Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.

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.

Arterial Spin Labeling Cerebral Perfusion Magnetic Resonance Imaging in Migraine Aura: An Observational Study.

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.

Prediction of Early Reperfusion From Repeated Arterial Spin Labeling Perfusion Magnetic Resonance Imaging During Intravenous Thrombolysis.

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<0.01). The development of ATA preceded the normalization of tissue perfusion. 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.

Access, timing and frequency of very early stroke rehabilitation - insights from the Baden-Wuerttemberg stroke registry.

BACKGROUND: While the precise timing and intensity of very early rehabilitation (VER) after stroke onset is still under discussion, its beneficial effect on functional disability is generally accepted. The recently published randomized controlled AVERT trial indicated that patients with severe stroke might be more susceptible to harmful side effects of VER, which we hypothesized is contrary to current clinical practice. We analyzed the Baden-Wuerttemberg stroke registry to gain insight into the application of VER in acute ischemic stroke (IS) and intracerebral hemorrhage (ICH) in clinical practice. METHODS: 99,753 IS patients and 8824 patients with ICH hospitalized from January 2008 to December 2012 were analyzed. Data on the access to physical therapy (PT), occupational therapy (OT), and speech therapy (ST), the time from admission to first contact with a therapist and the average number of therapy sessions during the first 7 days of admission are reported. Multiple logistic regression models adjusted for patient and treatment characteristics were carried out to investigate the influence of VER on clinical outcome. RESULTS: PT was applied in 90/87% (IS/ICH), OT in 63/57%, and ST in 70/65% of the study population. Therapy was mostly initiated within 24 h (PT 87/82%) or 48 h after admission (OT 91/89% and ST 93/90%). Percentages of patients under therapy and also the average number of therapy sessions were highest in those with a discharge modified Rankin Scale score of 2 to 5 and lowest in patients with complete recovery or death during hospitalization. The outcome analyses were fundamentally hindered due to biases by individual decision making regarding the application and frequency of VER. CONCLUSIONS: While most patients had access to PT we noticed an undersupply of OT and ST. Only little differences were observed between patients with IS and ICH. The staff decisions for treatment seem to reflect attempts to optimize resources. Patients with either excellent or very unfavorable prognosis were less frequently assigned to VER and, if treated, received a lower average number of therapy sessions. On the contrary, severely disabled patients received VER at high frequency, although potentially harmful according to recent indications from the randomized controlled AVERT trial.

Outcome Predictors of Acute Stroke Patients in Need of Intensive Care Treatment.

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.

T2-based arterial spin labeling measurements of blood to tissue water transfer in human brain.

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 T(bl → ex) (blood to extravascular compartment transfer time) was derived voxelwise by nonlinear least-squares fitting. RESULTS: Whole-brain maps of T(bl → ex) 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.

Comparison of the European and Japanese guidelines for the management of ischemic stroke.

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.

Comparison of the European and Japanese guidelines for the acute management of intracerebral hemorrhage.

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; <170 mm Hg for patients with known hypertension in Europe and <180 mm Hg in Japan. The results of ongoing clinical trials are awaited for the optimal target level and optimal medications. Concerning ICH associated with oral anticoagulant therapy, both guidelines give similar recommendations, namely that anticoagulation should be discontinued and the international normalized ratio of prothrombin time should be normalized with prothrombin complex concentrate or fresh-frozen plasma and additional vitamin K. Patients with ICH were treated surgically, often based on individual decisions - more frequently in Japan, depending on the association with hypertension. Patients with large or intraventricular bleedings were only treated if a life-saving performance was considered, irrespective of the neurological outcome. Infra- and supratentorial differences were similarly addressed in both GLs. 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.

Immunoadsorption as maintenance therapy for refractory neuromyelitis optica spectrum disorder.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system, affecting mainly optic nerves and spinal cord. NMOSD pathophysiology is associated with anti-aquaporin-4 (AQP4) immunoglobulin G (IgG) autoantibodies. Rapid extracorporeal elimination of autoantibodies with apheresis techniques, such as immunoadsorption (IA), was proven to be an effective treatment of NMOSD attacks. Data on the long-term use of IA to prevent attacks or progression of NMOSD are lacking. Objectives: The aim of this study was to evaluate efficacy and safety of maintenance IA for preventing recurrence of NMOSD attacks in patients refractory to other immunotherapies. Design: Case study. Methods: Retrospective analysis of two female patients with severe NMOSD refractory to conventional immunotherapies was performed. Both patients had responded to tryptophan IA (Tr-IA) as attack therapy and subsequently were treated with biweekly maintenance Tr-IA. Results: Patient 1 (AQP4-IgG seropositive, age 42 years) had 1.38 attacks of optic neuritis per year within 10.1 years before commencing regular Tr-IA. With maintenance Tr-IA for 3.1 years, one mild attack occurred, which was responsive to steroid pulse therapy. Expanded Disability Status Scale (EDSS) was stable at 5.0. Visual function score of the last eye improved from 3 to 1. Patient 2 (AQP4-IgG seronegative, age 43 years) experienced 1.7 attacks per year, mainly acute myelitis and optic neuritis, during the period of 10.0 years before the start of Tr-IA. During regular Tr-IA treatment, no further NMOSD attack occurred. The patient was clinically stable without any additional immunosuppressive treatment for 5.3 years. EDSS improved from 6.0 to 5.0, and the ambulation score from 7 to 1. Tolerability of Tr-IA was good in both patients. No serious adverse events occurred during long-term clinical trajectories. Conclusion: Tr-IA was well tolerated as maintenance treatment and resulted in clinical stabilization of two patients with highly active NMOSD, who were refractory to standard drug therapy.

Cerebral network disruption as a possible mechanism for impaired recovery after acute pontine stroke.

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.

Predictors and early outcome of hemorrhagic transformation after acute ischemic stroke.

BACKGROUND: Hemorrhagic transformation (HT) after acute ischemic stroke is frequently detected using magnetic resonance imaging (MRI), in particular in patients treated with tissue plasminogen activator (tPA). Knowledge about causes and early clinical consequences of HT mostly arises from computed tomography-based studies. We analyzed potential predictors and early outcome of HT after stroke detected by MRI with T(2)*-weighted gradient echo sequences (T(2)*-MRI). METHODS: 122 consecutive stroke patients (mean age 65.5 years, 41% women) who underwent T(2)*-MRI within 6-60 h after stroke onset were included. 25.4% of patients were treated with tPA; the overall detection rate of HT on T(2)*-MRI was 20.5%. Potential predictors of HT, such as age, sex, blood pressure, stroke etiology, prior antithrombotic medication, neurological deficit on admission, tPA treatment, and specific MRI findings, were analyzed. In addition, we evaluated the effect of HT on early outcome: a decrease of >4 points on the National Institute of Health Stroke Scale (NIHSS) on day 5 was considered early improvement, and an increase of >4 points was considered early deterioration. RESULTS: The main predictor for occurrence of HT was tPA treatment (48.4 vs. 11.1%; odds ratio 7.50; 95% confidence interval 2.9-19.7; p < 0.001). Furthermore, the development of HT was associated with a severer neurological deficit on admission (mean NIHSS score 9.9 vs. 5.9; p = 0.003), and territorial infarction (88 vs. 58.8%; p = 0.007). 19 patients (15.6%) showed early improvement which was associated with the occurrence of HT (p = 0.011) and tPA treatment (p < 0.001). CONCLUSIONS: HT is a frequent finding on T(2)*-MRI in patients with acute ischemic stroke associated with tPA treatment, territorial infarction and severer neurological deficits on admission. However, HT does not cause clinical deterioration; it is rather related to a favorable early outcome likely reflecting early recanalization and better reperfusion in these patients.

Dynamic susceptibility contrast perfusion MRI identifies persistent vessel pathology in acute pontine stroke.

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.

Only a Minority of Thrombectomy Candidates Are Admitted During Night Shift: A Rationale for Diurnal Stroke Care Planning.

Background: Widespread quick access to mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is one of the main challenges in stroke care. It is unclear if newly established MT units are required 24 h/7 d. We explored the diurnal admission rate of patients with AIS potentially eligible for MT to provide a basis for discussion of daytime-adapted stroke care concepts. Methods: Data collected from the Baden-Württemberg Stroke Registry in Germany were assessed (2008-2012). We analyzed the admission rate of patients with AIS stratified by the National Institutes of Health Stroke Scale (NIHSS) score at admission in 3-h intervals. An NIHSS score ≥10 was considered a predictor of large vessel occlusion. The average annual admission number of patients with severe AIS were stratified by stroke service level and calculated for a three-shift model and working/non-working hours. Results: Of 91,864, 22,527 (21%) presented with an NIHSS score ≥10. The average admission rates per year for a hospital without Stroke Unit (SU), with a local SU, with a regional SU and a stroke center were 8, 52, 90 and 178, respectively. Approximately 61% were admitted during working hours, 54% in the early shift, 36% in the late shift and 10% in the night shift. Conclusions: A two-shift model, excluding the night shift, would cover 90% of the patients with severe AIS. A model with coverage during working hours would miss ~40% of the patients with severe AIS. To achieve a quick and area-wide MT, it seems preferable for newly implemented MT-units to offer MT in a two-shift model at a minimum.

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

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.

Gender differences in acute ischemic stroke: etiology, stroke patterns and response to thrombolysis.

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<0.001) was less frequent than in men. Internal carotid artery disease occurred more often in men (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. CONCLUSIONS: 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.

Hippocampal lesion patterns in acute posterior cerebral artery stroke: clinical and MRI findings.

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. CONCLUSIONS: 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.

Diagnosis of intracerebral hemorrhage with transcranial ultrasound.

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.

Assessment of intracranial collateral flow by using dynamic arterial spin labeling MRA and transcranial color-coded duplex ultrasound.

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. CONCLUSIONS: DynAngio provides anatomic and similar to transcranial color-coded duplex ultrasound functional information on collateral flow for the assessment of intracranial hemodynamics.

Improved detection of intracerebral hemorrhage with transcranial ultrasound perfusion imaging.

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.

Early spontaneous recanalization following acute carotid occlusion.

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.