Is it stroke, or something else?

Be alert to the signs of conditions masquerading as stroke
Seizure at the onset of the episode; isolated mild neurological deficits, such as ataxia, sensory loss, or dysarthria alone; and/or minimal weakness are contraindications to thrombolytic therapy, according to the American Academy of Neurology (AAN).¹⁰

Rapidly improving neurological status is a probable indicator of a TIA or nonstroke etiology. Decreased level of consciousness with normal eye movements increases the likelihood that the patient has a condition that mimics stroke.¹¹ Additional symptoms that strongly suggest a disorder other than stroke are convulsions (odds ratio [OR]: 0.1), loss of consciousness (OR: 0.1), confusion (OR: 0.2), headache (OR: 0.8), nausea (OR: 0.5), vomiting (OR: 0.6), and dizziness (OR: 0.3).⁹

Age is another consideration. The vast majority of patients with conditions that turn out to be stroke mimics are younger than 50 years of age. In patients older than 50, the prevalence of stroke misdiagnosis is just 3%.¹²

Watch for these stroke mimics

Seizures, either unwitnessed or unrecognized, and complex migraine are the most common stroke masqueraders. Other conditions frequently misdiagnosed as stroke include: systemic infections and early sepsis, central nervous system (CNS) tumors, and toxic-metabolic syndromes (including intoxication, hypoglycemia, hypercalcemia, and hyperosmolar nonketotic coma) (TABLE 2). Patients with cranial or peripheral neuropathy; dementia; labyrinthitis/benign positional vertigo; psychiatric disorders, in particular, conversion reaction; syncope; and transient global amnesia may also present with neurological symptoms suggestive of stroke. (For more on transient global amnesia, see this month’s Hospitalist Rounds at https://www.jfponline.com/CollectionContent.asp?CollectionID=286.) Characteristics of some of the more common mimics are detailed below.

Seizures. Neurologic deficits associated with seizures are reversible, with no structural CNS abnormalities. Postictal hemiparesis, also known as Todd’s paralysis—a focal weakness after a seizure, typically localized to 1 side of the body—occurs in approximately 13% of all seizures.¹³ Todd’s paralysis, which can be seen after either partial complex or generalized tonic-clonic seizures, may also affect speech and vision, producing a range of signs and symptoms easily mistaken for stroke. Duration ranges from minutes to 48 hours,¹⁴ but generally lasts only 3 to 22 minutes.¹³

Differentiating Todd’s paralysis from stroke is complicated by the fact that some strokes trigger focal seizures during the acute phase. However, a history of seizures or witnessed seizure activity points to Todd’s paralysis rather than stroke.

Complex migraine. Like Todd’s paralysis, complex migraine may result in hemiparesis. The presentation may also include vision loss, aphasia, or vertigo and other basilar symptoms—neurologic changes that can outlast the headache. Complex migraine is a diagnosis of exclusion, arrived at after a full neurologic assessment, including stroke work-up. Indeed, you can be certain of a diagnosis of complex migraine only after the patient has had recurrent complex migraine attacks.

Some basilar TIAs can also present with headache, but the onset is typically sudden, as opposed to the more gradual onset of migraine aura with posterior circulation symptoms.¹⁵ Age is a factor as well: Complex migraines usually develop well before the age of 40, while the mean age for ischemic stroke is 70. Although complex migraine is a risk factor for ischemic stroke, in most patients migraine is a benign condition.^15,16

Systemic infections. Sepsis from almost any infectious agent can cause delirium, altered speech, weakness, and less specific stroke-like symptoms. Microbial seeding of the CNS can result in focal lesions (eg, the lesions shown in FIGURE 1B are associated with cryptococcal meningoencephalitis) or abscess formation with focal neurologic deficits.

Mass lesions. Primary CNS tumors, metastatic tumors, and cerebral abscesses are among the lesions that can cause symptoms that mimic stroke. In most cases, symptoms develop gradually as the lesion enlarges, but a small subset of patients have symptoms lasting less than 1 day. This is thought to be due to hemorrhage into the tumor or the acute development of obstructive hydrocephalus.¹⁷

Metabolic disorders. Diabetic hypoglycemia, among other metabolic disorders, is a classic stroke mimic, as well as a cause of seizures, so early evaluation of blood glucose is a crucial step in evaluating a patient with neurologic signs and symptoms. Patients with diabetic hypoglycemia may present with hemiplegia and aphasia; similar symptoms may occur in patients with hypoglycemia secondary to alcoholism, among other causes. Those with hyperglycemic nonketotic hyperosmolar states, severe hyponatremia, and hepatic encephalopathy may also present with focal stroke-like symptoms. Neurologic changes associated with metabolic disorders generally resolve rapidly with the administration of IV glucose, but on rare occasions may take several hours to resolve.¹⁴

Psychiatric illness. Patients with certain psychiatric disorders—including conversion reaction, a psychological condition that presents as an alteration in, or loss of, physical function—may present with dramatic focal problems and apparent deficits that mimic neurologic disease. Subtle disparities in the physical exam, such as Hoover’s sign, give-away weakness,¹⁸ and “la belle indifference,” as well as negative neuroimaging, will establish this difficult-to-treat stroke mimic.¹⁹ Grand mal pseudo-seizures can be differentiated from actual grand mal seizures by the failure of a prolactin level (drawn 10 to 20 minutes post-event) to rise at least 2-fold.²⁰