Commentary on IL-1β associations with posttraumatic epilepsy development: A genetics and biomarker cohort study.

Human posttraumatic epilepsy (PTE), the most common acquired epilepsy in teenagers and young adults, is an unfortunate natural experiment that may provide insight into epileptogenesis and antiepileptogenic interventions. In PTE, epilepsy develops weeks to months after traumatic brain injury (TBI), and often in a previously nonepileptic and otherwise healthy brain. Particularly in severe TBI, the injury timing is well-documented, and by necessity for critical care, the patients are closely monitored with access to imaging, electrophysiologic, blood, and cerebrospinal fluid (CSF) biomarkers. Yet, the neurobiology of events that take place in the time between TBI and the first seizure of PTE, remains incompletely understood. This gap in knowledge about the mechanisms of posttraumatic epileptogenesis limits our capacity to develop successful antiepileptogenic interventions. As intriguing as the fundamental question of why PTE follows TBI after a seizure-free latent period, are the questions of why only a minority of patients with severe TBI, approximately 20%, develop PTE, and whether a biomarker measure may predict individual PTE likelihood. The selection for the 2015 Epilepsia Prize from Diamond et al., “IL-1b associations with posttraumatic epilepsy development: A genetics and biomarker cohort study,” addresses these important questions. The authors studied a sizeable (n = 256) and relatively homogenous cohort of patients with moderate-to-severe TBI who were part of an otherwise larger group enrolled in a study aimed to evaluate the contributions of genetics and related biomarkers to post-TBI outcomes. PTE developed in 16.4% of this group. Based on a growing literature that implicates autoimmune and inflammatory mechanisms in post-TBI pathophysiology, including in posttraumatic epileptogenesis, they formulated and tested a hypothesis that IL1b concentrations in the CSF and in serum are predictive of AcceptedMay 4, 2015; Early View publication June 15, 2015. Department of Neurology, Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A. Address correspondence to Alexander Rotenberg, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children’s Hospital, 300 Longwood Avenue, Fegan 9, BCH 3063, Boston, MA 02115, U.S.A.