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