Faculty Bibliography

Musicians' dystonia is an example of a focal task-specific dystonia, i.e., dystonia affecting one part of the body, only when it is engaged in performance of a specific task. Musicians' dystonia may involve the upper extremity (either the hand, arm, or shoulder) or the embouchure (the muscles of lower face, tongue, and pharynx that control the flow of air into a brass or woodwind instrument). Musicians' dystonia typically affects professionals at the peak of their performing careers, often with devastating consequences. Recent work has revealed that both genetic and environmental influences contribute to the development of the condition. Current treatments for musicians' dystonia include instrument modification, physical therapy, oral medication, injection of botulinum toxin, and even stereotactic surgery. Management remains challenging, and there is a need for more innovative approaches for treatment.
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Background/UNASSIGNED:Treatment of posthypoxic myoclonus (PHM) can be a challenge in patients not responsive to first-line medications. PMH is a rare condition that has a dramatic impact on patients' quality of life. Refractory cases are not uncommon. Case report/UNASSIGNED:We report a patient with PHM non-responsive to conventional treatments who showed a dramatic improvement with sodium oxybate (SBX). Cases of PHM treated with SBX reported in the literature were reviewed. Discussion/UNASSIGNED:Resting and stimulus-induced myoclonus respond robustly to SBX, with significant improvement in patients' quality of life. SBX may be considered in patients with PHM resistant to first-line medications.

Background: Fatigue is one of the most prevalent and underassessed non-motor symptoms in PD. Transcranial direct current stimulation (tDCS) is a portable non-invasive brain stimulation device that utilizes low current to alter brain activity. We designed a tele-monitored tDCS (tele-tDCS) protocol to assess feasibility, safety and explore the therapeutic potential of tele-tDCS for Parkinson's disease (PD) related fatigue. We utilized a live videoconferencing platform and specifically designed equipment.
Method(s): Preliminary analysis of eighteen PD patients, age 35-89 that participated in a double-blind, randomized, sham-controlled study. Each participant completed 10 tDCS sessions (20-minute, 2.0-mA, bi-frontal DLPFC montage, left anodal), over a span of two weeks. After completion, 10 additional open-label sessions were offered. Tolerability, safety, and compliance were evaluated. Preliminary clinical effects were measured with the Fatigue Severity Scale (FSS).
Result(s): Seventeen participants completed 330 tele-tDCS sessions; one subject chose not to complete the 10 optional sessions. Tolerability of 2.0 mA stimulation with = 6 on the Visual Analog Scale for Pain (VAS-Pain) was 100%. Systematically recorded side effects were comparable with previously published studies using conventional tDCS (in-lab). No serious adverse events were reported. Compliance was 100% as subjects completed all required visits with no attrition or interruptions. Preliminary fatigue clinical effects of 10 sessions showed a significant decrease of FSS only in real-tDCS (mean 16% decrease in FSS, p=0.05); however, there was no significant difference between groups. Further analysis of 20 real-tDCS sessions in nine subjects showed a further decrease in FSS (mean 27%; p=0.013).
Conclusion(s): At-home tele-tDCS therapy is safe and well tolerated by PD patients, with the advantages of ease of recruitment and subject compliance. Acceptability was achieved by easy setup and intuitive design of the device. At-home tele-tDCS therapy shows potential to remediate fatigue symptoms in PD, especially after 20 sessions. The small sample size limits efficacy conclusions. Our paradigm may be influential in designing future studies that will facilitate clinical trials with a larger subject population and extended trial duration. (Figure Presented)

INTRODUCTION/BACKGROUND:This study aimed to assess the outcomes of mirabegron for the treatment of overactive bladder (OAB) symptoms in patients with Parkinson disease (PD). METHODS:A retrospective study was conducted including patients with PD who received mirabegron 50 mg once daily for OAB symptoms between 2012 and 2017. The primary endpoint was clinical success defined as any improvement in overactive bladder symptoms self-assessed by the patients 6 weeks after mirabegron initiation. Secondary endpoints included number of pads per day, number of nocturia episodes and adverse events. RESULTS:Fifty patients (mean 74 years old) were included. Before being treated with mirabegron, 56% had failed prior anticholinergic therapy. After 6 weeks of mirabegron 50 mg, five patients (11.4%) had a complete resolution of their OAB symptoms; 25 patients (50%) reported improvement, 23 (46%) reported no change and 2(4%) reported worsening of their OAB symptoms. The number of pads per day decreased from 1.5 to 0.9 (p = 0.01) and so did the number of nocturia episodes (from 3 to 2.6/night; p = 0.02). Only 2 adverse events were reported during mirabegron treatment (4%): one dizziness and one diaphoresis, that disappeared after mirabegron discontinuation. After a median follow-up of 19 months, 23 patients (46%) persisted on mirabegron. Persistence rates were 51.5%, 44.6% and 36.4% at 1, 2 and 3 years respectively. CONCLUSION/CONCLUSIONS:Mirabegron has an excellent safety profile and appears to be an effective treatment for overactive bladder symptoms in patients with PD. Further prospective randomized trials are needed to properly assess mirabegron in PD patients.

OBJECTIVE:To assess the safety and efficacy of intradetrusor onabotulinum toxin A injections for the treatment of overactive bladder (OAB) in patients with Parkinson's disease (PD). METHODS:All PD patients who underwent intradetrusor injections of onabotulinum toxin A (BoNT-A) for storage symptoms between 2010 and 2017 were included in a retrospective study. A 100 U dose of BoNT-A (Botox®, Allergan Irvine, CA) was used for the first injection in all patients. The primary endpoint was clinical success defined as any subjective improvement in OAB symptoms self-assessed by the patients 4 weeks after the injections. RESULTS:Out of 24 patients analyzed, 19 reported improvement of their OAB symptoms 4 weeks after the first injection (79.2%) with complete resolution of urgency urinary incontinence in seven patients (29.1%; P < 0.001). The average post-void residual (PVR) increased significantly after the first injection from 17.6 to 125.3 mL (P < 0.001). Three of the patients had to start clean intermittent catheterization (CIC) after the first injection (12.5%). Out of 49 injections in total, only five caused incomplete bladder emptying requiring the use of CIC (10.2%). Higher pre-injection PVR was significantly associated with both a lower chance of symptomatic improvement (P = 0.04) and a higher risk of incomplete bladder emptying with institution of CIC (P = 0.047). CONCLUSION/CONCLUSIONS:Intradetrusor injections of BoNT-A 100 U appeared as a safe and effective option in PD patients with OAB symptoms and a low PVR before the injection. Higher preoperative PVR was the strongest predictor of both treatment failure and postoperative urinary retention requiring CIC.

Oral medications for the treatment of dystonia are not established. Currently, symptoms of focal dystonia are managed with botulinum toxin injections into the affected muscles. However, the injection effects are short-lived and not beneficial for all patients. We recently reported significant clinical improvement of symptoms with novel investigational oral drug, sodium oxybate, in patients with the alcohol-responsive form of laryngeal focal dystonia. Understanding the mechanism of action of this promising oral agent holds a strong potential for the development of a scientific rationale for its use in dystonia. Therefore, to determine the neural markers of sodium oxybate effects, which may underlie dystonic symptom improvement, we examined brain activity during symptomatic speech production before and after drug intake in patients with laryngeal dystonia and compared to healthy subjects. We found that sodium oxybate significantly attenuated hyperfunctional activity of cerebellar, thalamic and primary/secondary sensorimotor cortical regions. Drug-induced symptom improvement was correlated with decreased-to-normal levels of activity in the right cerebellum. These findings suggest that sodium oxybate shows direct modulatory effects on disorder pathophysiology by acting upon abnormal neural activity within the dystonic network.