Substantia Nigra Hyperechogenicity Predicts Parkinson's Disease Risk in Patients With Essential Tremor and Undetermined Tremor: Dual-Cohort Longitudinal Evidence With 8-Year Follow-Up and Bayesian Validation.

BACKGROUND AND OBJECTIVES: Transcranial sonography (TCS)-detected substantia nigra hyperechogenicity (SN+) is a potential biomarker for Parkinson's disease (PD). While SN+ may indicate PD risk in essential tremor (ET), longitudinal undetermined tremor (UT) data are lacking; insufficient cross-cohort validation hinders clinical translation. This study aimed to evaluate the predictive efficacy of SN+ for 8-year PD risk and its subtype-specific differences in ET/UT populations.

METHODS: 180 patients with tremors who underwent TCS were enrolled and categorized based on the tremor type (ET/UT) and SN echogenicity grade (SN+/SN-). 127 patients (59 with ET, 68 with UT) completed a mean follow-up period of 8.01 years (range: 7.41-8.67; median: 7.92), during which new-onset PD was documented.

RESULTS: In the ET cohort, 52.4% of SN+ individuals developed PD, compared to 7.9% in the SN- group. For UT, the PD incidence was 91.2% in SN+ individuals and 50.0% in SN- individuals. Multivariable-adjusted Firth logistic regression revealed significant associations between SN+ and PD in the ET and UT groups. Moreover, Bayesian logistic regression confirmed SN+ was significantly associated with PD risk in both groups. The posterior probability of an odds ratio exceeding 5 for SN+ was greater than 80% in both cohorts. Subgroup interaction analysis demonstrated no evidence of effect modification by tremor subtype, indicating consistent SN+ effects across cohorts.

CONCLUSIONS: TCS-detected SN+ is a predictor of PD progression over 8 years in both ET and UT cohorts. The consistent risk association across tremor subtypes in SN+ subgroups supports its clinical potential as a cross-tremor subtype biomarker.