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Riedel O.,TU Dresden | Klotsche J.,Deutsches Rheumaforschungszentrum | Forstl H.,TU Munich | Wittchen H.-U.,TU Dresden
Journal of Geriatric Psychiatry and Neurology | Year: 2013

Despite the wide use of clock drawing tests (CDTs) for screening cognitive impairment, their use in patients having Parkinson disease (PD) with dementia has not been systematically investigated until date. In this cross-sectional study, neurological and neuropsychiatric statuses of 1449 outpatients having PD with and without dementia were comprehensively assessed. The CDT revealed cognitive impairment in 42.7% of the 1383 patients whose drawings were available. Overall, CDT sensitivity and specificity were 70.7% and 68.9%, respectively. The positive and negative predictive values were 48.0% and 85.3%, respectively. In patients with depression, CDT specificity dropped significantly to 55.8% (71.3% in nondepressed patients, P <.001). Classification performance was not impacted by motor symptoms. The estimated classification performances and predictive values correspond to those reported previously for non-PD populations. Our results indicate that CDT is a suitable screening instrument in patients with PD, but test results from patients with depression warrant careful consideration. © The Author(s) 2013. Source

Poddubnyy D.,Charite - Medical University of Berlin | Conrad K.,Charite - Medical University of Berlin | Haibel H.,Charite - Medical University of Berlin | Syrbe U.,Charite - Medical University of Berlin | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To investigate the role of serum vascular endothelial growth factor (VEGF) as a predictor of radiographic spinal progression in patients with axial spondyloarthritis (axSpA). Methods: Altogether, 172 patients with definite axSpA (95 with ankylosing spondylitis and 77 with non-radiographic axSpA) were included in this study. Spinal radiographs obtained at baseline and after 2 years of follow-up were scored independently by two trained readers in a concealed and randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) scoring system and for the presence of syndesmophytes. Radiographic spinal progression after 2 years was defined as (1) mSASSS worsening by ≥2 units, and (2) new syndesmophyte formation or formation of a bridging syndesmophyte from two single syndesmophytes. Serum VEGF levels were detected at baseline. Results: Mean baseline VEGF values were significantly higher in patients with mSASSS worsening by ≥2 units after 2 years (n=22) than in those without progression (562±357 vs 402±309 pg/mL, respectively, p=0.027) and in patients with syndesmophyte formation (n=18) again as compared with those without new bone formation (579±386 vs 404±307 pg/mL, respectively, p=0.041). VEGF as a predictor of radiographic spinal progression performed especially well in patients who were already at high risk for such a progression due to the presence of syndesmophytes at baseline (n=48). In these patients, a VEGF serum level of >600 pg/mL had a sensitivity of 53%, a specificity of 97% and an OR=36.6 (95% CI 3.9 to 341.5) as a predictor of mSASSS worsening by ≥2 units. For syndesmophyte formation, elevated VEGF demonstrated a sensitivity of 47%, a specificity of 94% and an OR=13.6 (95% CI 2.4 to 78.3). Conclusions: An elevated serum level of VEGF (>600 pg/mL) is highly specific as a predictor of radiographic spinal progression in patients with axSpA, especially in patients who are at high risk for further progression due to the presence of syndesmophytes. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism. Source

Riedel O.,Leibniz Institute for Prevention Research and Epidemiology | Riedel O.,TU Dresden | Klotsche J.,Deutsches Rheumaforschungszentrum | Wittchen H.-U.,TU Dresden
Parkinsonism and Related Disorders | Year: 2014

Introduction: Clinical Global Impression of Severity (CGIS) is a common measure in clinical research on Parkinson's disease (PD). However, patient features that contribute to the impression of the physician remain unclear. In particular, the impact of cognitive impairment and depression is understudied. Methods: In a nationwide study on 1449 outpatients with PD, examined by 315 office-based neurologists, PD severity was documented with the Unified Parkinson's Disease Rating Scale (UPDRS-I, II, and IV). All patients were screened with the Montgomery-Asberg Depression Rating Scale (MADRS) for depression. The diagnosis of dementia was based on Diagnostic and Statistical Manual of Mental Disorders IV Text Revision criteria. Each patient was rated on the CGIS. Results: CGIS ratings were available for 1438 patients, of which 50.8% were rated as "borderline" to "moderately ill" and 49.2% as "markedly" to "extremely ill." Worse ratings were associated with higher age (p<0.001), longer PD duration (p<0.001), and female sex (p<0.001). The impact of patient and physician variables on CGIS rating was calculated with three regression models (A: single bivariate regression; B: multivariate regression; and C: multivariate, multilevel regression, including physician variables). In all models, higher UPDRS-II scores and longer disease duration of PD were the strongest predictors for a worse CGIS rating. In the multivariate models (B and C), neuropsychiatric symptoms were unrelated to the CGIS rating. Conclusion: The additional burden of dementia and depression was underestimated in the CGIS rating, suggesting that they are possibly relativized against the motor impairment. © 2014 Elsevier Ltd. Source

Poddubnyy D.A.,Charite - Medical University of Berlin | Marker-Hermann E.,Dr. Horst Schmidt Hospital | Kaluza-Schilling W.,University Hospital | Zeidler H.,Hannover Medical School | And 4 more authors.
Journal of Rheumatology | Year: 2011

Objective. In a pilot study, a distinct T cell cytokine pattern associated with HLA-B27 status and a tumor necrosis factor-α (TNF-α) promoter gene polymorphism was found at -308 (TNF-308). The objective of our study was to assess these associations in a different cohort of patients with ankylosing spondylitis (AS) and to evaluate any effect on clinical measurements. Methods. Peripheral T cell cytokine production of patients with AS (n = 121) from the German Spondyloarthritis Inception Cohort was assessed by flow cytometry and correlated with HLA-B27, TNF-238, and TNF-308, and with clinical measurements. Results. In HLA-B27-positive, anti-TNF-naive patients with AS, the percentages of TNF-α-producing (5.02%) and interleukin 10-producing (0.31%) CD8+ cells were significantly lower in comparison to HLA-B27-negative patients (9.52%, p = 0.048, and 0.46%, p = 0.037, respectively). A non-significant trend was found for a lower production of TNF-α by CD4+ and interferon-γ by both CD4+ and CD8+ T cells, as compared to HLA-B27-negative patients with AS (p > 0.05 for all comparisons). The A allele at TNF-308 was associated with a lower percentage of TNF-α-producing CD4+ T cells. No significant correlations were found between clinical or radiological measurements and cytokine production or with TNF-α promoter gene polymorphisms. Conclusion. Modulation of T cell cytokines by HLA-B27 might play a role in AS pathogenesis in B27-positive individuals. No conclusive data were obtained for the TNF-308 polymorphism on cytokine production, and no effect of cytokines or genetic polymorphisms on clinical manifestations was observed. The Journal of Rheumatology Copyright © 2011. All rights reserved. Source

Conrad K.,Charite - Medical University of Berlin | Wu P.,Deutsches Rheumaforschungszentrum | Sieper J.,Charite - Medical University of Berlin | Syrbe U.,Charite - Medical University of Berlin
Arthritis Research and Therapy | Year: 2015

Introduction: Innate immune responses, including monocyte functions, seem to play an important role in the pathogenesis of axial spondyloarthritis (axSpA). Therefore, we characterized the phenotype and functional state of monocytes of patients with axSpA. Methods: Fifty-seven patients with axSpA, 11 patients with rheumatoid arthritis (RA), and 29 healthy controls were included in the study. We determined the percentage of classic, intermediate, and non-classic monocytes according to CD14 and CD16 expression and the expression of Toll-like receptor (TLR) 1, 2, and 4 in whole blood by flow cytometry. The percentage of monocytes producing interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha (TNFaα), IL-12/23p40, and IL-1 receptor antagonist (IL-1ra) was detected by flow cytometry after stimulation of whole blood without and with different TLR and nucleotide-binding oligomerization domain ligands-i.e., lipopolysaccharide (LPS), fibroblast-stimulating lipopeptid-1, PAM3CSK4, and muramyl dipeptide (MDP)-for 5 h. IL-10 production was measured after 18 h of stimulation in supernatants by enzyme-linked immunosorbent assay. Results: In patients with axSpA but not patients with RA, we found higher frequencies of classic monocytes than in controls (median of 90.4 % versus 80.4 %, P < 0.05), higher frequencies of monocytes spontaneously producing IL-1beta and IL-1ra (P < 0.05), and a higher percentage of monocytes producing IL-1beta after MDP stimulation (P < 0.05). Elevated cytokine production was confined to axSpA patients under conventional therapy (non-steroidal anti-inflammatory drugs) and not found in patients under TNFaα inhibitor treatment. The LPS-induced production of IL-6 and IL-10 was lower in axSpA patients compared with controls (P < 0.05). Monocytic TLR expression was unaffected in patients with axSpA. Conclusion: Enhanced spontaneous and MDP-induced cytokine secretion by monocytes suggests in vivo pre-activation of monocytes in axSpA patients under conventional therapy which is reverted under TNF inhibitor treatment. © 2015 Conrad et al. Source

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