Incobotulinum Toxin-A in Professional Musicians with Focal Task-Specific Dystonia: A Double Blind, Placebo Controlled, Cross-Over Study.

Background: Musician's focal task-specific dystonia is a complex disorder of fine motor control, with incomplete understanding of its etiology. There have been relatively few trials of botulinum toxin in upper limb task-specific dystonia, and prior studies have yielded variable results, leading to skepticism regarding the utility of this approach in elite performers. Methods: We conducted a double-blind, placebo-controlled, randomized, cross-over study of incobotulinum toxin-A in 21 professional musicians with focal upper extremity task-specific dystonia affecting performance on their instrument, using a novel paradigm of initial injections followed by booster injections at two- and four-week intervals. The primary outcome measure was the change in blinded dystonia rating of the active arm by two expert raters using a Clinical Global Impression numeric scale at week 8 compared to enrollment. Findings: 19 men and 2 women with musicians' dystonia were enrolled over a six-year period. Nineteen patients completed the study. Analysis of the primary outcome measure in comparison to baseline revealed a change in dystonia severity of P = 0.04 and an improvement in overall musical performance of P = 0.027. No clinically significant weakness was observed, and neutralizing antibodies to toxin were not found. Interpretation: Despite its small sample size, our study demonstrated a statistically significant benefit of incobotulinum toxin-A injections as a treatment for musicians' task-specific dystonia. Tailoring the use of toxin with booster injections allowed refinement of dosing strategy and outcomes, with benefits that were meaningful to patients clearly visible on videotaped evaluations. In addition to its application to musicians' dystonia, this approach may have relevance to optimize application of botulinum toxin in other forms of focal dystonia such as blepharospasm, cervical dystonia, writer's cramp, and spasmodic dysphonia.

The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.

BACKGROUND AND OBJECTIVES: Executive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials. METHODS: We used cross-sectional and longitudinal follow-up data from PD participants enrolled in the PD Cognitive Genetics Consortium, a multicenter setting focused on PD. All PD participants with Trail Making Test, Digit Symbol, Letter-Number Sequencing, Semantic Fluency, and Phonemic Fluency neuropsychological data collected from March 2010 to February 2020 were included. Baseline executive functioning data were used to create the Parkinson's Disease Composite of Executive Functioning (PaCEF) through confirmatory factor analysis. We examined the changes in the PaCEF over time, how well baseline PaCEF predicts time to cognitive progression, and the required sample size estimates for PD clinical trials. PaCEF results were compared with the Montreal Cognitive Assessment (MoCA), individual tests forming the PaCEF, and tests of visuospatial, language, and memory functioning. RESULTS: A total of 841 participants (251 no cognitive impairment [NCI], 480 mild cognitive impairment [MCI], and 110 dementia) with baseline data were included, of which the mean (SD) age was 67.1 (8.9) years and 270 were women (32%). Five hundred forty five PD participants had longitudinal neuropsychological data spanning 9 years (mean [SD] 4.5 [2.2] years) and were included in analyses examining cognitive decline. A 1-factor model of executive functioning with excellent fit (comparative fit index = 0.993, Tucker-Lewis index = 0.989, and root mean square error of approximation = 0.044) was used to calculate the PaCEF. The average annual change in PaCEF ranged from 0.246 points per year for PD-NCI participants who remained cognitively unimpaired to -0.821 points per year for PD-MCI participants who progressed to dementia. For PD-MCI, baseline PaCEF, but not baseline MoCA, significantly predicted time to dementia. Sample size estimates were 69%-73% smaller for PD-NCI trials and 16%-19% smaller for PD-MCI trials when using the PaCEF rather than MoCA as the endpoint. DISCUSSION: The PaCEF is a sensitive measure of executive functioning decline in PD and will be especially beneficial for PD clinical trials.

Sex Differences in Dystonia.

BACKGROUND: Prior studies have indicated that female individuals outnumber male individuals for certain types of dystonia. Few studies have addressed factors impacting these sex differences or their potential biological mechanisms. OBJECTIVES: To evaluate factors underlying sex differences in the dystonias and explore potential mechanisms for these differences. METHODS: Data from individuals with various types of dystonia were analyzed in relation to sex. Data came from two different sources. One source was the Dystonia Coalition database, which contains predominantly idiopathic adult-onset focal and segmental dystonias. The second source was the MDSGene database, which contains predominantly early-onset monogenic dystonias. RESULTS: The 3222 individuals from the Dystonia Coalition included 71% female participants and 29% male participants for an overall female-to-male ratio (F:M) of 2.4. This ratio varied according to body region affected and whether dystonia was task-specific. The female predominance was age-dependent. Sex did not have a significant impact on co-existing tremor, geste antagoniste, depression or anxiety. In the 1377 individuals from the MDSGene database, female participants outnumbered male participants for some genes (GNAL, GCH1, and ANO3) but not for other genes (THAP1, TH, and TOR1A). CONCLUSIONS: These results are in keeping with prior studies that have indicated female individuals outnumber male individuals for both adult-onset idiopathic and early onset monogenic dystonias. These results extend prior observations by revealing that sex ratios depend on the type of dystonia, age, and underlying genetics.

Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy.

OBJECTIVES: To evaluate the effect of Alzheimer's disease (AD) -related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). METHODS: Data from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4-R-Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD-positive (CBS/PSP-AD) and AD-negative (CBS/PSP-noAD) groups based on fluid biomarkers and amyloid PET scans. Cognitive, motor, and depression scores; AD fluid biomarkers (cerebrospinal p-tau, t-tau, and amyloid-beta, and plasma ptau-217); and neuroimaging data (amyloid PET, MRI and fMRI) were collected. Clinical features, whole-brain gray matter volume and functional networks connectivity were compared across groups. RESULTS: Data were analyzed from 87 CBS/PSP-noAD and 23 CBS/PSP-AD, 18 AD, and 30 healthy controls. CBS/PSP-noAD showed worse performance in comparison to CBS/PSP-AD in the PSPRS [mean(SD): 34.8(15.8) vs 23.3(11.6)] and the UPDRS scores [mean(SD): 34.2(17.0) vs 21.8(13.3)]. CBS/PSP-AD demonstrated atrophy in AD signature areas and brainstem, while CBS/PSP-noAD patients displayed atrophy in frontal and temporal areas, globus pallidus, and brainstem compared to healthy controls. The default mode network showed greatest disconnection in CBS/PSP-AD compared with CBS/PSP-no AD and controls. The thalamic network connectivity was most affected in CBS/PSP-noAD. INTERPRETATION: AD biomarker positivity may modulate the clinical presentation of CBS/PSP, with evidence of distinctive structural and functional brain changes associated with the AD pathology/co-pathology. ANN NEUROL 2024;96:99-109.

Clinical gait analysis using video-based pose estimation: Multiple perspectives, clinical populations, and measuring change.

Gait dysfunction is common in many clinical populations and often has a profound and deleterious impact on independence and quality of life. Gait analysis is a foundational component of rehabilitation because it is critical to identify and understand the specific deficits that should be targeted prior to the initiation of treatment. Unfortunately, current state-of-the-art approaches to gait analysis (e.g., marker-based motion capture systems, instrumented gait mats) are largely inaccessible due to prohibitive costs of time, money, and effort required to perform the assessments. Here, we demonstrate the ability to perform quantitative gait analyses in multiple clinical populations using only simple videos recorded using low-cost devices (tablets). We report four primary advances: 1) a novel, versatile workflow that leverages an open-source human pose estimation algorithm (OpenPose) to perform gait analyses using videos recorded from multiple different perspectives (e.g., frontal, sagittal), 2) validation of this workflow in three different populations of participants (adults without gait impairment, persons post-stroke, and persons with Parkinson's disease) via comparison to ground-truth three-dimensional motion capture, 3) demonstration of the ability to capture clinically relevant, condition-specific gait parameters, and 4) tracking of within-participant changes in gait, as is required to measure progress in rehabilitation and recovery. Importantly, our workflow has been made freely available and does not require prior gait analysis expertise. The ability to perform quantitative gait analyses in nearly any setting using only low-cost devices and computer vision offers significant potential for dramatic improvement in the accessibility of clinical gait analysis across different patient populations.

Concomitant Medications for Progressive Supranuclear Palsy: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial examines changes in the progression of progressive supranuclear palsy (PSP) associated with 31 concomitant medication classes used by study participants over 1 year.

An Empirical Comparison of Commonly Used Universal Rating Scales for Dystonia.

Background: There are several widely used clinical rating scales for documenting the severity and distribution of various types of dystonia. Objectives: The goal of this study was to evaluate the performance of the most commonly used scales in a large group of adults with the most common types of isolated dystonia. Methods: Global Dystonia Rating Scale (GDRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) scores were obtained for 3067 participants. Most had focal or segmental dystonia, with smaller numbers of multifocal or generalized dystonia. These scales were also compared for 209 adults with cervical dystonia that had Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores and 210 adults with blepharospasm that had Blepharospasm Severity Scale (BSRS) scores. Results: There were strong correlations between the GDRS and BFM total scores (r = 0.79) and moderate correlations for their sub scores (r > 0.5). Scores for both scales showed positive skew, with an overabundance of low scores. BFM sub-scores were not normally distributed, due to artifacts caused by the provoking factor. Relevant sub-scores of the GDRS and BFM also showed moderate correlations with the TWSTRS (r > 0.5) for cervical dystonia and the BSRS (r > 0.5) for blepharospasm. Conclusions: The BFM is more widely used than the GDRS, but these results suggest the GDRS may be preferable for focal and segmental dystonias. The overabundance of very low scores for both scales highlights challenges associated with discriminating very mild dystonia from other abnormal movements or variants of normal behavior.

Remote at-home wearable-based gait assessments in Progressive Supranuclear Palsy compared to Parkinson's Disease.

BACKGROUND: Wearable sensors can differentiate Progressive Supranuclear Palsy (PSP) from Parkinson's Disease (PD) in laboratory settings but have not been tested in remote settings. OBJECTIVES: To compare gait and balance in PSP and PD remotely using wearable-based assessments. METHODS: Participants with probable PSP or probable/clinically established PD with reliable caregivers, still able to ambulate 10 feet unassisted, were recruited, enrolled, and consented remotely and instructed by video conference to operate a study-specific tablet solution (BioDigit Home ™) and to wear three inertial sensors (LEGSys™, BioSensics LLC, Newton, MA USA) while performing the Timed Up and Go, 5 × sit-to-stand, and 2-min walk tests. PSPRS and MDS-UPDRS scores were collected virtually or during routine clinical visits. RESULTS: Between November, 2021- November, 2022, 27 participants were screened of whom 3 were excluded because of technological difficulties. Eleven PSP and 12 PD participants enrolled, of whom 10 from each group had complete analyzable data. Demographics were well-matched (PSP mean age = 67.6 ± 1.3 years, 40% female; PD mean age = 70.3 ± 1.8 years, 40% female) while disease duration was significantly shorter in PSP (PSP 14 ± 3.5 months vs PD 87.9 ± 16.9 months). Gait parameters showed significant group differences with effect sizes ranging from d = 1.0 to 2.27. Gait speed was significantly slower in PSP: 0.45 ± 0.06 m/s vs. 0.79 ± 0.06 m/s in PD (d = 1.78, p < 0.001). CONCLUSION: Our study demonstrates the feasibility of measuring gait in PSP and PD remotely using wearable sensors. The study provides insight into digital biomarkers for both neurodegenerative diseases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04753320, first posted Febuary 15, 2021.

[18F]PI-2620 Binding Patterns in Patients with Suspected Alzheimer Disease and Frontotemporal Lobar Degeneration.

Tau PET has enabled the visualization of paired helical filaments of 3 or 4 C-terminal repeat tau in Alzheimer disease (AD), but its ability to detect aggregated tau in frontotemporal lobar degeneration (FTLD) spectrum disorders is uncertain. We investigated 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c']dipyridine ([18F]PI-2620), a newer tracer with ex vivo evidence for binding to FTLD tau, in a convenience sample of patients with suspected FTLD and AD using a static acquisition protocol and parametric SUV ratio (SUVr) images. Methods: We analyzed [18F]PI-2620 PET data from 65 patients with clinical diagnoses associated with AD or FTLD neuropathology; most (60/65) also had amyloid-ß (Aß) PET. Scans were acquired 30-60 min after injection; SUVr maps (reference, inferior cerebellar cortex) were created for the full acquisition and for 10-min truncated sliding windows (30-40, 35-45,…50-60 min). Age- and sex-adjusted z score maps were computed for each patient, relative to 23 Aß-negative cognitively healthy controls (HC). Mean SUVr in the globus pallidus, substantia nigra, subthalamic nuclei, dentate nuclei, white matter, and temporal gray matter was extracted for the full and truncated windows. Results: Patients with suspected AD neuropathology (Aß-positive patients with mild cognitive impairment or AD dementia) showed high-intensity temporoparietal cortex-predominant [18F]PI-2620 binding. At the group level, patients with clinical diagnoses associated with FTLD (progressive supranuclear palsy with Richardson syndrome [PSP Richardson syndrome], corticobasal syndrome, and nonfluent-variant primary progressive aphasia) exhibited higher globus pallidus SUVr than did HCs; pallidal retention was highest in the PSP Richardson syndrome group, in whom SUVr was correlated with symptom severity (ρ = 0.53, P = 0.05). At the individual level, only half of PSP Richardson syndrome, corticobasal syndrome, and nonfluent-variant primary progressive aphasia patients had a pallidal SUVr above that of HCs. Temporal SUVr discriminated AD patients from HCs with high accuracy (area under the receiver operating characteristic curve, 0.94 [95% CI, 0.83-1.00]) for all time windows, whereas discrimination between patients with PSP Richardson syndrome and HCs using pallidal SUVr was fair regardless of time window (area under the receiver operating characteristic curve, 0.77 [95% CI, 0.61-0.92] at 30-40 min vs. 0.81 [95% CI, 0.66-0.96] at 50-60 min; P = 0.67). Conclusion: [18F]PI-2620 SUVr shows an intense and consistent signal in AD but lower-intensity, heterogeneous, and rapidly decreasing binding in patients with suspected FTLD. Further work is needed to delineate the substrate of [18F]PI-2620 binding and the usefulness of [18F]PI2620 SUVr quantification outside the AD continuum.

Feasibility and Proof-of-Concept of Delivering an Autonomous Music-Based Digital Walking Intervention to Persons with Parkinson's Disease in a Naturalistic Setting.

BACKGROUND: Reduced motor automaticity in Parkinson's disease (PD) negatively impacts the quality, intensity, and amount of daily walking. Rhythmic auditory stimulation (RAS), a clinical intervention shown to improve walking outcomes, has been limited by barriers associated with the need for ongoing clinician input. OBJECTIVE: To assess the feasibility, proof-of-concept, and preliminary clinical outcomes associated with delivering an autonomous music-based digital walking intervention based on RAS principles to persons with PD in a naturalistic setting. METHODS: Twenty-three persons with PD used the digital intervention independently for four weeks to complete five weekly 30-minute sessions of unsupervised, overground walking with music-based cues. The intervention progressed autonomously according to real-time gait sensing. Feasibility of independent use was assessed by examining participant adherence, safety, and experience. Intervention proof-of-concept was assessed by examining spatiotemporal metrics of gait quality, daily minutes of moderate intensity walking, and daily steps. Preliminary clinical outcomes were assessed following intervention completion. RESULTS: Participants completed 86.4% of sessions and 131.1% of the prescribed session duration. No adverse events were reported. Gait speed, stride length, and cadence increased within sessions, and gait variability decreased (p < 0.05). Compared to baseline, increased daily moderate intensity walking (mean Δ= +21.44 minutes) and steps (mean Δ= +3,484 steps) occurred on designated intervention days (p < 0.05). Quality of life, disease severity, walking endurance, and functional mobility were improved after four weeks (p < 0.05). CONCLUSIONS: Study findings supported the feasibility and potential clinical utility of delivering an autonomous digital walking intervention to persons with PD in a naturalistic setting.

Utilizing speech analysis to differentiate progressive supranuclear palsy from Parkinson's disease.

INTRODUCTION: Distinguishing Parkinson's disease (PD) from Progressive supranuclear palsy (PSP) at early disease stages is important for clinical trial enrollment and clinical care/prognostication. METHODS: We recruited 21 participants with PSP(n = 11) or PD(n = 10) with reliable caregivers. Standardized passage reading, counting, and sustained phonation were recorded on the BioDigit Home tablet (BioSensics LLC, Newton, MA USA), and speech features from the assessments were analyzed using the BioDigit Speech platform (BioSensics LLC, Newton, MA USA). An independent t-test was performed to compare each speech feature between PSP and PD participants. We also performed Spearman's correlations to evaluate associations between speech measures and clinical scores (e.g., PSP rating scales and MoCA). In addition, the model's performance in classifying PSP and PD was evaluated using Rainbow passage reading analysis. RESULTS: During Rainbow passage reading, PSP participants had a significantly slower articulation rate (2.45(0.49) vs 3.60(0.47) words/minute), lower speech-to-pause ratio (2.33(1.08) vs 3.67(1.18)), intelligibility dynamic time warping (DTW, 0.26(0.19) vs 0.53(0.26)), and similarity DTW (0.43(0.27) vs 0.67(0.13)) compared to PD participants. PSP participants also had longer pause times (17.24(5.47) vs 8.45(3.13) sec) and longer total signal times (52.44(6.67) vs (36.67(6.73) sec) when reading the passage. In terms of the phonation 'a', PSP participants showed a significant higher spectral entropy, spectral centroid, and spectral spread compared to PD participants and no differences were found for phonation 'e'. PD participants had more accurate reverse number counts than PSP participants (14.89(3.86) vs 7.36(4.67)). PSP Rating Scale (PSPRS) dysarthria (r = 0.79, p = 0.004) and bulbar item scores (r = 0.803, p = 0.005) were positively correlated with articulation rate in reverse number counts. Correct reverse number counts were positively correlated with total Montreal Cognitive Assessment scores (r = 0.703, p = 0.016). Machine learning models using passage reading-derived measures obtained an AUC of 0.93, and the sensitivity/specificity in correctly classifying PSP and PD participants were 0.95 and 0.90, respectively. CONCLUSION: Our study demonstrates the feasibility of differentiating PSP from PD using a digital health technology platform. Further multi-center studies are needed to expand and validate our initial findings.

A case of familial frontotemporal dementia caused by a progranulin gene mutation.

After Alzheimer's disease, Frontotemporal dementia (FTD) is the most common cause of early-onset dementia. Several genetic mutations have been identified in familial FTD, with mutations in progranulin (GRN) accounting for approximately 20-25% of familial FTD cases and about 10% of total FTD cases. We report the case of a familial FTD patient with atypical parkinsonism who was found to have GRN frontotemporal dementia (GRN-FTD) with a pathogenic splice site mutation (c.709-2A > G) and notable phenotypic heterogeneity among family members.

Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome.

Importance: Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)-associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology. Objective: To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS. Design, Setting, and Participants: This multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort. Main Outcome and Measures: Plasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-ß (Aß) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling. Results: Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aß PET results (mean [SD], 0.57 [0.43] pg/mL) or FTP PET (mean [SD], 0.75 [0.30] pg/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aß PET of 0.87 (95% CI, 0.76-0.98; P < .001) and FTP PET of 0.93 (95% CI, 0.83-1.00; P < .001). At baseline, individuals with CBS-AD (n = 12), defined by a PET-validated plasma p-tau217 cutoff 0.25 pg/mL or greater, had increased temporoparietal atrophy at baseline compared to individuals with CBS-FTLD (n = 39), whereas longitudinally, individuals with CBS-FTLD had faster brainstem atrophy rates. Individuals with CBS-FTLD also progressed more rapidly on a modified version of the PSP Rating Scale than those with CBS-AD (mean [SD], 3.5 [0.5] vs 0.8 [0.8] points/year; P = .005). Conclusions and Relevance: In this cohort study, plasma p-tau217 had excellent diagnostic performance for identifying Aß or FTP PET positivity within CBS with likely underlying AD pathology. Plasma P-tau217 may be a useful and inexpensive biomarker to select patients for CBS clinical trials.

Dopamine facilitates the translation of physical exertion into assessments of effort.

Our assessments of effort are critically shaped by experiences of exertion. However, it is unclear how the nervous system transforms physical exertion into assessments of effort. Availability of the neuromodulator dopamine influences features of motor performance and effort-based decision-making. To test dopamine's role in the translation of effortful exertion into assessments of effort, we had participants with Parkinson's disease, in dopamine depleted (OFF dopaminergic medication) and elevated (ON dopaminergic medication) states, exert levels of physical exertion and retrospectively assess how much effort they exerted. In a dopamine-depleted state, participants exhibited increased exertion variability and over-reported their levels of exertion, compared to the dopamine-supplemented state. Increased exertion variability was associated with less accurate effort assessment and dopamine had a protective influence on this effect, reducing the extent to which exertion variability corrupted assessments of effort. Our findings provide an account of dopamine's role in the translation of features of motor performance into judgments of effort, and a potential therapeutic target for the increased sense of effort observed across a range of neurologic and psychiatric conditions.

Factors impacting quality of life in multiple system atrophy.

Background: Multiple system atrophy (MSA) is an atypical parkinsonian disorder marked by autonomic dysfunction, parkinsonism, cerebellar dysfunction, and poor response to dopaminergic medications such as levodopa. Patient-reported quality of life is an important benchmark for clinicians and clinical trials. The Unified Multiple System Atrophy Rating Scale (UMSARS) allows healthcare providers to rate and assess MSA progression. The MSA-QoL questionnaire is a health-related quality of life scale intended to provide patient-reported outcome measures. In this article, we investigated inter-scale correlations between the MSA-QoL and UMSARS to determine factors impacting the quality of life of patients with MSA. Methods: Twenty patients at the Johns Hopkins Atypical Parkinsonism Center's Multidisciplinary Clinic with a diagnosis of clinically probable MSA and who filled out the MSA-QoL and UMSARS questionnaires within 2 weeks of each other were included. Inter-scale correlations between MSA-QoL and UMSARS responses were examined. Linear regressions were also performed to examine relationships between both scales. Results: Significant inter-scale correlations were found between the MSA-QoL and UMSARS, both between MSA-QoL total score and UMSARS Part I subtotal scores and for individual scale items. There were no significant correlations between MSA-QoL life satisfaction rating and UMSARS subtotal scores or any specific UMSARS items. Linear regression analysis found significant associations between MSA-QoL total score and UMSARS Part I and total scores, and between MSA-QoL life satisfaction rating and UMSARS Part I, Part II, and total scores (after adjustment for age). Conclusions: Our study demonstrates significant inter-scale correlations between MSA-QoL and UMSARS, particularly relating to activities of daily living and hygiene. MSA-QoL total score and UMSARS Part I subtotal scores, which assess patients' functional status, were significantly correlated. The lack of significant associations between MSA-QoL life satisfaction rating and any UMSARS item suggests there may be aspects to quality of life that are not fully captured by this assessment. Larger cross-sectional and longitudinal analyses utilizing UMSARS and MSA-QoL are warranted and modification of the UMSARS should be considered.

Neurologic music therapy combined with EEG-tDCS for upper motor extremity performance in patients with corticobasal syndrome: Study protocol for a novel approach.

BACKGROUND: Corticobasal syndrome (CBS) is an atypical parkinsonian disorder that involves degeneration of brain regions associated with motor coordination and sensory processing. Combining transcranial direct current stimulation (tDCS) with rehabilitation training has been shown to improve upper-limb performance in other disease models. Here, we describe the protocol investigating whether tDCS with neurologic music therapy (NMT) (patterned sensory enhancement and therapeutic instrumental music performance) enhances functional arm/hand performance in individuals with CBS. METHODS: Study participants are randomly assigned to six 30-min sessions (twice per week for 3 weeks) of NMT + either sham tDCS or active tDCS. We aim to stimulate the frontoparietal cortex, which is associated with movement execution/coordination and sensory processing. The hemisphere contralateral to the more affected arm is stimulated (total stimulation current of 2 mA from 5 dime-sized electrodes). Individualized NMT sessions designed to exercise the upper limb are provided. Participants undergo gross/fine motor, cognitive and emotional assessments at baseline and follow-up (one month after the final session). To investigate the immediate effects of tDCS and NMT training, gross /fine motor, affective level, and kinematic parameter measurements using motion sensors are collected before and after each session. Electroencephalography is used to collect electrical neurophysiological responses before, during, and after tDCS+NMT sessions. The study participants, neurologic music therapist and outcome assessor are blinded to whether participants are in the sham or active tDCS group. CONCLUSION: This noninvasive and patient-centered clinical trial for CBS may provide insight into rehabilitation options that are sorely lacking in this population.