A Longitudinal Exploration of CACNA1A-Related Hemiplegic Migraine in Children Using Electronic Medical Records
Donna Schaare1,2, Laina Lusk3,4, Alexis Karlin3,4
1Ph.D. Program in Healthcare Genetics and Genomics, School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, SC.
Insights
The longitudinal course of CACNA1A-related hemiplegic migraine (HM) is unpredictable, with no clear patterns in event timing or severity. Close monitoring is crucial, even after symptom-free periods, for individuals with CACNA1A-related HM.
Area of Science:
- Genetics and Neurology
- Neurodevelopmental Disorders
Background:
- CACNA1A-related hemiplegic migraine (HM) spectrum ranges from mild to life-threatening, impacting individuals with developmental and epileptic encephalopathies.
- The longitudinal course of CACNA1A-related HM throughout childhood remains largely unknown.
Purpose of the Study:
- To analyze the longitudinal course of HM and seizure history in individuals with CACNA1A-related HM.
- To delineate the frequency and severity of HM events over time.
- To assess the efficacy of different medications in preventing or reducing HM severity.
Main Methods:
- Retrospective analysis of electronic medical records for 15 individuals with CACNA1A-related HM.
- Standardized approach to delineate HM frequency and severity in monthly increments.
- Assessment of medication response for HM events.
Main Results:
- HM onset ranged from 14 months to 13 years; 25% of events were severe (>3 days).
- Levetiracetam and acetazolamide showed no efficacy, while verapamil and valproate offered modest HM prevention.
- Epilepsy severity weakly correlated with HM frequency and severity.
Conclusions:
- The longitudinal course of CACNA1A-related HM lacks predictable patterns in timing and severity.
- Strong correlation between seizure patterns and HM events was not observed.
- Highlights the unpredictability of CACNA1A-related HM and the need for continuous surveillance.
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.
