ArticleJournal of neurology2025
Rate of change in upper and lower motor neuron burden is associated with survival in amyotrophic lateral sclerosis.
Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundWe hypothesize that the rate of change in upper (ΔUMN) and lower (ΔLMN) motor neuron signs from symptom onset to first clinical assessment represent best predictors of survival and disease progression in amyotrophic lateral sclerosis (ALS) compared to singular quantification of UMN and LMN involvement.
methodsA retrospective inpatient cohort of 1000 ALS patients was evaluated. The burden of UMN and LMN signs was assessed using the Penn Upper Motor Neuron Score and Lower Motor Neuron Score, respectively. For 421 patients, we compute the ENCALS survival model. Univariate and regularized Cox regressions were conducted to estimate the effect of the aforementioned variables on survival. The ROC curve analysis was then employed to a training sub-cohort to identify a ΔLMN cut-off value discriminating ALS patients with prolonged vs short survival. This cut-off value was then cross validated on a test sub-cohort. A multinomial regression model was used to compare different ΔUMN and ΔLMN scores among ENCALS groups.
resultsΔUMN and ΔLMN showed a negative association with survival (ΔUMN: HR = 1.30; ΔLMN: HR = 4.22). A cut-off value of 0.22 for ΔLMN was identified to predict patients with estimated short vs prolonged survival. ENCALS groups characterized by shorter survival presented significantly higher ΔUMN and ΔLMN scores compared to those with longer survival. No significant association of PUMNS or LMNS gross scores with the above-mentioned variables was observed.
conclusionBy reflecting the progressing degeneration of the two distinct motor neuron subpopulations, ΔUMN and ΔLMN might represent reliable and easily measurable clinical indexes to estimate survival in ALS.
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