Epilepsia
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Observational Study
Anterior temporal encephaloceles: Elusive, important, and rewarding to treat.
To investigate the etiology and longitudinal clinical, neuropsychological, psychosocial, and surgical outcome profile of patients with medication refractory epilepsy and temporal encephaloceles with a view to highlight diagnostic clues and management strategies. ⋯ Genetic factors and a possible association with idiopathic intracranial hypertension (given female predominance and elevated BMI) may contribute to the causation of temporal lobe encephaloceles. It is notable that a targeted surgical approach in the management of patients with TLE associated with encephaloceles has an excellent long-term clinical and neuropsychological outcome. Subtle encephaloceles should be actively searched for in patients with drug-resistant TLE because they significantly change surgical strategy and prognostication.
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In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity. ⋯ Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.
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Approximately one-third of people living with epilepsy are unable to obtain seizure control with the currently marketed antiseizure medications (ASMs), creating a need for novel therapeutics with new mechanisms of action. Cenobamate (CBM) is a tetrazole alkyl carbamate derivative that received US Food and Drug Administration approval in 2019 for the treatment of adult partial onset (focal) seizures. Although CBM displayed impressive seizure reduction in clinical trials across all seizure types, including focal aware motor, focal impaired awareness, and focal to bilateral tonic-clonic seizures, the precise mechanism(s) through which CBM exerts its broad-spectrum antiseizure effects is not known. ⋯ CBM's preclinical performance in tests, including the mouse 6-Hz model of treatment-resistant seizures, the chemoconvulsant seizure models of generalized epilepsy, and the rat hippocampal kindling model of focal epilepsy, was distinct from other voltage-gated sodium channel blockers and GABAA modulators. This distinction, in light of its proposed mechanism(s) of action, provides insight into the impressive clinical efficacy of CBM in the adult patient with focal onset epilepsy. The results of this comparative reverse translational analysis suggest that CBM is a mechanistically distinct ASM that offers an important advancement in drug development for treatment of therapy-resistant epilepsy.
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Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy characterized by seizures occurring mostly during sleep, ranging from brief seizures with paroxysmal arousals (SPAs) to hyperkinetic seizures and ambulatory behaviors. SPAs are brief and stereotypic seizures representing the beginning of a major seizure. Distinguishing SPAs from disorders of arousal (DOAs) and their briefest episodes called simple arousal movements (SAMs) is difficult. We performed a characterization of SPAs and SAMs to identify video-polysomnographic (VPSG) features that can contribute to the diagnosis of SHE or DOA. ⋯ SPAs and SAMs present different semiological and clinical features. Their recognition could be useful to drive the diagnosis when major episodes are not recorded during VPSG in patients with a clear clinical history of SHE or DOA.
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The rapid spread of the SARS-CoV-2 pandemic poses particular challenges to the management of persons with chronic disease. Reports of a possible neuroinvasiveness of SARS-CoV-2 as well as pathophysiological mechanisms and indirect consequences in severe COVID-19 cases raise the question of whether the infection can be associated with an increased risk of seizure recurrence or the development of new onset and acute symptomatic seizures. Although the literature does not provide relevant evidence for seizure worsening in persons with epilepsy during the course of a SARS-CoV-2 infection, there are theoretical risks, for example, seizures triggered by fever. ⋯ This is further confirmed by reports of occasional seizures in COVID-19 patients. Although the low number of reports so far suggests that the risk may be relatively low, the reports indicate that an early neurological manifestation with seizures should not be ruled out. In the context of these cases, we discuss possible pathophysiological mechanisms that may trigger ictogenesis in patients with SARS-CoV-2 infection.