Clinical and genetic analysis of 5 pediatric patients with hemiplegic migraine presenting as acute encephalopathy

Objective: To analyze the clinical and genetic characteristics, diagnosis and treatment of hemiplegic migraine (HM) manifested as acute encephalopathy in children, so as to improve the understanding of this disease. Methods: The clinical data of 5 children diagnosed with HM characterized by acute encephalopathy who were admitted to Beijing Children's Hospital affiliated to Capital Medical University from August 2018 to June 2020 were retrospectively analyzed. Results: Among the 5 cases, 3 were males and 2 females with an age of 9.7 (3.9-12.7) years. The age of disease onset was 7.0(2.1-12.7) years. The peak symptoms of 5 children showed encephalopathy such as drowsiness and coma, as well as other clinical manifestations including headache, visual abnormality, hemiplegia, aphasia, convulsions, and fever, etc. The time to reach the peak was on the 2nd-6th day of the course of the disease. Before the onset of the disease 2 cases were found to have mild brain trauma and 2 cases had similar attacks in the past. Brain magnetic resonance imaging (MRI) showed hemispheric or partial cerebral cortex swelling and restricted diffusion of subcortical white matter in all cases, and cerebellar atrophy in 3 cases. All children received symptomatic treatment, and 2 of them were also treated with low-dose corticosteroids in the meantime. Finally all cases recovered clinically from the attack, but one had atrophic changes left in the affected area on brain MRI. Whole exon sequencing revealed variations of CACNA1A gene in all cases, among which 4 were de novo mutations and 1 case inherited from the mother who had migraine without aura. After the diagnosis, the 5 children were treated with long-term flunarizine and followed up for 22(7-29) months by telephone or in the outpatient clinic. Before the last follow-up, none of them showed weakness or encephalopathy, but one still had intermittent headaches and occasional transient right limb numbness. Conclusions: Hemipleg is often accompanied by impaired consciousness in addition to headache, hemiplegia, aphasia, visual abnormality, etc. Most patients recover completely after a short period, while a few recover slowly and may suffer sequelae such as brain atrophy and cognitive impairment and even death. CACNA1A gene variation is the most common genetic variation. Flunarizine could prevent recurrence of severe attack.