No abstract

Summary: Purpose:In limbic or mesial temporal lobe epilepsy, much attention has been given to specific regions or cell populations (e.g., the hippocampus or dentate granule cells). Epileptic seizures may involve broader changes in neural circuits, and evidence suggests that subcortical regions may play a role. In this study we examined the midline thalamic regions for involvement in limbic seizures, changes in anatomy and physiology, and the potential role for this region in limbic seizures and epilepsy Methods: Using two rat models for limbic epilepsy (hippocampal kindled and chronic spontaneous limbic epilepsy) we examined the midline thalamus for evidence of involvement in seizure activity, alterations in structure, changes in the basic in vitro physiology of the thalamic neurons. We also explored how this region may influence limbic seizures. Results:The midline thalamus was consistently involved with seizure activity from the onset, and there was significant neuronal loss in the medial dorsal and reuniens/rhomboid nuclei. In addition, thalamic neurons had changes in synaptically mediated and voltage-gated responses. Infusion of lidocaine into the midline thalamus significantly shortened afterdischarge duration.Conclusions: These observations suggest that this thalamic region is part of the neural circuitry of limbic epilepsy and may play a significant role in seizure modulation. Local neuronal changes can enhance the excitability of the thalamolimbic circuits.

No abstract

Summary:Kindling is one of the most widely used models of seizures and epilepsy, and it has been used in its more than three decade history to provide many key insights into seizures and epilepsy. It remains a mainstay of epilepsy related research, but the question remains how the results from kindling experiments further our understanding of the underlying neurobiology of human epilepsy. In this article we compare the basic features of kindling and human epilepsy, especially human limbic or temporal lobe epilepsy. In this review we focus on a limited number of topics that may show areas in which kindling has been often cited as a tool for better understanding of human epilepsy. These areas include the underlying circuits, the importance of seizure spontaneity, the associated neuropathology, the contribution of genetics, seizure susceptibility, and the underlying pathophysiology of epilepsy. In the course of this article we will show that there are many features that kindling can teach us by direct comparison or implication about human temporal epilepsy. We will also see that not all findings associated with kindling may be applicable to the human condition. Ultimately we wish to encourage critical thinking about kindling and the similarities that it shares and does not share with the human epilepsy so the results from studies using this model are applied rationally to further our insights the mechanisms of human epilepsy. Key Words: Kindling-Epilepsy-Animal models of human disease.This first paragraph is a disclaimer. One should be wary of articles and authors that start with disclaimers. What follows is a very personal view of kindling and what it can teach us about human epilepsy. The article starts philosophically from the perspective of human epilepsy and its neurobiology, based on the idea that we use models of human disorders to understand the mechanisms of the disorder that we cannot study directly in people. The logic then follows that to understand the human condition, the model ideally must have identical features. If the features are not identical, then, before one draws conclusions from the model, one must be very specific about how exactly the two states match and how they differ. Otherwise one risks the potential of drawing conclusions that may be inappropriate for the clinical situation. It is in this light that this article is written. It is highly selective in the issues discussed, and no doubt somewhat biased in its presentation. But it is based on some thought of what are some of the issues that are important in understanding human epilepsy, and then using those issues to compare reality to the model. The reader will no doubt notice the limited topics as well as the relatively sparse referencing, especially for a subject that has been researched as much as this one. There are no doubts some readers who will object significantly to some of the conclusions that are drawn, and "intense" discussions may ensue. Those objections are a good thing, because it is the ferment of scientific disagreement...

Surgery has become the standard of care for patients with intractable temporal lobe epilepsy with anterior temporal lobe resection the most common operation performed for adults with hippocampal sclerosis. This procedure leads to significant improvement in the lives of the overwhelming majority of patients. Despite improved techniques in neuroimaging that have facilitated the identification of potential surgical candidates, the short and long term success of epilepsy surgery has not changed substantially in recent decades. The basic surgical goal, removal of the amygdala, hippocampus, and parahippocampal gyrus, is based on the hypothesis that these structures represent a uniform and contiguous source of seizures in the mesial temporal lobe epilepsy syndrome. Recent observations from the histopathology of resected tissue, preoperative neuroimaging and the basic science laboratory suggest that the syndrome is not always a uniform entity. Despite clinical similarity, not all patients become seizure free. Improving surgical outcomes requires a re-examination of why patients fail surgery. This review will examine recent findings from the clinic and laboratory. Historically, we have considered MTLE a single disorder, but it may be time to view it as a group of closely related syndromes with variable type and extent of histopathology. That recognition may lead to identifying the appropriate subgroups that will require different diagnostic and surgical approaches to improve surgical outcomes.