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Spatio-temporal clustering of amyotrophic lateral sclerosis in France: A population-based study

  • NEURO-EPIDEMIOLOGY
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Abstract

Objective

To assess spatial aggregates of amyotrophic lateral sclerosis (ALS) incident cases, using a solid geo-epidemiological statistical method, in France.

Methods

This population-based study (2003–2011) investigated 47.1 million person-years of follow-up (PYFU). Case ascertainment of incident ALS cases was based on multiple sources (ALS referral centers, hospital centres and health insurance data). Neurologists confirmed all ALS diagnoses. Exhaustiveness was estimated through capture-recapture. Aggregates were investigated in four steps: (a) geographical modelling (standardized incidence ratio (SIR) calculation), (b) analysis of the spatial distribution of incidence (Phothoff-Winttinghill’s test, Global Moran’s Index, Kulldorf’s spatial scan statistic, Local Moran’s Index), (c) classification of the level of certainty of spatial aggregates (i.e. definite cluster; probable over-incidence area; possible over-incidence area) and (d) evaluation of the robustness of the results.

Results

The standardized incidence of ALS was 2.46/100,000 PYFU (95% CI 2.31–2.63, European population as reference) based on 1199 incident cases. We identified 13 areas of spatial aggregates: one cluster (stable in robustness analysis), five probable over-incidence areas (2 stable in robustness analysis) and seven possible over-incidence areas (including 4 stable areas in robustness analysis). A cluster was identified in the Rhône-Alpes region: 100 observed vs 54.07 expected cases for 2,411,514 PYFU, SIR: 1.85 (95% CI 1.50–2.25).

Conclusion

We report here one of the largest investigations of incidence and spatial aggregation of ALS ever performed in a western country. Using a solid methodology framework for case ascertainment and cluster analysis, we identified 13 areas that warrant further investigation.

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Acknowledgements

We thank all the French bodies coordinating the ALS referral centers, public and private hospitals, health insurance sources and neurologists who collaborated with the BMAALS consortium. BMAALS consortium (in alphabetical order by last name): Eric Abadie, Béatrice Bec, Gérard Besson, Dominique Bicout, Vincent Bonneterre, Farid Boumédiene, Luc Brient, William Camu, Audrey Combes, Philippe Couratier, Aurelie Delzor, Saïda El Abdellaoui, Edwige Garnier, Emmeline Lagrange, Jean Philippe Leleu, Marion Lengronne, Jaime Luna, Benoit Marin, Estelle Masseret, Annick Mejean, Raoul Juntas-Morales, Marie Nicol, Nicolas Pageot, François Paraf, Valérie Pichon, Olivier Ploux, Pierre-Marie Preux, Véronique Rigaud.

Funding

This work was supported by the French National Research Agency (ANR) grant number programme ANR-11-CESA-0014 (Project “BMAALS”) and by the French Association against ALS (BMAA-LIM project).Agence Nationale de la Recherche,ANR-11-CESA-0014

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    Authors and Affiliations

    1. Inserm U1094, IRD U270, USC1501 INRAE, Univ. Limoges, CHU Limoges, EpiMaCT - Epidemiology of chronic diseases in tropical zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, Limoges, France

      Farid Boumédiene, Benoît Marin, Jaime Luna, Pierre Marie Preux & Philippe Couratier

    2. Department of Neurology, Centre de Reference SLA et Autres Maladies du Neurone Moteur, CHU Limoges, Limoges, France

      Jaime Luna, Géraldine Lautrette & Philippe Couratier

    3. University Grenoble Alpes, CNRS, Grenoble INP, TIMC, 38000, Grenoble, France

      Vincent Bonneterre

    4. Explorations Neurologiques et Centre SLA, CHU et Université de Montpellier, INSERM, Montpellier, France

      William Camu, Florence Esselin & Elisa De La Cruz

    5. Department of Neurology, CHU Grenoble-Alpes (Grenoble Teaching Hospital), Grenoble, France

      Emmeline Lagrange & Gérard Besson

    6. CEBIMER, Centre d’Epidémiologie, de Biostatistique et de Méthodologie de la Recherche, CHU Limoges, Limoges, France

      Pierre Marie Preux

    Author notes

    1. Farid Boumédiene and Benoît Marin have contributed equally.

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      1. Farid Boumédiene
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      Correspondence to Philippe Couratier.

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      The collection of data was authorized by the CCTIRS (Comité consultatif sur le traitement de l’information en matière de recherche dans le domaine de la santé, authorization no. 10487bis) on 20th January 2011 and the CNIL (Commission Nationale de l’Informatique et des Libertés, authorization no. 911038) on 27 May 2011. The protocol was reviewed by an ethics review board (Comité de Protection des Personnes Sud-Ouest Outre Mer IV) on 10th February 2011.

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      Boumédiene, F., Marin, B., Luna, J. et al. Spatio-temporal clustering of amyotrophic lateral sclerosis in France: A population-based study. Eur J Epidemiol 37, 1181–1193 (2022). https://doi.org/10.1007/s10654-022-00904-2

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