Familial hemiplegic migraine due to CACNA1A and PNKD mutations in epilepsy with forced normalization: A case report

Abstract

Rationale: Hemiplegic migraine (HM) is a rare subtype of migraine characterized by complex aura and transient hemiparesis. It is infrequently associated with refractory focal epilepsy, and there are no previous reports of forced normalization (FN) in this context. This case highlights a novel clinical association and the diagnostic and therapeutic challenges it presents. Patient concerns: A 31-year-old right-handed woman presented with episodes of cognitive impairment following seizure control, as well as recurrent episodes of HM and prolonged focal seizures. She had a history of familial HM associated with CACNA1A and PNKD mutations. Diagnoses: Genetic testing confirmed the presence of CACNA1A and PNKD mutations, consistent with familial HM. The patient was also diagnosed with focal refractory epilepsy and exhibited clinical and electroencephalographic features suggestive of FN. Interventions: The patient received various antiseizure medications, with adjustment of dosages and regimens in response to status epilepticus and evolving cognitive symptoms. Treatment was tailored to balance seizure control while minimizing adverse neuropsychiatric effects. Outcomes: Seizure control was partially achieved with adjustment of antiseizure medications; however, episodes of cognitive dysfunction persisted during electroencephalogram normalization periods, consistent with FN. Functional status improved gradually with individualized treatment, but neurological deficits and migraine persisted intermittently. Lessons: This case illustrates a rare coexistence of familial HM, focal refractory epilepsy, and FN. It emphasizes the need for heightened clinical awareness of FN in similar complex neurogenetic disorders and highlights the importance of individualized pharmacological strategies.