Martin Ebinger

Charité Universitätsmedizin Berlin, Berlín, Berlin, Germany

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Publications (83)355.16 Total impact

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    ABSTRACT: Background: Common carotid artery intima-media thickness (CCA-IMT) is an established marker for atherosclerosis. The role of triglycerides in CCA-IMT remains controversial. We sought to determine if elevated fasting and post-challenge triglycerides are associated with CCA-IMT. Methods: All acute ischemic stroke patients who participated in the Berlin "Cream & Sugar" study in the Charité Virchow and Charité Mitte Campuses between January 2009 and January 2014 and underwent carotid artery ultrasound studies were eligible for inclusion. A combined oral glucose and triglyceride tolerance test was performed 3-7 days after first ever ischemic stroke. Patients were classified according to triglyceride metabolism-namely, (1) patients reaching a maximum triglyceride levels 3 h post-challenge ("fast metabolizers," n = 37), (2) patients with increasing triglycerides 4 (medium metabolizers, n = 64), and (3) 5 h post-challenge ("slow metabolizers," n = 44; 13 missing). Results: We included 158 patients (34% female; mean age 63 years, SD 14). Absolute non-fasting triglyceride levels were positively associated with CCA-IMT. A final multiple regression model revealed that older age, more severe strokes, and higher levels of fasting triglycerides were significantly and independently associated with higher mean CCA-IMT. Older age, higher waist-to-hip ratio, and higher levels of thyroid-stimulating hormone were independently associated with higher maximum CCA-IMT. Conclusion: Fasting triglycerides but not post-challenge triglycerides associate with CCA-IMT. An oral fat challenge may not add information on atherosclerotic status in ischemic stroke patients. Clinical trial registration information: The Berlin "Cream & Sugar" study is registered with EudraCT (2009-010356-97) and (NCT 01378468).
    Atherosclerosis 09/2015; 243(1):186-191. DOI:10.1016/j.atherosclerosis.2015.09.003 · 3.99 Impact Factor
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    ABSTRACT: Objective: Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as a risk factor for ischemic stroke remains controversial. We conducted a meta-analysis to determine the relative strength of the association between Lp(a) and ischemic stroke and identify potential subgroup-specific risk differences. Methods: A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein a" AND "stroke" was performed in PubMed and ScienceDirect for case-control studies from June 2006 and prospective cohort studies from April 2009 until December 20th 2014. Data from eligible papers published before these dates were reviewed and extracted from previous meta-analyses. Studies that assessed the relationship between Lp(a) levels and ischemic stroke and reported generic data-i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]-were eligible for inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke and transient ischemic attack were excluded. Random effects meta-analyses with mixed-effects meta-regression were performed by pooling adjusted OR or RR. Results: A total of 20 articles comprising 90,904 subjects and 5029 stroke events were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the pooled estimated OR was 1.41 (95% CI, 1.26-1.57) for case-control studies (n = 11) and the pooled estimated RR was 1.29 (95% CI, 1.06-1.58) for prospective studies (n = 9). Sex-specific differences in RR were inconsistent between case-control and prospective studies. Study populations with a mean age of ≤55 years had an increased RR compared to older study populations. Reported Lp(a) contrast levels and ischemic stroke subtype significantly contributed to the heterogeneity observed in the analyses. Conclusion: Elevated Lp(a) is an independent risk factor for ischemic stroke and may be especially relevant for young stroke patients. Sex-specific risk differences remain conflicting. Further studies in these subgroups may be warranted.
    Atherosclerosis 08/2015; 242(2):496-503. DOI:10.1016/j.atherosclerosis.2015.08.021 · 3.99 Impact Factor
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    ABSTRACT: Copeptin levels are increased in patients diagnosed with stroke and other vascular diseases. Copeptin elevation is associated with adverse outcome, predicts re-events in patients with transient ischemic attack and is used in ruling-out acute myocardial infarction. We evaluated whether copeptin can also be used as a diagnostic marker in the prehospital stroke setting. We prospectively examined patients with suspected stroke on the Stroke Emergency Mobile-an ambulance that is equipped with computed tomography and point-of-care laboratory. A blood sample was taken from patients immediately after arrival. We analyzed copeptin levels in patients with final hospital-based diagnosis of stroke or stroke mimics as well as in vascular or nonvascular patients. In addition, we examined the associations of symptom onset with copeptin levels and the prognostic value of copeptin in patients with stroke. Blood samples of 561 patients were analyzed. No significant differences were seen neither between cerebrovascular (n=383) and other neurological (stroke mimic; n=90) patients (P=0.15) nor between vascular (n=391) and nonvascular patients (n=170; P=0.57). We could not detect a relationship between copeptin levels and time from onset to blood draw. Three-month survival status was available in 159 patients with ischemic stroke. Copeptin levels in nonsurviving patients (n=8: median [interquartile range], 27.4 [20.2-54.7] pmol/L) were significantly higher than in surviving patients (n=151: median [interquartile range], 11.7 [5.2-30.9] pmol/L; P=0.024). In the prehospital setting, copeptin is neither appropriate to discriminate between stroke and stroke mimic patients nor between vascular and nonvascular patients. URL: Unique identifier: NCT01382862. The Pre-Hospital Acute Neurological Therapy and Optimization of Medical Care in Stroke Patients study (PHANTOM-S) was registered (NCT01382862). This sub-study was observational and not registered separately, therefore. © 2015 American Heart Association, Inc.
    Stroke 08/2015; 46(9). DOI:10.1161/STROKEAHA.115.009877 · 5.72 Impact Factor
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    ABSTRACT: Background. Stroke can be a challenging diagnosis in an emergency-setting. We sought to determine whether copeptin may be a useful biomarker to differentiate between ischemic stroke (IS), transient ischemic attack (TIA), and stroke-mimics. Methods. In patients with suspected stroke arriving within 4.5 hours of symptom-onset, copeptin-levels were measured in initial blood-samples. The final diagnosis was adjudicated by vascular neurologists blinded to copeptin-values. Results. Of all 36 patients with available copeptin-values (median age 71 years, IQR: 54-76; 44% female), 20 patients (56%) were diagnosed with IS, no patient was diagnosed with hemorrhagic stroke, nine patients (25%) were diagnosed with TIA, and seven patients (19%) were stroke-mimics. Copeptin-levels (in pmol/L) tended to be higher in patients with IS [19.1 (11.2-48.5)] compared to TIA [9.4 (5.4-13.8)]. In stroke-mimics the range of values was extremely broad [33.3 (7.57-255.7)]. The diagnostic accuracy of copeptin for IS was 63% with a sensitivity of 80% and a positive predictive value of 64%. Conclusion. In this cohort of patients copeptin-levels within 4.5 hours of symptom onset were higher in patients with IS compared to TIA but the broad range of values in stroke-mimics limits diagnostic accuracy. This trial is registered with UTN: U1111-1119-7602.
    Stroke Research and Treatment 07/2015; 2015:1-4. DOI:10.1155/2015/768401
  • Joachim Weber · Martin Ebinger · Heinrich J Audebert
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    ABSTRACT: Over the last 15 years, new approaches regarding neuroprotective and thrombolytic strategies in stroke management have been evaluated in the prehospital setting. These efforts have provided exciting new potentials of hyperacute stroke care. Trials have shown that the use of specialized stroke ambulances increases the proportion of patients receiving intravenous thrombolysis and shortens alarm-to-treatment time by approximately half an hour compared to standard care. Intravenous thrombolysis within the ultra-early time window of the 'golden hour' has become a realistic scenario. However, direct effects of prehospital stroke care on functional outcome have yet to be shown and other approaches such as neuroprotective treatments could not demonstrate clinical benefit so far. There is a clear need for systematic research in the prehospital field to test the clinical effectiveness and cost-effectiveness of new therapeutic strategies. It will be necessary to test various components of prehospital stroke care alone and in combination.
    Expert Review of Neurotherapeutics 07/2015; 15(7):753-61. DOI:10.1586/14737175.2015.1051967 · 2.78 Impact Factor
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    ABSTRACT: Background: Insulin-like Growth Factor-1 (IGF-1) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) have been ascribed neuroprotective effects. We sought to determine whether levels of IGF-1 and IGFBP-3 predict functional outcome after ischemic stroke. Methods: IGF-1 and IGFBP-3 levels were measured in the first week after stroke in patients with first ischemic stroke who were enrolled in the Berlin Cream&Sugar Study. National Institutes of Health Stroke Scale (NIHSS) was collected at admission. Lesion volume was determined from acute MRI if available. Functional outcome according to the modified Rankin Scale (mRS) was assessed after one year. In multivariate analyses we identified parameters associated with unfavourable functional outcome (mRS>2). Results: We included 100 patients. 21 patients had an unfavourable functional outcome. IGF-1 levels were<- 2 standard deviation score (SDS) in 7 patients, and>2 SDS in 12 patients. IGFBP-3 levels were<the 5(th) percentile in 13 patients, and no patient had IGFBP-3 levels>the 95(th) percentile. Low levels of IGFBP-3 (p=0.002), NIHSS at admission (p=0.043) and age (p=0.001) were associated with unfavourable functional outcome in the univariate analyses. In multivariate analysis including IGFBP-3, IGF-1, age, thrombolysis and NIHSS only low IGFBP-3 levels (OR 7.2, 95%CI 1.8-29.0, p=0.006) were associated with unfavourable functional outcome. If lesion volume was incuded (n=71), only IGFBP-3 levels (OR 7.2, 95%CI 1.5-35.5, p=0.015) were associated with unfavourable functional outcome. Conclusion: IGFBP-3 levels after ischemic stroke may independently predict functional outcome after one year. © Georg Thieme Verlag KG Stuttgart · New York.
    Experimental and Clinical Endocrinology & Diabetes 06/2015; DOI:10.1055/s-0035-1554632 · 1.56 Impact Factor
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    ABSTRACT: Hyperintense vessels on baseline FLAIR MR imaging of patients with ischemic stroke have been linked to leptomeningeal collateralization, yet the ability of these to maintain viable ischemic tissue remains unclear. We investigated whether hyperintense vessels on FLAIR are associated with the severity of hypoperfusion and response to thrombolysis in patients treated with intravenous tissue-plasminogen activator. Consecutive patients with ischemic stroke with an MR imaging before and within 24 hours of treatment, with proved vessel occlusion and available time-to-maximum maps were included (n = 62). The severity of hypoperfusion was characterized on the basis of the hypoperfusion intensity ratio (volume with severe/mild hypoperfusion [time-to-maximum ≥ 8 seconds / time-to-maximum ≥ 2 seconds]). The hypoperfusion intensity ratio was dichotomized at the median to differentiate moderate (hypoperfusion intensity ratio ≤ 0.447) and severe (hypoperfusion intensity ratio > 0.447) hypoperfusion. Good outcome was defined as a modified Rankin Scale score of ≤2. Hyperintense vessels on FLAIR were identified in 54 patients (87%). Patients with extensive hyperintense vessels on FLAIR (>4 sections) had higher NIHSS scores, larger baseline lesion volumes, higher rates of perfusion-diffusion mismatch, and more severe hypoperfusion (hypoperfusion intensity ratio). In stepwise backward multivariate regression analysis for the dichotomized hypoperfusion intensity ratio (including stroke etiology, age, perfusion deficit, baseline lesion volume, smoking, and extent of hyperintense vessels on FLAIR), extensive hyperintense vessels on FLAIR were independently associated with severe hypoperfusion (OR, 6.8; 95% CI, 1.1-42.7; P = .04). The hypoperfusion intensity ratio was an independent predictor of a worse functional outcome at 3 months poststroke (OR, 0.2; 95% CI, 0.5-0.6; P < .01). Hyperintense vessels on FLAIR are associated with larger perfusion deficits, larger infarct growth, and more severe hypoperfusion, suggesting that hyperintense vessels on FLAIR most likely indicate severe ischemia as a result of insufficient collateralization. © 2015 American Society of Neuroradiology.
    American Journal of Neuroradiology 05/2015; 36(8). DOI:10.3174/ajnr.A4320 · 3.59 Impact Factor
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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; 25(11). DOI:10.1007/s00330-015-3749-5 · 4.01 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.
    Stroke 03/2015; 46(4). DOI:10.1161/STROKEAHA.114.006886 · 5.72 Impact Factor
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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; 84(11). DOI:10.1212/WNL.0000000000001366 · 8.29 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. Unique identifier: NCT01382862. © 2015 American Heart Association, Inc.
    Stroke 01/2015; 46(3). DOI:10.1161/STROKEAHA.114.008159 · 5.72 Impact Factor
  • Martin Ebinger · Jochen B Fiebach · Heinrich J Audebert
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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 · 5.31 Impact Factor
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    ABSTRACT: Importance 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.Objective To determine the achievable rate of golden hour thrombolysis in prehospital care and its effect on outcome.Design, Setting, and Participants The prospective controlled Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke study was conducted in Berlin, Germany, within an established infrastructure for stroke care. Weeks were randomized according to the availability of a specialized ambulance (stroke emergency mobile unit (STEMO) from May 1, 2011, through January 31, 2013. We included 6182 consecutive adult patients for whom a stroke dispatch (44.1% male; mean [SD] age, 73.9 [15.0] years) or regular care (45.0% male; mean [SD] age, 74.2 [14.9] years) were included.Interventions The STEMO was deployed when the dispatchers suspected an acute stroke during emergency calls. If STEMO was not available (during control weeks, when the unit was already in operation, or during maintenance), patients received conventional care. The STEMO is equipped with a computed tomographic scanner plus a point-of-care laboratory and telemedicine connection. The unit is staffed with a neurologist trained in emergency medicine, a paramedic, and a technician. Thrombolysis was started in STEMO if a stroke was confirmed and no contraindication was found.Main Outcomes and Measures Rates of golden hour thrombolysis, 7- and 90-day mortality, secondary intracerebral hemorrhage, and discharge home.Results Thrombolysis rates in ischemic stroke were 200 of 614 patients (32.6%) when STEMO was deployed and 330 of 1497 patients (22.0%) when conventional care was administered (P < .001). Among all patients who received thrombolysis, the proportion of golden hour thrombolysis was 6-fold higher after STEMO deployment (62 of 200 patients [31.0%] vs 16 of 330 [4.9%]; P < .01). Compared with patients with a longer time from symptom onset to treatment, patients who received golden hour thrombolysis had no higher risks for 7- or 90-day mortality (adjusted odds ratios, 0.38 [95% CI, 0.09-1.70]; P = .21 and 0.69 [95% CI, 0.32-1.53]; P = .36) and were more likely to be discharged home (adjusted odds ratio, 1.93 [95% CI, 1.09-3.41]; P = .02).Conclusions and Relevance The use of STEMO increases the percentage of patients receiving thrombolysis within the golden hour. Golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes.Trial Registration Identifier: NCT01382862
    JAMA Neurology 11/2014; 72(1). DOI:10.1001/jamaneurol.2014.3188 · 7.42 Impact Factor
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    ABSTRACT: Background and purpose: 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. Methods: We analyzed data of patients with MCA stroke from a prospective observational study of DWI and fluid-attenuated inversion recovery in acute stroke. DWI-ASPECTS and lesion volume were calculated. The population was divided into subgroups based on lesion localization (superficial MCA territory, deep MCA territory, or both). Correlation of ASPECTS and infarct volume was calculated, and receiver-operating characteristics curve analysis was performed to identify the optimal ASPECTS threshold for ≥100-mL lesion volume. Results: A total of 496 patients were included. There was a significant negative correlation between ASPECTS and DWI lesion volume (r=-0.78; P<0.0001). With regards to lesion localization, correlation was weaker in deep MCA region (r=-0.19; P=0.038) when compared with superficial (r=-0.72; P<0.001) or combined superficial and deep MCA lesions (r=-0.72; P<0.001). Receiver-operating characteristics analysis revealed ASPECTS≤6 as best cutoff to identify ≥100-mL DWI lesion volume; however, positive predictive value was low (0.35). Conclusions: ASPECTS has limitations when lesion location is not considered. Identification of patients with malignant profile by DWI-ASPECTS may be unreliable. ASPECTS may be a useful tool for the evaluation of noncontrast computed tomography. However, if MRI is used, ASPECTS seems dispensable because lesion volume can easily be quantified on DWI maps.
    Stroke 10/2014; 45(12). DOI:10.1161/STROKEAHA.114.006694 · 5.72 Impact Factor
  • International Journal of Stroke 10/2014; 9:211-211. · 3.83 Impact Factor
  • Martin Ebinger · Ulrike Grittner · Heinrich J Audebert
    JAMA The Journal of the American Medical Association 09/2014; 312(9):961-2. DOI:10.1001/jama.2014.8378 · 35.29 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 · 3.96 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. Identifier: NCT01382862.
    JAMA The Journal of the American Medical Association 04/2014; 311(16):1622-31. DOI:10.1001/jama.2014.2850 · 35.29 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

Publication Stats

857 Citations
355.16 Total Impact Points


  • 2009–2015
    • Charité Universitätsmedizin Berlin
      • • Center for Stroke Research Berlin
      • • Department of Urology
      • • 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