Drooling disrupts the brain functional connectivity network in Parkinson's disease

Aims

This study aimed to investigate the causal interaction between significant sensorimotor network (SMN) regions and other brain regions in Parkinson's disease patients with drooling (droolers).

Methods

Twenty-one droolers, 22 PD patients without drooling (non-droolers), and 22 matched healthy controls underwent 3T-MRI resting-state scans. We performed independent component analysis and Granger causality analysis to determine whether significant SMN regions help predict other brain areas. Pearson's correlation was computed between imaging characteristics and clinical characteristics. ROC curves were plotted to assess the diagnostic performance of effective connectivity (EC).

Results

Compared with non-droolers and healthy controls, droolers showed abnormal EC of the right caudate nucleus (CAU.R) and right postcentral gyrus to extensive brain regions. In droolers, increased EC from the CAU.R to the right middle temporal gyrus was positively correlated with MDS-UPDRS, MDS-UPDRS II, NMSS, and HAMD scores; increased EC from the right inferior parietal lobe to CAU.R was positively correlated with MDS-UPDRS score. ROC curve analysis showed that these abnormal ECs are of great significance in diagnosing drooling in PD.

Conclusion

This study identified that PD patients with drooling have abnormal EC in the cortico-limbic-striatal-cerebellar and cortio-cortical networks, which could be potential biomarkers for drooling in PD.     

Diurnal and nocturnal drooling in Parkinson’s disease

Drooling as symptom of Parkinson’s disease (PD) has thus far been poorly defined. This uncertainty is reflected by high variations in published prevalence rates. The aim of this study was to investigate the prevalence of saliva loss versus accumulation of saliva as a possible preliminary stage, and diurnal drooling versus nocturnal drooling. In addition, we evaluated the association between drooling severity and the severity of facial and oral motor disorders. We collected age, disease duration, UPDRS III and Hoehn & Yahr stage from 104 consecutive outpatients with PD. Diurnal and nocturnal drooling was evaluated with a validated questionnaire (ROMP-saliva). A speech pathologist, blinded for drooling severity, rated facial expression, involuntary mouth opening and difficulty with nose breathing and also interviewed patients about sleeping position and nose-breathing during the night. Thirty patients (29%) had no complaints with saliva control (‘non-droolers’), 45 patients (43%) experienced accumulation of saliva or only nocturnal drooling (‘pre-droolers’), and 29 (28%) had diurnal drooling (24 of which also drooled during the night; ‘droolers’). The droolers had longer disease duration (10 vs. 7 years, p = 0.01) and drooling was independently associated with involuntary mouth opening (OR = 2.0; 95% CI 1.02–3.99) and swallowing complaints (OR = 1.2; 95% CI 1.03–1.31). Diurnal drooling—defined as dribbling of saliva while awake—is present in about 28% of PD patients. This is less than usually reported. Diurnal drooling typically appeared later in the disease course. The association with oral motor behavior should encourage the development of behavioral treatment approaches.     

Non-motor symptoms in Chinese Parkinson’s disease patients

This study was designed to survey the prevalence and distribution of non-motor symptoms (NMS) in Parkinson’s disease (PD) patients in Shanghai, China, and to investigate the association between NMS and health-related quality of life (HRQoL). One hundred fifty-five PD patients were evaluated using the NMS Questionnaire 30 (NMSQuest), Unified Parkinson’s Disease Rating Scale (UPDRS) and Parkinson’s Disease Questionnaire-39 (PDQ-39). These data were compared with an international cross-sectional study, and the associations of motor and non-motor measures with HRQoL were estimated. Predictors of HRQoL were sought through multiple linear regression analyses. Each PD patient had eight different individual NMS on average. The problems of memory (65.82%), constipation (64.56%) and nocturia (61.39%) were the most frequent complaints. NMS prevalence in PD patients in Shanghai was consistent with that in the international study, although the composition proportions were different. There was a significant association of PDQ-39 score with NMSQuest score (rs = 0.433, p = 0.000), UPDRS III score (rs = 0.473, p = 0.000), Hoehn and Yahr (H-Y) stage (rs = 0.567, p = 0.000), disease duration (rs = 0.220, p = 0.005), and levodopa equivalent dosage (rs = 0.263, p = 0.001). H-Y stage (disease severity) and NMS score were the strongest predictors for PDQ-39 score. This study confirmed that NMS are common in PD, occurring across all disease stages and have a great impact on quality of life. NMS progression contributes significantly to HRQoL decline, and should be well recognized and treated.     

Advanced therapies in Parkinson’s disease: Long-term retrospective study

BackgroundLevodopa/carbidopa intestinal gel infusion (LCIG) and subthalamic nucleus deep brain stimulation (STN-DBS) are approved therapies for advanced Parkinson’s disease (PD) whose long-term comparability remains unclear.MethodsWe reviewed the 5-year data on activities of daily living (ADL) and motor complications (OFF time, dyskinesia duration, and dyskinesia severity), as measured by the Unified Parkinson Disease Rating Scale (UPDRS) section-II and section-IV (items 39, 32, and 33, respectively) in 60 PD patients exposed to STN-DBS (n = 20), LCIG (n = 20), and oral medical therapy (OMT) (n = 20) at similar baseline disability and cognitive state.ResultsSTN-DBS and LCIG showed a similar magnitude of deterioration in ADL (+6.1 vs. +5.7 UPDRS-II; p = 0.709), but lesser than with OMT (+13.7 UPDRS-II; p = 0.005). OFF time also improved to the same extent in STN-DBS and LCIG (−62% vs. −54.5%; p = 0.830), while worsened with OMT (+78.6%; p < 0.001). STN-DBS and LCIG yielded greater improvement on dyskinesia compared to OMT (dyskinesia duration: −66.1% vs. −9.0% vs. +24.2% [p = 0.001]; dyskinesia severity: −68.8% vs. −18.0% vs. +16.2% [p = 0.002]), with relative superiority of STN-DBS over LCIG (p = 0.004 for duration; p = 0.014 for severity). The annualized rate of complication was lower in STN-DBS vs. LCIG (0.13 vs. 0.68; p < 0.001) but not different between STN-DBS and OMT (0.13 vs. 0.10; p = 0.795).ConclusionsSTN-DBS and LCIG showed comparable efficacy in ADL and OFF time, superior to OMT. STN-DBS yielded greater improvement in dyskinesia and lower long-term rate of complications than LCIG.     

The impact of sleep and mood disorders on quality of life in Parkinson’s disease patients

Sleep disturbances are common and often severe in patients with Parkinson’s disease (PD) and their symptoms can be present at any time of day. The purpose of our study was to examine how excessive daytime sleepiness or poor nocturnal sleep quality and mood disorders influence the quality of life (QoL) in PD patients. Ninety-three PD patients from eastern Slovakia were recruited (49.5% males, mean age 68.0 ± 9.5 years, mean disease duration 6.1 ± 5.9 years). Sleep disturbances were measured using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI); QoL with the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39); depression and anxiety with the Hospital Anxiety and Depression Scale (HADS) and disease severity with the Unified Parkinson’s Disease Rating Scale (UPDRS). χ ² test, bivariate correlations and multiple linear regressions were performed. PSQI and ESS had significant correlations with worse QoL (p < 0.01, p < 0.05, respectively). HADS-D (p < 0.01), HADS-A (p < 0.01), UPDRS (p < 0.01) and disease duration (p < 0.05) were also significantly related to worse QoL. In the linear regression analysis, however, only PSQI (p < 0.01), anxiety (p < 0.001) and UPDRS (p < 0.001) remained significant. The model with PSQI explained 74% of the variance, and the model with ESS explained 63% of the variance in PDQ-39 when analyses were performed separately. In an overall model, however, only PSQI remained significant, accounting for 82% of the variance in PDQ-39. Nighttime poor sleep and anxiety are important contributors leading to a worse QoL. As these are treatable conditions, they should be recognized by clinicians and managed properly.     

Pathophysiology underlying drooling in Parkinson’s disease: oropharyngeal bradykinesia

We aimed to investigate the association between drooling and possible etiological factors in Parkinson’s disease (PD) and to determine its effect on the quality of life. Demographic data of the 63 patients with idiopathic PD were recorded. Radboud Oral Motor Inventory for Parkinson’s disease (ROMP) test was administered to all patients to evaluate speech, swallowing functions, and saliva control. The freezing of gait questionnaire (FOGQ) was used to evaluate gait and freezing of gait. Dynamic Parkinson gait scale (DYPAGS) was administered for the objective quantification of PD gait features. Disease severity was assessed by UPDRS and modified Hoehn & Yahr Scale. PD specific health-related quality was evaluated by PDQ-39 questionnaire. Drooling was only significantly correlated to UPDRS score; a stronger association was found between drooling and UPDRS 3 motor score; and a more significant association was determined between drooling and the bradykinesia questions of the motor part of UPDRS 3. Interestingly, no significant association was found between sialorrhea score and PDQ-39 score. Based on the results of this study, we concluded that oropharyngeal bradykinesia may be responsible for drooling in PD. In contrast to a general expectation, we did not find any adverse impact of drooling on the quality of life.     

Prevalence and profile of Restless Legs Syndrome in Parkinson's disease and other neurodegenerative disorders: A case-control study

BackgroundRestless Legs Syndrome (RLS) is associated with impaired central dopaminergic neurotransmission. Though a link between RLS and parkinsonism has been proposed, the prevalence of RLS in parkinsonian disorders is poorly documented.ObjectiveTo determine the prevalence of RLS in patients with Parkinson's Disease (PD), Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB).MethodsWe evaluated 187 consecutive patients with parkinsonian disorders (PD = 134, PSP = 27, MSA = 21, DLB = 5) and 172 healthy controls. RLS was diagnosed using the International RLS Study Group (IRLSSG) criteria and the severity of RLS was assessed in patients with definite RLS. Quality of sleep was evaluated with established scales.ResultsThe prevalence of RLS was higher in patients compared to controls (9.6% vs. 2.9%; p = 0.009) and was highest in PD (11.9%). RLS was present in only one patient each with MSA and PSP and none with DLB. The mean IRLSSG severity score of patients was 16.2 ± 6.5. The global Pittsburgh Sleep Quality Index score and Epworth Sleepiness Scale score were significantly higher in patients compared to controls (p < 0.001). PD patients with RLS had lower Parkinson's Disease Sleep Scale (PDSS) score compared to patients without RLS (p = 0.023). There was no significant difference in gender, age, duration and severity of PD between the two groups.ConclusionsOur study found a higher prevalence of RLS in PD compared to healthy controls or other parkinsonian disorders. Apart from PDSS score, there was no significant difference in the clinical characteristics of PD patients with and without RLS.     

Small intestinal bacterial overgrowth in Parkinson's disease

BackgroundRecent studies reported a high prevalence of small intestinal bacterial overgrowth (SIBO) in Parkinson's disease (PD), and a possible association with gastrointestinal symptoms and worse motor function. We aimed to study the prevalence and the potential impact of SIBO on gastrointestinal symptoms, motor function, and quality of life in a large cohort of PD patients.Methods103 Consecutive PD patients were assessed using the lactulose-hydrogen breath test; questionnaires of gastrointestinal symptoms and quality of life (PDQ-39); the Unified PD Rating Scale (UPDRS) including “on”-medication Part III (motor severity) score; and objective and quantitative measures of bradykinesia (Purdue Pegboard and timed test of gait). Patients and evaluating investigators were blind to SIBO status.Results25.3% of PD patients were SIBO-positive. SIBO-positive patients had a shorter mean duration of PD (5.2 ± 4.1 vs. 8.1 ± 5.5 years, P = 0.007). After adjusting for disease duration, SIBO was significantly associated with lower constipation and tenesmus severity scores, but worse scores across a range of “on”-medication motor assessments (accounting for 4.2–9.0% of the variance in motor scores). There was no association between SIBO and motor fluctuations or PDQ-39 Summary Index scores.ConclusionsThis is the largest study to date on SIBO in PD. SIBO was detected in one quarter of patients, including patients recently diagnosed with the disease. SIBO was not associated with worse gastrointestinal symptoms, but independently predicted worse motor function. Properly designed treatment trials are needed to confirm a causal link between SIBO and worse motor function in PD.     

Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinson’s disease: An open-label prospective observational study of effectiveness,tolerability and healthcare costs

BackgroundContinuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinson’s disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG.MethodsThe seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naïve (N = 37), or had previous LCIG treatment for <2 (N = 22), or ≥2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS), 39-item Parkinson’s Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored.ResultsMean monthly costs per patient (€8226 ± 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naïve patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations.ConclusionsCosts in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naïve patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The long-term safety was consistent with the established LCIG profile.     

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.     

Impact of psychiatric symptoms and sleep disorders on the quality of life of patients with Parkinson’s disease

The objective of this study is to assess how the non-motor symptoms of Parkinson’s disease (PD), such as depression, cognitive deterioration, neuropsychiatric and sleep disorders, affect the quality of life, and to compare them with the motor symptoms in order to determine their real impact. A cross-sectional study was designed including 99 patients (mean age 68.5 ± 9.9 years, duration of disease 8.7 ± 6.2 years). Demographic data, onset of PD, years on treatment with levodopa (LD), class of dopaminergic drug prescribed, and dosages were obtained. The following scales were used: quality of life (PDQ-39), Unified Parkinson’s Disease Rating Scale (UPDRS I–IV), Parkinson Disease Sleep Scale (PDSS) and daytime sleepiness (Epworth), Mini-Mental State Examination, depression (HAM-D), and the neuropsychiatric inventory (NPI-10). The PDQ-39 summary index (PDQ-39 SI) was 24.7 ± 13.2. A linear regression model including all variables showed that four independent variables accounted for 67.2% of the variance in the PDQ-39 SI (F = 33,277; p < 0.001): NPI, PDSS, UPDRS IV, and UPDRS I. When sub-items of the NPI, PDSS and UPDRS IV scales are analyzed, significant correlations (p < 0.001) are found between the PDQ-39 SI and depression, agitation, apathy, anxiety, hallucinations, delusions, incontinence of urine, morning painful posturing, restlessness in bed, morning fatigue, duration of off periods, unpredictable and predictable off periods, early morning dystonia, and sudden off periods. Neuropsychiatric symptoms, especially depression, nighttime sleep disorders such as urinary incontinence, nighttime restlessness, morning fatigue and somnolence, off-period dystonia and motor fluctuations are the variables that most affect the quality of life of patients with PD.     

Caregiver strain in Parkinson's disease: National Parkinson Foundation Quality Initiative Study

BackgroundNational Parkinson Foundation Quality Improvement Initiatives (NPF-QII) is the first large scale data-driven initiative in Parkinson's disease (PD) aimed at identifying variables predicting best care models and outcomes.ObjectiveTo determine what measures of PD disability, demographics, and patient quality of life are associated with caregiver strain among caregivers of patients with PD.MethodsAll PD patients at 18 participating sites are eligible for enrollment into the NPF-QII registry. Dataset includes multidimensional measures of disease severity, health care utilization, PD quality of life questionnaire-39 (PDQ-39) and multidimensional caregiver strain inventory (MCSI). A univariate as well as an adjusted analysis was performed to examine the relationship between caregiver strain and variables of PD disability.ResultsThe single best factor associated with high caregiver strain was the PDQ-39 total score (c-statistic of continuous variable = 0.792, p < 0.001) followed by the PDQ-mobility subscore (c = 0.776, p < 0.001). PDQ-39 ≥ 47 was the optimal cut off associated with a high caregiver strain with a sensitivity = 83% and specificity = 64%. A multiple logistic regression model with stepwise selection showed that in addition to PDQ-39 ≥ 47 (OR and 95% confidence interval = 5.1 (3.2, 8.2), the following subject characteristics were associated with high caregiver strain: (model p < 0.001, c = 0.838): Hoehn and Yahr stage >3 (2.0 (1.3, 3.1)), presence of concomitant medications such as antidepressants (2.1 (1.5, 3.1)) and antipsychotics (2.5 (1.5, 4.2)), social worker visits (1.6 (1.2, 2.1)), male gender (2.3 (1.5, 3.5)), and decreased verbal fluency (0.95 (0.92, 0.98)).ConclusionsThere is a high prevalence of caregiver strain in PD. PDQ-39 total score has the strongest association with high levels of caregiver strain. These results could guide clinicians in the assessment of caregivers at risk.     

Sex differences in cerebral energy metabolism in Parkinson's disease: A phosphorus magnetic resonance spectroscopic imaging study

ObjectiveTo test the hypothesis that there are sex differences in cerebral energy metabolism in Parkinson's disease (PD).MethodsPhosphorus magnetic resonance spectroscopy (³¹P MRS) was used to determine high-energy phosphate (phosphocreatine and ATP) and low-energy phosphate (free phosphate) levels in the striatum and temporoparietal cortical gray matter (GM) in 10 men and 10 women with PD, matched for age at onset, disease duration, and UPDRS scores.ResultsIn the hemisphere more affected by PD, both ATP and high energy phosphate (HEP: phosphocreatine + ATP) content in striatum was 15% lower in men versus women with PD (p = .050 and p = .048, respectively). Similar decreases by 16% in ATP (p = .023) and 12% in HEP (p = .046) were observed in GM in men versus women with PD. In contrast, there were no detectable sex differences in ATP or HEP in healthy age-matched controls.ConclusionsMen with PD have lower levels of ATP and high energy phosphate than women in brain regions affected by PD. These findings suggest that there may be a greater burden of mitochondrial dysfunction in PD in men versus women with PD.     

A study of voice profiles and acoustic signs in patients with Parkinson’s disease in North India

We aimed to study the voice profiles of patients with Parkinson’s disease (PD) and correlate the profiles with disease severity. A total of 133 patients with PD were recruited. Patients were divided into two groups: Group 1 with a Unified Parkinson’s Disease Rating Scale (UPDRS) score of ?45; and Group 2 with a UPDRS >45. Speech was analyzed using the Indian Speech and Hearing Association (ISHA) articulation assessment and Vaghmi software. A total of 87 patients (65.41%) reported a history of speech problems. Examination revealed slow reading speed (64.7% of patients), hoarseness of voice (60.2%), articulatory defect (39.8%) and jerky speech (32.3%) as common abnormalities. Misarticulation was most often observed among the labial (42.1%), followed by lingual and palatal syllables. The ISHA articulation test demonstrated significant differences in mean numbers of words distorted (p < 0.001) and intelligible speech (p = 0.004) between patients with early and advanced PD. Vaghmi software analysis (Speech and Voice Systems, Bangalore, India) also revealed significant difference between the two groups in maximum phonation duration (p = 0.034), inability to phonate (noiseless speech, Z; p = 0.002) and the mean noise-to-noiseless speech (S/Z) ratio (p = 0.006).     

Rankin scale as a potential measure of global disability in early Parkinson’s disease

We conducted an exploratory analysis of the utility of the modified Rankin Scale (mRS) as a global measure of disability in early Parkinson’s diesase (PD) using the baseline data from a large cohort of PD patients enrolled in a longitudinal study of creatine. The mRS is scored 0–6 with lower scores reflecting less disability. For the analysis the mRS score was dichotomized at <2 versus ?2. We explored the association of the mRS with multiple measures of PD-related impairments, including the Unified Parkinson Disease Rating Scale (UPDRS); cognitive function characterized by the Symbol Digit Modalities – verbal, and Scales for Outcomes in Parkinson’s disease – cognition (SCOPA-COG); quality of life (Parkinson’s disease questionnaire [PDQ-39]) and EuroQOL; Beck Depression Inventory II (BDI); and Total Functional Capacity (TFC). We also investigated the interaction between variables. One thousand seven hundred forty-one patients were included in the analysis of which 374 had a mRS score of 2 or above. In the univariate model, all interested measures except SCOPA-COG (p = 0.23) had significant association with mRS (p < 0.001) after controlling for confounders. In the multivariate model, UPDRS Part II and III (activities of daily living and motor), BDI, TFC and PDQ-39 were significant (p < 0.05). The mRS has a significant association with the wide spectrum of measures of impairment and quality of life in early PD and shows good potential to be a global measure of disability in early PD. The sensitivity of the mRS to change and performance of the scale in more advanced PD will have to be established longitudinally.     

Visual complaints and visual hallucinations in Parkinson's disease

BackgroundVisual symptoms are common in Parkinson's disease (PD) and are frequently under-diagnosed. The detection of visual symptoms is important for differential diagnosis and patient management.AimTo establish the prevalence of recurrent visual complaints (RVC) and recurrent visual hallucinations (RVH) and to investigate their interaction in PD patients and controls.MethodsThis cross-sectional study included 88 PD patients and 90 controls. RVC and RVH were assessed with a visual symptom questionnaire and the North-East-Visual-Hallucinations-Interview (NEVHI).ResultsDouble vision (PD vs. Controls: 18.2% vs. 1.3%; p < 0.001), misjudging objects when walking (PD vs. Controls: 12.5% vs. 1.3%; p < 0.01), words moving whilst reading (PD vs. Controls: 17.0% vs. 1.3%; p < 0.001) and freezing in narrow spaces (PD vs. Controls: 30.7% vs. 0%; p < 0.001) were almost exclusively found in PD patients. The same was true for recurrent complex visual hallucinations and illusions (PD vs. Controls: both 17.0% vs. 0%; p < 0.001). Multiple RVC (43.2% vs. 15.8%) and multiple RVH (29.5% vs. 5.6%) were also more common in PD patients (both p < 0.001). RVC did not predict recurrent complex visual hallucinations; but double vision (p = 0.018, R² = 0.302) and misjudging objects (p = 0.002, R² = 0.302) predicted passage hallucinations. Misjudging objects also predicted the feeling of presence (p = 0.010, R² = 0.321).ConclusionsMultiple and recurrent visual symptoms are common in PD. RVC emerged as risk factors predictive of the minor forms of hallucinations, but not recurrent complex visual hallucinations.     

Clinical manifestations of nonmotor symptoms in 1021 Japanese Parkinson's disease patients from 35 medical centers

IntroductionWe aimed to investigate the prevalence and severity of nonmotor symptoms (NMSs) and to identify factors affecting NMSs and the health-related quality of life of Japanese patients with Parkinson's disease (PD).MethodsA total of 1021 patients with PD who had one or more NMS and showed wearing-off under anti-parkinsonian treatment were enrolled from 35 medical centers in Japan for this observational study. The primary measurements were the Movement Disorder Society unified Parkinson's disease rating scale (MDS-UPDRS) part I and the Parkinson's Disease Questionnaire (PDQ-8). The relationships of MDS-UPDRS and PDQ-8 with the patient's clinical background and undertaken medical interventions were determined. Here, we report baseline data of our 52-week ongoing study.ResultsThe mean MDS-UPDRS part I and PDQ-8 scores were 10.9 and 7.3, respectively. The most common NMSs were constipation problems (85.4%), sleep problems (73.7%), pain and other sensations (72.7%) and daytime sleepiness (72.0%). Fatigue was an NMS that affected 79.6% of females but only 72.6% of males, whereas features of dopamine dysregulation syndrome affected only 5.6% of females and 10.8% of males. Positive correlations were found between the MDS-UPDRS part I and the PDQ-8 (p < 0.0001, r = 0.56) and between the number of NMSs and the PDQ-8 score (p < 0.0001, r = 0.47).ConclusionsThis study revealed distinctive patterns of NMSs in Japanese patients with PD and suggested that the prevalence and severity of NMSs vary between sexes, and that the NMSs are important factors affecting the long-term quality of life of PD patients.     

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.     

Side onset influences motor impairments in Parkinson disease

In right-handers, the left hemisphere has greater ipsilateral control of the upper extremities than the right hemisphere. This asymmetry is not as profound among left-handers. We sought to determine whether Parkinson disease (PD) maintains this pattern of ipsilateral control and affects motor impairment. Using right- and left-hand sub-scores from the Unified Parkinson Disease Rating Scale (UPDRS), we calculated a lateralized impairment score to compare ipsilateral influence among four groups: right-handed-right-sided onset (RH-RSO), right-handed-left-sided onset (RH-LSO), left-handed-right-sided onset (LH-RSO), and left-handed-left-sided onset (LH-LSO). We hypothesized that right-handed patients with RSO (left hemisphere dysfunction) would have lower scores, hence more deficits in both hands, than the other groups. Among right-handers, the RSO patients (left dominant hemisphere dysfunction) had a significantly lower mean lateralized impairment score than LSO patients (μ = 2.09 versus μ = 4.06; p < 0.001). Further, RHRSO also had lower scores than both the LHLSO (μ = 4.52, p < 0.05) and LHRSO (μ = 4.27, p < 0.05) groups. The symmetry of impairments indicates deficits in both hands and supports more ipsilateral involvement of the affected left hemisphere in RH-RSO patients. Therefore, we suggest that PD does retain an asymmetric ipsilateral influence. The low numbers of left-handed subjects and the significant percentage of left-handers with a dominant left hemisphere prevented a clear interpretation of our findings in left-handed subjects.     

Social and clinical determinants of quality of life in Parkinson's disease in a Russian cohort study

Parkinson's disease (PD) is a chronic neurodegenerative disorder that has a major impact on health and longevity in Eastern countries. Studies investigating health-related quality of life (HRQoL) in Eastern European and Asian countries are scarce. The objective of this cross-sectional survey was to assess HRQoL in Russian patients with PD and identify its social and clinical determinants.The study included 100 outpatients with idiopathic PD and 100 controls. Patients were consecutively recruited from the neurological department of the Russian Medical State University in Moscow between October 2004 and December 2005. Regional healthy controls were matched for age and sex. The evaluation of HRQoL was performed using the EuroQol instrument (EQ-5D and EQ VAS). Disease severity was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Multivariate regression analyses were used to identify independent determinants of HRQoL.HRQoL was more notably decreased in PD patients than in controls (98% versus 74% of individuals with moderate or severe problems in at least one dimension of the EQ-5D (p < 0.001), respectively). As compared to patients, the controls reported a higher mean EQ VAS score (74.0 ± 16.0 versus 47.7 ± 16.7, p < 0.001). Social and clinical determinants of HRQoL were age, disease severity, dystonia, depression, dementia and social support.While the HRQoL of patients with PD in Western countries is predominately affected by clinical parameters, social factors play an important role in Eastern countries. Our data should be considered in the development of national healthcare programs that seek to provide better social services support for patients with PD.