1. Transient Ischemic Attack (TIA): The Calm Before the Storm
Raymond Reichwein, M.D.
Associate Professor of Neurology
Penn State University College of Medicine
Milton S. Hershey Medical Center
January 8, 2009

2. Disclosures
Boehringer Ingelheim
Genentech
AGA Medical Corp

3. OBJECTIVES Discuss the importance of TIA and future stroke risk.
Discuss optimal TIA evaluation and management.
Briefly discuss future stroke prevention, from both an antiplatelet/anticoagulant therapy and risk factor management standpoint.

4. Stroke in the US 730,000 new or recurrent strokes each year1
167,366 deaths in 1999 (1 of every 14.3 deaths)2
4,600,000 stroke survivors alive today2
Origin of strokes3
80% ischemic
20% hemorrhagic
Stroke is highly prevalent and is associated with significant morbidity and mortality.
Annually, about 730,000 Americans develop a new or recurrent stroke, according to Broderick and colleagues.[1]
Stroke is the third largest cause of death in the US, accounting for approximately 1 of 14 deaths.[2]
Stroke resulted in nearly 170,000 deaths in 1999.[2] More than 4 million Americans have a history of stroke.[2]
Approximately 80% of all strokes are ischemic, due to arterial occlusion or stenosis, and the remaining 20% are hemorrhagic, due to leakage or rupture of an artery. Emboli may be of arterial or cardiac origin. Common cardiac sources are atrial fibrillation, sinoatrial disorder, recent acute MI, bacterial endocarditis and valvular disorders.[3]
Broderick J, Brott T, Kothari R, et al. The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks. Stroke. 1998;29:
American Heart Association Heart and Stroke Statistical Update
Pulsinelli WA. Cerebrovascular diseases. Cecil Textbook of Medicine
1. Broderick J et al. Stroke. 1998;29: American Heart Association Heart and Stroke Statistical Update
3. Pulsinelli WA. Cerebrovascular diseases. Cecil Textbook of Medicine
4/19/2017

5. TIA
Underrecognized
Underreported
Undertreated

6. TIA Knowledge Among 10,112 participants
8.2% correctly related the definition of TIA
8.6% could identify a typical symptom
Men, non-whites, and those with lower income and fewer years of education were less likely to be knowledgeable about TIA.
Johnston, et al, Neurology 2003

7. TIA Definition
Resolution of acute neurological/stroke deficits within 24 hours.
No imagable acute ischemic stroke changes.

8. TIAs
The majority of TIAs resolve within 60 minutes, and most resolve within 30 minutes.
Less than 15% chance of complete resolution of symptoms if last >1 hour (Levy).
NINDS IV t-PA trial data revealed only 2% chance of complete symptom 24 hours, for neurological symptoms/deficits that didn’t completely resolve within 1 hour or rapidly improve within 3 hours.

11. TIA Epidemiology
>200,000 events per year (compared to >730,000 strokes per year).
Approximately 10-20% of patients will experience a stroke after a TIA within the first 90 days, and in approx. 50% of these patients, the stroke occurs in the first hours.
Factors associated with increased stroke risk: advanced age, diabetes mellitus, symptoms more than 10 minutes, weakness, and impaired speech. Large artery atherothrombotic disease more likely to present with a TIA before a stroke, versus other etiologies.

12. TIA Epidemiology
Several recent studies reveal a >10% stroke risk in the 90 days after a TIA.
The risk of stroke within the first 48 hours after TIA is approximately 5% (greater than MI risk after presenting with acute chest pain syndrome).
Blacks and men had higher stroke risk.

13. Event Risk Within 3 Months After TIA
12.7%
age > 60 years
diabetes mellitus
duration of episode greater than 10 min
weakness and speech impairment with the episode
Independent risk factors for stroke within 90 days
after TIA:
10.5%
Event Rate
5% in
48 h
CORE SLIDE
2.6%
2.6%
Talking Points
This study investigated the short-term risk of stroke and other adverse events in 1,707 patients after emergency department diagnosis of transient ischemic attack (TIA).1
During the 90 days after an index TIA, a total of 428 patients (25.1%) experienced a stroke or other adverse events.1
This included strokes (10.5%), recurrent TIAs (12.7%), cardiovascular events (2.6%) and deaths (2.6%).1
Background
The study results indicate that the short-term risk of stroke, other adverse events and deaths among patients who present to an emergency department with a TIA is substantial.1 Half of the strokes occurred within 2 days of the TIA. Short-term risks of cardiovascular events, death and recurrent TIA were also high.
This study identified 5 independent risk factors for stroke within 90 days after TIA: age older than 60 years, diabetes mellitus, duration of episode greater than 10 minutes, and weakness and speech impairment with the episode.
Johnston SC, Gress DR, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA. 2000; 284:
Recurrent
TIA
Cardiac
Event
Stroke
Death
Johnston SC, et al. JAMA. 2000;284:2901­2906. 13

14. TIA before Stroke by Subtype
Large-artery atherothrombotic disease: 25-50%.
Cardioembolic sources: 10-30%.
Small vessel/lacunar disease: 10-15%.

15. Symptomatic Internal Carotid Artery Disease
NASCET Medical Arm Data (600 patients)
Two-day risk was 5.5%.
90-day ipsilateral stroke risk was 20%.
Degree of stenosis (>70% stenosis) didn’t confer increased stroke risk.
Infarct on brain imaging and presence of intracranial major-artery disease doubled the early stroke risk.
Benefit from CEA declines rapidly over several weeks, particularly in women (Oxford data).

16. Cumulative Risk of Stroke
Post-TIA (%)
Post-Stroke (%)
30 days
1 year
5 years
4 – 8
12 – 13
24 – 29
3 – 10
5 – 14
25 – 40
Sacco. Neurology. 1997;49(suppl 4):S39.
Feinberg et al. Stroke. 1994;25:1320.

17. TIA and ischemic stroke pathophysiology are the same
TIA and ischemic stroke pathophysiology are the same. The only difference is transient versus persistent neurological deficits. Certainly, a TIA state is a much better clinical state to intervene and prevent a future disabling stroke.

18. Risk Factors for First Ischemic Stroke
Modifiable
(value established)
Nonmodifiable
Hypertension
Atrial fibrillation
Cigarette smoking
Hypercholesterolemia
Heavy alcohol use
Asymptomatic carotid stenosis
Transient ischemic attack
Age
Gender
Race/Ethnic
Heredity
The initial occurrence of stroke is associated with several risk factors. Although there are some that the patient cannot change, such as age, gender, race/ethnicity, and genetics, other factors can be modified to reduce risk. These modifiable factors include hypertension (the highest attributable risk), atrial fibrillation, cigarette and heavy alcohol use, elevated cholesterol levels, asymptomatic carotid stenosis, and TIA.
Sacco RL. Identifying patient populations at high risk for stroke. Neurology. 1998;51(suppl 3):S27-S30.
Adapted from Sacco RL. Neurology 1998;51(suppl 3):S27-S30.

19. Stroke in Young Individuals
Clotting disorders
Migraine
Birth control pills
Illicit drug use
Arterial dissection
Patent foramen ovale
Autoimmune disorders (lupus)

20. TIA Evaluation Prompt evaluation and intervention is the key.
Most TIA patients should be admitted for diagnostic evaluation and management (Observation unit or equivalent); often significant delay if done as outpatient.
TIA and ischemic stroke diagnostic evaluations should be the same.

21. Who should be admitted??
Anyone with no prior/recent TIA/stroke diagnostic workup; new suspected etiology despite prior workup.
Suspected large vessel (anterior or posterior circulation) events.
Most suspected lacunar/small vessel events, particularly if no prior workup (? calm before the storm).
Recurrent/crescendo TIAs.

22. ABCD2 Score Age 60 or older 1 point Blood pressure >140/90 1 point
Clinical
- Unilateral weakness 2 points
- Speech impairment point
Duration
- 60 minutes or more 2 points
- Less than 60 minutes 1 point
Diabetes 1 point

24. ABCD2 Score
Score 4 or greater – admit to hospital (moderate-high stroke risk).
Score predicted risk similarly among all ethnic backgrounds.
Best predictor of 2, 7, and 90 day stroke risk among validated scales.

25. Inpatient TIA Management
Neurochecks; follow blood pressures.
? Cardiac telemetry (paroxysmal a. fib).
? Intravenous Heparin for suspected high risk TIA sources, pending completion of diagnostic evaluation.
Diagnostic evaluation should be completed within 24 hours; make decision regarding admission or discharge at that point.
Potential IV t-PA use for recurrent event (acute ischemic stroke) while hospitalized.

26. Presumptive TIA/stroke etiology determines optimal treatment, as well as risk for recurrent events.

27. Stroke Subtypes and Incidence
Hemorrhagic stroke 15%
Other 5%
Cryptogenic 30%
Atherosclerotic
cerebrovascular
disease
20%
Small vessel
disease
“lacunes”
25%
Cardiogenic embolism 20%
80–85% of all acute strokes are caused by cerebral infarction, usually resulting from partial or complete blockage of a cerebral artery. The remainder are caused by intracerebral or subarachnoid haemorrhage.
Ischaemic stroke 85%
Albers et al. Chest 2004; 126 (3 Suppl): 438S–512S.

28. TIA BRAIN IMAGING
Prior CT(brain) studies revealed a 15-20% incidence of cerebral infarction in a vascular territory related to the patient’s symptoms/deficits.
Newer MRI(brain) studies, using diffusion-weighted imaging (DWI), reveal approx % acute ischemic stroke findings, and about half of these persisted on follow-up imaging. Best correlated with prolonged TIA symptoms.

29. MRI Diffusion Imaging Distinguish new versus old ischemic areas.
Distinguish new ischemic areas even with clinical TIA.
Differentiate stroke etiology (small vessel vs. large vessel; embolic sources).

30. Acute Embolic Strokes

31. Acute Ischemic Stroke