Ultra-Low Level Somatic Mutations and Structural Variations in Focal Cortical Dysplasia Type II.

Objective: Brain somatic mutations in mTOR pathway genes are a major genetic etiology of focal cortical dysplasia type II (FCDII). Despite a greater ability to detect low-level somatic mutations in the brain by deep sequencing and analytics, about 40% of cases remain genetically unexplained.

Methods: We included 2 independent cohorts consisting of 21 patients with mutation-negative FCDII without apparent mutations on conventional deep sequencing of bulk brain.

Frequency of and factors associated with antiseizure medication discontinuation discussions and decisions in patients with epilepsy: A multicenter retrospective chart review.

Objective: Guidelines suggest considering antiseizure medication (ASM) discontinuation in patients with epilepsy who become seizure-free. Little is known about how discontinuation decisions are being made in practice. We measured the frequency of, and factors associated with, discussions and decisions surrounding ASM discontinuation.

Computer-assisted analysis of routine electroencephalogram to identify hidden biomarkers of epilepsy: protocol for a systematic review.

Introduction: The diagnosis of epilepsy frequently relies on the visual interpretation of the electroencephalogram (EEG) by a neurologist. The hallmark of epilepsy on EEG is the interictal epileptiform discharge (IED). This marker lacks sensitivity: it is only captured in a small percentage of 30 min routine EEGs in patients with epilepsy.

Adaptive Remote Sensing Paradigm for Real-Time Alerting of Convulsive Epileptic Seizures.

Epilepsy is a debilitating neurological condition characterized by intermittent paroxysmal states called fits or seizures. Especially, the major motor seizures of a convulsive nature, such as tonic-clonic seizures, can cause aggravating consequences. Timely alerting for these convulsive epileptic states can therefore prevent numerous complications, during, or following the fit.

Cost-effectiveness of cenobamate for focal seizures in people with drug-resistant epilepsy.

Objective: This study was undertaken to estimate the cost-effectiveness of add-on cenobamate in the UK when used to treat drug-resistant focal seizures in adults who are not adequately controlled with at least two prior antiseizure medications, including at least one used adjunctively.

Methods: We estimated the cost per quality-adjusted life-year (QALY) for cenobamate compared to brivaracetam, eslicarbazepine, lacosamide, and perampanel in the UK National Health Service over a lifetime time horizon. We used a Markov cohort structure to determine response to treatment, using pooled data from three long-term studies of cenobamate.

Verbal fluency functional magnetic resonance imaging detects anti-seizure effects and affective side effects of perampanel in people with focal epilepsy.

Perampanel, a noncompetitive antagonist of the postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping-derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in anti-seizure medication (ASM) regimen in-between.

The spatial relationship between the MRI lesion and intraoperative electrocorticography in focal epilepsy surgery.

MRI and intraoperative electrocorticography are often used in tandem to delineate epileptogenic tissue in resective surgery for focal epilepsy. Both the resection of the MRI lesion and tissue with high rates of electrographic discharges on electrocorticography, e.g.

Psychomotor Vigilance Performance in Participants with Excessive Daytime Sleepiness in Obstructive Sleep Apnea or Narcolepsy Compared with SAFTE-FAST Model Predictions.

Introduction: Excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA) can impair vigilance/attention. Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved to treat EDS associated with narcolepsy (75-150 mg/day) or OSA (37.5-150 mg/day).

Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment.

Advance care planning (ACP) in glioblastoma patients: Evaluation of a disease-specific ACP program and impact on outcomes.

Background: The feasibility of implementing an advance care planning (ACP) program in daily clinical practice for glioblastoma patients is unknown. We aimed to evaluate a previously developed disease-specific ACP program, including the optimal timing of initiation and the impact of the program on several patient-, proxy-, and care-related outcomes.

Methods: The content and design of the ACP program were evaluated, and outcomes including health-related quality of life (HRQoL), anxiety and depression, and satisfaction with care were measured every 3 months over 15 months.

Psychiatric comorbidities among people with epilepsy: A population-based assessment in disadvantaged communities.

Unlabelled: Psychiatric disorders are frequent among people with epilepsy but often under-recognized. The diagnosis and treatment of these disorders in low- and low-middle-income countries (LMICs) are challenging.

Methods: This cross-sectional survey included people recruited during a community epilepsy screening program involving 59,509 individuals from poor communities in Ludhiana in Northwest India.

Brain molecular mechanisms in Rasmussen encephalitis.

Objective: This study was undertaken to identify molecular mechanisms in brain tissue of Rasmussen encephalitis (RE) when compared to people with non-RE epilepsy (PWE) and control cases using whole exome sequencing (WES), RNAseq, and proteomics.

Methods: Frozen brain tissue (ages = 2-19 years) was obtained from control autopsy (n = 14), surgical PWE (n = 10), and surgical RE cases (n = 27). We evaluated WES variants in RE associated with epilepsy, seizures, RE, and human leukocyte antigens (HLAs).

Somatic symptoms and related disorders in a large cohort of people with epilepsy: A cohort study.

Objective: This study was undertaken to characterize somatic symptoms and related disorders (SSD) in epilepsy.

Methods: Adults with epilepsy under active follow-up at a tertiary epilepsy center were consecutively enrolled. The diagnosis of SSD was performed by an experienced psychologist based on the structured clinical interview for Statistical Manual of Mental Disorders, 5th edition.

Altered Extracellular Matrix as an Alternative Risk Factor for Epileptogenicity in Brain Tumors.

Seizures are one of the most common symptoms of brain tumors. The incidence of seizures differs among brain tumor type, grade, location and size, but paediatric-type diffuse low-grade gliomas/glioneuronal tumors are often highly epileptogenic. The extracellular matrix (ECM) is known to play a role in epileptogenesis and tumorigenesis because it is involved in the (re)modelling of neuronal connections and cell-cell signaling.

GABA receptor function is enhanced by Interleukin-10 in human epileptogenic gangliogliomas and its effect is counteracted by Interleukin-1β.

Gangliogliomas (GGs) are low-grade brain tumours that cause intractable focal epilepsy in children and adults. In GG, as in epileptogenic focal malformations (i.e.

Astrocytes in the initiation and progression of epilepsy.

Epilepsy affects ~65 million people worldwide. First-line treatment options include >20 antiseizure medications, but seizure control is not achieved in approximately one-third of patients. Antiseizure medications act primarily on neurons and can provide symptomatic control of seizures, but do not alter the onset and progression of epilepsy and can cause serious adverse effects.

A cluster-randomized trial comparing home-based primary health care and usual clinic care for epilepsy in a resource-limited country.

Objective: To ascertain whether home-based care with community and primary healthcare workers' support improves adherence to antiseizure medications, seizure control, and quality of life over routine clinic-based care in community samples of people with epilepsy in a resource-poor country.

Methods: Participants included consenting individuals with active epilepsy identified in a population survey in impoverished communities. The intervention included antiseizure medication provision, adherence reinforcement and epilepsy self- and stigma management guidance provided by a primary health care-equivalent worker.

Attention-Deficit/Hyperactivity Disorder and Delayed Sleep Phase Syndrome in Adults: A Randomized Clinical Trial on the Effects of Chronotherapy on Sleep.

Delayed sleep phase syndrome (DSPS) is the most common sleep disturbance in adults with attention-deficit/hyperactivity disorder (ADHD). We previously showed that chronotherapy with melatonin effectively advanced the dim-light melatonin onset (DLMO), a biomarker for the internal circadian rhythm, by 1.5 h and reduced ADHD symptoms by 14%.

Drugs Used in Narcolepsy and Other Hypersomnias.

Lifestyle adjustment, in combination with symptomatic pharmacologic treatment, allows most patients, particularly those with an inability to stay awake during the day, to live a relatively normal life. New pharmacologic substances show encouraging results in phase 2 and 3 studies to improve the current situation. More dedicated studies in IH, particularly in those who suffer from an increased need for sleep, are needed.