Monika Balzer-Geldsetzer

Naturally Occurring Autoantibodies against β-Amyloid: Investigating Their Role in Transgenic Animal and In Vitro Models of Alzheimer's Disease

Alzheimers disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against β-amyloid (Aβ) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against Aβ (NAbs–Aβ) being reduced in Alzheimers disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs–Aβ recognized the mid-/C-terminal end of Aβ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs–Aβ were able to interfere with Aβ peptide toxicity, but NAbs–Aβ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs–Aβ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs–Aβ to dispose of proteins or peptides that are prone to forming toxic aggregates.

Health-related quality of life in patients with Gilles de la Tourette's syndrome†

To investigate the health‐related quality of life (HrQoL) of adult patients with Gilles de la Tourettes syndrome (GTS) in Germany. HrQoL was evaluated in 200 adult patients with GTS (Mean age: 34.9 ± 11.8 years). Patients were recruited from three outpatient departments in Germany and completed a semi‐structured, self‐rating interview. HrQoL was measured using the EQ‐5D. Depression was assessed using the Becks depression inventory (BDI) and clinical symptoms using the Yale Tourette syndrome symptom list (TSSL) and the Shapiro Tourette‐syndrome severity scale (STSSS). Multivariate regression analyses were performed to identify independent predictors of HrQoL. Patients with GTS proved to have a worse HrQoL than a sample from the general German population. The domains most affected were anxiety/depression (57.1%), followed by pain/discomfort (47.5%), usual activities (38.4%), mobility (14%), and self‐care (6.6%). The mean EQ‐5D visual analog scale (EQ‐VAS) was 65.4 ± 21.9. The patients had a mean BDI score of 12.3 ± 9.9, which was considerably worse compared to a healthy group who had a score of 6.45 ± 5.2. The mean STSSS value was 3.2 ± 1.1. In multivariate analyses, depressive symptoms contributed considerably, whereas the severity of symptoms as well as age only contributed minimally to HrQoL in the model (R2 = 0.54). HrQoL is considerably reduced in adult patients with GTS. The main independent factors for determining HrQoL were depression, severity of symptoms, and age. Although, treatment of tics is important, co‐morbidities such as depression should be diagnosed and treated vigorously.

The Role of Macrophage Inhibitory Factor in Tumorigenesis and Central Nervous System Tumors

Macrophage migration inhibitory factor (MIF) has been described as a protein that plays an important role in both innate and acquired immunity. Further research has shown that MIF plays a particularly critical part in cell cycle regulation and therefore in tumorigenesis as well. Over the past few years, the significance of the role of MIF in a variety of both solid and hematologic tumors has been established. More recently, interest has increased in the role of MIF in the development of central nervous system (CNS) tumors, in which it appears to influence cell cycle control. In addition, MIF has been identified as an essential actor in metastasis and angiogenesis. Vascular growth factor concentration raises because of increased levels of MIF in brain tumors. Recently, the MIF receptor complex has been described, and it appears that this may be a suitable drug target for treatment of brain tumors. In light of these findings, the authors chose to conduct a systematic search for information regarding MIF that has been published within the past 15 years using the terms “inflammation,” “glioblastoma,” “brain tumor,” “astrocytoma,” “microglia,” “glioblastoma,” “immune system and brain tumors,” “glioblastoma and MIF,” and “brain tumor and MIF.” The aim of this article was thus to present a detailed review of current knowledge regarding the role of MIF in CNS tumor pathophysiology. Cancer 2009.

Health-Related Quality of Life in Patients with Subarachnoid Haemorrhage

Background: Aneurysmal subarachnoid haemorrhage (SAH) is a devastating disease with high mortality and disability. The data from large longitudinal studies on health-related quality of life (HRQoL) in patients with SAH are limited. The objective was to investigate HRQoL in patients after SAH and to identify predictors of HRQoL. Methods: 113 patients with aneurysmal SAH were assigned to either neurosurgery (n = 57) or endovascular coiling (n = 56). Clinical assessments (Barthel Index, modified Rankin Scale) and evaluation of HRQoL [36-Item Short-Form Survey, EuroQol (EQ5D), EQ visual analogue scale (EQ VAS)] were performed at discharge, and at 6 and 12 months of follow-up. Independent predictors of HRQoL were determined using multiple regression analysis. Results: HRQoL in SAH patients was considerably reduced compared to the normal population. At discharge, 92.2% of the patients had moderate or severe problems on the EQ5D. The EQ VAS score was 57.8 ± 19.3. However, HRQoL still showed improvement from 3 months up to 1 year. At 12 months after SAH, the EQ VAS score was approximately 12–14% higher than at discharge. The independent predictors of decreased HRQoL included female gender, severe SAH, functional disability, depression, a lower level of education and the lack of a stable partnership. Conclusions: The long-term HRQoL outcome after SAH is unfavourable. HRQoL outcome measures should be included in future studies to provide better evidence of the long-term outcomes after SAH. In addition, the independent determinants of HRQoL identified in this study should be considered in the healthcare programmes aimed at increasing the HRQoL in SAH survivors.

Costs of illness and care in Parkinson's disease: an evaluation in six countries.

We investigated the costs of Parkinsons Disease (PD) in 486 patients based on a survey conducted in six countries. Economic data were collected over a 6-month period and presented from the societal perspective. The total mean costs per patient ranged from EUR 2620 to EUR 9820. Direct costs totalled about 60% to 70% and indirect costs about 30% to 40% of total costs. The proportions of costs components of PD vary notably; variations were due to differences in country-specific health system characteristics, macro economic conditions, as well as frequencies of resource use and price differences. However, inpatient care, long-term care and medication were identified as the major expenditures in the investigated countries.

Longitudinal study of the socioeconomic burden of Parkinson’s disease in Germany

Objective:  To determine the health economic burden on patients with Parkinson’s disease (PD) in Germany over a 12‐month observation period and provide a comprehensive analysis of cost‐driving factors.

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

Parkinsons 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 Parkinsons 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.

Parkinson’s Disease and Dementia: A Longitudinal Study (DEMPARK)

Background: Parkinson’s disease (PD) is a progressive neurodegenerative motor disorder. However, non-motor complications frequently alter the course of the disease. A particularly disabling non-motor symptom is dementia. Methods/Design: The study is designed as a multicentre prospective, observational cohort study of about 700 PD patients aged 45–80 years with or without dementia and PD-mild cognitive impairment (MCI). The patients will be recruited in eight specialized movement disorder clinics and will be followed for 36 months. Information about the patients’ functional status will be assessed at baseline and 6-/12- month intervals. In addition, 120 patients with dementia with Lewy bodies (DLB) will be included. Well-established standardized questionnaires/tests will be applied for detailed neuropsychological assessment. In addition, patients will be asked to participate in modules including volumetric MRI, genetic parameters, and neuropsychology to detect risk factors, early diagnostic biomarkers and predictors for dementia in PD. Results: The study included 604 PD patients by March 2011; 56.3% were classified as having PD alone, with 30.6% of patients suffering from PD-MCI and 13.1% from PD with dementia. The mean age of the cohort was 68.6 ± 7.9 years, with a mean disease duration of 6.8 ± 5.4 years. There was a preponderance of patients in the earlier Hoehn and Yahr stages. Conclusion: The main aim of the study is to characterize the natural progression of cognitive impairment in PD and to identify factors which contribute to the evolution and/or progression of the cognitive impairment. To accomplish this aim we established a large cohort of PD patients without cognitive dysfunction, PD patients with MCI, and PD patients with dementia, to characterize these patients in a standardized manner, using imaging (serial structural MRI), genetic and proteomic methods in order to improve our understanding of the course of the PD process and the development of cognitive dysfunction and dementia in this disease. The inclusion of the DLB patients will start in the second quarter of 2011 in the BMBF-funded follow-up project LANDSCAPE.

Trends in resource utilization for Parkinson's disease in Germany.

OBJECTIVE The prevalence of Parkinsons disease (PD) and costs of healthcare resources for this disease have been increasing in recent years. The objective was to determine the trends in the resource utilization for PD in Germany. METHODS AND PATIENTS We compared resource utilization in two cohorts of PD patients recruited in 2000 (n=145) and 2004 (n=133) from two clinical departments, two office-based neurologists and several general practitioners. Direct and indirect costs were assessed based on a patient diary and structured personal interviews. Clinical status was classified in Hoehn and Yahr (HY) stages. Cost-driving factors were determined using multivariate regression analysis. RESULTS In 2004, total annual costs for PD ranged from EUR 18,660 for HY I-II to EUR 31,660 for HY II-V. As compared to costs in 2000, total costs increased in 2004 by 25-31%. Drug costs increased by 14-20% during this time. The largest increase in direct costs was observed in the early disease (HY I-II), primarily due to rising costs for inpatient care and drugs. Motor complications, age, HY stage and study year were independent cost-driving factors. CONCLUSION The resource utilization in PD increased rapidly over the four year study period. Increasing consumption of healthcare resources due to medical progress is a major factor of rising costs. Future studies should attend more to trends in the utilization of healthcare resources and identify factors which could slow down the expanding costs of healthcare.

Who was the man who discovered the “Lewy bodies”?†

In 1912, Fritz Heinrich Lewy described neuronal inclusions in the brain of patients who had suffered from Paralysis agitans (i.e., Parkinsons disease). Later, these findings became the so‐called “Lewy bodies.” However, little is known about the man who made this discovery. Our aim was to investigate Lewys private and professional life and to gather information for a detailed biography. We contacted over 100 archives, libraries, and museums in Germany, Poland, Switzerland, United Kingdom, and United States. Over 300 documents, publications, and photos were collected. Lewy was born in Berlin, Germany in 1885 and lived there until 1933. After his dismissal on racial grounds by the Nazis, Lewy emigrated to England in 1933 and to the United States of America in 1934, where he lived and worked until his death in 1950. This article gives a summary of Lewys life and briefly presents his contribution to German and American neurology.