Soft Signs in Essential Tremor Plus: A Prospective Study

Abstract

Essential tremor plus (ET plus) is a new terminology added in the recent (2018) tremor classification.1 ET plus was defined as a tremor with the characteristics of essential tremor (ET) with additional soft neurological signs such as questionable dystonic posturing, impaired tandem gait, or memory impairment.1 In this prospective study, we evaluated the soft neurological signs in patients with ET plus. To the best of our knowledge, there is no prospective data regarding ET plus. A detailed description of the methodology and results are available as Appendix S1 and Table S1. We recruited 45 consecutive patients, and 43 were classified as ET plus based on the presence of soft signs, and 2 were classified as ET plus because of the presence of rest tremor. In our cohort, 13 patients reported alcohol responsiveness in their tremor symptoms. The majority (30/45; 66.66%) of the patients had only 1 soft sign, 7 (15.55%) patients had 2 soft signs, and 6 patients (13.33%) had 3 soft signs (Table 1). Questionable dystonia was the most common soft sign observed in our patients, which was most frequent in the upper limbs (41/45; 91.11%; unilateral > bilateral) followed by the neck (29/45; 64.44%). All of the patients with questionable neck dystonia also had questionable upper limb dystonia. Our findings are consistent with our previous study where questionable dystonia was more frequent in the upper limbs.2 None of the patients with leg tremors had any dystonia in their legs. A total of 8 (voice = 6, head = 3, and face = 1) patients had cranial tremor, and 7 of them had both cranial tremor and neck dystonia, suggesting a clear association between them. The presence of questionable dystonia was significantly more common in older patients (median age, ≥51 years; P = 0.04); however, the sex difference was not different significantly (P = 0.13). Also, the older patients (≥51 years) had more (2 or 3) soft signs than the younger patients. However, the number of soft signs present in patients with longer durations (median duration, ≥7 years) of symptoms was statistically not different from the patients with shorter durations (<7 years) of symptoms. The presence of more than 1 soft sign including questionable dystonia in patients of the older age group is consistent with the current literature.2 Ul= 41 (unilateral=27, bilateral=14) Neck=29 (Torticaput=15, laterocollis=7, laterocaput=3, retrocollis=2, anterocollis=1, lateral shift=1) Following the new tremor classification, many researchers have reclassified their ET cohort, and a significant proportion of them were classified as ET plus.2, 3 Most of the studies reported a high rate of discordance in defining questionable dystonia as it lacks a clear definition.3 Depending on the opinion of the examiner, individuals with tremor combined with dystonia might be diagnosed with ET plus or dystonic tremor.3 Also, questionable signs of dystonia such as spooning posture of the extended hands, index finger extension, and mild head tilt occur frequently in the normal population, and their clinical use remains doubtful.4, 5 Also, jerkiness and asymmetry are features of dystonic tremor, but they have never been defined.6 The second most common soft sign present in our patients were impaired tandem gait, which has been considered as evidence of cerebellar involvement, but it has never been validated, raising a question about its clinical usefulness. Mild cognitive impairment was the third most common soft sign present in our patients, but the neurological significance of this finding is unclear. In movement disorders, an emphasis only on the phenomenology to make diagnoses may lead to diagnostic disagreement. This is illustrated in the difficulty deciding whether soft signs are present. In a recent study, Becktepe and colleagues used a new clinical tool, the “Standardized Tremor Elements Assessment,” for evaluating additional neurological signs of uncertain significance in patients with ET plus.7 The authors suggested that clinician's training, research interests, or clinical practice greatly influence the identification of soft signs. Our study has several limitations, the most important of which is a small sample size. However, the observations reported in our study are important considering the prospective design of the study. The findings reported in our study again highlight the need for finding a tool for assessing the questionable clinical signs. This can be computerized video analysis, motion transducers, electrophysiology techniques, functional neuroimaging, or genetic testing. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. S.P.: 1A, 1B, 1C, 2A, 2B, 2C, 3A, 3B S.B.: 1A, 1B, 1C, 2A, 2B, 2C, 3A, 3B The study was approved by the institutional ethics committee of Maulana Azad Medical College, New Delhi. An informed consent was obtained from all the patients recruited in the study. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The authors declare that there are no conflicts of interest relevant to this work. The authors declare that there are no additional disclosures to report. Table S1: Clinical details of patients with essential tremor plus. Appendix S1: Supporting Information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.