Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.

Methods And Analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.

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.

Correlates and trajectories of relapses in relapsing-remitting multiple sclerosis.

Background And Aims: In people with relapsing-remitting multiple sclerosis (pwRRMS), data from studies on non-pharmacological factors which may influence relapse risk, other than age, are inconsistent. There is a reduced risk of relapses with increasing age, but little is known about other trajectories in real-world MS care.

Methods: We studied longitudinal questionnaire data from 3885 pwRRMS, covering smoking, comorbidities, disease-modifying therapy (DMT), and patient-reported outcome measures, as well as relapses during the past year.

Measuring disability in amyotrophic lateral sclerosis/motor neuron disease: the WHODAS 2.0-36, WHODAS 2.0-32, and WHODAS 2.0-12.

To investigate whether the World Health Organization Disability Assessment Schedule 2.0 (WHODAS) can provide interval level measurement of disability in Amyotrophic Lateral Sclerosis (ALS), allowing parametric analyses. : Data on the WHODAS 12, 32, and 36-item versions, from 1120 patients studied at one or more time points, were fit to the Rasch model and comparisons made against ALSFRS-R, King's staging, and mortality.

The impact of smoking cessation on multiple sclerosis disease progression.

The negative impact of smoking in multiple sclerosis is well established; however, there is much less evidence as to whether smoking cessation is beneficial to progression in multiple sclerosis. Adults with multiple sclerosis registered on the United Kingdom Multiple Sclerosis Register (2011-20) formed this retrospective and prospective cohort study. Primary outcomes were changes in three patient-reported outcomes: normalized Multiple Sclerosis Physical Impact Scale (MSIS-29-Phys), normalized Multiple Sclerosis Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS).

Quality of life in multiple sclerosis is dominated by fatigue, disability and self-efficacy.

Background And Objective: Quality of life in multiple sclerosis (MS) reflects complex relationships between symptoms (fatigue, spasticity pain, and bladder or vision dysfunction), disability, health perceptions, and self-efficacy.

Methods: In this cross-sectional study, a self-report questionnaire pack of patient reported outcome measures was collected from 5695 people with MS (pwMS) alongside clinical data from their neurologists. Each patient reported outcome measure was converted to interval-scaled estimates following fit to the Rasch model.

Measuring quality of life in ALS/MND: validation of the WHOQOL-BREF.

The World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF) is a generic QOL measure with four domains covering Physical, Psychological, Social and Environment. Providing the opportunity to contrast QoL with other conditions, or with population norms, the current study had three aims: 1) can the established domains of the WHOQOL-BREF be validated within a large ALS/MND population; 2) can a total score be validated and 3) can they provide interval level measurement? Data were obtained from the Trajectories of Outcomes in Neurological Conditions study. Internal construct validity was determined by fit of the data to the Rasch measurement model.

Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.

Background: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS].

Methods: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure.

Health state utility values (QALY weights) for Huntington's disease: an analysis of data from the European Huntington's Disease Network (EHDN).

Background: Huntington's Disease (HD) is a hereditary neurodegenerative disorder which affects individuals' ability to walk, talk, think, and reason. Onset is usually in the forties, there are no therapies currently available that alter disease course, and life expectancy is 10-20 years from diagnosis. The gene causing HD is fully penetrant, with a 50% probability of passing the disease to offspring.

Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2).

Background: Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis.

The relationships between symptoms, disability, perceived health and quality of life in amyotrophic lateral sclerosis/motor neuron disease.

: Using the Wilson and Cleary model linking clinical variables to quality of life, we explored the associations between physical and psychological factors, disability, perceived health and quality of life in ALS/MND. : The ongoing UK study of Trajectories of Outcomes in Neurological Conditions (TONiC) recruited participants with ALS/MND to complete a questionnaire pack including demographic factors and several patient reported outcome measures (PROMs); a clinician provided data on disease onset type and duration since diagnosis. All PROMs were transformed from ordinal raw scores to interval-scaled latent estimates via the Rasch measurement model.

Outcome of cell suspension allografts in a patient with Huntington's disease.

For patients with incurable neurodegenerative disorders such as Huntington's (HD) and Parkinson's disease, cell transplantation has been explored as a potential treatment option. Here, we present the first clinicopathological study of a patient with HD in receipt of cell-suspension striatal allografts who took part in the NEST-UK multicenter clinical transplantation trial. Using various immunohistochemical techniques, we found a discrepancy in the survival of grafted projection neurons with respect to grafted interneurons as well as major ongoing inflammatory and immune responses to the grafted tissue with evidence of mutant huntingtin aggregates within the transplant area.

Cost-effectiveness analysis of abobotulinumtoxinA for the treatment of cervical dystonia in the United Kingdom.

Background: Cervical dystonia (CD) involves painful involuntary contraction of the neck and shoulder muscles and abnormal posture in middle-aged adults. Botulinum neurotoxin type A (BoNT-A) is effective in treating CD but little is known about its associated cost-effectiveness.

Objective: To evaluate the cost-effectiveness of abobotulinumtoxinA for treating CD from the UK payer perspective.

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.

AbobotulinumtoxinA in the management of cervical dystonia in the United Kingdom: a budget impact analysis.

Background: Cervical dystonia (CD) can be effectively managed by a combination of botulinum neurotoxin A (BoNT-A) and conventional therapy (skeletal muscle relaxants and rehabilitative therapy), but the costs of different interventions in the UK vary.

Methods: A budget impact model was developed from the UK payer perspective with a 5-year time horizon to evaluate the effects of changing market shares of abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA, and best supportive care from the UK payer perspective. Epidemiological and resource use data were retrieved from the published literature and clinical expert opinion.

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls.

Management of sialorrhoea in motor neuron disease: a survey of current UK practice.

Our objective was to better understand UK-wide practice in managing sialorrhoea in motor neuron disease among specialist clinicians. We used a survey of neurologists in the UK with a special interest in motor neuron disease designed to establish clinicians' attitudes towards treatment options and resources for sialorrhoea management. Twenty-three clinicians replied, representing 21 centres.

The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease.

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease involving progressive motor, cognitive and behavioural decline, leading to death approximately 20 years after motor onset. The disease is characterised pathologically by an early and progressive striatal neuronal cell loss and atrophy, which has provided the rationale for first clinical trials of neural repair using fetal striatal cell transplantation. Between 2000 and 2003, the 'NEST-UK' consortium carried out bilateral striatal transplants of human fetal striatal tissue in five HD patients.

Stent placement for management of a small parasagittal meningioma. Technical note.

The patient in this report had a parasagittal meningioma with an intrasinus extension that presented with features of benign intracranial hypertension and no focal neurological deficit or seizure. The meningioma was managed with a combination of endovascular stent placement and radiotherapy. The authors describe the investigation and technical aspects of stent placement for the stenosed sinus.

POLG1 mutations manifesting as autosomal recessive axonal Charcot-Marie-Tooth disease.

Background: Although a molecular diagnosis is possible in most patients having Charcot-Marie-Tooth disease (CMT), recessively inherited and axonal neuropathies still present a diagnostic challenge.

Objective: To determine the cause of axonal CMT type 2 in 3 siblings.

Design: Case report.

Cell therapies for neurological disease--from bench to clinic to bench.

The lack of any meaningful regeneration in the adult central nervous system (CNS) subsequent to damage or degeneration stimulated the concept of replacement of the deficient cells by transplantation. Thus, much time and effort has been spent on investigating the potential of cell replacement therapy for repair in a range of conditions of the CNS over the last 25 years. As promising proof of principle basic science results were slowly converted to success in clinical transplantation trials in Parkinson's disease (PD), the future seemed very encouraging for cell therapy.

Is there a future for neural transplantation?

Traditionally neural transplantation has had as its central tenet the replacement of missing neurons that have been lost because of neurodegenerative processes, as exemplified by diseases such as Parkinson disease (PD). However, the effectiveness and widespread application of this approach clinically has been limited, primarily because of the poor donor supply of human fetal neural tissue and the incomplete neurobiological understanding of the circuit reconstruction required to normalize function in these diseases. So, in PD the progress from promising neural transplantation in animal models to proof-of-principle, open-labeled clinical transplants, to randomized, placebo-controlled studies of neural transplantation has not been straightforward.

The emerging technologies of neural xenografting and stem cell transplantation for treating neurodegenerative disorders.

Neural transplantation has normally been considered in the context of the neurodegenerative disorders, Parkinson's and Huntington's disease, which are characterized pathologically by the predominant loss of specific cells in the basal ganglia. This approach has now emerged from the experimental arena into the level of clinical trial, at least with respect to fetal human allografts. However the ethical and practical problems with using such tissue has led to the search for alternative sources of cells of which two of the most promising are cells from another species, such as the pig (xenografts), and stem cells.