Objective: To investigate sympathetic nervous system (SNS) activity in idiopathic REM behavior disorder (iRBD) subjects at risk for Parkinson’s disease (PD), and the effect of treatment with adrenergic blocker carvedilol.

Background: iRBD is associated with high risk of synucleinopathy. SNS abnormalities play a role in iRBD pathogenesis and explain other pre-motor symptoms of PD.

Method: 15 iRBD subjects (12M, age 65.7±8.2) with at least another pre-motor PD symptom (hyposmia, constipation, depression) and abnormal Iodine¹²³ meta-iodobenzylguanidine (MIBG) scintigraphy were assessed for multimodal markers of SNS activity. Eight of them (7M, age 61.8±6.3) received carvedilol (12.5mg or 25mg BID) and were re-assessed after 6 months. Study variables included MIBG late H/M ratio and washout rate (WR), heart rate variability (HRV) time and frequency domains; neuromelanin sensitive MRI (NM-MRI) contrast-to-noise ratio (CNR) between locus coeruleus (LC) and pons, and SCOPA-AUT questionnaire. MDS-UPDRS part III and dopamine transporter scan (DaTscan) uptake ratios were used to exclude PD. Wilcoxon t-test was used to analyze results.

Results: Evidence of SNS overactivity included reduced average MIBG late H/M ratio (1.5±0.3), increased WR (32.1±14.6), HRV variables  (SDNN 102.5±71.4ms; RMSSD 26.8±18.7ms; PNN50% 8.2±9.7%; LF/HF 3.2±1.8), enhanced LC CNR (3.1±1.3), increased average SCOPA-AUT score (11.7±6.5), with elevated gastrointestinal (2.3±2.0), urinary (5.1±2.8) and cardiovascular (0.9±1.1) subscores.  Treatment with carvedilol resulted in improved RBDQ questionnaire (10.1±1.5 vs 7.4±3.4; p<0.05) and depression average scores (4.4±2.3 vs 2.6±2.3; p=0.06), higher hyposmia percentile average (32.5±26.8 vs 20.4±16.0; p<0.05), reduced average MIBG WR (22.7±9.1; p=0.14), LF/HF ratio (2.52±1.72; p=0.11) and LC NM-MRI intensity (2.68±0.46; P=0.21). MDS-UPDRS part III scores and DaTscan uptake remained normal.

Conclusion: Our data show that iRBD subjects at risk for PD show multimodal evidence of SNS 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. Treatment with adrenergic blockers can reverse such indicators in this population, suggesting that accepted markers of neurodegeneration may be reversible in the pre-motor stages.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sympathetic-nervous-system-overactivity-in-the-pre-motor-stage-of-parkinsons-disease-therapeutic-implications/