Parkinson's Rating Scale Part Research Articles

Linking Invasive and Noninvasive Brain Stimulation in Parkinson's Disease: A Randomized Trial.

Recent imaging studies identified a brain network associated with clinical improvement following deep brain stimulation (DBS) in Parkinson's disease (PD), the PD response network. This study aimed to assess the impact of neuromodulation on PD motor symptoms by targeting this network noninvasively using multifocal transcranial direct current stimulation (tDCS). In a prospective, randomized, double-blinded, crossover trial, 21 PD patients (mean age 59.7 years, mean Hoehn & Yahr [H&Y] 2.4) received multifocal tDCS targeting the a-priorinetwork. Twenty-minute sessions of tDCS and sham were administered on 2 days in randomized order. Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) scores were assessed. Before intervention, MDS-UPDRS-III scores were comparable in both conditions (stimulation days: 37.38 (standard deviation [SD] = 12.50, confidence interval [CI] = 32.04, 42.73) vs. sham days: 36.95 (SD = 13.94, CI = 30.99, 42.91), P = 0.63). Active stimulation resulted in a reduction by 3.6 points (9.7%) to 33.76 (SD = 11.19, CI = 28.98, 38.55) points, whereas no relevant change was observed after sham stimulation (36.43 [SD = 14.15, CI = 30.38, 42.48], average improvement: 0.5 [1.4%]). Repeated-measures analysis of variance (ANOVA) confirmed significance (main effect of time: F(1,20)=4.35, P < 0.05). Tukey's post hoc tests indicated MDS-UPDRS-III improvement after active stimulation (t [20] = 2.9, P = 0.03) but not after sham (t [20] = 0.42, P > 0.05). In a subset of patients that underwent DBS surgery later, their DBS response correlated with tDCS effects (R = 0.55, P(1) = 0.04). Noninvasive, multifocal tDCS targeting a DBS-derived network significantly improved PD motor symptoms. Despite a small effect size, this study provides proof of principle for the successful noninvasive neuromodulation of an invasively identified network. Future studies should investigate repeated tDCS sessions and their utility for screening before DBS surgery. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Impact of Physical Exercise on Levodopa Therapy Across Parkinson's Disease Stages.

Levodopa is the gold standard of treatment in Parkinson's disease (PD). Its clinical effect changes as the disease progresses. Wearing off is a frequent first manifestation of motor fluctuations. Some patients with advanced PD report faster wearing off after physical exercise. The aim was to assess if pharmacokinetics of levodopa is influenced by physical exercise in patients with different disease advancement. 22 patients with PD (12 untreated with levodopa and 10 with motor fluctuations) and 7 healthy controls (HC) were included. Plasma samples were collected at 9 fixed timepoints following administration of levodopa/benserazide 200/50 mg for two days: rest day and standardized physical exercise day. Clinical assessment with Unified Parkinson Disease Rating Scale part III (UPDRS III) was performed in fixed timepoints. Liquid chromatography-tandem mass spectrometry was used to measure levodopa concentrations. No differences between the HC, levodopa naïve and advanced PD groups were observed regarding selected pharmacokinetic parameters. In advanced PD and HC no differences in pharmacokinetic parameters of levodopa with and without effort were observed. In levodopa naïve PD group higher mean residence time after rest than after exercise (168.9±48.3 min vs. 145.5±50.8 min; p = 0.026) was observed. In advanced PD group higher UPDRS III score (14.45±5.5 versus 20.9±6.1 points, p = 0.04) was observed after exercise. The deterioration of motor status of advanced PD patients after physical effort is not reflected by changes in pharmacokinetics but rather mediated by central mechanisms.

Levodopa-Induced Dyskinesias are Frequent and Impact Quality of Life in Parkinson's Disease: A 5-Year Follow-Up Study.

Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD). To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL). PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL. The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (β = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (β = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ-39SI. LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.

Personalizing Deep Brain Stimulation Therapy for Parkinson's Disease With Whole-Brain MRI Radiomics and Machine Learning.

Background Deep brain stimulation (DBS) is a well-recognised treatment for advanced Parkinson's disease (PD) patients. Structural brain alterations of the white matter can correlate with disease progression and act as a biomarker for DBS therapy outcomes. This study aims to develop a machine learning-driven predictive model for DBS patient selection using whole-brain white matter radiomics and common clinical variables. Methodology A total of 120 PD patients underwent DBS of the subthalamic nucleus. Their therapy effect was assessed at the one-year follow-up with the Unified Parkinson's Disease Rating Scale-part III (UPDRSIII) motor component. Radiomics analysis of whole-brain white matter was performed with PyRadiomics. The following machine learning methods were used: logistic regression (LR), support vector machine, naïve Bayes, K-nearest neighbours, and random forest (RF) to allow prediction of clinically meaningful UPRDSIII motor response before and after. Clinical variables were also added to the model to improve accuracy. Results The RF model showed the best performance on the final whole dataset with an area under the curve (AUC) of 0.99, accuracy of 0.95, sensitivity of 0.93, and specificity of 0.97. At the same time, the LR model showed an AUC of 0.93, accuracy of 0.88, sensitivity of 0.84, and specificity of 0.91. Conclusions Machine learning models can be used in clinical decision support tools which can deliver true personalised therapy recommendations for PD patients. Clinicians and engineers should choose between best-performing, less interpretable models vs. most interpretable, lesser-performing models. Larger clinical trials would allow to build trust among clinicians and patients to widely use these AI tools in the future.

Effect of robot-assisted gait training on motor dysfunction in Parkinson's patients:A systematic review and meta-analysis.

Robot-assisted gait training (RAGT) has been reported to treat motor dysfunction in patients with Parkinson's disease (PD) in the last few years. However, the benefits of RAGT for treating motor dysfunction in PD are still unclear. To investigate the efficacy of RAGT for motor dysfunction in PD patients. We searched PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang, Chinese Biomedical Literature Database (CBM), and Chinese VIP Database for randomized controlled trials investigating RAGT to improve motor dysfunction in PD from the databases' inception dates until September 1, 2022. The following outcome indexes were employed to evaluate motor dysfunction: the Berg Balance Scale (BBS), Activities-specific Balance Confidence Scale (ABC), 10-Meter Walk Test gait speed (10-MWT), gait speed, stride length, cadence Unified Parkinson Disease Rating Scale Part III (UPDRS III), 6-Minute Walk Test (6MWT), and the Timed Up and Go test (TUG). The meta-analysis was performed using the proper randomeffect model or fixed-effect model to evaluate the difference in efficacy between the RAGT and the control groups. The Cochrane Risk of Bias Tool was used for the included studies and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to interpret the certainty of the results. The results consisted of 17 studies comprising a total of 670 participants. Six hundred and seven PD patients with motor dysfunction were included: 335 in the RAGT group and 335 in the control group. This meta-analysis results established that when compared with the control group, robot-assisted gait training improved the BBS results of PD patients (MD: 2.80, 95%CI: 2.11-3.49, P< 0.00001), ABC score (MD: 7.30, 95%CI: 5.08-9.52, P< 0.00001), 10-MWT (MD: 0.06, 95%CI: 0.03-0.10, P= 0.0009), gait speed (MD: 3.67, 95%CI: 2.58-4.76, P< 0.00001), stride length (MD: 5.53, 95%CI: 3.64-7.42, P< 0.00001), cadence (MD: 4.52, 95%CI: 0.94-8.10, P= 0.01), UPDRS III (MD: -2.16, 95%CI: -2.48--1.83, P< 0.00001), 6MWT (MD: 13.87, 95%CI: 11.92-15.82, P< 0.00001). However, RAGT did not significantly improve the TUG test result of patients with PD (MD =-0.56, 95% CI: -1.12-0.00, P= 0.05). No safety concerns or adverse reactions among robot-assisted gait training patients were observed. Even though RAGT can improve balance function, walking function, and gait performance and has demonstrated positive results in several studies, there is currently insufficient compelling evidence to suggest that it can improve all aspects of lower motor function.

Different impulse control disorder evolution patterns and white matter microstructural damage in the progression of Parkinson's disease.

The course of impulse control disorders (ICD) varies in the early stage of Parkinson's disease (PD). We aimed to delineate the association between the evolution pattern of ICD and the progression of PD. A total of 321 de novo PD patients from the Parkinson's Progression Markers Initiative database were included. Patients were followed up for a mean of 6.8 years and were classified into different groups according to the evolution patterns of ICD. Disease progression was compared among groups using survival analysis, in which the endpoint was defined as progression to Hoehn and Yahr stage 3 or higher for motor progression and progression to mild cognitive impairment for cognitive decline. In the fourth year of follow-up, four types of ICD evolution patterns were identified: (1) non-ICD-stable (68.2%), a patient who is consistently free of ICD; (2) late-ICD (14.6%), ICD developed during the follow-up of patients; (3) ICD-stable (11.5%), patients showed persistent ICD; and (4) ICD-reversion (5.6%), baseline ICD disappeared during the follow-up of patients with ICD. The ICD-reversion type shows daily life non-motor symptoms [Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) part I], daily life motor symptoms (MDS-UPDRS part II), rapid eye movement sleep behavior disorder, and anxiety symptoms has a greater impact. PD patients with different ICD evolution patterns had different changes in white matter microstructure at the onset of the disease. Those relevant brain regions are involved in ICD and non-motor functions. Four early ICD evolution patterns are identified in de novo PD, with different prognoses and brain white matter microstructural damage patterns, and they may predict motor progression and cognitive decline in PD patients.

One-pass deep brain stimulation of subthalamic nucleus and ventral intermediate nucleus for levodopa-resistant tremor-dominant Parkinson's disease.

Tremor-dominant Parkinson's disease (TD-PD) can be further separated into levodopa-responsive and levodopa-resistant types, the latter being considered to have a different pathogenesis. Previous studies indicated that deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the globus pallidus internus (GPi) individually was not sufficient for tremor control, especially for the levodopa-resistant TD-PD (LRTD-PD). The thalamic ventral intermediate nucleus (VIM) has been regarded as a potent DBS target for different kinds of tremors. Therefore, we focused on the LRTD-PD subgroup and performed one-pass combined DBSs of STN and VIM to treat refractory tremors, aiming to investigate the safety and effectiveness of this one-trajectory dual-target DBS scheme. We retrospectively collected five LRTD-PD patients who underwent a one-pass combined DBS of STN and VIM via a trans-frontal approach. The targeting of VIM was achieved by probabilistic tractography. Changes in severity of symptoms (measured by the Unified Parkinson Disease Rating Scale part III, UPDRS-III), levodopa equivalent daily doses (LEDD), and disease-specific quality of life (measured by the 39-item Parkinson's Disease Questionnaire, PDQ-39) were evaluated. Three-dimensional reconstruction of electrodes illustrated that all leads were successfully implanted into predefined positions. The mean improvement rates (%) were 53 ± 6.2 (UPDRS-III), 82.6 ± 11.4 (tremor-related items of UPDRS), and 52.1 ± 11.4 (PDQ-39), respectively, with a mean follow-up of 11.4 months. One-pass combined DBS of STN and VIM via the trans-frontal approach is an effective and safe strategy to alleviate symptoms for LRTD-PD patients.

The 'PD Warrior' exercise programme improves motor outcomes and quality of life in patients with early Parkinson disease: results of a pilot study.

'PD Warrior' (PDW) is a popular exercise programme for Parkinson disease; however, there are no published studies on the outcomes of the programme. To investigate short-term functional and quality of life (QoL) outcomes after the PDW 10-week programme in a pilot study of individuals with early Parkinson Disease (PD). Twenty individuals with PD (Hoehn & Yahr 1-3) attending a hospital outpatient clinic were recruited into the PDW 10-week programme, comprising a weekly 1-h supervised class complemented by an individualised daily home exercise programme. Participants had the following assessments at baseline and after completion of the programme: Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part III, timed up-and-go (TUG), 10-m walk test (10mWT), 6-min walking test (6MWT), balance tests, fine motor skills, 7-day Parkinson KinetiGraph (PKG) and PDQ-39 QoL scale. Seventeen individuals completed the programme. Significant improvements were observed in MDS-UPDRS motor score (P = 0.019, d = 0.68, MCID 7); 6MWT distance (P < 0.001, d = 1.16); walking time during motor or cognitive dual tasking (P = 0.006, d = 0.77; P = 0.005, d = 0.79, respectively); and the PDQ-39 emotional well-being subdomain (P = 0.009; MCID 4.2); as well as improvements trending to significance in bradykinesia (P = 0.025, d = 0.73), 10mWT walking time (P = 0.023, d = 0.61) and borderline improvement in balance (P = 0.056, d = 0.50). The outcomes of this study support the efficacy of the PDW programme in individuals with early PD and provide justification for future trials and investigation of its effects.

Impact of deep brain stimulation on gait in Parkinson disease: A kinematic study

BackgroundThe effect of Deep Brain Stimulation (DBS) on gait in Parkinson’s Disease (PD) is poorly understood. Kinematic studies utilizing quantitative gait outcomes such as speed, cadence, and stride length have shown mixed results and were done mostly before and after acute DBS discontinuation. ObjectiveTo examine longitudinal changes in kinematic gait outcomes before and after DBS surgery. MethodWe retrospectively assessed changes in quantitative gait outcomes via motion capture in 22 PD patients before and after subthalamic (STN) or globus pallidus internus (GPi) DBS, in on medication state. Associations between gait outcomes and clinical variables were also assessed. ResultGait speed reduced from 110.7 ± 21.3 cm/s before surgery to 93.6 ± 24.9 after surgery (7.7 ± 2.9 months post-surgery, duration between assessments was 15.0 ± 3.8 months). Cadence, step length, stride length, and single support time reduced, while total support time, and initial double support time increased. Despite this, there was overall improvement in the Movement Disorder Society-Unified Parkinson Disease Rating Scale-Part III score “on medication/on stimulation” score (from 19.8 ± 10.7–13.9 ± 8.6). Change of gait speed was not related to changes in levodopa dosage, disease duration, unilateral vs bilateral stimulation, or target nucleus. ConclusionQuantitative gait outcomes in on medication state worsened after chronic DBS therapy despite improvement in other clinical outcomes. Whether these changes reflect the effects of DBS as opposed to ongoing disease progression is unknown.

A Longitudinal Two-Armed Randomized Controlled Trial Protocol to Evaluate the Efficacy of Yoga on Progression of Disease in Early Parkinson’s Disease

Background Numerous studies have shown that yoga can aid patients with Parkinson’s disease (PD) in managing their motor function, functional mobility, balance, anxiety, and overall quality of life. However, most of the reported research either needed more power or evaluated the results during or after the intervention. Due to the long-standing nature of PD, there are still few longitudinal studies investigating the potential of yoga to decrease the progression of the disease. Purpose We study whether sustained adjunct yoga intervention slows PD progression. Methods Over 18 months, this study will investigate the long-term benefits of yoga-based intervention in Parkinson’s patients. The concept of “intention-to-treat (ITT)” will be employed. From the outpatient clinic of the Swami Vivekananda Yoga Anusandhana Samsthana in India, 160 patients with PD will be chosen. They will then be randomly assigned to either the interventional or control groups (1:1). The adjunct intervention group will participate in 21 daily contact yoga sessions (60 min) at the University Medical Center, followed by continued tele-supervised home practice and at-home self-practice. The effectiveness of the adjunct intervention will be evaluated at four different time points (baseline, 3-, 9-, 12-, and 18-month post-randomization). The primary endpoint will be the difference in the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part III score at baseline and after 18 months of intervention. Secondary outcomes will include subscores of MDS-UPDRS I, II, and IV, Parkinson’s Disease Questionnaire (PDQ)-39 scores, treatment adherence, the PDQ-39, the Depression, Anxiety, and Stress Scale-21, and the Scales for Outcomes in PD-Sleep Scale (SCOPA-S). The primary outcome will be analyzed using mixed-effect models for repeated measures, adjusted for covariates as fixed effects. Results The protocol was conceptualized in October 2021 and approved by the Institutional Ethics Committee of SVYASA. Recruitment began in February 2022 and is underway with patient enrollment. Conclusion To our knowledge, this is the first controlled study to examine the long-term effects of yoga as an adjuvant therapy on the progression of PD. Key message This would be the first long-term trial to assess the potential of an adjunct yoga intervention to modulate disease progression in early Parkinson’s patients.

Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder.

Reduced cortical acetylcholinesterase activity, as measured by 11 C-donepezil positron emission tomography (PET), has been reported in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD). However, its progression and clinical implications have not been fully investigated. Here, we explored the relationship between longitudinal changes in brain acetylcholinesterase activity and cognitive function in iRBD. Twelve iRBD patients underwent 11 C-donepezil PET at baseline and after 3 years. PET images were interrogated with statistical parametric mapping (SPM) and a regions of interest (ROI) approach. Clinical progression was assessed with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III). Cognitive function was rated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). From baseline to follow-up, the mean 11 C-donepezil distribution volume ratio (DVR) decreased in the cortex (p = 0.006), thalamus (p = 0.013), and caudate (p = 0.013) ROI. Despite no significant changes in the group mean MMSE or MoCA scores being observed, individually, seven patients showed a decline in their scores on these cognitive tests. Subgroup analysis showed that only the subgroup of patients with a decline in cognitive scores had a significant reduction in mean cortical 11 C-donepezil DVR. Our results show that severity of brain cholinergic dysfunction in iRBD patients increases significantly over 3 years, and those changes are more severe in those with a decline in cognitive test scores.

Autophagy markers, cognitive deficits and depressive symptoms in Parkinson's disease.

Depressive symptoms are common in Parkinson's disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients.A total of 163 PD patients aged 50-80years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively.There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = -0.002, t = -2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = -0.001, t = -2.452, p = 0.017).LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall.

Fluctuations in Parkinson's disease and personalized medicine: bridging the gap with the neuropsychiatric fluctuation scale.

Neuropsychiatric fluctuations (NpsyF) are frequent and disabling in people with Parkinson's disease (PD). In OFF-medication, NpsyF entail minus neuropsychiatric symptoms (NPS) like anxiety, apathy, sadness, and fatigue. In ON-medication, NpsyF consist in plus NPS, such as high mood, hypomania, and hyperactivity. Accurate identification of these NpsyF is essential to optimize the overall PD management. Due to lack of punctual scales, the neuropsychiatric fluctuation scale (NFS) has been recently designed to assess NpsyF in real time. The NFS comprises 20 items with two subscores for plus and minus NPS, and a total score. To evaluate the psychometric properties of the NFS in PD. PD patients with motor fluctuations and healthy controls (HC) were assessed. In PD patients, the NFS was administrated in both the ON-and OFF-medication conditions, together with the movement disorders society-unified Parkinson disease rating scale parts I-IV. Depression (Beck depression scale II), apathy (Starkstein apathy scale) and non-motor fluctuations items of the Ardouin scale of behaviour in PD (ASBPD OFF and ON items) were also assessed. NFS internal structure was evaluated with principal component analysis consistency (PCA) in both medication conditions in PD patients and before emotional induction in HC. NFS internal consistency was assessed using Cronbach's alpha coefficient. NFS convergent and divergent validity was measured through correlations with BDI-II, Starktein, and ASBPD OFF and ON non motor items. Specificity was assessed comparing NFS global score between the HC and PD populations. Sensitivity was evaluated with t-student test comparing the ON-and the OFF-medication conditions for NFS global score and for minus and plus subscores. In total, 101 consecutive PD patients and 181 HC were included. In PD patients and HC, PCA highlighted one component that explained 32-35 and 42% of the variance, respectively. Internal consistency was good for both the NFS-plus (alpha =0.88) and NFS-minus items (alpha =0.8). The NFS showed a good specifity for PD (p < 0.0001) and a good sensitivity to the medication condition (p < 0.0001). The satisfactory properties of the NFS support its use to assess acute neuropsychiatric fluctuations in PD patients, adding to available tools.

Deep brain stimulation of the subthalamic nucleus improves sleep in Parkinson disease patients: A systematic review and meta-analysis.

Sleep disorders significantly affect the quality of life in Parkinson disease (PD) patients. Deep brain stimulation of the subthalamic nucleus has been reported to improve motor symptoms and decrease medication usage. However, the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on sleep quality in PD patients remains to be definitively determined. This systematic review and meta-analysis, conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines, aimed to clarify the effect of STN-DBS on sleep quality in PD patients. A rigorous literature search identified 6 studies, including 1 randomized controlled trial and 5 self-controlled trials, totaling 154 patients who underwent deep brain stimulation, providing 308 pairs of data for analysis. Parkinson disease sleep scale was the primary measure of interest, while the Movement Disorder Society-sponsored revision of the unified Parkinson disease rating scale was documented in all trials. Study quality was assessed using the Newcastle-Ottawa scale. STN-DBS significantly improved Parkinson disease sleep scale scores (mean difference = 20.41, 95% CI: [13.03, 27.79], I² = 60.8%, P < .001), indicating enhanced sleep quality. Furthermore, a significant reduction in movement disorder society unified Parkinson disease rating scale part III scores postoperatively (mean difference = -12.59, 95% CI: [-14.70, -10.49], I² = 89.9%, P < .001) suggested improved motor function. PD medication usage was also significantly reduced postoperatively (mean difference = -314.71, 95% CI: [-468.13, -161.28], I² = 52.9%, P < .001). A sensitivity analysis confirmed the robustness of the main findings. The sample size was adequate, allowing for conclusive inferences. The present study, which comprises a comprehensive systematic review and meta-analysis, offers compelling evidence that STN-DBS can ameliorate sleep quality, augment motor function, and curtail medication consumption among individuals afflicted with PD.

Minor Phenomena in Parkinson's Disease-Prevalence, Associations, and Risk of Developing Psychosis.

Minor phenomena, including passage phenomena, feeling of presence, and illusions, are common and may represent a prodromal form of psychosis in Parkinson's disease (PD). We examined the prevalence and clinical correlates of minor phenomena, and their potential role as a risk factor for PD psychosis. A novel questionnaire, the Psychosis and Mild Perceptual Disturbances Questionnaire for PD (PMPDQ), was completed by Fox Insight cohort participants with and without PD. Additional assessments included the Non-Motor Symptoms Questionnaire (NMSQuest), REM Sleep Behavior Disorder Single Question Screen (RBD1Q), Movement Disorder Society-Unified Parkinson Disease Rating Scale Part II, demographic features, and medication usage. For participants with PD, we used regression models to identify clinical associations and predictors of incident psychosis over one year of follow-up. Among participants with PD (n = 5950) and without PD (n = 1879), the prevalence of minor phenomena was 43.1% and 31.7% (P < .001). Of the 3760 participants with PD and no baseline psychosis, independent correlates of minor phenomena included positive responses on the NMSQuest apathy/attention/memory (OR 1.7, 95% CI 1.3-2.1, P < .001) or sexual function domain (OR 1.3, 95% CI 1.1-1.6, P = .01) and positive RBD1Q (OR 1.3, 95% CI 1.05-1.5, P = .01). Independent risk factors for incident PD psychosis included the presence of minor phenomena (HR 3.0, 95% CI 2.4-3.9, P < .001), positive response on the NMSQuest apathy/attention/memory domain (HR 1.8, 95% CI 1.3-2.6, P < .001), and positive RBD1Q (HR 1.5, 95% CI 1.1-1.9, P = .004). Minor phenomena are common, associated with specific non-motor symptoms, and an independent predictor of incident psychosis in PD.

Serial deep gray nuclear DTI changes in Parkinson's disease over twelve years.

Deep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson's disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years. Participating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time. MD progressively increased over time and was higher in the putamen (p < 0.001) and globus pallidus (p = 0.002). FA increased (p < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal (p = 0.0210), pallidal (p = 0.0066) and caudate MD (p < 0.0001) correlated with disease duration. Caudate MD (p < 0.05) also correlated with UPDRS-III and H&Y scores. Pallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.

The first and foremost unilateral pallidothalamic tractotomy done in India for Parkinson’s Disease

Background. Pallidothalamic tractotomy” can be effective in Parkinson’s disease by exhibiting anti-parkinsonian effects. Case presentation. The patient was a 53 years old gentleman, having Parkinson’s disease for the last 14 years. The disease onset was on the left side and slowly moved to the right side. He had tremors, slowness of body movements and stiffness of the movements. The first right Pallidotomy was done in January 2019. There was a noticeable improvement in a few weeks. He continued to have symptoms on the right side. The preoperative Unified Parkinson Disease Rating Scale (UPDRS) part 3 score in 2019 was 53 while the postoperative score was only 26 showing drastic improvement after right Pallidotomy. After 2 years of the first surgery, a new technique called Pallido Thalamic Tractotomy (PTT), an MRI-guided stereotactic surgery was done on the left side. Tremors reduced gradually by 99% in 3 weeks after surgery. This is the first case of PTT performed on a patient with Parkinson’s disease in India. Conclusion. PTT is an effective procedure in PD that acts by disconnecting the pallidothalamic tract. Unilateral pallidothalamic tractotomy done on the left side improved contralateral side rigidity, tremors and bradykinesia.

Ulotaront, a Trace Amine-Associated Receptor 1/Serotonin 5-HT1A Agonist, in Patients With Parkinson Disease Psychosis: A Pilot Study.

Ulotaront (SEP-363856) is a trace amine-associated receptor 1 agonist with 5-HT1A receptor agonist activity currently in phase 3 clinical development for the treatment of schizophrenia. In this exploratory, flexibly dosed study, ulotaront was evaluated for the treatment of Parkinson disease psychosis (PDP). Patients with PDP requiring antipsychotic therapy were randomized, double-blind to ulotaront (25, 50, or 75 mg/d) or placebo. Mixed Model for Repeated Measures was used to assess change from baseline in the Scale for the Assessment of Positive Symptoms for Parkinson Disease (SAPS-PD) at 6 weeks (primary end point). The efficacy analysis sample comprised 38 patients (ulotaront, n = 24; placebo, n = 14). SAPS-PD total scores were numerically reduced in ulotaront-treated vs placebo-treated patients from week 1 to week 6: Least squares mean (95% confidence interval) difference in change from baseline at week 6 was -1.1 (-6.5, 4.3, p = 0.681). PDP symptom complete remission (≥100% improvement [reduction] from baseline in SAPS-PD total score) was observed in 25% of ulotaront-treated vs 0% of placebo-treated patients. SAPS-PD and Neuropsychiatric Inventory hallucinations subscales were numerically reduced vs placebo, and SAPS-PD total scores were reduced in patients with greater cognitive impairment (baseline Mini-Mental State Examination [MMSE] scores ≤24). Ulotaront improved Scales for Outcomes in Parkinson Disease Sleep Scale - Daytime Sleepiness scores (p = 0.022). There was no worsening of Unified Parkinson Disease Rating Scale Part III motor score, MMSE, or vital signs. Adverse events (≥10%) with ulotaront vs placebo included hallucinations (24% vs 14%), confusional state (20% vs 14%), dizziness (16% vs 7%), nausea (12% vs 7%), and falls (12% vs 21%). In this exploratory pilot study, ulotaront may decrease PDP symptoms without worsening motor function, particularly in patients with cognitive impairment. ClinicalTrials.gov identifier: NCT02969369; submitted: November 17, 2016; study start date: December 31, 2016. This Class II study was an exploratory pilot study that was underpowered to detect a statistically significant difference between ulotaront and placebo in the treatment of patients with Parkinson disease psychosis without worsening motor function.

Mindfulness or meditation therapy for Parkinson's disease: A systematic review and meta-analysis of randomized controlled trials.

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Mindfulness and meditation therapies have been demonstrated as effective alternative treatments for patients with neurological disorders. However, the effects of mindfulness and meditation therapies on PD remain unclear. This meta-analysis investigated the effects of mindfulness and meditation therapies in PD patients. A literature search was conducted using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials comparing mindfulness and meditation therapies with control treatments in patients with PD. Nine articles involving eight trials were included, with a total of 337 patients. Our meta-analysis revealed that mindfulness and meditation therapies significantly improved Unified Parkinson's Disease Rating Scale-Part III score (mean difference [MD] = -6.31, 95% confidence interval [95% CI] = -8.57 to -4.05) and cognitive function (standard mean difference [SMD] = 0.62, 95% CI = 0.23 to 1.02). However, no significant differences were discovered between mindfulness therapies and control in gait velocity (MD = 0.05, 95% CI = -0.23 to 0.34), Parkinson's Disease Questionnaire-39 Summary Index (MD = 0.51, 95% CI = -1.12 to 2.14), activities of daily living (SMD = -1.65, 95% CI = -3.74 to 0.45), depression (SMD = -0.43, 95% CI = -0.97 to 0.11), anxiety (SMD = -0.80, 95% CI = -1.78 to 0.19), pain (SMD = 0.79, 95% CI = -1.06 to 2.63), or sleep disturbance (SMD = -0.67, 95% CI = -1.58 to 0.24). Mindfulness and meditation therapies may serve as complementary and alternative treatments for PD patients.

Deep Brain Stimulation of Subthalamic Nucleus Improves Quality of Life in General and Mental Health Domains in Parkinson’s Disease to the Level of the General Population

ObjectivesParkinson’s disease (PD) leads to significant impairment in quality of life (QoL) across various domains. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is known to improve motor and nonmotor symptoms in PD. The aim was to study whether STN-DBS could improve the QoL of patients with PD to the level of the general population, and to determine factors predicting better motor outcomes. Materials and MethodsThe retrospective analysis included 43 patients who underwent either primary or revision STN-DBS. Patients filled out a general QoL questionnaire (RAND 36-item health survey) before and 12 months after surgery, and scores were compared with age- and sex-adjusted national population values. In addition, motor scores were calculated using Unified Parkinson Disease Rating Scale part 3 (UPDRS 3) with the best PD medication. Levodopa equivalent daily dose (LEDD) was also collected. Changes in the QoL were compared with operation age, disease duration, and preoperative QoL. ResultsPreoperatively, patients had significantly impaired QoL in all subsections compared with that of the general population. The mean postoperative UPDRS 3 improvement was 50.0%, and reduction in LEDD was 69.0%. Statistically significant QoL improvements were found in Physical Function, Mental Health, Social Function, Vitality, and Role Physical 12 months postoperatively compared with baseline. The mean differences compared with a healthy population were not statistically significant in General Health, Mental Health, Vitality, and Role Emotional. Furthermore, disease duration was found to be negatively correlated with improvements in UPDRS 3 score, and worse preoperative QoL positively correlated with changes in Physical Function. ConclusionsPatients experienced significant QoL improvements after STN-DBS. The General Health and Mental Health of patients were postoperatively most comparable with age- and sex-adjusted population values. Moreover, earlier stimulation predicted better motor improvements, which emphasizes the importance of earlier timing of STN-DBS surgery and minimizing loss of function at a critical disease stage.