The patterns of EEG changes in early-onset Parkinson's disease patients

The aim of this study was to investigate the patterns of brain activity changes in early-onset Parkinson's disease (EOPD) patients and its relationship with the severity of disease and motor deterioration. Electroencephalography (EEG) was performed in a sample of 52 nondemented EOPD patients and 20 healthy controls with similar age. All patients underwent a battery to assess PD severity and motor deterioration. The EEG data were rated by visual and quantitative analyses with the grant total EEG (GTE) score and NicoletOne Software. The parameters of relative band power and coherences for various frequency bands were calculated. In addition, all parameters were compared between groups and examined for correlations with the severity of disease and motor deterioration. The GTE score and two subscores including “Diffuse Slow Waves” and “Frequency of Rhythmic Background Activity” of EOPD increased comparing to control group. The relative beta band powers in seven regions (O1,O2,T5,T6,P3,P4 and C3) indicated significant decreases in EOPD patients and obvious increases in interhemispheric beta coherences were observed in the midtemporal area and frontal area (T3T4 and F3F4). Furthermore, correlation analyses revealed that longer duration was associated with the subscore of “background wave frequency”. The beta frequency bands in the right posterior temporal (T6) showed negative relationship with the modified Hoehn–Yahr grading scores. This study is the first to depict the patterns of EEG changes in EOPD patients without dementia and offer a better understanding of the pathophysiological mechanisms underlying and prognostic purposes in EOPD. Some of these changes could serve as useful biomarkers in the study of EOPD.     

Impact of belief in neuroprotection on therapeutic intervention in Parkinson's disease

We explored the hypotheses that an investigator's belief in a putative neuroprotective agent might influence the timing of symptomatic intervention and the assessment of signs and symptoms of patients with Parkinson's disease with the Unified Parkinson's Disease Rating Scale (UPDRS). These hypotheses were tested with Cox and general linear modeling, using data from a previously published double‐blind placebo‐controlled futility trial of coenzyme Q₁₀ and GPI‐1485. We found the investigators' level of confidence in these agents had no effect on the time to symptomatic therapy or on the change in UPDRS during 12 months of treatment. © 2010 Movement Disorder Society     

A two‐year randomized controlled trial of progressive resistance exercise for Parkinson's disease

The effects of progressive resistance exercise (PRE) on the motor signs of Parkinson's disease have not been studied in controlled trials. The objective of the current trial was to compare 6‐, 12‐, 18‐, and 24‐month outcomes of patients with Parkinson's disease who received PRE with a stretching, balance, and strengthening exercise program. The authors conducted a randomized controlled trial between September 2007 and July 2011. Pairs of patients matched by sex and off‐medication scores on the Unified Parkinson's Disease Rating Scale, motor subscale (UPDRS‐III), were randomly assigned to the interventions with a 1:1 allocation ratio. The PRE group performed a weight‐lifting program. The modified fitness counts (mFC) group performed a stretching, balance, and strengthening exercise program. Patients exercised 2 days per week for 24 months at a gym. A personal trainer directed both weekly sessions for the first 6 months and 1 weekly session after 6 months. The primary outcome was the off‐medication UPDRS‐III score. Patients were followed for 24 months at 6‐month intervals. Of 51 patients, 20 in the PRE group and 18 in the mFC group completed the trial. At 24 months, the mean off‐medication UPDRS‐III score decreased more with PRE than with mFC (mean difference, ?7.3 points; 95% confidence interval, ?11.3 to ?3.6; P<0.001). The PRE group had 10 adverse events, and the mFC group had 7 adverse events. PRE demonstrated a statistically and clinically significant reduction in UPDRS‐III scores compared with mFC and is recommended as a useful adjunct therapy to improve Parkinsonian motor signs. © 2013 Movement Disorder Society     

Early treatment benefits of ropinirole prolonged release in Parkinson's disease patients with motor fluctuations

We performed a retrospective analysis of the Efficacy And Safety Evaluation in Parkinson's Disease (EASE‐PD) Adjunct Study, assessing the minimum time to symptom improvement after initiation of ropinirole prolonged release (2–24 mg/day) versus placebo in patients with moderate‐to‐advanced PD not optimally controlled with levodopa. Ropinirole prolonged release was superior to placebo at Week 2 for change from baseline in “off” time (adjusted mean treatment difference [AMTD] – 0.7 hours; 95% confidence interval [CI], –1.1, –0.2; P = 0.0029), and “on” time without troublesome dyskinesia (0.4 hours; 95%CI, 0.01, 0.88; P = 0.0444). At Week 4, improvements were seen in change from baseline in Unified Parkinson's Disease Rating Scale total motor score (AMTD, –3.1; 95%CI, –4.4, –1.8; P < 0.0001), activities of daily living score (AMTD, –1.1; 95%CI, –1.7, –0.5; P = 0.0004), and the cardinal symptoms of PD compared with placebo. These analyses indicate that once‐daily, adjunctive ropinirole prolonged release can offer PD symptom control 2 weeks after treatment initiation. © 2010 Movement Disorder Society     

The Unified Parkinson's Disease Rating Scale (UPDRS): Status and recommendations

The Movement Disorder Society Task Force for Rating Scales for Parkinson's Disease prepared a critique of the Unified Parkinson's Disease Rating Scale (UPDRS). Strengths of the UPDRS include its wide utilization, its application across the clinical spectrum of PD, its nearly comprehensive coverage of motor symptoms, and its clinimetric properties, including reliability and validity. Weaknesses include several ambiguities in the written text, inadequate instructions for raters, some metric flaws, and the absence of screening questions on several important non‐motor aspects of PD. The Task Force recommends that the MDS sponsor the development of a new version of the UPDRS and encourage efforts to establish its clinimetric properties, especially addressing the need to define a Minimal Clinically Relevant Difference and a Minimal Clinically Relevant Incremental Difference, as well as testing its correlation with the current UPDRS. If developed, the new scale should be culturally unbiased and be tested in different racial, gender, and age‐groups. Future goals should include the definition of UPDRS scores with confidence intervals that correlate with clinically pertinent designations, “minimal,” “mild,” “moderate,” and “severe” PD. Whereas the presence of non‐motor components of PD can be identified with screening questions, a new version of the UPDRS should include an official appendix that includes other, more detailed, and optionally used scales to determine severity of these impairments. © 2003 Movement Disorder Society     

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.     

Teaching program for the movement disorder society‐sponsored revision of the Unified Parkinson's Disease Rating Scale: (MDS‐UPDRS)

To accompany the newly developed Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), we developed a teaching program. The DVD‐based program covers the four parts of the scale with visual and verbal instructions for uniform application. For the motor section (Part III), all items except rigidity are shown with an example of each rating option (0–4) as agreed upon by a panel of experts. The rate of agreement for the selected samples was always significant, with Kendall's coefficient of concordance W ranging between 0.99 and 0.72. The teaching program also provides a full patient examination with rating answers provided and four full MDS‐UPDRS cases for a Certificate Program exercise of Part III. This training program is in English, but as non‐English official translations of the MDS‐UPDRS are developed, the program can be potentially modified into different languages. © 2010 Movement Disorder Society     

Effect of daily repetitive transcranial magnetic stimulation on motor performance in Parkinson's disease.

Previous studies in patients with Parkinson's disease have reported that a single session of repetitive transcranial magnetic stimulation (rTMS) can improve some or all of the motor symptoms for 30 to 60 minutes. A recent study suggested that repeated sessions of rTMS lead to effects that can last for at least 1 month. Here we report data that both confirm and extend this work. Fifty-five unmedicated PD patients were classified into four groups: two groups (early and late PD) received 25 Hz rTMS bilaterally on the motor arm and leg areas; other groups acted as control for frequency (10 Hz) and for site of stimulation (occipital stimulation). All patients received six consecutive daily sessions (3,000 pulses for each session). The first two groups then received a further three booster sessions (3 consecutive days of rTMS) after 1, 2, and 3 months, while the third group had only one additional session after the first month. Unified Parkinson's Disease Rating Scale (UPDRS), walking time, key-tapping speed, and self-assessment scale were measured for each patient before and after each rTMS session and before and after the monthly sessions. Compared to occipital stimulation, 25 Hz rTMS over motor areas improved all measures in both early and late groups; the group that received 10 Hz rTMS improved more than the occipital group but less than the 25 Hz groups. The effect built up gradually during the sessions and was maintained for 1 month after, with a slight reduction in efficacy. Interestingly, the effect was restored and maintained for the next month by the booster sessions. We conclude that 25 Hz rTMS can lead to cumulative and long-lasting effects on motor performance.     

Unified Parkinson's disease rating scale motor examination: Are ratings of nurses,residents in neurology,and movement disorders specialists interchangeable?

The Unified Parkinson's Disease Rating Scale (UPDRS) is widely used for the clinical evaluation of Parkinson's disease (PD). We assessed the rater variability of the UPDRS Motor examination (UPDRS-ME) of nurse practitioners, residents in neurology, and a movement disorders specialist (MDS) compared to a senior MDS. We assessed the videotaped UPDRS-ME of 50 PD patients. Inter-rater and intra-rater variability were estimated using weighted kappa (kappa(w)) and intraclass correlation coefficients (ICC). Additionally, inter-rater agreement was quantified by calculation of the mean difference between 2 raters and its 95% limits of agreement. Intra-rater agreement was also estimated by calculation of a 95% repeatability limits. The kappa(w) and ICC statistics indicated good to very good inter-rater and intra-rater reliability for the majority of individual UPDRS items and the sum score of the UPDRS-ME in all raters. However, for inter-rater agreement, it appeared that both nurses, residents, and the MDS consistently assigned higher scores than the senior MDS. Mean differences ranged between 1.7 and 5.4 (all differences P < 0.05), with rather wide 95% limits of agreement. The intra-rater 95% repeatability limits were rather wide. We found considerable rater difference for the whole range of UPDRS-ME scores between a senior MDS and nurse practitioners, residents in neurology, and the MDS. This finding suggests that the amount by which raters may disagree should be quantified before starting longitudinal studies of disease progression or clinical trials. Finally, evaluation of rater agreement should always include the assessment of the extent of bias between different raters.     

Magnetic resonance spectroscopic evidence for presupplementary motor area neuronal dysfunction in Parkinson's disease.

The anterior cingulate (AC) gyrus and the presupplementary motor area (pre-SMA) show pathological changes in Parkinson's disease (PD). We examined if PD patients show magnetic resonance spectroscopy (MRS) changes in NAA/Cr in the AC, pre-SMA, or posterior cingulate (PC). Forty-four (27 male, 17 female) healthy nondemented PD patients and 38 controls (18 male, 20 female) 65 years of age and older were examined using the Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental State Examination, Frontal Assessment Battery, and Geriatric Depression Scale. MRS was performed at 1.5 T. Voxels (8 cc; PRESS; TE = 80; TR = 1,600 ms) were placed mid-sagittally. Gray matter and white matter volumes were measured within voxels using SPM2. Spectra were analyzed using LC model to yield NAA/Cr and Cho/Cr. Demographic and cognitive measures did not differ between groups. Motor UPDRS was 17.7 +/- 8.8 for PD. Pre-SMA NAA/Cr was lower in PD (PD: 1.39 +/- 0.17; control: 1.47 +/- 0.16; P = 0.045) and correlated negatively with age (r = 0.39; P = 0.01), but not with UPDRS, disease duration, or dopamine equivalents. AC and PC NAA/Cr and Cho/Cr in any region did not differ (P > 0.05). In conclusion, pre-SMA NAA/Cr was selectively decreased in PD, consistent with neuronal dysfunction. This should be further examined as a biomarker of disease in PD.     

Metric attributes of the unified Parkinson's disease rating scale 3.0 battery: part II, construct and content validity.

This article is the second of a two-part series concerning the metric properties of the following three Parkinson's disease (PD) scales: modified Hoehn and Yahr staging (H&Y), Schwab and England (S&E), and Unified Parkinson's Disease Rating Scale (UPDRS) 3.0. Part II focuses on construct and content validity. To assess construct validity, a sample of 1,136 PD patients completed the above-mentioned PD scales. Correlation coefficients between measures of disability and dysfunction [S&E, UPDRS Activities of Daily Living (ADL), and UPDRS Motor Examination] were |r| = 0.69-0.77, indicating good convergent validity. Results showed that the S&E (F(5,945) = 193.47; P < 0.0001) and UPDRS subscales discriminated between modified H&Y stages (F(20,2784) = 25.28; P < 0.001). A panel of 12 to 13 international experts rated the relevance of the scales and items. This enabled the scales' content validity index to be calculated, which ranged from 41.7% (UPDRS Mentation) to 83.3% (UPDRS Motor Examination). In conclusion, while the modified H&Y, S&E, and UPDRS displayed satisfactory construct validity, the content validity of all scales except UPDRS Motor Examination failed to attain adequate standards.     

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

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

The modified bradykinesia rating scale for Parkinson's disease: Reliability and comparison with kinematic measures

Bradykinesia encompasses slowness, decreased movement amplitude, and dysrhythmia. Unified Parkinson's Disease Rating Scale–based bradykinesia‐related items require that clinicians condense abnormalities in speed, amplitude, fatiguing, hesitations, and arrests into a single score. The objective of this study was to evaluate the reliability of a modified bradykinesia rating scale, which separately assesses speed, amplitude, and rhythm and its correlation with kinematic measures from motion sensors. Fifty patients with Parkinson's disease performed Unified Parkinson's Disease Rating Scale–directed finger tapping, hand grasping, and pronation–supination while wearing motion sensors. Videos were rated blindly and independently by 4 clinicians. The modified bradykinesia rating scale and Unified Parkinson's Disease Rating Scale demonstrated similar inter‐ and intrarater reliability. Raters placed greater weight on amplitude than on speed or rhythm when assigning a Unified Parkinson's Disease Rating Scale score. Modified bradykinesia rating scale scores for speed, amplitude, and rhythm correlated highly with quantitative kinematic variables. The modified bradykinesia rating scale separately captures bradykinesia components with interrater and intrarater reliability similar to that of the Unified Parkinson's Disease Rating Scale. Kinematic sensors can accurately quantify speed, amplitude, and rhythm to aid in the development and evaluation of novel therapies in Parkinson's disease. © 2011 Movement Disorder Society     

Executive dysfunction using behavioral assessment of the dysexecutive syndrome in Parkinson's disease

The objective of this study was to evaluate the executive dysfunction (ExD) in Parkinson's disease (PD) using the Behavioral Assessment of the Dysexecutive Syndrome (BADS), which provides a wide‐range assessment of ExD. The BADS and the Unified Parkinson's Disease Rating Scale (UPDRS) were investigated in 63 nondemented PD patients who revealed scores of ≥24 points on the Mini‐Mental State Examination based on the DSM‐IV. Multiple logistic regression analysis was performed to evaluate the predisposing factors to ExD, which was defined as <70 points on the age‐controlled standardized score. The total score on the UPDRS was a significant independent predisposing factor to ExD. Among the various parts of the UPDRS, part II was the significant factor for ExD. The profile scores of all subtests on the BADS in patients with ExD were significantly lower than those of patients without ExD. All profile scores decreased with severity of PD, but the changes among these scores differed. ExD in nondemented PD predisposed to a greater severity of PD, particularly as regards the activity of daily living impairment. Nondemented PD revealed wide‐range components of ExD. All components of ExD were impaired with severity of PD, but the patterns of each component exhibited variety. © 2007 Movement Disorder Society     

Randomized, double-blind study of pramipexole with placebo and bromocriptine in advanced Parkinson's disease.

We compared the efficacy and safety of pramipexole (PPX) with placebo in the treatment of advanced Parkinson's disease (PD) as an adjunct to levodopa. A bromocriptine (BR) group was included to enable determination of the noninferiority of PPX relative to BR as the standard treatment.