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Acute Stroke. The Basics. It’s Not Just t-PA. Nina T. Gentile, MD Associate Professor Department of Emergency Medicine Temple University Hospital & School of Medicine Philadelphia, PA. Nina T. Gentile, MD, FAAEM. Stroke Basics. How important is blood pressure control?

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Acute stroke l.jpg

Acute Stroke

The Basics

It’s Not Just t-PA


Slide2 l.jpg
Nina T. Gentile, MDAssociate ProfessorDepartment of Emergency MedicineTemple University Hospital & School of MedicinePhiladelphia, PA

Nina T. Gentile, MD, FAAEM


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Stroke Basics

  • How important is blood pressure control?

  • How do early ischemic changes on CT impact on decision-making and treatment?

  • What roles do aspirin and heparin play?

  • Is hyperglycemia really a problem?

  • What are the indications for immediate transfer?


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Case Example

  • 72-year-old woman

  • History: hypertension, diabetes

  • Sudden slurred speech, left facial droop, left-sided weakness

  • Family calls 911


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Case Example

  • ACLS squad dispatched, evaluates, transports patient to nearest ED

  • En route the squad notifies the receiving hospital of a possible stroke patient

  • And asks….


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“Hey Doc… How About Aspirin?”

“Isn’t it…

…the sooner the better?”

Nina T. Gentile, MD, FAAEM


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Aspirin in Stroke Meta-Analysis

  • 41,399 subjects

  • Nine trials

  • For every 1,000 patients…

    …7 fewer early recurrent strokes

    …13 fewer dead or dependent at 6 months

    …~ 2 intracerebral bleeds


Aspirin trials for stroke l.jpg
Aspirin Trials for Stroke

  • International Stroke Trial (IST)

  • Chinese Acute Stroke Trial (CAST)

  • Treatment within 48 hours

    • IST time to treatment: 19 hours

    • CAST time to treatment: 25 hours


International stroke trial l.jpg
International Stroke Trial

  • 19,435 patients

  • 300 mg/d aspirin within 48 hours of stroke onset

  • Slightly fewer deaths at 14 days: 9.0% vs 9.44%, p=.02, NNT =91


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0.8%

3.9%

0.9%

2.8%

IST – 14 DAY OUTCOME

Hemorrhagic

5

Ischemic

4.5

p=.05

4

3.5

3

2.5

2

p=.05

1.5

1

0.5

0

Aspirin

Avoid Aspirin


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38.8%

36.5%

IST – 6 MONTH OUTCOME

Dead or Dependent

40

38

36

34

32

p=.05

30

28

26

24

22

20

Aspirin

Avoid Aspirin


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Chinese Acute Stroke Trial

  • 21,106 patients

  • 160 mg/d dose within 48 hours of stroke onset

  • Primary end points:

    • Death at 4 weeks

    • Death or dependence at discharge


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Chinese Acute Stroke Trial

Recurrent Stroke

8

4-wk Mortality

7

6

p=.01

5

2.1

1.6

4

3

p=.04

2

3.9

3.3

1

0

Aspirin

Avoid Aspirin


Chinese acute stroke trial14 l.jpg
Chinese Acute Stroke Trial

Dead or Dependent

36

34

32

30

28

p=.08

26

31.6%

30.5%

24

22

20

Aspirin

Avoid Aspirin


Aspirin in acute stroke 6 hours l.jpg
Aspirin in Acute Stroke: <6 Hours

  • Not studied

  •  ICH when used with lytic

    • Early thrombolytic trials

    • Phase IV trials


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Thrombolysis: Early Studies

  • ASK (1996): SK or Placebo plus ASA within 4 hours of symptom onset


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Thrombolysis: Early Studies

  • MAST- I (1995): within 6 hours of symptom onset

    • streptokinase,

    • aspirin,

    • both or

    • neither


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Thrombolysis: MAST-I

*OR 3.5; 95% CI 1.9-6.5; 2p < 0.00001


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Phase IV: IV t-PA in Stroke

The Cleveland Area Experience

  • Symptomatic ICH: 15.7%

  • Protocol violation: 50%

    • Received aspirin within 24 hours: 37%


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Phase IV: IV t-PA in Stroke

STARS 2000

  • Symptomatic ICH: 3.3%

  • Asymptomatic ICH: 8.2%

  • Protocol violation in 33%

    • rt-PA >180 minutes: 13%

    • Received aspirin or anticoagulant within 24 hours: 9%


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Aspirin in Acute Stroke

  • Recommendation: 160 to 325 mg/day within 24 to 48 hours

  • Avoid in potential candidates for thrombolytic therapy

  • Delay for at least 24 hours after the administration of rt-PA

  • Do not administer prehospital

    (i.e. pre-CT)


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Our Patient Arrives…

  • Right gaze preference

  • Left face droop

  • Dysarthria

  • Left arm paresis

  • Mild left side neglect


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Three Questions…

  • Is this a stroke?

  • How would you quantify or describe the stroke?

  • Would you give t-PA?


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Intracerebral hemorrhage

Hypoglycemia

Hyperglycemia

Seizure

Migraine headache

Hypertensive crisis

Tumor

Meningitis

Encephalitis

Brain abscess

Differential Diagnosis


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‘Misdiagnosis of Stroke’

  • 821 patients admitted to acute stroke unit

  • 108 (13%) incorrect diagnosis

    • Seizure: 39%

    • Confusional states, syncope: 24%

Lancet. 1982 Feb 6;1(8267):328-31


Stroke mimics libman 1995 l.jpg
Stroke Mimics: Libman 1995

  • Evaluator: stroke team

  • Studies: history, physical

  • Misdiagnosis: 19%

  • Mimics identified: seizure, infection, tumor, metabolic, positional vertigo, cardiac syncope, subdural, C- spine fracture, transient amnesia, conversion disorder, MS, myasthenia gravis, parkinsonism, hypertensive encephalopathy


Stroke mimics kothari 1995 l.jpg
Stroke Mimics: Kothari 1995

  • Evaluator: emergency physician

  • Studies: history, physical, CT

  • Misdiagnosis: 4%

  • Mimics identified: paresthesia, seizure, migraine, neuropathy, psychogenic, others


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Stroke Mimics: Allder 1999

  • Evaluator: neurologist

  • Studies: history, physical, CT

  • Misdiagnosis: 9%

  • Mimics identified: metabolic, migraine, conversion disorder, withdrawal


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Stroke Mimics: Ay 1999

  • Evaluator: neurologists

  • Studies: history, physical, CT

  • Misdiagnosis: 1.2%

  • Mimics identified: seizure, migraine, tumor, transient global amnesia


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NIH Stroke Scale (NIHSS)

  • Designed as research tool

  • Widely used in clinical practice

  • Good interobserver reliability

  • Helps predict outcome


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NIH Stroke Scale (NIHSS)

  • Helps assess risk of hemorrhage after t-PA treatment

  • Provides quantitative mechanism for following individual patient


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Item

Description

Range

Pt score

1a

Level of consciousness

0-3

1

1b

LOC Questions

0-2

1

1c

LOC Commands

0-2

1

2

Best Gaze

0-2

1

3

Best Visual

0-3

0

4

Facial Palsy

0-3

2

5

Motor Arm Left

0-4

3

6

Motor Arm Right

0-4

0

Our Patient’s NIHSS Score (Part 1)


Our patient s nihss score part 2 l.jpg

Item

Description

Range

Pt score

7

Motor Leg Left

0-4

1

8

Motor Leg Right

0-4

0

9

Limb Ataxia

0-2

0

10

Sensory

0-2

1

11

Neglect

0-2

1

12

Dysarthria

0-2

1

13

Best Language

0-3

0

Our Patient’s NIHSS Score (Part 2)

Total = 13


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Would you Give t-PA?

  • Potential Benefit

  • Potential Risks

  • Exclusion Criteria

    • Historical features

    • CT findings


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IV t-PA: Potential Benefit

  • 2775 patients in 6 trials

Lancet. 2004



Complete resolution in 24 hours l.jpg

(NIHSS<1)

25

20

15

10

5

0

t-PA

placebo

Complete Resolution in 24 Hours


Ninds 1 year follow up l.jpg

t-PA

Placebo

NINDS 1 Year Follow-up

80

70

60

50

Favorable Outcome

40

30

20

10

0

<9

10-14

15-20

>20

Presenting NIHSS Score


Iv t pa potential risk l.jpg
IV t-PA: Potential Risk

  • Intracranial hemorrhage

    • Pooled analysis of 2775 patients treated within 6 hours of sx onset

    • rt-PA: 82 (5.9%)

    • Placebo:15 (1.1%)


Clinical exclusion criteria l.jpg

Bleeding Risk

Active GI or GU bleeding

Bleeding Diathesis

PLT < 100K

INR > 1.7

 PTT

Potential Major Bleeding Site

 BP sys>185, dias >110

Stroke Mimic

BS < 50, > 400

Seizure at onset

Rapidly improving or minor symptoms

Clinical Exclusion Criteria



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Early Ischemic Changes

  • Loss of insular ribbon

  • Loss of gray-white interface

  • Loss of sulci

  • Acute hypo density

  • Mass effect

  • Dense MCA sign


Early ischemic changes43 l.jpg

Insular Cortex

Sylvian Fissure

Early Ischemic Changes


Early ischemic changes44 l.jpg
Early Ischemic Changes

  • Loss of insular ribbon

  • Loss of gray-white interface

  • Loss of sulci

  • Acute hypo density

  • Mass effect

  • Dense MCA sign


Early ischemic changes45 l.jpg
Early Ischemic Changes

  • Loss of insular ribbon

  • Loss of gray-white interface

  • Loss of sulci

  • Acute hypo density

  • Mass effect

  • Dense MCA sign


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Early Ischemic Changes

  • Loss of insular ribbon ()

  • Loss of gray-white interface ()

  • Loss of sulci ( )

  • Acute hypodensity

  • Mass effect

  • Dense MCA sign


Early ischemic changes47 l.jpg
Early Ischemic Changes

  • Loss of insular ribbon

  • Loss of gray-white interface

  • Loss of sulci

  • Acute hypodensity

  • Mass effect

  • Dense MCA sign


Early ischemic changes48 l.jpg
Early Ischemic Changes

  • Loss of insular ribbon

  • Loss of gray-white interface

  • Loss of sulci

  • Acute hypo density

  • Mass effect

  • Dense MCA sign


Would you give t pa to our patient l.jpg
Would You Give t-PA to Our Patient?

“No hemorrhage…

…large area of hypoattenuation with edema….”



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Significance

Early ischemic changes can…

…assist in decision-making

…predict outcome

…predict ICH


Eic assists decision making l.jpg
EIC Assists Decision-Making

…findings change over time

…are correlated with perfusion deficits



Eic predicts outcome l.jpg
EIC Predicts Outcome

43 patients, t-PA (30-100 mg)

PPV for death

  • Hypodensity > 50% MCA: 85%

  • Localbrain swelling: 70%

  • Hyperdense MCA: 32%

Amer J Neurorad 1994


Eic predict outcome l.jpg
EIC Predict Outcome

Favors Placebo

Favors tPA


Eic predict outcome56 l.jpg
EIC Predict Outcome

Favors Placebo

Favors tPA


Eic predicts ich l.jpg
EIC Predicts ICH

ECASS I

  • If >1/3 MCA involvement: increased risk of bleed

    • OR 3.6, 95% CI, 2.3 to 5.3

      NINDS

  • Only CT exclusion: hemorrhage

  • No association with EIC extent


What to look for on ct l.jpg
What To Look For On CT

  • Any signs of blood

  • Hypodensity >1/3 MCA territory

  • EICs difficult to appreciate

    • Should not dissuade use of appropriate therapy

  • Correlate with the history


Neurology resident oh no she ll be sure to bleed with t pa let s start heparin instead l.jpg

Neurology Resident: “Oh no…she’ll be sure to bleed with t-PA….Let’s start Heparin instead.”

We “have to do something”

Nina T. Gentile, MD, FAAEM


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Potential Indications

  • Cardioembolic Stroke

  • Progressing Stroke

  • Stroke due to documented large-artery stenosis

  • Arterial Dissection


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IV Administration

  • 225 patients

  • IV Heparin vs Placebo for 7 days

  • No difference at 7 days, 3 mos, 1yr

    • stroke progression

    • functional activity

  • More patients in heparin group died at 1 year

    Ann Intern Med. 1986 Dec;105(6):825-8


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SubQ Heparin:IST

  • 19,435 Patients

  • 4 Groups:

    • ASA, Heparin 5,000U or 12,500U bid, Both, or Neither

  • 1o Outcome:

    • Death at 14 days

    • Death or dependency at 6 mos


Slide63 l.jpg
IST

14-Mortality (NS)

10

9

8

9.3

7

9.0

6

5

Heparin

Avoid Heparin


Slide64 l.jpg

62.9

62.9

IST

6-mo Dead/Dependent (NS)

70

60

50

40

30

20

10

0

Avoid Heparin

Heparin


Ist no net benefit l.jpg

0.4

1.4

3.8

2.9

IST: No Net Benefit

Ischemic

Hemorrhagic

5

4

3

2

1

0

Heparin

Avoid Heparin


Immediate use in atrial fibrillation l.jpg

Ischemic

Hemorrhagic

0.4

2.1

4.9

2.8

Immediate Use in Atrial Fibrillation

6

5

4

3

2

1

0

Heparin

Avoid Heparin


Eusi and aha heparin in stroke l.jpg
EUSI and AHA:Heparin in Stroke

1. No recommendation for general use of heparin, LMWH or heparinoids after ischemic stroke (Level I)

2. Full dose heparin for selected indications such as AF, other cardiac sources with high risk of re-embolism, arterial dissection, or high grade arterial stenosis (Level IV)

3. DVT-prophylaxis


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What are the Options?

  • Intravenous t-PA

  • Excluded from Thrombolytics

    • Nothing

    • Aspirin

    • Heparin

  • Intra-arterial thrombolysis


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Neuroimaging

  • Assessment of blood flow and tissue viability

    • CT Angiography

    • MRI with perfusion imaging


Slide70 l.jpg
MRI

Acute CBF

DWI


72 yr old right mca stroke l.jpg

5:05 Angiography reveals multiple thrombi proximal MCA and segmental arteries

5:25 Microangiocatheter IA t-PA administration

6:30 Patient goes to ICU

72-yr-old Right MCA stroke


Slide72 l.jpg

10-day T2 segmental arteries

MRI

DWI

Acute CBF


72 yr old s p t pa l.jpg
72-yr-old S/P t-PA segmental arteries

  • Day 2: PT and speech therapy started

  • Day 10: Hospital discharge to resume managing her brokerage company

Stroke Survivors.com


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Case #2 segmental arteries

  • 43 year old black male with headache, right sided face, arm, leg weakness and vertigo x 30 minutes

  • PMH: Hypertension, diabetes

  • Exam: Dysarthria, profound weakness and ataxia


Initial vital signs l.jpg
Initial Vital Signs segmental arteries

  • BP: 220/120 mm Hg

  • Pulse: 64 regular

  • Resp Rate: 24 regular

  • Accucheck: 428 mg%


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Severe Hypertension segmental arteries

  • What is the optimal BP?

    …with fibrinolytic therapy?

  • When to initiate treatment?

  • Which antihypertensive?


Severe hypertension77 l.jpg
Severe Hypertension segmental arteries

  • Worsens cerebral blood flow

  • Decreases odds of full recovery

  • Promotes hemorrhagic transformation and ICH after t-PA

    Dutka, 1987

    Chamorro,1998


Opt imal bp l.jpg
Opt segmental arteriesimal BP

  • No controlled studies to guide

  • “Permissive hypertension”

    • Target BP in patients with prior hypertension: 180 / 100-105 mmHg

    • Target BP in previously normotonic patients: 160-180 / 90-100 mmHg

  • Avoid hypotension, drastic reductions in BP


Bp management l.jpg
BP Management: segmental arteries

Not Eligible for Thrombolytic Therapy 1

  • Systolic<220 or Diastolic<120

    • Observe

    • Except with end-organ involvement (aortic dissection,AMI,pulmonary edema, hypertensive encephalopathy)


Bp management80 l.jpg
BP Management: segmental arteries

Not Eligible for Thrombolytic Therapy 2

  • Systolic>220 or Diastolic 121–140

    Labetalol 10–20 mg IV;

    may repeat Q 10 min

    (max 300 mg)

    Nicardipine 5 mg/hr IV initial dose; increase 2.5 mg/hr Q 5 min (max 15 mg/hr)

  • Diastolic>140

    Nitroprusside 0.5 µg/kg/min IV infusion initial dose, titrate


Bp management81 l.jpg
BP Management: segmental arteries

Pretreatment for Thrombolytic Therapy

  • Systolic >185 or Diastolic >110

    Labetalol 10–20 mg IV over 1–2 min, may repeat x 1

    Nicardipine 5 mg/hr IV initial dose; increase 2.5 mg/hr Q 5 min

    (max 15 mg/hr)

    Nitropaste 1–2 inches

    ***If BP systolic>185 or diastolic>110, do not give r-TPA***


Bp management82 l.jpg
BP Management: segmental arteries

During & After Thrombolytic Therapy

  • Diastolic >140: Nitroprusside

    0.5 µg/kg/min IV initial dose and titrate

  • Systolic 180-230 or Diastolic 105–140:

    -Labetalol bolus then drip at 2-8 mg/min

    -Nicardipine 5 mg/hr IV initial dose,

     2.5 mg/hr Q 5 min (max15 mg/hr)


Induced hypertension l.jpg
Induced Hypertension segmental arteries

  • Phenylephrine or Norepinephrine can improve neurologic deficits

  • IV NS, LR, or 10% hydroxyethyl starch 200/0.5 (HES) augments local perfusion to ischemic tissue

    Rordorf, Stroke, 1997

    Hillis, Cerebrovasc Dis, 2003

    Aichner, 2003


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Returning to our Case segmental arteries

  • BP remains ~220/120 mm Hg

  • Anticipating IV t-PA or with the possibility of ICH….

    …..give Labetalol (10 mg bolus IV ) or Cardene by IV infusion if available


The nurse wants to know l.jpg

The Nurse Wants to Know segmental arteries

What about the Blood Sugar?

Do you want to hang fluids?

Give Insulin?

Nina T. Gentile, MD, FAAEM


Hyperglycemia in stroke l.jpg
Hyperglycemia in Stroke segmental arteries

  • Accounts for 25 to 50% of patients

  • Associated with worsened outcome

    • increases cerebral edema

    • hemorrhagic transformation of ischemic strokes

    • increases mortality with BS > 130mg%


Hyperglycemia after stroke l.jpg

Normal BS segmental arteries

(<130 mg%)

High BS

(>130 mg%)

P

Ischemic

n=259

n=385

Mortality

6 (2%)

18 (7%)

<.0001

ICH

1 (2%)

17 (7%)

<.0001

Hemorrhagic

n=109

n=89

Mortality

16 (15%)

46 (52%)

<.0001

Hyperglycemia after Stroke


Hyperglycemia after stroke88 l.jpg

GLYCEMIC CONTROL segmental arteries

Control

P

No control

Ischemic

n= 259

n=81

D/C Home

161 (62%)

52 (64%)

.01

Mortality

18 (7%)

1 (1.3%)

<.0001

Hemorrhagic

n=37

n=35

Mortality

24 (65%)

15 (43%)

<.0001

Hyperglycemia after Stroke


Hypercoagulability l.jpg
Hypercoagulability segmental arteries


Hyperglycemia l.jpg
Hyperglycemia segmental arteries

  • EUSI and AHA Recommendations:

    - Treat hypoglycemia- Give Insulin for Blood Glucose > 300 mg%


Insulin l.jpg
Insulin segmental arteries

NEJM


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Returning to our Case segmental arteries


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43 yo with ICH segmental arteries

  • Patient given 50 gm Mannitol

  • Emergently intubated and ventilated to maintain pCO2 of 32 mmHg

  • Given with 8 mg midazolam and 10 mg vecuronium

  • Nurse wants to know if you’ll need a bed or will you be transferring the patient


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Surgical Rx of ICH - 1 segmental arteries

1. Large clots in the frontal, temporal or occipital regions with progressive clinical deterioration.


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Surgical Rx of ICH - 2 segmental arteries

2. Deep basal ganglia clot in the non-dominant hemisphere with progressive deficit


Surgical rx of ich 3 l.jpg
Surgical Rx of ICH - 3 segmental arteries

3. Acute cerebellar hematoma larger than 3cm.


Nonsurgical rx for ich l.jpg
Nonsurgical Rx for ICH segmental arteries

  • Small bleeds or GCS >12

  • No chance for recovery or GCS < 4


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Returning to our case segmental arteries

  • Undergoes craniotomy and evacuation of hemorrhage with ventriculostomy placement

24o p ED Presentation

ED Presentation


43 yo s p ich evacuation l.jpg
43 yo s/p ICH Evacuation segmental arteries

  • Intermittently following commands with left arm, right-sided hemiparesis

  • Discharged to extended care facility 24 days after admission

  • Antihypertensive regimen

    • Clonidine

    • Minoxidil

    • Atenolol


30 day stroke mortality l.jpg
30-day Stroke Mortality segmental arteries

Period

Ischemic

Lacunar or Cortical

Hemorrhagic

ICH or SAH

Overall

1981-88

10%

48%

19%

10%

1996-00

36%

22%


Disability among stroke survivors l.jpg

71 segmental arteries

80

70

60

50

31

40

20

30

20

10

0

% Stroke Survivors

Disability Among Stroke Survivors

Need Help caring for Themselves

Need Help Walking

Impaired Vocational Capacity


Stroke patients views on stroke outcome l.jpg
Stroke Patients’ Views segmental arterieson Stroke Outcome

  • Elderly stroke patients with disability vs age-matched controls

  • Preferred death to severe disability

    • 69% of stroke patients

    • 82% of controls

  • Over 1/3 preferred painless death to even minor disability

Clin Rehab 2000; 14:417-424


Acute stroke care it s not just t pa l.jpg
Acute Stroke Care- segmental arteriesIt’s Not Just t-PA

  • Aspirin should be avoided until after CT and the question of t-PA is answered

  • Individualize BP management

  • Early ischemic changes on CT help with decision-making

  • Heparin has no role (other than DVT prophylaxis)

  • Intensify blood sugar management

  • Transfer: imaging, interventional neurorad, or surgery


Stroke team l.jpg

PHYSICAL MEDICINE and REHABILITATION segmental arteries

Stroke Team

Neurology

4 WEST

ED

STAT LAB

NICU

Neurosurgery

Neuroradiology, Diagnostic

Neurovascular Research

Neuroradiology, Interventional


Stroke l.jpg
Stroke segmental arteries


Questions www ferne org ferne@ferne org nina gentile md ngentile@temple edu 215 707 8402 l.jpg
Questions?? segmental [email protected] Gentile, [email protected] 707 8402

formatted_gentile_stroke_aaem_2005.ppt 2/11/2005 10:31 PM

Nina T. Gentile, MD, FAAEM


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