Recurrent transient hemiparesis and a novel ATP1A2 mutation (P3.220)

Objective: Report a novel mutation in the ATP1A2 gene in a patient with cognitive delay, febrile seizures, and recurrent hemiparesis with associated transient neuroimaging abnormalities. Background: Conditions causing transient, lateralized neurologic symptoms include stroke/transient ischemic attack, postictal state, alternating hemiplegia of childhood, and hemiplegic migraine, among others. Hemiplegic migraine, a migraine with aura including reversible motor weakness and often associated transient sensory, visual, or speech symptoms, is a rare migraine variant with mean onset in the second decade of life.1 Neuroimaging can show cerebral vasoconstriction or vasodilation and regional perfusion changes during attacks, but classically normalizes between attacks.2 Some familial and sporadic cases have been linked to mutations in genes involved in ion transportation, including ATP1A2, CACNA1A, and SCN1A. ATP1A2 encodes a sodium-potassium ATPase, and its mutations exhibit significant phenotypic heterogeneity but have been associated with hemiplegic migraine and seizures.3,4 Design/Methods: Case study of a patient evaluated at our tertiary medical center. Results: The patient was a 5-year-old right-handed boy with a history of language delay, complex febrile seizures, abnormal electroencephalography (EEG), and transient left-sided weakness. Family history was unremarkable. He presented with acute onset right-sided weakness, expressive aphasia, and dysarthria, without headache. Magnetic resonance imaging (MRI) performed to rule-out stroke showed decreased left hemisphere perfusion without restricted diffusion, asymmetric venous prominence on susceptibility-weighted imaging, and pruning of the left hemispheric peripheral arteries on MR angiography. Symptoms resolved within two hours, though the next day left-sided visuospatial neglect transiently developed. Repeat MRI while asymptomatic was normal. The patient was found to have a novel mutation (c.1091Cu003eG) in the ATP1A2 gene predicted to alter the protein’s phosphorylation site. Parental testing is pending. Conclusions: This case identifies a novel, potentially pathogenic mutation of the ATP1A2 gene corresponding to a phenotype of a rare migraine variant and contributes to our evolving understanding of migraine molecular genetics and pathophysiology. Study Supported by: Disclosure: Dr. Stredny has nothing to disclose. Dr. Winden has nothing to disclose. Dr. Danehy has nothing to disclose. Dr. Robertson has nothing to disclose. Dr. Trenor has nothing to disclose. Dr. Rivkin has nothing to disclose. Dr. Lehman has nothing to disclose. Dr. Bernson-Leung has nothing to disclose.