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Advances in Primary Stroke Prevention
Walter N. Kernan
2019
Stroke in California
Annual Incidence rd
• Age 60: 0.3% 3 Leading Cause of
• Age 80: 0.8% Death
2 nd
Leading
Lifetime Risk
• 15-20% Cause of Neurological
Disability
Prevalence
• 2.3% of all adults
• 8.5% in adults ≥ age 65 years
• 500,000 (1 in 12)
PM Rothwell Lancet 2004;363:1925. S Koton. JAMA 2014;312:259. EJ

Benjamin Circulation 2019;139:e56. CDPH Website 3.27.2019. HCHS 2016
data 3.27.2019. GBD Lancet Neurology 2017;16:877-97
Adult With No Cerebrovascular Disease
History and physical

Council for
& Healthy
continued health
Fasting lipid profile
Non-Atherosclerosis Atherosclerosis-Related Risk Factors Carotid Stenosis

Stroke Risk Factors Lifestyle Disease States
• Valvular disease
• Sickle cell anemia • Inactivity • Hypertension
• Thrombophilia • Poor Diet • Diabetes
• PFO • Smoking • Dyslipidemia
• Atrial fibrillation • Obesity
• Aneurysm
• AVM
• Others
Aspirin?
Specific Management
AHA Advisory on Brain Health in Adults
. . . the health of the brain is inextricably related to

cardiovascular and cerebrovascular health, and interventions
aimed at promoting cardiovascular health would be expected
to promote brain health and vica versa.
PB Gorelick. Stroke 2017;48:e284-e303


Council for
& Healthy
continued health

• Aneurysm
• AVM
• Others
Aspirin?
Specific Management

Council for
& Healthy
continued health

• Aneurysm
• AVM
• Others
Aspirin?
Specific Management
Prevalence of Diagnosed Atrial Fibrillation
Women
Prevalence Men
(%)
Prevalence of Undiagnosed AF Age 75: 3%

AS Go JAMA 2001;285:2370; E Svennberg Circ 2015;131:2176;
P Wolf Stroke 1991;22:983
Should we Screen?
European Society for Cardiology

Opportunistic screening for AF is recommended by
pulse taking or ECG rhythm strip in patients >65 years
of age. (Class of Recommendation I, LOE B)
USPSTF
Not yet (Insufficient Evidence)
P Kirshhof Europace 2016;18:1609-1678; SJ Curry JAMA 2018;320:478

AHA/ACC Guidance on A-Fib
• Anticoagulate based on stroke risk: CHA2DS2-VASc score ≥2

men, ≥3 women.
• Regardless of burden/duration of A-Fib
• A-flutter treated same as A-Fib
• NOACs recommended over warfarin EXCEPT IF:
• Mitral stenosis
• Mechanical heart valve
• Modify choice of agent based on eGFR
• Apixaban or warfarin OK in ESRD on HD
CT January JACC 2019;

2017 ACC/AHA Guideline on
High Blood Pressure in Adults
Categories of Blood Pressure in Adults*

Category SBP (mm Hg) DBP (mm Hg)
Normal <120 and <80
Elevated 120-129 and <80
Hypertension
Stage 1 130-139 or 80-89
Stage 2 ≥140 or ≥90
*Individuals with SBP and DBP in 2 categories should be
designated to the higher BP category
PK Whelton JACC 2018;71:e127
Prevalence of Hypertension
Use of Antihypertensive Medication

Age Group Men Women
All 48% 43%
20-44 30% 19%

45-54 50% 44%
55-64 70% 63%
65-74 77% 75%
75+ 79% 85%
PK Whelton JACC;2018:71:e127
2017 ACC/AHA Guideline on Hypertension
Threshold For
Patient Category Drug Therapy Goal
Secondary Prevention
Clinical CVD ≥130/80 <130/80
Primary Prevention
10 year risk ASCVD ≥ 10% ≥130/80 <130/80
10 year risk ASCVD < 10% ≥140/80 <130/80
Older Persons* ≥130 SBP <130 SBP
*>65, non-institutionalized, ambulatory, community-living
PK Whelton JACC 2018;71:2275
Systolic Hypertension in the Elderly
Mean and women > 60 years
SBP > 160 mm/Hg, DPB <90 mmHg
Treatment: chlorthalidone +/- atenolol

Duration: mean 4.5 years
Mean Achieved difference SBP: ~12 mmHg
# Events (%)
Active Rx Placebo
° Outcome ARR
Stroke 103 (5.2%) 159 (8.2%) 3% 0.64 (0.50-0.82)
JAMA 1991;265:3255
<60% of adults with HTN are at goal BP <140/90
Things that may help

No co-pays
Education
Simple regimens
Once daily
Combination pills
Self-monitoring
Case management (Pharmacist)
M. Viswanathan Ann Intern Med 2012;157:785. BB Green JAMA 2009;229:2857.

Whelton Circulation 2017; Y Zhang HTN 2017;70:736
Antihyperglycemic Strategies
1. How low to go?

2. Which glucose lowering strategies to choose?
4 Agents Reduce Risk for MACE*
Results from Placebo-Controlled Trials
Patients
Other
High Risk MACE*
Agent Trial CVD for CVD HR (95% CI)
Empagliflozin EMPA-REG No 0.86 (0.75-0.99)
Liraglutide LEADER 0.87 (0.78-0.97)
Canagliflozin CANVAS 0.86 (0.75-0.97)
Semaglutide SUSTAIN 0.74 (0.58-0.95)
*MACE=Major Adverse Cardiovascular Event (non-fatal
myocardial infarction, non-fatal stroke, cardiovascular death).
SP Marso NEJM 2016;375:311. B Zinman NEJM 2015;373:2117. S Yaghi Circulation
2018;137:455. SP Marso NEJM 2017;375:1834. B Neal NEJM 2017.
Semaglutide Prevents Non-Fatal Stroke
HR=0.61; 95 CI=0.38-0.99
% Placebo
Patients
With Non-Fatal
Stroke
Semaglutide
Months in Trial
SP Marso NEJM 2016;375:1834.

Management of Hyperglycemia
HbA1c > 6.5% Consistent With T2DM
Lifestyle Optimization
Metformin first-line pharmacotherapy
HbA1c <7% No No Other Factors Affect Choice

Does Patient
After Lifestyle of Pharmacotherapy
have CVD?
Therapies? • CKD
Yes Yes • Obesity
GLP1-RA or SGLT2i • Risk of hypoglycemia
Continue Diet • Cost
with proven CV
and Activity • Patient preference
benefit
DK Arnett Circulation 2019; Davies Diab Care 2018;

Remission of Diabetes in the DiRECT Trial
Mean Weight Loss at One Year:
Control Group 1 kg
Intervention Group 10 Kg
46%
Remission
Of
Diabetes at
One Year* 4%
(% Patients)
Control Intervention
Group Group†
*HbA1c<6.5%, no diabetes drugs
MJ Lean Lancet 2018;391:541

Management of Cholesterol
For Primary Prevention
Age Range, Statin Goal LDL
Clinical Status* Years Intensity Reduction
LDL ≥ 190 20-75 high ≥50%
Diabetes, LDL > 70 40-75 Moderate ≥30%
High-Risk†, LDL > 70 40-75 High ≥50%
Intermed-risk‡, LDL > 70 40-75 Maybe ≥30%
Moderate
All Others - Variable -
*LDL units = mg/dL
†High risk = > 20 risk ASCVD in 10 years.
‡Intermediate risk= 7.5%-19.9%
FJ Alenghat JAMA 2019; SM Grundy JACC 2018
Managing Patient on Statin Therapy
70% of patients with ASCVD stop therapy within 2 years

• Persistence in primary prevention likely even less
Statin associated muscle symptoms affect 5-20% of patient

• Nocebo effect likely large
• In HOPE3, 5.8% rosuvastatin, 4.7% of placebo
• Severe rhabdomyolysis and statin-associated autoimmune
myositis are very rare
Strategies to address muscle symptoms

• Discontinue until symptoms improve
• Check CK if severe symptoms or weakness
• Most patients succeed in a re-challenge
SM Grundy. JACC 2018

About Triglycerides
Triglyceride-rich lipoproteins (VLDL) are now important.
Reduce-it Trial
8000 patients with
• CVD or DM + other risk factors
• Fasting TG 135-499
• LDL chol 41-100 mg/dL on statin therapy
Treatment: 2 g Icosapent ethyl twice daily or placebo
Findings:
• at 4.9 years, 25% reduction in CV death, stroke, MI,
coronary revascularization, angina
• 36% reduction in ischemic stroke
• Safe (+/- atrial fibrillation)
DL Bhatt NEJM 2019;380:11-22.

Internal
Carotid
Artery
Stenosis
Asymptomatic Carotid Artery Study
(Age 40 to 69 years, 60-99% stenosis)
-Year Risk
Outcome Med Surg NNTBT P
Ipsilateral stroke or any peri-
11.0% 5.1% 17 0.004
operative stroke or death*
Major ipsilateral stroke or any

6.0% 3.4% 38 0.12
peri-operative stroke or death
*Includes perioperative stroke or death in 2.3% of surgical group
and 0.4% of medical group
Executive Committee for the ACAS. JAMA 1995;273:1421-1428

DEVELOPMENTS SINCE ACAS . . .
Favoring Carotid Revascularization
• Perioperative stroke or death risk has fallen
Favoring Medical Therapy

• Low rates of progression of carotid atherosclerosis
• Reduced risk for ipsilateral stroke without surgery – now
~1%/year
• Wider use of statin therapy
• Reduced cigarette smoking
• Better blood pressure control
S Chaturvedi JAMA Neurol 2017;72:1233. LS Hirt Stroke 2014; 45:702. K
Rosenfield NEJM 2016;374:1011. AR Naylor Curr Opin Neurol 2017;30:15. AB
Munster Neurology 2015;85:365.
Internal Carotid Artery Stenosis
It is common
Surgery can fix it
Medical therapy may be just as good
DV Heck Neurology 2017;88:2016

Physicians Health Study
Men
40-85 years
No history of MI or stroke
Treatment Group
Aspirin* Placebo
N=11,037 N=11,034 RR 95% CI
CV Mortality 81 83 0.96 0.60-1.54
MI 139 239 0.56 0.45-0.70
Stroke 119 98 1.22 0.93-1.60
Hemorrhage† 48 28 1.71 1.09-2.69
*325 mg every other day. †Requiring transfusion
PHS NEJM 1989;321:129
Aspirin for Primary Prevention - A Meta-Analysis of 13 Trials
Outcome Aspirin No Aspirin HR ARD*

Composite 5.71 6.14 0.89† -0.43
CV Mortality 1.91 1.95 0.94 -0.04
MI 2.81 3.12 0.85† -0.31
Stroke
Total 2.40 2.50 0.93 -0.10
Ischemic 1.84 2.14 0.81† -0.30
Major Bleed 2.46 1.75 1.43† +0.71
*ARD=absolute risk difference
†95% confidence interval excludes 1.
SL Zheng JAMA 2019;32:277-287

2019 ACC/AHA Guideline on 1° Prevention
of Cardiovascular Disease - ASPIRIN
1. Consider low-dose aspirin for select adults at high ASCVD
risk, but not at high risk for bleeding*
2. Do not use aspirin for adults > 70 years of age
3. Do not use aspirin for adults at increased risk of bleeding
“Aspirin should be used infrequently in the 1° prevention of ASCVD”
*High ASCVD risk not specified. High bleeding risk includes:

H/O GI bleed or ulcer, age >70 years, thrombocytopenia,
coagulopathy, CKD, and concurrent use of other medications
that increase bleeding risk.
DK Arnett Circulation 2019

Asymptomatic
Carotid Stenosis
Aspirin?
Two High-Value Interventions for
The Future for Stroke Primary Prevention
• Lifestyle Improvement
Top 4/10 priorities in the AHA/ACC primary
prevention guideline refer to lifestyle
4/7 items in AHA’s “life’s simple 7’s” refer to
lifestyle
• Primary Care
Accessibility
Longitudinality
Comprehensiveness
Coordination
B Starfield. Primary Care. Oxford University Press 1992.DK Arnett Circulation 2019. E.
Sanchez JAHA 2019;
END
Thank
Thank You
you
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The Transformative
Power of Lifestyle
Medicine
Dean Ornish, M.D.
Founder & President
Preventive Medicine Research Institute
Clinical Professor of Medicine
University of California, San Francisco
Lifestyle Medicine=
lifestyle as treatment to
reverse disease as well
as prevention
Optimal Lifestyle Program
Whole foods plant-
based diet
naturally low in fat
& refined
carbohydrates
Stress management
Moderate exercise
Psychosocial support
What is
the cause?
Your body often has a
remarkable capacity to begin
healing itself if you give it a
chance to do so—
and quickly.
Can Lifestyle
Changes Reverse
Heart Disease?
Ornish D, Gotto AM, Miller RR, et al. Clinical Research. 1979;27:720A.
There was a 91%
reduction in the frequency
of angina in 24 days.
--Ornish D, et al. JAMA. 1983 Jan 7;249(1):54-9.
.
Lifestyle Heart Trial
Men and women with moderate to
severe CHD were randomly assigned
to intensive lifestyle changes or to
usual care
Major endpoints = quantitative
coronary arteriography, cardiac PET,
and cardiac events
% Diameter Stenosis: Quantitative Coronary Arteriography
52%
50%
48%
46%
44%
42%
40%
38%
Control
36% Treatment
Baseline (n.s.) 1 year (P<.02) 5 years (P<.001)
Ornish D et al. Lancet. 1990; 336:129 & JAMA. 1998;280:2001.

None of the experimental group
patients took lipid-lowering drugs; more
than 50% of the control group patients
began taking them during the study.
Progression was significantly greater in
control group patients not taking lipid-
lowering drugs (40.7 to 59.7%) than
those who were (45.7 to 51.7%).
Statins increased the risk of developing
type 2 diabetes by 46% in 9,000 men
over six years. A major complication of
diabetes is heart disease.
—Cederberg H et al. Diabetologia. 2015 May;58(5):1109-17.
There was a 40% reduction
in LDL-cholesterol in the first
year without cholesterol-
lowering drugs.
--Ornish D et al. JAMA. 1998;280:2001.
There was a 400%
improvement in coronary
blood measured by cardiac
PET scans after 5 years.
--Gould KL, Ornish D, et al. JAMA. 1995;274:894-901.
99% of patients stopped or reversed their
heart disease as measured by cardiac
PET scans after 5 years.
In contrast, 45% of controls got worse,
50% showed no change, and
only 5% improved (p = 0.03).
--Gould KL, Ornish D, et al. JAMA. 1995;274:894-901.
Adherence and Change in Coronary Atherosclerosis
after Five Years
US
6%
3%
1%
0%
0%
-3%
-6%
-7%
-9%
Low (<56%) Intermediate (56–88%) High (>88%)
Ornish D et al. JAMA. 1998;280:2001

There were 2.5 times as

many cardiac events in the
control group as in the
lifestyle group after five
years.
The image part with relationship ID rId3 was not found in the file.
Can Lifestyle
Changes Reverse
Prostate Cancer?
Principal Investigators:
Dean Ornish, M.D. Peter Carroll, M.D. William Fair, M.D.
Chairman and Professor, Dept.

of Urologic Surgery
Clinical Professor of Chairman and Professor, Dept.
Medicine, UCSF of Urology, UCSF
Memorial Sloan-Kettering
Cancer Center
Patient Selection Criteria
93 men with biopsy-proven prostate
cancer, PSA 4–10, Gleason <7
All patients chose to do watchful
waiting for reasons unrelated to this
study
Randomly assigned to intensive
cardiac rehabilitation or usual care
Changes in PSA
6.80 6.74
6.55
6.36
6.30
6.23
6.05
5.98
P=0.002
5.80
Baseline 12 Months
Control (n=41) Experimental (n=43)
Ornish D et al. Journal of Urology. 2005;174:1065

Degree of Lifestyle Change
and Changes in PSA
8% US
7%
4%
2%
1%
-1%
-3%
-5%
-6% P=0.001

Change in Prostate Tumor
Growth (LNCaP)
0%
-9%
-16%
-32%
-48%
-64%
-70%
-80% t=6.9, P=.000

%FBS
Control Experimental

Degree of Lifestyle Change and Inhibition of LNCaP
Tumor Growth
0%
-8%
-20%
-40% -39%
-60%
-72%
-80% P=0.0001
Baseline-12m Change in LNCAP Cell Growth

Baseline 1 year later
PSA—6.4 ng/ml PSA—4.5 ng/ml
None of the experimental group
patients but six control group
patients had conventional treatment
during the first year.
In the Physicians Health Study, men who ate
mostly a Western diet had a 250% higher risk of
prostate cancer-related death—and a 67%
increased risk of death from any cause. In contrast,
men who ate mostly a whole foods plant-based diet
had a 36% lower risk of death from all causes.
Yang M. et al. Cancer Prevention Research, June 2015 DOI: 10.1158/1940-6207.
Unifying Theory
Same diet and lifestyle

program for all of these
improvements.
Shared Underlying Mechanisms
Chronic inflammation
Chronic sympathetic nervous system stimulation
Microbiome
Oxidative stress
Apoptosis
Angiogenesis
Gene expression
Telomeres
Immune System
Epic Study
In 23,000 people, exercising 3.5 hours a

week, not smoking, eating a healthy diet,
and keeping a healthy weight prevented
93% of diabetes, 81% of heart attacks,
50% of strokes and 36% of all cancers.
EPIC study, Arch Intern Med. 2009;169(15):1355-1362.
Egg yolks and red meat increase TMAO levels,
causing atherosclerosis.
Hazen S et al. N Engl J Med. 2013 Apr 25;368(17):1575-84
TMAO levels were 3.3 on an Atkins diet, 2.6 on

a Mediterranean diet, and 1.8 on an Ornish diet.
Park JE, Hazen S et al. Nutr. Metab. Cardiovasc Dis. Feb 22, 2019
can lifestyle changes
beneficially affect
gene expression?
Gene expression in 501
genes was beneficially
affected in only 3 months
Ornish et al. Proc Nat Acad Sci USA 2008; 105: 8369.
RAS family oncogenes (RAN,
RAB14, RAB8A) that promote
prostate cancer and breast
cancer were downregulated.
change in genes
linked with
breast cancer and
prostate cancer
(red = turned on
green = turned off)
After 12 weeks, this lifestyle medicine program
downregulated genes involved in causing
atherosclerosis, chronic inflammation, oxidative
stress, angiogenesis, and cholesterol
metabolism. Over five times as many genes
were beneficially changed during this time.
Ellsworth D et al. Circ Cardiovasc Genet. 2014 Apr;7(2):151-60.

Our Genes are Not our Fate
Genes can double the risk of heart

disease, but a good lifestyle cuts it in
half.
Healthy lifestyles lower risk of heart
disease regardless of genes.
Khera AV, Fuster V, et al. N Engl J Med Nov 16, 2016

Downregulated
Genes:
Upregulated
Genes:
Dusek JA et al, PLoS One

2008;3(7): e2576.
Can Lifestyle Changes
Reverse Cellular Aging?
Telomerase increased 30%
in only 3 months
Telomerase Activity (Ln)
2.4
P < 0.05 (two tailed)
2.3
2.2
2.1
1.9
1.8
1.7
1.6
1.5
Baseline 3 Months
1 SEM
Ornish D et al. Lancet Oncol. 2008; 9: 1048–57.

Mean Changes in Telomere Length After 5 Years
0.06
0.045
0.03
0.015
0
p<0.004
-0.015
-0.03
Exp Group Control Group
Ornish D et al Lancet Oncol. 2013 Oct;14(11):1112-20.

There was a significant
correlation between adherence
and telomere length (p<0.007)
Ornish D et al. Lancet Oncology 2013.

Reverse Dementia?
The MIND diet score was associated with a
slower rate of cognitive decline equivalent to
7.5 years of younger age among the
participants in the top third of MIND diet scores
compared with the lowest third.
--Morris MC et al. Alzheimer’s & Dementia 2014;10:P166.
In the Finnish Geriatric Intervention Study
(FINGER) study, a radomized trial of men and
women 60-77 in age with CAIDE scores of at
least 6 points and cognition at mean or slightly
lower, an intervention of diet, exercise, cognitive
training, vascular risk monitoring maintained or
improved cognitive function after 2 years.
--Ngandu T et al. Lancet 2015 June 6;385(9984):2255-63.
Duke Study
160 men and women, randomly-assigned, 6
months
Cognitive impairment, no dementia, age >55 years
Cognitive function 28 years older than bio age
4 groups: DASH diet; exercise; both; or neither
Exercise improved cognitive function (p = 0.046)
DASH diet was not significant (p = 0.059)
Exercise + diet showed greatest improvement:
9 years improvement (84 vs 93 years, p = 0.012)
—Blumenthal JA et al Neurology. 2019;92.

Reverse Alzheimer’s
Disease?
Can Lifestyle Changes Reverse
Early-Stage Alzheimer’s Disease?
100 men and women with early-stage

Alzheimer’s disease (MOCA =16-25) living
in the Bay area
Study conducted at the nonprofit
Preventive Medicine Research Institute in
collaboration with the Memory & Aging
Center at UCSF, Harvard Medical School,
UCSD, & UCLA.
Randomly assigned to two groups.

Both groups tested at baseline; one
receives the intervention for 20 weeks
and both groups are retested.
The other group crosses over and
receives the intervention for 20 weeks
and both groups are retested again
after a total of 40 weeks.
Primary endpoint = measures of cognitive function
(UCSF)
MOCA
ADAS-cog (Alzheimer’s Disease Assessment
Scale-cognitive)
Comprehensive NTB (neurological test battery)
MRI with quantitation of hippocampal volume
PET with FDG to detect amyloid (when needed)
Biomarkers
Telomere length (Dr. Elizabeth Blackburn, UCSF)

Gene expression (Dr. David Sinclair, Harvard)
Proteomics (Dr. David Sinclair, Harvard)
Microbiome (Dr. Rob Knight, UCSD)
DNA Clock (Dr. Steve Horvath, UCLA)
No costs to participants
21 meals/week provided to patients + caregivers
Transportation provided when needed
Periodic home visits
What enables people to make
sustainable changes in their
lives?
Fun, freedom,
pleasure, & love
Risk factor modification =
fear-based
Fear is not a
sustainable
motivator
Adherence to Statin Therapy
% of 37,000 New-to-Statin Patients Remaining on Therapy
100
90
80
70
60
50
40
Lipitor
30
Lescol
20
Mevacor
10
Pravachol
0 Zochor
Oct ‘97 Nov Dec Jan ‘98 Feb Mar Apr May Jun Jul Aug Sept
Source: NDC Health Invormation Services, 1998

Adherence was 85-90% in
3,780 men and women at all 24
sites after 1 year
When people feel loved and cared for,
they are more likely to make lifestyle
choices that are life-enhancing than
self-destructive.
There’s no point in giving
up something you enjoy
unless you get something
back that’s even better—
and quickly!
Dynamic
What is an optimal
way of eating?
It’s not low carb vs. low fat.
It’s low in bad carbs & bad fats;
higher in good carbs and good fats.
Very low in animal protein.
Convergence of Nutrition Advice
Consume mostly plants: fruits,
vegetables, whole grains, legumes, &
soy products in their natural forms
What you include in your diet is as
important as what you exclude
Eat food as close as possible in its
natural form
Convergence of Nutrition Advice
Reduce intake of hydrogenated fats,
saturated fats, and trans fats
Consume 4 grams/day of omega-3
fatty acids
Organic is better (taste + health)
Reduce intake of sugar and refined
carbohydrates
A higher frequency of organic food
consumption was associated with a
reduced risk of cancers of the breast,
colon, prostate, and lymphoma.
Baudry J et al. JAMA Intern Med. 2018;178(12):1597-1606.
Diets high in animal protein:
• 75% increase in total mortality
• 400% increase in cancer risk
• 500% increase in diabetes
• significantly higher IGF-1 levels
—Levine ME et al. Cell Metabolism 19, 407–417, March 4, 2014
The only diet proven in randomized
controlled trials to reverse heart disease
without drugs is a whole foods plant-based
diet very low in fat & refined carbohydrates.
—Ornish D et al. JAMA. 1983;249:54.
—Ornish D et al. Lancet. 1990;336:129.
—Gould KL, Ornish D, et al. JAMA. 1995;274:894.
—Ornish D et al. JAMA. 1998;280:2001.
A low carb diet high in animal protein
and fat was associated with a 33%
higher all-cause premature mortality
and a 51% higher cardiovascular
mortality in a dose-response pattern.
Li S, et al. J Am HeartAssoc. 2014;3:e001169 doi: 10.1161/JAHA.114.001169
Smith S. N Engl J Med 2009;361:2286-2288
`
Mediterranean Diet (PREDIMED)
“low fat” reduced 39% to 37% fat
increased consumption of sugar and
refined carbohydrates
no significant reduction in the rates of
heart attack, death from CV causes, or
death from any cause
significant reduction only in stroke rates
N Engl J Med 2013; 368:1279-1290.
Highmark Blue Cross Blue Shield
Demonstration Project
In 3,780 patients who went through this lifestyle

medicine program at 24 sites in Pennsylvania,
Nebraska, and West Virginia, there were
significant improvements in all metrics after 12
weeks and after 1 year.
Silberman A et al, Am J Health Promot 2010;24[4]:260–266.

Weight Loss
All Participants (N=1,908)
200 199lbs
195
190
188lbs
185
180lbs
180
175
170 P<.000
Baseline 12 Weeks 1 Year
Reduced Angina (% of Participants with Any Angina in
Preceding 40 Days)
30
27
25
20
15 14
10
8
5 P<.000
96.5% of patients reported
significant improvements in
angina severity after one month
Increased Functional Capacity (METs)
11 METs 11 METs
11
10
9 METs
9
8 P<.000
Improvements in Quality of Life (SF-36)
75
71
70
70
65
60
56
55 P<.000
Reduced Systolic Blood Pressure
Systolic BP (mm HG)
150
150
145
140
136
135
130 129
125
120
115 All P<.001

Reduced Diastolic Blood Pressure
Diastolic BP (mm Hg)
86 86
84
82
80
79
78
76
76
74
72
70 All P<.001
Improvements in Blood Sugar
Fasting Glucose (mg/dl)
160
150
150
140
130
125
120
120
110
100 All P<.001

CED-D Depression Scores
12
11
6 6
6
0 P<.000
We train a team of six health care professionals:
• Physician = Quarterback
• Nurse
• Stress management
specialist
• Exercise physiologist
• Registered dietitian
• Clinical psychologist
1
4
6
Patients come for 18 four-hour

sessions with 15 patients/class
(twice/week for 9 weeks):
• 1 hour of supervised exercise The image part with relationship ID rId2 was not found in the file.
• 1 hour of stress management

• 1 hour of a support group
• 1 hour lecture + group meal
1
4
7
Reclaiming our role
as healers, not just
technicians
The deepest roots of healing—
both personal and social—
come from transforming
isolation into intimacy.
Ornish D. Love & Survival. New York: HarperCollins, 1998.
Information is not sufficient to
motivate most people to make
sustainable lifestyle changes
Love is more
powerful than fear
Social Isolation & Stroke
479,054 individuals from the UK
Biobank followed for 7.1 years
Social isolation was associated
with a 43% higher risk of AMI
and a 39% higher risk of stroke
Hakulinen C et al. Heart. 2018 Sep;104(18):1536-1542.
Social Isolation & Stroke
Systematic review of 11 longitudinal
CHD studies and 8 stroke studies
Poor social relationships were
associated with a 29% increase in risk
of incident CHD and a 32% increase in
risk of stroke
Valtorta NK et al. Heart. 2016 Jul 1;102(13):1009-16.
Social Support & Atherosclerosis
Rabbits on a 2% cholesterol diet were petted,
held, talked to, and played with.
Compared to the randomized control group, the
experimental group showed a 60% reduction in
sudanophilic lesions.
Serum cholesterol levels, heart rate, and BP
were comparable in both groups.
Nerem R et al. Science. 1980;208:1475-6.
Depression and Mortality 6 months After a
Heart Attack
30
25
20
% Mortality
15
Depressed (n=35)
10
Nondepressed (n=187)
5
0
0 1 2 3 4 5 6
Months Post—MI
Frasure-Smith, N. JAMA 1993;270:1819.

Duke Study
1,400 men & women had
angiography; at least one vessel
severely stenosed.
After 5 years, those who were
unmarried and did not have a
close confidant were more than
three times as likely to have died
(15% vs. 50%).
Williams RB, et al. JAMA. 1992;267(4):520-524.
Social Networks & Health
If your friends are obese, your risk of obesity is 45%
higher
If your friend’s friends are obese, your risk of obesity
is 25% higher
If your friend’s friend’s friend is obese, your risk is
10% higher--even if you’ve never met them
Christakis N, Fowler J. N Engl J Med. 2007; 357 (4): 370–379.

Social Networks & Health
This pattern also seen with smoking, drinking,
depression, happiness, altruism, and predicting
epidemics
Social distance is more important than geographic
distance
Christakis N, Fowler J. N Engl J Med. 2007; 357 (4): 370–379.

Support Groups DOUBLED
Survival in Breast Cancer
1
0.8
0.6
% Surviving
0.4
0.2
0
0 20 40 60 80 100 120 140
Control Treatment
Spiegel D et al. Lancet 1989;2:1209
Trust→
Intimacy→
Healing & Meaning
Twitter Language Predicts
Coronary Heart Disease Mortality
In 148 million tweets, language patterns
reflecting negative social relationships,
disengagement, and negative emotions—
especially anger—predicted CHD mortality
better than 10 factors including smoking,
diabetes, hypertension, and obesity.,
Eichstaedt JC et al. `Psychol Sci. 2015 Feb;26(2):159-69. doi: 10.1177/0956797614557867. Epub 2015 Jan 20.
“I feel deprived because I
can’t eat this food” is not
sustainable.
“I’m choosing not to eat this because what
I gain is much more than what I give up” is
sustainable.
Choosing notto do something imbues it with deep meaning &
purpose, making it sustainable.
“Why do you want to live
longer?”
Not just how long
we live but how
well we live.
Meaning is the antithesis of
depression.
If it’s meaningful,
it’s sustainable
If it’s pleasurable,
it’s sustainable
Transformation
Menu
Return to Menu
EMS Diversion for Stroke
Jeffrey L. Saver, MD
SA Vice-Chair and Professor of Neurology
Director, UCLA Comprehensive Stroke and Vascular Neurology Program
UCLA Stroke Center

JLS Disclosures
• Unpaid site investigator in multicenter trials run by Medtronic, Stryker,
and Lundbeck, for which the UC Regents received payments on the
basis of clinical trial contracts for the number of subjects enrolled.
• Receives funding for services as a scientific consultant regarding trial
design and conduct to Medtronic, Stryker, Neuravi, BrainsGate, Pfizer,
Boehringer Ingelheim (prevention only), and St. Jude Medical.
• Serves as an unpaid consultant to Genentech advising on the design
and conduct of the PRISMS trial; neither the University of California nor
Dr. Saver received any payments for this voluntary service
• Employee of the University of California. The University of California
has patent rights in retrieval devices for stroke.
UCLA Stroke Center

Talk Outline
• Stroke from the perspective of EMS
Regional Systems of Stroke Care
» Types of stroke
» Types of emergency stroke treatments
» Types of emergency stroke centers
• Time is Brain
• Building Efficient Prehospital Care
Systems
» Calling 911
» Dispatch
» Paramedic care
• Stroke recognition
• LVO recognition
• Routing
• Future directions
UCLA Stroke Center

Major Stroke Subtypes
Ischemic Hemorrhagic
Small/Medium Large Vessel Intraparenchymal Subarachnoid
Vessel Occlusion Occlusion
Stroke
Subtypes
Typical Focal Deficits Focal Deficits Focal Deficits Non-Focal

Presentation Deficits
Major 1) ≤4.5h: IV TPA 1) ≤4.5h: IV TPA plus ET 1) Anticoag reversal 1) Coiling/ clipping
Treatments 2) ≤ 6h: ET 2) BP moderation 2) NICU
3) 6-24h: ET in imaging- 3) Ventriculostomy vasospasm
selected subset 4) Surgical evac management
Population 65% 35% 10% N/A
Freq of Focal
EMS 40% 35% 25% N/A
Freq of Forcal
Stroke
Subtypes

Freq of Focal
EMS 40% 35% 25% N/A
Freq of Forcal
Stroke
Subtypes

Freq of Focal
EMS 40% 35% 25% N/A
Freq of Forcal
Stroke
Subtypes

Freq of Focal
EMS 40% 35% 25% N/A
Freq of Forcal
Stroke
Subtypes

Freq of Focal
EMS 40% 35% 25% N/A
Freq of Focal
Key Treatment Capabilities of TJC
Stroke-Designated Hospitals
IV Therapies in Stroke Unit Inpt Endovascular Neurosurgery
ED (tPA, Kcentra, Management Thrombectomy Coiling
etc) NeuroICU Care
Non-
Stroke
Hospital
Acute
Stroke
Ready
Hospitals
UCLA Stroke Center
The Ischemic Penumbra
Irreversible
Core Infarct
Ischemic Penumbra
zone of salvageable
tissue surrounding
core infarct
Brief Time Window in Animal Stroke
Models
Permanent Early Medium Late
•UCLA Stroke Center

In a typical acute ischemic
stroke, every minute the
brain loses
• 1.9 million neurons

• 14 billion synapses
• 7.5 miles myelinated fibers
-- Saver, Stroke 2006
Onset to Treatment Time for IV TPA and Excellent
Outcome
RCTs (8 trials) GWTG-Stroke
3760 patients 65,384 patients
OR for mRS 0-1 Prob of mRS 0-1
UCLA Stroke Center --Lees et al, Lancet 2010; Saver + Levine, Lancet 2010; Saver, Stroke 2012; Kim JT et al. Circulation 2017
IV TPA Under 3 Hours – Patient Education
• Joint AHA-AAN-ACEP
text tool to educate
patients and families
• UCLA icon array tool
based on AHA-AAN-
ACEP
--Gadhia et al, Stroke 2010
UCLA Stroke Center

Dissemination of Preferential EMS Routing to PSCs
--Song and Saver, Stroke 2012
2000 2004 2005
2006 2007 2008
60
2009 2010
50
P 40
e
r
c 30
e
n
t 20
10
UCLA Stroke Center 0

Catheter-Based Reperfusion Therapies
Era of Highly Effective Reperfusion Therapy
NNTs for Cerebral and Cardiac Ischemia Binary Outcomes
Thrombectomy
(4)
for AIS (vs Lysis)
Independence
IV Lytics
(10)
for AIS (vs ASA)
Nondisability
PCI
(29)
for STEMI (vs Lysis)
Mortality
UCLA Stroke Center --Huyn et al, Circulation 2009 / Emberson et al, Lancet 2014 / Saver et al, NEJM 2015
Time from Onset to Expected Puncture Odds
of Reduced Disability with EVT vs Medical
HERMES
Collaboration
•2019-04-11 •192
Time from Onset to Expected Puncture Odds
of Reduced Disability with EVT vs Medical
HERMES
Collaboration
43 Benefit Per Hundred

40
34
29
24
18
12
2019-04-11 193
Time from Onset to Puncture and Outcome
from Endovascular Thrombectomy
•GWTG-Stroke
•6756 EVT patients
•231 hospitals
•1/2015 – 12/2016
--Jahan et al, ISC 2019

Minutes Matter
• IV TPA
» Every 8 minute delay
causes 1 fewer of 100
treated patients to benefit
in improved ambulation
• IA Neurothrombectomy
reperfused patients to
benefit in reduced final
disability
--Saver, Stroke 2013; Saver et al,

JAMA 2013; Sheth et al, Ann Neurol
UCLA Stroke Center 2015; Saver et al, JAMA 2016
Minutes Matter
• IV TPA
treated patients to benefit
in improved ambulation
• IA Neurothrombectomy
reperfused patients to 1 worse
benefit in reduced final outcome
disability every 4
minutes
UCLA Stroke Center
Target: Stroke
Best Practice Strategies
1. *EMS Pre-Notification 7. *POC Laboratory Testing

2. Stroke Toolkit 8. *Premix TPA
3. Rapid Triage and Stroke 9. *Rapid TPA Access - store
Team Notification TPA in ED/radiology, start
4. *Single Call Activation in imaging suite
System 10.Team approach
5. *Transfer Directly to CT 11.*Prompt data feedback
6. Rapid Brain Imaging
Trend in DTN Times
Target: Stroke Pre, Phase I, and II
-Fonarow et al, ISC 2019

Target: Stroke Phase 2
• Target: Stroke Elite

» DTN ≤ 60m in 75%
» DTN ≤ 45m in 50%
UCLA Stroke Center

• Endovascular
» Door to Device (DTD)
• EMS: DTD ≤ 90m in 50%
• Tx: DTD ≤ 60m in 50%
• Intravenous
» Primary
• DTN ≤ 60m in 85%
» Secondary
• DTN ≤ 45m in 75%
• DTN ≤ 30m in 50%
*Door-to-device: arrival to first pass of thrombectomy device
• Endovascular
» Door to Device (DTD)
• EMS: DTD ≤ 90m in 50%
• Tx: DTD ≤ 60m in 50%
• Intravenous
» Primary
• DTN ≤ 60m in 85%
» Secondary
• DTN ≤ 45m in 75%
• DTN ≤ 30m in 50%
*Door-to-device: arrival to first pass of thrombectomy device
Target: Stroke III
Best Practice Strategies
1. Rapid alteplase start to neuroangio suite

2. Rapid CTA/MRA 8. Tx direct from brain
3. Rapid additional imaging imaging to angio suite
(6-24h) 9. Team-based, parallel
4. Pre-Notification/Activation approach (ED, stroke, NI)
of Neurointerventional 10. Endovascular-ready
Team neuroangio suite
5. Rapid availability of NI 11. Anesthesia rapid protocols
Team 12. Prompt data feedback
6. Time attached to chart,
clip board, or bed
7. In select patient, tx direct
Endovascular Thrombectomy - Patient Education
--Tokunboh et al, Stroke 2010

Progressors: Fast / Slow / Variable
DEFUSE 2
--Wheeler et al, Int J Stroke 2015
Progressors: Fast / Slow / Variable
DEFUSE 2 UCLA Series

--Wheeler et al, Int J Stroke 2015 --Liebeskind, 2016
Tissue Status Perfusion Status Vessel Status
CBV CT PCT CTA
Multimodal
CT
DWI PWI MRA
Multimodal
MRI
Bioenergetic Hemodynamic Occlusions or

Compromise Compromise Stenoses
Strategies to Identify LVO Patients with
Salvageable Ischemic Penumbra
< 6 Hrs > 6 Hrs
% Patients with Penumbra

Imaging required to assess
pathophysiology
= 100
75
50
25
Hyperacute therapy when nearly 0 3 6 9 12 15 18 24
all patients have penumbra

Time From Onset (Hours)
Pathophysiology of Variation in Speed of
Stroke Progression
• Perfusion pressure
» Ejection fraction
• Blood oxygenation
» Hemoglobin
» Respiratory compromise
• Collaterals
» Circle of Willis
» Leptomeningeal
» Deep
• Tissue ischemic tolerance
» White vs gray matter
» Excitatory vs inhibitory
» Ischemic pre-conditioning
--Leemans, Neuro Bureau 2015

--Shuaib et al, Lancet Neurol 2011
--Bristow et al, JCBFM 2005
Populations for Thrombectomy:
Time and Penumbra
6- 7-
Mismatch 0-3h 3-6h 8-12h 12-16h 16-20h 20-24h >24h
7h 8h
Not
performed
>200%
150-199%
100-149%
50-99%
20-49%
Time and Penumbra
6- 7-
7h 8h
Not
performed
>200%
150-199%
100-149%
50-99%
20-49%
Time and Penumbra
6- 7-
7h 8h
Not
performed
>200%
150-199%
100-149%
50-99%
20-49%
Vessel Occlusoin Occlusion

Freq of Focal
EMS 40% 35% 25% N/A
Freq of Forcal
Warning Signs and
Activation of EMS System
UCLA Stroke Center

Who To Activate EMS for?
Ubiquitous Monitoring and Ambient Intelligence
Accelerated Stroke Onset Detection
Las Vegas Casinos
Home Cameras/Voice Assistants

Home Health Robots
Smart Phones
Acclerometer and
Computer Vision - Fall
Detection
--Example: Leone et al. Detecting falls with 3d range camera in ambient assisted living
UCLA Stroke Center applications. Medical Engineering & Physics 2011
Stroke and EMS
• Narrow therapeutic time
window
• Early intervention critical for
stroke care
• Prehospital personnel
» 35-70% of stroke patients
arrive by ambulance
» Unique position: first medical
professional to come in
contact with stroke patient
UCLA Stroke Center

Goal of EMS Dispatch
• To send the right things to the right people at the right

time in the right way and to do the right thing until help
arrives
UCLA Stroke Center

Dispatch and Stroke
• Enhanced 911 systems automatically
display caller’s address
» Especially helpful for dysarthric/aphasic
patients
• Dispatcher assesses complaint and
determines
» Dispatch priority
» Level of expertise (ALS or BLS)
• Structured algorithms for caller
interaction
» National Academy Medical Priority
Dispatch System QA Dispatcher Guide
• Protocols for 36 chief complaints, including
stroke (28)
UCLA Stroke Center

Prehospital Paramedic Stroke Recognition and
Characterization: Applications
• Rapid prehospital care
» “Scoop and go”
• One-tier Stroke Center systems
» Route directly to designated Stroke
Centers
» Pre- arrival notification
• Activate stroke team
• Clear head CT/MR scanner
• Preregister and issue temporary medical
record number
» Direct to CT/MR transport
• Two-tier Stroke Center systems
» Selective direct transport to
Comprehensive Stroke Centers
• Treatment in the field
» Paramedic
• Neuroprotectives
• BP moderation
» Physician
• Thrombolysis
UCLA Stroke Center

Strokes Are Only 2-3%
of Prehospital Transports
Neurologically Final Dx Stroke 1298 consecutive

Relevant Hx n=36 (3%) transports
n=410 (32%)
Non-Neurologically Relevant Hx
n=852 (65%)
UCLA Stroke Center
--Stroke 2000;31:71-6
“Stroke Recognition” Tools “Stroke Severity” Tools
Stroke vs Non-Stroke LVO vs Non-LVO Stroke
CSC Approp (LVO+ICH) vs not
• Los Angeles Prehospital Stroke Screen • Los Angeles Motor Scale (LAMS)
(LAPSS)* ** • 3 Item Stroke Scale (3I-SS)
• Cincinnati Prehospital Stroke Scale • Rapid Arterial OcClusion
(CPSS)* Evaluation Score (RACE)
• Face Arm Speech Test** • Cincinnati Prehospital Stroke
• Paramedic Quick Screen (San Diego) Severity Scale (CPSSS)
• Miami Evaluation of Neurologic Deficit • Field Assessment Stroke Triage
(MEND) for Emergency Destination (Fast-
• UAB Stroke Observational Scale (SOS) ED)
• Expanded LAPSS (Melbourne Acute • Vision, Aphasia, Neglect (VAN)
Stroke Screen) ** • …
• …
*Endorsed in ACLS Cardiopulmonary Resuscitation Guidelines, Circulation 2010
**Prospectively validated in field testing
Selected Approaches to Improving EMS
Prehospital Stroke Recognition
• Los Angeles Prehospital Stroke Screen (LAPSS)* **

• Cincinnati Prehospital Stroke Scale (CPSS)*
• Face Arm Speech Test**
• Paramedic Quick Screen (San Diego)
• Miami Evaluation of Neurologic Deficit (MEND)
• UAB Stroke Observational Scale (SOS)
• Expanded LAPSS (Melbourne Acute Stroke Screen) **
*Endorsed in ACLS Cardiopulmonary Resuscitation Guidelines, Circulation 2010
**Prospectively validated in field testing
UCLA Stroke Center

• History (4 items)
» onset/duration of symptoms
» age
» history of seizure disorder
» baseline functional status
• Exam (3 items): identifies
unilateral weakness
» facial weakness
» arm drift
» grip strength
• Fingerstick blood glucose (1
item)
UCLA Stroke Center

Motor Deficits in Acute Stroke
• LAPSS and CPSS emphasize motor deficits:

» Present in 83-90% of all strokes
» Major determinant of long-term disability
» Testing performed reliably and briefly by health personnel not
specifically trained in neurology
UCLA Stroke Center

LAPSS: Prospective Field Performance
LAPSS Completed Runs (Neuro Sx Runs)
Sensitivity 91% (76-98%)

Specificity 99% (97-99%)
Positive Predictive Value 97% (84-99%)
Negative Predictive Value 98% (96-99%)
--Stroke 2000;31:71-6
UCLA Stroke Center

Prehospital Stroke Management
• Perform • Avoid
» Determine and document » Delay transport
time of onset » Give large volumes of fluid
» Initiate cardiac monitoring » Give dextrose (unless
» Insert intravenous line hypoglycemic)
» Perform serum glucose
measure
» Administer oxygen
» Notify ED quickly
» Transport as soon as
possible (“scoop and go”)
UCLA Stroke Center

Pre-notification by Emergency Medical Services is
Associated with More Timely Evaluation and
Treatment of Acute Ischemic Stroke
• 2003-2011, 1,585 sites

• 372,000 EMS-transported patients
• Hospital pre-notification in 67%
--Lin et al, Circ Cardiovasc Qual

Outcomes. 2012
Timely Evaluation
EMS Pre-notification
vs No EMS Pre- Adjusted OR
Parameter notification (95% CI)
Time from symptom onset to arrival ≤180 min 61% vs 54% 1.32 (1.26-1.38)
Door-to-Imaging times ≤25 min (arrive by 3 hr) 49% vs 41% 1.53 (1.44-1.63)
Door-to-needle times ≤60 min 27% vs 26% 1.20 (1.10-1.31)
Onset-to-needle times ≤120 min 32% vs 30% 1.17 (1.09-1.25)

*Variables in the model included age, Female (vs. male), Race (AA, Hispanic, Asia, other vs. Caucasians), Insurance: Medicare, Medicaid, other (HMO, VA etc) vs. no
insurance, Atrial Fibrillation/Flutter, Prosthetic Heart Valve, Previous Stroke/TIA, CAD/Prior MI, Carotid Stenosis, Diabetes Mellitus, PVD, Hypertension, Smoker,
Dyslipidemia, and HF, Arrived at off-hours (holiday or before 7AM/after 6PM on Monday-Friday); and hospital characteristics variables: region, number of beds, teaching
hospital, annual IV t-PA volume and annual ischemic stroke volume.
TPA Treatment Rates
EMS Pre-notification
vs No EMS Pre- Adjusted OR (95%
Parameter notification CI)
tPA treatment rate (arrive by 2 hr, Rx by 3 hr) 73% vs 64% 1.64 (1.50-1.79)
32% vs 28% 1.46 (1.38-1.55)

tPA Rx Rate (arrive by 3.5 hr, Rx by 4.5hr)
Regional Stroke Systems of Care:
Four Tier US Model
• EMS
--Trained dispatchers, high priority triage
--Paramedics trained in stroke recognition (e.g. LAPSS)
--Deliver patients to nearest stroke capable hospital
--Pre-arrival notification
• Spokes
– Acute Stroke Ready Hospitals
--Able to provide initial, ED care, often via telemedicine
--Able to use rt-PA and other acute therapies safely and efficiently
– Primary Stroke Centers
--Able to provide initial, ED care
--Able to use rt-PA and other acute therapies in a safe and efficient manner
--Have Stroke Units and can admit patients
• Hubs
– Thrombectomy Stroke Centers
--PSC level care, plus
--Endovascular thrombectomy
– Comprehensive Stroke Centers
--Able to care for complex patients
--Advanced treatments (i.e. coils, stents, IA recanalization, etc)
--Trained specialists in key areas (Vascular neurology, Neurointerventional
procedures, Neurocritical Care, Vascular Neurosurgery)
Identifying Likely Large Vessel
Occlusion Patients in Field
• Medium (distal) vessel and

small (penetrator) occlusions
» IV tPA - works well, want asap
» Thrombectomy – not an option
» → Primary Stroke Center or
Acute Stroke Ready Hospital
• Large vessel occlusions
» IV tPA - works poorly
» Thrombectomy – works well
» → Thrombectomy Stroke
Center or Comprehensive
Stroke Center
Examples of Prehospital Stroke Scales to
Identify LVO / CSC-Approp
• Los Angeles Motor Scale (LAMS)
» 3 elements
» Facial droop, arm drift, grip weakness
• 3 Item Stroke Scale (3I-SS)
» 6 elements
» Level of consciousness, gaze deviation, facial droop, arm drift, R/L leg weakness
• Rapid Arterial OcClusion Evaluation Score (RACE)
» 7 elements
» Facial droop, arm drift, R/L leg weakness, gaze deviation, aphasia, denial of hemiparesis
• Cincinnati Prehospital Stroke Severity Scale (CPSSS)
» 4 elements
» Gaze deviation, arm drift, LOC command, LOC questions
• Field Assessment Stroke Triage for Emergency Destination (Fast-ED)
» 5 elements
» Face, Arm weakness, speech, eye deviation, Denial/Neglect
• VAN
» 3 elements
» Vision, Aphasia, Neglect
Variations in Scale Complexity
KISS Principle in Prehospital Care
LAMS RACE
Facial Palsy
Facial Droop Absent 0
Absent 0 Mild 1
Present 1 Mod-severe 2
Arm Motor Fxn
Arm Drift Normal to mild 0
Absent 0 Moderate 1
Drifts Down 1 Severe 2
Leg Motor Fxn
Falls Rapidly 2 Normal to mild 0
Grip Strength Moderate 1
Normal 0 Severe 2
Head + Gaze Dev
Weak Grip 1 Absent 0
No Grip 2 Present 1
Aphasia (if right HP) 1
Normal to mild 0
Moderate 1
Severe 2
Agnosia (if left HP) 1
Normal to mild 0
Moderate 1
Severe 2
LAMS Comparable to or Better than 6 Other Proposed
Prehospital LVO Scales and the Full NIHSS
LVO among All Acute Cerebral CSC-Appropriate (LVO+ICH) among

Ischemia Transports All Suspected Stroke Transports
--Noorian et al, Stroke 2018

LAMS Comparable to or Better than 6 Other Proposed
Prehospital LVO Scales and the Full NIHSS
LVO among All Acute Cerebral CSC-Appropriate (LVO+ICH) among

Ischemia Transports All Suspected Stroke Transports
--Noorian et al, Stroke 2018

Comparative Scale Performance in Identifying LVO
among All Acute Cerebral Ischemia Patients
--Noorian et al, Stroke 2018 --Vidale et al, Acta Neurologica Scand 2018
Clinical prediction of large vessel occlusion in anterior circulation
stroke: mission impossible?
--Heldner et al, J Neurol 2016
• 1085 consecutive patients

» Within 6h of LKW
» CTA or MRA
• Derived 5 data-driven NIHSS
LVO pattern-specific scores
» Total NIHSS outperformed all
pattern-specific scores
• Best NIHSS cutoff ≥ 7
• Sens 81%, Spec 77%
UCLA Stroke Center

Hyperacute Course Fluctuations -
Constraint on All Prehospital Evaluations
1690 FAST-MAG Patients
Median LKW to Paramedic exam: 25 min

Median LKW to ED Study Nurse exam: 149 min
Stroke Type Evolution from Frequency
Ambulance to ED
Acute Cerebral Ischemia Substantial Improvement 31%
Substantial Worsening 7%
Stable 62%
Intracranial Hemorrhage Substantial Improvement 5%
Stable 71%
--Tipirneni et al, ISC 2017; Shkirkova et al, JAMA Neurol 2018
Hyperacute Course Fluctuations -
Constraint on All Prehospital Evaluations
1690 FAST-MAG Patients
Median LKW to Paramedic exam: 25 min

Median LKW to ED Study Nurse exam: 149 min
Stroke Type Evolution from Frequency
Ambulance to ED
Acute Cerebral Ischemia Substantial Improvement 31%
Stable 62%
Intracranial Hemorrhage Substantial Improvement 5%
Stable 71%
--Tipirneni et al, ISC 2017; Shkirkova et al, JAMA Neurol 2018
Stroke physician prehospital real-time telestroke assessment of the National
Institutes of Health Stroke Scale in the moving ambulance
Liman T G et al. Stroke 2012;43:2086-2090
Copyright © American Heart Association

Mobile Stroke Diagnosis
Emerging Helmet Technologies
• Ultrasound
» Burl – Sonas
» Neural Analytics
• EEG
» Samsung – EDSAP
• Near infra-red
» B+W Tek – i-Spec
• Microwave
» Australia - Strokefinder
helmet
UCLA Stroke Center

MSUs for Prehospital Thrombolysis and LVO/ICH Diagnosis/Routing
--Walter et al, PLOS One, 2010, Homburg --Audebert et al, Berlin

Routing Protocols in Tiered Systems:
ASRHs, PSCs, CSCs (AHA-ASA 2013)
• Tiered routing options

» None
» Time (e.g. 3.5-6-24h)
» Severity (e.g. LAMS 4-5)
» Type (H/A, ICH)
• Considerations
» Urban v rural
» Geography
» Traffic
» Resources
» Minimize time out of service
area
UCLA Stroke Center

Los Angeles County
Two-Tier EMS Stroke Routing
• Population and Resources
» 10.1 million individuals
» 31 EMS agencies, 161 ambulances (1
MSU)
» 50 designated stroke hospitals (~30
PSC, 5 TSC, 15 CSC)
• New routing policy - 2018
» If suspected stroke (mLAPSS positive)
» Direct to nearest CSC or TSC, if
» ≥ 4, likely LVO if ACI, AND,
» Last known well is within 24h, AND
» TSC or CSC is within 30 mins
» Otherwise, direct to PSC
• Accelerated inter-facility transfer if
needed
UCLA Stroke Center

Initial Impact of Two-Tiered Routing in a
Major Metropolitan Region (LA)
--Bosson et al, ISC 2019
UCLA Stroke Center

Optimal workflows all sites Slower workflow at PSCs
--Holodinsky et al, JAMA Neurol 2018

Optimal workflows all sites Slower workflow at PSCs
--Holodinsky et al, JAMA Neurol 2018

Geographic Influences
on Stroke Systems of Care
• Horizontal over land
» Most regions
• Ground/air ambulance
• Vertical over land
» Norway/Colorado
• Helicopter
• Subterranean under traffic
» Manhattan
• Subway
• Horizontal over water
» Hawaii
• Boat/air ambulance
Systems of Care Trials
• Systems of care
» Drip and ship
• Faster IV TPA, slower cath
» Mothership
• Slower IV TPA, faster cath
» BATmobile trip (mobile
CT)
• Fastest IV TPA, fast cath
• Trial designs
» Cluster Control
» Stepped wedge --Saver et al, The Stroke Interventionalist 2013
UCLA Stroke Center

RACECAT Trial
• Cluster-control RCT Spain
» 12 hospitals, 1754 patients
• Key entry criteria
» LVO by RACE and
teleneurology
» Can reach an EVT-SC within
7h of onset
• Randomized strata
» Daytime vs evening
» Weekday vs weekend
» Urban vs rural
• Outcome: mRS 0-2
• Timeline: 2017-2020
UCLA Stroke Center

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Stroke: The Post-CHANCE and POINT Era of
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Dawn M Meyer PhD,FNP-C,FAHA

Associate Professor
UC San Diego, School of Medicine, Stroke Center
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Disclosures
• Dawn Meyer discloses the following relevant
relationships:
• Portola Pharmaceuticals-Speaker’s Bureau
• Chiesi Pharmaceuticals- Speaker’s Bureau
• UNLABELED/UNAPPROVED USES DISCLOSURE:

• Use of antiplatelet loading is not FDA approved for
transient ischemic attack/low severity acute ischemic
stroke as of this presentation
Objectives
By the end of the session, participants will be able to:
• Understand the current evidence for the use of antiplatelets in secondary stroke
prevention
• Critically appraise the CHANCE trial
• Critically appraise the POINT trial
• Incorporate the evidence from CHANCE and POINT into clinical practice in
stroke
Standard Anti- Platelet Therapy Use in
Stroke
Aspirin
Clopidogrel (Plavix®)
Aspirin + ER Dipyridamole (Aggrenox)
Aspirin
• In multiple trials of multiple doses ASA there is a 15-18% RRR
• No ideal dosage
*81 and 325mg most common
• 2016 Pooled analysis from 15,778 participants reviewed 12 trials of aspirin

versus placebo in secondary prevention.
• Aspirin reduced the 6 week risk of recurrent ischemic stroke by 60% (HR 0·42, 95% CI
0·32–0·55, p<0·0001)
• Aspirin reduced the 6 week risk of disabling or fatal ischemic stroke by 70% (HR 0·29,
0·20–0·42, p<0·0001)
• Greatest benefit seen in patients with TIA/minor stroke for reducing disabling or fatal
stroke (HR 0·07, 95% CI 0·02–0·31, p=0·0004)
• Effects were independent of dose, patient characteristics, or etiology of TIA or stroke.
• NNT is 100
Rothwell PM, et al. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic
attack and ischaemic stroke: time-course analysis of randomised trials. Lancet. 2016;388(10042):365
Aspirin
Aspirin
• CAPRIE: A randomised, blinded, trial of clopidogrel versus aspirin in patients at
risk of ischaemic events
• Clopidogrel(75mg) vs ASA(325mg)
• 19,185 pts with recent stroke, MI, or PAD
• Primary end point was a composite outcome of stroke, MI, or vascular death
• Incidence of primary outcome was 5.83% (ASA) vs 5.32% (Clopidogrel) annually
(RRR 8.7%, 95% CI 0.3-16.5, p=0.043)
• 9.4% RRR per protocol
• NNT 60
CAPRIE. Lancet. 1996;378:1329-1339

CAPRIE. Lancet. 1996;378:1329-1339

CAPRIE. Lancet. 1996;378:1329-1339

• Polymorphisms in the hepatic enzymes involved in the metabolism
of clopidogrel (eg, CYP1A2, CYP3A4, CYP2C19) or P2Y12 receptor may affect the
ability of clopidogrel to inhibit platelet aggregation
• There are no convincing prospective data to support routine testing for clopidogrel
resistance with in vitro tests of platelet function or genotyping
• A 2010 clinical alert from the ACC Foundation and the AHA noted that adherence
to existing guidelines for the use of antiplatelet therapy should remain the basis for
therapy and that there is insufficient evidence to recommend routine platelet
function testing or genetic testing for clopidogrel
Combination Therapy
• ESPS-2 Trial: European Stroke Prevention Study 2

• 6,602 pts with prior stroke/TIA
• 4 treatment groups: 1) Placebo, 2) ASA 25mg bid, 3) ER dipyridamole 200 mg bid;
and 4) ASA 25 mg bid PLUS ER dipyridamole 200 mg bid
• Primary outcome was recurrent stroke, death, and stroke or death combined. TIA
and other vascular events were secondary endpoints.
• Incidence of primary outcome was 9.9% in the aspirin-ER dipyridamole group versus
12.9% in the aspirin alone group (RRR 23%, 95% CI 9.2-37.0, p=0.006)
• *37% RRR vs placebo
• NNT 50
Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study. 2.
Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143(1-2):1
Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study. 2.
Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143(1-2):1
• ESPIRIT Trial
• 2,739 patients within 6 months of TIA or minor stroke
• Open-label aspirin (30-325 mg/day) VS aspirin (30-325 mg/day) plus dipyridamole (200 mg
twice daily).
• Median ASA dose was 75mg, 83% of patients used ER dipyridamole
• Composite primary outcome of death from all vascular causes, nonfatal stroke, nonfatal MI,
or major bleeding complication
• Incidence of at least 1 primary outcome was 16% in the ASA group vs 13% in the aspirin
plus dipyridamole group (HR 0.80, 95% CI 0.66-0.98)
• ARR 1.0 percent per year
ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin
(ESPRIT): randomised controlled trial. Lancet. 2006;367(9523):1665.
ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin
(ESPRIT): randomised controlled trial. Lancet. 2006;367(9523):1665.
Aspirin PLUS Clopidgrel
• MATCH Study
• Clopidogrel 75mg + ASA 75mg VS Clopidogrel 75mg

• 7,599 high risk pts c (Stroke/ TIA + 1 Risk Factor)
• 18 month follow up
• Primary Outcome composite of ischemic stroke, myocardial
infarction, vascular death, or rehospitalization for acute
ischemia
• Event Rate = 15.7% vs. 16.7% RRR 6.4% (p=0.244) **nss
• Hemorrhage Rate = 2.6% vs. 1.3% RRE 100% (p=0.029)
**ss
Diener HC, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or
transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial.
Lancet. 2004;364(9431):331.
Aspirin PLUS Clopidogrel-MATCH
Primary Primary ICH

Outcome Outcome
Diener HC, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or
transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial.
Lancet. 2004;364(9431):331.
Aspirin PLUS Clopidgrel
• CHARISMA
• Aspirin (75-162 mg/day) plus clopidogrel (75 mg/day) VS Aspirin (75-
162 mg/day) plus placebo
• 15,603 patients with either CVD or multiple atherothrombotic risk factors (DM,
HTN, primary hypercholesterolemia, current smoking, asymptomatic carotid
stenosis ≥70 percent)
• Composite primary end point (MI, stroke of any cause, or death from
cardiovascular causes)
• Median follow-up 28 months
• Aspirin plus clopidogrel did not reduce the risk of the composite primary end
point compared VS aspirin alone (6.8% vs 7.3%, RRR 0.93, 95% CI 0.83-1.05,
p=0.22)
• Combination therapy was associated with a significant increase in moderate
bleeding (2.1% versus 1.3%, p<0.01) and a nonsignificant increase in severe
bleeding (1.7 versus 1.3 percent, p=0.09)
Bhatt DL, Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J
Med. 2006;354(16):1706.
Aspirin PLUS Clopidgrel-CHARISMA
Bhatt DL, Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J
Med. 2006;354(16):1706.
When We Combine Things…We
Don’t Always Get What We Expect
Clopidogrel Versus ASA+ER-DP for Long Term Secondary
Stroke Prevention
• PROFESS Trial: Prevention Regimen for Effectively Avoiding Second Strokes
• 20,332 patients with a noncardioembolic ischemic stroke within the previous 90-120
days
• Aspirin-ER dipyridamole VS clopidogrel
• Primary end point: Recurrent stroke
• Mean follow-up of 2.5 years
• No difference in the primary outcome of any recurrent stroke (9.0% vs. 8.8%, HR 1.01;
95% CI, 0.92 to 1.11)
• No difference in composite secondary outcome of stroke, MI, or CV death.
• Compared with clopidogrel, aspirin-dipyridamole was associated with
• *less heart failure
• *more major hemorrhages including intracranial hemorrhages(HR 1.42; 95% CI, 1.11 to
1.83)
• *more discontinuation of treatment due to adverse events, mainly headaches
Sacco et al. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke. N Engl J
Med 2008; 359:1238-1251
PROFESS
GP IIb-IIIa Antagonists
• Abciximab (Reopro), Eptifibatide (Integrelin), Tirofiban
(Aggrastat)
• Inhibits the final mediator of platelet aggregation and leads to

reduction of ADP-induced plt aggregation
• Agents have varying ½ life
• Long term use of GP IIb-IIIa lotrafiban+ASA in AIS or CAD

resulted in 3x higher rate of severe hemorrhage and 33%
increase in mortality
Antiplatelet Loading in TIA and Low Severity
Acute Ischemic Stroke
The Implications of CHANCE and POINT on Clinical Stroke Practice
Antiplatelet Loading in TIA/AIS
• CHANCE: Clopidogrel in High-risk patients with Acute Nondisabling
Cerebrovascular Events (CHANCE) trial
• Randomized 5,170 Chinese patients with high-risk TIA or minor ischemic
stroke within 24 hours of symptom onset
*Minor ischemic stroke (NIHSS score ≤3
*High-risk TIA (ABCD2 score ≥4)
• 1) Aspirin group received aspirin 75-300mg on day one followed by
75mg daily plus placebo x 90 days
• 2) Aspirin+clopidogrel group received clopidogrel 300mg and aspirin
75-300mg on day one, followed by clopidogrel 75mg daily; aspirin was
continued at 75mg daily through day 21 and placebo aspirin was given
thereafter to 90 days
• Primary Outcome was recurrent stroke (ischemic or hemorrhagic)
• Age ≥40 years
Wang et al. Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack.. 2013. 369(1):11-19
The New England Journal of Medicine
CHANCE
• Recurrent stroke occurred in 8.2% of the Aspirin+Clopidogrel group and 11.7% of the
ASA alone group (HR 0.68; 95% CI 0.57 to 0.81; p<0.001)
• The risk of recurrent stroke in the first 90 days was 32% lower (HR 0.68, 95% C.I.
0.57-0.81)
• Absolute reduction was 3.5% (7.9% vs. 11.4%)
• Number needed to treat (NNT) of 29.
• The rate of any bleeding was 2.3% in the clopidogrel–aspirin group VS .6% in the
aspirin group (HR 1.41; 95% CI, 0.95 to 2.10; p=0.09)
• The rate of hemorrhagic stroke was about 0.3% in both groups (nss).
CHANCE
CHANCE
• Limitations
• Chinese only patients, a population with a much higher rate of stroke (and more
large-vessel strokes) than in the US
• Low treatment of comorbid diseases increasing risk for stroke in the trial population
(eg, HTN, DM)
• Low rate of screened patients included as participants
• Polymorphisms affecting clopidogrel metabolism are more common in Chinese

patients
• Unknown benefit after 90 days

POINT
• POINT: Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke
• 4,881 patients within 12 hours of a minor stroke or high-risk TIA

*Minor ischemic stroke (NIHSS score ≤3
*High-risk TIA (ABCD2 score ≥4)
• 1) Aspirin group received aspirin 50-325 mg/d (150-200 mg/d for 5 days
followed by 75-100 mg/d) plus matching placebo x 90 days
• 2) Aspirin+clopidogrel group received same aspirin dose as above PLUS
clopidogrel 600-mg loading dose followed by 75 mg/d x 90 days
• Primary composite outcome of ischemic stroke, MI, or ischemic vascular death.
• Primary safety outcome, major hemorrhage (symptomatic intracranial
hemorrhage, intraocular bleeding causing vision loss, transfusion of ≥2 units of
red cells or an equivalent amount of whole blood, hospitalization or prolongation
of an existing hospitalization, or death due to hemorrhage),
• Age ≥18 years
Johnston et al. Wang et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med
2018; 379:215-225
POINT
• 43% TIA, median ABCD2 score 5 (IQR 4.0-6.0)
• 57% Minor stroke, median NIHSS score 2 (IQR 1.0-2.0)
• The study was halted after 83.6% of planned enrollment when a safety signal for
excess major hemorrhage was noted in the aspirin/clopidogrel group.
• Primary efficacy outcome occurred in 5.0% A+C vs. 6.5% ASA alone subjects.
(HR 0.75; 95% CI 0.59-0.95p=0.02; NNT=66)
• More major bleeding in the A+C group (0.9% vs. 0.4%; HR 2.32; 95% CI 1.10-
4.87; p=0.02; NNH=200).
POINT
• Among patients with minor ischemic stroke or high-risk TIA, clopidogrel plus aspirin
was associated with a reduction in ischemic events
• Among patients with minor ischemic stroke or high-risk TIA, clopidogrel plus aspirin
was associated with increase in major hemorrhage
• The POINT investigators estimated that for every 100 patients treated with this
regimen
• *15 ischemic events would be prevented
• * 5 excess major hemorrhages would occur
• The longer treatment duration (90 days) in this trial may have contributed to the
bleeding risk, which was not observed in the CHANCE trial (21 days of treatment).
Subgroups with
Benefit of DAPT in
POINT
Black race
US patients
Minor stroke
Time to
Randomization
>6hr
Infarct on brain
imaging
HX HTN
POINT Pre-specified Secondary Analysis
• A pre-specified analysis looked at outcomes on a week-by-week basis over the course of 90 days of
treatment
• During the first 21 days, the rate of major ischemic events was 5.6% ASA VS 3.6% DAPT (HR 0.65;
95%CI, 0.50-0.85; p=0.0015)
• During the subsequent 69 days on treatment, the incidence of major ischemic events was roughly 1% in
both arms
• Beyond the 21-day period, the difference in proportion of major ischemic events and major hemorrhage
did not favor DAPT
• *Ischemic events: 1.4% versus 0.9%, HR 1.38; 95%CI, 0.81-2.35; p=0.24)
• *Major hemorrhage (0.5% DAPT VS 0.2% ASA)
• The rate of major hemorrhages (mostly reversible GI bleeds) with DAPT, compared with aspirin alone,
occurred at a relatively uniform rate throughout the 90 days of treatment
• Limiting DAPT to 21 days could POTENTIALLY prevent excess hemorrhages
Elm et al. World Stroke Congress 2018.

Summary Antiplatelet Loading in TIA/AIS
• The POINT trial is more racially generalizable than the CHANCE trial
• The overall benefit of dual antiplatelet appears to be in the first 7-21 days
• The rate of major hemorrhages (mostly reversible GI bleeds) with DAPT, occur at a
relatively uniform rate
• Discontinuation of the second antiplatelet within 21 days may optimize benefit and
decrease risk
• Short treatment course could result in better compliance, and less bleeding risk in
TIA/low severity AIS
• Use caution with 90 day DAPT in stroke patients who either do not get a follow-up
appointment in the first three months or lose to follow-ups.
2018 AHA/ASA Secondary Stroke Prevention
Guidelines
• Administration of aspirin is recommended in patients with AIS within 24 to 48 hours after
onset.
• For those treated with IV alteplase, aspirin administration is generally delayed until 24 hours
later but might be considered in the presence of concomitant conditions for which such
treatment given in the absence of IV alteplase is known to provide substantial benefit or
withholding such treatment is known to cause substantial risk
• Aspirin is not recommended as a substitute for acute stroke treatment in patients who are
otherwise eligible for IV alteplase or mechanical thrombectomy.
• The efficacy of IV tirofiban and eptifibatide is not well established. Further clinical trials are
needed.
• The administration of other glycoprotein IIb/IIIa receptor antagonists, including abciximab, in
the treatment of AIS is potentially harmful and should not be performed. Further research
testing the safety and efficacy of these medications in patients with AIS is required
• In patients presenting with minor stroke, treatment for 21 days with dual antiplatelet therapy
(aspirin and clopidogrel) begun within 24 hours can be beneficial for early secondary stroke
prevention for a period of up to 90 days from symptom onset
• Ticagrelor is not recommended (over aspirin) in the acute treatment of patients with minor
stroke
Thank you
for your attention
UC San Diego Stroke Center
Emily Perrinez, Stroke Coordinator
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Patty Graham, CNS
Kunal Agrawal, Asst Professor
Thomas Hemmen, Director
Dawn Meyer, Assoc Professor
Brett Meyer, Co-Director
Navaz Karanjia, Asst Professor NCCU
Love Hailey, NP
Karen Rapp, Program Manager
Chia-Chun Chiang, Fellow
Julian Duda, Fellow
Syed Ali, Fellow
Alyssa Bautista, Fellow
Royya Modir, Asst Professor
Brittney Miller, RA
Melissa Mortin, NP
Jennifer Kruse, AA
Alex Khalessi, Assoc Professor
Scott Pannell, NIR
Scott Olson, NIR
Mobile Stroke Units—why, how, and worth it
James C. Grotta MD
Director, Mobile Stroke Unit Consortium
Clinical Innovation and Research Institute
Memorial Hermann Hospital-TMC
Houston, Texas
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Disclosures
1. Grants/Research Support: PCORI, AHA, Genentech (tPA for MSU)
2. Consulting Fees: Frazer Ltd
3. I am blinded to group outcome study data
What we will cover–
1. tPA will remain the most common treatment for most strokes
a) But we need to do better
2. A Mobile Stroke Unit is the best way to reduce time to treatment
with both tPA and ET
3. Mobile Stroke Units are probably cost effective
Time vs Tissue
“Timing is everything” or “Everyone is different”
tPA will remain the most frequent treatment c/w thrombectomy
NIHSS scores in overall population who are candidates for tPA and for ET
30
25
20
% 15
10
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
NIHSS
Reeves M, Kleindorfer D et al, abstract ISC 2012

tPA vs Thrombectomy
1. tPA
• Fastest gun in the wild west; everyone has one
• But can’t bring down big game
• Challenge:
• Speeding tPA treatment
2. Thrombectomy
• Big bubba with the big gun
• Important advance for severe strokes
• Challenge:
• How to quickly triage
Suboptimal Outcomes Despite
Current Reperfusion Therapy
42%
Unfavorable Outcome - mRS 3-6

58%
NINDS 48%
52% Favorable Outcome
ECASS-3 41%
59%
IMS-3
33%
67%
MR CLEAN 46%
54%
ESCAPE 39%
61%
SWIFT-PRIME 44%
56%
REVASCAT
49%
51%
EXTEND-IA
Next Steps:
MOST Trial
• Multi-arm Optimization of Stroke Thrombolysis Stroke Trial
U01 NIH
First patients mid 2019
1) Response Adaptive Randomization of 3-arms
• tPA-alone, tPA+Argatroban, tPA+Eptifibatide
• Bayesian predictive probabilities with ability to drop non-
performing arm
2) Endovascular Therapy allowed
3) Minimum n=500 with maximum n=1200

BUT--The most potent way to improve tPA outcomes is to give it faster-
Ultra-early treatment should be our main goal
The only way to accomplish this….

Is to bring the treatment to the patient
Kim et al, GWTG, Circulation 11/4/16

MSU on scene time < EMS transport time
HFD average on scene 15 minutes

20-45 min HFD arrive on scene to ED
HFD transport time to a CSC 5- 30 minutes
Mobile Stroke Unit avg time on scene to tPA 25 minutes
and so…..
1. We save the entire ED door to tPA needle time (U.S. ave 60 min)
2. We ensure appropriate triage to ET center
3. We shorten Door to Groin Puncture time

By getting tPA and LVO identification done pre-hospital
ET team pre-notification en route
Mobile Stroke Units Don’t Need to be Fancy
Standard 12 foot ambulance

Portable CT scanner
Point-of-care laboratory
Tele-radiology & neurology
VN, RN, CT tech, Medic
Involving all community stakeholders is essential
• Houston Mobile Stroke Treatment Unit Consortium
• HFD-EMS
• All Comprehensive Stroke Centers (MHH, Methodist, Baylor-CHI)
• Community Philanthropic support

• Patient-Stakeholder Advisory Subcommittee
MSU Dispatch Process
EMS MSU team

ambulance MSU team meets EMS
911 call immediately dispatched to ambulance at
dispatched site emergency
per routine site
Dispatch and Response
Dispatch by:
1. Dispatch center after 911 call,

or
2. On-scene FR (if they identify possible stroke--rendezvous allowed),

or
3. We monitor EMS radio and add ourselves on

MSUs are Practical
2016 to 2018: 290 acute ischemic stroke patients treated with tPA on our MSU
(~3/wk)
• 140 (48.3%) treated on scene by direct 911 dispatch-- median 7 miles from MSU base
• 150 (51.7%) patients treated by rendezvous-- their strokes occurred median 13 miles from base (p<0.0001)
26 mi
• Time (min) from 911 alert to tPA bolus

37 ± 10 with on-scene
38 ± 13 with rendezvous (p=0.89).
On-Scene Process--Triage
• Quick screening evaluation by the VN/Nurse on scene.

• Pt loaded into MSU and further Hx, VS and Labs obtained
On-Scene Process—CT and Decision
• NIHSS and labs (FS Glu and ? INR) obtained

• CT viewed by OB-VN, or
• CT sent to cloud-based PACS for TM-VN viewing
• OB-VN or TM-VN completes their evaluation and makes tPA decision
The on board MD can be replaced by a TM MD
Satisfactory connectivity
169/173 (98%) of MSU consults
Agreement between On-Board and TM VN

88% (Kappa = 0.73) (compared with in-
person agreement in ED of 88%)
Wu et al. Stroke 2017; 48:493-97, Ramadan et al. Stroke. 2017; 48:222-24
• TM VN and On Board VN on all MSU runs

• Evaluate the patient together on board the MSU
• Make rtPA decision independently
• Test Reliability of TM and Agreement on decision
Physician N Mean SD
MSU Arrival to tPA

Decision (minutes) OB 163 7.7
18.9
TM 39 7.6
21.2
MSU Arrival to OB 110 6.3
tPA Bolus
24.1
TM 26 6.4
(minutes) 23.6
• 20-25 alerts/wk
• 2/5 disregarded enroute
• 2/5 screened out on-site
• 1/5 tPA eligible and transported
• 60% treated with tPA (2.5/wk)
• others excluded b/o:
• ICH
• TIA/improvement
• Other new information
• Seizure, other mimic
BEST-MSU Study
Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit
Compared to Standard Management by Emergency Medical
Services
Patient Centered Outcomes Research Institute (PCORI)
$6M over 6 years
“If I have a stroke and call 911, am I better off if treated in a MSU vs EMS?”
SPECIFIC AIMS
1. How much less disability at 3 months?
2. Health Utilities/Cost-Effectiveness
–pts followed up to 1 yr
Outcomes (MSU vs Standard Management)
• Disability
• Utility weighted mRS at 90 days
• Secondary: standard mRS dichotomized and shift; time metrics,
response in 1st hr pts, mimics
• Healthcare Utilization
• RUF at discharge, 3rd, 6th, 9th and 12th months
• Costs
• Fixed Costs: outfitting, staffing, training, M&O
• Cost of stroke hospitalization
• Post discharge costs during the first year after discharge
• Life time costs after first year using modeling
• Effectiveness
• EQ5D, Quality Adjusted Life Years (QALYs)
• discharge, 3rd, 6th, 9th and 12th months
Adopting a Patient-Centered Approach to Primary Outcome Analysis of Acute Stroke Trials Using a Utility-Weighted Modified Rankin Scale, Volume: 46, Issue: 8, Pages: 2238-
2243, DOI: (10.1161/STROKEAHA.114.008547)
Sample Size
Assuming a 3:2 (1.5) imbalance, keeping the 10% LTFU, and using the pooled standard
deviation of STEMO& No STEMO group (sd=0.385),numbers of patients needed to detect a
differenceof 0.06, 0.065, 0.07, 0.075, 0.08, or 0.09 are summarizedin the table below.
Difference in Mean uW Sample Size

0.06 1490
0.065 1270
0.07 1095
0.075 955
0.08 840
0.09 663
Started 2014: PCORI start 2016
Colorado (Aurora and Colo Spgs) 2017
Memphis 2017
Indianapolis 2019
LA-UCLA 2018
Sutter-Peninsula 2019
New York 2018

BEST-MSU Study Process
EMS MSU team

ambulance MSU team meets EMS
911 call immediately dispatched to ambulance at
dispatched site emergency
per routine site
Alternating weeks 8 am- 6 pm

SM weeks, nurse dispatched without MSU to ensure same data and comparable patients
Alternating Locations---TMC vs West Side
Rapid improvement on arrival to ED occurs with ultra fast treatment
Bowry et al ESOC 2019 abstract

At least one third of MSU patients are treated within 60 min of onset
MSU AND SM GROUPS COMBINED

And average onset to puncture is probably ~ 2 hrs
MSU AND SM GROUPS COMBINED

Current MSU Reimbursement
Ambulance transport codes set by CMS—depends on mileage
ALS-2 = 2 IV meds, CPR etc ~$480
Proposal: create ALS-3= IV meds, diagnostics, treatment I calculate we would need ~$1000
CT billing
Technical Fee $0
Professional Fee can be billed
Drugs including TPA

In-pt code $3000 (TPA)
Out-pt code (per mg + bolus administration fee) $3000+ (TPA)
But no code for ambulance or MSU treatment $0
Physician consultation currently 0; TM codes in 2019

In the Senate of the United States,
February 9, 2018.
Page 351……
‘‘(B) INCLUSION OF CERTAIN SITES.—With

respect to telehealth services described in sub- paragraph
(A), the term ‘originating site’ shall include any hospital (as
defined in section 1861(e)) or critical access hospital (as
defined in section 1861(mm)(1)), any mobile stroke unit….”
5 yr Cost/Effectiveness Analysis
Cost of CT Scanner $ 400,000
Ambulance /Chassis/ALS Equip $ 600,000
TM equipment $ 30,000
Other Stuff $ 70,000
Operating Costs X 5 yrs $ 500,000
Staff: Paramedic/EMT/Nurse and TM MD X 5 yrs (1 shift/d) $ 2,000,000
Total fixed and continuing costs for 1 MSTU X 5 yrs $ 3,600,000
$$
=
Lifetime direct cost per stroke (1999 dollars) $ 140,000 (Circulation. 2009;119:e21-e181)
Therefore, cost neutral if:
1 MSU results in 5 more patients/yr completely recovering
5 Yr Pro Forma— Hospital System
Costs:
Cost of CT Scanner $ 400,000
Ambulance /Chassis/ALS Equip $ 600,000
TM equipment $ 30,000
Other Stuff $ 70,000
Operating Costs X 5 yrs $ 500,000
Staff: Paramedic/EMT/Nurse and TM MD X 5 yrs (1 shift/d) $ 2,000,000
Total fixed and continuing costs for 1 MSTU X 5 yrs $ 3,600,000
vs
Revenue (also projecting 1 shift/d)

Transports (3/wk @ $500 ea) $ 390,000
Incremental tPA cases (1/mo @ $28,795 collect- 11,814 cost) $ 1,018,860
Incremental IAT cases (1/mo @ $54,074 collect- 13,419 cost) $ 2,439,300
Total revenue (excluding tPA costs/reimbursement, TM and CT reimbursement) $ 3,848,160
PRESTO—PRE-hospital Stroke Treatment Organization
Toledo (OH, USA)
New York (NY, USA)
Berlin (Germany)
Chicago (IL, USA) Leuven Marburg Drobak
Cleveland
(Belgium) (Germany)
Edmonton (Alberta, (OH, USA) (Norway) Helsinki (Finland)
Canada)
Southend (UK)
Denver (CO, USA) Lille (France)

Trenton (NJ, USA)
Allentown (PA, USA)
Burlingame Columbus (OH, USA)
(CA, USA) Zhengzhou
Indianapolis (Henan, China)
(IN, USA) Paris (France) Doha
(Qatar)
Los Angeles
Homburg/Saar
(CA, USA)
(Germany) Coimbatore
Aarau (Switzerland) (Tamil Nadu, India) Bangkok
Phoenix (AZ, USA) (Thailand)
Houston (TX, USA)
Memphis (TN, USA)

Buenos Aires (Argentina) Melbourne
(Australia)
sites with active mobile stroke units

sites with projects in planning or implementation state
Lesmeister/Fassbender 2018
We will arrest early hematoma growth with
quicker hemostatic therapy
1 hr
FASTEST STUDY FUNDED !

• rFVIIa
< 2 hrs from onset
ICH > 2 and < 60 cc
860 pts
Stroke Net +
At least 12 international MSUs
In Conclusion
• Effective stroke treatments are available
• Speeding these treatments is the best way to

improve outcomes
• MSUs in the pre-hospital arena ---

both treatment and triage….
….is where good stroke outcomes will be won or lost
Return to Menu
Return to Menu
Fine Tuning Your Competency in Performing the National

Institute of Health Stroke Scale (NIHSS)
Pat Zrelak RN PhD NEA-bc CNRN SCRN

Clinical Practice Consultant
Kaiser Foundation Hospital, Sacramento, CA
Objectives
1. Describe common mistakes in scoring the NIHSS
2. Name at least 2 steps examiners can take to increase competency in
performing the NIHSS
Agenda
1. Background information
2. Common rules
3. Keys point to each examination component
Assumptions
It is assumed that participates are familiar with how to perform the NIHSS
Overview of the NIHSS
• Developed as an ischemic stroke severity tool
• Score ranges from 0-42
• ASA/ASA I B-NR recommendation as a severity rating scale
• Widely used as an assessment tool and a predictor of outcomes
• Standardizes communication
• Takes on average 8 minutes to complete
• Good test statistics
• Reliable, valid, reproducible
350
Instructions for performing the NIHSS
• Follow the FULL instructions
• Perform the test components in order
• Score all items
• Score the first effort (not the best or corrected response)
• Do not coach the patient
• Score what the patient does, not what you think the patient can do
• Include presenting deficits
351
The more difficult patients to score
• Intubated
• Comatose
• Aphasic
• Confused or agitated
This Photo by Unknown Author is licensed under CC BY-SA-NC
352
Don’t assume that zero means no stroke
• The NIHSS is not a full neurological assessment

• Targets anterior circulation
• Overrates left hemispheric strokes by 4 points (average)
• Does not include many signs of posterior circulation strokes
• The scale also does not accurately reflect a patient’s:
coordination
gait impairment
cortical sensory function
distal motor function
memory or cognition
This Photo by Unknown Author is licensed under CC BY-NC-ND

353
Understand what you are assessing
• Level of Consciousness – Items 1 a, b, c
• Vision and Eye Movement – Items 2 & 3
• Movement and Coordination– Items 4,5,6 & 7
• Sensation – Item 8 & 11
• Speech and Language Function – Items 9 & 10
• Extinction and Inattention – Item 11
354
• You must chose a response, even if a full evaluation is prevented by
such obstacles as an endotracheal tube, language barrier, orotracheal
trauma/bandages
• Don’t confuse aphasia with a decrease in alertness
• A "3" is scored only if the patient makes no movement (other than
reflexive posturing) in response to noxious stimulation
• If the patient’s tires during the examination, stay with the first score
355
• The answer must be correct - there is no partial credit for being close
• Only score the initial answer (even if they correct the answer)
• Don’t "help" the patient with verbal or non-verbal cues
• Patients unable to speak because of endotracheal intubation, orotracheal trauma, severe
dysarthria from any cause, language barrier or any other problem not secondary to aphasia
are given a "1"
• Score aphasic and stuporous patients who do not comprehend the questions score a "2"
• Patients with aphasia can write the answer
• Don’t base the answer on other orientation questions
• It is okay if they use visual clues- such as the white board (don’t assist)
356
• You CAN repeat the question ONCE
• Credit is given if an unequivocal attempt is made but not completed
due to weakness.
• If the patient does not respond to commands, the task should be
demonstrated to them (pantomime) and score the result (i.e., follows
none, one or two commands).
357
2. Best gaze
• Only horizontal eye movements are tested

• Patients with ocular trauma, bandages, pre-existing blindness or other disorder of visual acuity or fields
should be tested with reflexive movements and a choice made by the investigator.
• Establishing eye contact and then moving about the patient from side to side will occasionally clarify the
presence of a partial gaze palsy.
• Gaze is testable in patients with aphasia
• Do not include calorie testing.
• If the patient has a conjugate deviation of the eyes that can be overcome by voluntary or reflexive activity,
the score will be "1."
• If a patient has an isolated peripheral nerve paresis (CN, III, IV or VI) score a "1."
• Tonic gaze deviation/total gaze paresis (not overcome with oculocephalic maneuver) is a 2
358
• Visual fields (upper and lower quadrants) are tested by finger counting,
finger movements, confrontation, or visual threat as appropriate.
• Patient must be encouraged, but if they look at the side of the moving
fingers appropriately, this can be scored as normal.
• If there is unilateral blindness or enucleation, visual fields in the remaining
eye are scored.
• Score 1 only if a clear-cut asymmetry, including quadrantanopia is found.
• If patient is blind (both eyes) from any reason, score "3."
• Double simultaneous stimulation is performed at this point. If there is
extinction, patient receives a "1" and the results are used to answer
question #11.
359
• https://www.bing.com/images/search?view=detailV2&id=374796628439061CD55B7030E8B0B711B7B239DF&thid=OIP.Zxn7b9i4COq75gMQsI0wEgHaGW&mediau
rl=https%3A%2F%2Fnursekey.com%2Fwp-
360 content%2Fuploads%2F2017%2F03%2Fc04f006.jpg&exph=528&expw=616&q=visual+hemianopsia&selectedindex=2&ajaxhist=0&vt=0&eim=1,2,6
• Ask, or use pantomime to encourage the patient to show teeth or
raise eyebrows and close eyes
• Score symmetry of grimace in response to noxious stimuli in the
poorly responsive or non-comprehending patient
• If facial trauma/bandages, orotracheal tube, tape or other physical
barrier obscures the face, these should be removed to the extent
possible
• Look for grimace in aphasia
361
Facial palsy continued
• Score 0 for perfectly normal
• A score of 2 on this item corresponds to a definite upper motor neuron
pattern (total or near-total paralysis of the lower facial muscles)
• A score of 3 on this item corresponds to any degree of lower motor
paralysis (both upper and motor facial muscle groups of the hemi-face
• Score a 1 for everything else
362
Upper vs lower motor neuron motor weakness
363
• Each limb is tested in turn, beginning with the non-paretic arm
• Test with palms down
• Count with fingers
• Can be tested with patient sitting or supine
• The aphasic patient is encouraged using urgency in the voice and
pantomime but not noxious stimulation
364
Motor movement continued
• Arthritis/joint pain: use your best judgement
• Initial dip of the limb is allowed
• Only in the case of amputation or joint fusion at the shoulder or hip may
the score be "9" and the examiner must clearly write the explanation for
scoring as a "9"
• If comatose (posturing): items 5ab and 6ab are each scored as 4
365
• Test with eyes open
• In case of visual defect, insure testing is done in intact visual field
• The finger-nose-finger and heel-shin tests are performed on both
sides, and ataxia is scored only if present out of proportion to
weakness
• Ataxia is absent in the patient who cannot understand or is paralyzed
• Only in the case of amputation or joint fusion may the item be scored
"9", and the examiner must clearly write the explanation for not
scoring
• In case of blindness test by touching nose from extended arm position
366
• Compare sides: don’t ask sharp or dull
• Score bare skin: not through clothing
• Sensation or grimace to pin prick when tested, or withdrawal from
noxious stimulus in the obtunded or aphasic patient
• Only sensory loss attributed to stroke is scored as abnormal and the
examiner should test as many body areas [arms (not hands), legs,
trunk, face] as needed to accurately check for hemisensory loss
367
Sensory continued
• No deficit is a 0 and a severe deficit in arm plus leg is a 2 , else score as 1
• A score of 2, "severe or total," should only be given when a severe or
total loss of sensation can be clearly demonstrated
• Comatose patients
• Brainstem stroke or quadriplegia with bilateral sensory loss
• Stuporous and aphasic patients will probably score 1 or 0
• Patients in coma (item 1a=3) are arbitrarily given a 2 on this item
368
• Comprehension is judged from responses here as well as to all of the
commands in the preceding general neurological exam
• If visual loss interferes with the tests, ask the patient to identify
objects placed in the hand, repeat, and produce speech
• The intubated patient should be asked to write
• The patient in coma (question 1a=3) will arbitrarily score 3 on this
item
• The examiner must choose a score in the patient with stupor or
limited cooperation but a score of 3 should be used only if the patient
is mute and follows no one step commands.
369
Best language (aphasia) continued
• Test fluency, naming, repetition, comprehension, and reading (+/- writing)
• Objective tests: cookie jar picture, read sentences, naming objects
• Confusion, inattentiveness, alteration in cognition may impact the results
• May have trouble reading if visual field cuts
• Visual impairment: hold objects in the hand
• Mute patient able to follow commands score 2
• Allow for cultural bias – such as with the hammock
• The feather may look like a leaf to patients with poor eyesight
• The glove is often interrupted as a hand
• Coma or stupor: score 3
370
• Evaluate speech clarity by asking patient to repeat listed words
• If patient is thought to be normal, an adequate sample of speech must be
obtained by asking patient to read or repeat words from the attached list
• If the patient has severe aphasia, the clarity of articulation of spontaneous
speech can be rated
• Only if the patient is intubated or has other physical barrier to producing
speech, may the item be scored "9", and the examiner must clearly write an
explanation for not scoring
• Do not tell the patient why he/she is being tested
• Normal is 0, mute is 3, and everything else is either 1 or 2 depending on
severity. You may have to score a 1 even though you suspect the cause is a
non-stroke issue
371
• Sufficient information to identify neglect may be obtained during the prior
testing.
• If the patient has a severe visual loss preventing visual double simultaneous
stimulation, and the cutaneous stimuli are normal, the score is normal.
• If the patient has aphasia but does appear to attend to both sides, the score
is normal.
• The presence of visual spatial neglect or anosognosia may also be taken as
evidence of abnormality.
• Since the abnormality is scored only if present, the item is never
untestable.
• Sensory loss alone is not extinction
372
Scoring of comatose patient
1a. LOC/alertness= 3
1b. LOC = 2
1c. LOC commands= 3
2. Gaze (perform oculocephalic maneuver) = 2
3. Visual fields (blink to threat) = 3
4. Facial paresis (to noxious stimulation) = 2 (or other)
7. Ataxia = must see to score

8. Sensory = 2
9. Aphasia = 3
10. Dysarthria = u if intubated or other physical barrier, else 2
373
The intubated patient
• Address sedation
• Dysarthria is the only non-testable item
• LOC question 1b = 1
• Attempt to have the patient write their responses
• Must see to score
374
Summary
• Follow the FULL set of instructions
• Perform the test elements in order
• Score all items
• Score the first effort (not the best or corrected response)
• Do not coach the patient
• Score what the patient does, not what you think the patient can do
• Include presenting deficits
• Practice and compare your results with experts
• When re-certifying, watch the instructional videos
• Even patients with difficulty presentation can and must be scored
375
On-line Stroke Scale Certification course may be
376
Questions
Pat Zrelak RN PhD NEA-bc CNRN SCRN

Clinical Practice Consultant, Kaiser Foundation Hospital, Sacramento, CA
Patricia.a.Zrelak@kp.org
(916) 973-4849
377
References
Return to Menu
• Lyden P. Using the National Institutes of Health Stroke Scale:
A Cautionary Tale. Stroke 2017;48(2):513-519.
• MaMartin-Schild S, Siegler JE, Kumar AD, Lyden P. Troubleshooting the
Nihss: question-and-answer session with one of the designers.
Stroke 2015;10(8): 1285-1286.
• The National Institute of Neurological Disorders and Stroke Stroke Scale scoring sheet,
http://www.nihstrokescale.org/
• The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue
plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–1587.
• Lyden P, Raman R, Liu L, Emr M, Warren M, Marler J. National Institutes of Health Stroke
Scale certification is reliable across multiple venues. Stroke. 2009;40:2507–2511.
378
Return to Menu
Communication Strategies for

Patients with Aphasia
Heather Field, MA, CCC-SLP

Assistant Director Physical Medicine & Rehabilitation
Los Angeles Medical Center
379 | Copyright © 2017 Kaiser Foundation Health Plan, Inc.

Communication Strategies for Patients with Aphasia
Learning Objectives
1. Define types of aphasia:

• Expressive Vs. Receptive
• Fluent Vs. Non-Fluent
2. Impairment-based Vs. Communication-based
therapies
3. Specific communication strategies
I have no financial disclosures. I am affiliated with Kaiser Permanente

Los Angeles Medical Center & am a member of the American Speech-
language & Hearing Association.
380
What is Aphasia?
• Aphasia is an acquired neurogenic
language disorder resulting from an injury to
the brain—most typically, the left
hemisphere. Aphasia involves varying
degrees of impairment in four primary areas:
• Spoken language expression
• Language comprehension
• Written expression
• Reading comprehension
• A person with aphasia often has relatively

intact nonlinguistic cognitive skills, such
as memory and executive function, although
these and other cognitive deficits may co-
occur with aphasia.
381
Typical Language Circuit

1. Sound is transmitted to the auditory cortex
2. Auditory cortices relay the sound to Wernicke’s

area for processing & construction of an overall
message (E.g. literal vs figurative meaning)
3. Wernicke’s area retrieves words & sentence

structure to send via Arcuate fasciculus to Broca’s
area
4. Broca’s area formulates an action plan which is

sent to the primary motor cortex
5. Primary motor cortex refines it and sends to cranial

nerves for speech muscles via the pyramidal Pop Quiz:
What single language task can test the
system entire circuit?
382
Aphasia Types
There are many forms of aphasia often broken into three major categories.
Expressive Aphasia Global Aphasia

Receptive Aphasia
Difficulty with spoken Difficulty with all aspects of
Difficulty comprehending
language, may have trouble language
others, difficulty recognizing
writing own language is
incomprehensible, may
have trouble reading
383
384
Intervention Principles
• Therapy goals focus on repairing areas of damage

• Patients are instructed to focus their attention on tasks that allow them to comprehend or speak as successfully as
possible
• Examples:
Impairment- • Constraint-induced therapy (CIT) (E.g. gestures vs. spoken language)
• Melodic Intonation Therapy (MIT)
based
• Therapy goals focus on assisting the person to convey messages and feelings with alternative means of communication
• Communication-based activities continue to encourage use of any remaining language, and often incorporate
impairment-based objectives simultaneously
• Examples:
• Promoting Aphasics’ Communicative Effectiveness (PACE therapy) – variation to picture naming drills with partners
Communication- taking turns
• Conversation coaching (E.g. scripted conversations)
based • Supported conversation – often found in community support groups & aims to increase communication confidence
385
Verbal Communication Strategies
• Talk to the patient – not the caregiver
• Talk about one topic at a time
• Keep topics clear (short, simple sentences)
• Allow processing time
• Descriptive yes/no questions

• E.g. Is it an animal?
• Increase redundancy (repeat or rephrase)
386
Physical Communication Strategies
• Use meaningful & recognizable gestures (e.g.

thumb up/down, nodding)
• Pointing to an object, person, word or picture
• Facial expressions and body language
387
Visual Support
• Fixed choices and key words

• Scripts
• Pictures, drawings, icons
• Visual Scales
• Calendars, maps, newspapers, event flyers
• Photos of familiar people, places or objects
• White board
• Communication books, flip charts, wallets
388
Verification
• Check comprehension – Don’t assume comprehension
• Review message (e.g., “Are you telling me…”)
• Expand message (e.g., “You were saying…”, “What else…”)
• Summarize their message
389
Communication Strategy Review

Intellect and non-linguistic cognition is typically intact
Speak to the patient in a normal volume
Allow processing time
Use visual & physical strategies to support verbal communication
Rely on familiar topics, photos, objects in acute stages
Check for understanding and verify messages received & delivered
390
Questions?

References
Aphasia. (n.d.). Retrieved from
https://www.asha.org/PRPSpecificTopic.aspx?folderid=8589934663§ion=Treatment
Brown, J., & Thiessen, A. (2018). Using Images With Individuals With Aphasia: Current Research and
Clinical Trends. American Journal of Speech-Language Pathology, 27(1S), 504-515.
doi:10.1044/2017_ajslp-16-0190
Elman, R. J. (1999). Long-Term Care Approaches to Aphasia Treatment and Management. Perspectives
on Neurophysiology and Neurogenic Speech and Language Disorders, 9(5), 15.
doi:10.1044/nnsld9.5.15
Marshall, R. C. (1997). Aphasia Treatment in the Early Postonset Period. American Journal of Speech-
Language Pathology, 6(1), 5-11. doi:10.1044/1058-0360.0601.05
Minkina, I., Martin, N., Spencer, K. A., & Kendall, D. L. (2018). Links Between Short-Term Memory and
Word Retrieval in Aphasia. American Journal of Speech-Language Pathology, 27(1S), 379-391.
doi:10.1044/2017_ajslp-16-0194
Pierce, J. E., Ohalloran, R., Togher, L., & Rose, M. L. (2019). What Is Meant by “Multimodal Therapy” for
Aphasia? American Journal of Speech-Language Pathology, 1-11. doi:10.1044/2018_ajslp-18-0157 Return to Menu
392
Kaiser Permanente 2019 Inter-Regional Stroke Conference
Care Transitions for Stroke

Survivors: State of the
Science
Michelle Camicia, PhD, MSN, CRRN, CCM, NEA-BC, FAHA

Director
Kaiser Foundation Rehabilitation Center
Return to Menu
Learning Objectives
1. Identify key recommendations from current research

on care transitions for stroke survivors
2. Describe the role of the family caregiver in care

transitions
3. Explore application to health professionals in various

roles and settings
When? Acute Care Participation in D/C Process
Hospital must provide Likelihood of needing Use the evaluation to

patient with discharge PAC & availability of establish appropriate
planning evaluation services discharge plan
• Patients capacity for self-care in pre-

hospital environment
• Discuss results of evaluation with the
patient or a representative
Improving transitions is a national priority
Right Care
Right Right
Resources Time
Right Right
Setting Providers
Care Transitions Defined
Emergent
care
Acute care
Post-acute Long Term Care

Acute Inpatient
Skilled Nursing Home Health
care Hospital (LTCH)
Rehabilitation
Facility (IRF)
Facility (SNF) Agency (HHA)
Community
care
5
PAC Transitions
Post-stroke Care Trajectory
Used with permission from Janet Prvu-Bettger

Page 39
Stroke Survivor Inpatient Post-acute Care Trajectory
24% Inpatient Rehab Facility (n=37,064) 27% Skilled Nursing Facility (n=41,547)
5% IRF only 20% IRF & HH 16% IRF & OP 16% IRF & SNF 30% SNF only 19% SNF & HH 12% SNF & OP
8% IRF, HH, & OP 6% IRF, HH & Readmit 5.8% IRF, SNF, & HH 21% SNF & Readmit 6% SNF, HH & Readmit
+ SNF post Readmit

Plus SNF or HH after
Readmit
+SNF or HH/OP post
Readmit
Bettger, J.P., Liang, L., Xian, Y., Peterson, E.D., Bushnell, C., Duncan, P. W., Federspiel, J., Stein, J., Montalvo, C., Lutz, B.J., Hoenig, H. Schwamm, L.H., Wu, J. Stafford, J., &
Thomas, L. (2015), Inpatient Rehabilitation Facility Care Reduces the Likelihood of Death and Rehospitalization After Stroke Compared with Skilled Nursing Facility Care (Abstract
146). Stroke, 46, A146. Funding: PCORI ID #130, PI: Prvu Bettger
Post-stroke Care Trajectory
Used with permission from Janet Prvu-Bettger

Page 39
Care Transitions
Often ineffective & inefficient Result in unmet patient and

Particularly problematic for stroke
caregiver needs, increased safety
patients transitioning from an IRF
risks, high rates of preventable
to home
readmissions
IRF vs. SNF
44
IRF SNF
MD Oversight At least 3x/week Seen by MD day 14;
then every 30 days
RN Coverage 24 hours/day 8 hours/day
“Intensive”
Therapy Provided 3 hours per day Varies;
‹41›
‹42›
Comparison of Outcomes: IRF v SNF
45
IRF vs SNF for Rehabilitation after Stroke
Early Admission to Inpatient Rehabilitation
Earlier IRF admission was beneficial

As early as possible once patient is among severely and moderately
medically stable and can tolerate therapy impaired patients
Multidisciplinary rehabilitation within the first IRF admission within 7 days is
20 days: strong inverse relationship recommended for patients who achieve
between start date & functional outcomes medical stability
Hospital Requirement for D/C Planning under the IMPACT Act
Counsel patients & family to

prepare them for PAC
Reassess discharge planning

process and discharge plans Supply lists of local Medicare-participating SNFs
to ensure they are & HHAs to patients when these services are
responsive to patient’s indicated
discharge needs
• Should not recommend facility/provider

• Must ID facilities w/ financial interest
Acute Care Participation in D/C Process
Hospital must provide patient

Likelihood of needing PAC & Use the evaluation to establish
with discharge planning
availability of services appropriate discharge plan
evaluation
• Patients capacity for self-care in pre-

hospital environment
• Discuss results of evaluation with the
patient or a representative
Winstein, C.J., Stein, J., Arena, R., Bates, B., Cherney, L. R., Cramer, S., … Zorowitz, R.D. (2016). Guidelines for adult stroke
rehabilitation and recovery. Stroke, 47(6), 98-169. https://doi.org/10.1161/STR.0000000000000098
PAC in a Value-Based Environment
Encouraging Medicare beneficiaries to use
higher quality post-acute care providers
“At discharge from an inpatient stay, the selection of a provider within a PAC category
can be crucial because the quality of care varies widely among providers.”
Least expensive Best post-acute

option setting for the
(HH or SNF) patient
Medicare Payment Advisory Commission (2018). MedPAC Report to Congress. Washington, DC: MedPAC
Retrieved from http://www.medpac.gov/docs/default-source/reports/mar18_medpac_entirereport_sec.pdf?sfvrsn=0
Who influences what setting (IRF or
SNF) a stroke patient goes after acute
care?
1. Physicians
2. Other professionals (nurses, therapists)
3. Family members
Factors that Influence Post-acute Care Decisions
77 (16%) discharge planners

471 hospitals
NE US
Online survey
• Patients and families more influential than
Nonclinical physicians (P < 0.001) and other clinicians
factors are
perceived by
>50%
(P = 0.04) in influencing post-discharge care
discharge
pressure to • Other clinicians more influential than
planners to
discharge
have a major
influence on
patients physicians (P < 0.001)
quickly
postacute
stroke care
impacts a • Insurance and -acute care
patients' final
decision
destination were the factors likely to most affect the
making.
selection of post-acute care facility.
(Magdon-Ismail, Sicklick, Hedeman, Bettger, & Stein, 2016)

Discharge Planning under IMPACT Act
Improve consumer transparency and beneficiary

experience during the discharge planning process
Considers both quality and resource use measures
Encourages patients to be active partners including

the patients goals of care and treatment preferences
Nursing’s Role in Successful Transitions Across Settings
Camicia, M., & Lutz, B. J. (2016). Nursing’s Role in

Successful Transitions Across Settings. Stroke,
47(11), e246-e249.
doi:10.1161/strokeaha.116.012095
Transitional Care Models
Improving Care Transitions: 7 Components
Medication Management
Transition Planning
Patient/Family
Engagement/Education
Information Transfer
Follow-up Care
Healthcare Provider
Engagement
Shared Accountability across

Providers & Organizations
NTOCC
What additional needs do STROKE patients have that traditional TC models
• Stroke Patients often have complex needs & functional

impairments requiring
• Special caregiving skills, e.g. transfers, assistance with mobility
& ADLs
• Specialized treatments, PT, OT, SLT, Skilled Nursing
• Multiple follow-up appointments with multiple
providers from different systems of care
• Complex case management
• Family members usually assume these roles with little
preparation
Early Supported Discharge (ESD)
Inter-professional team approach

1. During hospital stay
ESD provider meets with patient & family
Conduct home assessment
Plan discharge home
Agree on rehab goals
2. Discharge home
Implement rehab plan
Access appropriate services Team reviews
progress
Plan for separation of ESD services
Early Supported Discharge (ESD)
Home as a • The couples' experiences of a well-informed discharge from hospital

• Trust in the health professionals' assessment that patient was ready to
go home.
healing place • Described home as a comforting and calm place, where recovery
could meaningfully take place.
Flow of • The experiences of adapting to and continuing everyday life.

• Most of the interviewees had relatively minor physical & cognitive
impairments
everyday life • The patients and their partners were hopeful for a full recovery in the
foreseeable future.
Professional • The much appreciated stroke team

• Although most participants only had 1 visit from the team, knowing
safety net that they were an accessible resource was very important
Lou S, Carstensen K, Moldrup M, Shahla S, Zakharia E, Nielsen CP. Early supported discharge following mild stroke: a
qualitative study of patients' and their partners' experiences of rehabilitation at home. Scandinavian journal of caring sciences.
2016.
COMPASS Care Model
1. Early supported discharge + stroke trained

advanced practice provider (APP) and post-acute
coordinator (RN) for care coordination
2. Individualized electronic care plan addresses the
needs of stroke survivors and their caregivers
3. Connects hospitals, community providers, and
community agencies for improved chronic disease
management
https://www.nccompass-study.org/
COMPASS Trial
• Statewide Hospital to Home Transitional Care

Model in NC
• Multi-site pragmatic clinical trial
• 41 hospitals (~6000 patients)
• 20 Intervention / 21 Usual Care
If patients go to a transitional stroke clinic, they are less likely to be readmitted

(phone calls are not enough)
MISTT
>physical health
SWCM program + QOL, >Patient
informational activation
website > Self efficacy
> Modified Rankin
Emerging Evidence
Patel, N. @ Duke: Phone call by APP

Knowledge deficits r/t meds
Ø scheduled F/U appt
Falls
Jacoby, R. @NYU: D/C Education
Health beliefs, e.g. empowerment SBP
Monacci, K. @ MedStar Health: Nurse Navigator

No difference
Gaines, K. @ Vanderbilt: C3FIT
Technology-enabled care coordination via “Stroke
Connect”
A focus on the family unit: “Family Integrated Care”
Spot light on care Flood light on

recipients needs needs of the family
unit
“Family Integrated Care”

SS & CG Reports of CG Engagement
Developed a 10-item Stroke Caregiver
Engagement Scale (SCES) SS and CG reports of engagement were highly
• Administered to 71 SSs and CGs 9 months correlated
post-stroke • > CG engagement associated with > SS
• Engagement limitations
• at onset • ~25% SSs and CGs reported higher
• during hospitalization engagement led to better outcomes
• post-discharge
• Covers primarily IADLs
Key Conclusions – (Haley, et al., 2017, p. 7)

• Stroke survivors and caregivers agree caregivers’ emotional, tangible, and informational
assistance affects stroke outcomes
• Caregiver engagement significantly affects stroke care at symptom onset
• Professionals who work in stroke rehabilitation and care should attend to and work to
enhance the important roles that family members can play throughout(Haley,the
et al.,course
2017) of care
following stroke.
• Future research should examine the roles of caregivers in enhancing quality and outcomes
of stroke care
Factors that Influence Engagement
• Being marginalized by HC systems

• Lack of support
• Feeling abandoned
• Care that is not individualized
• Poor communication
• Limited sharing of information
• Passivity of relationship b/t HCP and dyad
• Poor or no follow-up – HC silos
• Difficulties with access
• No community services to address post-dc needs
• Fluidity of SS and CG needs – needs change over time
• HC system not designed to address changing needs
•
Communication, Information Pindus, et al.,
Factors that Influence Engagement
Systemic barriers
• Concept of individual autonomy
• HIPAA
• Payment regs that limit time spent /
don’t reimburse for time with CGs
• Health insurance focused on individual
coverage
• Limited access to care based on
proximity, esp. specialty services
IOM report
Factors that Influence Engagmeent
• CG Perspectives of Interactions with Providers
• Qualitative study with 14 stroke survivor / CG dyads
Creasy, K.R., et al., 2013

Factors that Influenced Engagement
Caregiver Interaction Styles
Creasy, K.R., et al., 2013, p. 92

Strategies to Improve Engagement
•
•
•
• Providing and communicating information to the family caregiver
•
•
• Understanding family systems and changing family structures

• Assessing and addressing needs of family CGs
Including cultural aspects
Assessing CG commitment and capacity to provide IOM
carereport, pg. 237
•
State & Federal Regulations
RAISE Family Caregiver Act-National Care Act: Caregiver Advise, Record,
Recognize, Assist, Include, Support, Engage
• Enable
• Developed by AARP
• Directs US DHHS to develop, maintain, and update an integrated national
•
strategy supporting caregivers
Identifies actions to support family CGs
• Identify actions to support family CGs • Record family caregiver name in the medical record
• government •
• Provide family caregiver with education and live instruction on medical tasks
• communities https://www.aarp.org/politics-society/advocacy/caregiving-advocacy/info-2014/aarp-creates-model-state-
bill.html
• health providers
• employers
• others
https://www.forbes.com/sites/nextaven
ue/2018/01/10/what-the-new-raise-
family-caregivers-act-will-
do/#5b45d2e70b9d
Development of The Preparedness Assessment for the
Transition Home after Stroke (PATH-s) Instrument
Draft Instrument
Stage 1
Content Validity Review by Experts (n=8)
Instrument Selection (n=22)

Stage 2: Cognitive
Interviews (n=42)
Refine Instrument (n=20) KMO=0.85; 26 items-1=25
Internal Consistency
Reliability α=0.90
Stage 3: Field Testing
Exploratory Factor Analysis Criterion Validity PCS & PATH-s
(n=183)
Correlation with Other PCS & PATH-s w/

Convergent Validity
Measures PHQ-9, PSS, GHS
PATH-s w/ PHQ-9, PSS,

Predictive Validity (n=102) GHS, BCOS, CSI, PAM; SS Fx,
Readmit
Camicia, M., Lutz, B., Kim, K., Harvath, T., Drake, C., and Joseph, J (2019). Development of an Instrument to Assess
Stroke Caregivers’ Readiness for the Transition Home. Rehabilitation Nursing. Doi. 10.1097/rnj.0000000000000204.
The Preparedness Assessment for the Transition Home after Stroke
(PATH-s)©
How much do you understand about the stroke survivor's expected recovery over the next 6 months?
How much do you understand about how the stroke will affect your lives over the next 6 months?
How much do you understand about what you need to do to get things ready before the stroke
survivors goes home?
How much do you understand about what assistance the stroke survivor will need with personal care
(such as bathing, using the toilet, dressing, and moving around) when he/she goes home?
How much experience have you had providing physical help with personal care (such as bathing,
using the toilet, dressing and moving around) for someone who has a stroke or other disability?
How prepared are you to provide the stroke survivor assistance with personal care (such as bathing,
using the toilet, dressing and moving around) when he/she goes home?
How willing are you to provide personal care (such as bathing, using the toilet, dressing, and moving
around) for the stroke survivor when he/she goes home?
Camicia, M., Lutz, B., Kim, K., Harvath, T., Drake, C., and Joseph, J (2019).
Development of an Instrument to Assess Stroke Caregivers’ Readiness.
Rehabilitation Nursing. doi:10.1097/rnj.0000000000000204
PATH-7 ©
using the toilet, dressing and moving around) when he/she goes home?
stooping, back or joint problems, heart issues, memory, depression, anxiety or other health
challenges)?
maintenance and yard work)?
-workers, your church, a club or social group) who

childcare, pet care, meal preparation, laundry, home maintenance and yard work)?
the toilet or shower (for example, the width of doorways, stairs, ramp access) in the home
where he/she will be living?
store)?
patient?
PATH-7 ©
1. How prepared are you to provide the patient assistance with

personal care (such as bathing, using the toilet, dressing and
moving around) when he/she goes home?
1. I am not prepared to provide the patient assistance
with personal care when he/she goes home.
2. I am a little prepared to provide the patient assistance
3. I am somewhat prepared to provide the patient
assistance with personal care when he/she goes home.
4. I am very prepared to provide the patient assistance
Comparison of PATH-7 against other caregiver preparedness
assessments
Domains PATH- Preparedness CMS Discharge

for Caregiving Planning
Scale Checklist
Designed to assess caregivers √ √ X
Developed as a scale √ √ X
Protocol for Family Caregiving (Messecar, 2012)

-topics/family-caregiving
(a)Assess the context of caregiving √ X X
√ √ √ (partial)
caregiving role
√ X X
√ X X
Number of items 7 8 7
Caregiver Assessment & Plan of Care
Study outcomes of innovative

programs
Provide targeted interventions at the

right time along the stroke caregiving
trajectory
Predict which families/caregivers are at

risk for poorer outcomes
Associated Caregiver Plan of Care
1. How prepared are you to provide the patient assistance with personal care (such as
bathing, using the toilet, dressing & moving around) when he/she goes home?
• Observe CG providing transfers & other care w/ nurses and therapists,
•
including morning & evening care.
Educate regarding roles of team members (home set up and accessibility, • Discus deficits &functional limitations
equipment, medications, bowel and bladder management, mobility,
transportation, follow up, further therapy) • Review assistive devices
• Identify and prioritize required preparation.
•
•
Develop a plan and timelines for required preparation activities
Provide written resources and review with contacting services/agencies.
• Review written materials & verbally in
Assist as needed
lay terms
• Video of performing activities (e.g.
transfers, dressing)
• Assist w/ scheduling their time so can
be present for observing care &
attend to self-care & other personal
required activities/commitments (e.g.
outstanding physician visits and other
personal needs/obligations)
• If not willing to provide care, explore
why not willing; identify ways to
rectify barriers. ID other resources
Questions ?
Michelle.Camicia@kp.org
DaVanzo, et al. 2014 Study –Stroke
Measure IRF SNF Diff IRF-SNF P-value

LOS – avg. days 15.5 32.1 -16.5 <.0001
Mortality 2 yrs post-D/C from facility 34.2% 48.4% -14.3% <.0001
Average days alive 572.2 475.5 +96.8 <.0001
Average # of days home 518.4 426.4 +92 <.0001
# of ER visits/1000 patients 785.9 823.0 -37.1 <.0001
#Hospital Readmissions /1000 pts 1123.1 1227.1 -104/1 0.9040
Average Medicare payment $19,149 $10,482 +$8667 <.0001
Average Medicare payment per $ 2,227 $ 2,162 +$65 <.0001

person per month over 2 yrs.
Discharge to Community
Deutsch et al. (2006) Community D/Cs in IRF > SNF
Hoenig et al. (2001) Patients in IRF had ↑odds of D/C to home
compared to SNF
Physical Functioning
Chan et al. (2013) Mobility, self-care, & cognition gains IRF > SNF
Chen et al. (2002) SNF made > gains in mobility compared to IRF
Deutsch et al. (2006) ↑functional gains in IRF compared to SNF
Kane et al. (2000) ↑gain in ADLs IRF vs. SNF at 12 months
Hospital Readmission
Bettger et al. (2015) SNF readmission ~2-3 % > IRF up to 1 year
Kind et al. (2010) Predicted probabilities of readmit IRF < SNF in
all racial groups
All-cause Mortality
Bettger et al. (2015) Higher IRF vs SNF up to 1 year
Buntin et al. (2010) IRF mortality ↓2.6% compared to SNF
Kind et al. (2010) Death in IRF < SNF in each racial/ethnic group
Wang et al. (2011) Patients in IRF died at rate <1/2 of SNF
Length of Stay
Deutsch et al. (2006) Medial IRF LOS < SNF LOS
Hoenig et al. (2001) LOS in IRF > SNF
Cost
Deutsch et al. (2006) IRF costs > SNF
Alcusky, M., Ulbricht, C. M., & Lapane, K. L. (2018). Postacute Care Setting, Facility Characteristics, and Poststroke Outcomes: A Systematic Review. Arch Phys Med
Rehabil, 99(6), 1124-1140.e1129. doi:10.1016/j.apmr.2017.09.005
Bettger, J.P., Liang, L., Xian, Y., Peterson, E.D., Bushnell, C., Duncan, P. W., Federspiel, J., Stein, J., Montalvo, C., Lutz, B.J., Hoenig, H. Schwamm, L.H., Wu, J. Stafford, J., &
Thomas, L. (2015), Inpatient Rehabilitation Facility Care Reduces the Likelihood of Death and Rehospitalization After Stroke Compared with Skilled Nursing Facility Care (Abstract
146). Stroke, 46, A146. Funding: PCORI ID #130, PI: Prvu Bettger
Buntin, M. B., Colla, C. H., Deb, P., Sood, N., & Escarce, J. J. (2010). Medicare spending and outcomes after postacute care for stroke and hip fracture. Med Care, 48(9), 776-784.
doi:10.1097/MLR.0b013e3181e359df
Chan, L., Sandel, M. E., Jette, A. M., Appelman, J., Brandt, D. E., Cheng, P., . . . Rasch, E. K. (2013). Does postacute care site matter? A longitudinal study assessing functional
recovery after a stroke. Arch Phys Med Rehabil, 94(4), 622-629. doi:10.1016/j.apmr.2012.09.033
DaVanzo, J.E., El-Gamil, A., Li, J.W., Shimer, M., Manalov, N. & Dobson, A. (2014). Assessment of Patient Outcomes of Rehabilitative Care Provided in Inpatient Rehabilitation
Facilities (IRFs) and After Discharge. A Report submitted to the American Rehabilitation Association Research Institute. Vienna, VA: Dobson DaVanzo & Associates, LLC.
Deutsch, A., Granger, C. V., Heinemann, A. W., Fiedler, R. C., DeJong, G., Kane, R. L., . . . Trevisan, M. (2006). Poststroke rehabilitation: outcomes and reimbursement of inpatient
rehabilitation facilities and subacute rehabilitation programs. Stroke, 37(6), 1477-1482. doi:10.1161/01.STR.0000221172.99375.5a Return to Menu
Hoenig, H., Sloane, R., Horner, R. D., Zolkewitz, M., & Reker, D. (2001). Differences in rehabilitation services and outcomes among stroke patients cared for in veterans hospitals.
Health Serv Res, 35(6), 1293-1318.
Hong, I., Karmarkar, A., Chan, W., Kuo, Y. F., Mallinson, T., Ottenbacher, K. J., . . . Reistetter, T. A. (2018). Discharge Patterns for Ischemic and Hemorrhagic Stroke Patients Going
From Acute Care Hospitals to Inpatient and Skilled Nursing Rehabilitation. Am J Phys Med Rehabil, 97(9), 636-645. doi:10.1097/phm.0000000000000932
Kind, A. J., Smith, M. A., Pandhi, N., Frytak, J. R., & Finch, M. D. (2007). Bouncing-back: rehospitalization in patients with complicated transitions in the first thirty days after
hospital discharge for acute stroke. Home Health Care Serv Q, 26(4), 37-55. doi:10.1300/J027v26n04_04
Wang, H., Camicia, M., Terdiman, J., Hung, Y. Y., & Sandel, M. E. (2011). Time to inpatient rehabilitation hospital admission and functional outcomes of stroke patients. Pm r, 3(4),
296-304; quiz 304. doi:10.1016/j.pmrj.2010.12.018
Return to Menu
Predictors of Outcome
The ICH Score
Component ICH score

points
30-day Mortality
3-4 2 100
GCS 5-12 1
80
13-15 0
>30 1 60
ICH volume (cc)
<30 0
40
Intraventricular Yes 1
hemorrhage No 0 20
Infratentorial Yes 1
origin No 0 0
Overall 0 1 2 3 44 5
>80 1
Age (y) ICH Score
<80 0
Total ICH score 0-6
Reproduced with permission from Hemphill JC III, et al. Stroke. 2001;32:891-987.

ICH volume on CT
can be estimated by
AxBxC
2
Select CT slice with largest ICH
A = longest axis (cm)
B = longest axis perpendicular to A (cm)
C = no. of slices x slice thickness (cm)
Estimated spheroid volume

correlates well with planimetric
CT analysis
Kothari RU, et al. Stroke. 1996;27:1304-1305.

• Don’t forget other target organs, including kidneys
not
• NO
Return to Menu
Diagnostic Accuracy: Measurement,
Implications and Improving Patient Outcomes
Adam L. Sharp, MD, MS

Emergency Physician- Los Angeles Med Center Return to Menu
Research Scientist- Research & Evaluation Dept

Assistant Professor- KP School of Medicine
Thank you to Collaborators!
• David E. Newman-Toker • Navdeep Sangha
• Ketan K. Mane • Ahmed Hassoon
• Ejaz A. Shamim • Mehdi Fanai
• Kevin B. Rubenstein • Zheyu Wang
• Najilla Nassery • Carla V. Rodriguez
Daniel (Danny) Kahneman
and
Amos Tversky
“Their papers showed the ways in

which the human mind erred,
systematically, when forced to
make judgments in uncertain
situations.”
JAMA Intern Med. 2017;177(3):407-419. doi:10.1001/jamainternmed.2016.8254 Published online January 9, 2017.
Overview
• Background: Diagnostic Accuracy
• Measuring “Missed” Strokes
• SPADE Methods
• Stroke misdiagnosed as dizziness
• Diagnostic accuracy dashboard
• Summary
Background
1. > 12 Million diagnostic errors per year in the U.S.
2. 1 in 3 diagnostic errors leads to serious patient harm
3. >$100 Billion annual US costs
1. Sing H, et al. BMJ Qual Saf 2014;23:727-31

2. Sing H, et al. JAMA Intern Med 2013;173:418-25
3. Liberman AV, Newman-Toker DE. BMJ Qual Saf. 2018;27;557-566
“improving the diagnostic process
is not only possible, but it also
represents a moral, professional,
and public health imperative.”
National Academies of Sciences, Engineering, and Medicine. 2015. Improving diagnosis in health care. Washington, DC:
The National Academies Press.
Measuring Diagnostic Errors
• Mortality and Morbidity (M&M) Conferences
• Malpractice claims
• Near misses
• Other?
1. Newman-Toker DE, et al. Diagnosis. 2014 Jun:1(2);155-166.
1. Kim AS, et al. j.annemergmed.2010.06.559
Symptom-Disease Pair Analysis of Diagnostic
Error (SPADE)
Liberman AV, Newman-Toker DE. BMJ Qual Saf. 2018;27;557-566

How do we improve diagnostic accuracy?
• Policies and Recommendations
• Leadership commitment
• Education
• Patients
• Physicians, RNs, paramedics, others.
• Decision support
• Incentives / Penalties
• Performance Reporting
• Quality Improvement Dashboard
Durand, DJ, et al. N Engl J Med. 2015;373;1691-93.
“people approach risk very
differently when it involve[s] loss
than when it involve[s] gains
“People [do] not respond to

probability in a straightforward
manner.”
Possible Unintended Consequences
• CT angiograms and MRIs
• Costs
• Overall worse patient outcomes with incidentaloma/false positives
• Physician well being (burnout)

Summary
• Diagnostic accuracy is vital and errors are common
• SPADE methods help identify/measure errors
• Stroke misdiagnosed as benign dizziness offers a target population
• Diagnostic dashboards offer a tool to help improve
• Evaluating for unintended consequences will be important
Return to Menu
Acute Stroke Imaging:
Essentials and Controversies
Anne Catherine Kim, MD
KP NCAL Physician Lead for Stroke Imaging
@Kaiser National Stroke Conference
Return to Menu
April 11, 2019
Outline
Pathophysiology of stroke
Current treatment guidelines and role of imaging
Types
○ CT/CTA
○ MRI
○ “Advanced” imaging
Acute Ischemic Stroke - what is it?
Acute clot in a brain artery
→ ischemia of the area fed by

the artery
→ eventual infarction
Illustration courtesy of T. Leslie-Mazwi, MD

Time is brain -
1.9 million
neurons die
per minute in
untreated
stroke. - J.
Saver 2006
Illustration courtesy of
T. Leslie-Mazwi, MD
Time is brain!!
Acute Ischemic Stroke
Factors influencing
outcome
● Severity (NIHSS score)
● Clot burden
● Infarct core
● Tissue-at-risk aka “penumbra”
● Treatment
● Time from onset to treatment

Time is brain!!
P. Khatri, Neurology
2009
Time is brain!!
Imaging Strategy
Alteplase: first line treatment → Noncontrast head CT
Find large vessel occlusion (LVO) → CTA Head and Neck

and retrieve
Noncon head CT
WHY?
(NOT to look for infarct!)
To look for reasons to not give alteplase
(90% are negative)

Reasons to not give alteplase
Hemorrhage
large area of already infarcted tissue

a mass
IV alteplase is first line,
but clot retrieval is definitive
even if no alteplase,
clot retrieval may still be possible!!
STROKE
2015!!
How do we find clots?
CTA head and neck
CTA head and neck
Find LVO (in head)
Detect treatable cause of clot (in

neck)
CTA head and neck
Find LVO (in head)
Detect treatable cause of clot (in

neck)
KP NCAL algorithm
Acute Stroke <= 4.5 h Noncon Head CT CTA head and neck
Acute Stroke 4.5 -6 h

Or ineligible for Noncon Head CT CTA head and neck
alteplase
LVO cases
These patients go to clot retrieval
KP NCAL algorithm

Or ineligible for Noncon Head CT CTA head and neck
alteplase
Since implementing Stroke Express:
DNT ~ 30 mins (50% decrease)
-
2x tPA cases
-
Stroke. 2018 Jan;49(1):133-139

What About Pts > 6h???
Clinical trials with specific, focused
question:
Is it feasible to treat pts with LVO

outside 6h window?
DAWN and DEFUSE 3
Answer is yes*: For context:
DAWN NNT = 3 Statins after heart attack: NNT ~20s
DEFUSE 3 NNT = 2 tPA for acute stroke: NNT ~ 14

*
Extended window pts
Not everyone! Past 6h LKWT
No hemorrhage/mass/advanced
infarct on CT
LVO on CTA
Small core infarct

“Small core infarct”
LVO → entire vascular territory at risk
Core = already dead
Penumbra = salvageable tissue (rest

of vascular territory)

KEY is large amt of tissue to save
i.e. SMALL CORE in setting of LVO

KEY is large amt of

tissue to save
i.e. SMALL CORE in
setting of LVO

How to find core?
MRI
CTP
Multiphase CTA
Head CT
Menon, BK et.al. Radiology, 2015 May;275(2):510-20.

MRI - gold standard for infarct
Muir KW, J Neurol Neurosurg Psychiatry 2005; 76(Suppl III):iii19–iii28
“If MRI >>> CT
Why don’t we just use it all the time?”
MRI vs CT
MRI: CT:
Gold standard Noisier
Long appointments + Fewer scanners = Short appointments + More scanners
LESS ACCESS GREAT ACCESS

MRI
Gold standard but harder to get
CTP
CTP limitations
Significant radiation
Second contrast bolus
Large margin of error for detecting core infarct
High failure rate
M ay under or overselect treatable patients

CTP subgroup within MR CLEAN
71 pts enrolled also got CTP
40% would have been excluded by EXTEND IA

criteria
35% had technically inadequate CTP
Geuskens RREG, MR CLEAN Investigators. PLoS One. 2015;10:e0141571.

Predicted infarct Final Misclassified
from infarct infarct
baseline CTP on baseline CTP
Geuskens RREG, MR CLEAN Investigators. PLoS One. 2015;10:e0141571.
Schaefer PW. Stroke. 2015;46:419-424.
CTP limitations
Noisy → large margins of error for detecting core infarct
→ under or overselecting treatable patients
Significant radiation
Second contrast bolus
Requires proprietary software: $$$$
Technical factors can lead to frequent unusable data - 35% in literature

Multiphase CTA
Multiphase CTA
Collateral status highly correlated with outcome
Not trying to image core infarct
Reliable, robust, little radiation, no contrast

Courtesy of Bijoy Menon, U. Calgary
good collaterals
Courtesy of Bijoy Menon, U. Calgary
poor collaterals
filling on phase 3 with very few vessels
in MCA territory
In summary
Noncon head CT
● to make sure it’s OK to give alteplase
CTA head and neck
● Look for target for clot retrieval (head)

● Look for source of preventable future events (neck)
In summary: late presenters
CTP (with caveats) and/or MRI to look for infarct size
Collateral imaging (multiphase CTA) more future role?

KP NCAL algorithm

Noncon Head CT/
Or ineligible for
CTA head and neck
alteplase
6 -24h?
KP NCAL algorithm

Noncon Head CT/
Or ineligible for
CTA head and neck
alteplase
Noncon Head CT/

6 -24h CTP and/or DWI
CTA head and neck
In summary
Time is brain!*
Thank you!
anne.c.kim@kp.org
Twitter: @ACKimMD
Return to Menu
Carotid and Vertebral Dissection
Nidhi Gupta, M.D.
MidAtlantic Permanente Medical Group Return to Menu
Disclosures
• None
Patients presenting to ER with cervical artery
dissection (CeAD)
• Trauma dissections – 1 in every 1000 trauma patients(approx.)
• Spontaneous dissection – 2 to 3 in 100,000 people per year
Carotid artery (CAD)dissections – 1.7 in 100, 000
Vertebral artery (VAD)dissections – 0.97 in 100, 000
EBMedicine.NET 2016: 18 (7)

Most common sites and mechanisms of dissection
For CAD:
• Travels over C2-C3 (A)
• Supraclinoid segment (B)
For VAD:
• C1-C2 as it enters the foramen magnum (C)
• C5-C6 as it enters the transverse foramen (D)
EBMedicine.NET 2016: 18 (7)
RadioGraphics 2018; 38:542–563
Screening recommendations for blunt
cerebrovascular trauma
Based of Signs and Symptoms Based of risk factors
• Arterial hemorrhage from the neck, nose, and/ or • High-energy mechanism
mouth • Displaced midface fracture (Le Fort II or III);
• basilar skull fracture with carotid canal involvement; or
• Expanding cervical hematoma • DAI and GCS <6 or ≤8
• Cervical spine fracture or subluxation,
• Cervical bruit in a patient <50 years old • including vertebral body fracture, transverse foramen fracture,
subluxation or ligamentous injury at any level, or any fracture at C1
• Focal neurologic defect (including TIA, hemiparesis, through C3
• vertebrobasilar symptoms, Horner syndrome) • Near-hanging with anoxia
• Clothesline-type injury or seat belt abrasion
• Ischemic stroke findings at CT or MR imaging • with swelling, pain, and/or altered mental status
• Mandible fractures
• Neurologic deficit, inconsistent with head CT findings • Complex skull fractures
J Trauma. 2009;67: 1150 –1153 • Scalp degloving
• Thoracic vascular injuries
• TBI with thoracic injuries
RadioGraphics 2018; 38:542–563
Cervical manipulations
AHA / ASA scientific statement
Although the incidence of CMT-associated CeAD in patients who have previously received CMT is NOT well established, and probably LOW,
practitioners should strongly consider the possibility of CeAD as a presenting symptom, and patients should be informed of the statistical
association between CeAD and CMT prior to undergoing manipulation of the cervical spine. (Stroke. 2014;45:3155-3174)
Cureus. 2016 Feb 16;8(2):e498. doi: 10.7759/cureus.498

Symptoms of Spontaneous Cervical Artery Dissection
Frequency of local symptoms according to vessel segment involvement
Journal of Stroke 2019;21(1):112-115

Pathophysiology of cervical artery dissection
Arch Neurosci. 2015 October ; 2(4): .doi:10.5812/archneurosci.26670

Imaging for cervical artery dissection by computed
tomography angiography (CTA)
PROS CONS
Fast speed of image acquisition Allergy to iodinated contrast
Widespread availability Renal dysfunction
Modality of choice for clinically unstable Compromised by
patients -Poor vascular access
-Reduced EF
-Valvular heart disease
CT Perfusion can be done in addition to obtain Involves exposure to radiation
information on resulting intracranial Relatively contraindicated
hemodynamics -During pregnancy
-In children
Compared to DSA Compromised by

-Sensitivity 64%-100% -Poor vascular access
-Specificity 67%-100% -Reduced EF
-Positive predictive value 65 %-100% -Valvular heart disease
-Negative predictive value 70%-100%
Current Pain and Headache Reports (2019) 23:2

Imaging for cervical artery dissection by magnetic
resonance angiography (MRA)
PROS CONS
TOF, Phase contrast techniques can be used in Not widely available
patients with renal dysfunction
And / or iodinated contrast allergy
High resolution 3T fat suppressed sequences Not as quick as CTA
provide excellent visualization of vessel lumen Not a study of choice for unstable patients
MRI brain done in tandem can help diagnose Intramural hematoma hard to detect in first
ischemic infarctions few to first 48 hours
Compared to DSA Use of gadolinium requires GFR >30ml/min to
-Sensitivity 50-100% decrease chance of nephrogenic systemic
-Specificity 29-100% sclerosis
-Positive predictive value 43-100%
-Negative predictive value 89%
Current Pain and Headache Reports (2019) 23:2

Imaging for cervical artery dissection CTA vs MRA
43 cervical artery dissections

29 internal carotid arteries and 14 vertebral arteries
J Neuroimaging 2017;27:607-612
MRA CTA CTA
J Neuroimaging 2017;27:607-612
Duplex
PROS CONS
-Direct visualization of dissected vessel Inability to visualize
-Real time information about flow dynamics -At or near skull base (common area of
dissection)
-Vertebral artery as it courses through the
transverse foramina
Digital Subtraction Angiography

PROS CONS
-Gold standard -Risk of vascular perforation, stroke,
-Dynamic characterization of blood flow retroperitoneal hematoma
across the lesion -Can miss dissection involving subadvential
layer
Cervical artery dissection and stroke
• Cervical artery dissection as cause of stroke
• 2 % of strokes in all ages
• 20% of strokes in patients aged <45 years
• TIA or stroke as consequence of cervical artery dissection
• occurs in up to 67 % of all patient with cervical artery dissection
• Timing of incident stroke risk after cervical artery dissection presenting without ischemia
limited to first two weeks
EBMedicine.NET 2016: 18 (7); 7 Stroke.2017;48:551-555

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M
E
Penetrating
C
H
A
N
I
S
M
J Chiropr Med. 2007 Summer; 6(3): 110–120

Intravenous thrombolysis with t-PA in patients with CeAD
presenting with stroke up
AHA/ASA Guideline to 4.5 hours
2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke
A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association
Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons
Table 6. Eligibility Recommendations for IV Alteplase in Patients With AIS
Extracranial cervical IV alteplase in AIS known or suspected to be associated with extracranial cervical arterial dissection is reasonably
dissections safe within 4.5 h and probably recommended.† (Class IIa; LOE C-LD)‡
Intracranial arterial IV alteplase usefulness and hemorrhagic risk in AIS known or suspected to be associated with intracranial arterial
dissection dissection remain unknown, uncertain, and not well established.† (Class IIb; LOE C-LD)‡
Severe head trauma In AIS patients with recent severe head trauma (within 3 mo), IV alteplase is contraindicated.† (Class III: Harm; LOE
within 3 mo C-EO)‡§
Recent major trauma In AIS patients with recent major trauma (within 14 d) not involving the head, IV alteplase may be carefully
considered, with the risks of bleeding from injuries related to the trauma weighed against the severity and potential
disability from the ischemic stroke. (Recommendation modified from 2015 IV Alteplase to specify that it does not
apply to head trauma. [Class IIb; LOE C-LD])‡
History of intracranial IV alteplase administration in patients who have a history of intracranial hemorrhage is potentially harmful.† (Class
hemorrhage III: Harm; LOE C-EO)‡§
Subarachnoid IV alteplase is contraindicated in patients presenting with symptoms and signs most consistent with an SAH.†
hemorrhage (Class III: Harm; LOE C-EO)‡§
†Recommendation unchanged or reworded for clarity from 2015 IV Alteplase.

‡LOE amended to conform with ACC/AHA2015 Recommendation Classification System.
§COR amended to conform withACC/AHA2015 Recommendation Classification System.
See also the text of these guidelines for additional information on these recommendations
Safety and outcomes of intravenous thrombolysis in dissection-related
ischemic stroke: an international multicenter study and comprehensive meta-analysis of
reported caseseries
Dissection-related ischemic stroke patients treated with intravenous thrombolysis

A. Favorable functional outcome
B. Functional independence rates J Neurol (2015) 262:2135–2143
Endovascular therapy in CeAD ischemic stroke patients
presenting with in 6 hours
2018 AHA /ASA guidelines do not comment on whether to consider or not to consider
EVT in patients with dissection as the cause.
3. Patients should receive mechanical thrombectomy with a stent retriever if Recommendation revised from 2015 Endovascular.
they meet all the following criteria: (1) prestroke mRS score of 0 to 1; (2)
causative occlusion of the internal carotid artery or MCA segment 1 (M1); (3)
age 18 years; (4) NIHSS score of 6; (5) ASPECTS of 6; and (6) treatment I A
can be initiated (groin puncture) within 6 hours of symptom onset.
Endovascular studies with in 6 ICA dissection

hours time window
MR CLEAN Did not exclude
ESCAPE Excluded suspected intracranial
dissection
REVASCAT Excluded dissection in extracranial or
petrous segment
EXTEND IA Excluded carotid dissection
SWIFT PRIME Excluded carotid dissection
THRACE Excluded carotid dissection
THERAPY Excluded carotid dissection
Thrombectomy in Acute Stroke With Tandem
Occlusions From Dissection Versus
Atherosclerotic Cause
Outcomes According to the Cervical Internal Carotid Artery Lesion Cause
Atherosclerosis Dissection P Value OR (95% CI)† P Value†
90-d mRS 0–2 109/229 (47.6) 36/64 (56.3) 0.22 1.08 (0.50–2.30) 0.85 Questions:
mTICI 2b-3 169/230 (74.5) 51/65 (78.5) 0.42 1.87 (0.82–4.23) 0.13 -Difference in status of
mTICI 3 86/230 (37.4) 20/65 (30.8) 0.33 0.81 (0.39–1.66) 0.56 collaterals
Any procedural(s) 26/230 (11.3) 9/65 (13.9) 0.58 0.81 (0.24–2.76) 0.73
complication(s)*
90-d mortality 35/229 (15.3) 5/64 (7.8) 0.12 1.05 (0.31–3.42) 0.94
-Proximal to distal vs
sICH 12/230 (5.2) 3/65 (4.6) 1.00 … …
distal to proximal
approach
Distribution of 90-day modified Rankin Scale score according to the cervical internal carotid artery lesion cause -Stent thrombosis
-Hemorrhage from
anti-thrombotic used
for stent placement.
Stroke. 2017;48:3145-3148
Endovascular therapy in CeAD ischemic stroke patients
presenting up to 24 hours
2018 AHA /ASA guidelines do not comment on whether to consider or not
to consider EVT in patients with dissection as the cause
7. In selected patients with AIS within 6 to 16 hours of last New recommendation.
known normal who have LVO in the anterior circulation and I A
meet other DAWN or DEFUSE 3 eligibility criteria,
mechanical thrombectomy is recommended.
8. In selected patients with AIS within 16 to 24 hours of last New recommendation.
known normal who have LVO in the anterior circulation and IIa B-R
meet other DAWN eligibility criteria, mechanical
thrombectomy is reasonable.
Imaging Exclusion Criteria Imaging Exclusion Criteria
1. Evidence of internal carotid artery flow limiting dissection on CTA/MRA 1. Evidence of internal carotid artery flow limiting dissection or aortic dissection
2. Severe proximal extra-cranial carotid artery stenosis, or occlusion of any etiology, 2. Intracranial stent implanted in the same vascular territory that would
where concurrent vessel angioplasty or stenting is expected to be necessary and the
procedure cannot be delayed until after the 24 (-6/+24) hours assessments have been completed
precludethe safe deployment/removal of the neuro thrombectomy device
Indications for Intensive care admission
remains the same as for acute ischemic stroke
• Clinically unstable
• On watch for possible Intubation / Intubated
• NIHSS >17
• Status epilepticus
• Predicted malignant course (especially in younger patient)
• Multiorgan failure
• Post thrombolysis
• Post thrombectomy
• Subarachnoid hemorrhage
• Enlarging hemorrhagic transformation
Unanswered question: Blood Pressure Goal
Cervical artery dissection Hypertension Need to enhance collateral blood

flow
AIM:
To determine whether antiplatelet agents or anticoagulation are more
effective in preventing stroke in acute cervical dissections
Inclusion criteria:
• Symptom( Ipsilateral TIA/Stroke, Horner syndrome, neck pain or
headache) onset with in 7 days
• Extracranial dissections only
• No contraindications to either antiplatelets or anticoagulants
• Imaging evidence of dissection on CTA, MRI/MRA or DSA
Study design:
• Randomization antiplatelet agents or anticoagulation agent
• Open treatment
• Blinded adjudication of end points
• Trial treatment until 3 months
• Follow up to 3 months with repeat CTA/MRA
Intention-to-treat population Per-protocol population
Antiplatelet Anticoagulant OR (95% CI)* p value Antiplatelet Anticoagulant OR (95% CI)* p value
group (n=126) group (n=124) group (n=101) group (n=96)
Ipsilateral stroke or death 3 (2%) 1 (1%) 0·335 (0·006–4·233) 0·63 3 (3%) 1 (1%) 0·346 (0·006–4·390) 0·66
Secondary endpoints
Any stroke or death 3 (2%) 1 (1%) 0·335 (0·006–4·233) 0·63 3 (3%) 1 (1%) 0·346 (0·006–4·390) 0·66
Any stroke, death, or major bleed 3 (3%) 2 (2%) 0·673 (0·055– 5·983) 1·00 3 (3%) 2 (2%) 0·696 (0·057–6·220) 1·00
Any stroke 3 (2%) 1 (1%) 0·335 (0·006–4·233) 0·63 3 (3%) 1 (1%) 0·346 (0·006–4·390) 0·66
Ipsilateral stroke, TIA, or death 4 (3%) 5 (4%) 1·280 (0·268–6·614) 0·98 4 (4%) 4 (4%) 1·054 (0·190–5·835) 1·00
Any stroke or TIA 5 (4%) 5 (4%) 1·017 (0·228–4·540) 1·00 5 (5%) 4 (4%) 0·836 (0·161–4·015) 1·00
Major bleeding 0 (0%) 1 (1%) ·· ·· 0 (0%) 1 (1%) ·· ··
Death 0 (0%) 0 (0%) ·· ·· 0 (0%) 0 (0%) ·· ··
Data for presence of residual stenosis (>50%) at 3 months have not yet been analysed. OR=odds ratio. TIA=transient ischaemic attack. *Tested with exact logistic regression.
Table 2:
Conclusions:
• No difference between two treatment arms
• Showing a difference would require 10,000 patients (approximately)
• Recurrent stroke rate 1.6% 2%
• 20 % of dissections not confirmed on central imaging review
Ongoing study: TREAT- CAD – Recruiting

Endovascular Management of cervical artery dissection
Characteristics Carotid Vertebral p Value
(n=93) (n=23)
Age, mean±SD, years 45.4±14.5 42.3±16.9 0.36
Sex, male 52 (55.9) 10 (43.5) 0.37

Type of dissection 0.18
Spontaneous 57 (61.3) 10 (43.5)
Traumatic 27 (29.0) 9 (39.1)
Iatrogenic 9 (9.7) 4 (17.4)
Failed medical therapy 47 (50.5) 4 (17.4) 0.004
Bilateral dissections 15 (16.1) 3 (13.0) >0.99
Pseudoaneurysm 57 (61.3) 5 (21.7) 0.001
Pretreatment mRS results 0.36
Not disabled (score, 0–2) 60 (64.5) 11 (47.8)
Disabled (score, 3–6) 31 (33.3) 10 (43.5)
Follow-up mRS results 0.84
Not disabled (score, 0–2) 69 (85.2)† 18 (78.3)
Disabled (score, 3–6) 12 (14.8)† 3 (13.0)
Indication for intervention
Thromboembolism 53 (57.0) 5 (21.7) 0.004
Enlarging 48 (51.6) 5 (21.7) 0.01
pseudoaneurysm
Flow-limiting dissection 40 (43.0) 8 (34.8) 0.58
Traumatic occlusion with 2 (2.2) 6 (26.1) <0.001
recanalization
Treatment <0.001
Stent 93 (100) 11
(47.8)
Coil Occlusion 0 11
(47.8)
Stent and contralateral coil 0 1 (4.3)

occlusion
J NeuroIntervent Surg 2017;9:952–957

Prognosis of cervical artery dissection
• As per CADISS trial only 2% of patients had recurrent stroke at 3 months ( all were patients whose
initial presenting symptom was stroke).
• Across studies relatively low mortality rates for both CAD and VAD, ranging from 1.5% to 5%.
• Patients with more severe stroke symptoms tend to fare worse.
• Patients with localized symptoms (headache, neck pain, tinnitus and Horner’s syndrome tend to have
better overall outcome.
• Patients with occlusive subtypes tend to do worse than aneurysmal and stenotic subtypes.
Emerg Med Clin N Am 35 (2017) 727–741

Thank You
Return to Menu
An open-minded look at decompressive craniectomy for hemispheric
ischemic stroke
Return to Menu
Paul T. Akins, MD, PhD
Director
Neurocritical Care
Kaiser Sacramento Medical Center
Outline
• Brief look at surgical trials of cerebral hemorrhage (STICH)
• Historical Perspective on hemispheric stroke
• European stroke trials for decompressive craniectomy
• Treatment trends in new era of neurocritical care/acute stroke
interventions
• AHA/ASA Guidelines
• Clinical cases
Is early surgery better than initial conservative treatment for
cerebral hemorrhage?
Early surgery arm n=496 randomized; 465 surgeries (94%

craniotomy rate)
Conservative treatment arm-529 randomized; 140 surgeries

(26% craniotomy rate)
craniotomies
STICH Trial- No difference in outcomes
Good prognosis
Early surgery=49%
Trial of conservative
treatment=51%
52 y F
R ICA occlusion
Not eligible for iv tPA or

thrombectomy
IVF/Pressors for SBP>140
Somnolent with R
hemisphere syndrome on
Hospital Day 1
NIHSS 26
Admit
CT head nc obtained
Werner Hacke
Werner Hacke
Hypothermia for cytotoxic edema is not the solution
Mannitol
Hyperventilate
‘Surgical decompression is an intellectually

rational approach to minimizing tissue shifts
Frank, Jeffrey I.
Ventriculostomy Neurology. Jul;45(7):1286-90
w enrollment into European stroke trials of craniectomy for MCA occlusion
-
DEATH
- 22%
52 y F with R ICA occlusion
Not eligible for iv tPA or

thrombectomy
IVF/pressors SBP>140
Somnolent with R
hemisphere syndrome on
Hospital Day 1
CT head nc obtained
Admit
Manage at PSC?
Transfer to CSC?
Counsel patient and family regarding b/r/a early

decompressive craniectomy?
Trial of conservative medical management?
612
Monro-Kellie Doctrine
no longer applies
“Cranial compartment
is inelastic and the
volume of the cranium
is fixed”
Early Complications of Craniectomy
Brain Tamponade
20
15
GCS
10 ICP
5 EVD
0
1 3 5 7 9 11 13 15 17
Sinking skin flap syndrome
26% of stroke patients in DECIMAL trial
52 y F with R ICA occlusion/infarct
PSC admission or CSC transfer?
Early decompressive craniectomy?
Trial of conservative medical management?

What about initial trial of conservative management?
Admit HD 2 HD 4
52 y F, R ICA occlusion, CT HD0,1,2,3,4

BP support, mannitol, NeuroICU, daily am CT head nc
42 y patient with L ICA occlusion from dissection
Manage medically?
Refer for decompressive craniectomy?
Day 2
Awake
Global
aphasia
L gaze
deviation
Dense R HP
Manage medically?
Offer decompressive craniectomy after discussing b/r/a?
Somnolent
Severe HA
Nauseated
Equal pupils
L gaze
deviation
Global
aphasia
Dense R HP
Refer for decompressive craniectomy

decompressive
craniectomy rates
69 y o female (retired teacher) with L hemisphere syndrome
NIHSS=28
LKWT<2 hours
Received iv tPA without improvement
L carotid angiography and clot extraction
New onset atrial fibrillation

Hospital day 1
NIHSS 30
Somnolent
MRI brain (see above)
Refer for early decompressive craniectomy?
Trial of conservative management?
Dialogue with patient/family regarding goals of care?

Neurocritical care and palliative care consultants met with
patient and family to discuss diagnosis/prognosis and clarify
goals of care
Patient/family had difficult/emotional conversation and

concluded:
“Survival with severe disability (especially language)

unacceptable.”
“. . . agreeable to conservative medical management.”
“. . . No surgical intervention if fails medical management.”
Mannitol for two days (Day 4) and then tapered off.
Managed by clinical exam without serial CT imaging.
Afib was managed with rate control

Motor exam improved
Aphasia persisted.
Discharged to acute rehabilitation on hospital day 7.
Warfarin was started on post-stroke day 14.
Modified Rankin 3 (needs some help with ADL’s,

independent with walking)
Mixed receptive/expressive nonfluent aphasia.
Reperfusion can lead to incomplete infarction rather than pan-
What is the current status of decompressive craniectomy for
hemispheric ischemic stroke?
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Evolving Role of PFO Closure
Return to Menu
Molly Burnett, MD
Medical Director, KP Northern California Telestroke Program
April 11.2019

Disclosures
• None
641
What is a PFO?
642
How are PFO’s relevant to stroke?
Historical Perspective
• Link was first described by Julius Cohnhein, a German pathologist
• Performed autopsy on 35 year old woman with fatal stroke
• Found a long thrombus in the lower extremity and a large PFO
• Hypothesized that an embolus from the thrombus traveled to the right atrium to the
left and into the cerebral vessels
643
How are PFO’s diagnosed?
• Start with TTE and “bubble study”

• TEE may be required for further characterization
• TCD ultrasonography may also be used
644
How are PFO’s relevant to stroke?
Cryptogenic stroke
• Definition: no clear cause despite thorough evaluation
• Represent ~1/3 of strokes1
• Link between PFO and cryptogenic stroke has been controversial
~25% of adults have PFO
PFO alone has not been shown to increase stroke risk2,3
…but PFO prevalence is higher in pts with cryptogenic stroke and up to 40% of
cryptogenic stroke patients have a PFO4
• …so paradoxical embolism through PFO may be implicated in cryptogenic stroke?
1.
2.
3.
4..
645
CLOSURE I (2012) PC trial (2013) RESPECT (2013)
Inclusion Age 18-60 (46) Age < 60 (44) Age 18-60 (45)
Stroke/ “definite” TIA in 6 mos Stroke verified by imaging Stroke within 270 days (non-lacunar)
mRS < 3 “Independent daily activities”
Exclusion Large vessel disease Large vessel disease Large vessel disease
Atrial fibrillation Atrial fibrillation Atrial fibrillation
Cardiac dysfunction Cardiac dysfunction Cardiac dysfunction
Hypercoagulable states Hypercoagulable states Hypercoagulable state
Uncontrolled DM or HTN
PFO adjudication TEE with bubble TEE with bubble TEE with bubble
Closure device STARFlex Amplatzer PFO occluder Amplatzer PFO occluder
Control arm Aspirin and/or warfarin Antiplatelet or anticoagulation Antiplatelet or warfarin
N 909 414 980

Mean F/u (y) 2 4.1 2.6
1° endpoint Composite: stroke/TIA, mortality, Composite: death, stroke, TIA, Composite: stroke or early death
neurologic death peripheral embolism
Closure v. control 5.5% v. 6.8 % 3.4% v. 5.2% ITT: 0.66 v 1.38 events/100 pt yrs
PP: 0.39 v 1.45 events/100 pt yrs
P value P=0.37 P=0.34 ITT: HR 0.49; [CI] 0.22-1.11, P=0.08
PP: HR 0.37, [CI] 0.10-0.75, P=0.007
Conclusion Closure not superior to meds Closure not superior to meds No sig benefit in ITT analysis
646 Closure superior in PP analysis
RESPECT Long term follow up (2017) CLOSE (2017) REDUCE (2017)
Inclusion Age 18-60 (45) Age 16-60 (43) Age 18-59

Non-lacunar stroke within 270 Non-lacunar stroke verified by Non-lacunar stroke within 180 days
days (imaging if sx transient) imaging w/in 6 months; mRS < 3 (imaging if sx transient), mRS < 3
Exclusion Large vessel disease Large vessels disease Lage vessel disease
Atrial fibrillation Cardioembolic source Cardioembolic source
Cardiac dysfunction Hypercoagulable state Hypercoagulable state
Hypercoagulable state Uncontrolled DM or HTN
Uncontrolled DM or HTN
PFO criteria R L shunt on bubble study large shunt (> 30 microbubbles), R L shunt on bubble study
or ASA
Closure device Amplatzer PFO occluder Any CE marked device Helix/cardioform septal occluder
Control arm(s) Antiplatelet or warfarin 1) Antiplatelet Antiplatelet

2) Anticoagulation
N 980 663 664
Median F/u (y) 5.9 5.3 (mean) 3.2
1° endpoint Composite: stroke or early death Recurrent stroke Stroke or silent infarct on MRI
Closure v. control ITT: 0.58 v 1.07 events/100 pt yrs 0/238 vs 14/235 Stroke: 1.4% v 5.4%
Silent infarct: 5.7% v 11.3%
P value HR 0.55; [CI] 0.31-1.0, P=0.046 HR 0.03; [CI] 0-0.26, P<0.001 HR 0.23; [CI] 0.09-0.62, P=0.002
HR 0.51, [CI] 0.29-0.91m P=0.04
Conclusion
647
Closure superior to medical tx Closure superior to antiplatelets Closure is superior to antiplatelets
Saver JL, Carroll JD, Thaler DE, et al. Long-Term Outcomes of Patent Foramen Ovale Closure
or Medical Therapy after Stroke. N Engl J Med 2017; 377:1022
What was the difference between earlier and later RCTs?
• All RCTs have found point estimates suggesting closure is more effective than
medical therapy
• Results not significant in earlier trials
• Results were significant in later trials
Longer follow up
Careful patient selection
• Neuroimaging requirement
• Exclusion of lacunes
• Select PFO features
649
Stratification by size or presence of ASA
• REDUCE: 81% had moderate or large shunt

• CLOSE: 100% had either large shunt or ASA
• RESPECT follow up
49% had grade 3 shunt
36% had ASA
650
Saver JL, Carroll JD, Thaler DE, et al. Long-Term Outcomes of Patent
Foramen Ovale Closure or Medical Therapy after Stroke. N Engl J Med
651 2017; 377:1022
Saver JL, Carroll JD, Thaler DE, et al. Long-Term
Outcomes of Patent Foramen Ovale Closure or Medical
Therapy after Stroke. N Engl J Med 2017; 377:1022.
652
653
How to measure benefit?
• 2018 meta-analysis (PC, RESPECT extended follow up, REDUCE, CLOSE)

Closure reduced risk of recurrent stroke: 5.1% 1.8%
NNT ~ 30 to prevent 1 recurrent stroke
654
Adverse effects of PFO closure
• Higher rate of venous thromboembolism?

Due to lower rates of anticoagulation?
• Higher rates of atrial fibrillation/atrial flutter
655
Summary: what is the bottom line for our patients?
• Newer evidence suggests PFO closure is beneficial to prevent recurrent stroke

Meta-analyses suggest NNT ~30
• Some risk of adverse events
Atrial fibrillation
• Selection of the right patients is crucial
Multidisciplinary team evaluation
656
Additional references
• Furlan AJ, Reisman M, Massaro J, et al. Closure or medical therapy for cryptogenic
stroke with patent foramen ovale. N Engl J Med 2012;366:991.
• Meier B, Kalesan B, Mattle HP, et al. Percutaneous closure of Patent Foramen
Ovale in Cryptogenic Embolism. N Engl J Med 2013; 368:1083.
• Carroll JD, Saver JL, Thaler DE, et al. N Engl J Med 2013; 368:1092.
• Saver JL, Carroll JD, Thaler DE, et al. Long-Term Outcomes of Patent Foramen
Ovale Closure or Medical Therapy after Stroke. N Engl J Med 2017; 377:1022.
• Mas JL, Derumeaux G, Guillon B, et al. Patent Foramen Ovale Closure or
Anticoagulation vs. Antiplatelets after Stroke. N Engl J Med 2017; 377:1011.
• Søndergaard L, Kasner SE, Rhodes JF, et al. Patent Foramen Ovale Closure or
Antiplatelet Therapy for Cryptogenic Stroke. N Engl J Med 2017; 377:1033.
657
Optimal medical therapy?
• Unclear, no good RCTs exist
• One group put forth a “weak recommendation” for anticoagulation in patients for
whom closure is contraindicated/declined1, however anticoagulants have not been
proven superior to antiplatelets but have been associated with increased bleeding
risk
• AAN recommends antiplatelet therapy2
“In the absence of another indication for anticoagulation, clinicians may routinely offer
antiplatelet medications instead of anticoagulation to patients with cryptogenic stroke and
PFO” (Level C)
• AHA/ASA: 3
“There are insufficient data to establish whether anticoagulation is equivalent or
superior to aspirin for secondary stroke prevention in patients with PFO”
• Canadian best stroke practice recommendations
“either antiplatelet or anticoagulant therapy is recommended for secondary stroke
prevention, unless there is a separate evidence-based indication for chronic 1.BMJ 2018;362:k2515
2. Neurology 2016;87:815-821.
anticoagulation” 4 3. Stroke 2014;45:2160-2236.
4. Int J Stroke. 2018;13(4):410-443.
658
Meta-analyses
DeRosa et al1
Included 4 of the major trials
Excluded CLOSURE I
Shah et al2
Included same studies as above
NNT ~ 30 to prevent 1 recurrent stroke
1. Ann Intern Med. 2018;168:343

2. Ann Intern Med. 2018;168:335.
659
Trial limitations
• Heterogeneity of devices and medical therapy

• Heterogeneous afib results
• Majority of trials had more patients lost to follow up than the number of primary
endpoints
• Unblinded investigators determining events
660
ASCOD stroke classification system
• A: atherothrombosis
• S: Small vessel disease
• C: Cardiac pathology
• O: Other
• D: Dissection
661
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662
CEREBRAL VENOUS SINUS THROMBOSIS
Jeremy Fields, MD
Return to Menu Director, Interventional Neuroradiology, KP NW
Director, Comprehensive Stroke Center, KP NW
CVT: INTRO
CVT: INTRO
Wildlings
Bearded
Less civilized
Fiercely independent
CVT: SIGNS AND SYMPTOMS
Four IIH
presentations
(based on Focal neurologic deficit +/- sz
involved vein)
Encephalopathy – deep system
Painful
ophthalmoplegia/proptosis/chemosis –
cavernous sinus
Neurosurg Clin N Am 29 (2018) 585–594

CVT: ANATOMY
Elevated intracranial pressure
IIH
Focal signs
ICH
Seizure
CVT: ANATOMY
Cavernous sinus
Sick
III, IV, V1, V2, VI
Chemosis/proptosis
CVT: ANATOMY
Deep venous system
Decreased level of
consciousness
Neurocrit Care (2009) 11:330–337

ISCVT Prospective, multi-national

observational
Defined presentation, RF’s, and
outcomes
n=624
75% F
Median age: 37yo
83% anti-coagulated
Stroke 2005;36;1720-1725; Stroke. 2004;35:664-670

Increased ICP % Mental Status % Focal % Seizure %

Headache 88 Coma/Stupor 14 Paresis 37 Any 40
Sudden onset headache 15 Other mental status change 22 Sensory loss 5 Focal 20
Papilledema 28 Aphasia 19 Generalized 30
Visual loss 13 Posterior fossa 5
Diplopia 13
CVT: RISK FACTORS
Major % Other
Thrombophilia* 34 OCP or HRT use was present in greater than 50% of females > 50
Pregnancy or puerperium 15 Hematologic: polycythemia, essential thrombocytosis
CNS or head/neck infection 10 Inflammatory: SLE, Behcet’s, RA, sarcoid, IBD, sprue, thrombangiitis obliterans, etc.
Malignancy 7 Abnormal venous anatomy: dural fistula, venous anomaly, AVM
No risk factor identified 13 Mechanical: neurosurgery, ENT surgery, or trauma
CVT: DIFFERENTIAL DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
Arterial stroke
Meningitis/encephalitis
PRES
ICH/SAH
Endocarditis
Brain abscess
ADEM
Key differential features:

Timing of onset
Vascular distribution
Prominent seizures and HA
Elevated ICP
CVT: DIFFERENTIAL DIAGNOSIS
Standard diagnostic approach
–MRI/MRV or CT/CTA/CTV once suspected
–Unless septic or surgical etiology, hypercoagulable work-up
–Send blood cultures early

CVT: IMAGING
ISCHEMIA/VENOUS HTN HEMORRHAGE
CT ICH
Focal hypodensity Frontoparietal (SSS, trollard) 41%
Generalized swelling Temporal (labbe, transverse sinus) 22%
Gyral or falcine enhancement
Occipital (transverse sinus) 7%
MRI Deep (straight sinus, deep system)
Heterogeneous T2/FLAIR Thalamic 7%
signal Caudate 4%
Often some true restricted SAH (convexity; isolated in up to ¾) 15%
DWI
(this is often reversible)
Not in arterial distribution
Eur Radiol (2004) 14:215–226; Neurocrit Care (2009) 11:330–337

CVT: IMAGING
INDIRECT EVIDENCE
Swelling (CT hypodense; T2/FLAIR hyperintense) in non-arterial distribution
Heterogenous ICH
Cortical SAH
IMAGING THE CLOT
CT
Hyperdensity within venous sinuses
Delta sign (non con CT)
Empty delta sign (post con CT)
Lack of opacification (CTV)
MRI
Absent flow voids on T2
May be visible on GRE
Clot visualized in sinuses:
d1-5 (deoxyhb): T1 iso; T2 dark (can be mistaken for flow voids)
d6-15: T1 bright; T2 evolves from dark to bright
d15+: T1 iso; T2 bright
Peripheral enhancement of vein or sinus on post-gad images
CVT: IMAGING
Delta sign Hyperdense sinus Empty Delta
T1 Iso FLAIR Hyper MRV Peripheral Filling defect with

enhancement on MRI peripheral enhancement
(empty delta)
GRE SWI
CVT: TREATMENT
Standard treatment approach
–Acute anticoagulation, unless etiology is surgical or septic
–Transition to warfarin or dabigatran when clinically stable

(warfarin length of therapy guided by DVT guidelines
and hypercoagulable wu)
–Endovascular treatment reserved for patients failing warfarin or with

refractory ICP
–Consider repeat imaging at 3-6 mo to assess for recanalization

CVT: ACUTE TREATMENT
Meta-analysis of 4 trials
RCT
Anticoag vs. Placebo (OR) for mortality 0.31 (0.07-1.45) and

disability 0.3 (0.09 to 1.01)
Three new ICH placebo; no ICH anticoag
LMWH vs. UFH OR for mortality 0.21 (0.02 to 2.44,

p = 0.21) and disability 0.5 (95% CI 0.11 to
2.23).
No new ICH in either group
Conclusion Anticoag likely effective, even with ICH
LMWH acceptable, unless decompression

may be necessary
Thromb Res 2018 Sep 165-169
Severe/refractory
Neurosurg Focus 27 (5):E6, 2009;

Direct aspiration
Mechanical thrombectomy
Angio-Jet irrigation
Thrombolysis with tPA

infusion
Balloon disruption with

aspiration
CVT: CHRONIC TREATMENT
Novel 4 trials
anticoagulant
vs. warfarin
Dabigatran vs. Two trials; one complete; no results
warfarin reported
Rivaroxaban vs. Two trials; one complete; no results

warfarin reported
Conclusion Warfarin standard; NoAg likely options in

future
No trials on duration; European 2017

guidelines recommend 3-12 months;
Journal of Thrombosis and Haemostasis 2018, 16: 1918–1931

European Journal of Neurology 2017, 24:1203–1213
CVT: PROGNOSIS
ISCVT Prognosis RF for poor outcome

Risk factor HR Risk factor HR
77% mRS 0-1 Age>37 2.0 Deep venous thrombosis 2.9
13% dead or severely disabled Male 1.6 (i.e., not sinuses)
GCS<9 2.7 ICH 1.9
Any mental status change 2.0 Any malignancy 2.9
CNS infection 3.3
OTHER Recurrence: 5-10%

Complete or partial recanalization:
90%
Stroke 2005;36;1720-1725; Neurocrit Care (2009) 11:330–337

CVT: SEQUELAE
DAVF Location depends on site of occlusion

Treatment based on presence of cortical venous reflux or
intolerable symptoms (pulsatile tinnitus)
Intracranial Partial recanalization or chronic occlusion with symptoms of

Hypertension IIH or venous hypertension if severe
Consider stenting
CVT: QUESTIONS
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Medical Therapies to
Facilitate Stroke Recovery
Kaiser Permanente National Stroke Conference
Kwan Ng MD, PhD
University of California, Davis Medical Center
Why are we so aggressive with stroke?
function
no treatment
Timeline of Recovery
Mechanisms of Stroke Recovery
• Three fundamental themes
• (1) Timeline for stroke recovery
• (2) Excitatory neuronal signaling
• (3) Promotion of growth
programs
• Neurogenesis
• Surviving peri-infarct zone • Oligodendrogenesis
• Heightened neuroplasticity • Axonal sprouting
• Re-mapping of sensory and motor
functions from damaged areas
• Promoting recovery from stroke
Acute Phase of Recovery
• Resolution of Edema
• Normalization of blood flow to penumbra
• Diaschisis improves
Acute
Dirnagl
Subacute Phase of Recovery
Subacute
• Microvasculature and glial establish a recovery-enhancing environment

• Endogenous mechanisms of neural repair
• Primed and engagement
• Potentially most beneficial for stroke recovery
•
Chronic Phase of Recovery
Chronic
• Improvement by rehabilitative therapies

Timing
Stroke
Recovery
Therapy Pharmacological
Interventions Interventions
Heterogeneity
Pharmacological Targeting
• Targets
• What are the potential effects of different drugs on the injured brain?
• After a stroke, does it modulate neurotransmission improve or worsen the
recovery of motor function?
• Clinical Data
• When to use?
• Time frame of use – acute, subacute, or chronic
• Clinically Available
• Duration
• Possible Contraindications
Early SSRI Clinical Trials
• SSRI have a positive effect on motor recovery

• Double-blind, placebo-controlled trial, from 9 stroke centers in France
• Hemiplegia or hemiparesis
• Fugl-Meyer motor scale (FMMS) scores of 55 or less
• Inclusion - 18 to 85 years old
• Fluoxetine (20 mg once per day) or placebo for 3 months starting 5–10
days after the onset of stroke.
• All patients had physiotherapy.
• The primary outcome measure was the change on the FMMS between
day 0 and day 90 after the start of the study drug.
• Enrolled 118 patients
Montgomery Asberg depression rating scale (MADRS) Fugl-Meyer motor scale (FMMS)
0 to 6 – normal/symptom absent Total score 100
7 to 19 – mild depression
20 to 34 – moderate depression
>34 – severe depression
Chollet
Chollet
FMMS
Fluoxetine vs Placebo
Chollet
Modified Rankin Scale
5.8 vs 6.9 p = 0.151
NIHSS Motor Scores
4.7 vs 6.3 p = 0.012
-0.1 vs 3.2 p = 0.032
mRS -2
15 vs 5 p = 0.015
Chollet
Meta-analysis 52 SSRI Trials
🙂🙂
• Multicenter, parallel group, double-blind, randomized, placebo-controlled trial
• 103 hospitals in the UK
• 18 years or older
• Ischemic stroke and ICH
• 2 days and 15 days post-stroke onset
• Persistent focal neurological deficit
• Centralized randomized process
• Fluoxetine 20 mg or placebo
• Goal of at least 3000 patients
• Total 3127 randomized patients
• 1564 Fluoxetine and 1563 Placebo
• Primary outcome
• mRS at 6 months
• Secondary outcomes via questionnaire
• Functional status
• Adverse events
No difference
Primary measure of medication adherence
2/3 took study medication for at least 150 days
Median duration of treatment

- 185 days in the ﬂuoxetine group
- 183 days in the placebo group.
Fluoxetine increase
Risk of fractures
Fluoxetine decrease
Onset of depression
Fluoxetine less likely

To be started on a new
antidepressant
Fluoxetine and Stroke
• No indication for empirically starting Fluoxetine
• Questions
• Access to Physiotherapy
• mRS may not be adequate to measure improvement
• Ongoing clinical trials pending AFFINITY and EFFECTS

• Prospective, randomized, placebo-controlled, double-blind study
• 28 stroke patients with aphasia for at least 1 year
• Single unilateral cortical-subcortical stroke
• Drug: Memantine 20mg/day or placebo for 16 weeks
• NMDA receptor antagonist
• Drug + CIAT for weeks 16-18
• Drug alone for weeks 18-20
• Washout for weeks 20-24
• Open label Menantine for both groups for weeks 24-48
• Outcomes based on Western Aphasia Battery-Aphasia Quotient
Memantine
CIAT
• Combination of Memantine and CIAT significantly

improved aphasia severity
• Memantine alone improved aphasia
• Transplantation in rats
• 1 month post MCAo/stroke
• Rat BMSC
• Human BMSCs
• Neurological improvement in both groups Human BMSCs
• 5-7% graft survival
Yasuhara et al Stem Cells Dev 2009

Steinberg et al Stroke 2016
Timing
Stroke
Recovery
Therapy Pharmacological
Interventions Interventions
How can we understand
better understand
rehabilitation and therapy
Interactions?
Issues
• Difficult to predict outcomes even for expert clinicians
• Patients with similar motor deficits will have different outcomes
• Biomarkers
• Research efforts
• Determination of multiple therapy interactions
• Considerations for rehabilitation
• Impact on acute hospital resources
• Access
• Inpatient vs. outpatient vs. SNF
• Insurance
Governing Factors
• Age
• Severity of stroke
• Neuroimaging markers - MRI
• Ipsilesional corticomotor pathways do not overlap with stroke
• Degree of asymmetry fractional anisotropy (FA) of bilateral posterior limb
(corticospinal tracts)
• Transcranial magnetic stimulation (TMS) to look at motor evoked
potentials (MEPS)
• Early return of finger extension, shoulder shrug and abduction, and active ROM
• Prognostic determinants of the outcome for the paretic upper limb at 6 months after stroke.
• GOAL
• Measure upper extremity function at 72 hours
• Outcome of upper limb function at 6 months
• Outcomes
• 2 simple bedside tests, finger extension and shoulder abduction
• Functional recovery of the hemiplegic arm at 6 months can be predicted early in a
hospital stroke unit within 72 hours after stroke onset
192 patients
Positive predictive power of 80%
SAFE = Shoulder Abduction Finger Extension

0-10
207 patients
Predictive power of 75%
Practicable use
Future
• Understanding the targets at each phase of recovery
• Heterogeneity of stroke
• Understanding the interactions with other modalities of
therapy
• Physiotherapy
• Transcranial direct current stimulation (tDCS)
• Transcranial magnetic stimulation (TMS)
• Constraint-Induced Movement Therapy (CIMT)
• Opening and closing windows of recovery
Summary
• Rehabilitation should be considered at all stages of stroke recovery
• SSRI should not be started the stroke patients until there is more data
• Recovery can be augment by pharmacology is still a process that

needs to more investigation
• Stem cell trials pending
• EARLY predication of extend of injury will help direct patients into

clinical trials and assist in rehabilitation decisions
Thank you!
Management of Post-Stroke
Depression
Richard L. Delmonico, Ph.D.

Director - Neuropsychology
Kaiser Foundation Rehabilitation Center
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Regional Lead, NCAL Neuropsychology Services
The Permanente Medical Group

Objectives
Understand the types and symptoms of a depressive disorder and
normal psychological responses to a stroke.
Describe the frequency of depression following a stroke.
Describe pharmacological approaches to treating post-stroke
depression (PSD).
Understand the effectiveness of psychological and other treatments in
PSD.
DISCLOSURE
NO RELEVANT DISCLOSURES
Stroke Emotional Changes: Initial Reaction to being in the hospital
Importance of allowing for initial adjustment to new setting
Comfort and privacy; missing home/family
Begin therapy routine
Develop a sense of “where is all this headed…”
Grief
– Denial: Disbelief
– Anger: Toward Self or Others
– Bargaining: If I can Just Walk Again…
– Depression: Realization
– Acceptance: Acknowledgement
– Hope: Life Can Still be Fulfilling
Common Emotional Changes to Medical Conditions
Sadness
Emotional Lability
Mood Changes
Anxiety
Worry
Frustration
Apathy/Decreased Motivation
Feeling Overwhelmed
Unsure of Future
What is Post Stroke-Depression
“Many stroke survivors experience feelings of anger,

frustration, anxiety, sadness, fear, and hopelessness
in varying degrees. These emotions are common
with post-stroke depression” (National Stroke Association website:
https://www.stroke.org/we-can-help/survivors/stroke-recovery/post-stroke-
conditions/emotional/depression/)
Depressive symptoms that occur at any time

following a stroke
Depressive Disorders: DSM-5
Adjustment Disorders (Precipitating Event)
– Sadness, tearfulness, hopelessness, ANXIETY
Depressive Disorder Due to Another Medical Condition (CVA)
Unspecified Depressive Disorder (atypical or minor depression)
Other Specified Depressive Disorder
– Short Duration Depressive Disorder (4-13 days; 4 symptoms)
– Depressive Episode w/Insufficient Symptoms (Sad + 1 symptom)
Major Depressive Disorder
– Persistent Sadness or Loss of Interest or Pleasure
– Sleep; Appetite; Wt; Fatigue; Agitation/Retardation; Concentration/Indecision
– Recurrent Death Thoughts; Suicidal Ideation; Worthlessness or Guilt;
– Distress or Impairment in Social, Occupational, Other Functioning
Persistent Depressive Disorder (Dysthymia – Chronic)
Assessment of Depressive Symptoms: Measures
Depressed mood
Interest
Guilt or worthlessness
Sleep disturbance
Psychomotor agitation or retardation
Appetite change
Concentration decreased
Energy loss or fatigue
Suicidal ideation, intent, plan
Anxiety often co-existing
Assessment of Depressive Symptoms: General
Risk Factors
Hx of depression
Multiple somatic complaints
Medical conditions
Age >60
Persistent sadness
Apathy or irritability
Family Hx of mood disorders
Poor sleep; fatigue; domestic violence;
Substance abuse
Emotional Lability
Mood Congruent Crying: Normal or consistent with psychological
condition
Pseudobulbar Affect (PBA)
– Uncontrolled crying or laughter (less common)
– Misdiagnosed as depression
– Mood Incongruent
– Inappropriate to situation
– Due to Stroke or another neurological condition
Treatment Options
– Mild – Deep Breaths
– Antidepressants: TCA or SSRI at lower doses
– Detromethorphan and Quinidine Sulfate (Nuedexta)
736April 11, 2019 | © 2011 Kaiser Foundation Health Plan, Inc. For internal use only.
How Do We Effectively Measure Post Stroke
Depressive Symptoms? (Meader et al., 2014; Laures-Gore, et al.,
2017; Towfighi et al., 2017; Das & G.K., 2018)
Patient Health Questionnaire (PHQ-9) (Spitzer et al.,
1999)
Center for Epidemiological Studies – Depression

Scale (CES-D) (Radloff, 1977)
Hamilton Depression Rating Scale (HDRS or HAMD)
(Hamilton, 1960)
Stroke Aphasic Depression Questionnaire – 10

(SADQ-10) (Sutcliffe et al., 1998)
Aphasic Depression Rating Scale (ADRS) (Benaim, et
al., 2004)
Risk Factors in Post Stroke Depression
(Winstein, et al., 2016; Towfighi, et al., 2017; Das & G.K., 2018)
Physical disability
Stroke severity
Pre-stroke depression
Cognitive impairment
Lack of family/social support
Family history of psychiatric disorder
Female
Some studies suggest: accumulation of white matter lacunes; right
posterior; left anterior BUT reviews have found NO CONSISTENT
LOCALIZATION findings
How Common is Post Stroke Depression and
When is it MOST LIKELY to Occur?
One Third of stroke survivors affected

–31% (Hackett & Pickles, 2014)
–33% (Hackett, Yapa, Parag, et al., 2005)
–29% (Ayerbe, Ayis, Wolfe, et al., 2013)
Depression is most common within the first
year and declines up to 5 years post-stroke
Post-Stroke Depression: Impact on Outcomes
(Towfighi, et al., 2017)
Poorer functional outcomes/poor long-term

recovery
Reduced Quality of Life
Longer length of stay
Higher medical utilization
Higher mortality
SSRI Effects in NON-Depressed Stroke
Survivors
FLAME Study: 113 Ss acute ischemic stroke w/mod-sev motor deficits;
(Fluoxetine (20 mg) vs. Placebo) + Physical Therapy; 90 day FU motor
improvements were significantly improved in fluoxetine Ss (Chollet et
al., 2011)
FOCUS: 3127 Ss fluoxetine (20 mg) vs. placebo; No significant
improvement in modified Rankin score (functional improvement) at 6
or 12 months but less depression at 6 months (FOCUS Trial
Collaboration, 2019).
Ischemic and Hemorrhagic strokes; escitalopram vs. problem solving
therapy or placebo; Improved global neuropsychological functioning
and less depression found in escitalopram Ss at 12 month FU
(Robinson, et al., 2008; Jorge et al., 2010)
Post Stroke Depression: Pharmacologic
Treatments
Problems: Lack of RCTs, small Ns, lack of generalizable samples (no
aphasia), short duration, contradictory findings, side effects (TCAs in
older adults; SSRIs- GI, sleep, HA), no clear results on prophylactic
use (Paolucci, 2017)
Findings suggest antidepressants are effective in reducing depressive
symptoms (Xu, et al., 2016; Das & G.K., 2018)
Meta-analysis rank in effectiveness: Paroxetine, imipramine,
reboxetine, nortriptyline, citalopram, fluoxetine. Duloxtine quick results
and effect on anxiety (Deng et al., 2018)
NEW No PSD studies: vilazodone, levomilnacipran, vortioxetine
(Paolucci, 2017)
Limited case studies on psychostimulants (methylphenidate) but
problems with cardiovascular side effects (Towfighi, 2017)
Post Stroke Depression: Psychotherapy
Cochrane: No evidence of a benefit in reducing PSD (Hackett,
Anderson, House, & Xia, 2008)
Counseling focused on problem solving, mood, adjustment to stroke.
Reduction in depressive symptoms 9weeks, 6 mos, 1 yr (Mitchell et
al., 2009. Another study similar protocol but phone vs. in-person vs.
controls found equal reductions in all Ss No Tx Effect (Kirkness et al.,
2017)
20 1-hour behavior therapy sessions x3 mos reduced depression
symptoms (Thomas et al., 2013)
Meta-analysis CBT: Both CBT and CBT+AD improved depressive
symptoms, response, and remission of PSD. BUT studies variable and
poor quality – more research is needed. (Wang et al., 2018)
Post Stroke Depression: Other Treatment
Approaches
Relaxation: Few studies and none specifically on PSD. Study with
CVA, PD, MS, TBI in LTC found Group instruction led to reduction in
Anxiety and Depression (Hampson, et al., 2019)
Mindfulness-Based Interventions trend decrease in depressive and
anxiety symptoms but limited studies and small Ns (Lawrence et al,
2013)
Noninvasive Brain Stimulation: rTMS repetitive transcranial magnetic
stimulation; tDCS transcranial direct current stimulation. Some studies
have found a decrease in depressive symptoms but there is a lot of
variability across studies and small Ns. More research is needed.
(Bucur & Papagno, 2018)
Exercise can reduce depressive symptoms but effects diminish after
exercise stops (Eng & Reime, 2014)
Conclusions
Post Stroke Depression – 1/3rd survivors
Diagnosis is important, distinguish from normal reaction to stroke, and
simple screening measures like PHQ-9 are helpful
Most common during first year and decreases over 5 years
PSD Outcomes: Poor functioning, QOL, utilization, mortality
FLAME studies: Prophylactic use of SSRIs maybe/maybe not
Antidepressants can reduce depressive symptoms but unsure about
impact on functional measures
Other approaches: Exercise, limited directive psychological treatments
can be helpful
CONSULT: Psychiatry/Behavioral Medicine
Suggest: Health Education; Increasing social/rec activities
QUESTIONS
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Advances in Primary Stroke Prevention

PM Rothwell Lancet 2004;363:1925. S Koton. JAMA 2014;312:259. EJ

History and physical

Non-Atherosclerosis Atherosclerosis-Related Risk Factors Carotid Stenosis

. . . the health of the brain is inextricably related to

PB Gorelick. Stroke 2017;48:e284-e303

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Prevalence of Undiagnosed AF Age 75: 3%

European Society for Cardiology

P Kirshhof Europace 2016;18:1609-1678; SJ Curry JAMA 2018;320:478

• Anticoagulate based on stroke risk: CHA2DS2-VASc score ≥2

CT January JACC 2019;

Categories of Blood Pressure in Adults*

Use of Antihypertensive Medication

20-44 30% 19%

Treatment: chlorthalidone +/- atenolol

Mean Achieved difference SBP: ~12 mmHg

Things that may help

M. Viswanathan Ann Intern Med 2012;157:785. BB Green JAMA 2009;229:2857.

1. How low to go?

SP Marso NEJM 2016;375:1834.

HbA1c > 6.5% Consistent With T2DM

HbA1c <7% No No Other Factors Affect Choice

DK Arnett Circulation 2019; Davies Diab Care 2018;

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MJ Lean Lancet 2018;391:541

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Strategies to address muscle symptoms

SM Grundy. JACC 2018

DL Bhatt NEJM 2019;380:11-22.

Major ipsilateral stroke or any

Executive Committee for the ACAS. JAMA 1995;273:1421-1428

Favoring Medical Therapy

Surgery can fix it

Medical therapy may be just as good

DV Heck Neurology 2017;88:2016

Outcome Aspirin No Aspirin HR ARD*

SL Zheng JAMA 2019;32:277-287

*High ASCVD risk not specified. High bleeding risk includes:

DK Arnett Circulation 2019

Ornish D et al. Lancet. 1990; 336:129 & JAMA. 1998;280:2001.

Ornish D et al. JAMA. 1998;280:2001

There were 2.5 times as

Chairman and Professor, Dept.

Control (n=41) Experimental (n=43)

Ornish D et al. Journal of Urology. 2005;174:1065

Ornish D et al. Journal of Urology. 2005;174:1065

-80% t=6.9, P=.000

Ornish D et al. Journal of Urology. 2005;174:1065

Baseline-12m Change in LNCAP Cell Growth

Ornish D et al. Journal of Urology. 2005;174:1065

Same diet and lifestyle

In 23,000 people, exercising 3.5 hours a

TMAO levels were 3.3 on an Atkins diet, 2.6 on

Ellsworth D et al. Circ Cardiovasc Genet. 2014 Apr;7(2):151-60.

Genes can double the risk of heart

Khera AV, Fuster V, et al. N Engl J Med Nov 16, 2016

Dusek JA et al, PLoS One

1. EMS Pre-Notification 7. POC Laboratory Testing