Researchers at University of Arkansas, Little Rock, AR report 3 cases of familial hemiplegic migraine complicated by reversible cerebral edema and followed by neurocognitive impairment. Patient 1, a 13-year-old girl developed a severe headache during a volleyball game and on neurologic examination she had global aphasia, right-sided weakness, and ataxia. The initial MRI was normal, but the initial EEG revealed generalized slowing, 1-2 Hz, in the left hemisphere. Follow-up MRI 9 days after onset of signs revealed increased T2 signal involving the left hemisphere, with mild mass effect and midline shift. Her mother and brother had frequent migraine episodes accompanied by confusion, aphasia and hemiplegia. Treatment included verapamil, valproic acid, methylprednisolone, and IV immunoglobulin. The diagnosis of familial hemiplegic migraine was supported by CACNA1A gene mutations. She was maintained without further migraine episodes while taking verapamil as prophylactic. MRI and EEG repeated at 4 months follow-up were normal, but she had attention and memory problems in school. Two male patients, ages 8 and 15 years, with similar histories to that of case 1 had EEGs that revealed slowing in one hemisphere, 1-2 Hz, consistent with the MRI finding of unilateral cerebral edema. Mutation was located on ATP1A2 gene in case 2, and gene mutation was lacking in case 3; minor head trauma may have precipitated this patient’s migraine attack. Neuropsychological evaluation and/or school reports at follow-up revealed cognitive impairment, memory and attention problems in all 3 patients. [1]

COMMENT. Genetic heterogeneity and persistent cognitive impairment are illustrated by these case reports of variable manifestations of familial hemiplegic migraine. EEG slowing was consistent with the temporary cerebral edema as a feature of FHM. A triad of prolonged hemiplegic migraine, cerebellar ataxia, and epileptic seizures is linked to CACNA1A gene mutations and may be complicated by status epilepticus [2]. This report recommends that patients with prolonged hemiplegic migraine attacks and confusion be tested with continuous EEG to rule out electrographic status.

Sporadic hemiplegic migraine presenting as acute encephalopathy. A 10-year-old boy with psychomotor delay and cerebellar vermis atrophy developed right hemiplegia with vomiting, loss of consciousness, convulsions, and fever. EEG showed delta activity over the left hemisphere, and MRI revealed swelling of the left temporo-occipital cortex. Interleukin-6 was elevated in the CSF. Acute symptoms resolved after 3 weeks and recurred 7 months later with migraine attacks. A de novo mutation in the CACNA1A gene was identified. Family history was negative for migraine. Both familial and sporadic hemiplegic migraines are genetically heterogeneous, the majority caused by CACNA1A mutations. [3]