EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis.
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.
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BibTeX
@article{cordts2026earlyals,
title = {{EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis.}},
author = {Isabell Cordts and Ana Galhoz and Laura Tzeplaeff and Anne Gründel and Florian Kohlmayer and Andreas Schwersenz and Ines Marschalkowski and Bogdan Bjelica and Verena Panitz and Christian Schulze and Martin Svačina and Petra Rau and André C. Dorigan and Marcus Deschauer and Simon Witzel and David Brenner and Jochen H. Weishaupt and Sarah K. Bublitz and Stefan Lorenzl and Andreas Hermann and Tim Hagenacker and Joachim Wolf and Martin Regensburger and Helmar C. Lehmann and Maike F. Dohrn and Johannes Dorst and René Guenther and André Maier and Thomas Meyer and Daniel Zeller and Christoph Neuwirth and Markus Weber and Jan C. Koch and Matthias Boentert and Markus Weiler and Susanne Petri and Ute Weyen and Torsten Grehl and Michael P. Menden and Paul Lingor},
journal = {EBioMedicine},
year = {2026},
month = oct,
doi = {10.1016/j.ebiom.2026.106505},
url = {https://europepmc.org/article/MED/42854356},
note = {CC BY},
}
RIS
TY - JOUR
TI - EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis.
AU - Isabell Cordts
AU - Ana Galhoz
AU - Laura Tzeplaeff
AU - Anne Gründel
AU - Florian Kohlmayer
AU - Andreas Schwersenz
AU - Ines Marschalkowski
AU - Bogdan Bjelica
AU - Verena Panitz
AU - Christian Schulze
AU - Martin Svačina
AU - Petra Rau
AU - André C. Dorigan
AU - Marcus Deschauer
AU - Simon Witzel
AU - David Brenner
AU - Jochen H. Weishaupt
AU - Sarah K. Bublitz
AU - Stefan Lorenzl
AU - Andreas Hermann
AU - Tim Hagenacker
AU - Joachim Wolf
AU - Martin Regensburger
AU - Helmar C. Lehmann
AU - Maike F. Dohrn
AU - Johannes Dorst
AU - René Guenther
AU - André Maier
AU - Thomas Meyer
AU - Daniel Zeller
AU - Christoph Neuwirth
AU - Markus Weber
AU - Jan C. Koch
AU - Matthias Boentert
AU - Markus Weiler
AU - Susanne Petri
AU - Ute Weyen
AU - Torsten Grehl
AU - Michael P. Menden
AU - Paul Lingor
PY - 2026
DA - 2026/10/09
JO - EBioMedicine
DO - 10.1016/j.ebiom.2026.106505
UR - https://europepmc.org/article/MED/42854356
AB - 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.
SN - 2352-3964
ER -