Background In patients with acute stroke, the plasma concentrations of direct oral anticoagulants (DOACs) need to be known for further treatment decisions. The point-of-care test DOAC Dipstick contains two test pads that determine levels of direct factor Xa (FXA) inhibitors and thrombin (THR) inhibitors in urine samples; thereby determining DOAC plasma levels of > 30 ng/mL within 10 minutes. Aim This study aimed to test the feasibility of using the DOAC Dipstick to detect the presence of DOACs in patients with acute stroke and transient ischemic attack (TIA) during the early phase of intrahospital stroke management. Methods Urine samples from patients with acute stroke and TIA with or without DOAC intake were obtained within 8 hours after hospitalisation. The urine samples were tested using the DOAC Dipstick. After incubation, colour change on the DOAC Dipstick pads were analysed visually and using a semi-automated reader. Primary endpoints were the success rate of evaluable pad results and time to results after urine sampling. Results From January 2023 to April 2024, 70 patients were recruited, 66 of whom fulfilled the inclusion criteria (39% female, mean age 73 ± 11.9 years). The median (interquartile range) times from urine sample collection to visual and reader test pad results were 20 (15–26) mins and 24 (16–37) mins, respectively. The test procedure was uncomplicated in most patients (n = 60). Complications in the test procedure were delays in urine sampling (n = 3), need for repeated testing due to dry strip (n = 2), no visual evaluability of the test result (n = 1), and abnormal urine colour (n = 1). The urine samples of all patients with prior DOAC intake (n = 26) were positive for DOACs while those for all patients without prior DOAC intake (n = 39) were negative for DOACs (one patient was excluded because the urine sample was not collected in time). Conclusion The DOAC Dipstick rapidly and reliably detects DOACs in urine samples from patients with acute stroke and TIA

Introduction In acute stroke or transient ischemic attack (TIA), rapid information about the plasma concentration of direct oral anticoagulants (DOAC) is important for treatment decisions such as systemic thrombolysis, endovascular therapy, or antidote administration in case of hemorrhagic stroke. As standard coagulation assays are either not sufficiently reliable or have long turn-around times, point-of-care-testing with DOAC dipstick may be of additional value in this setting.

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

Background Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran that reverses its anticoagulant effects within minutes. It may exhibit the potential for patients under dabigatran therapy suffering ischemic stroke to regain eligibility for thrombolysis with rt-PA and may inhibit lesion growth in patients with intracerebral hemorrhage on dabigatran. Aims To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of ischemic stroke or intracranial hemorrhage. Methods Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January to August 2016 were used. Results Thirty-one patients presenting with signs of stroke received idarucizumab in 22 stroke centers. Nineteen patients treated with dabigatran presented with ischemic stroke and 12 patients suffered from intracranial bleeding. In patients receiving rt-PA thrombolysis following idarucizumab, 79% benefitted from i.v. thrombolysis with a median improvement of five points in NIHSS. No bleeding complications occurred. Hematoma growth was observed in 2 out of 12 patients with intracranial hemorrhage. The outcome was favorable with a median NIHSS improvement of 5.5 points and mRS 0-3 in 67%. Overall, mortality was low with 6.5% (one patient in each group). Conclusion Administration of rt-PA after reversing dabigatran activity with idarucizumab in case of ischemic stroke is feasible, easy to manage, effective, and appears to be safe. In dabigatran-associated intracranial hemorrhage, idarucizumab has the potential to prevent hematoma growth and improve outcome. Idarucizumab represents a new therapeutic option for patients under dabigatran treatment presenting with ischemic stroke or intracranial hemorrhage.

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.

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. (c) 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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.

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: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.

Background and purposeIn Europe intravenous thrombolysis (IVT) for ischaemic stroke is still not approved for patients aged >80 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.MethodsThe 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.ResultsThe highest IVT rate was 15% in patients aged <50 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) (P < 0.0001) and 1.25 (0.88–1.78) (P = 0.21) for patients >90 years of age, compared to patients of the same age decade not treated with IVT.ConclusionsThe 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.