Faculty Bibliography

OBJECTIVE:The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming that captures extensive brain networks, including cognitive, language and afferent/efferent visual pathways. MULES performance is slower in concussion and multiple sclerosis, conditions in which vision dysfunction is common. Visual aspects captured by the MULES may be impaired in Parkinson's disease (PD) including color discrimination, object recognition, visual processing speed, and convergence. The purpose of this study was to compare MULES time scores for a cohort of PD patients with those for a control group of participants of similar age. We also sought to examine learning effects for the MULES by comparing scores for two consecutive trials within the patient and control groups. METHODS:MULES consists of 54 colored pictures (fruits, animals, random objects). The test was administered in a cohort of PD patients and in a group of similar aged controls. Wilcoxon rank-sum tests were used to determine statistical significance for differences in MULES time scores between PD patients and controls. Spearman rank-correlation coefficients were calculated to examine the relation between MULES time scores and PD motor symptom severity (UPDRS). Learning effects were assessed using Wilcoxon rank-sum tests. RESULTS: = 0.37, P = .02). Learning effects were greater among patients with PD (median improvement of 14.8 s between two MULES trials) compared to controls (median 7.4 s, P = .004). CONCLUSION/CONCLUSIONS:The MULES is a complex test of rapid picture naming that captures numerous brain pathways including an extensive visual network. MULES performance is slower in patients with PD and our study suggests an association with the degree of motor impairment. Future studies will determine the relation of MULES time scores to other modalities that test visual function and structure in PD.

In addition to redefining essential tremor (ET), the 2018 consensus statement of the Movement Disorder Society on tremor coined a new term: essential tremor-plus (ET-plus). This term is uncertainly defined as tremor with the characteristics of ET, with additional neurological signs of uncertain clinical significance. If ET-plus had been defined on the basis of a difference in underlying pathology or an appreciable difference in prognosis, it would have a valid, scientific rationale, as does the term Parkinson-plus. However, there is no such evidence, so the basis for the term is questionable. In fact, ET-plus might only represent a state condition (ie, patients with ET might develop these additional clinical features when the disease is at a more advanced stage). We caution against coining new terms that are not supported by a firm scientific basis and encourage research into the creation of essential tremor subsets that are defined with respect to differences in underlying causes or pathophysiology.

Background/UNASSIGNED:Parkinson's disease (PD) is associated with α-synuclein (αS) aggregation within the enteric nervous system (ENS) and constipation. Squalamine displaces proteins that are electrostatically bound to intracellular membranes and through this mechanism suppresses aggregation of αS monomers into neurotoxic oligomers. Objective/UNASSIGNED:We sought to evaluate the safety of ENT-01 oral tablets (a synthetic squalamine salt), its pharmacokinetics, and its effect on bowel function in PD patients with constipation. Methods/UNASSIGNED:In Stage 1, 10 patients received escalating single doses from 25 to 200 mg/day or maximum tolerated dose (MTD). In Stage 2, 34 patients received daily doses escalating from 75 to a maximum of 250 mg/day, a dose that induced change in bowel function or MTD, followed by a fixed dose for 7 days, and a 2-week washout. Primary efficacy endpoint was defined as an increase of 1 complete spontaneous bowel movement (CSBM)/week, or 3 CSBM/week over the baseline period, as defined by FDA guidelines for prokinetic agents. Safety was also assessed. Results/UNASSIGNED:). Common adverse events included nausea in 21/44 (47%) and diarrhea in 18/44 (40%) patients. Systemic absorption was <0.3%. Conclusions/UNASSIGNED:Orally administered ENT-01 was safe and significantly improved bowel function in PD, suggesting that the ENS is not irreversibly damaged in PD. Minimal systemic absorption suggests that improvements result from local stimulation of the ENS. A double-blind, placebo-controlled study is now ongoing.

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)

PURPOSE/OBJECTIVE:To assess the urodynamic findings in patients with Parkinson disease (PD) with overactive bladder symptoms. METHODS:We performed a retrospective chart review of all PD patients who were seen in an outpatient clinic for lower urinary tract symptoms (LUTS) between 2010 and 2017 in a single-institution. Only patients who complained of overactive bladder (OAB) symptoms and underwent a video-urodynamic study for these symptoms were included. We excluded patients with neurological disorders other than PD and patients with voiding LUTS but without OAB symptoms. RESULTS:We included 42 patients (29 men, 13 women, 74.5±8.1 years old). Seven patients (16.7%) had a postvoid residual (PVR) bladder volume >100 mL and only one reported incomplete bladder emptying. Detrusor overactivity (DO) was found in all 42 patients (100%) and was terminal in 19 (45.2%) and phasic in 22 patients (52.4%). Eighteen patients had detrusor underactivity (DU) (42.3%). Later age of PD diagnosis was the only parameter associated with DU (P=0.02). Patients with bladder outlet obstruction (BOO) were younger than patients without BOO (70.1 years vs. 76.5 years, P=0.004), had later first sensation of bladder filling (173.5 mL vs. 120.3 mL, P=0.02) and first involuntary detrusor contraction (226.4 mL vs. 130.4 mL, P=0.009). CONCLUSION/CONCLUSIONS:DO is almost universal in all patients with PD complaining of OAB symptoms (97.1%). However, a significant percentage of patients also had BOO (36.8%), DU (47%), and increased PVR (16.7%) indicating that neurogenic DO may not be the only cause of OAB symptoms in PD patients.

Introduction: To date, only very few series have aimed to assess the outcomes of botulinum toxin injections in patients with Parkinson's Disease (PD). The aim of this study was to assess the safety and efficacy of intradetrusor onabotulinum toxin A injections for the treatment of overactive bladder (OAB) in patients with PD.
Method(s): 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 four weeks after the injections.
Result(s): Out of 24 patients analyzed, 19 reported improvement of their OAB symptoms four weeks after the first injection (79.2%) with complete resolution of urgency urinary incontinence in 7 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(s): Botox appeared effective in PD patients with a relatively low rate of retention requiring CIC. Higher preoperative PVR was the stronger predictor of both treatment failure and postoperative urinary retention requiring CIC while urodynamic obstruction was also associated with treatment failure in male patients. 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

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.