Harrison’s Manual of Medicine
A stroke is the sudden onset of a neurologic deficit from a vascular mechanism. 20% are primary hemorrhages, including subarachnoid and hypertensive lobar and deep cerebral hemorrhages. 80% are related to ischemia; ischemic brain tissue rapidly loses function but can remain viable with potential for recovery for hours. An ischemic deficit that rapidly resolves is termed a transient ischemic attack (TIA); 24 h is a useful boundary between TIA and stroke, although most TIAs last between 5 and 15 min. It is important to differentiate the clinical terms TIA and stroke from the underlying tissue processes of ischemia and infarction, as temporal correlation is imperfect. Stroke is the leading cause of adult neurologic disability, and much can be done to limit morbidity and mortality through prevention and acute intervention.
PATHOGENESIS Ischemic stroke is most often due to embolic occlusion of large cerebral vessels. Source of emboli may be the heart, aortic arch, or a more proximate arterial lesion. Primary involvement of intracerebral vessels with atherosclerosis is much less common than in coronary vessels. Small, deep ischemic lesions are most often related to intrinsic small-vessel disease (lacunar strokes), with hypertension and diabetes as main risk factors. Low-flow strokes are seen with severe proximal stenosis and inadequate collaterals challenged by significant hypotensive episodes. Hemorrhage most frequently results from rupture of aneurysms or small vessels within brain tissue.
CLINICAL PRESENTATION Stroke Abrupt and dramatic onset of focal neurologic symptoms; temporal pattern can suggest the underlying vascular mechanism. Vascular mechanisms causing TIA are the same as those causing ischemic stroke (Table 34-1). Symptoms reflect the vascular territory involved and provide clues to localization and identification of the vessel and pathology (Table 34-2). Transient monocular blindness (amaurosis fugax) is a particular form of TIA due to retinal ischemia; pts describe a shade descending over the visual field. Rapid resolution of TIA symptoms suggests resolution of the underlying ischemia, although small areas of tissue infarction are often found when symptoms persist more than 1–2 h. Variability in stroke recovery is influenced by collateral vessels, blood pressure, and specific site and mechanism of vessel occlusion. Reversible ischemia and salvage of tissue at risk have become real concepts with application of thrombolytic and neuroprotective agents.
Table 34-1 Causes of Stroke
Table 34-2 Anatomic Localization of Cerebral Lesions in Stroke
Lacunar Syndromes Most common are (1) Pure motor hemiparesis of face, arm, and leg (internal capsule or pons; (2) pure sensory stroke (ventrolateral thalamus); (3) ataxic hemiparesis (pons); (4) dysarthria–clumsy hand (pons or genu of internal capsule); and (5) pure motor hemiparesis with motor (Broca’s) aphasia (internal capsule and adjacent corona radiata).
Intracranial Hemorrhage Includes hypertensive and lobar hemorrhages (50%), ruptured saccular aneurysm (Chap. 35), and ruptured arteriovenous malformation (AVM). Vomiting occurs in most cases, and headache in about one- half. Signs and symptoms not usually confined to a single vascular territory. Hypertensive hemorrhage typically occurs in (1) the putamen, adjacent internal capsule, and central white matter; (2) thalamus; (3) pons; and (4) cerebellum. A neurologic deficit that evolves relentlessly over 5–30 min strongly suggests intracerebral bleeding. Ocular signs are important in localization: (1) putaminal—eyes deviated to side opposite paralysis (toward lesion); (2) thalamic— eyes deviated downward, sometimes with unreactive pupils; (3) pontine—reflex lateral eye movements impaired and small (1–2 mm), reactive pupils; (4) cerebellar—eyes deviated to side opposite lesion (early on, in absence of paralysis).
RISK FACTORS Atherosclerosis is a systemic disease affecting arteries throughout the body. Multiple factors including hypertension, diabetes, hyperlipidemia, and familial tendencies influence stroke and TIA risk. Cardioembolic risk factors include atrial fibrillation, MI, valvular heart disease, and cardiomyopathy. Prolonged hypertension and diabetes are also specific risk factors for lacunar stroke with small-vessel lipohyalinotic disease. Smoking is a potent risk factor for all vascular mechanisms of stroke. Identification of modifiable risk factors and prophylactic interventions to lower risk is probably the best treatment for stroke overall.
COMPLICATIONS Neurologic deficits can worsen after presentation because of several possible complications. Embolic stroke carries the risk of early recurrence. This can occur from cardiac sources and arterial stenoses and from acute arterial occlusions as distal stump emboli. Large, deep ischemic infarcts can develop hemorrhage into the affected tissue. Large cerebral or cerebellar infarcts can develop edema sufficient to lead to neurologic deterioration. While most intracerebral hemorrhages bleed only briefly, some may continue to expand with resultant mass effect. Seizures are uncommon in acute stroke but develop as a delayed complication in 5–10%.
LABORATORY EVALUATION CT Initial CT study without contrast is indicated to exclude hemorrhage or other mass lesions. Early signs of ischemic stroke can be recognized within the first few hours of large strokes, but small cortical infarcts can be difficult to assess by CT.
MRI Compared with CT, increased sensitivity for small infarcts of cortex and brainstem.
MR Angiography Special sequences that image blood flow can evaluate patency of intracranial vessels and extracranial carotid and vertebral vessels.
Noninvasive Carotid Tests Most commonly used are “duplex” studies, combining ultrasound imaging of the vessel with Doppler evaluation of blood flow characteristics.
Cerebral Angiography “Gold standard” for evaluation of vascular disease. Detects ulcerative lesions, severe stenosis, and mural thrombosis; can also visualize atherosclerotic disease or dissection in carotid siphon or intracranial vessels, demonstrate collateral circulation around the circle of Willis, and show embolic occlusion of cerebral branch vessels. Best method to demonstrate atherothrombotic disease of the basilar artery. It causes substantial morbidity (1– 5%) and may precipitate a threatened stroke, and thus is used only when noninvasive studies fail to detect an arterial lesion that, if identified, would influence management.
Cardiac Evaluation Indicated in suspected cardiogenic embolization; ECG, cardiac ultrasound with attention to right-to-left shunts, and 24-h Holter monitoring.
Blood Studies Routine initial studies include CBC/platelets, electrolytes, ESR, PT, PTT, and serologic tests for syphilis. In cases where a hypercoagulable state is suspected, further studies of coagulation are indicated.
TREATMENT Table 34-3
Table 34-3 Clinical Management of Acute Stroke
Acute Ischemic Stroke Careful evaluation and treatment are essential to minimize infarction and reduce recurrent stroke risk. Blood pressure should never be lowered precipitously (exacerbates the underlying ischemia), and only in the most extreme situations (systolic bp >220 mmHg) should gradual decreases be undertaken. Intravascular volume should be maintained with isotonic fluids as volume restriction is rarely helpful. Osmotic therapy with mannitol may be necessary to control edema in large infarcts, but isotonic volume must be replaced to avoid hypovolemia. In cerebellar infarction (or hemorrhage), rapid deterioration can occur from brainstem compression and hydrocephalus. These pts require neurosurgical evaluation and careful neurologic monitoring.
Thrombolysis Ischemic deficits of❤ h duration, with no hemorrhage by CT criteria, may benefit from thrombolytic therapy with IV recombinant tissue plasminogen activator (Table 34-4). This therapy has been shown to improve neurologic outcome, but currently only a small percentage of stroke pts are seen early enough to receive treatment with this agent.
Table 34-4 Administration of Intravenous Recombinant Tissue Plasminogen Activator (rtPA) for Acute Ischemic Strokea
Anticoagulation Indications for heparin are empirically based; objective clinical data are lacking. IV heparin is generally used when atherothrombotic vascular stenosis or occlusion is suspected, particularly in ischemic stroke with progression of symptoms (“stuttering stroke”), unstable TIA (crescendo or recent onset), or posterior circulation involvement. Heparin is usually administered as an infusion (without bolus) for 2–5 days with the PTT maintained at twice normal. The role of low-molecular-weight heparin remains to be determined. Warfarin (INR=2–3) may be used long term for atherothrombotic disease when carotid surgery (see below) is not an option or for cardiac sources of embolism (anterior MI, atrial fibrillation, or valvular disease).
Antiplatelet agents Aspirin (325 mg/d) has a small but definite benefit in acute stroke and can reduce risk of further TIA and stroke in symptomatic patients thus providing an alternative to anticoagulation. Other useful antiplatelet agents include clopidogrel (blocks the platelet ADP receptor) and dipyridamole (inhibits platelet uptake of adenosine). In general, antiplatelet agents reduce new stroke events by 25–30%.
Prevention of Embolic Stroke In pts with atrial fibrillation, the choice between warfarin or aspirin prophylaxis is determined by age and risk factors (Table 34-5). Anticoagulation reduces the risk of embolism in acute MI; most clinicians recommend a 3-month course of therapy when there is anterior Q- wave infarction or other complications; warfarin is recommended long term if atrial fibrillation persists. For prosthetic heart valve pts, a combination of aspirin and warfarin (INR 3–4) is recommended. If an embolic source cannot be eliminated, anticoagulation is usually continued indefinitely. For patients who “fail” one form of therapy, many neurologists recommend combining antiplatelet agents with anticoagulation. Secondary prophylaxis for ischemic stroke of unknown origin is controversial; some physicians prescribe anticoagulation for 3–6 months followed by antiplatelet treatment.
Table 34-5 Consensus Recommendation for Antithrombotic Prophylaxis in Atrial Fibrillation
Surgical Therapy Carotid endarterectomy benefits many pts with symptomatic severe (>70%) carotid stenosis; the relative risk reduction is approximately 65%. However, if the perioperative stroke rate is >6% for any surgeon, the benefit is lost. Surgical results in pts with asymptomatic carotid stenosis are less robust, and medical therapy for reduction of atherosclerosis risk factors (including hypertension, hypercholesterolemia, diabetes, and smoking) and aspirin are generally recommended in this group.
Noncontrast head CT will confirm diagnosis. It is important to identify and correct any coagulopathy rapidly. Neurosurgical consultation should be sought for possible urgent evacuation of hematoma, especially in the case of cerebellar hemorrhage. Prophylactic anticonvulsant therapy is usually undertaken in supratentorial hemorrhage, especially when extending to the cortical surface. Treatment for edema and mass effect with mannitol may be necessary, and while glucocorticoids may be helpful in some cases, routine use leads to many complications.
For a more detailed discussion, see, Smith WS, Hauser SL, Easton JD, Martin JB: Cerebrovascular Diseases, Chap. 361, p. 2369 in HPIM-15.