'Outcomes of genetic testing in the London MND Center: the importance of achieving timely results and correlations to family history'.

: Despite recognition of the importance of genetic factors in the pathogenesis of MND and the increasing availability of genetic testing, testing practice remains highly variable. With the arrival of gene-targeted therapies there is a growing need to promptly identify actionable genetic results and patient death before receipt of results raises ethical dilemmas and limits access to novel therapies. : To identify pathogenic mutations within a London tertiary MND center and their correlation with family history.

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.

Participant experiences of guided self-help Acceptance and Commitment Therapy for improving quality of life in muscle disease: a nested qualitative study within the ACTMus randomized controlled trial.

Introduction: In adults, muscle disease (MD) is typically a chronic long-term condition that can lead to a reduced quality of life (QoL). Previous research suggests that a psychological intervention, in particular Acceptance and Commitment Therapy (ACT), may help improve QoL for individuals living with chronic conditions such as MD.

Methods: This nested qualitative study was incorporated within a randomized controlled trial which evaluated a guided self-help ACT intervention for people living with MD to explore their experiences of the intervention.

Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis.

Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls.

Identifying key signs of motor neurone disease in primary care: a nested case-control study using the QResearch database.

Objective: To confirm the symptoms and signs for motor neuron disease (MND) in the Red Flag tool; to quantify the extent to which the key symptoms and signs are associated with MND; and to identify additional factors which may be helpful within the primary care setting in recognition of possible MND and triggering timely referral to neurology specialists.

Design: A nested case-control study.

Setting: 1292 UK general practices contributing to the QResearch primary care database, linked to hospital and mortality data.

Bedside and laboratory diagnostic testing in myasthenia.

Myasthenia gravis (MG) and congenital myasthenic syndromes (CMS) are a group of disorders with a well characterised autoimmune or genetic and neurophysiological basis. We reviewed the literature from the last 20 years assessing the utility of various neurophysiological, immunological, provocative and genetic tests in MG and CMS. Diagnostic sensitivity of repetitive nerve stimulation test ranges between 14 and 94% and specificity between 73 and 100%; sensitivity of single-fibre EMG (SFEMG) test ranges between 64 and 100% and specificity between 22 and 100%; anti-acetylcholine receptor (AChR) antibody sensitivity ranges from 13 to 97% and specificity ranges from 95 to 100%.

Analysis of incidence of motor neuron disease in England 1998-2019: use of three linked datasets.

This study uses three linked datasets to provide an estimate of incidence of motor neuron disease (MND) in England from 1998 to 2019. Comparison is made to previous British studies. It examines age at diagnosis and ethnicity of those affected.

Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective.

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019.

Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy.

Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP.

Initial seronegative immune-mediated necrotising myopathy with subsequent anti-HMGCR antibody development and response to rituximab: case report.

Background: Immune-mediated necrotising myopathy (IMNM) is characterised by severe muscle weakness and necrosis with a paucity of inflammation on muscle biopsy. Around 60% of cases are associated with antibodies to the signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR); the remainder are seronegative. IMNM is more treatment resistant than inflammatory myopathies.

Acceptance and Commitment Therapy for Muscle Disease (ACTMus): protocol for a two-arm randomised controlled trial of a brief guided self-help ACT programme for improving quality of life in people with muscle diseases.

Introduction: In adults, muscle disease (MD) is often a chronic long-term condition with no definitive cure. It causes wasting and weakness of the muscles resulting in a progressive decline in mobility, alongside other symptoms, and is typically associated with reduced quality of life (QoL). Previous research suggests that a psychological intervention, and in particular Acceptance and Commitment Therapy (ACT), may help improve QoL in MD.

Mobility shift of beta-dystroglycan as a marker of gene-related muscular dystrophy.

Background: Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies. Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy. Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (), have been reported to date.

Guillain-Barré syndrome with exaggerated pleocytosis and anti-GM1 ganglioside antibodies.

An 81-year-old man presented with fever, confusion and rapidly-progressive flaccid tetraparesis. Clinical presentation and neurophysiology were consistent with a severe axonal polyneuropathy. Anti-GM1 and serology were both positive, consistent with postinfectious axonal-variant Guillain-Barré syndrome (GBS).

Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease.

Background: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a fatal neurodegenerative disease. Neuromuscular respiratory failure is the most common cause of death, which usually occurs within two to five years of the disease onset. Supporting respiratory function with mechanical ventilation may improve survival and quality of life.

Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1.

The Polycomb group gene BMI1 is essential for efficient muscle regeneration in a mouse model of Duchenne muscular dystrophy, and its enhanced expression in adult skeletal muscle satellite cells ameliorates the muscle strength in this model. Here, we show that the impact of mild BMI1 overexpression observed in mouse models is translatable to human cells. In human myoblasts, BMI1 overexpression increases mitochondrial activity, leading to an enhanced energetic state with increased ATP production and concomitant protection against DNA damage both in vitro and upon xenografting in a severe dystrophic mouse model.

The development of the UK National Institute of Health and Care Excellence evidence-based clinical guidelines on motor neurone disease.

The care of people with motor neuron disease/amyotrophic lateral sclerosis is often complex and involves a wide multidisciplinary team approach. The National Institute for Health and Care Excellence (NICE) in the UK has produced an evidence based guideline for the management of patients. This has made recommendations, based on clear evidence or consensus discussion.

Ilizarov method as limb salvage in treatment of massive femoral defect after unsuccessful tumor arthroplasty.

Introduction: Surgical management of massive bone defects is very challenging in terms of estimating possibilities of saving the extremity and adequate method that can make it possible. Selection of methods is additionally limited in the presence of infection at site of defect.

Case Report: The female patient, diagnosed with Ewing sarcoma was treated by segmental bone resection and implantation of Kotz modular tumor endoprosthesis.

An RYR1 mutation associated with malignant hyperthermia is also associated with bleeding abnormalities.

Malignant hyperthermia is a potentially fatal hypermetabolic disorder triggered by halogenated anesthetics and the myorelaxant succinylcholine in genetically predisposed individuals. About 50% of susceptible individuals carry dominant, gain-of-function mutations in RYR1 [which encodes ryanodine receptor type 1 (RyR1)], though they have normal muscle function and no overt clinical symptoms. RyR1 is predominantly found in skeletal muscle but also at lower amounts in immune and smooth muscle cells, suggesting that RYR1 mutations may have a wider range of effects than previously suspected.

Syntactic processing as a marker for cognitive impairment in amyotrophic lateral sclerosis.

Despite recent interest in cognitive changes in patients with amyotrophic lateral sclerosis (ALS), investigations of language function looking at the level of word, sentence and discourse processing are relatively scarce. Data were obtained from 26 patients with sporadic ALS and 26 healthy controls matched for age, education, gender, anxiety, depression and executive function performance. Standardized language tasks included confrontation naming, semantic access, and syntactic comprehension.

Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults.

Aims: To provide insight into the mechanism of sudden adult death syndrome (SADS) and to give new clinical guidelines for the cardiac management of patients with the most common mitochondrial DNA mutation, m.3243A>G. These studies were initiated after two young, asymptomatic adults harbouring the m.