Götz Thomalla

University Medical Center Hamburg - Eppendorf, Hamburg, Hamburg, Germany

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Publications (106)457.59 Total impact

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    ABSTRACT: 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.
    Journal of Neurology 04/2014; · 3.58 Impact Factor
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    ABSTRACT: Malignant infarction is characterized by the formation of cerebral edema, and medical treatment is limited. Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. We previously reported feasibility of the GAMES-Pilot study, a two-center prospective, open label, phase IIa trial of 10 subjects at high risk for malignant infarction based on diffusion weighted imaging (DWI) threshold of 82 cm(3) treated with RP-1127 (glyburide for injection). In this secondary analysis, we tested the hypothesis that RP-1127 may be efficacious in preventing poor outcome when compared to controls. Controls suffering large hemispheric infarction were obtained from the EPITHET and MMI-MRI studies. We first screened subjects for controls with the same DWI threshold used for enrollment into GAMES-Pilot, 82 cm(3). Next, to address imbalances, we applied a weighted Euclidean matching. Ninety day mRS 0-4, rate of decompressive craniectomy, and mortality were the primary clinical outcomes of interest. The mean age of the GAMES cohort was 51 years and initial DWI volume was 102 ± 23 cm(3). After Euclidean matching, GAMES subjects showed similar NIHSS, higher DWI volume, younger age and had mRS 0-4-90 % versus 50 % in controls p = 0.049; with a similar trend in mRS 0-3 (40 vs. 25 %; p = 0.43) and trend toward lower mortality (10 vs. 35 %; p = 0.21). In this pilot study, RP-1127-treated subjects showed better clinical outcomes when compared to historical controls. An adequately powered and randomized phase II trial of patients at risk for malignant infarction is needed to evaluate the potential efficacy of RP-1127.
    Neurocritical Care 03/2014; · 3.04 Impact Factor
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    ABSTRACT: WAKE-UP is a randomized, placebo-controlled MRI-based trial of thrombolysis in wake-up stroke using the mismatch between a lesion's visibility in diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) sequences as its main imaging inclusion criterion. Visual judgment of lesion conspicuity on FLAIR is however methodically limited by moderate inter-rater agreement. We therefore sought to improve rating homogeneity by incorporating quantitative signal intensity measurements. One hundred forty-three data sets of patients with acute ischemic stroke were visually rated by 8 raters with respect to WAKE-UP study inclusion and exclusion criteria, and inter-rater agreement was calculated. A subanalysis was performed on 45 cases to determine a threshold value of relative signal intensity (rSI) between the ischemic lesion and contralateral healthy tissue which best corresponded to a visually established verdict of FLAIR positivity. The usefulness of this threshold in improving inter-rater agreement was evaluated in an additional sample of 50 patients. Inter-rater agreement for inclusion into the WAKE-UP trial was 73% with a free-marginal κ of 0.46. A threshold of rSI which best correlated with the visual rating of lesions as FLAIR positive was 1.20. The addition of rSI measurements to visual evaluation did not change the inter-rater agreement. Introducing a semiquantitative measure for FLAIR rSI did not improve the agreement between individual raters. However, enhancing visual assessment with rSI measurements can provide reassurance to local investigators in cases of uncertainty.
    Stroke 02/2014; · 6.16 Impact Factor
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    ABSTRACT: The aim of this study is to investigate whether different spatial perfusion-deficit patterns, which indicate differing compensatory mechanisms, can be recognized and used to predict recanalization success of intravenous fibrinolytic therapy in acute stroke patients. Twenty-seven acute stroke data sets acquired within 6 hours from symptom onset including diffusion- (DWI) and perfusion-weighted magnetic resonance (MR) imaging (PWI) were analyzed and dichotomized regarding recanalization outcome using time-of-flight follow-up data sets. The DWI data sets were used for calculation of apparent diffusion coefficient (ADC) maps and subsequent infarct core segmentation. A patient-individual three-dimensional (3D) shell model was generated based on the segmentation and used for spatial analysis of the ADC as well as cerebral blood volume (CBV), cerebral blood flow, time to peak (TTP), and mean transit time (MTT) parameters derived from PWI. Skewness, kurtosis, area under the curve, and slope were calculated for each parameter curve and used for classification (recanalized/nonrecanalized) using a LogitBoost Alternating Decision Tree (LAD Tree). The LAD tree optimization revealed that only ADC skewness, CBV kurtosis, and MTT kurtosis are required for best possible prediction of recanalization success with a precision of 85%. Our results suggest that the propensity for macrovascular recanalization after intravenous fibrinolytic therapy depends not only on clot properties but also on distal microvascular bed perfusion. The 3D approach for characterization of perfusion parameters seems promising for further research.Journal of Cerebral Blood Flow & Metabolism advance online publication, 29 January 2014; doi:10.1038/jcbfm.2014.13.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 01/2014; · 5.46 Impact Factor
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    ABSTRACT: This study aimed to relate growth of the infarct core with time to recanalization in patients receiving mechanical recanalization in whom the time of recanalization is known. We analyzed data from patients with anterior circulation acute ischemic stroke who underwent mechanical recanalization. Demographic and angiographic characteristics, initial apparent diffusion coefficient (ADC) infarct volume, time-to-peak defect volume, revascularization grade, 24-48 h nonenhanced computed tomography (CT) infarct volume, symptom onset to recanalization time, diffusion-weighted imaging to recanalization time, and discharge National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were compared between minimal and substantial infarct growth groups. Substantial infarct growth was defined as an increase of infarct volume >10 cm(3) assessed by subtracting initial ADC infarct core volume from infarct volume at 24-48 h CT. Of 25 patients, 9 had minimal infarct growth (median 0 cm(3), interquartile range (IQR) -3 to 5 cm(3)) and 16 had substantial infarct growth (median 103 cm(3), IQR 48-132 cm(3)). Patients with minimal infarct growth had a median time from symptom onset to recanalization of 329 min (IQR 314-412 min) and a median time from imaging to recanalization of 231 min (IQR 198-309 min). On univariate analysis, minimal infarct growth was related to male gender (p = 0.04), smaller initial ADC volume (p = 0.04), higher recanalization grade (p < 0.001), and lower discharge NIHSS (p = 0.04) and mRS grades (p = 0.04). There was no or minimal infarct core growth in at least one third of patients despite an exceptionally long median time from magnetic resonance imaging to recanalization of almost 4 h.
    Neuroradiology 01/2014; · 2.70 Impact Factor
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    ABSTRACT: Tics in Gilles de la Tourette syndrome (GTS) are repetitive patterned movements, resembling spontaneous motor behaviour, but escaping voluntary control. Previous studies hypothesised relations between structural alterations in prefrontal cortex of GTS adults and tic severity using voxel-based morphometry (VBM), but could not demonstrate a significant association. The relation between prefrontal cortex structure and tic inhibition has not been investigated. Here, we used VBM to examine 14 GTS adults without associated comorbidities, and 15 healthy controls. We related structural alterations in GTS to clinical measures of tic severity and tic control. Grey matter volumes in the right inferior frontal gyrus and the left frontal pole were reduced in patients relative to healthy controls. These changes were not related to tic severity and tic inhibition. Prefrontal grey matter volume reductions in GTS adults are not related to state measures of tic phenomenology.
    Journal of psychosomatic research 01/2014; 76(1):84-7. · 2.91 Impact Factor
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    ABSTRACT: Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. We assessed the feasibility of recruiting and treating patients with severe stroke while obtaining preliminary information on the safety and tolerability of RP-1127 (glyburide for injection). We studied 10 patients with acute ischemic stroke, with baseline diffusion-weighted imaging lesion volumes of 82 to 210 cm(3), whether treated with intravenous recombinant tissue-type plasminogen activator, age 18 to 80 years, and time to RP-1127 ≤10 hours. Recruitment was completed within 10 months. The mean age was 50.5 years, and baseline diffusion-weighted image lesion volume was 102±23 cm(3). There were no serious adverse events related to drug and no symptomatic hypoglycemia. The increase in ipsilateral hemisphere volume was 50±33 cm(3). The proportion of 90-day modified Rankin Scale ≤4 was 90% (40% modified Rankin Scale, ≤3). RP-1127 at a dose of 3 mg/d was well tolerated and did not require any dose reductions. A clinical trial of RP-1127 is feasible. http://www.clinicaltrials.gov. Unique identifier: NCT01268683.
    Stroke 11/2013; · 6.16 Impact Factor
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    ABSTRACT: Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by an impaired ability to inhibit unwanted behaviour. Although the presence of chronic motor and vocal tics defines Tourette's syndrome, other distinctive behavioural features like echo- and coprophenomena, and non-obscene socially inappropriate behaviour are also core features. We investigated neuronal activation during stimulus-driven execution and inhibition of prepared movements in Tourette's syndrome. To this end, we performed event-related functional magnetic resonance imaging and structural diffusion tensor imaging in 15 moderately affected uncomplicated patients with 'pure' Tourette's syndrome and 15 healthy control participants matched for age and gender. Subjects underwent functional magnetic resonance imaging during a Go/NoGo reaction time task. They had to withhold a prepared finger movement for a variable time until a stimulus instructed them to either execute (Go) or inhibit it (NoGo). Tics were monitored throughout the experiments, combining surface electromyogram, video recording, and clinical assessment in the scanner. Patients with Tourette's syndrome had longer reaction times than healthy controls in Go trials and made more errors in total. Their functional brain activation was decreased in left primary motor cortex and secondary motor areas during movement execution (Go trials) but not during response inhibition (NoGo trials) compared with healthy control subjects. Volume of interest analysis demonstrated less task-related activation in patients with Tourette's syndrome in primary and secondary motor cortex bilaterally, but not in the basal ganglia and cortical non-motor areas. They showed reduced co-activation between the left primary sensory-motor hand area and a network of contralateral sensory-motor areas and ipsilateral cerebellar regions. There were no between-group differences in structural connectivity of the left primary sensory-motor cortex as measured by diffusion tensor imaging-based probabilistic tractography. Our results link reduced sensory-motor cortical activation during movement execution to a decreased co-activation between the sensory-motor cortex and other brain areas involved in motor processing. These functional changes in patients with Tourette's syndrome might result from adaptive reorganization in fronto-parietal brain networks engaged in motor and behavioural control, possibly triggered by abnormal processing and presumably overactivity in cortico-striato-cortical circuits. This might enable patients with Tourette's syndrome to better suppress unwanted movements but comes at a price of behavioural deficits in other domains.
    Brain 10/2013; · 9.92 Impact Factor
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    Stroke 07/2013; · 6.16 Impact Factor
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    New England Journal of Medicine 06/2013; · 51.66 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Nearly 50% of patients have residual motor deficits after stroke, and long-term motor outcome is difficult to predict. We assessed the predictive value of axonal damage to the corticospinal tract indexed by diffusion tensor imaging fractional anisotropy for long-term motor outcome. METHODS: Consecutive patients with middle cerebral artery stroke underwent multimodal MRI, including diffusion tensor imaging ≤12 hours, 3 days, and 30 days after onset. Clinical severity, infarct volume, location of corticospinal tract damage on diffusion tensor tractography, and ratios of fractional anisotropy (rFA) between affected and unaffected sides of the corticospinal tract at the pons were evaluated. Severity of motor deficit at 2 years was categorized using the Motricity Index as no deficit (Motricity Index, 100), slight-moderate deficit (Motricity Index, 99-50), or severe deficit (Motricity Index, <50). RESULTS: We evaluated 70 patients (28 women; 72±12 years). rFA values at day 30 correlated with the degree of motor deficit at 2 years (P<0.001). rFA at day 30 was the only independent predictor of long-term motor outcome (odds ratio, 1.60; 95% confidence interval, 1.26-2.03; P<0.001). The sensitivity, specificity, and positive and negative predictive values of the cutoffs rFA<0.982 for predicting slight-moderate deficit and rFA<0.689 for severe deficit were 94.4%, 84.6%, 73.9%, and 97.1%, respectively, and 100%, 83.3%, 81.3%, and 100%, respectively. CONCLUSIONS: rFA at day 30 is an independent predictor of long-term motor outcome after stroke.
    Stroke 05/2013; · 6.16 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE:The mismatch between lesions identified in perfusion- and diffusion-weighted MR imaging is typically used to identify tissue at risk of infarction in acute stroke. The purpose of this study was to analyze the variability of mismatch volumes resulting from different time-to-peak or time-to-maximum estimation techniques used for hypoperfused tissue definition.MATERIALS AND METHODS:Data of 50 patients with middle cerebral artery stroke and intracranial vessel occlusion imaged within 6 hours of symptom onset were analyzed. Therefore, 10 different TTP/Tmax techniques and delay thresholds between +2 and +12 seconds were used for calculation of perfusion lesions. Diffusion lesions were semiautomatically segmented and used for mismatch quantification after registration.RESULTS:Mean volumetric differences up to 40 and 100 mL in individual patients were found between the mismatch volumes calculated by the 10 TTP/Tmax estimation techniques for typically used delay thresholds. The application of typical criteria for the identification of patients with a clinically relevant mismatch volume resulted in different mismatch classifications in ≤24% of all cases, depending on the TTP/Tmax estimation method used.CONCLUSIONS:High variations of tissue-at-risk volumes have to be expected when using different TTP/Tmax estimation techniques. An adaption of different techniques by using correction formulas may enable more comparable study results until a standard has been established by agreement.
    American Journal of Neuroradiology 03/2013; · 3.17 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; · 2.75 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: The role of diffusion tensor imaging in determining stroke age remains unclear. We tested the ability of diffusion tensor imaging metrics to discriminate ischemic stroke <4.5 hours of onset. METHODS: We enrolled 60 consecutive patients for multimodal 1.5 T MRI within 12 hours of middle cerebral artery ischemic stroke onset. We measured fractional anisotropy (FA), mean diffusivity (MD), apparent diffusion coefficient (ADC), and T2-weighted signal intensity in affected ipsilateral and unaffected contralateral deep gray matter, cortical gray matter, deep white matter in the corticospinal tract (CST), and subcortical white matter and calculated ipsilateral-to-contralateral ratios (r). Hyperintensity in infarcted tissue was considered fluid-attenuated inversion recovery-positive. RESULTS: We analyzed the 48 patients (17 women; mean age, 68±14 years) with known onset. In 25 (52.1%) patients, onset was ≤4.5 hours (mean, 182.3±65.6 minutes). Variables differing significantly between infarcts <4.5 hours and >4.5 hours were rFA CST (P=0.001), rMD cortical gray matter (P=0.036), rADC cortical gray matter (P=0.009), rT2 CST (P=0.006), and fluid-attenuated inversion recovery (P<0.001). rFA at CST was the most reliable to discriminate infarcts <4.5 hours (Goodman-Kruskal=0.76). The sensitivity, specificity, and positive and negative predictive values for infarct <4.5 hours of onset by rFA at CST >0.970 were 93.8%, 84.6%, 88.2%, and 91.7%, respectively. CONCLUSIONS: These preliminary results suggest rFA at CST may be a surrogate marker of acute stroke age.
    Stroke 03/2013; · 6.16 Impact Factor
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    ABSTRACT: The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke.Journal of Cerebral Blood Flow & Metabolism advance online publication, 27 February 2013; doi:10.1038/jcbfm.2013.18.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 02/2013; · 5.46 Impact Factor
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    ABSTRACT: Gilles de la Tourette syndrome (GTS) is a common developmental neuropsychiatric disorder characterized by tics and frequent psychiatric comorbidities, often causing significant disability. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of actions, particularly structural and functional disorders in the striatum and cortico-striato-thalamo-cortical loops. We therefore applied structural diffusion tensor imaging (DTI) to characterize changes in intrahemispheric white matter connectivity in cortico-subcortical circuits engaged in motor control in 15 GTS patients without psychiatric comorbidities. White matter connectivity was analyzed by probabilistic fiber tractography between 12 predefined cortical and subcortical regions of interest. Connectivity values were combined with measures of clinical severity rated by the Yale Global Tic Severity Scale (YGTSS). GTS patients showed widespread structural connectivity deficits. Lower connectivity values were found specifically in tracts connecting the supplementary motor areas (SMA) with basal ganglia (pre-SMA-putamen, SMA-putamen) and in frontal cortico-cortical circuits. There was an overall trend towards negative correlations between structural connectivity in these tracts and YGTSS scores. Structural connectivity of frontal brain networks involved in planning, controlling and executing actions is reduced in adult GTS patients which is associated with tic severity. These findings are in line with the concept of GTS as a neurodevelopmental disorder of brain immaturity.
    NeuroImage. Clinical. 01/2013; 4:174-81.
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    ABSTRACT: In acute stroke magnetic resonance imaging, a 'mismatch' between visibility of an ischemic lesion on diffusion-weighted imaging (DWI) and missing corresponding parenchymal hyperintensities on fluid-attenuated inversion recovery (FLAIR) data sets was shown to identify patients with time from symptom onset ≤4.5 hours with high specificity. However, moderate sensitivity and suboptimal interpreter agreement are limitations of a visual rating of FLAIR lesion visibility. We tested refined image analysis methods in patients included in the previously published PREFLAIR study using refined visual analysis and quantitative measurements of relative FLAIR signal intensity (rSI) from a three-dimensional, segmented stroke lesion volume. A total of 399 patients were included. The rSI of FLAIR lesions showed a moderate correlation with time from symptom onset (r=0.382, P<0.001). A FLAIR rSI threshold of <1.0721 predicted symptom onset ≤4.5 hours with slightly increased specificity (0.85 versus 0.78) but also slightly decreased sensitivity (0.47 versus 0.58) as compared with visual analysis. Refined visual analysis differentiating between 'subtle' and 'obvious' FLAIR hyperintensities and classification and regression tree algorithms combining information from visual and quantitative analysis also did not improve diagnostic accuracy. Our results raise doubts whether the prediction of stroke onset time by visual image judgment can be improved by quantitative rSI measurements.Journal of Cerebral Blood Flow & Metabolism advance online publication, 10 October 2012; doi:10.1038/jcbfm.2012.129.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 10/2012; · 5.46 Impact Factor
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    ABSTRACT: Patients waking up with stroke symptoms are generally excluded from intravenous thrombolysis. It was shown that magnetic resonance imaging (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. The WAKE-UP trial is an investigator initiated, European, randomized, double-blind, placebo-controlled trial designed to test efficacy and safety of MRI-based thrombolysis with alteplase (tPA) in stroke patients with unknown time of symptom onset, e.g. due to symptom recognition on awakening. A total of 800 patients showing MRI findings of a DWI-FLAIR-mismatch will be randomized to either tPA or placebo. The primary efficacy endpoint will be favourable outcome defined by a modified Rankin scale score 0-1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin scale score 4-6 at 90 days. If positive the WAKE-UP trial is expected to change clinical practice and to make effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute treatment.
    Der Nervenarzt 09/2012; 83(10):1241-51. · 0.80 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Hyperintense vessels (HVs) have been observed in fluid-attenuated inversion recovery imaging of patients with acute ischemic stroke and been linked to slow flow in collateral arterial circulation. Given the potential importance of HV, we used a large, multicenter data set of patients with stroke to clarify which clinical and imaging factors play a role in HV. METHODS: We analyzed data of 516 patients from the previously published PRE-FLAIR study (PREdictive value of FLAIR and DWI for the identification of acute ischemic stroke patients ≤3 and ≤4.5 hours of symptom onset-a multicenter study) study. Patients were studied by MRI within 12 hours of symptom onset. HV were defined as hyperintensities in fluid-attenuated inversion recovery corresponding to the typical course of a blood vessel that was not considered the proximal, occluded main artery ipsilateral to the diffusion restriction. Presence of HV was rated by 2 observers and related to clinical and imaging findings. RESULTS: Presence of HV was identified in 240 of all 516 patients (47%). Patients with HV showed larger initial ischemic lesion volumes (median, 12.3 versus 4.9mL; P<0.001) and a more severe clinical impairment (median National Institutes of Health Stroke Scale 10.5 versus 6; P<0.001). In 198 patients with MR angiography, HVs were found in 80% of patients with vessel occlusion and in 17% without vessel occlusion. In a multivariable logistic regression model, vessel occlusion was associated with HV (OR, 21.7%; 95% CI, 9.6-49.9; P<0.001). HV detected vessel occlusion with a specificity of 0.86 (95% CI, 0.80-0.90) and sensitivity of 0.76 (95% CI, 0.69-0.83). CONCLUSIONS: HVs are a common finding associated with proximal arterial occlusions and more severe strokes. HVs predict arterial occlusion with high diagnostic accuracy.
    Stroke 08/2012; 43(11):2957-2961. · 6.16 Impact Factor

Publication Stats

1k Citations
457.59 Total Impact Points


  • 2004–2014
    • University Medical Center Hamburg - Eppendorf
      • Department of Neurology
      Hamburg, Hamburg, Germany
  • 2013
    • Universität zu Lübeck
      • Institute for Medical Informatics
      Lübeck, Schleswig-Holstein, Germany
  • 2010–2012
    • Heinrich-Heine-Universität Düsseldorf
      • Institut für Klinische Neurowissenschaften und Medizinische Psychologie
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2003–2011
    • University of Hamburg
      • • Department of Neurology
      • • Department of Diagnostic and Interventional Neuroradiology
      Hamburg, Hamburg, Germany