Traumatic brain injury and epilepsy: Underlying mechanisms leading to seizure

Abstract

Post-traumatic epilepsy continues to be a major concern for those experiencing traumatic brain injury. Post-traumatic epilepsy accounts for 10-20% of epilepsy cases in the general population. While seizure prophylaxis can prevent early onset seizures, no available treatments effectively prevent late-onset seizure. Little is known about the progression of neural injury over time and how this injury progression contributes to late onset seizure development. In this comprehensive review, we discuss the epidemiology and risk factors for post-traumatic epilepsy and the current pharmacologic agents used for treatment. We highlight limitations with the current approach and offer suggestions for remedying the knowledge gap. Critical to this pursuit is the design of pre-clinical models to investigate important mechanistic factors responsible for post-traumatic epilepsy development. We discuss what the current models have provided in terms of understanding acute injury and what is needed to advance understanding regarding late onset seizure. New model designs will be used to investigate novel pathways linking acute injury to chronic changes within the brain. Important components of this transition are likely mediated by toll-like receptors, neuroinflammation, and tauopathy. In the final section, we highlight current experimental therapies that may prove promising in preventing and treating post-traumatic epilepsy. By increasing understanding about post-traumatic epilepsy and injury expansion over time, it will be possible to design better treatments with specific molecular targets to prevent late-onset seizure occurrence following traumatic brain injury.

Demographic and Clinical Findings of Epilepsy Patients who Underwent Follow-up at the Newly Established Clinic of the Muğla Sıtkı Koçman University Faculty of Medicine

“…Total "travma sonrası" epilepsi insidansı yaklaşık %2 iken, travmatik beyin hasarından beş yıl sonra insidansı %22-43 (ortalama %34) arasında değişmektedir. [6,7] Travma sonrası epilepside altta yatan mekanizma tam olarak bilinmemekle birlikte, yapılan deneysel çalışmalarda GABA-A kanal ve glutamat sinyalizasyonundaki değişikliklerin travmatik beyin hasarını izleyen erken dönem nöbetlerde rol oynayabileceğine dair kanıtlar vardır. [6,8] Febril konvülziyon öyküsü olan hastalarda epilepsi gelişme riski yaklaşık %3'tür.…”

“…[6,7] Travma sonrası epilepside altta yatan mekanizma tam olarak bilinmemekle birlikte, yapılan deneysel çalışmalarda GABA-A kanal ve glutamat sinyalizasyonundaki değişikliklerin travmatik beyin hasarını izleyen erken dönem nöbetlerde rol oynayabileceğine dair kanıtlar vardır. [6,8] Febril konvülziyon öyküsü olan hastalarda epilepsi gelişme riski yaklaşık %3'tür. [9] Epilepsi gelişim riski en çok komplike febril nöbette artar.…”

Monitoring the Neuroinflammatory Response Following Acute Brain Injury

“…Claassen and coworkers found an association between the inflammatory response following SAH (TNF-receptor 1 and high-sensitivity C-reactive protein) and the presence of seizures (129). Several reviews covering this field have been published, and all do suggest a strong link between neuroinflammatory cascades, increased excitotoxicity, and epileptogenesis in the aftermath of brain injury (130, 131). …”

GABA-ergic cell therapy for epilepsy: Advances, limitations and challenges

“…In such scenario, development of improvised donor cell preparation and grafting strategies that enhance the survival and integration of graft-derived interneurons in chronically epileptic brain regions is critical (Rao et al, 2006, 2007). Furthermore, efficacy of GABA-ergic cell grafting needs to be examined in post-traumatic or post-stroke epilepsy models because post-traumatic epilepsy accounts for 10–20% of epilepsy cases in the general population (Lucke-Wold et al, 2015) and post-stroke seizures are a frequent cause of remote symptomatic epilepsy in adults, especially in older age (Gilad, 2012). …”