Epilepsy research
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Intra-operative electrocorticography (ECoG) is useful in epilepsy surgery to delineate margins of epileptogenic zone, guide resection and evaluate completeness of resection in surgically remediable intractable epilepsies. The study evaluated 157 cases (2000-2008). The preoperative evaluation also included ictal SPECT (122) and PET in 32 cases. ⋯ The improvement in ECoG correlated significantly with clinical improvement [Sensitivity: 100% (95% CI; 96-100%); specificity: 68.3% (95% CI; 51.8-81.4%); positive predictive value: 89.9% (95% CI, 83.1-94.3%); negative predictive value: 100% (95% CI, 85-100%)]. The level of agreement was 91.72% (kappa: 0.76). Concluding, pre and post resection ECoG correlated with its grade of severity and clinical outcome.
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Direct brain stimulation is an emerging treatment of epilepsy especially in patients that are not candidates for epilepsy surgery. Several different approaches of brain stimulation in epilepsy have been developed: stimulation is applied to interrupt epileptic networks in subcortical structures or a stimulus is directly applied to the seizure onset zone. Scheduled stimulation targets mainly subcortical structures like the anterior thalamic nucleus or the centromedian nucleus of the thalamus. ⋯ An automated implanted device for seizures detection and stimulation has been developed and shown to be safe for human use. A large clinical trial is currently ongoing. In conclusion, the optimal target and mode of stimulation for the treatment of epilepsy remains under investigation and requires large and costly controlled trials.
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Exposure of the brain to a stressful stimulus that is sub-threshold for permanent injury can temporarily protect against cell death during a subsequent and otherwise damaging insult. One or more brief, non-harmful seizure episode(s) (seizure preconditioning) can dramatically reduce hippocampal damage when given prior to status epilepticus (epileptic tolerance). We recently reported that status epilepticus-induced hippocampal damage in C57BL/6 mice could be reduced by approximately 50% when preceded 24h earlier by a brief, non-injurious generalized seizure induced by 15mg/kg systemic kainic acid (KA). ⋯ Seizure preconditioning using 20mg/kg systemic KA, but not 15mg/kg, significantly reduced hippocampal damage after status epilepticus by 37% in the dorsal hippocampus and by 65% in the ventral hippocampus. These studies suggest status epilepticus induced by intra-amygdala KA in SJL mice models aspects of the pathophysiology of human mesial temporal sclerosis. Moreover, seizure preconditioning effectively produces neuroprotection in SJL mice, further establishing epileptic tolerance as a conserved endogenous neuroprotection paradigm.
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Mitochondrial oxidative stress and dysfunction are contributing factors to various neurological disorders. Recently, there has been increasing evidence supporting the association between mitochondrial oxidative stress and epilepsy. Although certain inherited epilepsies are associated with mitochondrial dysfunction, little is known about its role in acquired epilepsies such as temporal lobe epilepsy (TLE). ⋯ Mitochondria are the primary site of reactive oxygen species (ROS) production making them uniquely vulnerable to oxidative stress and damage which can further affect cellular macromolecule function, the ability of the electron transport chain to produce ATP, antioxidant defenses, mitochondrial DNA stability, and synaptic glutamate homeostasis. Oxidative damage to one or more of these cellular targets may affect neuronal excitability and increase seizure susceptibility. The specific targeting of mitochondrial oxidative stress, dysfunction, and bioenergetics with pharmacological and non-pharmacological treatments may be a novel avenue for attenuating epileptogenesis.
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Use of medication with a desired effect on the central nervous system (as with anti-epileptic drugs) in children will undoubtedly cause concern about neurodevelopment. Data are emerging to suggest an effect of anticonvulsants on the developing brain of the unborn child when administered to mothers with epilepsy. ⋯ Although data are available with regard to some anti-epileptic drugs (AEDs) they remain lacking particularly in the very young with regard to efficacy as well as neurodevelopmental effects of the newer anti-epileptic drugs. Ongoing evaluation is required to ensure the best clinical practice in each individual.