Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (5): 1505-1512.doi: 10.4103/NRR.NRR-D-23-01359

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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis: a retrospective observational study

Jieying Wu1, 2 , Shan Ye1, 2 , Xiangyi Liu1, 2 , Yingsheng Xu1, 2 , Dongsheng Fan1, 2, 3, *   

  1. 1 Department of Neurology, Peking University Third Hospital, Beijing, China;  2 Beijing Municipal Key Laboratory of Biomarker and Translattonal Research in Neurodegenerattve Diseases, Beijing, China;  3 Key Laboratory for Neuroscience, Nattonal Health Commission/Ministry of Educatton, Peking University, Beijing, China
  • Online:2025-05-15 Published:2024-10-31
  • Contact: Dongsheng Fan, MD, PhD, dsfan2010@aliyun.com.
  • Supported by:
    This study was supported by the Nattonal Natural Science Foundatton of China, Nos. 82071426, 81873784; and Clinical Cohort Constructton Program of Peking University Third Hospital, No. BYSYDL2019002 (all to DF).

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Abstract:

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons. Early bilateral limb involvement significantly affects patients’ daily lives and may lead them to be confined to bed. However, the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear. To address this issue, we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022. A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis. We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients. Multiple factor analyses revealed that higher upper motor neuron scores (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01–1.09, P = 0.018), onset in the left limb (HR = 0.72, 95% CI = 0.58–0.89, P = 0.002), and a horizontal pattern of progression (HR = 0.46, 95% CI = 0.37–0.58, P < 0.001) were risk factors for a shorter interval until bilateral limb involvement. The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients. These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

Key words:

amyotrophic lateral sclerosis, bilateral limb involvement, Cox proportional hazards regression model, horizontal spread, restricted cubic spline analysis, time interva, upper motor neuron, vertical spread