Using Unified Parkinson's Disease Rating Scale Research Articles

Microstructural alterations of the hypothalamus in Parkinson's disease and probable REM sleep behavior disorder

BackgroundWhether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial. ObjectivesWe aimed to quantify microstructural changes in hypothalamus using a novel deep learning-based tool in patients with PD and those with probable rapid-eye-movement sleep behavior disorder (pRBD). We further assessed whether these microstructural changes associated with clinical symptoms and free thyroxine (FT4) levels. MethodsThis study included 186 PD, 67 pRBD, and 179 healthy controls. Multi-shell diffusion MRI were scanned and mean kurtosis (MK) in hypothalamic subunits were calculated. Participants were assessed using Unified Parkinson's Disease Rating Scale (UPDRS), RBD Questionnaire-Hong Kong (RBDQ-HK), Hamilton Depression Rating Scale (HAMD), and Activity of Daily Living (ADL) Scale. Additionally, a subgroup of PD (n = 31) underwent assessment of FT4. ResultsPD showed significant decreases of MK in anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tubular (supTub), and inferior tubular hypothalamus when compared with healthy controls. Similarly, pRBD exhibited decreases of MK in a-iHyp and supTub. In PD group, MK in above four subunits were significantly correlated with UPDRS-I, HAMD, and ADL. Moreover, MK in a-iHyp and a-sHyp were significantly correlated with FT4 level. In pRBD group, correlations were observed between MK in a-iHyp and UPDRS-I. ConclusionsOur study reveals that microstructural changes in the hypothalamus are already significant at the early neurodegenerative stage. These changes are associated with emotional alterations, daily activity levels, and thyroid hormone levels.

Clinical characteristics and reaction to dopaminergic treatment of drug-naïve patients with Parkinson's disease in central China: A cross sectional study

BackgroundThe symptoms of early Parkinson's disease (PD) are complex and hidden. The aim of this study is to explore and summarize the characteristics of the symptoms of drug naïve patients with PD. Objectivesand Methods Drug-naïve patients with PD and age-matched healthy controls were recruited from the outpatient clinic of Wuhan Union Hospital. The motor and non-motor symptoms were evaluated for further analysis using Unified Parkinson's Disease Rating Scale (UPDRS) I, II, and III; Sniffin’ Sticks Screening 12 test; Mini-Mental State Exam (MMSE); Montreal Cognitive Assessment (MoCA); Hamilton Anxiety Scale (HAMA); and Hamilton Depression Scale (HAMD) scores. The acute levodopa challenge test (ALCT) was adopted to assess the reaction to dopaminergic treatment. ResultsWe recruited 80 drug-naïve patients with PD and 40 age-matched healthy controls (HCs). Approximately 53.7% of the patients were females. The mean onset age was 59.96 ± 10.40 years. The mean UPDRS I, II, and III were 2.01 ± 1.90, 6.18 ± 3.68, and 26.13 ± 12.09, respectively. Compared with HCs, PD patients had lower scores in MMSE and MoCA; and higher scores in HAMA and HAMD (p < 0.05). In ALCT, 54 patients showed good responses to levodopa while 26 patients did not. The mean improvement rate of UPDRS III was 34.09% at 120 min. ConclusionThe motor symptoms of patients with early PD were mild but virous. They also suffered from different non-motor symptoms. In ALCT, about two thirds of patients (54/80) with early PD showed good response to levodopa. Among four aspects of motor symptoms, bradykinesia reacted best to ALCT, while axial symptoms were the worst.

Optical coherence tomography in patients with Parkinson\u2019s disease

BackgroundThe changes in the different retinal layers in Parkinson’s disease (PD) patients can be easily assessed using optical coherence tomography (OCT). Our aim was to evaluate retinal structural changes in patients with PD using OCT. Structural measurements of the retinal nerve fiber layer (RNFL), macular and ganglion cell complex (GCC) thicknesses were obtained using spectral domain optical coherence tomography. Disease severity was assessed using Unified Parkinson Disease Rating Scale (UPDRS).ResultsRetinal nerve fiber layer parameters, except for the superonasal and inferonasal quadrants, were significantly reduced in PD patients compared to controls. All macular parameters and GCC thickness were also reduced in PD patients compared to controls. Hoehn and Yahr (HY) staging was inversely correlated with all macular parameters, GCC and temporal RNFL thicknesses. UPDRS score showed a significant negative correlation with macular volume, inferior and nasal parafoveal thicknesses, nasal and temporal RNFL thicknesses and GCC thickness. The disease duration was inversely correlated with macular volume, inferior and temporal parafoveal thicknesses and GCC thickness. Using the multivariate linear regression analysis, the HY scale was a significant predictor for both the average GCC thickness and the macular volume. The sensitivity and specificity of average GCC thickness and macular volume to detect disease severity were 58.8%, 86.7%, 64.7% and 86.7%, respectively.ConclusionParkinson’s disease causes axonal damage in the RNFL along with retinal thinning that can be detected using SD-OCT. Patients with greater axonal damage tend to have longer duration of the disease and more severe PD symptoms.

Comparisons of vesicular monoamine transporter type 2 signals in Parkinson's disease and parkinsonism secondary to carbon monoxide poisoning

Parkinson’s disease (PD) and carbon monoxide (CO) poisoning demonstrate parkinsonian features related to presynaptic dopaminergic deficits. However, their clinical features and treatment responses are different, indicating other roles of neurotransmitters in symptomatic modulation. In this study, we used 18F-FP-(+)-DTBZ PET to explore vesicular monoamine transporter type 2 (VMAT2) distributions in 31 patients with PD, 39 patients with CO poisoning and parkinsonian features (n = 39), and 24 age-matched controls. In addition to the disease-specific VMAT2 topographies in PD and CO poisoning, we also constructed feature-specific functional networks. The cardinal features included tremor, rigidity, akinesia, and rapid alternating movements (RAM), and the overall motor severity was scored using Unified Parkinson Disease Rating Scale (UPDRS) and modified Hoehn-Yahr (mH-Y) Scale scores. Our results suggested that a reduction in VMAT2 signals in the caudate, amygdala, and hippocampus were more specific to CO poisoning, while low uptake in the putamen and substantia nigra was more specific to PD. UPDRS and mH-Y scores were related to striatum signals in both groups and hippocampus and raphe in the CO poisoning group. With regards to the cardinal features, the putamen was related to akinesia in both groups. The substantia nigra was related to rigidity in PD, and the caudate and nucleus accumbens were related to akinesia, RAM and rigidity in CO poisoning. Our study enhances the current understanding of different patterns of monoaminergic terminal deficits in patients with CO poisoning and PD.

Zonisamide improves wearing off in Parkinson's disease without exacerbating dyskinesia: Post hoc analysis of phase 2 and phase 3 clinical trials

IntroductionAlthough phase 2 and 3 clinical trials in Japan showed that zonisamide improved wearing off in patients with Parkinson's disease (PD), no studies to date have evaluated whether zonisamide improves wearing off in patients with PD without exacerbating dyskinesia. Therefore, we examined this hypothesis in a post hoc analysis of pooled data from the previous phase 2 and 3 trials. MethodsBoth trials evaluated zonisamide 25 mg and 50 mg versus placebo during a 12-week treatment period. In our analysis, primary efficacy variables were adjusted mean change in wearing off (evaluated as change in “off” time) and dyskinesia from baseline to 12 weeks. Dyskinesia was evaluated using Unified Parkinson's Disease Rating Scale (UPDRS) part 4 items 32 (4-32; duration of dyskinesia) and 33 (4-33; disability of dyskinesia) score. Criteria outcomes included rates of patients meeting specific criteria based on off time plus UPDRS part 4-32 or 4-33. ResultsA total of 212 patients were included in this analysis. Zonisamide 50 mg significantly reduced off time and UPDRS part 4-33 score at week 12 versus placebo without increasing UPDRS part 4-32 score. The proportion of patients receiving zonisamide 50 mg who met the criterion “Off time decreased and UPDRS part 4-33 score did not increase” was significantly higher than that of patients receiving placebo. ConclusionZonisamide improves wearing off without exacerbating dyskinesia in Japanese patients with PD. Moreover, zonisamide 50 mg may improve dyskinesia. Further studies are needed to prospectively determine the benefits and clinical relevance of zonisamide on dyskinesia.

Generation of induced pluripotent stem cells (NIMHi002-A and NIMHi003-A) from two sporadic Parkinson's disease patient of East Indian ethnicity.

Epidemiological studies suggest that about 95% of PD have a sporadic component. We have generated induced pluripotent stem cells (iPSCs) using Sendai-virus reprogramming-method from peripheral blood mononuclear cells of two sporadic PD-patient of East-Indian ethnicity carrying no PD-related gene mutations. PD diagnosis was performed using Unified Parkinson's Disease rating scale (UPDRS) score and confirmed by [18F]fluoro-L-dopa [F-DOPA] positron emission tomography (F-DOPA PET). The iPSC lines were characterized for self-renewal and pluripotency. These generated lines will provide a valuable resource to understand the pathophysiology of this disease and a drug-screening platform.

Generation of induced pluripotent stem cells (NIMHi001-A) from a Parkinson's disease patient of East Indian ethnicity carrying LRRK2 I1371V variant.

Mutations in the Leucine Repeat Rich Kinase-2 (LRRK2) gene have been reported in familial Parkinson's disease (PD) cases. We have generated induced pluripotent stem cells (iPSCs) using Sendai-virus reprogramming-method from peripheral blood mononuclear cells of PD-patient of East-Indian ethnicity carrying the I1371V mutation in LRRK2 gene. PD diagnosis was performed using Unified Parkinson's Disease rating scale (UPDRS) score and confirmed by [18F]fluoro-l-dopa [F-DOPA] positron emission tomography (F-DOPA PET). The iPSC line was characterized for self-renewal and pluripotency. This cellular model will provide a valuable resource not only for drug-screening platform but also to understand the pathophysiology of this disease.

Presynaptic dopaminergic function in early-onset Alzheimer's disease: an FP-CIT image study

We aimed to investigate whether amyloid-β (Aβ) positive early-onset Alzheimer's disease (EOAD) patients have presynaptic dopaminergic deficits on in vivo 18F-FP-CIT PET imaging. We enrolled 34 EOAD patients and 9 cognitively normal controls (NC), all of whom underwent 18F-florbetaben and 18F-FP-CIT PET at Samsung Medical Center. We assessed motor symptoms using Unified Parkinson's Disease Rating Scale (UPDRS) and divided the EOAD patients into 2 groups using a UPDRS cutoff of 10. We compared regional florbetaben and FP-CIT uptake across the NC and the 2 EOAD groups with lower and higher UPDRS and investigated the associations between regional florbetaben or FP-CIT uptake and UPDRS in EOAD patients. Among the 30 EOAD patients who were Aβ positive on florbetaben PET, the higher UPDRS (>10) group (n = 9) had a longer disease duration (7.2 ± 3.3 vs. 4.1 ± 1.8, p = 0.002), and had a tendency to have lower Mini-Mental State Examination (9.6 ± 7.9 vs. 15.0 ± 6.0, p = 0.052) than the lower UPDRS (≤10) group (n = 21). Across the NC and the 2 EOAD groups, there were no significant differences in FP-CIT uptake in caudate (p = 0.122) and putamen (p = 0.685) or florbetaben uptake in midbrain (p = 0.890). Finally, regression analyses showed that UPDRS was not associated with FP-CIT uptake in caudate (p = 0.913) or putamen (p = 0.407), or with florbetaben PET uptake in caudate (p = 0.553), putamen (p = 0.617), midbrain (p = 0.843), or global cortex (p = 0.658). This study showed that parkinsonian signs in EOAD patients may be related with mechanisms other than presynaptic dopaminergic deficit. Our finding is clinically important because it suggests that L-dopa treatment in EOAD with parkinsonian signs may not improve motor symptoms.

Exploring the association between Cerebral small-vessel diseases and motor symptoms in Parkinson's disease.

Objectivesto explore the association between cerebral small‐vessel diseases (CSVDs) and motor symptoms in Parkinson's disease (PD).Methods137 PD patients were recruited into the study. Detailed motor symptoms, including tremor, rigidity, bradykinesia, and axial impairment, were evaluated using Unified Parkinson's disease Rating Scale (UPDRS). Non‐motor symptoms, including cognition, anxiety, and depression, were evaluated using Montreal Cognitive Assessment (MoCA), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD). Brain MRI was used to assess the subtypes of CSVDs, including lacunes, enlarged perivascular spaces (EPVS), and white matter hyperintensities (WMH). WMH were furtherly divided into deep WMH (DWMH) and periventricular hyperintensities (PVH). The association between CSVDs and motor symptoms was analyzed. Patients were divided into the postural instability and gait disability (PIGD) group and non‐PIGD group. Demographic, clinical and CSVDs variables were compared between the two groups.Results CSVDs subtypes were all detected in the participants with different prevalence rates and severity degrees. We found a close association between EPVS in basal ganglia and the tremor score (p = 0.032), and between DWMH in the frontal and occipital lobes and the axial motor score (p < 0.05) through the spearman and multivariate liner regression analysis. Compared with the non‐PIGD group, the PIGD group demonstrated more serious cognitive impairment and DWMH in the frontal and occipital lobes (p < 0.05). The demographic characteristics and vascular risk factors of the PIGD group were not different from those of the non‐PIGD group. Cognitive impairment and DWMH in the frontal lobe were identified to be independent risk factors of PIGD motor phenotype.ConclusionsWe identified a close association between the CSVDs and motor symptoms in PD and DWMH in the frontal lobe was a risk factor of PIGD motor phenotype, which supports the contribution of vascular pathology in PD.

Effect of using a wearable device on clinical decision-making and motor symptoms in patients with Parkinson's disease starting transdermal rotigotine patch: A pilot study

BackgroundFeedback from wearable biosensors may help assess motor function in Parkinson's disease (PD) patients and titrate medication. Kinesia 360 continuously monitors motor symptoms via wrist and ankle sensors. MethodsPD0049 was a 12-week pilot study to investigate whether using Kinesia 360 at home could improve motor symptom management in PD patients starting transdermal dopamine agonist rotigotine. Adults with PD and insufficiently controlled motor symptoms (prescribed rotigotine) were randomized 1:1 to Control Group (CG) or Experimental Group (EG) before starting rotigotine. Motor symptoms were assessed in all patients at baseline and Week 12 (W12) using Unified PD Rating Scale (UPDRS) III and Kinesia ONE, which measures standardized motor tasks via a sensor on the index finger. Between baseline and W12, EG used Kinesia 360 at home; clinicians used the data to supplement standard care in adjusting rotigotine dosage. ResultsAt W12, least squares mean improvements in UPDRS II (−2.1 vs 0.5, p = 0.004) and UPDRS III (−5.3 vs −1.0, p = 0.134) were clinically meaningfully greater, and mean rotigotine dosage higher (4.8 vs 3.9 mg/24 h) in EG (n = 19) vs CG (n = 20). Mean rotigotine dosage increase (+2.8 vs + 1.9 mg/24 h) and mean number of dosage changes (2.8 vs 1.8) during the study were higher in EG vs CG. Tolerability and retention rates were similar. ConclusionContinuous, objective, motor symptom monitoring using a wearable biosensor as an adjunct to standard care may enhance clinical decision-making, and may improve outcomes in PD patients starting rotigotine.

Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease

Background/Aims: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. Methods: In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. Results: We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. Conclusion: Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS.

Interleukin-18 promoter polymorphisms and idiopathic Parkinson disease: an Egyptian study.

Etiology of sporadic Parkinson's disease (PD) is largely unknown. The contribution of genetic factors to the pathogenesis of PD is supported by the demonstration of high concordance in twins, increased risk among relatives of PD patients and existence of familial cases. This study aimed to examine the relation between interleukin 18 (IL-18) gene promoter polymorphisms and idiopathic PD, and its impact on clinical presentation and disease severity. 30 idiopathic PD patients and 15 age- and sex-matched healthy subjects were included. Disease severity was assessed using Unified Parkinson's Disease Rating Scale (UPDRS). Genetic testing for IL-18 gene promoter -607C/A single nucleotide polymorphisms (SNP) was done using real-time polymerase chain reaction (PCR) technique. A raised risk of PD development was found in patients with A/C and C/C genotypes of the site -607C/A (odds ratios = 1.83 and 1.98, respectively). The distribution of the genotypes showed no significant relation to gender or predominant clinical presentation. The age at onset of disease was significantly lower in C/C and A/A genotypes compared to A/C genotype (p = 0.001 and 0.04, respectively). Patients with A/A genotype showed significantly higher mentation score of UPDRS compared to patients with A/C and C/C genotypes (p = 0.003 and p = 0.002, respectively). Polymorphisms of IL-18 gene promoter increase the risk of developing idiopathic PD. The polymorphisms may affect phenotypic expression rather than being a direct cause of idiopathic PD.

Basal Ganglia and Prefrontal Regions Influence Postural Control and Cognitive Impairment in Parkinson's Disease

ObjectivePostural instability is one of clinical manifestations caused by the deterioration of basal ganglia (BG) in Parkinson's disease (PD). It has frequently been found in moderate and advanced stages of the disease, simultaneously, impairments of cognition and executive function are also commonly present. Several studies reported interferences between postural control and cognitive tasks passing the prefrontal regions. We aimed to reveal the roles of BG and prefrontal regions in postural control and cognitive impairment in PD patients who exhibit freezing of gait (FOG).MethodsWe measured postural control in 60 patients with Parkinson's disease (PD) in on‐medication (39 PD patients with FOG and 21 PD patients without FOG). A Nintendo Wii balance board was utilized to measure postural stability in terms of center of pressure (CoP). A modified Hoehn and Yahr scale (H&amp;Y) was used to classify clinical staging of PD. Subjects' disease severities were evaluated by using Unified Parkinson's Disease Rating Scale (UPDRS) (part III). Levodopa Equivalent Dose (LED), New Freezing of Gait questionnaire (NFOG‐Q), and Montreal Cognitive Assessment were also assessed. The participants were instructed to stand naturally on the balance platform and look at a marker, which was 3 meters from the board. The subjects were asked to perform counting days backward for a total of 170 seconds. A computer program collected the data automatically (Buated, W., et.al. Gerontology and Geriatric Medicine, 2016). Regression analysis were performed for posturographic and clinical variables to identify relationships of mild cognitive impairment, postural instability and FOG. An important parameter of CoP; path length (PL), which was found to be dominant factor of the balance analysis (Buated, W., et al. The 19th International Congress of Parkinson's Disease and Movement Disorders, 2015), was also calculated. Principal component analysis was used to analyze all clinical variables and determined the statistical significance of the variance.ResultsAssociations between PL and clinical variables were observed in all patients; LED (R2 = 0.150, p = 0.001), H&amp;Y (R2 = 0.060, p = 0.060), duration of disease (R2 = 0.065, p &lt; 0.049) and NFOG‐Q (R2 = 0.108, p = 0.010). In PD patients with FOG, relationship was found in LED (R2 = 0.125, p = 0.032). On the other hand, no relationship was noticed in PD patients without FOG.ConclusionsBasal ganglia and prefrontal regions play important roles in postural control and cognitive function in PD patients. Freezing of gait (FOG), cognitive impairment and postural control are associated with the effects of medication. Among the clinical variables, the correlation between LED and PL was found to be most important. These influences of the interruption of the neural circuitry were expressed in the postural control of PD patients, especially those subjects with FOG symptoms.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Relation of overactive bladder with motor symptoms and dopamine transporter imaging in drug-naïve Parkinson's disease

ObjectivesThe aim of the present study was to determine the relation of urinary dysfunction with motor symptoms and nigrostriatal neuron loss in drug-naïve patients with Parkinson's disease (PD). We therefore examined the relation of overactive bladder (OAB) symptoms with motor symptoms and striatal dopamine transporter (DAT) binding measured by [123-Iodine]-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenylnortropane) dopamine transporter single-photon emission computed tomography (123I-FP-CIT SPECT). Patients and methodsThirty-one untreated PD patients (12 men and 19 women with a mean age of 71.2 ± 6.7 years) were included in this study. Patients were evaluated with overactive bladder symptom score (OABSS) and divided into an OAB group and Non-OAB group. They underwent clinical assessments and 123I-FP-CIT SPECT imaging. Motor symptoms were assessed using Unified Parkinson's Disease Rating Scale (UPDRS). ResultsThe results showed that UPDRS motor score (p = 0.01) and akinetic-rigid score (p = 0.002) were higher and that striatal DAT availability (p = 0.01) was lower in the OAB group than in the Non-OAB group. However, tremor score, age, and duration of PD showed no significant differences between the OAB group and Non-OAB group. ConclusionsUrinary dysfunction in untreated PD is related with increase in motor symptoms (especially bradykinesia and axial symptoms) and reduction of striatal DAT availability.

Neurotoxicity of carbon monoxide targets caudate-mediated dopaminergic system

The clinical features of parkinsonism in carbon monoxide (CO) intoxication have been associated with striatal-related neuronal networks. As parkinsonian and neuropsychiatric features are both related to presynaptic dopaminergic integrity, the aim of this study was to explore the clinical significance of 99mTcTRODAT-1 in grading neurobehavioral scores and parkinsonian severity in CO intoxication.We enrolled 64 patients with CO intoxication, including 29 with parkinsonism (parkinsonism[+] group) and 35 without (parkinsonism[−] group). All of the patients received 99mTcTRODAT-1 neuroimaging evaluations, comprehensive neurobehavioral tests and assessments of the severity of parkinsonism using Unified Parkinson's Disease Rating Scale (UPDRS)-part III motor score. Univariate and multivariate regression analyses were used to test the predictive factors and scores for a diagnosis of parkinsonism and its severity.The parkinsonism(+) group had significantly lower cognitive scores and higher neuropsychiatric total scores compared with the parkinsonism(−) group, both of which were independently related to the severity of parkinsonism. 99mTcTRODAT-1 regional caudate signals were correlated with tremors at rest, action or postural tremors of the hands, bradykinesia and hypokinesia, and visuospatial, verbal fluency, abstract thinking and digit backwards scores. Scores of the neurobehavioral tests and UPDRS items were highly correlated (p<0.01).Our results validated the initial hypothesis in that neurobehavioral deficits and parkinsonian symptoms were highly related. This association was independent of demographic factors and initial carboxyhemoglobin level. Within the presynaptic dopaminergic circuit, the clinical role of the caudate in mediating the clinical symptoms in CO intoxication may outweigh the putamen.

Analyzing the effectiveness of vocal features in early telediagnosis of Parkinson's disease

The recently proposed Parkinson’s Disease (PD) telediagnosis systems based on detecting dysphonia achieve very high classification rates in discriminating healthy subjects from PD patients. However, in these studies the data used to construct the classification model contain the speech recordings of both early and late PD patients with different severities of speech impairments resulting in unrealistic results. In a more realistic scenario, an early telediagnosis system is expected to be used in suspicious cases by healthy subjects or early PD patients with mild speech impairment. In this paper, considering the critical importance of early diagnosis in the treatment of the disease, we evaluate the ability of vocal features in early telediagnosis of Parkinson's Disease (PD) using machine learning techniques with a two-step approach. In the first step, using only patient data, we aim to determine the patient group with relatively greater severity of speech impairments using Unified Parkinson’s Disease Rating Scale (UPDRS) score as an index of disease progression. For this purpose, we use three supervised and two unsupervised learning techniques. In the second step, we exclude the samples of this group of patients from the dataset, create a new dataset consisting of the samples of PD patients having less severity of speech impairments and healthy subjects, and use three classifiers with various settings to address this binary classification problem. In this classification problem, the highest accuracy of 96.4% and Matthew’s Correlation Coefficient of 0.77 is obtained using support vector machines with third-degree polynomial kernel showing that vocal features can be used to build a decision support system for early telediagnosis of PD.

134 VANTAGE Trial

INTRODUCTION: Deep brain stimulation (DBS) has been demonstrated to be effective for Parkinson disease (PD) symptom relief. We sought to characterize the benefit of subthalamic nucleus (STN) DBS for PD patients using a recently CE-marked multiple-source, constant-current system that permits a well-defined distribution of applied current. We report the 3-year results of the first clinical trial using multiple independent current control (MICC) DBS in the management of symptoms of PD. METHODS: VANTAGE is a monitored, prospective, multicenter, nonrandomized, open-label interventional trial sponsored by Boston Scientific Corporation. Forty subjects with idiopathic PD were implanted bilaterally with a DBS system (Vercise) targeting the STN and followed up to 3 years after lead placement. Motor improvement was evaluated using Unified Parkinson's Disease Rating Scale (UPDRS) III scores in stim ON/meds OFF in comparison with preoperative scores. Other assessments such as CAPSIT motor tests, Tremor Rating Scale, Dyskinesia Rating Scale, PDQ-39, SF-36, Schwab and England, and resource utilization were administered. Patient motor diaries were collected over 3 days. Adverse events were also recorded. RESULTS: This study will report the safety and effectiveness outcomes of VANTAGE subjects at 3 years postimplantation as compared with baseline. CONCLUSION: The VANTAGE trial is the first reported trial of a multiple-source, constant-current rechargeable system for use in the management of PD symptoms. Study outcomes will inform clinicians on the use of this system and its flexibility to manage the symptoms of idiopathic PD.

Mirror movements in Parkinson's disease: An under-appreciated clinical sign

IntroductionMirror movements (MM) have been previously reported in patients with Parkinson's disease (PD). Despite being potentially relevant in PD, MM as a neurological sign have remained less recognized. In this study we critically evaluated the characteristic features of MM and their attributes among a cohort of PD patients from a tertiary care center of eastern part of India. MethodsIn this analytical cross-sectional study, 70 patients with PD were evaluated using Unified Parkinson's Disease Rating Scale (UPDRS) and a previously used scale to score MM in the OFF and ON phases of l-Dopa therapy. MM was video-recorded for 4 motor tasks (finger- tapping, hand-movement, pronation–supination, rapid ankle-flexion-extension) and scored for the MM attributes i.e. amplitude, distribution and proportion. ResultsA vast majority of PD patients (95.7%) exhibited MM and there was a trend of higher MM score with lesser severity of disease affection. Marked differences in amplitude, distribution and proportion of MM in the upper and lower limbs were evident in response to l-Dopa therapy in certain motor tasks. In addition, less involved limbs exhibited higher MM and the MM scores were higher for lower limb tasks in the ON phase. ConclusionsThe high prevalence of MM in PD patients and its correlation to disease severity echoed previous studies across the globe. In addition, this study provides evidence for a differential response of MM attributes to l-Dopa.To our knowledge, this is the first study that characterized MM in a cohort of PD patients from India. Our findings suggest the significance of MM as a clinical neurological sign in PD.

Burden among Parkinson's disease care givers for a community based study from India

Aim was to analyze predictors of burden among primary caregivers (CGs) of Indian Parkinson's disease (PD) patients. 150 PD patients were administered using Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr Scale (H&Y), Montgomery Asberg Depression Rating Score (MADRS) and Mini Mental State Examination (MMSE) in this cross-sectional evaluation study. CG burden was assessed by Caregiver's Burden Scale (CBS), Hospital Anxiety and Depression Scale (HADS), SF-36 and 20-item Burden Assessment Schedule (BAS). Linear regression methods were used to evaluate factors contributing to burden and stress. Mean age of CG was 50.38±16.04 (range: 25-83yrs). Marital status of CGs was noted to have significant relationship with CBS score (F=9.525, P<0.0001). Siblings (brother/sister) reported the highest CBS score while the wives reported the least. Correlations were strong between CBS and HADS anxiety (r=0.228, P=0.0048) and HADS depression (r=0.2172, P=0.0076). High correlations were found in caregiving duration, patients' stage of illness and motor disability among all the scales (CBS, HADS, SF36) determined. Step-wise regression analysis showed UPDRS (beta=1.364–0.202 ranging among all scales) and H&Y stages (beta=2.786–7.257) to have the strongest influence on CGs. CGs of patients with depression (MADRS: P=0.007 (SF36 mental) and dementia (MMSE: P=0.01) experienced greater stress. Social and financial status was disrupted in ~60% to 80% of the CGs. Motor imbalances with disability of PD patients and severity of disease are the main factors contributing to burden and stress in CGs.

Neuropsychiatric co-morbidities in non-demented Parkinson′s disease

Objective:To evaluate neuropsychiatric co-morbidities (depression, psychosis and anxiety) in non-demented patients with Parkinson's disease (PD).Background:Non-motor symptoms like neuropsychiatric co-morbidities are common in Parkinson's disease and may predate motor symptoms. Currently there is scarcity of data regarding neuropsychiatry manifestations in Indian patients with PD.Methods:In this cross-sectional study consecutive 126 non-demented patients with PD (MMSE ≥25) were enrolled. They were assessed using Unified Parkinson's disease rating scale (UPDRS), Hoehn & Yahr (H&Y) stage, Schwab and England (S&E) scale of activity of daily life. Mini-international neuropsychiatric interview (MINI) was used for diagnosis of depression, psychosis and anxiety. Beck's depression inventory (BDI), Brief psychiatric rating scale (BSRS) and Hamilton rating scale for anxiety (HAM-A) scales were used for assessment of severity of depression, psychosis and anxiety respectively.Results:Mean age and duration of disease was 57.9 ± 10.9 years and 7.3 ± 3.6 years respectively. At least one of the neuropsychiatric co-morbidity was present in 64% patients. Depression, suicidal risk, psychosis and anxiety were present in 43.7%, 31%, 23.8% and 35.7% respectively. Visual hallucinations (20.6%) were most frequent, followed by tactile (13.5%), auditory (7.2%) and olfactory hallucinations (1.6%). Patients with depression had higher motor disability (UPDRS-motor score 33.1 ± 14.0 vs 27.3 ± 13.3; and UPDRS-total 50.7 ± 21.8 vs 41.0 ± 20.3, all p values <0.05). Patients with psychosis were older (63.6 ± 8.0 years vs 56.1 ± 11.1 years, p < 0.05) and had longer duration of illness (8.6 ± 3.4 years vs 6.9 ± 3.5, p < 0.05).Conclusions:About two third patients with Parkinson's disease have associated neuropsychiatric co-morbidities. Depression was more frequent in patients with higher disability and psychosis with longer duration of disease and older age. These co-morbidities need to be addressed during management of patients with PD.