The differences in clinical characteristics and natural history between essential tremor and essential tremor plus

The diverse clinical manifestation of essential tremor (ET) has led to the question whether the different phenotypes may affect the clinical outcome and progression. This study aimed to estimate the clinical characteristics and natural history of ET and ET-plus. A total of 221 patients with ET were included, 117 (52.9%) reclassified as ET and 104 (47.1%) as ET-plus. Patients with ET-plus were significantly older in age at onset (P < 0.001); had a higher frequency of cranial tremors (P < 0.001), neurological comorbidities (P < 0.001) and psychiatric comorbidities (P = 0.025); more tremor progression (P < 0.001); and poorer response to medical treatment (P < 0.001) compared to ET patients. Regression analysis revealed that late-onset tremor (OR 11.02, 95% CI 2.79-43.53), neurological comorbidities (OR 3.38, 95% CI 1.56-7.31), psychiatric comorbidities (OR 4.29, 95% CI 1.48-12.44), cranial tremors (OR 2.10, 95% CI 1.02-4.30), and poor response to medical treatment (OR 3.67, 95% CI 1.87-7.19) were associated with ET-plus diagnosis. ET and ET-plus differ in the age of onset, tremor distribution, comorbidities, treatment response rate, and progression. Identifying the ET phenotypes may increase the clinical value in therapeutic strategies and clinical research in the future.