Objective: To study autonomic dysfunction in subjects with idiopathic REM sleep behavior disorder (iRBD) and at least one pre-motor symptom of Parkinson’s disease (PD).

Background: There is evidence that autonomic impairment plays a key role in the pathophysiology of iRBD, which is associated with a high risk of synucleinopathy. Sympathetic denervation has been described in iRBD using MIBG scintigraphy. However, most studies included patients with PD diagnosis or motor symptoms suggestive of phenoconversion.

Method: iRBD subjects with at least one pre-motor PD symptom (hyposmia, constipation, depression) and abnormal MIBG scintigraphy were assessed with a series of autonomic tests including Heart Rate Variability (HRV), neuromelanin sensitive MRI (NSMRI) and SCOPA-AUT questionnaire. Analyzed variables included: 1) MIBG late heart/mediastinum (H/M) ratio and washout ratio (WR); 2) HRV time and frequency domain measures; 3) NSMRI contrast-to-noise ratio (CNR) between 1) locus coeruleus (LC) and pons, and 2) substantia nigra (SN) and cerebral peduncles. MDS-UPDRS part III and dopamine transporter scan (DaTscan) were used to rule out existing PD. Results were compared with available normative ranges.

Results: 22 iRBD subjects were screened, of which 7 were excluded (2 abnormal DaTscan, 2 younger than 50, 1 atrial fibrillation, 1 sleep apnea and 1 normal MIBG) and 15 (12M, age 65.7±8.2) were enrolled. Average MIBG late H/M ratio was reduced (1.47±0.30) with increased WR (32.1±14.6). HRV results showed enhanced sympathetic and low parasympathetic activity both in time (SDNN 102.5±71.4ms; RMSSD 26.8±18.7ms; PNN50% 8.2±9.7%) and frequency domains (LF/HF 3.2±1.8). NMSMRI showed high LC CNR (3.1±1.3 vs 2.4±0.5) and high SN CNR (5.2±1.8 vs 3.7±0.6). Average SCOPA-AUT score was increased (11.7±6.5), with elevated gastrointestinal (2.3±2.0), urinary (5.1±2.8) and cardiovascular (0.9±1.1) subscores. MDS-UPDRS motor scores (2.6±3.2) were below clinically meaningful cutoff.

Conclusion: iRBD subjects at risk for PD show sympathetic overactivity, as suggested by increased MIBG WR, elevated LF/HF HRV ratios and increased LC NSMRI signal, in the absence of clinical or imaging evidence of nigrostriatal degeneration. Pre-motor stages of neurodegeneration in PD may be driven by sympathetic overactivity, a potentially reversible state.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sympathetic-tone-abnormalities-in-subjects-at-risk-for-parkinsons-disease-without-evidence-of-nigrostriatal-neurodegeneration-a-multimodal-biomarker-study/