Recent neuropathological and imaging studies support the concept of “brain-first vs. body-first” Parkinson’s disease (PD), which is based on the α-synuclein origin site and connectome model. The body-first phenotype is characterized by early involvement of the peripheral autonomic nervous system, particularly the cardiac sympathetic nerves and enteric nerves. 123I-meta-iodobenzylguanidine (123I-MIBG) myocardial scintigraphy is a well-established method for evaluating cardiac sympathetic innervation. This review explores the potential of 123I-MIBG scintigraphy as a biomarker to differentiate the body-first phenotype from the brain-first phenotype. Reduced 123I-MIBG uptake has been observed in idiopathic rapid eye movement (REM) sleep behavior disorder, pure autonomic failure, and incidental Lewy body disease—conditions strongly associated with prodromal or early-stage PD. Postmortem and biopsy evidence indicates α-synuclein accumulation in cardiac nerves and other peripheral sites, which is consistent with bottom-up progression. α-Synuclein seed amplification assays further corroborate the association between the peripheral α-synuclein burden and reduced 123I-MIBG uptake. While 123I-MIBG myocardial scintigraphy is a promising tool, its limitations include cost, limited availability, and potential confounding from underlying cardiac conditions. Nonetheless, early detection of cardiac sympathetic denervation via 123I-MIBG imaging may enhance diagnosis, support subtype classification, and improve the understanding of PD pathogenesis.

Background: and Purpose The wearing-off (WO) phenomenon is the most common motor complication in advanced Parkinson’s disease (PD), but its identification remains challenging. The 9- and 19-item Wearing-off Questionnaires (WOQ-9 and WOQ-19) are self-assessment tools for motor and nonmotor symptoms that are widely used for WO screening. We produced Korean versions of the WOQ-19 and WOQ-9 (K-WOQ-19 and K-WOQ-9) and investigated their validity and reliability. Methods: We used the translation–back translation method to produce K-WOQ-19 and KWOQ-9, which were self-administered by 124 patients with PD. We conducted in-depth 10-minute interviews for confirming the presence of the WO phenomenon, and then stratified the participants into groups with and without WO. Diagnostic accuracy was assessed by analyzing receiver operating characteristic curves. Concurrent validity was assessed using the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Hoehn and Yahr stage with Spearman’s rank correlation analysis. Reliability was assessed based on test–retest Cohen’s kappa (κ) values and intraclass correlation coefficients (ICCs). Results: The optimal cutoff scores on the K-WOQ-19 and K-WOQ-9 for WO screening were 4 and 2, respectively. The test–retest ICCs of K-WOQ-19 and K-WOQ-9 were 0.943 and 0.938, respectively. Nineteen of the combined 20 items in K-WOQ-19 and K-WOQ-9 showed moderate-to-substantial agreement (κ=0.412–0.771, p<0.001). The scores on the translated scales were significantly correlated with MDS-UPDRS IV scores. Conclusions K-WOQ-19 and K-WOQ-9 are reliable and valid tools for detecting WO, with optimal cutoff scores of 4 and 2, respectively.