EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis

Background Neurodegenerative diseases often feature a prolonged phase of subtle changes preceding diagnosis. In amyotrophic lateral sclerosis (ALS), defining this prodromal period is critical for identifying early disease features and intervention windows. Methods In this case–control study, 475 patients with ALS and 285 controls from 20 centres in Germany and Switzerland completed a digital questionnaire on prodromal symptoms and health-related factors. Logistic regression included subgroup analyses by sex and clinical strata. Findings Patients with ALS reported a higher burden of prodromal complaints (OR 7.50, 95% CI 4.27–13.17; P < 0.001), particularly neuro-motor, sensory, and pain-related symptoms. Before symptom onset, patients consulted neurologists more often (OR 1.26, 1.10–1.44; P < 0.001) and females more often received speech therapy (OR 2.35, 1.05–5.28; P = 0.038). Prodromal herniated discs were more common in males (OR 2.21, 1.04–4.68; P = 0.038) and spinal-onset patients (OR 2.14, 1.25–3.67; P = 0.006). Patients more often had lower secondary education (OR 1.93, 1.24–3.01; P = 0.004), physically demanding occupations (OR 2.21, 1.42–3.43; P < 0.001), and higher consumption habits ( P < 0.005). Weight trajectories differed by sex ( P = 0.009), with pre-onset weight loss in male patients ( P < 0.001). Interpretation Patients with ALS retrospectively reported subtle motor impairment before recognised symptom onset, alongside altered healthcare use and sex- and subgroup-specific patterns. These findings suggest that sporadic ALS may be preceded by a prodromal period and identify mild motor impairment as a potential marker, pending prospective validation. Funding DGM e. V.

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Publication Details

Journal
EBioMedicine
Published
2026-10-09
DOI
https://doi.org/10.1016/j.ebiom.2026.106505
Primary Topic
Amyotrophic Lateral Sclerosis Research
Type
article
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article

EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis

Sarah Kristina Bublitz, Marcus Deschauer, Florian Kohlmayer, Maike Franziska Dohrn et al.
EBioMedicine
Amyotrophic Lateral Sclerosis Research
article

EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis

Sarah Kristina Bublitz, Marcus Deschauer, Florian Kohlmayer, Maike Franziska Dohrn, Ines Marschalkowski, Laura Tzeplaeff, Bogdan Bjelica, Markus Weiler, Simon Witzel, Christoph Neuwirth, Paul Lingor, Michael P. Menden, Ana Galhoz, Stefan Lorenzl, Ute Weyen, Isabell Cordts, Johannes Dorst, Martin Regensburger, Daniel Zeller, René Guenther, Anne Gründel, Andreas Schwersenz, André C. Dorigan, Christian Schulze, Petra Rau, Jan Christoph Koch, Martin Svačina, Verena Panitz, Torsten Grehl, Helmar C. Lehmann, Thomas Meyer, David Brenner, Matthias Boentert, Andreas Hermann, Markus Weber, Susanne Petri, Joachim Wolf, André Maier, Tim Hagenacker, Jochen H. Weishaupt
article en

Abstract

Background Neurodegenerative diseases often feature a prolonged phase of subtle changes preceding diagnosis. In amyotrophic lateral sclerosis (ALS), defining this prodromal period is critical for identifying early disease features and intervention windows. Methods In this case–control study, 475 patients with ALS and 285 controls from 20 centres in Germany and Switzerland completed a digital questionnaire on prodromal symptoms and health-related factors. Logistic regression included subgroup analyses by sex and clinical strata. Findings Patients with ALS reported a higher burden of prodromal complaints (OR 7.50, 95% CI 4.27–13.17; P < 0.001), particularly neuro-motor, sensory, and pain-related symptoms. Before symptom onset, patients consulted neurologists more often (OR 1.26, 1.10–1.44; P < 0.001) and females more often received speech therapy (OR 2.35, 1.05–5.28; P = 0.038). Prodromal herniated discs were more common in males (OR 2.21, 1.04–4.68; P = 0.038) and spinal-onset patients (OR 2.14, 1.25–3.67; P = 0.006). Patients more often had lower secondary education (OR 1.93, 1.24–3.01; P = 0.004), physically demanding occupations (OR 2.21, 1.42–3.43; P < 0.001), and higher consumption habits ( P < 0.005). Weight trajectories differed by sex ( P = 0.009), with pre-onset weight loss in male patients ( P < 0.001). Interpretation Patients with ALS retrospectively reported subtle motor impairment before recognised symptom onset, alongside altered healthcare use and sex- and subgroup-specific patterns. These findings suggest that sporadic ALS may be preceded by a prodromal period and identify mild motor impairment as a potential marker, pending prospective validation. Funding DGM e. V.

EBioMedicineVol. 133
Philipps University of Marburg (DE), The University of Melbourne (AU), University of Cologne (DE), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), Universität Ulm (DE), Heidelberg University (DE), University of Münster (DE), Universitätsklinikum Gießen und Marburg (DE), Paracelsus Medical University (AT), University Hospitals of the Ruhr-University of Bochum (DE), Kantonsspital St. Gallen (CH), German Center for Neurodegenerative Diseases (DE), University Hospital Heidelberg (DE), TUM Klinikum (DE), Helmholtz Zentrum München (DE), Medizinische Hochschule Hannover (DE), Krankenhaus Agatharied (DE), Munich Cluster for Systems Neurology (DE), Universitätsmedizin Göttingen (DE), Universitätsklinikum Würzburg (DE), Klinikum Osnabrück (DE), Universitätsmedizin Rostock (DE), BG University Hospital Bergmannsheil Bochum (DE), Alfried Krupp Hospital (DE), University Hospital Cologne (DE), University Hospital Carl Gustav Carus (DE), Medizinische Fakultät Mannheim, Stiftung Universitätsmedizin Essen (DE), University of Rostock (DE), University of Duisburg-Essen (DE), Technical University of Munich (DE), University of Göttingen (DE), Technische Universität Dresden (DE), Charité - Universitätsmedizin Berlin (DE), RWTH Aachen University (DE)
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Amyotrophic Lateral Sclerosis Research
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