Epilepsia
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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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HLA-B*15:02 screening is recommended before starting carbamazepine in Han Chinese and Southeast Asians because the allele is strongly predictive of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) induced by the drug. We examined whether other HLA-B alleles are also involved and whether the association extends to other antiepileptic drugs (AEDs). ⋯ SJS/TEN induced by carbamazepine and phenytoin is strongly and moderately associated with HLA-B*15:02 in Han Chinese, respectively. Possible protective associations with HLA-B*40:01 and HLA-B*58:01 warrant further investigation.
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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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The management of epilepsy in children is particularly challenging when seizures are resistant to antiepileptic medications, or undergo many changes in seizure type over time, or have comorbid cognitive, behavioral, or motor deficits. Despite efforts to classify such epilepsies based on clinical and electroencephalographic criteria, many children never receive a definitive etiologic diagnosis. Whole exome sequencing (WES) is proving to be a highly effective method for identifying de novo variants that cause neurologic disorders, especially those associated with abnormal brain development. Herein we explore the utility of WES for identifying candidate causal de novo variants in a cohort of children with heterogeneous sporadic epilepsies without etiologic diagnoses. ⋯ The finding that 7 of 10 children carried de novo mutations in genes of known or plausible clinical significance to neuronal excitability suggests that WES will be of use for the molecular genetic diagnosis of sporadic epilepsies in children, especially when seizures are of early onset and difficult to control.
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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.