{
  "abstract": "Background\n\nNeurodegenerative 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\n\nIn 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\n\nPatients 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\n\nPatients 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\n\nDGM e. V.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 40,
  "authors": [
    {
      "name": "Isabell Cordts",
      "orcid": "0000-0002-2078-1997"
    },
    {
      "name": "Ana Galhoz",
      "orcid": "0000-0001-7402-5292"
    },
    {
      "name": "Laura Tzeplaeff",
      "orcid": "0009-0003-7643-3232"
    },
    {
      "name": "Anne Gründel"
    },
    {
      "name": "Florian Kohlmayer"
    },
    {
      "name": "Andreas Schwersenz"
    },
    {
      "name": "Ines Marschalkowski"
    },
    {
      "name": "Bogdan Bjelica"
    },
    {
      "name": "Verena Panitz"
    },
    {
      "name": "Christian Schulze"
    },
    {
      "name": "Martin Svačina"
    },
    {
      "name": "Petra Rau"
    },
    {
      "name": "André C. Dorigan"
    },
    {
      "name": "Marcus Deschauer"
    },
    {
      "name": "Simon Witzel"
    },
    {
      "name": "David Brenner"
    },
    {
      "name": "Jochen H. Weishaupt"
    },
    {
      "name": "Sarah K. Bublitz"
    },
    {
      "name": "Stefan Lorenzl"
    },
    {
      "name": "Andreas Hermann"
    },
    {
      "name": "Tim Hagenacker"
    },
    {
      "name": "Joachim Wolf"
    },
    {
      "name": "Martin Regensburger",
      "orcid": "0000-0002-2172-7386"
    },
    {
      "name": "Helmar C. Lehmann"
    },
    {
      "name": "Maike F. Dohrn"
    },
    {
      "name": "Johannes Dorst"
    },
    {
      "name": "René Guenther"
    },
    {
      "name": "André Maier"
    },
    {
      "name": "Thomas Meyer"
    },
    {
      "name": "Daniel Zeller"
    },
    {
      "name": "Christoph Neuwirth",
      "orcid": "0000-0002-1874-8872"
    },
    {
      "name": "Markus Weber"
    },
    {
      "name": "Jan C. Koch"
    },
    {
      "name": "Matthias Boentert"
    },
    {
      "name": "Markus Weiler",
      "orcid": "0000-0002-8942-7662"
    },
    {
      "name": "Susanne Petri"
    },
    {
      "name": "Ute Weyen"
    },
    {
      "name": "Torsten Grehl"
    },
    {
      "name": "Michael P. Menden"
    },
    {
      "name": "Paul Lingor",
      "orcid": "0000-0001-9362-7096"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dhfwe8c0dxnjw.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ebiom.2026.106505",
  "fulltext_url": "https://europepmc.org/articles/PMC13677275",
  "id": "dhfwe8c0dxnjw",
  "issns": [
    "2352-3964"
  ],
  "landing_url": "https://europepmc.org/article/MED/42854356",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Amyotrophic Lateral Sclerosis Research"
    ]
  ],
  "openalex": "W7221103287",
  "pdf_url": "https://europepmc.org/articles/PMC13677275?pdf=render",
  "pmcid": "PMC13677275",
  "pmid": "42854356",
  "published": "2026-10-09",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/dhfwe8c0dxnjw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:12Z",
      "native_id": "MED:42854356",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42854356"
    },
    {
      "first_seen": "2026-10-30T12:19:49Z",
      "native_id": "10.1016/j.ebiom.2026.106505",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2352396426003890"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Amyotrophic Lateral Sclerosis Research",
      "subfield": "neurology"
    }
  ],
  "title": "EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis.",
  "title_text": "EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:49Z",
  "url": "https://research.draconitic.com/paper/dhfwe8c0dxnjw",
  "venue": "EBioMedicine",
  "versions": []
}