T21. Status epilepticus cessation during pyridoxine infusion in an infant with delayed diagnosis of ALDH7A1 mutation

Introduction Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder leading to neonatal intractable seizures and epileptic encephalopathy. Clinical seizures usually begin in the first hours of life, with poor response to anticonvulsants, evolving to refractory status epilepticus. Diagnostic assessment includes cerebrospinal fluid analysis, gene testing and clinical response to parenteral pyridoxine. Early recognition and treatment is highly desired to avoid unfavorable neurodevelopmental outcome. Electroencephalographic monitoring commonly reveals pretreatment multifocal epileptiform activity and burst suppression pattern; after pyridoxine injection, the incidence of sharp waves decreases and periods of suppression can occur. Methods Case report of a 11-month-old girl with first seizure with 4 h after birth and delayed genetic confirmation of pyridoxine-dependent epilepsy due to the gene ALDH7A1. EEG monitoring was performed during pyridoxine infusion. Results A 11 month-old girl, with unremarkable gestational and delivery history, started seizures 4 h after birth. Initially treated with phenobarbital, she evolved to convulsive status epilepticus (CSE), leading to orotracheal intubation and continuous sedation for 5 days. At 3 months, she had a new CSE, being hospitalized for 4 months and started on sodium valproate, vigabatrin, clobazam and levetiracetam. Epileptic seizures remained weekly. Phenobarbital and cannabidiol were added, with no further benefit. At 9 months, seizures became daily and she had a new CSE. In the ICU, it was started midazolam, ketamine, topiramate and ketogenic diet. After 1 month, she was discharged and referred to a tertiary hospital. An exome sequencing revealed 2 copies in homozygosis in the gene ALDH7A1, variant Chr5:125.894.936 C > T, previously associated with PDE. While being admitted for pyridoxin treatment, she started a new CSE. EEG showed diffuse spikes, polyspikes and sharp waves at intervals of 1–2 s. Immediately after intravenous injection of pyridoxine 200 mg, epileptiform activity became progressively less frequent, alternating with periods of attenuattion lasting from 2 to 8 s, with no longer SE after 3 min. After 3 days, EEG showed moderate diffuse disorganization, with no epileptiform activity. Discharge was after 10 days. Outpatient EEG monitoring showed left centrotemporal sharp waves and mild disorganization of background activity. Conclusion This case illustrates a clinical scenario of seizures starting in the neonatal period, with recurrent convulsive status epilepticus and little response to anticonvulsants and ketogenic diet. The delayed diagnosis can be explained by rarity of the condition and limited availability of gene testing in public health system in medium and low-income countries. It remarks the importance of empirical pyridoxine treatment in neonates with early beginning of refractory seizures and status epilepticus (SE). EEG evolution and SE cessation documents pyridoxine responsiveness.