Epilepsy & behavior : E&B
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Epilepsy & behavior : E&B · Aug 2017
MEG language lateralization in partial epilepsy using dSPM of auditory event-related fields.
Methods employed to determine hemispheric language dominance using magnetoencephalography (MEG) have differed significantly across studies in the choice of language-task, the nature of the physiological response studied, recording hardware, and source modeling methods. Our goal was to determine whether an analysis based on distributed source modeling can replicate the results of prior studies that have used dipole-modeling of event-related fields (ERFs) generated by an auditory word-recognition task to determine language dominance in patients with epilepsy. ⋯ In a parietal region that includes the angular and supramarginal gyri, language laterality estimates based on dSPM of ERFs during auditory word-recognition shows a degree of MEG-fMRI concordance that is comparable to previously published estimates for MEG-Wada concordance using dipole counting methods and the same task. Our data also suggest that MEG language laterality estimates based on this task may be influenced by the laterality of epileptic networks in some patients. This has not been reported previously and deserves further study.
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Epilepsy & behavior : E&B · Jun 2017
Randomized Controlled TrialPharmacokinetics, pharmacodynamics, and tolerability of USL261, midazolam nasal spray: Randomized study in healthy geriatric and non-geriatric adults.
Characterize pharmacokinetics, pharmacodynamics, and safety/tolerability of USL261 in geriatric adults to inform its potential for treating bouts of increased seizure activity. ⋯ Despite increased midazolam exposure in geriatric subjects, there were no differences between age groups in pharmacodynamic effects or adverse event rates. USL261 was rapidly absorbed and pharmacodynamic effects returned to baseline within ~4h, regardless of age. Dose-dependent pharmacokinetic and maximum pharmacodynamic effects were observed. Overall, pharmacokinetic findings for USL261 were similar to studies evaluating intravenous midazolam, whereas pharmacodynamic effects were less pronounced in the elderly than previously reported.
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Treatment-resistant epilepsy (TRE) affects 30% of epilepsy patients and is associated with severe morbidity and increased mortality. Cannabis-based therapies have been used to treat epilepsy for millennia, but only in the last few years have we begun to collect data from adequately powered placebo-controlled, randomized trials (RCTs) with cannabidiol (CBD), a cannabis derivative. Previously, information was limited to case reports, small series, and surveys reporting on the use of CBD and diverse medical marijuana (MMJ) preparations containing: tetrahydrocannabinol (THC), CBD, and many other cannabinoids in differing combinations. ⋯ On the other hand, open-label studies with 100mg/ml CBD (Epidiolex®, GW Pharmaceuticals) have provided additional evidence of its efficacy along with an adequate safety profile (including certain drug interactions) in children and young adults with a spectrum of TREs. Further, Phase 3 RCTs with Epidiolex support efficacy and adequate safety profiles for children with DS and LGS at doses of 10- and 20-mg/kg/day. This article is part of a Special Issue titled "Cannabinoids and Epilepsy".
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Epilepsy & behavior : E&B · May 2017
ReviewTherapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.
The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. ⋯ Moreover, risks and/or benefits associated with the use of unlicensed Δ9-THC containing marijuana extracts in pediatric epilepsies remain poorly understood. Therefore, in light of these paradigm-changing clinical events, the present review's findings aim to drive future drug development for newly-identified targets and indications, identify important limitations of animal models in the investigation of plant cannabinoid effects in the epilepsies, and focuses future research in this area on specific, unanswered questions regarding the complexities of endocannabinoid signaling in epilepsy. This article is part of a Special Issue titled Cannabinoids and Epilepsy.
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It is critically important to identify all factors that may play a role in the recent increase of the incidence of stroke among the young population. Considering the worldwide use of cannabinoids (cannabis and synthetic cannabinoids), the recent legalization of their consumption in some countries, and their supposed involvement in cardiovascular events, we evaluated their role in the occurrence of neurovascular complications among the young. Ninety-eight patients were described in the literature as having a cannabinoids-related stroke (85 after cannabis use and 13 after synthetic cannabinoids). ⋯ CT-angiography or cerebral MRA) in order to search for cerebral vasoconstriction. However, several questions remained unresolved and further research is still needed to assess the pathophysiological mechanisms involved in young cannabinoids users with stroke. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".