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.

Dyspnea (breathlessness) in amyotrophic lateral sclerosis/motor neuron disease: prevalence, progression, severity, and correlates.

Objective: Dyspnea, or breathlessness, is an important symptom in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). We examined the measurement properties of the Dyspnea-12.

Methods: Rasch analysis enabled conversion of raw Dyspnea-12 scores to interval level metric equivalents.

Opinion: more mouse models and more translation needed for ALS.

Amyotrophic lateral sclerosis is a complex disorder most of which is 'sporadic' of unknown origin but approximately 10% is familial, arising from single mutations in any of more than 30 genes. Thus, there are more than 30 familial ALS subtypes, with different, often unknown, molecular pathologies leading to a complex constellation of clinical phenotypes. We have mouse models for many genetic forms of the disorder, but these do not, on their own, necessarily show us the key pathological pathways at work in human patients.

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.

Objective: To identify the genetic variants associated with juvenile ALS.

Design, Setting, And Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation.

A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls.

The UK Myotonic Dystrophy Patient Registry: facilitating and accelerating clinical research.

Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy worldwide with complex, multi-systemic, and progressively worsening symptoms. There is currently no treatment for this inherited disorder and research can be challenging due to the rarity and variability of the disease. The UK Myotonic Dystrophy Patient Registry is a patient self-enrolling online database collecting clinical and genetic information.

ATXN2 trinucleotide repeat length correlates with risk of ALS.

We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS.

Diagnosis and management of motor neurone disease.

Motor neurone disease is a rapidly progressive and fatal neurodegenerative condition which causes progressive weakness, with normal sensation. It can occur at any age but is more frequent with increasing age. Key clinical presentations include bulbar (slurred or difficult speech, problems swallowing, tongue fasciculation), limb (typically in one limb with weakness and muscle wasting), respiratory (breathlessness, chest muscle fasciculation) and cognitive features (behavioural change, emotional lability, features of frontotemporal dementia).

A multicentre evaluation of oropharyngeal secretion management practices in amyotrophic lateral sclerosis.

Failure to clear oral secretions can be debilitating for patients with amyotrophic lateral sclerosis (ALS), but the treatment of this symptom is poorly defined and there is no consensus on best practice. The objective of this study was to identify the treatments that are commonly prescribed, and to describe how experienced clinicians manage a patient with treatment resistant symptoms. Twenty-three clinicians were approached, of which 19 from 16 centres across the UK provided case report forms for a total of 119 ALS patients identified as having problematic oral secretions.

Pharmacological treatments for Friedreich ataxia.

Background: Friedreich ataxia is a rare inherited autosomal recessive neurological disorder, characterised initially by unsteadiness in standing and walking, slowly progressing to wheelchair dependency usually in the late teens or early twenties. It is associated with slurred speech, scoliosis, and pes cavus. Heart abnormalities cause premature death in 60% of people with the disorder.

Pathogenesis of amyotrophic lateral sclerosis.

Introduction: Amyotrophic lateral sclerosis (ALS) or motor neuron disease is a rapidly progressive neurodegenerative disorder. The primary involvement is of motor neurons in the brain, spinal cord and peripherally. There is secondary weakness of muscles and primary involvement of other brain regions, especially involving cognition.

DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis - a randomised controlled trial.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4(®) diaphragm pacing system (DPS)™ (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure.

Systemic inflammatory response and neuromuscular involvement in amyotrophic lateral sclerosis.

Objective: To evaluate the combined blood expression of neuromuscular and inflammatory biomarkers as predictors of disease progression and prognosis in amyotrophic lateral sclerosis (ALS).

Methods: Logistic regression adjusted for markers of the systemic inflammatory state and principal component analysis were carried out on plasma levels of creatine kinase (CK), ferritin, and 11 cytokines measured in 95 patients with ALS and 88 healthy controls. Levels of circulating biomarkers were used to study survival by Cox regression analysis and correlated with disease progression and neurofilament light chain (NfL) levels available from a previous study.

Design, set-up and utility of the UK facioscapulohumeral muscular dystrophy patient registry.

Facioscapulohumeral dystrophy (FSHD) is a rare inherited neuromuscular disease estimated to affect 1/15,000 people. Through basic research, remarkable progress has been made towards the development of targeted therapies. Patient identification, through registries or other means is essential for trial-readiness.

Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.

Objective: To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS).

Methods: Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years.

C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis.

C9orf72 hexanucleotide repeat expansions are the most common cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. The clinical presentation is often indistinguishable from classic FTD or ALS, although neuropsychiatric symptoms are more prevalent and, for ALS, behavioural and cognitive symptoms occur more frequently. Pathogenic repeat length is in the hundreds or thousands, but the minimum length that increases risk of disease, and how or whether the repeat size affects phenotype, are unclear.

Investigation of next-generation sequencing technologies as a diagnostic tool for amyotrophic lateral sclerosis.

The future of genetic diagnostics will see a move toward massively parallel next-generation sequencing of a patient's DNA. Amyotrophic lateral sclerosis (ALS) is one of the diseases that would benefit from this prospect. Exploring this idea, we designed a screening panel to sequence 25 ALS-linked genes and examined samples from 95 patients with both familial and sporadic ALS.