ArticleNeurology2025
Proposed Research Criteria for Mild Motor Impairment as a Prodromal Syndrome in Amyotrophic Lateral Sclerosis.
Article in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Accuracy of muscle ultrasonography in detecting fasciculations for the diagnosis of amyotrophic lateral sclerosis: a systematic review and meta-analysis.Journal of neurology · 2026Pooled it
- Presymptomatic Amyotrophic Lateral Sclerosis: From Early Biomarker Detection to Phenoconversion Prediction.Diagnostics (Basel, Switzerland) · 2026Review
- Genetic ALS-Progressive Sleep Defects Precede the Onset of Clinical Disease.European journal of neurology · 2026Observational
- Longitudinal plasma proteomics predict phenoconversion to clinically manifest ALS.Nature medicine · 2026Article
- Distinct Prescription Patterns Emerge Years Before ALS Diagnosis: A Nationwide Registry-Based Study.Annals of neurology · 2026Article
- Predicting Phenoconversion to Clinically Manifest ALS: Results of a Large-Scale Proteomic Study.medRxiv : the preprint server for health sciences · 2025Article
- Design considerations for C9orf72 disease prevention trials.Brain : a journal of neurology · 2025Review
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThe presymptomatic stage of amyotrophic lateral sclerosis (ALS) is typically assumed to be clinically silent. Our previous work, however, has revealed evidence of a prodromal stage, termed mild motor impairment (MMI). In this study, we propose operational criteria for MMI, describe its frequency in a genetically diverse cohort, and examine the association between MMI and time to ALS phenoconversion.
methodsPre-Symptomatic Familial ALS (
resultsThe study cohort includes 49 controls (mean age 38.9, 61% female), 153 presymptomatic carriers (mean age 43.1, 61% female), and 31 ALS phenoconverters (mean age 54.4, 58% female). Seven criteria for MMI are proposed, each reflecting a different pattern of upper/lower motor neuron signs, without corresponding weakness, in 1 or more of 4 topographic regions. MMI, defined as meeting ≥1 of these criteria, was observed at 1 or more study visits in 17 of 31 phenoconverters (55%) before clinically manifest ALS, 66 of 153 presymptomatic carriers (43%) who had not yet phenoconverted, and 7 of 49 controls (14%). Among all mutation carriers, the 25th percentile (95% CI) of time to phenoconversion was, respectively, 3.7 (1.6-4.7) and 14.1 (8.9-∞) years for those with and without MMI at baseline, with a hazard ratio of 5.1 (95% CI 2.2-12.2, DISCUSSION: MMI is a recognizable syndrome. Although nonspecific, it identifies presymptomatic carriers at elevated risk of ALS phenoconversion. Combining MMI with emerging biomarkers of underlying pathology may help differentiate those who are prodromal from those who are not prodromal for ALS. Characterization and study of MMI, including replication in other studies, may empower early therapeutic intervention and ALS prevention efforts.
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