Parkinson's disease motor subtypes and bilateral GPi deep brain stimulation: One-year outcomes

ObjectiveWe aimed to explore the differences in motor symptoms and quality of life (QOL) outcomes following bilateral globus pallidus internus deep brain stimulation (GPi DBS), across well-defined motor subtypes of Parkinson's disease (PD), to improve clinical decision making.MethodsThis single-center retrospective study investigated bilateral GPi DBS outcomes in 65 PD patients. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire (PDQ-39) before and one year after surgery. Outcomes were compared between the tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtypes and between the TD and akinetic-rigid (AR) subtypes.ResultsFor the entire cohort, motor function (UPDRS III) in the Off-medication state, motor complications (UPDRS IV), activities of daily living (ADL, UPDRS II), and the ADL and discomfort domains of PDQ-39 significantly improved one year following GPi implantation compared to baseline (effect size = 1.32, 1.15, 0.25, 0.45, and 0.34, respectively). GPi DBS improved the Off-medication UPDRS III scores regardless of the motor subtypes. However, compared to the PIGD and AR patients, the TD patients showed greater improvement in overall UPDRS III postoperatively primarily due to greater tremor improvement in the Off-medication state. The outcomes in akinesia, rigidity, axial symptoms and QOL were similar among all subtypes.ConclusionBilateral GPi DBS was effective for advanced PD patients regardless of motor subtypes. Greater tremor improvement in the TD patients accounted for greater Off-medication motor improvement. Longer-term GPi DBS outcomes across different motor subtypes and brain targets should be further studied.     

Impact of deep brain stimulation on quality of life and motor symptoms in Parkinson's disease and X-linked dystonia parkinsonism: The Philippine experience

Background and objectivesDeep brain stimulation (DBS) is indisputable in improving motor symptoms of Parkinson's Disease (PD) and X-Linked Dystonia Parkinsonism (XDP)(4,9,22,23,26). However, a discrepancy between this improvement and the perceived quality of life (QoL) has been observed. This study aims to investigate changes and correlation between quality of life, motor symptoms and medication dosing.MethodologyThis prospective observational study enrolled 13 patients (6 PD, 7 XDP) who underwent DBS from 2017 to 2018. Quality of life changes were determined by Parkinson's Disease - 39 (PDQ-39 English and Filipino versions) at baseline, 6 months and 12 month after DBS. Motor symptoms and medication dosing were also evaluated within the same period and correlated with QoL changes.Results and discussionThere is a significant reduction of PDQ-39 mean scores[F(1.06,11.64) = 18.235; p = 0.001; ηp2 = 0.624] between baseline and 6 months among XDP patients (p = 0.018) and baseline and 12 months among PD patients (p = 0.027) and XDP patients (p < 0.001). Specific domains with significant improvement were stigma, cognition, mobility, ADLs, communication and bodily discomfort. Correlating these with changes in motor symptoms, only mobility for PD and ADLs for XDP were positively related.ConclusionThis study has shown the positive impact of DBS in improving QoL among PD and XDP patients over a 12-month period.     

Spiral drawing during self-rated dyskinesia is more impaired than during self-rated off

ObjectiveThe purpose of this study was to examine repeated measures of fine motor function in relation to self-assessed motor conditions in Parkinson's disease (PD).MethodsOne-hundred PD patients, 65 with advanced PD and 35 patients with different disease stages have utilized a test battery in a telemedicine setting. On each test occasion, they initially self-assessed their motor condition (from ‘very off’ to ‘very dyskinetic’) and then performed a set of fine motor tests (tapping and spiral drawings).ResultsThe motor tests scores were found to be the best during self-rated On. Self-rated dyskinesias caused more impaired spiral drawing performance (mean = 9.8% worse, P < 0.001) but at the same time tapping speed was faster (mean = 5.0% increase, P < 0.001), compared to scores in self-rated Off.ConclusionsThe fine motor tests of the test battery capture different symptoms; the spiral impairment primarily relates to dyskinesias whereas the tapping speed captures the Off symptoms.     

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.     

The impact of and the factors associated with drooling in Parkinson's disease

We administered a 7-question survey on drooling to PD patients and age-matched controls. Each subject was assigned a drooling severity score and categorized as a “drooler” or a “non-drooler”. The age, disease duration, motor scores, quality of life (PDQ-39), and levodopa equivalent daily dosage (LEDD) were compared between PD droolers vs. PD non-droolers.58 PD patients and 51 age-matched controls participated. In PD patients, the mean: disease duration was 10.96 years (SD 8.66) and UPDRS on motor score was 30.76 (SD 10.57). The drooling severity score was significantly different between patients vs. controls (3.41 vs. .58; p < .01). 14% of controls vs. 59% of patients were droolers (p < .01). PD droolers scored worse on the ADL subscale of the PDQ-39 (p = .031). Furthermore, PD droolers had significant difficulty speaking (7.27% vs. 0%; p < .01); eating (3.64% vs. 0%; p = .01); and socially interacting (12.73% vs. 0%; p < .01) compared to PD non-droolers. Interestingly, the hallucination component of the UPDRS Part I was significantly correlated with being a drooler (p = .016). None of the other variables have significant effect on drooling severity scores. There is a high prevalence of drooling among PD patients compared to controls.PD droolers had worse quality of life and had more difficulty speaking, eating and socially interacting compared to PD non-droolers. Experiencing hallucinations was the only factor that correlated with being a drooler and it may be confounded by medications.     

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.     

Effects of a formal exercise program on Parkinson's disease: A pilot study using a delayed start design

IntroductionParkinson's Disease (PD) is a progressive neurodegenerative disease. Increasing evidence shows that physical exercise is beneficial for motor and non-motor symptoms of PD, and animal models suggest that it may help slow progression of disease.MethodsUsing a randomized delayed-start design, 31 patients were randomized to an early start group (ESG) or a delayed start group (DSG) exercise program. The ESG underwent a rigorous formal group exercise program for 1 h, three days/week, for 48 weeks (November 2011–October 2012). The DSG participated in this identical exercise program from weeks 24–48. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), Walking Test (get-up-and-go), Tinetti Mobility Test, PDQ-39 Questionnaire, and the Beck Depression Inventory.ResultsThere was minimal attrition in this study, with only one patient dropping out. Results did not show improvement in total UPDRS scores with early exercise. At week 48, the mean change from baseline total UPDRS score was 6.33 in the ESG versus 5.13 in the DSG (p = 0.58). However, patients randomized to the ESG scored significantly better on the Beck Depression Inventory, with a mean improvement of 1.07 points relative to those in the DSG (p = 0.04).ConclusionsThe findings demonstrate that long-term, group exercise programs are feasible in the Parkinson's disease population, with excellent adherence and minimal drop out. While the outcome measures used in our study did not provide strong evidence that exercise has a neuroprotective effect on motor function, earlier participation in a group exercise program had a significant effect on symptoms of depression.     

Orthostatic hypotension in Parkinson's disease: Does it matter if asymptomatic?

IntroductionOrthostatic hypotension (OH) may frequently be asymptomatic in patients with Parkinson's disease (PD). However, the relationship between symptomatic/asymptomatic status and functional disability remains unclear.MethodsUsing orthostatic blood pressure (BP) measurements and the Orthostatic Hypotension Symptom Assessment (OHSA) questionnaire, 121 consecutive PD patients without history of chronic hypertension and not taking alpha-adrenergic antagonists for bladder disorders were classified according to (1) OH symptomatic status, based on presence/absence of orthostatic symptoms (symptomatic OH: OHSA item 1 ≥ 1), and (2) OH severity, based on the magnitude of BP fall on the lying-to-standing test: OH- (<20/10 mmHg); moderate OH+ (≥20/10 mmHg but < 30/15 mmHg); and severe OH+ (≥30/15 mmHg). The primary endpoints were the activities of daily living/instrumental activities of daily living (ADL/iADL) and the Ambulatory Capacity Measure (ACM). Secondary endpoints included PD quality of life (PDQ-8) and prevalence of falls.ResultsThe overall prevalence of OH+ was 30.6% (37/121 patients), with 62.2% symptomatic (23/37) and 37.8% asymptomatic (14/37). Symptomatic and asymptomatic OH + patients had similar impairments in ADL/iADL and ACM, significantly worse than OH- (p ≤ 0.035). There was a trend for worse ADL/iADL and ACM scores in severe OH + compared to moderate OH+, but both were worse than OH- (p ≤ 0.048). Symptomatic and asymptomatic OH + showed similar impairment in PDQ-8 and higher prevalence of falls compared to OH-.ConclusionsAsymptomatic OH+ was associated with similar impairments in ADL/iADL and ACM than symptomatic OH+. These findings support screening for OH in PD patients regardless of postural lightheadedness.     

Early DEtection of wEaring off in Parkinson disease: The DEEP study

ObjectiveAssessing the frequency of Wearing-Off (WO) in Parkinson's disease (PD) patients, and its impact on Quality of Life (QoL).MethodsConsecutive ambulatory patients, who were on dopaminergic treatment for ≥1 year, were included in this multicentre, observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as using the validated Italian version of a patient self-rated 19-question Wearing-Off Questionnaire (WOQ-19); WO was defined for scores ≥ 2. QoL was evaluated by the 8-item Parkinson's Disease Questionnaire (PDQ-8).Results617 subjects were included, with a mean anti-Parkinson treatment duration of 6.6 ± 4.6 years, 87.2% were on levodopa treatment. Neurologists identified presence of WO in 351 subjects (56.9%), whereas 415 subjects (67.3%) were identified by the self-administered WOQ-19. In patients with a <2.5 years disease duration, WO was diagnosed in 12 subjects (21.8%) by neurologists and in 23 subjects (41.8%) by the WOQ-19. The most frequent WO symptoms, as identified by WOQ-19, were “slowness of movements” (55.8%) and “reduced dexterity” (48.8%). Younger age, female gender, Unified Parkinson's Disease Rating Scale (UPDRS) part II score and duration of anti-Parkinson treatment were found significantly associated with WO. The number of motor (p < 0.0001) and non-motor (p < 0.0001) WO symptoms correlated with PDQ-8 total score.ConclusionsWO is common already at the early stages of PD and is underestimated by routine neurological clinical evaluation. The number of WO symptoms, both motor and non motor, increases along with disease duration and has a negative impact on patients QoL.     

Sleep problems affect quality of life in Parkinson's disease along disease progression

ObjectivesNon-motor symptoms (NMS) frequently impact health-related quality of life (HRQoL) in patients with Parkinson's Disease (PD). Sleep problems represent one of the main NMS complained by PD patients. In this observation study, sleep problems measured by Parkinson's Disease Sleep Scale - 2nd version (PDSS-2), and HRQoL measured by Parkinson's Disease Questionnaire-39 (PDQ39) were quantified in patients with PD ranging from mild to moderate-advanced disease stages, and correlated to motor impairment and anti-PD therapy.MethodsWe included idiopathic PD patients who underwent PDSS-2 and PDQ39. Moreover, we assessed patients' motor symptoms by rating the Unified Parkinson's Disease Rating Scale (UPDRS) - III section (motor examination), patients' PD status following H&Y stage, and levodopa equivalent daily dose (LEDD).ResultsOne-hundred and fifty-four patients with PD were included and distributed for H&Y stage. PDSS-2 and PDQ39 total and sub-items scores significantly increased with the H&Y stage. PDSS-2 total score significantly correlated with PDQ39 total score (γ = 0.63, P < 0.01). Finally, distributing PD patients according to the PDSS-2 cut-off for detecting sleep disturbances, we found in poor sleepers (n = 58) higher PDQ39 scores than good sleepers (n = 89).ConclusionsSleep problems are very common in patients with PD and severely impact on HRQoL. Sleep impairment and low HRQoL occur from the early stages of the disease and deteriorate along disease progression. Further studies investigating sleep and quality of life should be planned for targeting sleep improvement to increase HRQoL and possibly reduce motor impairment.     

Are the EEG microstates correlated with motor and non-motor parameters in patients with Parkinson's disease?

ObjectivesThis study compared electroencephalography microstates (EEG-MS) of patients with Parkinson's disease (PD) to healthy controls and correlated EEG-MS with motor and non-motor aspects of PD.MethodsThis cross-sectional exploratory study was conducted with patients with PD (n = 10) and healthy controls (n = 10) matched by sex and age. We recorded EEG-MS using 32 channels during eyes‐closed and eyes‐open conditions and analyzed the four classic EEG-MS maps (A, B, C, D). Clinical information (e.g., disease duration, medications, levodopa equivalent daily dose), motor (Movement Disorder Society - Unified Parkinson Disease Rating Scale II and III, Timed Up and Go simple and dual-task, and Mini-Balance Evaluation Systems Test) and non-motor aspects (Mini-Mental State Exam [MMSE], verbal fluency, Hospital Anxiety and Depression Scale, and Parkinson's Disease Questionnaire-39 [PDQ-39]) were assessed in the PD group. Mann-Whitney U test was used to compare groups, and Spearman's correlation coefficient to analyze the correlations between coverage of EEG-MS and clinical aspects of PD.ResultsThe PD group showed a shorter duration of EEG-MS C in the eyes-closed condition than the control group. We observed correlations (rho = 0.64 to 0.82) between EEG-MS B, C, and D and non-motor aspects of PD (MMSE, verbal fluency, PDQ-39, and levodopa equivalent daily dose).ConclusionAlterations in EEG-MS and correlations between topographies and cognitive aspects, quality of life, and medication dose indicate that EEG could be used as a PD biomarker. Future studies should investigate these associations using a longitudinal design.     

Severity of mild cognitive impairment in early Parkinson's disease contributes to poorer quality of life

BackgroundPoor quality of life (QoL) is a feature of people with Parkinson's disease (PD) who develop dementia. The relationship between mild cognitive impairment in PD (PD-MCI) and QoL is less clear. To address this, we studied the impact of varying severities of cognitive impairment on QoL in a cohort of non-demented patients with early PD.MethodPatients with newly diagnosed PD (n = 219) and age and sex matched healthy controls (n = 99) completed a schedule of neuropsychological tests, in addition to scales assessing QoL (PDQ-39), depression, sleep, neuropsychiatric symptoms and a clinical examination. The Movement Disorder Society criteria were used to define and classify PD-MCI.ResultsParticipants with PD-MCI were significantly older than those with normal cognition, had more severe motor symptoms, scored higher for depression and had poorer quality of life. Logistic regression showed that mild cognitive impairment, independent of other factors, was an indicator of poorer QoL. Using cognitive performance 2.0 standard deviations (SD) below normative data as a cut-off to define PD-MCI, there was a significant difference in QoL scores between patients with PD-MCI and those classified as having normal cognition. Subjects with less severe mild cognitive impairment did not exhibit significant differences in QoL.ConclusionsPD-MCI is a significant, independent factor contributing to poorer QoL in patients with newly diagnosed PD. Those classified with greatest impairment (2.0 SD below normal values) have lower QoL. This has implications for clinical practice and future interventions targeting cognitive impairments.     

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.     

Is heart rate variability related to gait impairment in patients with Parkinson's disease? A pilot study

Background and purposeImpairments in gait and autonomic function are common in patients with Parkinson's disease (PD). These are likely independent symptoms, based on different etiologic mechanisms. However, a few recent reports have observed an association between motor function, in particular gait impairment, and autonomic function in PD. In those studies, the Unified Parkinson's Disease Rating Scale (UPDRS) was used to evaluate gait and motor function. The present study was performed to further examine this putative relationship using quantitative measures of autonomic function and gait in order to shed light on the underlying pathophysiology of these symptoms.MethodsNine healthy young, 15 healthy elderly and 18 PD patients were studied. Heart rate variability (HRV) measures were collected during rest. Gait speed, swing time and swing time variability were measured during a 1-min walk at comfortable speed. The motor portion of the UPDRS was also evaluated in all subjects.ResultsHRV values were highest in the young adults, intermediate in the healthy elderly controls, and lowest in the PD patients. Gait measures tended to deteriorate with age and were significantly worse in the PD patients, compared to the elderly controls. HRV was not correlated with any measure of gait performance (p > 0.129) nor with the UPDRS-motor score (p > 0.147).Discussion and conclusionsThe present findings support the idea that gait and autonomic function impairments co-exist in PD, but their etiology is based on distinct pathophysiological pathways, with minimal overlap.     

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.     

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.     

Impact of carbidopa-levodopa enteral suspension on quality of life and activities of daily living in patients with advanced Parkinson's disease: Results from a pooled meta-analysis

IntroductionTo estimate the impact of carbidopa/levodopa enteral suspension (CLES) on key patient-centered outcomes in patients with advanced Parkinson's disease (PD).MethodsA comprehensive literature review identified relevant studies, from which data were meta-analyzed over 3-month intervals up to 24 months. Patient-centered outcomes of interest included mean (95% CI) changes from baseline (Δ) in quality of life (QoL), measured using PD-specific (PDQ-8, PDQ-39) and generic (EQ-5D) instruments; activities of daily living (ADL), measured in On and Off states using UPDRS Part II; and motor symptoms (i.e., Off time/day and motor examination [measured in On and Off states using UPDRS Part III]).ResultsThe pooled meta-analysis included data from 26 studies evaluating 1556 patients on CLES. At 3 months, all outcomes showed significant improvement: QoL (ΔPDQ-39 = −10.26 [-11.54, −8.97], ΔEQ-5D_VAS = 15.42 [12.58, 18.26]); ADL (ΔUPDRS II_ON = −4.32 [-5.63, −3.01]); motor symptoms (ΔOff time hours/day = −3.48 [-4.15, −2.82], ΔUPDRS III_ON = −6.20 [-9.88, −2.51]). At 24 months, there were statistically significant mean improvements in QoL (ΔPDQ-39 = −7.74 [-12.40, −3.07], ΔEQ-5D_VAS = 11.18 [6.90, 15.45]) and ADL (ΔUPDRS II_OFF = −3.88 [-5.34, −2.42]), and Off time (−4.21 [-5.16, −3.26] hours/day).ConclusionsImpact of CLES on significantly reducing Off time/day was observed to be rapid and durable (i.e., remained consistent across 24 months). Most QoL and ADL measures showed a consistent pattern of improvement with initiation of treatment and remained significantly improved from baseline at 24 months.     

Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

IntroductionThe non-motor symptoms (NMSs) of Parkinson's disease (PD) significantly impact the patient's health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A_2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD.MethodsPatients with PD and ≥1 NMS and ‘wearing-off’ with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 1 total, individual sub-items scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model.ResultsOverall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score.ConclusionNMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.     

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.