Cerebrovascular accidents (CVA) consistently rank within the top five causes of death worldwide and are the number one cause of disability in the United States. Ischemic CVAs typically present with the sudden onset of a focal neurological deficit in a vascular distribution, and many non-vascular conditions, called stroke mimics, can present with similar symptoms, presenting a diagnostic conundrum. The diagnosis of CVA and its differentiation from potential stroke mimics is extremely time-sensitive: the two available treatments in ischemic CVA, pharmacologic thrombolysis and endovascular thrombectomy, are limited by strict timing criteria and contraindications, and the benefit of both these treatments decreases with delays in treatment initiation. This focus on minimizing the time from symptom onset to treatment initiation makes the differentiation between true CVAs and stroke mimics challenging. Because of the time-sensitive nature of CVA diagnosis and the recent emphasis on metrics such as "door-to-needle time," a high level of sensitivity for CVA diagnosis is necessary, though this necessarily leads to decreased specificity in the diagnostic evaluation and therefore an increased number of stroke mimics being evaluated and treated as true ischemic strokes. The treatment for CVA is associated with potentially harmful side effects, including life-threatening intracranial hemorrhage, highlighting the importance of distinguishing a true ischemic CVA from a potential stroke mimic. Thus, in this era of "time equals brain," the evaluation and treatment of strokes and stroke mimics walk a fine line between timely treatment initiation in CVAs and overtreatment of stroke mimics.
Several conditions can present with acute focal neurological deficits, which may be misdiagnosed as an acute stroke presentation. This rate of misdiagnosis is augmented by the similarity of some stoke mimics to true CVA on imaging, including MRI. Hypoglycemia is a common cause of acute focal neurologic deficits. On MRI, severe hypoglycemia may present with restricted diffusion similar to that seen in CVA due to the similarity of their pathophysiology: hypoglycemia leads to insufficient brain cell energy reserves, resulting in the failure of active membrane ion pumps and therefore cytotoxic edema. MRI changes secondary to hypoglycemia may cross several vascular territories, distinguishing them from those caused by cerebrovascular ischemia. Nevertheless, this similarity, even on high-specificity imaging, highlights the importance of immediate blood glucose testing in patients presenting with acute neurological deficits, as this is a rapid and cost-effective method of evaluating for this common stroke mimic. Seizures are another common stroke mimic.  Seizures may present with postictal neurological deficits, known as Todd paralysis or Todd paresis. Further complicating this situation is the fact that both acute and chronic strokes can cause seizures, making this stroke mimic very difficult to exclude from an acute stroke presentation. Complex migraines may likewise present with focal neurological deficits. Hemiplegic migraines, while rare, can also be misdiagnosed as stroke. Finally, intracranial and intrathecal tumors may manifest with focal neurologic deficits that may be misdiagnosed as stroke. Acute neurologic deficits may result from a tumor-provoked seizure, a hemorrhage inside the tumor, and extrinsic compression of the surrounding vessels resulting in vascular-distribution neurologic deficits.
Estimates of misdiagnosis of CVA range from 5% to 31%. The most common conditions misdiagnosed as strokes are peripheral vertigo, seizures, and primary headache disorders. Other stroke mimics include intracranial space-occupying lesions, demyelinating disease, movement disorders, sepsis, delirium, metabolic disturbances, hepatic encephalopathy, and functional psychiatric disorders.
Like CVAs, stroke mimics may present with negative neurological symptoms, including speech difficulties, weakness or numbness of the extremities, and facial asymmetry. Stroke mimics may also present with positive neurological symptoms, such as aura, hallucinations, or delusions. The presence of positive neurological symptoms may help distinguish stroke mimics from CVAs. 
Patients who present with sudden onset focal neurological deficits should immediately have a blood glucose level checked. Hypoglycemia may mimic the focal symptoms of an ischemic CVA and may also exacerbate symptoms of prior CVAs. Ancillary laboratory testing includes a basic metabolic panel, complete blood count, troponin, coagulation studies, and an electrocardiogram. Non-contrast computed tomography (CT) is the first-line imaging of choice due to its non-invasive and rapid nature, as well as its widespread availability. CT is, however, not sensitive for the presence of acute CVA, especially in the first 48 hours, with estimates of sensitivity as low as 12%. MRI is more sensitive and specific for the diagnosis of ischemic stroke, but its availability is limited, particularly in the acute setting. Patient characteristics may help identify potential stroke mimics. Patients under the age of 50 years and those with minimal risk factors for CVA (hypertension, atrial fibrillation, diabetes mellitus, and hyperlipidemia) are more likely to have a stroke mimic than a CVA. Stroke mimics were also disproportionately seen in females. Other variables identified to differential stroke mimics from CVAs include the absence of intracranial atherosclerosis on CT angiography, the lack of focal weakness on examination, and history of migraine, seizure disorders, or prior psychiatric history.
Two treatment pathways exist for patients presenting with symptoms consistent with CVA that meet strict timing criteria and lack contraindications: thrombolysis or endovascular reperfusion therapy. Studies show that an estimated 4% of patients who receive thrombolytics for a presentation of acute neurological symptoms later receive a diagnosis of a stroke mimic. Importantly, studies have repeatedly shown that the administration of thrombolytics in stroke mimics carries a more favorable side effect profile than the administration of thrombolytics in true ischemic CVA. For example, the risk of symptomatic intracranial hemorrhage following thrombolytic administration in stroke mimics was 0.5% versus 5.2% in true ischemic CVA patients.
There is no specific historical detail or physical examination finding that differentiates strokes from stroke mimics, which include metabolic disturbances, intracranial lesions, seizures, and psychiatric disorders. Stroke mimics may present with neurological deficits in a vascular territory or symptoms may span multiple vascular territories or follow no vascular pattern. The mapping of symptoms to a vascular territory may help differentiate true CVAs from stroke mimics, though it is important to remember that stroke mimics may follow a vascular territory as well. Gradual onset is suggestive of a stroke mimic rather than a CVA, since CVAs, with the exception of some vertebrobasilar strokes, typically present with acute onset of symptoms. The presence of positive neurological symptoms, such as hemiballismus or hallucinations, suggests a stroke mimic rather than a CVA, which typically present with only negative neurological symptoms such as loss of sensation or paralysis. Finally, decreased level of consciousness is more suggestive of a stroke mimic, such as toxic or metabolic encephalopathy, than CVA.
The prognosis of stroke mimics largely depends on the underlying etiology, as stroke mimics can result from a broad spectrum of diseases. Patients with transient neurological symptoms from conditions such as complex migraines or metabolic derangements have a better prognosis than those with neurological symptoms from conditions such as multiple sclerosis, sepsis, and decompensated cirrhosis.
The relatively favorable safety profile of thrombolytic use in stroke mimics has been well-established. Despite being relatively safe, the administration of thrombolytics in stroke mimics is unnecessary and costly, adding an estimated $5400 to the cost of treatment. It also leads to unnecessary or prolonged hospital stays, additional testing, and unnecessary invasive procedures, further burdening the patient and the healthcare system and using resources that would be more appropriately directed toward true cerebrovascular events. Additionally, while uncommon, complications from thrombolytic administration, such as intracranial hemorrhage and allergic reaction, do exist and contribute to the rate of iatrogenic morbidity and mortality in the healthcare system.
The frequency of stroke mimics being misdiagnosed as true CVAs is lower in hospitals with higher neurological expertise and those with designated stroke units. Thus, in patients presenting with acute focal neurological deficits, early neurology consultation, where available, is helpful in both diagnostic evaluation, development of a treatment plan, and appropriate disposition.
Several campaigns targeting early stroke symptom recognition exist for the education of the lay public. The most well-known of these is the FAST campaign, which employs the FAST acronym (Face-Arm-Speech-Time) to teach classic symptoms of stroke and emphasizes the importance of prompt medical evaluation. Communication between healthcare providers and patients diagnosed with stroke mimics is of utmost importance. Patients should be encouraged not to ignore neurological symptoms should they develop in the future, as many patients with stroke mimics may also have risk factors for the development of true ischemic CVA.
Stroke mimics are projected to increase substantially in the coming years, leading to an increase in resource consumption in an already-taxed healthcare system. One potential strategy to decrease the burden of stroke mimics on hospital resources is to increase MRI availability in the acute setting to detect stroke mimics earlier, thus decreasing the rate of inappropriate stroke unit admissions and freeing up resources for the treatment of true CVAs. Other potential strategies include the development and use of scoring systems to help identify potential stroke mimics and targeted use of acute MRI in these patients.
Interprofessional collaboration and communication are of utmost importance in the treatment of strokes and stroke mimics. Timely communication between emergency medicine physicians, nurse practitioners, neurologists, and emergency and neurology specialty-trained nursing staff decreases delays to the initiation of thrombolysis if appropriate, which leads to increased efficacy of treatment. This early communication between members of the healthcare team may likewise lead to earlier identification of stroke mimics, helping to mitigate their burden on the healthcare system, including the increased cost to the patient and healthcare system, unnecessary use of stroke facilities, and inappropriate and unnecessary treatment.
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