From Stroke Suspicion to Genetic Confirmation: Familial Hemiplegic Migraine Type 2 as a Rare Stroke Mimic With Persistent Hemiplegia

TL;DR

A rare genetic condition, familial hemiplegic migraine type 2, can mimic stroke with severe neurological symptoms and requires genetic testing for accurate diagnosis.

Contribution

Highlights FHM2 as a rare stroke mimic and emphasizes the importance of genetic testing and clinical awareness for accurate diagnosis.

Findings

FHM2 can present with stroke-like symptoms including seizures, encephalopathy, and MRI diffusion restriction.

Genetic confirmation via ATP1A2 mutation testing is critical for diagnosis and prognosis.

Nimodipine therapy showed variable outcomes in FHM2, highlighting the need for further therapeutic studies.

Abstract

Hemiplegic migraine (HM) is a rare migraine subtype characterized by reversible motor aura that can closely mimic acute ischemic stroke. Familial HM (FHM) is an autosomal dominant condition linked to mutations in CACNA1A, ATP1A2, and SCN1A genes. FHM type 2 (FHM2), associated with ATP1A2 mutations, disrupts astrocytic Na⁺/K⁺-ATPase function and may present with seizures, encephalopathy, or prolonged neurological deficits. Accurate recognition is critical, as misdiagnosis can result in inappropriate interventions.

We report the case of a 33-year-old woman who presented with a gradual onset of severe left-sided headache, dysphasia, and hemiparesis over a two-day period. Shortly after initial imaging, she developed tonic-clonic seizures, loss of consciousness, and pyrexia, requiring intubation and intensive care unit (ICU) admission. Non-contrast computed tomography (CT) of the brain excluded hemorrhage. Magnetic resonance imaging (MRI) demonstrated right parietal and temporal cortical diffusion restriction. CT angiography suggested right middle cerebral artery (MCA) occlusion, but digital subtraction angiography (DSA) confirmed vasospasm without thromboembolism. Electroencephalography revealed diffuse encephalopathy. A family history of recurrent transient hemiparesis was noted. Genetic testing with whole-exome sequencing (WES) confirmed an ATP1A2 mutation consistent with FHM2. The patient improved in consciousness and language after nimodipine therapy but had persistent hemiplegia at discharge.

This case illustrates the significant diagnostic overlap between HM and acute ischemic stroke. The combination of seizures, encephalopathy, fever, and diffusion restriction on MRI is atypical for FHM and can complicate diagnosis. Inappropriate thrombolysis or invasive interventions may result if stroke mimics are not considered. Previous reports of ATP1A2-associated FHM2 describe variable phenotypes, including seizures and prolonged neurological deficits. The use of nimodipine remains controversial, with both clinical improvement and deterioration reported in the literature. Genetic confirmation provides diagnostic clarity, informs prognosis, and aids in family counseling.

FHM2 should be considered in patients with stroke-like presentations, particularly when accompanied by seizures or encephalopathy and in the context of a suggestive family history. Radiological findings may resemble ischemic stroke, underscoring the importance of comprehensive evaluation. This case highlights the need for increased awareness of FHM2 as a rare but important stroke mimic, and further studies are warranted to clarify optimal therapeutic strategies.

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