Ulrich Bogdahn

Bio: Ulrich Bogdahn is an academic researcher from University of Regensburg. The author has contributed to research in topics: Neural stem cell & Neurogenesis. The author has an hindex of 67, co-authored 344 publications receiving 32279 citations. Previous affiliations of Ulrich Bogdahn include Hoffmann-La Roche & Volkswagen Foundation.

Depressive symptoms and quality of life after thrombolysis in stroke: the TEMPiS study

Abstract: Intravenous thrombolysis leads to a reduction of post-stroke disability. No data exist about whether depression and poor quality of life (QoL) remain relevant problems in patients with good functional outcome. We assessed mood and QoL at 3 and 6 months after stroke in consecutive patients who received intravenous thrombolysis in stroke centers and telemedicine hospitals within the TEMPiS network. The Beck Depression Inventory (BDI) was used with BDI ≥18 indicating clinically relevant depressive symptoms. Stroke specific quality of life (SSQOL) was used for QoL assessment with the definition of SSQOL total score <60% for poor QoL. Associations of BDI and SSQOL with baseline parameters and modified Rankin scale (mRS) in follow-up were analyzed. In patients with known mRS 0–4 at 3 months (N = 213), BDI was available in 74% and SSQOL in 77%. At 3 and 6 months, 23 and 18% of patients had clinically relevant depressive symptoms; 25 and 24% reported a poor QoL. The mRS at 3 months correlated with BDI (r = 0.43, p < 0.01) and SSQOL (r = −0.75, p < 0.01). BDI ≥18 was observed in 11% of patients with mRS 0–1 and 16% in mRS 0–2. Severe stroke (NIHSS ≥12) at admission (OR 1.23, 0.57–2.66; p = 0.57) was not predictive for depressive symptoms but for poor QoL (OR 2.77, 95%CI 1.34–5.74). Depressive symptoms and impaired QoL are observed in a substantial proportion of stroke patients at 3 months after intravenous thrombolysis. Health professionals should be aware that thrombolysed patients may have relevant mood disorders despite good functional outcome.

The relationship between plasma D-dimer concentrations and acute ischemic stroke subtypes.

Abstract: Elevated concentrations of D-dimers (DDs) in patients with acute ischemic stroke may cause differential diagnostic problems with regard to pulmonar or deep venous thrombosis The true relationship between plasma DDs and acute ischemic stroke remains uncertain We studied acute stroke patients admitted to a single acute neurology department with a specialized stroke unit As part of our clinical protocol, blood samples of each patient had been taken within the first 24 hours after the onset of stroke symptoms and before anticoagulant treatment had been started, to evaluate the coagulation profile Each patient’s medical record was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted Univariate and multivariate statistical analyses were performed A total of 59 patients admitted to our stroke unit between October 2003 and March 2004 with different stroke subtypes according to the TOAST criteria were evaluated to characterize the impact of stroke category on DD concentration Family members (n = 23) served as controls in this study Multivariate regression analysis revealed that patients who sustained cardioembolic stroke had significantly higher DD concentrations than controls and patients who sustained transient ischemic attacks We identified a correlation between plasma DD levels and different acute ischemic stroke subtypes before any stroke treatment was started Thus DD concentrations may be considered a direct consequence of marked cerebral infarction and may be useful for physicians when making decisions on treatment for acute ischemic stroke

Underutilization of deep brain stimulation for Parkinson's disease? A survey on possible clinical reasons.

Abstract: Only 10% of the up to 15% of patients with advanced Parkinson’s disease (PD) eligible for deep brain stimulation (DBS) are referred to specialized centers. This survey evaluated the reasons for the reluctance of patients and referring physicians regarding DBS. Two different questionnaires containing multiple choice and open verbalized questions were developed, one for neurologists and one for patients with PD. The first questionnaire was sent to 87 neurologists in private practice in the catchment area of the authors’ medical center, the second to patient support groups in the same region with the help of the German Parkinson Association. Of the addressed neurologists, 56.3% completed the questionnaire; 61.2% of them estimated the risk of intracerebral hemorrhage as the most severe complication at 4.3% on average; 30.6% were concerned about patients developing mood changes or depression after DBS. Only 16.3% felt unable to care for patients after DBS; 61.2% already had personal experience with patients after DBS and reported good clinical outcome in 90.0% of patients. Although 87.8% claimed to know the specific criteria for DBS, only 40.8% could actively describe them. Only 14.0% could state each of the three main criteria. Of the 46 patients, 88.1% completing the questionnaire had obtained information on DBS from regional patient organizations and 54.8% also from a physician; 44.7% assumed the risk of severe complications to be ≥5.0%. Not being satisfied with their medical treatment was reported by 22.2%, of whom more than 70% considered DBS a further treatment option. The latter numbers indicate that treating neurologists tend to overestimate the reluctance of their patients to undergo DBS. Therefore, education of patients and neurologists should be improved and give more realistic figures on the actual outcomes and frequencies of possible complications.

Tenascin-C protein is induced by transforming growth factor-beta1 but does not correlate with time to tumor progression in high-grade gliomas

Abstract: Background Tenascin-C is an extracellular matrix protein known to correlate with prognosis in patients with glioblastoma, probably by stimulation of invasion and neoangiogenesis. Transforming Growth Factor-s1 (TGF-s1) plays an important role in the biology of high-grade gliomas, partly by regulating invasion of these tumors into parenchyma. This study was designed to evaluate if TGF-s1 induces the expression and deposition of Tenascin-C in the extracellular matrix of high-grade gliomas which may be pivotal for the invasion of these tumors into healthy parenchyma.

Smad7 Regulates the Adult Neural Stem/Progenitor Cell Pool in a Transforming Growth Factor β- and Bone Morphogenetic Protein-Independent Manner

Abstract: Members of the transforming growth factor beta (TGF-beta) family of proteins modulate the proliferation, differentiation, and survival of many different cell types. Neural stem and progenitor cells (NPCs) in the adult brain are inhibited in their proliferation by TGF-beta and by bone morphogenetic proteins (BMPs). Here, we investigated neurogenesis in a hypomorphic mouse model for the TGF-beta and BMP inhibitor Smad7, with the hypothesis that NPC proliferation might be reduced due to increased TGF-beta and BMP signaling. Unexpectedly, we found enhanced NPC proliferation as well as an increased number of label-retaining cells in vivo. The enhanced proliferation potential of mutant cells was retained in vitro in neurosphere cultures. We observed a higher sphere-forming capacity as well as faster growth and cell cycle progression. Use of specific inhibitors revealed that these effects were independent of TGF-beta and BMP signaling. The enhanced proliferation might be at least partially mediated by elevated signaling via epidermal growth factor (EGF) receptor, as mutant cells showed higher expression and activation levels of the EGF receptor. Conversely, an EGF receptor inhibitor reduced the proliferation of these cells. Our data indicate that endogenous Smad7 regulates neural stem/progenitor cell proliferation in a TGF-beta- and BMP-independent manner.

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Abstract: Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition

Abstract: The 3rd edition of the International Classification of Headache Disorders (ICHD-3) may be reproduced freely for scientific, educational or clinical uses by institutions, societies or individuals. Otherwise, copyright belongs exclusively to the International Headache Society. Reproduction of any part or parts in any manner for commercial uses requires the Society’s permission, which will be granted on payment of a fee. Please contact the publisher at the address below. International Headache Society 2013–2018. Applications for copyright permissions should be submitted to Sage Publications Ltd, 1 Oliver’s Yard, 55 City Road, London EC1Y 1SP, United Kingdom (tel: þ44 (0) 207 324 8500; fax: þ44 (0) 207 324 8600; permissions@sagepub.co.uk) (www.uk.sagepub.com). Translations

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial

Abstract: BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. METHODS: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. FINDINGS: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. INTERPRETATION: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. FUNDING: EORTC, NCIC, Nelia and Amadeo Barletta Foundation, Schering-Plough.

MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma

Abstract: background Epigenetic silencing of the MGMT (O 6 -methylguanine–DNA methyltransferase) DNArepair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. methods We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. results The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. conclusions Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.