23: Cerebrovascular Disease

Stroke recently declined from the third to the fourth leading cause of death in the United States, which is testament to a half century of progress in cerebrovascular disease prevention and acute care. It remains, however, a leading cause of disability, with up to half of all patients who survive a stroke failing to regain independence and needing long-term health care. Stroke primarily affects the elderly, and for each successive decade after the age of 55 years, the stroke rate doubles for both men and women.

The majority of strokes (80% of cases) result from insufficient blood flow to the brain (ischemic stroke), whereas bleeding that destroys and compresses the brain parenchyma accounts for 15% (intracerebral hemorrhage [ICH]). Bleeding that occurs in the subarachnoid space (subarachnoid hemorrhage) accounts for 5% of strokes.

Signs & Symptoms

A stroke presents as an acute neurologic deficit. The neurologic impairment reflects the area of the brain affected. Although the presenting focal neurologic symptoms are variable, 80% of patients present with unilateral weakness; 90% have a speech and/or motor deficit. In addition, deficits in sensation, vision, language, cognition and balance may occur.

Older patients have more severe stroke deficits at presentation than do younger patients. After the onset of symptoms, timely evaluation and diagnosis are paramount. This is because the effect of thrombolysis is time dependent. Thus, neurologic screening tools like the Cincinnati Stroke Scale (Table 23–1) can be useful in early triage.

Special Tests

In patients suspected of stroke, diagnostics occur in 2 phases: (a) acute triage and (b) investigations into etiology after stroke is established as the diagnosis.

In the acute triage phase, several tests should be performed routinely in all patients with suspected stroke. This is to establish a diagnosis, identify systemic conditions that may mimic or cause stroke, and identify conditions that influence therapeutic options. Immediate diagnostic studies in all patients should include noncontrast brain CT, blood glucose, serum electrolytes/renal function tests, electrocardiogram (ECG) markers of cardiac ischemia, complete blood count including platelet count, prothrombin time/international normalized ratio (INR), activated partial thromboplastin, oxygen saturation.

Given the clinical history and examination, additional acute tests may be indicated. These include hepatic function tests, toxicology screen, blood alcohol level, arterial blood gas (if hypoxia is suspected), and chest radiography (if lung disease is suspected). For those patients in which diagnostic uncertainty remains, lumbar puncture may be performed (if subarachnoid hemorrhage is suspected and CT scan is negative for blood) or an electroencephalogram (EEG) may be necessary (if seizures are suspected as the cause of their neurologic symptoms).

The diagnosis of stroke can be firmly established with history, examination and advanced imaging techniques. Intracerebral hemorrhage is visible immediately on CT (Figure 23–1). Diffusion-weighted imaging (DWI) MRI sequences are approximately 90% sensitive in detecting cerebral infarction (Figure 23–2). Therefore, once the diagnosis of stroke is made, the differential diagnosis lies with investigating the etiology of the stroke (Table 23–2).

Whether an ischemic stroke or intracerebral hemorrhage is diagnosed, etiology needs to be established to determine the most effective secondary stroke prevention measures. For ischemic stroke the work-up should aim to establish the stroke subtype: (a) large artery atherosclerosis (ie, carotid or intracranial vessel stenosis), (b) cardioembolism (ie, atrial fibrillation), (c) small vessel occlusion (ie, lacunar stroke), (d) stroke of other determined cause (ie, arterial dissection), or (e) stroke of an undetermined cause (ie, cryptogenic).

For the majority of primary intracerebral hemorrhages, the underlying etiology is hypertension (hypertensive vasculopathy), cerebral amyloid angiopathy, or anticoagulation-related hemorrhage.

Following stroke onset, some patients may deteriorate neurologically over the next few hours or days. Clinical manifestation may take the form of decreased level in consciousness, an exacerbation of the previous neurological deficit, or the appearance of a new deficit. Both neurologic and nonneurologic causes of deterioration are often treatable if recognized promptly.

Common neurologic causes of deterioration are progressive stroke, brain swelling, recurrent ischemic stroke, hemorrhagic transformation, and, less commonly, seizures. Large strokes of the cerebral hemisphere or cerebellum are at the highest risk for complicating brain edema and increased intracranial pressure. Swelling in cerebellar strokes may cause obstructive hydrocephalus requiring acute neurosurgical intervention.

Medical complications are a common and an important problem after acute stroke as they can be barriers to optimal recovery. During hospital admission infection is common. Urinary tract infection or pneumonia may occur in up to one-quarter of patients, and both are associated with increasing age. The appearance of fever after stroke should prompt a search for pneumonia, as it is an important cause of death. The risk of deep venous thrombosis and pulmonary embolism is highest among immobilized and older patients with severe stroke. Pain, falls, and depression are all common during hospitalization and after discharge.

Initial Management & Acute Ancillary Care

The acute care of patients with ischemic stroke should include: (a) stabilization and initial assessment, (b) decision making regarding thrombolysis with the only approved treatment in the United States—intravenous tissue plasminogen activator (t-PA), (c) consideration of endovascular therapies, and (d) effective communication with patients and families.

As in any other emergency, the management of acute stroke starts with assessment of the “ABCs”: Airway, Breathing, Circulation. Most stroke patients do not require intubation; however, those with a depressed level of consciousness are at the highest risk of requiring ventilator support. Acute assessment of the circulatory status includes ECG, blood pressure monitoring, and cardiac enzyme determination.

Most patients with acute ischemic stroke have an elevated blood pressure. This elevation is usually transient and helps maintain perfusion to ischemic brain tissue, therefore rapid reduction should be avoided. No treatment is recommended unless the mean arterial pressure is >130 mm Hg or systolic pressure is >220 mm Hg. Exceptions to this rule involves IV thrombolytic therapy, which requires a blood pressure <185/110 mm Hg.

After initial emergency room management, patients should be admitted to stroke units, as specialized care improves survival and functional outcome, regardless of age.

Specific Therapies

Acute ischemic stroke—

Reperfusion of the ischemic brain is the most effective therapy for acute ischemic stroke. By restoring blood flow to threatened tissues before they progress to infarction, reperfusion therapies salvage viable brain tissue (the ischemic penumbra) and improve clinical outcomes.

The association between thrombolysis treatment and improved outcome is maintained in all age groups, even very elderly people. Thus, age alone should not be a barrier to treatment. Regarding the risk of intracerebral hemorrhage in older individuals, studies have varied. A recent meta-analysis of pooled thrombolysis data concluded that the risk of symptomatic intracerebral hemorrhage did not increase among elderly patients, despite less-favorable outcomes, which were attributed to comorbidities.

The benefit of thrombolytic therapy is strongly time dependent: the more rapid the treatment, the more favorable the outcome. Patients are candidates for IV t-PA if the medicine is administered within 3 hours of symptom onset, and there are no contraindications. A recent European study (ECASS III) showed that benefit could be extended to the 3–4.5-hour window, but this is only available in patients younger than 80 years of age. Patients and families should be given an explanation of the risks and benefits of t-PA.

Endovascular treatment, including intraarterial thrombolysis and mechanical thrombectomy, is a promising alternative treatment that can be used as isolated therapy or in combination with intravenous thrombolysis (“bridging therapy”). In carefully selected patients with large vessel occlusions (ie, middle cerebral artery), such techniques have been shown to be safe and effective. Limited data exist regarding the benefits of endovascular therapies in the oldest old population, >80 years of age.

Intracerebral hemorrhage—

ICH remains the least-treatable form of stroke. Apart from management in a specialized stroke or neurologic intensive care unit, no specific therapies have been shown to improve outcome after ICH. Age is an independent predictor of outcome after ICH, with age >80 years associated with 30-day mortality.

For the majority of elderly patients with intracerebral hemorrhages, the underlying etiology is (a) hypertension (hypertensive vasculopathy), (b) anticoagulation-related hemorrhage, or (c) cerebral amyloid angiopathy. Longstanding hypertension causes weakening of the small, deep-penetrating arteries that can rupture causing hemorrhage into the deep structures of the brain. Anticoagulation with warfarin increases the risk of ICH and worsens the severity of hemorrhage, doubling its mortality. Cerebral amyloid angiopathy (CAA), defined as amyloid deposition in the cerebral vessel walls, may cause large and symptomatic hemorrhage or small and clinically silent hemorrhage (Figure 23–3). Severe CAA is present in 12% of patients >85 years of age, and patients with symptomatic hemorrhages should be taken off of all antithrombotics.

Secondary Prevention Strategies

The successful prevention of a recurrent ischemic stroke hinges upon a comprehensive approach. This involves the identification and treatment of stroke risk factors, such as hypertension, diabetes, and hyperlipidemia. Of equal if not greater importance is the modification of life styles that increase the risk of a stroke, such as diet, exercise, and smoking cessation.

Antihypertensive therapy forms the cornerstone of secondary stroke prevention. A recent meta-analysis of several large trials of blood pressure reduction for secondary stroke prevention found a 24% relative risk reduction. It is generally recommended that blood pressure reduction begin after 24 hours of a stroke if the patient is neurologically and hemodynamically stable.

Although few trials have included the very old, there is convincing evidence that lowering low-density lipoprotein with statins reduces vascular events, including ischemic stroke.

Antiplatelet agents are the first choice to prevent recurrent strokes in patients with noncardioembolic strokes. Available alternatives are aspirin, aspirin and dipyridamole, and clopidogrel. The combination of aspirin and clopidogrel should be avoided, as it is associated with major bleeding events.

Atrial fibrillation—

Atrial fibrillation dramatically increases in prevalence with age, and is associated with a nearly 5-fold increase in stroke risk. Cardioembolic stroke related to atrial fibrillation is the most frequently encountered stroke subtype in very old patients. Warfarin reduces the stroke risk by 68%. Despite this, many physicians assume that a combination of warfarin therapy and head trauma from falls leads to a substantially high risk of subdural hemorrhage and they decide not to anticoagulate their elderly patients whom they believe are prone to falling. Evidence contrary to this practice shows that the risk of this complication is outweighed by the benefit of stroke protection provided by warfarin.

Urgent anticoagulation (heparin infusion) with the goal of preventing early recurrent stroke is not recommended because of the risk of hemorrhage. Typically, patients are placed on aspirin during the acute phase as a “bridge” to eventual oral anticoagulation with warfarin. Anticoagulation should be initiated within 2 weeks.

New oral anticoagulants dabigatran, rivaroxaban, and apixaban have become available. They are at least as effective as warfarin in the prevention of stroke in patients with atrial fibrillation. These agents share common properties such as high fixed oral dosing, no interaction with food, no need for anticoagulation monitoring, and rapid onset and offset of action. However, the safety of these newer agents in elderly patients with low body weight and impaired renal function has yet to be rigorously determined.

Carotid stenosis—

Carotid artery stenosis is another major risk factor for ischemic stroke in the elderly. Evidence is clear that carotid endarterectomy (CEA) is more effective than medical therapy for preventing recurrent stroke in patients with symptomatic carotid stenosis (those who have had a recent stroke or transient ischemic attack), particularly in those with severe (70% to 99%) stenosis. CEA is also efficacious in patients with moderate (50% to 69%) symptomatic carotid stenosis, although the efficacy is less dramatic. Early surgery in symptomatic patients (within 2 weeks if possible) is recommended as the risk of a recurrent stroke is front-loaded. Recent studies show that CEA is safer than carotid artery stenting for older patients.

Transient ischemic attack—

In the era of advanced neuroimaging, transient ischemic attack (TIA) has been redefined from a time based diagnosis (<24 hours) to a brain tissue-based diagnosis. The new definition is as follows: “A TIA is a brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than 1 hour, and without evidence of acute infarction. The corollary is that persistent clinical signs or characteristic imaging abnormalities define infarction—that is, stroke.”

After having a TIA, the short-term risk of having a stroke is high: 10% of patients have a stroke within 90 days, with half of those occurring in the first 2 days. Thus, TIA should trigger the same prompt evaluation and work-up as a persistent neurologic deficit (ie, stroke) and requires the implementation of proven interventions to reduce this substantial short term stroke risk.

Advanced age increases the risk of mortality after a stroke and is also a risk factor for recurrence. Compared with younger patients, older stroke survivors recover more slowly and have more severe deficits. The severity of stroke and prestroke medical condition heavily influence the outcome. Of those patients >80 years of age who receive thrombolysis, 20% end up with no significant disability and are eventually discharged home.