Faculty Bibliography

Background/UNASSIGNED:Dystonia is a debilitating disease that causes abnormal, often repetitive, movements, postures or both. The pathophysiology is unknown but related to loss of neuronal inhibition, aberrant sensorimotor integration, and/or derangements of synaptic plasticity. Current treatments include pharmacotherapy, botulinum toxin injections and deep brain stimulation (DBS). The response to these treatments are often limited and carry the risk of side effects requiring alternative therapies such as non-invasive brain stimulation. Case presentation/UNASSIGNED:We present a case report of a 65-year -old man with refractory focal 'task-specific' dystonia. The treatment plan included 10-daily sessions of 1 Hz, 2600 pulses of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex. Conclusion/UNASSIGNED:There were no clinical benefits noticed. Currently, there are no rTMS protocol treatments for dystonia. Publication of negative results will help in refining the optimal stimulation parameters, thus maximizing the effectiveness and reproducibility of future therapeutic protocols.

Background: Symptoms related to impaired visuospatial function are relatively common in patients with Parkinson's disease (PD). Restricted visual processing can directly hamper patients' motor function. For example, systematic biases in visual perception may influence navigational veering, thus directly affecting locomotion. In patients with PD, an impaired visual function is linked to negative feelings including depression, fearfulness and reduced self-efficacy. Art Therapy (AT) has the potential of recruiting different neural networks, including those concerned with high visual conscious perception. As such, AT may serve as a neurobehavioral intervention to improve multiple functional domains, including visuospatial functions and emotional wellness.
Method(s): This is a dual-phase exploratory study. 1: cross-sectional, controlled, biomarker study on 30 non-demented PD patients (H&Y 2-3) and 30 age-matched controls; 2: prospective, open label study involving 20 sessions of AT (2sessions/week). Motor and gait functions were assessed by MDS-UPDRS, Timed Up and Go test (TUG), and wearable accelerometers. Cognitive and Visuospatial functions were assessed by neuropsychological inventories (MoCA, Rey-Osterrieth FigureTest, Benton Visual Test), computerized testing (Navon VisualTest, Visual Research Test, and visual reaction time), and binocular eyetracking (Eyelink 2). Psychological wellness was assessed by Beck Depression Index (BDI), Modified Fatigue Impact Scale, and PROMIS-Self-Efficacy scales. Brain imaging included T1-weighted 3D high resolution, DWI, and RSfMRI sequences. Preliminary analyses were conducted on clinical data from 18 PD-patients and 14 controls completing the study. Eye tracking from 4 subjects was analyzed for exploratory purposes.
Result(s): PD-patients and controls were significantly different with respect to BDI score, Navon Visual Test, Rey Figure Test, UPDRSIII, and TUG-3 (maximum gait speed). Following AT, PD patients showed significant improvements in UPDRS-III, UPDRS-total, PROMIS (symptoms management), and Navon Visual Test (number of errors). A strong trend towards improved ReyeFigureTest was observed. On eye tracking analysis, significant increases in exploratory eye movements and fixation patterns were observed spatiotopically during examined stimulus regions.
Discussion(s): According to our preliminary findings, AT may improve visual-constructional abilities, visual recognition, and motor function. These improvements are accompanied by increased self-efficacy and changes in oculomotor behavior characterized by a more efficient visual exploration strategy. The duration of these potential benefits as well as their underlying mechanisms remain to be determined

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)

Objective: To explore the applicability of an ambulatory inertial sensor (G-walk) to characterize gait function during the Timed Up and Go (TUG) Test under three different conditions.
Background(s): In Parkinson's disease (PD), the current lack of both reliable and feasible biomarkers of gait function and mobility limits the objective characterization of motor ability, clinical progression, and responsiveness to treatments. Current assessments of motor function rely on a clinicians' subjective judgement and/or the patient's self-reported questionnaires, which are not sensitive in capturing subtle changes over time and restrict comparability across raters. Ambulatory inertial sensors allow for non-invasive, wireless transmission of accurate quantitative data and therefore, may represent a useful tool in ambulatory settings. Design/Methods: Nineteen (19) PD patients (H&Y <4) and 10 agematched controls (CTRL) were consecutively enrolled to undergo inertial TUG (iTUG) testing under three experimental conditions: normal walking (iTUGnorm), dual task walking (iTUGcog), and at maximum speed (iTUGfast). The time needed to complete each test was sub-divided into six distinct phases quantified by the sensor: sitto- stand (1), forward gait (2), mid-turn (3), return gait (4), end-turn (5) and stand-to-sit (6). Other assessments included UDPRS Part III, MoCA, depression, fatigue, Benton and Rey-Osterrieth visual tests.
Result(s): A total of nineteen PD patients and ten CTRLs completed all assessments. PD patients were divided into mild (H&Y=2, n=12) and moderate (H&Y=3, n=7) disease severity. One-way-ANOVA and correlation analysis were performed. Different patterns of kinematic performance were observed (figure 1.A and 1.B). In PD, iTUG correlations were found with cognitive function, visual performance and motor severity, while in CTRLs there was only a correlation with motor performance only. iTUGfast performance seemed more sensitive experimental condition when PD was stratify by severity (figure 1.B).
Conclusion(s): iTUG assessed by an ambulatory inertial sensor is a quick, sensitive and feasible tool for objective measurements of functional mobility in PD. Utilizing validate tests for mobility and gait under different stress conditions can provide distinct information of gait function and mobility. Future longitudinal studies are warranted to better characterize the sensitivity to disease progression and the potential for monitoring and optimizing therapeutic interventions in this patient population. (Figure Presented)

BACKGROUND:Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown to improve common symptoms of neurological disorders like depressed mood, fatigue, motor deficits and cognitive dysfunction. tDCS requires daily treatment sessions in order to be effective. We developed a remotely supervised tDCS (RS-tDCS) protocol for participants with multiple sclerosis (MS) to increase accessibility of tDCS, reducing clinician, patient, and caregiver burden. The goal of this protocol is to facilitate home use for larger trials with extended treatment periods. In this study we determine the generalizability of RS-tDCS paired with cognitive training (CT) by testing its feasibility in participants with Parkinson's disease (PD). METHODS:Following the methods in our MS protocol development, we enrolled sixteen participants (n = 12 male, n = 4 female; mean age 66 years) with PD to complete ten open-label sessions of RS-tDCS paired with CT (2.0 mA × 20 min) at home under the remote supervision of a trained study technician. Tolerability data were collected before, during, and after each individual session. Baseline and follow-up measures included symptom inventories (fatigue and sleep) and cognitive assessments. RESULTS:RS-tDCS was feasible and tolerable for patients with PD, with at-home access leading to high protocol compliance. Side effects were mostly limited to mild sensations of transient itching and burning under the electrode sites. Similar to prior finding sin MS, we found preliminary efficacy for improvement of fatigue and cognitive processing speed in PD. CONCLUSIONS:RS-tDCS paired with CT is feasible for participants with PD to receive at home treatment. Signals of benefit for reduced fatigue and improved cognitive processing speed are consistent across the PD and MS samples. RS-tDCS can be generalized to provide tDCS to a range of patients with neurologic disorders for at-home rehabilitation. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier: NCT02746705 . Registered April 21st 2016.

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.

BACKGROUND:Transcranial direct current stimulation (tDCS) has been explored as a potential intervention in Parkinson's disease (PD) and recent studies have shown promising results in cognitive, gait and motor function. However, evidence of efficacy is limited due to small size studies, short treatment periods, lack of standardization of methodologies and other study design limitations. Remotely supervised-tDCS (RS-tDCS) allows "at-home" study participation, potentially easing recruitment, compliance and overall feasibility for clinical studies. OBJECTIVE:Here, we aim to explore preliminary effects of RS-tDCS paired with cognitive training in PD by delivering RS-tDCS neuromodulation at participant's home while still maintaining clinical trial standards. METHODS:This was a prospective, open-label study using RS-tDCS paired with cognitive training. Each PD participant completed 10 tDCS sessions (20-min, 1.5-2.0-mA, bi-hemispheric DLPFC montage, left anodal), over a span of two weeks. All tDCS sessions were supervised in real-time through videoconferencing. Outcomes included the Unified Parkinson's Disease Rating Scale (UPDRS) and Grooved Pegboard Test. RESULTS:All RS-tDCS sessions were well tolerated and completed successfully. Total UPDRS and motor UPDRS-III scores decreased significantly. Pegboard completion time improved significantly for the non-dominant hand. There was a strong positive correlation between the time of the sessions, and motor improvements in UPDRS part-III. CONCLUSION/CONCLUSIONS:RS-tDCS paradigm through a 'telemedicine protocol' holds therapeutic potential for motor symptoms in PD while maximizing compliance and ease of recruitment. Conducting afternoon sessions might be more effective than during the morning. Our paradigm may be influential in designing future studies and facilitating larger and longer duration clinical trials.