Levodopa Equivalent Daily Dose Research Articles

Non-motor symptoms depending on motor severity in Japanese patients with Parkinson's disease: A multicenter cross-sectional study

BackgroundAlthough non-motor symptoms (NMS) in patients with Parkinson's disease (PD) often worsen as the severity of motor symptoms (MS) increases, few studies have assessed the associated factors of non-motor symptoms. ObjectiveThis study aims to determine whether the presence of NMS in PD patients is associated with or independent from the severity of MS considering confounders. MethodsThe registry of PD patients from seven facilities in Japan was used. Multiple logistic regression was performed with each domain and item of the Non-motor Symptoms Scale (NMSS) as objective variables. Severity of motor symptoms was assessed by Hoehn & Yahr stage (HY stage) as an explanatory variable. The analysis was adjusted for sex, age, disease duration, presence/absence of wearing off and dyskinesia, clinical phenotypes and Levodopa equivalent daily dose. ResultsA total of 1037 patients were analyzed. Analysis by NMSS domain showed higher odds ratios (ORs) in patients with higher HY stages compared with patients with lower HY stages for domains D1 (cardiovascular), D2 (sleep/fatigue), D3 (mood/apathy), D4 (perceptual problems/hallucinations), D5 (attention/memory), and D6 (gastrointestinal) (ORs: 1.54–2.72, P < .05). However, only domains D7 (urinary) and D8 (sexual dysfunction) were not associated with HY stage. Item 2 (fainting) and Item 14 (delusions) showed higher ORs in the HY stage 4–5 (ORs: 9.95 and 5.92, P < .05). ConclusionsMost NMS worsened with exacerbation of MS in PD patients, however some NMS domains were also affected with other factors. These findings contribute to the understanding of the clinical picture of PD and may improve personalized medicine and research in PD.

White matter tracts involved by deep brain stimulation of the subthalamic nucleus in Parkinson’s disease: a connectivity study based on preoperative diffusion tensor imaging tractography

Purpose: To depict the specific brain networks that are modulated by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD), using diffusion tensor imaging-based fibre tractography (DTI-FT).Materials and methods: Nine patients who received bilateral STN-DBS for PD were included. Electrodes were localized by co-registering preoperative magnetic resonance imaging and postoperative computed tomography. The volume of tissue activated (VTA) was estimated as an isotropic, spherical electric field distribution centred at each effective electrode contact’s centroid coordinates, taking into account individual stimulation parameters (i.e. voltage, impedance). Brain connectivity analysis was undertaken using a deterministic DTI-FT method, seeded from a single region of interest corresponding to the VTA. The labelling of the reconstructed white matter fibre tracts relied on their path and (sub)cortical termination territories.Results: Six months after surgery, we observed a statistically significant reduction in both the Unified Parkinson Disease Rating Scale part III and L-dopa equivalent daily dose. Areas consistently connected to the VTA included the brainstem (100%), cerebellum (94%), dorsal (i.e. supplementary motor area) and lateral premotor cortex (94%), and primary motor cortex (72%). An involvement of the hyperdirect pathway (HDP) connecting the STN and the (pre)motor cortex was demonstrated.Conclusions: The connectivity patterns observed in this study suggest that the therapeutic effects of STN-DBS are mediated through the modulation of distributed, large-scale motor networks. Specifically, the depiction of projection neurons connecting the stimulated area/STN to the (pre)motor cortex, reinforce the growing evidence that the HDP might be a potential therapeutic target in PD. If further replicated, these findings could raise the possibility that DTI-FT reconstruction of the HDP may critically improve DBS targeting and stimulation parameters selection, through the development of programming tools that incorporate VTA modelling and patient-specific DTI-FT data.

Effect of LRRK2 G2385R Variant on Subthalamic Deep Brain Stimulation Efficacy in Parkinson's Disease in a Han Chinese Population

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD). The G2385R variant of LRRK2 is a risk factor for PD in Han Chinese individuals. We retrospectively compared the clinical outcomes of STN-DBS surgery between PD Han Chinese G2385R variant carriers and non-carriers. Fifty-seven PD patients with bilateral STN-DBS were enrolled, including 8 G2385R+ variant carriers (G2385R+ group) and 49 non-carriers (G2385R– group). Clinical data included Unified Parkinson's Disease Rating Scale (UPDRS) parts I to IV, levodopa equivalent daily dose (LEDD), Mini-Mental State Examination Scale (MMSE) score, and Hamilton Depression Rating Scale (HAMD) score measured prior to DBS and 12 months post-DBS. DBS settings were also recorded. All PD patients benefited from STN-DBS surgery. There were no statistical differences between the two groups in terms of motor function, daily living activities, and LEDD reductions at 12 months post-DBS. The rigidity of the post-surgical G2385R+ group was significantly improved compared with that of the G2385R– group (P = 0.045). Post-surgical voltage in the G2385R+ group was significantly higher than that in the G2385R– group (P = 0.033). STN-DBS outcomes were not influenced by the LRRK2 G2385R variant in Han Chinese patients.

Subjective memory decline in Parkinson's disease patients with and without fatigue

IntroductionPrevious studies on Parkinson's disease (PD) have shown that memory complaints and fatigue co-occur since premotor stages of disease, but whether Subjective Memory Decline (SMD, defined as memory complaints with normal objective cognitive performance) and fatigue were associated in PD has not been explored yet. MethodsOne-hundred PD patients underwent measures of memory complaints (Multifactorial Memory Questionnaire, MMQ), neuropsychological test (Parkinson's Disease-Cognitive Rating Scale), and assessment of behavioural symptoms. Fatigue was diagnosed according to current diagnostic criteria. Mann-Whitney test or Pearson chi-square test were used to compare fatigued and nonfatigued patients for prevalence of SMD and for demographic, clinical, and behavioural features, memory complaint, and objective cognitive measures. The confounding effect of sample's features on results was controlled by logistic regression and Quade's rank analysis. ResultsTwenty-three patients were diagnosed as fatigued whereas 15 patients met SMD criteria. Fatigued patients showed higher levodopa equivalent daily dose and more marked behavioural symptoms than nonfatigued patients (ps< 0.01). The prevalence of SMD was higher in fatigued patients than in those nonfatigued (35% vs 9%, p < 0.01). After controlling for confounds, the patients with fatigue had an odds ratio for SMD 5.97 [CI 95%, 1.18–30.03] times higher and presented significantly lower scores on Contentment subscales of MMQ (p < 0.01) than those without fatigue. ConclusionFatigue in PD is associated with SMD mainly characterized by less contentment with one's own memory ability. These findings suggest possible shared pathogenic mechanisms underlying these two nonmotor manifestations and foster to identify potential phenotypes of patients requiring multistrategic therapeutic approaches.

Prevalence and clinical aspects of mild cognitive impairment in Parkinson's disease: A meta-analysis.

Mild cognitive impairment associated with Parkinson's disease (PD) is a risk factor for the development of dementia. Despite the importance of early identification of mild cognitive impairment in PD, its prevalence and clinical correlates are still debated. The present meta-analysis provides a robust estimate of prevalence rate of mild cognitive impairment in PD according to the Movement Disorder Society clinical criteria and to explore the differences between PD patients with and without mild cognitive impairment in demographic, clinical, and neuropsychiatric features. A systematic literature search was performed up to April 2019 using PsycInfo (PROQUEST), PubMed, and Scopus. From 4706 titles and abstracts, 41 studies were selected (n = 7053 patients). Pooled mild cognitive impairment prevalence was 40% on a total sample of 7053 PD patients (95% confidence interval = 36-44; Q = 490.14, P < 0.0001; I2 = 91.84%) with a higher frequency for the multiple domain subtype (31%; 95% confidence interval = 23-41, Q = 93.24; P < 0.0001; I2 = 92.49%). Meta-regression analysis revealed that stage of PD moderate prevalence estimates of mild cognitive impairment (β = 2.80; P = 0.008). Mild cognitive impairment in PD was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose, more severe motor symptoms, and postural instability/gait difficulty motor subtype, poorer quality of life, higher levels of apathy, and depression. The present meta-analysis indicated that mild cognitive impairment in PD is a frequent cognitive status deserving to be early detected by means of standardized cognitive assessments in clinical practice. © 2019 International Parkinson and Movement Disorder Society.

Abnormal subpopulations of peripheral blood lymphocytes are involved in Parkinson's disease.

Abnormal immune responses are involved in the development of Parkinson's disease (PD), and also affect peripheral blood lymphocytes. The profile of lymphocyte subsets in peripheral blood and whether it is relevant to the clinical features of PD patients remains controversial. To explore the role of peripheral blood lymphocytes (NK cells, B cells, CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells) in the development of PD, a case-control study including 127 patients and 148 healthy controls was conducted, and peripheral blood lymphocyte subpopulations of participants were analysed by a FACSCalibur flow cytometer. PD patients had a significantly higher percentage of NK cells and a lower percentage of CD3+ T cells and CD3+CD4+ T cells than controls [16.4% (12.3%) vs. 12.6% (6.2%), 63.7% (14.2%) vs. 69.0% (6.6%), 33.1% (13.1%) vs. 38.9% (7.6%), P<0.05, respectively]. Through a binary logistic regression model adjusted for gender and age, we found that those who were outside of the reference range of peripheral blood lymphocytes (NK cell, B cell, CD3+ T cell and CD3+CD4+ T cell) had an increased risk of PD [odds ratio (OR): 2.3, 5.1, 3.1 and 4.1, P<0.05, respectively]. Through a multivariable linear regression model adjusted for gender, age and levodopa equivalent daily dose, we found that deviation from the reference range of CD3+CD8+ T cells (regression coefficient =3.474, P=0.015), course of disease (regression coefficient =0.411, P=0.004) and the Non-Motor Symptoms Scale (NMSS) scores (regression coefficient =0.553, P=5.92E-11) had a positive association with the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-III score (adjusted R2=0.364, F=13.004). Abnormal peripheral blood lymphocyte subpopulations have clinical relevance for PD.

Characterization of Parkinson's disease using blood-based biomarkers: A multicohort proteomic analysis.

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disease affecting about 5 million people worldwide with no disease-modifying therapies. We sought blood-based biomarkers in order to provide molecular characterization of individuals with PD for diagnostic confirmation and prediction of progression.Methods and findingsIn 141 plasma samples (96 PD, 45 neurologically normal control [NC] individuals; 45.4% female, mean age 70.0 years) from a longitudinally followed Discovery Cohort based at the University of Pennsylvania (UPenn), we measured levels of 1,129 proteins using an aptamer-based platform. We modeled protein plasma concentration (log10 of relative fluorescence units [RFUs]) as the effect of treatment group (PD versus NC), age at plasma collection, sex, and the levodopa equivalent daily dose (LEDD), deriving first-pass candidate protein biomarkers based on p-value for PD versus NC. These candidate proteins were then ranked by Stability Selection. We confirmed findings from our Discovery Cohort in a Replication Cohort of 317 individuals (215 PD, 102 NC; 47.9% female, mean age 66.7 years) from the multisite, longitudinally followed National Institute of Neurological Disorders and Stroke Parkinson’s Disease Biomarker Program (PDBP) Cohort. Analytical approach in the Replication Cohort mirrored the approach in the Discovery Cohort: each protein plasma concentration (log10 of RFU) was modeled as the effect of group (PD versus NC), age at plasma collection, sex, clinical site, and batch. Of the top 10 proteins from the Discovery Cohort ranked by Stability Selection, four associations were replicated in the Replication Cohort. These blood-based biomarkers were bone sialoprotein (BSP, Discovery false discovery rate [FDR]-corrected p = 2.82 × 10−2, Replication FDR-corrected p = 1.03 × 10−4), osteomodulin (OMD, Discovery FDR-corrected p = 2.14 × 10−2, Replication FDR-corrected p = 9.14 × 10−5), aminoacylase-1 (ACY1, Discovery FDR-corrected p = 1.86 × 10−3, Replication FDR-corrected p = 2.18 × 10−2), and growth hormone receptor (GHR, Discovery FDR-corrected p = 3.49 × 10−4, Replication FDR-corrected p = 2.97 × 10−3). Measures of these proteins were not significantly affected by differences in sample handling, and they did not change comparing plasma samples from 10 PD participants sampled both on versus off dopaminergic medication. Plasma measures of OMD, ACY1, and GHR differed in PD versus NC but did not differ between individuals with amyotrophic lateral sclerosis (ALS, n = 59) versus NC. In the Discovery Cohort, individuals with baseline levels of GHR and ACY1 in the lowest tertile were more likely to progress to mild cognitive impairment (MCI) or dementia in Cox proportional hazards analyses adjusting for age, sex, and disease duration (hazard ratio [HR] 2.27 [95% CI 1.04–5.0, p = 0.04] for GHR, and HR 3.0 [95% CI 1.24–7.0, p = 0.014] for ACY1). GHR’s association with cognitive decline was confirmed in the Replication Cohort (HR 3.6 [95% CI 1.20–11.1, p = 0.02]). The main limitations of this study were its reliance on the aptamer-based platform for protein measurement and limited follow-up time available for some cohorts.ConclusionsIn this study, we found that the blood-based biomarkers BSP, OMD, ACY1, and GHR robustly associated with PD across multiple clinical sites. Our findings suggest that biomarkers based on a peripheral blood sample may be developed for both disease characterization and prediction of future disease progression in PD.

Restless legs syndrome - the under-recognised non-motor burden: a questionnaire-based cohort study

ABSTRACTObjectives: Non-motor symptoms (NMS) range from neuropsychiatric to pain and are an important but underexplored feature of restless legs syndrome (RLS). There are currently no tools available which enable the holistic assessment of NMS in RLS in clinical practice. The primary aim of this study was to systematically assess NMS prevalence and burden in patients with RLS using the NMS Questionnaire (NMSQuest) validated for Parkinson’s disease.Methods: Patients with idiopathic RLS according to the criteria of the international RLS study group (IRLSSG) were included. Patients underwent a physical examination and clinical interview as well as completed the NMS Questionnaire and the international restless legs syndrome study group (IRLSSG) rating scale.Results: Seventy-four patients with primary RLS were included (mean age 64.6 ± 14.4 years, 62.2% female, mean disease duration 23.5 ± 17.8 years, mean Levodopa equivalent daily dose 63.3 ± 67.4 mg). On average patients reported an IRLSSG rating scale score of 24.8 ± 8.2 (maximum 40) and NMSQuest score of 9.9 ± 5.0 (maximum 30). Patients reported a minimum of two NMS with the majority (39.2%) reporting a moderate NMS burden, followed by severe (28.4%) and very severe (17.6%) burden. The most frequent NMS were insomnia (89.2%) followed by nocturia (70.3%), feeling sad (59.5%), forgetfulness (54.1%), urgency (47.3%), feeling anxious (43.2%), unexplained pain (41.9%), difficulty concentrating (40.5%) and dizziness (40.5%). There were no significant differences in NMSQuest total scores according to disease duration and gender (p = 0.739, p = 0.849).Conclusion: In conclusion, this study is one of the first to address NMS in RLS systematically and the data underlines the need to holistically assess NMS in RLS in order to deliver true value-based healthcare for these patients.

Two-year clinical outcomes associated with robotic-assisted subthalamic lead implantation in patients with Parkinson’s disease

Few centers have routinely implemented robotic stereotactic systems for deep brain stimulator (DBS) placement. Thepresent study compares clinical outcomes associated with robotic-assisted subthalamic nucleus (STN)-targeted DBS surgery in patients with Parkinson's disease (PD) to those of the traditional frame-based method. A retrospective chart review was performed (February 2013-June 2017). Thirty-three patients were implanted using the Cosman-Roberts-Wells (CRW) frame and 27 patients were implanted using the ROSA robot. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) or UPDRS part III motor scores and levodopa equivalent daily doses (LEDD) were examined preoperatively and at 6, 12, and 24months of follow-up. Operative times and complication rates were recorded. For the frame-based group, the reduction in the mean MDS-UPDRS part III motor score compared to baseline was 27% both at 6 and 12months, and 36.7% at 24months. For the robotic-assisted group, the reduction in the mean motor score from baseline was 17.6% at 6months, 19% at 12months and 21.4% at 24months. The mean LEDD for the frame-based group decreased by 48.7% at 6months, 56.7% at 12months, and 29.7% at 24months. For the robotic-assisted group, the mean LEDD decreased by 42% at 6months, 45% at 12months and 50% at 24months. There were no significant differences in the mean motor scores and the LEDD reduction between the two groups. Operative times tended to be longer for robotic-assisted DBS surgery. Clinical outcomes associated with robotic-assisted surgery are comparable to those with frame-based surgery.

Quality of Life Improvement Following Deep Brain Stimulation for Parkinson Disease: Development of a Prognostic Model.

There is a growing attention to determine the factors that predict quality of life (QoL) improvement after deep brain stimulation (DBS) for Parkinson's disease. Prior literature has largely focused on examining predictors one at a time, sometimes controlling for covariates. To develop a model that could be used as a nomogram to predict improvement in QoL following DBS surgery in patients with Parkinson's disease. All patients with complete pre- and postoperative movement disorder and neuropsychological testing who underwent DBS at a single institution between 2007-2012 were analyzed. The Parkinson's Disease Questionnaire-39 (PDQ-39) was used to measure QoL. Potential predictive factors, including patient demographics, clinical presentation characteristics, radiographic imaging, and motor and psychological testing were analyzed for impact on QoL. Sixty-seven patients were identified, 36 (53.73%) of whom had meaningfully improved QoL following surgery. Five baseline variables showed significant relationships with the outcome: years since symptom onset, percent change in on/off motor evaluation, levodopa equivalent daily dose, bilateral vs unilateral DBS implantation, and PDQ-39 score. The final model includes PDQ-39, percent change in UPRS-III, and years since symptom onset and is able to predict improvement in QoL with 81% accuracy. Our model accurately predicted whether QoL would improve in patients undergoing subthalamic nucleus DBS 81% of the time. Our data may serve as the foundation to further refine a clinically relevant prognostic tool that would assist the decision-making process for clinicians and DBS multidisciplinary teams assessing patient candidacy for surgery.

A comparative study of bilateral subthalamic nucleus DBS in Parkinson’s disease in young versus old: A single institutional study

To compare outcome between young [<65 yrs] and old [>65 yrs] patients of Parkinson’s disease who underwent bilateral STN DBS a non-randomized retrospective study was done. 20 young (Young group) and 20 elderly (Old group) patients with matched baseline UPDRS were selected and followed up for 2 years after deep brain stimulation (DBS) surgery. The total and motor UPDRS, before, one year and two years after surgery was compared. PDQ39 a quality of life questionnaire and MMSE were also recorded. Zarit care burden interview (ZCBI) was used to analyse caregiver burden. Analysis of data was done using Mann-Whitney Test as the data was ordinal. The difference was not statistically significant at 1st and 2nd year of follow up in total and motor UPDRS. A significant reduction in Levodopa equivalent daily dose was seen in young and old group from preoperative period to 1st & then 2nd year of follow up. The difference was not statistically significant (P = 0.946) at 1st (P = 0.946) and at 2nd year (P = 0.989). Both the groups showed improvement in their PDQ39. The difference was not statistically significant at 1st (P = 0.636) and at 2nd year of follow up (P = 0.417). Caregiver burden (ZCBI) improved in both the groups and the difference was not statistically significant at 1st (P = 0.105) and at 2nd year of follow up (P = 0.078).In this study STN DBS didn’t lead to any cognitive decline (MMSE) whatever is the age of patient during follow up. Bilateral STN DBS for Parkinson’s disease is equally effective in young and elderly patients.

Combination Targeting of Subthalamic Nucleus and Ventral Intermediate Thalamic Nucleus in Deep Brain Stimulation for Tremor-Dominant Parkinson's Disease: Experience and Outcomes

Abstract INTRODUCTION Deep brain stimulation (DBS) has traditionally been used to target the subthalamic nucleus (STN) or globus pallidus internus (GPi) to treat the bradykinesia and rigidity of Parkinson's disease (PD) and the ventral intermediate thalamic nucleus (VIM) to treat essential tremor (ET). Recent case reports have described targeting both the STN and VIM with a single trajectory to treat patients with tremor-dominant PD; yet, outcome data for this procedure remain sparse. METHODS We conducted a single-center retrospective review of all patients who underwent combined STN-VIM DBS. Demographic and outcome data, including Unified Parkinson Disease Rating Scale (UPDRS), changes in symptom severity, and levodopa equivalent daily dose (LEDD), were collected and analyzed. RESULTS Nineteen patients underwent combined STN-VIM trajectory DBS between January 2013 and April 2019. Patients were 90% male and 10% female, with an average age of 63.6 ± 12 yr. Average preoperative UPDRS was 24.2 and LEDD was 807.8. At an average follow-up of 23.9 mo, UPDRS and LEDD decreased by an average of 9.25 and 404.8, respectively. A total of 95% of our patients reported an improvement in tremor symptoms, and 58% were able to decrease the total medication burden. CONCLUSION Combined targeting of STN and VIM thalamus for tremor-dominant PD results in an excellent control of tremor symptoms, as well as a decrease in UPDRS and LEDD. Larger multicenter studies are necessary to validate this as the optimal DBS target for tremor-dominant PD.

Asymmetric Deep Brain Stimulation Electrodes for Parkinson's Disease: A Pilot Study of Symptom-Tailored Stimulation

Abstract INTRODUCTION Bilateral subthalamic nucleus (STN) and globus pallidus interna (GPi) deep brain stimulation (DBS) are well established targets for the management of Parkinson's disease (PD). Each target has its own advantage, we presume the simultaneous unilateral STN and contralateral GPi DBS may compromise side effects of bilateral stimulation and keep each nucleus and its own efficacy on the motor and nonmotor symptoms. METHODS Eight patients with idiopathic PD with this kind of procedure were retrospectively reviewed. Motor, nonmotor symptoms, quality of life were measured before surgery, 6 mo, 1-yr post surgery under following conditions: medication on and off, bilateral stimulation on and off, unilateral STN stimulation on. Medication and stimulation parameters were noted. RESULTS Unilateral STN and contralateral GPi DBS significantly improved the UPDRS-? scores, with a 45% reduction at 6 mo and a 43% reduction at 1 yr. In total, 41% of levodopa equivalent daily dose was reduced at 1-yr follow-up. In the medication on condition, bilateral stimulation improved axial symptoms by 28.4% at 1-yr follow-up. In total, 3 m TUG (Time-Up Go test) improved by 41% at 6-mo follow-up compared to baseline, which lasts for 1 yr. In total, 64% reduction was found between baseline and 1-yr follow-up in gait and fall questionnaires. No deterioration was found in nonmotor measurements. No adverse events other than stimulation related were reported. CONCLUSION Our results provide the first evidence that supports unilateral STN and contralateral GPi DBS might be effective and safe in advanced PD patients. Future efforts are needed to explore the potential advantage in axial and cognitive symptoms in long term.

Gastric dysmotility in Parkinson's disease is not caused by alterations of the gastric pacemaker cells

The enteric nervous system is involved in the pathology of Parkinson´s disease and patients frequently have symptoms related to delayed gastric emptying. However, the pathophysiology of gastric dysmotility is yet not well understood. The objective of this study was to assess interdigestive gastric motility in Parkinson´s disease. Using an electromagnetic capsule system, the dominant gastric contraction frequency (primary outcome measure) and the gastric transit time were assessed in 16 patients with Parkinson´s disease and 15 young healthy controls after a fasting period of 8 h. Motor and non-motor symptoms were assessed using the Movement Disorder Society Unified Parkinson´s Disease Rating Scale III (MDS-UPDRS III), the Non-Motor Symptoms Questionnaire (NMS-Quest), and Hoehn & Yahr staging. The Gastroparesis Cardinal Symptom Index was used to record symptoms related to delayed gastric emptying. In healthy controls and patients with Parkinson's disease, the dominant contraction frequency was 3.0 cpm indicating normal function of interstitial cells of Cajal. In patients with Parkinson's disease, the gastric transit time was longer than in younger controls (56 vs. 21 min). The dominant contraction frequency and gastric transit time did not correlate with age, disease duration, Hoehn & Yahr stage, levodopa equivalent daily dose, MDS-UPDRS III, NMS-Quest, and Gastroparesis Cardinal Symptom Index. Changes of gastric motility in Parkinson´s disease are not caused by functional deficits of the gastric pacemaker cells, the interstitial cells of Cajal. Therefore, gastroparesis in Parkinson's disease can be attributed to disturbances in neurohumoral signals via the vagus nerve and myenteric plexus.

Postural Abnormalities in Parkinson's Disease: An Epidemiological and Clinical Multicenter Study.

The overall frequency of postural abnormalities (PA) in Parkinson's disease (PD) is unknown. We evaluated the overall prevalence of PA and assessed the association with demographic and clinical variables. For this multicenter, cross-sectional study, consecutive PD outpatients attending 7 tertiary Italian centers were enrolled. Patients were evaluated and compared for the presence of isolated PA such as camptocormia, Pisa syndrome, and anterocollis and for combined forms (ie, camptocormia + Pisa syndrome) together with demographic and clinical variables. Of the total 811 PD patients enrolled, 174 (21.5%; 95% confidence interval [CI], 18.6%-24.3%) presented PA, 144 of which had isolated PA and 30 had combined PA. The prevalence of camptocormia was 11.2% (95% CI, 9%-13.3%), Pisa syndrome 8% (95% CI, 6.2%-9.9%), and anterocollis 6.5% (95% CI, 4.9%-8.3%). Patients with PA were more often male and older with longer disease duration, more advanced disease stage, more severe PD symptoms, a bradykinetic/rigid phenotype, and poorer quality of life. They were initially treated with levodopa, and more likely to be treated with a combination of levodopa and dopamine agonist, took a higher daily levodopa equivalent daily dose, and had more comorbidities. Falls and back pain were more frequent in PD patients with PA than in those without PA. Multiple logistic regression models confirmed an association between PA and male gender, older age, Hoehn and Yahr stage, and total Unified Parkinson's Disease Rating Scale score. PA are frequent and disabling complications in PD, especially in the advanced disease stages.

Pisa Syndrome in Chinese Patients With Parkinson's Disease

Objective: To investigate the prevalence and the clinical factors related to Pisa syndrome (PS) in Chinese Parkinson's disease (PD) patients.Methods: A total of 2,167 PD patients were continuously included in this observational study. Patients with PS were identified as presented with a lateral trunk flexion of at least 10° that can be completely alleviated by passive mobilization or supine positioning. The data of the motor and non-motor symptoms including depression, anxiety and cognitive dysfunction was collected and analyzed.Results: We found seventy-seven (3.6%) PD patients presenting with PS. The following variables including age, disease duration, levodopa equivalent daily doses (LEDD), the proportion of males, the proportion of participants using levodopa, dopaminergic agonist, amantadine and entacapone, the proportion of motor fluctuations, scores of Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Unified PD Rating Scale (UPDRS) part III, and Hoehn and Yahr (H&Y) stage were significantly higher in patients with PS compared with patients without PS (P < 0.05). Scores of the Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) were not different between the two groups. The binary logistic regression model indicated that the presence of PS was associated with older age (OR = 1.027, P = 0.030), higher LEDD (OR = 1.002, P < 0.001) and a higher UPDRS III score (OR = 1.060, P < 0.001), but had no relationship with HAMD and HAMA scores.Conclusion: PS is relatively rare (3.6%) in Chinese PD patients. It is likely associated with older age, higher LEDD and more severe motor disabilities. However, non-motor symptoms such as depression, anxiety, and cognitive dysfunction have no association with PS in PD. These findings provided important complementary information for identifying the underlying mechanisms of PS.

The effect of postural deformities on back function and pain in patients with Parkinson's disease.

Postural deformities, such as Pisa syndrome (PS), and camptocormia and antecollis (C&A) are common in patient with Parkinson's disease (PwPD). These deformities can lead to back disability and pain with different mechanisms, including abnormal loading or stress on soft tissues as muscles, lumbar discs and ligaments. To evaluate the effect of different postural deformities including PS and C&A on back function and pain in PwPD. The function, disability and pain were assessed by Oswestry disability index (ODI) and brief pain inventory (BPI). All participants completed clinical assessments by the Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoenh & Yahr (mH&Y) staging and the Levodopa Equivalent Daily Dose (LEDD). PS and C&A groups significantly showed worse disability ODI and pain BPI, and higher LEDD and mH&Y stage compared with PD groups. However, no differences were found in PD duration and UPDRS in the same groups. Moreover, no differences were observed between PS and C&A groups in the mentioned scales. These results demonstrated that PS and C&A are associated with severe impairment of back functions and pain. Rehabilitation programs for PwPD and PS, and C&A should include spine alignment and postural training.

The Characteristics of Patients Associated With High Caregiver Burden in Parkinson's Disease in Singapore.

Introduction: Given the complex multitude of Parkinson's disease (PD) symptoms, caregiving for PD patients can be highly demanding. Our study was aimed to investigate the characteristics of PD patients related to different levels of caregiver burden.Methods: This cross-sectional study recruited 104 idiopathic PD patient-caregiver pairs. Patients were evaluated on motor, non-motor symptoms, and quality of life (QoL). Caregiver burden was quantified using Zarit Burden Inventory and subsequently stratified into 3 subgroups. Statistical analysis was performed to identify differences in the no-or little, mild-moderate, and high caregiver burden subgroups.Results: The mean disease duration was significantly longer in the high caregiver burden group compared to no-or little group (9.63 vs. 5.17 years; p-value 0.003). The mean levodopa equivalent daily dose (LEDD) and mean total UPDRS Part IV scores (UPDRS4) were significantly higher in the high caregiver burden group compared to no-or little group (p-value 0.011 and 0.004, respectively). The high caregiver burden group had significantly higher median QoL scores (PDQ-39) for PD patients for domain 2 (ADL, p-value 0.005), domain 4 (stigma, p-value 0.005), and domain 6 (cognition, p-value 0.002) compared to no-or little group.Conclusion: Greater caregiver burden was observed in PD patients with more prolonged disease duration, higher LEDD to control motor symptoms as well as greater levodopa related motor complications. Further studies on potential interventions to mitigate or delay levodopa related motor complications may reduce caregiver burden. Marked worsening in patient's QoL, specifically ADL, stigma and cognition in the high compared to no-or little caregiver burden group suggests the possible utility of monitoring these factors for early identification of increasing caregiver stress and burden.

Factors Associated With Dyskinesia in Parkinson's Disease in Mainland China.

Background and Objectives: Studies examining the risk factors for dyskinesia in Parkinson's disease (PD) have been inconsistent, and racial differences exist. Since there have been no systematic studies of the characteristics of dyskinesia in the Mainland Chinese population, we sought to elucidate the risk factors for dyskinesia.Methods: A total of 1974 PD patients from Mainland China were systematically investigated by univariable and multivariable analyses. PD patients with and without dyskinesia were stratified into 4 groups according to levodopa equivalent daily dose (LEDD) and analyzed by a Cox proportional hazards model. A longitudinal study of 87 patients with dyskinesia was classified into 3 groups according to the duration from onset of PD to the initiation of levodopa, and comparisons among groups were analyzed by the Mann-Whitney test.Results: Early age of onset, long disease duration, being female, high LEDD, low UPDRS III scores (ON-state) and high Hoehn-Yahr stage (ON-state) were predictors of dyskinesia. Dyskinesia was levodopa dosage-dependent, and the incidence increased remarkably when LEDD exceeded 300 mg/d (p < 0.05). The emergence of dyskinesia had no association with the initiation time of levodopa, and if the latter was more than 4 years, the duration of time on chronic levodopa free of motor complications was significantly shortened.Conclusions: We found risk factors for the prediction of dyskinesia. Our data shows that physicians should be cautious if the LEDD exceeds 300 mg/d. The development of dyskinesia was not correlated with the time of levodopa initiation.

L-dopa responsiveness in early Parkinson's disease is associated with the rate of motor progression

BackgroundL-dopa responsiveness in Parkinson's disease (PD) varies, but the clinical correlates and significance of this are ill-defined. MethodsPatients were assessed before and after their usual morning L-dopa dose, using the MDS Unified PD Rating Scale Part 3 (MDS UPDRS 3), and rated as definite responders (≥24.5% improvement) or limited responders (<24.5%). Results1007 cases, mean age 66.1 years (SD 9.1) at diagnosis, were assessed 3.4 (SD 0.9) years after diagnosis. The L-dopa response was definite in 614 cases (61.0%), median reduction in MDS UPDRS 3 scores was 42.0%, (IQR 33.3, 53.1), and was limited in 393 cases (39.0%), median reduction in MDS UPDRS 3 scores 11.5% (IQR 4.3, 18.2). Definite responders were younger (66.3 years at study entry, SD 9.3) than limited responders (69.2 years, SD 8.4, p < 0.001). The MDS UPDRS 3 score at study entry in definite responders (21.0, SD 10.5) was significantly lower than in limited responders (24.7, SD 13.4, p < 0.001). The MDS UPDRS 3 increase over 18 months was less in definite responders at 3.0 (SD 10.4), compared to limited responders (6.4, SD 11.0, p < 0.001). The levodopa equivalent daily dose (LEDD) was not significantly different at study entry (definite responders 317 mg, SD 199, vs limited responders 305 mg, SD 191, p = 0.53). However, LEDD was significantly higher at the time of the L-dopa challenge test in definite responders (541 mg, SD 293) compared to limited responders (485 mg, SD 215, p = 0.01). Responsiveness to L-dopa was unaffected by the challenge test dose (p = 0.54). ConclusionsThe main determinants of variation in the L-dopa response in early PD are age and motor severity. A limited L-dopa response is associated with faster motor progression.