Cluster analysis of heart rate variability reveals subgroups with preserved and early- impaired autonomic regulation in amyotrophic lateral sclerosis

Background Patients with amyotrophic lateral sclerosis (ALS) occasionally exhibit autonomic nervous system dysregulation. We examined whether autonomic regulation differed across patients with ALS with varying severity and progression. Methods A total of 45 patients with ALS were enrolled and classified into three subgroups using cluster analysis. Heart rate variability was assessed using the maximum entropy method. The low-frequency (LF) and high-frequency (HF) components, LF/HF ratio (LF/HF), and heart rate (HR) were measured. Temporal changes in each parameter during rest, mental tasks, and post-task rest were evaluated. The values for all patients and subgroups were compared with those of 11 healthy control subjects. Between-group differences were evaluated at rest and using the Task/Rest and After/Task ratios, and within-group changes across the three phases were also analyzed, with non-parametric statistical tests applied and significance set at p < 0.05. Results Cluster analysis classified the patients into three groups: “Group 1: early-preserved group”, “Group 2: late-preserved group”, and “Group 3: late-impaired group”. Overall, the patients showed lower HF and higher LF/HF at rest than the controls, indicating parasympathetic hypoactivity and sympathetic predominance. Abnormalities were more prominent in Groups 1 and 3 than in Group 2. The former two groups showed blunted HF, LF/HF and HR responses during the tasks. The late-preserved group showed no difference in the Task/Rest ratios of HF, LF/HF and HR compared with the controls. Conclusion Autonomic regulatory functions differ depending on the severity and progression of ALS. Autonomic dysregulation in ALS may be associated with a decline in motor function. The presence of HRV abnormalities in early-preserved patients suggests that autonomic dysfunction may precede overt motor decline in rapidly progressing cases. This supports the hypothesis that autonomic dysregulation is not merely a late complication but a fundamental component of ALS pathophysiology. Recognizing HRV abnormalities from early stages may help identify patients at risk of faster progression and guide timely interventions. Future longitudinal studies are needed to confirm whether disease-modifying therapies can alter HRV trajectories and improve prognosis.