Results of phase II levetiracetam trial following acute head injury in children at risk for posttraumatic epilepsy.

Posttraumatic seizures develop in up to 20% of children following severe traumatic brain injury (TBI). Children ages 6-17 years with one or more risk factors for the development of posttraumatic epilepsy, including presence of intracranial hemorrhage, depressed skull fracture, penetrating injury, or occurrence of posttraumatic seizure were recruited into this phase II study. Treatment subjects received levetiracetam 55 mg/kg/day, b.i.d., for 30 days, starting within 8 h postinjury. The recruitment goal was 20 treated patients. Twenty patients who presented within 8-24 h post-TBI and otherwise met eligibility criteria were recruited for observation. Follow-up was for 2 years. Forty-five patients screened within 8 h of head injury met eligibility criteria and 20 were recruited into the treatment arm. The most common risk factor present for pediatric inclusion following TBI was an immediate seizure. Medication compliance was 95%. No patients died; 19 of 20 treatment patients were retained and one observation patient was lost to follow-up. The most common severe adverse events in treatment subjects were headache, fatigue, drowsiness, and irritability. There was no higher incidence of infection, mood changes, or behavior problems among treatment subjects compared to observation subjects. Only 1 (2.5%) of 40 subjects developed posttraumatic epilepsy (defined as seizures >7 days after trauma). This study demonstrates the feasibility of a pediatric posttraumatic epilepsy prevention study in an at-risk traumatic brain injury population. Levetiracetam was safe and well tolerated in this population. This study sets the stage for implementation of a prospective study to prevent posttraumatic epilepsy in an at-risk population.

Partial Pyridoxine Responsiveness in PNPO Deficiency.

OBJECTIVE: Autosomal-recessive pyridox(am)ine phosphate oxidase (PNPO) deficiency causes pyridoxal-5-phosphate (PLP)-dependent epilepsy. We describe partial PNPO deficiency with a transient response to pyridoxine (B6). METHODS: CSF neurotransmitter metabolites, PLP, and amino acids were analyzed while the patient was receiving pyridoxine. PNPO gene sequencing was performed by standard techniques. RESULTS: A full-term 3,220 g male with refractory neonatal seizures became seizure free for 6 weeks on pyridoxine (B6). Breakthrough seizures followed. These stopped upon the first dose of PLP although episodes occurred as a dose became due. An unidentified peak was detected on the chromatographic system used to measure CSF PLP. PNPO gene sequencing identified a homozygous mutation in a highly conserved area in exon 3: c.352G>A p.G118R, predicting substitution of arginine for glycine. At age 28 months the child has hypotonia and developmental delay, both mild in severity. CONCLUSIONS: Transient pyridoxine responsiveness may be seen in partial PNPO deficiency. A CSF metabolite peak, likely pyridoxine phosphate, is identifiable in patients with PNPO deficiency who are taking supplemental pyridoxine. Partial B6 responsiveness is an indication for possible PNPO deficiency and trial of PLP.