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.     

Comparison of sleep and other non-motor symptoms between SWEDDs patients and de novo Parkinson's disease patients

BackgroundSWEDDs (Scans Without Evidence of Dopaminergic Deficits) was defined from a series of pharmaceutical trials on Parkinson's disease (PD). Non-motor features including sleep-related problems are common even in early-stage PD patients; however, little is known about the burden of the non-motor symptoms in SWEDDs patients.MethodsThe Non-motor Symptoms Assessment Scale (NMSS), revised version of the Parkinson's Disease Sleep Scale (PDSS-2), Epworth Sleepiness Scale (ESS), and EuroQol 5-Dimension (EQ-5D) were applied to evaluate 17 SWEDDs patients and 28 de novo PD patients. The presence of clinically probable rapid eye movement sleep behavior disorder (cpRBD) was assessed using the International Classification of Sleep Disorders-Revised (ICSD-R) criteria.ResultsThe total NMSS score for the SWEDDs group was significantly lower than for the de novo PD group (p = 0.032). The most distinct difference was in taste or smell change (p < 0.000). Prevalence of cpRBD was higher in de novo PD patients than in SWEDDs patients (p = 0.030), though no significant differences in the PDSS-2 total score (p = 0.496) or the ESS score (p = 0.517) were found. The SWEDDs patients did not significantly differ from the de novo PD patients with regard to quality of life, as measured by the EQ-5D index score (p = 0.177).ConclusionsThe patients with SWEDDs have less non-motor problems than newly diagnosed untreated PD patients. Given the difficulty distinguishing between SWEDDs and early PD, identifying some of non-motor symptoms, such as RBD or olfactory impairment, could aid clinicians in their work.     

Determinants and impact of alexithymia on quality of life in Parkinson's disease

IntroductionAlexithymia is a neuropsychiatric symptom conceptualized as difficulty identifying and describing feelings. Although associated with other non-motor symptoms, mainly neuropsychiatric, alexithymia may present as an isolated symptom in persons with Parkinson's Disease (PwP). The objective of the study is to identify determinants of alexithymia and its association with quality of life (QoL) in Parkinson's disease.MethodsSubjects with Parkinson's disease were recruited. The following instruments were applied: Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment (MoCA), Toronto alexithymia scale (TAS-20) and Parkinson's Disease Questionnaire (PDQ-8). Matched healthy controls were screened using TAS-20. Clinical and demographical variables were compared between alexithymic and non-alexithymic. Regression models were used to find determinants of alexithymia. Impact of alexithymia on QoL was estimated with a linear regression model.Results98 patients were included. 56.1% PwP and 28.8% controls were alexithymic (p < 0.001). Education level (OR 0.86) and NMSS urinary score (OR 1.09) determined alexithymia as well as TAS-20 score. Alexithymia was an independent determinant of QoL.ConclusionsAlexithymia is a prevalent independent non-motor symptom in PwP with impact on QoL. Low education level and urinary symptoms are important determinants of alexithymia.     

Motor,behavioural, and cognitive correlates of fatigue in early,de novo Parkinson disease patients

IntroductionFatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.MethodsEighty-one consecutive de novo PD patients (64% men; mean age 65.73 ± 8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score ≥ 8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue.ResultsTwelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p = 0.04), “episodic anxiety” subscale of PAS (p = 0.005), and “cognitive apathy” subscale of AES (p = 0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p = 0.745).ConclusionIn a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.     

Prolonged-release melatonin in Parkinson's disease patients with a poor sleep quality: A randomized trial

BackgroundThe present study was a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of prolonged-release melatonin (PRM) in Parkinson's disease (PD) patients with poor sleep quality.MethodsPD patients with a global Pittsburgh Sleep Quality Index (PSQI) score > 5 were included. Patients were assessed using the PSQI, a rapid eye movement sleep behavior disorder screening questionnaire, the Epworth Sleepiness Scale, Non-Motor Symptoms Scale (NMSS), Parkinson's Disease Quality of Life-39 (PDQ-39), and Unified Parkinson's Disease Rating Scale (UPDRS)-III at the beginning of the study and after 4 weeks of treatment with 2 mg of PRM. Partial correlation analysis was performed to investigate the relationship between PSQI score and the other scales.ResultsThirty-four PD patients with poor sleep quality were enrolled and divided into 2 groups based on medication; PRM (n = 16) and placebo (n = 18). Regarding efficacy, PSQI was significantly improved in the PRM group compared to the control group. Improvement in the NMSS and PDQ-39 summary index were observed in the PRM but not in the placebo group; UPDRS-III score was not significantly changed in either group. PSQI improvement correlated with improvement in NMSS score and PDQ-39 summary index. Regarding safety, all enrolled subjects did not complain of side effects due to PRM.ConclusionPRM is an effective and safe treatment option for subjective sleep quality in PD patients and beneficial effects on sleep quality are associated with improved non-motor symptoms and quality of life in PD patients.     

Independent validation of the Non motor Symptoms Scale for Parkinson's disease in Brazilian patients

ObjectiveIndependent validation of the Non motor Symptoms Scale in Parkinson's disease (NMSS) based on a cross-culturally adapted Brazilian version.MethodsParkinson's disease (PD) patients were evaluated by means of the Scales for Outcomes in Parkinson's disease-Motor (SCOPA-M), Autonomic, Cognition, and Psychosis; Hoehn and Yahr staging (H&Y); Berg Balance Scale; PD Sleep Scale; Clinical Impression of Severity Index for PD (CISI-PD); PDQ-39; and EQ-5D. The following clinimetric attributes were explored for the NMSS: acceptability, scaling assumptions, reliability, construct validity, and precision.Results150 patients were assessed (mean age 63.1 years; 56.7% males; mean duration of illness 8.7 years; HY median: 2). Mean NMSS was 48.9 (SD 36.3; median 42; skewness 1.3). Neither floor nor ceiling effect was observed on the NMSS total score. For domains, the Cronbach's alpha coefficient ranged from 0.40 to 0.82. The NMSS total score correlated significantly with SCOPA-AUT (r_S = 0.65) and with those scales measuring related constructs (r_S = 0.46–0.57). NMSS significantly increased as the H&Y stage increased (Kruskal–Wallis, p < 0.0001). These values were quite close to those from the original validation studies.ConclusionsThe NMSS is a reliable and valid measure to evaluate non motor symptoms in Brazilian PD patients.     

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.     

Peripheral insulin and amylin levels in Parkinson's disease

BackgroundType-2-diabetes (T2D) has surfaced as a potential risk factor for Parkinson's disease (PD) in some epidemiological studies. Evidence of glucose metabolism alterations in PD from molecular studies remains conflicting. Amylin, the T2D amyloid protein, has been implicated in PD in pathological studies. We aimed to assess peripheral levels of amylin and insulin in PD patients and control subjects (Cs).MethodsWe conducted an observational cross-sectional study of 111 participants: 73 PD and 38 Cs, similar in age, sex and body mass index. All underwent motor (UPDRS-MDS-III), non-motor (NMSS) and cognitive (MDRS) scales as well as determination of four parameters: fasting glycaemia, glycated haemoglobin, fasting plasma insulin (FPI) and fasting plasma amylin (FPA).ResultsFPI was significantly lower in PD than Cs (p = 0.034). In participants with age above cohort-median-age, FPA was higher in PD than Cs (p = 0.046). The FPA/FPI ratio (FPAIR) was significantly higher in PD than Cs (p = 0.024). In PD, modest correlation was found between higher insulin-resistance and NMSS scores.ConclusionsPD patients had lower FPI and increased FPAIR. In older PD subgroup, FPA was increased. The more the insulin resistance, the higher the non-motor scores. These findings provide an additional link between pathophysiology of diabetes and PD. This might be related to a dissociated insulin and amylin secretion in PD, in line with recent evidence of endocrine pancreas role in PD pathogeny.     

Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson's disease

BackgroundThe relative impact of motor- and non-motor symptoms on health-related quality of life in early Parkinson's disease is poorly documented.Methods188 patients with incident Parkinson's disease from a population-based study were examined at the time of diagnosis, before initiation of dopaminergic treatment, with follow-up of 166 patients three years later. Health-related quality of life was assessed by the 36-item Short-form Health Survey (SF-36). Motor and non-motor variables were derived from the Unified Parkinson's disease rating scale and other established scales.ResultsMultiple regression analyses showed that the non-motor symptoms strongest associated with reduced SF-36 scores at diagnosis and three years later were depression, fatigue and sensory complaints. The motor symptoms most related to impaired SF-36 scores were problems with gait and activities of daily living that cover personal needs. The variance of SF-36 mental summary scores was much better explained by non-motor vs. motor symptoms, both at baseline (R² = 0.384 vs. 0.095) and 3 years later (R² = 0.441 vs. 0.195). Also SF-36 physical summary scores were better explained by non-motor vs. motor symptoms with R² = 0.372 vs. 0.322 at baseline and R² = 0.468 vs. 0.315 after 3 years.ConclusionIn early PD, including the phase before dopaminergic treatment is initiated, non-motor symptoms are more important for reduced health-related quality of life than motor symptoms. Fatigue, depression, sensory complaints and gait disturbances emerge as the most relevant symptoms and should be given corresponding attention in the management of patients with early PD.     

Unexplained lower limb pain in Parkinson's disease: A phenotypic variant of “painful Parkinson's disease”

Unexplained pain is a key non-motor symptom (NMS) of Parkinson's disease (PD) that is prevalent throughout the condition and often unrecognized and under treated. We have identified a cluster of patients with unexplained refractory and intrusive lower limb pain.MethodsPatients with ‘unexplained’ pain were identified from a survey using a non-motor symptom questionnaire and scale (NMSQuest, NMSS). Patients reporting unexplained severe proximal lower limb pain were then assessed using a newly devised PD pain scale. Co-morbid conditions were excluded and all had lower spine imaging.ResultsFrom a cohort of 225 patients we have identified 22 with unexplained lower limb pain described as persistent leg pain ranging from unilateral to bilateral sometimes associated with whole body pain. None had significant spinal pathology or evidence of large fiber neuropathy. 14 were on regular analgesics with poor effect while 9 took morphine based remedies. Severe unremitting pain led to accidental overdose and death in one patient. All took a combination of levodopa and dopamine agonist treatment including 3 on intrajejunal levodopa infusion. All had high NMSQuest (mean = 17/30) and NMSS (mean = 95 (normal range 30–60)) scores.ConclusionsWe believe that unexplained lower limb pain is a specific non-motor phenotype in Parkinson's disease that is problematic and often undisclosed. This may be a variant of central pain and merits recognition.     

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.     

Relationships among cognitive impairment,sleep, and fatigue in Parkinson's disease using the MDS-UPDRS

BackgroundNon-motor complications of Parkinson's disease (PD), specifically cognitive impairment, sleep disturbances, and fatigue, are recognized as important contributors to poor patient outcomes and quality of life. How sleep problems and fatigue interrelate and impact cognitive function, however, has not systematically been investigated across the stages of PD. The aim of our study was to investigate the relationships among cognitive impairment, night-time sleep problems, daytime sleepiness, and fatigue across all severities of PD.MethodsWe examined these non-motor problems using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) in a study of 1319 PD patients drawn from three large cohort studies: the Parkinson's Progressive Markers Initiative, the Rush University PD Cognitive-Behavioral-Imaging study, and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Clinimetric testing program study, which spanned the gamut of disease, from early to advanced PD. Generalized linear mixed models with logit linking functions and covariates including study cohort, age, PD duration, and presence/absence of PD medications were used to examine relationships between these three non-motor symptoms and cognitive impairment.ResultsOf these three frequent, and often inter-twined, non-motor complications, greater daytime sleepiness and fatigue were associated with worse cognitive impairment across the full spectrum of PD (F[16,1158] = 2.40 and F[16,1158] = 3.45 respectively, p's < 0.0005), but an association with night-time sleep was not detected (p = 0.83).ConclusionsGiven this association of daytime sleepiness and fatigue with cognitive impairment, clinical monitoring for these problems should be considered across all points in the PD spectrum, from early to more advanced disease.     

Clinical features and varieties of non-motor fluctuations in Parkinson's disease: A Japanese multicenter study

ObjectiveThis multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD).MethodsTo identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis.ResultsThe patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p < 0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p < 0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation.ConclusionForty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.     

Association between fatigue and other motor and non-motor symptoms in Parkinson’s disease patients

Although fatigue is a common non-motor symptom in patients affected by Parkinson’s disease (PD), its association with motor and other non-motor symptoms is still largely unclear. We assessed fatigue in PD patients studying the possible association with motor and non-motor symptoms. Eighty-one PD patients were included in the study. The PD Fatigue Scale (PFS) and the Fatigue Severity Scale (FSS) scale were used to measure fatigue. Non-motor symptoms were assessed with the Non-Motor Symptoms Scale (NMSS). Motor impairment was assessed using the modified Hoehn and Yahr (HY) staging and the Unified PD Rating Scale (UPDRS) part-III and IV. Bivariate tests comparing all independent variables between patients with our without fatigue were used. Significant predictors of presence and severity of fatigue were determined with different models of logistic regression analyses. Fatigue severity was significantly higher in female patients. Bivariate test showed significant higher NMSS score in fatigued patients according to PFS (p < 0.00001) and FFS (p < 0.001), while HY was higher only in fatigued patients according to FSS (p < 0.022). Significant correlations between severity of fatigue and HY stage (p < 0.002) and UPDRS-III score (p < 0.001) were found, while, among specific non-motor symptoms, anhedonia presented with the most significant correlation (p < 0.003). Binary logistic regression confirmed NMSS as the main variable predicting presence of fatigue, while HY was significant as predicting variable only in the FSS model. Strongest non-motor symptoms predictors of severity were those included in Domain 3 (mood/anxiety) and Domain 2 (sleep disorders) of the NMSS. A significant increase in severity of fatigue related to the burden of non-motor symptoms (mainly affective and sleep disorders) was observed. Our findings indicate a moderate discrepancy in the ratings of the two fatigue scales, with PFS principally directed towards the burden of non-motor symptoms. Finally, the accurate individuation of the factors underlying fatigue, assessed with the systematic administration of holistic evaluation scales such as the NMSS, might improve current strategies used in the treatment of this disabling condition.     

Validation of the Chinese Non-Motor Symptoms Scale for Parkinson's disease: Results from a Chinese pilot study

Objectives

To evaluate a Chinese version of the Non-Motor Symptoms Scale (NMSS) in Parkinson's disease (PD) as an instrument for measuring non-motor symptoms (NMSs) in Chinese patients with Parkinson's disease.

Methods

We conducted a psychometric analysis of the Chinese version of NMSS using a cross-sectional study of 126 patients with PD. The battery also included the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Hamilton Anxiety Scale (HAMA), and was conducted by neurologists.

Results

There were significant correlations between the NMSS and PSQI scores (rS = 0.63, P < 0.001), as well as the NMSS and ESS scores (rS = 0.38, P < 0.001). Furthermore, significant positive correlations between NMSS and GDS, NMSS and HAMA, and NMSS and disease duration were also observed. Importantly, the sleep/fatigue index of the NMSS significantly correlated with the PSQI and ESS findings, the mood/cognition index of the NMSS significantly correlated with the GDS and HAMA findings, and the attention/memory index of the NMSS significantly correlated with the MMSE findings.

Conclusion

The Chinese version of the NMSS can be considered a comprehensive, useful measure for NMS evaluation in Chinese PD patients.     

Non-motor symptoms and the quality of life in multiple system atrophy with different subtypes

BackgroundThe differences in non-motor symptoms (NMS) and quality of life (QOL) between MSA patients with different subtypes remain unknown, so do the determinants of poor QOL in both subtypes.MethodsA total of 172 MSA patients were enrolled in the study. NMS of patients with MSA were assessed using the non-motor symptoms scale (NMSS) and Parkinson's Disease Questionnaire-39 item version (PDQ-39) was used to evaluate the QOL of patients with MSA.ResultsThe most prevalent NMS domain was urinary (91.3%) in both subtypes. The mood/apathy domain was more severe in MSA-P than MSA-C patients (P < 0.05). Drooling, constipation, and pain symptoms were more prevalent and severe in the MSA-P patients compared to the MSA-C patients (P < 0.05). We found that the MSA-C patients had a higher score of mobility than the MSA-P patients (P = 0.002); However, the MSA-P patients had a higher score of bodily discomfort than the MSA-C patients (P = 0.036). There were close correlations between NMS and PDQ-39 in both subtypes. Disease severity, cardiovascular symptoms, sleep/fatigue symptoms and gastrointestinal symptoms were determinants of poor QOL in MSA-P patients. While in MSA-C patients, longer disease duration, disease severity and mood/apathy symptoms were determinants of poor QOL.ConclusionNMS are more severe and prevalent in MSA-P patients, especially for mood/apathy and gastrointestinal symptoms. There is a close relationship between NMS and QOL in both MSA subtypes. Disease severity, longer disease duration and severe NMS are determinants of poor QOL in MSA.     

Doxepin and cognitive behavioural therapy for insomnia in patients with Parkinson's disease – A randomized study

IntroductionAlthough a variety of pharmacologic and non-pharmacologic treatments are effective for insomnia in the general population, insomnia in Parkinson's disease differs in important ways and may need different treatments. No studies have conclusively demonstrated effective insomnia treatments in Parkinson's disease.MethodsWe conducted a three-arm six-week randomized pilot study assessing non-pharmacologic treatment (cognitive behavioural therapy with bright light therapy) or doxepin (10 mg daily), compared to an inactive placebo in Parkinson's patients with insomnia. Sleep outcomes included insomnia scales, clinical global impression, sleep diaries and actigraphy. Secondary outcomes included motor severity, fatigue, depression and quality of life.Results18 patients were randomized, 6 to each group. Compared to placebo, doxepin improved the Insomnia Severity Index (?9 ± 5.4 vs. ?2 ± 3.9, p = 0.03), the SCOPA-night score (?5.2 ± 1.5 vs. ?2.3 ± 2.8, p = 0.049), the Pittsburgh Sleep Quality Index-sleep disturbances subscale (?0.5 ± 0.5 vs 0.2 ± 0.4, p = 0.02), and both patient and examiner-rated clinical global impression of change (1.7 ± 0.8 vs. 0.5 ± 0.8, p = 0.03 and 1.4 ± 0.5 vs. 0.3 ± 0.5, p = 0.003). On secondary outcomes doxepin reduced the fatigue severity scale (p = 0.02) and improved scores on the Montreal Cognitive Assessment (p = 0.007). Non-pharmacological treatment reduced the Insomnia Severity Index (?7.8 ± 3.8 vs. ?2.0 ± 3.9, p = 0.03), and the examiner-reported clinical global impression of change (p = 0.006), but was associated with decline in Parkinson Disease Questionnaire-39. There were no changes in other primary and secondary outcomes, including actigraphy outcomes. Adverse events were comparable in all groups.ConclusionDoxepin and non-pharmacologic treatment substantially improved insomnia in Parkinson's disease. These potential benefits must be replicated in a full confirmatory randomized controlled trial.     

Sleep and impulsivity in Parkinson's disease

BackgroundImpulsive behavior and poor sleep are important non-motor features of Parkinson's disease (PD) that negatively impact the quality of life of patients and their families. Previous research suggests a higher level of sleep complaints in PD patients who demonstrate impulsive behaviors, but the nature of the sleep disturbances has yet to be comprehensively tested.MethodsConsecutive idiopathic PD patients (N = 143) completed the Minnesota Impulse Disorder Interview and a sleep questionnaire that assessed sleep efficiency, excessive daytime sleepiness, restless legs symptoms, snoring, dreams/nightmares, and nocturia. Patients were also given a Unified Parkinson's Disease Rating Scale motor examination and they completed cognitive testing.ResultsImpulsive PD patients endorsed more sleep complaints than non-impulsive PD patients. The group difference was primarily attributable to poor sleep efficiency (e.g., greater nocturnal awakenings), p < .01, and greater daytime sleepiness, p < .01, in the impulsive PD patients. Interestingly, restless legs symptoms were also greater in the impulsive PD patients, p < .05. The results could not be explained by medications or disease severity.ConclusionsPoor sleep efficiency, restless legs symptoms, and increased daytime sleepiness are associated with impulsivity in PD. Longitudinal studies are needed to determine whether sleep disturbances precede impulsivity in PD.     

Rotigotine for nocturnal hypokinesia in Parkinson's disease: Quantitative analysis of efficacy from a randomized,placebo-controlled trial using an axial inertial sensor

BackgroundNocturnal hypokinesia is a common symptom in Parkinson's disease (PD), negatively affecting quality of life of both patients and caregivers. However, evidence-based treatment strategies are limited.ObjectiveTo evaluate the efficacy of rotigotine transdermal patch, using a wearable sensor, in the management of nocturnal immobility.Methods34 PD subjects with nocturnal immobility were randomized to receive rotigotine transdermal patch (mean ± SD of 10.46 ± 4.63 mg/24 h, n = 17) or placebo patch (n = 17). Treatment was titrated to an optimal dose over 1–8 weeks, then maintained for 4 weeks. Primary endpoints were objective parameters assessing axial rotation measured using an axial inertial sensor (the NIGHT-Recorder) over two nights at the patients' home. Scale-based assessments were also performed.ResultsThere was a significant difference, in favor of rotigotine, in change from baseline score in the number of turns in bed (ANCOVA, p = 0.001), and degree of axial turn (p = 0.042). These objective improvements were mirrored by significantly greater improvements in clinical scale-based assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS) total scores (p = 0.009), UPDRS-motor scores (p < 0.001), UPDRS-axial scores (p = 0.01), the Modified Parkinson's Disease Sleep Scale (p < 0.001), the Nocturnal Akinesia Dystonia and Cramp Scale (p = 0.003) and the eight-item PD Questionnaire (PDQ-8) scores (p = 0.01) from baseline to end of treatment in patients given rotigotine compared to placebo.ConclusionWe show that the rotigotine patch provides a significant improvement in nocturnal symptoms as assessed using both objective measures and clinical rating scales. The study demonstrates the feasibility of using wearable sensors to record objective outcomes in PD-related clinical trials.     

Motor and non-motor features of Parkinson's disease that predict persistent drug-induced Parkinsonism

BackgroundDrug-induced Parkinsonism is common, causes significant morbidity, and can be clinically indistinguishable from idiopathic Parkinson's disease. Additionally, drug-induced Parkinsonism may, in some cases, represent “unmasking” of incipient Parkinson's disease. Clinical features or tests that distinguish degenerative from pharmacologic Parkinsonism are needed.MethodsWe performed a retrospective case-control study of 97 drug-induced Parkinsonism subjects and 97 age-matched patients with Parkinson's disease. We compared the frequency of subjective motor and non-motor complaints, objective motor findings (Unified Parkinson's Disease Rating Scale Part III) and, where available, objective olfactory tests. We also performed a nested case-control study wherein we compared these same features between drug-induced Parkinsonism patients based on whether or not they recovered after changing the offending agent.ResultsNon-motor symptoms including constipation and sexual dysfunction were more common in Parkinson's disease than in drug-induced Parkinsonism. While total motor scores were similar between groups, Postural Instability-Gait Difficulty scores were also higher in Parkinson's disease. Features that were significantly different or showed a trend towards significance in both comparisons included subjective loss of facial expression, dream-enactment behavior, autonomic complaints and Postural Instability-Gait Difficulty scores. Hyposmia was more common in Parkinson's disease and was strongly predictive of persistent drug-induced Parkinsonism after therapy change (odds ratio 30.3, 95% confidence interval: 1.5–500, p = 0.03).ConclusionsA constellation of motor and non-motor features may differentiate unmasked Parkinson's disease from drug-induced Parkinsonism. In particular, olfactory testing may offer a simple and inexpensive method to help predict outcomes in drug-induced Parkinsonism and, potentially, identify a cohort of pre-motor Parkinson's disease.