Determinants of clinical and neurophysiological features in essential tremor and essential tremor plus

The 2018 Movement Disorder Society classification introduced essential tremor plus (ETP) as a category for patients with essential tremor (ET) accompanied by additional features of uncertain significance. While earlier studies have characterized clinical features of ETP, the factors that characterize the phenotypic expression of ETP remain unclear. We prospectively evaluated 70 consecutive patients with ET or ETP. Clinical and neurophysiological assessments included tremor severity (Clinical Rating Scale for Tremor, CRST), cognitive functions (Addenbrooke's Cognitive Examination Revised, ACE-R), and accelerometric analysis. Statistical analyses examined between-group differences and factors influencing tremor characteristics. The prevalence of ETP (61%) exceeded that of ET. Among ETP patients, 77% exhibited two or more additional motor and/or cognitive features. Compared to ET patients, ETP patients demonstrated significantly higher tremor severity, lower tremor frequency, older age at assessment and onset, and poorer cognitive function, despite comparable disease duration. The accelerometric analysis revealed similar tremor patterns in both groups with quantitative differences in tremor amplitude and frequency. The propensity score matching and multiple regression analyses suggested that tremor severity and frequency are more influenced by age than by disease duration or diagnostic classification of ET/ETP. ACE-R score and the presence of resting tremor were also significant predictors of tremor severity. ETP represents a heterogeneous population with diverse neurological features, and age is likely a key determinant of severity and phenotypic expression. Comprehensive analysis is needed to identify other factors that may determine phenotype and treatment responsiveness.