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 Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to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.     

Pre-fracture quality of life predicts 1-year survival in elderly patients with hip fracture—development of a new scoring system

Summary

Hip fractures are common in elderly people. Despite great progress in surgical care, the outcome of patients with hip fracture remains disappointing. This study determined four prognostic factors (lower ASA score, higher pre-fracture EQ-5D index, higher MMSE score, and female gender) to predict 1-year survival in patients with hip fracture.

Introduction

This study determined the prognostic factors for 1-year survival in patients with hip fracture. Based on these predictors, a scoring system was developed for use upon patients’ admission to the hospital.

Methods

Hip fracture patients, aged ≥60 years, were prospectively enrolled. Upon admission, patients’ sociodemographic data, type of fracture, American Society of Anesthesiologists (ASA) score, health-related quality of life scores (EQ-5D index) and Mini-Mental State Examination (MMSE) scores were recorded, among other parameters.Correlational analysis was performed on all potential variables to identify relevant predictor variables of 1-year survival. Univariate regression analysis was performed on all selected variables, followed by a multivariate analysis for variables that were significant in the univariate analysis. The final score was developed by converting the β-coefficients of each variable from the multivariate analysis into a scoring system.

Results

For 391 hip fracture patients, complete data were available at the time of the 1-year follow-up. In multivariate regression analysis, independent predictors of 1-year survival were lower ASA score, higher pre-fracture EQ-5D index, higher MMSE score, and female gender.The different variables were weighted according to their β-coefficient to build the prognostic score, which ranged from 0 to 10 points. The ROC curve for 1-year mortality after hip fracture showed an area under the curve of 0.74 (R ²?=?0.272; 95 % CI 0.68–0.79; p?<?0.001).

Conclusions

With only four instruments, the new score represents a useful tool for estimating 1-year survival in elderly patients with hip fractures. At present, the score is limited due to a lack of validation. A validation study is currently underway to prove its reliability.

     

The neuroprotective role of microglial cells against amyloid beta‐mediated toxicity in organotypic hippocampal slice cultures

During Alzheimer’s disease (AD) progression, microglial cells play complex roles and have potentially detrimental as well as beneficial effects. The use of appropriate model systems is essential for characterizing and understanding the roles of microglia in AD pathology. Here, we used organotypic hippocampal slice cultures (OHSCs) to investigate the impact of microglia on amyloid beta (Aβ)‐mediated toxicity. Neurons in OHSCs containing microglia were not vulnerable to cell death after 7 days of repeated treatment with Aβ_1‐42 oligomer‐enriched preparations. However, when clodronate was used to remove microglia, treatment with Aβ_1‐42 resulted in significant neuronal death. Further investigations indicated signs of endoplasmic reticulum stress and caspase activation after Aβ_1‐42 challenge only when microglia were absent. Interestingly, microglia provided protection without displaying any classic signs of activation, such as an amoeboid morphology or the release of pro‐inflammatory mediators (e.g., IL‐6, TNF‐α, NO). Furthermore, depleting microglia or inhibiting microglial uptake mechanisms resulted in significant more Aβ deposition compared to that observed in OHSCs containing functional microglia, suggesting that microglia efficiently cleared Aβ. Because inhibiting microglial uptake increased neuronal cell death, the ability of microglia to engulf Aβ is thought to contribute to its protective properties. Our study argues for a beneficial role of functional ramified microglia whereby they act against the accumulation of neurotoxic forms of Aβ and support neuronal resilience in an in situ model of AD pathology.     

Alpha2 macroglobulin and the risk of Alzheimer's disease

BACKGROUND: alpha2 Macroglobulin is a panproteinase inhibitor that is found immunohistochemically in neuritic plaques, a requisite neuropathologic feature of AD. Recently, a pentanucleotide deletion near the 5' end of the "bait region" of the alpha2 macroglobulin (A2M) gene was reported to be associated with AD in a large cohort of sibpairs, in which the mutation conferred a similar odds ratio with AD as the APOE-epsilon4 allele for carriers of at least one copy of the A2M gene (Mantel-Haenszel odds ratio, 3.56). METHODS: We studied three independent association samples of AD patients (n = 309) with an age range of 50 to 94 years and representative controls (n = 281) to characterize the allele frequency of the pentanucleotide deletion in this cohort. We detected the mutation near the 5' splice site of exon 18 using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender, education, and APOE polymorphism. RESULTS: We found that the A2M gene polymorphism conferred an increased risk for AD, with an estimated Mantel-Haenszel ratio of 1.5 (95% CI 1.1 to 2.2; p = 0.025). There was no age- or gender-dependent increase in A2M gene allele frequencies in AD patients compared with controls. The combined sample showed the expected association between AD and APOE-epsilon 4. In one of our three samples there was an interaction between the A2M and APOE-epsilon4 genes, but the other two samples showed no interaction between the two risk factors. CONCLUSIONS: Our data support an association between the A2M gene and AD. This association is less pronounced, however, in our cohort than in the previously reported sample of sibpairs.     

Kosten der Stroke-Unit-Care in Deutschland

BACKGROUND: Stroke care has a high impact on health costs. Therefore, the costs and reimbursements of integrated stroke care were calculated in a German neurological university hospital. PATIENTS AND METHODS: Patient cohorts of 2002 and 2003 were considered. All patients were included who presented with ischemic stroke, intracerebral hemorrhage, or transient ischemic attacks. G-DRG reimbursements were calculated by using the 3M grouper versions 2.2.0 for 2003 and 3.1 for 2004. RESULTS: There were no significant differences between the two patient cohorts. Compared to the former reimbursement system based on fixed daily charges, a base rate of EUR 3,204 was required for a neutral budget in 2002. The actual base rate was EUR 3,169. Assuming this base rate, an average reimbursement of EUR 4,201 (grouper 2.2.0) and of EUR 3,657 (grouper 3.1) was achieved per patient in 2002. An average reimbursement of EUR 4,107 (grouper 2.2.0) and of EUR 3,351 (grouper 3.1) was achieved per patient in 2003. CONCLUSION: The development of reimbursements by the G-DRGs shows a clear downward trend and shows that the high resource use in stroke unit care is inadequately reflected by the G-DRGs.     

Prevalence and incidence of Parkinson's disease in Europe.

OBJECTIVE: To provide an overview on the prevalence and incidence of Parkinson's disease (PD) in selected European countries. BACKGROUND: PD is a common disease of unknown etiology. Accurate information on the epidemiology of PD is critical to inform health policy. An aging population will lead to more patients with PD; thus, the high financial burden PD places on society will increase. MATERIAL AND METHODS: A systematic literature search was performed to identify studies on the prevalence and incidence of PD in the following European countries: Austria, the Czech Republic, France, Germany, Italy, The Netherlands, Portugal, Spain, Sweden and United Kingdom. Only published studies were included. Abstracts, reviews, meta-analyses and letters to the editor were excluded. There were no language restrictions. Data were extracted using a standardized assessment form, and evidence tables were used to systematically report and compare the data. RESULTS: Of 39 identified studies, most (87%) reported estimates of PD prevalence rates, while only a few (13%) reported estimates of PD annual incidence rates. Crude prevalence rate estimates ranged from 65.6 per 100,000 to 12,500 per 100,000 and annual incidence estimates ranged from 5 per 100,000 to 346 per 100,000. No publications could be identified for Austria or the Czech Republic. DISCUSSION AND CONCLUSION: The observed variations in prevalence and incidence rates may result from environmental or genetic factors, but might also be a consequence of differences in methodologies for case ascertainment, diagnostic criteria, or age distributions of the study populations. The comparability of existing studies is limited.