No Harmful Effect of Endovascular Treatment before Decompressive Surgery-Implications for Handling Patients with Space-Occupying Brain Infarction.

This study explored short- and mid-term functional outcomes in patients undergoing decompressive hemicraniectomy (DHC) due to space-occupying cerebral infarction and asked whether there is a potentially harmful effect of a priorly performed endovascular treatment (EVT). Medical records were screened for patients requiring DHC due to space-occupying cerebral infarction between January 2016 and July 2021. Functional outcomes at hospital discharge and at 3 months were assessed by the modified Rankin Scale (mRS). Out of 65 patients with DHC, 39 underwent EVT before DHC. Both groups, i.e., EVT + DHC and DHC alone, had similar volumes (280 ± 90 mL vs. 269 ± 73 mL, t-test, p = 0.633) and proportions of edema and infarction (22.1 ± 6.5% vs. 22.1 ± 6.1%, t-test, p = 0.989) before the surgical intervention. Patients undergoing EVT + DHC tended to have a better functional outcome at hospital discharge compared to DHC alone (mRS 4.8 ± 0.8 vs. 5.2 ± 0.7, Mann-Whitney-U, p = 0.061), while the functional outcome after 3 months was similar (mRS 4.6 ± 1.1 vs. 4.8 ± 0.9, Mann-Whitney-U, p = 0.352). In patients initially presenting with a relevant infarct demarcation (Alberta Stroke Program Early CT Score ≤ 5), the outcome was similar at hospital discharge and after 3 months between patients with EVT + DHC and DHC alone. This study provided no evidence for a harmful effect of EVT before DHC in patients with space-occupying brain infarction.

Outcomes After Decompressive Surgery for Severe Cerebral Venous Sinus Thrombosis Associated or Not Associated with Vaccine-Induced Immune Thrombosis with Thrombocytopenia: A Multicenter Cohort Study.

BACKGROUND: Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome. METHODS: This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS. RESULTS: Both groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission (p = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months (p = 0.043). CONCLUSIONS: Although the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.

Endovascular treatment of cerebral sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

INTRODUCTION: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT. PATIENTS AND METHODS: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria. RESULTS: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58). DISCUSSION AND CONCLUSION: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence.

Long-Term Course of Circulating Elastin, Collagen Type I, and Collagen Type III in Patients with Spontaneous Cervical Artery Dissection: a Prospective Multicenter Study.

An impaired integrity of vascular elements and the extracellular matrix (ECM) has been discussed to play a critical role in the pathophysiology of spontaneous cervical artery dissection (sCAD). This study aimed to explore the temporal course of circulating elastin, collagen type I, and collagen type III in patients with sCAD and evaluated their eligibility as diagnostic biomarkers. Patients with sCAD were prospectively enrolled in four German stroke centers. Blood samples were collected at baseline (acute phase), at day 10 ± 3 (subacute phase), and after 6 ± 1 months (chronic phase). Patients with acute ischemic stroke not related to sCAD, healthy probands, and patients undergoing thromboendarterectomy of the carotid artery served as control groups. Serum levels of elastin and collagen types I and III were determined by ELISAs. Fifty-seven patients with sCAD were enrolled. Compared to all three control groups, patients with sCAD had significantly lower levels of elastin and collagen type III at baseline and after 6 months. Compared to healthy probands, patients with sCAD showed similar collagen type I levels at baseline and in the subacute phase, but significantly increased levels after 6 months. As serum levels of elastin, collagen types I and III were not elevated in the acute phase, they do not appear eligible as biomarkers for the diagnosis of sCAD. Persisting low serum levels of elastin and collagen type III towards the chronic phase of sCAD strengthens the hypothesis of a subtle, in most cases clinically inapparent affection of the ECM in patients with sCAD.

Stroke survivors' preferences on assessing patient-reported outcome measures.

BACKGROUND: To assess quality of life and unmet needs after stroke, patient-reported outcome measures (PROMs) have gained increasing attention. However, patients' perspectives on assessing PROMs remain unclear, potentially hindering implementation into clinical practice. Therefore, this study explored patients' preferences on assessing PROMs after ischemic stroke. METHODS: A paper-based questionnaire was sent to stroke survivors treated at the Department of Neurology, University of Leipzig, Germany. Health-related quality of life (HRQoL, EQ-5D-5L) and preferences regarding different aspects of data collection to assess PROMs were investigated and linked to socio-demographic and medical characteristics. RESULTS: 158 persons were contacted and 80 replies were subsequently analyzed. Mean age was 70.16 years and mean HRQoL was 68.79 (visual analogue scale with a theoretical maximum of 100). Participants showed positive attitudes towards PROMs as they saw potential to improve care of other patients (n = 66/79; 83.54%) or to improve their own situation (n = 53/74; 71.62%). Participants preferred an annual interview after stroke (n = 39/80; 48.75%) and would preferably spend 15-30 min (n = 41/79; 51.90%) to answer a written survey (n = 69/80; 86.25%). The initially treating clinic was preferred as initiator of such surveys (n = 43/79; 54.43%). Stratification revealed that participants with more than 1 h of daily digital media usage preferred email as way of communication. CONCLUSIONS: For the first time, this study showed individual preferences on assessing PROMs after ischemic stroke, focusing on the way, time interval, duration, and initiation site of surveys. These insights might help to successfully implement PROMs after stroke and subsequently detect unmet needs and deficits in stroke care.

Combining atomic force microscopy and fluorescence-based techniques to explore mechanical properties of naive and ischemia-affected brain regions in mice.

Knowledge of the brain's structure and function is essential for understanding processes in health and disease. Histochemical and fluorescence-based techniques have proven beneficial in characterizing brain regions and cellular compositions in pre-clinical research. Atomic force microscopy (AFM) has been introduced for mechanical tissue characterization, which may also help investigate pathophysiological aspects in disease-related models such as stroke. While combining AFM and fluorescence-based techniques, this study explored the mechanical properties of naive and ischemic brain regions in mice. Ischemia-affected regions were identified by the green signal of fluorescein isothiocyanate-conjugated albumin. A semi-automated protocol based on a brain atlas allowed regional allocations to the neocortex, striatum, thalamus, hypothalamus, hippocampus, and fiber tracts. Although AFM led to varying measurements, intra-individual analyses indicated a gradually increased tissue stiffness in the neocortex compared to subcortical areas, i.e., the striatum and fiber tracts. Regions affected by ischemia predominantly exhibited an increased tissue stiffness compared to those of the contra-lateral hemisphere, which might be related to cellular swelling. This study indicated intra-individual differences in mechanical properties among naive and ischemia-affected brain regions. The combination of AFM, semi-automated regional allocations, and fluorescence-based techniques thus qualifies for mechanical characterizations of the healthy and disease-affected brain in pre-clinical research.

Tricellulin, α-Catenin and Microfibrillar-Associated Protein 5 Exhibit Concomitantly Altered Immunosignals along with Vascular, Extracellular and Cytoskeletal Elements after Experimental Focal Cerebral Ischemia.

Along with initiatives to understand the pathophysiology of stroke in detail and to identify neuroprotective targets, cell-stabilizing elements have gained increasing attention. Although cell culture experiments have indicated that tricellulin, α-catenin and microfibrillar-associated protein 5 (MFAP5) contribute to cellular integrity, these elements have not yet been investigated in the ischemic brain. Applying immunofluorescence labeling, this study explored tricellulin, MFAP5 and α-catenin in non-ischemic and ischemic brain areas of mice (24, 4 h of ischemia) and rats (4 h of ischemia), along with collagen IV and fibronectin as vascular and extracellular matrix constituents and microtubule-associated protein 2 (MAP2) and neurofilament light chain (NF-L) as cytoskeletal elements. Immunosignals of tricellulin and notably MFAP5 partially appeared in a fiber-like pattern, and α-catenin appeared more in a dotted pattern. Regional associations with vascular and extracellular constituents were found for tricellulin and α-catenin, particularly in ischemic areas. Due to ischemia, signals of tricellulin, MFAP5 and α-catenin decreased concomitantly with MAP2 and NF-L, whereby MFAP5 provided the most sensitive reaction. For the first time, this study demonstrated ischemia-related alterations in tricellulin, MFAP5 and α-catenin along with the vasculature, extracellular matrix and cytoskeleton. Confirmatory studies are needed, also exploring their role in cellular integrity and the potential for neuroprotective approaches in stroke.

Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism-the Find-AF 2 study-rationale and design.

BACKGROUND: Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, ie, ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. METHODS: Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. CONCLUSIONS: The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care.

Early or late initiation of dabigatran versus vitamin-K-antagonists in acute ischemic stroke or TIA: The PRODAST study.

BACKGROUND: The optimal timing of initiating or resuming anticoagulation after acute ischemic stroke (AIS) or transient ischemic attack (TIA) in patients with atrial fibrillation (AF) is debated. Dabigatran, a non-vitamin K oral anticoagulant (NOAC), has shown superiority against vitamin K antagonists (VKA) regarding hemorrhagic complications. AIMS: In this registry study, we investigated the initiation of dabigatran in the early phase after AIS or TIA. METHODS: PRODAST (Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA) is a prospective, multicenter, observational, post-authorization safety study. We recruited 10,039 patients at 86 German stroke units between July 2015 and November 2020. A total of 3,312 patients were treated with dabigatran or VKA and were eligible for the analysis that investigates risks for major hemorrhagic events within 3 months after early (⩽ 7 days) or late (> 7 days) initiation of dabigatran or VKA initiated at any time. Further endpoints were recurrent stroke, ischemic stroke, TIA, systemic embolism, myocardial infarction, death, and a composite endpoint of stroke, systemic embolism, life-threatening bleeding and death. RESULTS: Major bleeding event rates per 10,000 treatment days ranged from 1.9 for late administered dabigatran to 4.9 for VKA. Early or late initiation of dabigatran was associated with a lower hazard for major hemorrhages as compared to VKA use. The difference was pronounced for intracranial hemorrhages with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval (CI): 0.10-2.21) for early dabigatran use versus VKA use and an adjusted HR of 0.09 (95% CI: 0.00-13.11) for late dabigatran use versus VKA use. No differences were found between early initiation of dabigatran versus VKA use regarding ischemic endpoints. CONCLUSIONS: The early application of dabigatran appears to be safer than VKA administered at any time point with regards to the risk of hemorrhagic complications and in particular for intracranial hemorrhage. This result, however, must be interpreted with caution in view of the low precision of the estimate.

Increasing reproducibility in preclinical stroke research: the correlation of immunofluorescence intensity measurements and Western blot analyses strongly depends on antibody clonality and tissue pre-treatment in a mouse model of focal cerebral ischemia.

In the setting of stroke, ischemia not only impairs neuronal function, but also detrimentally affects the different components of the neurovascular unit, which are shown to be involved in the transition from reversible to long-lasting tissue damage. In this context, the glial proteins myelin basic protein (MBP) and the 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) as well as the vasculature-associated basement membrane proteins laminin and collagen IV have been identified as ischemia-sensitive elements. However, available data from immunofluorescence and Western blot analyses are often found to be contradictory, which renders interpretation of the respective data rather difficult. Therefore, the present study investigates the impact of tissue pre-treatment and antibody clonality on immunofluorescence measurements of the mentioned proteins in a highly reproducible model of permanent middle cerebral artery occlusion. Here, immunofluorescence labeling using polyclonal antibodies revealed an increased immunofluorescence intensity of MBP, CNP, laminin and collagen IV in ischemic areas, although Western blot analyses did not reveal increased protein levels. Importantly, contrary to polyclonal antibodies, monoclonal ones did not provide increased fluorescence intensities in ischemic areas. Further, we were able to demonstrate that different ways of tissue pre-treatment including paraformaldehyde fixation and antigen retrieval may not only impact on fluorescence intensity measurements in general, but rather one-sidedly affect either ischemic or unaffected tissue. Therefore, immunofluorescence intensity measurements do not necessarily correlate with the actual protein levels, especially in ischemia-affected tissue and should always be complemented by different techniques to enhance reproducibility and to hopefully overcome the translational roadblock from bench to bedside.

Large diameter hemicraniectomy does not improve long-term outcome in malignant infarction.

INTRODUCTION: In malignant cerebral infarction decompressive hemicraniectomy has demonstrated beneficial effects, but the optimum size of hemicraniectomy is still a matter of debate. Some surgeons prefer a large-sized hemicraniectomy with a diameter of more than 14 cm (HC > 14). We investigated whether this approach is associated with reduced mortality and an improved long-term functional outcome compared to a standard hemicraniectomy with a diameter of less than 14 cm (HC ≤ 14). METHODS: Patients from the DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY) registry who received hemicraniectomy were dichotomized according to the hemicraniectomy diameter (HC ≤ 14 cm vs. HC > 14 cm). The primary outcome was modified Rankin scale (mRS) score ≤ 4 after 12 months. Secondary outcomes were in-hospital mortality, mRS ≤ 3 and mortality after 12 months, and the rate of hemicraniectomy-related complications. The diameter of the hemicraniectomy was examined as an independent predictor of functional outcome in multivariable analyses. RESULTS: Among 130 patients (32.3% female, mean (SD) age 55 (11) years), the mean hemicraniectomy diameter was 13.6 cm. 42 patients (32.3%) had HC > 14. There were no significant differences in the primary outcome and mortality by size of hemicraniectomy. Rate of complications did not differ (HC ≤ 14 27.6% vs. HC > 14 36.6%, p = 0.302). Age and infarct volume but not hemicraniectomy diameter were associated with outcome in multivariable analyses. CONCLUSION: In this post-hoc analysis, large hemicraniectomy was not associated with an improved outcome or lower mortality in unselected patients with malignant middle cerebral artery infarction. Randomized trials should further examine whether individual patients could benefit from a large-sized hemicraniectomy. CLINICAL TRIAL REGISTRATION INFORMATION: German Clinical Trials Register (URL: https://www.drks.de ; Unique Identifier: DRKS00000624).

Ability of patients with acute ischemic stroke to recall given information on intravenous thrombolysis: Results of a prospective multicenter study.

Introduction: Intravenous thrombolysis (IVT) is an on label treatment for selected patients with acute ischemic stroke (AIS). As major bleeding or allergic shock may occur, the need to ensure patients' informed consent for IVT is a matter of debate. Patients and methods: Prospective investigator-initiated multi-center observational study to assess the ability of AIS patients to recall information, provided by a physician during a standardized educational talk (SET) on IVT use. The recall of 20 pre-defined items was assessed in AIS after 60-90 min (n = 93) or 23-25 h (n = 40) after SET. About 40 patients with subacute stroke, 40 non-stroke patients, and 23 relatives of AIS patients served as controls, and were surveyed 60-90 min after SET. Results: Within 60-90 min after SET, AIS patients (median age 70 years, 31% female, median NIHSS score on admission 3 points) who were considered capable to provide informed consent recalled 55% (IQR 40%-66.7%) of the provided SET items. In multivariable linear regression analysis recapitulation by AIS patients was associated with their educational level (ß = 6.497, p < 0.001), self-reported excitement level (ß = 1.879, p = 0.011) and NIHSS score on admission (ß = -1.186, p = 0.001). Patients with subacute stroke (70 years, 40% female, median NIHSS = 2) recalled 70% (IQR 55.7%-83.6%), non-stroke patients (75 years, 40% female) 70% (IQR 60%-78.7%), and AIS relatives (58 years, 83% female) 70% (IQR 60%-85%). Compared to subacute stroke patients, AIS patients less often recalled the frequency of IVT-related bleeding (21% vs 43%), allergic shock (15% vs 39%), and bleeding-related morbidity and mortality (44% vs 78%). AIS patients recalled 50% (IQR 42.3%-67.5%) of the provided items 23-25 h after SET. Conclusion: AIS patients eligible for IVT remember about half of all SET-items after 60-90 min or 23-25 h, respectively. The fact that the recapitulation of IVT-associated risks is particularly poor should be given special consideration.

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

Topics Mentioned by Stroke Patients during Supportive Phone Calls-Implications for Individualized Aftercare Programs.

By understanding stroke as a chronic disease, aftercare becomes increasingly important. For developing aftercare programs, the patients' perspective regarding, for example, stroke-related symptoms and interactions with the healthcare system is necessary. Records from a local stroke pilot program were used to extract relevant topics from the patients' perspective, as mentioned during a phone call two months after hospital discharge. Data from 157 patients with ischemic stroke or transient ischemic attack (TIA) were included. "Rehabilitation" was mentioned by 67.5% of patients, followed by "specialist physician", "symptoms", and "medication". Compared with severely disabled patients, those with no relevant disability at hospital discharge mentioned "symptoms" significantly more often. Regarding rehabilitation, "outpatient care" was mentioned more often by patients in an inpatient setting, and 11.8% without rehabilitation mentioned "depression". Patients in single-compared to multi-person households differed, for example, in the frequency of mentioning "specialist physicians" and gradually "outpatient care". A multivariate model yielded associations between the disability at discharge and the probability of mentioning relevant topics afterward. This study provided insights into the patients' perspective and identified topics that need attention while accompanying stroke and TIA patients after discharge. Further, the degree of disability at discharge might be helpful for planning individual aftercare.

Association of stroke lesion shape with newly detected atrial fibrillation - Results from the MonDAFIS study.

Paroxysmal Atrial fibrillation (AF) is often clinically silent and may be missed by the usual diagnostic workup after ischemic stroke. We aimed to determine whether shape characteristics of ischemic stroke lesions can be used to predict AF in stroke patients without known AF at baseline. Lesion shape quantification on brain MRI was performed in selected patients from the intervention arm of the Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS) study, which included patients with ischemic stroke or TIA without prior AF. Multiple morphologic parameters were calculated based on lesion segmentation in acute brain MRI data. Multivariate logistic models were used to test the association of lesion morphology, clinical parameters, and AF. A stepwise elimination regression was conducted to identify the most important variables. A total of 755 patients were included. Patients with AF detected within 2 years after stroke (n = 86) had a larger overall oriented bounding box (OBB) volume (p = 0.003) and a higher number of brain lesion components (p = 0.008) than patients without AF. In the multivariate model, OBB volume (OR 1.72, 95%CI 1.29-2.35, p < 0.001), age (OR 2.13, 95%CI 1.52-3.06, p < 0.001), and female sex (OR 2.45, 95%CI 1.41-4.31, p = 0.002) were independently associated with detected AF. Ischemic lesions in patients with detected AF after stroke presented with a more dispersed infarct pattern and a higher number of lesion components. Together with clinical characteristics, these lesion shape characteristics may help in guiding prolonged cardiac monitoring after stroke.

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Regionally Altered Immunosignals of Surfactant Protein-G, Vascular and Non-Vascular Elements of the Neurovascular Unit after Experimental Focal Cerebral Ischemia in Mice, Rats, and Sheep.

The surfactant protein-G (SP-G) has recently been discovered in the brain and linked to fluid balance regulations. Stroke is characterized by impaired vessel integrity, promoting water influx and edema formation. The neurovascular unit concept (NVU) has been generated to cover not only ischemic affections of neurons or vessels but also other regionally associated cells. This study provides the first spatio-temporal characterization of SP-G and NVU elements after experimental stroke. Immunofluorescence labeling was applied to explore SP-G, vascular and cellular markers in mice (4, 24, and 72 h of ischemia), rats (24 h of ischemia), and sheep (two weeks of ischemia). Extravasated albumin indicated vascular damage within ischemic areas. Quantifications revealed decreasing SP-G signals in the ischemia-affected neocortex and subcortex. Inverse immunosignals of SP-G and vascular elements existed throughout all models. Despite local associations between SP-G and the vasculature, a definite co-localization was not seen. Along with a decreased SP-G-immunoreactivity in ischemic areas, signals originating from neurons, glial elements, and the extracellular matrix exhibited morphological alterations or changed intensities. Collectively, this study revealed regional alterations of SP-G, vascular, and non-vascular NVU elements after ischemia, and may thus stimulate the discussion about the role of SP-G during stroke.

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.