Objective: To characterize the clinical phenotype and disease course of patients with an ET-to-PD diagnostic trajectory in a tertiary-care setting.

Background: The longitudinal clinical features of patients diagnosed with both essential tremor (ET) and Parkinson’s disease (PD) have not been well described in deeply phenotyped cohorts.

Method: Electronic health records from Turku University Hospital were screened to identify patients diagnosed with ET (ICD-10 G25.0) and/or PD (G20) between 2005 and 2024 within a source population of 717,119 individuals. During this period, 1,355 patients were diagnosed with ET and 3,835 with PD. Patients with both diagnoses were classified according to the temporal sequence of diagnoses. ET-to-PD patients were compared with sex- and age-matched tremor-dominant PD (TD-PD) controls without ET. Clinical variables were extracted by structured manual chart review, including tremor characteristics, family history, dopamine transporter imaging (DAT-SPECT), medication use, and disease severity at last follow-up.

Results: A total of 103 patients had received both ET and PD diagnoses and 82 were included after exclusions. 52 patients (63%) were classified as ET-to-PD, representing 1.4% of all PD cases and 3.8% of all ET cases in the source population. Compared with TD-PD controls (n=104), ET-to-PD patients had earlier tremor onset (median 59 vs. 71 years, p<0.001), more frequent bilateral tremor (54% vs. 14%, p<0.001), and higher prevalence of family history of tremor (42% vs. 4%, p<0.001). All ET-to-PD patients presented with isolated tremor at onset, whereas 56% of TD-PD patients had additional parkinsonian features (p<0.001). At last follow-up, ET-to-PD patients exhibited milder motor disability (Hoehn & Yahr stage 4 vs. 5, p=0.001) and fewer dyskinesias (12% vs. 26%, p=0.038), despite similar levodopa equivalent daily doses. DAT-SPECT was abnormal in all imaged ET-to-PD patients, and 44% remained on ET-specific medications at last follow-up.

Conclusion: Patients with an ET-to-PD diagnostic trajectory constitute a small but clinically distinct subgroup of PD, characterized by long-standing, often bilateral tremor, familial tremor aggregation, and relatively milder parkinsonian motor progression. This pattern suggests that ET preceding PD may represent a recognizable clinical phenotype rather than solely early diagnostic misclassification.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-features-of-patients-with-an-essential-tremor-to-parkinsons-disease-diagnostic-trajectory/