Epilepsy after penetrating brain injury

University Of Virginia, Charlottesville VA

Investigators

Abstract

Brain trauma is a common cause of epilepsy, especially trauma from penetrating injuries (e.g. gun shot wounds) in which 60% of the injury survivors may develop epilepsy. There are over 3000 surviving veterans of the recent wars with penetrating brain injuries, and an estimated 11,000 new head wound survivors in the American civilian population each year, so the potential for epilepsy among this group is significant. Data also suggest that severe head injury survivors have an increased risk for the later development of dementia. One of the established risk factors for subsequent epilepsy is the presence of foreign materials, including metallic fragments (e.g. copper and lead) from bullets. At present very little is known about the pathophysiology of this form of epilepsy and how the risk factors contribute to the development of the seizures. Copper and lead are toxic materials that have the potential to cause greater damage over the long term . We have recently developed a model of penetrating brain injury that has an incidence of epilepsy over 80%, and the presence of copper in the lesion is the critical factor, as the lesion alone has a much lower incidence of epilepsy. In addition to the epilepsy, these metal fragments also are associated with significant brain necrosis and volume loss over the 6 months that the animals were followed. This extensive added damage is not seen in lesioned animals without the added metal. These observations raise a number of questions about the causes of epilepsy, and they also have implications for the clinical care of the survivors of these injuries, especially if these metals cause further damage beyond the initial injury. Before we can start to investigate the many mechanistic questions about the progressive injuries and the development of epilepsy, we have to focus on two fundamental issues which will set the direction for all subsequent studies and which may help direct future clinical care. The questions in this project are 1) Is it the duration of the exposure to the toxic metals that lead to epilepsy? and 2) Is the extent of the damage associated with copper and lead related to the duration of exposure to the metals? The central hypothesis for this project is The damage and the epilepsy related to the presence retained toxic metal fragments result from the duration of exposure to the metals. We will answer these questions with our new model of post traumatic epilepsy by first creating a penetrating injury in rats, adding to the injury stainless steel (control), lead or copper and evaluating the animals for the development of epilepsy and the severity of the injury following predetermined exposures to the two metals. Determining that the severity of damage and the development of epilepsy are influenced by the length of exposure will have a significant impact on clinical care directed to reducing the risks for epilepsy and long term functional deterioration. The results will also provide a basis for more in depth future studies on the mechanisms of this type of acquired focal epilepsy.