Rigidity Subscores Research Articles

Impaired Gait, Postural Instability, and Rigidity in Relation to CB1 Receptor Availability in Parkinson's Disease.

In Parkinson's disease (PD), postural instability and gait disorder (PIGD) symptoms are associated with a worse prognosis for an unknown reason. The objective was to explore the relationship between cannabinoid receptor type 1 (CB1R) availability and motor symptoms in PD with [18F]FMPEP-d2 positron emission tomography (PET). Fifteen individuals with PD underwent [18F]FMPEP-d2 PET to measure cerebral CB1R availability. The Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) was used to evaluate the motor symptoms. A negative correlation was observed between [18F]FMPEP-d2 VT and PIGD score (P = 0.002) as well as rigidity subscore (P < 0.001). Both clusters covered widespread areas of both hemispheres. In contrast, tremor or bradykinesia did not correlate to [18F]FMPEP-d2 VT. Gait, postural instability, and rigidity in PD are associated with decreased CB1R availability, unlike tremor or bradykinesia, suggesting that the endocannabinoid system has a role in the pathophysiology of different motor symptoms in PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Added forearm weights for gait pattern normalization in patients with Parkinson’s disease

Patients with Parkinson’s Disease presented gait impairment. Applying additional weights to enhancing sensory input may improve gait impairment. We assumed that gait impairment could be improved when patients walked with additional forearm weights, and the gait improvement was associated with clinical characteristic of Parkinson’s Disease. Thirty patients with Parkinson’s Disease and 30 age-sex matched controls were recruited. Spatiotemporal and joint kinematics parameters were evaluated by a three-dimensional motion capture system in normal walking and walking with sandbags, respectively. The comparisons of spatiotemporal parameters were analyzed using t-test or nonparametric tests. The comparison of joint kinematic data was analyzed using statistical parametric mapping. The correlation between motor symptom and gait parameters changes was analyzed using Pearson’s correlation analysis. During normal walking, patients showed deteriorated gait compared with controls. After applying weights to forearms patients increased cadence (p = 0.004), speed (p < 0.001) and step length (p = 0.048), and decreased stride time (p = 0.003). The hip angles significantly increased during 5%–23% and 87%–100% of gait cycle, while knee angles during 9%–25% and 88%–98% of the gait cycle, and ankle angles in 92%-100% of gait cycle. The gait parameters of patients with forearm-loading showed no significant difference compared with healthy subjects walking normally. The change of gait parameters correlated positively with the axial and tremor severity while correlated negatively with the rigidity sub-score. Patients with tremor dominant subtype also showed greater improvement of speed and step time compared with patients with postural instability/gait difficulty subtype. Applying added weights bilaterally to the forearms of patients can normalize gait patterns. Notably, patients with higher scores on axial and tremor and lower rigidity scores gained more benefits.

Clinical and Physiological Effects of Single Day Accelerated Theta Burst Transcranial Focused Ultrasound in Parkinson’s Disease (P4-11.008)

<h3>Objective:</h3> To evaluate the tolerability and efficacy of an accelerated schedule of theta burst focused ultrasound stimulation (tbTUS) delivered to the primary motor cortex in Parkinson’s disease (PD) patients assessed by transcranial magnetic stimulation (TMS) and United Parkinson’s Disease Rating Scale (UPDRS)-Part III. <h3>Background:</h3> Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate deeper in the brain with more focal stimulation compared to currently used forms of NIBS. TUS delivered in a theta burst pattern (tbTUS) for 80s induces sustained increases in motor cortex excitability lasting at least 30 minutes and is a promising NIBS protocol for treatment of neurological disorders. Accelerated stimulation schedules with several treatments per day can shorten treatment duration and improve accessibility. <h3>Design/Methods:</h3> Three sets of tbTUS were delivered in consecutive order to the right and left primary motor cortices at 30-minute intervals. 10 PD patients attended one visit each for real and sham treatments in random order. Before and after interventions, TMS measures of motor-evoked potentials (MEP), short-interval intracortical inhibition (SICI), short-interval intracortical excitation (SICF), and UPDRS-Part III scores were collected. Patients and UPDRS raters were blinded to the stimulation condition. <h3>Results:</h3> Real but not sham tbTUS treatment led to increased MEP amplitude and SICF. While both conditions led to similar changes in UPDRS-III scores, rigidity subscores were reduced only with real treatment. There were no adverse effects. <h3>Conclusions:</h3> The study is ongoing, and more patients are being recruited. Preliminary findings show that accelerated tbTUS is a safe and tolerable treatment schedule for PD patients. Improvements in rigidity suggests that tbTUS could be further studied as a non-invasive treatment for PD. Future research may investigate the optimal time between sonications with a longer treatment duration and a larger number of patients. <b>Disclosure:</b> Yi Rong Ding has nothing to disclose. Dr. Samuel has nothing to disclose. Dr. Grippe has nothing to disclose. Dr. SARICA has nothing to disclose. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Insightec. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Scientific. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Functional Neuromodulation. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Paladin Labs. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Chen has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Canadian Journal of Neurological Sciences. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorders. The institution of Dr. Chen has received research support from Canadian Institutes of Health Research. The institution of Dr. Chen has received research support from NIH. The institution of Dr. Chen has received research support from Natural Science and Engineering Research Council of Canada. Dr. Chen has received research support from Parkinson Foundation. The institution of Dr. Chen has received research support from National Organization for Rare Disease. The institution of Dr. Chen has received research support from Merz.

Neurophysiological Predictors of Response to Medication in Parkinson's Disease.

Background: Although dopaminergic medication has been the foundation of Parkinson's disease (PD) therapy for decades, sensitive and specific therapeutic response biomarkers that allow for better treatment optimization are lacking.Objective: We tested whether the features of Transcranial Magnetic Stimulation-based neurophysiological measures taken off-medication are associated with dopaminergic medication-induced clinical effects.Method: Motor cortex excitability [short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), and input-output (IO) curve], and plasticity [paired associative stimulation (PAS) protocol] neurophysiological measures were examined in 23 PD patients off-medication. Clinical features were quantified by the motor section of the Unified Parkinson's Disease Scale (total score and lateralized total, bradykinesia, and rigidity sub-scores), and the differences between measures off-medication and on-medication (following the usual morning dose), were determined. Total daily dopaminergic medication dose (expressed as levodopa equivalent daily dose-LEDD), was also determined.Results: SICI significantly correlated with changes in lateralized UPDRS motor and bradykinesia sub-scores, suggesting that patients with stronger basal intracortical inhibition benefit more from dopaminergic treatment than patients with weaker intracortical inhibition. Also, ICF significantly negatively correlated with LEDD, suggesting that patients with stronger intracortical facilitation require less dopaminergic medication to achieve optimal therapeutic benefit. Both associations were independent of disease severity and duration.Conclusions: The results suggest variability of (patho) physiological phenotypes related to intracortical inhibitory and facilitatory mechanisms determining clinical response to dopaminergic medication in PD. Measures of intracortical excitability may help predict patients' response to dopaminergic therapy, thus potentially providing a background for developing personalized therapy in PD.

Surrogates for rigidity and PIGD MDS-UPDRS subscores using wearable sensors

BackgroundTelemedicine has the advantage of expanding access to care for patients with Parkinson’s Disease (PD). However, rigidity and postural instability in PD are difficult to measure remotely, and are important measures of functional impairment and fall risk. Research questionCan measures from wearable sensors be used as future surrogates for the MDS-UPDRS rigidity and Postural Instability and Gait Difficulty (PIGD) subscores? MethodsThirty-one individuals with mild to moderate PD wore 3 inertial sensors at home for one week to measure quantity and quality of gait and turning in daily life. Separately, we performed a clinical assessment and balance characterization of postural sway with the same wearable sensors in the laboratory (On medication). We then first performed a traditional correlation analysis between clinical scores and objective measures of gait and balance followed by multivariable linear regression employing a best subset selection strategy. ResultsThe number of walking bouts and turns correlated significantly with the rigidity subscore, while the number of turns, foot pitch angle, and sway area while standing correlated significantly with the PIGD subscore (p < 0.05). The multivariable linear regression showed that rigidity subscore was best predicted by the number of walking bouts while the PIGD subscore was best predicted by a combination of number of walking bouts, gait speed, and postural sway. SignificanceThe correlation between objective sensor data and MDS-UPDRS rigidity and PIGD scores paves the way for future larger studies that evaluate use of objective sensor data to supplement remote MDS-UPDRS assessment.

Surgical Management of Parkinson’s Disease: The Role of Lesioning Procedures in Developing Countries in the Modern Era

BACKGROUND: The known loss of dopaminergic cells in the pars-compacta of the substantia nigra that is the hallmark of PD. The cellular pathophysiology of the motor dysfunction is beginning to be better understood, thereby providing a stronger scientific rationale for surgical interventions. Yet, to date, there are no treatments that prevent, halt, or cure PD. Surgical strategies, offer symptomatic relief or control of motor complications associated with drug treatment.&#x0D; Both pallidotomy and thalamotomy were extensively used in the treatment of PD in the1950’s and 1960’s. With the introduction of levodopa (L-dopa) in the1960’s and the realization of its striking benefits, surgery was almost abandoned and used only for patients with severe tremor. Surgical therapy is now being used earlier and more often. There are currently three brain regions being considered as targets for functional neurosurgery for PD (other than transplantation). Either CNS lesions (thalamotomy, pallidotomy or subthalamic nucleus lesions) or deep brain stimulation [DBS]. These targets are: The ventral intermediate nucleus of the thalamus (Vim), the internal segment of the Globus Pallidus (GPi) and the subthalamic nucleus (STN).&#x0D; OBJECTIVE: To assess the outcome (3 months &amp; 6 months) of lesioning procedures in parkinson’s disease (PD) patients meeting the inclusion criteria.&#x0D; METHODS: A prospective clinical study conducted on 10 IPD patients during the period from October 2018 to March 2021 at Cairo University Hospitals. This study was concerned to improve the motor symptoms of IPD patients by stereotactic radiofrequency ablative procedures. Cases were restricted to 10 patients due to the Covid-19 pandemic and restriction of elective cases for chronic patients at Cairo University hospitals.&#x0D; RESULTS: In our study we operated upon 10 IPD patients who were meeting our selection criteria by ablative procedures contralateral to parkinsonian symptoms.&#x0D; Age of the patients ranged 17 – 70y with mean of 50.5 ± 16.35 y with predominance in males representing 6 patients. Mean duration of Parkinson`s disease according to history ranged from 2 to 12 y with mean of 8 ± 3.1 years. Patients were divided into three groups according to their presentation and the operation done for them. Thalamotomy group: Pre-operatively, the UPDRS III off &amp; on respectively was 24.4/15.2 and post-operatively was 13/7.4 with improvement 47% / 51%. The tremor subscore was 5.4/2.8 pre-operatively and 1.4/0.8 post-operatively with average of 72% improvement. The UPDRS II pre was 17.2/11.6 and post it became 10.6/7 with 39% improvement. Modified H&amp;Y 2.4/1.7 pre &amp; post-operatively (29% improvement). Pallidotomy group: Pre-operatively, the UPDRS III off &amp; on respectively was 38.5/23.5 and post-operatively was 28/16 with improvement 27% / 32%. The rigidity subscore was 5/2.5 pre-operatively and 2/1 post-operatively with average of 60% improvement. The bradykinesia subscore was 9/5.5 pre-operatively and 5.5/2.5 post-operatively with average of 47% improvement. The dyskinesia subscore was 4.5 pre-operatively and 1.2 post-operatively with average of 71% improvement. The UPDRS II pre was 22/12.5 and post it became 16/10 with 25% improvement. Modified H&amp;Y 2.75/2.25 pre &amp; post-operatively (18% improvement). Combined group: Pre-operatively, the UPDRS III off &amp; on respectively was 41.33/28.67 and post-operatively was 15.67/11.33 with improvement 62% /60%. The rigidity subscore was 5/3.33 pre-operatively and 1.67/1 post-operatively with average of 68% improvement. The bradykinesia subscore was 10/6 pre-operatively and 4/1.33 post-operatively with average of 72% improvement. The UPDRS II pre was 28.33/19.33 and post it became 16.33/10.67 with 43% improvement. Modified H&amp;Y 2.83/2 pre &amp; post-operatively (29% improvement). Postoperatively, there was a high significant statistical finding in all clinical score and subscore of parkinsonian symptoms.&#x0D; CONCLUSION: The study concludes that lesioning procedure should be revisited globally using the modern techniques of targeting and controlled thermal lesion protocols guided by capsular somatotopy and intraoperative macroelectrode stimulation, that will improve the outcome dramatically. Ablative procedures proved their efficacy in controlling motor symptoms of IPD and their cost-benefit in low &amp; middle-income nations.

Clinical features and related factors of freezing of gait in patients with Parkinson's disease.

BackgroundFreezing of gait (FOG) is a disabling paroxysmal gait disorder that prevents starting or resuming walking, which seriously negatively affects patients’ quality of life (QOL). The diagnosis and treatment of FOG remain a huge medical challenge. The purpose of this study was to explore the clinical characteristics and related factors of FOG in patients with Parkinson's disease (PD).MethodsThe motor and nonmotor symptoms of a total number of 77 PD patients were evaluated. Patients with or without FOG were defined as a score ≥1 in the new freezing of gait questionnaire (NFOG‐Q). A comparative study between patients with and without FOG was conducted.ResultsIn this investigation, the prevalence of FOG was 48%. The patients with FOG had longer disease duration, higher Hoehn‐Yahr stage (H‐Y stage), higher dose of dopaminergic agents, and higher nonmotor and motor symptom scores. A significant positive correlation was found between the NFOG‐Q score and the H‐Y stage, PIGD subscore, PDQ‐39, and the attention/memory in the nonmotor symptoms assessment scale (NMSS) subitem (r > 0.5, p < .05). The binary logistic regression analysis showed that the higher H‐Y stage, higher rigidity subscore and Unified Parkinson's Disease Rating Scale II (UPDRS II) score, and UPDRS III score were significantly correlated with the occurrence of FOG (p < .05). In the analysis of the frequency of FOG, the prevalence of FOG in H‐Y stage was higher in the middle and late stages, and the prevalence of FOG increased with the increase in PDQ‐39 scores.ConclusionThe severity of FOG was significantly positively correlated with the H‐Y stage, PIGD subscore, PDQ‐39 score, and attention/memory score. Based on our findings, we conclude that the clinical characteristics of rigidity can be used as a potential predictor of FOG.

Hypomimia in Parkinson's disease: an axial sign responsive to levodopa.

Hypomimia is a prominent clinical feature in people with Parkinson's disease (PD), but it remains under-investigated. We aimed to examine the clinical correlates of hypomimia in PD and to determine whether this is a levodopa-responsive sign. We included 89 people with PD. Hypomimia was assessed from digital video recordings by movement disorder specialists. Clinical evaluation included use of the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), and assessment of motor and non-motor symptoms using standardized clinical scales. The relationships between hypomimia and other clinical data were analysed using Mann-Whitney U-tests and regression analysis. Hypomimia occurred in up to 70% of patients with PD. Patients with hypomimia had worse UPDRS-III 'off-medication' scores, mainly driven by bradykinesia and rigidity subscores. Patients with hypomimia also had worse apathy than patients without hypomimia. Finally, we found that hypomimia was levodopa-responsive and its improvement mirrored the change by levodopa in axial motor symptoms. Our study provides novel information regarding the clinical correlates of hypomimia in people with PD. A better understanding of hypomimia may be relevant for improving treatment and quality of life in PD.

L-dopa treatment increases oscillatory power in the motor cortex of Parkinson's disease patients.

Parkinson's disease (PD) is a movement disorder caused by dopaminergic neurodegeneration. Levodopa (L-dopa) is an effective medication for alleviating motor symptoms in PD that has been shown previously to reduce subcortical beta (13-30Hz) oscillations. How L-dopa influences oscillations in the motor cortex is unclear. In this study, 21 PD patients were recorded with magnetoencephalography (MEG) in L-dopa ON and OFF states. Oscillatory components of resting-state power spectra were compared between the two states and the significant effect was localized using beamforming. Unified Parkinson's Disease Rating Scale (UPDRS) III akinesia and rigidity sub-scores for the most affected hemibody were correlated with source power values for the contralateral hemisphere. An L-dopa-induced power increase was found over the central sensors significant in the 18-30Hz range (F(1,20) >14.8, PFWE corr<0.05, cluster size inference with P=0.001 cluster-forming threshold). Beamforming localization of this effect revealed distinct peaks at the bilateral sensorimotor cortex. A significant correlation between the magnitude of L-dopa induced 18-30Hz oscillatory motor-cortical power increase and the degree of improvement in contralateral akinesia and rigidity was found (F(2, 19)=4.9, pone-tailed=0.02, R2=0.2). Power in the same range was also inversely correlated with combined akinesia and rigidity scores in the L-dopa OFF state (F(2, 19)=9.2, ptwo-tailed=0.007, R2=0.33) but not in the L-dopa ON state (F(2, 19)=0.27, ptwo-tailed=0.6, R2=0.01). These results suggest that the role of motor cortical beta oscillations in PD is distinct from that of subcortical beta.

Lower Limb Rigidity Is Associated with Frequent Falls in Parkinson's Disease.

The role of muscle rigidity as an etiological factor of falls in Parkinson's disease (PD) is poorly understood. Our objective was to determine whether lower leg rigidity was differentially associated with frequent falls in PD compared to upper limb, neck, and total rigidity measures. We examined the associations between Unified Parkinson's Disease Rating Scale-Part III (motor) rigidity subscores and the history of monthly or more frequent falls in 216 individuals with PD (age, 66 ± 10 years; 36% female; disease duration, 7 ± 5 years) with logistic regression. A total of 35 individuals were frequent fallers. Significant associations were identified between lower limb rigidity and frequent falls (P = 0.01) after controlling for age, sex, PD duration, total Unified Parkinson's Disease Rating Scale- Part III score, and presence of freezing of gait. No significant associations (P ≥ 0.14) were identified for total, arm, or neck rigidity. Lower limb rigidity is related to frequent falls in people with PD. Further investigation may be warranted into how parkinsonian rigidity could cause falls.

Frequency-dependent effects of subthalamic deep brain stimulation on motor symptoms in Parkinson’s disease: a meta-analysis of controlled trials

This study aims to investigate how the frequency settings of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) influence the motor symptoms of Parkinson’s disease (PD). Stimulation with frequencies less than 100 Hz (mostly 60 or 80 Hz) is considered low-frequency stimulation (LFS) and with frequencies greater than 100 Hz (mostly 130 or 150 Hz) is considered high-frequency stimulation (HFS). We conducted a comprehensive literature review and meta-analysis with a random-effect model. Ten studies with 132 patients were included in our analysis. The pooled results did not show significant differences in the total Unified Parkinson Disease Rating Scale part III (UPDRS-III) scores (mean effect, -1.50; p=0.19) or the rigidity subscore between HFS and LFS. Compared to LFS, HFS reduced the tremor subscore more in the medication-off condition (mean effect, 1.01; p=0.002), but not in the medication-on condition (mean effect, 0.01; p=0.92). LFS was more effective than HFS in reducing the akinesia subscore (mean effect, -1.68, p=0.003) and the time to complete the stand-walk-sit (SWS) test as well as the number of freezing of gait (FOG) (mean effect, -4.84; p<0.00001 and mean effect, -1.71; p=0.03). Our results suggest that HFS induces a better response for tremors, while LFS may induce a greater response for akinesia, gait, and FOG. These results provide optimized STN-DBS programs for different motor symptoms in PD.

Frequency-dependent effects of subthalamic deep brain stimulation on motor symptoms in Parkinson\u2019s disease: a meta-analysis of controlled trials

This study aims to investigate how the frequency settings of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) influence the motor symptoms of Parkinson’s disease (PD). Stimulation with frequencies less than 100 Hz (mostly 60 or 80 Hz) is considered low-frequency stimulation (LFS) and with frequencies greater than 100 Hz (mostly 130 or 150 Hz) is considered high-frequency stimulation (HFS). We conducted a comprehensive literature review and meta-analysis with a random-effect model. Ten studies with 132 patients were included in our analysis. The pooled results showed no significant difference in the total Unified Parkinson Disease Rating Scale part III (UPDRS-III) scores (mean effect, −1.50; p = 0.19) or the rigidity subscore between HFS and LFS. Compared to LFS, HFS induced greater reduction in the tremor subscore within the medication-off condition (mean effect, 1.01; p = 0.002), while no significance was shown within the medication-on condition (mean effect, 0.01; p = 0.92). LFS induced greater reduction in akinesia subscore (mean effect, −1.68, p = 0.003), the time to complete the stand-walk-sit (SWS) test (mean effect, −4.84; p < 0.00001), and the number of freezing of gait (FOG) (mean effect, −1.71; p = 0.03). These results suggest that two types of frequency settings may have different effects, that is, HFS induces better responses for tremor and LFS induces greater response for akinesia, gait, and FOG, respectively, which are worthwhile to be confirmed in future study, and will ultimately inform the clinical practice in the management of PD using STN-DBS.

Patterns of grey matter loss associated with motor subscores in early Parkinson's disease.

Classical motor symptoms of Parkinson's disease (PD) such as tremor, rigidity, bradykinesia, and axial symptoms are graded in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III. It is yet to be ascertained whether parkinsonian motor symptoms are associated with different anatomical patterns of neurodegeneration as reflected by brain grey matter (GM) alteration. This study aimed to investigate associations between motor subscores and brain GM at voxel level. High resolution structural MRI T1 scans from the Parkinson's Progression Markers Initiative (PPMI) repository were employed to estimate brain GM intensity of PD subjects. Correlations between GM intensity and total MDS-UPDRS III and its four subscores were computed. The total MDS-UPDRS III score was significantly negatively correlated bilaterally with putamen and caudate GM density. Lower anterior striatal GM intensity was significantly associated with higher rigidity subscores, whereas left-sided anterior striatal and precentral cortical GM reduction were correlated with severity of axial symptoms. No significant morphometric associations were demonstrated for tremor subscores. In conclusion, we provide evidence for neuroanatomical patterns underpinning motor symptoms in early PD.

Chronic pain in Parkinson's disease: Frequency, characteristics, independent factors, and relationship with health-related quality of life.

Although there are studies evaluating pain in Parkinson's disease (PD), to our knowledge, there is no study evaluating the following topics in a cohort of PD patients; (1) frequency of chronic pain, (2) characteristics of chronic pain, (3) severity of chronic pain, (4) types of chronic pain, (5) independent predictors of chronic pain, (6) impact of chronic pain on health-related quality of life (HRQoL), and (7) the role of chronic pain among the independent predictors of HRQoL. The purpose of this study was to evaluate the frequency, characteristics, severity, types, and independent factors of chronic pain, as well as the relationship of chronic pain with HRQoL in a cohort of PD patients. One-hundred and thirteen individuals with a confirmed diagnosis of PD who were consecutively referred to the Ministry of Health Ankara Diskapi Yildirim Beyazit Training and Research Hospital, Movement Disorders Outpatient Clinic were included in the study. Demographic variables, disease characteristics, disease-related motor symptoms and motor complications, comorbid conditions, and health-related quality of life were evaluated and recorded. Pain lasting longer than three months was defined as `chronic pain' and participants were questioned relating to the characteristics of the chronic pain. The Visual Analogue Scale was used for assessment of pain. Seventy-three patients (64.6%) suffered from chronic pain. Of these, 12 (16.4%) had previous pain at the time of diagnosis of PD. The sources of pain experienced by patients were 89.0% musculoskeletal, 31.5% radicular/peripheral neuropathic, 15.1% dystonic, and 4.1% central parkinsonian, respectively. Twenty-six patients (35.6%) had different types of pain simultaneously. The pain type with the highest severity was a central parkinsonian pain.The independent predictors of chronic pain included gender (female), Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of daily living), UPDRS part III (motor symptoms) rigidity subscore, and depression.When compared with individuals not having chronic pain, Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) Physical Component Summary and Mental Component Summary scores were lower in patients with chronic pain. Also, it was shown that the most significant factor on SF-36 was chronic pain. This study demonstrated that chronic pain is a common problem in patients with PD, that different pain types may co-exist, and that they may negatively affect the HRQoL of patients. Chronic pain was correlated with both disease-related factors such as rigidity and daily living activities and also general factors such as gender and depression. We found that chronic pain is the most significant predictor of quality of life in PD patients. We believe, that in addition to treating motor symptoms and complications associated with them, treatment of comorbid conditions such as pain and depression bear significance for improving the quality of life in PD patients. The study indicates that PD patients who are optimally treated, may require additional rehabilitation treatment for non-motor associated pain and thus improve their HRQoL.

P307: Levodopa responsiveness of blink reflex recovery index – an objective method of differentiating Parkinson’s disease from Parkinson plus syndromes

P307: Levodopa responsiveness of blink reflex recovery index – an objective method of differentiating Parkinson’s disease from Parkinson plus syndromes

Surgical outcome of deep brain stimulation of subthalamic nucleus with beta oscillation in PD patients

Objective the aim of this study is to observe therapeutic effect of subthalamic nucleus deep brain stimulation (STN-DBS)for parkinsonian patients with beta neural oscillation pattern in subthalamic nucleus.Methods Clinical data of 6 parkinsonian patients underwent STN-DBS were analyzed retrospectively.The UPDRS-Ⅲ and levodopa equivalent doses (LEDD) were recorded preoperatively and 1,6,12 months postoperatively.Results As compared with base line,the patients' UPDRS-]]Ⅲ at 1 month,6 months and 12 months after operation while off medication/on medication improved by 28.1％/33.4％,50.4％/48.7％ and 57.7％/56.6％ (P ＜ 0.01).UPDRS-Ⅲ rigidity subscore improved by 50.4％/44.9％,66.7％/50.3％ and 74.4％/54.5％ (P ＜ 0.01).UPDRS tremor subscore improved by 10.7％/8.3％,20.7％/38.9％ and 29.0％/38.9％ (P ＜ 0.05).The dose of dopaminergic treatment were reduced with reductions of 53.8％,60.8％ and 64.5％ (P ＜ 0.01),compared with baseline.Conclusions STN-DBS could effectively improve the movement symptoms of patients with beta neural oscillation pattern in subthalamic nucleus.Rigidity improvement was more obvious than tremor improvement after surgery.Dopaminergic medication could be reduced prominently after surgery. Key words: Subthalamic nucleus ; Deep brain stimulation ; Parkinson's disease ; Beta oscillation

Spontaneous parkinsonism is associated with cognitive impairment in antipsychotic-naive patients with first-episode psychosis: a 6-month follow-up study.

There is now growing evidence that parkinsonism and other extrapyramidal signs are highly prevalent in patients with first-episode psychosis who have never been exposed to antipsychotic drugs. However, the neurocognitive correlates of parkinsonism in this population remained to be clarified. A sample comprising 100 consecutive drug-naive patients with first-episode psychosis were enrolled on the study and followed up for 6 months. Seventy-seven completed assessments at 3 time points (baseline, 1 mo, and 6 mo), involving clinical and cognitive examinations and a specific assessment of motor abnormalities. The Simpson-Angus Scale (SAS) was used for the assessment of extrapyramidal signs, and each motor domain was evaluated with a standard assessment scale. Linear mixed models were built to explore the longitudinal relationships between parkinsonism scores and cognitive impairment. Parkinsonism scores showed significant strong longitudinal associations with deficits in memory, executive functioning, and attention. Spontaneous parkinsonism (total SAS score and hypokinesia and rigidity subscores at baseline) showed high 6-month predictive values for cognitive impairment. In addition, they also had high predictive values for neurologic soft-sign abnormalities but not for dyskinesia, akathisia, and pure catatonic abnormalities. No predictive value was found for glabella-salivation or tremor subscores on the SAS scale. These results emphasize the relevance of the assessment of parkinsonism signs prior to starting to administer antipsychotic drugs, as core manifestations of psychotic illness with a high predictive value for cognitive impairment.

Differential modulation of STN-cortical and cortico-muscular coherence by movement and levodopa in Parkinson's disease

Previous research suggests that oscillatory coupling between cortex, basal ganglia and muscles plays an important role in motor behavior. Furthermore, there is evidence that oscillatory coupling is altered in patients with movement disorders such as Parkinson's disease (PD). In this study, we performed simultaneous magnetoencephalography (MEG), local field potential (LFP) and electromyogram (EMG) recordings in PD patients selected for therapeutic subthalamic nucleus (STN) stimulation. Patients were recorded (i) after withdrawal of anti-parkinsonian medication (OFF) and (ii) after levodopa administration (ON). We analyzed STN-cortical and cortico-muscular coherence during static forearm contraction and repetitive hand movement in order to evaluate modulations of coherence by movement and medication. Based on previous results from studies investigating resting state coherence in PD patients, we selected primary motor cortex (M1) and superior temporal gyrus (STG) as regions of interest. We found beta coherence between M1 and STN to be suppressed by administration of levodopa. M1-muscular coherence was strongly reduced in the alpha and beta band during repetitive movement compared to static contraction, but was unaffected by administration of levodopa. Strong STG-STN but not STG-muscular coherence could be observed in the alpha band. Coherence with STG was modulated neither by movement nor by medication. Finally, we found both M1-STN and M1-muscular beta coherence to be negatively correlated with UPDRS akinesia and rigidity sub-scores in the OFF state. The present study provides new insights into the functional roles of STN-cortical and cortico-muscular coherence and their relationship to PD symptoms. The results indicate that STN-cortical and cortico-muscular coupling are correlated, but can be modulated independently. Moreover, they show differences in their frequency-specific topography. We conclude that they represent partly independent sub-loops within the motor system. Given their negative correlation with akinesia, neither can be considered "antikinetic".

Natural History of UPDRS Motor Scores in an Observational Parkinson's Disease Cohort (S22.004)

Objective: This study estimated the annual rate of change on The United Parkinson9s Disease Rating Scale (UPDRS) motor section in Parkinson9s disease (PD) patients and assessed the influence of early-onset PD on motor progression. Background The UPDRS is the standard clinical measure of PD motor symptoms. Most data describing the rate of change on the UPDRS are derived from clinical trials or other interventional studies (e.g. DATATOP). More data is needed from studies with broad inclusion criteria. Design/Methods: Idiopathic PD patients were enrolled in longitudinal study consisting of biannual motor, cognitive, and psychiatric assessments. The UPDRS motor section was rated in the off state. Random effect models estimated the rate of change in UPDRS motor scores per year of disease duration controlling for age, sex, education, and depression. An interaction term for young-onset PD ( Results: On average patients were 67.4 years old (SD 10.5), had PD for 9.6 (6.7) years, and were followed for 3.0 years (3.0; Min-Max 0-10). Thirty-five patients (22.4%) had young-onset PD. Total UPDRS motor scores increased by 1.2 points/year (SE 0.2). The bradykinesia subscore increased by 0.4 points/year (0.07), the rigidity subscore increased by 0.2 points/year (0.05), and the axial subscore increased by 0.3 points/year (0.04). The tremor subscore increased by 0.02 points/year (0.05), but the slope was not statistically significant. Early-onset PD was associated with a decreased rate of change in axial symptoms [-.2 points/year (0.07)], but was not associated with a differential rate of change on the total motor score or other subscores. Conclusions: The average UPDRS motor score increase was 1.2 points/year; however, tremor scores did not change over time. This study suggests that young-onset PD is associated with milder axial symptoms but does not support the notion of an overall milder disease course in young-onset patients. Supported by: NINDS grant P50-NS-58377 (the Morris K. Udall Parkinson9s Disease Research Center of Excellence at Johns Hopkins) and NIA grant T32-AG-027668 (Williams). Disclosure: Dr. Williams has received personal compensation for activities with Biogen Idec and Johns Hopkins University as an employee. Dr. Mari has received personal compensation for activities with Teva, Merz, and Ipsen. Dr. Mari has received research support from Merz, Allergan, and PharmaNet. Dr. Pontone has received research support from The Michael J. Fox Foundation, EMD (Merck) Serono, and Acadia Pharmaceuticals. Dr. Bassett has nothing to disclose.

Somatomotor mu rhythm amplitude correlates with rigidity during deep brain stimulation in Parkinsonian patients

ObjectiveParkinsonian patients have abnormal oscillatory activity within the basal ganglia-thalamocortical circuitry. Particularly, excessive beta band oscillations are thought to be associated with akinesia. We studied whether cortical spontaneous activity is modified by deep brain stimulation (DBS) in advanced Parkinson’s disease and if the modifications are related to the clinical symptoms. MethodsWe studied the effects of bilateral electrical stimulation of subthalamic nucleus (STN) on cortical spontaneous activity by magnetoencephalography (MEG) in 11 Parkinsonian patients. The artifacts produced by DBS were suppressed by tSSS algorithm. ResultsDuring DBS, UPDRS (Unified Parkinson’s Disease Rating Scale) rigidity scores correlated with 6–10Hz and 12–20Hz somatomotor source strengths when eyes were open. When DBS was off UPDRS action tremor scores correlated with pericentral 6–10Hz and 21–30Hz and occipital alpha source strengths when eyes open.Occipital alpha strength decreased during DBS when eyes closed. The peak frequency of occipital alpha rhythm correlated negatively with total UPDRS motor scores and with rigidity subscores, when eyes closed. ConclusionSTN DBS modulates brain oscillations both in alpha and beta bands and these oscillations reflect the clinical condition during DBS. SignificanceMEG combined with an appropriate artifact rejection method enables studies of DBS effects in Parkinson’s disease and presumably also in the other emerging DBS indications.