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Interaction of sex and onset site on the disease trajectory of amyotrophic lateral sclerosis

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Abstract

Background

Studies showed the impact of sex and onset site (spinal or bulbar) on disease onset and survival in ALS. However, they mainly result from cross-sectional or survival analysis, and the interaction of sex and onset site on the different proxies of disease trajectory has not been fully investigated.

Methods

We selected all patients with repeated observations in the PRO-ACT database. We divided them into four groups depending on their sex and onset site. We estimated a multivariate disease progression model, named ALS Course Map, to investigate the combined temporal changes of the four sub-scores of the revised ALS functional rating scale (ALSFRSr), the forced vital capacity (FVC), and the body mass index (BMI). We then compared the progression rate, the estimated age at onset, and the relative progression of the outcomes across each group.

Results

We included 1438 patients from the PRO-ACT database. They were 51% men with spinal onset, 12% men with bulbar onset, 26% women with spinal onset, and 11% women with bulbar onset. We showed a significant influence of both sex and onset site on the ALSFRSr progression. The BMI decreased 8.9 months earlier (95% CI [3.9, 13.8]) in women than men, after correction for the onset site. Among patients with bulbar onset, FVC was impaired 2.6 months earlier (95% CI [0.6, 4.6]) in women.

Conclusion

Using a multivariable disease modelling approach, we showed that sex and onset site are important drivers of the progression of motor function, BMI, and FVC decline.

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Acknowledgements

We warmly thank Igor Koval for the review of the data processing and all the team members of ARAMIS for their input and advice.

Funding

This paper is funded in part by grant number 826421 (TVB-Cloud) from the H2020 program, and ANR-10-IAIHU-06 (IHU ICM), ANR-19-P3IA-0001 (PRAIRIE 3IA Institute), and ANR-19-JPW2-000 (E-DADS) from ANR.

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Author notes

  1. Sophie Tezenas Du Montcel and Stanley Durrleman contributed equally to this work as senior authors.

Authors and Affiliations

  1. Sorbonne Université, Institut du Cerveau, Paris Brain Institute, ICM, CNRS, InriaInserm, AP-HP, Hôpital de La Pitié Salpêtrière, 75013, Paris, France

    Juliette Ortholand, Sophie Tezenas du Montcel & Stanley Durrleman

  2. Laboratoire d’Imagerie Biomédicale, Sorbonne Université, CNRS, INSERM, Paris, France

    Pierre-François Pradat

  3. APHP, Département de Neurologie, Hôpital Pitié-Salpêtrière, Centre Référent SLA, Paris, France

    Pierre-François Pradat

  4. Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute Ulster University, C-TRIC, Altnagelvin Hospital, Derry, Londonderry, UK

    Pierre-François Pradat

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  1. Juliette Ortholand
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Contributions

JO contributed to drafting/revision of the manuscript for content, including medical writing for content; study concept or design; and analysis or interpretation of data. P-FP performed drafting/revision of the manuscript for content, including medical writing for content; STdM contributed to drafting/revision of the manuscript for content, including medical writing for content; study concept or design; and analysis or interpretation of data. SD contributed to drafting/revision of the manuscript for content, including medical writing for content; study concept or design; and analysis or interpretation of data.

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Correspondence to Juliette Ortholand.

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Ortholand, J., Pradat, PF., Tezenas du Montcel, S. et al. Interaction of sex and onset site on the disease trajectory of amyotrophic lateral sclerosis. J Neurol 270, 5903–5912 (2023). https://doi.org/10.1007/s00415-023-11932-7

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