A Longitudinal Exploration of CACNA1A-Related Hemiplegic Migraine in Children Using Electronic Medical Records.

Abstract

Background and objectives: Since the initial description of CACNA1A-related hemiplegic migraine (HM), the phenotypic spectrum has expanded from mild episodes in neurotypical individuals to potentially life-threatening events frequently seen in individuals with developmental and epileptic encephalopathies. However, the overall longitudinal course throughout childhood remains unknown.

Methods: We analyzed HM and seizure history from electronic medical records in individuals with CACNA1A-related HM, delineating frequency and severity of events in monthly increments through a standardized approach. Combining these data with medication prescription information, we assessed the response of HM to different agents.

Results: Our cohort involved 15 individuals between 3 and 29 years (163 patient years) and included 11 unique and 2 recurrent variants (p.R1349Q and p.V1393M; both n = 2). The age of first confirmed HM ranged from 14 months to 13 years (average 3 years). 25% of all HM events were severe (lasting >3 days), and 73% of individuals had at least 1 severe occurrence. Spacing of HM events ranged from 1 month to 14 years, and changes in HM severity over time showed increases or decreases of >2 severity levels in 12 of 122 events. Eight individuals had epilepsy, but severity of epilepsy was only weakly correlated with frequency and severity of HM events. While levetiracetam (n = 6) and acetazolamide (n = 5) were the most frequently used medications, they did not show efficacy in HM prevention or severity reduction. However, verapamil (risk differences [RD] 0.10, CI 0.05-0.15) and valproate (RD 0.08, CI 0.04-0.12) were associated with a modest prevention of HM, but not reduction in severity.

Discussion: The longitudinal course of CACNA1A-related HM lacks recognizable patterns for timing and severity of HM events or strong correlation with seizure patterns. Our data underscore the unpredictability of CACNA1A-related HM, highlighting the need for close surveillance for reoccurring HM events even in individuals with symptom-free periods.