Tremor stability index: a new tool for differential diagnosis in tremor syndromes

Journal article

Background Misdiagnosis among tremor syndromes is common, and can impact on both clinical care and research. To date no validated neurophysiological technique is available that has proven to have good classification performance, and the diagnostic gold standard is the clinical evaluation made by a movement disorders expert. We present a robust new neurophysiological measure, the Tremor Stability Index, which can discriminate Parkinson’s disease tremor and essential tremor with high diagnostic accuracy. Methods The Tremor Stability Index is derived from kinematic measurements of tremulous activity. It was assessed in a test cohort comprising 16 rest tremor recordings in tremor-dominant Parkinson’s disease and 20 postural tremor recordings in essential tremor, and validated on a second, independent cohort comprising a further 50 tremulous Parkinson’s disease and essential tremor recordings. Clinical diagnosis was used as gold standard. 100 seconds of tremor recording were selected for analysis in each patient. The classification accuracy of the new index was assessed by binary logistic regression, and by receiver operating characteristic (ROC) analysis. The diagnostic performance was examined by calculating the sensitivity, specificity, accuracy, likelihood ratio positive, likelihood ratio negative, area under the ROC curve, and by cross-validation. Results Tremor Stability Index with a cutoff of 1.05 gave good classification performance for Parkinson’s disease tremor and essential tremor, in both test and validation datasets. Tremor Stability Index maximum sensitivity, specificity and accuracy were 95%, 95% and 92%, respectively. ROC analysis showed an AUC of 0.916 (95% C.I. 0.797 – 1.000) for the Test dataset and a value of 0.855 (95% C.I. 0.754 – 0.957) for the Validation dataset. Classification accuracy proved independent of recording device and posture. Conclusion The Tremor Stability Index can aid in the differential diagnosis of the two most common tremor types. It has a high diagnostic accuracy, can be derived from short, cheap, widely available and noninvasive tremor recordings, and is independent of operator or postural context in its interpretation.

Authors: di Biase, L; Brittain, J; Shah, S; Pedrosa, D; Cagnan, H

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Brain
• Volume: 140
• Issue: 7
• Pages: 1977-1986
• Publication date: 2017-04-27
• Acceptance date: 2017-02-12
• DOI: 10.1093/brain/awx104
• EISSN: 1460-2156
• ISSN: 0006-8950
• Keywords: clinical neurophysiology; movement disorders; Parkinson's disease: neurophysiology; tremor; Parkinson;s disease