Abstracts

To report the neurological manifestations in two sisters with a mutation in SLC4A4. SLC4A4 is a gene encoding a sodium bicarbonate cotransporter. Mutations in the SLC4A4 gene are known to cause proximal renal tubular acidosis, glaucoma, severe mental retardation and growth delay early on in childhood. Although this gene is widely expressed in the brain, neurological complications other than mental retardation have not been described in sodium bicarbonate cotransporter gene mutations. Review of neurological manifestations in two adult sisters with proximal renal tubular acidosis, glaucoma, band keratopathy and normal intelligence and stature with a mutation in the SLC4A4 gene (Igarashi et al. Nature Genetics 1999; 23:264-266). The older sister was 50 years old and suffered from refractory partial epilepsy and migraine, which often co-occurred. From the age of 29 years, she had 5 episodes over around 17 years characterized by a transient left hemisensorimotor deficit folowed by a migrainous headache. Four years ago, she was admitted with an occipital lobe complex partial status epilepticus, characterized by stupor and continuous epileptic activity on EEG over the right posterior brain region, and followed by severe migraine. Since then, she has had almost weekly episodes of migraine headaches preceded by left-sided paresthesias and elementary visual hallucinations. She also had further episodes of status epilepticus and status migrainosus. Interictal EEGs showed frequent epileptic activity over right posterior brain regions. MRI of the brain was normal.
The younger sister was 42 years and had recurrent episodes of hemiplegic migraine since the age of 15 years and episodes of coma. The attacks began with blurred vision and a hemiparesis, followed by a migraine headache lasting for several hours. She has had a mean of five attacks per year. She was admitted twice in a somnolent and confused state during a severe hemiplegic migraine attack lasting two to three days. EEGs showed generalized slowing, but no epileptiform discharges. MRI of the brain was within normal limits.
Both sisters had only a partial response to several anti-epileptic and anti-migrainous drugs. These two sisters are the first reported patients in whom a mutation in the sodium bicarbonate cotransporter SLC4A4 gene causes both hemiplegic migraine and partial epilepsy. As the same mutation can give rise to epilepsy, migraine and a complex interaction between the two conditions, this study provides evidence for a close link between the pathophysiology of migraine with aura and partial epilepsy involving posterior brain regions.