Validation of the Italian version of the Non Motor Symptoms Scale for Parkinson's disease

ObjectiveTo validate the adapted Italian version of the Non-Motor Symptoms Scale (NMSS), a tool to assess non-motor symptoms (NMS) in Parkinson's disease (PD).MethodsA cross cultural adaptation of the NMSS into Italian and a psychometric analysis of the translated version of the NMSS was carried out in patients with PD from two university centres–affiliated hospitals. The quality of data and the acceptability, reliability and construct validity of NMSS were analyzed. The following standard scales were also applied: Hoehn and Yahr staging, Unified Parkinson's Disease Rating Scale (UPDRS) part III, Montreal Cognitive Assessment, Beck Depression Inventory, Neuropsychiatric Inventory, Epworth Sleepiness Scale, Autonomic Scale for Outcomes in Parkinson's disease-Motor, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part I and Modified Cumulative Illness Rating Scale (CIRS). Levodopa equivalent daily dose (LEDD) was calculated.ResultsSeventy-one patients with PD were assessed (mean age years 69.8 ± 9.6 SD; 31% women; mean length of disease 6.3 ± 4.6 years; H&Y median: 2). Mean NMSS was 39.76 (SD 31.9; skewness 0.95). The total score of NMSS was free of floor or ceiling effects and showed a satisfactory reliability (Cronbach's alpha coefficient on total score was 0.72 [range for domains: 0.64–0.73], SEM value was 3.88 [½ SD = 31.90]). Significant positive correlations were found among total NMSS and other NMS standard tests, but no significant correlation appeared with UPDRS part III, CIRS and LEDD.ConclusionsThe Italian NMSS is a comprehensive and helpful measure for NMS in native Italian patients with PD.     

The impact of non-motor symptoms on the Health-Related Quality of Life of Parkinson's disease patients from Southwest China

BackgroundThe impact of non-motor symptoms (NMS) on the Health-Related Quality of Life (HRQoL) of patients with Parkinson's disease (PD) in the Chinese population are largely unknown.ObjectivesTo study the impact of NMS on the HRQoL in Chinese PD patients.MethodsA total of 693 PD patients from Southwest China were included in the study. NMS of patients were evaluated by non-motor symptoms scale (NMSS) and Parkinson's disease questionnaire-39 item version (PDQ-39) was used to evaluate the HRQoL of PD.ResultsThe mean total score of NMSS was 37.2 ± 33.0 and the most prevalent NMS domain was sleep/fatigue (79.8%). There was a significant strong positive correlation between total NMSS score (r_s = 0.71, P < 0.01), sleep/fatigue domain (r_s = 0.60, P < 0.01) and PDQ-39 SI. Mood/apathy (r_s = 0.55, P < 0.01), attention/memory (r_s = 0.42, P < 0.01), gastrointestinal (r_s = 0.44, P < 0.01) and Miscellany domains (r_s = 0.46, P < 0.01) moderately correlated with PDQ-39 SI. A strong correlation was found between PDQ-39 SI (r_s = 0.71, P < 0.01), emotional well-being (r_s = 0.62, P < 0.01), cognitions (r_s = 0.62, P < 0.01), and the total score of NMSS. Moderate correlation was found between mobility (r_s = 0.45, P < 0.01), activities of daily living (r_s = 0.43, P < 0.01), stigma (r_s = 0.42, P < 0.01), communication (r_s = 0.47, P < 0.01), bodily discomfort (r_s = 0.46, P < 0.01) and the total score of NMSS. Female, H–Y stage, UPDRS-III and NMSS total score were the potential determinants of worse HRQoL of PD patients.ConclusionsNMS have close association with various aspects of the HRQoL. Severe NMS may be related to dramatic decline of the HRQoL of PD patients.     

Reasons driving treatment modification in Parkinson's disease: Results from the cross-sectional phase of the REASON study

ObjectivesTo assess the association between clinical and socio-demographic features and anti-Parkinson drug (APD) treatment modifications in patients with PD and to describe neurologist and patient opinions regarding the need for changes in APD therapy.MethodsSubjects with PD with stable APD treatment over ≥3 months prior to baseline were enrolled and evaluated for socio-demographic data, disability, disease severity and neurologist and patient views on the need to modify APD treatment.Results775 Patients were included, 51% with Hoehn and Yahr (HY) stage 1–2 (early PD) and 49% with HY stage 2.5–4 (advanced PD). Neurologists modified APD treatment in 255 patients, 97 (25%) early PD and 158 (41%; p < 0.0001) advanced PD. APD modification was strongly associated with a low educational level and UPDRS part IV score. The most common reasons behind the APD therapy changes among neurologists were presence/worsening of motor or non-motor symptoms (88% and 37% of subjects respectively). Out of 216 patients, 92% and 51% were willing to undergo APD changes to therapy because of the presence/worsening of motor or non-motor symptoms.ConclusionsNeurologist decision to change APD therapy and patients reasons for dissatisfaction with it can be prevalently attributed to the presence/worsening of motor symptoms and motor fluctuations in the advanced stages. Non-motor symptoms were considered more often by patients. The patient educational level played a key role in treatment decision.     

Validation of the Korean-Version of the Nonmotor Symptoms Scale for Parkinson's Disease

Background and Purpose

Non-motor symptoms are common in Parkinson''s disease (PD), and are the primary cause of disability in many PD patients. Our aim in this study was to translate the origin non-motor symptoms scale for PD (NMSS), which was written in English, into Korean (K-NMSS), and to evaluate its reliability and validity for use with Korean-speaking patients with PD.

Methods

In total, 102 patients with PD from 9 movement disorders sections of university teaching hospitals in Korea were enrolled in this study. They were assessed using the K-NMSS, the Unified Parkinson''s Disease Rating Scale (UPDRS), the Korean version of the Mini-Mental Status Examination (K-MMSE), the Korean version of the Montgomery-Asberg Depression Rating Scale (K-MADS), the Epworth Sleepiness Scale (ESS), and Parkinson''s Disease Questionnaire 39 (PDQ39). Test-retest reliability was assessed over a time interval of 10-14 days in all but one patient.

Results

The K-NMSS was administered to 102 patients with PD. The internal consistency and reliability of this tool was 0.742 (mean Cronbach''s α-coefficient). The test-retest correlation reliability was 0.941 (Guttman split-half coefficient). There was a moderate correlation between the total K-NMSS score and the scores for UPDRS part I [Spearman''s rank correlation coefficient, (rS)=0.521, p<0.001] and UPDRS part II (rS=0.464, p=0.001), but there was only a weak correlation between the total K-NMSS score and the UPDRS part III score (rS=0.288, p=0.003). The total K-NMSS score was significantly correlated with the K-MADS (rS=0.594, p<0.001), K-MMSE (rS=-0.291, p=0.003), and ESS (rS=0.348, p<0.001). The total K-NMSS score was also significantly and positively correlated with the PDQ39 score (rS=0.814, p<0.001).

Conclusions

The K-NMSS exhibited good reliability and validity for the assessment of non-motor symptoms in Korean PD patients.     

Response of non-motor symptoms to levodopa in late-stage Parkinson's disease: Results of a levodopa challenge test

BackgroundNon-motor symptoms (NMS) are extremely common among late-stage Parkinson's disease (LSPD) patients. Levodopa (L-dopa) responsiveness seems to decrease with disease progression but its effect on NMS in LSPD still needs to be investigated.ObjectiveTo assess the response of blood pressure (BP), pain, fatigue and anxiety to L-dopa in LSPD patients.Methods20 LSPD patients, defined as Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 (MED ON) and 22 PD patients treated with subthalamic deep brain stimulation (advanced PD group) underwent an L-dopa challenge. BP and orthostatic hypotension (OH) assessment, a visual analogue scale (VAS) for pain and fatigue and the Strait Trait Anxiety (STAI) were evaluated before and after the L-dopa challenge.ResultsSystolic BP dropped significantly after L-dopa intake (p < 0.05) in LSPD patients, while there was no change in pain, fatigue or anxiety. L-dopa significantly improved (p < 0.05) pain and anxiety in the advanced PD group, whereas it had no effect on BP or fatigue. L-dopa-related adverse effects (AEs), namely OH and sleepiness, were more common among LSPD patients. 40% and 65% of LSPD patients were not able to fill out the VAS and the STAI, respectively, while measurement of orthostatic BP was not possible in four LSPD patients.ConclusionsThis exploratory study concludes that some non-motor variables in LSPD do not benefit from the acute action of L-dopa while it can still induce disabling AEs. There is a need for assessment tools of NMS adapted to these disabled LSPD patients.     

Validation of a non-motor fluctuations questionnaire in Parkinson's disease

IntroductionNon-motor fluctuations (NMF) in Parkinson's disease (PD) remain poorly recognized but have a high impact on patients’ quality of life. The lack of assessment tools limits our understanding of NMF, compromising appropriate management. Our objective was to validate a hetero-questionnaire for NMF in PD patients at different stages of the disease: without treatment, without motor fluctuations, with motor fluctuations.MethodsWe included patients in 15 centers in France. Our questionnaire, NMF-Park, resulted from previous studies, allowing us to identify the more pertinent NMF for evaluation. Patients reported the presence (yes or no) of 22 selected NMF, and their link with dopaminergic medications. The assessment was repeated at one and two years to study the progression of NMF. We performed a metrological validation of our questionnaire.ResultsWe included 255 patients (42 without treatment, 88 without motor fluctuations and 125 with motor fluctuations). After metrological validation, three dimensions of NMF were found: dysautonomic; cognitive; psychiatric. The sensory/pain dimension described in the literature was not statistically confirmed by our study.DiscussionOur questionnaire was validated according to clinimetric standards, for different stages of PD. It was clinically coherent with three homogeneous dimensions. It highlighted a link between fatigue, visual accommodation disorder, and cognitive fluctuations; and the integration of sensory/pain fluctuations as part of dysautonomic fluctuations. It focused exclusively on NMF, which is interesting considering the described differences between non-motor and motor fluctuations.ConclusionOur study validated a hetero-questionnaire of diagnosis for NMF for different stages of PD.     

Risk of Parkinson's disease following severe constipation: A nationwide population-based cohort study

IntroductionConstipation is a non-motor symptom of Parkinson's disease (PD). We investigated the association between the severity of constipation and subsequent risk of PD in a population-based sample.Methods551,324 participants free of PD, dementia, and stroke were retrospectively ascertained between January 1, 2005 and December 31, 2005 using the Taiwan National Health Insurance Research Database. The association between constipation at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities and concomitant medications use was adjusted in the proportional hazards models.ResultsAfter an average follow-up of 5.5 years, 2336 incident PD cases were diagnosed. The crude incidence rate of PD per 1,000,000 person-days was 1.57 for subjects without constipation and 4.04, 5.28, and 12.67 for mild, moderate, and severe constipation, respectively. After adjusting for age, sex, comorbidities, and concomitant medication use, patients with constipation were more likely to develop PD than subjects without constipation; the adjusted hazard ratio (aHR) was 3.28 (95% CI: 2.14–5.03), 3.83 (2.51–5.84), and 4.22 (2.95–6.05) for individual constipation severity categories. Constipation severity was also associated with an increased likelihood of PD in the time-varying analysis; the aHR was 2.84 (2.43–3.33), 5.22 (4.61–5.92), and 10.47 (9.46–11.58) for mild, moderate, and severe constipation, respectively (P < 0.0001). After excluding PD patients diagnosed within 3 years of constipation, the association remained significant.ConclusionsOur study suggests that the severity of constipation is associated with a future diagnosis of PD in a dose-dependent manner.     

The effect of Origanum majorana tea on motor and non-motor symptoms in patients with idiopathic Parkinson's disease: A randomized controlled pilot study

AimsThe effect of Origanum majorana tea consumption on motor and non-motor symptoms was investigated in patients with idiopathic Parkinson's disease, measured by validated tools.MethodsSixty patients with idiopathic Parkinson's disease and under conventional medication were enrolled voluntarily in the study. All participants were randomized on double-blind to placebo or Origanum majorana. Clinical assessment with validated tools (UPDRSIII, NMSS, and BDI) was done before Origanum majorana or placebo consumption (Day 0) and at the end of the experiment (Day 30).ResultsThe treatment groups were similar at baseline on demographic and clinical variables. During the course of study, nine participants withdrew for reasons of noncompliance and inability to follow-up. Fifty-one participants completed the study. Upon completion of 30 days of treatment, Origanum majorana tea consumption did not decrease the UPDRSIII score ([UPDRSIII^] D0 = 18.76 ± 8.58, D30 = 16.52 ± 7.96, p = 0.069) at the p value was 0.07. However, a statistically significant improvement was noted in NMSS and BDI scores (p < 0.0001 and p < 0.0001, respectively). Assessment of the UPDRSIII, NMSS and BDI scores of the patients did not reflect any improvement with placebo. No side effect was detected during the study^.ConclusionThese findings show improvement of depressive and non-motor signs in patients with Parkinson's disease in the group that consumed Origanum majorana tea in combination with conventional therapy. Improvement of motor signs may need an extended treatment period. However, more research with a large number of participants and lasting longer than 1 month is needed to argue these findings.     

Cognitive profile of Parkinson's disease patients: a comparative study between early-onset and late-onset Parkinson's disease

Aim: To investigate the influence of onset age on the occurrence and progression of cognitive dysfunction using neuropsychological tests and the electrophysiological component P300 in both early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD) patients. Methods: A cohort of 76 EOPD patients and 166 LOPD patients was recruited for this study. Demographic information and clinical features, including age, disease duration, education level, family history, the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr stage, and depression scores were documented for each patient. The Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale – Revised, Chinese version (WAIS-RC) and Wechsler Memory Scale – Revised, Chinese version (WMS-RC) were used. In addition, P300 was also examined to assess cognitive function. Results: Although EOPD patients had longer disease duration, their cognitive dysfunction progressed more slowly. The MoCA tests revealed that EOPD patients had higher scores in visuospatial function, attention, delayed recall, and orientation than the LOPD patients. The difference between the two groups on the WMS-RC test did not reach significance, whereas the scores in executive function, visuospatial function and attention as measured on the WAIS-RC test were significantly lower in the LOPD group. In addition, P300 latencies were markedly delayed and P300 amplitudes were reduced in the LOPD group. Conclusions: The current findings demonstrated that cognitive dysfunction progressed more slowly in the EOPD group. Although the LOPD patients exhibited shorter disease durations, their cognitive abilities, including executive function, visuospatial function and attention, may have been impaired.     

Validation of the MDS-UPDRS Part I for nonmotor symptoms in Parkinson's disease

The UPDRS has been the main outcome measure in studies of PD. Modifications have been made to improve scale properties and represent the breadth of manifestations of PD, particularly nonmotor symptoms (NMS), resulting in the Movement Disorder Society's revision of the UPDRS (MDS-UPDRS). This study was undertaken to determine the validity of MDS-UPDRS Part I (nonmotor experiences of daily living). The MDS-UPDRS and a number of validated scales for the NMS in PD were used in 94 patients with PD from Hoehn and Yahr stage I to V. We assessed reliability, floor and ceiling effects, and correlations with validated scales for the nonmotor symptoms of PD. MDS-UPDRS Part I showed high internal consistency (Cronbach's alpha: 0.85), small floor and ceiling effects (2% floor and 0% ceiling effect), and good concurrent validity (correlation with the original UPDRS Part I: r = 0.81, P < 0.001). The standardized z-score of the MDS-UPDRS Part I score demonstrated high convergent validity with the composite z-score of nonmotor scales (r = 0.89, P < 0.0001), and the two subscores based on the original factor analysis of Part I also had high correlations with the composite z-scores of corresponding nonmotor scales (depression, anxiety, apathy factor score: r = 0.72, P < 0.0001; other nonmotor features factor score: r = 0.87, P < 0.0001). Our data demonstrate that the MDS-UPDRS Part I total score has a strong relationship with a composite score of validated scales for the nonmotor aspects of PD.     

Validation of a UPDRS-/MDS-UPDRS-based definition of functional dependency for Parkinson's disease

IntroductionFunctional dependency in basic activities of daily living (ADLs) is a key outcome in Parkinson's disease (PD). We aimed to define dependency in PD, using the original and MDS versions of the Unified Parkinson's Disease Rating Scale (UPDRS).MethodsWe developed two algorithms to define dependency from items of UPDRS Part 2 and MDS-UPDRS Part 2 relating to basic ADLs (feeding, dressing, hygiene and walking, and getting out of a chair). We validated both algorithms using data from 1110 patients from six community-based PD incidence cohorts, testing concurrent validity, convergent validity, and predictive validity.ResultsOur optimal algorithm showed high specificity and moderate to high sensitivity versus Schwab & England <80% (specificity 95% [95% confidence interval (CI) 93–97] and sensitivity 65% [95% CI 55–73] at baseline; 88% [95% CI 85–91] and 85% [95% CI 79–97] respectively at five-years follow-up). Convergent validity was demonstrated by strong associations between dependency defined by the algorithm and cognition (MMSE), quality of life (PDQ39), and impairment (UPDRS part 3) (all p < 0.001). Algorithm-defined dependency status also predicted mortality: HR for mortality in those dependent vs independent at baseline was 1.6 (95%CI 1.2–2.1) and in those dependent vs independent at five-years’ follow-up was 2.2 (1.6–3.0).DiscussionWe have demonstrated the concurrent validity, convergent validity, and predictive validity of a UPDRS-/MDS-UPDRS-based algorithm to define functional dependency in PD. This can be used for studying dependency in any study where UPDRS or MDS-UPDRS part 2 data have been collected.     

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann-Whitney, Kruskal-Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.     

Prevalence of non-motor dysfunction among Parkinson's disease patients from a tertiary referral center in Mexico City

Data on the frequency of non-motor symptoms among patients with Parkinson's disease (PD) in Mexico has not been reported.     

Segmental progression of cardinal motor symptoms in Parkinson's disease: A pilot study suggesting a practical approach to rate disease course in the early stages

Little is known about the anatomical progression over the body segments of extrapyramidal signs in Parkinson's disease (PD); furthermore a great unmet need is the availability of instruments able to detect disease progression, even in the early phase.The purpose of this study is to demonstrate that assessing topographical distribution of the cardinal motor features of PD may significantly improve the evaluation of disease progression in the early stages.Forty-four drug-naïve PD patients were included in the study. Presence or absence of bradykinesia, rest tremor and rigidity was derived from Unified Parkinson's disease rating scale part III (UPDRS-III) in five different anatomical segments: axial, right and left upper- and lower-limbs. Based on this approach, four new scores were computed evaluating the anatomical spread of the cardinal motor symptoms of PD on the five body segments over a 18-month follow-up period. The four new scores included: the Bradykinesia Segmental Score, the Tremor Segmental Score, the Rigidity Segmental Score, measuring the occurrence of each motor symptom in different segments and the Combined Segmental Score evaluating the occurrence of any motor symptom in different anatomical regions. Data were analyzed using a repeated measures analysis of variance.The Combined Segmental Score showed a significant progression over time whereas the Hoehn and Yahr and the UPDRS-III scores did not.We suggest that a simple approach evaluating the anatomical distribution of motor symptoms and their progression over the body segments may be a useful complement to the classical rating tools to assess progression in early PD.     

Digital health technology for non-motor symptoms in people with Parkinson's disease: Futile or future?

IntroductionThere is an ongoing digital revolution in the field of Parkinson's disease (PD) for the objective measurement of motor aspects, to be used in clinical trials and possibly support therapeutic choices. The focus of remote technologies is now also slowly shifting towards the broad but more “hidden” spectrum of non-motor symptoms (NMS).MethodsA narrative review of digital health technologies for measuring NMS in people with PD was conducted. These digital technologies were defined as assessment tools for NMS offered remotely in the form of a wearable, downloadable as a mobile app, or any other objective measurement of NMS in PD that did not require a hospital visit and could be performed remotely. Searches were performed using peer-reviewed literature indexed databases (MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane CENTRAL Register of Controlled Trials), as well as Google and Google Scholar.ResultsEighteen studies deploying digital health technology in PD were identified, for example for the measurement of sleep disorders, cognitive dysfunction and orthostatic hypotension. In addition, we describe promising developments in other conditions that could be translated for use in PD.ConclusionUnlike motor symptoms, non-motor features of PD are difficult to measure directly using remote digital technologies. Nonetheless, it is currently possible to reliably measure several NMS and further digital technology developments are underway to offer further capture of often under-reported and under-recognised NMS.     

Rotigotine and specific non-motor symptoms of Parkinson's disease: Post hoc analysis of RECOVER

BackgroundNon-motor symptoms of Parkinson's disease (PD) represent major causes of morbidity. RECOVER, a randomized controlled trial of rotigotine transdermal system, was the first prospective controlled trial to use the Non-Motor Symptoms Scale (NMSS) as an exploratory outcome for assessment of treatment effects on non-motor symptoms in PD. Rotigotine improved NMSS total score compared with placebo, and the “Sleep/fatigue” and “Mood/apathy” domains. This post hoc analysis further characterizes the effects of rotigotine on sleep/fatigue and mood/apathy.MethodsPatients with PD and unsatisfactory early-morning motor impairment were randomized to transdermal patches of rotigotine (2–16 mg/24 h) or placebo. Treatment was titrated to optimal dose over 1–8 weeks, maintained for 4 weeks. The NMSS was assessed at baseline and end of treatment. Post hoc analyses are presented for individual items of the “Sleep/fatigue” and “Mood/apathy” domains. The interpretation of p-values is considered exploratory in nature.ResultsOf 287 patients randomized, NMSS data were available for 267 patients (178 rotigotine, 89 placebo). Within the “Sleep/fatigue” domain there was a significant difference, in favor of rotigotine, in change from baseline score in 1 of 5 items: “fatigue (tiredness) or lack of energy” (ANCOVA, p < 0.0001). Within the “Mood/apathy” domain, there were significant differences in favor of rotigotine in 4 of 7 items: “lost interest in surroundings” (p < 0.0001), “lost interest in doing things” (p < 0.0001), “seems sad or depressed” (p < 0.01), and “difficulty experiencing pleasure” (p < 0.05).ConclusionsRotigotine transdermal system may improve non-motor symptoms such as fatigue, symptoms of depression, anhedonia, and apathy in patients with PD; further prospective controlled studies are required to confirm this post hoc analysis.