Publications by authors named "Götz Thomalla"

237 Publications

How Does SARS-CoV-2 Infection Affect Survival of Emergency Cardiovascular Patients? A Cohort Study From a German Insurance Claims Database.

Eur J Vasc Endovasc Surg 2021 Mar 12. Epub 2021 Mar 12.

Department of Neurology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Objective: A previous study revealed a preliminary trend towards higher in hospital mortality in patients admitted as an emergency with acute stroke during the COVID-19 pandemic in Germany. The current study aimed to further examine the possible impact of a confirmed SARS-CoV-2 infection on in hospital mortality.

Methods: This was a retrospective analysis of health insurance claims data from the second largest insurance fund in Germany, BARMER. Patients hospitalised for ST elevation (STEMI) and non-ST elevation (NSTEMI) myocardial infarction, acute limb ischaemia (ALI), aortic rupture, acute stroke, or transient ischaemic attack (TIA) between 1 January 2017, and 31 October 2020, were included. Admission rates per 10 000 insured and mortality were compared between March - June 2017 - 2019 (pre-COVID) and March - June 2020 (COVID). Mortality rates were determined by the occurrence of a confirmed SARS-CoV-2 infection.

Results: A total of 316 718 hospitalisations were included (48.7% female, mean 72.5 years), and 21 191 (6.7%, 95% CI 6.6% - 6.8%) deaths occurred. In hospital mortality increased during the COVID-19 pandemic when compared with the three previous years for patients with acute stroke from 8.3% (95% CI 8.0 - 8.5) to 9.6% (95% CI 9.1 - 10.2), while no statistically significant changes were observed for STEMI, NSTEMI, ALI, aortic rupture, and TIA. When comparing patients with confirmed SARS-CoV-2 infection (2.4%, 95% CI 2.3 - 2.5) vs. non-infected patients, a higher in hospital mortality was observed for acute stroke (12.4% vs. 9.0%), ALI (14.3% vs. 5.0%), and TIA (2.7% vs. 0.3%), while no statistically significant differences were observed for STEMI, NSTEMI, and aortic rupture.

Conclusion: This retrospective analysis of claims data has provided hints of an association between the COVID-19 pandemic and increased in hospital mortality in patients with acute stroke. Furthermore, confirmed SARS-CoV-2 infection was associated with increased mortality in patients with stroke, TIA, and ALI. Future studies are urgently needed to better understand the underlying mechanism and relationship between the new coronavirus and acute stroke.
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http://dx.doi.org/10.1016/j.ejvs.2021.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953451PMC
March 2021

Number of Retrieval Attempts Rather Than Procedure Time Is Associated With Risk of Symptomatic Intracranial Hemorrhage.

Stroke 2021 Apr 5:STROKEAHA120031242. Epub 2021 Apr 5.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. (M.E.M., C.B., G.B., H.L., R.M., J.F., F.F.).

Background And Purpose: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. A direct association between the number of device passes and the occurrence of symptomatic intracranial hemorrhage (SICH) has been suggested. This study represents an in-depth investigation of the hypothesis that >3 retrieval attempts is associated with an increased rate of SICH in a large multicenter patient cohort.

Methods: Two thousand six hundred eleven patients from the prospective German Stroke Registry were analyzed. Patients who received Endovascular therapy for acute large-vessel occlusion of the anterior circulation with known admission National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction, and number of retrieval passes were included. The primary outcome was defined as SICH. The secondary outcome was any type of radiologically confirmed intracranial hemorrhage within the first 24 hours. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers, as well as for confounders.

Results: Five hundred ninety-three patients fulfilled the inclusion criteria. The median number of retrieval passes was 2 [interquartile range, 1-3]. SICH occurred in 26 cases (4.4%), whereas intracranial hemorrhage was identified by neuroimaging in 85 (14.3%) cases. More than 3 retrieval passes was the strongest predictor for SICH (odds ratio, 3.61 [95% CI, 1.38-9.42], =0.0089) following adjustment for age, admission National Institutes of Health Stroke Scale, admission Alberta Stroke Program Early CT Score, and Thrombolysis in Cerebral Infarction, as well as time from symptom onset to flow restoration. Baseline Alberta Stroke Program Early CT Score of 8 to 9 (odds ratio, 0.26 [95% CI, 0.07-0.89], =0.032) or 10 (odds ratio, 0.21 [95% CI, 0.06-0.78], =0.020) were significant protective factors against the occurrence of SICH.

Conclusions: More than 3 retrieval attempts is associated with a significant increase in SICH risk, regardless of patient age, baseline National Institutes of Health Stroke Scale, or procedure time. This should be considered when deciding whether to continue a procedure, especially in patients with large baseline infarctions.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.
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http://dx.doi.org/10.1161/STROKEAHA.120.031242DOI Listing
April 2021

Trimethyllysine, vascular risk factors and outcome in acute ischemic stroke (MARK-STROKE).

Amino Acids 2021 Mar 31. Epub 2021 Mar 31.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Trimethyllysine (TML) is involved in the generation of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO) by gut microbiota. In clinical studies, elevated TML levels predicted major adverse cardiovascular events (MACE) in patients with acute or stable coronary artery disease (CAD). In contrast to cardiovascular patients, the role of TML in patients with acute cerebral ischemia is unknown. Here, we evaluated circulating TML levels in 374 stroke patients from the prospective biomarkers in stroke (MARK-STROKE) study. Compared with 167 matched healthy controls, acute ischemic stroke patients had lower median TML plasma concentrations, i.e. 0.71 vs. 0.47 µmol/L (p < 0.001) and this difference persisted after adjusting for age and sex. TML plasma concentrations were associated with age, serum creatinine, glucose, cholesterol and lysine. Patients with prevalent arterial hypertension, atrial fibrillation or a history of myocardial infarction had increased TML levels, but this observation was not independent of age, sex and GFR. In 274 patients, follow-up data were available. During a median follow-up of 284 [25th-75th percentile: 198, 431] days, TML was not associated with incident MACE (stroke, myocardial infarction, death). In summary, our data suggests a different role of TML in acute ischemic stroke compared with CAD patients.
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http://dx.doi.org/10.1007/s00726-021-02969-xDOI Listing
March 2021

Global Impact of COVID-19 on Stroke Care and Intravenous Thrombolysis.

Authors:
Raul G Nogueira Muhammed M Qureshi Mohamad Abdalkader Sheila Ouriques Martins Hiroshi Yamagami Zhongming Qiu Ossama Yassin Mansour Anvitha Sathya Anna Czlonkowska Georgios Tsivgoulis Diana Aguiar de Sousa Jelle Demeestere Robert Mikulik Peter Vanacker James E Siegler Janika Kõrv Jose Biller Conrad W Liang Navdeep S Sangha Alicia M Zha Alexandra L Czap Christine Anne Holmstedt Tanya N Turan George Ntaios Konark Malhotra Ashis Tayal Aaron Loochtan Annamarei Ranta Eva A Mistry Anne W Alexandrov David Y Huang Shadi Yaghi Eytan Raz Sunil A Sheth Mahmoud H Mohammaden Michael Frankel Eric Guemekane Bila Lamou Hany M Aref Ahmed Elbassiouny Farouk Hassan Tarek Menecie Wessam Mustafa Hossam M Shokri Tamer Roushdy Fred S Sarfo Tolulope Oyetunde Alabi Babawale Arabambi Ernest O Nwazor Taofiki Ajao Sunmonu Kolawole Wahab Joseph Yaria Haytham Hussein Mohammed Philip B Adebayo Anis D Riahi Samia Ben Sassi Lenon Gwaunza Gift Wilson Ngwende David Sahakyan Aminur Rahman Zhibing Ai Fanghui Bai Zhenhui Duan Yonggang Hao Wenguo Huang Guangwen Li Wei Li Ganzhe Liu Jun Luo Xianjin Shang Yi Sui Ling Tian Hongbin Wen Bo Wu Yuying Yan Zhengzhou Yuan Hao Zhang Jun Zhang Wenlong Zhao Wenjie Zi Thomas W Leung Chandril Chugh Vikram Huded Bindu Menon Jeyaraj Durai Pandian P N Sylaja Fritz Sumantri Usman Mehdi Farhoudi Elyar Sadeghi Hokmabadi Anat Horev Anna Reznik Rotem Sivan Hoffmann Nobuyuki Ohara Nobuyuki Sakai Daisuke Watanabe Ryoo Yamamoto Ryosuke Doijiri Naoki Tokuda Takehiro Yamada Tadashi Terasaki Yukako Yazawa Takeshi Uwatoko Tomohisa Dembo Hisao Shimizu Yuri Sugiura Fumio Miyashita Hiroki Fukuda Kosuke Miyake Junsuke Shimbo Yusuke Sugimura Yoshiki Yagita Yohei Takenobu Yuji Matsumaru Satoshi Yamada Ryuhei Kono Takuya Kanamaru Hidekazu Yamazaki Manabu Sakaguchi Kenichi Todo Nobuaki Yamamoto Kazutaka Sonoda Tomoko Yoshida Hiroyuki Hashimoto Ichiro Nakahara Aida Kondybayeva Kamila Faizullina Saltanat Kamenova Murat Zhanuzakov Jang-Hyun Baek Yangha Hwang Jin Soo Lee Si Baek Lee Jusun Moon Hyungjong Park Jung Hwa Seo Kwon-Duk Seo Sung Il Sohn Chang Jun Young Rechdi Ahdab Wan Asyraf Wan Zaidi Zariah Abdul Aziz Hamidon Bin Basri Law Wan Chung Aznita Binti Ibrahim Khairul Azmi Ibrahim Irene Looi Wee Yong Tan Nafisah Wan Yahya Stanislav Groppa Pavel Leahu Amal M Al Hashmi Yahia Zakaria Imam Naveed Akhtar Maria Carissa Pineda-Franks Christian Oliver Co Dmitriy Kandyba Adel Alhazzani Hosam Al-Jehani Carol Huilian Tham Marlie Jane Mamauag Narayanaswamy Venketasubramanian Chih-Hao Chen Sung-Chun Tang Anchalee Churojana Esref Akil Ozlem Aykaç Atilla Ozcan Ozdemir Semih Giray Syed Irteza Hussain Seby John Huynh Le Vu Anh Duc Tran Huy Hoang Nguyen Thong Nhu Pham Thang Huy Nguyen Trung Quoc Nguyen Thomas Gattringer Christian Enzinger Monika Killer-Oberpfalzer Flavio Bellante Sofie De Blauwe Geert Vanhooren Sylvie De Raedt Anne Dusart Robin Lemmens Noemie Ligot Matthieu Pierre Rutgers Laetitia Yperzeele Filip Alexiev Teodora Sakelarova Marina Roje Bedeković Hrvoje Budincevic Igor 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Sedghi Timo Siepmann Kristina Szabo Götz Thomalla Lina Palaiodimou Dimitrios Sagris Odysseas Kargiotis Peter Klivenyi Laszlo Szapary Gabor Tarkanyi Alessandro Adami Fabio Bandini Paolo Calabresi Giovanni Frisullo Leonardo Renieri Davide Sangalli Anne V Pirson Maarten Uyttenboogaart Ido van den Wijngaard Espen Saxhaug Kristoffersen Waldemar Brola Małgorzata Fudala Ewa Horoch-Lyszczarek Michal Karlinski Radoslaw Kazmierski Pawel Kram Marcin Rogoziewicz Rafal Kaczorowski Piotr Luchowski Halina Sienkiewicz-Jarosz Piotr Sobolewski Waldemar Fryze Anna Wisniewska Malgorzata Wiszniewska Patricia Ferreira Paulo Ferreira Luisa Fonseca João Pedro Marto Teresa Pinho E Melo Ana Paiva Nunes Miguel Rodrigues Vítor Tedim Cruz Cristian Falup-Pecurariu Georgi Krastev Miroslav Mako María Alonso de Leciñana Juan F Arenillas Oscar Ayo-Martin Antonio Cruz Culebras Exuperio Diez Tejedor Joan Montaner Soledad Pérez-Sánchez Miguel Angel Tola Arribas Alejandro Rodriguez Vasquez Michael Mazya Gianmarco Bernava 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Neurology 2021 Mar 25. Epub 2021 Mar 25.

Radiation Oncology, Boston Medical Center.

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI, -11.7 to - 11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI, -13.8 to -12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI, -13.7 to -10.3, p=0.001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
March 2021

Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial.

Eur J Neurol 2021 Mar 3. Epub 2021 Mar 3.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Background And Purpose: The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD.

Methods: This post hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90 days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale.

Results: Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p = 0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS.

Conclusions: Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90 days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD.
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http://dx.doi.org/10.1111/ene.14797DOI Listing
March 2021

Extent of FLAIR Hyperintense Vessels May Modify Treatment Effect of Thrombolysis: A Analysis of the WAKE-UP Trial.

Front Neurol 2020 4;11:623881. Epub 2021 Feb 4.

Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial. One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30). Here, 85% of all patients ( = 140) and 95% of middle cerebral artery (MCA) occlusion patients ( = 127) showed FHVs at baseline. Between MCA occlusion patients with few and extensive FHVs, no differences were identified in relative lesion growth ( = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) <2 at 90 days poststroke; = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96-3.36; = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2-24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3-3.8), -value for interaction was 0.11. While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis. Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012.
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http://dx.doi.org/10.3389/fneur.2020.623881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890254PMC
February 2021

Imaging-Based Outcome Prediction of Acute Intracerebral Hemorrhage.

Transl Stroke Res 2021 Feb 6. Epub 2021 Feb 6.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

We hypothesized that imaging-only-based machine learning algorithms can analyze non-enhanced CT scans of patients with acute intracerebral hemorrhage (ICH). This retrospective multicenter cohort study analyzed 520 non-enhanced CT scans and clinical data of patients with acute spontaneous ICH. Clinical outcome at hospital discharge was dichotomized into good outcome and poor outcome using different modified Rankin Scale (mRS) cut-off values. Predictive performance of a random forest machine learning approach based on filter- and texture-derived high-end image features was evaluated for differentiation of functional outcome at mRS 2, 3, and 4. Prediction of survival (mRS ≤ 5) was compared to results of the ICH Score. All models were tuned, validated, and tested in a nested 5-fold cross-validation approach. Receiver-operating-characteristic area under the curve (ROC AUC) of the machine learning classifier using image features only was 0.80 (95% CI [0.77; 0.82]) for predicting mRS ≤ 2, 0.80 (95% CI [0.78; 0.81]) for mRS ≤ 3, and 0.79 (95% CI [0.77; 0.80]) for mRS ≤ 4. Trained on survival prediction (mRS ≤ 5), the classifier reached an AUC of 0.80 (95% CI [0.78; 0.82]) which was equivalent to results of the ICH Score. If combined, the integrated model showed a significantly higher AUC of 0.84 (95% CI [0.83; 0.86], P value <0.05). Accordingly, sensitivities were significantly higher at Youden Index maximum cut-offs (77% vs. 74% sensitivity at 76% specificity, P value <0.05). Machine learning-based evaluation of quantitative high-end image features provided the same discriminatory power in predicting functional outcome as multidimensional clinical scoring systems. The integration of conventional scores and image features had synergistic effects with a statistically significant increase in AUC.
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http://dx.doi.org/10.1007/s12975-021-00891-8DOI Listing
February 2021

Rationale and design of an interventional study of cross-sectoral, coordinated treatment of stroke patients with patient-orientated outcome measurement (StroCare).

Neurol Res Pract 2021 Feb 2;3(1). Epub 2021 Feb 2.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Introduction: Stroke has a long-term impact on functional status and quality of life in multiple health domains. A well-coordinated managed care program for stroke patients is crucial for ameliorating patients' health and cost-efficient use of resources. The aim of this study is the implementation and evaluation of an optimised cross-sectoral, coordinated and managed care program for stroke patients bridging secondary and tertiary care.

Methods: In this multi-center mixed method sequentially controlled intervention study, stroke patients with ischemic stroke (I63), transient ischemic attack and related syndromes (G45), or intracerebral haermorrhage (I64) will be invited to participate. For a 12-months period, 235 consecutive patients are expected to be enrolled and assigned standard of care treatment as an active control group. During the following 12 months, 235 consecutive patients will be enrolled and assigned to a post stroke intervention program. The StroCare intervention consists of repeated outpatient visits with specialized stroke teams, the implementation of a case manager, the use of an electronical tool for communication between acute care, rehabilitation facilities, and out-patient care, and the definition of individualized treatment targets. Patients will be followed up for 24 months. The primary outcome is health-related quality of life measured by the Patient-Reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) at 12 months after the index event, i.e. stroke or TIA. For the qualitative survey of the implementation process, 21 patients in the intervention group will be interviewed after implementation of the interventions. In addition, 20 health care providers and staff members will be interviewed before and after implementation. Additionally, economic outcomes will be evaluated after 6 and 12 months.

Perspective: The study will not only provide information about the tested intervention but is likely to be helpful for clinicians, suppliers of reimbursement, and researchers in implementing and evaluating complex interventions in stroke care in general. With this program, the health care system will have a reference model at its disposal for transfer to other regions and settings.

Trial Registration: The trial is registered at ClinicalTrials.gov ( NCT04159324 ). Approval of the local ethics committee (Ethik-Kommission der Ärztekammer Hamburg, Niedersachsen, Schleswig-Holstein) has been obtained.
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http://dx.doi.org/10.1186/s42466-021-00107-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850714PMC
February 2021

ASPECTS Interobserver Agreement of 100 Investigators from the TENSION Study.

Clin Neuroradiol 2021 Jan 27. Epub 2021 Jan 27.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.

Purpose: Evaluating the extent of cerebral ischemic infarction is essential for treatment decisions and assessment of possible complications in patients with acute ischemic stroke. Patients are often triaged according to image-based early signs of infarction, defined by Alberta Stroke Program Early CT Score (ASPECTS). Our aim was to evaluate interrater reliability in a large group of readers.

Methods: We retrospectively analyzed 100 investigators who independently evaluated 20 non-contrast computed tomography (NCCT) scans as part of their qualification program for the TENSION study. Test cases were chosen by four neuroradiologists who had previously scored NCCT scans with ASPECTS between 0 and 8 and high interrater agreement. Percent and interrater agreements were calculated for total ASPECTS, as well as for each ASPECTS region.

Results: Percent agreements for ASPECTS ratings was 28%, with interrater agreement of 0.13 (95% confidence interval, CI 0.09-0.16), at zero tolerance allowance and 66%, with interrater agreement of 0.32 (95% CI: 0.21-0.44), at tolerance allowance set by TENSION inclusion criteria. ASPECTS region with highest level of agreement was the insular cortex (percent agreement = 96%, interrater agreement = 0.96 (95% CI: 0.94-0.97)) and with lowest level of agreement the M3 region (percent agreement = 68%, interrater agreement = 0.39 [95% CI: 0.17-0.61]).

Conclusion: Interrater agreement reliability for total ASPECTS and study enrollment was relatively low but seems sufficient for practical application. Individual region analysis suggests that some are particularly difficult to evaluate, with varying levels of reliability. Potential impairment of the supraganglionic region must be examined carefully, particularly with respect to the decision whether or not to perform mechanical thrombectomy.
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http://dx.doi.org/10.1007/s00062-020-00988-xDOI Listing
January 2021

Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy: Beyond the First-Pass Effect.

Stroke 2021 Jan 20;52(2):482-490. Epub 2021 Jan 20.

Department of Neuroradiology (M.E.M.), Heidelberg University, Mannheim, Germany.

Background And Purpose: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort.

Methods: For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0-2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders.

Results: The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0-10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7-7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8-5.6]).

Conclusions: Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.
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http://dx.doi.org/10.1161/STROKEAHA.120.029830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834657PMC
January 2021

Quality of Stroke Patient Information Applied in Randomized Controlled Trials-Literature Review.

Front Neurol 2020 7;11:526515. Epub 2020 Dec 7.

Institute of Nursing Science, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Strokes have a huge impact on patients' quality of life. Although there are potentially effective secondary preventions and treatment options for stroke patients, adherence is mostly low. Low disease and treatment-related knowledge and, consequently, a lack of informed decision-making in stroke patients may contribute to this problem. However, stroke patient information did not seem to have relevant effects on patients' knowledge in randomized controlled trials. contributing factor may be the lack of thoroughly developed patient information materials. We aimed to evaluate the quality of patient information materials for stroke patients by using randomized controlled trials, applying quality criteria for evidence-based patient information (EBPI). We conducted a literature search (MEDLINE, Embase, CINAHL, PsycINFO, and CENTRAL). To be included in the review, research had to be randomized controlled trials that provided stroke patient information, were published in English, and had knowledge assessed as the primary endpoint. Authors of primary studies were contacted and asked for information materials applied. We screened 15,507 hits and identified 30 eligible studies. Information materials were available for only eight studies. Analyses revealed that all available materials had important shortcomings concerning EBPI quality criteria [concerning, for example, structural information (e.g., reporting conflicts of interest), content information (e.g., reporting sources of information), or comprehensive descriptions of treatment effects and side effects]. Frequently, treatment effects were reported only narratively without providing absolute numbers, values, or frequencies. Quality of materials differed, but none sufficiently fulfilled EBPI quality criteria. Unsatisfactory trial results concerning patient knowledge and patient involvement in decision-making may at least partially be explained by limitations of the provided materials. Future patient information should consider EBPI quality criteria.
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http://dx.doi.org/10.3389/fneur.2020.526515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750452PMC
December 2020

Sex Differences in Outcome After Thrombectomy for Acute Ischemic Stroke are Explained by Confounding Factors.

Clin Neuroradiol 2020 Dec 21. Epub 2020 Dec 21.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Purpose: The aim of this study was to analyze sex differences in outcome after thrombectomy for acute ischemic stroke in clinical practice in a large prospective multicenter registry.

Methods: Data of consecutive stroke patients treated with thrombectomy (June 2015-April 2018) derived from an industry-independent registry (German Stroke Registry-Endovascular Treatment) were prospectively analyzed. Multivariable binary logistic regression analyses were applied to determine whether sex is a predictor of functional independence outcome (defined as a modified Rankin scale [mRS] 0-2) 90 days after stroke.

Results: In total, 2316 patients were included in the analysis, 1170 (50.5%) were female and 1146 (49.5%) were male. Women were older (median age 78 vs. 72 years; p < 0.001) and more frequently had a prestroke functional impairment defined by mRS >1 (24.8% vs. 14.1%; p < 0.001). In unadjusted analyses, independent outcome at 90 days was less frequent in women (33.2%) than men (40.6%; p < 0.001). Likewise, mortality was higher in women than in men (30.7% vs. 26.4%; p = 0.024). In adjusted regression analyses, however, sex was not associated with outcome. Lower age, a lower baseline National Institutes of Health Stroke Scale score, a higher Alberta Stroke Program Early CT score, prestroke functional independence, successful reperfusion, and concomitant intravenous thrombolysis therapy predicted independent outcome.

Conclusion: Women showed a worse functional outcome after thrombectomy for acute ischemic stroke in clinical practice; however, after adjustment for crucial confounders sex was not a predictor of outcome. The difference in outcome thus appears to result from differences in confounding factors such as age and prestroke functional status.
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http://dx.doi.org/10.1007/s00062-020-00983-2DOI Listing
December 2020

Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial.

Neurol Res Pract 2020 20;2:40. Epub 2020 Nov 20.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Background: One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial.

Methods: WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0-1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase.

Results: Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years,  <  0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%,  = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome ( = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047-4.236).

Conclusions: Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.
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http://dx.doi.org/10.1186/s42466-020-00087-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678217PMC
November 2020

Symptoms and probabilistic anatomical mapping of lacunar infarcts.

Neurol Res Pract 2020 3;2:21. Epub 2020 Aug 3.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Background: The anatomical distribution of acute lacunar infarcts has mainly been studied for supratentorial lesions. In addition, little is known about the association with distinct stroke symptoms, not summarized as classical lacunar syndromes. We aimed to describe the spatial lesion distribution of acute supra- and infratentorial lacunar infarcts and their association with stroke symptoms in patients eligible for thrombolysis.

Methods: All patients enrolled in the WAKE-UP trial (efficacy and safety of magnetic resonance imaging [MRI]-based thrombolysis in wake-up stroke) were screened for lacunar infarcts on diffusion-weighted imaging (DWI). The relationship between the anatomical distribution of supra- and infratentorial lacunar infarcts, their demographic characteristics and acute stroke symptoms, defined by the National Institutes of Health Stroke Scale (NIHSS) score, were correlated and compared.

Results: Maps of lesion distribution from 224 lacunar infarct patients (76 [33.9%] females, mean age [standard deviation] of 63.4 [11.5] years) were generated using computational image mapping methods. Median infarct volume was 0.73 ml (interquartile range [IQR] 0.37-1.15 ml). Median NIHSS sum score on hospital arrival was 4 (IQR 3-6). 165 (73.7%) patients had lacunar infarcts in the supratentorial deep white or grey matter, while 59 (26.3%) patients had infratentorial lacunar infarcts. Patients with supratentorial lacunar infarcts presented with a significantly lower occurrence of deficits in the NIHSS items gaze ( < 0.001) and dysarthria ( = 0.008), but had more often a paresis of the left arm ( = 0.009) and left leg ( = 0.068) compared to patients with infratentorial infarcts.

Conclusions: The anatomical lesion distribution of lacunar infarcts reveals a distinct pattern and supports an association of localization with different stroke symptoms.

Trial Registration: NCT01525290.
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http://dx.doi.org/10.1186/s42466-020-00068-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650076PMC
August 2020

Protocol for a multicenter observational prospective study of functional recovery from stroke beyond inpatient rehabilitation - The Interdisciplinary Platform for Rehabilitation Research and Innovative Care of Stroke Patients (IMPROVE).

Neurol Res Pract 2020 6;2:10. Epub 2020 Apr 6.

Department of Neurology, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Introduction: Stroke and its long-term consequences pose major challenges for the lives of those affected and healthcare systems. Neurological rehabilitation therefore primarily attempts to improve function in order to increase independence in activities of daily living, and to enable social participation. There is only scarce data on dynamics of functional recovery after patients discharge from inpatient neurological rehabilitation. Even less is known about the patient's perspective on long-term recovery from stroke. The Interdisciplinary Platform for Rehabilitation Research and Innovative Care of Stroke Patients (IMPROVE) aims to address this knowledge gap by providing new insights into the dynamics and extent of functional recovery from stroke beyond inpatient rehabilitation treatment.

Methods: We provide the protocol for an observational, longitudinal, multicenter study conducted in an Universitary Stroke Center in cooperation with five Neurological Rehabilitation Centers in Northern Germany. Patients who suffered from ischemic or hemorrhagic stroke will be enrolled by the end of inpatient rehabilitation and followed up to 1 year. In addition, a group of chronic stroke patients and a group of craniocerebral trauma patients will be enrolled as a comparison group. Data on stroke characteristics, vascular risk factors, co-morbidities, social support, and demographics will be recorded. Comprehensive clinical evaluation will be performed at baseline, three, six, and twelve months after enrollment. The assessments and scores used reflect the three components of the International Classification of Functioning, Disability and Health (ICF), some of them are tests regularly used in rehabilitation settings. Tests of motor function, cognition, and mood are included, as are tests of self-reported health-related quality of life. Primary outcome measure is a hand motor score, built by the sum of the hand items of the Fugl-Meyer Assessment as an objective measurement of hand function at 12 months after enrollment. Predictors of the primary outcome will be analyzed using linear regression analysis.

Perspective: The results of IMPROVE will inform about the long-term dynamics of functional stroke recovery after patients' discharge from inpatient rehabilitation and will provide insights into the association of clinical and demographic factors with recovery of function.

Trial Registration: The protocol is registered at ClinicalTrials.gov (NCT04119479).
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http://dx.doi.org/10.1186/s42466-020-00056-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650143PMC
April 2020

Outcome evaluation by patient reported outcome measures in stroke clinical practice (EPOS) protocol for a prospective observation and implementation study.

Neurol Res Pract 2019 1;1:28. Epub 2019 Nov 1.

Department of Neurology, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Introduction: The impact of stroke-related impairment on activities of daily living may vary between patients, and can only be estimated by applying patient-reported outcome measures. The International Consortium for Health Outcome Measurement has developed a standard set of instruments that combine clinical and longitudinal patient-reported outcome measures for stroke. The present study was designed (1) to implement and evaluate the feasibility of the use of it as a consistent outcome measure in clinical routine at the stroke center of a German university hospital, (2) to characterize impairment in everyday life caused by stroke, and (3) to identify predictive factors associated with patient-relevant outcomes.

Methods: We plan to enroll 1040 consecutive patients with the diagnosis of acute ischemic stroke, transient ischemic attack, or intracerebral hemorrhage in a prospective observational study. Demographics, cardiovascular risk factors, and living situation are assessed at inpatient surveillance. At 90 days and 12 months after inclusion, follow-up assessments take place including the Patient-reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10), the Patient- Health Questionnaire-4, and the simplified modified Ranking Scale questionnaire. The acceptance and feasibility (1) will be assessed by a process evaluation through qualitative semi-structured interviews with clinical staff and patients and quantitative analyses of the data quality evaluating practicability, acceptance, adoption, and fidelity to protocol. The primary outcome of objective 2 and 3 is health-related quality of life measured with the PROMIS-10. Additional outcomes are depressive and anxiety symptoms and patient participation in their social roles. Patient-reported outcomes will be assessed in their longitudinal course using (generalized) mixed regressions. Exploratory descriptive and inference statistical analyses will be used to find patterns of patient characteristics and predictive factors of the outcome domains.

Perspective: The results will describe and further establish the evaluation of stroke patients of a stroke center by standardized PROMs in everyday life.

Trial Registration: The trial is registered at ClinicalTrials.gov (NCT03795948). Approval of the local ethics committee (Ethik-Kommission der Ärztekammer Hamburg) has been obtained.
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http://dx.doi.org/10.1186/s42466-019-0034-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650080PMC
November 2019

Which Imaging Approach Should Be Used for Stroke of Unknown Time of Onset?

Stroke 2021 01 11;52(1):373-380. Epub 2020 Dec 11.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany (G.T.).

Reperfusion therapy with intravenous thrombolysis or mechanical thrombectomy is effective in improving outcome for ischemic stroke but remains underused. Patients presenting with stroke of unknown onset are a common clinical scenario and a common reason for not offering reperfusion therapy. Recent studies have demonstrated the efficacy of reperfusion therapy in stroke of unknown time of onset, when guided by advanced brain imaging. However, translation into clinical practice is challenged by variability in the available data. Comparison between studies is difficult because of use of different imaging modalities (magnetic resonance imaging or computed tomography), different imaging paradigms (imaging biomarkers of lesion age versus imaging biomarkers of tissue viability), and different populations studied (ie, both patients with large vessel occlusion or those with less severe strokes). Physicians involved in acute stroke care are faced with the key question of which imaging approach they should use to guide reperfusion treatment for stroke with unknown time of onset. In this review, we provide an overview of the available evidence for selecting and treating patients with strokes of unknown onset, based on the underlying imaging concepts. The perspective provided is from the viewpoint of the clinician seeing these patients acutely, to provide pragmatic recommendations for clinical practice.
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http://dx.doi.org/10.1161/STROKEAHA.120.032020DOI Listing
January 2021

White matter integrity and structural brain network topology in cerebral small vessel disease: The Hamburg city health study.

Hum Brain Mapp 2021 Apr 8;42(5):1406-1415. Epub 2020 Dec 8.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Cerebral small vessel disease is a common finding in the elderly and associated with various clinical sequelae. Previous studies suggest disturbances in the integration capabilities of structural brain networks as a mediating link between imaging and clinical presentations. To what extent cerebral small vessel disease might interfere with other measures of global network topology is not well understood. Connectomes were reconstructed via diffusion weighted imaging in a sample of 930 participants from a population based epidemiologic study. Linear models were fitted testing for an association of graph-theoretical measures reflecting integration and segregation with both the Peak width of Skeletonized Mean Diffusivity (PSMD) and the load of white matter hyperintensities of presumed vascular origin (WMH). The latter were subdivided in periventricular and deep for an analysis of localisation-dependent correlations of cerebral small vessel disease. The median WMH volume was 0.6 mL (1.4) and the median PSMD 2.18 mm /s x 10 (0.5). The connectomes showed a median density of 0.880 (0.030), the median values for normalised global efficiency, normalised clustering coefficient, modularity Q and small-world propensity were 0.780 (0.045), 1.182 (0.034), 0.593 (0.026) and 0.876 (0.040) respectively. An increasing burden of cerebral small vessel disease was significantly associated with a decreased integration and increased segregation and thus decreased small-worldness of structural brain networks. Even in rather healthy subjects increased cerebral small vessel disease burden is accompanied by topological brain network disturbances. Segregation parameters and small-worldness might as well contribute to the understanding of the known clinical sequelae of cerebral small vessel disease.
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http://dx.doi.org/10.1002/hbm.25301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927298PMC
April 2021

"Neurological manifestations of COVID-19" - guideline of the German society of neurology.

Neurol Res Pract 2020 2;2:51. Epub 2020 Dec 2.

Interdisciplinary Center for Smelling and Tasting, University ENT Hospital Dresden, German Society for ENT Medicine, Dresden, Germany.

Infection with the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a previously unknown clinical picture, which is known as COVID-19 (COrona VIrus Disease-2019) and was first described in the Hubei region of China. The SARS-CoV-2 pandemic has implications for all areas of medicine. It directly and indirectly affects the care of neurological diseases. SARS-CoV-2 infection may be associated with an increased incidence of neurological manifestations such as encephalopathy and encephalomyelitis, ischemic stroke and intracerebral hemorrhage, anosmia and neuromuscular diseases. In October 2020, the German Society of Neurology (DGN, Deutsche Gesellschaft für Neurologie) published the first guideline on the neurological manifestations of the new infection. This S1 guideline provides guidance for the care of patients with SARS-CoV-2 infection regarding neurological manifestations, patients with neurological disease with and without SARS-CoV-2 infection, and for the protection of healthcare workers. This is an abbreviated version of the guideline issued by the German Neurological society and published in the Guideline repository of the AWMF (Working Group of Scientific Medical Societies; Arbeitsgemeinschaft wissenschaftlicher Medizinischer Fachgesellschaften).
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http://dx.doi.org/10.1186/s42466-020-00097-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708894PMC
December 2020

Linking cortical atrophy to white matter hyperintensities of presumed vascular origin.

J Cereb Blood Flow Metab 2020 Dec 1:271678X20974170. Epub 2020 Dec 1.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

We examined the relationship between white matter hyperintensities (WMH) and cortical neurodegeneration in cerebral small vessel disease (CSVD) by investigating whether cortical thickness is a remote effect of WMH through structural fiber tract connectivity in a population at increased risk of CSVD. We measured cortical thickness on T1-weighted images and segmented WMH on FLAIR images in 930 participants of a population-based cohort study at baseline. DWI-derived whole-brain probabilistic tractography was used to define WMH connectivity to cortical regions. Linear mixed-effects models were applied to analyze the relationship between cortical thickness and connectivity to WMH. Factors associated with cortical thickness (age, sex, hemisphere, region, individual differences in cortical thickness) were added as covariates. Median age was 64 [IQR 46-76] years. Visual inspection of surface maps revealed distinct connectivity patterns of cortical regions to WMH. WMH connectivity to the cortex was associated with reduced cortical thickness ( = 0.009) after controlling for covariates. This association was found for periventricular WMH ( = 0.001) only. Our results indicate an association between WMH and cortical thickness via connecting fiber tracts. The results imply a mechanism of secondary neurodegeneration in cortical regions distant, yet connected to subcortical vascular lesions, which appears to be driven by periventricular WMH.
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http://dx.doi.org/10.1177/0271678X20974170DOI Listing
December 2020

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Lancet 2020 11 8;396(10262):1574-1584. Epub 2020 Nov 8.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.

Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).

Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)32163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734592PMC
November 2020

Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity.

Brain Commun 2020 20;2(2):fcaa111. Epub 2020 Jul 20.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany.

Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.
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http://dx.doi.org/10.1093/braincomms/fcaa111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585696PMC
July 2020

Clinical Characteristics and Outcome of Patients With Hemorrhagic Transformation After Intravenous Thrombolysis in the WAKE-UP Trial.

Front Neurol 2020 28;11:957. Epub 2020 Aug 28.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. We performed a analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0-1 at 90 days. Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28-3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05-1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01-1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00-1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57-5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01-1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93-6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05-0.86]), while HI was not. Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window.
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http://dx.doi.org/10.3389/fneur.2020.00957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483750PMC
August 2020

Structural brain networks and functional motor outcome after stroke-a prospective cohort study.

Brain Commun 2020 10;2(1):fcaa001. Epub 2020 Jan 10.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.

The time course of topological reorganization that occurs in the structural connectome after an ischaemic stroke is currently not well understood. We aimed to determine the evolution of structural brain networks in stroke patients with motor deficits and relate changes in their global topology to residual symptom burden and functional impairment. In this prospective cohort study, ischaemic stroke patients with supratentorial infarcts and motor symptoms were assessed longitudinally by advanced diffusion MRI and detailed clinical testing of upper extremity motor function at four time points from the acute to the chronic stage. For each time point, structural connectomes were reconstructed, and whole-hemisphere global network topology was quantified in terms of integration and segregation parameters. Using non-linear joint mixed-effects regression modelling, network evolution was related to lesion volume and clinical outcome. Thirty patients were included for analysis. Graph-theoretical analysis demonstrated that, over time, brain networks became less integrated and more segregated with decreasing global efficiency and increasing modularity. Changes occurred in both stroke and intact hemispheres and, in the latter, were positively associated with lesion volume. Greater change in topology was associated with larger residual symptom burden and greater motor impairment 1, 3 and 12 months after stroke. After ischaemic stroke, brain networks underwent characteristic changes in both ipsi- and contralesional hemispheres. Topological network changes reflect the severity of damage to the structural network and are associated with functional outcome beyond the impact of lesion volume.
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http://dx.doi.org/10.1093/braincomms/fcaa001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425342PMC
January 2020

Altered topology of large-scale structural brain networks in chronic stroke.

Brain Commun 2019 4;1(1):fcz020. Epub 2019 Oct 4.

Department of Neurology, University Medical Center Hamburg-Eppendorf, D20246 Hamburg, Germany.

Beyond disruption of neuronal pathways, focal stroke lesions induce structural disintegration of distant, yet connected brain regions via retrograde neuronal degeneration. Stroke lesions alter functional brain connectivity and topology in large-scale brain networks. These changes are associated with the degree of clinical impairment and recovery. In contrast, changes of large scale, structural brain networks after stroke are less well reported. We therefore aimed to analyse the impact of focal lesions on the structural connectome after stroke based on data from diffusion-weighted imaging and probabilistic fibre tracking. In total, 17 patients (mean age 64.5 ± 8.4 years) with upper limb motor deficits in the chronic stage after stroke and 21 healthy participants (mean age 64.9 ± 10.3 years) were included. Clinical deficits were evaluated by grip strength and the upper extremity Fugl-Meyer assessment. We calculated global and local graph theoretical measures to characterize topological changes in the structural connectome. Results from our analysis demonstrated significant alterations of network topology in both ipsi- and contralesional, primarily unaffected, hemispheres after stroke. Global efficiency was significantly lower in stroke connectomes as an indicator of overall reduced capacity for information transfer between distant brain areas. Furthermore, topology of structural connectomes was shifted toward a higher degree of segregation as indicated by significantly higher values of global clustering and modularity. On a level of local network parameters, these effects were most pronounced in a subnetwork of cortico-subcortical brain regions involved in motor control. Structural changes were not significantly associated with clinical measures. We propose that the observed network changes in our patients are best explained by the disruption of inter- and intrahemispheric, long white matter fibre tracts connecting distant brain regions. Our results add novel insights on topological changes of structural large-scale brain networks in the ipsi- and contralesional hemisphere after stroke.
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http://dx.doi.org/10.1093/braincomms/fcz020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425306PMC
October 2019

Lesion Age Imaging in Acute Stroke: Water Uptake in CT Versus DWI-FLAIR Mismatch.

Ann Neurol 2020 12 2;88(6):1144-1152. Epub 2020 Oct 2.

Department of Neuroradiology, Westpfalz-Klinikum, Kaiserslautern, Germany.

Purpose: In acute ischemic stroke with unknown time of onset, magnetic resonance (MR)-based diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) estimates lesion age to guide intravenous thrombolysis. Computed tomography (CT)-based quantitative net water uptake (NWU) may be a potential alternative. The purpose of this study was to directly compare CT-based NWU to magnetic resonance imaging (MRI) at identifying patients with lesion age < 4.5 hours from symptom onset.

Methods: Fifty patients with acute anterior circulation stroke were analyzed with both imaging modalities at admission between 0.5 and 8.0 hours after known symptom onset. DWI-FLAIR lesion mismatch was rated and NWU was measured in admission CT. An established NWU threshold (11.5%) was used to classify patients within and beyond 4.5 hours. Multiparametric MRI signal was compared with NWU using logistic regression analyses. The empirical distribution of NWU was analyzed in a consecutive cohort of patients with wake-up stroke.

Results: The median time between CT and MRI was 35 minutes (interquartile range [IQR] = 24-50). The accuracy of DWI-FLAIR mismatch was 68.8% (95% confidence interval [CI] = 53.7-81.3%) with a sensitivity of 58% and specificity of 82%. The accuracy of NWU threshold was 86.0% (95% CI = 73.3-94.2%) with a sensitivity of 91% and specificity of 78%. The area under the curve (AUC) of multiparametric MRI signal to classify lesion age <4.5 hours was 0.86 (95% CI = 0.64-0.97), and the AUC of quantitative NWU was 0.91 (95% CI = 0.78-0.98). Among 87 patients with wake-up stroke, 46 patients (53%) showed low NWU (< 11.5%).

Conclusion: The predictive power of CT-based lesion water imaging to identify patients within the time window of thrombolysis was comparable to multiparametric DWI-FLAIR MRI. A significant proportion of patients with wake-up stroke exhibit low NWU and may therefore be potentially suitable for thrombolysis. ANN NEUROL 2020;88:1144-1152.
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http://dx.doi.org/10.1002/ana.25903DOI Listing
December 2020

Early clinical surrogates for outcome prediction after stroke thrombectomy in daily clinical practice.

J Neurol Neurosurg Psychiatry 2020 10;91(10):1055-1059

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background And Purpose: To investigate early clinical surrogates for long-term independency of patients treated with thrombectomy for large vessel occlusion stroke in daily clinical routine.

Methods: All patients with anterior circulation stroke enrolled in the German Stroke Registry-Endovascular Treatment from 07/2015 to 04/2018 were analysed. National Institute of Health Stroke Scale (NIHSS) on admission, NIHSS percentage change, NIHSS delta and NIHSS at 24 hours as well as existing binary definitions of early neurological improvement (ENI; improvement of 8 (major ENI)/10 (dramatic ENI) NIHSS points or reaching 0/1 were compared for predicting functional outcome at 90 days using the modified Rankin Scale (mRS). Excellent and favourable outcome were defined as 0-1 and 0-2, respectively.

Results: Among 2262 endovasculary treated patients with acute ischaemic anterior circulation stroke, NIHSS at 24 hours had the highest discriminative ability to predict excellent (receiver operator characteristics (ROC) area under the curve (AUC) 0.86 (0.84-0.88)) and favourable long-term functional outcome (ROC AUC 0.86 (0.85-0.88)) in comparison to NIHSS percentage change (ROC AUC mRS ≤1: 0.81 (0.78-0.83) mRS ≤2: 0.81 (0.79-0.83)), NIHSS delta change (ROC AUC mRS ≤1: 0.74 (0.72-0.77), mRS ≤2: 0.77 (0.74-0.79)) and NIHSS admission (ROC AUC mRS ≤1: 0.70 (0.68-0.73), mRS ≤2: 0.67 (0.68-0.71)). Advanced age was the only independent predictor (adjusted OR 1.05, 95% CI 1.03 to 1.07, p<0.001) for turning the outcome prognosis from favourable (mRS ≤2) to poor (mRS ≥4) at 90 days.

Conclusion: The NIHSS at 24 hours postintervention with a threshold of ≤8 points serves best as a surrogate for long-term functional outcome after thrombectomy for anterior circulation stroke in daily clinical practice. Only advanced age significantly decreases its predictive value.
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http://dx.doi.org/10.1136/jnnp-2020-323742DOI Listing
October 2020

Integrated care in stroke survivors: When and how much?

EClinicalMedicine 2020 Aug 18;25:100489. Epub 2020 Aug 18.

Department of Cardiology, University Heart and Vascular Center UKE Hamburg, Building O70 Martinistrasse 52, Hamburg 20246, Germany.

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http://dx.doi.org/10.1016/j.eclinm.2020.100489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452461PMC
August 2020

Clinical and Imaging Characteristics in Patients with SARS-CoV-2 Infection and Acute Intracranial Hemorrhage.

J Clin Med 2020 Aug 6;9(8). Epub 2020 Aug 6.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, 20251 Hamburg, Germany.

Background And Purpose: Intracranial hemorrhage has been observed in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19), but the clinical, imaging, and pathophysiological features of intracranial bleeding during COVID-19 infection remain poorly characterized. This study describes clinical and imaging characteristics of patients with COVID-19 infection who presented with intracranial bleeding in a European multicenter cohort.

Methods: This is a multicenter retrospective, observational case series including 18 consecutive patients with COVID-19 infection and intracranial hemorrhage. Data were collected from February to May 2020 at five designated European special care centers for COVID-19. The diagnosis of COVID-19 was based on laboratory-confirmed diagnosis of SARS-CoV-2. Intracranial bleeding was diagnosed on computed tomography (CT) of the brain within one month of the date of COVID-19 diagnosis. The clinical, laboratory, radiologic, and pathologic findings, therapy and outcomes in COVID-19 patients presenting with intracranial bleeding were analyzed.

Results: Eighteen patients had evidence of acute intracranial bleeding within 11 days (IQR 9-29) of admission. Six patients had parenchymal hemorrhage (33.3%), 11 had subarachnoid hemorrhage (SAH) (61.1%), and one patient had subdural hemorrhage (5.6%). Three patients presented with intraventricular hemorrhage (IVH) (16.7%).

Conclusion: This study represents the largest case series of patients with intracranial hemorrhage diagnosed with COVID-19 based on key European countries with geospatial hotspots of SARS-CoV-2. Isolated SAH along the convexity may be a predominant bleeding manifestation and may occur in a late temporal course of severe COVID-19.
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http://dx.doi.org/10.3390/jcm9082543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464657PMC
August 2020

Temporal trends in the presentation of cardiovascular and cerebrovascular emergencies during the COVID-19 pandemic in Germany: an analysis of health insurance claims.

Clin Res Cardiol 2020 Dec 4;109(12):1540-1548. Epub 2020 Aug 4.

Research Group GermanVasc, Department of Vascular Medicine, University Heart and Vascular Center UKE Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Aims: The first reports of declining hospital admissions for major cardiovascular emergencies during the COVID-19 pandemic attracted public attention. However, systematic evidence on this subject is sparse. We aimed to investigate the rate of emergent hospital admissions, subsequent invasive treatments and comorbidities during the COVID-19 pandemic in Germany.

Methods And Results: This was a retrospective analysis of health insurance claims data from the second largest insurance fund in Germany, BARMER. Patients hospitalized for acute myocardial infarction, acute limb ischemia, aortic rupture, stroke or transient ischemic attack (TIA) between January 1, 2019, and May 31, 2020, were included. Admission rates per 100,000 insured, invasive treatments and comorbidities were compared from January-May 2019 (pre-COVID) to January-May 2020 (COVID). A total of 115,720 hospitalizations were included in the current analysis (51.3% females, mean age 72.9 years). Monthly admission rates declined from 78.6/100,000 insured (pre-COVID) to 70.6/100,000 (COVID). The lowest admission rate was observed in April 2020 (61.6/100,000). Administration rates for ST-segment elevation myocardial infarction (7.3-6.6), non-ST-segment elevation myocardial infarction (16.8-14.6), acute limb ischemia (5.1-4.6), stroke (35.0-32.5) and TIA (13.7-11.9) decreased from pre-COVID to COVID. Baseline comorbidities and the percentage of these patients treated with interventional or open-surgical procedures remained similar over time across all entities. In-hospital mortality in hospitalizations for stroke increased from pre-COVID to COVID (8.5-9.8%).

Conclusions: Admission rates for cardiovascular and cerebrovascular emergencies declined during the pandemic in Germany, while patients' comorbidities and treatment allocations remained unchanged. Further investigation is warranted to identify underlying reasons and potential implications on patients' outcomes.
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http://dx.doi.org/10.1007/s00392-020-01723-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402080PMC
December 2020