Pharmacokinetics of Staccato alprazolam in healthy adult participants in two phase 1 studies: An open-label smoker study and a randomized, placebo-controlled ethnobridging study.

Objective: Staccato alprazolam is a single-use, drug-device combination delivering alprazolam to the deep lung that is being evaluated as treatment for rapid and early seizure termination. This article reports pharmacokinetic (PK) data from two phase 1 studies of Staccato alprazolam in healthy adult participants.

Methods: The smoker study (EPK-002/NCT03516305) was an open-label, nonrandomized, single-dose, PK study in smokers and nonsmokers aged 21-50 years, administered a single inhaled dose of 1 mg Staccato alprazolam.

Predicting seizure recurrence after an initial seizure-like episode from routine clinical notes using large language models: a retrospective cohort study.

Background: The evaluation and management of first-time seizure-like events in children can be difficult because these episodes are not always directly observed and might be epileptic seizures or other conditions (seizure mimics). We aimed to evaluate whether machine learning models using real-world data could predict seizure recurrence after an initial seizure-like event.

Methods: This retrospective cohort study compared models trained and evaluated on two separate datasets between Jan 1, 2010, and Jan 1, 2020: electronic medical records (EMRs) at Boston Children's Hospital and de-identified, patient-level, administrative claims data from the IBM MarketScan research database.

Optical coherence tomography in autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a rare neurodegenerative disorder caused by mutations in the SACS gene. Thickened retinal nerve fibres visible on fundoscopy have previously been described in these patients; however, thickening of the retinal nerve fibre layer as demonstrated by optical coherence tomography appears to be a more sensitive and specific feature. To test this observation, we assessed 292 individuals (191 patients with ataxia and 101 control subjects) by peripapillary time-domain optical coherence tomography.

Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.

Objective: Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy.

Methods: Three hundred people with epilepsy attending specialist clinics and 90 healthy controls were included in this cross-sectional cohort study.

Epilepsy treatment: a paradigm shift is urgently need.

Epilepsy affects between 5 and 10 people in a 1,000 and carries considerable morbidity and premature mortality. The complex inheritance pattern of a lowered seizure threshold is not fully understood but is likely to be polygenic. In the majority of people with epilepsy, we do not understand the pathophysiology, how a seizure is triggered, and how it can be prevented.

Altered distribution of striatal activity-dependent synaptic plasticity in the 3-nitropropionic acid model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder characterized by involuntary choreiform movements, neuropsychiatric disturbances and cognitive decline. The hyperkinetic phenomenology has commonly been attributed to a disturbance of the basal ganglia function, mainly the neostriatum, but its pathophysiology mechanisms remain unclear. Activity-dependent long-term changes in synaptic efficacy, such as long-term potentiation (LTP) and long-term depression (LTD), are widely considered to be the cellular models for acquisition and storage of information in neuronal networks.