Heart-rate variability as a new marker for freezing predisposition in Parkinson's disease

Introduction: Freezing of gait (FoG) is a debilitating symptom of advanced Parkinson's disease (PD) characterized by a sudden, episodic stepping arrest despite the intention to continue walking. The etiology of FoG is still unknown, but accumulating evidence unraveled physiological signatures of the autonomic nervous system (ANS) around FoG episodes. Here we aim to investigate for the first time whether detecting a predisposition for upcoming FoG events from ANS activity measured at rest is possible. Methods: We recorded heart-rate for 1-min while standing in 28 persons with PD with FoG (PD + FoG), while OFF, and in 21 elderly controls (EC). Then, PD + FoG participants performed walking trials containing FoG-triggering events (e.g., turns). During these trials, n = 15 did experience FoG (PD + FoG+), while n = 13 did not (PD + FoG-). Most PD participants (n = 20: 10 PD + FoG+ and 10 PD + FoG-) repeated the experiment 2–3 weeks later, while ON, and none experienced FoG. We then analyzed heart-rate variability (HRV), i.e., the fluctuations in time intervals between adjacent heartbeats, mainly generated by brain-heart interactions. Results: During OFF, HRV was significantly lower in PD + FoG + participants, reflecting imbalanced sympathetic/parasympathetic activity and disrupted self-regulatory capacity. PD + FoG- and EC participants showed comparable (higher) HRV. During ON, HRV did not differ among groups. HRV values did not correlate with age, PD duration, levodopa consumption, nor motor -symptoms severity scores. Conclusions: Overall, these results document for the first time a relation between HRV at rest and FoG presence/absence during gait trials, expanding previous evidence regarding the involvement of ANS in FoG.