Associations Among Tremor Amplitude, Activities of Daily Living, and Quality of Life in Patients with Essential Tremor.

Background: Essential tremor (ET) is a disabling syndrome consisting of tremor, primarily in the upper limbs. We assessed the correlation of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Item 4 ratings of upper limb tremor with the TETRAS activities of daily living (ADL) subscale and with 2 quality of life (QoL) scales. Methods: This noninterventional, cross-sectional, point-in-time survey of neurologists(n = 60), primary care physicians (n = 38), and their patients with ET (n = 1,003) used real-world data collected through the Adelphi ET Disease Specific Programme™. Physician-reported measures (TETRAS Performance Item 4 and TETRAS ADL total) and patient-reported QoL measures (generic EuroQol-5 Dimension 5 Level [EQ-5D-5 L] and ET-specific Quality of Life in Essential Tremor Questionnaire (QUEST)) were assessed with bivariate and multivariable analyses. Sensitivity analyses were also conducted. Results: The bivariate association between TETRAS Performance Item 4 score and TETRAS ADL total score was high (Pearson r = 0.761, P < 0.001). The bivariate associations between TETRAS Performance Item 4 score and EQ-5D-5 L index score (r = -0.410, P < 0.001) and between TETRAS ADL total score and EQ-5D-5 L index score (r = -0.543, P < 0.001) were moderate. The bivariate associations between TETRAS Performance Item 4 score and QUEST total score (r = 0.457, P < 0.001), and between TETRAS ADL total score and QUEST total score (r = 0.630, P < 0.001) were also moderate. These associations were unaltered by the inclusion of covariates. Discussion: This study showed that greater tremor severity (TETRAS Performance Item 4) was positively correlated with ADL impairment (TETRAS ADL) and negatively associated with QoL (EQ-5D-5 L and QUEST). TETRAS Performance Item 4 score is a robust predictor of TETRAS ADL total score, and TETRAS Performance Item 4 and TETRAS ADL total scores were robust predictors of the 2 QoL scales. The results demonstrate the value of TETRAS scores as valid endpoints for future clinical trials. Highlights: This real-world study assessed TETRAS scores as predictors of impaired QoL in ET. TETRAS Performance Item 4 and ADL were associated with EQ-5D-5 L and QUEST. TETRAS scores may serve as valid endpoints for future clinical trials.

Bedside clinical assessment of patients with common upper limb tremor and algorithmic approach.

The diagnostic approach for patients with tremor is challenging due to the complex and overlapping phenotypes among tremor syndromes. The first step in the evaluation of tremor is to identify the tremulous movement and exclude the tremor mimics. The second step is to classify the tremor syndrome based on the characteristics of tremor from historical clues and focused examination (Axis 1). Comprehensive tremor examinations involve the assessment of tremor in different conditions (rest, action or mixed, position or task-specific), distribution of tremor (upper limb, lower limb, head, jaw), positive signs for functional tremor (FT) if suspected (distractibility, entrainment, co-contraction), and associated neurological signs including parkinsonism, dystonic posture, cerebellar/brainstem signs, neuropathy, and cognitive impairment. A pivotal feature in this step is to determine any distinct feature of a specific isolated or combined tremor syndrome. In this review, we propose an algorithm to assess upper limb tremors. Ancillary testing should be performed if clinical evaluation is unclear. The choice of investigation depends on the types of tremors considered to narrow down the spectrum of etiology (Axis 2). Laboratory blood tests are considered for acute onset and acute worsening of tremors, while structural neuroimaging is indicated in unilateral tremors with acute onset, nonclassical presentations, and a combination of neurological symptoms. Neurophysiological study is an important tool that aids in distinguishing between tremor and myoclonus, etiology of tremor and document specific signs of FT. Treatment is mainly symptomatic based depending on the etiology of the tremor and the patient's disabilities.

Real-World Longitudinal Experience of Botulinum Toxin Therapy for Parkinson and Essential Tremor.

BACKGROUND: Botulinum toxin type A (BoNT-A) therapy for upper-limb tremor has emerged as a promising option. However, it is unclear in real-world practices whether a technology-guided approach can compare with expert clinical assessments (including surface anatomy and palpation) for improving outcomes. This retrospective study aims to review our clinical outcomes of treating essential tremor (ET) and Parkinson's disease (PD) tremor using either clinical- or kinematic-based injection pattern determination methods. METHODS: 68 ET and 45 PD patients received at least one injection for their upper-limb tremor (unilateral or bilateral) in the last 7 years. Demographics of patients and BoNT-A injections were collected. A Mann-Whitney U statistical test was used to compare outcome measures between ET and PD cohorts. RESULTS: Mean age (72 ± 9 years), number of injections (5), years receiving therapy (~2 years), clinic- (~57%) or kinematic-based patterns, and self-paying (52%) were similar between both cohorts. BoNT-A as a monotherapy in both upper limbs was received in more ET than PD patients. Double reconstitution of Xeomin® in the wrist flexors/extensors, supinator, biceps, and triceps were most injected. Discontinuation due to no benefit/weakness was not dependent on the injection pattern determination approach. CONCLUSIONS: Kinematic-based BoNT-A injections produced similar treatment outcomes to injections based on the clinical expertise of the expert injector. This suggests that kinematics could be used by a non-expert to attain equivalent efficacy potentially improving access to this treatment.

Developing a Consistent, Reproducible Botulinum Toxin Type A Dosing Method for Upper Limb Tremor by Kinematic Analysis.

Botulinum toxin type A (BoNT-A) injection patterns customized to each patient's unique tremor characteristics produce better efficacy and lower adverse effects compared to the fixed-muscle-fixed-dose approach for Essential Tremor (ET) and Parkinson's disease (PD) tremor therapy. This article outlined how a kinematic-based dosing method to standardize and customize BoNT-A injections for tremors was developed. Seven ET and eight PD participants with significant tremor reduction and minimal perceived weakness using optimized BoNT-A injections determined by clinical and kinematic guidance were retrospectively selected to develop the kinematic-based dosing method. BoNT-A dosages allocated per joint were paired to baseline tremor amplitudes per joint. The final kinematic-based dosing method was prospectively utilized to validate BoNT-A injection pattern selection without clinical/visual assessments in 31 ET and 47 PD participants with debilitating arm tremors (totaling 122 unique tremor patterns). Whole-arm kinematic tremor analysis was performed at baseline and 6-weeks post-injection. Correlation and linear regression analyses between baseline tremor amplitudes and the change in tremor amplitude 6-weeks post-injection, with BoNT-A dosages per joint, were performed. Injection patterns determined using clinical assessment and interpretation of kinematics produced significant associations between baseline tremor amplitudes and optimized BoNT-A dosages in all joints. The change in elbow tremor was only significantly associated with the elbow total dose as the change in the wrist and shoulder tremor amplitudes were not significantly associated with the wrist and shoulder dosages from the selected 15 ET and PD participants. Using the kinematic-based dosing method, significant associations between baseline tremor amplitudes and the change (6-weeks post-first treatment) in tremor at each joint with BoNT-A dosages for all joints was observed in all 78 ET and PD participants. The kinematic-based dosing method provided consistency in dose selection and subsequent tremor reduction and can be used to standardize tremor assessments for whole-arm tremor treatment planning.

Treatment with Botulinum Neurotoxin Improves Activities of Daily Living and Quality of Life in Patients with Upper Limb Tremor.

Background: Botulinum neurotoxin's degree of effectiveness on upper limb tremor is subject to debate; although this treatment reduces the tremor's amplitude, a clear functional benefit has not been demonstrated. The objective of this study was to assess the effect of botulinum neurotoxin type A treatment on activities of daily living and quality of life in patients with upper limb tremor. Methods: We retrospectively examined the medical records of 50 consecutive patients treated with botulinum neurotoxin for upper limb tremor that was refractory to oral medication. One month after the injection, the patient was evaluated according to the Quality of Life in Essential Tremor Questionnaire, and the Essential Tremor Embarrassment Assessment. Results: Full data sets were available for 38 patients suffering variously from essential tremor (n = 21), Holmes tremor secondary to a focal brain lesion (n = 8), idiopathic dystonic tremor (n = 4), primary writing tremor (n = 4), and Parkinson's disease (n = 1). The Quality of Life Essential Tremor Questionnaire and the Essential Tremor Embarrassment Assessment scores improved significantly (p < 0.001) in the study population as a whole, and in the essential tremor and Holmes tremor subgroups. Discussion: Botulinum neurotoxin treatment of patients with upper limb tremor is associated with improved quality of life and activities of daily living, irrespective of the tremor's etiology. Long-term treatment enables the physician to adjust the injection strategy to the patient's needs. Our study was limited by its retrospective design. The results must therefore be confirmed in a prospective, double-blind, placebo-controlled, randomized clinical trial.

Differential effects of propranolol on head and upper limb tremor in patients with essential tremor and dystonia.

Propranolol is used as the first-line treatment in essential tremor and it has also been proposed as a treatment for tremor in dystonia. However, several issues remain uncertain. For example, it is still not clear whether propranolol exerts a beneficial effect on head tremor. Moreover, no studies have investigated whether the effect of propranolol on head and upper limb tremor in essential tremor differs from that in dystonia. We aimed to assess the effects of propranolol on tremor in different body parts in essential tremor and in patients with tremor and dystonia. Twenty-nine patients with head and upper limb tremor were enrolled in the study, 14 with essential tremor, and 15 with dystonia. Participants underwent a clinical and kinematic analysis of tremor in two sessions, i.e., without (baseline) and 'on therapy' with propranolol. We found that head tremor was more severe in patients with dystonia, while upper limb tremor was more evident in patients with essential tremor (P < 0.05). Propranolol had no effect on head tremor in either group (all Ps > 0.05), but it did reduce upper limb tremor in patients with essential tremor. The present study demonstrates differential effects of propranolol on head and upper limb tremor in patients with essential tremor. The lack of effect on head and upper limb tremor in patients with dystonia suggests that the pathophysiological mechanisms underlying tremor in these two conditions and in different body parts may be distinct.

Somatosensory temporal discrimination in Parkinson's disease, dystonia and essential tremor: Pathophysiological and clinical implications.

OBJECTIVE: To investigate whether changes in the somatosensory temporal discrimination threshold (STDT) in Parkinson's disease (PD) and dystonia reflect the involvement of specific neural structures or mechanisms related to tremor, and whether the STDT can discriminate patients with PD, dystonia or essential tremor (ET). METHODS: We tested STDT in 223 patients with PD, dystonia and ET and compared STDT values in patients with PD and dystonia with tremor with those of PD and CD without tremor. Data were compared with those of age-matched healthy subjects. RESULTS: STDT values were high in patients with dystonia and PD but normal in ET. In PD, STDT values were similar in patients with resting or postural/action tremor and in those without tremor. In dystonia, STDT values were higher in patients with tremor than in those without tremor. The ROC curve showed that STDT discriminates tremor in dystonia from ET. CONCLUSIONS: In PD, STDT changes likely reflect basal ganglia abnormalities and are unrelated to tremor mechanisms. In dystonia, the primary somatosensory cortex and cerebellum play an additional role. SIGNIFICANCE: STDT provides information on the pathophysiological mechanisms of patients with movement disorders and may be used to differentiate patients with dystonia and tremor from those with tremor due to ET.

A Pilot Study of Botulinum Toxin for Jerky, Position-Specific, Upper Limb Action Tremor.

BACKGROUND: We aimed to investigate the efficacy and safety of botulinum toxin (BT) injections for jerky action tremor of the upper limb. METHODS: We performed an uncontrolled, prospective study of electromyography (EMG)-guided BT injections for jerky, position-specific, upper limb action tremor. The primary outcome was clinical global impression at 3-6 weeks after baseline. RESULTS: Eight patients with jerky, position-specific action tremor involving the upper limb were consecutively recruited. After a median follow-up of 4.4 weeks (interquartile range [IQR] 3.6-6 weeks), four of them rated themselves as "improved" and two as "much improved." Five of these six subjects reported improvements in specific activities of daily living (bringing liquids to mouth, feeding, shaving, and dressing). Upper limb subscore of the Fahn-Tolosa-Marin Tremor Rating Scale (FTM) significantly decreased from 4.5 (4-6) to 3 (2-5) (p = 0.01). DISCUSSION: This pilot, prospective cohort study suggests that EMG-guided BT injections may improve jerky, position-specific, upper limb action tremor. Placebo-controlled studies evaluating larger samples of patients are warranted to confirm these findings.

Inverse dynamics modelling of upper-limb tremor, with cross-correlation analysis.

A method to characterise upper-limb tremor using inverse dynamics modelling in combination with cross-correlation analyses is presented. A 15 degree-of-freedom inverse dynamics model is used to estimate the joint torques required to produce the measured limb motion, given a set of estimated inertial properties for the body segments. The magnitudes of the estimated torques are useful when assessing patients or evaluating possible intervention methods. The cross-correlation of the estimated joint torques is proposed to gain insight into how tremor in one limb segment interacts with tremor in another. The method is demonstrated using data from a single patient presenting intention tremor because of multiple sclerosis. It is shown that the inertial properties of the body segments can be estimated with sufficient accuracy using only the patient's height and weight as a priori knowledge, which ensures the method's practicality and transferability to clinical use. By providing a more detailed, objective characterisation of patient-specific tremor properties, the method is expected to improve the selection, design and assessment of treatment options on an individual basis.