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Journal article
Amyotrophic lateral sclerosis established as a multistep process across phenotypes
European journal of neurology, e16532
2024
PMID: 39475283
Abstract
Background and purpose
Given the accepted multistep process of disease causation in amyotrophic lateral sclerosis (ALS), the present study was undertaken to determine the number of steps required for disease onset across each of the ALS phenotypes.
Methods
Clinical and demographic data were prospectively accumulated using the Australian Motor Neurone Disease Registry (2005–2016), and age-specific incidence rates were calculated. Poisson regression was utilized to assess the relationship between log age-specific incidence and log age of onset, with McFadden's R2 used to assess the goodness of fit of the model.
Results
In total, 2647 ALS patients were included, with mean disease-onset age being 62.2 ± 12.1 years. A linear relationship between log incidence and log age was established across ALS phenotypes, with variable slope estimates: bulbar 5.1 (95% confidence interval [CI] 4.6–5.6); cervical 2.7 (95% CI 2.3–3.0); lumbar 3.5 (95% CI 3.2–3.9); flail arm 4.7 (95% CI 3.9–5.5); flail leg 3.6 (95% CI 2.6–4.5); primary lateral sclerosis 2.7 (95% CI 1.8–3.7). Slope estimates were significantly higher in the bulbar compared to the cervical, lumbar and primary lateral sclerosis phenotypes. McFadden's R2 values were >0.4 for all phenotypes indicating excellent model fit.
Discussion
A multistep process has been established across all ALS phenotypes with variable slope estimates, suggesting that the number of steps to develop disease is different across clinical presentations. Identification of mechanisms underlying slope estimate variability could exert pathophysiological significance.
Details
- Title
- Amyotrophic lateral sclerosis established as a multistep process across phenotypes
- Authors/Creators
- Laura Ziser - The University of QueenslandRuben P. A. van Eijk - University Medical Center UtrechtMatthew C. Kiernan - Neuroscience Research AustraliaAllan McRae - The University of QueenslandRobert D. Henderson - Royal Brisbane and Women's HospitalDavid Schultz - Flinders Medical CentreMerrilee Needham - Fiona Stanley HospitalSusan Mathers - Calvary Health Care BethlehemPam McCombe - Royal Brisbane and Women's HospitalPaul Talman - Deakin UniversitySteve Vucic - Concord Repatriation General Hospital
- Publication Details
- European journal of neurology, e16532
- Publisher
- John Wiley & Sons Ltd on behalf of European Academy of Neurology.
- Number of pages
- 8
- Grant note
- National Health and Medical Research Council
National Health and Medical Research Council
- Identifiers
- 991005712748007891
- Copyright
- © 2024 The Author(s).
- Murdoch Affiliation
- Health Futures Institute; Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.765 ALS Mechanisms
- Web Of Science research areas
- Clinical Neurology
- Neurosciences
- ESI research areas
- Neuroscience & Behavior