Unified Parkinson's Disease Rating Scale Subscores Research Articles

Quality of life and resource utilization-Swedish data from the Care of Late-Stage Parkinsonism (CLaSP) study.

Few studies have investigated the health-related quality of life (HRQoL), resource use and costs in patients with late-stage Parkinson's disease (PD), and data from the Swedish setting are scarce. First, we analyse the HRQoL in late-stage PD in Sweden. Second, we analyse the resource use and costs per severity level. Third, we analyse the relationship between costs and physician- and patient reported-outcome measures. The study was based on Swedish data from the Care of Late-Stage Parkinsonism (CLaSP) study. The costs of healthcare contacts, drugs, formal and informal care, and productivity loss were collected over three months. Assessments at baseline were used for outcomes (EQ-5D, Hoehn and Yahr (H&Y), Schwab and England Scale, Unified Parkinson's Disease Rating Scale subscales (UPDRS) and Non-Motor Symptoms Scale (NMSS)). Costs were estimated in € 2016. In total, 106 patients were included. The mean EQ-5D score in the total group was 0.24 (±0.33). The mean total cost excluding informal care per patient in the three-month period was approximately €14,097 (BCa 95% CI €12,007 and €16,039). Professional care accounted for the largest share (75 percent) of the total costs. The EQ-5D, H&Y, Schwab and England Scale, and NMSS were statistically significant predicting factors for total costs. Patients with late-stage PD are a vulnerable patient group that is costly to society and the impairment in patients' HRQoL is immense. Thus, healthcare decision-makers should optimize the organization and provision of healthcare for these patients.

Long-Term Selegiline Monotherapy for the Treatment of Early Parkinson Disease.

The aim of this open-label study was to investigate the long-term safety and efficacy of selegiline as monotherapy in Japanese patients with early Parkinson disease (PD). We conducted a 56-week prospective study in patients with early PD (N = 134) who had previously completed the randomized, double-blind, placebo-controlled phase III trial of selegiline monotherapy for 12 weeks. In the present study, dosing was titrated from 2.5 to 10 mg/d in increments of 2.5 mg/d for 2 weeks. From the seventh week, the dosage was maintained at 10 mg/d until week 56. The primary outcome was any change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score (part I + II + III) from baseline. Secondary outcomes, including changes in the UPDRS subscores and safety profile, were also evaluated. Ninety-one (67.9%) patients completed the 56-week study. Treatment with selegiline significantly reduced total UPDRS score from week 4 (mean ± SD, -2.62 ± 3.83; P < 0.0001) to week 56 (-3.39 ± 9.27; P < 0.01). The peak effect was seen at week 20 (-5.79 ± 5.57; P < 0.0001). In addition, we found similar improvements in the UPDRS parts II and III scores. The incidence rate of adverse drug reactions was 44.3% (58 patients) and did not increase during the period of 10 mg selegiline administration. Long-term monotherapy with selegiline (10 mg/d) was effective and well tolerated in patients with early PD in this 56-week study.

Impaired finger dexterity and nigrostriatal dopamine loss in Parkinson's disease.

Impaired finger dexterity occurs in Parkinson's disease (PD) and has been considered a limb-kinetic apraxia associated with primary sensory cortical dysfunction. To study the role of nigrostriatal dopamine loss and elementary parkinsonian motor deficits in impaired finger dexterity of PD. Thirty-two right-handed untreated PD patients and 30 right-handed healthy controls were included. All patients underwent [18F] FP-CIT positron emission tomography studies. We examined the associations among unilateral coin rotation (CR) score, Unified Parkinson's Disease Rating Scale (UPDRS) subscores for bradykinesia and rigidity of the corresponding arm, and contralateral regional striatal dopamine transporter (DAT) uptake. We also measured the effect of oral levodopa dose on CR scores and UPDRS subscores. PD patients performed worse than controls on the CR task. Unilateral arm UPDRS bradykinesia scores were associated with DAT uptake in the contralateral putamen. The left CR score was associated with left arm bradykinesia and rigidity scores and DAT uptake in the right posterior putamen, whereas no such associations were found for the right CR score. There was a significant effect of handedness on the association of putamen DAT uptake with CR scores, but not with UPDRS subscores. An oral levodopa challenge improved CR scores and UPDRS subscores on both sides. Impaired finger dexterity in PD is related to elementary parkinsonian motor deficits and nigrostriatal dopamine loss. Impaired dominant hand dexterity associated with nigrostriatal dopamine loss seems to be compensated to some extent by the dominant cerebral cortex specialized for controlling precise finger movements.

Parkinsonian axial signs in schizophrenia

IntroductionWe have recently demonstrated evidence of nigro-striatal denervation, disease progression and response to levodopa in a subgroup of patients with schizophrenia who developed parkinsonism. ObjectiveIn the present study, we investigated whether axial parkinsonian signs might be an early manifestation of parkinsonism in schizophrenia not necessarily related to chronic administration of antipsychotic drugs (AP) drugs. MethodsFrom a baseline cohort of 299 schizophrenic patients who did not satisfy the diagnostic criteria for parkinsonism (presence of at least two of the following appendicular signs: bradykinesia, tremor, rigidity), we identified a group of patients who manifested two out of three axial parkinsonian signs (abnormality of trunk posture, hypomimia and short-step gait). Accordingly, we obtained two sub-groups of patients with schizophrenia, with (Schiz-Axial, N = 26), and without parkinsonian axial signs (Schiz-NO-Axial, N = 273). Clinical and demographical variables were compared between groups. The motor section of the Unified Parkinson's disease rating scale (UPDRS) was employed to measure motor disability. ResultsSchiz-Axial patients were significantly older (p = 0.007) and had longer disease duration (p = 0.04) compared to Schiz-NO-Axial. The two groups did not differ for variables related to AP treatment. Total UPDRS motor score (p < 0.0001) as well as limb (p < 0.0001) and axial (p < 0.0001) UPDRS sub-scores were increased in Schiz-Axial patients compared to Schiz-NO-Axial. ConclusionsOur findings provide evidence that axial parkinsonian signs might be an early manifestation of parkinsonism in schizophrenia associated to older age and longer disease duration.

Tremor and clinical fluctuation are related to sleep disorders in Chinese patients with Parkinson’s disease

ObjectiveTo study the relationship between sleep disturbances and symptoms in patients with Parkinson’s disease (PD).MethodsThe Parkinson’s Disease Sleep Scale-Chinese Version (PDSS-CV) was used to evaluate the sleep disturbances of PD patients in a cross sectional study. The Unified Parkinson’s Disease Rating Scale (UPDRS) parts II-IV, and the Hoehn & Yahr (H&Y) stage were used to determine the level of motor function in PD and the severity of PD. The Spearman correlation and a multiple regression analysis were used to identify the relationship between sleep disturbances and symptoms of PD. The quantities derived from the UPDRS and the H&Y stage and disease duration were compared between groups of patients either with or without sleep disturbances identified by the PDSS. This study was conducted from December 2011 to March 2012 at the First Affiliated Hospital of Sun Yat-sen University, in Guangzhou.ResultsA total of 136 PD patients were included in this study. The overall total PDSS score in PD patients was 107.58 ± 23.35 points (range: 30–146). There were significant differences in the disease duration, the H&Y stage, and the UPDRS section subscores between groups of patients either with or without sleep disturbances (Kruskal-Wallis Test, p <0.05). There were significant negative correlations between PDSS scores and the UPDRS subscores, the H&Y stage and the disease duration (Spearman correlation, p < 0.05). The multiple regression analysis indicated that sleep disturbances identified by the PDSS were only associated with daily life activity, tremor intensity and clinical fluctuation (R2 = 0.22, F(3,132) = 12.4, p < 0.001). The correlations were also significant when the contribution of the other two factors was excluded using partial correlations.ConclusionsThe level of daily life activity and the occurrences of tremor and clinical fluctuation are likely to be important factors that lead to PD patients’ sleep disturbances. This study may elucidate an important clue for the relationship between sleep disturbances and PD symptoms.

The impact of high intensity physical training on motor and non-motor symptoms in patients with Parkinson's disease (PIP): A preliminary study

Parkinson's disease (PD) is a neurodegenerative disease caused by loss of dopaminergic nigrostriatal neurons. Several studies have investigated various physical interventions on PD. The effects of a high intensity exercise program with focus on resistance; cardio; equilibrium; and flexibility training have not been evaluated previously. The aim of this study was to investigate the effects of a complex, high intensity physical training program, with a long duration, on motor and non-motor symptoms in patients with PD. 24 patients with PD Hoehn and Yahr stage 1-3 were non-randomly allocated to an intervention group (n = 12) and a control group (n = 12). The intervention group underwent 32 weeks of high intensity personalized physical training twice a week, with an optional extra training session once a week. The control group received general recommendations regarding physical activity. The primary outcomes were the change in Unified Parkinson's Disease Rating Scale Subscores (UPDRS) and the Parkinson's Disease Questionnaire (PDQ-39). At week 32, the training significantly improved both UPDRS motor subscores (p = 0.045), activities of daily living subscores (ADL) (p = 0.006), mentation subscores (p = 0.004) and complication subscores (p = 0.019). The effect on the PDQ39 total score was not statistically significant. The intervention group however experienced a substantial improvement of the PDQ39 items emotional well-being (-11.0) and bodily discomfort (-7.14). The results suggest that a personal high intensity exercise program may favorably influence both motor and non-motor symptoms in patients with mild to moderate PD. More studies with both higher methodology in study design and a follow-up examination are recommended.

Physical Therapy Found to Have Short-Term Benefit in Parkinson's

Physical Therapy Found to Have Short-Term Benefit in Parkinson's

The Relationship Between the Grooved Pegboard Test and Clinical Motor Symptom Evaluation Across the Spectrum of Parkinson's Disease Severity

The Unified Parkinson's Disease Rating Scale (UPDRS) is the gold standard for assessing Parkinsonian symptoms, yet objective outcome measures are needed to complement the UPDRS in research and clinical practice. This study aimed to investigate the relationship between performance on the Grooved Pegboard Test (GP) and clinical assessment of Parkinson's motor symptoms with the UPDRS. A large sample of individuals with Parkinson's disease (n = 191) were assessed with the GP and UPDRS motor section. The GP was separated into a place (more representative of visuospatial accuracy) and remove phase (general representation of motor speed and bradykinesia). Both tests were completed at peak anti-parkinsonian medication levels, and UPDRS subscores were calculated to represent upper-limb control, rigidity, bradykinesia, and tremor. A subsequent correlation analysis was completed. The strongest relationships were between the GP place phase (both limbs) and total UPDRS motor score (affected: r = 0.604, less-affected: r = 0.587), upper-limb control (affected: r = 0.367, less-affected: r = 0.426), rigidity (affected: r = 0.479, less-affected: r = 0.457) and body bradykinesia (affected: r = 0.375, less-affected: r = 0.438). The GP remove phase had weak positive relationships with total UPDRS scores (affected: r = 0.31, less-affected r = 0.31) and body bradykinesia (r = 0.31). Clinical assessment of upper-limb control, rigidity and bradykinesia are well represented by the GP place phase. Interestingly, it appeared that GP performance of the more affected limb may be more representative of motor severity in the early stages of disease, while more research is needed to understand the utility of the GP in the advanced stages of disease.

BILATERAL EFFECTS OF UNILATERAL SUBTHALAMIC DEEP BRAIN STIMULATION ON PARKINSON'S DISEASE AT 1 YEAR

To quantify the benefit of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on contralateral, ipsilateral, and axial symptoms of advanced Parkinson's disease. Thirty-seven patients received unilateral STN DBS and were rated on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed tests of motor function in the "practically defined off" state at baseline and at 3, 6, and 12 months postoperatively. UPDRS motor scores improved significantly at 3, 6, and 12 months relative to the preoperative baseline (P < 0.001, 37.1% at 1 year). There was improvement in the contralateral UPDRS subscores (P < 0.001, 54.6% at 1 year), and although contralateral benefit was larger on all outcome measures, ipsilateral benefit was present at 3 and 6 months on the UPDRS subscore (P = 0.013 and 23.5%, P = 0.005 and 27.7%, respectively). A trend toward ipsilateral benefit was present on the UPDRS subscore at 12 months; however, the effect was not statistically significant. Two timed tests of motor function in the upper extremities showed significant ipsilateral benefit in bradykinesia at 12 months (P < 0.001 and P = 0.014, respectively). Significant benefit was also observed in the UPDRS part 2 "off" medications and the UPDRS part 4 after unilateral STN DBS at 12 months (both P < 0.001). Considering the bilateral effects and tolerability of unilateral STN DBS, unilateral stimulation followed by a contralateral procedure later, if necessary, is a reasonable option for patients with advanced Parkinson's disease, especially with prominent asymmetry.

Istradefylline as monotherapy for Parkinson disease: Results of the 6002-US-051 trial

Objective 6002-US-051 was a 12-week, double-blind study evaluating the safety and efficacy of istradefylline, a selective A 2A adenosine receptor antagonist, as monotherapy in patients with Parkinson's disease (PD). Methods Patients with Hoehn–Yahr stages 1–2.5 who had not received dopaminergic drugs in the past 30 days or levodopa for >30 days at anytime were randomized to 40 mg/day istradefylline or placebo. The primary efficacy outcome was the change from Baseline to Endpoint in the Unified Parkinson's Disease Rating Scale (UPDRS) Subscale III score. Safety was assessed by physical examination, laboratory tests, electrocardiograms, and adverse event monitoring. Results 176 patients comprised the intent-to-treat population. Although istradefylline showed numerically greater improvements in UPDRS Subscale III at each time point and reached statistical significance at Week 2 (LS mean difference = −1.47), it did not show statistically significant improvement from placebo for the primary endpoint (least square [LS] mean difference = −1.11). Similar proportions of patients in each group experienced treatment-emergent adverse events (63% istradefylline, 65% placebo). Conclusions Istradefylline, as monotherapy in patients with PD, is safe and well tolerated. However, efficacy in improving motor symptoms in early PD was not statistically demonstrated by this study.

UPDRS activity of daily living score as a marker of Parkinson's disease progression

The activities of daily living (ADL) subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) captures the impact of Parkinson's disease (PD) on daily function and may be less affected than other subsections by variability associated with drug cycle and motor fluctuations. We examined UPDRS mentation, ADL and motor subscores in 888 patients with idiopathic PD. Multiple linear regression analyses determined the association between disease duration and UPDRS subscores as a function of medication status at examination and in a subset of patients with multiple examinations. Independent of medication status and across cross-sectional and longitudinal analyses, ADL subscores showed a stronger and more stable association with disease duration than other UPDRS subscores after adjusting for age of disease onset. The association between disease duration and the motor subscore depended on medication status. The strong association between ADL subscore and disease duration in PD suggests that this measure may serve as a better marker of disease progression than signs and symptoms assessed in other UPDRS sections.

Optimal frequency for measuring health care resource utilization in Parkinson's disease using participant recall: The FS-TOO resource utilization substudy

Objective: The aim of this substudy was to determine the agreement between 2 approaches for measuring health care resource utilization (eg, number of hospital visits, number of primary care physician visits) in trial participants with Parkinson's disease (PD). Methods: A substudy of the 1-year multicenter futility trial of GPI-1485 and coenzyme Q 10 (FS-TOO) was performed to assess health care resource utilization agreement by measuring participant utilization recall after 12 months versus measuring participant utilization recall at regular 3-month intervals. Trial participants were selected from patients in the National Institutes of Health—sponsored FS-TOO multicenter study. Persons aged ≥30 years with confirmed PD diagnosis within the previous 5 years were eligible for inclusion in the substudy. Participants were also required to have at least 2 of 3 cardinal manifestations of PD (tremor, rigidity, and bradykinesia). Participants were excluded from the study if they had presence of atypical Parkinson's syndromes due to drugs, metabolic identified neurogenetic disorders, encephalitis, or other degenerative diseases. Agreement was determined using Lin's concordance and Cohen's kappa statistics. Results: Between March and July of 2004, a total of 424 potential subjects were identified and evaluated for trial eligibility. Of these, 213 subjects (139 men, 74 women; mean [SD] age, 61.5 [10.3] years) met entry criteria and were included in the study. Trial participants were randomized equally to 1 of 3 groups. The 3 groups had similar baseline characteristics in terms of demographic data (age, race, sex, employment status, and annual income), total Unified Parkinson Disease Rating Scale (UPDRS) score, and UPDRS subscores. In this substudy, 141 participants had a true baseline visit, indicating a clinical baseline date, and 182 participants completed the Baseline Resource Utilization Form within 3 months of the true baseline visit. The comparison of concordance between the summed information over 3-month recalls and the 12-month recall from baseline was derived from these 182 participants. The level of agreement between the 2 approaches was high, ranging from 64.4% to 95.1%. Where disagreement was identified, the more frequent measurement approach (every 3 months) led to higher estimates, ranging from 20.4% to 77.4%. Conclusion: The results of this trial indicate internal consistency with the self-reported measures of health care resource utilization, suggesting that these simple measures might provide reliable information about units of health care resource utilization in the context of clinical trials for PD.

Selegiline in de novo parkinsonian patients: The French selegiline multicenter trial (FSMT)

The French selegiline multicenter trial was conducted in 1990 to test the possibility to improve disability of de novo parkinsonian patients (P.P.) during the first three months of treatment with selegiline (S) (10 mg/day) monotherapy. 93 P.P. were included in this double-blind, randomized, placebo controlled, clinical trial, in which 13 centers participated. Both parallel groups were followed up from inclusion (D0) to D30, D60 and D90. Drug efficacy was judged with Hoehn and Yahr (HY), Hamilton Depression Rating Scale (HDRS), Unified Parkinson's Disease Rating Scale (UPDRS), Schwab and England scores, decision to introduce levodopa and selfassessment. Biological and clinical parameters (cardio- vascular, weight, side-effects reports) were assessed for tolerability. 84 P.P. (38 P, 46 S) were evaluable for efficacy at D90. When considering the main parameters, S appears superior to placebo: HY scores (p less than 0.001), global UPDRS scores (p less than 0.001) and UPDRS subscores: mental (p less than 0.001), daily living activities (p less than 0.01), motor activities (p less than 0.01). Depressive scores (HDRS) are significantly improved only at D90 (p = 0.005). Levodopa therapy was introduced in 45% of the cases in S groups versus 18.4% in P group. Global impression of efficacy was largely in favor of S; failure was noted in half of the cases in P group and only in 1/5th of the cases in S group. Side-effects were rare and minor. S 10 mg/day monotherapy is statistically superior to placebo in improving de novo P.P. during the first three months treatment. Motor symptoms rapidly improve; mood is only modified after 3 months. S appears to be well tolerated. S may be considered as a good candidate for the initial treatment of P.P.