(+)Scott C.

Sherman, MD Associate Professor of Emergency Medicine, Rush Medical College; Assistant Program Director, Cook County Emergency Medicine Residency, Chicago, Illinois

Subtle Presentations of Devastating Neurological Conditions

How does the expert clinician manage to sort through a sea of seemingly vague and disconnected complaints to pick up that rare but critically ill patient whose condition is potentially devastating if missed? What clues do astute physicians hone in on and why what tipped them off? Our patients dont read the textbook ahead of time and rarely volunteer the key pieces of information needed to come up with the tough diagnosis. Test your skills as the presenter works through challenging cases will you sort out the clues and make the right call? Identify common symptoms and signs that are associated with life-threatening neurological conditions. Describe diagnostic mishaps that get providers in trouble. Describe processes that increase the likelihood of making the tough diagnosis. Describe imaging and ancillary testing that enhances physical examination skills.

TH-289 Thursday, October 8, 2009 11:00 AM - 11:50 AM Boston Convention & Exhibition Center

(+)No significant financial relationships to disclose

Subtle Manifestations of Devastating Neurologic Disease

Scott C Sherman, MD Department of Emergency Medicine Cook County Hospital Chicago, IL

Case 1. Vertigo
58 year old man presents with one day of vertigo and vomiting. Vertigo is worse with head movement and he states he becomes nauseous when he attempts to sit up. He has to crawl out of bed for fear of falling. He denies tinnitus, weakness, numbness, or headaches. His past medical history is significant for an episode of V1 zoster on the left. On exam, there is rotatory nystagmus with the Dix-Hallpike test. He was given a dose of meclizine and the sign-out you receive is likely peripheral vertigo, reevaluate after medication. On re-exam, the patient reports diplopia in addition to vertigo and you note other exam findings

Diagnosis: Lateral Medullary (Wallenbergs) Syndrome

Clinical Features of Wallenbergs Syndrome Nystagmus, diplopia, vertigo, nausea, vomiting (vestibular nucleus) Ipsilateral Facial pain/numbness (5th nerve nucleus and tract) Limb ataxia (cerebellar fibers) Horners syndrome (descending sympathetic tract) Dysphagia and hoarseness (9th and 10th fibers) Loss of taste (nucleus and tractus solitaries) Numbness of arm, trunk, or leg (cuneate and gracile nuclei) Contralateral Impaired pain and temperature (spinothalamic tract) Differential Diagnosis of Binocular Vertical Diplopia1,2 o Myasthenia gravis o Cranial nerve pathology (Oculomotor nerve palsy) o Mechanical processes o Skew deviation: vertical divergence of the eyes that is associated with lesions in the posterior fossa, particularly the brainstem3,4

Peripheral vs. Central Vertigo

Clinical Features Nausea and vomiting Nystagmus Vertigo Severity Vertigo Pattern Gait imbalance Neurologic deficits *Resolves on repeated testing Peripheral +++ Horizontal or rotatory; Fatigable*; Suppressed with fixation +++ Paroxysmal, intermittent 0 to + 0 Central + to ++ Any direction, but classically vertical + to ++ Constant ++ to +++ 0 to +++

Why is this case subtle?

There are a couple of challenges here. First, classic syndromes like Wallenbergs often dont present classically. Incomplete lesions with incomplete syndromes are not uncommon. Second, it is easy to miss many of the neurologic findings and explain away the others, especially when alternate evidence support a more common (although benign) diagnosisBPPV.

Bottom Line: Vertigo

o When evaluating a patient with vertigo, additional neurologic deficits, including diplopia, suggest a central cause o Brainstem lesions present with a complex array of subtle neurologic deficits. It is difficult to recognize or remember all of these lesions, just sense when the signs and symptoms arent adding up

Case 2. Headache
32 year old woman with a history of migraine presents with left sided head and neck pain. She states that the headache started gradually after her yoga class and is aching in quality. She states that the headache is similar to previous migraines. Physical examination is unremarkable except that the pupil on the left is 2 mm smaller than the right and there is slight ptosis of the left eyelid.

Diagnosis: Carotid Dissection

Incidence Accounts for only 2% of ischemic strokes, but 10-25% of cases in the young and middle-aged5. Affects all age groups, but peak in 5th decade. Clinical Features

Minor precipitating event is frequently elicited (yoga, painting ceiling, coughing, sneezing). Chiropractic manipulation of the neck causes stroke in 1 in 20,000 cases Triad: 1. Pain (one side of face, head, neck) 2. Partial Horners syndrome (Ptosis, miosis without anhidrosis. Sweat glands are innervated by the sympathetic plexus surrounding the external carotid artery) 3. Retinal/cerebral CVA. All three present in less than one-third of patients. 2/3 strongly suggests the diagnosis. Pain is usually the initial symptom, followed approx. 4 days later (median) by stroke/Horners syndrome One fourth of patients with history of migraine consider this HA to be similar to their migraines May also present with cranial nerve abnormalities (12% of patients). 3, 5, 7, 12 are most common. Impairment of taste in 10%. Pulsatile tinnitus is reported in of patients. Bruit may be present Ischemic symptoms in 50-95% of patients. TIA may precede, but 1/5 have CVA without warning signs. Diagnostic Tests Angiography has traditionally been gold standard, but is being replaced by MRI Ultrasound may show an abnormal pattern of flow (90%), but the site of dissection is generally not seen Helical CTA is comparable to MRI/A Prognosis 90% of stenoses resolve and 2/3 of occlusions recanalize within first 2-3 months Treatment Anticoagulation (heparin/coumadin) to prevent thromboembolic complications because 90% of infarcts due to dissection are thromboembolic Theory that this treatment (or TPA) may extend the dissection appears to be unfounded Usually anticoagulation is continued for 6 months

Why is this case subtle?

This is a tough diagnosis to make even when symptoms are classic. Headache may mimic a patients typical symptoms and Horners syndrome can be overlooked without a thorough exam.

Bottom Line: Carotid Dissection

o Unilateral headache + partial Horners or TIA/CVA is a carotid dissection until proven otherwise o Anticoagulation is the treatment of choice and will not extend the dissection

Case 3. Weakness
32 year old man presents with weakness in his arms and legs that has been progressive over the last 2 days. His past medical history is significant only for a recent hospitalization for pneumonia. He denies any difficulty with breathing or voice. His exam is significant for weakness in distal muscles greater than proximal. He is areflexic.

Diagnosis: Guillain-Barr Syndrome

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) 95% of cases in North America and Europe6 Other variants involve axons (ie, acute motor axonal neuropathy) Incidence 1 in 100,000 Most common cause of nontraumatic acute paralysis in industrialized countries7,8 Occurs at any age; Four times more likely in patients > 75 Etiology Autoimmune attack on myelinated peripheral motor nerves due to cross-reactivity with infectious trigger Antibodies to epitopes within the infectious trigger cross react with to GM1 ganglioside, which is present in high concentrations in peripheral nerve myelin Clinical Features Antecedent viral illness (CMV, EBV, HSV, HIV), Mycoplasma pneumoniae or Campylobacter jejuni identified in two-thirds of patients. Usually within the preceding 6 weeks. C. jejuni is most common, occurring in one quarter of patients. Classic: symmetric weakness of thighs, legs, and then arms and eventually involving all four limbs (ascending paralysis) Symptoms peak in < 4 weeks with many cases presenting more rapidly Numbness or tingling of the lower extremities with sensory complaints in onethird. Occasionally sharp-shooting pains. Cranial nerve involvement in 50% and suggests more severe course Variants: Miller Fisher Syndrome (partial or complete ophthalmoplegia, severe ataxia and areflexia)9. May also have overlap with limb weakness and respiratory involvement. Other variants include isolated facial paralysis and paresthesias, pharyngeal-cervical-brachial weakness, and pure ataxia10 Normal sensory exam with absent reflexes. Presence of reflexes essentially rules out GBS.11 May be confused with acute flaccid paralysis of West Nile virus, which frequently presents with fever, leukocytosis, asymmetric distribution, no sensory deficits, concurrent encephalopathy, and pleocytosis in CSF12,13 Intubation recommended by 20/30/40 rule o Vital capacity < 20 mL/kg o Negative inspiratory pressure < -30 cmH2O 4

o Maximum expiratory pressure < 40 cmH2O o Alternatively, a reduction in any of these values by > 30% suggests the need for mechanical ventilation14,15. Laboratory findings High CSF protein with normal glucose and cell count is seen 1 week from onset of symptoms. Protein is usually between 55 and 250 mg/dl. Present in 80% of patients Treatment Plasmapheresis (4-5 50 mL/kg exchanges over 10-14 days). Improved outcome and more rapid recovery16,17 IVIG (0.4 g/kg/day) for 5 days has similar efficacy and is the preferred method because of greater convenience18-20. IVIG is also preferred in pregnancy21. Mechanism is thought to be antibody binding to anti-ganglioside antibodies. Plasma exchange or IVIG is indicated in patients that are unable to walk unaided when therapy is initiated within 4 weeks

Why is this case subtle?

If it presents in one of its variants or in a non-classic manner, it could be missed. Over time (days-weeks), the patient may progress to respiratory failure and death.

Bottom Line: Guillain-Barr Syndrome

o The presence of normal reflexes effectively rules out the diagnosis o Mechanical ventilation is required in almost a third of patients o Bedside spirometry is easy to perform. Remember the 20/30/40 rule

Case 4. Diplopia and Ptosis

29 year old female presents with diplopia and headache. The symptoms started one day ago and she notices that if she covers either eye, the double vision goes away. She denies vomiting. On physical examination, you note obvious ptosis and the left pupil is dilated and not reactive to light. Extra-ocular movements are abnormal in that the patient has difficulty looking medially, down, or up with her left eye.

Diagnosis: Oculomotor Nerve Palsy

Etiology of Nerve Palsy: 1) Aneurysm: Third nerve palsy (TNP) can occur when the nerve is compressed by a vascular structure. The most common structure is the posterior communicating artery, which passes in close proximity to the oculomotor nerve in the subarachnoid space. The average time to rupture from the time of onset of TNP is 29 days. Other less common aneurysm locations include the intracavernous internal carotid artery and basilar artery apex. 2) Microinfarction: Third nerve palsy can occur when the nerve becomes ischemic. This etiology is found in one-third to one-half of all patients with isolated third nerve palsies. Risk factors include diabetes and hypertension, as well as smoking, hypercholesterolemia, and advanced age. The natural history of these palsies is much different than when caused by an aneurysm. The majority of palsies resolve with observation alone. Improvement is noted in 68% within 4 weeks; 96% within 8 weeks; and 100% within 12 weeks. Oculomotor Nerve Palsy22 Cause % Microinfarction 43% Aneurysm 19% Trauma23 14% Tumor 12% Syphilis 2% Other* 10% * Other includes: Sinusitis, Hodgkins disease, herpes zoster, temporal arteritis, meningitis, encephalitis, collagen vascular disease, Pagets disease, operative complications, pituitary apoplexy24, migraine, uncal herniation, myasthenia gravis25 Definitions: Motor Dysfunction: Complete: Complete ptosis and ophthalmoplegia (eye is depressed and abducteddown and out). Incomplete: Partial ptosis or incomplete ROM in the appropriate directions of gaze with or without eye deviation in the primary position. Patients who present with isolated ptosis or gaze deficits in only one direction (adduction, supraduction, or infraduction) usually have a diagnosis other than a TNP22. Pupil Dysfunction: Normal: Pupil that is equal in size with normal light reflex. Comparison to contralateral pupil is 1mm. Partial: Pupil with 1mm of anisocoria or pupils equal in size with diminished light reaction. This is sometimes referred to as relative pupil sparing. Complete: A dilated pupil that does not react well (or at all) to light.

Rule of the Pupil: Pupil fibers reside in the most superficial and dorsomedial portion of the nerve in the subarachnoid space. A posterior communicating artery aneurysm almost always causes compression in this location (TNP with pupil involvement). Previous studies have documented pupil involvement in 96% of cases. On the other hand, ischemia to the vasa nervosum of the third nerve affects the central somatomotor fibers and tends to spare the peripherally located pupil fibers (TNP with pupil sparing). Pupil sparing is present in approximately 75% of cases of microinfarction. Caveats to the Rule of the Pupil26 1. Only when the third nerve is isolated. Other neurologic deficits suggest another diagnosis. 2. Be careful in patients less than 50. These patients are less likely to have microinfarct of the oculomotor nerve even if the pupil is spared. 3. Does not apply when there is partial pupillary involvement (relative pupil sparing). These patients may have an aneurysm. 4. Does not apply when incomplete motor involvement is present. Intracavernous aneurysms spare the inferior division of the nerve, which carries innervation to the inferior and medial rectus, inferior oblique, and pupillary sphincter. Basilar artery aneurysms compress from below the third nerve and, therefore, may not compress the dorsomedially located pupillary fibers. Clinical Situation Normal motor with partial/complete pupil Complete motor with normal pupil Complete motor with partial pupil** Partial/complete motor with complete pupil Partial motor with normal pupil Partial motor with partial pupil Risk of Aneurysm Extremely unlikely Very low Low risk 67% 30-40% 30-40% Neuroimaging27-30 None None* MRI/A MRI/A + Angio MRI/A Angio*** MRI/A Angio

* The normal pupil should be re-examined within the first 24-48 hours to ensure that it remains normal. The usual progression from the onset of symptoms to the severity of both motor and pupillary findings is 3 days in both ischemic and aneurysmal TNP. The usual sequence of development of TNP when caused by an aneurysm is levator, medial rectus, pupil, and then the remainder of the extraocular muscles. **These patients are more likely to have microinfarction as the cause, but anisocoria of > 2 mm is unusual, and should prompt concern for an aneurysm. ***Angiography is recommended if (1) worsening of motor or pupillary dysfunction beyond 2 weeks, anisocoria > 1 mm, no recovery within 12 weeks. Imaging Modalities: CT/LP: Testing sequence of choice when clinical history suggests ruptured SAH MRI: Tumor or other non-aneurysmal cause for the TNP. Also provides information about aneurysms if present, including anatomy, size, compression of adjacent structures, associated intraluminal thrombus.

MRA: Sensitivity depends on the size of the aneurysm (97% if 5 mm; 54% if < 5 mm). Fortunately, 91% of posterior communicating aneurysms that cause isolated TNP are > 5 mm. Overall MRA failure rate (missed aneurysm that will rupture in 8 years) is 1.5%28. CT-angiography: Sensitivity 95%; Specificity 74%. Like MRA, less sensitive for aneurysms < 5 mm Angiography: Despite advances, still the gold standard. 1-2% risk for systemic or neurologic morbidity. Higher risk in patients with cardiovascular disease (2.5%). If the likelihood of aneurysm is low, then non-invasive work-up.

Why is this case subtle?

A third nerve palsy usually isnt always challenging to diagnose, but the cause isnt always easily determined. Distinguishing between an aneurysm and microinfarction is important and knowing which patients require further imaging and which patients do not will aid the clinician in making the proper diagnosis.

Bottom Line: Oculomotor nerve palsy

o The evaluation of a third nerve palsy (TNP) is important to the emergency physician because it may be the only symptom of a non-ruptured intracranial aneurysm. o Older, vasculopathic patients with complete motor involvement (down and out) and normal pupil function can be observed closely without imaging studies. o All other patients require imaging and consultation.

Case 5. Diplopia
29 year old man with diplopia when looking to the left. The symptoms were present for 5 days. He denied headache, neck pain, or vomiting. He had no dysphagia or difficulty speaking. He reported no weakness or numbness. He had no past medical history. On physical exam the only abnormality noted was when he looked to the left31.

Diagnosis: Abducens Nerve Palsy

Abducens Nerve Palsy32 Cause % Unknown 26% Vasculopathy (DM, HTN) 35% Aneurysm 2% Trauma 12% Tumor* 5% Multiple Sclerosis** 7% Other*** 15%
* The incidence of intracranial tumors has been estimated to be as high as 30% in some studies. Referral bias is likely.

**Abducens nerve palsy is rarely the presenting feature of multiple sclerosis (0.5%)33 *** Other includes: Increased ICP (pseudotumor cerebri)34, herpes zoster, syphilis, Wernickes encephalopathy, meningitis, sarcoidosis, post-LP complications, operative complications, migraine, petrous apicitis (Gradenigo syndrome)35, and sinusitis.

In nontraumatic cases, coexisting neurologic signs/symptoms and co-morbidities are essential to determine the appropriate ED course32. 1. Isolated Abducens Nerve Palsy (CN VI palsy is the only sign/symptom) Undetermined or HTN/DM (84%), MS (8%), intracranial neoplasm (2%), neurosarcoid (1%) If patient has DM/HTN and no other co-morbidities, probable undetermined etiology: No neuroimaging indicated, arrange close follow-up. 2. Nonisolated Abducens Nerve Palsy (Additional neurologic symptoms or signs are presentother CN palsies, headache, ataxia, paresthesias) CVA (21%), intracranial neoplasm (18%), aneurysm (11%), pituitary apoplexy (4%), meningitis (4%) Full neurologic evaluation including neuroimaging and CSF analysis. 3. Young adults (< 50 year olds)36 NonisolatedCNS mass lesion (33%), MS (24%), meningitis (7%) IsolatedMS (33%), postviral (12%), CNS mass lesion (9%) Full neurologic evaluation including neuroimaging and CSF analysis.

Why is this case subtle?

In this case, the diagnosis is not subtle, but the need for neuroimaging and the risk of serious pathology must be determined.

Bottom Line: Abducens nerve palsy

o Pursue neuroimaging (MRI better than CT), consultation, and possible admission if: 1. Nonisolated abducens nerve palsy 2. Isolated and < 50 years old o Arrange close follow-up without ED neuroimaging if: 1. Isolated abducens nerve palsy in a patient > 50 years old with DM/HTN

Case 6. Back Pain

54 year old man presents with neck pain radiating down to the back. He states that he developed weakness in his upper extremities two days ago and today he could not walk. He reports subjective fevers. His past medical history is significant for HIV. On exam, he is afebrile. His strength exam is abnormal in all extremities. WBC count is 13.9. An MRI is obtained.

Diagnosis: Spinal Epidural Abscess

Background Rare (1 in 10,000 hospital admissions), but increasing due to aging population, increasing rate of spinal surgery, and spread of injection drug use37 Predisposing conditions o Immunocompromise (DM, HIV, elderly)38,39 o Spinal abnormality (DJD, trauma, surgery) o Potential source of infection (Injection drug use, indwelling catheter) Occurs through contiguous spread from vertebral osteomyelitis (33%) or hematogenous spread (50%) with the remainder of cases unknown Staphylococcus aureus in 2/3rds of cases with MRSA in 40%. Other pathogens include S epidermidis, gram negative bacteria (E. coli and Pseudomonas) Neurologic deficits due to cord compression, infarction, and edema Most commonly involves 3-5 vertebral spaces Clinical Features Location (thoracic 50%, lumbar 35%, cervical 15%) o Thoracolumbar and posterior epidural space is more common because of a larger amount of infection prone fat in these locations Progression of disease o Stage 1: back pain at the level of the affected spine o Stage 2: nerve root pain radiating from the involved spinal area o Stage 3: motor weakness, sensory deficit, bladder and bowel dysfunction o Stage 4: paralysis Duration of symptoms before hospitalization range from 1 day to 2 months Progression from one stage to next is highly variable (hours to days) Most common symptoms at presentation o Back pain (75%) o Fever (50%) o Neurologic deficit (33%) o All three is rare (only 13% at time of diagnosis40) Tenderness is common, especially over the spinous processes, but paraspinous muscle spasm and tenderness may also be present41 Diagnosis Leukocytosis (66%) C-reactive protein and sedimentation rate elevated in all, but nonspecific Blood cultures positive (60%) Lumbar puncture contraindicated MRI with IV gadolinium is > 90% sensitive CT may reveal narrowing of disk (ie, diskitis) and bone lysis (ie, osteomyelitis), but does not take the place of MRI Treatment Surgical drainage (decompressive laminectomy and debridement) and systemic antibiotics42 Surgical drainage ideally within 24 hours of presentation43 10

Empiric antibiotics against Staphylococcus (vancomycin), gram negative bacilli (3rd generation cephalosporin) No surgery if: patient refuses, high operative risk, paralysis > 24-36 hours, panspinal infection. May also take nonsurgical route if patient is neurologically intact, microbial etiology is identified, and patient is monitored closely44. If the abscess is small, sometimes CT guided aspiration alone is all that is needed43

Why is this case subtle?

A rare condition that may present with nonspecific findings causes epidural abscess to be frequently misdiagnosed on presentation. Overall, approximately half of cases are initially misdiagnosed (range 11-75%)37

Bottom Line: Spinal epidural abscess

o While dramatic in presentation when late, epidural abscess is a subtle diagnosis early in its course and is misdiagnosed in approximately half of patients during the initial physician visit o The outcome depends on early treatment. Left untreated, irreversible paralysis occurs in 4-22% of patients o Decompressive laminectomy in appropriate patients should be arranged as soon as possible to avoid a poor outcome

Case 7. Headache and Fever

45 year-old female presents with right sided headache, malaise, and fever. She denies neck stiffness, but states that the light bothers her eyes. She states the symptoms are similar in nature to previous bouts of sinusitis, but also states that she has had two previous episodes of bacterial meningitis. On examination, her temperature is 100.8F. Kernigs and Brudzinskis signs are negative and there is no nuchal rigidity. CT of the head demonstrates right sphenoid sinusitis with mild mucosal thickening. Based on her prior history of bacterial meningitis, a lumbar puncture is performed

Diagnosis: Bacterial MeningitisCSF Fistula

Bacterial Meningitis
Classic triad of fever, neck stiffness, and altered mental status is present in less than half of patients45. Absence of all three eliminates the diagnosis46 2 of 4 symptoms (fever, neck stiffness, altered mental status, headache) is present in 95% of patients45

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Signs and symptoms of Meningitis Headache Fever Meningismus Altered sensorium Vomiting Seizure Focal findings Papilledema

Frequency (%)46 50% 85-95% 70% 67% 30% 20% 25% 2-4%

CSF Fistula

EtiologyExtension of sinusitis47, head injury, previous surgery, spontaneous48 Most common site of CSF leakage is through the floor of the anterior cranial fossa which communicates with the ethmoid or frontal sinuses or nasal fossa MRI is an effective tool for making the diagnosis49. CT cisternography is also effective at localizing the site. Surgery (nasal endoscopic) is curative.

Why is this case subtle?

Headache and fever is a common presentation and doesnt necessarily equate to bacterial meningitis, especially in the absence of neck stiffness or confusion. Had it not been for this patients previous history of bacterial meningitis, the diagnosis could have easily been missed.

Bottom Line: Bacterial meningitis and CSF fistula

o Fever is almost universally present in bacterial meningitis, while meningismus is not o Consider a CSF fistula in a patient with previous history of meningitis and a similar presentation

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