Bayesian Interpretation of Essential Tremor Plus

Abstract

Essential tremor (ET) plus is a new tremor classification that was introduced in 2018 by a task force of the International Parkinson and Movement Disorder Society. Patients with ET plus meet the criteria for ET but have one or more additional systemic or neurologic signs of uncertain significance or relevance to tremor ("soft signs"). Soft signs are not sufficient to diagnose another tremor syndrome or movement disorder, and soft signs in ET plus are known to have poor interrater reliability and low diagnostic sensitivity and specificity. Therefore, the clinical significance of ET plus must be interpreted probabilistically when judging whether a patient is more likely to have ET or a combined tremor syndrome, such as dystonic tremor. Such a probabilistic interpretation is possible with Bayesian analysis. This review presents a Bayesian analysis of ET plus in patients suspected of having ET versus a dystonic tremor syndrome, which is the most common differential diagnosis in patients referred for ET. Bayesian analysis of soft signs provides an estimate of the probability that a patient with possible ET is more likely to have an alternative diagnosis. ET plus is a distinct tremor classification and should not be viewed as a subtype of ET. ET plus covers a more-comprehensive phenotyping of people with possible ET, and the clinical interpretation of ET plus is enhanced with Bayesian analysis of associated soft signs.

Keywords: Bayesian analysis; classification; dystonia; essential tremor; tremor.

Fig. 1. Flow diagram for the clinical diagnosis and interpretation of essential tremor (ET) and ET plus. People fulfilling the criteria for ET are examined for any signs of uncertain abnormality or uncertain clinical significance (i.e., “soft signs”). People with one or more soft signs are classified as ET plus. Bayesian analysis can be used to estimate the probability of a combined tremor syndrome, based on the soft signs and any associated electrodiagnostic results (Supplementary Materials 2 in the online-only Data Supplement). Patients with ET and ET plus should be re-examined periodically for additional neurologic signs that could result in a different tremor classification (e.g., dystonic tremor syndrome).