Psychogenic non-epileptic (functional) seizures in adults with intellectual disability and epilepsy: A matched case-control study.

Objective: To describe the characteristics of psychogenic non-epileptic (functional) seizures (PNES) in adults with epilepsy and intellectual disability (ID) and to establish differences and risk factors regarding psychosocial functioning between individuals with and without PNES.

Methods: Adults with ID and epilepsy living in epilepsy care facilities in The Netherlands were screened for PNES by a neurologist. A control group consisting of people with epilepsy and ID, without PNES, was matched according to age, sex, and level of ID.

Clinical features and genotype-phenotype correlations in epilepsy patients with de novo DYNC1H1 variants.

Objective: DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1-related epilepsy has been reported in small cohorts. We dissect the electroclinical features of 34 patients harboring de novo DYNC1H1 pathogenic variants, identify subphenotypes on the DYNC1H1-related epilepsy spectrum, and compare the genotype-phenotype correlations observed in our cohort with the literature.

SCN1A-deficient excitatory neuronal networks display mutation-specific phenotypes.

Dravet syndrome is a severe epileptic encephalopathy, characterized by (febrile) seizures, behavioural problems and developmental delay. Eighty per cent of patients with Dravet syndrome have a mutation in SCN1A, encoding Nav1.1.

Human de novo mutations underlie epilepsy and intellectual disability.

We identified six novel de novo human variants in children with motor/language delay, intellectual disability (ID), and/or epilepsy by whole exome sequencing. These variants, comprising two nonsense and four missense alterations, were functionally characterized by electrophysiology in HEK293/CHO cells, together with four previously reported missense variants (Lehman A, Thouta S, Mancini GM, Naidu S, van Slegtenhorst M, McWalter K, Person R, Mwenifumbo J, Salvarinova R; CAUSES Study; EPGEN Study; Guella I, McKenzie MB, Datta A, Connolly MB, Kalkhoran SM, Poburko D, Friedman JM, Farrer MJ, Demos M, Desai S, Claydon T. 101: 65-74, 2017).

Epilepsy and Sleep in the ATR-X Syndrome.

Background: This study explores the prevalence, clinical characteristics, and treatment of epilepsy and sleep disorders in α thalassemia mental retardation (ATR-X) syndrome.

Design: In this cross-sectional study, 37 participants with ATR-X syndrome aged 1.8 to 44 years were studied using a customized epilepsy questionnaire, review of electroencephalography (EEG) findings, the modified Sleep Questionnaire of Simonds and Parraga and 2-week sleep diary.

People with epilepsy and intellectual disability: More than a sum of two conditions.

Background: Around 25% of people with Intellectual Disability (PwID) have comorbid epilepsy with seizures in up to two-thirds being drug-resistant. Little is known of the general characteristics and prescribing practices to this population.

Aim: Describe and compare characteristics of two cohorts of PwID and epilepsy in two different countries to inform clinical practice better.

Efficacy and tolerability of brivaracetam in patients with intellectual disability and epilepsy.

Patients with intellectual disability (ID) are often excluded from clinical trials, and little is known about the best approach to treat their epilepsy. Brivaracetam (BRV) is a new antiepileptic drug (AED) for adjunctive treatment in patients with focal-onset seizures with or without secondary generalization. We analyzed the efficacy and tolerability of BRV in patients with ID and epilepsy who either had or had not previously received treatment with levetiracetam (LEV).

Breath analysis in detecting epilepsy.

The aim of this proof of concept study is to investigate if an electronic nose (eNose) is able to make a distinction between breath profiles of diagnosed epilepsy patients and epilepsy-free control subjects. An eNose is a non-invasive device, with a working mechanism that is based on the presence of volatile organic compounds (VOCs) in exhaled breath. These VOCs interact with the sensors of the eNose, and the eNose has to be trained to distinguish between breath patterns from patients with a specific disease and control subjects without that disease.

Mood, anxiety, and perceived quality of life in adults with epilepsy and intellectual disability.

Objective: Depression and anxiety symptoms are common among patients with epilepsy, but are relatively under-researched in patients with both epilepsy and intellectual disability (ID). The aim was to investigate whether epilepsy and ID characteristics are associated with mood, anxiety, and quality of life.

Materials And Methods: Adult patients with epilepsy and ID who rely on tertiary epilepsy care were included (N = 189).

Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability.

Objective: Epilepsy is highly prevalent among patients with intellectual disability (ID), and seizure control is often difficult. Identification of the underlying etiology in this patient group is important for daily clinical care. We assessed the diagnostic yield of whole exome sequencing (WES).

De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias.

Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α-subunit of the voltage-gated Ca2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission.

Classification of intellectual disability according to domains of adaptive functioning and between-domains discrepancy in adults with epilepsy.

Background: In the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition (DSM-5), the diagnostic criteria of intellectual disability (ID) include three domains of adaptive deficits: the conceptual, social and practical. Substantial intra-individual differences between domains can be considered an ID domain discrepancy.

Method: We explored the associations between ID domains, discrepancies and epilepsy in 189 adults (mean age = 47.

Psychogenic nonepileptic seizures in adults with epilepsy and intellectual disability: A neglected area.

Purpose: To describe the main characteristics of psychogenic nonepileptic seizures (PNES) in adults with epilepsy and intellectual disability (ID), and to analyse the differences regarding psychosocial functioning, epilepsy severity and ID between patients with PNES and a control group without PNES.

Methods: Medical records of adults with ID and epilepsy living at an epilepsy care facility (N = 240) were screened for PNES and evaluated by a neurologist. A control group consisting of patients with epilepsy and ID, without PNES, was matched according to age, sex and level of ID.

Phenytoin as a last-resort treatment in encephalopathy.

encodes Nav1.6, one of the main voltage-gated sodium channel subunits in the brain, and mutations lead to epileptic encephalopathy. Particular mutations render the mutant channel more susceptible to inhibition by phenytoin.

Defining the phenotypic spectrum of SLC6A1 mutations.

Objective: Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients.

Methods: We collected 24 SLC6A1 probands and 6 affected family members.

Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis.

Background: Glycosylphosphatidylinositol biosynthesis defects (GPIBDs) cause a group of phenotypically overlapping recessive syndromes with intellectual disability, for which pathogenic mutations have been described in 16 genes of the corresponding molecular pathway. An elevated serum activity of alkaline phosphatase (AP), a GPI-linked enzyme, has been used to assign GPIBDs to the phenotypic series of hyperphosphatasia with mental retardation syndrome (HPMRS) and to distinguish them from another subset of GPIBDs, termed multiple congenital anomalies hypotonia seizures syndrome (MCAHS). However, the increasing number of individuals with a GPIBD shows that hyperphosphatasia is a variable feature that is not ideal for a clinical classification.

Vagus Nerve Stimulation in children: A focus on intellectual disability.

Introduction: Vagus Nerve Stimulation (VNS) can be an efficacious add-on treatment in patients with drug-resistant epilepsy, who are not eligible for surgery. Evidence of VNS efficacy in children with intellectual disability (ID) is scarce.

Objectives: The purpose of this study was to review all available VNS data in the pediatric population (≤18 years old) and focus on the subpopulation with ID since appropriate treatment of these children is often challenging and complex.

Accuracy of WISC-III and WAIS-IV short forms in patients with neurological disorders.

The assessment of intellectual abilities is intensive, time-consuming, and might be considered burdensome for patients. We examined psychometric qualities of short forms (SFs) of the Wechsler Intelligence Scales for Children (WISC-third edition) and for adults (WAIS-fourth edition), in children (n = 986; M = 10.9) and adults (n = 324; M = 40.

Evaluation of perampanel in patients with intellectual disability and epilepsy.

Introduction: Initial registration studies of perampanel (PMP), an AMPA receptor antagonist, have now been followed up by 'clinical' studies that confirmed its efficacy and safety in patients with refractory epilepsy. Publications on the use of PMP among patients with intellectual disability (ID) are still limited. This study extends our knowledge with respect to the relevance of PMP for patients with both ID and epilepsy, and furthermore specifies the behavioral side effects of PMP in this specific population.

Tau Rather than TDP-43 Proteins are Potential Cerebrospinal Fluid Biomarkers for Frontotemporal Lobar Degeneration Subtypes: A Pilot Study.

Background: Frontotemporal dementia (FTD) is a heterogeneous disease both at the clinical, genetic, and pathobiological level. The underlying pathological spectrum (termed FTLD, frontotemporal lobar degeneration) is in most cases defined by accumulation of either tau (FTLD-tau) or TDP-43 proteins (FTLD-TDP). Biomarkers to differentiate these subtypes are not yet available, whereas these are essential requirements to study the natural course of disease and for homogeneous inclusion of patients in clinical studies.

A systematic review of neuropsychiatric comorbidities in patients with both epilepsy and intellectual disability.

Epilepsy is a neurological condition that is particularly common in people with intellectual disability (ID). The care for people with both epilepsy and ID is often complicated by the presence of neuropsychiatric disorders, defined as psychiatric symptoms, psychiatric disorders, and behavioral problems. The aim of this study was to investigate associations between epilepsy or epilepsy-related factors and neuropsychiatric comorbidities in patients with ID and between ID and neuropsychiatric comorbidities in patients with epilepsy.

A LRSAM1 mutation links Charcot-Marie-Tooth type 2 to Parkinson's disease.

LRSAM1 mutations have been found in recessive and dominant forms of Charcot-Marie-Tooth disease. Within one generation of the original Dutch family in which the dominant LRSAM1 mutation was identified, three of the five affected family members have developed Parkinson's disease between ages 50 and 65 years, many years after neuropathy onset. We speculate that this late-onset parkinsonism is part of the LRSAM1 phenotype, thus associating a hitherto peripheral nerve disease with a central nervous system phenotype.