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Sympathetic tone abnormalities in subjects at risk for Parkinson’s Disease without evidence of nigrostriatal neurodegeneration: a multimodal biomarker study

M. Gregorio, H. Maghzi, G. Obialisi, E. Hogg, C. Malatt, E. Tan, H. Pomeroy, R. Artal, M. Shehata, B. Renner, P. Sati, G. Pagano, M. Tagliati (Los Angeles, USA)

Meeting: 2023 International Congress

Abstract Number: 447

Keywords: Autonomic nervous system, Parkinson’s, Rapid eye movement(REM)

Category: Parkinson's Disease: Non-Motor Symptoms

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.

To cite this abstract in AMA style:

M. Gregorio, H. Maghzi, G. Obialisi, E. Hogg, C. Malatt, E. Tan, H. Pomeroy, R. Artal, M. Shehata, B. Renner, P. Sati, G. Pagano, M. Tagliati. Sympathetic tone abnormalities in subjects at risk for Parkinson’s Disease without evidence of nigrostriatal neurodegeneration: a multimodal biomarker study [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/sympathetic-tone-abnormalities-in-subjects-at-risk-for-parkinsons-disease-without-evidence-of-nigrostriatal-neurodegeneration-a-multimodal-biomarker-study/. Accessed May 25, 2025.
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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/

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