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Parkinson’s disease is the second most common neurodegenerative disorder, affecting 1 to 2 % of people older than 60 years. Rasagiline is a potent and irreversible monoamine oxidase type B (MAO-B) inhibitor which has been approved for the treatment of Parkinson’s disease. Rasagiline inhibits MAO-B more potently than selegiline and has the advantage of once-daily dosing. In several large, randomized, placebo-controlled trials, rasagiline has demonstrated efficacy as monotherapy in early Parkinson’s disease and as adjunctive therapy in advanced Parkinson’s disease. Rasagiline has been shown to have disease-modifying, neuroprotective and anti-apoptotic effects. The data on its effectiveness in motor disorders in Parkinson’s disease and the rate of development of the effect against the background of its administration are presented. At the same time, taking rasagiline is not accompanied by serious adverse events, both with monotherapy and in combination with levodopa and dopamine agonists., Болезнь Паркинсона (БП) — второе по распространенности нейродегенеративное заболевание, затрагивающее от 1 до 2 % людей старше 60 лет. Разагилин — мощный и необратимый ингибитор моноаминоксидазы типа В (MAO-В), который был одобрен для лечения БП. Разагилин ингибирует MAO-В более эффективно, чем селегилин, и имеет преимущество — прием один раз в день. В нескольких крупных рандомизированных плацебо-контролируемых исследованиях разагилин показал свою эффективность в качестве монотерапии при ранней БП и в качестве дополнительной терапии при поздней стадии БП. Было показано, что разагилин оказывает болезнь-модифицирующее, нейропротекторное и антиапоптотическое действие. Представлены данные о его эффективности при моторных нарушениях при болезни Паркинсона и скорости развития эффекта на фоне его назначения. При этом прием разагилина не сопровождается серьезными нежелательными явлениями как при монотерапии, так и в сочетании с леводопой и агонистами дофамина., Хвороба Паркінсона (ХП) — друге за поширеністю нейродегенеративне захворювання, що торкається від 1 до 2 % осіб віком понад 60 років. Разагілін — потужний і необоротний інгібітор моноаміноксидази типу В (MAO-В), який був схвалений для лікування ХП. Разагілін пригнічує MAO-В більш ефективно, ніж селегілін, і має перевагу у вигляді прийому один раз на день. У кількох великих рандомізованих плацебо-конт-рольованих дослідженнях разагілін показав свою ефективність як у монотерапії при ранній ХП, так і в додатковій терапії при пізній стадії ХП. Було показано, що разагілін чинить хвороба-модифікуючу, нейропротекторну й антиапоптотичну дію. Наведені дані про його ефективність при моторних порушеннях при хворобі Паркінсона і швидкість настання ефекту на тлі його призначення. При цьому прийом разагіліну не супроводжується серйозними небажаними явищами як при монотерапії, так і в поєднанні з леводопою й агоністами дофаміну.

This is a case study of 32 year old Mrs. M, a case of Young Onset Parkinson's Disease (YOPD) with hypothyroidism. With informed consent, Mrs. M was selected for the case report because Young Onset Parkinson’s Disease is a rare diagnosis. She was assessed using MDS-UPDRS pre- and post-intervention .She was provided Occupational Therapy intervention using the Person-Environment-Occupation Model for a period of three months and has shown significant improvement in UPDRS scores. Her primary diagnosis is Young Onset Parkinson’s Disease, secondary diagnosis being hypothyroidism.The patient, being in her early 30s, many of her life roles were altered. The patient’s main concerns are that she has difficulty in performing her basic and instrumental ADLs and difficulty in caring for her loved ones. Mrs. M was treated on weekly basis for an intervention period of three months using the Person Environment Occupation Model and assessed using the Unified Parkinson’s Disease Rating Scale; pre and post treatment. She was in stage 3 of Hoehn and Yahr scale of classification of Parkinson’s Disease. Scores were assessed on Unified Parkinson’s Disease Rating Scale, pre and post three months of intervention; showed improvement in non motor and motor aspects of experiences of daily living, motor examination and motor complications. Component scores were decreased dramatically especially in the areas of anxious mood, fatigue, tremors, posture and bradykinesia which revealed that functional levels improved following intervention. Keywords: Young Onset Parkinson’s Disease, Unified Parkinson’s Disease Rating Scale, Person Environment Occupation (PEO) based Occupational Therapy Intervention, case report.

BACKGROUND Gait and balance disturbance are challenging symptoms in advanced Parkinson's disease (PD). Anatomic and clinical data suggest that the fields of Forel may be a potential surgical target to treat these symptoms. OBJECTIVE To test whether bilateral stimulation centered at the fields of Forel improves levodopa unresponsive freezing of gait (FOG), balance problems, postural instability, and falls in PD. METHODS A total of 13 patients with levodopa-unresponsive gait disturbance (Hoehn and Yahr stage ≥3) were included. Patients were evaluated before (on-medication condition) and 1 yr after surgery (on-medication-on-stimulation condition). Motor symptoms and quality of life were assessed with the Unified Parkinson's Disease Rating scale (UPDRS III) and Quality of Life scale (PDQ-39). Clinical and instrumented analyses assessed gait, balance, postural instability, and falls. RESULTS Surgery improved balance by 43% (95% confidence interval [CI]: 21.2-36.4 to 35.2-47.1; P = .0012), reduced FOG by 35% (95% CI: 15.1-20.3 to 8.1-15.3; P = .0021), and the monthly number of falls by 82.2% (95% CI: 2.2-6.9 to -0.2-1.7; P = .0039). Anticipatory postural adjustments, velocity to turn, and postural sway measurements also improved 1 yr after deep brain stimulation (DBS). UPDRS III motor scores were reduced by 27.2% postoperatively (95% CI: 42.6-54.3 to 30.2-40.5; P

Background There is paucity of data about African American (AA) patients with Parkinson’s disease (PD) and parkinsonism which may precede PD in older adults. Prior studies suggest that there are lower rates of PD in the AA population, with more cognitive impairment in AA with PD. This study aimed to investigate differences in PD, parkinsonism, and cognition between White and AA populations in 3 longitudinal epidemiologic cohort studies of aging. Methods This study examined parkinsonism, PD frequency, and cognition of community-dwelling older individuals in 3 longitudinal epidemiologic cohort studies. Parkinsonism was based on an exam utilizing the modified Unified Parkinson’s Disease Rating Scale performed by a nurse. PD was based on self-report, medications used for treatment of PD, and examination findings. Cognition was assessed using 19 performance-based tests that assess 5 cognitive domains. Results AA participants were less likely to have parkinsonism compared to Whites, even with age and gender differences. Frequency of PD was not significant between groups. AA were more likely to have lower cognitive scores as compared to Whites. AA were less likely to have parkinsonism even with controlling for cognitive differences between groups. Conclusions Parkinsonian signs are present among AA in the community at lower rates than in White individuals. Cognitive profiles of AA and Whites with parkinsonism may be different, suggesting differing contributions of pathology to cognitive decline and parkinsonism between groups. Additional research is needed to understand the progression of parkinsonism to PD, as well as to understanding the cognitive differences in AA with parkinsonism.

Background Parkinson disease (PD) impairs daily functioning for an increasing number of patients and has a growing national economic burden. Deep brain stimulation (DBS) may be the most broadly accepted procedural intervention for PD, but cost-effectiveness has not been established. Moreover, magnetic resonance image-guided focused ultrasound (FUS) is an emerging incisionless, ablative treatment that could potentially be safer and even more cost-effective. Objective To (1) quantify the utility (functional disability metric) imparted by DBS and radiofrequency ablation (RF), (2) compare cost-effectiveness of DBS and RF, and (3) establish a preliminary success threshold at which FUS would be cost-effective compared to these procedures. Methods We performed a meta-analysis of articles (1998-2018) of DBS and RF targeting the globus pallidus or subthalamic nucleus in PD patients and calculated utility using pooled Unified Parkinson Disease Rating Scale motor (UPDRS-3) scores and adverse events incidences. We calculated Medicare reimbursements for each treatment as a proxy for societal cost. Results Over a 22-mo mean follow-up period, bilateral DBS imparted the most utility (0.423 quality-adjusted life-years added) compared to (in order of best to worst) bilateral RF, unilateral DBS, and unilateral RF, and was the most cost-effective (expected cost: $32 095 ± $594) over a 22-mo mean follow-up. Based on this benchmark, FUS would need to impart UPDRS-3 reductions of ∼16% and ∼33% to be the most cost-effective treatment over 2- and 5-yr periods, respectively. Conclusion Bilateral DBS imparts the most utility and cost-effectiveness for PD. If our established success threshold is met, FUS ablation could dominate bilateral DBS's cost-effectiveness from a societal cost perspective.

Advancing age and greater number of medical comorbidities are well-known risk factors for higher rates of surgical complications and undesirable outcomes. We sought to determine the risk of increasing medical comorbidities on surgical outcomes for patients with Parkinson disease undergoing deep brain stimulation (DBS) surgery.We retrospectively reviewed 107 consecutive patients who underwent DBS for Parkinson disease at Ochsner Medical Center in 2008-2018. Patients were stratified into 3 groups based on Elixhauser comorbidity index (ECI) at the time of surgery: 0, 1, or ≥2. Outcome measures were changes in Unified Parkinson's Disease Rating Scale III scores, changes in medications, and surgical complications. Analysis of variance, paired t test, and nonparametric equivalents were used for statistical analysis.Of patients, 31 (29.0%) had ECI score 0, 44 (41.1%) had ECI score 1, and 32 (29.9%) had ECI score ≥2. For all groups, Unified Parkinson's Disease Rating Scale III scores decreased significantly postoperatively (P = 0.0014, P0.0001, P0.0001). All groups had a reduction in mean levodopa equivalent daily dose after surgery; however, only the group with ≥2 comorbidities achieved statistical significance (P = 0.0026). The rate of postoperative complications was significantly correlated with comorbidity score on univariate logistic regression analysis (P = 0.0425).Our findings indicate that DBS is efficacious in patients with multiple medical comorbidities. However, patients with ≥1 medical comorbidities may be more likely to have complications. The most common observed complication was wound infection. Patients with medical comorbidities may still benefit significantly from DBS when performed at experienced centers.

In recent years, there is an increasing interest in building e-health systems. The systems built to deliver the health services with the use of internet and communication technologies aim to reduce the costs arising from outpatient visits of patients. Some of the related recent studies propose machine learning-based telediagnosis and telemonitoring systems for Parkinson's disease (PD). Motivated from the studies showing the potential of speech disorders in PD telemonitoring systems, in this study, we aim to estimate the severity of PD from voice recordings of the patients using motor Unified Parkinson's Disease Rating Scale (UPDRS) as the evaluation metric. For this purpose, we apply various speech processing algorithms to the voice signals of the patients and then use these features as input to a two-stage estimation model. The first step is to apply a wrapper-based feature selection algorithm, called Boruta, and select the most informative speech features. The second step is to feed the selected set of features to a decision tree-based boosting algorithm, extreme gradient boosting, which has been recently applied successfully in many machine learning tasks due to its generalization ability and speed. The feature selection analysis showed that the vibration pattern of the vocal fold is an important indicator of PD severity. Besides, we also investigate the effectiveness of using age and years passed since diagnosis as covariates together with speech features. The lowest mean absolute error with 3.87 was obtained by combining these covariates and speech features with prediction level fusion. Graphical Abstract Framework for the proposed UPDRS estimation model.

Introduction Dementia with Lewy bodies (DLB) is the third most common type of dementia after Alzheimer’s disease (AD) and vascular dementia. Treatment is targeted at specific disease manifestations/symptoms. While donepezil is approved for the treatment of DLB in Japan, to date no other treatment has been approved for this indication anywhere in the world. Notwithstanding, many of the medications that are approved for AD are widely used in the treatment of DLB with varying degrees of success. Consequently, clinical evidence is limited, and there is a need to understand the comparative efficacy and safety of currently used therapies for DLB. The aim of this study was to conduct a network meta-analysis (NMA) to evaluate the outcomes of the available treatment options based on currently used trial endpoints. Methods Using data from a previously published systematic review, we conducted an NMA to investigate the efficacy and safety of treatments in patients with DLB. Networks were based on change from baseline of efficacy endpoints (Mini-Mental State Examination; Neuropsychiatric Inventory; Unified Parkinson’s Disease Rating Scale) and rate of safety events (overall adverse events [AEs]; discontinuations; discontinuations due to AEs; psychiatric events). Results Focused around a common treatment option of placebo, the NMA comprised studies on donepezil, rivastigmine, memantine and quetiapine. Donepezil 3 mg, 5 mg and 10 mg doses were compared against each other and placebo. Overall, donepezil consistently performed better than the alternative treatments when compared to placebo for all efficacy and safety endpoints. However, the small sample size and/or heterogeneity of the studies led to uncertainty, resulting in no statistically significant differences favouring any treatment above another or placebo. Conclusion Despite the lack of statistical significance, when assessing the efficacy and safety outcomes for each drug in the evidence network, donepezil appeared to have a more favourable overall benefit/risk profile for patients with DLB. Further comparative trials are required to improve understanding of the true difference between existing and potential future treatment options. Electronic Supplementary Material The online version of this article (10.1007/s40120-020-00198-0) contains supplementary material, which is available to authorized users.

Background Few studies assess the relationships between nonmotor aspects of experiences of daily living and cognitive functioning in Parkinson's disease (PD). Objective To evaluate the relationships among the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I items and neuropsychological tests in PD.Methods: We assessed 151 PD patients with the MDS-UPDRS part I and a battery of cognitive tests focused on the following 5 cognitive domains: attention/working memory, executive functioning, recent memory, language, visuoperception. Raw scores for individual cognitive tests were transformed to z scores, and cognitive domain scores were calculated by averaging z scores within each domain. Individual items from the MDS-UPDRS part I were entered in a stepwise linear regression analysis assessing item contribution to cognitive domain scores. Results The MDS-UPDRS part I item scores for hallucinations and psychosis and light headedness on standing predicted attention/working memory domain scores (P = 0.004). These same item scores, along with apathy, depressed mood, and dopamine dysregulation syndrome, predicted executive functioning (P = 0.044). The apathy and dopamine dysregulation syndrome items predicted language (P = 0.006). In addition, the cognitive impairment and sleep items were predictors of recent memory (P = 0.031). None of the items were predictors of visuoperception (P = 0.006). Other part I items were not significantly related to cognitive domain scores. Conclusions Specific nonmotor MDS-UPDRS part I items, particularly mood, behavior, and autonomic-related items, exhibited significant relationships with cognitive domains. The highest number of items were predictive of the executive functioning domain, which is the hallmark cognitive dysfunction in PD.

The rehabilitation evaluation of Parkinson’s disease has always been the research focus of human assistive systems. It is a research hotspot to objectively and accurately evaluate the gait condition of Parkinson’s disease patients, thereby adjusting the actuators of the human–machine system and making rehabilitation robots better adapt to the recovery process of patients. The rehabilitation evaluation of Parkinson’s disease has always been the research focus of rehabilitation robots. It is a research hotspot to be able to objectively and accurately evaluate the recovery of Parkinson’s disease patients, thereby adjusting the driving module of the human–machine collaboration system in real time, so that rehabilitation robots can better adapt to the recovery process of Parkinson’s disease. The gait task in the Unified Parkinson’s Disease Rating Scale (UPDRS) is a widely accepted standard for assessing the gait impairments of patients with Parkinson’s disease (PD). However, the assessments conducted by neurologists are always subjective and inaccurate, and the results are determined by the neurologists’ observation and clinical experience. Thus, in this study, we proposed a novel machine learning-based method of automatically assessing the gait task in UPDRS with wearable sensors as a more convenient and objective alternative means for PD gait assessment. In the design, twelve gait features, including three spatial–temporal features and nine kinematic features, were extracted and calculated from two shank-mounted IMUs. A novel nonlinear model is developed for calculating the score of gait task from the gait features. Twenty-five PD patients and twenty-eight healthy subjects were recruited for validating the proposed method. For comparison purpose, three traditional models, which have been used in previous studies, were also tested by the same dataset. In terms of percentages of participants, 84.9%, 73.6%, 73.6%, and 66.0% of the participants were accurately assigned into the true level with the proposed nonlinear model, the support vector machine model, the naive Bayes model, and the linear regression model, respectively, which indicates that the proposed method has a good performance on calculating the score of the UPDRS gait task and conformance with the rating done by neurologists.

BackgroundIncreasing evidence connects the gut microbiome to Parkinson's disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features.ObjectiveWe aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features.MethodsIn a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function).ResultsPD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis pathway. PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. Two genera were associated with motor function.ConclusionPD patients differed from controls in gut microbiome composition and its predicted metagenome. Clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression.

Purpose: The purpose of this study was to investigate the presence and progression of self-perceived speech and swallowing impairments in newly diagnosed people with Parkinson's disease (PD) longitudinally across 6 years. Method: Longitudinal data from the Parkinson's Progression Markers Initiative were analyzed across six consecutive years in a cohort of 269 newly diagnosed people with PD, and a subset of those ( n = 211) who were assessed at every time point across the 6 years. Dependent variables included self-perceived ratings of speech and swallowing impairment severity from the Unified Parkinson's Disease Rating Scale. Patient-centered factors of age at diagnosis and motor phenotype were also assessed to determine if they were related to the change in self-perceived speech and swallowing impairments. Results: Overall, self-perceived speech and swallowing impairments were present in newly diagnosed people with PD, although over time, the degree of severity for both remained in the mild range. However, the rate of change over time was significant for perceived speech impairment, F (5.5, 1158.8) = 21.1, p < .001), and perceived swallowing impairment, F (5.2, 1082.6) = 8.6, p < .001. Changes for speech and swallowing impairment were both in the direction of progressive severity. There were no effects of age at diagnosis or motor phenotype on the degree of change for either speech or swallowing. Conclusions: Self-perceptions of speech and swallowing impairment changed significantly over time in newly diagnosed people with PD (PWPD). Consistent with existing literature, self-perceptions of speech impairment were rated as more severe than those of swallowing impairment. These findings reveal that even in the early years postdiagnoses, PWPD are experiencing changes to speech and swallowing function, albeit within the mildly severe range. The presence of self-perceived mild speech and swallowing impairments in the initial years postdiagnosis may support the need for intervention to improve and or sustain function over time.

Background: The MDS-Unified Parkinson’s disease (PD) Rating Scale (MDS-UPDRS) is the most used scale in clinical trials. Little is known about the predictive potential of its single items. Objective: To systematically dissect MDS-UPDRS to predict PD progression. Methods: 574 de novo PD patients and 305 healthy controls were investigated at baseline (BL) in the single-center DeNoPa (6-year follow-up) and multi-center PPMI (8-year follow-up) cohorts. We calculated cumulative link mixed models of single MDS-UPDRS items for odds ratios (OR) for class change within the scale. Models were adjusted for age, sex, time, and levodopa equivalent daily dose. Annual change and progression of the square roots of the MDS-UDPRS subscores and Total Score were estimated by linear mixed modeling. Results: Baseline demographics revealed more common tremor dominant subtype in DeNoPa and postural instability and gait disorders-subtype and multiethnicity in PPMI. Subscore progression estimates were higher in PPMI but showed similar slopes and progression in both cohorts. Increased ORs for faster progression were found from BL subscores I and II (activities of daily living; ADL) most marked for subscore III (rigidity of neck/lower extremities, agility of the legs, gait, hands, and global spontaneity of movements). Tremor items showed low ORs/negative values. Conclusion: Higher scores at baseline for ADL, freezing, and rigidity were predictors of faster deterioration in both cohorts. Precision and predictability of the MDS-UPDRS were higher in the single-center setting, indicating the need for rigorous training and/or video documentation to improve its use in multi-center cohorts, for example, clinical trials.

Studies have shown the spatial specificity of cranial iron deposition in different regions in Parkinson's disease (PD). However, the time-specific patterns of iron deposition are not yet clear. The purpose of this study was to investigate the time pattern of iron variations and its clinical relevance in multiple gray matter nuclei in PD using quantitative susceptibility mapping (QSM). Thirty controls and 33 PD patients were enrolled, namely, 11 cases of early stage of PD (ESP) and 22 cases of advanced stage of PD (ASP) according to the Hoehn-Yahr stages. The iron content in the subcortical nuclei covering substantia nigra (SN), red nucleus (RN), head of the caudate nucleus (CN), globus pallidus (GP), and putamen (PT) was measured using QSM, and the clinical symptoms of PD were evaluated by various rating scales. The QSM values in SN, RN, GP, and PT significantly increased in PD patients compared with the controls. Further subgroup comparison with the controls indicated that the iron content in SN and GP (paleostriatum) gradually elevated in the whole disease duration and was related to clinical features. While the iron content in RN and PT (neostriatum) only elevated significantly in ESP patients, further iron deposition was not obvious in ASP patients. Our study confirmed that QSM could be used as a disease biomarker and could be suitable for longitudinal monitoring. However, considering the temporal characteristics of iron deposition in neostriatum, iron deposition in the neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage, in future research.

The authors examined the associations between the performance of upper- and lower-extremity motor tasks across task complexity and motor symptom severity, overall disease severity, and the physical aspects of quality of life in persons with Parkinson’s disease. The performance was assessed for three lower-extremity tasks and two upper-extremity tasks of different levels of complexity. The motor symptoms and overall disease severity correlated significantly with all motor tasks with higher correlation coefficients in the complex tasks. Thus, the strength of the association between disease severity or severity of motor symptoms and motor performance is task-specific, with higher values in complex motor tasks than in simpler motor tasks. Mobility-related and activity-of-daily-living-related quality of life correlated with lower-extremity tasks of low and medium complexity and with the complex upper-extremity task, respectively; this suggests that Parkinson’s Disease Questionnaire-39 is capable of differentiating between the impact of gross and fine motor function on quality of life.

Manganese (Mn) is a neurotoxicant that many workers are exposed to daily. There is limited knowledge about how changes in exposure levels impact measures in magnetic resonance imaging (MRI). We hypothesized that changes in Mn exposure would be reflected by changes in the MRI relaxation rate R1 and thalamic γ-aminobutyric acid (GABAThal). As part of a prospective cohort study, 17 welders were recruited and imaged on 2 separate occasions approximately 2 years apart. MRI relaxometry was used to assess changes of Mn accumulation in the brain. Additionally, GABA was measured using magnetic resonance spectroscopy in the thalamic and striatal regions of the brain. Air Mn exposure ([Mn]Air) and cumulative exposure indexes of Mn (Mn-CEI) for the past 3 months (Mn-CEI3M), past year (Mn-CEI12M), and lifetime (Mn-CEILife) were calculated using personal air sampling and a comprehensive work history, whereas toenails were collected for analysis of internal Mn body burden. Finally, welders’ motor function was examined using the Unified Parkinson’s Disease Rating Scale (UPDRS). Median exposure decreased for all exposure measures between the first and second scan. ΔGABAThal was significantly correlated with ΔMn-CEI3M (ρ = 0.66, adjusted p = .02), ΔMn-CEI12M (ρ = 0.70, adjusted p = .006), and Δ[Mn]Air (ρ = 0.77, adjusted p = .002). ΔGABAThal significantly decreased linearly with ΔMn-CEI3M (quantile regression, β = 15.22, p = .02) as well as Δ[Mn]Air (β = 1.27, p = .04). Finally, Mn-CEILife interacted with Δ[Mn]Air in the substantia nigra where higher Mn-CEILife lessened the ΔR1 per Δ[Mn]Air (F-test, p = .005). Although R1 and GABA changed with Mn exposure, UPDRS was unaffected. In conclusion, our study shows that effects from changes in Mn exposure are reflected in thalamic GABA levels and brain Mn levels, as measured by R1, in most brain regions.

Motor dysfunctions in Parkinson disease (PD) patients are not completely normalized by deep brain stimulation (DBS), and there is an obvious difference in the degree of symptom improvement after DBS for each patient.To test our hypothesis that each patient has their own restoration capacity for motor improvement after DBS, and to investigate whether regional cerebral glucose metabolism in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans is associated with the capacity for off-medication motor improvement (MIoff) after DBS.The MIoff (%) was calculated using the Unified Parkinson's Disease Rating Scale part III in 27 PD patients undergoing DBS in the globus pallidus interna. The standardized uptake value ratios (SUVRs) on FDG-PET were quantitatively measured, and the areas where the SUVR correlated with the MIoff (%) were identified. Also, the areas where the SUVR was significantly different between the 2 MIoff groups (≥60% vs 60%) were determined.Ten patients achieved MIoff 60% at 12 mo after DBS. In general, the MIoff (%) was positively correlated with preoperative SUVR in the temporo-parieto-occipital lobes, while it was inversely correlated with the metabolism in the primary motor cortex. The patients in the MIoff 60% group showed a significant decrease in SUVR in the parieto-occipital lobes, while parieto-occipital metabolism in those with MIoff ≥ 60% was relatively preserved (Mann-Whitney U test, P = .03).Our findings suggest that the parieto-occipital lobes may be implicated more generally in the prognosis of motor improvement after DBS in advanced PD than other regions.

Parkinson’s disease has a long prodromal stage with various subclinical motor and non-motor manifestations; however, their evolution in the years before Parkinson’s disease is diagnosed is unclear. We traced the evolution of early motor and non-motor manifestations of synucleinopathy from the stage of idiopathic rapid eye movement (REM) sleep behaviour disorder until defined neurodegenerative disease. During 2004–16, we recruited and then annually followed 154 polysomnography-proven patients with idiopathic REM sleep behaviour disorder, of whom 55 phenoconverted to defined parkinsonism or dementia. Longitudinal data on multiple prodromal features, including the Unified Parkinson’s Disease Rating Scale parts I–III, quantitative motor tests, olfaction, colour vision, cognition, and autonomic functions were gathered annually (average = five follow-up visits, range: 2–12 years). The same measures were also assessed in 102 age- and sex-matched healthy control subjects. By looking backward from the time of dementia or parkinsonism diagnosis, we examined trajectories of each prodromal feature using mixed effect models. Based on analysis, olfactory loss was first to develop, with predicted onset >20 years before phenoconversion. This was followed by impaired colour vision, constipation, and erectile dysfunction, starting 10–16 years prior to phenoconversion. At 7–9 years before phenoconversion, slight urinary dysfunction and subtle cognitive decline could be detected. Among motor symptoms altered handwriting, turning in bed, walking, salivation, speech, and facial expression began to be disrupted starting 7–11 years prior to parkinsonism diagnosis, but remained mild until soon before phenoconversion. Motor examination abnormalities began 5–7 years before phenoconversion, with the alternate tap test having the longest interval (8 years before phenoconversion). Among cardinal motor phenotypes, bradykinesia appeared first, ∼5–6 years prior to phenoconversion, followed by rigidity (Year −3) and tremor (Year −2). With direct prospective evaluation of an idiopathic REM sleep behaviour disorder cohort during phenoconversion, we documented an evolution of prodromal manifestations similar to that predicted by pathological staging models, with predicted prodromal intervals as long as 20 years.

BACKGROUND Clinical trials have established subthalamic deep-brain-stimulation (STN-DBS) as a highly effective treatment for motor symptoms of Parkinson disease (PD), but in clinical practice outcomes are variable. Experienced centers are confronted with an increasing number of patients with partially "failed" STN-DBS, in whom motor benefit doesn't meet expectations. These patients require a complex multidisciplinary and standardized workup to identify the likely cause. OBJECTIVE To describe outcomes in a series of PD patients undergoing lead revision for suboptimal motor benefit after STN-DBS surgery and characterize selection criteria for surgical revision. METHODS We investigated 9 PD patients with STN-DBS, who had unsatisfactory outcomes despite intensive neurological management. Surgical revision was considered if the ratio of DBS vs levodopa-induced improvement of UPDRS-III (DBS-rr) was below 75% and the electrodes were found outside the dorsolateral STN. RESULTS Fifteen electrodes were replaced via stereotactic revision surgery into the dorsolateral STN without any adverse effects. Median displacement distance was 4.1 mm (range 1.6-8.42 mm). Motor symptoms significantly improved (38.2 ± 6.6 to 15.5 ± 7.9 points, P

BACKGROUND Stereotactic lesion in the Forel's field H (campotomy) was proposed in 1963 to treat Parkinson disease (PD) symptoms. Despite its rationale, very few data on this approach have emerged. Additionally, no study has assessed its effects on nonmotor symptoms, neuropsychological functions and quality of life. OBJECTIVE To provide a prospective 2-yr assessment of motor, nonmotor, neuropsychological and quality of life variables after unilateral campotomy. METHODS Twelve PD patients were prospectively evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS), the Dyskinesia Rating Scale and the Parkinson's disease quality of life questionnaire (PDQ39) before campotomy, and after 6 and 24 mo. Nonmotor, neuropsychiatric, neuropsychological and quality of life variables were assessed. The impact of PD on global health was also rated. RESULTS A significant reduction in contralateral rest tremor (65.7%, P

BACKGROUND Parkinsonism like features can be seen in cirrhotics, possibly related to alterations in brain dopamine metabolism, transport and receptor integrity at basal ganglia. Hepatic parkinsonism is often not suspected and only ammonia-reducing therapies are given to such patients. We investigated the efficacy and safety of bromocriptine, a dopaminergic agent, in patients with hepatic parkinsonism. PATIENTS AND METHODS Cirrhotics were screened for the presence of extrapyramidal symptoms and were diagnosed as hepatic parkinsonism if any two of tremor, bradykinesia and/or rigidity were present, supported by MRI brain showing T1 hyperintensities in basal ganglia and substantia nigra. Patients were randomized to receive placebo (Gr A, n = 22) or bromocriptine (Gr B, n = 24) for 12 weeks. Complete, partial and non-response were defined as 30%, 10%-30% and

Background Although nontremor and tremor Part 3 Movement Disorder Society–Unified Parkinson's Disease Rating Scale items measure different impairment domains, their distinct progression and drug responsivity remain unstudied longitudinally. The total score may obscure important time‐based and treatment‐based changes occurring in the individual domains. Objective Using the unique advantages of item response theory (IRT), we developed novel longitudinal unidimensional and multidimensional models to investigate nontremor and tremor changes occurring in an interventional Parkinson's disease (PD) study. Method With unidimensional longitudinal IRT, we assessed the 33 Part 3 item data (22 nontremor and 10 tremor items) of 336 patients with early PD from the STEADY‐PD III (Safety, Tolerability, and Efficacy Assessment of Isradipine for PD, placebo vs. isradipine) study. With multidimensional longitudinal IRT, we assessed the progression rates over time and treatment (in overall motor severity, nontremor, and tremor domains) using Markov Chain Monte Carlo implemented in Stan. Results Regardless of treatment, patients showed significant but different time‐based deterioration rates for total motor, nontremor, and tremor scores. Isradipine was associated with additional significant deterioration over placebo in total score and nontremor scores, but not in tremor score. Further highlighting the 2 separate latent domains, nontremor and tremor severity changes were positively but weakly correlated (correlation coefficient, 0.108). Conclusions Longitudinal IRT analysis is a novel statistical method highly applicable to PD clinical trials. It addresses limitations of traditional linear regression approaches and previous IRT investigations that either applied cross‐sectional IRT models to longitudinal data or failed to estimate all parameters simultaneously. It is particularly useful because it can separate nontremor and tremor changes both over time and in response to treatment interventions.

Aim The multi-part Unified Parkinson's Disease Rating Scale is the standard instrument in clinical trials. A sum of scores for all items in one or more parts of the instrument is usually analysed. Without accounting for relative importance of individual items, this sum of scores conceivably does not optimize the power of the instrument. The aim was to compare the ability to detect drug effect in slowing down motor function deterioration, as measured by Part III of the Scale - motor examinations - between the item scores and the sum of scores. Methods We used data from 423 patients in a Parkinson's disease progression trial to estimate the symptom severity by item response modelling; modelled symptom progression using the severity and the sum of scores; and conducted simulations to compare the sensitivity of detecting a broad range of hypothetical drug effects on progression using the severity and the sum of scores. Results The severity endpoint was far more sensitive than the sum of scores for detecting treatment effects, e.g., requiring 275 versus 625 patients per arm to achieve 60% probability of trial success for detecting a range of potential effects in a 2-year trial. Non-tremor items related to the left side of the body seemed most informative; and the domain relevance of tremor items appeared questionable. Conclusion This analysis generated clear evidence that longitudinal modelling of item scores can enhance trial efficiency and success. It also called for reassessing the placement of the tremor items in the instrument.

Purpose: Parkinson's Disease (PD) is a neuro-degenerative interminable issue causing dynamic loss of dopamine-creating synapses, which is one of the most far reaching ailments after Alzheimer's infection. In this paper, a system for the classification of Parkinson’s disease tremor using noninvasive measurement and frequency domain features is represented. Materials and Methods: Tremor time-series of Parkinson's disease patients were recorded via a smartphone’s accelerometer sensor. Short-Time Fourier Transform (STFT) was applied to transform the time-domain signal into the frequency domain with high time-frequency resolution. Several frequency features, including mean, max of power spectral density and side frequency have been extracted and by using the FDR algorithm combinations of features carried enough information to reliably assess the severity of tremor in Parkinson patients were determined. Results: Four different classifiers were implemented to estimate the severity of tremors based on the Unified Parkinson's Disease Rating Scale (UPDRS) in Parkinson's disease patients. Conclusion: Classifiers’ estimation was compared to clinical scores derived via neurologist UPDRS annotation on Parkinson's disease patients’ tremor. The best accuracy achieved was 95.91±1.51.

Objective Parkinson's disease (PD) is a chronic neurodegenerative disorder with increasing prevalence in the elderly. Especially patients with advanced PD often require complex medication regimens due to fluctuations, that is abrupt transitions from ON to OFF or vice versa. Current gold standard to quantify PD-patients’ motor symptoms is the assessment of the Unified Parkinson's Disease Rating Scale (UPDRS), which, however, is cumbersome and may depend upon investigators. This work aimed at developing a mobile, objective and unobtrusive measurement of motor symptoms in PD. Methods Data from 45 PD-patients was recorded using surface electromyography (sEMG) electrodes attached to a wristband. The motor paradigm consisted of a tapping task performed with and without dopaminergic medication. Our aim was to predict UPDRS scores from the sEMG characteristics with distinct regression models and machine learning techniques. Results A random forest regression model outnumbered other regression models resulting in a correlation of 0.739 between true and predicted UPDRS values. Conclusions PD-patients’ motor affection can be extrapolated from sEMG data during a simple tapping task. In the future, such records could help determine the need for medication changes in telemedicine applications. Significance Our findings support the utility of wearables to detect Parkinson's symptoms and could help in developing tailored therapies in the future.

Aim. The multi-part Unified Parkinson’s Disease Rating Scale is the standard instrument in clinical trials. A sum of scores for all items in one or more parts of the instrument is usually analyzed. Without accounting for relative importance of individual items, this sum of scores conceivably does not optimize the power of the instrument. The aim was to compare the ability to detect drug effect in slowing down motor function deterioration, as measured by Part III of the Scale - motor examinations - between the item scores and the sum of scores. Methods. We used data from 423 patients in a Parkinson’s disease progression trial to estimate the symptom severity by item response modelling; modelled symptom progression using the severity and the sum of scores; and conducted simulations to compare the sensitivity of detecting a broad range of hypothetical drug effects on progression using the severity and the sum of scores. Results. The severity endpoint was far more sensitive than the sum of scores for detecting treatment effects, e.g., requiring 280 versus 570 patients per arm to achieve 60% Probability of Success for detecting a range of potential effects in a 2-year trial. Items related to the left side of the body were most informative; and the domain relevance of tremor items was questionable. Conclusion. This analysis generated clear evidence that longitudinal modelling of item scores can enhance trial efficiency and success. It also prompted the needs for a consensus on the placement of the tremor items in the instrument.

This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used to identify the baseline features predicting phenoconversion to parkinsonism or dementia. After quality check of the data, 263 iRBD patients (67.6 ± 7.3 years, 229 males) and 243 control subjects (67.2 ± 10.1 years, 110 males) were analysed. Fifty-two (20%) patients developed a synucleinopathy after average follow-up of 2 years. The best combination of risk factors was putamen dopaminergic dysfunction of the most affected hemisphere on imaging, defined as the lower value between either putamina (P

BACKGROUND Although deep brain stimulation (DBS) of the dorsolateral subthalamic nucleus (STN) is a well-established surgical treatment for patients with Parkinson disease (PD), there is still controversy about the relationship between the functional segregation of the STN and clinical outcomes. OBJECTIVE To correlate motor and neuropsychological (NPS) outcomes with the overlap between the volume of activated tissue (VAT) and the tractography-defined regions within the STN. METHODS Retrospective study evaluating 13 patients with PD treated with STN-DBS. With the aid of tractography, the STN was segmented into 4 regions: smaSTN (supplementary motor area STN), m1STN (primary motor area STN), mSTN (the sum of the m1STN and the smaSTN segments), and nmSTN (non-motor STN). We computed the overlap coefficients between these STN regions and the patient-specific VAT. The VAT outside of the STN was also calculated. These coefficients were then correlated with motor (Unified Parkinson's Disease Rating Scale, UPDRS III) and NPS outcomes. RESULTS Stimulation of the mSTN segment was significantly correlated with UPDRS III and bradykinesia improvement. Stimulation of the smaSTN segment, but not the m1STN one, had a positive correlation with bradykinesia improvement. Stimulation of the nmSTN segment was negatively correlated with the improvement in rigidity. Stimulation outside of the STN was correlated with some beneficial NPS effects. CONCLUSION Stimulation of the tractography-defined motor STN, mainly the smaSTN segment, is positively correlated with motor outcomes, whereas stimulation of the nmSTN is correlated with poor motor outcomes. Further validation of these results might help individualize and optimize targets prior to STN-DBS.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with increasing disability and limitations in performance of activities of daily living (ADL) despite availability of effective symptomatic therapy. Following an overview of classical test theory (CTT) and Rasch measurement theory (RMT), the case of a clinical PD trial aiming to demonstrate ADL improvements by using the ADL section (part II) of the Unified PD Rating Scale (UPDRS) to measure ADL outcomes is considered and central questions related to its validity and interpretation are addressed. It is found that while CTT did not detect any issues, RMT in combination with conceptual considerations seriously challenged the role of the UPDRS II as an ADL outcome measure. Results are discussed from historical, methodological and clinical perspectives.

Introduction A dopamine agonist patch could be an important treatment option for Parkinson's disease. This study evaluated the long-term efficacy and safety of the ropinirole hydrochloride patch. The steady state plasma ropinirole concentration was also assessed. Methods In a multicenter, open-label, uncontrolled study, Parkinson's disease patients with/without basal levodopa and with/without prior dopamine agonist therapy (any of these four regimens) received application of a ropinirole patch once daily for up to 52 weeks with unforced titration from 8 to 64 mg. For patients with prior dopamine agonist therapy, the initial dose of ropinirole patch was determined from the prior dopamine agonist dose by using a conversion table. Results Most adverse events were mild or moderate. All application site adverse events were mild, except for moderate application site erythema in one patient. In patients with prior dopamine agonist therapy, switching to ropinirole patch did not lead to a significant early increase of adverse events. A change from baseline in the UPDRS Part III total score, the primary efficacy endpoint, showed improvement until Week 16 compared with baseline, followed by little subsequent change until Week 52, indicating maintenance of efficacy. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase. Conclusion Once-daily application of ropinirole patch showed long-term efficacy and safety (52 weeks) for Parkinson's disease. Switching from other dopamine agonists to ropinirole patch was effective and safe. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase.

Background. In 2008, the Movement Disorders Society (MDS) published a new Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson’s Disease (PD). We have translated and validated the Polish version of the MDS-UPDRS, explored its dimensionality, and compared it to the original English one. Methods. The MDS-UPDRS was translated into Polish by a team of Polish investigators led by JS and GO. The back-translation was completed by colleagues fluent in both languages (Polish and English) who were not involved in the original translation, and was reviewed by members of the MDS Rating Scales Programme. Then the translated version of the MDS-UPDRS underwent cognitive pretesting, and the translation was modified based on the results. The final translation was approved as the Official Working Document of the MDS-UPDRS Polish version, and was tested on 355 Polish PD patients recruited at movement disorders centres all over Poland (at Katowice, Gdansk, Łodź, Warsaw, Wroclaw, and Krakow). Confirmatory and explanatory factor analyses were applied to determine whether the factor structure of the English version could be confirmed in the Polish version. Results. The Polish version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Polish version was satisfactory. In the confirmatory factor analysis, all four parts had greater than 0.90 comparative fit index (CFI) compared to the original English MDS-UPDRS. Explanatory factor analysis suggested that the Polish version differed from the English version only within an acceptable range. Conclusions and clinical implications. The Polish version of the MDS-UPDRS meets the requirements to be designated as the Official Polish Version of the MDS-UPDRS, and is available on the MDS web page. We strongly recommend using the MDS-UPDRS instead of the UPDRS for research purposes and in everyday clinical practice.

Objectives: This study aims to evaluate the base-peak difference in levodopa response for detecting patients with motor fluctuations in Parkinson’s disease (PD). Methods: Two independent PD samples were evaluated at baseline and 2 h after the administration of the usual morning dose of levodopa using the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). The presence of motor fluctuations was defined by the UPDRS-IV. We quantified the magnitude of motor variation as absolute (Δ) and percentage (Δ%) change in UPDRS-III scores. Optimal cut-offs for each index distinguishing patients with or without fluctuations were calculated on the exploratory population. The accuracy of the identified cut-offs was then verified in a testing population. Results: In the exploratory population (N = 26), the optimal cut-off for detecting fluctuations was a Δ of 6 points and a Δ% of 18.4%. When we applied the identified thresholds to the testing population (N = 139), we found a sensitivity of 93.8% (95% CI: 89.7 to 97.8) and a specificity of 91.2% (95% CI: 86.5 to 95.9) for Δ, 83.3% (95% CI: 77.1 to 89.5) and 86.8% (95% CI: 81.2 to 92.4) for Δ%, respectively. Conclusions: The assessment of levodopa usual morning dose response through the base-peak evaluation represents an accurate method for detecting parkinsonian patients with motor fluctuations, and for defining the Minimal Important Difference (MID) in levodopa response suggesting the presence of motor fluctuations in PD patients demanding further therapeutic interventions.

Background Deep brain stimulation (DBS) surgery for Parkinson's disease (PD) is usually performed as awake surgery allowing sufficient intraoperative testing. Recently, outcomes after asleep surgery have been assumed comparable. However, direct comparisons between awake and asleep surgery are scarce. Objective To investigate the difference between awake and asleep surgery comparing motor and nonmotor outcome after subthalamic nucleus (STN)-DBS in a large single center PD population. Methods Ninety-six patients were retrospectively matched pairwise (48 asleep and 48 awake) and compared regarding improvement of Unified PD Rating Scale Motor Score (UPDRS-III), cognitive function, Levodopa-equivalent-daily-dose (LEDD), stimulation amplitudes, side effects, surgery duration, and complication rates. Routine testing took place at three months and one year postoperatively. Results Chronic DBS effects (UPDRS-III without medication and with stimulation on [OFF/ON]) significantly improved UPDRS-III only after awake surgery at three months and in both groups one year postoperatively. Acute effects (percentage UPDRS-III reduction after activation of stimulation) were also significantly better after awake surgery at three months but not at one year compared to asleep surgery. UPDRS-III subitems "freezing" and "speech" were significantly worse after asleep surgery at three months and one year, respectively. LEDD was significantly lower after awake surgery only one week postoperatively. The other measures did not differ between groups. Conclusions Overall motor function improved faster in the awake surgery group, but the difference ceased after one year. However, axial subitems were worse in the asleep surgery group suggesting that worsening of axial symptoms was risked improving overall motor function. Awake surgery still seems advantageous for STN-DBS in PD, although asleep surgery may be considered with lower threshold in patients not suitable for awake surgery.

Background For quality analysis, we applied the Six Sigma concept to define quality indicators and their boundaries as well as to compare treatment-dependent outcome data of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). Methods The Unified Parkinson Disease Rating Scale (UPDRS) III with on medication and on stimulation, the reduction of daily levodopa equivalence doses (LED), and the stimulation amplitude 1 year after surgery were registered. Regarding the results of the EARLYSTIM study, sigma values for applicable studies were calculated and compared. Further, the impact of perioperative conditions on patients' outcomes was analyzed. Results Forty-one studies with 2184 patients were included. The bleeding risk was 1.36%. In median, UPDRS III on/on improved by 19.9% while the LED was reduced by 45.2%. The median stimulation amplitude was 2.84 V. With the Six Sigma principle, a comparison between different centers was possible. Microelectrode recordings (MER) did not correlate with occurrence of bleedings and did not impact patient outcome. Conclusions The Six Sigma principle can be simply used to analyze, improve and compare complex medical processes, particularly, the DBS surgery. Based on these data, higher sigma values were reached for clinical improvement in UPDRS III on/on for patients who underwent surgery in local anesthesia with intraoperative test stimulation compared to surgery in general anesthesia. However, the difference was not statistically significant. Application of MER was found to be optional with no increased bleeding risk and no improvement on patient's outcome.

OBJECTIVERecent studies have shown similar clinical outcomes between Parkinson disease (PD) patients treated with deep brain stimulation (DBS) under general anesthesia without microelectrode recording (MER), so-called “asleep” DBS, and historical cohorts undergoing “awake” DBS with MER guidance. However, few studies include internal controls. This study aims to compare clinical outcomes after globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS using awake and asleep techniques at a single institution.METHODSPD patients undergoing awake or asleep bilateral GPi or STN DBS were prospectively monitored. The primary outcome measure was stimulation-induced change in motor function off medication 6 months postoperatively, measured using the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Secondary outcomes included change in quality of life, measured by the 39-item Parkinson’s Disease Questionnaire (PDQ-39), change in levodopa equivalent daily dosage (LEDD), stereotactic accuracy, stimulation parameters, and adverse events.RESULTSSix-month outcome data were available for 133 patients treated over 45 months (78 GPi [16 awake, 62 asleep] and 55 STN [14 awake, 41 asleep]). UPDRS-III score improvement with stimulation did not differ between awake and asleep groups for GPi (awake, 20.8 points [38.5%]; asleep, 18.8 points [37.5%]; p = 0.45) or STN (awake, 21.6 points [40.3%]; asleep, 26.1 points [48.8%]; p = 0.20) targets. The percentage improvement in PDQ-39 and LEDD was similar for awake and asleep groups for both GPi (p = 0.80 and p = 0.54, respectively) and STN cohorts (p = 0.85 and p = 0.49, respectively).CONCLUSIONSIn PD patients, bilateral GPi and STN DBS using the asleep method resulted in motor, quality-of-life, and medication reduction outcomes that were comparable to those of the awake method.

Background Falls and postural instability (PI) are major sources of morbidity in Parkinson disease (PD). Deep brain stimulation (DBS) is a major therapy for PD. The effects of DBS on PI and falls remain controversial. Objective To study if DBS worsens PI, validated measures of PI (Timed Up and Go, Berg Balance Scale, Unified Parkinson's Disease Rating Scale 3.12 [Pull Test], and the Biodex Sway Index with eyes closed on a firm and soft surface) and reported falls were used to prospectively evaluate the effect of DBS on PI at 3 and 12 mo postoperatively compared to baseline measurements. The primary outcomes were a positive result on 4 out of the 5 PI tests and falls. Methods Patients presenting for DBS were prospectively enrolled and evaluated at presentation and, 3 and 12 mo postoperatively. All tests were performed at each visit. Results At 3 mo 4 of 5 positive showed noninferiority to baseline, with a rate of 28% vs 41% (relative risk [RR] 0.8 [0.5-1.3]). At 12 mo, 4 of 5 positive had a rate of 35% vs 30% (RR 1.2 [0.8-1.8]) and falls had a rate of 54% vs 46% (RR 1.2 [0.6-2.3]). These did not meet criteria to prove noninferiority. Sensitivity analysis at 12 mo showed noninferiority for 4 of 5 (RR 0.9 [0.6-1.5]) but not falls (RR 1.1 [0.5-2.3]). Conclusion This evidence is consistent with the hypothesis that DBS does not worsen PI when measured at 3 and 12 mo postoperatively.

BACKGROUND Subthalamic nucleus (STN) and globus pallidus interna (GPi) are the most effective targets in deep brain stimulation (DBS) treatment for Parkinson disease (PD). However, the individualized selection of targets remains a clinical challenge. OBJECTIVE To combine unilateral STN and contralateral GPi stimulation (STN DBS in one brain hemisphere and GPi DBS in the other) to maximize the clinical advantages of each target while inducing fewer adverse side effects in selected patients with PD because each target has its own clinical effects and risk profiles. METHODS We reviewed the clinical outcomes of 8 patients with idiopathic PD treated with combined unilateral STN and contralateral GPi DBS. Clinical outcome assessments, focusing on motor and nonmotor symptoms, were performed at baseline and 6-mo and 12-mo follow-up. We performed the assessments under the following conditions: medication on and off (bilateral stimulation on and off and unilateral STN stimulation on). RESULTS Patients showed a significant improvement in motor symptoms, as assessed by the Unified Parkinson Disease Rating Scale III (UPDRS-III) and Timed Up-and-Go Test (TUG), in the off-medication/on-stimulation state at 6-mo and 12-mo follow-up. Also, patients reported a better quality of life, and their intake of levodopa was reduced at 12-mo follow-up. In the on-medication condition, bilateral stimulation was associated with an improvement in axial symptoms, with a 64% improvement in measures of gait and falls at 12-mo follow-up. No irreversible adverse side effects were observed. CONCLUSION Our findings suggest that combined unilateral STN and contralateral GPi DBS could offer an effective and well-tolerated DBS treatment for certain PD patients., Graphical Abstract Graphical Abstract

BACKGROUND Recent advances in methods used for deep brain stimulation (DBS) include subthalamic nucleus electrode implantation in the "asleep" patient without the traditional use of microelectrode recordings or intraoperative test stimulation. OBJECTIVE To examine the clinical outcome of patients who have undergone "asleep" DBS for the treatment of Parkinson disease using robot-assisted electrode delivery. METHODS This is a retrospective review of clinical outcomes of 152 consecutive patients. Their outcomes at 1 yr postimplantation are reported; these include Unified Parkinson's Disease Rating Scale (UPDRS) assessment, Tinetti Mobility Test, Parkinson's Disease Questionnaire (PDQ)-39 quality of life assessment, Mattis Dementia Rating Scale, Beck Depression Inventory, and Beck Anxiety. We also report on a new parietal trajectory for electrode implantation. RESULTS A total of 152 patients underwent assessment at 1 yr. UPDRS III improved from 39 to 20.5 (47%, P

Objective History of traumatic brain injury (TBI) is a potential risk factor for cognitive decline and neurodegenerative disease later in life, but findings have been inconsistent. We evaluate if past history of TBI affects rate of cognitive decline in clinically normal older adults. Method Participants were 190 cognitively normal (CDR Results TBI+ showed a faster rate of decline in executive functioning (Stroop interference: p = 0.04), and a faster increase in functional impairment (Physical Activity Scale for the Elderly (PASE) total: p Conclusions History of TBI was associated with faster rate of executive functioning decline and more rapid increase in objective and subjective functional impairment in cognitively normal older adults. Findings suggest that sustaining a TBI earlier in life could accelerate cognitive and functional changes even among clinically normal older adults.

IMPORTANCE: The travel required to receive deep brain stimulation (DBS) programming causes substantial burden on patients and limits who can access DBS therapy. OBJECTIVE: To evaluate the efficacy of home health DBS postoperative management in an effort to reduce travel burden and improve access. DESIGN, SETTINGS, AND PARTICIPANTS: This open-label randomized clinical trial was conducted at University of Florida Health from November 2017 to April 2020. Eligible participants had a diagnosis of Parkinson disease (PD) and were scheduled to receive DBS independently of the study. Consenting participants were randomized 1:1 to receive either standard of care or home health postoperative DBS management for 6 months after surgery. Primary caregivers, usually spouses, were also enrolled to assess caregiver strain. INTERVENTIONS: The home health postoperative management was conducted by a home health nurse who chose DBS settings with the aid of the iPad-based Mobile Application for PD DBS system. Prior to the study, the home health nurse had no experience providing DBS care. MAIN OUTCOMES AND MEASURES: The primary outcome was the number of times each patient traveled to the movement disorders clinic during the study period. Secondary outcomes included changes from baseline on the Unified Parkinson’s Disease Rating Scale part III. RESULTS: Approximately 75 patients per year were scheduled for DBS. Of the patients who met inclusion criteria over the entire study duration, 45 either declined or were excluded for various reasons. Of the 44 patients enrolled, 19 of 21 randomized patients receiving the standard of care (mean [SD] age, 64.1 [10.0] years; 11 men) and 23 of 23 randomized patients receiving home health who underwent a minimum of 1 postoperative management visit (mean [SD] age, 65.0 [10.9] years; 13 men) were included in analysis. The primary outcome revealed that patients randomized to home health had significantly fewer clinic visits than the patients in the standard of care arm (mean [SD], 0.4 [0.8] visits vs 4.8 [0.4] visits; P

Date Presented 04/200/21 OT has a valuable role in promoting quality of life for individuals with PD in all aspects of daily life. The Canadian Occupational Performance Measure (COPM) enables practitioners to address the holistic needs of clients, rather than exclusively focusing on predetermined areas of disability. This study has shown that the full breadth of clients' needs are vast and varied and exist beyond those included in standardized assessment tools because only one-third of the items identified by the COPM were included in the Movement Disorder Society—Unified Parkinson's Disease Rating Scale. Primary Author and Speaker: Abdullah Alsaeed Additional Authors and Speakers: Kristen A. Pickett Contributing Authors: Maria Widmer

Objective:To explore the association between metabolic syndrome and the Unified Parkinson’s Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT).Methods:This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome.Results:Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p < 0.0001), were more likely to be male (75.3% vs 57.0%; p < 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, p < 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS (p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS (p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores.Conclusions:Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding.ClinicalTrials.gov identifier:NCT00449865.

Background In essential tremor and Parkinson disease (PD) tremor, administration of onabotulinumtoxinA via a fixed injection approach improves the tremor, but many patients (30%-70%) develop moderate to severe hand weakness, limiting the use of onabotulinumtoxinA in clinical practice. Objective To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for the treatment of tremor in PD. Patients and Methods In this double-blind, placebo-controlled, crossover trial, 30 patients each received 7 to 12 (mean, 9) IncoA injections into hand and forearm muscles using a customized approach. The study was performed from June 1, 2012, through June 30, 2015, and participants were followed for 24 weeks. Treatment efficacy was evaluated by the tremor subsets of the Unified Parkinson's Disease Rating Scale and the Patient Global Impression of Change 4 and 8 weeks after each of the 2 sets of treatments. Hand strength was assessed using an ergometer. Results There was a statistically significant improvement in clinical rating scores of rest tremor and tremor severity 4 and 8 weeks after the IncoA injection and of action/postural tremor at 8 weeks. There was a significant improvement in patient perception of improvement at 4 and 8 weeks in the IncoA group. There was no statistically significant difference in grip strength at 4 weeks between the 2 groups. Conclusion Injection of IncoA via a customized approach improved PD tremor on a clinical scale and patient perception, with a low occurrence of significant hand weakness. Trial Registration clinicaltrials.gov Identifier: NCT02419313.

Background Postural instability and gait disorder (PIGD) in Parkinson disease (PD) has been a great challenge in clinical practice because PIGD is closely linked to major morbidity and mortality in PD. Pedunculopontine nucleus (PPN) has been considered as a potential promising target for deep brain stimulation (DBS) in the treatment of PIGD. A meta-analysis of individual patient data was performed to assess the effects of PPN DBS on PIGD in patients with PD and explore the factors predicting good outcome. Methods According to the study strategy, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, and other sources. After searching the literature, 2 investigators independently screened the literature, assessed the quality of the included trials, and extracted the data. The outcome measures included PIGD, freezing of gait, and falling in PD. Then, individual patient data were incorporated into SPSS software for statistical analyses across series. Results Six studies reporting individual patient data were included for final analysis. PPN DBS significantly improved PIGD as well as freezing of gait and falling after PD, which was depending on the duration of follow-up and types of outcome measures. In addition, patient age, disease duration, levodopa-equivalent dosage, and the choice of unilateral or bilateral stimulation were similar in groups of patients with PD with or without improvement in PIGD after PPN DBS. Conclusions Our study provides evidence that PPN DBS may improve PIGD, which should be interpreted with caution and needs further verification before making generalization of our results.

Background Deep brain stimulation of the subthalamic nucleus (STN) has demonstrated efficacy in improving motor disability in Parkinson's disease. The recently developed quantitative susceptibility mapping (QSM) technique, which can accurately map iron deposits in deep brain nuclei, promises precise targeting of the STN. Objective To demonstrate the use of QSM to target STN effectively by correlating with classical physiological-based targeting measures in a prospective study. Methods The precision and accuracy of direct targeting with QSM was examined in a total of 25 Parkinson's disease patients between 2013 and 2015 at our institution. QSM was utilized as the primary magnetic resonance imaging (MRI) method to perform direct STN targeting on a stereotactic planning station utilizing computed tomography/MR fusion. Intraoperative microelectrode recordings (MER) were obtained to confirm appropriate trajectory through the sensorimotor STN. Results Estimations of STN thickness between the MER and QSM methods appeared to be correlated. Mean STN thickness was 5.3 mm. Kinesthetic responsive cells were found in > 90% of electrode runs. The mean radial error (±SEM) was 0.54 ± 0.1 mm. Satisfactory clinical response as determined by Unified Parkinson's Disease Rating Scale (UPDRS III) was seen at 12 mo after surgery. Conclusion Direct targeting of the sensorimotor STN using QSM demonstrates MER correlation and can be safely used for deep brain stimulation lead placement with satisfactory clinical response. These results imply that targeting based on QSM signaling alone is sufficient to obtain reliable and reproducible outcomes in the absence of physiological recordings.

To evaluate the effects of 12-week polestriding intervention on gait and disease severity in people with mild to moderate Parkinson disease (PD).A-B-A withdrawal study design.Outpatient movement disorder center and community facility.Individuals (N=17; 9 women [53%] and 8 men [47%]; mean age, 63.7±4.9y; range, 53-72y) with mild to moderate PD according to United Kingdom brain bank criteria with HoehnYahr score ranging from 2.5 to 3.0 with a stable medication regimen and ability to tolerate "off" medication state.Twelve-week polestriding intervention with 12-week follow-up.Gait was evaluated using several quantitative temporal, spatial, and variability measures. In addition, disease severity was assessed using clinical scales such as Unified Parkinson's Disease Rating Scale (UPDRS), HoehnYahr scale, and Parkinson's Disease Questionnaire-39.Step and stride lengths, gait speed, and step-time variability were improved significantly (P.05) because of 12-week polestriding intervention. Also, the UPDRS motor score, the UPDRS axial score, and the scores of UPDRS subscales on walking and balance improved significantly after the intervention.Because increased step-time variability and decreased step and stride lengths are associated with PD severity and an increased risk of falls in PD, the observed improvements suggest that regular practice of polestriding may reduce the risk of falls and improve mobility in people with PD.