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.

Objective To determine whether the initial symptom associates with motor progression in spinocerebellar ataxias (SCAs). Background SCAs are clinically heterogeneous and the initial presentation may represent different subtypes of SCA with different motor progression. Methods We studied 317 participants with SCA1, 2, 3, and 6 from the Clinical Research Consortium for SCAs (CRC-SCA) and repeatedly measured the severity of ataxia for 2.5 years. SCA patients were divided into gait-onset and non-gait-onset (speech, vision, and hand dexterity) groups based on the initial presentation. In addition to demographic comparison, we employed regression models to study ataxia progression in these two groups after adjusting for age, sex, and pathological CAG repeats. Results The majority of SCA patients had gait abnormality as an initial presentation. The pathological CAG repeat expansions were similar between the gait-onset and non-gait-onset groups. In SCA1, gait- onset group progressed slower than non-gait-onset group, while gait-onset SCA6 group progressed faster than their counterpart. In addition, the disease presented nine years later for SCA2 gait-onset group than non-gait-onset group. Initial symptoms of SCA3 did not influence age of onset or disease progression. Conclusions The initial symptom in each SCA has a different influence on age of onset and motor progression. Therefore, gait and non-gait-onset groups of SCAs might represent different subtypes of the diseases.

Gait and balance disorders are major problems that contribute to falls among subjects with Parkinson’s disease (PD). Strengthening the compensatory responses through the use of balance perturbations may improve balance in PD. To date, it is unclear how PD affects the ability to react and adapt to perturbations delivered while walking. This study aims to investigate how PD affects the ability to walk, respond to balance perturbations, and produce acute short-term effects to improve compensatory reactions and gait stability. A cable-driven robot was used to train nine patients with PD and nine age-matched controls with multidirectional waist-pull perturbations while walking on a treadmill. Margin of stability and base of support were evaluated while walking without cables and reacting to the perturbations. PD was associated with a reduced stability in the forward direction and the inability to produce proactive anticipatory adjustments. Both groups were able to improve the response to the disturbances and produce short-term aftereffects of increased gait stability once the cables were removed. A single session of perturbation-based balance training produced acute effects that ameliorated gait instability in PD. This result is encouraging for designing new therapeutic interventions that remediate falls risk.

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