Publications by authors named "Johannes Trenkler"

38 Publications

Cytomegalovirus Encephalitis Under Fingolimod Mimicking Progressive Multifocal Leukoencephalopathy?

Neurol Neuroimmunol Neuroinflamm 2021 07 9;8(4). Epub 2021 Apr 9.

From the Department of Neurology (D.O., R.T.), Academic Teaching Hospital Wels-Grieskirchen; Institute of Hygiene and Microbiology (K.R.-H.), Academic Teaching Hospital Wels-Grieskirchen, Wels; and Institute of Neuroradiology (J.T.), Neuromed Campus, Kepler University Hospital, Linz, Austria.

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http://dx.doi.org/10.1212/NXI.0000000000000996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042783PMC
July 2021

Evaluation of the Temporal Muscle Thickness as an Independent Prognostic Biomarker in Patients with Primary Central Nervous System Lymphoma.

Cancers (Basel) 2021 Feb 2;13(3). Epub 2021 Feb 2.

Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.

In this study, we assessed the prognostic relevance of temporal muscle thickness (TMT), likely reflecting patient's frailty, in patients with primary central nervous system lymphoma (PCNSL). In 128 newly diagnosed PCNSL patients TMT was analyzed on cranial magnetic resonance images. Predefined sex-specific TMT cutoff values were used to categorize the patient cohort. Survival analyses, using a log-rank test as well as Cox models adjusted for further prognostic parameters, were performed. The risk of death was significantly increased for PCNSL patients with reduced muscle thickness (hazard ratio of 3.189, 95% CI: 2-097-4.848, < 0.001). Importantly, the results confirmed that TMT could be used as an independent prognostic marker upon multivariate Cox modeling (hazard ratio of 2.504, 95% CI: 1.608-3.911, < 0.001) adjusting for sex, age at time of diagnosis, deep brain involvement of the PCNSL lesions, Eastern Cooperative Oncology Group (ECOG) performance status, and methotrexate-based chemotherapy. A TMT value below the sex-related cutoff value at the time of diagnosis is an independent adverse marker in patients with PCNSL. Thus, our results suggest the systematic inclusion of TMT in further translational and clinical studies designed to help validate its role as a prognostic biomarker.
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http://dx.doi.org/10.3390/cancers13030566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867149PMC
February 2021

Clinical Diffusion Mismatch to Select Pediatric Patients for Embolectomy 6 to 24 Hours After Stroke: An Analysis of the Save ChildS Study.

Neurology 2021 01 3;96(3):e343-e351. Epub 2020 Nov 3.

From the Department of Neuroradiology (P.B.S., M.-N.P., A.B.), Clinic for Radiology & Nuclear Medicine, University Hospital Basel, Switzerland; Department of Diagnostic and Interventional Neuroradiology (P.B.S., U.H., G.B., J.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Departments of Pediatrics (R.S.), and Neurology (J.M.), University Hospital of Muenster; Department of Neuroradiology (R.C.), Alfried-Krupp Hospital, Essen; Department of Neuroradiology (H.H., E.H.), Klinikum Stuttgart, Germany; Department of Neuroradiology (A.G.), Medical University of Innsbruck, Austria; Department for Diagnostic and Interventional Neuroradiology (F.D.), University of Munich (LMU), Campus Grosshadern; Department of Neuroradiology (O.N., M.W.), RWTH Aachen University; Diagnostic and Interventional Neuroradiology (G.B.), Eberhard Karls University Tuebingen; Department of Radiology and Neuroradiology (A.W.), University Hospital Knappschaftskrankenhaus Bochum Langendreer; Department of Neuroradiology (D.K.), University Hospital Carl Gustav Carus, Dresden7; Department of Neuroradiology (U.Y.), Saarland University Hospital, Homburg, Germany; ASST Valcamonica (A.M.), Ospedale di Esine, UOSD Neurologia, Esine, Italy; Division of Neuroradiology and Musculoskeletal Radiology (W.M.), Department of Biomedical Imaging and Image-Guided Therapy, and Department of Biomedical Imaging and Image-Guided Therapy (R.N.), Division of Cardiovascular and Interventional Radiology, Medical University of Vienna, Austria; Department of Radiology and Neuroradiology (U.J.-K.), University Hospital of Schleswig-Holstein, Kiel; Section of Neuroradiology (M.B.), University of Ulm, Guenzburg; Department for Neuroradiology (S.S.), University Hospital Leipzig; Department of Neuroradiology (O.B.), University Hospital of Magdeburg; Department of Diagnostic and Interventional Neuroradiology (F.G.), Hannover Medical School, Germany; Institute of Neuroradiology (J.T.), Kepler University Hospital, Johannes Kepler University Linz, Austria; Institute of Neuroradiology (B.T.), University Hospital Duesseldorf; Department of Neuroradiology at Heidelberg University Hospital (M.M.); Department of Radiology (C.W.), University Hospital Regensburg; Department of Neuroradiology (P.S., A. Kemmling), University Hospital of Luebeck, Germany; Department of Neurology (P.L.M.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Child Neurology (S.L.), Department of Neurology, Stanford University, CA; Department of Neuroradiology (M.S.), University Hospital of Cologne; Department of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), University Hospital Essen, University of Duisburg-Essen; Institute of Epidemiology and Social Medicine (A. Karch, N.R.), University of Muenster; and Department of Radiology, University of Munich (LMU) (M.W.), Campus Grosshadern, Germany.

Objective: To determine whether thrombectomy is safe in children up to 24 hours after onset of symptoms when selected by mismatch between clinical deficit and infarct.

Methods: A secondary analysis of the Save ChildS Study (January 2000-December 2018) was performed, including all pediatric patients (<18 years) diagnosed with arterial ischemic stroke who underwent endovascular recanalization at 27 European and United States stroke centers. Patients were included if they had a relevant mismatch between clinical deficit and infarct.

Results: Twenty children with a median age of 10.5 (interquartile range [IQR] 7-14.6) years were included. Of those, 7 were male (35%), and median time from onset to thrombectomy was 9.8 (IQR 7.8-16.2) hours. Neurologic outcome improved from a median Pediatric NIH Stroke Scale score of 12.0 (IQR 8.8-20.3) at admission to 2.0 (IQR 1.2-6.8) at day 7. Median modified Rankin Scale (mRS) score was 1.0 (IQR 0-1.6) at 3 months and 0.0 (IQR 0-1.0) at 24 months. One patient developed transient peri-interventional vasospasm; no other complications were observed. A comparison of the mRS score to the mRS score in the DAWN and DEFUSE 3 trials revealed a higher proportion of good outcomes in the pediatric compared to the adult study population.

Conclusions: Thrombectomy in pediatric ischemic stroke in an extended time window of up to 24 hours after onset of symptoms seems safe and neurologic outcomes are generally good if patients are selected by a mismatch between clinical deficit and infarct.

Classification Of Evidence: This study provides Class IV evidence that for children with acute ischemic stroke with a mismatch between clinical deficit and infarct size, thrombectomy is safe.
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http://dx.doi.org/10.1212/WNL.0000000000011107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884981PMC
January 2021

In the borderland of multifocal motor neuropathy and chronic inflammatory demyelinating polyradiculopathy.

Neurol Sci 2021 Mar 19;42(3):1131-1134. Epub 2020 Oct 19.

Institute of Neuroradiology, Kepler University Hospital, Linz, Austria.

Chronic inflammatory demyelinating polyradiculopathy (CIDP) and multifocal motor neuropathy (MMN) are seen as distinct entities with marked differences in pathophysiology and clinical, laboratory, and imaging features. We report a patient with an immune-mediated neuropathy in the borderland of CIDP and MMN, whose magnetic resonance imaging and cerebrospinal fluid (CSF) features strongly resembled CIDP, while the clinical course and treatment response suggested the diagnosis of MMN without conduction blocks. There is strong evidence that MMN is not a variant of CIDP and that these conditions can be separated pathologically. Our case report widens the spectrum of MMN presentations, indicating the existence of a clinical overlap syndrome of MMN and CIDP, and emphasizing the need for more precise criteria regarding CSF and nerve root imaging abnormalities in the differentiation of chronic immune-mediated neuropathies.
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http://dx.doi.org/10.1007/s10072-020-04804-9DOI Listing
March 2021

De novo arteriovenous shunts after endovascular cure of cerebrospinal macro arteriovenous fistulas. A role for the vasa vasorum?

J Neuroradiol 2021 Mar 27;48(2):127-131. Epub 2020 Jun 27.

Department of Diagnostic and Interventional Neuroradiology, Hôpital Foch, Suresnes, France. Electronic address:

Background And Purpose: Macro-arteriovenous fistulas (MAVFs) are arteriovenous shunts draining into a giant venous ectasia. They can be treated by surgery or embolisation. Angiographic controls are usually performed rapidly after treatment in order to prove the cure of the lesion but no long term angiographies are generally scheduled. We wanted to control the stabilities of such lesions at follow-up.

Method: Clinical history and imaging of ninety-five patients with high flow shunts draining into venous ectasias (MAVFs, Vein of Galen malformations and dilatations) were reviewed.

Results: De novo arteriovenous shunts related to angiogenesis involving vasa vasorum developed in three patients with MAVFs at various intervals. Genetic underlying conditions as HHT or RASA 1 mutations were suspected in each patient.

Conclusions: Neo-angiogenesis can occur after cure of MAVFs. Long term imaging follow-ups should be considered as the natural history of such recurrent shunts is currently unknown.
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http://dx.doi.org/10.1016/j.neurad.2020.06.004DOI Listing
March 2021

Sex-Specific Differences in Primary CNS Lymphoma.

Cancers (Basel) 2020 Jun 16;12(6). Epub 2020 Jun 16.

Division of Neuropathology & Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.

Sex-specific differences have been increasingly recognized in many human diseases including brain cancer, namely glioblastoma. Primary CNS lymphoma (PCNSL) is an exceedingly rare type of brain cancer that tends to have a higher incidence and worse outcomes in male patients. Yet, relatively little is known about the reasons that contribute to these observed sex-specific differences. Using a population-representative cohort of patients with PCNSL with dense magnetic resonance (MR) imaging and digital pathology annotation ( = 74), we performed sex-specific cluster and survival analyses to explore possible associations. We found three prognostically relevant clusters for females and two for males, characterized by differences in (i) patient demographics, (ii) tumor-associated immune response, and (iii) MR imaging phenotypes. Upon a multivariable analysis, an enhanced FoxP3+ lymphocyte-driven immune response was associated with a shorter overall survival particularly in female patients (HR 1.65, = 0.035), while an increased extent of contrast enhancement emerged as an adverse predictor of outcomes in male patients (HR 1.05, < 0.01). In conclusion, we found divergent prognostic constellations between female and male patients with PCNSL that suggest differential roles of tumor-associated immune response and MR imaging phenotypes. Our results further underline the importance of continued sex-specific analyses in the field of brain cancer.
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http://dx.doi.org/10.3390/cancers12061593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352658PMC
June 2020

Does Device Selection Impact Recanalization Rate and Neurological Outcome?: An Analysis of the Save ChildS Study.

Stroke 2020 04 2;51(4):1182-1189. Epub 2020 Mar 2.

Institute of Neuroradiology, University Hospital Duesseldorf, Germany (B.T.).

Background and Purpose- The recent Save ChildS study provides multicenter evidence for the use of mechanical thrombectomy in children with large vessel occlusion arterial ischemic stroke. However, device selection for thrombectomy may influence rates of recanalization, complications, and neurological outcomes, especially in pediatric patients of different ages. We, therefore, performed additional analyses of the Save ChildS data to investigate a possible association of different thrombectomy techniques and devices with angiographic and clinical outcome parameters. Methods- The Save ChildS cohort study (January 2000-December 2018) analyzed data from 27 European and United States stroke centers and included all pediatric patients (<18 years), diagnosed with arterial ischemic stroke who underwent endovascular recanalization. Patients were grouped into first-line contact aspiration (A Direct Aspiration First Pass Technique [ADAPT]) and non-ADAPT groups as well as different stent retriever size groups. Associations with baseline characteristics, recanalization rates (modified Treatment in Cerebral Infarction), complication rates, and neurological outcome parameters (Pediatric National Institutes of Health Stroke Scale after 24 hours and 7 days; modified Rankin Scale and Pediatric Stroke Outcome Measure at discharge, after 6 and 24 months) were investigated. Results- Seventy-three patients with a median age of 11.3 years were included. Currently available stent retrievers were used in 59 patients (80.8%), of which 4×20 mm (width×length) was the most frequently chosen size (36 patients =61%). A first-line ADAPT approach was used in 7 patients (9.6%), and 7 patients (9.6%) were treated with first-generation thrombectomy devices. In this study, a first-line ADAPT approach was neither associated with the rate of successful recanalization (ADAPT 85.7% versus 87.5% No ADAPT) nor with the complication rate or the neurological outcome. Moreover, there were no associations of stent retriever sizes with rates of recanalization, complication rates, or outcome parameters. Conclusions- Our study suggests that neurological outcomes are generally good regardless of any specific device selection and suggests that it is important to offer thrombectomy in eligible children regardless of technique or device selection. Registration- URL: https://www.drks.de/; Unique identifier: DRKS00016528.
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http://dx.doi.org/10.1161/STROKEAHA.119.028221DOI Listing
April 2020

Spontaneous Intracerebral Hemorrhage Due to Delta Storage Pool Disease in a Patient on a Serotonin-Norepinephrine Reuptake Inhibitor.

Front Neurol 2019 26;10:1257. Epub 2019 Nov 26.

Department of Neurology 1, Kepler University Hospital, Medical Faculty of the Johannes Kepler University Linz, Linz, Austria.

We report a case of spontaneous intracerebral hemorrhage (sICH) due to delta storage pool disease in a 60-year-old female on a serotonin-norepinephrine reuptake inhibitor (SNRI). Increased susceptibility to SNRI-effects on hemostasis was due to a genetic disposition mediated by a polymorphism of the SLC6A4 gene coding for the human serotonin transporter (SERT). Pathophysiological and clinical implications of these findings are discussed.
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http://dx.doi.org/10.3389/fneur.2019.01257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902021PMC
November 2019

Feasibility, Safety, and Outcome of Endovascular Recanalization in Childhood Stroke: The Save ChildS Study.

JAMA Neurol 2020 01;77(1):25-34

Institute of Neuroradiology, University Hospital Duesseldorf, Duesseldorf, Germany.

Importance: Randomized clinical trials have shown the efficacy of thrombectomy of large intracranial vessel occlusions in adults; however, any association of therapy with clinical outcomes in children is unknown.

Objective: To evaluate the use of endovascular recanalization in pediatric patients with arterial ischemic stroke.

Design, Setting, And Participants: This retrospective, multicenter cohort study, conducted from January 1, 2000, to December 31, 2018, analyzed the databases from 27 stroke centers in Europe and the United States. Included were all pediatric patients (<18 years) with ischemic stroke who underwent endovascular recanalization. Median follow-up time was 16 months.

Exposures: Endovascular recanalization.

Main Outcomes And Measures: The decrease of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score from admission to day 7 was the primary outcome (score range: 0 [no deficit] to 34 [maximum deficit]). Secondary clinical outcomes included the modified Rankin scale (mRS) (score range: 0 [no deficit] to 6 [death]) at 6 and 24 months and rate of complications.

Results: Seventy-three children from 27 participating stroke centers were included. Median age was 11.3 years (interquartile range [IQR], 7.0-15.0); 37 patients (51%) were boys, and 36 patients (49%) were girls. Sixty-three children (86%) received treatment for anterior circulation occlusion and 10 patients (14%) received treatment for posterior circulation occlusion; 16 patients (22%) received concomitant intravenous thrombolysis. Neurologic outcome improved from a median PedNIHSS score of 14.0 (IQR, 9.2-20.0) at admission to 4.0 (IQR, 2.0-7.3) at day 7. Median mRS score was 1.0 (IQR, 0-1.6) at 6 months and 1.0 (IQR, 0-1.0) at 24 months. One patient (1%) developed a postinterventional bleeding complication and 4 patients (5%) developed transient peri-interventional vasospasm. The proportion of symptomatic intracerebral hemorrhage events in the HERMES meta-analysis of trials with adults was 2.79 (95% CI, 0.42-6.66) and in Save ChildS was 1.37 (95% CI, 0.03-7.40).

Conclusions And Relevance: The results of this study suggest that the safety profile of thrombectomy in childhood stroke does not differ from the safety profile in randomized clinical trials for adults; most of the treated children had favorable neurologic outcomes. This study may support clinicians' practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.
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http://dx.doi.org/10.1001/jamaneurol.2019.3403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802048PMC
January 2020

Risks and Benefits of Glioblastoma Resection in Older Adults: A Retrospective Austrian Multicenter Study.

World Neurosurg 2020 Jan 24;133:e583-e591. Epub 2019 Sep 24.

Department of Neurosurgery, University Hospital Munich, Ludwig-Maximilians-University, Munich, Germany.

Objective: To assess the prognostic profile, clinical outcome, treatment-associated morbidity, and treatment burden of elderly patients with glioblastoma (GBM) undergoing microsurgical tumor resection as part of contemporary treatment algorithms.

Methods: We retrospectively identified patients with GBM ≥65 years of age who were treated by resection at 2 neuro-oncology centers. Survival was assessed by Kaplan-Meier analyses; log-rank tests identified prognostic factors.

Results: The study population included 160 patients (mean age, 73.1 ± 5.1 years), and the median contrast-enhancing tumor volume was 31.0 cm. Biomarker analyses revealed O(6)-methylguanine-DNA methyltransferase-promoter methylation in 62.7% and wild-type isocitrate dehydrogenase in 97.5% of tumors. The median extent of resection (EOR) was 92.3%, surgical complications were noted in 10.0% of patients, and the median postoperative hospitalization period was 8 days. Most patients (60.0%) received adjuvant radio-/chemotherapy. The overall treatment-associated morbidity was 30.6%. The median progression-free and overall survival were 5.4 months (95% confidence interval [CI], 4.6-6.4 months) and 10.0 months (95% CI, 7.9-11.7 months). The strongest predictors for favorable outcome were patient age ≤73.0 years (P = 0.0083), preoperative Karnofsky Performance Status Scale score ≥80% (P = 0.0179), postoperative modified Rankin Scale score ≤1 (P < 0.0001), adjuvant treatment (P < 0.0001), and no treatment-associated morbidity (P = 0.0478). Increased EOR did not correlate with survival (P = 0.5046), but correlated significantly with treatment-associated morbidity (P = 0.0031).

Conclusions: Clinical outcome for elderly patients with GBM remains limited. Nonetheless, the observed treatment-associated morbidity and treatment burden were moderate in the patients, and patient age and performance status remained the strongest predictors for survival. The risks and benefits of tumor resection in the age of biomarker-adjusted treatment concepts require further prospective evaluation.
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http://dx.doi.org/10.1016/j.wneu.2019.09.097DOI Listing
January 2020

About our paper "Intradural spinal cord arteriovenous shunts in the pediatric population: natural history, endovascular management and follow-up".

Childs Nerv Syst 2019 08 18;35(8):1281. Epub 2019 Jun 18.

Diagnostic and Interventional Neuroradiology, Foch Hospital, 40 rue Worth, 92150, Suresnes, France.

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http://dx.doi.org/10.1007/s00381-019-04249-2DOI Listing
August 2019

Future Neuroradiology.

Clin Neuroradiol 2019 Jun;29(2):187-188

Institut für Neuroradiologie, Kepler Universitätsklinikum, Linz, Austria.

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http://dx.doi.org/10.1007/s00062-019-00796-yDOI Listing
June 2019

Intradural spinal cord arteriovenous shunts in the pediatric population: natural history, endovascular management, and follow-up.

Childs Nerv Syst 2019 06 7;35(6):945-955. Epub 2019 Mar 7.

Diagnostic and Interventional Neuroradiology Department, Foch Hospital, 40 rue Worth, 92150, Suresnes, France.

Background: Intradural spinal cord arteriovenous shunts represent a rare entity, particularly in the pediatric population, and clinical diagnosis can be challenging.

Methods: We report the analysis of clinical, angioarchitectural, procedural, and follow-up data in a population of 36 children managed by our team between 2002 and 2017.

Results: Hemorrhage occurred in 26 children (72%). Age at onset was 9.22 ± 3.65 years. Lesions were located at the thoracic level in 16 cases, at the cervical level in 15 cases, and the thoraco-lumbar region in 5 cases. A genetic or metameric syndrome was associated in 18 children (50%). Glue embolization provided complete occlusion in 5 children, subtotal in 7, and extensive in 14 without intraprocedural complications. We observed clinical normalization in 11 children, improvement in 11 cases, and stability in 3. Four children worsened during the follow-up, and one child died.

Conclusions: Endovascular staged glue embolization performed in experienced centers is safe in the treatment of pediatric intradural spinal cord arteriovenous shunts. Clinical and neuroradiological follow-up is mandatory, especially for pediatric patients.
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http://dx.doi.org/10.1007/s00381-019-04108-0DOI Listing
June 2019

Identification of pathogenic YY1AP1 splice variants in siblings with Grange syndrome by whole exome sequencing.

Am J Med Genet A 2019 02 17;179(2):295-299. Epub 2018 Dec 17.

Department of Human Genetics, University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.

Grange syndrome is an autosomal recessive condition characterized by arterial occlusions and hypertension. Syndactyly, brachydactyly, bone fragility, heart defects, and learning disabilities have also been reported. Loss-of-function variants in YY1AP1 have only recently been associated with Grange syndrome. YY1AP1 encodes for the transcription coactivator yin yang 1-associated protein 1 which regulates smooth muscle cell proliferation and differentiation. We here report on three siblings with steno-occlusive arterial disorder and syndactyly in two of them. Whole exome sequencing including near-splice regions led to the identification of two intronic YY1AP1 variants which were predicted to interfere with normal splicing. Sanger sequencing demonstrated compound-heterozygosity in all affected siblings. RT-PCR analyses confirmed skipping of exon 6 on one allele and exonization of 22 bp in intron 6 on the other. This is the first report of biallelic YY1AP1 variants in noncoding regions and just the second family with multiple affected siblings. Therefore, our report further delineates the phenotypic spectrum of Grange syndrome.
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http://dx.doi.org/10.1002/ajmg.a.60700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590215PMC
February 2019

The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space.

Nat Med 2018 10 27;24(10):1611-1624. Epub 2018 Aug 27.

Department of Internal Medicine, Neuromed Campus Wagner-Jauregg, Kepler University Hospital, Johannes Kepler University of Linz, Linz, Austria.

Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples, and we validate bisulfite sequencing as a multipurpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. On the basis of these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data collected as part of routine clinical practice.
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http://dx.doi.org/10.1038/s41591-018-0156-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181207PMC
October 2018

Anti-NMDA receptor encephalitis triggered by epilepsy surgery.

J Neurol 2018 Jul 30;265(7):1708-1710. Epub 2018 May 30.

Department of Neurology 1, Kepler University Hospital, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020, Linz, Austria.

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http://dx.doi.org/10.1007/s00415-018-8918-4DOI Listing
July 2018

The Neuroform Atlas stent to assist coil embolization of intracranial aneurysms: a multicentre experience.

J Neurointerv Surg 2018 Dec 20;10(12):1192-1196. Epub 2018 Apr 20.

Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.

Objective: To assess the clinical safety and efficacy of the Atlas microstent in stent-assisted coil embolization of wide-necked intracranial aneurysms.

Methods: Single-center observational study in 36 patients (24 female, 12 male, mean age 56 years) with 37 aneurysms for the endovascular treatment of wide-necked aneurysms. After giving informed consent, patients were included according to the following criteria: aneurysm dome-to-neck ratio <2 or neck diameter >4 mm, and a parent vessel diameter of ≤4.5 mm. Primary endpoint for clinical safety was absence of death, absence of major or minor stroke, and absence of transient ischemic attack. Primary endpoint for treatment efficacy was complete angiographic occlusion according to the Raymond-Roy occlusion classification (RROC) immediately after the procedure.

Results: In 36/37 (97%) cases, the primary endpoint of safety was reached, one patient had a transitory ischemic attack which completely resolved until discharge. In 31/37 (84%) cases, complete occlusion (RROC 1) was reached, and in 6/36 (17%), a residual neck remained (RROC 2). A sequential approach (first stent, then coiling through the same catheter) was used in 21 cases; the other 16 were treated with the jailing technique. Deployment was technically successful in all cases. Follow-up at a median of 6.1 months was available for 29/37 (78%) aneurysms and showed complete occlusion in 27/29 aneurysms (93%) and a neck remnant in 2 cases (7%).

Conclusion: Deployment of the Neuroform Atlas microstent is a safe and effective method for the treatment of intracranial wide-necked aneurysms.
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http://dx.doi.org/10.1136/neurintsurg-2017-013516DOI Listing
December 2018

Virtual Cerebral Aneurysm Clipping with Real-Time Haptic Force Feedback in Neurosurgical Education.

World Neurosurg 2018 Apr 11;112:e313-e323. Epub 2018 Jan 11.

Department of Neurosurgery, Kepler University Hospital, Linz, Austria.

Objective: Realistic, safe, and efficient modalities for simulation-based training are highly warranted to enhance the quality of surgical education, and they should be incorporated in resident training. The aim of this study was to develop a patient-specific virtual cerebral aneurysm-clipping simulator with haptic force feedback and real-time deformation of the aneurysm and vessels.

Methods: A prototype simulator was developed from 2012 to 2016. Evaluation of virtual clipping by blood flow simulation was integrated in this software, and the prototype was evaluated by 18 neurosurgeons. In 4 patients with different medial cerebral artery aneurysms, virtual clipping was performed after real-life surgery, and surgical results were compared regarding clip application, surgical trajectory, and blood flow.

Results: After head positioning and craniotomy, bimanual virtual aneurysm clipping with an original forceps was performed. Blood flow simulation demonstrated residual aneurysm filling or branch stenosis. The simulator improved anatomic understanding for 89% of neurosurgeons. Simulation of head positioning and craniotomy was considered realistic by 89% and 94% of users, respectively. Most participants agreed that this simulator should be integrated into neurosurgical education (94%). Our illustrative cases demonstrated that virtual aneurysm surgery was possible using the same trajectory as in real-life cases. Both virtual clipping and blood flow simulation were realistic in broad-based but not calcified aneurysms. Virtual clipping of a calcified aneurysm could be performed using the same surgical trajectory, but not the same clip type.

Conclusions: We have successfully developed a virtual aneurysm-clipping simulator. Next, we will prospectively evaluate this device for surgical procedure planning and education.
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http://dx.doi.org/10.1016/j.wneu.2018.01.042DOI Listing
April 2018

Effective cerebrovascular thrombectomy requires well-organized structures : Real world experiences of a regional stroke network between 2012-2015.

Wien Klin Wochenschr 2017 Feb 20;129(3-4):96-101. Epub 2017 Jan 20.

Department of Neurology, Neuromed Campus - Kepler University Hospital, Wagner Jauregg Weg 15, 4020, Linz, Austria.

Background: The objective of this study was to analyse the Neurothrombectomy Network registry of the Neuromed Campus (NMC) of the Kepler University Hospital in Linz (Austria). The data were compared to the results of recently published thrombectomy trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, REVASCAT and THRACE).

Methods: We retrospectively studied 246 patients with acute ischemic stroke who underwent thrombectomy between January 2012 and December 2015 at the NMC in Upper Austria. The main outcome measures were modified Rankin scale (mRS) score 0-2 at 90 days, all-cause mortality and stroke or thrombectomy-related mortality at discharge, as well as 90 days postdischarge.

Results: The median age was 70.4 years (IQR 59.9-76.9) and the median NIHSS at admission 16 (IQR 13-20). The thrombolysis in cerebral infarction (TICI) scale 2b-3 recanalization was achieved in 87.4%, 11.0% of the patients died in hospital and an additional 6.1% within 90 days after discharge. After 90 days, 56.5% had a mRS score 0-2.

Conclusions: These data suggest that the positive results of thrombectomy reported in several randomized controlled studies can be achieved in routine clinical practice; therefore, the setting of an organized, regional stroke network proved an effective and appropriate method for delivering regional thrombectomy stroke treatment.
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http://dx.doi.org/10.1007/s00508-016-1163-xDOI Listing
February 2017

Interactive knowledge discovery with the doctor-in-the-loop: a practical example of cerebral aneurysms research.

Brain Inform 2016 Sep 24;3(3):133-143. Epub 2016 Feb 24.

Research Unit HCI-KDD, Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Graz, Austria.

Established process models for knowledge discovery find the domain-expert in a customer-like and supervising role. In the field of biomedical research, it is necessary to move the domain-experts into the center of this process with far-reaching consequences for both their research output and the process itself. In this paper, we revise the established process models for knowledge discovery and propose a new process model for domain-expert-driven interactive knowledge discovery. Furthermore, we present a research infrastructure which is adapted to this new process model and demonstrate how the domain-expert can be deeply integrated even into the highly complex data-mining process and data-exploration tasks. We evaluated this approach in the medical domain for the case of cerebral aneurysms research.
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http://dx.doi.org/10.1007/s40708-016-0038-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999567PMC
September 2016

Safety of endovascular treatment in acute stroke patients taking oral anticoagulants.

Int J Stroke 2017 06 5;12(4):412-415. Epub 2016 Nov 5.

1 Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany.

Background The endovascular treatment of acute cerebral ischemia has been proven beneficial without major safety concerns. To date, the role of endovascular treatment in patients treated with oral anticoagulants, which may be associated with periprocedural intracranial bleeding, remains uncertain. Aims The objective of the current analysis is to evaluate the safety of endovascular treatment in patients treated with oral anticoagulants. Methods The ENDOSTROKE-Registry is a commercially independent, prospective observational study in 12 stroke centers in Germany and Austria collecting pre-specified variables about endovascular stroke therapy. Results Data from 815 patients (median age 70 (interquartile range (IQR) 20), 57% male) undergoing endovascular treatment with known anticoagulation status were analyzed. A total of 85 (median age 76 (IQR 8), 52% male) patients (10.4%) took vitamin-K-antagonists prior to endovascular treatment. Anticoagulation status as measured with international normalized ratio was above 2.0 in 31 patients. Intracranial hemorrhage occurred in 11.8% of patients taking vitamin-K-antagonists compared to no-vitamin-K-antagonists (12.2%, p = 0.909). After adjustment for confounding factors which were unbalanced at univariate level such as NIHSS and age, anticoagulation status was not found to significantly influence clinical outcome (modified Rankin Scale 3-6) and occurrence of intracranial hemorrhage in a multivariate logistic regression analysis. Conclusion Prior use of vitamin-K-antagonists was not associated with a higher rate of periprocedural intracranial hemorrhage after endovascular treatment or worse outcome. Endovascular treatment should be considered as an important treatment option in patients taking vitamin-K-antagonists.
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http://dx.doi.org/10.1177/1747493016677986DOI Listing
June 2017

A case of variably protease-sensitive prionopathy treated with doxycyclin.

J Neurol Neurosurg Psychiatry 2015 Jul 9;86(7):816-8. Epub 2015 Jan 9.

Institute of Neurology, Medical University of Vienna and Austrian Reference Centre for Human Prion Diseases, Vienna, Austria.

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http://dx.doi.org/10.1136/jnnp-2014-309871DOI Listing
July 2015

Mechanical recanalization in basilar artery occlusion: the ENDOSTROKE study.

Ann Neurol 2015 Mar 13;77(3):415-24. Epub 2015 Jan 13.

Department of Neurology, Goethe University, Frankfurt, Germany.

Objective: A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion.

Methods: ENDOSTROKE is an investigator-initiated multicenter registry for patients undergoing EVT. This analysis includes 148 consecutive patients with BA occlusion, with 59% having received intravenous thrombolysis prior to EVT. Recanalization (defined as Thrombolysis in Cerebral Infarction [TICI] score 2b-3) and collateral status (using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral grading system) were assessed by a blinded core laboratory. Good (moderate) outcome was defined as a modified Rankin Scale score of 0 to 2 (0-3) assessed after at least 3 months (median time to follow-up = 120 days).

Results: Thirty-four percent had good and 42% had moderate clinical outcome; mortality was 35%. TICI 2b-3 recanalization was achieved by 79%. Age, hypertension, National Institutes of Health Stroke Scale scores, collateral status, and the use of magnetic resonance imaging prior to EVT predicted clinical outcome, the latter 3 remaining independent predictors in multivariate analysis. Independent predictors of recanalization were better collateral status and the use of a stent retriever. However, recanalization did not significantly predict clinical outcome.

Interpretation: Beside initial stroke severity, the collateral status predicts clinical outcome and recanalization in BA occlusion. Our data suggest that the use of a stent retriever is associated with high recanalization rates, but recanalization on its own does not predict outcome. The role of other modifiable factors, including the choice of pretreatment imaging modality and time issues, warrants further investigation.
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http://dx.doi.org/10.1002/ana.24336DOI Listing
March 2015

Age dependency of successful recanalization in anterior circulation stroke: the ENDOSTROKE study.

Cerebrovasc Dis 2013 23;36(5-6):437-45. Epub 2013 Nov 23.

Department of Neurology, Goethe University, Frankfurt, Germany.

Background: Clinical outcome after endovascular stroke therapy (EVT) for proximal anterior circulation stroke is often disappointing despite high recanalization rates. The ENDOSTROKE study aims to determine predictors of clinical outcome in patients undergoing EVT. Here we focus on the impact of age and recanalization on proximal middle cerebral artery (M1-MCA) or carotid T occlusion.

Methods: ENDOSTROKE is an investigator-initiated, industrially independent multicenter registry launched in January, 2011, for consecutive patients undergoing EVT for large-vessel stroke. This analysis focuses on patients treated in 11 academic and nonacademic stroke centers with angiographically proven M1-MCA (n = 259) or carotid T occlusion (n = 103). Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) score 2 or 3, and in patients with available Thrombolysis in Cerebral Ischemia (TICI) data (n = 309) as TICI scores 2b-3. Good outcome was defined as modified Rankin Scale (mRS) score of 0-2 assessed after 3 months or later.

Results: The median age was 68 years (25th and 75th percentiles: 56, 76 years), and the median National Institutes of Health Stroke Scale (NIHSS) score at admission was 16 (13, 19); 41% of the patients had a favorable (mRS scores 0-2), and 59% had an unfavorable (mRS scores 3-6) outcome; 83% reached TIMI 2-3 flow. Independent predictors of good outcome were younger age, lower initial NIHSS scores, TIMI 2/3 recanalization and lower serum glucose levels. Outcome was highly dependent on patients' age: 60% of the patients within the lowest age quartile (range: 18-56 years) experienced good clinical outcome, decreasing stepwise over 47% (57-68 years) and 37% (69-76 years) to 17% in the highest age quartile (77-94 years). The proportion of patients with poor clinical outcome despite TIMI 2/3 recanalization ('futile recanalization') increased dramatically from only 29% in the lowest age quartile over 34% and 40% (2nd and 3rd age quartiles) up to 53% in the highest age quartile. Results were similar in patients with available TICI scores, with 'futile recanalization' rates increasing from 24% to 46% (lowest to highest age quartile).

Conclusions: This study emphasizes the dramatic impact of patients' age on outcome in EVT for M1-MCA or carotid T occlusion, even in the presence of recanalization. Reasons for this age-related decrease in clinically successful recanalization rates urgently need clarification and may comprise patient-related factors (age-related increase in cardioembolic strokes, collateral status, comorbidities) as well as periprocedural issues (tortuous vessel anatomy in the elderly, age-dependent negative impact of general anesthesia in EVT).
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http://dx.doi.org/10.1159/000356213DOI Listing
October 2014

Endovascular thrombectomy for acute ischemic stroke patients anticoagulated with dabigatran.

Clin Neurol Neurosurg 2013 Oct 3;115(10):2257-9. Epub 2013 Aug 3.

Department of Neurology, Landes-Nervenklinik Wagner-Jauregg, Linz, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.clineuro.2013.07.017DOI Listing
October 2013

Periprocedural aspects in mechanical recanalization for acute stroke: data from the ENDOSTROKE registry.

Neuroradiology 2013 Sep 28;55(9):1143-51. Epub 2013 Jun 28.

Department of Neurology, Goethe University, Schleusenweg 2-16, 60528, Frankfurt/Main, Germany.

Introduction: The ENDOSTROKE registry aims to accompany the spreading use of endovascular stroke treatment (EVT) in academic and non-academic hospitals. This analysis focuses on preprocedural imaging, patient handling and referral, as well as on different treatment modalities in mechanical recanalization.

Methods: Data for this study were from observational registry study in 12 stroke centers in Germany and Austria with online assessment of prespecified variables concerning endovascular stroke therapy.

Results: Data from 734 patients undergoing EVT were analyzed. Preferred imaging modality prior to EVT was CT (83 %) and CTA (78 %). In 95 %, EVT was performed under general anesthesia. In 55 % of patients, a combination of intravenous (IV) thrombolysis and EVT was used, followed by pure EVT (25 %), intra-arterial (IA) thrombolysis plus EVT (13 %) and IV + IA thrombolysis plus EVT (7 %). Intrahospital time delay until start of EVT was 91 and 99 min in anterior and vertebrobasilar circulation stroke, respectively. Average duration of EVT was 60 min. Overall thrombolysis in myocardial infarction grade 2/3 recanalization rate was 85 %. Stent retrievers were used in 75 %, being associated with higher recanalization rates than non-stent retrievers. Hemorrhagic complications (symptomatic and asymptomatic) occurred in 12 %. Overall vessel occlusion time was approximately 60 min longer in patients being referred from a primary care hospital for EVT.

Conclusion: This study gives an overview of procedure-related factors in current EVT practice. It gives estimates on preprocedural imaging modalities, periprocedural handling, and treatment combinations used for EVT. Patient referral for EVT from primary care hospitals is associated with longer vessel occlusion times.
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http://dx.doi.org/10.1007/s00234-013-1219-9DOI Listing
September 2013

Complication rates using balloon-expandable and self-expanding stents for the treatment of intracranial atherosclerotic stenoses : analysis of the INTRASTENT multicentric registry.

Neuroradiology 2012 Jan 11;54(1):43-50. Epub 2011 Jan 11.

Department of Neuroradiology, Alfried Krupp Krankenhaus, Alfried Krupp Strasse 21, 45131, Essen, Germany.

Introduction: Using balloon-expandable stents (BES) for treatment of intracranial stenoses, high inflation pressures and rigidity of the device are regarded as major drawbacks limiting feasibility and safety of the procedure. Self-expanding stents (SES) were developed to facilitate lesion access and to allow for less aggressive dilatation. We analyzed data of the INTRASTENT multicentric registry to assess whether self-expanding stents significantly reduced peri-interventional complication rates.

Methods: Records of intracranial stent procedures were entered consecutively into the registry. Datasets were divided into two groups according to the type of stent used. For outcome measurement, we chose three categories: TIA/minor stroke [modified Rankin score (mRS) <2], disabling stroke, and patient death. Clinical outcome was compared between BES and SES. We analyzed types of adverse events occurring in each group in addition.

Results: Of 409 atherosclerotic lesions, 254 were treated with BES and 155 with SES. Technical success rates were 97.6% and 98.7%, respectively. Adverse event rates were 4.9%, 3.7%, and 0.8% for TIA/nondisabling stroke, disabling stroke, and death in the BES group compared with 5.3%, 6.0%, and 4.0% in the SES group. The differences were not statistically significant. We observed more perforator strokes after use of BES, but thromboembolic events occurred more often in the SES treatment group.

Conclusion: Data of the INTRASTENT registry do not support the hypothesis that introduction of SES lowered the overall complication rate of intracranial stent procedures. There might be an advantage using self-expanding stents in vessel segments with important perforating arteries.
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http://dx.doi.org/10.1007/s00234-010-0826-yDOI Listing
January 2012

In-hospital complication rates after stent treatment of 388 symptomatic intracranial stenoses: results from the INTRASTENT multicentric registry.

Stroke 2010 Mar 14;41(3):494-8. Epub 2010 Jan 14.

Department of Neuroradiology, University of Frankfurt, Schleusenweg 2-16, 60528 Frankfurt, Germany.

Background And Purpose: Stenting is increasingly used as an adjunct to medical therapy in symptomatic intracranial stenoses. High periprocedural adverse event rates are one of the limitations of endovascular treatment. Data from the INTRASTENT multicentric registry should demonstrate in-hospital complications at the current stage of clinical development of the stent procedure.

Methods: Participating centers entered the records of all their consecutive intracranial stent procedures into the database. To determine the clinical outcome in the acute phase, we distinguished transient ischemic attack/nondisabling stroke (modified Rankin Scale <2), disabling stroke, death, and intracranial hemorrhage as clinical complications and analyzed whether they were associated with patient- or stenosis-related risk factors.

Results: Data from 372 patients with 388 stenoses proved 4.8% disabling strokes and 2.2% deaths. Transient or minor events were detected in 5.4% of the cases. Hemorrhagic events (3.5%) occurred more frequently after treatment of middle cerebral artery stenoses (P=0.004) and were associated with significantly higher morbidity and mortality rates. Ischemic strokes by compromise of perforating branches were detected mainly in the posterior circulation. However, the overall rate of severe adverse events was not dependent from location, degree, and morphology of the stenosis or from patient's age, gender, vascular risk factors, or type of qualifying event.

Conclusions: The complication rates within the registry are within the limits of previously published data. Severe adverse events were equally distributed between potential risk groups with similar rates but different types of main complications in the anterior and posterior circulation.
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http://dx.doi.org/10.1161/STROKEAHA.109.568063DOI Listing
March 2010

Capillary telangiectasias of the pons. Does diffusion-weighted MR increase diagnostic accuracy?

Eur J Radiol 2010 Jun 23;74(3):e112-6. Epub 2009 May 23.

Institute of Diagnostic Radiology, University of Regensburg, Germany.

Background And Purpose: Capillary telangiectasias are benign lesions of the brainstem which are sometimes difficult to distinguish from other lesions in standard MRI. The purpose of this study was to evaluate if diffusion-weighted imaging (DWI) could help to improve diagnostic accuracy.

Methods: 148 MR examinations of patients with pontine lesions were evaluated retrospectively and revealed capillary telangiectasia (n=18), presumed microvascular disease (n=20), encephalitis disseminata (n=21), pontine myelinolysis (n=16), tumor (n=20), acute infarction (n=20), subacute infarction (n=13) and chronic infarction (n=20). All patients were examined using identical measurement parameters for DWI, Fluid attenuated inversion recovery, T2-weighted turbo spin-echo, and T1-weighted spin-echo before and after application of contrast agent in transverse orientation.

Results: All capillary telangiectasias showed low signal intensity in DWI and significant contrast enhancement after application of gadolinium. Hypointense signal on DWI was very rare for the remaining lesions: only 1 pontine myelinolysis, 1 tumor, 4 subacute infarctions, and 19 chronic infarctions also revealed low signal intensity on DWI. The combination of high signal intensity on T1-weighted post-contrast images and low signal intensity on DWI was found for all capillary telangiectasias, but only for 1/20 tumor and for 4/13 subacute infarctions. These lesions could be differentiated by their clinical course and/or MRI follow-up examinations. The results of the visual assessment were confirmed by quantitative evaluation.

Conclusion: DWI seems to be a useful adjunct for the diagnosis of capillary telangiectasias which will facilitate the differential diagnosis concerning tumorous, inflammatory and ischemic lesions.
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http://dx.doi.org/10.1016/j.ejrad.2009.04.036DOI Listing
June 2010

Does carotid stent cell design matter?

Stroke 2008 Mar 31;39(3):905-9. Epub 2008 Jan 31.

Department of Angiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Background And Purpose: Carotid stent cell design has recently been suggested to be a determinant of periprocedural and early postprocedural neurologic complications. We investigated the impact of closed- versus open-cell stent design on neurologic adverse events and mortality after carotid artery stenting.

Methods: We studied 1684 consecutive patients (1010 asymptomatic, 674 symptomatic) from 10 European centers who underwent carotid artery stenting with either closed-cell (n=859, 51%) or open-cell (n=825, 49%) design stents. Rates of transient ischemic attack, stroke, and death on the day of the procedure (acute events) and from day 1 to day 30 after the procedure (subacute events) were analyzed (95% CIs).

Results: Combined transient ischemic attack, stroke, or death rates, and stroke or death rates within 30 days of treatment were 6.1% (95% CI, 5.0 to 7.2) and 3.1% (95% CI, 2.3 to 3.9) for the closed-cell design versus 4.1% (95% CI, 3.2 to 5.0) and 2.4% (95% CI, 1.7 to 3.1) for the open-cell design stents (P=0.077, P=0.38), respectively, without significant differences in asymptomatic and symptomatic patients. By propensity-score-adjusted multivariable analysis, the open-cell carotid stent design was not associated with a differential risk for combined acute and subacute neurologic complications compared with closed-cell stents (adjusted odds ratio=0.84, P=0.53). When analyzed separately, the risk for acute events on the day of the procedure (adjusted odds ratio=0.83, P=0.57) and the risk for subacute events at days 1 to 30 (adjusted odds ratio=1.61, P=0.51) also were not significantly different between the groups.

Conclusions: Current data do not support the superiority of a specific carotid stent cell design with respect to neurologic complications, stroke, and mortality risk.
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http://dx.doi.org/10.1161/STROKEAHA.107.499145DOI Listing
March 2008
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