Martin Ebinger

Charité Universitätsmedizin Berlin, Berlín, Berlin, Germany

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Publications (72)295.26 Total impact

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    ABSTRACT: The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients. We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images. HARM was detected in 97 patients (18.3 %). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation. A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages. • Hyperintense acute reperfusion marker on MRI indicates blood-brain barrier disruption. • This observational study on stroke patients characterizes HARM. • Incidence depends on contrast agent dosage on the previous day. • HARM is also associated with older age and poor kidney function. • Interpretation of HARM must take dosage into consideration.
    European Radiology 04/2015; DOI:10.1007/s00330-015-3749-5 · 4.34 Impact Factor
  • Martin Ebinger, Heinrich J Audebert
    04/2015; 72(4):476-477. DOI:10.1001/jamaneurol.2014.4574
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    ABSTRACT: We aimed to assess the risk of recurrent ischemic events during hospitalization for stroke or transient ischemic attack (TIA) with optimal current management and to identify associated risk factors. We performed a retrospective analysis of all patients treated for acute ischemic stroke or TIA in 3 stroke units between 2010 and 2013. Recurrent stroke was defined as new persisting (≥24 hours) neurological deficit occurring >24 hours after the index event and not attributable to other causes of neurological deterioration. Cox proportional hazard regression identified risk factors associated with recurrent stroke. The study included 5106 patients. During a median length of stay of 5 days (interquartile range, 4-8), stroke recurrence (or stroke after TIA) occurred in 40 patients (0.8%) and was independently associated with history of TIA, symptomatic carotid stenosis (≥70%), or other determined etiology. Patients with recurrent stroke and other determined etiology had cervical arterial dissection (n=2), primary angiitis of the central nervous system (n=1), giant cell arteritis (n=1), and lung cancer with nonbacterial thrombotic endocarditis (n=1). In patients with initial TIA or minor stroke (National Institutes of Health Stroke Scale ≤5) recurrence was associated additionally with pneumonia after the inciting ischemic event but before stroke recurrence. Patients with initial stroke and aphasia had a lower stroke recurrence rate and there were no recurrences in patients with lacunar stroke. Recurrence was associated with significantly higher in-hospital mortality (17.5% versus 3.1%; P<0.001). In-hospital stroke recurrence was low with optimal current management. Patients with a history of TIA, severe symptomatic carotid stenosis, or uncommon causes of stroke were at higher risk. Pneumonia was associated with a higher risk of stroke recurrence in patients with initial TIA or minor stroke but not in the overall population studied. Aphasia may bias the detection rate by concealing new neurological symptoms. © 2015 American Heart Association, Inc.
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    ABSTRACT: To analyze the cost-effectiveness of shorter delays to treatment and increased thrombolysis rate as shown in the PHANTOM-S (Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke) Study. In addition to intermediate outcomes (time to thrombolysis) and treatment rates, we registered all resource consequences of the intervention. The analyzed treatment effects of the intervention were restricted to distribution of IV thrombolysis (IVT) administrations according to time intervals. Intermediate outcomes were extrapolated to final outcomes according to numbers needed to treat derived from pooled IVT trials and translated to gains in quality-adjusted life-years (QALYs). The net annual cost of the Stroke Emergency Mobile (STEMO) prehospital stroke concept was €963,954. The higher frequency of IVT administrations per year (310 vs 225) and higher proportions of patients treated in the early time interval (within 90 minutes: 48.1% vs 37.4%; 91-180 minutes: 37.4% vs 50%; 181-270 minutes: 14.5% vs 12.8%) resulted in an annual expected health gain of avoidance of 18 cases of disability equaling 29.7 QALYs. This produced an incremental cost-effectiveness ratio of €32,456 per QALY. Depending on willingness-to-pay thresholds in societal perspectives, the STEMO prehospital stroke concept has the potential of providing a reasonable innovation even in health-economic dimensions. © 2015 American Academy of Neurology.
    Neurology 02/2015; DOI:10.1212/WNL.0000000000001366 · 8.30 Impact Factor
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    ABSTRACT: Specialized management of patients with stroke is not available in all hospitals. We evaluated whether prehospital management in the Stroke Emergency Mobile (STEMO) improves the triage of patients with stroke. STEMO is an ambulance staffed with a specialized stroke team and equipped with a computed tomographic scanner and point-of-care laboratory. We compared the prehospital triage of patients with suspected stroke at dispatcher level who either received STEMO care or conventional care. We assessed transport destination in patients with different diagnoses. Status at hospital discharge was used as short-term outcome. From May 2011 to January 2013, 1804 of 6182 (29%) patients received STEMO care and 4378 of 6182 (71%) patients conventional care. Two hundred forty-five of 2110 (11.6%) patients with cerebrovascular events were sent to hospitals without Stroke Unit in conventional care when compared with 48 of 866 (5.5%; P<0.01%) patients in STEMO care. In patients with ischemic stroke, STEMO care reduced transport to hospitals without Stroke Unit from 10.1% (151 of 1497) to 3.9% (24 of 610; P<0.01). The delivery rate of patients with intracranial hemorrhage to hospitals without neurosurgery department was 43.0% (65 of 151) in conventional care and 11.3% (7 of 62) in STEMO care (P<0.01). There was a slight trend toward higher rates of patients discharged home in neurological patients when cared by STEMO (63.5% versus 60.8%; P=0.096). The triage of patients with cerebrovascular events to specialized hospitals can be improved by STEMO ambulances. http://www.clinicaltrials.gov. Unique identifier: NCT01382862. © 2015 American Heart Association, Inc.
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    ABSTRACT: Mobile computed tomography (CT) scanning in specialized ambulances has recently become feasible. Two randomized trials have used mobile CTs for prehospital thrombolysis. This short review summarizes the available literature on this topic and provides an outlook on potential future developments. Mobile CT in acute suspected stoke is feasible and helps to diagnose, triage and treat patients. It is an integral component of a novel and promising stroke research platform in specialized ambulances with telemedicine connection and neurological expertise on board. Mobile CTs can speed up stroke treatment, especially thrombolysis; they allow for selecting the most adequate hospital destinations; and they offer new means of stroke research.
    Current Opinion in Neurology 12/2014; 28(1). DOI:10.1097/WCO.0000000000000165 · 5.73 Impact Factor
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    ABSTRACT: The effectiveness of intravenous thrombolysis in acute ischemic stroke is time dependent. The effects are likely to be highest if the time from symptom onset to treatment is within 60 minutes, termed the golden hour.
    JAMA Neurology 11/2014; DOI:10.1001/jamaneurol.2014.3188 · 7.01 Impact Factor
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    ABSTRACT: Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a malignant profile defined by lesion volume ≥100 mL.
  • JAMA The Journal of the American Medical Association 09/2014; 312(9):961-2. DOI:10.1001/jama.2014.8378 · 30.39 Impact Factor
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    ABSTRACT: We sought to determine if an association exists between overall, deep, and periventricular white matter hyperintensities and depression. We searched PubMed (Medline) and Scopus (Embase) from April-October 2012 using the MeSH terms: "White matter lesions" OR "white matter disease" OR "Cerebrovascular Disease" OR "Leukoencephalopathies" AND "Depressive Disorder" AND "magnetic resonance imaging," and "Depression" AND "leukoaraiosis." No language limits were implemented. Hand searching was performed of all included studies and relevant review articles. 913 PubMed and 188 Scopus citations were identified. Relevant, human, non-overlapping magnetic resonance imaging studies were eligible for inclusion if they reported generic data. We extracted the most adjusted odds ratios reported generated from comparing depression across severe (determined either volumetrically or visually) and mild/no white matter lesion groups. 19 reports were included. Cross-sectional subgroup analyses showed that deep white matter hyperintensities significantly associated with depression (N = 2261, odds ratio 1.02, 95% confidence interval 1.00-1.04, p = 0.02), whereas periventricular (N = 3813, odds ratio 1.08, 95% confidence interval 0.99-1.17, p = 0.07) and overall did not (N = 5876, odds ratio 1.12, 95% confidence interval 0.96-1.30, p = 0.14). Overall longitudinal analysis revealed a pooled odds ratio of 1.12 (N = 2015; 95% confidence interval 0.97-1.29; p = 0.13; Q = 7.19, p = 0.07; I(2) = 58.3%). Longitudinal subgroup analyses revealed that overall white matter hyperintensities (N = 1882, odds ratio 1.22, 95% confidence interval, 1.06-1.4, p < 0.01) significantly associated with depression but deep did not (N = 660, odds ratio 2.02, 95% confidence interval, 0.56-7.22, p = 0.281). No significant heterogeneity was present in subgroup analyses. In conclusion, we found a significant, but weak association between white matter hyperintensities and depression.
    Journal of Psychiatric Research 06/2014; DOI:10.1016/j.jpsychires.2014.05.005 · 4.09 Impact Factor
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    ABSTRACT: Time to thrombolysis is crucial for outcome in acute ischemic stroke. To determine if starting thrombolysis in a specialized ambulance reduces delays. In the Prehospital Acute Neurological Treatment and Optimization of Medical care in Stroke Study (PHANTOM-S), conducted in Berlin, Germany, we randomly assigned weeks with and without availability of the Stroke Emergency Mobile (STEMO) from May 1, 2011, to January 31, 2013. Berlin has an established stroke care infrastructure with 14 stroke units. We included 6182 adult patients (STEMO weeks: 44.3% male, mean [SD] age, 73.9 [15.0] y; control weeks: 45.2% male, mean [SD] age, 74.3 [14.9] y) for whom a stroke dispatch was activated. The intervention comprised an ambulance (STEMO) equipped with a CT scanner, point-of-care laboratory, and telemedicine connection; a stroke identification algorithm at dispatcher level; and a prehospital stroke team. Thrombolysis was started before transport to hospital if ischemic stroke was confirmed and contraindications excluded. Primary outcome was alarm-to-thrombolysis time. Secondary outcomes included thrombolysis rate, secondary intracerebral hemorrhage after thrombolysis, and 7-day mortality. Time reduction was assessed in all patients with a stroke dispatch from the entire catchment area in STEMO weeks (3213 patients) vs control weeks (2969 patients) and in patients in whom STEMO was available and deployed (1804 patients) vs control weeks (2969 patients). Compared with thrombolysis during control weeks, there was a reduction of 15 minutes (95% CI, 11-19) in alarm-to-treatment times in the catchment area during STEMO weeks (76.3 min; 95% CI, 73.2-79.3 vs 61.4 min; 95% CI, 58.7-64.0; P < .001). Among patients for whom STEMO was deployed, mean alarm-to-treatment time (51.8 min; 95% CI, 49.0-54.6) was shorter by 25 minutes (95% CI, 20-29; P < .001) than during control weeks. Thrombolysis rates in ischemic stroke were 29% (310/1070) during STEMO weeks and 33% (200/614) after STEMO deployment vs 21% (220/1041) during control weeks (differences, 8%; 95% CI, 4%-12%; P < .001, and 12%, 95% CI, 7%-16%; P < .001, respectively). STEMO deployment incurred no increased risk for intracerebral hemorrhage (STEMO deployment: 7/200; conventional care: 22/323; adjusted odds ratio [OR], 0.42, 95% CI, 0.18-1.03; P = .06) or 7-day mortality (9/199 vs 15/323; adjusted OR, 0.76; 95% CI, 0.31-1.82; P = .53). Compared with usual care, the use of ambulance-based thrombolysis resulted in decreased time to treatment without an increase in adverse events. Further studies are needed to assess the effects on clinical outcomes. clinicaltrials.gov Identifier: NCT01382862.
    JAMA The Journal of the American Medical Association 04/2014; 311(16):1622-31. DOI:10.1001/jama.2014.2850 · 30.39 Impact Factor
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    ABSTRACT: Thyroid-stimulating hormone (TSH) concentrations are frequently altered in acute ischemic stroke patients. It is becoming increasingly apparent that various hormones in the hypothalamus-pituitary-thyroid axis may be associated with functional stroke outcome. We have previously shown that white matter hyperintensities (WMH) of presumed vascular origin are strong indicators of functional outcome. It is unclear whether an association exists between WMH and TSH. We therefore sought to determine whether TSH levels, measured in acute ischemic stroke patients, are associated with WMH and functional outcome. We analyzed all first ischemic stroke patients who participated in the Berlin 'Cream & Sugar' Study (NCT 01378468) and completed a 1-year follow-up assessment from January 2009 to March 2013. Patients were stratified into 3 groups: (1) low TSH (0.1-0.44 μU/ml); (2) normal TSH (0.44-2.5 μU/ml), and (3) high TSH (2.5-20 μU/ml). WMH were assessed using the Fazekas and Wahlund visual rating scales. Functional outcome was assessed using the modified Rankin Scale and was performed via telephone at 1 year by a certified rater. 183 patients were included [median age 66, interquartile range (IQR) 54-75; 33% females; median National Institute of Health Stroke Scale 3, IQR 1-4, range 0-24]. Venous samples were collected a median of 4 days (IQR 3-5) following initial symptom onset between 8 and 9 a.m. following a 10-hour fast. Patients with normal TSH levels (n = 132; 72%) had significantly higher rates of prestroke diabetes than patients with high TSH levels (normal TSH 17%; high TSH 1%; p = 0.03). Additionally, patients with normal TSH levels tended to have higher estimated glomerular filtration rates than patients with high and low TSH concentrations (normal TSH median estimated glomerular filtration rates: 83 ml/min/1.73 m(2); high TSH median estimated glomerular filtration rates: 76 ml/min/1.73 m(2); low TSH median: 78 ml/min/1.73 m(2); p = 0.068). Logistical regression analysis force-adjusted for age (quartiles), NIHSS (quartiles), prestroke diabetes status, and stroke subtype revealed significant associations between WMH and TSH [Wahlund scores: odds ratio 2.547, 95% confidence interval (CI) 1.159-5.598, p = 0.020; Fazekas scores: odds ratio 2.530, 95% CI 1.115-5.741, p = 0.003]. Functional outcome was not significantly associated with TSH levels in univariate or multivariate models. TSH levels are independently associated with WMH in acute ischemic stroke patients. Based on our findings, we cannot recommend assessing TSH to estimate the 1-year functional outcome following ischemic stroke.
    03/2014; 4(1):61-8. DOI:10.1159/000360217
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    ABSTRACT: In acute stroke, the DWI-FLAIR mismatch allows for the allocation of patients to the thrombolysis window (<4.5 hours). FLAIR-lesions, however, may be challenging to assess. In comparison, DWI may be a useful bio-marker owing to high lesion contrast. We investigated the performance of a relative DWI signal intensity (rSI) threshold to predict the presence of FLAIR-lesions in acute stroke and analyzed its association with time-from-stroke-onset. In a retrospective, dual-center MR-imaging study we included patients with acute stroke and time-from-stroke-onset ≤12 hours (group A: n = 49, 1.5T; group B: n = 48, 3T). DW- and FLAIR-images were coregistered. The largest lesion extent in DWI defined the slice for further analysis. FLAIR-lesions were identified by 3 raters, delineated as regions-of-interest (ROIs) and copied on the DW-images. Circular ROIs were placed within the DWI-lesion and labeled according to the FLAIR-pattern (FLAIR+ or FLAIR-). ROI-values were normalized to the unaffected hemisphere. Adjusted and nonadjusted receiver-operating-characteristics (ROC) curve analysis on patient level was performed to analyze the ability of a DWI- and ADC-rSI threshold to predict the presence of FLAIR-lesions. Spearman correlation and adjusted linear regression analysis was performed to assess the relationship between DWI-intensity and time-from-stroke-onset. DWI-rSI performed well in predicting lesions in FLAIR-imaging (mean area under the curve (AUC): group A: 0.84; group B: 0.85). An optimal mean DWI-rSI threshold was identified (A: 162%; B: 161%). ADC-maps performed worse (mean AUC: A: 0.58; B: 0.77). Adjusted regression models confirmed the superior performance of DWI-rSI. Correlation coefficents and linear regression showed a good association with time-from-stroke-onset for DWI-rSI, but not for ADC-rSI. An easily assessable DWI-rSI threshold identifies the presence of lesions in FLAIR-imaging with good accuracy and is associated with time-from-stroke-onset in acute stroke. This finding underlines the potential of a DWI-rSI threshold as a marker of lesion age.
    PLoS ONE 03/2014; 9(3):e92295. DOI:10.1371/journal.pone.0092295 · 3.53 Impact Factor
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    ABSTRACT: Given the rising number of strokes worldwide, and the large number of individuals left with disabilities after stroke, novel strategies to reduce disability, increase functions in the motor and the cognitive domains, and improve quality of life are of major importance. Physical activity is a promising intervention to address these challenges but, as yet, there is no study demonstrating definite outcomes. Our objective is to assess whether additional treatment in the form of physical fitness-based training for patients early after stroke will provide benefits in terms of functional outcomes, in particular gait speed and the Barthel Index (co-primary outcome measures) reflecting activities of daily living (ADL). We will gather secondary functional outcomes as well as mechanistic parameters in an exploratory approach.Methods/design: Our phase III randomised controlled trial will recruit 215 adults with moderate to severe limitations of walking and ADL 5 to 45 days after stroke onset. Participants will be stratified for the prognostic variables of "centre", "age", and "stroke severity", and randomly assigned to one of two groups. The interventional group receives physical fitness training delivered as supported or unsupported treadmill training (cardiovascular active aerobic training; five times per week, over 4 weeks; each session 50 minutes; total of 20 additional physical fitness training sessions) in addition to standard rehabilitation treatment. The control intervention consists of relaxation sessions (non-cardiovascular active; five times per week week, over 4 weeks; each session 50 minutes) in addition to standard rehabilitation treatment. Co-primary efficacy endpoints will be gait speed (in m/s, 10 m walk) and the Barthel Index (100 points total) at 3 months post-stroke, compared to baseline measurements. Secondary outcomes include standard measures of quality of life, sleep and mood, cognition, arm function, maximal oxygen uptake, and cardiovascular risk factors including blood pressure, pulse, waist-to-hip ratio, markers of inflammation, immunity and the insulin-glucose pathway, lipid profile, and others. The goal of this endpoint-blinded, phase III randomised controlled trial is to provide evidence to guide post-stroke physical fitness-based rehabilitation programmes, and to elucidate the mechanisms underlying this intervention.Trial registration: Registered in ClinicalTrials.gov with the Identifier NCT01953549.
    Trials 02/2014; 15(1):45. DOI:10.1186/1745-6215-15-45 · 2.12 Impact Factor
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    ABSTRACT: Physical activity is believed to exert a beneficial effect on functional and cognitive rehabilitation of patients with stroke. Although studies have addressed the impact of physical exercise in cerebrovascular prevention and rehabilitation, the underlying mechanisms leading to improvement are poorly understood. Training-induced increase of cerebral perfusion is a possible mediating mechanism. Our exploratory study aims to investigate training-induced changes in blood biomarker levels and magnetic resonance imaging in patients with subacute ischemic stroke.Methods/design: This biomarker-driven study uses an observational design to examine a subgroup of patients in the randomized, controlled PHYS-STROKE trial. In PHYS-STROKE, 215 patients with subacute stroke (hemorrhagic and ischemic) receive either 4 weeks of physical training (aerobic training, 5 times a week, for 50 minutes) or 4 weeks of relaxation sessions (5 times a week, for 50 minutes). A convenience sample of 100 of these patients with ischemic stroke will be included in BAPTISe and will receive magnetic resonance imaging (MRI) scans and an additional blood draw before and after the PHYS-STROKE intervention. Imaging scans will address parameters of cerebral perfusion, vessel size imaging, and microvessel density (the Q factor) to estimate the degree of neovascularization in the brain. Blood tests will determine several parameters of immunity, inflammation, endothelial function, and lipometabolism. Primary objective of this study is to evaluate differential changes in MRI and blood-derived biomarkers between groups. Other endpoints are next cerebrovascular events and functional status of the patient after the intervention and after 3 months assessed by functional scores, in particular walking speed and Barthel index (co-primary endpoints of PHYS-STROKE). Additionally, we will assess the association between functional outcomes and biomarkers including imaging results. For all endpoints we will compare changes between patients who received physical fitness training and patients who had relaxation sessions. This exploratory study will be the first to investigate the effects of physical fitness training in patients with ischemic stroke on MRI-based cerebral perfusion, pertinent blood biomarker levels, and functional outcome. The study may have an impact on current patient rehabilitation strategies and reveal important information about the roles of MRI and blood-derived biomarkers in ischemic stroke.Trial registration: NCT01954797.
    BMC Neurology 12/2013; 13(1):197. DOI:10.1186/1471-2377-13-197 · 2.49 Impact Factor
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    ABSTRACT: Background and Purpose: Although the presence of cavitating lacunes on brain imaging may have prognostic implications, the modifiable risk factors underlying these frequently observed lesions are not completely understood. We sought to determine if fasting and post-challenge triglycerides associate with cavitating lacunes. Methods: All first ischemic stroke patients who completed a novel combined oral triglyceride and glucose tolerance test and MRI between January 2009 and June 2012 were included. Fluid-attenuated inversion recovery or T2 MRI sequences were used to visualize cavitating lacunes and white matter hyperintensities, which were graded using the Wahlund visual scale. Results: One hundred and ninety patients were included (median age 66, IQR 52–73; 33% female; median National Institute of Health Stroke Scale 2, IQR 1–4). A forward stepwise binary logistical regression analysis applying the Hosmer–Lemeshow goodness of fit test adjusted for parameters significant in univariate analyses (at the p < 0.10 level) revealed that Wahlund scores (Wahlund 0–4: reference; Wahlund 5–10: adjusted odds ratio, 5.1; 95% confidence interval, 1.3–20.0, p = 0.019; Wahlund>10: adjusted odds ratio 9.6; 95% CI, 1.55–59.35; p = 0.015) and the highest quartile of post-challenge triglycerides (>295 mg/dL; adjusted odds ratio, 7.36; 95% confidence interval 1.24–43.70; p = 0.028) independently associated with the presence of cavitating lacunes. Conclusion: Post-challenge serum triglycerides are independently associated with the presence of cavitating lacunes.
    Frontiers in Neurology 07/2013; 4:92. DOI:10.3389/fneur.2013.00092
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    ABSTRACT: DSC-MRI is the most widely used method for perfusion imaging (PI) in brain, especially for stroke patients. However, the relationship between tracer concentration and signal change is only strictly valid for a network of capillaries and not in case of estimating the arterial input function (AIF). To investigate that impact, an analysis of 211 PI measurements regarding peak signal drop and relative concentration was performed. We found a descending linearity between the micro- and macrovascular signal with an increasing size of the AIF-defining artery. We conclude that in case of standard imaging techniques more distal arteries are preferable.
    ISMRM 21st Annual Meeting & Exhibition, Salt Lake City; 04/2013
  • Anna Kufner, Christian H Nolte, Martin Ebinger
    Stroke 04/2013; 44(5):e59. DOI:10.1161/STROKEAHA.113.001287 · 6.02 Impact Factor
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    ABSTRACT: RATIONALE: In about 20% of acute ischemic stroke patients stroke occurs during sleep. These patients are generally excluded from intravenous thrombolysis. MRI can identify patients within the time-window for thrombolysis (≤4·5 h from symptom onset) by a mismatch between the acute ischemic lesion visible on diffusion weighted imaging (DWI) but not visible on fluid-attenuated inversion recovery (FLAIR) imaging. AIMS AND HYPOTHESIS: The study aims to test the efficacy and safety of MRI-guided thrombolysis with tissue plasminogen activator (rtPA) in ischemic stroke patients with unknown time of symptom onset, e.g., waking up with stroke symptoms. We hypothesize that stroke patients with unknown time of symptom onset with a DWI-FLAIR-mismatch pattern on MRI will have improved outcome when treated with rtPA compared to placebo. DESIGN: WAKE-UP is an investigator initiated, European, multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients with unknown time of symptom onset who fulfil clinical inclusion criteria (disabling neurological deficit, no contraindications against thrombolysis) will be studied by MRI. Patients with MRI findings of a DWI-FLAIR-mismatch will be randomised to either treatment with rtPA or placebo. STUDY OUTCOME: The primary efficacy endpoint will be favourable outcome defined by modified Rankin Scale 0-1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin Scale 4-6 at 90 days. DISCUSSION: If positive, WAKE-UP is expected to change clinical practice making effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute therapy.
    International Journal of Stroke 03/2013; 9(6). DOI:10.1111/ijs.12011 · 4.03 Impact Factor

Publication Stats

726 Citations
295.26 Total Impact Points

Institutions

  • 2009–2015
    • Charité Universitätsmedizin Berlin
      • • Center for Stroke Research Berlin
      • • Department of Nephrology
      Berlín, Berlin, Germany
    • University of Melbourne
      Melbourne, Victoria, Australia
  • 2008–2010
    • Royal Melbourne Hospital
      • Department of Radiology
      Melbourne, Victoria, Australia
    • Max Planck Institute of Psychiatry
      München, Bavaria, Germany