• Bridgette D Semple, Akram Zamani, Genevieve Rayner, Sandy R Shultz, and Nigel C Jones.
• Department of Neuroscience, Monash University, 99 Commercial Road, Melbourne, VIC, Australia; Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Royal Parade, Parkville, VIC, Australia. Electronic address: bridgette.semple@monash.edu.
• Neurobiol. Dis. 2019 Mar 1; 123: 27-41.

AbstractSurvivors of traumatic brain injury (TBI) often develop chronic neurological, neurocognitive, psychological, and psychosocial deficits that can have a profound impact on an individual's wellbeing and quality of life. TBI is also a common cause of acquired epilepsy, which is itself associated with significant behavioral morbidity. This review considers the clinical and preclinical evidence that post-traumatic epilepsy (PTE) acts as a 'second-hit' insult to worsen chronic behavioral outcomes for brain-injured patients, across the domains of emotional, cognitive, and psychosocial functioning. Surprisingly, few well-designed studies have specifically examined the relationship between seizures and behavioral outcomes after TBI. The complex mechanisms underlying these comorbidities remain incompletely understood, although many of the biological processes that precipitate seizure occurrence and epileptogenesis may also contribute to the development of chronic behavioral deficits. Further, the relationship between PTE and behavioral dysfunction is increasingly recognized to be a bidirectional one, whereby premorbid conditions are a risk factor for PTE. Clinical studies in this arena are often challenged by the confounding effects of anti-seizure medications, while preclinical studies have rarely examined an adequately extended time course to fully capture the time course of epilepsy development after a TBI. To drive the field forward towards improved treatment strategies, it is imperative that both seizures and neurobehavioral outcomes are assessed in parallel after TBI, both in patient populations and preclinical models.Copyright © 2018 Elsevier Inc. All rights reserved.

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