Refractory seizures in a term neonate due to pyridoxine dependent epilepsy

A 4-day-old former 38-week term neonate was transferred to the NICU from a community emergency center (EC) due to concern for seizure activity. She was born at term via emergent Cesarean section for chorioamnionitis. The mother was group B streptococcus (GBS) positive and treated with clindamycin less than 4 hours before delivery. A blood culture was obtained which was negative. The baby did not receive postnatal antibiotics and was discharged home on the second day of life. On the third day of life, the mother witnessed an episode of whole body cyanosis with “stiffening of the arms and legs with jerking movements.” This prompted the parents to take the patient to the EC. At the community EC, the patient had respiratory distress with continued episodes of desaturations necessitating intubation. Rapid respiratory syncytial virus and influenza testing were negative. Patient also noted to exhibit upper and lower extremity flexion and extension concerning for seizure activity that transiently improved with Ativan 0.05 mg/kg. Blood cultures were obtained, and intravenous (IV) ampicillin and gentamicin were started. The patient was transferred to our level 4 NICU where electroencephalogram (EEG) showed multifocal sharp wave transients and depressed background activity in all regions. Antiepileptic treatment with Keppra 30 mg/kg/day divided three times a day was started. The blood cultures from the outside EC later grew Bacillus species in both aerobic and anaerobic culture bottles, but these had been considered a contaminant by the microbiology lab and were therefore discarded. Blood and cerebrospinal fluid (CSF) cultures obtained after treatment did not grow any pathogens, however there was a mild CSF leukocytosis (White Blood Cell 36). As no definitive bacteria were identified, the infant was treated for presumed meningitis with 14 days of IV vancomycin and cefotaxime. Magnetic resonance imaging (MRI) of the brain on day of life 4 showed multiple foci of restricted diffusion in the bilateral frontal lobes, right temporal lobe and bilateral pareito-occipital regions concerning for septic emboli or venous thrombosis (Figure 1A, B). A subsequent MRA/MRV was normal. Due to concern for hyper-coagulable state causing these MRI findings, hematology was consulted. After extensive testing, the results returned within normal limits. An echocardiogram also did not show any abnormalities. The patient’s seizure activity continued to worsen throughout the hospitalization despite increasing Keppra to 100 mg/ kg/day and adding phenobarbital up to 8 mg/kg/day. The patient’s anti-epileptic drugs (AEDs) were ultimately escalated to include versed drip. EEG showed numerous right hemispheric electroclinical seizures (Figure 2). The patient had pyridoxine challenges on day of life 17 and day of life 28. Neither challenge produced an immediate change in clinical or electrographic seizures (Figure 3). After the second challenge, pyridoxine 50 mg/day was continued for 3 days with improvement in EEG (Figure 4). However, clinical improvement was believed to be related to changes in AEDs or improvement in meningitis rather than pyridoxine supplementation and pyridoxine was discontinued. Notably, repeat MRIs demonstrated improvement in the parietal-occipital lesions (Figure 1C, D) and repeat infectious work-ups including blood and CSF cultures remained negative. CSF