Epilepsia
-
Prevention of posttraumatic epilepsy (PTE) is of primary importance to reduce the degree of functional morbidity following traumatic brain injury (TBI). However, the effects of antiepileptic drugs (AEDs) in patients with TBI must be assessed separately in terms of prevention and control of provoked seizures (which include immediate and early posttraumatic seizures) and prevention of subsequent unprovoked seizures (late posttraumatic seizures or PTE). ⋯ The failure to influence the risk of PTE in studies of patients with TBI are similar to findings of meta-analysis of randomized clinical trials on seizure prevention in other conditions, such as febrile seizures, cerebral malaria, craniotomy, and excessive alcohol intake. For these reasons, the prophylactic use of AEDs should be short-lasting and limited to the prevention of immediate and early seizures. Chronic treatment should be considered only after a diagnosis of PTE.
-
Annually in the U. S. about 500,000 head injuries are severe enough to require hospitalization. Past studies of severe head trauma estimate the risk of late seizures, which are synonymous with epilepsy, to be from 26 to 53%. ⋯ The data suggest that a limited time domain exists for VPA to intervene in the epileptogenic process, requiring the earliest possible intervention. We contend that protection from posttraumatic epileptogenesis can be conferred only if agents are given soon after trauma. A pilot study is proposed to begin to translate these findings to explore the feasibility of early VPA delivery to severe head trauma patients admitted to Kings County Hospital Center in Brooklyn, NY, a Level 1 trauma center.
-
Generalized epilepsy involves abnormally synchronized activity in large-scale neuronal networks. Burst firing of action potentials is a potent mechanism for increasing neural synchrony and is thought to enhance cortical and thalamic rhythmic network activity. Absence seizures, a form of generalized epilepsy, occur in children as brief 5- to 10-s periods of behavioral arrest associated with massive 3- to 4-Hz spike-wave discharges in cortical and thalamic networks. ⋯ Can enhanced burst firing in one region of the nervous system, such as the cortex, transform the entire thalamocortical network from normal activity to spike-and-wave seizures? Enhanced burst firing in corticothalamic neurons may increase gamma-aminobutyric acid-B (GABAB) receptor activation in the thalamus, leading to the slower, more synchronous oscillations seen in spike-and-wave seizures. Does "generalized" spike-wave activity homogeneously involve the entire brain, or are there crucial nodes that are more important than others for the generation and behavioral manifestations of generalized seizures? Animal and human data suggest that so-called generalized seizures involve selective thalamocortical networks while sparing others. A greater understanding of these molecular and network mechanisms will ultimately lead to improved targeted therapies for generalized epilepsy.
-
The occurrence of abnormal dynamics in a physiological system can become manifest as a sudden qualitative change in the behavior of characteristic physiologic variables. We assume that this is what happens in the brain with regard to epilepsy. We consider that neuronal networks involved in epilepsy possess multistable dynamics (i.e., they may display several dynamic states). To illustrate this concept, we may assume, for simplicity, that at least two states are possible: an interictal one characterized by a normal, apparently random, steady-state of ongoing activity, and another one that is characterized by the paroxysmal occurrence of a synchronous oscillations (seizure). ⋯ We present an overview of these basic models, based on neurophysiologic recordings combined with signal analysis and on simulations performed by using computational models of neuronal networks. We pay especial attention to recent model studies and to novel experimental results obtained while analyzing EEG features preceding limbic seizures and during intermittent photic stimulation that precedes the transition to paroxysmal epileptic activity.
-
Traumatic brain injury has long been known to be a cause of epilepsy. Most information on risk factors for developing posttraumatic seizures is from before computed tomography (CT) scanning became universal. This article looks at factors about the injury or individual that put people at especially high risk of developing posttraumatic seizures. ⋯ Both the risk factors and the time course of the risk are important for designing seizure-prophylaxis studies and, if an effective prophylactic regimen is identified, for deciding on appropriate candidates for prophylaxis.