Publications by authors named "Joachim Röther"

113 Publications

Cerebral aneurysm: De novo genesis and rupture within 15 days.

Eur J Neurol 2021 Mar;28(3):1084-1085

Department of Neurology, Asklepios Klinik Altona, Hamburg, Germany.

We report the first case of de novo formation of a small 4- × 3-mm symptomatic aneurysm with subsequent subarachnoid haemorrhage (SAH) within 15 days. A pre-existing aneurysm was excluded by magnetic resonance angiography, as well as conventional angiography. In this case, there was no history of SAH, which is in contrast to other reported cases of de novo aneurysms that developed after previous aneurysm rupture.
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http://dx.doi.org/10.1111/ene.14645DOI Listing
March 2021

Brainstem encephalitis in neuroborreliosis: typical clinical course and distinct MRI findings.

J Neurol 2021 Feb 28;268(2):502-505. Epub 2020 Aug 28.

Institute of Radiology and Neuroradiology, Klinikum Ingolstadt, Ingolstadt, Germany.

Objective: In this retrospective observational study and referring to a historical case presented in 2009, we searched for typical clinical and imaging features of brainstem encephalitis in neuroborreliosis.

Methods: In addition to the historical case we describe five affected patients.

Results: All patients had a very similar prolonged clinical course with unspecific symptoms such as wasting, fatigue and headache. Brainstem signs were irregularly observed. MRI showed symmetrical brainstem alterations in all patients. In coronary FLAIR imaging these changes formed a figure resembling a Philippine tarsier.

Conclusions: A subset of patients with neuroborreliosis develops a brainstem encephalitis with a typical clinical course and distinct MRI findings.
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http://dx.doi.org/10.1007/s00415-020-10188-9DOI Listing
February 2021

[Stroke and intracerebral hemorrhage under anticoagulation or platelet inhibition-when should treatment be restarted and how?]

Authors:
Joachim Röther

Internist (Berl) 2020 Apr;61(4):424-430

Kopf- und Neurozentrum, Neurologische Abteilung mit überregionaler Stroke Unit, Neurophysiologie und Neurologischer Intensivmedizin, Asklepios Klinik Altona, Asklepios Campus Hamburg der Semmelweis Universität, Paul-Ehrlich-Straße 1, 22763, Hamburg, Deutschland.

Recurrent stroke is a frequent event and clinical trials that addressed the best secondary prevention are sparse. If patients take a thrombocyte aggregation inhibitor (TAI) before the recurrent stroke, clopidogrel can be chosen instead of aspirin or vice versa but evidence is lacking. A 3-week period of dual antiplatelet treatment might be a good alternative after acute reinfarction. The results of the recently published RESTART trial support resuming TAI treatment after a hemorrhagic stroke and showed that the intracerebral hemorrhage (ICH) rate is not elevated in comparison with a study group without TAI. Patients with ICH associated with oral anticoagulation (OAC) and atrial fibrillation should be restarted on novel OACs, if there are no relevant contraindications and the risk of ischemia is high. The anticoagulation treatment of patients with cerebral amyloid angiopathy is still a clinical dilemma as there is a high risk of recurrent ICH. These patients might be candidates for left appendage closure.
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http://dx.doi.org/10.1007/s00108-020-00747-7DOI Listing
April 2020

Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany-Updated series of 120 cases.

Int J Stroke 2020 Aug 19;15(6):609-618. Epub 2020 Jan 19.

Department for Neurology, Klinikum rechts der Isar, TU München, München, Germany.

Background: Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth.

Aims: To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage.

Methods: Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used.

Results: One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in  = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0-3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay.

Conclusion: Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.
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http://dx.doi.org/10.1177/1747493019895654DOI Listing
August 2020

Association of Surgical Hematoma Evacuation vs Conservative Treatment With Functional Outcome in Patients With Cerebellar Intracerebral Hemorrhage.

JAMA 2019 10;322(14):1392-1403

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Importance: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established.

Objective: To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH.

Design, Setting, And Participants: Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015).

Exposure: Surgical hematoma evacuation vs conservative treatment.

Main Outcomes And Measures: The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH.

Results: Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% [P = .003]; ARD, -34.7% [-38.8% to -30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02).

Conclusions And Relevance: Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.
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http://dx.doi.org/10.1001/jama.2019.13014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784768PMC
October 2019

Functional Outcome Following Stroke Thrombectomy in Clinical Practice.

Stroke 2019 09 24;50(9):2500-2506. Epub 2019 Jul 24.

Department of Neuroradiology (F.F., J.F.), University Medical Center Hamburg-Eppendorf, Germany.

Background and Purpose- Endovascular treatment for large vessel occlusion in ischemic stroke has proven to be effective in large clinical trials. We aimed to provide real-world estimates of endovascular treatment reperfusion rates and functional outcome on a countrywide scale. Methods- Two thousand seven hundred ninety-four patients with large vessel occlusion were included into an investigator-initiated, industry-independent, prospective registry in 25 sites in Germany between June 2015 and April 2018. The primary outcome was the score on the modified Rankin Scale ranging from zero (no symptoms) to 6 (death) at 3 months. Secondary analyses included the prediction of a good outcome (modified Rankin Scale, 0-2). Dichotomized analyses of predictors were performed using logistic regression adjusted for potential confounders. Results- Median age was 75 years (interquartile range, 64-82); median National Institutes of Health Stroke Scale score was 15 (interquartile range, 10-19). Vessel occlusion was in the anterior circulation in 2265 patients (88%) and in the posterior circulation in 303 patients (12%). Intravenous alteplase before endovascular treatment was given in 1457 patients (56%). Successful reperfusion was achieved in 2143 subjects (83%). At 3 months, 854 patients (37%) showed a good outcome; mortality was 29%. There was no difference between anterior and posterior circulation occlusions (P=0.27). Significant predictors for a good outcome were younger age (odds ratio [OR], 1.06; 95% CI, 1.05-1.07), no interhospital transfer (OR, 1.39; 95% CI, 1.03-1.88), lower stroke severity (OR, 1.10; 95% CI, 1.08-1.13), smaller infarct size (OR, 1.26; 95% CI, 1.15-1.39), alteplase use (OR, 1.49; 95% CI, 1.08-2.06), and reperfusion success (OR, 1.69; 95% CI, 1.45-1.96). Conclusions- High rates of favorable outcome can be achieved on a countrywide scale by endovascular treatment. Mortality appears to be greater in the daily routine than otherwise reported by authors of large randomized trials. There were no outcome differences between the anterior and posterior circulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.
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http://dx.doi.org/10.1161/STROKEAHA.119.026005DOI Listing
September 2019

Association of Multiple Enrichment Criteria With Ischemic and Bleeding Risks Among COMPASS-Eligible Patients.

J Am Coll Cardiol 2019 07;73(25):3281-3291

FACT, French Alliance for Cardiovascular Trials, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France; Hôpital Avicenne, Assistance Publique-hôpitaux de Paris, Bobigny, France; Imperial College, Royal Brompton Hospital, London, United Kingdom. Electronic address:

Background: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial found clinical benefit of low-dose rivaroxaban plus aspirin, but at the expense of increased bleeding risk in patients with stable vascular disease.

Objectives: This study evaluated the balance of ischemic and bleeding risks according to the presence of ≥1 enrichment criteria in "COMPASS-eligible" patients.

Methods: Key COMPASS selection criteria were applied to identify a COMPASS-eligible population (n = 16,875) from the REACH (REduction of Atherothrombosis for Continued Health) Registry of stable atherothrombotic patients. Ischemic outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Bleeding outcome was serious bleeding (hemorrhagic stroke, hospitalization for bleeding, transfusion).

Results: Patients were categorized according to the enrichment criteria: age >65 years (81.5%), diabetes (41.0%), moderate renal failure (40.2%), peripheral artery disease (33.7%), current smoker (13.8%), heart failure (13.3%), ischemic stroke (11.1%), and asymptomatic carotid stenosis (8.7%). Each criterion was associated with a consistent increase in ischemic and bleeding events, but no individual subgroup derived a more favorable trade-off. Patients with multiple criteria had a dramatic increase in ischemic risk (7.0% [95% confidence interval (CI): 5.6% to 8.7%], 12.5% [95% CI: 11.1% to 14.1%], 16.6% [95% CI: 14.7% to 18.6%], and 21.8% [95% CI: 19.9% to 23.9%] with 1, 2, 3, and ≥4 enrichment criteria, respectively), but a more modest absolute increase in bleeding risk (1.5% [95% CI: 0.9% to 2.1%], 1.8% [95% CI: 1.3% to 2.2%], 2.0% [95% CI: 1.5% to 2.6%], 3.2% [95% CI: 2.6% to 3.9%]).

Conclusions: In a population of stable vascular patients at high risk of atherothrombotic events, the subset with multiple enrichment criteria had a greater absolute increase in ischemic than in bleeding risk and may be good candidates for low-dose rivaroxaban in addition to aspirin.
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http://dx.doi.org/10.1016/j.jacc.2019.04.046DOI Listing
July 2019

Characteristics in Non-Vitamin K Antagonist Oral Anticoagulant-Related Intracerebral Hemorrhage.

Stroke 2019 06 16;50(6):1392-1402. Epub 2019 May 16.

From the Department of Neurology (S.T.G., J.B.K., J.A.S., M.I.S., M. Hagen, R.U.K., S. Schwab, H.B.H.), University of Erlangen-Nuremberg, Germany.

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.
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http://dx.doi.org/10.1161/STROKEAHA.118.023492DOI Listing
June 2019

Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage.

J Neurol Neurosurg Psychiatry 2019 07 16;90(7):783-791. Epub 2019 Apr 16.

Neurology, University of Erlangen-Nürnberg, Erlangen, Germany

Objective: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH.

Methods: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC.

Results: IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC.

Conclusions: Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.
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http://dx.doi.org/10.1136/jnnp-2018-319786DOI Listing
July 2019

Time to Loading Dose and Risk of Recurrent Events in the SOCRATES Trial.

Stroke 2019 03;50(3):675-682

Department of Medicine & Therapeutics, The Chinese University of Hong Kong (K.S.L.W.).

Background and Purpose- Recurrent ischemia risk is high in the acute period after cerebral ischemic events. Effects of antiplatelet agents may vary by time to loading dose (TLD). We explored the risk of recurrent events and safety and efficacy of ticagrelor versus aspirin in relation to TLD. Methods- We randomized 13 199 patients with noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to 90-day ticagrelor or aspirin treatment within 24 hours of symptom onset. For this analysis, 13 126 patients were categorized by TLD as <12 hours or ≥12 hours from start of index event. The primary end point was the composite of stroke, myocardial infarction, or death within 90 days. Major bleeding was the primary safety end point. Results- TLD was <12 hours in 4403 (33.5%) and ≥12 hours in 8723 (66.5%). The Kaplan-Meier% for the primary end point for all patients with TLD<12 hours was 7.5% versus 6.9% in TLD≥12 hours. Among patients with TLD<12 hours, the primary end point occurred in 147/2196 (6.8%) randomized to ticagrelor and in 184/2207 (8.3%) randomized to aspirin (hazard ratio, 0.79; 95% CI, 0.64-0.98; P=0.036). Among patients with TLD≥12 hours, the primary end point occurred in 6.7% patients randomized to ticagrelor versus 7.0% to aspirin (hazard ratio, 0.95; 95% CI, 0.81-1.12; P=0.55). There was no significant treatment-by-TLD interaction. Major bleeding rates were comparable on ticagrelor and aspirin, regardless of TLD. Conclusions- The event rate for the primary end point was higher in patients treated early (<12 hours) versus later (≥12 hours). In this exploratory analysis, a larger numerical difference in the primary end point was observed among patients on ticagrelor than on aspirin when TLD was <12 hours compared with ≥12 hours, although the interaction terms for treatment-by-TLD were not significant. For major bleeding, no relation to TLD was observed. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01994720.
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http://dx.doi.org/10.1161/STROKEAHA.118.022675DOI Listing
March 2019

Systematic evaluation of stroke thrombectomy in clinical practice: The German Stroke Registry Endovascular Treatment.

Int J Stroke 2019 06 22;14(4):372-380. Epub 2018 Oct 22.

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

Background: Endovascular treatment has become standard of care for the treatment of acute ischemic stroke with large vessel occlusion. However, patients treated in clinical practice differ from the selected populations randomized in clinical trials.

Aims: The German Stroke Registry Endovascular Treatment (GSR-ET) aims at a systematic evaluation of outcome, safety, and process parameters of endovascular stroke treatment in standard of care in Germany.

Methods: The GSR-ET is an academic, independent, prospective, multicenter, observational registry study. Participating stroke centers from all over of Germany consecutively enroll patients transferred to the angiography suite with an intention to be treated with endovascular stroke treatment. Patients receive regular care. Data are collected as part of clinical routine. Baseline clinical and procedural information and clinical follow-up information after 90 days are recorded. Here, we present an analysis of baseline data of the first 1662 patients included in the GSR-ET.

Results: The registry was established in June 2015. By 31 December 2017, 1662 patients were enrolled in 23 active sites. Mean age was 72 ± 13 years, 50% were female, and median National Institutes of Health Stroke Scale on admission was 15 (IQR 10-19), 88% had anterior circulation occlusion. Median ASPECT score was 8 (IQR 7-10) prior to intervention. Fifty-nine percent of patients received intravenous thrombolysis prior to thrombectomy. Mean "onset-to-groin" time was 224 ± 176 min.

Conclusions: Baseline characteristics of stroke patients undergoing thrombectomy in clinical practice differ from those in the randomized trials. The GSR-ET will provide valuable insights into practices of endovascular treatment in routine care of acute ischemic stroke. (GSR-ET ClinicalTrials.gov Identifier: NCT03356392.).
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http://dx.doi.org/10.1177/1747493018806199DOI Listing
June 2019

Expert opinion paper on atrial fibrillation detection after ischemic stroke.

Clin Res Cardiol 2018 Oct 27;107(10):871-880. Epub 2018 Apr 27.

Atrial Fibrillation NETwork (AFNET) e.V., Münster, Germany.

This expert opinion paper on atrial fibrillation detection after ischemic stroke includes a statement of the "Heart and Brain" consortium of the German Cardiac Society and the German Stroke Society. This paper was endorsed by the Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork. In patients with ischemic stroke, detection of atrial fibrillation should usually lead to a change in secondary stroke prevention, since oral anticoagulation is superior to antiplatelet drugs. The detection of previously undiagnosed atrial fibrillation can be improved in patients with ischemic stroke to optimize stroke prevention. This paper summarizes the present knowledge on atrial fibrillation detection after ischemic stroke. We propose an interdisciplinary standard for a "structured analysis of ECG monitoring" on the stroke unit as well as a staged diagnostic scheme for the detection of atrial fibrillation. Since the optimal duration and mode of ECG monitoring has not yet been finally established, this paper is intended to give advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on the expert opinion, reported case series and clinical experience. Therefore, this paper is not intended as a guideline.
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http://dx.doi.org/10.1007/s00392-018-1256-9DOI Listing
October 2018

Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves.

Eur Heart J 2018 05;39(19):1709-1723

Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, Erlangen 91054, Germany.

Aims: Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH.

Methods And Results: We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67-35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33-21.37; P < 0.01). The hazard for the composite-balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10-5.70; P = 0.03).

Conclusion: Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing-between least risks for thromboembolic and haemorrhagic complications-provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk.
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http://dx.doi.org/10.1093/eurheartj/ehy056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5950928PMC
May 2018

Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage.

Ann Neurol 2018 01;83(1):186-196

Department of Neurology, University of Erlangen-Nuremberg, Erlangen.

Objective: To investigate parameters associated with hematoma enlargement in non-vitamin K antagonist oral anticoagulant (NOAC)-related intracerebral hemorrhage (ICH).

Methods: This retrospective cohort study includes individual patient data for 190 patients with NOAC-associated ICH over a 5-year period (2011-2015) at 19 departments of neurology across Germany. Primary outcome was the association of prothrombin complex concentrate (PCC) administration with hematoma enlargement. Subanalyses were calculated for blood pressure management and its association with the primary outcome. Secondary outcomes include associations with in-hospital mortality and functional outcome at 3 months assessed using the modified Rankin Scale.

Results: The study population for analysis of primary and secondary outcomes consisted of 146 NOAC-ICH patients with available follow-up imaging. Hematoma enlargement occurred in 49/146 (33.6%) patients with NOAC-related ICH. Parameters associated with hematoma enlargement were blood pressure ≥ 160mmHg within 4 hours and-in the case of factor Xa inhibitor ICH-anti-Xa levels on admission. PCC administration prior to follow-up imaging was not significantly associated with a reduced rate of hematoma enlargement either in overall NOAC-related ICH or in patients with factor Xa inhibitor intake (NOAC: risk ratio [RR] = 1.150, 95% confidence interval [CI] = 0.632-2.090; factor Xa inhibitor: RR = 1.057, 95% CI = 0.565-1.977), regardless of PCC dosage given or time interval until imaging or treatment. Systolic blood pressure levels < 160mmHg within 4 hours after admission were significantly associated with a reduction in the proportion of patients with hematoma enlargement (RR = 0.598, 95% CI = 0.365-0.978). PCC administration had no effect on mortality and functional outcome either at discharge or at 3 months.

Interpretation: In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC-related ICH. Our findings support the need of further investigations exploring new hemostatic reversal strategies for patients with factor Xa inhibitor-related ICH. Ann Neurol 2018;83:186-196.
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http://dx.doi.org/10.1002/ana.25134DOI Listing
January 2018

Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany - A national case collection.

Int J Stroke 2017 06 24;12(4):383-391. Epub 2017 Mar 24.

9 Department of Neurology, Klinikum Mittelbaden, Rastatt, Germany.

Background Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran that reverses its anticoagulant effects within minutes. It may exhibit the potential for patients under dabigatran therapy suffering ischemic stroke to regain eligibility for thrombolysis with rt-PA and may inhibit lesion growth in patients with intracerebral hemorrhage on dabigatran. Aims To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of ischemic stroke or intracranial hemorrhage. Methods Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January to August 2016 were used. Results Thirty-one patients presenting with signs of stroke received idarucizumab in 22 stroke centers. Nineteen patients treated with dabigatran presented with ischemic stroke and 12 patients suffered from intracranial bleeding. In patients receiving rt-PA thrombolysis following idarucizumab, 79% benefitted from i.v. thrombolysis with a median improvement of five points in NIHSS. No bleeding complications occurred. Hematoma growth was observed in 2 out of 12 patients with intracranial hemorrhage. The outcome was favorable with a median NIHSS improvement of 5.5 points and mRS 0-3 in 67%. Overall, mortality was low with 6.5% (one patient in each group). Conclusion Administration of rt-PA after reversing dabigatran activity with idarucizumab in case of ischemic stroke is feasible, easy to manage, effective, and appears to be safe. In dabigatran-associated intracranial hemorrhage, idarucizumab has the potential to prevent hematoma growth and improve outcome. Idarucizumab represents a new therapeutic option for patients under dabigatran treatment presenting with ischemic stroke or intracranial hemorrhage.
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http://dx.doi.org/10.1177/1747493017701944DOI Listing
June 2017

Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS): Rationale and design of a prospective randomized multicenter study.

Am Heart J 2016 Feb 21;172:19-25. Epub 2015 Oct 21.

Center for Stroke Research Berlin & Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany; German Stroke Society, Berlin, Germany; Excellence Cluster NeuroCure, Charité-Universitätsmedizin Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases, Partner Site Berlin, Berlin, Germany; German Center for Cardiovascular Diseases, Partner Site Berlin, Berlin, Germany.

Background: Atrial fibrillation (AF) is estimated to account for approximately every fifth ischemic stroke. In routine clinical practice, detection of undiagnosed, clinically silent AF represents a major diagnostic challenge, and in up to 30% of patients with ischemic stroke, AF remains undetected. The MonDAFIS study has been designed to quantify the diagnostic yield and clinical relevance of systematic electrocardiogram (ECG) monitoring for patients with acute ischemic stroke during the subsequent in hospital stay.

Study Design: A prospective randomized multicenter study in 3,470 patients with acute ischemic stroke or transient ischemic attack and without known AF on hospital admission. Over a period of approximately 2years, patients will be enrolled in about 30 German-certified stroke units and randomized 1:1 to receive either usual stroke unit diagnostic procedures for detection of AF (control group) or usual stroke unit diagnostic procedures plus standardized and centrally analyzed Holter ECG recording for up to 7days in hospital (intervention group). Results of the ECG core laboratory analysis will be provided to the patients and treating physicians. All patients will be followed up for treatment and cardiovascular outcomes at 6, 12, and 24months after enrollment.

Outcomes: The primary outcome of the randomized MonDAFIS study is the proportion of patients who receive anticoagulation therapy 12months after the index stroke. Secondary outcomes include the number of stroke patients with newly detected AF in hospital and the rate of recurrent stroke, major bleedings, myocardial infarction, or death 6, 12, and 24months after the index event. MonDAFIS will also explore patient-reported adherence to anticoagulants, the clinical relevance of short atrial tachycardia, or excessive supraventricular ectopic activity as well as cost-effectiveness of prolonged, centrally analyzed ECG recordings.

Conclusion: MonDAFIS will be the largest study to date to evaluate whether a prolonged and systematic ECG monitoring during the initial in hospital stay has an impact on secondary stroke prevention. In addition, prognosis as well as adherence to medication up to 2 years after the index stroke will be analyzed. The primary results of the MonDAFIS study may have the potential to change the current guidelines recommendations regarding ECG workup after ischemic stroke.
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http://dx.doi.org/10.1016/j.ahj.2015.10.010DOI Listing
February 2016

Ruptured basilar artery perforator aneurysms--treatment regimen and long-term follow-up in eight cases.

Neuroradiology 2016 Mar 23;58(3):285-91. Epub 2015 Dec 23.

Department of Neuroradiology, Institute of Clinical Radiology, Grosshadern Campus, Marchioninistr 15, D-81377, Munich, Germany.

Introduction: Basilar artery (BA) perforator aneurysms may lead to severe subarachnoid hemorrhage (SAH). The acute management is uncertain. The anatomic approach is challenging both for coiling and clipping, and flow diverter stenting may be dangerous due to the required antiplatelet therapy. We report on our experiences in eight patients.

Methods: We retrospectively analyzed eight patients with ruptured BA perforator aneurysm, including clinical characteristics, imaging data, treatment regimen, clinical course, and long-term outcome.

Results: Patients presented with major SAH and World Federation of Neurosurgical Societies (WFNS) scores of I in three, II in two, and V in three cases. In four patients, the aneurysm was detected in the initial angiography, in four only in follow-up angiography. Five patients were treated conservatively and three patients had endovascular therapy. In the conservative group, the aneurysm spontaneously thrombosed in three cases. One patient suffered from a re-SAH and stayed permanently dependent due to an associated perforator stroke (modified Rankin Scale (mRS) 5). The remaining four patients recovered well (mRS 0 and 1 in two cases, each) including three patients also exhibiting perforator strokes. Regarding the endovascular group, one parent vessel was an angioma feeder and embolized with Onyx. The second aneurysm spontaneously thrombosed periinterventionally. The third patient underwent coiling. Two parent vessels were occluded postinterventionally, resulting in perforator strokes. Final mRS scores were 0, 2, and 2, respectively.

Conclusion: Conservative management of ruptured BA aneurysms might be a first-line treatment option with common spontaneous aneurysm occlusion, low rate of re-SAH, and promising clinical outcome.
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http://dx.doi.org/10.1007/s00234-015-1634-1DOI Listing
March 2016

[Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke].

Dtsch Med Wochenschr 2015 Jun 11;140 Suppl 1:S5-6. Epub 2015 Jun 11.

Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin Berlin.

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http://dx.doi.org/10.1055/s-0041-101292DOI Listing
June 2015

Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage.

JAMA 2015 Feb;313(8):824-36

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Importance: Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH).

Objective: To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption.

Design, Setting, And Participants: Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption.

Exposures: Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment.

Main Outcomes And Measures: Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome.

Results: Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of ≥1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs ≥160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%).

Conclusions And Relevance: Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies.

Trial Registration: clinicaltrials.gov Identifier: NCT01829581.
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http://dx.doi.org/10.1001/jama.2015.0846DOI Listing
February 2015

Interaction between diabetes and a high ankle-brachial index on mortality risk.

Eur J Prev Cardiol 2015 May 29;22(5):615-21. Epub 2014 Apr 29.

Paris Diderot University, Paris, France INSERM U1148, Paris, France Cardiology, Hôpital Bichat, and Département Hospitalo-Universitaire FIRE, AP-HP, Paris, France NHLI, Imperial College, Royal Brompton Hospital, London, UK.

Objective: Low ankle-brachial index (ABI) is a predictor of increased mortality. The impact of a high ABI on mortality is less studied. Moreover, diabetes is frequently associated with high ABI and, because of specific mechanisms in diabetic vascular diseases, the relationship with prognosis may be unique. Therefore, our aim was to compare mortality in individuals with and without diabetes according to abnormally low and high ABI.

Design And Methods: We studied the association between ABI and all-cause and cardiovascular mortality in 6986 participants from the REACH registry, a cohort of 45 years and older stable outpatients at high cardiovascular risk (2875 (41.1%) with diabetes) followed for 4 years.

Results: ABI was normal (0.91-1.29) in 49.5%, low (≤0.9) in 47.5%, and high (≥1.3) in 2.9% of participants. During follow up, 9.9% of participants died (6.5% from cardiovascular causes). A low ABI was associated with cardiovascular mortality (adjusted hazard ratio, HR, 1.98, 95% CI 1.62-2.41) and all-cause mortality (HR 2.01, 95% CI 1.72-2.36), without heterogeneity according to diabetes. In contrast, high ABI was associated with higher risk of all-cause mortality in individuals with diabetes (HR 2.11, 95% CI 1.16-3.84), but not without diabetes (HR 0.82, 95% CI 0.36-1.85; p-value for interaction 0.07). The trend was similar for cardiovascular mortality (HR 2.13, 95% CI 1.03-4.44 and HR 1.05, 95% CI 0.43-2.59 with and without diabetes, respectively; p-value for interaction 0.24).

Conclusions: In the REACH registry, low ABI was associated with mortality, similarly in individuals without and with diabetes, whereas the association with high ABI was only observed in patients with diabetes.
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http://dx.doi.org/10.1177/2047487314533621DOI Listing
May 2015

A simple brain atrophy measure improves the prediction of malignant middle cerebral artery infarction by acute DWI lesion volume.

J Neurol 2014 Jun 1;261(6):1097-103. Epub 2014 Apr 1.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany,

In patients with malignant middle cerebral artery infarction (MMI) decompressive surgery within 48 h improves functional outcome. In this respect, early identification of patients at risk of developing MMI is crucial. While the acute diffusion weighted imaging (DWI) lesion volume was found to predict MMI with high predictive values, the potential impact of preexisting brain atrophy on the course of space-occupying middle cerebral artery (MCA) infarction and the development of MMI remains unclear. We tested the hypothesis that the combination of the acute DWI lesion volume with simple measures of brain atrophy improves the early prediction of MMI. Data from a prospective, multicenter, observational study, which included patients with acute middle cerebral artery main stem occlusion studied by MRI within 6 h of symptom onset, was analyzed retrospectively. The development of MMI was defined according to the European randomized controlled trials of decompressive surgery. Acute DWI lesion volume, as well as brain and cerebrospinal fluid volume (CSF) were delineated. The intercaudate distance (ICD) was assessed as a linear brain atrophy marker by measuring the hemi-ICD of the intact hemisphere to account for local brain swelling. Binary logistic regression analysis was used to identify significant predictors of MMI. Cut-off values were determined by Classification and Regression Trees analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the resulting models were calculated. Twenty-one (18 %) of 116 patients developed a MMI. Malignant middle cerebral artery infarctions patients had higher National Institutes of Health Stroke Scale scores on admission and presented more often with combined occlusion of the internal carotid artery and MCA. There were no differences in brain and CSF volume between the two groups. Diffusion weighted imaging lesion volume was larger (p < 0.001), while hemi-ICD was smaller (p = 0.029) in MMI patients. Inclusion of hemi-ICD improved the prediction of MMI. Best cut-off values to predict the development of MMI were DWI lesion volume > 87 ml and hemi-ICD ≤ 9.4 mm. The addition of hemi-ICD to the decision tree strongly increased PPV (0.93 vs. 0.70) resulting in a reduction of false positive findings from 7/23 (30 %) to 1/15 (7 %), while there were only slight changes in specificity, sensitivity and NPV. The absolute number of correct classifications increased by 4 (3.4 %). The integration of hemi-ICD as a linear marker of brain atrophy, that can easily be assessed in an emergency setting, may improve the prediction of MMI by lesion volume based predictive models.
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http://dx.doi.org/10.1007/s00415-014-7324-9DOI Listing
June 2014

Combining magnetic resonance imaging within six-hours of symptom onset with clinical follow-up at 24 h improves prediction of 'malignant' middle cerebral artery infarction.

Int J Stroke 2014 Feb 9;9(2):210-4. Epub 2013 Jul 9.

Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Background: A large diffusion-weighted imaging lesion ≤six-hours of symptom onset was found to predict the development of 'malignant' middle cerebral artery infarction with high specificity, positive predictive value, and negative predictive value, but sensitivity was low.

Hypothesis: We tested the hypothesis that sensitivity can be improved by adding information from clinical follow-up examination after 24 h.

Methods: We analyzed data from a prospective, multicenter, observational cohort study of patients with acute ischemic stroke and middle cerebral artery occlusion studied by stroke magnetic resonance imaging ≤six-hours of symptom onset. We used the National Institutes of Health Stroke Scale to assess severity of symptoms after 24 h. We used the Classification and Regression Trees analysis to define the optimal thresholds of diffusion-weighted imaging lesion volume and the National Institutes of Health Stroke Scale after 24 h in patients developing 'malignant' middle cerebral artery infarction. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for two simple predictive models based on acute diffusion-weighted imaging lesion volume alone and acute diffusion-weighted imaging lesion volume together with the National Institutes of Health Stroke Scale after 24 h.

Results: Of 135 patients, 27 (20%) developed a 'malignant' middle cerebral artery infarction. The Classification and Regression Trees analysis identified acute diffusion-weighted imaging lesion ≥78 ml and the National Institutes of Health Stroke Scale score after 24 h ≥22 as optimal cut-offs. Inclusion of the National Institutes of Health Stroke Scale score after 24 h in a simple two-step decision tree increased sensitivity from 0·59 to 0·79, while specificity, positive predictive value, and negative predictive value remained largely unchanged.

Conclusion: Clinical follow-up examination after 24 h helps identify patients at risk of 'malignant' middle cerebral artery infarction that are missed by predictive algorithms based on early diffusion-weighted imaging lesion volume alone.
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http://dx.doi.org/10.1111/ijs.12060DOI Listing
February 2014

Treatment of acute ischaemic stroke with thrombolysis or thrombectomy in patients receiving anti-thrombotic treatment.

Lancet Neurol 2013 Jul 31;12(7):677-88. Epub 2013 May 31.

Department of Neurology and Stroke Centre, University Hospital Essen, Essen, Germany.

Systemic thrombolysis with alteplase is the only approved medical treatment for patients with acute ischaemic stroke. Thrombectomy is also increasingly used to treat proximal occlusions of the cerebral arteries, but has not shown superiority over systemic thrombolysis with alteplase. Many patients with acute ischaemic stroke are pretreated with antiplatelet or anticoagulant drugs, which can increase the bleeding risk of thrombolysis or thrombectomy. Pretreatment with aspirin monotherapy increases the bleeding risk of alteplase in both observational and randomised trials with no effect on clinical outcome, and the risk of intracerebral haemorrhage is increased with the combination of aspirin and clopidogrel. Antiplatelet drugs should not be given in the first 24 h after alteplase treatment. Data from pooled randomised trials and a large observational study show that thrombolysis can probably be done safely in patients given vitamin-K antagonists if the international normalised ratio is less than 1·7, although bleeding risk is slightly raised. Almost no data are available for the safety of alteplase in patients with atrial fibrillation who have been given novel oral anticoagulants (NOAC) for stroke prevention. Some coagulation parameters could help to identify patients treated with NOAC who might be eligible for thrombolysis. Thrombectomy can be done in patients given antiplatelets and probably in those given anticoagulants; however, conclusions about anticoagulants are based on findings from observational studies with small patient numbers.
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http://dx.doi.org/10.1016/S1474-4422(13)70101-7DOI Listing
July 2013

Thrombolytics in acute ischaemic stroke: historical perspective and future opportunities.

Cerebrovasc Dis 2013 23;35(4):313-9. Epub 2013 Apr 23.

Department of Neurology, Asklepios Klinik Altona, Hamburg, Germany.

The discovery of thrombolytic agents goes back to the 1930s, when it was shown that substances derived from bacteria (streptokinase, staphylokinase), tissue (fibrinokinase), urine (urokinase) or bat saliva could activate the fibrinolytic system. The potential to treat arterial thrombosis with plasmin was recognized, but it was not until 1958 that its first use in acute ischaemic stroke (AIS) was described. However, since computer tomography (CT) was not available until the mid 1970s, optimal selection of patients was not possible. Early studies with streptokinase in AIS showed an increased risk of intracranial haemorrhage and lack of efficacy, which was associated with low fibrin specificity. The search for new agents with a better risk-benefit profile continued until 1979 when tissue plasminogen activator (t-PA) was discovered. In 1983 it became possible to produce recombinant t-PA (rt-PA) by expression of a cloned gene which enabled clinical trials to be started, mainly for coronary thrombolysis. In 1995, the National Institute of Neurological Disorders and Stroke study showed that rt-PA was an effective treatment for AIS, nowadays for use up to 4.5 h after onset. However, rt-PA still often fails in achieving rapid reperfusion, has relatively low recanalization rates and is associated with an increased bleeding risk. Several attempts have been made to develop thrombolytics with a better risk-benefit profile than rt-PA, but no real impact on clinical practice was observed. In 1994, it was shown that tenecteplase (rt-PA-TNK) had a higher fibrin specificity than rt-PA, but its clinical use in AIS was described only in 2005. The recently reported results of a small phase 2B trial showed significantly better reperfusion and clinical outcome with rt-PA-TNK compared to rt-PA; patients were selected by CT perfusion and angiography, and treated within 6 h after stroke onset. Currently, a phase 3 trial of rt-PA-TNK versus rt-PA is being planned in patients at an onset up to 4.5 h. The most fibrin-specific recombinant plasminogen activator desmoteplase originates from 1991, and its clinical development in AIS started in 2005. Desmoteplase is in phase 3 development for the treatment of AIS between 3 and 9 h after onset in AIS patients presenting with occlusion or high-grade stenosis.
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http://dx.doi.org/10.1159/000348705DOI Listing
January 2014

Symptoms and clinical course of EHEC O104 infection in hospitalized patients: a prospective single center study.

PLoS One 2013 27;8(2):e55278. Epub 2013 Feb 27.

Department of Medicine I (Gastroenterology), Asklepios Klinik Altona, Hamburg, Germany.

Objectives: Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli (STEC/EHEC) is one of the most common causes of Haemolytic Uraemic Syndrome (HUS) related to infectious haemorrhagic colitis. Nearly all recommendations on clinical management of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first to be caused by the serotype O104:H4. This EHEC strain was found to carry genetic features of Entero Aggregative E. coli (EAEC) and extended spectrum β lactamase (ESBL). We report symptoms and complications in patients at one of the most affected centres of the 2011 EHEC O104 outbreak in Northern Germany.

Methods: The courses of patients admitted to our hospital due to bloody diarrhoea with suspected EHEC O104 infection were recorded prospectively. These data include the patients' histories, clinical findings, and complications.

Results: EHEC O104 infection was confirmed in 61 patients (female = 37; mean age: 44±2 years). The frequency of HUS was 59% (36/61) in our cohort. An enteric colonisation with co-pathogens was found in 57%. Thirty-one (51%) patients were treated with plasma-separation/plasmapheresis, 16 (26%) with haemodialysis, and 7 (11%) with Eculizumab. Patients receiving antibiotic treatment (n = 37; 61%) experienced no apparent change in their clinical course. Twenty-six (43%) patients suffered from neurological symptoms. One 83-year-old patient died due to comorbidities after HUS was successfully treated.

Conclusions: EHEC O104:H4 infections differ markedly from earlier reports on O157:H7 induced enterocolitis in regard to epidemiology, symptomatology, and frequency of complications. We recommend a standard of practice for clinical monitoring and support the renaming of EHEC O104:H4 syndrome as "EAHEC disease".
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055278PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584059PMC
September 2013

Carotid atherosclerosis and risk of subsequent coronary event in outpatients with atherothrombosis.

Stroke 2013 Feb 10;44(2):373-9. Epub 2013 Jan 10.

Department of Neurology and Stroke Center, AP-HP, Bichat-Claude Bernard Hospital, University of Paris Diderot, Sorbonne Paris Cité, Paris, France.

Background And Purpose: The presence of carotid plaque reflects overall atherosclerotic burden and may predict coronary artery disease events. We examined the association among carotid atherosclerosis, history of atherothrombotic events, and risk of coronary events.

Methods: Among 45 227 patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry with 4-year follow-up, 23 364 patients with information on carotid atherosclerosis at baseline were analyzed. The primary outcome was the composite of first occurrence of cardiovascular death, myocardial infarction, or coronary hospitalization.

Results: The carotid atherosclerosis was present in 46% of patients (n=10 725) and was associated with increasing conventional cardiovascular risk factors and extent of symptomatic vascular disease. During 4-year follow-up, 4304 patients experienced ≥1 coronary event. After adjustment for cardiovascular risk factors and geographic region, the risk of coronary events increased by 22% (95% confidence interval [CI], 14%-30%) in patients with versus without carotid atherosclerosis. The relative increase was 18% (95% CI, -7%-51%) in patients enrolled with multiple risk factors only, 25% (95% CI,16%-35%) in patients with coronary artery disease, 46% (95% CI,28%-65%) in patients with cerebrovascular disease, and 37% (95% CI,17%-60%) in patients with peripheral artery disease. Carotid atherosclerosis was associated with increased risk, even among patients with previous myocardial infarction but no known stroke (P=0.001) or among patients with previous stroke but no known myocardial infarction (P<0.001).

Conclusions: Carotid atherosclerosis was an independent predictor of coronary events across all types of symptomatic vascular disease and had an incremental effect on risk regardless of risk factors or location of vessel disease.
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http://dx.doi.org/10.1161/STROKEAHA.112.673129DOI Listing
February 2013