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.

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.

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.

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.

Diurnal Variation of Intravenous Thrombolysis Rates for Acute Ischemic Stroke and Associated Quality Performance Parameters.

INTRODUCTION: Based on data from the Baden-Wuerttemberg stroke registry, we aimed to explore the diurnal variation of acute ischemic stroke (IS) care delivery. MATERIALS AND METHODS: 92,530 IS patients were included, of whom 37,471 (40%) presented within an onset-to-door time ≤4.5 h. Daytime was stratified in 3-h time intervals and working vs. non-working hours. Stroke onset and hospital admission time, rate of door-to-neurological examination time ≤30 min, onset-/door-to-imaging time IV thrombolysis (IVT) rates, and onset-/door-to-needle time were determined. Multivariable regression models were used stratified by stroke onset and hospital admission time to assess the relationship between IVT rates, quality performance parameters, and daytime. The time interval 0:00 h to 3:00 h and working hours, respectively, were taken as reference. RESULTS: The IVT rate of the whole study population was strongly associated with the sleep-wake cycle. In patients presenting within the 4.5-h time window and potentially eligible for IVT stratification by hospital admission time identified two time intervals with lower IVT rates. First, between 3:01 h and 6:00 h (IVT rate 18%) and likely attributed to in-hospital delays with the lowest diurnal rate of door-to-neurological examination time ≤30 min and the longest door-to-needle time Second, between 6:01 h and 15:00 h (IVT rate 23-25%) compared to the late afternoon and evening hours (IVT rate 27-29%) due to a longer onset-to-imaging time and door-to-imaging time. No evidence for a compromised stroke service during non-working hours was observed. CONCLUSION: The analysis provides evidence that acute IS care is subject to diurnal variation which may affect stroke outcome. An optimization of IS care aiming at constantly high IVT rates over the course of the day therefore appears desirable.

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.

Restriction of therapy mainly explains lower thrombolysis rates in reduced stroke service levels.

OBJECTIVE: To assess the influence of preexisting disabilities, age, and stroke service level on standardized IV thrombolysis (IVT) rates in acute ischemic stroke (AIS). METHODS: We investigated standardized IVT rates in a retrospective registry-based study in 36,901 patients with AIS from the federal German state Baden-Wuerttemberg over a 5-year period. Patients admitted within 4.5 hours after stroke onset were selected. Factors associated with IVT rates (patient-level factors and stroke service level) were assessed using robust Poisson regression modeling. Interactions between factors were considered to estimate risk-adjusted mortality rates and potential IVT rates by service level (with stroke centers as benchmark). RESULTS: Overall, 10,499 patients (28.5%) received IVT. The IVT rate declined with service level from 44.0% (stroke center) to 13.1% (hospitals without stroke unit [SU]). Especially patients >80 years of age and with preexisting disabilities had a lower chance of being treated with IVT at lower stroke service levels. Interactions between stroke service level and age group, preexisting disabilities, and stroke severity (all p < 0.0001) were observed. High IVT rates seemed not to increase mortality. Estimated potential IVT rates ranged between 41.9% and 44.6% depending on stroke service level. CONCLUSIONS: Differences in IVT rates among stroke service levels were mainly explained by differences administering IVT to older patients and patients with preexisting disabilities. This indicates considerable further potential to increase IVT rates. Our findings support guideline recommendations to admit acute stroke patients to SUs.

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.

Intravenous Thrombolysis is Effective in Young Adults: Results from the Baden-Wuerttemberg Stroke Registry.

BACKGROUND: The efficacy of intravenous thrombolysis (IVT) is sufficiently proven in ischemic stroke patients of middle and older age by means of randomized controlled trials and large observational studies. However, data in young stroke patients ≤50 years are still scarce. In this study, we aimed to evaluate the effectiveness and safety of IVT in young adults aged 18-50 years. Data from a consecutive and prospective stroke registry was analyzed that covers a federal state with 10.8 million inhabitants in southwest Germany. METHODS: Our analysis comprises 51,735 ischemic stroke patients aged 18-80 years and hospitalized from January 2008 to December 2012. Of these, 4,140 (8%) were aged 18-50 years and 7,529 (15%) underwent IVT. Data on 8,439 patients (16% of the study population) were missing for National Institutes of Health stroke severity score at admission and/or modified Rankin Scale (mRS) at discharge and were excluded from outcome analysis. In sensitivity analysis, patients with incomplete data were also examined. Binary logistic regression models were used adjusted for patient, hospital, and procedural parameters and stratified by age group (18-50 and 51-80 years, subgroup analyses 18-30, 31-40, and 41-50 years) to assess the relationship between IVT and mRS at discharge. RESULTS: IVT appears equally effective in young adults 18-50 years (adjusted odds ratio 1.40, 95% confidence interval 1.12-1.75; p = 0.003), compared to patients 51-80 years of age (1.33, 1.23-1.43; p < 0.001). Age-stratified analyses suggest an inverse relation of age and effectiveness, which appears to be highest in very young patients 18-30 years of age (2.78, 1.10-7.05; p = 0.03). DISCUSSION: Ischemic stroke etiology, vascular dynamics, and recovery in young patients differ from those of middle and older age. The evidence from routine hospital care in Germany indicates that IVT in young stroke patients appears to be at least equally effective as in the elderly.

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.

Intracranial perfusion imaging with ultrasound.

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.

Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials.

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.

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.

Non-pharmacological strategies for the treatment of acute ischaemic stroke.

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.

Real-time ultrasound perfusion imaging in acute stroke: assessment of cerebral perfusion deficits related to arterial recanalization.

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 ß 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 ß (ß [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 Axß. 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, ß showed a higher slope than at the first examination: ß [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).

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.

Acute posterior ischemic optic neuropathy mimicking posterior cerebral artery stroke visualized by 3-tesla MRI.

Acute ischemic lesions of the posterior optic nerve and optic tract can produce a variety of visual field defects. A 71-year-old woman presented with acute hemianopia, which led to rt-PA thrombolysis for suspected posterior cerebral artery ischemia. 3-Tesla cMRI, however, revealed the cause to be an acute posterior ischemic optic neuropathy. Cases like this may be more common than thought and quite regularly overlooked in clinical practice, especially when there is no high-resolution MRI available. This case strengthens the importance of repeat MR imaging in patients with persistent visual field defects.

Lower risk of decompression sickness after recommendation of conservative decompression practices in divers with and without vascular right-to-left shunt.

INTRODUCTION: 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). METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: Recommendation for CDP seems to significantly reduce the risk of recurrent DCS.