Neonatal-onset epilepsy: Clinico-etiological spectrum and developmental outcomes

Introduction: Neonatal-onset epilepsies are rare but distinct group with significant neurodevelopmental morbidity. The data on etiology and outcomes is scarce. Methods: Prospective observational study by cross sectional design of infants with epilepsy onset within 2 months of life. Results: One hundred twenty five infants included over two years period: Males were 66 (52.8%), mean age at onset of seizures was 11 days (1-54 days). The commonest seizure was focal clonic (83%) and multiple seizure types seen in 55 (44%). Most common EEG finding was multifocal epileptic discharges (27%) followed by epileptic encephalopathy pattern (20%). Of 98 infants with complete work-up (biochemical/metabolic/imaging/ genetic), 88 had confirmed diagnosis-yield of 89.7%: structural abnormalities (20%), metabolic disorders (16.4%), BNE (20%) and genetic disorders (32.6%). Gene abnormality was found in 54/65(83%) cases tested. Most common gene was KCNQ2. Enzyme/ enzyme cofactor encoding genes were found in 28/54 (51.8%) followed by channelopathies (24%). Follow up of more than 6 months (6- 96months) was available for 119 cases. Seizure control was attained in 50%. Poor developmental outcome was seen in 50% (death/severe/profound delay) in all categories except for BNE. Normal development was seen in 30% (BNE/Pyridoxine dependent epilepsy). Infants with poor seizure control (p=0.00001), epileptic spasms (p=0.0034) and epileptic encephalopathy on EEG (p=0.00001) predict poor outcome. Normal EEG and early seizure control (~9months) had better outcome (p=0.0039). Polymorphic seizures, age at seizure onset, normal MRI, number of drugs required were not associated with developmental outcome. Conclusion: Neonatal-onset epilepsies have high diagnostic yield, and significant neuro-developmental morbidity.
Keywords: neonatal epilepsy, developmental epileptic encephalopathy, genetic testing, etiology, developmental outcome