Improvement In UPDRS Research Articles

A Silent Threat: Deep Vein Thrombosis in Early-Stage Parkinson's Disease.

The primary clinical manifestation of venous thrombosis is discomfort in the lower extremities. Some early Parkinson's disease (PD) patients feel discomfort in the lower limbs. Venous thrombosis can risk lives by causing pulmonary embolism. This study examines the incidence of DVT in early PD patients and its correlation with different clinical and lab features. A cross-sectional study was conducted on 117 patients with early-stage PD. Ultrasonography was employed to detect the presence of DVT. Factors such as age, gender, body mass index, lifestyle habits (smoking and drinking), medical history (hypertension, diabetes, atrial fibrillation, and tumor), and other lab tests linked to thrombosis were analyzed. In 117 patients, 11 (9.4%) had DVT, while 106 (90.6%) did not. There were no significant differences in gender, BMI, habits, medical history, or other thrombosis-related tests between both groups. However, DVT patients were older with higher d-dimer levels. They also showed an increased right substantia nigra ultrasound echo area, higher HY grades, higher UPDRS 3 scores, less improvement in UPDRS 3 scores and levodopa response. The primary risk factors for lower extremity venous thrombosis were found to be age, d-dimer levels, and low-dose levodopa. Therefore, for elderly patients with early-stage PD, it is crucial to conduct d-dimer and lower extremity vascular ultrasound tests. The prevention of venous thrombosis in the lower extremities of early PD patients is of utmost importance.

Levodopa And Pramipexole Combination Therapy Efficacy In Vietnamese Patients With Parkinson’s Disease: A Randomized Controlled Trial

Early diagnosis and appropriate treatment of Parkinson's disease to minimize the adverse effects of the disease and drug side effects on the patient. Using levodopa combined with pramipexole is an effective therapy for treating Parkinson's disease. Objectives — This study aims to evaluate the treatment outcome of combination therapy with levodopa and pramipexole compared to levodopa monotherapy in Vietnamese Parkinson's patients. Material and Methods — A randomized controlled clinical trial with a 1:1 randomized ratio of 80 individuals with Parkinson's disease. The intervention group received a combination therapy with levodopa/benserazide and pramipexole, and the control group received a monotherapy with levodopa/benserazide. Motor symptoms, non-motor symptoms, The Unified Parkinson's Disease Rating (UPDRS), and The Parkinson's Disease Questionnaire (PDQ-39) scores were assessed before, after, and a follow-up period of 1 and 4 weeks after discharge to evaluate the treatment outcome. Results — Combining therapy with levodopa and pramipexole led to statistically significant improvements in UPDRS and PDQ-39 scores (p<0.05). The mean difference in UPDRS parts I, II, and III after 4 weeks of discharge was -0.5 (p=0.014), -1.68 (p=0.005), and -2.52 (p=0.010) respectively. The quality of life was also enhanced by combining therapy due to a better reduction of PDQ-39 score: 26.0±6.3 versus 32.7±6.4 (p<0.001). The most common side effects were headache, nausea/vomiting, and somnolence. Conclusions — Treatment with levodopa combined with pramipexole improves clinical symptoms and quality of life in patients with Parkinson's, as evidenced by improvements in UPDRS and PDQ-39 scores.

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.

Gender-specific outcomes of deep brain stimulation for Parkinson’s disease — results from a single movement disorder center

Introduction and goalThe investigation of gender differences in treatment response is crucial for effective personalized therapies. With only 30%, women are underrepresented in trials for deep brain stimulation (DBS) in Parkinson’s disease (PD). It is therefore important to evaluate gender-specific outcomes of DBS in PD in order to improve therapeutic counseling.MethodsWe analyzed clinical outcome parameters of 203 patients with PD that underwent DBS surgery targeting the subthalamic nucleus (STN) at our movement disorder center. A total of 27.6% of patients were female and 72.4% male. Motor and non-motor scores were compared before and 1 year after DBS surgery (1y FU) using Wilcoxon signed-rank tests and gender specific outcomes were analyzed with chi-square tests.ResultsAt 1y FU, we found significant improvement in UPDRS II, UPDRS III (35.78 ± 36.14% MedOFF vs. StimON-MedOFF), UPDRS IV, depression (BDI-II), and health-related disability as (ADL) that showed no gender-specific differences. No significant change was revealed for UPDRS I, QUIP, and DemTect for the entire cohort. However, when analyzing both groups separately, only women improved in general cognition (plus 1.26 ± 3.03 DemTect points, p = 0.014*), whereas only men ameliorated in depression (minus 1.97 ± 6.92 BDI-II points, p = 0.002**) and impulsivity (minus 2.80 ± 7.27 QUIP points, p = 0.004**). Chi-square tests, however, revealed no significant differences between genders.Conclusion and outlookSTN-DBS is a highly effective treatment for motor and non-motor symptoms of PD for both women and men but our study hints towards gender-specific outcomes in non-motor-domains like cognition, depressive symptoms, and impulsivity. To explore this in more detail, larger cohorts need to be investigated in multicenter trials.

Striatal dopamine transporter availability and individual clinical course within the 1-year follow-up of deep brain stimulation of the subthalamic nucleus in patients with Parkinson's disease.

Degeneration of dopaminergic neurons in the substantia nigra projecting to the striatum is responsible for the motor symptoms in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure to alleviate these symptoms in advanced PD. Yet the mechanism of action, especially the effects of STN-DBS on the availability of striatal dopamine transporter (DAT) as a marker of nigrostriatal nerve cell function, remains largely unknown. The aim of this study was therefore to evaluate whether 1) DAT availability changes within 1 year of STN-DBS and 2) the clinical outcome can be predicted based on preoperative DAT availability. Twenty-seven PD patients (mean age 62.7 ± 8.9 years; mean duration of illness 13.0 ± 4.9 years; PD subtypes: akinetic-rigid, n = 11; equivalence, n = 13; and tremor-dominant, n = 3) underwent [123I]FP-CIT SPECT preoperatively and after 1 year of STN-DBS. DAT availability as determined by the specific binding ratio (SBR) was assessed by volume of interest (VOI) analysis of the caudate nucleus and the putamen ipsilateral and contralateral to the clinically more affected side. Unified Parkinson's Disease Rating Scale (UPDRS) III scores improved significantly (mean preoperative on medication 25.6 ± 12.3, preoperative off medication 42.3 ± 15.2, postoperative on medication/off stimulation 41.4 ± 13.2, and postoperative on medication/on stimulation 16.1 ± 9.4; preoperative on medication vs postoperative on medication/on stimulation, p = 0.006), while the levodopa-equivalent daily dose was reduced (mean preoperative 957 ± 440 mg vs postoperative 313 ± 189 mg, p < 0.001). The SBR did not differ significantly before and 1 year after DBS, regardless of PD subtype. Preoperative DAT availability was not related to the change in UPDRS III score, but the change in DAT availability was significantly correlated with the change in UPDRS III score (contralateral head of the caudate VOI, p = 0.014; contralateral putamen VOI, p = 0.018). Overall, DAT availability did not change significantly after 1 year of STN-DBS. However, on an individual basis, the improvement in UPDRS III score was associated with an increase in DAT availability, whereas DAT availability before STN-DBS surgery did not predict the clinical outcome. Whether a subtype-specific pattern of preoperative DAT availability can become a reliable predictor of successful STN-DBS must be evaluated in larger study cohorts.

Effects of safinamide on pain in patients with fluctuating Parkinson's disease.

BackgroundNon‐motor symptoms (NMS) are integral to Parkinson's Disease (PD) and management remains a challenge. Safinamide is a novel molecule in relation to addressing NMS due to its multifocal mechanism of action with both dopaminergic and non‐dopaminergic properties.ObjectiveTo investigate the efficacy of safinamide on NMS and its burden in PD patients with motor fluctuations after 6 months of treatment.MethodsThis observational, multicenter, open‐label, pilot study assessed a wide range of NMS using the following rating scales, NMSS (non‐motor symptom scale), KPPS (King's PD pain scale), HADS (hospital anxiety and depression scale), PDQ‐8 (Parkinson's disease quality of life questionnaire), and PDSS‐2 (Parkinson's disease sleep scale), EuroQol‐5D 3 level version (EQ‐5D‐3L), CGI‐I (clinical global impression of improvement), and PGI‐C (patient global impression of change). Motor examination using UPDRS part III (Unified Parkinson's disease rating scale, motor examination), UPDRS IV (complications of therapy) and Hoehn and Yahr staging were also obtained.Results27 patients were included in the analysis and were evaluated at baseline and ≥ 6 months after safinamide treatment. 26 patients had a daily maintenance dose of 100 mg and 1 patient a daily dose of 50 mg. Significant improvements in UPDRS IV, KPPS item 5 (region‐specific “off” dystonia), KPPS domain 3 (items 4–6, fluctuation related pain) and KPPS total score were observed after treatment with safinamide, while maintaining stable dopaminergic medication. No statistically significant differences were found in NMSS, HADS, PDSS‐2, EQ‐5D‐3L, and PDQ‐8 after treatment.ConclusionsOur results suggest that safinamide may have a beneficial effect on pain, a key unmet need in fluctuating PD patients.

Rhythm and groove as cognitive mechanisms of dance intervention in Parkinson's disease.

Parkinson's disease (PD) is associated with a loss of internal cueing systems, affecting rhythmic motor tasks such as walking and speech production. Music and dance encourage spontaneous rhythmic coupling between sensory and motor systems; this has inspired the development of dance programs for PD. Here we assessed the therapeutic outcome and some underlying cognitive mechanisms of dance classes for PD, as measured by neuropsychological assessments of disease severity as well as quantitative assessments of rhythmic ability and sensorimotor experience. We assessed prior music and dance experience, beat perception (Beat Alignment Test), sensorimotor coupling (tapping to high- and low-groove songs), and disease severity (Unified Parkinson's Disease Rating Scale in PD individuals) before and after four months of weekly dance classes. PD individuals performed better on UPDRS after four months of weekly dance classes, suggesting efficacy of dance intervention. Greater post-intervention improvements in UPDRS were associated with the presence of prior dance experience and with more accurate sensorimotor coupling. Prior dance experience was additionally associated with enhanced sensorimotor coupling during tapping to both high-groove and low-groove songs. These results show that dance classes for PD improve both qualitative and quantitative assessments of disease symptoms. The association between these improvements and dance experience suggests that rhythmic motor training, a mechanism underlying dance training, impacts improvements in parkinsonian symptoms following a dance intervention.

Antidiabetic Agents for Treatment of Parkinson's Disease: A Meta-Analysis.

Background: Clinical and epidemiological studies suggest that two of the most common geriatric diseases, type 2 diabetes and Parkinson’s disease (PD), are linked. These studies notably suggest that treatment of insulin resistance in type 2 diabetes may beneficially modify the pathophysiology of PD and help to maintain motor and nonmotor function. In this meta-analysis, we evaluate the efficacy of new antidiabetic agents in the treatment of PD. Methods: We systematically searched PubMed, Medline, ProQuest, ScienceDirect, ClinicalKey, and Cochrane Library from the date of their inception until 15 March 2020. Multiple efficacy parameters were compared between treatment groups. The results are expressed as mean differences with 95% confidence intervals (CIs) in a random-effects model. Results: A meta-analysis of the data extracted from three randomized control trials revealed that treatment with exenatide yielded significant improvements in scores on the Unified Parkinson’s Disease Rating Scale Part I (UPDRS-I) (−0.438, 95% CI, −0.828 to −0.048, p = 0.028), UPDRS Part IV (UPDRS-IV) (−0.421, 95% CI, −0.811 to −0.032, p = 0.034) and the Mattis Dementia Rating Scale (MDRS) (−0.595, 95% CI, −1.038 to −0.151, p = 0.009). At the 12-month follow-up, the UPDRS Part III (UPDRS-III) scores in the off-medication phase revealed significant improvements in patients using exenatide (−0.729; 95% CI, −1.233 to −0.225, p = 0.005). Treatment with pioglitazone did not yield significant improvements in UPDRS, MDRS, or Parkinson’s Disease Questionnaire scores. Conclusion: This meta-analysis suggests that exenatide use is associated with the alleviation of cognitive, motor and nonmotor symptoms. However, long-term studies with a large sample size of patients with PD of varying severity are required.

Cortical thickness in visuo-motor areas is related to motor outcomes after STN DBS for Parkinson's disease

IntroductionDeep brain stimulation (DBS) is a widely accepted therapy for Parkinson's disease. While outcome predictors such as levodopa-response are well established, there remains a need for objective and unbiased predictors in clinical practice. We performed an exploratory study to examine whether cortical thickness, derived from preoperative MRI, correlates with postoperative outcome. MethodsUsing freesurfer, we retrospectively measured cortical thickness on the preoperative MRI of 38 patients who underwent bilateral STN-DBS for PD during a 4-year period. The Unified Parkinson Disease Rating motor (UPDRS III) and experiences of daily living subscales (UPDRS II) were collected at baseline and six months after surgery. As an initial analysis, a series of partial correlations was conducted to evaluate the association between postoperative outcome scores and average cortical thickness from predefined regions of interest, adjusting for candidate confounders, without correcting for multiple comparisons. A confirmatory vertex-wise analysis was performed using a cluster-wise correction for multiple comparisons. ResultsBased on the ROI analysis, the strongest correlation with motor outcome was found to be with the left lateral-occipital cortex. Patients with greater cortical thickness in this area presented with greater improvements in motor scores. This relationship was also supported by the vertex-wise analysis. Greater cortical thickness in frontal and temporal regions may be correlated with greater post-operative improvements in UPDRS II, but this was not confirmed in the vertex-wise analysis. ConclusionsOur data indicate that greater cortical thickness in visuo-motor areas is correlated with motor outcomes after DBS for PD. Further prospective investigations are needed to confirm our findings and better-investigate potential image biomarkers.

Clinical outcomes of step-synchronized vibration training in patients of Parkinson’s disease with freezing of gait

OBJECTIVE: To elucidate the effect of step-synchronized vibration training using PDShoe on balance, gait, and quality of life in patients of Parkinson’s disease (PD) with freezing of gait (FOG).MATERIALS AND METHODS: In a pilot study, 17 patients of PD with FOG were recruited for step-synchronized vibration training. The training involved 10 sessions of gait training over 2 weeks. Each session included three 6-min bouts of walking with step-synchronized vibration applied to the second metatarsal head and medial surface of calcaneus. Participants were assessed with the Unified Parkinson’s Disease Rating Scale-III (UPDRS III), Timed Up and Go (TUG) test, Berg Balance Scale (BBS), Timed 10-Meter Walk Test, Freezing of Gait Questionnaire (FOG-Q), Falls Efficacy Scale-International (FES-I), and Parkinson’s Disease Questionnaire-39 (PDQ-39). Measurements were collected pre-intervention, post-intervention, and at a 2-week follow-up. Friedman test followed by Wilcoxon signed-rank test were used for statistical analysis.RESULTS: All participants completed the intervention without any adverse effects. Fifteen participants reported for a follow-up evaluation 2 weeks after intervention. There was statistically significant improvement in UPDRS III (P = 0.044) and significant improvement in TUG test (P = 0.005), BBS (P = 0.026), FES-I (P = 0.041), and PDQ-39 (P = 0.021) scores between pre and follow-up evaluations. No significant changes were seen in FOG-Q and Timed 10-Meter Walk Test.CONCLUSION: Step-synchronized vibration is a novel intervention to improve balance, gait, motor features, and quality of life in patients of PD with FOG. Further research is warranted to confirm the results found in this pilot study.

Deep brain stimulation outcomes in patients implanted under general anesthesia with frame-based stereotaxy and intraoperative MRI.

OBJECTIVEThe authors' aim in this study was to evaluate placement accuracy and clinical outcomes in patients who underwent implantation of deep brain stimulation devices with the aid of frame-based stereotaxy and intraoperative MRI after induction of general anesthesia.METHODSThirty-three patients with movement disorders (27 with Parkinson's disease) underwent implantation of unilateral or bilateral deep brain stimulation systems (64 leads total). All patients underwent the implantation procedure with standard frame-based techniques under general anesthesia and without microelectrode recording. MR images were acquired immediately after the procedure and fused to the preoperative plan to verify accuracy. To evaluate clinical outcome, different scales were used to assess quality of life (EQ-5D), activities of daily living (Unified Parkinson's Disease Rating Scale [UPDRS] part II), and motor function (UPDRS part III during off- and on-medication and off- and on-stimulation states). Accuracy was assessed by comparing the coordinates (x, y, and z) from the preoperative plan and coordinates from the tip of the lead on intraoperative MRI and postoperative CT scans.RESULTSThe EQ-5D score improved or remained stable in 71% of the patients. When in the off-medication/on-stimulation state, all patients reported significant improvement in UPDRS III score at the last follow-up (p < 0.001), with a reduction of 25.2 points (46.3%) (SD 14.7 points and 23.5%, respectively). There was improvement or stability in the UPDRS II scores for 68% of the Parkinson's patients. For 2 patients, the stereotactic error was deemed significant based on intraoperative MRI findings. In these patients, the lead was removed and replaced after correcting for the error during the same procedure. Postoperative lead revision was not necessary in any of the patients. Based on findings from the last intraoperative MRI study, the mean difference between the tip of the electrode and the planned target was 0.82 mm (SD 0.5 mm, p = 0.006) for the x-axis, 0.67 mm (SD 0.5 mm, p < 0.001) for the y-axis, and 0.78 mm (SD 0.7 mm, p = 0.008) for the z-axis. On average, the euclidian distance was 1.52 mm (SD 0.6 mm). In patients who underwent bilateral implantation, accuracy was further evaluated comparing the first implanted side and the second implanted side. There was a significant mediolateral (x-axis) difference (p = 0.02) in lead accuracy between the first (mean 1.02 mm, SD 0.57 mm) and the second (mean 0.66 mm, SD 0.50 mm) sides. However, no significant difference was found for the y- and z-axes (p = 0.10 and p = 0.89, respectively).CONCLUSIONSFrame-based DBS implantation under general anesthesia with intraoperative MRI verification of lead location is safe, accurate, precise, and effective compared with standard implantation performed using awake intraoperative physiology. More clinical trials are necessary to directly compare outcomes of each technique.

Land Plus Aquatic Therapy Versus Land-Based Rehabilitation Alone for the Treatment of Balance Dysfunction in Parkinson Disease: A Randomized Controlled Study With 6-Month Follow-Up

ObjectivesTo assess whether a specific land-based physical intervention with the inclusion of aquatic therapy is more effective than land-based rehabilitation alone for the treatment of balance dysfunction in patients with Parkinson disease (PD), immediately after therapy and at 6 months' follow-up. DesignRandomized controlled study with 6-month follow-up. SettingA PD and brain injury rehabilitation department in a general hospital. ParticipantsPatients (N=34) with moderate-stage PD. InterventionSeventeen patients underwent a land-based rehabilitation protocol called multidisciplinary intensive rehabilitation treatment (MIRT), and 17 underwent MIRT plus aquatic therapy (MIRT-AT). Main Outcome MeasuresThe primary outcome measure was the Berg Balance Scale (BBS); secondary outcome measures were the Unified Parkinson Disease Rating Scale parts II and III (UPDRS II/III) and the Timed Up and Go (TUG) test. These measures were assessed in both groups at admission, at discharge, and after 6 months. ResultsBBS improved after treatment in both groups. Even though no statistically significant difference between groups was observed at each observation time, BBS scores at follow-up were significantly higher than at baseline in MIRT-AT patients. Both groups also showed an improvement in UPDRS II/III and TUG at the end of treatment compared with baseline, but these findings were lost at the 6-month follow-up. ConclusionsAquatic therapy added to land-based rehabilitation could provide a contribution to the treatment of balance dysfunction in patients with moderate-stage PD.

Analysis of pramipexole dose-response relationships in Parkinson's disease.

BackgroundPramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson’s disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined.MethodsChinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson’s Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment.ResultsSustained-release (SR) and immediate-release (IR) PPX showed similar efficacy based on score changes at 18 weeks, with comparable tolerability. Approximately two-third of patients received PPX at ≥1.5 mg/d, and one fourth of patients had ≥20% tremor contribution to UPDRS II+III. After treatment, patients receiving PPX ≥1.5 mg/d showed better improvement in UPDRS II+III scores (P=0.0025), with similar trends with the IR and SR formulations. Patients with ≥20% tremor contribution showed better improvement in UPDRS II+III scores (P=0.0017). No differences were seen based on PD stage or combined levodopa dose. The overall proportions of adverse events (AEs) were similar. More patients discontinued because of intolerable side effects, and more investigator-defined drug-related AEs were recorded in the <1.5 mg/d subgroup.ConclusionUPDRS II+III improvement was better with PPX ≥1.5 than with <1.5 mg/d in Chinese PD patients after 18 weeks of treatment, with similar trends seen with IR and SR formulations. The frequency of AEs in PPX ≥1.5 and <1.5 mg/d subgroups was similar.

Effects of Nordic walking training on functional parameters in Parkinson's disease: a randomized controlled clinical trial.

We compare the effects of Nordic walking training (NW) and Free walk (FW) on functional parameters (motor symptoms, balance) and functional mobility (Timed Up and Go at Self-selected Speed - TUGSS, and at forced speed, TUGFS; Self-selected Walking Speed, SSW; locomotor rehabilitation index, LRI) of Parkinson's disease (PD) patients. The study included 33 patients with clinical diagnosis of idiopathic PD, and staging between 1 and 4 in the Hoehn and Yahr scale (H&Y) randomized into two groups: NW (N=16) and FW (N=17) for 6weeks. Baseline characteristics were compared trough a one-way ANOVA. Outcomes were analyzed using the Generalized Estimation Equations (GEE) with a Bonferroni post-hoc. Data were analyzed using SPSS v.20.0. Improvements in UPDRS III (P<0.001), balance scores (P<0.035), TUGSS distance (P<0.001), TUGFS distance (P<0.001), SSW (P<0.001), and LRI (P<0.001) were found for both groups. However, the NW group showed significant differences (P<0.001) when compared to the FW group for the functional mobility. We conclude the NW improves functional parameters and walking mobility demonstrating that NW is as effective as the FW, including benefits for FW on the functional mobility of people with PD.

Connecting with Kinect(R) To Improve Motor and Gait Function in Parkinson Disease (P01.176)

Objective: To investigate whether the Xbox Kinect® system provides benefit in reducing motor abnormalities of Parkinson Disease (PD) Background Recent studies suggest patients with PD benefit from enhanced physical activity and exercise, including Tai Chi, Qi Kong, Yoga and others. We previously explored the effect of large amplitude exercise and Nintendo Wii ® in Parkinson Disease (PD) and found it to be effective in reducing motor symptoms in PD. The Xbox Kinect® system provides a similar platform for exercise, but without need of external controllers. We investigated whether use of this system would provide similar benefits for PD patients. Design/Methods: Prospective case series. We randomly selected 12 PD patients who enrolled in the Xbox Kinect ® game exercise program; exercises included aquarium, trackf week #8: 1-10/9-38 (average 7.3/23.9). Mean improvement on UPDRS II/III: 21%/20% [week #4] and 45%/32% [week #8]. Baseline TGB score ranged 16-25 (average 19.5). TGB scores following treatment: week #4: 15-26 (average 20.6); week #8: 8-28 (average 24.4). Mean improvement on TGB: 2% [week #4] and 20% [week #8]. Conclusions: In our study, motor abnormalities and gait dysfunction improved in participants utilizing Xbox Kinect® exercise as demonstrated by improvements in UPDRS and TGB endpoints. Disclosure: Dr. Alvarez has received personal compensation for activities with Teva Neuroscience, Pfizer Inc, and USWorldMeds as a speaker and/or consultant. Dr. Grogan has received personal compensation for activities with Pfizer Inc. and US Worldmeds as a speaker.

Motor Cortex Stimulation in Parkinson's Disease

Motor Cortex Stimulation (MCS) is less efficacious than Deep Brain Stimulation (DBS) in Parkinson's disease. However, it might be proposed to patients excluded from DBS or unresponsive to DBS. Ten patients with advanced PD underwent unilateral MCS contralaterally to the worst clinical side. A plate electrode was positioned over the motor cortex in the epidural space through single burr hole after identification of the area with neuronavigation and neurophysiological tests. Clinical assessment was performed by total UPDRS, UPDRS III total, UPDRS III-items 27–31, UPDRS IV, and UPDRS II before implantation in off-medication and on-medication states and after surgery at 1, 3, 6, 12, 18, 24, and 36 months in on-medication/on-stimulation and off-medication/on-stimulation states. We assessed changes of quality of life, throughout the Parkinson's disease quality of life scale (PDQoL-39), and the dose of anti-Parkinson's disease medications, throughout the Ldopa equivalent daily dose (LEDD). During off-medication state, we observed moderate and transitory reduction of total UPDRS and UPDRS total scores and significant and long-lasting improvement in UPDRS III items 27–31 score for axial symptoms. There was marked reduction of UPDRS IV score and LEDD. PDQL-39 improvement was also significant. No important complications and adverse events occurred.

Chronic Subcutaneous Infusion Therapy with Apomorphine in Advanced Parkinson's Disease Compared to Conventional Therapy: A Real Life Study of Non Motor Effect

Apomorphine infusion therapy remains under-used and there are no comparative studies of motor and non-motor effects of apomorphine infusion. In this paper we report preliminary results from an ongoing clinical observational "real life" surveillance-based study focused on effects of this therapy on non-motor symptoms and health-related quality of life in a group of patients on apomorphine. Apomorphine infusion led to highly significant improvements in UPDRS 3 (p = 0.0003), UPDRS 4 (p = 0.0003), PDQ-8 (Parkinson's disease questionnaire, p = 0.001) and NMSS total (non motor symptoms scale, p = 0.0003). Furthermore, apomorphine was tolerated in patients with visual hallucinations, illusions and paranoid ideations while significant improvement in specific non-motor symptoms such as hyperhidrosis, nocturia, urgency of micturition, and fatigue was recorded. Levodopa equivalent dose decreased significantly (1077.81 ± 446.26 to 458.75 ± 282.29, p < 0.0001) and a large effect size of intervention was noted. In an untreated group no such improvement was noted. The number needed to treat (NNT) for improvement >1 SEM in the Apo group was calculated and was lower than 2 for >1 SEM improvement of UPDRS 3, NMSS, and PDQ-8 total scores. This pilot observational study suggests that non-motor effects are evident with apomorphine therapy and patients suitable for apomorphine deteriorate in the absence of therapy.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.

Relationship Between the Striatal and Cerebellar Glucose Metabolism and the Response to Levodopa Treatment in Patients With Multiple System Atrophy

Introduction: About two thirds of the patients w ith multiple system atrophy (MSA) do not respond to levodopa treatment. Postmortem pathological studies and one retrospective [F]-deoxyglucose positron em ission tom ography (FDG PET) study attributed such poor response to the stria ta l degeneration. W e prospective ly investigated the re lationsh ip between levodopa respons iveness and the m etabo lic activ ities o f the stria tum and cerebellum in M SA patients. M ethods: In 39 patients w ith M SA, the UPDRS m otor score was assessed and two sets of tim ed m otor tests were performed before and after the levodopa treatment. After quantitative FDG PET and baseline eva luation, treatm ent was started w ith 3 tab lets o f S inem et 25/250 m g a day. C lin ica l assessm ents were perform ed m onth ly for three m onths. M etabo lic activ ities o f the caudate, anterior putam en, posterior putam en, cerebe llar cortex and cerebe llar verm is were m easured. W e com pared the m easurem ents w ith m ean percentage changes of m otor function. A lso, us ing statistica l param etric m app ing (SPM ) ana lys is, we tried to find bra in areas in wh ich m etabo lism corre lated w ith the c lin ica l changes. Resu lts: M ean percentage im provem ents of UPDRS m otor scores were corre la ted w ith g lucose m etabo lism in the posterior putam en and cerebellar verm is. The m ean percentage im provem ents of perform ance in Purdue peg board test correlated w ith the glucose metabolism in the cerebellar cortex and verm is. In SPM analysis, cerebellar glucose metabolism correlated w ith the im provem ent of UPDRS m otor score and the perform ance o f two tim ed m otor tests . Conc lus ion: The integrity o f cerebe llum , as we ll as posterior putam en, m ay be an im portant factor for show ing the response to levodopa. Journal of Movement Disorders 1(1):26-32, 2008

The Parkinson–Control study: A 1‐year randomized, double‐blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease

Dopamine agonists have been recommended as early treatment for Parkinson's disease (PD), alone or combined with levodopa. Piribedil is a non-ergot selective D(2)/D(3) agonist with alpha(2) antagonist properties shown to be effective in the treatment of PD. This 12-month international, randomized, double-blind trial aimed to assess the efficacy of piribedil 150 mg versus bromocriptine 25 mg, in early combination with levodopa in Stage I to III PD patients. Motor efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS III, Items 18-31) as improvement from baseline. Response rate was defined as a 30% improvement. Among the 425 randomly assigned patients, 178 were also included in a substudy on cognitive follow-up evaluated by a dysexecutive syndrome oriented battery. A relevant improvement in UPDRS III over the 12-month study duration was observed both in the piribedil and bromocriptine groups (-7.9 +/- 9.7 points from baseline versus -8.0 +/- 9.5; not significant [n.s.]) with a response rate of 58.4% and 55.3% (n.s.), respectively. Piribedil and bromocriptine resulted in similar improvement on all UPDRS III subscores. Piribedil patients required less levodopa dose increase than those on bromocriptine. Cognitive performance remained generally unchanged in both groups, with a significant effect of piribedil limited to the Wisconsin Card Sorting Test. An overall good tolerability of piribedil was observed. Early combination of piribedil 150 mg with levodopa resulted in significant long-term improvement of all motor symptoms in PD patients insufficiently controlled by levodopa alone. Taking into account both efficacy and acceptability in the long-term, piribedil proved in this bromocriptine controlled study to be an effective and safe treatment for PD.