1. Stroke: An Introduction
Maarten Lansberg, MD, PhD
Neil Schwartz, MD, PhD
Stanford Stroke Center

2. Outline
Background
Stroke Diagnosis
Stroke Treatment
Stroke Prevention

3. What is a Stroke? (Brain Attack)
Disruption of blood flow to part of the brain caused by:
Occlusion of a blood vessel (ischemic stroke) OR
Rupture of a blood vessel (hemorrhagic stroke)

4. Types of Stroke
Mohr JP, Caplan LR, Melski JW, et al. Neurology 1978;28:754-62

5. Anatomy

7. MR Angiogram

8. What happens with cutoff of blood supply?
Oxygen deprivation to nerve cells in the affected area of the brain -->
Nerve cells injured and die -->
The part of the body controlled by those nerve cells cannot function.

9. What Causes Ischemic Stroke?
Thrombotic
Embolic
Thrombus
Embolus

10. Ischemic Stroke

12. What happens with rupture of a blood vessel?
Oxygen deprivation to nerve cells in the affected area of the brain and local destruction of nerve cells-->
Nerve cells injured and die -->
The part of the body controlled by those nerve cells cannot function.

13. Intracerebral Hemorrhage

16. Head CT: Ischemic or Hemorrhagic Stroke?

17. Head CT: Ischemic or Hemorrhagic Stroke?

18. Stroke Impact 750,000 strokes per year Third leading cause of death
(1st: heart disease, 2nd: all cancers)
Over 160,000 deaths per year
Over 4 million stroke survivors
1. Williams GR, Jiang JG, Matchar DB, et al. Stroke 1999; 30:
2. Hoyert DL, Kochanek KD, Murphy SL. National Vital Statistics Report 1999; 47:19.

19. Stroke Impact (2) Leading cause of adult disability
Of those who survive, 90% have deficit
Half of all patients hospitalized for acute neurological disease.
Stroke costs the U.S. $30 to $40 billion per year.

20. The Stroke Belt
Perry HM, Roccella EJ. Hypertension 1998;6:

21. 2. Stroke Diagnosis

22. Symptoms of Stroke
Sudden numbness or weakness of face, arm or leg, especially on one side of the body
Sudden confusion, trouble speaking or understanding
Sudden trouble seeing from one or both eyes
Sudden unsteadiness, dizziness, loss of balance or coordination
Sudden severe headache with no known cause

23. Also common following stroke
Other Stroke Symptoms
Also common following stroke
Depression
Other emotional problems
Memory problems

24. Common Stroke Patterns
Left (Dominant) Hemisphere:
Aphasia
Right hemiparesis
Right hemisensory loss
Right visual field defect
Left gaze preference
Dysarthria
Difficulty reading, writing, or calculating

25. Common Stroke Patterns (2)
Right (Nondominant) Hemisphere:
Left hemiparesis
Left hemisensory loss
Left neglect
Left visual field defect
Right gaze preference
Dysarthria

26. Common Stroke Patterns (3)
Brainstem/Cerebellum/Posterior Circulation
Motor or sensory loss in all 4 limbs
Crossed signs (face vs. body)
Limb or gait ataxia
Dysarthria
Dysconjugate gaze
Nystagmus
Amnesia
Cortical blindness

27. Common Stroke Patterns (4)
Small Vessel (Lacunar) Strokes (Subcortical or Brain Stem)
Pure Motor
Weakness of face, arm, leg
Pure Sensory
Decreased sensation of face, arm, leg

28. Differential Diagnosis
Stroke (ischemic; hemorrhagic)
Intracranial mass
Tumor
Subdural hematoma
Seizure with persistent neurological signs
Migraine with persistent neurological signs
Metabolic
Hyper/Hypoglycemia
Infectious
Meningitis / Encephalitis / Cerebral abscess
Systemic

29. 3. Stroke Treatment

30. Time is Brain

31. EMS/ED evaluation of acute stroke
Assure adequate airway
Monitor vital signs
Conduct general assessment
Evidence of trauma to head or neck
Cardiovascular abnormalities

32. EMS/ED evaluation of acute stroke (cont.)
Conduct neurological examination
Level of consciousness (Glasgow Coma Scale)
Presence of seizure activity
NIH Stroke Scale

33. ED evaluation of acute stroke: diagnostic tests
Non-contrast Head CT
EKG
Blood Glucose
CBC, platelets, PTT, PT/INR
Serum electrolytes

34. t-PA therapy

35. tPA therapy for acute stroke
Candidate for IV tPA?
Stroke onset < 3 hours (When was the patient last seen at baseline ?)
Benefit: 12 % increased chance of good recovery
Risk: bleeding (up to 6%)

36. tPA exclusion criteria
Symptoms mild or rapidly resolving
SBP > 180 or DBP > 110
Blood on head CT
History of ICH
CNS tumor or vascular malformation
Bacterial endocarditis
Known bleeding disorder
PTT > 40; PT > 15 (INR > 1.7)
Stroke within 3 months
Significant trauma in last 3 months
GI/GU/Resp hemorrhage within 21 days
Major surgery within 14 days / minor surgery within 10 days
Peritoneal dialysis or hemodialysis
Seizure at onset of stroke
Glucose <50 or >400
Pregnant

37. Other therapies for acute stroke
IV t-Pa outside the three hour window
IA t-PA
IA mechanical thrombolysis/thrombectomy
Neuroprotective agents

38. Stroke Management
If not a candidate for acute intervention, then focus on:
Prevention of recurrent stroke
Diagnostic evaluation for stroke etiology
Risk factor assessment
Rehabilitation (PT/OT/SLP)
Prevention of Complications
DVT, aspiration PNA, decubitus ulcers, falls

39. Diagnostic stroke evaluation
Purpose: Identify location, size, and cause of stroke
Tests may include:
Follow-up head CT
Brain MRI/MRA
Carotid ultrasound
Cardiac echo (transthoracic or transesophageal)
Cerebral angiogram or CT angiogram
Lipid panel
Hemoglobin A1c
Hypercoagulable tests: antiphospholipid antibodies, Protein C & S, Antithrombin III, Factor V Leiden mutation, Prothrombin 20210A mutation…

40. 4. Stroke Prevention

41. Stroke survivor’s greatest risk is another stroke16
Stroke
Heart Attack
14% 14
13%
13% 12
10% 10
Percent of patients with events 8 7% 6
Talking Points
This study collected data from four secondary prevention trials, the CATS trial with aspirin, the TASS trial with ticlopidine, the CAPRIE trial with clopidogrel and ESPS 2 with ASA/ER-DP. Virtually all studies have shown that stroke-related deaths are considerably more common than cardiac deaths during the first few years after stroke onset, when patients participate most commonly in clinical trials of antiplatelet agents. In later years cardiac-related deaths increase (16). 4 3% 3% 2% 2
CATS
TASS
CAPRIE*
ESPS 2
* Stroke patient subgroup only (n = 6,431)
Albers, G.W. Neurology. 2000;14;54(5):

42. Transient Ischemic Attack (TIA)
Stroke symptoms resolve in less than 24 hours (most resolve in < 1 hour)
Warning sign for stroke and heart attack
One third go on to have a stroke within 5 years
Stroke risk can be reduced
Opportunity to prevent full stroke

43. Stroke risk factors Non - Modifiable Age Gender (men)
Heredity: family history of stroke, hypercoagulable states
Race/ethnicity (e.g. African Americans)
Sacco RL, Benjamin EJ, Broderick JP, et al. Stroke: 1997;28:

44. Stroke risk factors Modifiable Medical Conditions Hypertension
Heart disease
Atrial fibrillation
High Cholesterol
Diabetes
Carotid stenosis
Prior stroke or TIA
Behaviors
Cigarette smoking
Alcohol abuse
Physical inactivity
Sacco RL. et al. Stroke. 1997;28: Pancioli AM et al. JAMA. 1998;279:

45. How many strokes can be prevented?*
Adapted from Gorelick PB. Arch Neurol 1995;52:347-55
*Based on an estimated 731,000 strokes annually

46. Hypertension JNC VII Guidelines

47. Lower blood pressure = Lower Risk
< 120/80
< 130/85
< 140/90
Cardiovascular Events
Vasan RS et al N Engl J Med 345; , 2001
< 120/80
< 130/85
< 140/90
Cardiovascular Events (%)

48. Blood pressure reduction following stroke
PROGRESS Trial
Blood pressure reduction following stroke 20
28% relative risk reduction
14% 15
Stroke Rate (%)
10% 10
Placebo
Active 5
Follow-up time (years)
Progress, Lancet. 2001;358:

49. Risk factor modifications for blood lipids National Cholesterol Education Program (NCEP) Guidelines
Condition
Hyperlipidemia or
atherosclerotic disease
(LDL >100 mg/dL)
Recommendation
Diet: decrease fat and cholesterol
Exercise
Add pharmacologic therapy: statin agents
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 1993;269:

50. Risk factor modifications for DM ADA Recommendations to Reduce Microvascular Complications
Average pre-prandial glucose <120 mg/dL
Average bedtime glucose 100 to 140 mg/dL
HbA1c <7%
1. Lukovitis TG, Mazzone T, Gorelick PB. Neuroepidemiology 1999;18:1-14.
2. Diabetes Care 1998;21 (Suppl 1):1-200

51. Lifestyle Risk Factor Modifications
Lifestyle Factor
Cigarette Smoking
Alcohol use
Physical activity
Diet
Recommendation
Counseling
Nicotine replacement therapy
Bupropion
Up to 2 drinks/day for men, 1 drink/day for women, or lighter individuals
Brisk activity (30 to 60 min/day)
5 servings/day fruit and vegetables
Limit saturated fat (<30% total energy)
Gorelick PB, Sacco RL, Smith DB, eet al. JAMA 1999;281:

52. Prevention of Blood Clot Formation
Slide M 1: Pathophysiology of Ischaemic Events
This slide is a schematic picture of a vascular occlusion by platelet aggregates as a result of a lesion or atherosclerosis of the endothelium.
Drugs preventing platelet over-reactivity are helpful in preventing this kind of arterial occlusion in the brain or in the heart.
The vascular endothelium has a surface area of approximately 500 m2.
Müller, 1997

53. Medications that prevent stroke “Blood thinners”
Anticoagulants
Coumadin (warfarin)
Exanta
Heparins
Antiplatelet Agents
Aspirin
Aspirin/extended release dipyridamole (Aggrenox)
Clopidogril (Plavix)
Ticlopidine (Ticlid)

54. Aspirin for prevention of stroke
Aspirin benefit independent of dose and gender
FDA, AHA & ACCP all recommend
an aspirin dose between 50 and 325 mg/day
Talking Points
The Food and Drug Administration (FDA) and the American College of Chest Physicians (ACCP) have issued treatment guidelines for the use of aspirin for secondary stroke prevention.
Both of these agencies recommend low-dose aspirin, in the range of 50 to 325 mg/day, for stroke prevention.
These recommendations are based on the preponderance of evidence that no dose of aspirin is superior to any other, but that gastrointestinal side effects may increase with increasing doses.
Albers GW at al Neurology 1999;53(suppl. 4):S25-S38
FDA. Federal Register. 1998;63:56802.
Albers GW, et al. Chest 2001, 119: 300S-320S.

55. Choice of medication for stroke prevention
What is the cause of the stroke?
Atherosclerosis
Unknown
Heart
Talking Points
Antiplatelet agents are recommended for noncardioembolic strokes, which constitute the majority of ischemic strokes, as well as for long-term prevention after carotid endarterectomy (21, 22).
Anticoagulation, usually with warfarin, is the recommended therapy after cardioembolic stroke (21).
Background
Anticoagulants are indicated after most types of cardioembolic stroke and for prevention of first stroke in patients with atrial fibrillation (9). Antiplatelet agents are recommended for recurrent stroke prevention in all other situations, including after carotid endarterectomy (21, 22).
Antiplatelet therapy
Warfarin (Coumadin)
Albers GW, et al. Chest 1998;114:683S-698S
Barnett HJ et al. N Engl J Med. 1998;339:

56. Prevention of recurrent stroke Stroke caused by atrial fibrillation
Relative Risk Reduction
80%
66%
Benefit of aspirin
60%
Benefit of warfarin
40%
Talking Points
Patients with atrial fibrillation and ischemic stroke are at higher risk for recurrent stroke. A controlled double blind prospective trial, the European Atrial Fibrillation Trial, including 728 patients, compared the efficacy of warfarin versus placebo for primary prevention of stroke. The relative risk reduction for recurrent stroke in the population that received anticoagulation versus placebo was 66%. The remaining patients were randomized to 300 mg aspirin versus placebo. Here the relative risk reduction for recurrent stroke was 15%, which was statistically not significant (52).
20%
15% 0%
EAFT Study Group Lancet 1993, 342:

57. How to prevent a stroke Control treatable risk factors
Take an anti-platelet agent or an anti-coagulant
Surgical therapy for carotid stenosis
Talking Points
Stroke is the third leading cause of death in the United States, ranking behind cancer and heart disease, and surpassed only by heart disease worldwide (1,2). It accounts for about 10% of all deaths in most developed countries, including the United States.(3) About 30% of stroke victims die within 1 year; this percentage is higher among those over 65 years old (1). The average hospital stay is 7.3 days for stroke victims in the United States (4).
Among stroke survivors in the Framingham Study (5)
- 31 % required help in caring for themselves
- 20 % required help in walking
- 71 % had impairments that affected their ability to work in their previous capacity
Background
In 1948, the Framingham Heart Disease Epidemiology Study enrolled 5,209 residents of the Framingham, Massachusetts community between the ages of 28 and 62, and followed up by examining them every 2 years since that time (6). Framingham study data have been used to help establish stroke incidence, recurrence, and mortality rates, risk factors, and stroke-related morbidities. The severity of the stroke and the brain territory it affects determine the type and severity of residual disabilities, which may include speech difficulties, loss of sensory function, bilateral loss of motor control, or hemiparesis (5).

58. Changing the perception of stroke
MYTH
Stroke is unpreventable
Cannot be treated
Strikes only the elderly
Recovery ends 6 months after a stroke
REALITY
Stroke is largely preventable
Requires urgent treatment
Can happen to anyone
Stroke recovery can continue throughout life

59. Stroke Websites American Stroke Association:
National Stroke Association:
Stanford Stroke Center