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Background Available essential tremor (ET) therapies have limitations. Objectives The objective of this study was to evaluate CX-8998, a selective T-type calcium channel modulator, in essential tremor. Methods Patients 18-75 years old with moderate to severe essential tremor were randomized 1:1 to receive CX-8998 (titrated to 10 mg twice daily) or placebo. The primary end point was change from baseline to day 28 in The Essential Tremor Rating Assessment Scale performance subscale scored by independent blinded video raters. Secondary outcomes included in-person blinded investigator rating of The Essential Tremor Rating Assessment Scale performance subscale, The Essential Tremor Rating Assessment Scale activities of daily living subscale, and Kinesia ONE accelerometry. Results The video-rated The Essential Tremor Rating Assessment Scale performance subscale was not different for CX-8998 (n = 39) versus placebo (n = 44; P = 0.696). CX-8998 improved investigator-rated The Essential Tremor Rating Assessment Scale performance subscale (P = 0.017) and The Essential Tremor Rating Assessment Scale activities of daily living (P = 0.049) but not Kinesia ONE (P = 0.421). Adverse events with CX-8998 included dizziness (21%), headache (8%), euphoric mood (6%), and insomnia (6%). Conclusions The primary efficacy end point was not met; however, CX-8998 improved some assessments of essential tremor, supporting further clinical investigation. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Introduction Patients with Parkinson's disease (PD) are at increased risk for hospitalization and often experience worsening of PD when hospitalized. It is therefore important to identify strategies to prevent hospitalization. Methods Hospital encounter rates in different Parkinson's Foundation Centers of Excellence in United States, Canada, Israel and the Netherlands were analyzed as part of the Parkinson Foundation Parkinson's Outcomes Project (PF-POP). Multivariate logistic regression was used to estimate the odds ratio for hospitalization, adjusted for risk factors. Results Baseline age, disease duration, other relative than spouse/partner as care giver, cancer, arthritis, other comorbidities, falls, use of levodopa, use of dopamine agonist, use of COMT inhibitor, occupational therapy before the baseline visit, PDQ-39, MSCI total score and time between visits were significantly associated with the risk of hospital encounters. After adjustment for these factors, two centers had significantly lower odds for hospitalization admission and ER visit (minimum OR 0.3) and four centers had significantly higher odds (maximum OR 1.5) than the average center. Four centers had significantly lower hazard ratios for time to re-hospitalization compared to the average center. Reducing hospital admission rates in those centers with higher than average rates would reduce overall hospitalizations by 11%. Applied to PD patients over 65 nationwide this represents a potential for cost savings of greater than $1 billion over 48 months. Conclusion Encounter rates vary even across expert centers and suggest that practices carried out in some centers may reduce the risk of hospitalization. Further research will be necessary to identify these practices and implement them more widely to improve care for people with PD.

Background Levodopa is the most efficacious medication in controlling the motor symptoms of Parkinson's disease (PD). There continues to be a controversy as to whether levodopa remains effective after years of therapy. Objective To assess the long-term effectiveness of levodopa in PD patients. Methods The response to levodopa in PD patients undergoing a levodopa challenge for deep brain stimulation (DBS) surgery evaluation from June 1997 through March 2017 were evaluated. The patients were broken into four groups based on disease duration (Group I: 0- 5 years, Group II: 6- 10 years, Group III: 11- 15 years, and Group IV:≥16 years). Levodopa response was calculated based on the changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor and activities of daily living (ADL) scores in the medication ON and OFF states. Results A total of 361 PD patients were included. The mean age in Group I was 59.4 years with a mean disease duration of 3.9 years (n = 29), Group II was 61 years with a mean disease duration of 8.1 years (n = 131), Group III was 64 years with a mean disease duration of 12.8 years (n = 143), and IV was 66.5 years with a mean disease duration of 18.5 years (n = 58). There was a significant improvement in UPDRS motor and ADL scores after the levodopa challenge for all groups. Conclusions In a subgroup of PD patients who were evaluated for DBS surgery, there was a marked improvement in UPDRS motor and ADL scores which did not decrease with disease progression.

Levodopa is the mainstay of treatment in Parkinson's disease (PD). As the disease progresses, variations in plasma levodopa levels lead to motor fluctuations. The common reasons behind variations in the plasma levels include delayed gastric emptying, small intestinal bacterial overgrowth, protein interaction with levodopa absorption, and limited oral bioavailability of levodopa. Efforts to find newer delivery systems for older drugs to avoid the problems associated with oral delivery of medications are continuing. This review aims to provide up-to-date information about the newer delivery options for drugs used for PD and provides a summary of infusion therapy with apomorphine, modifications to other dopamine agonists, various oral formulations of carbidopa/levodopa, inhaled levodopa, intrajejunal infusion of levodopa, and sublingual apomorphine. The advantages, dose, and adverse effects of each treatment modality are reviewed. We also discuss several drugs under investigation, such as the subcutaneous carbidopa/levodopa infusion and subcutaneous rotigotine.

Highlights • 2864 persons from the IETF database responded to the survey. • 28% of respondents were not receiving medical care for their tremor. • In 33% of respondents, tremor was not treated., Introduction Essential tremor (ET) is one of the most common movement disorders; however, many patients are misdiagnosed and do not receive effective treatment. It is important to better understand the diagnosis, symptoms and treatment patterns to improve care for those with ET. Methods Persons in the International Essential Tremor Foundation database were invited to complete an online survey, focusing on symptoms, diagnosis, and treatment of ET. Results The survey was emailed to 19,206 persons, with 2864 (14.9%) respondents. Mean age was 65.4 years, median age of tremor onset was 36–40 years, 61% were women, and 64% had a known family history of tremor. Forty-five percent saw multiple physicians before a diagnosis of ET with 65% being diagnosed by a neurologist. Current care is provided by a neurologist in 42%, a family physician in 26% and 28% do not see a physician for ET. Tremor was most commonly reported in the hands/arms (95%). The most commonly affected daily activities included writing, eating, drinking and carrying. Beta-blockers were the most commonly used treatment (42%); however, 33% had no benefit and 35% discontinued due to side effects. Of note, 33% had never received treatment for their tremor. Conclusion This survey highlights the need for more effective treatments with greater tolerability. Increased awareness among physicians and patients in the diagnosis and treatment of ET is also warranted, with nearly half the respondents seeing multiple physicians before receiving an ET diagnosis and nearly 30% not seeing a physician and/or not receiving treatment for ET.

Background: Individuals with Parkinson’s disease (PD) may need to spend more mental and physical effort (i.e., cognitive workload) to maintain postural control. Pupillary response reflects cognitive workload during postural control tasks in healthy controls but has not been investigated as a measure of postural demand in PD.Objectives: To compare pupillary response during increased postural demand using vision occlusion and dual tasking between individuals with PD and healthy controls.Methods: Thirty-three individuals with PD and thirty-five healthy controls were recruited. The four conditions lasted 60 s and involved single balance task with eyes open; single balance task with eyes occluded; dual task with eyes open; dual task with eyes occluded. The dual task comprised the Auditory Stroop test. Pupillary response was recorded using an eye tracker. The balance was assessed by using a force plate. Two-way Repeated Measures ANOVA and LSD post-hoc tests were employed to compare pupillary response and Center of Pressure (CoP) displacement across the four conditions and between individuals with PD and healthy controls.Results: Pupillary response was higher in individuals with PD compared to healthy controls (p = 0.009) and increased with more challenging postural conditions in both groups (p < 0.001). The post-hoc analysis demonstrated increased pupillary response in the single balance eyes occluded (p < 0.001), dual task eyes open (p = 0.01), and dual task eyes occluded (p < 0.001) conditions compared to single task eyes open condition.Conclusion: Overall, the PD group had increased pupillary response with increased postural demand compared to the healthy controls. In the future, pupillary response can be a potential tool to understand the neurophysiological underpinnings of falls risk in the PD population.

Dopaminergic mechanisms regulating cognitive and motor control were evaluated comparing visuoperceptual and perceptuomotor functions in Parkinson’s disease (PD). The performance of PD patients (n = 40) was contrasted with healthy controls (n = 42) across two separate visits (on and off dopaminergic medications) on computerized tasks of perception and aiming to a target at variable stimulus lengths (4, 8, 12 cm). Novel visuoperceptual tasks of length equivalence and width interval estimations without motor demands were compared with tasks estimating spatial deviation in movement termination. The findings support the presence of spatial deficits in early PD, more pronounced with increased discrimination difficulty, and with shorter stimulus lengths of 4 cm for both visuoperceptual and perceptumotor functions. Dopaminergic medication had an adverse impact on visuoperceptual accuracy in particular for length equivalence estimations, in contrast with dopaminergic modulation of perceptuomotor functions that reduced angular displacements toward the target. The differential outcomes for spatial accuracy in perception versus movement termination in PD are consistent with involvement of the direct pathway and models of progressive loss of dopamine through corticostriatal loops. Future research should develop validated and sensitive standardized tests of perception and explore dopaminergic selective deficits in PD to optimize medication titration for motor and cognitive symptoms of the disease.

Background Parkinson’s disease (PD) and essential tremor (ET) are movement disorders that can have similar clinical characteristics including tremor and gait difficulty. These disorders can be misdiagnosed leading to delay in appropriate treatment. The aim of the study was to determine whether balance and gait variables obtained with wearable inertial motion sensors can be utilized to differentiate between PD and ET using machine learning. Additionally, we compared classification performances of several machine learning models. Methods This retrospective study included balance and gait variables collected during the instrumented stand and walk test from people with PD (n = 524) and with ET (n = 43). Performance of several machine learning techniques including neural networks, support vector machine, k-nearest neighbor, decision tree, random forest, and gradient boosting, were compared with a dummy model or logistic regression using F1-scores. Results Machine learning models classified PD and ET based on balance and gait characteristics better than the dummy model (F1-score = 0.48) or logistic regression (F1-score = 0.53). The highest F1-score was 0.61 of neural network, followed by 0.59 of gradient boosting, 0.56 of random forest, 0.55 of support vector machine, 0.53 of decision tree, and 0.49 of k-nearest neighbor. Conclusions This study demonstrated the utility of machine learning models to classify different movement disorders based on balance and gait characteristics collected from wearable sensors. Future studies using a well-balanced data set are needed to confirm the potential clinical utility of machine learning models to discern between PD and ET.

Deep brain stimulation (DBS) of subthalamic nucleus (STN) can effectively control motor complications in Parkinson disease (PD). The outcome of DBS therapy depends on lead placement in the dorsolateral aspect of STN, as well as post-DBS programming. Effective DBS programming requires knowledge of side effects/complications related to stimulation. One of the infrequent complications of STN DBS is stimulation-induced dyskinesia, which can present similar to levodopa-induced dyskinesia with choreiform, ballistic, or dystonic movements. Stimulation-induced dyskinesia can be bothersome and can interfere with effective control of motor symptoms because typically the contact causing dyskinesia is the most effective in improving motor symptoms. This chapter discusses clinical presentation and management strategies in a patient with tremor-predominant PD who developed stimulation-induced dyskinesia. After trying multiple programming parameters, patient tremor and dyskinesia were effectively controlled on interleaved programming settings. The authors conclude that interleaving DBS programming can be a potential option for management of stimulation-induced dyskinesia.

Objective To investigate the reliability and validity of pupillary response during dual-task balance conditions in individuals with Parkinson disease (PD). Design Cross-sectional study. Setting University of Kansas Medical Center Parkinson's Disease and Movement Disorder Center. Participants Participants (N=68) included individuals with PD (n=33) and healthy controls (n=35). Interventions Not applicable. Main Outcome Measures Pupillary response was the main outcome measure that was measured during the following conditions: single-task balance eyes open, single-task balance eyes occluded, dual-task eyes open, and dual-task eyes occluded. After each condition, the National Aeronautics and Space Administration-Task Load Index (NASA-TLX) was administered to assess self-reported cognitive workload. To examine the test-retest reliability of the pupillary response, the conditions were administered twice for each individual within 2 hours. Intraclass correlation coefficients (ICC) were used to analyze the test-retest reliability of pupillary response in each condition for both groups. Pearson’s r correlation was used to assess the convergent validity of pupillary response against the NASA-TLX. Results The test-retest reliability was excellent for both groups in almost all conditions (ICC>0.75). There were no correlations between pupillary response and the NASA-TLX. However, increased mental demand (a subitem of the NASA-TLX) significantly correlated with increased pupillary response in individuals with PD (r=0.38; P=.03). Conclusions Pupillary response showed excellent test-retest reliability and validity during dual-task balance for individuals with PD and healthy controls. Overall, these results suggest that pupillary response represents a stable index of cognitive workload during dual-task balance in individuals with PD.

BackgroundWe undertook this study to identify patients with Parkinson disease (PD) with no or rare falls who may progress to frequent falling by their next annual follow-up visit.MethodsWe analyzed data in the National Parkinson Foundation Quality Improvement Initiative database to identify factors predicting which patients with PD with no or rare falls at the baseline visit will report at least monthly falls at the annual follow-up visit. Multivariable models were constructed using logistic regression. Variables were introduced in 4 blocks: in the 1st block, variables present at or before the baseline visit were entered; in the 2nd, baseline visit assessments; in the 3rd, interventions implemented during baseline visit; and, in the 4th block, changes in comorbidities, living situation, and treatment between visits.ResultsOf 3,795 eligible participants, 3,276 (86.3%) reported no or rare falls at baseline visit, and of them, 382 (11.7%) reported at least monthly falls at follow-up visit. Predictors included female sex, ConclusionsThis large-scale analysis identified several predictors of progression to falling in PD. Such identifiers may help target patient subgroups for falls prevention intervention. Some factors are modifiable, offering opportunities for developing such interventions.

Levodopa-induced dyskinesia (LID) is a common motor complication in patients with Parkinson's disease on chronic levodopa therapy. The management of LID is important as dyskinesia can be disabling and impair quality of life. Currently, there are limited treatment options for the medical management of LID. Amantadine extended-release capsules (Gocovri™) is the first medication that received US Food and Drug Administration approval for the treatment of LID. The following is a review of the pharmacodynamics, efficacy and safety profile, and current state of treatment of amantadine for LID.

Object We review our experience with Parkinson's disease (PD) patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) and then developed noninfectious, non-hemorrhagic, delayed, symptomatic brain edema associated with a DBS lead. Methods All PD patients who underwent STN DBS lead implantation from 2007 to 2015 were included. The same neurosurgeon performed all surgeries, typically in staged fashion, utilizing single pass microelectrode recordings (MER) within a stereotactic frame. A brain CT was obtained in recovery and subsequently if indicated. Results There were 189 patients who underwent 363 STN lead implantations among which 35 (9.6%) represent re-implantations of removed leads in 28 (14.8%) patients. Among the 363 STN leads implanted, there were 12 (3.3%) cases of delayed symptomatic edema associated with a DBS lead involving 10 (5.3%) of the patients studied. Of the 328 leads representing first-time operations, there were 9 (2.1%) cases of delayed symptomatic edema in 7 (3.7%) patients, one of whom (14.3%) presented with seizures. For lead re-implantations, there were 3 (8.6%) cases of the brain edema in 3 (10.7%) patients; all presenting with seizures. For the 35 re-implantations, the trajectory to target was the same or very similar via the same burr hole as prior surgery in 17 (48.6%); 3 (17.6%) of whom developed edema. There was no case of brain edema in the 18 re-operated cases using a different burr opening. Edema patients were treated with a course of anticonvulsant medication and dexamethasone. Lead-associated edema resolved over generally a 4 to 6-week course. Conclusions Noninfectious, non-hemorrhagic, delayed, symptomatic brain edema occurs in approximately 3% of implanted leads and is more common in re-implantations (9%) compared to new implantations (2%). In re-implantations, the edema is more common when the same trajectory is used (18%) compared to a new trajectory (0%). The edema generally occurs 3 to 8 days after implantation, although immediate post-op CT is normal and seizures are a common presenting feature.

Post-operative, non-hemorrhagic, non-infectious symptomatic delayed edema around the DBS lead is an uncommon complication of DBS surgery. We investigated whether this complication impacts clinical outcomes or has long-term sequelae.All Parkinson's disease (PD) patients with subthalamic nucleus (STN) DBS implantation who developed delayed symptomatic lead edema were identified. UPDRS part III motor, Parkinson's Disease Questionnaire (PDQ-39) total and MoCA scores were analyzed to assess motor outcome, quality of life and cognitive status at 1 year.A total of 260 patients underwent 482 STN lead placements. Of these, 16 patients (20 leads, 4.1% of total 482 leads) developed this delayed complication. None of the patients had edema on immediate post-operative scan. Patients presented with varied symptoms including speech difficulty (n = 8), mild confusion (n = 6), headaches (n = 4), gait difficulty (n = 4) and seizures (n = 3). The mean duration for the diagnosis was 5.8 days after lead implantation and the mean duration for which follow-up CT scans reported complete/near complete resolution or improvement of edema was 4.7 weeks (range 2-10 weeks). At 1-year post-DBS, UPDRS motor scores improved significantly (42.5%, p .001); quality of life improved, but the change was not statistically significant (21.3%, p = .197). There was no decline in cognitive function at 1 year (26.6 vs 26.4, p = .567). No long-term complication related to lead edema occurred in these patients.Symptomatic lead edema after DBS surgery is an uncommon complication which typically resolves over time. In our series, there were no long-term sequelae of this complication and clinical outcomes were comparable to that reported in the literature.

INTRODUCTION Levodopa-induced dyskinesia (LID) is a significant impediment to the long-term use of levodopa for Parkinson's disease (PD). Relatively few studies exist that have described safe and effective therapy for LID. There is thus a significant need for therapy that can control LID to allow for greater sustainability of levodopa therapy. Amantadine extended release (ER) is currently the only FDA-approved medication for the treatment of LID. While other medications have demonstrated efficacy in treating the motor symptoms of PD, amantadine ER is the only one that has been shown, in several clinical trials, to reduce LID and reduce OFF time. Areas Covered: In this review, the authors present the findings of amantadine ER including its efficacy and safety. The authors also provide their expert perspectives on its use and its future prospects. Expert opinion: Several therapies are currently being used and studied for controlling LID, an unmet need in therapy for PD. Amantadine ER has potential to supplement levodopa therapy in PD and improve patient therapeutic outcomes.

© 2019 International Parkinson and Movement Disorder Society, Background: Essential tremor is one of the most prevalent movement disorders. Many treatments for essential tremor have been reported in clinical practice, but it is uncertain which options have the most robust evidence. The International Parkinson and Movement Disorder Society commissioned a task force on tremor to review clinical studies of treatments for essential tremor. Objectives: To conduct an evidence-based review of current pharmacological and surgical treatments for essential tremor, using standardized criteria defined a priori by the International Parkinson and Movement Disorder Society. Methods: We followed the recommendations of the International Parkinson and Movement Disorder Society Evidence Based Medicine Committee. Results: Sixty-four studies of pharmacological and surgical interventions were included in the review. Propranolol and primidone were classified as clinically useful, similar to Topiramate, but only for doses higher than 200 mg/day. Alprazolam and botulinum toxin type A were classified as possibly useful. Unilateral Ventralis intermedius thalamic DBS, radiofrequency thalamotomy, and MRI-guided focused ultrasound thalamotomy were considered possibly useful. All the above recommendations were made for limb tremor in essential tremor. There was insufficient evidence for voice and head tremor as well as for the remaining interventions. Conclusion: Propranolol, primidone, and topiramate (>200 mg/day) are the pharmacological interventions in which the data reviewed robustly supported efficacy. Their safety profile and patient preference may guide the prioritization of these interventions in clinical practice. MRI-guided focused ultrasound thalamotomy was, for the first time, assessed and was considered to be possibly useful. There is a need to improve study design in essential tremor and overcome the limitation of small sample sizes, cross-over studies, short-term follow-up studies, and use of nonvalidated clinical scales.

Background We aimed at critically appraising the clinimetric properties of existing pain scales or questionnaires and to give recommendations for their use in Parkinson's disease (PD). Methods Clinimetric properties of pain scales used in PD were systematically evaluated. A scale was classified as ‘recommended’ if was used in PD, showed adequate clinimetric properties, and had been used by investigators other than the original developers; as ‘suggested’ if it was used in PD and fulfilled only one other criterion; and as ‘listed’ if it was used in PD but did not meet the other criteria. Only scales rating pain intensity or for syndromic classification were assessed. Results Eleven of the 34 scales initially considered fulfilled inclusion criteria. Among the scales rating pain intensity, the “Brief Pain Inventory short form,” “McGill Pain Questionnaire short and long forms,” “Neuropathic Pain Symptoms Inventory,” “11-point Numeric Rating Scale,” “10-cm Visual Analog Scale,” and “Pain-O-Meter” were “recommended with caution” because of lack of clinimetric data in PD, whereas the “King's PD Pain Scale” was “recommended.” Among scales for pain syndromic classification, the “DN4” was “recommended with caution” because of lack of clinimetric data in PD; the “Leeds Assessment of Neuropathic Symptoms and Signs,” “Pain-DETECT,” and the “King's PD Pain Scale” were “suggested.” Conclusions King's PD pain scale can be recommended for the assessment of pain intensity in PD. Syndromic classification of pain in PD may be achieved by the DN4, but clinimetric data in PD are needed for this scale.

Non-motor symptoms (NMS) including sleep disorders, anxiety, depression, fatigue, and cognitive decline can significantly impact quality of life in people with PD. Qigong exercise is a mind-body exercise that shows a wide range of benefits in various medical conditions. The purpose of this study was to investigate the effect of Qigong exercise on NMS with a focus on sleep quality. Seventeen participants completed a 12-week intervention of Qigong (n = 8) or sham Qigong (n = 9). Disease severity, anxiety and depression levels, fatigue, cognition, quality of life, and other NMS of the participants were evaluated prior to the intervention and at the end of the 12-week intervention. After the intervention, both Qigong and sham-Qigong group showed significant improvement in sleep quality (p < 0.05) and overall NMS (p < 0.05). No significant difference was found between groups. Qigong exercise has the potential as a rehabilitation method for people with PD, specifically alleviating NMS in PD. However, this finding needs to be carefully considered due to the small sample size and potentially low intervention fidelity of this study.

Deep brain stimulation (DBS) is an effective therapy for Parkinson's disease (PD). However, its effect in older patients is not extensively studied, as they are often excluded from DBS surgery due to concerns of complications or reduced benefit. We assessed clinical outcomes after subthalamic nucleus (STN) DBS in older patients (age 75 years) with PD.All PD patients above 75 years who underwent STN-DBS between 1999 and 2015 were included. Unified Parkinson's Disease Rating Scale (UPDRS) scores and Parkinson's Disease Questionnaire (PDQ-39) scores were assessed up to 4 years after surgery. Other measures included were complications/adverse events, levodopa equivalent dose, and cognitive function.A total of 30 patients underwent 52 lead placements. Mean age at surgery was 77.5 years (range 75.0-84.5 years). Post-DBS, motor scores improved by 30.8% after 1-year and 27.3% after a mean of 2.5 years (p .001). All motor sub-scores improved, however axial signs did not change over time. OFF time and dyskinesia duration reduced significantly (p .001), whereas quality of life, activities of daily living and cognitive function did not significantly change. The following adverse events were noted: transient post-operative confusion (36% of patients), gait difficulty (13.3% of patients), hemorrhage (3.8% of leads), personality changes (3.3% of patients), lead revision (1.9% of leads), seizure (1.9% of leads), and infection (1.9% of leads).STN-DBS improves motor outcomes in patients over 75 years of age; however, there was no change in quality of life. Although post-surgical transient confusion was common, there were no serious adverse events and the incidence of other complications was typical for DBS surgery.

OBJECTIVE To evaluate the safety and effectiveness of a wrist-worn peripheral nerve stimulation device in patients with essential tremor (ET) in a single in-office session. METHODS This was a randomized controlled study of 77 ET patients who received either treatment stimulation (N = 40) or sham stimulation (N = 37) on the wrist of the hand with more severe tremor. Tremor was evaluated before and immediately after the end of a single 40-minute stimulation session. The primary endpoint compared spiral drawing in the stimulated hand using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) Archimedes spiral scores in treatment and sham groups. Additional endpoints included TETRAS upper limb tremor scores, subject-rated tasks from the Bain and Findley activities of daily living (ADL) scale before and after stimulation as well as clinical global impression-improvement (CGI-I) rating after stimulation. RESULTS Subjects who received peripheral nerve stimulation did not show significantly larger improvement in the Archimedes spiral task compared to sham but did show significantly greater improvement in upper limb TETRAS tremor scores (p = 0.017) compared to sham. Subject-rated improvements in ADLs were significantly greater with treatment (49% reduction) than with sham (27% reduction; p = 0.001). A greater percentage of ET patients (88%) reported improvement in the stimulation group as compared to the sham group (62%) according to CGI-I ratings (p = 0.019). No significant adverse events were reported; 3% of subjects experienced mild adverse events. CONCLUSIONS Peripheral nerve stimulation in ET may provide a safe, well-tolerated, and effective treatment for transient relief of hand tremor symptoms.

Previous studies have shown that pupillary response, a physiological measure of cognitive workload, reflects cognitive demand in healthy younger and older adults. However, the relationship between cognitive workload and cognitive demand in Parkinson’s disease (PD) remains unclear. The aim of this pilot study was to examine the pupillary response to cognitive demand in a letter-number sequencing (LNS) task between 16 non-demented individuals with PD (age, median (Q1–Q3): 68 (62–72); 10 males) and 10 control participants (age: 63 (59–67); 2 males), matched for age, education, and Montreal Cognitive Assessment (MOCA) scores. A mixed model analysis was employed to investigate cognitive workload changes as a result of incremental cognitive demand for both groups. As expected, no differences were found in cognitive scores on the LNS between groups. Cognitive workload, exemplified by greater pupil dilation, increased with incremental cognitive demand in both groups (p = 0.003). No significant between-group (p = 0.23) or interaction effects were found (p = 0.45). In addition, individuals who achieved to complete the task at higher letter-number (LN) load responded differently to increased cognitive demand compared with those who completed at lower LN load (p < 0.001), regardless of disease status. Overall, the findings indicated that pupillary response reflects incremental cognitive demand in non-demented people with PD and healthy controls. Further research is needed to investigate the pupillary response to incremental cognitive demand of PD patients with dementia compared to non-demented PD and healthy controls.Highlights-Pupillary response reflects cognitive demand in both non-demented people with PD and healthy controls-Although not significant due to insufficient power, non-demented individuals with PD had increased cognitive workload compared to the healthy controls throughout the testing-Pupillary response may be a valid measure of cognitive demand in non-demented individuals with PD-In future, pupillary response might be used to detect cognitive impairment in individuals with PD

The purpose of this study is to characterize the base-width neutral step (BNS) as the first step in a compensatory step response in persons with moderate Parkinson's disease (PD), and its effect on balance recovery.Ten PD and 10 healthy controls (HCs) responded to a posterior waist pull. A BNS was defined if the first step was less than 50 mm. The length, height, duration and velocity of the BNS and its effect on balance recovery time and center of mass location at recovery were compared to the first step within other stepping strategies (single step (SS), multiple step (MS)). A linear mixed model was used to compare across strategies.Six of ten persons with PD compared to zero HC used a BNS. The BNS was shorter in length and duration compared to MS responses in HC, and shorter in duration compared to MS responses in PD. The BNS was slower in velocity compared to every other strategy. BNS use resulted in a longer recovery time compared to all strategies in HC and SS responses in PD, and trended toward a longer recovery time compared to MS responses in PD.The BNS as the first step in a MS response may be an unreported strategy for compensatory stepping in PD. This study suggests that the cost of utilizing the BNS may be a longer time for recovery, but further work is necessary to understand the progression of the BNS as PD severity increases.

Oxidative stress is one of the underlying causes of Parkinson’s disease (PD). Because of its antioxidant effect, we hypothesize that green tea consumption (3 cups daily for 3 months) would improve antioxidant status and reduces oxidative damage in Parkinson’s disease. Fifteen subjects who were within the first five years of PD, on stable PD medication, and not regular green tea consumers were recruited. Iron status, oxidative stress and PD status were evaluated before and after 3 months of green tea consumption. Hemoglobin, serum iron, iron saturation and ferritin concentrations were used to assess iron status. Antioxidant enzymes including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured to determine antioxidant status. Lipid peroxidation and protein carbonyls were measured as oxidative damage markers. There were no changes in total motor scores of the Unified Parkinson’s Disease Rating Scale (UPDRS), PDQ-39 total scores and various iron status markers after 3 months. Catalase (p < 0.05) and SOD activities (p < 0.005) were increased significantly indicating an improvement of antioxidant status. Both lipid peroxidation and protein carbonyls decreased by ~52% (p < 0.01) with green tea consumption, indicating less oxidative stress. In conclusion, 3 cups of green tea consumption for 3 months can improve antioxidant status and reduce oxidative damage in PD patients. Further studies are needed to determine if these changes result in slowing the disease progression.

Tremor is an involuntary rhythmic, oscillatory movement produced by synchronous or alternating contractions of antagonist muscles. Tremor is the most common movement disorder and one of the most common neurological symptoms. A wide variety of etiologies can cause tremor, with essential tremor being the most common. Parkinson’s disease, multiple sclerosis, and drug-induced tremors are other etiologies commonly seen in clinical practice. The diagnosis of the specific etiology of tremor is based on the clinical characteristics of the tremor as well as associated symptoms. The phenomenology of tremor including whether the tremor is present at rest, with posture or with action, allows classification of tremor. Imaging studies, while not in themselves diagnostic, can help rule out structural etiologies. Dopamine transporter imaging is a recent modality that can help distinguish essential tremor from parkinsonism. The treatment of tremor is based on etiology and, where possible, treatment of the underlying disease state. Deep brain stimulation of the thalamus can be an effective treatment modality in intractable cases of tremor.

ObjectiveIPX066 is an extended release carbidopa/levodopa formulation designed to rapidly attain and maintain therapeutic plasma concentrations for a prolonged duration, allowing dosing intervals of approximately 6 h. The objective was to assess the efficacy, safety, and impact on quality of life of IPX066 in the treatment of levodopa-naive Parkinson's disease (PD) patients.MethodsThis was a randomized, double-blind, placebo-controlled, 30-week study of 381 levodopa-naïve patients assigned to placebo or IPX066 containing 145, 245 or 390 mg of levodopa administered three times daily (TID). The primary efficacy measure was change from Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (Part II) + motor scores (Part III), at 30 weeks. Secondary outcome measures included UPDRS total and subscores, patient and clinician global impressions (PGI-I, CGI-I), and the Parkinson's Disease Questionnaire (PDQ-39).ResultsAll IPX066 dosages were superior to placebo throughout the study and at 30 weeks (P

The aims of this systematic review were to investigate (1) real-time brain activity during DT gait and balance, (2) whether changes in brain activity correlate with changes in behavioral outcomes in older adults and people with age-related neurodegenerative conditions. PubMed, PsycINFO, and Web of Science were searched from 2009 to 2019 using the keywords dual task, brain activity, gait, balance, aging, neurodegeneration, and other related search terms. A total of 15 articles were included in this review. Functional near-infrared spectroscopy and electroencephalogram measures demonstrated that older adults had higher brain activity, particularly in the prefrontal cortex (PFC), compared to young adults during dual task gait and balance. Similar neurophysiological results were observed in people with age-related neurodegenerative conditions. Few studies demonstrated a relationship between increased brain activity and better behavioral outcomes. This systematic review supports the notion that aging and age-related neurodegenerative conditions are associated with neuronal network changes, resulting in increased brain activity specifically in the PFC. Further studies are warranted to assess the relationship between increased PFC activation during dual task gait and balance and behavioral outcomes to better optimize the rehabilitation interventions.

Background: Non-motor symptoms such as sleep disturbance, cognitive decline, fatigue, anxiety, and depression in Parkinson’s disease (PD) impact quality of life. Increased levels of pro-inflammatory cytokines in individuals with PD have been reported, which may contribute to non-motor symptoms. A mind-body exercise, Qigong, has demonstrated benefits across different medical conditions. However, a lack of evidence causes clinicians and patients to be uncertain about the effects of Qigong in individuals with PD. This study will examine the effects of Qigong on non-motor symptoms and inflammatory status in individuals with PD. Methods: Sixty individuals with PD will be recruited. Qigong and sham Qigong group (n = 30 for each) will receive a 12-week intervention. Participants will practice their assigned exercise at home (2×/day) and attend routinely group exercise meetings. Results: Clinical questionnaires and neuropsychological tests will measure non-motor symptoms including sleep quality (primary outcome). Biomarker assays will measure inflammatory status. A two-way mixed-design analysis of variance (ANOVA) will be utilized. Conclusions: This study may generate evidence for the benefits of Qigong on non-motor symptoms of PD and the effect on inflammatory status. Findings may lead to the development of a novel, safe, and cost-effective rehabilitation approach for individuals with PD.

Rotigotine transdermal system is a nonergot, 24-hour dopamine agonist approved for the treatment of early and advanced Parkinson's disease (PD). Recent studies have demonstrated significant improvements with rotigotine in motor function in early PD and significant improvements in daily off-time and motor function in advanced PD. In addition to motor improvements, nonmotor symptoms have been shown to be improved with rotigotine in both early and advanced PD. Rotigotine has been shown in large, controlled studies to be safe and efficacious for the treatment of motor and some nonmotor symptoms of early and advanced PD.

Carbidopa/levodopa enteral suspension (CLES; Duopa) is a suspension or gel formulation of carbidopa/levodopa that is approved by the USA Food and Drug Administration for the treatment of advanced Parkinson's disease patients with motor fluctuations. CLES is delivered at a constant rate continuously throughout the day into the jejunum through an infusion pump via a PEG-J tube implanted surgically. The efficacy of CLES was established in the USA based on a randomized, double-blind, double-dummy, active controlled, parallel group and 12-week study, in which mean daily OFF time was reduced by 4.0 h, compared to 1.9 h with oral immediate release carbidopa/levodopa. The CLES hardware consists of a cassette containing the drug, a pump to deliver the drug and tubing to connect the PEG-J to the pump. It is critical to understand the appropriate conversion of the carbidopa/levodopa daily dosages to the CLES dosage and how to program the pump and titrate CLES to achieve the most effective dose. We describe one methodology for patient selection, outpatient titration and pump programming.

Object The goal of this study was to evaluate short- and long-term benefits in quality of life (QOL) after unilateral deep brain stimulation (DBS) for essential tremor (ET). Methods Patients who received unilateral DBS of the ventral intermediate nucleus of the thalamus between 1997 and 2010 and who had at least 1 follow-up evaluation at least 1 year after surgery were included. Their QOL was assessed with the Parkinson Disease Questionnaire-39 (PDQ-39), and ET was measured with the Fahn-Tolosa-Marin tremor rating scale (TRS) prior to surgery and then postoperatively with the stimulation in the on mode. Results Ninety-one patients (78 at 1 year; 42 at 2–7 years [mean 4 years]; and 22 at > 7–12 years [mean 9 years]) were included in the analysis. The TRS total, targeted tremor, and activities of daily living (ADL) scores were significantly improved compared with presurgical scores up to 12 years. The PDQ-39 ADL, emotional well-being, stigma, and total scores were significantly improved up to 7 years after surgery compared with presurgical scores. At the longest follow-up, only the PDQ-39 stigma score was significantly improved, and the PDQ-39 mobility score was significantly worsened. Conclusions Unilateral thalamic stimulation significantly reduces ET and improves ADL scores for up to 12 years after surgery, as measured by the TRS. The PDQ-39 total score and the domains of ADL, emotional well-being, and stigma were significantly improved up to 7 years. Although scores were improved compared with presurgery, other than stigma, these benefits did not remain significant at the longest (up to 12 years) follow-up, probably related in part to changes due to aging and comorbidities.

Summary Background The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus. Methods This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18–80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474. Findings Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87–4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups. Interpretation Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation. Funding St Jude Medical Neuromodulation Division.

Item does not contain fulltext OBJECTIVES: To explore current practices and opinions regarding hospital management of Parkinson disease (PD) patients in specialized PD Centers. METHODS: Fifty-one out of 54 National Parkinson Foundation (NPF) Centers worldwide completed an online survey regarding hospitalization of PD patients. RESULTS: Many Centers were concerned about the quality of PD-specific care provided to their patients when hospitalized. Primary concerns were adherence to the outpatient medication schedule and poor understanding by hospital staff of medications that worsen PD. Few Centers had a policy with their primary hospital that notified them when their patients were admitted. Rather, notification of hospitalization came often from the patient or a family member. Several Centers (29%) reported not finding out about a hospitalization until a routine clinic visit after discharge. Quick access to outpatient PD care following discharge was a problem in many Centers. Elective surgery, fall/fracture, infection, and mental status changes, were identified as common reasons for hospitalization. CONCLUSIONS: There is a perceived need for PD specialists to be involved during hospitalization of their patients. Improvement in communication between hospitals and PD Centers is necessary so that hospital clinicians can take advantage of PD specialists' expertise. Education of hospital staff and clinicians regarding management of PD, complications of PD, and medications to avoid in PD is critical. Most importantly, outpatient access to PD specialists needs to be improved, which may prevent unnecessary hospitalizations in these patients.

Evaluation of: Olanow CW, Kieburtz K, Odin P et al. Continuous intrajejunal infusion of levodopa–carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol . 13(2), 141–149 (2014). Levodopa-induced motor complications, including motor fluctuations and dyskinesia, can be a major source of disability for Parkinson’s disease patients. The development of levodopa-induced motor complications has been attributed to the pulsatile dopaminergic stimulation characteristic of conventional oral levodopa regimens. This is a review of a 12-week, randomized, controlled, double-blind, double-dummy study of continuous jejunal infusion of levodopa–carbidopa intestinal gel to determine if the continuous infusion of levodopa reduces motor complications in Parkinson’s disease. Results demonstrated that levodopa–carbidopa intestinal gel significantly reduced off-time without increasing troublesome dyskinesia compared with standard oral levodopa therapy. Adverse effects were common in both the levodopa–carbidopa intestinal gel and placebo groups and were related primarily to the infusion hardware.

While the use of deep brain stimulation (DBS) for the treatment of neurological disorders has risen substantially over the last decade, it is often difficult to compare the results from different studies due to the lack of consistent reporting of key study parameters. We present guidelines to standardize the reporting of clinical studies of DBS for Parkinson's disease (PD). These guidelines provide a minimal set of required data elements to facilitate the interpretation and comparison of results across published clinical studies. The guidelines, summarized in the format of a checklist, may also have utility in the planning of clinical studies of DBS for PD as well as other neurological and psychiatric disorders.

The objective of this study was to examine the experience with and safety of brain 1.5 Tesla (T) magnetic resonance imaging (MRI) in deep brain stimulation (DBS) patients. This was a retrospective review of brain MRI scanning performed on DBS patients at the University of Kansas Medical Center between January 1995 and December 2007. A total of 249 DBS patients underwent 445 brain 1.5 T MRI scan sessions encompassing 1,092 individual scans using a transmit-receive head coil, representing the cumulative scanning of 1,649 DBS leads. Patients with complete implanted DBS systems as well as those with externalized leads underwent brain imaging. For the majority of scans, specific absorption rates localized to the head (SAR(H)) were estimated and in all cases SAR(H) were higher than that specified in the present product labeling. There were no clinical or hardware related adverse events secondary to brain MRI scanning. Our data should not be extrapolated to encourage MRI scanning beyond the present labeling. Rather, our data may contribute to further defining safe MRI scanning parameters that might ultimately be adopted in future product labeling as more centers report in detail their experiences.

Deep brain stimulation of the subthalamic nucleus (DBS-STN) is an approved treatment for advanced Parkinson disease (PD) patients; however, there is a need to further evaluate its effect on gait. This study compares logistic regression (LR), probabilistic neural network (PNN) and support vector machine (SVM) classifiers for discriminating between normal and PD subjects in assessing the effects of DBS-STN on ground reaction force (GRF) with and without medication. Gait analysis of 45 subjects (30 normal and 15 PD subjects who underwent bilateral DBS-STN) was performed. PD subjects were assessed under four test conditions: without treatment (mof-sof), with stimulation alone (mof-son), with medication alone (mon-sof), and with medication and stimulation (mon-son). Principal component (PC) analysis was applied to the three components of GRF separately, where six PC scores from vertical, one from anterior-posterior and one from medial-lateral were chosen by the broken stick test. Stepwise LR analysis employed the first two and fifth vertical PC scores as input variables. Using the bootstrap approach to compare model performances for classifying GRF patterns from normal and untreated PD subjects, the first three and the fifth vertical PCs were attained as SVM input variables, while the same ones plus the first anterior-posterior were selected as PNN input variables. PNN performed better than LR and SVM according to area under the receiver operating characteristic curve and the negative likelihood ratio. When evaluating treatment effects, the classifiers indicated that DBS-STN alone was more effective than medication alone, but the greatest improvements occurred with both treatments together.

Rotigotine is a highly lipophilic dopamine-receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce "off" hours in levodopa-treated patients with advanced Parkinson's disease. The rotigotine pharmacophore is nonergolinic and demonstrates high affinity for dopamine D(2) and D(3) receptors. With once-daily application, the patch matrix provides continuous, nonfluctuating plasma drug levels at steady state, resulting in continuous and steady plasma and brain levels and striatal dopamine-receptor stimulation. In early Parkinson's disease, doses of rotigotine up to 8 mg/24 hours demonstrate comparable efficacy to ropinirole (at doses up to 12 mg/day); in advanced Parkinson's disease, doses of rotigotine up to 16 mg/24 hours demonstrate comparable efficacy and tolerability to pramipexole (at doses up to 4.5 mg/day). In the registration trials for early and advanced Parkinson's disease, the adverse effects most commonly observed with rotigotine were minor application site reactions, dizziness, nausea, and somnolence. Doses of transdermal rotigotine can be titrated to a maintenance dose within 2-3 weeks, and the once-daily regimen minimizes complexity of therapy. The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24-hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine-receptor agonist class. This review summarizes the key pharmacologic and clinical data for rotigotine and provides a focused clinical context for its use in early-to-advanced Parkinson's disease, as well as a brief summary for its role in restless legs syndrome.

Background—Purkinje cell axonal swellings (“torpedoes”), described in several cerebellar disorders as well as essential tremor (ET), have not been quantified in common neurodegenerative conditions.

The objective of this study was to evaluate the safety, tolerability, and preliminary efficacy of intravenous glutathione in Parkinson's disease (PD) patients. This was a randomized, placebo-controlled, double-blind, pilot trial in subjects with PD whose motor symptoms were not adequately controlled with their current medication regimen. Subjects were randomly assigned to receive intravenous glutathione 1,400 mg or placebo administered three times a week for 4 weeks. Twenty-one subjects were randomly assigned, 11 to glutathione and 10 to placebo. One subject who was assigned to glutathione withdrew from the study for personal reasons prior to undergoing any postrandomization efficacy assessments. Glutathione was well tolerated and there were no withdrawals because of adverse events in either group. Reported adverse events were similar in the two groups. There were no significant differences in changes in Unified Parkinson's Disease Rating Scale (UPDRS) scores. Over the 4 weeks of study medication administration, UPDRS ADL + motor scores improved by a mean of 2.8 units more in the glutathione group (P = 0.32), and over the subsequent 8 weeks worsened by a mean of 3.5 units more in the glutathione group (P = 0.54). Glutathione was well tolerated and no safety concerns were identified. Preliminary efficacy data suggest the possibility of a mild symptomatic effect, but this remains to be evaluated in a larger study.

The management of early Parkinson’s disease (PD) involves the treatment of motor symptoms and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews motor symptom efficacy data for the newest PD treatment options, as well as for established therapies. Safety and tolerability data are also reviewed. Part 2 of the article reviews key findings relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.

Background: In patients experiencing motor fluctuations, a major treatment challenge is the reduction of “off” time, particularly upon awakening. Rotigotine (Neupro) is a novel dopaminergic agonist with 24-hour transdermal delivery. Methods: A randomized, double-blind, placebo-controlled trial (PREFER Study) was performed to assess efficacy and safety with two targeted transdermal doses of rotigotine in subjects with advanced Parkinson disease with ≥2.5 hours of daily “off” time. Subjects were randomized to receive placebo patches (n = 120) or rotigotine up to either 8 mg/24 hours (n = 120) or 12 mg/24 hours (n = 111). The primary efficacy measures compared changes from baseline to the end of week 24 in the number of daily hours “off” and responder rates for subjects achieving ≥30% reduction in “off” time. Results: Compared to placebo, there were significant decreases in mean “off” time of 1.8 hours/day for the rotigotine 8 mg/24 hours group and 1.2 hours/day for the 12 mg/24 hours group. For rotigotine 8 and 12 mg/24 hours groups, ≥30% responder rates were 56.6% and 55.1% compared to the 34.5% placebo response. “On” time without dyskinesia after awakening was more than doubled in both rotigotine treatment groups vs placebo. Drug-related adverse effects included typical dopaminergic side effects, which were generally mild/moderate in intensity. Patch application site reactions including erythema and pruritus were mild to moderate and transient in the majority of instances. Conclusions: Transdermal rotigotine significantly improved “off” time in subjects with Parkinson disease not optimally controlled with levodopa and was safe and well tolerated, with typical dopaminergic side effects and occasional application site reactions.

Objective: To determine if future studies of coenzyme Q10 and GPI-1485 in Parkinson disease (PD) may be warranted. Methods: We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold. Results: The primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed. Conclusions: Coenzyme Q10 and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies. NEUROLOGY 2007;68:20-28

Levodopa responsiveness has been shown to be the best predictor of improvement after subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson’s disease (PD). The objective of this study was to assess the effect of STN DBS on PD patients intolerant to levodopa due to severe acute side effects such as intolerable nausea. There were 10 patients in the study who received STN DBS for PD. Five patients who were intolerant to levodopa were matched based on age, disease duration, sex and presurgical disease severity to 5 patients taking levodopa and demonstrating a good levodopa response. Both groups had a significant improvement in Unified Parkinson’s Disease Rating Scale activities of daily living and motor subscales as well as tremor, rigidity and bradykinesia scores at 3, 6 and 12 months after surgery compared to baseline, and these improvements were equivalent between the two groups. Patient global ratings also indicated significant improvements at all follow-up visits. There were no differences in stimulator settings between the two groups at the 3-, 6- or 12-month follow-up visits. In conclusion, although levodopa responsiveness is the best predictor for outcome after STN DBS, carefully selected PD patients intolerant to levodopa can have significant improvement.

Contains fulltext : 153006.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To determine (1) the relationship between assisted timed Up and Go (TUG) performance and the Parkinson's Disease Questionnaire-39 (PDQ-39), and (2) whether adjusting the TUG score (adding time) improves the relationship between TUG performance and the PDQ-39 in persons with Parkinson disease (PD) who use assistive devices or push off, or both. DESIGN: Cross-sectional. SETTING: Twenty participating National Parkinson Foundation Centers of Excellence. PARTICIPANTS: Data were obtained from participants (N=6624) without exclusion at the 20 participating sites. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The relationship between TUG scores and PDQ-39 mobility scores was determined using the method of linear least squares. Adjusted scores were determined through minimizing the sum of the squared error. RESULTS: The correlation between assisted TUG scores and PDQ-39 mobility scores was slightly lower (R(2)=.384) compared with the correlation between nonassisted TUG scores and PDQ-39 mobility scores (R(2)=.409). Adjusting assisted TUG performance scores for push off and for use of an assistive device resulted in a modest increase in correlation (R(2)=.399). CONCLUSIONS: Applying adjustments to assisted TUG may provide clinically important information for evaluating balance, mobility, and falls, and for determining the most effective therapeutic strategies for persons with PD.

This study evaluates the effects of sequential tui na massage, acupuncture, and instrument-delivered qigong for patients with Parkinson disease (PD) over a 6-month period.Patients received weekly treatments, which included tui na massage prior to acupuncture followed by instrument-delivered qigong. Each patient was assessed at baseline and at 6 months.The setting was an outpatient research/academic clinic for patients with PD and nonacademic acupuncture clinic.Twenty-five (25) patients with idiopathic PD were the subjects.Before and after treatment patients were evaluated with the Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr Staging (HY), Schwab and England Activities of Daily Living (SE), Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39) quality of life assessment, and patient global assessments.There were no significant improvements in treatment measures; however, there was a 2.4-point worsening in UPDRS motor scores (24.0 versus 26.4, p = 0.018). There was a 16% improvement in the PDQ- 39 total score (23.2 versus 19.6, p = 0.044) and a 29% improvement in the BDI (9.6 versus 6.8, p = 0.006). Sixteen (16) patients reported moderate to marked improvement. There were no adverse effects.Acupuncture is safe and well tolerated in patients with PD. Most patients reported subjective improvement. The BDI and PDQ-39 total score, measuring depression and quality of life, demonstrated some improvement, but UPDRS motor scores worsened.

Objective: To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS?Methods: A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004.Results, Conclusions, and Recommendations: 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).