Longitudinal brain MRI findings in two patients presenting with neonatal, pyridoxine-dependent seizures and followed for 5 to 9 years are reported from the University of California, Davis, CA. Each patient had three serial MRIs, showing progressive dilation of ventricles and atrophy of cortex and white matter. Patient 1 with AED-resistant seizures was diagnosed at 3.5 months by IV 100 mg pyridoxine administration during EEG monitoring. Seizures characterized by lip smacking, tonic eye deviation, and limb jerking began 2 hours after birth and were initially responsive to phenobarbital. Treatment with 25 mg oral pyridoxine daily controlled seizures, but noncompliance resulted in prolonged seizures and severe developmental disability with hypotonia at 5 year follow-up. Patient 2 developed seizures consisting of eye deviation and facial twitching and responsive to phenobarbital at 4 days after birth. They recurred occasionally up to 8 months of age, when seizures became refractory to anticonvulsants and were found to respond to pyridoxine. During follow-up for 9 years, minor motor seizures, partial and generalized, occurred only during intercurrent illness or noncompliance with pyridoxine, 25 mg daily, treatment. Seizures were preceded by sleepiness and irritability. [1]

COMMENT. Pyridoxine-dependent seizures of neonatal onset and due to an inborn abnormality of GABA synthesis, if undiagnosed and untreated, can result in progressive cerebral atrophy and severe impairments of psychomotor development. Previous reports have emphasized that the control of seizures alone may not suffice in treating pyridoxine dependency. In order to prevent mental retardation and motor and language delay, it may be necessary to increase the dose of pyridoxine to 10 mg/kg/daily to normalize neurotoxic glutamate levels. Language and cognitive disabilities secondary to pyridoxine-dependency may be partially reversed using optimal pyridoxine dosage. (See Progress in Pediatric Neurology III, PNB Publ, 1997;pp93-98).