【 発表雑誌 】
BMC Neurology
1 May 2026 : Volume 26, article number 351, (2026) .　DOI：10.1186/s12883-026-04901-w

【 論文名 】
Cluster analysis of heart rate variability reveals subgroups with preserved and early-impaired autonomic regulation in amyotrophic lateral sclerosis
（ 臨床指標に基づくクラスター分析により同定されたALS患者サブグループの自律神経調整機能 ）

【 紹　介 】
　筋萎縮性側索硬化症（ALS）は、運動神経が選択的に障害を受ける疾患とされていますが、近年、運動神経だけにとどまらないことも、指摘されています。
　本研究では、ALS患者を疾患の重症度と進行度を示す臨床指標に基づいてクラスター分析を行い、病態像の異なる3つのサブグループに分類しました。その後、各グループの自律神経調整機能を示す心拍変動を比較した結果、経過とともに、運動機能障害と自律神経調整機能の異常がみられる群、発症早期で、運動機能が保たれているにも関わらず、自律神経調整機能の異常が認められる群、反対に、罹病期間が長くてもALSFRS-Rや肺活量が保たれていれば、自律神経調整機能も保持されている群があることがわかりました。
　以上により、自律神経障害の進み方には患者ごとの違い（異質性）があることを浮き彫りに致しました。
　今後は、縦断的な検討により更なる解明をめざします。

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.

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 (Group 2) showed no difference in the Task/Rest ratios of HF, LF/HF and HR compared with the controls.

Conclusions：Autonomic regulatory functions differ depending on the severity and progression of ALS. The presence of HRV abnormalities in early-preserved patients suggests that autonomic dysregulation in ALS may not be limited to a late-stage secondary complication but may also be present earlier stages. Recognizing HRV abnormalities from early stages may help identify patients at risk of faster progression. Future longitudinal studies in larger cohorts are needed to establish the pathophysiological significance of HRV abnormalities.