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© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.562 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., Objective: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. Methods: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. Results: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). Conclusions: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573., This research was funded by The Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005) and the Dr. C. J. Vaillant Foundation.

Background Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth. Aims To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage. Methods Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used. Results One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0–3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay. Conclusion Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

Contains fulltext : 245661.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). OBJECTIVE: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. EXPOSURES: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. MAIN OUTCOMES AND MEASURES: Clinical characteristics and mortality rate. RESULTS: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Background and Purpose— There are few in vivo data on the pathophysiology of reperfusion during systemic thrombolysis. We monitored the time course of cerebral perfusion changes in patients during thrombolysis with repeated arterial spin labeling perfusion magnetic resonance imaging. Methods— Ten patients with proximal arterial occlusion within 4.5 hours after symptom onset were prospectively enrolled. All patients received intravenous thrombolysis during the magnetic resonance imaging examination. Repeated arterial spin labeling perfusion images were acquired during the 60-minute therapy and at follow-up after 24 to 72 hours. Clinical data, magnetic resonance imaging features, and cerebral perfusion changes were analyzed. Results— Before thrombolysis, arterial spin labeling hypoperfusion and fluid-attenuation inversion recovery vascular hyperintensity in the territory of the occluded arteries were observed in all patients. In 5 patients, extensive arterial transit artifacts (ATA) developed in the hypoperfused area. The ATA corresponded with fluid-attenuation inversion recovery vascular hyperintensities. All 5 patients who developed extensive ATA in the hypoperfused area had complete reperfusion after thrombolysis, whereas the 5 without extensive ATA showed no or only partial reperfusion ( P Conclusions— The development of ATA during thrombolysis is associated with early reperfusion after thrombolysis. arterial spin labeling assessment during intravenous thrombolysis has the potential to guide subsequent therapeutic strategies in patients with acute stroke.

Background: The prognosis of stroke patients admitted to intensive care units (ICU) is commonly regarded to be poor. However, only limited data regarding outcome predictors are available. Patients and Methods: Out of 4,958 consecutive patients admitted to our stroke unit with the diagnosis of acute stroke, after analysis we identified 347 patients (164 male) in need of ICU management. In-hospital and post-rehabilitation mortality as well as functional outcome at discharge and after rehabilitation were analyzed. Results: Ischemic stroke was diagnosed in 252 patients (72.6%) and intracerebral hemorrhage occurred in 95 patients (27.4%). The mean age in our cohort was considerably high (70.8 years). One hundred patients were comatose at admission. The median NIHSS score at admission in the remaining patients was 12. Apart from stroke-related disturbances of consciousness (47.1%), the most common reasons for ICU treatment were cardiac (23.4%) and respiratory (12.1%) complications or interventional procedures requiring mechanical ventilation (11%). In all, 231/347 patients (66.6%) were mechanically ventilated (mean 84 h). In-hospital mortality (143/347; 41.2%) was associated with old age, poor NIHSS score at admission, intracerebral hemorrhage and mechanical ventilation (p < 0.001 in all). Further, admission to ICU because of stroke-related impairment of consciousness increased in-hospital mortality (p < 0.001). Similarly, poor outcome after rehabilitation was associated with old age (p = 0.029) and mechanical ventilation (p < 0.001). In patients ≥80 years with either intracerebral hemorrhage or need of mechanical ventilation, outcome was unfavorable in nearly any case. However, the overall post-rehabilitation outcome did not differ between patients with intracerebral hemorrhage and ischemic stroke (p = 0.275). Conclusion: The stroke population in our study was associated with an increased early mortality; however, given the same conditions, it was old with a high percentage of patients requiring mechanical ventilation. This did not result in increased in-hospital mortality rates compared to younger and less severely affected cohorts. Thus, ICU management is a life-saving initiative even among the elderly. However, the functional outcome was poor in older patients, thus limiting the benefits of ICU care in these patients.

Background Changes in cerebral perfusion during migraine with aura (MA) have been assessed mainly using dynamic susceptibility contrast (DSC) magnetic resonance perfusion imaging. A contrast agent-free method to assess these changes would be desirable. We assessed changes in cerebral perfusion during MA using arterial spin labeling (ASL) perfusion magnetic resonance imaging. Methods We investigated 4 patients with a standardized protocol including ASL perfusion imaging during MA (n = 2) or early headache phase (n = 2) and asymptomatic follow-up. Semiquantitative evaluation was done using a region of interest (ROI) within hypoperfused or hyperperfused areas and corresponding ROIs in the contralateral hemisphere. Relative ratios of mean perfusion in the corresponding ROIs were calculated. DSC imaging was done at initial time points and compared visually with ASL findings. Results In all patients, regional perfusion changes were detected in the acute phase. These abnormalities did not respect the boundaries of major cerebral vascular territories but overlapped onto adjoining regions. During MA, adjacent hypoperfused and hyperperfused areas were found, whereas during headache, regional hyperperfusion only was observed. Perfusion abnormalities normalized on follow-up. Conclusions ASL perfusion imaging is a contrast agent-free method suitable for assessment of reversible perfusion changes during or immediately after MA.

Summary Early recanalisation and an increase in collateral blood supply are predictors of favourable outcome in acute ischaemic stroke. Since individual responses to intravenous treatment with alteplase are heterogeneous, additional intra-arterial thrombolytic and mechanical endovascular treatment is increasingly given. Despite encouraging findings from single-centre studies, data from randomised clinical trials have not proven the hypothesis that interventional recanalisation leads to a better outcome. Advanced thrombectomy devices, the effect of ultrasound-enhanced thrombolysis, and imaging-guided selection of patients outside the currently approved time-window are all under investigation. Although neuroprotective agents have not shown benefit in clinical trials, non-pharmacological treatment strategies—such as decompressive surgery, therapeutic hypothermia, transcranial laser treatment, or augmentation of cerebral collateral perfusion by different means (eg, partial aortic occlusion or sphenopalatine ganglion stimulation)—are topics of current research. The future of acute stroke therapy relies on evidence for individually tailored, effective, safe, and rapidly accessible treatment probably consisting of combined pharmacological and improved non-pharmacological approaches.

We investigated whether real-time ultrasound perfusion imaging (rt-UPI) is able to detect perfusion changes related to arterial recanalization in the acute phase of middle cerebral artery (MCA) stroke. Twenty-four patients with acute territorial MCA stroke were examined with rt-UPI and transcranial color-coded duplex ultrasound (TCCD). Ultrasound studies were consecutively performed within 24 h and 72–96 h after stroke onset. Real-time UPI parameters of bolus kinetics (time to peak, rt-TTP) and of refill kinetics (plateau A and slope β of the exponential replenishment curve) were calculated from regions of interest of ischemic versus normal brain tissue; these parameters were compared between early and follow-up examinations in patients who recanalized. At the early examination, there was a delay of rt-TTP in patients with MCA occlusion (rt-TTP [s]: 13.09 ± 3.21 vs. 10.16 ± 2.6; p = 0.01) and a lower value of the refill parameter β (β [1/s]: 0.62 ± 0.34 vs. 1.09 ± 0.58; p = 0.01) in ischemic compared with normal brain tissue, whereas there were no differences of the parameters A and Axβ. At follow-up, the delay of rt-TTP was reversible once recanalization of an underlying MCA obstruction was demonstrated: rt-TTP [s], 13.09 ± 3.21 at 24 h versus 10.95 ± 1.5 at 72–96 h ( p = 0.03). Correspondingly, β showed a higher slope than at the first examination: β [1/s]: 0.55 ± 0.29 at 24 h versus 0.71 ± 0.27 at 72–96 h ( p = 0.04). We conclude that real-time UPI can detect hemodynamic impairment in acute MCA occlusion and subsequent improvement following arterial recanalization. This offers the chance for bedside monitoring of the hemodynamic compromise (e.g. during therapeutic interventions such as systemic thrombolysis).

Background: Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding intracerebral hemorrhage (ICH), Cerebrovascular Diseases published the 2006 European stroke initiative recommendations for the management of ICH. In 2009, the revised Japanese GLs for the management of stroke, including that of ICH, appeared in Japanese. Whereas GLs for the prevention and treatment of ischemic stroke were presented in detail, recommendations with regard to ICH are relatively rare both in Japan and Europe. Methods: Since 2011, the authors have met repeatedly and have compared the latest versions of published European and Japanese GLs for ischemic and hemorrhagic strokes. Many aspects have only been addressed in one but left out in the other GLs, which consequently founded the basis for the comparison. Classification of evidence levels and recommendation grades defined by the individual committees differed between both original GLs. Results: Aspects of major importance were similar and hence did not need extensive interpretation, mostly due to a lack of evidence from appropriate RCTs worldwide. The target level to which systolic blood pressure should be lowered is quite high; Conclusion: This brief survey - when compared with the lengthy original recommendations - provides a stimulating basis for an extended interest among Japanese and European stroke clinicians to learn from their individual experiences and to strengthen efforts for joint cooperation in treating and preventing stroke all around the globe.

Background: In 1998 Baden-Wuerttemberg (BW), a federal state in southwest Germany with 10.8 million inhabitants, implemented a structured medical concept for the treatment of acute stroke. Methods: Since 2004 participation in the BW stroke database is mandatory for all hospitals in BW involved in acute stroke care. The stroke database includes all inpatients ≥18 years of age who have suffered an ischemic or hemorrhagic stroke within 7 days before hospitalization. This article presents methodological aspects and first results of the BW stroke database in the time period from 2007 to 2011. Results: Annual inclusion numbers increased continuously (29,422 vs. 35,724, p < 0.001). Median age of stroke onset was stable over time. The proportion of stroke patients ≥80 years increased from 36.9 to 38.8% (p < 0.001). Rates of patients treated in neurology departments rose from 50.7 to 60.9% (p < 0.001) and numbers of patients treated in stroke units rose from 59.1 to 68.4% (p < 0.001). Admission via emergency medical systems increased from 42.8 to 49.7% (p < 0.001) and arrival within 3 h increased from 29.8 to 34.4% (p < 0.001). Conclusion: We present results from a large, prospective and consecutive stroke patient database. This first analysis demonstrates a continuous increase of absolute and relative numbers of stroke patients who arrive within 3 h after onset, are hospitalized in neurology departments and treated in stroke units, and are aged ≥80 years.

Background: Early recanalization and increase in collateral blood supply are powerful predictors of favourable outcome in acute ischaemic stroke. The factors contributing to the heterogeneous response to intravenous thrombolysis therapy in individual patients, however, are not fully understood. The on-going single-centre ‘MR perfusion imaging during thrombolysis' study uses repetitive arterial spin labelling (ASL) measurements to characterize the haemodynamic processes in acute stroke during therapy. The first milestone was to develop an appropriate infrastructure for thrombolysis in the magnetic resonance imaging (MRI) scanner without time delay and ensuring optimal patient safety and care. Methods: Between February and December 2011, 16 patients with acute neurological symptoms suggestive of hemispheric stroke within 4.5 h after symptom onset were included. In addition to clinical data, we documented the time from onset to arrival at the hospital, start and duration of MRI examination, start of thrombolytic therapy, and complications. The decision to thrombolyse was made after a routine stroke MRI protocol. During the 60-min systemic thrombolysis, repetitive ASL perfusion imaging was acquired, providing non-invasive information on cerebral perfusion. Continuous ECG monitoring, pulse oximetry, blood pressure measurements every 5 min, and short neurological assessments every 15 min were performed in every patient. Results: The median initial NIHSS score of the patients presenting with a mean of 84 min after onset was 4 (range 2-18). MRI examination was initiated within a mean of 45 min after arrival at the hospital. Five patients identified as stroke mimics were not treated with recombinant tissue plasminogen activator (rt-PA), and in 1 case with basilar artery occlusion bridging therapy was performed outside the scanner. In the remaining 10 patients, rt-PA therapy was started in the scanner directly after decision making on the basis of clinical information and baseline MRI. The mean door-to-needle time was 60 min (range 44-115) including approximately 10 min needed for acquiring informed consent. While 4 patients required antihypertensive treatment, no relevant complications were encountered. Conclusions: Fast and safe medical care in patients during systemic thrombolysis in the MRI scanner is feasible. Despite the process of obtaining informed consent, with a dedicated and experienced stroke team the door-to-needle time can be kept in a range recommended by current guidelines. Continuous real-time information about the dynamics of cerebral perfusion from ASL perfusion in acute stroke patients undergoing thrombolysis may provide additional information for the understanding of the events following acute arterial obstruction and its course.

Purpose: To investigate blood to tissue water transfer in human brain, in vivo and spatially resolved using a T2-based arterial spin labeling (ASL) method with 3D readout. Materials and Methods: A T2-ASL method is introduced to measure the water transfer processes between arterial blood and brain tissue based on a 3D-GRASE (gradient and spin echo) pulsed ASL sequence with multiecho readout. An analytical mathematical model is derived based on the General Kinetic Model, including blood and tissue compartment, T1 and T2 relaxation, and a blood-to-tissue transfer term. Data were collected from healthy volunteers on a 3 T system. The mean transfer time parameter Tblex (blood to extravascular compartment transfer time) was derived voxelwise by nonlinear least-squares fitting. Results: Whole-brain maps of Tblex show stable results in cortical regions, yielding different values depending on the brain region. The mean value across subjects and regions of interest (ROIs) in gray matter was 440 ± 30 msec. Conclusion: A novel method to derive whole-brain maps of blood to tissue water transfer dynamics is demonstrated. It is promising for the investigation of underlying physiological mechanisms and development of diagnostic applications in cerebrovascular diseases. J. Magn. Reson. Imaging 2013;37:332–342. © 2012 Wiley Periodicals, Inc.

Since decision-making for thrombolysis in acute stroke settings is restricted to a limited time window and based on clinical assessment and CT findings only, thrombolysis is sometimes applied to patients with a final diagnosis other than a stroke. From a prospectively collected stroke/MRI data bank (2004–2010) with 648 suspected ischemic stroke patients treated with rtPA, we identified patients without evidence of acute infarction on follow-up MRI and a final diagnosis other than a stroke or acute cerebrovascular event. We compared demographics, symptoms, complications, and outcome of patients with stroke mimics (SM) to those with acute infarction. In 42 patients, an SM was diagnosed: seizures in 20, conversion disorder in seven, dementia in six, migraine in three, brain tumor in two, and others in four patients. Patients with SM less often had typical stroke symptoms like dysarthria (p

Background: Patients with posterior circulation stroke (PCS) were underrepresented in or even excluded from the large clinical trials investigating acute therapy with thrombolysis. Therefore, the knowledge about potential benefits and risks of thrombolysis in PCS is sparse. Methods: From July 2004 until June 2007, 237 stroke patients were treated with thrombolysis within 3 h after onset of symptoms in our stroke unit. Baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of patients with PCS were compared to those with anterior circulation stroke (ACS). Results: There were 30 patients in the PCS group; 198 had ACS. In the PCS group, less patients had a history of prior stroke (0/30 vs. 31/198 (15.7%), p = 0.02) and less were treated with platelet inhibitors (6/30 (20.0%) vs. 83/198 (41.9%), p = 0.02). Onset to treatment time was higher in the PCS group (156.2 ± 23.2 vs. 141.1 ± 30.7, p = 0.01). Small vessel disease occurred more often in PCS patients (10/30 (33.3%) vs. 12/198 (6.1%), p < 0.001), whereas stroke of undetermined cause was less frequent (5/30 (16.7%) vs. 75/198 (37.9%), p = 0.02). Correspondingly, PCS patients had more lacunar (13/30 (43.3%) vs. 15/198 (7.3%), p < 0.001) strokes on CT/MRI. Patients with PCS had significantly lower median NIHSS scores after 2 and 24 h, whereas the median NIHSS and mRS scores at discharge as well as the mRS score at the 3-month follow-up, although still lower, did not differ significantly between both groups. Outcome was similar with regard to complications and mortality. Conclusions: Patients with PCS have a higher rate of small vessel disease and lacunar stroke. In terms of potential benefits and risks of thrombolysis, we could demonstrate no significant differences between PCS and ACS. Acute PCS patients should be diagnosed and treated with the same elaborateness as ACS patients.

Background and Purpose— Differences between women and men in relation to stroke are increasingly being recognized. Methods— From July 2004 until June 2007, 237 acute ischemic stroke (AIS) patients were treated with recombinant tissue plasminogen activator (rtPA) within 3 hours after onset of symptoms in our stroke unit. Baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of women were compared to those of men. Results— Of 237 AIS patients (mean age 70.7 years), 111 (46.8%) were women and 126 (53.2%) were men. Women were older ( P =0.001), but history of hyperlipidemia ( P =0.03), smoking ( P =0.03), and coronary heart disease ( P P =0.02), whereas atrial fibrillation was observed more often in women ( P =0.002). In men borderzone/small embolic and lacunar stroke was found more frequently (39.7 versus 27.2%), whereas women showed a higher percentage of large territorial stroke (72.8 versus 60.3%, P =0.09). Baseline National Institute of Health Stroke Scale scores (12.5 versus 11.3), NIHSS score at discharge (11.0 versus 9.5), 3-month-outcome modified Rankin Scale score, thrombolysis-related (17.1% versus 13.5%) or independent complications (32.4% versus 30.2%), and mortality after 3 months (13.5% versus 9.5%) were similar. Conclusion— Differences of stroke lesion patterns in genders are paralleled by differences in etiology and risk factor profiles (women, cardioembolism; men, large and small vessel disease). Baseline characteristics, rates of rtPA-related and independent complications, as well as clinical outcomes were not different between women and men with AIS.

In acute stroke, different sonographic methods can be used to assess structural and hemodynamic compromise. Structural abnormalities of brain parenchyma such as primary intracerebral hemorrhage (ICH) and epiphenomena such as midline shift can be detected by native transcranial B-mode ultrasound. Moreover, transcranial Doppler provides a functional approach to intracranial hemodynamics and may assist in predicting ICH growth and global intracranial pressure increase. New ultrasound technologies allow the visualization of ultrasound contrast agents in the cerebral microcirculation. According to recent data, ultrasound perfusion imaging provides additional information for the diagnosis of ICH and may differentiate ischemic from hemorrhagic stroke. This review summarizes the impact of these different transcranial ultrasound methods on diagnosis and monitoring of ICH.

Background and Purpose— To evaluate the potential of a new dynamic MRA sequence (DynAngio) based on arterial spin labeling for the assessment of intracranial collateral flow. Methods— Twelve patients with unilateral internal carotid artery obstruction were investigated. Different patterns of collateral flow were compared between DynAngio, transcranial color-coded duplex ultrasound, and time-of-flight MRA. Results— There was a good agreement between the methods, with sensitivities between 80% and 90%. Small collateral vessels were detected more frequently with DynAngio compared to time-of-flight MRA. Conclusion— DynAngio provides anatomic and similar to transcranial color-coded duplex ultrasound functional information on collateral flow for the assessment of intracranial hemodynamics.

Background: Ultrasound perfusion imaging (UPI) is a new approach for the assessment of brain perfusion. In contrast to the increasing experience with this method in patients with ischemic stroke, data on the value of UPI for the diagnosis of intracerebral hemorrhage (ICH) are lacking. Methods: We investigated 12 consecutive patients with sufficient temporal bone windows and a CT diagnosis of acute supratentorial ICH (basal ganglia n = 9 and lobar n = 3). Native transcranial B-mode ultrasound and UPI studies with echo contrast agents were performed on day 1 and on days 5–7 including volume measurements using the maximum extension on transverse and coronal ultrasound planes. Results: ICH was identified as hyperechogenic mass on B-mode ultrasound in 11/12 patients, but the correlation with CT volume measurements was poor (day 1: r = 0.4, 95% confidence interval, CI: –0.23–0.79; p = 0.1; follow-up: r = 0.58, 95% CI: 0.04–0.86; p = 0.21). Volume measurement was more precise using UPI with a significant correlation on day 1 (r = 0.8, 95% CI: 0.47–0.94; p < 0.001) and during the follow-up (r = 0.94, 95% CI: 0.81–0.98; p < 0.001). Using UPI the typical finding was a focal reduction of contrast agent arrival in the ICH core which led to better delineation of the lesion borders from adjacent tissue. Depiction of lobar ICH was difficult with ultrasound, and lesion sizes tended to be underestimated. Conclusions: This study supports earlier work demonstrating the usefulness of native transcranial ultrasound for the diagnosis of ICH. UPI further improves diagnostic reliability and allows very precise ICH volume measurements. If confirmed in larger studies, this approach may be useful for bedside monitoring of ICH progression and regression.

Stenting has increasingly been used for the treatment of carotid artery stenosis, although it is still unknown whether it is as safe and successful as carotid endarterectomy. Several studies have been published, and the preliminary results have been variable, with evidence both in favor of and against this procedure. In the past few months, primary outcome data have been published from two large European randomized multicenter trials (SPACE and EVA-3S). So far, both of these trials have evaluated whether carotid stenting shows noninferiority compared with carotid endarterectomy in symptomatic patients with severe carotid disease over a period of 30 days after intervention. In this Review, we summarize current knowledge on effectiveness of both procedures, and provide an updated meta-analysis based on randomized trial data, including SPACE and EVA-3S. This meta-analysis shows a lower procedure-related rate of stroke or death in surgically treated patients. The long-term risk/benefit ratio of carotid stenting remains to be determined. Two other randomized multicenter trials-ICSS and CREST-are ongoing. With an intended sample size of up to 7,000 patients, future meta-analyses will allow more-accurate treatment recommendations and subgroup analysis.

In Europe intravenous thrombolysis (IVT) for ischaemic stroke is still not approved for patients aged80 years. However, elderly patients are frequently treated based on individual decision making. In a retrospective observational study a consecutive and prospective stroke registry in southwest Germany was analysed.The data registry collected 101,349 patients with ischaemic stroke hospitalized from January 2008 to December 2012. Of these, 38,575 (38%) were aged 80 years and older and 10 286 (10.1%) underwent IVT. Favourable outcome at discharge was defined as modified Rankin Scale (mRS) ≤1 or not worse than prior to stroke. Multiple logistic regression models stratified by 10-year age groups were used to assess the relationship between IVT and mRS at discharge, adjusted for patient characteristics, admitting facility and length of hospital stay.The highest IVT rate was 15% in patients aged50 years, with a continuous decline down to 8% in patients aged ≥90 years. Adjusted odds ratios and 95% confidence intervals for patients 80-89 years of age were 2.20 (1.95-2.47) (P0.0001) and 1.25 (0.88-1.78) (P = 0.21) for patients90 years of age, compared to patients of the same age decade not treated with IVT.The evidence from routine hospital care in southwest Germany indicates that IVT is an effective treatment also for aged patients with ischaemic stroke in an age range between 80 and 89 years. Although no clear evidence for the effectiveness of IVT beyond 90 years was found, treatment should also be carefully considered in these patients. High age should not discourage from treatment.

In the last several years, great progress has been made in ultrasound perfusion imaging of the brain. Different approaches have been assessed and shown to be capable of the early detection of cerebral perfusion deficits in stroke patients. Real-time low-mechanical index imaging simplifies the acquisition of perfusion parameters and alleviates many of the previous imaging problems related to shadowing, uniplanar analysis, and temporal resolution. With the advent of this new, highly sensitive contrast-specific imaging technique, new possibilities of the real-time visualization of brain infarctions and cerebral hemorrhages have emerged. This review will detail the methodology of ultrasound perfusion imaging, discuss aspects of its safety and present the emerging clinical applications of brain perfusion assessment with ultrasound in acute stroke patients.

Although the natural history of extracranial carotid artery disease has been investigated systematically, limited data are available on the course of middle cerebral artery (MCA) disease.The authors observed 102 consecutive patients (67 men, 35 women; mean age 61.9 years) with significant MCA stenosis or occlusion as demonstrated by transcranial Doppler and transcranial color-coded duplex ultrasonography. Forty-six patients entered the study after TIA (n = 17) or stroke (n = 29); 56 patients were asymptomatic. Neurologic and ultrasound investigations were performed at regular intervals with a mean follow-up of 31 (range 6 to 117) months. Patients were continuously treated with either platelet inhibitors (n = 75) or anticoagulation (n = 27).Nineteen cerebral ischemic events (11 strokes, 8 TIAs) occurred during follow-up, resulting in an overall annual rate of 7.3%. Thirteen events (8 strokes, 5 TIAs) were attributable to the vascular territory ipsilateral to MCA disease. Patients with symptomatic MCA disease at study entry had an overall stroke risk of 12.5% per year (ipsilateral: 9.1%), whereas the annual incidence in primarily asymptomatic MCA disease was only 2.8% (ipsilateral: 1.4%; p0.01). Symptomatic MCA disease was an independent predictor for overall (hazard ratio [HR] 7.91, 95% CI 2.03 to 30.79; p0.01) and ipsilateral (HR 9.66, 95% CI 1.5 to 62.25; p = 0.02) cerebrovascular events.Compared with asymptomatic middle cerebral artery disease, there was a high and continuous recurrence rate of ischemic events in symptomatic patients, which was even higher than in patients with symptomatic extracranial carotid artery disease.

The purpose of this study was to define a standardized multiplanar approach for transcranial ultrasound (US) imaging of brain parenchyma based on matched data from 3-D US and 3-D magnetic resonance imaging (MRI). The potential and limitations of multiple insonation planes in transverse and coronal orientation were evaluated for the visualization of intracranial landmarks in 60 healthy individuals (18 to 83 years old, mean 41.4 years) with sufficient temporal bone windows. Landmarks regularly visualized even in moderate sonographic conditions with identification rates of > 75% were mesencephalon, pons, third ventricle, lateral ventricles, falx, thalamus, basal ganglia, pineal gland and temporal lobe. Identification of medulla oblongata, fourth ventricle, cerebellar structures, hippocampus, insula, frontal, parietal and occipital lobes was more difficult (< 75%). We hypothesize that multiplanar transcranial US images, with standardized specification of tilt angles and orientation, not only allow comparison with other neuroimaging modalities, but may also provide a more objective framework for US monitoring of cerebral disease than freehand scanning.

Background and Purpose— Cerebral perfusion imaging in acute stroke assists in determining the subtype and the severity of ischemia. Recent studies in perfusion models and in healthy volunteers have shown that ultrasound perfusion imaging based on microbubble destruction can be used to assess tissue perfusion. We applied ultrasound microbubble destruction imaging (MDI) to identify perfusion deficits in patients with acute middle cerebral artery (MCA) territory stroke. Methods— Fifteen acute MCA stroke patients with sufficient transtemporal bone windows were investigated with ultrasound MDI and perfusion-weighted MRI (PWI). MDI was performed using power pulse-inversion contrast harmonic imaging. Thirty seconds after a bolus injection of the echo contrast agent SonoVue, microbubbles were destroyed using a series of high-energy pulses. Local perfusion status was analyzed in selected regions of interest by destruction curves and acoustic intensity differences (ΔI) before and after microbubble destruction. Local perfusion status was then compared with perfusion compromise as identified on PWI. Results— The mean differences of acoustic intensity from the ischemic MCA territory were significantly diminished compared with the normal hemisphere (ΔI=2.52±1.75 versus ΔI=13.79±7.31; P Conclusions— MDI is a qualitative method that can rapidly detect perfusion changes in acute stroke. When combined with other ultrasound techniques and PWI, it may well be valuable in the care of stroke unit patients, eg, as a screening method and for follow-up assessments of perfusion deficits.

Background and Purpose— Real-time compound ultrasound imaging is a new technique for improving the image quality of B-mode scanning. We investigated the value of this method for the characterization of atherosclerotic plaques in the internal carotid artery. Methods— Thirty-two patients (22 men, 10 women; mean age, 75 years) with plaques of the internal carotid artery as identified by high-resolution B-mode scanning were investigated with real-time compound ultrasound imaging with the use of a 5- to 12-MHz dynamic range linear transducer on a duplex scanner. Two independent observers rated plaque morphology according to a standardized protocol. Results— The majority of plaques was classified as predominantly echogenic and as plaques of irregular surface, whereas ulcerated plaques were rarely observed. The interobserver agreement for plaque surface characterization was good for both compound ultrasound (κ=0.72) and conventional B-mode (κ=0.65). For the determination of plaque echogenicity, the reproducibility of compound ultrasound (κ w =0.83) was even higher than that of conventional B-mode ultrasound (κ w =0.74). According to a semiquantitative analysis, real-time compound ultrasound was rated superior in the categories plaque texture resolution, plaque surface definition, and vessel wall demarcation. Furthermore, there was a significant reduction of acoustic shadowing and reverberations. Conclusions— Real-time compound ultrasound is a suitable technique for the characterization of atherosclerotic plaques, showing good general agreement with high-resolution B-mode imaging. This advanced technique allows reduction of ultrasound artifacts and improves the assessment of plaque texture and surface for enhanced evaluation of carotid plaque morphology.

Object. Three-dimensional (3D) power Doppler ultrasonography imaging provides a rapid, noninvasive visualization of ruptured intracranial aneurysms, including their relationship to other vascular structures. Methods. The authors used transcranial 3D power Doppler imaging in the emergency room to examine patients with acute subarachnoid hemorrhage. In all patients, the ruptured aneurysm was rapidly located with 3D power Doppler imaging. Conventional x-ray angiography confirmed both the ultrasonography-based diagnosis and the location of aneurysmal bleeding. Conclusions. These preliminary results indicate that 3D power Doppler imaging is a rapid, noninvasive screening method for the visualization of ruptured aneurysms.

Arterial spin labeling (ASL) MRI provides information on tissue perfusion by consecutive readout of labeled blood captured in arteries or the microvasculature without using contrast agents.We used a single-shot 3D acquisition and readout technique for ASL with multiple inflow times (TI) to evaluate hemodynamic compromise and dynamics of arterial blood inflow expressed by the bolus arrival time (BAT). Thirty-six patients with ischemic stroke were examined with a standard multimodal MRI protocol including dynamic susceptibility contrast (DSC) and multi-TI ASL perfusion imaging. Time-to-peak maps were used to classify hemodynamic impairment as either hypo- or hyperperfusion.Overall there was a good agreement of ASL perfusion maps with DSC perfusion imaging on visual analysis. Correlations were found between ASL-BAT/(DSC-)Mean transit time (MTT) (r = .416; P.01) and ASL-CBF/MTT (r = -.489; P.01). Using ASL, BAT in ischemic territory was delayed by 55% (P = .001) in patients with hypoperfusion (n = 28); CBF was reduced by 39% (P.001). All patients with hyperperfusion (n = 6) had higher CBF on ASL.The use of ASL with multiple TI allows the contrast-free assessment of hemodynamic impairment in ischemic stroke patients. Quantitative ASL perfusion analysis reliably demonstrates areas of delayed BAT and reduced CBF matching findings of DSC.

PCA stroke was under-represented in or excluded from the clinical trials examining thrombolysis based on the PWI-DWI mismatch concept. We present 6 patients with PCA stroke treated with thrombolysis in an extended time window by using MR imaging criteria. Symptoms included aphasia, sensorimotor hemiparesis, hemineglect, and homonymous hemianopia. Initial MR imaging demonstrated circumscribed ischemic lesions in the thalamus or hippocampus; MR angiography showed PCA occlusion with corresponding hypoperfusion. Follow-up MR imaging showed partial/complete recanalization in 4 patients with minor infarction growth, while in 1 patient, PCA occlusion persisted, resulting in a large PCA infarction. Three patients improved within 2 hours; at discharge, homonymous hemianopia had resolved in 3 patients. At 3-month follow-up, 4 patients had an mRS score of 0 or 1. These results support the approach to treat patients with PCA stroke with thrombolysis based on the mismatch concept. Because rehabilitation options for hemianopia are limited, thrombolysis may enhance the chance of a favorable outcome.

Background: Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding stroke, GLs have been published by national and international organizations in different languages, most frequently in English. Cerebrovascular Diseases published the European GLs for the management of ischemic stroke and transient ischemic attacks in 2003, with an update in 2008. At about the same time (in 2004), the first Japanese GLs for the management of stroke appeared in Japanese. The first English version of the updated Japanese GLs was published only in 2011 and included differently approved drugs and drug dosages as compared with other American or European countries. Methods: Since 2011, the authors have met repeatedly and have compared the latest versions of published European and Japanese GLs for ischemic and hemorrhagic strokes. Many aspects have only been addressed in one but left out in the other GLs, which consequently founded the basis for the comparison. Classification of evidence levels and recommendation grades defined by the individual committees differed between both original GLs. Results: Aspects of major importance were surprisingly similar and hence did not need extensive interpretation. Other aspects of ischemic stroke management differed significantly, e.g. the dosage of recombinant tissue plasminogen activator approved in Japan is lower (0.6 mg/kg) than in Europe (0.9 mg/kg), which derived from different practices in cardiovascular treatment prior to the design of acute ischemic stroke RCTs. Furthermore, comedication with neuroprotective agents (edaravone), intravenous anticoagulants (argatroban) or antiplatelet agents within 1-2 days after stroke onset is recommended in Japan but not in Europe. For cardioembolic stroke prevention, a major difference consists in a higher international normalized ratio target (2.0-3.0) in younger subjects versus in those >70 years (1.6-2.6), without age restrictions in Europe. Conclusion: This brief survey - when compared with the lengthy original recommendations - provides a stimulating basis for an extended interest among Japanese and European stroke clinicians to learn from their individual experiences and to strengthen efforts for joint cooperation in treating and preventing stroke all around the globe.

Rapid advances in microbubble pharmacology together with novel ultrasound technologies for contrast-specific imaging of the macro- and microcirculation have led to a number of new applications for assessment of stroke patients. In particular, ultrasound perfusion imaging has added new perspectives for diagnosis and monitoring of both ischemic and hemorrhagic stroke. Recently, real-time brain perfusion imaging of middle cerebral artery infarctions has been introduced and new quantitative algorithms for evaluation of regional cerebral blood flow are being applied for the first time in humans. Microbubbles enable visualization of carotid artery plaque neovascularization to detect plaque vulnerability. There is growing interest in therapeutic applications of ultrasound, particularly in the field of sonothrombolysis. The treatment of acute ischemic stroke can be improved by ultrasound and microbubbles in combination with thrombolytic drugs. Excitingly, ultrasound and microbubbles may be effective in clot lysis of ischemic stroke even without additional thrombolytic drugs. New therapeutic avenues include opening of the blood-brain barrier (BBB) with ultrasound and microbubbles to enable novel drug delivery to the brain. Microbubbles are also assuming a central role in ultrasound molecular imaging with many targets of interest for evaluating pathophysiologic processes involved in cerebrovascular disease including angiogenesis, inflammation, and thrombus formation.

A 37-year-old woman presented 90 minutes after acute onset of mild motor aphasia with word-finding difficulties and hypesthesia of the right arm. MRI was immediately performed as she presented within the 3-hour time window for IV thrombolysis. Diffusion-weighted images (DWI) were normal, but perfusion MRI (dynamic susceptibility contrast) sequences showed marked hypoperfusion in the left hemisphere affecting both middle cerebral artery and posterior cerebral artery (PCA) territories. These findings were considered compatible with migraine aura. The patient subsequently developed a mild left-sided headache. Clinical symptoms gradually improved to full recovery after 6 hours without specific treatment. Follow-up MRI perfusion scans were obtained 24 hours and 2 months after the episode. Functional transcranial Doppler (fTCD) from the P2-segments of the PCA during visual stimulation was performed at the same time points as MRI (figure). The first follow-up MRI showed only mild residual hypoperfusion in the left hemisphere, and in the asymptomatic state 2 months later, no perfusion abnormality was detected. Correspondingly, initial severe changes of neurovascular coupling on fTCD …

Multiple acute ischemic lesions in different hemispheres or vascular territories are mainly considered to be of proximal embolic origin. However, despite careful diagnostic work-up, the etiological classification often stays undetermined. We propose that multiple acute ischemic lesions can sometimes be a phenomenon observed in small vessel disease (SVD). From a prospectively collected database of more than 7,000 stroke patients, 173 patients with acute bihemispheric infarction were identified. We analyzed those subjects with multiple small (< 15 mm O) subcortical acute ischemic lesions on diffusion-weighted MRI (DWI) and concomitant severe small vessel disease (Fazekas grades II–III) without a proximal embolic source as evaluated by cardiological investigations. Twenty patients (mean age 66 ± 12 years, 12 men) with a mean number of 2.95 ± 1.24 acute lesions on DWI (range of 2–7 lesions per patient) were identified (n = 5 Fazekas II°, n = 15 Fazekas III°). Most of the lesions were located in typical areas of lacunar infarction. The mean NIHSS score on admission was 2.95 ± 2.0 (range 0–8). Multiple acute ischemic lesions in different vascular territories might not always be of proximal cardiovascular embolic origin. Simultaneous small subcortical ischemic lesions may reflect remote ischemia due to small vessel disease reflecting simultaneous hemorheological dysfunction.

Background: The human hippocampus can be affected in a large variety of very different neurological diseases, of which acute ischemic stroke, transient global amnesia, epilepsy, and limbic encephalitis are the most common. Less frequent etiologies include various infections and encephalopathy of different origins. Clinical presentation notably comprises confusional state, altered vigilance, memory deficits of various extent and seizures. While in hypoxic or hypoglycemic encephalopathy, clinical presentation and surrounding circumstances provide some clues to reach the correct diagnosis, in the above-listed more common disorders, signs and symptoms might overlap, making the differential diagnosis difficult. This review presents recent studies using the diffusion-weighted imaging (DWI) technique in diseases involving the hippocampus. Methods: References for the review were identified through searches of PubMed from 1965 to January 2011. Only papers published in English were reviewed. Full articles were obtained and references were checked for additional material where appropriate. Results: All pathologies affecting the hippocampus are associated with distinct lesion patterns on magnetic resonance imaging, and especially DWI has the ability to demonstrate even minute and transient hippocampal lesions. In acute ischemic stroke in the posterior cerebral artery territory, involvement of the hippocampal formation occurs in four distinct patterns on DWI that can be easily differentiated and correspond to the known vascular anatomy of the hippocampus. In the subacute phase after transient global amnesia (TGA), dot-like hyperintense lesions are regularly found in the lateral aspect of the hippocampus on DWI. The DWI lesions described after prolonged seizures or status epilepticus include unilateral or bilateral hippocampal, thalamic, and cortical lesions of various extent, not restricted to vascular territories. In limbic encephalitis, DWI lesions are only infrequently found and usually affect the hippocampus, uncus and amygdala. Furthermore, in some rare cases DWI lesions of different etiology may coexist. Conclusion: In patients with diseases affecting the hippocampus, DWI appears to be useful in differentiating between underlying pathologies and may facilitate a definite diagnosis conducive to an optimal treatment. With a careful clinical examination, experience with the interpretation of DWI findings and knowledge of associated phenomena, it is indeed possible to differentiate between ischemic, ictal, metabolic, and TGA-associated findings.

Cerebral infarctions in the anterior cerebral artery (ACA) territory account for only up to 3–5% of strokes. Subject to the affected ACA branches, different clinical patterns can be defined. We report a case series of patients with isolated infarctions of the pericallosal (PC) artery territory. We analyzed 36 consecutive patients presenting over a 10-year period with isolated PC artery territory infarctions (15 left-sided, 19 right-sided, 2 bilateral) regarding clinical symptoms as well as MRI findings. Analysis of DWI lesion pattern showed complete PC artery infarctions in three patients. The majority of patients had partial infarctions predominantly involving either the superior frontal gyrus (n = 12), the corpus callosum (n = 1) or both (n = 20). Hemodynamic lesion patterns were found in 13 patients, while multiple cortical emboli occurred in six. Distal pathology of the ACA (n = 13) was the most frequent MRA finding. Core symptom was contralateral hemiparesis with lower limb predominance (n = 29), partly associated with early-onset spasticity. Interestingly, motor evoked potential recording was abnormal in only five patients. Further characteristic symptoms were psychomotor slowing (n = 9), often with speech disturbances such as decreased verbal fluency, and confusional state (n = 4). Visual or motor hemineglect (n = 5) as well as apraxia (n = 5) was confined to a few patients only. Pericallosal artery infarctions are a rare localization of stroke, mostly occurring as partial infarctions due to distal ACA pathology. Clinically, they are mainly characterized by hemiparesis predominately in the lower limb caused by involvement of supplementary motor cortex areas without affection of the corticospinal tract.

A vascular right-to-left shunt (r/l shunt) is a well-known risk factor for the development of decompression sickness (DCS). No studies to date have examined whether divers with a history of DCS with or without a r/l shunt have a reduced risk of suffering recurrent DCS when diving more conservative dive profiles (CDP).Twenty-seven divers with a history of DCS recommended previously to dive more conservatively were included in this study and retrospectively interviewed by phone to determine the incidence of DCS recurrence.Twenty-seven divers performed 17,851 dives before examination in our department and 9,236 after recommendations for conservative diving. Mean follow up was 5.3 years (range 0-11 years). Thirty-eight events of DCS occurred in total, 34 before and four after recommendation of CDP. Four divers had a closure of their patent foramen ovale (PFO). A highly significant reduction of DCS risk was observed after recommendation of CDP for the whole group as well as for the sub-groups with or without a r/l shunt. A significant reduction of DCS risk in respect to r/l shunt size was also observed.This study indicates that recommendations to reduce nitrogen load after DCS appear to reduce the risk of developing subsequent DCS. This finding is independent of whether the divers have a r/l shunt or of shunt size. The risk of suffering recurrent DCS after recommendation for CDP is less than or equal to an unselected cohort of divers.Recommendation for CDP seems to significantly reduce the risk of recurrent DCS.

Background: Brain imaging in stroke aims at the detection of the relevant ischemic tissue pathology. Cranial computed tomography (CT) is frequently used in patients with transient ischemic attack (TIA) but no data is available on how it directly compares to magnetic resonance imaging (MRI). Methods: We compared detection of acute ischemic lesions on CT and MRI in 215 consecutive TIA patients who underwent brain imaging with either CT (n = 161) or MRI (n = 54). An MRI was performed within 24 h in all patients who had CT initially. Results: An initial assessment with CT revealed no acute pathology in 154 (95.7%) and possible acute infarction in 7 (4.3%) patients. The acute infarct on CT was confirmed by diffusion-weighted imaging (DWI) in only 2 cases (28.6%). DWI detected an acute infarct in 50 of the 154 patients with normal baseline CT (32.5%). Among 54 patients without baseline CT, DWI showed acute ischemic lesions in 19 (35.2%). The ischemic lesions had a median volume of 0.87 cm3 (range: 0.08–15.61), and the lesion pattern provided clues to the underlying etiology in 13.7%. Conclusion: Acute MRI is advantageous over CT to confirm the probable ischemic nature and to identify the etiology in TIA patients.

Background: Recovery from stroke is presumed to be a function of a widespread cerebral network. Chronic white matter lesions (WML) have been proposed to be a predictor of poor outcome after acute stroke. We tested the hypothesis that the extent of WML has an effect on functional recovery in acute pontine stroke by disrupting the integrity of the supratentorial cerebral network. Methods: Seventeen patients with acute unilateral pontine stroke who had received a standardized stroke workup and additional diffusion tensor imaging (DTI) were studied. After grading the extent of WML according to the Fazekas scale and semiautomated lesion volume calculation, we compared patients with acute pontine infarction and advanced WML to those with absent or minimal WML regarding baseline characteristics, stroke subtype and clinical outcome. In addition, we used tract-based spatial statistics for voxel-wise analysis of the DTI-derived parameter fractional anisotropy in the white matter tracts. Results: The volume of WML ranged between 0.1 and 42.1 cm3 (mean = 15.9) and was graded as follows: 0 in 5.9%, 1 in 35.3%, 2 in 41.2% and 3 in 17.6%. Both patients with Fazekas grades 2–3 (p = 0.014) as well as those with larger WML volumes (p = 0.037) had severer functional deficits at the 3-month follow-up. White matter tracts displaying a significant decrease in fractional anisotropy values were the corpus callosum, the anterior thalamic radiation and the inferior fronto-occipital fasciculus. Conclusions: Chronic WML contribute to a less favorable clinical outcome after pontine stroke depending on (1) the extent of pre-existing WML and (2) the degree of disruption of cerebral connectivity as indicated by reduced tissue integrity in the white matter not affected by WML as detected by DTI and tract-based spatial statistics.

Isolated monoparesis is an uncommon symptom of acute ischaemic stroke, and in some cases the lack of additional clinical signs may make it difficult to decide on its peripheral or central origin. Acute ischaemic distal arm paresis presenting with radial- and ulnar-like distribution has been shown to be caused by small cortical lesions in the motor hand cortex.1 Similarly, monoparesis of the lower limb with peripheral-like appearance can in rare cases occur as a feature of cerebral ischaemia. We report six patients with acute ischaemic distal lower- limb paresis. Six patients with acute distal lower-limb paresis underwent cranial MR imaging using a standardised stroke protocol including T1-, T2-, diffusion-weighted images (DWI) and MR angiography (MRA) within 24 h after symptom onset. A detailed neurological examination was performed daily, and motor-evoked potentials were recorded in all patients. Additionally, all patients underwent further routine investigations including extra- and intracranial Doppler-/duplexsonography, 24 h electrocardiography and echocardiography. All patients presented with acute onset of painless and isolated distal lower-limb paresis. Three patients showed a peroneal distribution of palsy …

Background: In large territorial stroke of the anterior and the posterior circulation, the extent of affected tissue can be characterized by the demonstration of vessel occlusion on MR angiography (MRA), while the extent of hypoperfusion can be shown on dynamic susceptibility contrast perfusion-weighted MRI (PWI). The ability of MRA and conventional MRI sequences to demonstrate branches of the basilar artery (BA) is very limited. This study analyzes the value of the combined use of diffusion-weighted MRI (DWI), MRA and PWI in acute pontine stroke. Methods: A series of 24 consecutive patients with acute pontine stroke received an extensive MRI stroke workup including DWI, PWI and MRA. Results: In 11/24 patients visual analysis of PWI demonstrated persisting hypoperfusion, and in 1/24 patients indication of hyperperfusion was found. Vessel abnormalities were seen in 19/24 patients (15/24 hypoplastic vertebral artery, 9/24 stenosis or occlusion of the BA, 1/20 ectatic BA). Persistent pontine hypoperfusion was more frequently associated with BA pathology (9/11 vs. 1/13, p = 0.001), large-vessel disease (8/11 vs. 1/13; p = 0.001) and a more pronounced clinical deficit (NIHSS score on day 1: 7 vs. 3, p = 0.01). Conclusions: In pontine ischemia areas of hypoperfusion can be identified due to the strong contrast induced by ischemia on PWI and can be easily related to DWI lesion size. This is of use particularly as small vessels are frequently missed by MRA and occlusion of the BA can be better characterized with the help of PWI.

Background and Purpose— Reports of ischemic stroke affecting the hippocampus are rare. In this study we used diffusion-weighted MRI (DWI) to characterize patients with posterior circulation stroke involving the hippocampus. Methods— Fifty-seven consecutive acute stroke patients with hippocampal infarct (HI) on DWI were analyzed with regard to clinical features and ischemic lesion patterns. The last 20 of these underwent additional neuropsychological testing of short-term, working, and episodic long-term memory. Results— We found unilateral HI in 54 and bilateral HI in 3 patients. Visual analysis identified 4 patterns of DWI lesion affecting (1) the complete hippocampus (15/60), (2) the lateral (19/60) or (3) dorsal (22/60) parts of the hippocampal body and tail, and (4) circumscribed lesions in the lateral hippocampus (4/60), corresponding well to hippocampal vascular anatomy. In all cases DWI showed further ischemic lesions in the posterior circulation. Symptoms from lesions outside the hippocampus were the common leading clinical signs. Whereas mnestic deficits were prominent in only 11/57 patients, neuropsychological examination in 20 patients showed deficits of verbal episodic long-term memory in left and of nonverbal episodic long-term memory in right HI. Conclusion— Several phenotypic lesion patterns can be distinguished in HI that usually occur as part of multifocal PCA ischemia. A careful neuropsychological examination is necessary to detect resulting memory deficits.

In the last several years great progress has been made in the field of ultrasound perfusion imaging of the brain. Different approaches have been assessed and shown to be capable of early detection of cerebral perfusion deficits. Real-time low mechanical index imaging simplifies the acquisition of perfusion parameters and alleviates many of the previous imaging problems related to shadowing, uniplanar analysis, and temporal resolution. With the advent of this new, highly sensitive contrast-specific imaging technique new possibilities of real-time visualization of brain infarctions and cerebral hemorrhages have emerged. Microbubbles that traverse the blood-brain barrier (BBB) can also elicit bioeffects that may be used to open the BBB for targeted delivery of macromolecular agents to the brain. Possible ways in which substances cross the BBB after application of this novel approach include transcytosis, passage through endothelial cell cytoplasmic openings, opening of tight junctions, and free passage through injured endothelium. Although relatively little tissue damage occurs at low acoustic intensities capable of opening the BBB, no investigation has demonstrated a total lack of BBB injury when using ultrasound and microbubbles. Further studies are necessary to address the effects of ultrasound and microbubbles upon the various transport mechanisms of the BBB. Moreover, investigations aimed at elucidating how ultrasound and microbubbles interact at the molecular level of the BBB are necessary. Results of such studies will increase our understanding of the mechanisms of BBB opening and also allow a better appraisal of the safety of this technique for future clinical applications.

BACKGROUND AND PURPOSE Occlusion of the internal carotid artery (ICA) and stroke may be the consequence of either local thrombosis due to atherosclerosis or massive embolism. Up to date, there are only few reports of subsequent recanalization. METHODS We report 12/76 cases of acute ICA occlusion leading to ischemic stroke, in which early recanalization was identified. Ultrasound and stroke MRI findings, therapeutic options, and outcome are described. RESULTS 10/12 patients showed an- or hypoechogenic morphology of occlusion. While in 7/12 cases complete recanalization was seen, in 5/12 patients partial recanalization with filiform flow (4) or residual high-grade stenosis (1) was detected. 10/12 patients had territorial or subcortical infarction, while two showed small cortical lesions only. In 7/12 cases, a potential cardiac source of embolism was found. Five patients received tPA; four patients underwent early carotid endarterectomy of the partially recanalized ICA within 48 hours. In the 10-day follow-up examination 10/12 patients showed clinical improvement as measured by the NIHSS. CONCLUSIONS Spontaneous recanalization after occlusion of the ICA may occur and might be more frequent than hitherto assumed. Echogenicity analysis and serial examinations of symptomatic ICA occlusion is useful for identifying a patient subgroup that might benefit from further therapy.

Isolated inner ear injuries occurring during shallow scuba dives are an uncommon manifestation of decompression sickness in recreational divers. We describe a patient who presented with the typical symptoms of inner ear involvement after 2 independent dives within the decompression limits. The diver reported symptoms of unilateral (right-sided) hearing loss, tinnitus, and vertigo after dives to 35 and 50 m. After treatment with hyperbaric oxygen, his symptoms completely resolved. To confirm the hypothesis of inner ear decompression sickness (IEDCS), we examined the patient for a right-to-left shunt by cranial Doppler ultrasound and found a patent foramen ovale. The existence of a patent foramen ovale is suspected to be a risk factor for developing neurological symptoms of decompression sickness. There was no evidence of any other risk factors, so we suggest that the relevant right-to-left shunt in our patient may have been the predisposing factor that caused the inner ear symptoms during his scuba dive.

Objective To study the time dependent effectiveness of thrombolytic therapy for acute ischaemic stroke in daily clinical practice. Design A retrospective cohort study using data from a large scale, comprehensive population based state-wide stroke registry in Germany. Setting All 148 hospitals involved in acute stroke care in a large state in southwest Germany with 10.4 million inhabitants. Participants Data from 84 439 patients with acute ischaemic stroke were analysed, 10 263 (12%) were treated with thrombolytic therapy and 74 176 (88%) were not treated. Main outcome measures Primary endpoint was the dichotomised score on a modified Rankin scale at discharge (“favourable outcome” score 0 or 1 or “unfavourable outcome” score 2-6) analysed by binary logistic regression. Patients treated with recombinant tissue plasminogen activator (rtPA) were categorised according to time from onset of stroke to treatment. Analogous analyses were conducted for the association between rtPA treatment of stroke and in-hospital mortality. As a co-primary endpoint the chance of a lower modified Rankin scale score at discharge was analysed by ordinal logistic regression analysis (shift analysis). Results After adjustment for characteristics of patients, hospitals, and treatment, rtPA was associated with better outcome in a time dependent pattern. The number needed to treat ranged from 4.5 (within first 1.5 hours after onset; odds ratio 2.49) to 18.0 (up to 4.5 hours; odds ratio 1.26), while mortality did not vary up to 4.5 hours. Patients treated with rtPA beyond 4.5 hours (including mismatch based approaches) showed a significantly better outcome only in dichotomised analysis (odds ratio 1.25, 95% confidence interval 1.01 to 1.55) but the mortality risk was higher (1.45, 1.08 to 1.92). Conclusion The effectiveness of thrombolytic therapy in daily clinical practice might be comparable with the effectiveness shown in randomised clinical trials and pooled analysis. Early treatment was associated with favourable outcome in daily clinical practice, which underlines the importance of speeding up the process for thrombolytic therapy in hospital and before admission to achieve shorter time from door to needle and from onset to treatment for thrombolytic therapy.

Paradoxical gas embolism is a possible cause of neurologic sequelae after decompression in divers. The authors detected arterial bubbles after decompression from chamber dives in two of six divers using transcranial Doppler sonography (TCD). Arterial bubbles correlated with the size of right-to-left shunting as diagnosed by contrast TCD. The pathway of spontaneous paradoxical embolism was tracked for the first time, supporting the concept of paradoxical gas embolism as a cause of early neurologic sequelae after decompression in at-risk divers.