Parkinson’s Disease Multimodal Complex Treatment (PD-MCT): Analysis of Therapeutic Effects and Predictors for Improvement

Parkinson’s disease Multimodal Complex Treatment (PD-MCT) is a multidisciplinary inpatient treatment approach that has been demonstrated to improve motor function and quality of life in patients with Parkinson’s disease (PD). In this study, we assessed the efficacy of PD-MCT and calculated predictors for improvement. We performed a prospective analysis in a non-randomized, open-label observational patient cohort. Study examinations were done at baseline (BL), at discharge after two-weeks of inpatient treatment (DC) and at a six-week follow-up examination (FU). Besides Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III as a primary outcome, motor performance was measured by the Timed Up-and-Go (TUG), the Berg Balance Scale (BBS) and the Perdue Pegboard Test (PPT). Until DC, motor performance improved significantly in several parameters and was largely maintained until FU (MDS-UPDRS III BL-to-DC: −4.7 ± 1.2 (SE) p = 0.0012, BL-to-FU: −6.1 ± 1.3 p = 0.0001; TUG BL-to-DC: −2.5 ± 0.9 p = 0.015, BL-to-FU: 2.4 ± 0.9 p = 0.027; BBS BL-to-DC: 2.4 ± 0.7 p = 0.003, BL-to-FU: 1.3 ± 0.7 p = 0.176, PPT BL-to-DC: 3.0 ± 0.5 p = 0.000004, BL-to-FU: 1.7 ± 0.7 p = 0.059). Overall, nontremor items were more therapy responsive than tremor items. Motor complications evaluated with MDS-UPDRS IV occurred significantly less frequent at DC (−1.8 ± 0.5 p = 0.002). Predictor analyses revealed an influence of initial motor impairment and disease severity on the treatment response in different motor aspects. In summary, we demonstrate a significant positive treatment effect of PD-MCT on motor function of PD patients which can be maintained in several parameters for an extended time period of six weeks and identify predictors for an improvement of motor function.

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Low-Dose Niacin Supplementation Improves Motor Function in US Veterans with Parkinson’s Disease: A Single-Center, Randomized, Placebo-Controlled Trial

Biomedicines ◽

10.3390/biomedicines9121881 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1881

Author(s):

Chandramohan Wakade ◽

Raymond Chong ◽

Marissa Seamon ◽

Sharad Purohit ◽

Banabihari Giri ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Function ◽

Low Dose ◽

Rating Scale ◽

Controlled Trial ◽

Randomized Study ◽

Secondary Outcome ◽

Open Label ◽

Double Blind

A six-month double-blind, placebo-controlled randomized study was conducted to ascertain whether low-dose daily niacin supplementation would improve motor symptoms in Parkinson’s disease (PD) patients. A total of 47 PD patients were assigned to receive low-dose niacin or a placebo. At the end of the double-blind phase, all participants received open-label niacin for the next six months. All patients were evaluated at baseline, after six months, and after one year of treatment. The primary outcome measure was the Unified Parkinson’s Disease Rating Scale III (UPDRS III) scores. Secondary outcome measures were depression, sleep quality, mental flexibility and cognition, and physical fatigue. Niacin treatment was well-tolerated by forty-five subjects. The mean [95% CI] change in UPDRS III scores at six months of placebo was −0.05 [95% CI, −2.4 to 2.32], and niacin was −1.06 [95% CI, −3.68 to 1.57]. From six to twelve months when both groups received open-label niacin supplementation, the average UPDRS III scores significantly decreased for the placebo group by 4.58 [95% CI, −0.85 to 8.30] and the niacin group by 4.63 [95% CI, 1.42 to 7.83] points. Low-dose niacin supplementation is a well-tolerated adjunct therapy and may improve motor function in PD when taken over a longer period.

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Fluoxetine does not impair motor function in patients with Parkinson's disease: Correlation between mood and motor functions with plasma concentrations of fluoxetine/norfluoxetine

Vojnosanitetski pregled ◽

10.2298/vsp111114028k ◽

2012 ◽

Vol 69 (12) ◽

pp. 1067-1075 ◽

Cited By ~ 5

Author(s):

Vladimir Kostic ◽

Eleonora Dzoljic ◽

Zoran Todorovic ◽

Milija Mijajlovic ◽

Marina Svetel ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Function ◽

Selective Serotonin Reuptake Inhibitors ◽

Rating Scale ◽

Plasma Concentrations ◽

Mild Depression ◽

Open Label ◽

Motor Functions ◽

Finger Tapping Test

Background/Aim. Selective serotonin reuptake inhibitors are the most commonly chosen antidepressants in patients with Parkinson's disease (PD). The aim of our study was to assess the influence of fluoxetine (Flu) on motor functions in patients with PD. Methods. In this prospective, controlled, open-label study, 18 patients with PD and mild depression [(10 ? Hamilton Rating Scale for Depression (HDRS) ? 23)] without dementia [(25 ? Mini-Mental State Examination (MMSE)] were treated with Flu. Both single and repeated dose effects of Flu were assessed on days 1-80. Plasma concentrations of Flu and norfluoxetine (NORFlu) were correlated with the results of selected motor function performance scores: The Unified Parkinsons Disease Rating Score (UPDRS), Finger Tapping Test (FTT) and Purdue Pegboard Test (PPT). Severity of PD, depression and dementia were evaluated using standard tests [(Hoehn and Yahr stages (HY), activity of daily living (ADL), UPDRS, HDRS, MMSE)]. Results. Steady-state for Flu/NORFlu was reached after 18 days of treatment. Such a plateau correlated with significant improvements in both scores of depression and Parkinson's disability (HDRS, UPDRS and ADL, respectively). In addition, FTT and PPT scores also increased until day 18, with further slight fluctuations around the plateau. Optimal motor performances correlated with Flu concentrations of approximately 60-110 ?g/L. Conclusion. Flu (20 mg/day) significantly reduced depression in PD patients while it did not impair their motor performances. Because substantial placebo effects may arise in studies of PD and depression, large, prospective, randomized, placebo-controlled clinical trials are warranted.

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Effects of Onabotulinum Toxin A on Gait in Parkinson’s Disease Patients with Foot Dystonia

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.42 ◽

2021 ◽

pp. 1-6

Author(s):

Pei Huang ◽

Yuan-Yuan Li ◽

Jung E. Park ◽

Ping Huang ◽

Qin Xiao ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Botulinum Toxin ◽

Gait Analysis ◽

Rating Scale ◽

Analog Scale ◽

Toxin A ◽

Timed Up And Go ◽

Balance Test ◽

Onabotulinum Toxin A

ABSTRACT: We investigated the effects of botulinum toxin on gait in Parkinson’s disease (PD) patients with foot dystonia. Six patients underwent onabotulinum toxin A injection and were assessed by Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), visual analog scale (VAS) of pain, Timed Up and Go (TUG), Berg Balance Test (BBT), and 3D gait analysis at baseline, 1 month, and 3 months. BFMDRS (p = 0.002), VAS (p = 0.024), TUG (p = 0.028), and BBT (p = 0.034) were improved. Foot pressures at Toe 1 (p = 0.028) and Midfoot (p = 0.018) were reduced, indicating botulinum toxin’s effects in alleviating the dystonia severity and pain and improving foot pressures during walking in PD.

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Intensive Rehabilitation Enhances Lymphocyte BDNF-TrkB Signaling in Patients With Parkinson’s Disease

Neurorehabilitation and Neural Repair ◽

10.1177/1545968315600272 ◽

2015 ◽

Vol 30 (5) ◽

pp. 411-418 ◽

Cited By ~ 26

Author(s):

Cecilia Fontanesi ◽

Svetlana Kvint ◽

Giuseppe Frazzitta ◽

Rossana Bera ◽

Davide Ferrazzoli ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Function ◽

Rating Scale ◽

Cortical Plasticity ◽

Day Treatment ◽

Human Study ◽

Exercise Program ◽

Peripheral Lymphocytes ◽

Intensive Rehabilitation

Background. In a combined animal and human study, we have previously found that a 5-day treatment that enhances cortical plasticity also facilitates brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling and increases activated TrkB and N-methyl-d-aspartate receptor (NMDAR) association in both the cortex and the peripheral lymphocytes. Patients with Parkinson’s disease (PD), in general, show decreased cortical plasticity, as demonstrated by electrophysiological and behavioral studies. Here, we test the hypothesis that an exercise program that improves motor function and seems to slow down symptom progression can enhance BDNF-TrkB signaling in lymphocytes. Methods. A total of 16 patients with PD underwent a 4-week multidisciplinary intensive rehabilitation treatment (MIRT), which included aerobic training and physical and occupational therapy. Blood was collected before and after 2 and 4 weeks of MIRT. Lymphocytes were isolated to examine BDNF-TrkB signaling induced by incubation with recombinant human BDNF. TrkB signaling complexes, extracellular-signal-regulated kinase-2 and protein-kinase-B were immunoprecipitated; the content of immunocomplexes was determined by Western blotting. Results. After MIRT, all patients showed improvement in motor function. TrkB interaction with NMDAR and BDNF-TrkB signaling increased in peripheral lymphocytes at receptor, intracellular mediator, and downstream levels. The decrements in Unified Parkinson’s Disease Rating Scale II (UPDRSII) and total scores were significantly correlated with the increases in TrkB signaling at receptor, intracellular mediator, and NMDAR interaction levels. Conclusions. The significant correlation between reduced UPDRS scores and the changes in lymphocyte activity suggest that enhanced BDNF-TrkB signaling in lymphocyte and reduced severity of PD symptoms may be related.

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Urinary dysfunction with detrusor hyperactivity in women with Parkinson's disease cannot be blamed as a factor of worsening motor performance

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130101 ◽

2013 ◽

Vol 71 (9A) ◽

pp. 591-595 ◽

Cited By ~ 6

Author(s):

Raimundo Nonato Campos-Sousa ◽

Elizabeth Maria Aparecida Barasnevicius Quagliato ◽

Kelson James Almeida ◽

Inacio Augusto Dias de Castro ◽

Viriato Campelo

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Performance ◽

Rating Scale ◽

Clinical Symptoms ◽

Urinary Dysfunction ◽

Clinical Aspects ◽

Yahr Scale ◽

Disease Rating ◽

Detrusor Hyperactivity

Introduction Detrusor hyperactivity is the leading cause of urinary dysfunction in Parkinson's disease (PD). There are few studies correlating PD clinical aspects with this autonomic feature. Methods A cohort of 63 women with PD were prospectively examined for assessment of clinical aspects and disease severity using unified Parkinson's disease rating scale and Hoehn-Yahr scale, respectively. The urologic function was evaluated by the urodynamic study. Two groups were categorized at this time - groups with and without detrusor hyperactivity. After seven years, the same parameters were re-evaluated. Results Progression of the disease on mental scores was found in the group with detrusor hyperactivity. On follow-up, clinical symptoms and severity did not show significant worsening between the groups. Conclusion Detrusor hyperactivity is a frequent urodynamic finding in PD, and even though it is associated with dopaminergic dysfunction, it cannot be blamed as a factor of worsening motor performance, but is probably associated with poor cognitive and mental prognosis.

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Automated Stage Discrimination of Parkinson’s Disease

BIO Integration ◽

10.15212/bioi-2020-0006 ◽

2020 ◽

Vol 1 (2) ◽

pp. 55-63

Author(s):

Vered Aharonson ◽

Nabeel Seedat ◽

Simon Israeli-Korn ◽

Sharon Hassin-Baer ◽

Michiel Postema ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Motor Fluctuation ◽

Step Length ◽

Disease Stage ◽

Physical Parameters ◽

Timed Up And Go ◽

Step Velocity ◽

Treatment Plans

Abstract Background: Treatment plans for Parkinson’s disease (PD) are based on a disease stage scale, which is generally determined using a manual, observational procedure. Automated, sensor-based discrimination saves labor and costs in clinical settings and may offer augmented stage determination accuracy. Previous automated devices were either cumbersome or costly and were not suitable for individuals who cannot walk without support.Methods: Since 2017, a device has been available that successfully detects PD and operates for people who cannot walk without support. In the present study, the suitability of this device for automated discrimination of PD stages was tested. The device consists of a walking frame fitted with sensors to simultaneously support walking and monitor patient gait. Sixty-five PD patients in Hoehn and Yahr (HY) stages 1 to 4 and 24 healthy controls were subjected to supported Timed Up and Go (TUG) tests, while using the walking frame. The walking trajectory, velocity, acceleration and force were recorded by the device throughout the tests. These physical parameters were converted into symptomatic spatiotemporal quantities that are conventionally used in PD gait assessment.Results: An analysis of variance (ANOVA) test extended by a confidence interval (CI) analysis indicated statistically significant separability between HY stages for the following spatiotemporal quantities: TUG time (p < 0.001), straight line walking time (p < 0.001), turning time (p < 0.001), and step count (p < 0.001). A negative correlation was obtained for mean step velocity (p < 0.001) and mean step length (p < 0.001). Moreover, correlations were established between these, as well as additional spatiotemporal quantities, and disease duration, L-dihydroxyphenylalanine-(L-DOPA) dose, motor fluctuation, dyskinesia and the mobile part of the Unified Parkinson Disease Rating Scale (UPDRS).Conclusions: We have proven that stage discrimination of PD can be automated, even to patients who cannot support themselves. A similar method might be successfully applied to other gait disorders.

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Functional Performance and Associations between Performance Tests and Neurological Assessment Differ in Men and Women with Parkinson’s Disease

Behavioural Neurology ◽

10.1155/2015/519801 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Kadri Medijainen ◽

Mati Pääsuke ◽

Aet Lukmann ◽

Pille Taba

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Functional Performance ◽

Clinical Stage ◽

Performance Tests ◽

Neurological Assessment ◽

Timed Up And Go ◽

Men And Women ◽

Assessment Tests

Background. Neurological assessment of a patient with Parkinson’s disease (PD) is expected to reflect upon functional performance. As women are known to report more limitations even for same observed functional performance level, present study was designed to examine whether associations between neurological assessments and functional performance differ across genders.Methods. 14 men and 14 women with PD participated. Functional performance was assessed by measuring walking speeds on 10-meter walk test (10MWT) and by performing timed-up-and-go-test (TUG). Neurological assessment included Hoehn and Yahr Scale (HY), Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Schwab and England Activities of Daily Living Scale (S-E), and Mini Mental State Examination (MMSE).Results. In women with PD, Kendall’s tau-b correlation analyses revealed significant correlations between functional performance tests and neurological assessment measures, with the exception in MMSE. No corresponding associations were found for men, although they demonstrated better functional performance, as expected.Conclusion. Men in similar clinical stage of the PD perform better on functional tests than women. Disease severity reflects upon functional performance differently in men and women with PD. Results indicate that when interpreting the assessment results of both functional performance and neurological assessment tests, the gender of the patient should be taken into consideration.

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Low dose niacin versus placebo in the treatment of Parkinson’s Disease: A Randomized Controlled Trial

10.21203/rs.3.rs-776855/v1 ◽

2021 ◽

Author(s):

Chandramohan Wakade ◽

Raymond Chong ◽

Marissa Seamon ◽

Sharad Purohit ◽

Banabihari Giri ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Low Dose ◽

Rating Scale ◽

Controlled Trial ◽

Secondary Outcome ◽

Open Label ◽

Double Blind ◽

One Year ◽

Time Point

Abstract BackgroundParkinson’s Disease (PD) patients have lower niacin levels compared to their spouses. The main objective was to study low-dose daily niacin supplementation versus placebo on motor symptoms in Parkinson’s disease subjects.MethodsA randomized, placebo-controlled, double-blind, single-center clinical trial in Parkinson’s disease patients was performed in Augusta, GA, between September 2016 to September 2019. Randomized participants were 47 PD patients who received either low-dose niacin (N = 21 ) or placebo (N = 26) for the first six months (mean age 68.4 SD, 8.7; mean duration of disease 5.8 SD 4.9; H&Y scores between 0.5 to 4; 64% subjects were Veterans). The Veterans Affairs Pharmacy generated the randomized sequence. After the double-blind phase, all participants received open-label niacin for the next six months. All patients were evaluated at baseline, six months, and one year of treatment. The main outcome measure was the Unified Parkinson’s Disease Rating Scale III (UPDRS III) scores. Secondary outcome measures were depression, sleep quality, mental flexibility and cognition, and physical fatigue.Results39 subjects were analyzed with low-dose niacin (N = 18) and placebo (N = 21) for the completion of the first six months (randomized, double-blind), and 31 subjects were analyzed for the completion of the next six months (open-label) with low-dose niacin (N = 14) and placebo (N = 17). Niacin treatment was not tolerated by two subjects. The baseline mean UPDRS III score was 21.3 ± 15.8 for the niacin group and 22.4 ± 11.8 for placebo. The change with six months of placebo was 0.05 [95% CI, -2.4 to 2.32], and niacin was 1.06 [95% CI, -3.68 to 1.57]. From six to twelve months, the average UPDRS III score decreased for the placebo group by 4.58 [95% CI, -0.85 to 8.30] and the niacin group by 4.63 [95% CI, 1.42 to 7.83]. Eight subjects withdrew from the study before the 6-month time point and eight more before the one-year time point due to voluntary discontinuation, flushing, or inability to continue (SARS-CoV-2 shut-down).ConclusionLow-dose niacin supplementation may be helpful as an adjunct therapy in improving motor function in PD.Trial registrationClinicaltrials.gov, NCT03462680. Registered 12 March 2018- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03462680?term=gpr109A&draw=2&rank=1

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Exploring Movement Impairments in Patients With Parkinson's Disease Using the Microsoft Kinect Sensor: A Feasibility Study

Frontiers in Neurology ◽

10.3389/fneur.2020.610614 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ditte Rudå ◽

Gudmundur Einarsson ◽

Anne Sofie Schott Andersen ◽

Jannik Boll Matthiassen ◽

Christoph U. Correll ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Performance ◽

Rating Scales ◽

Rating Scale ◽

Motor Task ◽

Microsoft Kinect ◽

Healthy Controls ◽

Kinect Sensor ◽

Microsoft Kinect Sensor

Background: Current assessments of motor symptoms in Parkinson's disease are often limited to clinical rating scales.Objectives: To develop a computer application using the Microsoft Kinect sensor to assess performance-related bradykinesia.Methods: The developed application (Motorgame) was tested in patients with Parkinson's disease and healthy controls. Participants were assessed with the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) and standardized clinical side effect rating scales, i.e., UKU Side Effect Rating Scale and Simpson-Angus Scale. Additionally, tests of information processing (Symbol Coding Task) and motor speed (Token Motor Task), together with a questionnaire, were applied.Results: Thirty patients with Parkinson's disease and 33 healthy controls were assessed. In the patient group, there was a statistically significant (p < 0.05) association between prolonged time of motor performance in the Motorgame and upper body rigidity and bradykinesia (MDS-UPDRS) with the strongest effects in the right hand (p < 0.001). In the entire group, prolonged time of motor performance was significantly associated with higher Simson-Angus scale rigidity score and higher UKU hypokinesia scores (p < 0.05). A shortened time of motor performance was significantly associated with higher scores on information processing (p < 0.05). Time of motor performance was not significantly associated with Token Motor Task, duration of illness, or hours of daily physical activity. The Motorgame was well-accepted.Conclusions: In the present feasibility study the Motorgame was able to detect common motor symptoms in Parkinson's disease in a statistically significant and clinically meaningful way, making it applicable for further testing in larger samples.

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The efficacy of cognitive-cycling dual-task training in patients with early-stage Parkinson’s disease: A pilot study

Neurorehabilitation ◽

10.3233/nre-203090 ◽

2020 ◽

Vol 47 (4) ◽

pp. 415-426

Author(s):

Hsiu-Chen Chang ◽

Chiung-Chu Chen ◽

Yi-Hsin Weng ◽

Wei-Da Chiou ◽

Ya-Ju Chang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Performance ◽

Dual Task ◽

Rating Scale ◽

Early Stage ◽

Freezing Of Gait ◽

Timed Up And Go ◽

Gait Performance ◽

The Mean

BACKGROUND: Recent studies have suggested that cognitive-motor dual-task (DT) training might improve gait performance, locomotion automaticity, balance, and cognition in patients with Parkinson’s disease (PD). OBJECTIVE: We aimed to investigate the efficacy of cognitive-cycling DT training in patients with early-stage PD. METHODS: Participants were scheduled to perform cognitive tasks simultaneously with the cycling training twice per week for eight weeks for a total of 16 sessions during their on-states. Clinical assessments were conducted using the unified Parkinson’s disease rating scale (UPDRS), modified Hoehn and Yahr stage, Timed Up and Go (TUG) test, gait and cognitive performances under dual-task paradigm, the new freezing of gait questionnaire, Schwab and England Activities of Daily Living scale, 39-item Parkinson’s disease questionnaire, and cognitive performance. RESULTS: Thirteen eligible patients were enrolled in the study. The mean age was 60.64±5.32 years, and the mean disease duration was 7.02±3.23 years. Twelve PD patients completed 16 serial cognitive-cycling sessions for two months. After 16 sessions of training (T2), the UPDRS III scores improved significantly in both the off- and on-states, and TUG were significantly less than those at pretraining (T0). During both the single-task and the DT situations, gait performance and spatial memory cognitive performance significantly improved from T0 to T2. CONCLUSION: The present study demonstrated that cognitive-cycling DT training improves the motor functions, gait and cognitive performances of PD patients.

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