Autonomic nervous system dysfunction in idiopathic REM sleep behavior disorder as a short-term risk for a synucleinopathy

Idiopathic REM sleep behavior disorder (iRBD) is a prodromal marker of the alpha-synucleinopathies, in which autonomic nervous system (ANS) involvement may occur. We aimed to characterize the presence and severity of subjective and objective ANS dysfunction in iRBD and assess its capacity to predict short-term clinical progression to a synucleinopathy.

Prospective study of patients with polysomnography-confirmed iRBD in whom symptomatic ANS involvement was assessed using the Composite Autonomic Symptom Score (COMPASS-31) and objective dysfunction with the Composite Autonomic Severity Score (CASS). Baseline ANS data were compared between those who later developed a synucleinopathy and those who did not.

We evaluated 25 subjects with iRBD without risk factors for autonomic neuropathy and at least 6 months of follow-up (mean: 19 months). At the end of the study, seven (28%) patients developed a synucleinopathy, namely Parkinson's disease (n = 5) and dementia with Lewy bodies (n = 2). 73.7% of patients had COMPASS-31 scores above the normal cut-off, while no score differences regarding phenoconversion status were observed. At baseline, 85.7% of the subjects who phenoconverted exhibited at least one abnormal result in the CASS score, compared to 38.9% of subjects who remained disease-free (p = 0.035). Adrenergic dysfunction evaluated by an impaired overshoot in Valsalva phase IV and by pressure recovery time was associated with the development of overt synucleinopathy (p = 0.032 and 0.033, respectively).

Symptomatic and subclinical ANS dysfunctions are common in iRBD. ANS dysfunction affecting mainly the adrenergic system seems to be a short-term risk for the development of a synucleinopathy.