT + GSK-J4 were measured by animal survival studies. We are currently conducting DNA repair
assays to assess the effect of GSK-J4 on the DNA DSB repair pathways in DIPG cells.
Results: qPCR results showed that GSK-J4 significantly reduces DNA DSB repair genes such as PARP1, PARP2, SMARCB1 and
BRCA1, in irradiated DIPG cells. Immunocytochemistry results support that GSK- J4 sustains high levels of γH2AX and 53BP1 in
irradiated DIPG cells, thereby inhibiting DNA DSB repair. Western blotting revealed that GSK-J4 causes a sustained level of
phosphorylated Rad50 and yH2AX in irradiated DIPG cells. Animal survival studies revealed increased survival in animals that were
treated with combination therapy compared to monotherapy. DNA repair assay results will be reported at the meeting.
Conclusion: Treatment of DIPG with a combination of GSK-J4 and radiation significantly impairs DNA DSB repair while increasing
survival. These results highlight GSK-J4 as a potential radiosensitizer in DIPG treatment.
753. Analysis of hydrocephalus and Chiari malformation after prenatal and postnatal myelomeningocele closure: report from
a single institution
Tracy Ma Flanders (Philadelphia, PA), MD; Gregory Heuer; Peter Madsen; Catherine Mackell; Erin Alexander; Julie Moldenhauer;
Deborah Zarnow; Alan Flake; N Adzick
Introduction: The Management of Myelomeningocele Study (MOMS) demonstrated that prenatal myelomeningocele repair results in
improved hydrocephalus (HCP), hindbrain herniation (HH), and motor function outcomes when compared to postnatal repair. We
report on the outcomes of a single institution’s experience in the post-MOMS era with regards to HCP and HH.
Methods: A single-center retrospective study of a subset of post-MOMS patients who underwent fetal and postnatal
myelomeningocele repair was performed. Outcomes were based on the status of CSF diversion (i.e. VPS or ETV) and reversal of HH
(on imaging or need for decompression). Families were contacted via telephone for outcome information if they transitioned care to
outside institutions. Multivariate analyses were performed using the variables of age at repair, gestational age (GA) at delivery,
presence of syrinx, and resolution of HCP or HH.
Results: Data from January 2011 to May 2016 was either reviewed or obtained from contacted families of 62/100 postnatal and
115/174 fetal myelomeningocele repair patients. In the postnatal group, 24% exhibited HH reversal compared to 89% in the fetal
group (p<0.0001); 50/62 (81%) postnatal patients required CSF diversion compared to 44/115 (38%) in the fetal group (p<0.001). In
multivariate analysis, the best predictor of not requiring a shunt in the fetal population was HH resolution (p=0.0021). The best
predictor of HH resolution was GA at repair (p=0.00834) and no CSF diversion (p=0.0021). Similarly, the best predictor of not requiring
CSF diversion in the postnatal population was resolution of HH (p=0.0352). Presence of prenatal or postnatal syrinx was not
associated with HCP or HH resolution in both groups.
Conclusions: Our findings corroborate the outcomes of the MOMS trial and further demonstrate the benefit of fetal myelomeningocele
repair with regard to CSF dynamics. This study further demonstrates the important correlation between HCP and HH.
754. The genetic landscape of familial congenital hydrocephalus
Adeeb Sebai (Rochester, MN); Mohammed Adeeb Sebai; Eissa Faqeih; FOWZAN ALKURAYA; Lucie Dupuis; Elham Mardawi; Harry
Lesmana; S Sogaty; KURDI WESAM; NOUR EWIDA; Nisha Patel; Ranad Shaheen
Introduction: Congenital hydrocephalus is an important birth defect, the genetics of which remains incompletely understood. To date,
only
4 genes are known to cause Mendelian diseases in which congenital hydrocephalus is the main or sole clinical feature, 2
X-linked (L1CAM and AP1S2) and 2 autosomal recessive (CCDC88C and MPDZ). In this study, we aimed to determine the genetic
etiology of familial congenital hydrocephalus with the assumption that these cases represent Mendelian forms of the disease.
Methods: Exome sequencing combined, where applicable, with positional mapping.
Results: We identified a likely causal mutation in the majority of these families (21 of 27, 78%), spanning 16 genes, none of which is
X-linked. Ciliopathies and dystroglycanopathies were the most common etiologies of congenital hydrocephalus in our cohort (19% and
26%, respectively). In 1 family with 4 affected members, we identified a homozygous truncating variant in EML1, which we propose as
a novel cause of congenital hydrocephalus in addition to its suggested role in cortical malformation. Similarly, we show that recessive
mutations in WDR81, previously linked to cerebellar ataxia, mental retardation, and disequilibrium syndrome 2, cause severe
congenital hydrocephalus. Furthermore, we confirm the previously reported candidacy of MPDZ by presenting a phenotypic spectrum
of congenital hydrocephalus associated with 5 recessive alleles.
Conclusion: Our study highlights the importance of recessive mutations in familial congenital hydrocephalus and expands the locus
heterogeneity of this condition.
755. Does microelectrode recording affect lead location in DBS surgery? A retrospective analysis
Ryan B. Kochanski, MD; Kristen Kraimer, BS; Kavantissa Keppetipola, BS; Sander Bus, MD; Todd Beck , MS; Gian Pal, MD; Leo
Verhagen Metman, MD, PhD; Sepehr Sani, MD

Introduction: Debate exists regarding the utility of microelectrode recording (MER) during deep brain stimulation (DBS) surgery. Prior
studies have shown discordance between optimal subthalamic nucleus (STN) target utilizing image-based versus MER-based targeting
in 30-47% of cases. We aimed to: 1) determine the percent of cases where there was discordance between image-based and MER-
optimized targeting, and 2) determine whether MER resulted in a significant radial deviation of the DBS lead when compared to the
MER-optimized target (MER-O).
Methods: Patients with Parkinson’s disease who underwent STN DBS lead placement with MER between 2014 and 2016 were
retrospectively analyzed. Radial error between the microelectrode tip location of the first recorded tract and the intended MRI-defined
STN target (AT) was calculated in the axial plane. If the radial error was less than 1mm, the recorded tract was deemed an acceptable
electrophysiological representation of AT. Neurophysiological recordings were analyzed based on the presence/absence of kinesthetic
cells, length of recorded STN and stimulation side effect profile.The number of hemispheres by which the neurophysiological data was
suboptimal thus requiring multiple MER tracks despite radial error less than 1mm from AT were chosen for further analysis.The radial
distances/errors between 1) AT and MER-O; and 2) MER-O and DBS lead were calculated and compared.The Clark-Evans test was
performed to assess for directional bias.
Results: A total of 150 hemispheres were retrospectively reviewed. In 38(25%) hemispheres, MER was suboptimal. The mean radial
distance between AT and MER-O was 1.51±0.11mm. The mean radial error between MER-O and final DBS lead was 1.24±0.16mm.
There was no significant difference in the radial distance between AT and MER-O versus the radial error between the MER-O and DBS
lead. Furthermore, there was no directional bias in the error distribution between groups.
Conclusion: In almost one of four hemispheres, there is discordance between optimal neurophysiological and radiographic
dorsolateral STN.However, MER optimization in such hemispheres may not lead to a significant change in the final DBS lead location
compared to the initial target.
756. Bilateral network dynamics of speech production
Nitin Tandon, MD, FAANS (Houston, TX); Kiefer Forseth
Introduction: Humans can generate the name for an object and articulate that word with remarkable speed, precision, and fluency.
This process of speech production involves an integrated multistage process that seamlessly translates conceptual representations in
the brain to acoustic output - a defining human faculty. The study of this complex cortical network has been largely mediated by
analysis of lesions, neurodegenerative disease, functional imaging, and non-invasive electrophysiology. With these tools, much has
been learned about language in the brain; however, these predominant methodologies lack the spatiotemporal resolution to discern
the neural mechanisms driving a speech production network characterized by rapid, transient dynamics.
Methods: We leverage the excellent spatiotemporal resolution of electrocorticography in a large cohort (18193 electrodes, 106
patients) with both surface subdural and penetrating depth electrodes to study cognitive processes leading to articulation in a picture
naming paradigm. To delineate nodes of the bilateral articulatory network, we implemented a surface-based mixed-effects multilevel
analysis of broadband gamma activity.
Results: We identified 3 stages of cortical activation relative to articulatory onset. The first period - lexical selection - involves pre-
supplementary motor area, anterior insula, and pars triangularis. Next, the second period -phonological selection and articulatory
planning - involves supplementary motor area proper, pars opercularis, and ventral sensorimotor cortex. Finally, the third period -
articulatory execution and self-monitoring - involves ventral sensorimotor cortex, early auditory cortex, and the Sylvian-parietal-
temporal junction. Importantly, only activity in the first period is restricted to the language-dominant left hemisphere, while the other
processes are bilaterally represented.
Conclusion: This work answers several long-standing questions in the word production literature related to inter-regional interactions,
the role of the supplementary motor cortex and the insula, and the contribution of the non dominant hemisphere to speech. Inter-areal
dynamics are being modelled to further elaborate the networks involved in speech production.
757. Outcomes of a prospective, multi-center international registry of DBS for Parkinson's disease
Jan Vesper, MD, PhD (Dusseldorf, Germany); Roshini Jain, MS; Heleen Scholtes; Alex Wang; Steffen Paschen, MD; Michael Barbe,
MD; Andrea Kühn, MD; Monika Pötter-Nerger, MD; Jens Volkmann, MD; Yen Tai, MD; Guenther Deuschl, MD
Introduction: The effectiveness of Deep Brain Stimulation (DBS) to reduce motor complications associated with Parkinson’s disease
(PD) has been substantiated by several randomized controlled trials (Deuschl et al., 2006, Schuepbach et al., 2013 and can be
sustained for up to 10 years (Castrioto et al., 2011). Large patient data registries may facilitate insights regarding real-world, clinical
use of DBS. Here we report outcomes from a large scale registry of a DBS system capable of Multiple Independent Current Source
Control (MICC) in the management of symptoms of levodopa-responsive PD.
Methods: The Vercise DBS Registry is a prospective, on-label, multi-center, international registry sponsored by Boston Scientific. The
Vercise DBS system (Boston Scientific) is a CE-marked, multiple-source, constant-current system. Subjects were followed up to 3
years post-implantation where their overall improvement in quality of life and PD motor symptoms was evaluated. Clinical endpoints
evaluated at baseline and during study follow included Unified Parkinson's disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson's
disease Questionnaire (PDQ-39), and Global Impression of Change.
Results: A total of over 200 subjects have been enrolled in the registry and this report will provide an overview of the data collected
this far. A 36.2% improvement in MDS-UPDRS III scores (stim on/meds off) at 1 year compared with baseline was reported. This
improvement in motor function was supported by an improvement in quality of life as assessed by PDQ-39 Summary Index (5.6 point
improvement, n = 146) at 1 year. Furthermore, this improvement compared to baseline continued to trend up to 2 years post-implant.

Roughly 90% of patients and clinicians reported improvement as compared with Baseline.
Conclusion: The Vercise DBS registry represents the first comprehensive, large scale collection of real-world outcomes and includes
evaluation of the safety and effectiveness of the Vercise DBS System up to 2 years post-implant.
758. Temporal lobectomy for seizure control: outcomes and predictors of seizure recurrence
John Paul Andrews (New Haven, CT); Abhijeet Gummadavelli, MD; Jennifer Bonito; Pue Farooque, MD; Dennis Spencer, MD
Introduction: Anterior medial temporal lobectomy (AMTL) is the gold-standard treatment for medically refractory temporal lobe
epilepsy. While the majority of these patients achieve seizure freedom following surgery, seizures recur in a significant portion.
Methods: This study retrospectively analyzed a consecutive series of patients receiving an AMTL, without extratemporal resections,
by the senior author (DS) at a single comprehensive epilepsy center from 2000-2015. Engel and ILAE outcome scores were assigned
yearly. Kaplan-Meier analysis was used to compare seizure-freedom (Engel I outcome). Non-lesional pathology was defined as
absence of structural lesions (e.g. mesial temporal sclerosis or tumor) on post-operative pathology report. Concordance of MRI, EEG
and PET studies was confirmed by a panel of the authors. Rapid propagation to neocortex was defined as seizure spread in <10s.
Results: Over this 16 year period, 132 patients met inclusion criteria of which 119 (90%) had at least 1 year follow-up. Of 72 patients
operated on ≥10 years ago, 36 (50%) had ≥10 years follow-up. While absolute (Engel IA) seizure freedom falls from 70% at year 1 to
36% at year 10, 73-85% of patients are free from disabling seizures (Engel I) at any year over the first 10 post-operative years. Non-
lesional pathology, discordance of PET with scalp-EEG, and presence of intracranial EEG correlated with seizure recurrence on
Kaplan-Meier analysis (P<0.05). Multivariate analyses of these variables revealed presence intracranial EEG as the strongest
predictor of outcome (P<0.05). In the 19 patient cohort with intracranial EEG studies, rapid propagation to neocortex predicted
recurrence of seizures in 9 of 10 patients with recurrent seizures (P<0.05).
Conclusion: The experience of this institution shows high rates of Engel I seizure freedom through 10 years of follow-up. Intracranial
EEG was the strongest predictor of seizure recurrence and within this cohort rapid neocortical propagation was a strong predictor of
poor outcome.
759. Microglia-glioblastoma interactions influence clinical survival
Clark C. Chen, MD, PhD, FAANS (Minneapolis, MN); Jie Li, PhD; Megan Kaneda, PhD; jiangfei Wang, MD; Kunal Patel, MD; Valya
Ramakrishnan PhD; Siamak Amifakhri, PhD; Frank Furanri, PhD; Jiang Tao, MD, PhD; Bob Carter, MD, PhD; Christopher Glass,
PhD; Judith Varner, PhD
Introduction: Glioblastoma is a deadly disease, with most patients succumbing to the disease within two years of diagnosis. The
molecular basis for the rare patients who survive beyond expectation remain poorly understood.
Methods: Survival analysis was performed using three independent Isocitrate Dehydrogenase (IDH) wild type glioblastoma patient
cohorts, including The Cancer Genome Atlas (TCGA), REMBRANDT, and the Chinese Glioma Genome Atlas (CGGA). Tissue culture,
patient derived xenograft, and transgenic murine studies were conducted using previously published techniques.
Results: We identified an inflammatory gene signature that was consistently suppressed in the exceptional responders of all three
cohorts. Importantly, the survival effect of this inflammatory signature remains robust after accounting for variations in age, KPS,
concurrent tomozolomide/radiation therapy, and extent of surgical resection. We demonstrated that microglia was the principle
mediator of this inflammatory signature. Co-implantation of microglia with independent glioblastoma cell lines induced the expression
of this clinically-pertinent inflammatory signature and shortened the survival of the mice cohort harboring the co-implant intracranially.
Co-culture of microglia induced glioblastoma to adopt a stem-like cell state, as evidenced by increased tumorigenicity as well as
enhanced resistance to DNA damaging agents, including temozlomide. These effects were recapitulated using conditioned media
derived from microglia. Proteomic analysis suggests that microglia-glioblastoma interactions resulted from microglial secretion of key
cytokines and exosomes as well as contribution from the Stat3-Myc signaling axis.
Conclusion: There is great interest in personalizing oncologic care by tailoring targeted therapy to the intrinsic mutational landscape
of cancer. Here we provide compelling evidence that micro-environmental factors extrinsic to this landscape modulate clinical survival
for patients afflicted with glioblastomas.
760. Outcomes of adoptive cell transfer with tumor-infiltrating lymphocytes for metastatic melanoma patients with and
without brain metastases
Gautam Unmeel Mehta, MD (Houston, TX); Parisa Malekzadeh; Thomas Shelton; Donald White; John Butman; James Yang;
Stephanie Goff; Steven Rosenberg; Richard Sherry
Introducton: Brain metastases cause significant morbidity and mortality in patients with metastatic melanoma. Although adoptive cell
therapy (ACT) with tumor-infiltrating lymphocytes (TIL) can achieve complete and durable remission of advanced cutaneous
melanoma, the efficacy of this therapy for brain metastases is unclear.
Methods: Records of patients with M1c melanoma treated with ACT using TIL, including patients with treated and untreated brain
metastases, were analyzed. Treatment consisted of preparative chemotherapy, autologous TIL infusion, and high-dose interleukin-2.
Treatment outcomes, sites of initial tumor progression, and overall survival were analyzed.
Results: Among 144 total patients, 15 patients with treated and 18 patients with untreated brain metastases were identified. In-brain
objective responses (OR) occurred in 28% patients with untreated brain metastases. The systemic OR rates for patients with M1c
disease without identified brain disease, treated brain disease, and untreated brain disease, and were 49%, 33% and 33%,

respectively, of which 59%, 20% and 16% were durable at last follow-up. The site of untreated brain disease was the most likely site
of initial tumor progression (61%) in patients with untreated brain metastases.
Conclusion: Overall, we found that ACT with TIL can eliminate small melanoma brain metastases. However, following TIL therapy
these patients frequently progress in the brain at a site of untreated brain disease. Patients with treated or untreated brain disease are
less likely to achieve durable systemic ORs following TIL therapy compared with M1c disease and no history of brain disease.
Melanoma brain metastases likely require local therapy despite the systemic impact of ACT.
761. Tumor-induced immunosuppression promotes brain metastasis in patients with non-small cell lung cancer
Yuping Derek. Li (Chicago, IL); Jonathan Lamano; Jason Lamano; Dorina Veliceasa, PhD; Gurvinder Kaur, MD; Joseph DiDomenico;
Daniel Oyon; Orin Bloch, MD
Introduction: Brain metastases are a significant source of morbidity and mortality for patients with lung cancer. While effective innate
immune responses can combat early malignancy, many cancers have the potential to induce local and systemic immunosuppression,
promoting tumor growth and metastasis. One mechanism of immunosuppression is the tumor-induced expansion of PD-L1+
suppressive myeloid cells. Here we evaluate the role of tumor-induced suppressive myeloid cell expansion on development of brain
metastases in patients with lung cancer.
Methods: Peripheral blood was collected from patients undergoing resection of lung metastatic brain tumors (n=27).
Immunosuppressive monocytes (CD45+CD11b+CD163+/-PD-L1+/-) and myeloid-derived suppressor cells (MDSCs)
(CD11b+CD33+HLA-DRloPD-L1+/-) were quantified through flow cytometry. Tumors tissue was used to generate cell cultures (n=6)
from which tumor conditioned media (TCM) was collected. TCM was analyzed for immunosuppressive cytokines by ELISA, including
IL-6. Naïve monocytes were stimulated with TCM for 24 hours in the presence of anti-IL-6, anti-IL-6 receptor antibodies or IgG control.
Results: Patients with brain metastatic lung carcinoma demonstrated increased peripheral monocyte PD-L1 compared to healthy
controls (p<0.05), with an average 2.5-fold increase. All patients exhibited an increased abundance of MDSCs (p<0.05), with an
average 14.9-fold increase. TCM stimulated monocytes expressed increased PD-L1 compared to unstimulated controls (17.7 vs. 7.4%
positive, p<0.001). Correlation of TCM IL-6 levels with PD-L1 expression in TCM stimulated monocytes demonstrated a dose-
dependent relationship (R2=0.87, p<0.01). In addition, treatment with anti-IL-6 and anti-IL-6 receptor antibodies inhibited the increase
in monocyte PD-L1.
Conclusion: Patients with lung cancer and brain metastases exhibit signs of peripheral immunosuppression, including increased PD-
L1+ monocytes and MDSCs. IL-6 was found to stimulate induction of immunosuppressive myeloid cells. Monitoring of these
immunosuppressive factors in peripheral blood may be used as a biomarker to predict patients at risk for brain metastases and
suggest a new target for therapeutic intervention.
762. Activation of canonical EGFR Pathway in Cushing’s disease
Jacqueline Boyle (Peoria, IL); Jie Lu, PhD; Grégoire Chatain; Dragan Maric, PhD; Abhik Ray-Chaudhury, MD; Prashant Chittiboina,
MD, MPH
Introduction: Cushing’s Disease (CD) is caused by adrenocorticotrophic hormone (ACTH) secreting adenomas (corticotropinomas).
About 30-60% of corticotropinomas contain mutations in USP8 gene resulting in recycling of epidermal growth factor receptor (EGFR),
and activation of the canonical Ras-Raf/MAPK pathway. However, EGFR is activated in a larger proportion (80%) of corticotropinomas
via unknown mechanisms. Ligand-independent non-canonical EGFR signaling occurs via transcription factor IRF3 activation and
downstream cytokine gene transcription (IFIT1, IFI27, TRAIL). We investigated whether canonical EGFR signaling could underlie
tumorigenesis in USP8-wildtype (USP8-wt) corticotropinomas.
Methods: USP8 mutation status of tumors was determined by DNA sequencing of the 14-3-3 binding region. Fluorescent multiplex
IHC (mIHC) was performed on USP8-mutated (n=1) and USP8-wt (n=5) corticotropinomas with adjacent normal gland. Gene
expression in USP8-wt corticotropinoma and adjacent normal gland were analyzed/compared with Agilent 4*44K format microarray
using 27,958 probes.
Results: On mIHC, EGFR and phosphorylated EGFR (tyrosine-992) was detected in all corticotropinomas (USP8-mutated and USP8-
wt) and in adjacent normal tissue, suggesting broad, spillover EGFR activation in/around corticotropinomas. Gene expression analysis
revealed 8-fold higher proopiomelanocortin (POMC) mRNA (p <0.00004) in tumor, and no observed difference in EGF, EGFR, IRF3,
IFIT1, IFI27 and TRAIL mRNA suggesting canonical, post-translational modulation of EGFR signaling. Canonical EGFR pathway
proteins (MAPK, RRAGD, RASGRP3, RASGRF2) were 2.1-3.2-fold greater (p <.01) in corticotropinoma. Gene expression of EGFR
ligands amphiregulin (AREG) and neuregulin 1 (NRG1) were elevated 9.4 (p <.0003) and 5.8-fold (p <.000009), respectively, in
corticotropinoma, with no upregulation of other EGFR ligands.
Conclusion: Our results suggest that, unlike gliomas or other cancers, activation of EGFR in corticotropinomas occurs without
transcriptional overexpression or constitutive activation wildtype EGFR. We suspect that activation of the canonical EGFR pathway
occurs due to transcriptional overexpression of EGFR ligands including AREG and NRG1. If confirmed, these findings may lead to
new, targeted anti-tumor strategies in CD.
763. Antitumor efficacy Of anti-PDL-1 In ACTH-secreting pituitary adenomas: an immunotherapeutic approach for Cushing’s
disease
Hanna Kemeny (Durham, NC); Aladine Elsamadicy; S Farber, MD; Pakawat Chongsathidkiet; Karolina Woroniecka; Xiuyu Cui; Ian
Dunn, MD; Peter Fecci, MD, PhD

Introduction: Cushing’s disease (CD), caused by ACTH-secreting pituitary adenomas, is a highly morbid condition with few treatment
options beyond surgery and radiotherapy. Furthermore 25% of patients prove refractory to standard of care. Our groups recently
reported expression of PDL-1 on human pituitary adenomas, providing a viable and novel immunotherapeutic target. Here we test
anti-PDL-1 in vivo in a recapitulative murine model of CD.
Methods: PDL-1 on human ACTH-secreting adenomas was further assessed via IHC. The murine ACTH-secreting ATT20/D16v.2
adenoma cell line was utilized to establish subcutaneous (sc) and intracranial (ic) models of CD in syngeneic A/HeJ x C57L/J F1 or
nude athymic mice. Tumor PDL-1 was assessed by flow cytometry and IHC. Plasma ACTH was measured by ELISA in sc models.
Mice were treated intraperitoneally (ip) with anti-PDL1 or isotype every 3 days x 12 doses. For sc tumors, tumor volume and plasma
ACTH were assessed, while survival was evaluated in the ic model. Tumor-infiltrating lymphocytes (TILs) were harvested and
analyzed by flow cytometry.
Results: Human pituitary adenomas demonstrate significant (≥1% staining) PD-L1 expression in 32% of samples, including 22% of
ACTH-secreting adenomas. Murine ATT20/D16v.2 tumors also demonstrate elevated PD-L1 expression, as well as elevated plasma
ACTH, recapitulating CD. Anti-PDL1 treated mice demonstrated reductions to tumor volume (p=0.0069, unpaired t test) in the sc
model as well as long term survival in the ic model. TILs in treated mice expressed lower levels of the exhaustion markers PD-1, TIM-
3, and LAG-3. Accordingly, anti-PDL-1 efficacy was lost in athymic mice, revealing a T-cell-dependent treatment benefit.
Conclusion: PDL-1 is significantly elevated on ACTH-secreting pituitary adenomas in patients and mice, yielding a significant T-cell
dependent antitumor effect to treatment with anti-PDL1. These results demonstrate an appropriate murine model for pre-clinical
investigation and a promising immunotherapeutic approach for CD. A multi-institution clinical trial is planned.
764. Comparison of intraoperative imaging with receptor-specific versus passive delivery of near-infrared dyes in human
pituitary adenoma surgery
Steve Cho (Philadelphia, PA); Jun Jeon, BS; Love Buch, BS; Shayoni Nag, BA; Jarrod Predina, MD; Sunil Singhal, MD; John Lee
Introduction: In contrast to visible-light fluorophores (e.g. 5-ALA), near-infrared (NIR) fluorophores have increased tissue-penetration
and less signal contamination. The Second-Window-ICG (SWIG) technique relies on passive accumulation of indocyanine-green (ICG)
in neoplastic tissues over 24 hours through the enhanced-permeability-and-retention (EPR) effect. We hypothesized that folate-
receptor-targeted intraoperative NIR imaging with OTL38 (folate-analog conjugated to cyanine dye) would be more specific than
imaging with SWIG in nonfunctioning adenomas, which overexpress folate-receptor-alpha (FRa). However, SWIG would allow better
visualization of functioning adenomas, which do not overexpress FRa.
Methods: Nine patients with pituitary adenomas (3 nonfunctioning, 3 GH-secreting, 2 ACTH-secreting, 1 PRL-secreting) received
systemic ICG infusions prior to surgery, while another 22 patients (14 nonfunctioning, 6 ACTH-secreting, 2 GH-secreting) received
OTL38 infusions. NIR fluorescence signal-to-background-ratio (SBR) was recorded for tumor and its margins during resection.
Immunohistochemistry was performed on the 22 adenomas to determine FRa-expression.
Results: With SWIG, the average SBR was 3.9±0.76, with no statistical difference between the 6 functioning and 3 nonfunctioning
adenomas. With OTL38, 9 tumors overexpressed FRa (all of them nonfunctioning) with an average NIR SBR of 3.2±0.52. The 8
functioning adenomas did not overexpress FRa and SBR was 1.6±0.50. Tissue identification with white-light alone demonstrated 78%
sensitivity, 95% specificity, 95% positive-predictive-value (PPV), and 80% negative-predictive-value (NPV). SWIG demonstrated 100%
sensitivity, 20% specificity, 75% PPV, and 100% NPV. With OTL38, all test characteristics were 100% for the 9 FRa-overexpressing
adenomas. Conclusions: Intraoperative imaging with NIR fluorophores, targeted and non-targeted, demonstrates highly sensitive
detection of pituitary adenomas. OTL38, a folate-receptor-targeted NIR fluorophore, is highly specific for nonfunctioning adenomas,
but may have limited utility in functioning adenomas. SWIG, which relies on passive diffusion into neoplastic tissue, is applicable to all
pituitary adenomas, but is less specific. Thus, targeted and non-targeted NIR fluorophores play important, yet distinct, roles in
intraoperative imaging.
765. Treatment response assessment maps (TRAMs): increased/decreased sensitivity to tumor/treatment-effects as a

function of time post contrast injection
Yael Mardor, MD (Tel-Hashomer, Israel); David Last, PhD; Dianne Daniels, PhD; Arielle Tylim; David Guez, PhD; members TRAM
collaboration
Introduction: TRAMs calculated from delayed-contrast MRI enable reliable (sensitivity/specificity<70%) differentiation between tumor
(blue in the TRAMs) and non-tumoral tissues (red). The TRAMs are calculated by subtracting 3D T1-MRIs acquired 5min (early time
point) post-contrast injection from those acquired 60-105min (late point) later. Here we studied the sensitivity to tumor/treatment-
effects as a function of the early T1-MRI acquisition time.
Methods: 7 patients with high grade glioma and 6 with brain metastases were scanned by the standard TRAMs protocol wit the
addition of a rapid 3D T1-MRI sequence (20 sec) acquired 2, 5, 12, 17, 20, 24 and 70 min post-contrast. Rapid-TRAMs were
calculated using the rapid T1-MRIs, where the late time point was fixed at 70 min and the early time point changed from 2 to 24 min
post-contrast. Enhancing volumes were determined on the T1-MRIs and copied to the TRAMs. Blue/tumor and red/treatment-effects
volumes were calculated within the enhancing regions.
Results: The blue/tumor volumes, calculated from the rapid-TRAMs, increased by a factor of 4.4±2.6 when moving the early time
point from 2min to 15.7±2.2min, where they plateaued. The increase between 5min (standard) and 15.7min was by 1.5±0.3. In
contrast, when moving from 2 min to 15.7min the red/treatment-effects volumes decreased by 0.7±0.2, and by 0.8±0.1 when moving
from 5min to 15.7min.

Conclusions: The TRAMs were shown to provide reliable differentiation between tumor/treatment-effects. The early time point is fixed
at 5min post-contrast. Using shorter delays may significantly decrease the sensitivity to tumor. Still, increasing the delay to 15min may
increase the sensitivity to tumor. This over-estimation of the tumor volume may be explained by the tumor vasculature clearing
contrast diffusing into further brain regions surrounding the tumor. An additional 3D-T1 acquired at 15min may be applied for
calculating additional TRAMs with higher sensitivity to tumor, for depicting small tumor regions.
766. Subthalamic nucleus deep brain stimulation combined with duloxetine changes pain behavior in Parkinsonian rats
Miriam Mingxuan Shao; Teresa Maietta, B.S.; Ian Walling, B.S.; Brian Kaszuba, B.S.; Amelia Stapleton; Nathaniel Kim; Tarun
Prabhala; Damian Shin, PhD; Julie Pilitsis, MD, PhD
Introduction: Chronic pain is the most common non-motor symptom in Parkinson's disease (PD). It remains undertreated in more than
40% of PD patients suffering from pain due to a current lack of effective therapies. Subthalamic nucleus deep brain stimulation (STN
DBS) relieves PD pain for some individuals. To improve STN DBS efficacy, we supplemented it with duloxetine; we have shown that
this STN DBS-duloxetine combination decreases mechanical thresholds in the hemiparkinsonian 6-hydroxydopamine (6OHDA) lesion
rat model. In this study, we assess the effects of STN DBS-duloxetine on pain related behavior in the place escape/avoidance paradigm
(PEAP)
Methods: Non-PD rats, PD rats, and PD rats treated with STN DBS-duloxetine underwent PEAP testing in a chamber consisting of a
bright and dark side. When rats spent time in the dark side, they were poked with a suprathreshold (60.0 g) von Frey filament on their
left/parkinsonian neuropathy-affected hind paw; in the bright side, rats were poked on their right/non-parkinsonian hind paw. Because
rats inherently prefer dark environments, time spent in the bright side reflected escape/avoidance behavior
Results: PD rats spent a significantly larger proportion of time (p=0.0105) in the bright side (0.3184±0.0071, n=24) than non-PD rats
(0.1847±0.0050, n=26). Rats treated with STN DBS-duloxetine spent a significantly smaller proportion of time (p=0.0452) in the bright
side (0.1537±0.0278, n=7) compared to untreated PD rats. Specifically, the proportion of time spent in the bright side decreased by
52% in treated PD rats.
Conclusion: Our results present STN DBS-duloxetine as a potential new treatment for PD pain. Because escape/avoidance behavior
has been associated with the anterior cingulate cortex (ACC), STN DBS-duloxetine's mechanism may involve altering ACC neuronal
activity in the descending inhibitory pain pathway. The descending inhibitory pain pathway may therefore serve as a promising target for
further development of neuromodulation therapies to treat PD pain.
767. De novo mutations in inhibitors of Wnt, BMP, and Ras/ERK signaling pathways in non-syndromic midline
craniosynostosis
Charuta G. Furey (New Haven, CT); Andrew Timberlake, PhD; Carol Nelson-Williams; Michael DiLuna, MD; Kristopher Kahle, MD,
PhD; Derek Steinbacher, MD; Dawid Larysz, MD; John Persing, MD; Richard Lifton, MD, PhD
Introduction: Non-syndromic craniosynostosis (NSC), with an estimated prevalence of 1 in 2,300 births, is the second most common
craniofacial birth defect, resulting from premature fusion of cranial sutures and often requiring surgical intervention in infancy. Whereas
the genetic determinants of syndromic craniosynostoses are well characterized, eighty-five percent of craniosynostosis cases are non-
syndromic occurrences of unknown etiology. Additionally, more than 95% of patients with NSC have no family history of disease,
suggesting a contribution from both de novo mutation and extremely rare transmitted variants to disease risk.
Methods: We recruited and performed whole-exome sequencing on DNA isolated from 384 patients with non-syndromic midline
craniosynostosis, comprised of 291 patient-parent trios (affected patient and unaffected parents) and 93 singleton cases. Exome-
sequencing data from these 873 individuals was then analyzed to identify rare, de novo and transmitted mutations contributing to
NSC, and candidate mutations were subsequently confirmed by Sanger sequencing.
Results: Exome sequencing of families with non-syndromic midline craniosynostosis revealed 5% of patients have damaging, de novo
mutations in negative regulators of Wnt, bone morphogenetic protein (BMP), and Ras/ERK signaling pathways, developmental
cascades that converge on common nuclear targets to promote bone formation (p = 2.4 × 10-11). We demonstrated that another 5%
have rare, transmitted protein-damaging mutations in these pathways. Collectively, these mutations contribute to 10% of NSC cases.
Conclusion: These findings establish a genetic cause for 10% of NSC cases, revealing novel disease-causing mutations affecting
intracellular regulators of developmental signaling cascades essential for bone formation and induction of osteoblast differentiation.
Such results provide insight into the pathophysiology of craniosynostosis as well as new opportunities for improved genetic counseling
and prognostic assessment of risk of recurrence and adverse neurodevelopmental outcomes for treatment planning.
768. Enhanced 5-ALA induced fluorescence in hormone secreting pituitary adenomas
Akrita Bhatnagar (Reston, VA); Prashant Chittiboina, MD, MS; Jie Lu, MD, PhD; Jacqueline Boyle; Dragan Maric, PhD; Stuart
Walbridge, BS
Introduction: Cushing’s Disease (CD) is caused by millimeter-sized corticotropinomas (microadenomas) that lead to
supraphysiological levels of glucocorticoid. Up to 40% of microadenomas are not visualized on gold-standard MR imaging. Pituitary
adenomas metabolize exogenous 5-ALA (an endogenous metabolite) to protoporphyrin IX (PpIX) at rates 20-50 times higher
compared with normal tissues. PpIX intensely fluoresces red (635nm) when excited with blue light (375-440nm), enabling its use as
an intraoperative fluorescence imaging agent. 5-ALA is now an FDA approved orally available prodrug. In this novel study, we
examined the efficacy of ALA-induced-PpIX fluorescence in human derived adenomatous and normal pituitary samples. We also

explored the modulation of PpIX conversion with CRH or dexamethasone (DEX), and subcellular localization of PpIX.
Methods: We used flow cytometry for PpIX intensity analysis. A human-derived corticotropinoma, its adjacent normal gland, murine
normal pituitary cells, and AtT20 cells were incubated with 5-ALA (300 nM) with/without DEX (1µM) or CRH (50nM). For confocal
microscopy, live cells imaged for PpIX (405nm/615nm) and mitochondrial (550nm/615nm) fluorescence.
Results: We found a 10-fold-increase in 5-ALA induced PpIX fluorescence intensity in human-derived adenomatous compared to
adjacent normal pituitary tissue (p<0.05). AtT-20 cell lines (n=6, p<0.05) fluoresced 7-fold more intensely compared to normal murine
pituitary tissue (n=3, p<0.05). The addition of DEX, before or after 5-ALA exposure, increased the fluorescence intensity by 31% (n=4,
p<0.05). The addition of CRH did not have a significant effect on 5-ALA fluorescence (n=3, p<0.05). We saw localization of 5-ALA to
mitochondria, and mitochondrial disruption in 5-ALA treated At-T20s.
Conclusion: Our results support the use of 5-ALA for fluorescence guided resection in hormone secreting microadenomas. The
supraphysiological levels of glucocorticoids, as seen in CD, may enhance the 5-ALA fluorescence in corticotropinomas. We confirm
the mitochondrial localization and disruption by 5-ALA, a basis for photodynamic therapy.
769. The development of a technical skills test for objective assessment in neuroendoscopic education
Edin Nevzati, MD (Aurora, CO); Jennifer Wagner, BS; D. Ryan Ormond, MD
Introduction: Procedures relevant to neuroendoscopy have gradually increased in scope and complexity as surgeons’ skills and
technology have improved. Unfortunately, endoscopy requires a unique set of skills that are difficult to acquire in most training
programs. Additionally, a method to test technical skills in a validated manner has rarely been attempted. The Society of American
Gastrointestinal and Endoscopic Surgeons (SAGES) has developed a validated process for skills achievement and assessment for
laparoscopy and flexible endoscopy that is now widely used across North America. Using this as a guide, we developed a technical
skills examination for objective assessment in neuroendoscopic education.
Methods: 16 participants were included in the study, and were divided by their seniority level into two groups defined as less than
PGY5 (n=8, junior surgeons) or greater than PGY5 (n=8, senior surgeons). Study participants were assessed for baseline
performance and then again following a four-hour neuroendoscopy course. Two-tailed Student t-test was used to evaluate
performance differences between cohorts.
Results: Significant differences were observed in baseline task performance with senior surgeons performing better than junior
surgeons (p = 0.0136). Overall performance improved significantly in both cohorts following the course (p = 0.0021). The performance
differences between junior and senior surgeons remained significant after repeating the test (p = 0.019).
Conclusion: A neuroendoscopic skills test can distinguish between more or less experienced surgeons. Significant overall
performance improvement, regardless of seniority level, following neuroendoscopic training, demonstrates the accuracy of the model
at detecting operating improvement in all stages of learning. An affordable technical skills test, modeled after what has been
developed in laparoscopic surgery, may improve neuroendoscopic education for skills achievement and assessment, and may aid in
the development of better models and simulators in neurosurgical education.
770. When in doubt, operate: an international survey of neurosurgeon decision-making in severe TBI
Theresa Williamson, MD; Mary Carol Barks, BA; Monica Lemmon, MD; Jihad Abdelgadir; Rasheedat Zakare, BS; Carrie Muh, MD;
Peter Ubel, MD
Introduction: Neurosurgeons make quick, challenging decisions in severe TBI. It is not always clear if a patient is “better off”; with
surgery or comfort care when weighing outcomes. Physicians are poor prognosticators of severe TBI outcomes (Jennett 1976) and
their decisions on when to withdraw care varies (Turgeon 2013). The CRASH model provides prognostic estimates but doesn’t replace
clinical judgment (Honeybul 2014). We studied the effect of the CRASH calculator on neurosurgeon decision-making.
Methods: A survey study was conducted at the CNS Annual Meeting. A hypothetical 77-year-old TBI patient presenting GCS 5, intact
brainstem reflexes and 1cm SDH with 1cm MLS was a scenario. Respondents randomly received the CRASH calculator 14-day
mortality and 6-month unfavorable outcome estimates (CRASH group) or not (no CRASH) and were asked treatment recommendation
and to estimate hospitalization, 30-day, and 6-month functional survival. Distributional differences and association between prognostic
estimates, survey version (CRASH vs no CRASH) and treatment recommendation were analyzed using a Wilcoxon rank sum or Fisher
exact test as appropriate.
Results: 139 neurosurgeons responded. Median prognostic estimate for hospitalization survival was 60% (IQR: 40-80%), 30-day-
survival 50% (IQR: 30-75%) and 6-month ability to perform ADLs 25% (IQR 10-50%). Prognostic estimate (poor versus good)
significantly associated with having CRASH (p= 0.027). Having CRASH associated with surgical recommendation (30% no surgery in
CRASH group, 13% no surgery in no CRASH group, p= 0.023).
Conclusion: Experienced neurosurgeons do not agree on prognosis in severe TBI. With prognostic estimates from CRASH, variation
decreased. Concordance on poorer prognosis led to less surgery. However, there is still a high rate of surgery despite poor prognosis
pointing to both a modifiable effect of prognosis on decision not to operate but also fixed opinion regarding offering surgery.
Disclaimer: The Journal of Neurosurgery Publishing Group (JNSPG) acknowledges that the preceding abstracts are published as submitted and did not go through
JNSPG’s peer-review or editing process.

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AANS 2018 Annual Scientific Meeting Abstracts

Advanced Practice Provider (APP) Abstract Award

©AANS, 2018 J Neurosurg Volume 128 • April 2018 1

operative pain and narcotic use

Advanced Practice Provider (APP) Abstract Award

©AANS, 2018 J Neurosurg Volume 128 • April 2018 2

408. Peptide therapeutics to prevent delayed vasospasm after subarachnoid hemorrhage

©AANS, 2018 J Neurosurg Volume 128 • April 2018 3

409. Ribavirin as a potential therapeutic for atypical teratoid/rhabdoid tumors

410. Trigeminal nerve stimulation suppresses cortical spreading depolarization

Aubrey C. Rogers (Brooklyn, NY); Chunyan Li, PhD; Raj Narayan, MD

©AANS, 2018 J Neurosurg Volume 128 • April 2018 4

413. Clinicopathologic implications of genomic disruption in pituitary adenomas

©AANS, 2018 J Neurosurg Volume 128 • April 2018 5

Aaron Gelinne (South Burlington, VT), BS; Susan Durham, MD

©AANS, 2018 J Neurosurg Volume 128 • April 2018 6

©AANS, 2018 J Neurosurg Volume 128 • April 2018 7

©AANS, 2018 J Neurosurg Volume 128 • April 2018 8

502. Single-neuronal basis for interactive social behavior in a primate model

©AANS, 2018 J Neurosurg Volume 128 • April 2018 9

505. Systemic and local immunosuppression in patients with high-grade meningiomas

Young Neurosurgeons Medical Student Abstract Award

506. Genotype based local targeted therapy for glioma

Mahaley Clinical Research Award

©AANS, 2018 J Neurosurg Volume 128 • April 2018 10

Brainlab Neurosurgery Award

Ronald L. Bittner Award on Brain Tumor Research

Todd Hollon, MD (Ann Arbor, MI); Daniel Orringer, MD

Preuss Research Award

©AANS, 2018 J Neurosurg Volume 128 • April 2018 11

510. The risk of malignancy after stereotactic radiosurgery

AANS/CNS Joint Section on Tumors Neuro-Oncology Trainee Award

©AANS, 2018 J Neurosurg Volume 128 • April 2018 12

©AANS, 2018 J Neurosurg Volume 128 • April 2018 13

Sanford J. Larson, MD, PhD Award

©AANS, 2018 J Neurosurg Volume 128 • April 2018 14

Brian D. Silber Award

Stewart B. Dunsker, MD Award

©AANS, 2018 J Neurosurg Volume 128 • April 2018 15

©AANS, 2018 J Neurosurg Volume 128 • April 2018 16

©AANS, 2018 J Neurosurg Volume 128 • April 2018 17

has significant limitations in lumbar PSO.

©AANS, 2018 J Neurosurg Volume 128 • April 2018 18

529. Spondylolysis and spondylolisthesis in American professional baseball players

©AANS, 2018 J Neurosurg Volume 128 • April 2018 19

©AANS, 2018 J Neurosurg Volume 128 • April 2018 20

©AANS, 2018 J Neurosurg Volume 128 • April 2018 21

robotically-assisted minimally invasive (MIS) 1-3 level fusions.

Philip L. Gildenberg MD Resident Award

©AANS, 2018 J Neurosurg Volume 128 • April 2018 22

Kiefer Forseth (Houston, TX); Cristian Donos, PhD; Nitin Tandon, MD

©AANS, 2018 J Neurosurg Volume 128 • April 2018 23

543. Induction and quantification of plasticity in human cortical networks

©AANS, 2018 J Neurosurg Volume 128 • April 2018 24

©AANS, 2018 J Neurosurg Volume 128 • April 2018 25

©AANS, 2018 J Neurosurg Volume 128 • April 2018 26

©AANS, 2018 J Neurosurg Volume 128 • April 2018 27

©AANS, 2018 J Neurosurg Volume 128 • April 2018 28

555. Biomechanical finite element analysis of the developing craniocervical junction

Jeffrey Nadel (Ann Arbor, MI); D. Wilkinson, MD; Cormac Maher, MD

©AANS, 2018 J Neurosurg Volume 128 • April 2018 29

International Abstract Award

©AANS, 2018 J Neurosurg Volume 128 • April 2018 30