Antecedent neonatal hypoglycaemic brain injury, the most common cause of early childhood epilepsy in Indian children

Abstract

Prospective research from low- and middle-income countries on aetiologies of early childhood epilepsies using advanced diagnostic methods (3T-MRI and genetic testing), is lacking. Data on epilepsy outcomes is also not available in these patients. We enrolled consecutive patients with epilepsy onset upto five years of age, over 12 months. After ruling out a structural-acquired cause on MRI, genetic testing with exome sequencing (ES) and if required, chromosomal microarray (CMA)/multiplex ligand PCR assay (MLPA) was performed. Following this evaluation, patients were classified into aetiological groups defined by the International League Against Epilepsy. The epilepsy outcomes at 24-month follow-up was also confirmed. Novel data on differences in epilepsy and neurodevelopmental profile of the two common perinatal causes namely, neonatal hypoglycaemic brain injury (NHBI) and neonatal asphyxial brain injury (NABI), are also presented. Two hundred thirty-one children were recruited. The aetiology could be confirmed in 172 (74%) patients. The structural group (including structural-genetic) was the most common [126 (55%)], followed by genetic [41(18%)] and metabolic [5 (2%)]. The unknown group comprised [48 (21%)] patients. Eleven (5%) patients were ‘incompletely investigated’ (normal MRI but family refused genetic evaluation). Antecedent NHBI [50 (22%)] was the commonest cause of epilepsy. On comparing the phenotypic differences between the two common perinatal causes, the initial epileptic seizure was more often focal in NHBI (P<0.001) and infantile spasm in NABI patients (P=0.05). NABI patients were more likely to be assigned to epilepsy syndrome (P= 0.03) as compared to NHBI. Autistic features (P=.05) and hypotonia (P=.03) were more frequent in NHBI while NABI patients were more often hypertonic or dystonic (both P <0.001). In assessing the utility of investigations, MRI was helpful in 126 (54.5%) patients. Genetic evaluation was diagnostic in 57 (50%) of the 113 tested. The genetic yield was more likely with seizure onset in the first year (P=0.03), developmental and epileptic encephalopathy (P=0.01), developmental delay or hypotonia (both P<0.001). At the 24-month follow-up, 57 of 207 (28%) patients had poor seizure control. On multivariate regression, developmental delay (P=.04) had a negative effect while increasing age at seizure onset had a positive effect (P=0.018) on seizure control. In this study, we could confirm that NHBI, a preventable condition, was the commonest underlying cause of epilepsy. Our data also emphasizes the urgent need for developing guidelines to change the current newborn feeding practices in India which could decrease the subsequent risk of epilepsy in infancy and early childhood.