Faculty Bibliography

OBJECTIVE:Recent studies on a rodent model of Parkinson's disease (PD) have raised the possibility of increased blood-brain barrier (BBB) permeability, demonstrated by histology, autoradiography, and positron emission tomography (PET). However, in human PD patients, in vivo evidence of increased BBB permeability is lacking. We examined the hypothesis that levodopa treatment increases BBB permeability in human subjects with PD, particularly in those with levodopa-induced dyskinesia (LID). METHODS:Rb concentration in brain tissue and blood, was estimated with good stability as a local measure of the volume of distribution. RESULTS:measured off- and on-levodopa infusion were also not significant for dyskinetic and non-dyskinetic subjects. CONCLUSION/CONCLUSIONS:Rb PET did not reveal significant changes in BBB permeability in PD patients.

OBJECTIVE:To explore the potential rehabilitative effect of art therapy and its underlying mechanisms in Parkinson's disease (PD). METHODS:Observational study of eighteen patients with PD, followed in a prospective, open-label, exploratory trial. Before and after twenty sessions of art therapy, PD patients were assessed with the UPDRS, Pegboard Test, Timed Up and Go Test (TUG), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale and PROMIS-Self-Efficacy, Montreal Cognitive Assessment, Rey-Osterrieth Complex Figure Test (RCFT), Benton Visual Recognition Test (BVRT), Navon Test, Visual Search, and Stop Signal Task. Eye movements were recorded during the BVRT. Resting-state functional MRI (rs-fMRI) was also performed to assess functional connectivity (FC) changes within the dorsal attention (DAN), executive control (ECN), fronto-occipital (FOC), salience (SAL), primary and secondary visual (V1, V2) brain networks. We also tested fourteen age-matched healthy controls at baseline. RESULTS:At baseline, PD patients showed abnormal visual-cognitive functions and eye movements. Analyses of rs-fMRI showed increased functional connectivity within DAN and ECN in patients compared to controls. Following art therapy, performance improved on Navon test, eye tracking, and UPDRS scores. Rs-fMRI analysis revealed significantly increased FC levels in brain regions within V1 and V2 networks. INTERPRETATION/CONCLUSIONS:Art therapy improves overall visual-cognitive skills and visual exploration strategies as well as general motor function in patients with PD. The changes in brain connectivity highlight a functional reorganization of visual networks.

PURPOSE OF REVIEW/OBJECTIVE:This article describes and discusses new potential disease-modifying therapies for Huntington's disease that are currently in human clinical trials as well as promising new therapies in preclinical development. RECENT FINDINGS/RESULTS:Multiple potential disease-modifying therapeutics for HD are in active development, including direct DNA/gene therapies, RNA modulation, and therapies targeted at aberrant downstream pathways. The etiology of Huntington's disease (HD) is well-known as an abnormally expanded trinucleotide repeat within the huntingtin gene. However, the pathogenesis downstream of the mutant huntingtin gene is complex, involving multiple toxic pathways, including abnormal protein fragmentation and neuroinflammation. The current treatment of HD focuses largely on symptomatic management. This article discusses new, potential disease-modifying therapies that are currently in human clinical trials and preclinical development.

Huntington disease, a neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, is caused by a CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. Current treatments target symptom management because there are no disease-modifying therapies at this time. Investigation of RNA-based and DNA-based treatment strategies are emerging and hold promise of possible future disease-modifying therapy.

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.

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.