Post-traumatic epilepsy: an overview. Clin Neurol Neurosurg

Department of Neurosurgery, K.S. Hegde Medical Academy, Deralakatte, 575018 Mangalore, Karnataka, India.
Clinical Neurology and Neurosurgery (Impact Factor: 1.13). 08/2006; 108(5):433-9. DOI: 10.1016/j.clineuro.2005.09.001
Source: PubMed


Post-traumatic epilepsy (PTE) is a recurrent seizure disorder secondary to brain injury following head trauma. PTE is not a homogeneous condition and can appear several years after the head injury. The mechanism by which trauma to the brain tissue leads to recurrent seizures is unknown. Cortical lesions seem important in the genesis of the epileptic activity, and early seizures are likely to have a different pathogenesis than late seizures. Anti-epileptic drugs available for treatment are phenytoin, sodium valproate, and carbamazepine. Newer anti-epileptics are helpful, particularly in patients with associated post-traumatic stress disorders; however, no randomized controlled studies are available to prove that one of these drugs is better than the other. Current evidence is that the treatment of early post-traumatic seizures does not influence the incidence of post-traumatic epilepsy. Routine preventive anticonvulsants are not indicated for patients with head injuries, and treatment in the acute phase does not reduce death or disability rates.

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Available from: Amit Agrawal, May 26, 2014
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    • "The hallmark of PTE is the development of spontaneous recurrent seizures. In humans, these seizures develop months to years following the initial injury [56] . The progressive development of PTE suggests an evolving process that may begin early after injury. "
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    ABSTRACT: Following a traumatic brain injury (TBI), 5-50% of patients will develop posttraumatic epilepsy (PTE) with children being particularly susceptible. Currently, PTE cannot be prevented and there is limited understanding of the underlying epileptogenic mechanisms. We hypothesize that early after TBI the brain undergoes distinct cellular and synaptic reorganization that facilitates cortical excitability and promotes the development of epilepsy. To examine the effect of pediatric TBI on cortical excitability, we performed controlled cortical impact (CCI) on juvenile rats (postnatal day 17). Following CCI, animals were monitored for the presence of epileptiform activity by continuous in vivo electroencephalography (EEG) and/or sacrificed for in vitro whole-cell patch-clamp recordings. Following a short latent period, all animals subjected to CCI developed spontaneous recurrent epileptiform activity within 14 days. Whole-cell patch-clamp recordings of layer V pyramidal neurons showed no changes in intrinsic excitability or spontaneous excitatory postsynaptic currents (sEPSCs) properties. However, the decay of spontaneous inhibitory postsynaptic currents (sIPSCs) was significantly increased. In addition, CCI induced over a 300% increase in excitatory and inhibitory synaptic bursting. Synaptic bursting was prevented by blockade of Na+-dependent action potentials or select antagonism of glutamate or GABA-A receptors, respectively. Our results demonstrate that CCI in juvenile rats rapidly induces epileptiform activity and enhanced cortical synaptic bursting. Detection of epileptiform early after injury suggests it may be an important pathophysiological component and potential indicator of developing PTE. © 2014 John Wiley & Sons Ltd.
    Full-text · Article · Dec 2014 · CNS Neuroscience & Therapeutics
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    • "The development of TLE following TBI, accounts for 20% of symptomatic epilepsy (Agrawal et al., 2006). Evidence of increased Akt activation within the hippocampus as well as other regions has been observed following TBI (Zhang et al., 2006; Zhao et al., 2012). "
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    ABSTRACT: Aberrant ion channel function has been heralded as a main underlying mechanism driving epilepsy and its symptoms. However, it has become increasingly clear that treatment strategies targeting voltage-gated sodium or calcium channels merely mask the symptoms of epilepsy without providing disease-modifying benefits. Ion channel function is likely only one important cog in a highly complex machine. Gross morphological changes, such as reactive sprouting and outgrowth, may also play a role in epileptogenesis. Mechanisms responsible for these changes are not well-understood. Here we investigate the potential involvement of the neurite outgrowth-promoting molecule collapsin response mediator protein 2 (CRMP2). CRMP2 activity, in this respect, is regulated by phosphorylation state, where phosphorylation by a variety of kinases, including glycogen synthase kinase 3 β (GSK3β) renders it inactive. Phosphorylation (inactivation) of CRMP2 was decreased at two distinct phases following traumatic brain injury (TBI). While reduced CRMP2 phosphorylation during the early phase was attributed to the inactivation of GSK3β, the sustained decrease in CRMP2 phosphorylation in the late phase appeared to be independent of GSK3β activity. Instead, the reduction in GSK3β-phosphorylated CRMP2 was attributed to a loss of priming by cyclin-dependent kinase 5 (CDK5), which allows for subsequent phosphorylation by GSK3β. Based on the observation that the proportion of active CRMP2 is increased for up to 4 weeks following TBI, it was hypothesized that it may drive neurite outgrowth, and therefore, circuit reorganization during this time. Therefore, a novel small-molecule tool was used to target CRMP2 in an attempt to determine its importance in mossy fiber sprouting following TBI. In this report, we demonstrate novel differential regulation of CRMP2 phosphorylation by GSK3β and CDK5 following TBI.
    Full-text · Article · May 2014 · Frontiers in Cellular Neuroscience
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    • "As such, human post-traumatic seizures are often classified according to the time of their presentation after injury: immediate or impact-associated (<24 h after injury), early (<1 week after injury), and late (>1 week after injury; Haltiner et al., 1997; Frey, 2003; Agrawal et al., 2006). This classification scheme is thought to represent different pathophysiological processes (Semah et al., 1998; Agrawal et al., 2006). Understanding the epileptogenic process after TBI should help to elucidate the importance of these cellular mechanisms in PTE and promote new therapeutic targets. "
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    ABSTRACT: Traumatic brain injury (TBI) greatly increases the risk for a number of mental health problems and is one of the most common causes of medically intractable epilepsy in humans. Several models of TBI have been developed to investigate the relationship between trauma, seizures, and epilepsy-related changes in neural circuit function. These studies have shown that the brain initiates immediate neuronal and glial responses following an injury, usually leading to significant cell loss in areas of the injured brain. Over time, long-term changes in the organization of neural circuits, particularly in neocortex and hippocampus, lead to an imbalance between excitatory and inhibitory neurotransmission and increased risk for spontaneous seizures. These include alterations to inhibitory interneurons and formation of new, excessive recurrent excitatory synaptic connectivity. Here, we review in vivo models of TBI as well as key cellular mechanisms of synaptic reorganization associated with post-traumatic epilepsy (PTE). The potential role of inflammation and increased blood-brain barrier permeability in the pathophysiology of PTE is also discussed. A better understanding of mechanisms that promote the generation of epileptic activity versus those that promote compensatory brain repair and functional recovery should aid development of successful new therapies for PTE.
    Full-text · Article · Jun 2013 · Frontiers in Cellular Neuroscience
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