Epilepsia
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Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. ⋯ Our data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS.
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Functional magnetic resonance imaging (fMRI)-based resting functional connectivity is well suited for measuring slow correlated activity throughout brain networks. Epilepsy involves chronic changes in normal brain networks, and recent work demonstrated enhanced resting fMRI connectivity between the hemispheres in childhood absence epilepsy. An animal model of this phenomenon would be valuable for investigating fundamental mechanisms and testing therapeutic interventions. ⋯ These findings suggest that activity-dependent plasticity may lead to long-term changes in epileptic networks even at rest. The results show a marked difference between the epileptic and nonepileptic animals in cortical-cortical connectivity, indicating that this may be a useful interictal biomarker associated with the epileptic state.
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Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug-resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. ⋯ HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA1 predominant HS ILAE type 2 and CA4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control.
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Comparative Study Clinical Trial
Intravenous topiramate: comparison of pharmacokinetics and safety with the oral formulation in healthy volunteers.
Although oral topiramate (TPM) products are widely prescribed for migraines and epilepsy, injectable TPM is not available for human use. We have developed a solubilized TPM formulation using a cyclodextrin matrix, Captisol with the long-term goal of evaluating its safety and efficacy in neonatal seizures. This study in healthy adult volunteers was performed as required by the U.S. Food and Drug Administration (FDA) to demonstrate the pharmacokinetics and safety prior to initiation of studies involving children. This study allowed investigation of absolute bioavailability, absolute clearance, and distribution volume of TPM, information that could not be obtained without using an intravenous TPM formulation. ⋯ In healthy adults, oral TPM is bioequivalent to intravenous TPM, and infusion of 50-100 mg over 15 min is safe. Neurologic effects occurred during the infusion, demonstrating that TPM rapidly diffuses into the brain, which supports its evaluation for neonatal seizures. Results from this pilot study will inform the design of subsequent studies in children and newborns, including controlled clinical trials intended to assess the efficacy and safety of intravenous TPM for neonatal seizures. In addition, our results provide support for the further development of intravenous TPM as bridge therapy for older children and adults in whom oral TPM therapy is interrupted.
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The white matter (WM) is considered critical for linking cortical processing networks necessary for cognition. The aim of this study was to assess diffusion tensor imaging (DTI) measures of regional WM in children with nonlesional localization-related epilepsy in comparison to controls, and to determine the relation between lobar WM and neuropsychological performance. ⋯ There was widespread regional WM abnormality in children with nonlesional localization-related epilepsy, which was associated with impaired neuropsychological function. The impairment in WM may reflect disruption in the connectivity for cortical processing networks, which is necessary for the development of cognition.