James M. Gebel Jr., MD, MS, FAHA
Gabor Toth, MD
DESCRIPTION 
Transient ischemic attack (TIA) is a transient episode of 10 minutes or less of clinical symptoms indicating neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Recent TIA is considered a neurological emergency.
EPIDEMIOLOGY
The annual incidence of TIA in the US is estimated to vary from 1 in 200,000 to 1 in 500,000. However, the actual incidence may be higher because many of these attacks are not reported by the patients since their symptoms by definition resolve.
- Age
- It is more common in the elderly, as is stroke.
- Sex
- It is more common in females, as is stroke.
- Race
- It is probably more common in African Americans, Asians, and Hispanics, given the increased incidence of stroke in these populations.
RISK FACTORS
Risk factors include age, hypertension, diabetes mellitus, elevated C-reactive protein, hyperlipidemia, tobacco, sedentary life, obesity, family history of stroke, and prior history of stroke or TIA, and known coronary artery or peripheral vascular disease.
Pregnancy Considerations
There is an increased incidence of TIA and stroke in pregnancy.
Genetics
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, prothrombin variant, and Leiden factor V mutations are all genetic conditions that can present with TIA.
ETIOLOGY
- Cardiac emboli: Conditions that predispose to the formation of cardiac emboli include persistent or paroxysmal atrial fibrillation/flutter, mitral valve stenosis, sick sinus syndrome, prosthetic heart valve, infective endocarditis, marantic endocarditis,congestive heart failure with ejection fraction (EF) of 35% or less, dilated cardiomyopathy, myxomas, left atrial enlargement, and spontaneous echo contrast.
- Large artery disease: Stenosis of the extracranial internal carotid and vertebral arteries, and large intracranial vessels of the Circle of Willis and posterior circulation (intracranial vertebral and basilar arteries), usually due to atherosclerosis). Other diseases include dissection, vasculitis, moyamoya, and fibromuscular dysplasia.
- Small vessel disease: These TIAs can present as multiple, increasing frequency, stereotypical events termed crescendo TIAs or stuttering lacune and are often associated with completed lacunar cerebral infract radiologically even though the clinical symptoms are temporary.
- Hypercoagulable states, both inherited such as prothrombin variant mutation, and acquired such as antiphospholipid antibody syndrome, lupus anticoagulant, sickle cell anemia, and paraneoplastic (especially mucin-secreting carcinomas with elevated CA-125 levels).
COMMONLY ASSOCIATED CONDITIONS
Stroke, coronary artery disease, and peripheral arterial disease.
[Outline]
By the new definition, a TIA should resolve within 10 minutes; otherwise it is more likely to be a radiological stroke (cerebral infarct) than a TIA. As in ischemic stroke, the symptoms are typically sudden and abrupt. The clinical features depend on the brain area affected. Common symptoms include:
DIAGNOSTIC TESTS AND INTERPRETATION
Lab
- All patients with TIA should have blood drawn for fasting lipid profile, chemistry panel, BUN, creatinine, CBC and platelets, PT with INR, and PTT.
- Hypercoagulable profile including factor V mutation, factor II mutation, lupus anticoagulant, antiphospholipid antibodies, and homocysteine should be requested in young patients. Protein S, C, and antithrombin II deficiencies rarely cause TIA or stroke and much more often cause venous, not arterial, thromboembolic events.
- Serial blood cultures should be done when infective endocarditis is suspected. Anticoagulation should generally be avoided in patients with suspected infective endocarditis.
Imaging
- CT scan must be performed in all patients with suspected TIA because it is very sensitive in detecting intracerebral hemorrhage or subdural hematoma, which can mimic TIA.
- CT angiography of the neck and brain can also be simultaneously or subsequently performed to detect stenosis of the large neck or brain vessels. Both can often be performed quickly and relatively inexpensively.
- MRI of brain is much more sensitive than CT scan in detecting small or early infarction. The infarction is sometimes shown despite the resolution of the symptoms within 10 minutes.
- MR angiography of the neck and brain is another noninvasive testing option for assessing the major extracranial and intracranial arteries for stenosis, though it may overestimate the degree of stenosis.
- Transthoracic echocardiogram (TTE) is indicated in most patients with TIA. If the TTE is negative and a cardiac source of embolism is still suspected, the transesophageal echocardiogram (TEE) should be performed. TEE is also indicated in almost all young patients, in whom half of all strokes and TIAs are of cardioembolic origin.
- TEE is more accurate than TTE in showing atrial and ventricular thrombi, vegetations, and left atrial enlargement, detecting shunts, and evaluating the proximal aorta.
- Angiography is the gold standard for an accurate assessment of both the extra- and intracranial vasculature. However, it is an invasive expensive procedure with greater risk than CTA, MRA, or ultrasound, and should be reserved for patients in whom noninvasive testing has not definitely shown the source of TIA or gives conflicting estimation of degree of stenosis of the large neck or brain vessels.
- Ultrasound is a safe, portable, and less expensive. It includes transcranial Doppler to look for intracranial disease and carotid duplex to assess for extracranial carotid disease. It should be noted that carotid duplex is fairly insensitive for detecting extracranial vertebral artery stenosis and when possible should not be exclusively relied upon for this purpose.
Diagnostic Procedures/Other
ECG and cardiac monitoring, either inpatient telemetry or extended (48 hours to 3 weeks) Holter monitoring in select patients to evaluate for arrhythmias.
DIFFERENTIAL DIAGNOSIS
- Ischemic stroke
- Migraine aura
- Multiple sclerosis related transient neurological events (last seconds, may occur hundreds of times a day)
- Seizures (Todd's paralysis) (may last up to 1 day simulating stroke)
- Labyrinthine disorders (paroxysmal vertigo)
- Syncope
- Metabolic disorders
- Intracerebral hemorrhage
- Subdural hematoma
- Somatization disorders
[Outline]
MEDICATION
- Antiplatelet agents: Indicated for stroke prevention in small vessel disease, intracranial large artery disease, mild (<50%) extracranial carotid artery disease, extracranial vertebral artery disease, aortic arch disease without mobile plaque, irregular nonstenotic valve surfaces, and in patients who are not warfarin or dabigatran candidates whom would otherwise be anticoagulated.
- Anticoagulants
- Warfarin (Coumadin): Indicated in hypercoagulable states, cardiac sources like atrial fibrillation, intracardiac thrombi
- Dabigatran (Pradaxa): Indicated in patients with persistent or paroxysmal nonvalvular atrial fibrillation and is an alternative to warfarin therapy
- Contraindications
- Aspirin/Aggrenox: Mainly known allergic reaction to salicylic acid, active systemic bleeding, or active gastric ulcer
- Clopidogrel: Mainly active systemic bleeding, very rarely TTP
- Warfarin: Mainly active bleeding, bleeding tendency, noncompliance, drug interactions and dietary (vitamin K containing foods) interactions. Rarely warfarin skin necrosis
- Dabigatran: Known history of active/recent GI bleeding; other active bleeding, dyspepsia
- Precautions
- Clopidogrel: Monitor for any TTP symptoms at the beginning of treatment
- Warfarin: Watch for compliance, bleeding events, and falls
- Dabigatran: Watch for bleeding events (especially GI bleeding)
ADDITIONAL TREATMENT
General Measures
Management of coexisting medical illnesses and secondary stroke prevention.
COMPLEMENTARY AND ALTERNATIVE THERAPIES
- Symptomatic treatment
- Judicious control of blood pressure with avoidance of excessive reduction in the acute setting and adequate control in the long run
- Adjunctive treatment
- Management of underlying hyperlipidemia, diabetes and other medical problems
- Smoking cessation, if applicable
SURGERY/OTHER PROCEDURES
- Carotid endarterectomy (CEA) or carotid artery stenting (CAS) is indicated for most patients with significant (>50%) symptomatic extracranial carotid artery stenosis and for almost all patients with >70% symptomatic extracranial carotid stenosis. Patients with known concomitant coronary artery disease are generally better CAS candidates, and patients over the age of 72 are generally better CEA candidates. However, surgical risk is also affected by concomitant medical problems, which have to be taken into consideration in all age groups. CAS is associated with a higher rate of periprocedural stroke than CEA but a lower incidence of periprocedural MI and minimal risk of cranial nerve palsies which complicate up to 5–6% of CEA cases. Recent preliminary clinical trial data suggests that angioplasty and stenting of symptomatic large intracranial stenosis may be inferior to maximal medical management with antiplatelet medication + aggressive modifiable risk factor management. Therefore, angioplasty and stenting of symptomatic large intracranial stenosis at this time is reserved only for patients in clinical trials, or as a last resort for recurrent strokes on maximal medical therapy.
IN-PATIENT CONSIDERATIONS
Admission Criteria
In general any patient presenting with TIA, within 1 week from the onset of symptoms should be admitted to the hospital for the evaluation of etiology, frequent neurological check monitoring to promptly identify and treat stroke, and for appropriate empiric and then secondary stroke prevention measures. There is an approximately 5.1% risk of full blown stroke within 48 hours of TIA in patients presenting to the emergency room with a diagnosis of TIA. The ABCD2 TIA score and its recent modified renditions can help identify high risk (for stroke and other vascular events) TIA patients, but is not widely used in clinical practice at present time. Recent TIA should be considered a medical emergency like acute stroke. Specialized TIA observation units where a rapid initial workup for stroke mechanism is completed represent an innovative and growing care option which combines efficiency and quality care and can be categorized as observation stays rather than full-blown admissions if the work-up is completed and appropriate definitive secondary prevention treatment are initiated prior to discharge.
[Outline]
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Frequent follow-up visits are important to assess patients for recurrent ischemic events, modifiable risk factor assessment, compliance with treatment and recommendations, and adverse reactions from the treatment medications.
- Close monitoring of INR is crucial for the patients maintained on warfarin.
PATIENT EDUCATION
- American Stroke Association, National Center, 7272 Greenville Avenue, Dallas, TX, 75231, 1-888-478-7653. www.strokeassociation.org
PROGNOSIS
- Although by definition TIA patients promptly and fully resolve their neurological deficits and symptoms, TIA is often a precursor for a stroke, and is also associated with elevated risk of MI and vascular death. The risk of stroke, MI or vascular death in untreated patients, after a TIA, is about 10% in the first year and at least 25% over 5 years. The risk of stroke is highest within the first 48 hours to 1 month after the TIA, but remains elevated for at least 5 years.
- Appropriate secondary preventive measures significantly decrease the risk of stroke.
[Outline]
ICD9
435.9 Transcerebral ischemia NOS