To investigate the effect of the adrenergic blocker carvedilol on ¹²³I-MIBG myocardial uptake in a population of subjects at high risk for Parkinson’s disease (PD). 

¹²³I-MIBG myocardial scintigraphy, a marker of cardiac sympathetic innervation, is abnormal in PD patients, with a characteristic reduction of early and late heart/mediastinum (H/M) ratio and increased Washout Rate (WR). These ¹²³I-MIBG abnormalities are also typical in pre-motor PD, at a stage where there is no pathological evidence of cardiac sympathetic denervation. We hypothesized that in pre-motor PD ¹²³I-MIBG defect is secondary to sympathetic nervous system (SNS) hyperactivity and therefore reversible with adrenergic blockers.

Six subjects with idiopathic REM behavior disorder and at least one other pre-motor PD symptom were tested for ¹²³I-MIBG and ¹²³I-Ioflupane uptake at baseline and 26 weeks after treatment with carvedilol 12.5mg or 25mg twice daily. Early and late H/M ratios, as well as WR, were calculated. 

Five men and one woman (age 60.5±11.79) were enrolled. One subject was unable to tolerate study medication but was equally tested at 26 weeks. All subjects had reduced early and late H/M ratios at baseline, and 4/6 had abnormally increased WR (>20%). In treated subjects, early H/M ratio increased from 1.69±0.31 to 1.70±0.28, while late H/M ratio improved from 1.65±0.37 to 1.75±0.34. WR decreased significantly in 3 treated subjects (13.2% vs 34.2%), with no change in the two subjects with normal WR at baseline. The subject not taking carvedilol showed worsening of WR at 26 weeks (75.3% vs 57.6%). ¹²³I-Ioflupane uptake was normal at baseline and at 26 weeks in all subjects.

In the pre-motor phase of PD-associated neurodegeneration, ¹²³I-MIBG impairment appears to be reversible, suggesting SNS hyperactivity and not denervation. This observation may provide relevant information for the timing of disease modifying efforts in synucleinopathies.