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Cordts, I.* ; Galhoz, A. ; Tzeplaeff, L.* ; Gründel, A.* ; Kohlmayer, F.* ; Schwersenz, A.* ; Marschalkowski, I.* ; Bjelica, B.* ; Panitz, V.* ; Schulze, C.* ; Svačina, M.* ; Rau, P.* ; Dorigan, A.C.* ; Deschauer, M.* ; Witzel, S.* ; Brenner, D.* ; Weishaupt, J.H.* ; Bublitz, S.K.* ; Lorenzl, S.* ; Hermann, A.* ; Hagenacker, T.* ; Wolf, J.* ; Regensburger, M.* ; Lehmann, H.C.* ; Dohrn, M.F.* ; Dorst, J.* ; Guenther, R.* ; Maier, A.* ; Meyer, T.* ; Zeller, D.* ; Neuwirth, C.* ; Weber, M.* ; Koch, J.C.* ; Boentert, M.* ; Weiler, M.* ; Petri, S.* ; Weyen, U.* ; Grehl, T.* ; Menden, M.P. ; Lingor, P.*

EARLY-ALS: A multicentre study on prodromal amyotrophic lateral sclerosis.

EBioMedicine 133:106505 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 type Article: Journal article
Document type Scientific Article
Keywords Case–control Study ; Early Disease Detection ; Environmental Risk Factors ; Motor Neuron Disease ; Preclinical Neurodegeneration ; Sex-specific Differences
ISSN (print) / ISBN 2352-3964
e-ISSN 2352-3964
Journal EBioMedicine
Quellenangaben Volume: 133, Issue: , Pages: , Article Number: 106505 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)