Lipid-mediated resolution of inflammation and survival in amyotrophic lateral sclerosis.

Neuroinflammation impacts on the progression of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Specialized pro-resolving mediators trigger the resolution of inflammation. We investigate the specialized pro-resolving mediator blood profile and their receptors' expression in peripheral blood mononuclear cells in relation to survival in ALS.

Predicting ALS informant distress from cognitive and behavioural change in people with ALS.

Background: The cognitive and behavioural changes that occur in around 50% of people with amyotrophic lateral sclerosis (ALS) may significantly affect people around them, contributing to heightened burden, anxiety, and depression. Despite existing evidence linking behavioural impairment to caregiver distress, the role of cognitive impairment remains less clear, with mixed findings on its impact.

Methods: This study assessed the influence of cognitive and behavioural impairments in people with ALS on the distress of their nominated informants.

Brain distribution study of [C]-Riluzole following intranasal administration in mice.

Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal (IN) delivery to enhance the CNS delivery of riluzole (RLZ), a standard ALS treatment which is subject to blood-brain barrier efflux mechanisms. Additionally, the impact of elacridar (ELC), an efflux pump inhibitor, on IN RLZ CNS bioavailability was examined.

Determinants and progression of stigma in amyotrophic lateral sclerosis/motor neuron disease.

: Stigma in amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) may be felt or enacted; felt stigma covers feeling devalued by the illness, whereas enacted stigma refers to being treated differently because of it. Stigma in ALS/MND has been shown to increase social withdrawal, worsen quality of life, and reduce use of assistive devices, so we explored prevalence and factors influencing stigma. : Participants in the Trajectories of Outcome in Neurological Conditions-ALS study completed scales measuring stigma, fatigue, spasticity, functioning, mood, worry, self-esteem, and perceived health, as well as demographic information and symptoms like head drop or emotional lability.

Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics.

Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant 'local' genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation.

Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis.

Sex is an important covariate in all genetic and epigenetic research due to its role in the incidence, progression and outcome of many phenotypic characteristics and human diseases. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a sex bias towards higher incidence in males. Here, we report for the first time a blood-based epigenome-wide association study meta-analysis in 9274 individuals after stringent quality control (5529 males and 3975 females).

The GenoPred pipeline: a comprehensive and scalable pipeline for polygenic scoring.

Motivation: Polygenic scoring is an approach for estimating an individual's likelihood of a given outcome. Polygenic scores are typically calculated from genome-wide association study (GWAS) summary statistics and individual-level genotype data for the target sample. Going from genotype to interpretable polygenic scores involves many steps and there are many methods available, limiting the accessibility of polygenic scores for research and clinical application.

Investigating the impact of socioeconomic status on amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the gradual death of motor neurons in the brain and spinal cord, leading to fatal paralysis. Socioeconomic status (SES) is a measure of an individual's shared economic and social status, which has been shown to have an association with health outcomes. Understanding the impact of SES on health conditions is crucial, as it can influence and be influenced by health-related variables.

Harnessing transcriptomic signals for amyotrophic lateral sclerosis to identify novel drugs and enhance risk prediction.

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. This study integrates common genetic association results from the latest ALS genome-wide association study (GWAS) summary statistics with functional genomic annotations with the aim of providing mechanistic insights into ALS risk loci, inferring drug repurposing opportunities, and enhancing prediction of ALS risk and clinical characteristics.

Methods: Genes associated with ALS were identified using GWAS summary statistic methodology including SuSiE SNP-based fine-mapping, and transcriptome- and proteome-wide association study (TWAS/PWAS) analyses.

predicTTE: An accessible and optimal tool for time-to-event prediction in neurological diseases.

Time-to-event prediction is a key task for biological discovery, experimental medicine, and clinical care. This is particularly true for neurological diseases where development of reliable biomarkers is often limited by difficulty visualising and sampling relevant cell and molecular pathobiology. To date, much work has relied on Cox regression because of ease-of-use, despite evidence that this model includes incorrect assumptions.

Comparison of in-person vs. remote administration of cognitive screening tools for people with ALS.

Objective: This study investigated whether cognitive screening tools used for people with amyotrophic lateral sclerosis (pwALS) are affected by the screen being administered face-to-face or remotely online. It also investigated whether demographic variables predicted total cognitive screen scores.

Methods: The cognitive component of the Edinburgh Cognitive and Behavioural ALS Screen (ECASc), the cognitive component of the ALS Cognitive Behavioural Screen (ALS-CBSc), and the Mini Addenbrooke's Cognitive Examination (Mini-ACE) were administered to 41 pwALS and 41 controls face-to-face.

REVEALS-a longitudinal cohort study of multifaceted respiratory assessment in ALS.

Objective: To systematically assess decline in respiratory measures in amyotrophic lateral sclerosis (ALS) and to examine the impact of sex, disease onset type and baseline morbidity on progression.

Methods: The REVEALS study (Registry of Endpoints and Validated Experiences in ALS) was conducted between April 2018 and February 2021 in six European ALS centers. Slow and forced vital capacity (S/FVC), sniff nasal inspiratory pressure (SNIP), peak cough flow, amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R), and respiratory morbidity were collected.

Recent advances in the genetics of familial and sporadic ALS.

ALS shows complex genetic inheritance patterns. In about 5% to 10% of cases, there is a family history of ALS or a related condition such as frontotemporal dementia in a first or second degree relative, and for about 80% of such people a pathogenic gene variant can be identified. Such variants are also seen in people with no family history because of factor influencing the expression of genes, such as age.

Mutations in the tail and rod domains of the neurofilament heavy-chain gene increase the risk of ALS.

Objective: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.

Pharmacometabolomics applied to low-dose interleukin-2 treatment in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The immunosuppressive functions of regulatory T lymphocytes (Tregs) are impaired in ALS, and correlate to disease progression. The phase 2a IMODALS trial reported an increase in Treg number in ALS patients following the administration of low-dose (ld) interleukin-2 (IL-2).

The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology.

Increasing appreciation of the phenotypic and biological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, alongside evolving biomarker evidence for a pre-symptomatic stage of disease and observations that this stage of disease might not always be clinically silent, is challenging traditional views of these disorders. These advances have highlighted the need to adapt ingrained notions of these clinical syndromes to include both the full phenotypic continuum - from clinically silent, to prodromal, to clinically manifest - and the expanded phenotypic spectrum that includes ALS, frontotemporal dementia and some movement disorders. The updated clinical paradigms should also align with our understanding of the biology of these disorders, reflected in measurable biomarkers.

Methodological Quality of Clinical Trials in Amyotrophic Lateral Sclerosis: A Systematic Review.

Background: More than 200 clinical trials have been performed worldwide in ALS so far, but no agents with substantial efficacy on disease progression have been found.

Objective: To describe the methodological quality of all clinical trials performed in ALS and published before December 31, 2022.

Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta Analyses.

Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK.

Background: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease.

How the coronavirus pandemic affected the lives of people with ALS and their spouses in the UK from spouses' perspectives: a qualitative study.

Objective: This study set out to investigate, using qualitative methodology, the experiences of spouses of people with Amyotrophic Lateral Sclerosis (ALS) during the coronavirus pandemic, with particular focus on spouse distress and cognitive and behavioral change in people with ALS (pwALS).

Methods: Qualitative semi-structured interviews of nine spouses of pwALS living in England were conducted between 11/09/2020 and 20/04/2021, focusing on spouses' perspectives of how their lives and the lives of pwALS were affected by the pandemic and related lockdowns. Interviews were subject to thematic analysis.

Cost-effectiveness of acceptance and commitment therapy for people living with motor neuron disease, and their health-related quality of life.

Background: Given the degenerative nature of the condition, people living with motor neuron disease (MND) experience high levels of psychological distress. The purpose of this research was to investigate the cost-effectiveness of acceptance and commitment therapy (ACT), adapted for the specific needs of this population, for improving quality of life.

Methods: A trial-based cost-utility analysis over a 9-month period was conducted comparing ACT plus usual care (n = 97) versus usual care alone (n = 94) from the perspective of the National Health Service.