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Am Fam Physician. 2022;105(6):616-624

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Stroke accounts for significant morbidity and mortality and is the fifth leading cause of death in the United States, with direct and indirect costs of more than $100 billion annually. Expedient recognition of acute neurologic deficits with appropriate history, physical examination, and glucose testing will help diagnose stroke and rule out mimicking presentations. The National Institutes of Health Stroke Scale should be used to determine stroke severity and to monitor for evolving changes in clinical presentation. Initial neuroimaging is used to differentiate between ischemic and hemorrhagic stroke or other pathologic processes. If a stroke is determined to be ischemic within four and a half hours of last known well or baseline state, determining the patient's eligibility for the administration of intravenous recombinant tissue plasminogen activator is necessary to proceed with informed decision-making for diagnostic workup and appropriate treatment options. Additional evaluation with specialized magnetic resonance imaging studies can help determine if patients can receive recombinant tissue plasminogen activator within nine hours of last known well. Subarachnoid hemorrhage should be considered in the differential diagnosis if the patient presents with rapid onset of severe headache. If radiographic imaging is negative for hemorrhage when there is high suspicion for delayed presentation of stroke, a lumbar puncture should be considered for further evaluation. Patients with cerebellar symptoms should be evaluated with a HINTS (head-impulse, nystagmus, test of skew) examination because it is more sensitive for cerebellar stroke than early magnetic resonance imaging. Additional cerebrovascular imaging should be considered in patients with large vessel occlusions presenting within 24 hours of last known well to assess benefits of endovascular interventions. Once initial interventions have been implemented, poststroke evaluations such as telemetry, echocardiography, and carotid imaging should be performed as clinically indicated to determine the etiology of the stroke.

Stroke ranks fifth among all causes of death in the United States, accounting for one out of every 19 deaths, with costs of more than $100 billion annually. Cumulative all-cause mortality after a stroke is estimated to be 10.5% at 30 days and 21.2% at one year. An estimated 7.6 million Americans are self-reported to have experienced a transient ischemic attack (TIA) or stroke, with a climbing projection of an additional 3.4 million by 2030. The incidence of stroke is approximately 795,000 people per year, and 25% of these occurrences are recurrent episodes.1 Traditionally, stroke was defined as a focal injury to the central nervous system (CNS) caused by a vascular etiology lasting more than 24 hours, which primarily made this disease a clinical diagnosis. Given advancements in the understanding of cerebrovascular disease as a process and the widespread availability of rapid imaging, a more universal definition has emerged, defining stroke broadly as a concept encompassing CNS infarctions and hemorrhages based on imaging and pathologic and clinical findings.2 Clinical symptoms of neurologic dysfunction accompanied by evidence of infarction on brain imaging are classified as ischemic stroke, whereas transient symptoms without evidence of infarction are classified as TIA.
Clinical recommendation Evidence rating Comments
In patients who are eligible for rtPA treatment, it should be initiated as soon as possible and not be delayed for further diagnostic workup.8,9 C Practice guidelines based on moderate-quality evidence from one or more well-designed, well-executed, nonrandomized, observational, or registry studies
All patients with stroke symptoms should be sent for urgent neuroimaging with noncontrast computed tomography of the brain.8,16,17 C Expert opinion and consensus guideline in the absence of clinical trials
Patients eligible for intravenous rtPA should receive treatment, even if mechanical thrombectomy is being considered.9,18 C Practice guideline based on moderate-quality evidence from one or more well-designed, well-executed, nonrandomized, observational, or registry studies
In patients who present after six hours with signs or symptoms of subarachnoid hemorrhage, lumbar puncture should be performed if computed tomography or MRI results are negative or equivocal, and suspicion for subarachnoid hemorrhage is high based on the Ottawa Subarachnoid Hemorrhage Rule for Headache Evaluation.1921 C Expert opinion and consensus guideline in the absence of clinical trials
Patients who present with cerebellar symptoms should be evaluated with a HINTS examination and diffusion-weighted magnetic resonance imaging. Negative early magnetic resonance imaging may need to be repeated in three to seven days or followed up with a bedside HINTS examination.5,17,22 C Expert opinion and consensus guideline in the absence of clinical trials
Patients who present within 24 hours with severe neurologic deficits possibly caused by large vessel occlusions of the internal carotid arteries or proximal middle cerebral arteries should have noninvasive cerebrovascular imaging to assess eligibility for mechanical thrombectomy.9,18 C Practice guideline and clinical review based on consistent, good-quality, patient-oriented evidence
Rapid diagnosis and prompt treatment of stroke with consideration for use of recombinant tissue plasminogen activator (rtPA) can significantly reduce mortality and morbidity; risk factor modification can reduce recurrence.

Risk Factors

Numerous risk factors contribute to stroke. Approximately 87% of stroke risk is attributable to modifiable risk factors such as adiposity, diabetes mellitus, hypertension, and dyslipidemia. Behavioral factors such as smoking, sedentary lifestyle, and unhealthy dietary choices account for about 47% of these modifiable risk factors.1 Depending on the type of stroke, risk factors have variable associations. Diabetes increases the risk of an ischemic stroke but decreases the risk of a subarachnoid hemorrhage. Adiposity appears to increase the risk of ischemic stroke; however, its association with hemorrhagic stroke is unclear. Hypertension increases the risk of all types of stroke, but the risk tends to be higher with hemorrhagic vs. ischemic stroke.3 Radiographic findings of previous stroke are the greatest predictor of future stroke.4

Classification of Strokes

Stroke classification is based on the underlying pathologic process and vascular distribution. Appropriate classification of a stroke assists in formulating definitive treatment decisions and communicating potential short- and long-term prognoses. In the United States, approximately 87% of all strokes are ischemic, 10% are intracerebral hemorrhages, and 3% are subarachnoid hemorrhages.1 

An ischemic stroke is defined as an episode of neurologic dysfunction secondary to a focal CNS infarction. A silent ischemic infarction is defined as imaging or neuropathologic evidence of an infarction without neurologic dysfunction. 

Intracerebral and spontaneous subarachnoid hemorrhages are defined as rapidly developing neurologic dysfunction secondary to the focal accumulation of blood in the brain parenchyma and in the subarachnoid space, respectively, and are not precipitated by trauma. A silent cerebral hemorrhage is similar to a silent ischemic stroke in that both are without clinical symptoms. Imaging shows a focal collection of blood within the brain parenchyma or ventricular system, often presenting in the form of microhemorrhages.2 

A stroke caused by cerebral venous thrombosis is an infarction or hemorrhage in the brain, spinal cord, or retina due to thrombosis of a cerebral venous structure and represents 0.5% to 1% of all strokes. A stroke classified as “not otherwise specified” is defined as acute neurologic dysfunction presumed to be caused by ischemia or hemorrhage that persists for more than 24 hours or until death, but with indeterminate evidence to be classified as any other type of stroke.2 Attempting to localize the vascular distribution of a stroke based on clinical assessment has traditionally been used to assist in diagnosis and treatment and for rehabilitation purposes.

Clinical Diagnosis

The history is key in the initial assessment of stroke and should focus on the symptoms and signs of focal neurologic injury, such as unilateral weakness or sensory deficit, facial droop, dysarthria, or aphasia (Table 1).5 Patients typically present with a sudden and maximal focal neurologic deficit that is consistent with a vascular territory.6 The timing of events or symptom onset, specifically the last known well or baseline state, is crucial for assessment and determining treatment options.
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