Honing in on risk factors for prolonged remission off medication by reducing heterogeneity.

Commentary The study by Berg et al. presents the risk and risk factors for complete remission in children without electroclinical syndromes, developmental encephalopathies, and potential electroclinical syndromes that could not be well classified who were observed for at least 10 years. Such nonsyndromic epilepsy represents almost 60% of childhood-onset epilepsy. Taking this interesting approach permits an evaluation of the cumulative risk for remission, risk factors, and risk for relapse absent children with electroclinical syndromes, in which the prognosis is part of the definition. The remaining cohort of nonsyndromic epilepsy is a mixture of epilepsy of unknown cause and epilepsy caused by structural or metabolic factors and more closely mirrors epilepsy in adults, permitting better comparisons of risk factors for remission across the lifespan. Restriction in this manner also hones the risk factors for remission that are identified, providing more valid estimates of the magnitude of risk associated with these factors. In this study, remission is defined as at least 5 years free of seizures off medication and is called complete remission, not because it is the final endpoint for all children meeting criteria, but because it is a clinically meaningful endpoint that endures for most until the current time. This definition of remission has been used before by others, although it has not previously been called complete remission (1, 2). The more commonly used definition is 5 years free of seizures with or without medication (1–6), perhaps because, as pointed out in the paper, decisions to stop medication are multifactorial. In contrast, 5 years free of seizures can be observed uniformly across all people with epilepsy. Another facet that separates this study from others is the availability of MRI exams in almost 90% of all nonsyndromic epilepsy observed for 10 years or more. Among these, 21% had an MRI abnormality. A prior publication of the Connecticut cohort has reported imaging in almost 80% of the full cohort, with abnormal imaging rare but present (3.5%) in children who were clinically normal and with abnormal imaging more common (12.7%) in the full cohort (7). These findings suggest that most, but not all, of the MRI abnormalities examined in the current report represent overlap with underlying brain disorder, abnormal neurologic examination, intellectual disability only, or autism spectrum disorder. The occurrence of complete remission and risk factors for complete remission are examined in those with nonsyndromic epilepsy who were observed for 10 or more years. Others have also evaluated risk factors for remission in epilepsy cohorts observed for this long, including studies in Finland (5, 8), Complete Remission in Nonsyndromic Childhood-Onset Epilepsy.