Motor Neurone Disease In Scotland Research Articles

Exploratory study to evaluate the acceptability of a wearable accelerometer to assess motor progression in motor neuron disease.

Motor neuron disease (MND) is a rapidly progressive condition traditionally assessed using a questionnaire to evaluate physical function, the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). Its use can be associated with poor sensitivity in detecting subtle changes over time and there is an urgent need for more sensitive and specific outcome measures. The ActiGraph GT9X is a wearable device containing multiple sensors that can be used to provide metrics that represent physical activity. The primary aim of this study was to investigate the initial suitability and acceptability of limb-worn wearable devices to group of people with MND in Scotland. A secondary aim was to explore the preliminary associations between the accelerometer sensor data within the ActiGraph GT9X and established measures of physical function. 10 participants with MND completed a 12-week schedule of assessments including fortnightly study visits, both in-person and over videoconferencing software. Participants wore the device on their right wrist and right ankle for a series of movements, during a 6-min walking test and for a period of 24-h wear, including overnight. Participants also completed an ALSFRS-R and questionnaires on their experience with the devices. 80% of the participants found wearing these devices to be a positive experience and no one reported interference with daily living or added burden. However, 30% of the participants experienced technical issues with their devices. Data from the wearable devices correlated with established measures of physical function.

Genotype–phenotype characterisation of long survivors with motor neuron disease in Scotland

BackgroundWe investigated the phenotypes and genotypes of a cohort of ‘long-surviving’ individuals with motor neuron disease (MND) to identify potential targets for prognostication.MethodsPatients were recruited via the Clinical Audit Research and Evaluation for MND (CARE-MND) platform, which hosts the Scottish MND Register. Long survival was defined as > 8 years from diagnosis. 11 phenotypic variables were analysed. Whole genome sequencing (WGS) was performed and variants within 49 MND-associated genes examined. Each individual was screened for C9orf72 repeat expansions. Data from ancestry-matched Scottish populations (the Lothian Birth Cohorts) were used as controls.Results58 long survivors were identified. Median survival from diagnosis was 15.5 years. Long survivors were significantly younger at onset and diagnosis than incident patients and had a significantly longer diagnostic delay. 42% had the MND subtype of primary lateral sclerosis (PLS). WGS was performed in 46 individuals: 14 (30.4%) had a potentially pathogenic variant. 4 carried the known SOD1 p.(Ile114Thr) variant. Significant variants in FIG4, hnRNPA2B1, SETX, SQSTM1, TAF15, and VAPB were detected. 2 individuals had a variant in the SPAST gene suggesting phenotypic overlap with hereditary spastic paraplegia (HSP). No long survivors had pathogenic C9orf72 repeat expansions.ConclusionsLong survivors are characterised by younger age at onset, increased prevalence of PLS and longer diagnostic delay. Genetic analysis in this cohort has improved our understanding of the phenotypes associated with the SOD1 variant p.(Ile114Thr). Our findings confirm that pathogenic expansion of C9orf72 is likely a poor prognostic marker. Genetic screening using targeted MND and/or HSP panels should be considered in those with long survival, or early-onset slowly progressive disease, to improve diagnostic accuracy and aid prognostication.

Changing epidemiology of motor neurone disease in Scotland.

Scotland benefits from an integrated national healthcare team for motor neurone disease (MND) and a tradition of rich clinical data capture using the Scottish MND Register (launched in 1989; one of the first national registers). The Scottish register was re-launched in 2015 as Clinical Audit Research and Evaluation of MND (CARE-MND), an electronic platform for prospective, population-based research. We aimed to determine if incidence of MND is changing over time. Capture-recapture methods determined the incidence of MND in 2015-2016. Incidence rates for 2015-2016 and 1989-1998 were direct age and sex standardised to allow time-period comparison. Phenotypic characteristics and socioeconomic status of the cohort are described. Coverage of the CARE-MND platform was 99%. Crude incidence in the 2015-2017 period was 3.83/100,000 person-years (95% CI 3.53-4.14). Direct age-standardised incidence in 2015 was 3.42/100,000 (95% CI 2.99-3.91); in 2016, it was 2.89/100,000 (95% CI 2.50-3.34). The 1989-1998 direct standardised annual incidence estimate was 2.32/100,000 (95% CI 2.26-2.37). 2015-2016 standardised incidence was 66.9% higher than Northern European estimates. Socioeconomic status was not associated with MND. Our data show a changing landscape of MND in Scotland, with a rise in incidence by 36.0% over a 25-year period. This is likely attributable to ascertainment in the context of improved neurological services in Scotland. Our data suggest that CARE-MND is a reliable national resource and findings can be extrapolated to the other Northern European populations.

WED 225 Changing epidemiology of motor neurone disease in scotland

Clinical Audit Research and Evaluation for Motor Neurone Disease (CARE-MND) (formerly the Scottish MND Register) is an electronic platform for prospective, population-based research in Scotland. We present the results of recent epidemiological analyses.Capture-recapture methods were adopted to determine incidence of MND in 2015–2016: 1) notifications via CARE-MND, 2) Information Services Division (ISD) data i) hospital admissions, ii) death data, iii) riluzole prescriptions.Crude prevalence of MND in Scotland is 7.61–7.64/100,000 of the population. Direct age standardised incidence in 2015 was 3.42/100,000 (95% CI: 2.99 to 3.91); in 2016, 2.89/100,000 (95% CI: 2.50 to 3.34). Using maximum likelihood estimates, coverage of the CARE-MND platform was 99.6% (2015) and 98.1% (2016). In view of high coverage, CARE-MND estimates alone will be presented for 2017.Previous Scottish MND Register capture-recapture annual incidence estimates were 2.32/100,000 (95% CI: 2.26 to 2.37) in 1989–1998 (direct standardised). Our data suggest a changing landscape of MND in Scotland, with a rise in incidence by 36%. This could be attributed to improved neurological services in Scotland. Incidence is also 67% higher than Northern European estimates, which perhaps reflects our robust ascertainment methods. However, further work using population CARE-MND data aims to determine if genetic or environmental variables account for these findings.

11 Premorbid neuropsychiatric disease in patients with motor neurone disease in scotland

<h3>Objective</h3> Motor neurone disease (MND) is a rapidly progressive neurodegenerative disease, typically affecting limb, bulbar and respiratory muscles. Cognitive and behavioural change are also key features of the disease in up to 50% of patients (1). Neuropsychiatric symptoms may precede motor symptoms. A recent study highlighted that depression may be an independent risk factor for MND (2). We aimed to review the frequency of i) premorbid neuropsychiatric disease ii) premorbid psychotropic medication use iii) neuropsychiatric presentation of MND and iv) neuropsychiatric evolution of MND in an incident Scottish cohort. <h3>Method</h3> Patients were recruited via the Scottish MND Register (SMNDR). Patient characteristics (past medical and drug history, symptom onset and progression) were collected via the Scottish Clinical Audit Research and Evaluation for MND (CARE-MND) national care proforma. <h3>Results</h3> Incident cases of MND diagnosed in 2015/16 from a population-based national cohort will be presented. At interim analysis, 267 patients were eligible for review. 38 (14%) of patients had a documented past history of neuropsychiatric disease; 29 (11%) of mood disorder. 66 (25%) of patients had a history of psychotropic medication use. Frequency of premorbid neuropsychiatric disease will be compared with recent UK survey results (3). In 11 (4%) of patients, emotional lability, memory change or behavioural change was the presenting symptom. 32 (12%) of patients developed these features later in disease course. <h3>Conclusion</h3> From our preliminary analysis, rates of premorbid neuropsychiatric disease in patients with MND are comparable with population estimates. However, symptoms of low mood have been shown to have a negative impact on quality of life and are associated with faster disease progression (4). Clinical teams need to be mindful of these symptoms in all aspects of patient care, and ensure that appropriate therapies are offered and monitored.

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population.

Avoiding false positive diagnoses of motor neuron disease: lessons from the Scottish Motor Neuron Disease Register.

To describe the frequency and characteristics of those patients initially registered with the Scottish Motor Neuron Disease Register (SMNDR) but who subsequently had a diagnosis other than MND made (false positives), to analyse the features which led to a revised diagnosis, and to draw conclusions which might improve routine neurological practice. The Scottish Motor Neuron Disease Register is a community based, prospective disease register to identify and follow up all incident cases of motor neuron disease in Scotland. Fifty three patients out of a total of 552 registered are presented, who, after initial registration, were later excluded because they failed to satisfy the register's diagnostic criteria. Seven of these patients were labelled as "MND plus" syndromes and may represent a distinct subset of MND. The remaining 46 patients had an alternative diagnosis made (false positive group), accounting for 8% of the total. In half of these cases, potentially beneficial therapies are available. The predominant reasons which lead to a diagnostic revision were: failure of symptom progression, development of atypical clinical features for MND, and investigation results. Patients with MND should undergo thorough and relevant investigations at presentation with the emphasis on neuroradiological imaging and neurophysiology; all patients should be followed up by an experienced neurologist, particularly those in whom symptoms and signs are restricted to either the bulbar or spinal muscles; failure of symptom progression or development of atypical features should lead to an early reassessment; finally, patients should be informed of the diagnosis only when it is secure.

The Scottish Motor Neuron Disease Register: a prospective study of adult onset motor neuron disease in Scotland. Methodology, demography and clinical features of incident cases in 1989.

The Scottish Motor Neuron Disease Register (SMNDR) is a prospective, collaborative, population based study of motor neuron disease (MND) in Scotland. The register started in January 1989 with the aim of studying the clinical and epidemiological features of MND by prospectively identifying incident patients. It is based on a system of registration by recruitment from multiple sources, followed by the collection of complete clinical data and follow up, mainly through general practitioners. In this report the register's methodology and the demography and incidence data for the first year of study are presented. One hundred and fourteen newly diagnosed patients were identified in 1989 giving a crude incidence for Scotland of 2.24/100,000/year. Standardised incidence ratios showed a non-significant trend towards lower rates in north eastern regions and island areas.

The epidemiology of motor neuron disease in Scotland.

AbstractA study was made of the frequency of motor neuron disease in Scotland. The frequency of the disease was about the same as in most other countries of the world, but it may be increasing in Scotland. Individuals resident in the north and east of the country and those engaged in agricultural work were found to have an increased risk of developing the disease. It is suggested that motor neuron disease might be related to the use of insecticides or may result from a persistent viral infection.