Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

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...

/pdf/guidelines-for-the-early-management-of-patients-with-acute-19udbft6e7.pdf

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

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

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

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.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(09)70025-7.pdf

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

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.

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MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma

Das von Nowell (1) eingefuhrte Tumorstammzellmodell und der von Hamburger und Salmon (2) entwickelte Tumorstammzellassay fuhrten zu einer Vielzahl pratherapeutischer in vitro-Ansatze, die das klinische Ansprechen von Tumoren auf die Chemotherapie abschatzen wollten. Fur maligne Gliome existieren eine Reihe von Verfahren (u. a. R/3.), die einesehr gute (Correlation der pradiktiven Testergebnisse mit den tatsachlichen klinischen Verlaufen chemotherapierter Tumorpatienten erlauben. In der klinischen Neuroonkologie wird derzeit wie in der ubrigen Onkologie eine kombinierte Chemotherapie angestrebt, sodas wir uns darum bemuhten, ein in vitro-Modell zur Vorhersage der Substanzinteraktion einer kombi-nierten Chemotherapie zu entwickeln. Es gait hierbei das von Loewe und Muischnik (4) entwickelte Modell der Kombinationsisobolen auf die in vitro- Chemotherapie anzuwenden und gleichzeitig die in vivo und in vitro pharmakokinetischen Daten der verwandten Substanzen einzusetzen.

Individualisierte Kombinationschemotherapie maligner Gliome

MR imaging is the most comprehensive noninvasive means to assessstructural changes in injured central nervous system (CNS) tissue in humans over time. The fewpublished in vivo MR imaging studies of spinal cord injury in rodent models by using field strengths 7T suffer from low spatial resolution, flow, and motion artifacts. The aim of this study was to assessthe capacity of a 17.6T imaging system to detect pathologic changes occurring in a rat spinal cordcontusion injury model ex vivo and in vivo.

ORIGINAL RESEARCH In Vivo High-Resolution MR Imaging of Neuropathologic Changes in the Injured Rat Spinal Cord

We thank Dr. Greenland for raising an important issue concerning the interpretation of our data and we briefly respond to his points [1], as also presented in other recent articles [2, 3]. Before doing so, we would like to clarify that the title of his response is overstated because it leads the reader into believing that we interpreted the association between statin use and glioma as not being inverse across three studies. In contrast to the misleading wording of Dr. Greenland’s title, we interpreted the data of only one study (namely our own) as there being no association between statins and glioma [4], but consistently referred to previous studies [5, 6] as supporting an inverse relation between the two. Apart from Dr. Greenland’s title profoundly misrepresenting our paper, we agree with some but not all of his comments. One point we agree with is that our abstract did not state that our point estimate showed an inverse relation of statins to glioma. Thus, the wording should have been something like: ‘‘As compared with non-use of statins, use of statins showed a statistically non-significant inverse association with risk of glioma’’. Also, we should have made clear that our findings do support previous sparse evidence of a possible inverse association between statin use and glioma risk. Unfortunately, we were not able to present the full range of data within the context of the abstract, but as shown in our Results section, the point estimates for increasing levels of statin use versus non-use were largely null or slightly above unity for all but the top category (ORs for 2–9, 10–29, 30–59, 60–89, and C90 prescriptions = 1.01, 1.00, 1.11, 1.10, and 0.75). Despite the complete lack of a dose–response relation (p value for test for trend = 0.979), we cannot rule out a threshold effect beginning at 90 prescriptions. An additional point we agree with is that potential biases may be responsible for the magnitude of the inverse association observed between statins and glioma. For example, we were concerned about incomplete control for diabetes and congestive heart failure, variables that were consistently positively associated with statin use and strongly inversely associated with glioma in our dataset. We differ with Dr. Greenland on several of his comments. First, we do not agree with his conclusion that we seriously misinterpreted our data because we specifically discussed the possibility that statins protect against risk of glioma. We feel Dr. Greenland’s response would have been more balanced had he acknowledged our statement that long-term use of statins (approximately 10–20 years of use) was suggestively associated with protection from risk of glioma (please see second sentence of our Discussion section). Second, we do not agree with Dr. Greenland’s view that previous studies consistently show an inverse association between statins and glioma. For example, one previous study [5] actually comprised two datasets, one from & Corinna Seliger corinna.seliger@klinik.uni-regensburg.de

Reply to Greenland: A serious misinterpretation of a consistent inverse association of statin use with glioma across 3 case-control studies.

LP53: Electromyographic evidence for repair of motor neurons in patients with ALS

Die transcranielle farbcodierte real-time Sonographie (TCCS) ist eine neue nichtinvasive und mobil einsetzbare diagnostische Methode, die die zweidimensionale Real-Time Abbildung cerebraler parenchymatoser und vaskularer Strukturen erlaubt. Wir untersuchten 215 Probanden uber 18 Jahre durch die geschlossene Schadeldecke (53 Gesunde, 162 cerebral Erkrankte). Verwendet wurde ein Ultraschallsystem mit farbcodierter Wiedergabe intravasalen Blutflusphanomene, ausgestattet mit einer 2, 25 MHz Sonde. Akustische Knochenfenster fanden sich beim Erwachsenen in einer Zone, die von der linea temporalis inferior und dem processus zygomaticus begrenzt werden. Die TCCS erlaubt, weite Teile des basalen Gefaskranzes zweidimensional darzustellen. Eine genaue Analyse des intravasalen Blutflusses ist mit dem integrierten pW-Doppler moghch. Die Abgrenzung des venosen Systems gelingt noch nicht, da die Flusgeschwindigkeit die Nachweisgrenze von 30 cm/sec. nicht uberschreitet. Telencephale, diencephale, mesencephale und pontine parenchymatose Hirnareale sind mit der TCCS zweidimensional abbildbar, wobei verschiedene Gewebe unterschiedliche Echogenitat aufweisen. Blutungen und Hirntumoren sind in einem hohen Prozentsatz ebenso abzugrenzen wie cerebrale Gefasstenosen, Insulte, AV-Angiome und Aneurysmen. Auch Komplikationen neurologischer Erkrankungen wie Hydrocephalus, Hirnodem und Vasospasmus sind mit dieser Methode identifizierbar. Als Echzeitverfahren erlaubt die TCCS Einblick in die Dynamik cerebraler Prozesse.

Ulrich Bogdahn

Papers

Individualisierte Kombinationschemotherapie maligner Gliome

ORIGINAL RESEARCH In Vivo High-Resolution MR Imaging of Neuropathologic Changes in the Injured Rat Spinal Cord

Reply to Greenland: A serious misinterpretation of a consistent inverse association of statin use with glioma across 3 case-control studies.

LP53: Electromyographic evidence for repair of motor neurons in patients with ALS

Die transcranielle farbcodierte real-time Sonographie des Erwachsenen: Ein neues diagnostisches Verfahren