Post-traumatic epilepsy: current and emerging treatment options

Neuropsychiatric Disease and Treatment Dovepress open access to scientific and medical research Review Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Open Access Full Text Article Post-traumatic epilepsy: current and emerging treatment options This article was published in the following Dove Press journal: Neuropsychiatric Disease and Treatment 11 August 2014 Number of times this article has been viewed Jerzy P Szaflarski 1,3 Yara Nazzal 1,3 Laura E Dreer 2 Department of Neurology, Department of Ophthalmology, 3UAB Epilepsy Center, University of Alabama at Birmingham, Birmingham, AL, USA 1 2 Introduction Correspondence: Jerzy P Szaflarski UAB Epilepsy Center, University of Alabama at Birmingham, 312 Civitan International Research Center, 1719 6th Avenue South, Birmingham, AL 35294-0021, USA Email In about 6% of patients with epilepsy, seizures are thought to be the result of previous head trauma; frequently, seizures in these patients are difficult to control with standard antiepileptic drugs (AEDs).1 The presence of early and late seizures has significant effect on subsequent outcomes, including medication use, quality of life, employment, and psychosocial adjustment. In these patients, the original insult is frequently identified from the history, but the severity of the injury may be difficult to judge. Based on studies conducted over the last several decades, patients who have suffered moderate or severe traumatic brain injury (TBI) are typically placed on an AED right after the initial trauma, usually phenytoin (PHT), but more recently also on levetiracetam (LEV), in order to alter the progression of epileptogenesis to late seizures and epilepsy. If seizures are not present in the first 7 days after trauma, the AED is weaned, with an expectation that seizures will not occur in the future. Since the concept of seizure and epilepsy prevention after TBI is well established, it is incumbent upon us to determine 1469 submit your manuscript | www.dovepress.com Neuropsychiatric Disease and Treatment 2014:10 1469–1477 Dovepress © 2014 Szaflarski et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/NDT.S50421 Powered by TCPDF (www.tcpdf.org) Abstract: Traumatic brain injury (TBI) leads to many undesired problems and complications, including immediate and long-term seizures/epilepsy, changes in mood, behavioral, and personality problems, cognitive and motor deficits, movement disorders, and sleep problems. Clinicians involved in the treatment of patients with acute TBI need to be aware of a number of issues, including the incidence and prevalence of early seizures and post-traumatic epilepsy (PTE), comorbidities associated with seizures and anticonvulsant therapies, and factors that can contribute to their emergence. While strong scientific evidence for early seizure prevention in TBI is available for phenytoin (PHT), other antiepileptic medications, eg, levetiracetam (LEV), are also being utilized in clinical settings. The use of PHT has its drawbacks, including cognitive side effects and effects on function recovery. Rates of recovery after TBI are expected to plateau after a certain period of time. Nevertheless, some patients continue to improve while others deteriorate without any clear contributing factors. Thus, one must ask, ‘Are there any actions that can be taken to decrease the chance of post-traumatic seizures and epilepsy while minimizing potential short- and long-term effects of anticonvulsants?’ While the answer is ‘probably,’ more evidence is needed to replace PHT with LEV on a permanent basis. Some have proposed studies to address this issue, while others look toward different options, including other anticonvulsants (eg, perampanel or other AMPA antagonists), or less established treatments (eg, ketamine). In this review, we focus on a comparison of the use of PHT versus LEV in the acute TBI setting and summarize the clinical aspects of seizure prevention in humans with appropriate, but general, references to the animal literature. Keywords: traumatic brain injury, TBI, seizures, epilepsy, seizure prevention, cognition, EEG, antiepileptic drugs Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Szaflarski et al not only which factors, when present or absent in the latent period (time between trauma and late seizures), are important for initiating and completing the cascade of events that eventually lead to seizure occurrence, but also how we can modulate or abort this process so that seizures never occur. It is imperative to develop strategies that change the process of epileptogenesis while concurrently decreasing the chance of the development of unwanted comorbidities (eg, worsening of cognitive deficits related to TBI and AEDs). Finally, it is important to be mindful of the financial implications – PHT was found to be more cost effective than LEV in a setting of seizure prevention after TBI, but this gap may be disappearing with the costs becoming similar in the recent years, and this calculation did not take into account the effects of these treatments on long-term costs.2 In this review focusing on the comparison between PHT and LEV, we summarize the clinical aspects of seizure prevention in humans, with appropriate but general references to animal literature, and provide brief discussion of potential new developments. Epidemiology of early vs late post-traumatic epilepsy The epidemiology of post-traumatic epilepsy (PTE) is well established. Early seizures are defined as seizures occurring in the first 7 days of trauma, while PTE is defined as seizures occurring after this period.3 The incidence of early seizures after TBI is reported to be between 2.6% and 16.3%, with the differences being dependent mainly on study design.3,4 At least in univariate analysis, the presence of early seizures predisposes the development of late PTE; overall early seizures are thought of as an epiphenomenon and a result of an acute injury, with their presence not necessarily equating with the development of late PTE.3,4 In fact, the pathophysiologic mechanisms leading to early post-traumatic seizures are not clearly understood, and multiple factors are thought to play a role, including interruption of the blood–brain barrier, pr (...truncated)