Epilepsia
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Animal models of chronic epilepsy with spontaneous recurrent seizures (SRSs) may be useful in the discovery and mechanistic analyses of antiseizure drugs (ASDs). Carbamazepine (CBZ), a widely used ASD with a well-defined mechanism, was analyzed in this proof-of-principle study to determine how a traditional ASD affects the properties of SRSs. ⋯ Increased doses of CBZ (10-100 mg/kg) suppressed the frequency but not the duration of convulsive and nonconvulsive seizures in the repeated, low-dose kainate model. The repeated-measures, crossover protocol, which requires relatively few animals and compensates for progressive increases in seizure frequency during epileptogenesis after status epilepticus, allowed quantitative analyses of clinically relevant and translatable properties of SRSs.
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Observational Study
Response to antiseizure medications in neonates with acute symptomatic seizures.
In a prospective cohort of 534 neonates with acute symptomatic seizures, 66% had incomplete response to the initial loading dose of antiseizure medication (ASM). Treatment response did not differ by gestational age, sex, medication, or dose. The risk of incomplete response was highest for seizures due to intracranial hemorrhage and lowest for hypoxic-ischemic encephalopathy, although the difference was not significant after adjusting for high seizure burden and therapeutic hypothermia treatment. Future trial design may test ASMs in neonates with all acute symptomatic seizure etiologies and could target neonates with seizures refractory to an initial ASM.
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Randomized Controlled Trial
Cannabidiol in patients with Lennox-Gastaut syndrome: Interim analysis of an open-label extension study.
Patients with Lennox-Gastaut syndrome (LGS) who completed 1 of 2 randomized, double-blind, placebo-controlled trials of add-on cannabidiol (CBD) (GWPCARE3, NCT02224560 or GWPCARE4, NCT02224690) were invited to enroll in an open-label extension (OLE) study evaluating the long-term safety and efficacy of CBD (GWPCARE5, NCT02224573). Herein we present an interim analysis of the safety, efficacy, and patient-reported outcomes from this trial. ⋯ In this study, long-term add-on CBD treatment had an acceptable safety profile in patients with LGS and led to sustained reductions in seizures.
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Recent evidence suggests that three specific brain networks show state-dependent levels of synchronization before, during, and after episodes of generalized spike-wave discharges (GSW) in patients with genetic generalized epilepsy (GGE). Here, we investigate whether synchronization in these networks differs between patients with GGE (n = 13), their unaffected first-degree relatives (n = 17), and healthy controls (n = 18). All subjects underwent two 10-minute simultaneous electroencephalographic-functional magnetic resonance imaging (fMRI) recordings without GSW. ⋯ There was a trend toward higher synchrony in the GSW network in patients and in unaffected relatives. There was no difference between groups for the occipital network. Our findings provide evidence that elevated fMRI BOLD synchrony in a sensorimotor network is a state-independent endophenotype of GGE, present in patients in the absence of GSW, and present in unaffected relatives.
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Randomized Controlled Trial
Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial.
Add-on cannabidiol (CBD) significantly reduced seizures associated with Dravet syndrome (DS) in a randomized, double-blind, placebo-controlled trial: GWPCARE1 Part B (NCT02091375). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or a second placebo-controlled trial, GWPCARE2 (NCT02224703), were invited to enroll in a long-term open-label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient-reported outcomes from GWPCARE5. ⋯ This trial shows that long-term CBD treatment had an acceptable safety profile and led to sustained, clinically meaningful reductions in seizure frequency in patients with treatment-resistant DS.