Tardive dyskinesia (TD), characterized by oro-buccal-lingual stereotypy, can manifest in the form of akathisia, dystonia, tics, tremor, chorea, or as a combination of different types of abnormal movements. In addition to movement disorders (including involuntary vocalizations), patients with TD may have a variety of sensory symptoms, such as urge to move (as in akathisia), paresthesias, and pain. TD is a form of tardive syndrome-a group of iatrogenic hyperkinetic and hypokinetic movement disorders caused by dopamine receptor-blocking agents. The pathophysiology of TD remains poorly understood, and treatment of this condition is often challenging. In this update, we provide the most current information on the history, nomenclature, etiology, pathophysiology, epidemiology, phenomenology, differential diagnosis, and treatment of TD.

Highlights This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TET-RAS) and 68% (BF-ADL) of 'severe' or 'moderate' patients improving to 'mild' or 'slight'. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients.

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Background Essential tremor (ET) is typically measured in the clinic with subjective tremor rating scales which require the presence of a clinician for scoring and are not appropriate for measuring severity throughout the day. Motion sensors can accurately rate tremor severity during a set of predefined tasks in a laboratory. Methods We evaluated the ability of motion sensors to quantify tremor during unconstrained activities at home. 20 ET subjects wore a wireless sensor continuously for up to 10 hours daily on two days and completed hourly standardized tremor assessments involving pre-defined tasks. Mathematical models were used to predict tremor rating scores from the sensor data. Results At home tremor scores from hourly standardized assessments correlated with at home tremor scores estimated during unconstrained activities immediately following the standardized assessments. The hourly standardized assessments did not significantly fluctuate throughout the day, while fluctuations in the continuous assessments tended to follow changes in voluntary activity level. Both types of tremor ratings (standardized and continuous) showed high day-to-day test-retest reliability with intraclass correlation coefficients ranging from 0.67 to 0.90 for continuous ratings and 0.77 to 0.95 for standardized ratings. Conclusions Results demonstrate the feasibility of continuous monitoring of tremor severity at home, which should provide clinicians with a measure of the temporal pattern of tremor in the context of daily life and serve as a useful tool for the evaluation of novel anti-tremor medications in clinical trials.