Noninvasive assessment of cardiovascular autonomic reflexes in amyotrophic lateral sclerosis: a systematic review

Dysautonomia is gradually recognized in amyotrophic lateral sclerosis (ALS), raising concerns of secondary complications from heightened autonomic burden. Autonomic disturbances, particularly cardiac dysautonomia, significantly impact patient outcomes, contributing to increased cardiovascular risks and mortality rate. While the ALS Functional Rating Score-Revised (ALSFRS-R) measures functional decline as disease progress, it overlooks autonomic criteria – a critical factor in ALS progression. This review aims to analyze noninvasive applications of cardiovascular signal variability for continuous real-time monitoring of autonomic dysfunction in ALS, while addressing gaps in current clinical assessments. A total of 584 literatures were gathered from four databases (WoS, PubMed, Science Direct and MEDLINE EBSCOhost) – published from inception till December 2023. 21 peer-reviewed studies were included in this review after screening and meeting the inclusion criteria. Various cardiovascular signal variability metrics and autonomic protocols were discussed. Key findings highlight cardiac autonomic dysfunction in ALS is marked by reduced heart rate variability, absent blood pressure regulation upon orthostatic stress and circadian changes, prolonged QTc interval and low baroreflex sensitivity. Moreover, increased autonomic burden is associated with a shift from sympathetic to parasympathetic dysregulation as the disease progresses. Evidence highlights the need to integrate noninvasive autonomic biomarkers into digital ALS monitoring frameworks, enabling earlier detection of autonomic involvement and more precise longitudinal monitoring beyond motor decline.