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Epidemiology
Original research
Identifying key signs of motor neurone disease in primary care: a nested case–control study using the QResearch database
  1. Xue W Mei1,
  2. Judith Burchardt1,
  3. Tom A Ranger1,
  4. Christopher J McDermott2,
  5. Aleksandar Radunovic3,
  6. Carol Coupland1,4,
  7. Julia Hippisley-Cox1
  1. 1Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  2. 2Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
  3. 3Barts MND centre, Barts Health NHS Trust, London, UK
  4. 4School of Medicine, University of Nottingham, Nottingham, UK
  1. Correspondence to Professor Julia Hippisley-Cox; julia.hippisley-cox{at}phc.ox.ac.uk

Abstract

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.

Participants Baseline cohort included 16.8 million individuals aged 18 years and over without a diagnosis of MND at study entry and with more than 3 years of digitalised information available. The nested case–control data set comprised of 6437 cases of MND diagnosed between January 1998 and December 2019, matched by year of birth, gender, general practice and calendar year to 62 003 controls.

Main outcome measures Clinically recognised symptoms and signs of MND prior to diagnosis and symptoms and factors which are relevant in primary care setting.

Results This study identified 17 signs and symptoms that were independently associated with MND diagnosis in a multivariable analysis. Of these, seven were new to the Red Flag tool: ataxia, dysphasia, weight loss, wheeze, hoarseness of voice, urinary incontinence and constipation. Among those from the Red Flag tool, dysarthria had the strongest association with subsequent MND (adjusted OR (aOR): 43.2 (95% CI 36.0 to 52.0)) followed by muscle fasciculations (aOR: 40.2 (95% CI 25.6 to 63.1)) and muscle wasting (aOR: 31.0 (95% CI 19.5 to 49.4)). Additionally, the associations between MND diagnosis and family history, dropped foot, focal weakness and sialorrhoea remained robust after controlling for confounders. Patients who reported symptoms indicative of damage to the lower brainstem and its connections were diagnosed sooner than those who presented with respiratory or cognitive signs.

Conclusion This is the first study that has identified, confirmed and quantified the association of key symptoms and signs with MND diagnosis. In addition to known factors, the study has identified the following new factors to be independently associated with MND prior to diagnosis: ataxia, dysphasia, wheeze and hoarseness of voice. These findings may be used to improve risk stratification and earlier detection of MND in primary care.

  • Motor neurone disease
  • EPIDEMIOLOGY
  • PRIMARY CARE

Data availability statement

Data may be obtained from a third party and are not publicly available. To guarantee the confidentiality of personal and health information only the authors have had access to the data during the study in accordance with the relevant licence agreements. Access to the QResearch data is according to the information on the QResearch website (www.qresearch.org).

https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/bmjopen-2021-058383

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    Data availability statement

    Data may be obtained from a third party and are not publicly available. To guarantee the confidentiality of personal and health information only the authors have had access to the data during the study in accordance with the relevant licence agreements. Access to the QResearch data is according to the information on the QResearch website (www.qresearch.org).

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    Footnotes

    • Twitter @WinnieXueMei, @JudithBurchardt, @JuliaHCox

    • Contributors XWM undertook data manipulation, reviewed the literature, led the data analysis, undertook interpretation of the data and wrote the first draft of the paper. JH-C led the study, obtained funding, data approvals, designed the study, drafted the protocol, contributed to the data management and interpretation of the data. CJM contributed to the funding application, contributed to protocol development and interpretation of results. CC contributed to the funding application, the discussion on protocol development and provided critical feedback on drafts of the manuscript. JB reviewed the literature on presentation of MND and conducted a search of how it had presented in patients in her own general practice. TAR contributed to interpretation of findings and compilation of the manuscript. XWM, JH-C, CC, CJM, JB, AR, and TAR approved the protocol, contributed to the critical revision of the manuscript and approved the final version of the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. JH-C accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

    • Funding This study was funded by a grant from Motor Neurone Disease Association. The funders of this study contributed to the design and conduct of the study and reviewed and approve the manuscript. The funders had no role in analysis or interpretation of data. XM, TR, CC, JHC had full access to all the study data and JHC had final responsibility for submission.

    • Competing interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. JHC reports grants from grants from the John Fell Oxford University Press Research Fund; Cancer Research UK (CR-UK) grant number C5255/A18085, through the Cancer Research UK Oxford Centre and the Oxford Wellcome Institutional Strategic Support Fund (204826/Z/16/Z), during the conduct of the study. JHC is an unpaid director of QResearch, a not-for-profit organisation which is a partnership between the University of Oxford and EMIS Health who supply the QResearch database used for this work. JHC is a founder and shareholder of ClinRisk ltd and was its medical director until 31st May 2019. JHC is member of the SAGE subgroups on ethnicity and data and is chair of the risk stratification subgroup of NERVTAG. The views expressed are those of the authors only. CJM is supported by the NIHR Sheffield Biomedical Centre.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.