Dysfunctional sodium channel kinetics as a novel epilepsy mechanism in chromosome 15q11-q13 duplication syndrome.

Objective: Duplication of the maternal chromosome 15q11.2-q13.1 region causes Dup15q syndrome, a highly penetrant neurodevelopmental disorder characterized by severe autism and refractory seizures.

The role of UBE3A in the autism and epilepsy-related Dup15q syndrome using patient-derived, CRISPR-corrected neurons.

Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurodevelopmental disorder caused by maternal duplications of this region. Autism and epilepsy are key features of Dup15q. UBE3A, which encodes an E3 ubiquitin ligase, is likely a major driver of Dup15q because UBE3A is the only imprinted gene expressed solely from the maternal allele.

Facial Onset Sensory and Motor Neuronopathy: New Cases, Cognitive Changes, and Pathophysiology.

Purpose Of Review: To improve our clinical understanding of facial onset sensory and motor neuronopathy (FOSMN).

Recent Findings: We identified 29 new cases and 71 literature cases, resulting in a cohort of 100 patients with FOSMN. During follow-up, cognitive and behavioral changes became apparent in 8 patients, suggesting that changes within the spectrum of frontotemporal dementia (FTD) are a part of the natural history of FOSMN.

Cognitive reserve in amyotrophic lateral sclerosis (ALS): a population-based longitudinal study.

Background: Amyotrophic lateral sclerosis (ALS) is often associated with cognitive and/or behavioural impairment. Cognitive reserve (CR) may play a protective role in offsetting cognitive impairment. This study examined the relationship between CR and longitudinal change in cognition in an Irish ALS cohort.

A unifying mechanism of ketogenic diet action: The multiple roles of nicotinamide adenine dinucleotide.

The ability of a ketogenic diet to treat seizures and render a neuronal network more resistant to strong electrical activity has been observed for a century in clinics and for decades in research laboratories. Alongside ongoing efforts to understand how this therapy works to stop seizures, metabolic health is increasingly appreciated as critical buffer to resisting and recovering from acute and chronic disease. Accordingly, links between metabolism and health, and the broader emerging impact of the ketogenic diet in improving diverse metabolic, immunological and neurological conditions, have served to intensify the search for its key and/or common mechanisms.

Ketogenic Diet Modulates NAD-Dependent Enzymes and Reduces DNA Damage in Hippocampus.

The ketogenic diet's (KD) anti-seizure effects have long been documented. Recently, its therapeutic potential in multiple neurodegenerative and neurodevelopmental disorders has emerged. Yet experimental evidence for a fundamental mechanism underlying beneficial effects across numerous diseases remains lacking.

Ketone-Based Metabolic Therapy: Is Increased NAD a Primary Mechanism?

The ketogenic diet's (KD) anticonvulsant effects have been well-documented for nearly a century, including in randomized controlled trials. Some patients become seizure-free and some remain so after diet cessation. Many recent studies have explored its expanded therapeutic potential in diverse neurological disorders, yet no mechanism(s) of action have been established.

Assessing behavioural changes in ALS: cross-validation of ALS-specific measures.

The Beaumont Behavioural Inventory (BBI) is a behavioural proxy report for the assessment of behavioural changes in ALS. This tool has been validated against the FrSBe, a non-ALS-specific behavioural assessment, and further comparison of the BBI against a disease-specific tool was considered. This study cross-validates the BBI against the ALS-FTD-Q.

Semi-quantitative analysis of cerebral FDG-PET reveals striatal hypermetabolism and normal cortical metabolism in a case of VGKCC limbic encephalitis.

In the context of delayed autoimmune encephalitis antibody results, functional imaging can support the diagnosis of limbic encephalitis associated with anti-voltage-gated potassium channel complex (VGKCC) antibodies. Here we present a typical case of VGKCC encephalitis in a 69-year-old woman whose symptoms responded to plasmapheresis. A cerebral 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scan performed prior to commencing treatment revealed striatal hypermetabolism assessed qualitatively and semi-quantitatively, with normal uptake in the cortex and cerebellum when analysed semi-quantitatively.

Uncommon mutation in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS).

A 26-year-old man presented to the emergency department with new-onset generalised tonic-clonic seizures. His clinical picture suggested either autoimmune or infectious encephalitis while his brain imaging raised the possibility of a stroke. A detailed developmental and childhood medical history added suspicion of a mitochondrial defect to the differential.

Visual encoding, consolidation, and retrieval in amyotrophic lateral sclerosis: executive function as a mediator, and predictor of performance.

Objective: This study aimed to illustrate the variation of non-executive cognitive processes, i.e. visual memory, considering executive dysfunction in amyotrophic lateral sclerosis (ALS).

Screening for cognitive dysfunction in ALS: validation of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) using age and education adjusted normative data.

Background: Cognitive and behavioural changes are an important aspect in Amyotrophic Lateral Sclerosis (ALS). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) briefly assesses these changes in ALS.

Objective: To validate the ECAS against a standardised neuropsychological battery and assess its sensitivity and specificity using age and education adjusted cut-off scores.

Identifying behavioural changes in ALS: Validation of the Beaumont Behavioural Inventory (BBI).

Objective: Behavioural changes are an important part of amyotrophic lateral sclerosis (ALS). However, most tools do not account for the influence of motor impairment. Furthermore, they do not fully measure the broad range of behavioural changes specific to ALS.

Measurement of Social Cognition in Amyotrophic Lateral Sclerosis: A Population Based Study.

Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. Executive dysfunction is common in patients with ALS, with up to 50% of patients performing within an impaired range. There is evidence that social cognitive deficits associated with ALS are a function of deficits in executive function.

Discordant performance on the 'Reading the Mind in the Eyes' Test, based on disease onset in amyotrophic lateral sclerosis.

Executive dysfunction is a core feature of amyotrophic lateral sclerosis (ALS) and is associated with brain atrophy in cortical and subcortical regions. Social cognitive deficits may also be a prominent feature of ALS. This study investigated executive, and social cognitive performance, in a population based cohort of patients with ALS, stratified by disease onset.

Survival analysis of geospatial factors in the Irish ALS cohort.

Variations in environmental risk factors potentially influence incidence and progression in complex multifactorial diseases. Few studies have examined the association of survival in amyotrophic lateral sclerosis (ALS) with environmental geospatial variables. Here we use data from the Irish ALS cohort to perform such an analysis.

The selective anatomical vulnerability of ALS: 'disease-defining' and 'disease-defying' brain regions.

A large multiparametric MRI study has been undertaken to evaluate anatomical patterns of basal ganglia, white matter and cortical grey matter involvement in ALS. Unaffected brain regions are mapped in patients with significant disability. Multiple white matter diffusivity measures, cortical grey matter density alterations, basal ganglia volumes and subcortical grey matter atrophy patterns are evaluated.

The Utility of the Addenbrooke's Cognitive Examination Version Three in Early-Onset Dementia.

Background/aims: Early-onset dementia (EOD) is defined as functionally relevant cognitive decline with age of onset at less than 65 years. The aim of this study was to investigate the utility of the recently validated third version of the Addenbrooke's Cognitive Examination (ACE-III) in predicting dementia diagnoses in EOD.

Methods: ACE-III scores of EOD patients were compared to those of healthy controls (HC) and individuals with subjective memory impairment (SMI).

Functional Connectivity Changes in Resting-State EEG as Potential Biomarker for Amyotrophic Lateral Sclerosis.

Background: Amyotrophic Lateral Sclerosis (ALS) is heterogeneous and overlaps with frontotemporal dementia. Spectral EEG can predict damage in structural and functional networks in frontotemporal dementia but has never been applied to ALS.

Methods: 18 incident ALS patients with normal cognition and 17 age matched controls underwent 128 channel EEG and neuropsychology assessment.

Caregiver burden in amyotrophic lateral sclerosis: a cross-sectional investigation of predictors.

The objective of the study was to investigate whether cognitive and behavioural impairment in Amyotrophic Lateral Sclerosis (ALS) contributes to caregiver burden, and whether carer burden affects patient outcome. Thirty-three dyads of incident patients with ALS and their primary caregivers (n = 33) completed a series of measures to determine cognitive and behavioural profiles, (patients) and carer burden (carers) to investigate the psychological impact of ALS, and the impact of behavioural change since the onset of ALS. Caregivers were divided into high- and low-burden groups using previously established norms.

Predicting prognosis in amyotrophic lateral sclerosis: a simple algorithm.

The objective of the study was to develop and validate a practical prognostic index for patients with amyotrophic lateral scleroses (ALS) using information available at the first clinical consultation. We interrogated datasets generated from two population-based projects (based in the Republic of Ireland and Italy). The Irish patient cohort was divided into Training and Test sub-cohorts.

Spatial cluster analysis of population amyotrophic lateral sclerosis risk in Ireland.

Objective: Few spatial cluster analyses of amyotrophic lateral sclerosis (ALS) incidence have been conducted on prospective incident population-based cohorts; we report results of a formal cluster analysis of the Irish ALS cohort from January 1, 1995, to December 31, 2013.

Methods: We identified 1,684 incident cases from the Irish ALS register. Population data from 4 census years were used to calculate age- and sex-standardized expected ALS cases for 3,355 areas.