[Risk factors for Parkinson's disease: possibilities for prevention and intervention]. / Risicofactoren voor de ziekte van Parkinson.

Considering age to be the primary risk factor for developing Parkinson's disease and the observation that the Dutch population is rapidly aging, the parkinson prevalence is expected to increase over the coming years, as there is still no cure available for the disease. This has been confirmed by epidemiological data, which show a steady increase of the disease prevalence in the Netherlands for the period 2010-2021. Genetic risk factors only partially explain the disease pathogenesis. Environmental factors, such as exposure to pesticides and trichloroethylene are associated with a higher risk for developing Parkinson's disease. Lifestyle factors such as exercise, caffeine intake and the Mediterranean diet are associated with a lower risk for developing the disease and possibly delay the disease progression. Policy makers and healthcare providers should employ stricter regulations for pesticide use and should stimulate a healthy lifestyle to slow down the increasing prevalence.

Machine learning for automated EEG-based biomarkers of cognitive impairment during Deep Brain Stimulation screening in patients with Parkinson's Disease.

OBJECTIVE: A downside of Deep Brain Stimulation (DBS) for Parkinson's Disease (PD) is that cognitive function may deteriorate postoperatively. Electroencephalography (EEG) was explored as biomarker of cognition using a Machine Learning (ML) pipeline. METHODS: A fully automated ML pipeline was applied to 112 PD patients, taking EEG time-series as input and predicted class-labels as output. The most extreme cognitive scores were selected for class differentiation, i.e. best vs. worst cognitive performance (n = 20 per group). 16,674 features were extracted per patient; feature-selection was performed using a Boruta algorithm. A random forest classifier was modelled; 10-fold cross-validation with Bayesian optimization was performed to ensure generalizability. The predicted class-probabilities of the entire cohort were compared to actual cognitive performance. RESULTS: Both groups were differentiated with a mean accuracy of 0.92; using only occipital peak frequency yielded an accuracy of 0.67. Class-probabilities and actual cognitive performance were negatively linearly correlated (ß = -0.23 (95% confidence interval (-0.29, -0.18))). CONCLUSIONS: Particularly high accuracies were achieved using a compound of automatically extracted EEG biomarkers to classify PD patients according to cognition, rather than a single spectral EEG feature. SIGNIFICANCE: Automated EEG assessment may have utility for cognitive profiling of PD patients during the DBS screening.

What predicts quality of life after subthalamic deep brain stimulation in Parkinson's disease? A systematic review.

BACKGROUND AND PURPOSE: Subthalamic deep brain stimulation (STN DBS) is an effective therapy against medication-refractory motor complications in patients with Parkinson's disease. However, it remains difficult to predict which baseline patient characteristics are associated with quality of life (QoL) after surgery. The objective was to identify preoperative factors associated with QoL after STN DBS by systematically reviewing publications of sufficient methodological quality. METHODS: Main databases were systematically searched up to March 2019 to identify studies that investigated factors associated with QoL after STN DBS in patients with idiopathic Parkinson's disease. RESULTS: In all, 869 studies were identified, of which 18 fulfilled the inclusion criteria. Higher QoL after DBS appears to be associated with a large preoperative difference between ON and OFF motor function in some studies, although there was no clear association of severity of motor function or motor complications with postoperative QoL. Lower severity of dyskinesias was associated with greater postoperative QoL improvement but has been insufficiently studied. Higher baseline QoL was suggestive of higher postoperative QoL. Four studies suggested that older age at surgery is associated with a lower improvement, although six other studies reported no association. No or limited evidence was found for cognitive impairment or psychiatric dysfunction. CONCLUSION: Various relative contraindications for STN DBS such as cognitive impairment and psychiatric dysfunction appear to be unrelated to postoperative QoL. However, the lack of clear correlations with disease-related variables suggests that QoL may be individually influenced by other factors, indicating that an ideal preoperative patient profile with regard to QoL improvement cannot be readily provided.

Stimulation challenge test after STN DBS improves satisfaction in Parkinson's disease patients.

OBJECTIVE: Although subthalamic Deep Brain Stimulation (STN DBS) is proven effective in improving symptoms of Parkinson's Disease (PD), previous literature demonstrates a discrepancy between objective improvement and patients' perception thereof. We aimed to examine whether postoperative stimulation challenge tests (SCT) alters patients' satisfaction after STN DBS for PD. METHODS: Fifty-four PD patients underwent preoperative levodopa challenge tests and were routinely invited for SCT 1-2 years postoperatively. SEverity of predominantly Nondopaminergic Symptoms in PD (SENS-PD) scores quantified non-dopaminergic disease severity. Motor functioning was quantified using Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores; a ratio between conditions ON and OFF (preoperative Med-ON vs. Med-OFF, and postoperative Med-ON/Stim-ON vs. Med-OFF/Stim-OFF) reflected treatment benefit. 'Global Impression of Change' (GIC) and 'Global Satisfaction with Surgery' (GSS) Likert scales were filled out before and immediately after SCT. RESULTS: Postoperative Med-ON/Stim-ON severity was lower than preoperative ON severity. Disease severity scores were not different between assessments. GIC and GSS scores were higher after SCT versus before (GIC: Z = -3.80, r = 0.37, subjects indicating maximum scores before SCT: 32.1%, after SCT: 57.1%; GSS: Z = -3.69, r = 0.35, maximum scores before SCT: 25.0%, after SCT: 46.4%). Higher non-dopaminergic disease severity was associated with lower GIC and GSS scores (GIC: OR 1.2 (95%CI 1.0-1.3); GSS: OR 1.2 (95%CI 1.1-1.3), while motor-scores and magnitude of DBS-effects were not. CONCLUSION: SCT improves patients' satisfaction and is recommended especially in case of suboptimal subjective valuations. This information should be considered in clinical practice and in the context of clinical trials.

Selecting candidates for Deep Brain Stimulation in Parkinson's disease: the role of patients' expectations.

Patients with advanced Parkinson's Disease (PD) may be eligible for Deep Brain Stimulation (DBS) in case of medication-related motor fluctuations or tremor refractory to oral medication. However, several PD symptoms are unresponsive to DBS and constitute relative contra-indications for DBS. Patients referred for DBS undergo an eligibility screening during which motor functioning and contra-indications for surgery are assessed. During this pre-screening the potential benefits and drawbacks of surgery are discussed, together with patients' expectations of the results of DBS. Unrealistic expectations on the benefits of DBS may contribute to reduced patient satisfaction and poor clinical outcomes after surgery. The aim of this multicenter study (289 patients) was to assess the reasons for rejection after an outpatient-based pre-screening visit for DBS referrals, with particular emphasis on the role of patient expectations of DBS. The most frequent reason contributing to rejection was suboptimal oral treatment or satisfying symptom-control with oral medication (50% of rejections). Unrealistic expectations were identified in 38% of rejected patients and were the singular reason for rejection in 4%. Incorporating the assessment of unrealistic expectations increased the accuracy (Area Under the Curve) of determining DBS eligibility from 0.92 ((95% confidence interval (95%CI) 0.88-0.97) to 0.97 (95%CI 0.96-0.99). Patients' expectations of DBS are easily checked, and better education of patients and treating neurologists with regard to unrealistic expectations of this procedure may improve efficiency of referrals and avoid unnecessary stress and disappointments during screening.

Intraoperative test stimulation of the subthalamic nucleus aids postoperative programming of chronic stimulation settings in Parkinson's disease.

BACKGROUND: It is unknown whether intraoperative testing during awake Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) can be used to postoperatively identify the best settings for chronic stimulation. OBJECTIVE: To determine whether intraoperative test stimulation is indicative of postoperative stimulation results. METHODS: Records of consecutive Parkinson's Disease patients who received STN DBS between September 2012 and December 2017 were retrospectively analyzed. The best depth identified after intraoperative stimulation via the microelectrode's stimulation tip was compared with the depth of the contact selected for chronic stimulation after a standard monopolar contact review. Moreover, thresholds for induction of clinical effects (optimal improvement of rigidity and induction of side-effects) were compared between stimulation at the postoperatively selected contact and at the corresponding intraoperative depth. RESULTS: Records of 119 patients were analyzed (mean (SD) age 60.5 (6.5) years, 31.9% female, 238 STNs). In 75% of cases, the postoperatively selected contact corresponded with the intraoperative depth with the largest therapeutic window or was immediately dorsal to it. Higher stimulation intensities were required postoperatively than intraoperatively to relieve rigidity (p = 0.002) and induce capsular side-effects (p = 0.016). CONCLUSION: In the majority of cases, the postoperative contact for chronic stimulation was at a similar level or immediately dorsal with respect to the identified best intraoperative depth. Postoperatively, relief of rigidity and induction of capsular side-effects occur at higher stimulation intensities than during intraoperative test stimulation.

Onset and evolution of anxiety in Parkinson's disease.

BACKGROUND AND PURPOSE: Anxiety is common in Parkinson's disease (PD) and has a great influence on quality of life. However, little is known about risk factors for development of anxiety in PD. We investigated which factors were associated with longitudinal changes in severity of anxiety symptoms and development of future anxiety in patients who were not anxious at baseline. METHODS: Analyses were performed on data of the PROfiling PARKinson's disease (PROPARK) cohort, a 5-year hospital-based longitudinal cohort of over 400 patients with PD who have been examined annually. Linear mixed models were used to identify factors associated with longitudinal changes in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) scores. Survival analysis using data of patients who were not anxious at baseline was performed to identify predictors of future anxiety (i.e. HADS-A ≥ 11). RESULTS: Of 409 patients who were included at baseline, 67 (16%) had anxiety, whereas 64 (19%) of the remaining 342 non-anxious patients developed anxiety after a mean (SD) follow-up of 2.6 (1.3) years. Seventy percent of the patients with anxiety were also depressed. Female gender, cognitive impairment, depressive symptoms, dysautonomia, insomnia and excessive daytime sleepiness (EDS) at baseline were associated with higher HADS-A scores over time and, except for female gender and EDS, all of these variables were independent predictors of development of anxiety in patients who were not anxious at baseline. CONCLUSIONS: Anxiety is highly prevalent in PD. Higher anxiety scores over time and future development of anxiety are associated with female gender, cognitive impairment, autonomic dysfunction, insomnia and EDS. Anxiety and depression usually coexist and share similar determinants, suggesting a common pathophysiological mechanism.

Is the brain of complex regional pain syndrome patients truly different?

BACKGROUND: In recent years, changes in brain structure and function have been studied extensively in patients with complex regional pain syndrome (CRPS) following clinical observations of altered central processing of sensory stimuli and motor control. However, concerning MRI data, the evidence is complex to interpret due to heterogeneity in statistical methods and results. METHOD: The aim of this study was to determine if CRPS patients exhibit specific, clinically relevant changes in brain structure and function in rest. We do this by presenting MRI data on brain structure and function in 19 chronic, female CRPS patients and age- and sex-matched healthy controls (HCs). In addition, we analyse and report the data in multiple ways to make comparison with previous studies possible and to demonstrate the effect of different statistical methods, in particular, concerning the correction for multiple testing. RESULTS: Using family-wise error (FWE) correction for multiple testing, in our group of CRPS patients, we find no specific difference in brain structure or function in rest in comparison to HCs. In addition, we argue that previously found MRI results in the literature are inconsistent in terms of localization, quantity and directionality of the reported changes in brain structure and function. CONCLUSION: Previously published MRI-based evidence for altered brain structure and function in rest in CRPS patients is not consistent and our data suggests that no such phenomenon exists. WHAT DOES THIS STUDY ADD?: This article does not replicate the previous found results. The reported evidence in MRI literature of aberrant neuroplasticity in CRPS patients is inconsistent in terms of localization, quantity and directionality of changes in brain structure and function.

The influence of age and approaching death on the course of nondopaminergic symptoms in Parkinson's disease.

INTRODUCTION: The influence of approaching death in addition to age and their interaction on the course of a broad spectrum of nondopaminergic features in Parkinson's disease (PD) has not been well studied. This study addresses this issue in a prospectively designed study. METHODS: During five years, the severity of axial symptoms, cognitive impairment, psychotic symptoms, autonomic dysfunction, depressive symptoms, and daytime sleepiness was annually evaluated in PD patients. For each domain a linear mixed-effect model was used to examine changes during follow-up and relations with age and death. RESULTS: Of 378 included patients, 43 died during follow-up. Higher age was associated with increased severity of all nondopaminergic features except depression, and with a higher rate of progression of axial symptoms and cognitive impairment. Patients who died during follow-up had a higher severity of all nondopaminergic features except autonomic dysfunction, and a higher rate of progression of axial symptoms, cognitive impairment, and psychotic symptoms, compared to patients who survived. CONCLUSION: This study shows that the severity of most nondopaminergic features and the progression rate of axial and psychotic symptoms and cognitive impairment increase before PD patients die, independent of the influence of age. An interaction between age and approaching death did not have a significant effect on the course of the symptoms. Improving our understanding of the fundamental biology underlying these factors and the interaction with factors intrinsic to the disease, may have profound implications for the treatment of PD.

Protocol of a randomised delayed-start double-blind placebo-controlled multi-centre trial for Levodopa in EArly Parkinson's disease: the LEAP-study.

BACKGROUND: The aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson's disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Additionally, cost-effectiveness and cost-utility of early levodopa treatment will be assessed. METHODS: To differentiate between the direct symptomatic effects and possible disease modifying effects of levodopa, we use a randomised delayed-start double-blind placebo-controlled multi-centre trial design. Patients with early stage PD whose functional health does not yet necessitate initiation of PD-medication will be randomised to either 40 weeks of treatment with levodopa/carbidopa 100/25 mg TID including 2 weeks of dose escalation or to 40 weeks placebo TID. Subsequently, all patients receive levodopa/carbidopa 100/25 mg TID for 40 weeks. There are 8 assessments: at baseline and at 4, 22, 40, 44, 56, 68, and 80 weeks. The primary outcome measure is the difference in the mean total Unified Parkinson's Disease Rating Scale scores between the early- and delayed-start groups at 80 weeks. Secondary outcome measures are rate of progression, the AMC Linear Disability Score, side effects, perceived quality of life with the Parkinson's Disease Questionnaire-39, the European Quality of Life-5 Dimensions (EQ-5D), ability to (maintain) work, the use of (informal) care, caregiver burden, and costs. 446 newly diagnosed PD patients without impaired functional health need to be recruited in order to detect a minimal clinical relevant difference of 4 points on the total UPDRS at 80 weeks. DISCUSSION: The LEAP-study will provide insights into the possible disease modifying effects of early levodopa. TRIAL REGISTRATION: ISRCTN30518857, EudraCT number 2011-000678-72.

Intended and unintended (sensory-)motor coupling between the affected and unaffected upper limb in complex regional pain syndrome.

BACKGROUND: Motor dysfunction in complex regional pain syndrome (CRPS) has been associated with bilateral malfunction of sensory and motor circuits, which hints at abnormal coupling between the affected and the contralateral unaffected limb. In addition, clinical observations suggest that motor performance may depend on the (voluntary or automatic) context in which movements are executed. The present study aimed to examine the role of voluntary and automatic aspects of interlimb coupling in CRPS. METHODS: Twenty patients with unilateral chronic CRPS and 40 healthy controls performed a set of unimanual and bimanual motor tasks that differed in the degree to which intended bilateral planning, intended afference-based error correction and unintended reflex-like entrainment were involved. RESULTS: Stability of interlimb coordination was reduced in CRPS patients compared to controls, especially for tasks involving active control of the affected side. In CRPS patients, intended coupling between the hands (planning, error correction) was markedly impaired, whereas unintended coupling between the hands (entrainment) appeared normal. CONCLUSIONS: Impaired motor control of the affected limb interfered with bimanual coordination, in particular for tasks involving voluntary (intended) as opposed to automatic (unintended) interlimb coupling. Our findings suggest inappropriate functioning of higher order centres involved in motor control of the affected limb, probably due to pain-related processes and impaired processing of proprioceptive information. Motor function of the affected limb may benefit from intended synchronization with movements of the unaffected contralateral limb, suggesting that bilateral training may be useful in patients with unilateral CRPS.

Force modulation deficits in complex regional pain syndrome: a potential role for impaired sense of force production.

BACKGROUND: Compelling evidence points at both impaired proprioception and disturbed force control in patients with chronic complex regional pain syndrome (CRPS). Because force modulation at least partly relies on proprioception, we evaluated if impaired sense of force production contributes to disturbances of force control in patients with CRPS. METHODS: Characteristics of voluntary force modulation were examined in the affected upper extremity in 28 CRPS patients with abnormal postures, in 12 CRPS patients without abnormal postures, and in 32 healthy controls. Isometric grip-force matching was compared between conditions with and without visual feedback to identify potential deficits in the sense of force production in terms of force reproduction errors. RESULTS: Voluntary force modulation was impaired in CRPS patients, but more so in patients with abnormal postures. In particular, CRPS patients with abnormal postures were characterized by reduced maximum force, reduced ability to increase force output according to task instructions, higher variability of force output and less adequate correction of deviations from the target force. Although effects of visual feedback removal appeared largely similar for the two patient groups and controls, our findings with respect to force reproduction errors suggested that an impaired sense of force production may contribute to the motor dysfunction in CRPS. CONCLUSIONS: CRPS patients, in particular those with abnormal postures, showed impaired voluntary force control and an impaired sense of force production. This suggests that therapeutic strategies aimed at restoration of proprioceptive impairments, possibly using online visual feedback, may promote the recovery of motor function in CRPS.

Motor consequences of experimentally induced limb pain: a systematic review.

Compelling evidence exists that pain may affect the motor system, but it is unclear if different sources of peripheral limb pain exert selective effects on motor control. This systematic review evaluates the effects of experimental (sub)cutaneous pain, joint pain, muscle pain and tendon pain on the motor system in healthy humans. The results show that pain affects many components of motor processing at various levels of the nervous system, but that the effects of pain are largely irrespective of its source. Pain is associated with inhibition of muscle activity in the (painful) agonist and its non-painful antagonists and synergists, especially at higher intensities of muscle contraction. Despite the influence of pain on muscle activation, only subtle alterations were found in movement kinetics and kinematics. The performance of various motor tasks mostly remained unimpaired, presumably as a result of a redistribution of muscle activity, both within the (painful) agonist and among muscles involved in the task. At the most basic level of motor control, cutaneous pain caused amplification of the nociceptive withdrawal reflex, whereas insufficient evidence was found for systematic modulation of other spinal reflexes. At higher levels of motor control, pain was associated with decreased corticospinal excitability. Collectively, the findings show that short-lasting experimentally induced limb pain may induce immediate changes at all levels of motor control, irrespective of the source of pain. These changes facilitate protective and compensatory motor behaviour, and are discussed with regard to pertinent models on the effects of pain on motor control.

Motor control in complex regional pain syndrome: a kinematic analysis.

This study evaluated movement velocity, frequency, and amplitude, as well as the number of arrests in three different subject groups, by kinematic analysis of repetitive movements during a finger tapping (FT) task. The most affected hands of 80 patients with complex regional pain syndrome (CRPS) were compared with the most affected hands of 60 patients with Parkinson disease (PD) as well as the nondominant hands of 75 healthy control (HC) subjects. Fifteen seconds of FT with thumb and index finger were recorded by a 60-Hz camera, which allowed the whole movement cycle to be evaluated and the above mentioned movement parameters to be calculated. We found that CRPS patients were slower and tapped with more arrests than the two other groups. Moreover, in comparison with the hands of the HC subjects, the unaffected hands of the CRPS patients were also impaired in these domains. Impairment was not related to pain. Dystonic CRPS patients performed less well than CRPS patients without dystonia. In conclusion, this study shows that voluntary motor control in CRPS patients is impaired at both the affected as well as the unaffected side, pointing at involvement of central motor processing circuits.

SPES/SCOPA and MDS-UPDRS: formulas for converting scores of two motor scales in Parkinson's disease.

BACKGROUND: Motor impairment in Parkinson's disease (PD) can be evaluated with the Short Parkinson's Evaluation Scale/Scales for Outcomes in Parkinson's disease (SPES/SCOPA) and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The aim of this study was to determine equation models for the conversion of scores from one scale to the other. METHODS: 148 PD patients were evaluated with the SPES/SCOPA-motor and the MDS-UPDRS motor examination. Linear regression was used to develop equation models. RESULTS: Scores on both scales were highly correlated (r = 0.88). Linear regression revealed the following equation models (explained variance: 78%): CONCLUSION: With the equation models identified in this study, scores from SPES/SCOPA-motor can be converted to scores from MDS-UPDRS motor examination and vice versa.

Meta-analysis of the comparative efficacy and safety of adjuvant treatment to levodopa in later Parkinson's disease.

BACKGROUND: Levodopa initially provides good symptomatic control of the symptoms of Parkinson's disease, but motor complications often develop after long-term use. Other classes of antiparkinsonian drugs including dopamine agonists, catechol-O-methyl transferase inhibitors, or monoamine oxidase type B inhibitors are then added as adjuvant therapy. It is unclear whether one class of drug is more effective than another. This meta-analysis evaluates the comparative benefits and risks of these agents as adjuvant treatment in Parkinson's disease patients with motor complications. METHODS: A systematic review of the literature from 1966 to the end of June 2010 was conducted to identify randomized trials involving a dopamine agonist, catechol-O-methyl transferase inhibitor, or monoamine oxidase type B inhibitor versus placebo, as adjuvant to levodopa therapy. RESULTS: Forty-five trials involving nearly 9,000 participants were included. The meta-analysis confirms reports from individual trials that compared with placebo, adjuvant therapy significantly reduces patient off-time and levodopa dose, with improved symptom severity scores (e.g., Unified Parkinson's Disease Rating Scale). However, dyskinesia and numerous other side effects are increased with adjuvant therapy. Few randomized comparisons between drugs have been undertaken, but indirect comparisons suggest that dopamine agonist therapy may be more effective than catechol-O-methyl transferase inhibitor and monoamine oxidase type B inhibitor therapy, which have comparable efficacy. No differences between drugs within each class were observed other than the catechol-O-methyl transferase inhibitor tolcapone appearing more efficacious than entacapone. DISCUSSION: This meta-analysis highlights the need for direct head-to-head randomized trials to assess the impact of adjuvant therapy on patient-rated quality of life and health economic outcomes.

No mutations in the voltage-gated NaV1.7 sodium channel alpha1 subunit gene SCN9A in familial complex regional pain syndrome.

BACKGROUND: Mutations in the voltage-gated Na(V)1.7 Na(+) channel alpha1 gene SCN9A have been linked to pain disorders, such as inherited primary erythromelalgia and paroxysmal extreme pain disorder. Both show clinical overlap with complex regional pain syndrome (CRPS), a condition that is characterized by pain in association with combinations of vasomotor, sudomotor, sensory, and motor disturbances. Therefore, we here investigated the involvement of the SCN9A gene in familial CRPS. METHODS: We performed a mutation analysis of the SCN9A gene in four index cases of families with CRPS. All 26 coding exons and adjacent sequences of the SCN9A gene were analyzed for mutations using direct sequencing analysis. RESULTS: No causal gene mutations were identified in the SCN9A gene in any of the patients. CONCLUSIONS: Despite the fact that the SCN9A gene is an excellent candidate, we did not find evidence that it plays a major role in familial CRPS.

International study on the psychometric attributes of the non-motor symptoms scale in Parkinson disease.

BACKGROUND: Nonmotor symptoms (NMS) have a great impact on patients with Parkinson disease (PD). The Non-Motor Symptoms Scale (NMSS) is an instrument specifically designed for the comprehensive assessment of NMS in patients with PD. NMSS psychometric properties have been tested in this study. METHODS: Data were collected in 12 centers across 10 countries in America, Asia, and Europe. In addition to the NMSS, the following measures were applied: Scales for Outcomes in Parkinson's Disease (SCOPA)-Motor, SCOPA-Psychiatric Complications (SCOPA-PC), SCOPA-Cognition, Hoehn and Yahr Staging (HY), Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD), SCOPA-Autonomic, Parkinson's Disease Sleep Scale (PDSS), Parkinson's Disease Questionnaire-39 items (PDQ-39), and EuroQol-5 dimensions (EQ-5D). NMSS acceptability, reliability, validity, and precision were analyzed. RESULTS: Four hundred eleven patients with PD, 61.3% men, were recruited. The mean age was 64.5 +/- 9.9 years, and mean disease duration was 8.1 +/- 5.7 years. The NMSS score was 57.1 +/- 44.0 points. The scale was free of floor or ceiling effects. For domains, the Cronbach alpha coefficient ranged from 0.44 to 0.85. The intraclass correlation coefficient (0.90 for the total score, 0.67-0.91 for domains) and Lin concordance coefficient (0.88) suggested satisfactory reproducibility. The NMSS total score correlated significantly with SCOPA-Autonomic, PDQ-39, and EQ-5D (r(S) = 0.57-0.70). Association was close between NMSS domains and the corresponding SCOPA-Autonomic domains (r(S) = 0.51-0.65) and also with scales measuring related constructs (PDSS, SCOPA-PC) (all p < 0.0001). The NMSS total score was higher for women (p < 0.02) and for increasing disease duration, HY, and CISI-PD severity level (p < 0.001). The SEM was 13.91 for total score and 1.71 to 4.73 for domains. CONCLUSION: The Non-Motor Symptoms Scale is an acceptable, reproducible, valid, and precise assessment instrument for nonmotor symptoms in Parkinson disease.

Patterns of motor and non-motor features in Parkinson's disease.

OBJECTIVE: To evaluate the presence and nature of patterns of coherency among the motor and non-motor domains in Parkinson's disease (PD) and to examine which clinical parameters are related to the potential patterns. METHODS: A cohort of 397 patients with PD were randomly divided into two samples. Exploratory factor analysis (EFA) was performed on the motor and non-motor symptoms in PD in the first sample. Findings of the EFA were used to construct a model which was tested in the second sample by confirmatory factor analysis. Multiple regression analyses on the resulting factors were performed to evaluate the influence of clinical parameters on these factors. RESULTS: Four factors were identified. The first and strongest factor (cognitive impairment, autonomic dysfunction, psychotic symptoms, depression, daytime sleepiness and axial symptoms) reflected advancing disease. Another factor largely reflected motor complications of therapy and was related to dopaminergic medication. The other two factors reflected sleep/depression and tremor/bradykinesia/rigidity, and were only marginally related to disease severity or medication. CONCLUSIONS: The motor and non-motor features in PD can be characterised by four distinct patterns of coherency, which provide insight into the contributions of the primary disease process and antiparkinsonian medication to the broad clinical spectrum of PD. One factor, consisting of predominantly non-motor symptoms together with axial features, clearly reflected disease severity and may provide a new basis for monitoring disease progression in PD.