Statistical analysis plan for the motor neuron disease systematic multi-arm adaptive randomised trial (MND-SMART).

Background: MND-SMART is a platform, multi-arm, multi-stage, multi-centre, randomised controlled trial recruiting people with motor neuron disease. Initially, the treatments memantine and trazodone will each be compared against placebo, but other investigational treatments will be introduced into the trial later. The co-primary outcomes are the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALS-FRS-R) functional outcome, which is assessed longitudinally, and overall survival.

Motor Neuron Disease Systematic Multi-Arm Adaptive Randomised Trial (MND-SMART): a multi-arm, multi-stage, adaptive, platform, phase III randomised, double-blind, placebo-controlled trial of repurposed drugs in motor neuron disease.

Introduction: Motor neuron disease (MND) is a rapidly fatal neurodegenerative disease. Despite decades of research and clinical trials there remains no cure and only one globally approved drug, riluzole, which prolongs survival by 2-3 months. Recent improved mechanistic understanding of MND heralds a new translational era with many potential targets being identified that are ripe for clinical trials.

The novel MAPT mutation K298E: mechanisms of mutant tau toxicity, brain pathology and tau expression in induced fibroblast-derived neurons.

Frontotemporal lobar degeneration (FTLD) consists of a group of neurodegenerative diseases characterized by behavioural and executive impairment, language disorders and motor dysfunction. About 20-30% of cases are inherited in a dominant manner. Mutations in the microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T).

Use of intravenous immunoglobulin in the Department of Neurology at Ninewells Hospital, 2008-2009: Indications for utilization and cost-effectiveness.

Unlabelled: This study was designed to identify the indications for prescription of intravenous immunoglobulin (IVIg) in neurology and the cost effectiveness of this therapy.

Objectives: IVIg is a relatively costly therapy and the annual budget spent on providing this therapy for various indications at Ninewells Hospital was close to £1.5 million.

Incidence of amyotrophic lateral sclerosis in Europe.

Background: Geographical differences in the incidence of amyotrophic lateral sclerosis (ALS) have been reported in the literature but comparisons across previous studies are limited by different methods in case ascertainment and by the relatively small size of the studied populations. To address these issues, the authors undertook a pooled analysis of European population based ALS registries.

Methods: All new incident ALS cases in subjects aged 18 years old and older were identified prospectively in six population based registries in three European countries (Ireland, UK and Italy) in the 2 year period 1998-1999, with a reference population of almost 24 million.

50bp deletion in the promoter for superoxide dismutase 1 (SOD1) reduces SOD1 expression in vitro and may correlate with increased age of onset of sporadic amyotrophic lateral sclerosis.

The objective was to test the hypothesis that a described association between homozygosity for a 50bp deletion in the SOD1 promoter 1684bp upstream of the SOD1 ATG and an increased age of onset in SALS can be replicated in additional SALS and control sample sets from other populations. Our second objective was to examine whether this deletion attenuates expression of the SOD1 gene. Genomic DNA from more than 1200 SALS cases from Ireland, Scotland, Quebec and the USA was genotyped for the 50bp SOD1 promoter deletion.

The incidence of motor nueron disease in Scotland.

Between 1989 and 1998, 1226 cases of ALS/MND were identified in Scotland, with mean age of onset 65.2 (SD 11.9) years for men and 67.

A population based study of respiratory function in motor neuron disease patients living in Tayside and North East Fife, Scotland.

Respiratory failure is a major cause of morbidity and the principal cause of death in motor neuron disease; non-invasive ventilation is increasingly used worldwide to palliate the respiratory symptoms. This observational study was designed to evaluate the prevalence of respiratory insufficiency within the motor neuron disease population of Tayside and North East Fife, Scotland. Twenty-six patients were identified, their diagnosis confirmed according to agreed criteria and subjected to the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, the Epworth Sleepiness questionnaire; spirometry, sniff nasal inspiratory pressure and nocturnal pulse oximetry measurements.

Multiple sclerosis in Tayside, Scotland: detection of clusters using a spatial scan statistic.

Debate continues over the relative importance of genetic factors over infectious agents in the aetiology of multiple sclerosis (MS). Detection of clusters of MS in space and time in the Tayside region of Scotland, UK would provide valuable evidence for the movement of infectious agents into a genetically susceptible population. A spatial scan statistic was used to detect, locate and provide a robust statistical test of any clusters found, without prior knowledge of their location or size.

Frequency, timing and outcome of gastrostomy tubes for amyotrophic lateral sclerosis/motor neurone disease--a record linkage study from the Scottish Motor Neurone Disease Register.

Aims: To describe the frequency, timing and outcome from gastrostomy in amyotrophic lateral sclerosis/motor neurone disease (ALS/MND).

Methods: The Scottish MND Register, a population based disease register (1989-1998), with record linkage to the Scottish Morbidity 1 dataset of hospital discharges coded for gastrostomy procedure was used. Descriptive statistics of patients undergoing gastrostomy were extracted.

The epidemiology of amyotrophic lateral sclerosis (ALS/MND) in people aged 80 or over.

Objective: To describe the clinical features, incidence, survival and process of care of people with Amyotrophic Lateral Sclerosis/Motor Neurone Disease aged 80 years or more at diagnosis.

Design: Prospective, population-based descriptive epidemiological study.

Setting: Scotland (population 5.