Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation.

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74.

Blocking CCR5 activity by maraviroc augmentation in post-stroke depression: a proof-of-concept clinical trial.

BACKGROUND: Post-stroke depression (PSD) is a significant impediment to successful rehabilitation and recovery after a stroke. Current therapeutic options are limited, leaving an unmet demand for specific and effective therapeutic options. Our objective was to investigate the safety of Maraviroc, a CCR5 antagonist, as a possible mechanism-based add-on therapeutic option for PSD in an open-label proof-of-concept clinical trial. METHODS: We conducted a 10-week clinical trial in which ten patients with subcortical and cortical stroke, suffering from PSD. were administered a daily oral dose of 300 mg Maraviroc. Participants were then monitored for an additional eight weeks. The primary outcome measure was serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. The secondary outcome measure was a change in the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Maraviroc was well tolerated, with no reports of serious adverse events or discontinuations due to intolerance. The MADRS scores substantially reduced from baseline to week 10 (mean change: -16.4 ± 9.3; p < 0.001). By the conclusion of the treatment phase, a favorable response was observed in five patients, with four achieving remission. The time to response was relatively short, approximately three weeks. After the cessation of treatment, MADRS scores increased at week 18 by 6.1 ± 9.6 points (p = 0.014). CONCLUSIONS: Our proof-of-concept study suggests that a daily dosage of 300 mg of Maraviroc may represent a well-tolerated and potentially effective pharmacological approach to treating PSD. Further comprehensive placebo-controlled studies are needed to assess the impact of Maraviroc augmentation on PSD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05932550, Retrospectively registered: 28/06/2023.

Current advances in endovascular treatment.

PURPOSE OF REVIEW: Endovascular thrombectomy (EVT) is the most beneficial reperfusion therapy for acute ischemic stroke. Currently, much effort is done to promote trials examining EVT efficacy and safety in various conditions not included in the main randomized controlled trials established the superiority of EVT. This review summarizes the current advances of EVT patients' selection and periprocedural management. RECENT FINDINGS: Recent evidence points to beneficial effect of EVT among patients with relatively large ischemic core, premorbid independent nonagenarians and basilar artery occlusion, and suggest that intravenous thrombolysis bridging treatment is associated with better reperfusion rates. Ongoing trials currently examine EVT efficacy and safety in distal vessel occlusions and in large vessel occlusion with low NIHSS. Current evidence also support use of general anaesthesia and avoid postprocedural extremely low or high blood pressure as well as haemodynamic instability. SUMMARY: The field of EVT is rapidly evolving. The results of recent trials have dramatically increased the indications for EVT, with many ongoing trials examining further indications.

CCR5-Δ32 polymorphism-a possible protective factor from gait impairment amongst post-stroke patients.

BACKGROUND AND PURPOSE: Stroke and small vessel disease cause gait disturbances and falls. The naturally occurring loss-of-function mutation in the C-C chemokine receptor 5 gene (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether it also influences gait and balance measures up to 2 years after stroke. METHOD: Participants were 575 survivors of first-ever, mild-moderate ischaemic stroke or transient ischaemic attack from the TABASCO prospective study, who underwent a 3 T magnetic resonance imaging at baseline and were examined by a multi-professional team 6, 12 and 24 months after the event, using neurological, neuropsychological and mobility examinations. Gait rhythm and the timing of the gait cycle were measured by force-sensitive insoles. CCR5-Δ32 status and gait measures were available for 335 patients. RESULTS: CCR5-Δ32 carriers (16.4%) had higher gait speed and decreased (better) stride and swing time variability 6 and 12 months after the index event compared to non-carriers (p < 0.01 for all). The association remained significant after adjustment for age, gender, education, ethnicity and stroke severity. CONCLUSIONS: Significant associations were found between gait measurements and CCR5-Δ32 loss-of-function mutation amongst stroke survivors. This is the first study showing that genetic predisposition may predict long-term gait function after ischaemic stroke.

Factors influencing real-life use of direct oral anticoagulants in patients with cerebral sinus and venous thrombosis.

BACKGROUND: Direct oral anticoagulants (DOAC) are advocated as equally effective to vitamin K antagonists (VKA) for the treatment of patients with cerebral sinus and venous thrombosis (CSVT). However, data concerning the real-life management practices in CSVT patients are is lacking. METHODS: Prospective CSVT databases from four large academic medical centers were retrospectively studied. Demographics, clinical presentations, risk factors, radiological and outcome parameters were compared between CSVT patients treated with DOAC and VKA. RESULTS: Out of 504 CSVT patients, 43 (8.5%) were treated with DOAC, and the remaining 461 (91.5%) were treated with VKA. All patients with antiphospholipid syndrome (APLA) were treated with VKA (61 vs. 0, p=0.013). Patients with a history or presence of malignancy were also more often treated with VKA (16% vs. 5%, p=0.046). Other risk factors for thrombosis did not differ between the groups. There were no differences in clot extent or location and no differences in the percentage of favorable outcomes or mortality were observed. CONCLUSION: Our data suggests that only malignancy and antiphospholipid antibodies significantly influenced physician's decisions towards choosing VKA rather than DOAC. DOAC appear to be as effective and safe as VKA in patients with CSVT.

Posttraumatic Stress Symptoms After Stroke: The Effects of Anatomy and Coping Style.

BACKGROUND: Posttraumatic stress disorder (PTSD) can be triggered by life-threatening medical emergencies, such as stroke. Data suggest that up to 25% of stroke survivors will develop PTSD symptomatology, but little is known about predisposing factors. We sought to examine whether neuroimaging measures and coping styles are related to PTSD symptoms after stroke. METHODS: Participants were survivors of first-ever, mild-moderate ischemic stroke, or transient ischemic attack from the TABASCO study (Tel Aviv Brain Acute Stroke Cohort). All participants underwent a 3T magnetic resonance imaging at baseline and were examined 6, 12, and 24 months thereafter, using neurological, neuropsychological, and functional evaluations. At baseline, coping styles were evaluated by a self-reported questionnaire. PTSD symptoms were assessed using the PTSD checklist. Data were available for 436 patients. RESULTS: Forty-eight participants (11%) developed probable PTSD (PTSD checklist ≥44) during the first year after the stroke/transient ischemic attack. Stroke was more likely to cause PTSD than transient ischemic attack. Stroke severity, larger white matter lesion volume, and worse hippocampal connectivity were associated with PTSD severity, while infarct volume or location was not. In a multivariate analysis, high-anxious and defensive coping styles were associated with a 6.66-fold higher risk of developing poststroke PTSD ([95% CI, 2.08-21.34]; P<0.01) compared with low-anxious and repressive coping styles, after adjusting for age, education, stroke severity, brain atrophy, and depression. CONCLUSIONS: In our cohort, PTSD was a common sequela among stroke survivors. We suggest that risk factors for PTSD development include stroke severity, white matter damage, and premorbid coping styles. Early identification of at-risk patients is key to effective treatment.

Endovascular thrombectomy is beneficial for functional nonagenarians - a multicenter cohort analysis.

INTRODUCTION: The use of endovascular thrombectomy (EVT) has dramatically increased in recent years. However, most existing studies used an upper age limit of 80 and data regarding the safety and efficacy of EVT among nonagenarians is still lacking. METHODS: 767 consecutive patients undergoing EVT for large vessel occlusion (LVO) in three participating centers were recruited into a prospective ongoing database. Demographic, clinical and imaging characteristics were documented. Statistical analysis was done to evaluate EVT outcome among nonagenarians compared to younger patients. RESULTS: The current analysis included 41 (5.4%) patients older than 90 years. Compared to younger patients, nonagenarians were more often female (78% versus 50.3%, p ≤ 0.001), had worse baseline mRS scores (2 [0-3] versus 0 [0-2], p < 0.001), higher rates of hypertension and hyperlipidemia and a higher admission NIHSS (20 [14-23] versus 16 [11-20], p < 0.001). No differences were found between groups regarding the involved vessel, stroke etiology, time from symptoms to door or symptoms to EVT, successful recanalization rates and hemorrhagic transformation rates. Nonagenarians had worse mRS at 90 days (5 [3-6] versus 3 [2-5], p = 0.001), similar discharge NIHSS (5 [1-11] versus 4 [1-11], p = 0.78) and higher mortality rates (36.6% versus 15.8%, p < 0.001). All nonagenarians with baseline mRS 4 have died within 90 days. 36.4% of nonagenarian patients with baseline MRS of 3 or less had favorable outcome. DISCUSSION: This study demonstrates that nonagenarian stroke patients with baseline mRS of 3 or less benefit from EVT with no significant difference in the rate of favorable outcome compared to octogenarians.

CCR5-Δ32 polymorphism: a possible protective factor for post-stroke depressive symptoms.

Background: A naturally occurring loss-of-function mutation in the gene for C-C chemokine receptor type 5 (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether this mutation also prevented the development of depressive symptoms up to 2 years after a stroke. Methods: Participants were survivors of a first-ever mild to moderate ischemic stroke or transient ischemic attack from the TABASCO prospective study who underwent a 3 T MRI at baseline and were examined by a multiprofessional team 6, 12 and 24 months after the event, including an evaluation of depressive symptoms using the Geriatric Depression Scale. Results: CCR5-Δ32 status and a baseline depression evaluation were available for 435 patients. Compared with noncarriers, CCR5-Δ32 carriers (16.1%) had fewer depressive symptoms at admission (p = 0.035) and at 6 months (p < 0.001), 12 months (p < 0.001) and 24 months (p = 0.006) after the index event. This association remained significant at 6 and 12 months after adjustment for age, sex, education, antidepressant use, ethnicity and the presence of cortical infarcts. These findings were more robust in women. Compared to baseline, depressive symptoms in CCR5-Δ32 noncarriers tended to remain stable or grow worse over time, but in CCR5-Δ32 carriers, symptoms tended to improve. Limitations: A limitation of this study was the exclusion of patients who had a severe stroke or who had pre-stroke depression. Conclusion: Carriers of the CCR5-Δ32 allele had a lower tendency to develop depressive symptoms post-stroke, and this phenomenon was more prominent in women. These findings could have clinical implications; they suggest a mechanism-based treatment target for post-stroke depression. Drugs mimicking this loss-of-function mutation exist and could serve as a novel antidepressant therapy.

Protective effect of soluble Klotho in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass support-A pilot study.

OBJECTIVE: The Klotho protein family plays important roles in several metabolic pathways. Soluble Klotho has been recently put forward as an antiaging protein, demonstrating renal and cardiovascular protective traits. Cardiopulmonary bypass (CPB) support during cardiac surgery has been implicated in several adverse outcomes in pediatric and adult patients. Our goal was to assess whether serum Klotho levels can be used to predict outcomes in children undergoing cardiac surgery with CPB due to congenital heart defects (CHDs). METHODS: This prospective study was conducted on pediatric patients admitted to two Pediatric Cardiac Intensive Care Units, between 2012 and 2018. All patients were born with CHD and underwent corrective surgery with CPB. Sequential blood samples were analyzed by enzyme-linked immunosorbent assay for soluble Klotho levels at baseline, 2, 6, and 24 h after surgery. The association between Klotho levels and several demographic, intraoperative, and postoperative clinical and laboratory parameters was studied. RESULTS: Twenty-nine children undergoing cardiac surgery with CPB support were included. Serum Klotho levels were shown to significantly decrease 2 h after surgery and increase to baseline levels after 6 h (p < .001 and p < .05, respectively). Patients with low Klotho levels 2 h after surgery were at a 32-fold higher risk for developing postoperative complications (p = .015, odds ratio < 0.03). Moreover, Klotho levels at each of the four time points were lower in patients who developed postoperative complications. CONCLUSIONS: Cardiac surgery with CPB results in a significant decrease of serum Klotho levels 2 h after surgery in pediatric patients with CHDs, which can be used to predict development of postoperative complications in this patient population.

Working status is related to post stroke/TIA cognitive decline: data from the TABASCO study.

BACKGROUND AND AIMS: Occupational status may influence physical and mental post-stroke outcomes. We aimed to evaluate the association between occupational status and type, or engagement in social and family activities, neuroimaging measures and cognitive decline (CD) in a prospective cohort of stroke patients. METHODS: We included 273 first-ever stroke survivors at working age. All patients underwent 3T MRI at admission, as well as clinical and cognitive assessments at admission, 6, 12 and 24 months thereafter. RESULTS: Ninty nine (36.3%) of the participants were unemployed prior to the stroke. Age, sex, work type, other comorbidities, stroke severity or location were not associated with return to work. Patients who returned to work (87.4%) had better cognitive results and less depressive symptoms than those who retired after the event. Pre-stroke unemployment was associated with diabetes mellitus, hypertension, dyslipidemia, depression, poorer cognitive scores and brain atrophy. During the follow-up, 11% developed CD. CD was more common among previously unemployed than employed participants (19.2% vs. 6.3%, p = 0.001). Multiple regression adjusted for risk factors, revealed that pre-stroke unemployment was an independent predictor of CD (HR, 3.0; 95% CI: 1.06-8.44). Furthermore, engagement in mentally stimulating jobs decreased the risk for CD. CONCLUSIONS: Pre-stroke unemployment and post-stroke work disruption were each associated with depression and poorer cognitive performance up to two years post-stroke, as well as with brain atrophy at admission. Retirement after the stroke may increase the risk of developing CD. These results highlight the importance of continued employment in preserving cognitive abilities among stroke survivors.

Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline.

BACKGROUND AND PURPOSE: Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. METHODS: The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. RESULTS: At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. CONCLUSIONS: T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691.

Worse Outcome in Patients with Acute Stroke and Atrial Fibrillation Following Thrombolysis.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and a common cause of ischemic stroke. Stroke patients with AF have been shown to have a poorer neurological outcome than stroke patients without AF. OBJECTIVES: To determine the impact of pre-existing AF on residual degree of disability in patients treated with IV thrombolysis. METHODS: In this case-control study, data of 214 stroke patients (63 with AF and 151 without AF) were collected from the National Acute Stroke Israeli Registry, a nationwide quadrennial stroke database. Stroke severity and outcome were compared using the National Institute of Health Stroke Scale (NIHSS) on admission and the modified Rankin Scale (mRS) on admission and discharge. Demographics and stroke characteristics were also compared between the groups. RESULTS: Stroke severity, as determined by NIHSS at admission, was higher in the AF group than the non-AF. In the group of patients who were treated with intravenous tissue plasminogen activator (tPA), more patients had favorable outcomes (mRS = 0-1 on discharge) in the non-AF group than in the AF group (P = 0.058, odds ratio = 2.217, confidence interval 0.973 to 5.05). CONCLUSIONS: Our study suggests worse outcome in thrombolized patients with AF compared to non-AF stroke patients. Therefore, AF itself can be a poor prognostic factor for tPA sensitivity regarding the chance of revascularization and recovery after intravenous tPA.

Case report: Cerebral sinus vein thrombosis in VEXAS syndrome.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) syndrome is a newly described hemato-inflammatory acquired monogenic entity that presents in adulthood. One of the main features of VEXAS syndrome is a high venous thromboembolism (VTE) burden, with approximately 30-40% experiencing lower extremity deep vein thrombosis and a lower incidence of pulmonary embolism at approximately 10%. To date, VEXAS syndrome has not been associated with rarer forms of VTE such as cerebral sinus vein thrombosis (CSVT) and Budd-Chiari syndrome, which are well-recognized vascular manifestations in Behcet's disease, another autoinflammatory vasculitic disease. Herein, we describe a case of acute severe extensive and fatal CSVT in a patient with VEXAS syndrome. The event occurred during a period of apparently quiescent inflammatory status, while the patient was receiving tocilizumab and a low dose of glucocorticoids. Despite treatment with anticoagulation, high-dose glucocorticoids, endovascular thrombectomy, and intracranial pressure-lowering agents, the patient suffered severe neurologic damage and ultimately succumbed to the condition 3 weeks after the onset of CSVT. To the best of our knowledge, this is the first reported case of CVST in a patient with VEXAS syndrome.

Efficacy and safety of Apixaban in the treatment of cerebral venous sinus thrombosis: a multi-center study.

Background: Information regarding the safety and efficacy of specific direct oral anticoagulants (DOAC) in the treatment of cerebral sinus and venous thrombosis (CSVT) is scarce. Apixaban is one of the most frequently prescribed DOACs. Therefore, we aimed to compare the safety and efficacy of Apixaban with those of vitamin k antagonists (VKA) in patients with CSVT. Methods: Prospective CSVT databases from seven academic medical centers were retrospectively analyzed. Patients treated with Apixaban were compared to those treated with VKA. Data on demographics, clinical presentations, risk factors, radiological and outcome parameters were studied. Results: Overall, 403 patients were included in the analysis. Of them, 48 (12%) were treated with Apixaban, and 355 (88%) were treated with VKA. Rates of coagulopathies were significantly higher in the VKA-treated patients but no other differences between the groups were found in baseline characteristics and underlying etiology. No significant differences were found between groups in efficacy or safety parameters including the rates of recanalization, favorable outcomes, one-year mortality, seizures, intracranial hemorrhage or CSVT recurrences. Conclusion: Our data suggests that Apixaban may be safe and effective for patients with CSVT. These results should be tested in prospective randomized clinical studies.

Reducing the global burden of cerebral venous thrombosis: An international research agenda.

BACKGROUND: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. AIMS: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. SUMMARY OF REVIEW: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. CONCLUSIONS: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide.

Circle of Willis integrity in acute middle cerebral artery occlusion: does the posterior communicating artery matter?

BACKGROUND: Collateral circulation is an important determinant of outcome in people with acute ischemic stroke due to large vessel occlusion (LVO). OBJECTIVE: To explore the impact of the circle of Willis (CW) anatomical characteristics ipsilateral to the occlusion site, particularly the posterior communicating artery (PComA) and the A1-portion of the anterior cerebral artery (A1-ACA), on stroke outcomes in a cohort of patients with LVO and middle cerebral artery (MCA) occlusion, undergoing endovascular thrombectomy (EVT). METHODS: This is a retrospective cohort study performed in a comprehensive tertiary stroke center. The study population consisted of consecutive patients with LVO with proximal MCA occlusion (M1) between June 2016 and April 2021, undergoing EVT. Demographic, clinical, and imaging information was extracted from patient files. Patency and diameters of ipsilateral A1-ACA and PComA were manually measured on admission CT angiography images in the core laboratory. RESULTS: One hundred and five patients with LVO comprised the study cohort, mean age 72.3 years, 43.8% were male, mean National Institutes of Health Stroke Scale score at admission 15.2. The cohort was grouped according to CW vessel characteristics. On univariate analysis, a well-developed PComA was associated with lower rates of hemorrhagic transformation (1.8% vs 14.3%, P=0.01) and a trend towards lower mortality rates (8.9% vs 20.4%, P=0.08).On multivariable regression analysis a well-developed PComA emerged as an independent predictor for survival (aOR=0.09, 95% CI 0.01 to 0.4 for survival at discharge, P=0.009, aOR=0.22, 95% CI 0.05 to 0.8 for survival at 90 days, P=0.02). CONCLUSIONS: In a cohort of patients with LVO due to M1 occlusion undergoing EVT, a well-developed PComA was associated with significantly lower hemorrhagic transformation rates, a trend towards better functional outcomes, and independently predicted survival. Larger studies are needed to understand the differential effect of CW collateral conduits on stroke outcome and evaluate the practicality of incorporating such factors in the clinical decision-making process prior to EVT.

Association between intracranial vessel calcifications, structural brain damage, and cognitive impairment after minor strokes: a prospective study.

Background: Vascular calcifications are a hallmark of atherosclerosis, and in the coronary arteries are routinely used as a prognostic marker. Calcifications of intracranial vessels (ICC) are frequently observed on non-contrast CT (NCCT) and their effect on post-stroke cognitive impairment (PSCI) remains unclear. Our aim was to explore the association of ICC with prospective long-term cognitive function and advanced MRI-measures in a large prospective cohort of cognitively intact mild stroke survivors. Methods: Data from the Tel-Aviv brain acute stroke cohort (TABASCO) study [ClinicalTrials.gov #NCT01926691] were analyzed. This prospective cohort study (n = 575) aimed to identify predictors of PSCI, in cognitively intact mild stroke survivors. A quantitative assessment of the intracranial calcium content - The ICC score (ICCS) was calculated semi-automatically on NCCT using a validated calcium quantification application. Participants underwent a 3 T-MRI and prospective comprehensive cognitive clinical and laboratory assessments at enrollment, 6, 12, and 24-months. Results: Data were available for 531 participants (67.4 years, 59.5% males). The incidence of PSCI at two-years doubled in the high ICCS group (26% vs. 13.7%, p < 0.001). The high ICCS group had significantly greater small-vessel-disease (SVD) tissue changes and reduced microstructural-integrity assessed by Diffusion-Tensor-Imaging (DTI) maps (p < 0.05 for all). In multivariate analysis, a higher ICCS was independently associated with brain atrophy manifested by lower normalized white and gray matter, hippocampal and thalamic volumes (ß = -0.178, ß = -0.2, ß = -0.137, ß = -0.157; p < 0.05) and independently predicted PSCI (OR 1.83, 95%CI 1.01-3.35). Conclusion: Our findings suggest that the ICCS, which is a simple and readily available imaging marker on NCCT, is associated with brain atrophy, microstructural damage, the extent of SVD, and may predict PSCI. This finding has implications for identifying individuals at risk for PSCI and implementing targeted interventions to mitigate this risk.

Does Malignancy Status Effect Outcomes in Patients With Large Vessel Occlusion Stroke and Cancer Who Underwent Endovascular Thrombectomy?

Background Cancer is associated with an increased risk of acute ischemic stroke, including large vessel occlusions. Whether cancer status affects outcomes in patients with large vessel occlusions that undergo endovascular thrombectomy remains unknown. Methods and Results All consecutive patients undergoing endovascular thrombectomy for large vessel occlusions were recruited into a prospective ongoing multicenter database, and the data were retrospectively analyzed. Patients with active cancer were compared with patients with cancer in remission. Association of cancer status with 90-day functional outcome and mortality were calculated in multivariable analyses. We identified 154 patients with cancer and large vessel occlusions that underwent endovascular thrombectomy (mean age, 74±11; 43% men; median National Institutes of Health Stroke Scale 15). Of the included patients, 70 (46%) had a remote history of cancer or cancer in remission, and 84 (54%) had active disease. Outcome data at 90 days poststroke were available for 138 patients (90%) and was classified as favorable in 53 (38%). Patients with active cancer were younger and more often smoked but did not significantly differ from those without malignancy in other risk factors, stroke severity, stroke subtype, or procedural variables. Favorable outcome rates among patients with active cancer did not significantly differ compared with those seen in patients without active cancer, but mortality rates were significantly higher among patients with active cancer on univariate and multivariable analyses. Conclusions Our study suggests that endovascular thrombectomy is safe and efficacious in patients with history of malignancy as well as in those with active cancer at the time of stroke onset, although mortality rates are higher among patients with active cancer.

Characteristics of patients with cerebral sinus venous thrombosis and JAK2 V617F mutation.

OBJECTIVES: Janus kinase 2 (JAK2-V617F) mutations can cause thrombocytosis, polycythemia and hyper viscosity leading to cerebral sinus venous thrombosis (CSVT). However, data regarding the characteristics and prevalence of JAK2-V617F mutation in patients with CSVT are currently lacking. We aimed to evaluate the characteristics of CSVT patients that carry the JAK2 mutation. MATERIALS AND METHODS: Data of consecutive patients with CSVT, admitted to three large academic medical centers between 2010 and 2020, were retrospectively studied. Demographics, clinical presentations, radiological and clinical outcome parameters were compared between carriers of the JAK2-V617F mutation and controls. RESULTS: Out of 404 patients diagnosed with CSVT, 26 patients (6.5%) were carriers of the mutation. JAK2 mutation carriers more often had thrombocytosis (54% vs. 1%, p < 0.001). Furthermore, carriers of the JAK2 mutation less often had involvement of the transverse sinus (50% vs. 68%, p = 0.021). Finally, patients with the JAK2 mutation were more prone to have intracerebral hemorrhage (ICH, 31% vs. 17%, p = 0.044), but there was no significant difference between groups in terms of mortality nor functional outcome. CONCLUSIONS: JAK2 mutation is not uncommon in patients with CSVT and should be routinely screened for in this population. CSVT in JAK2 mutation carriers may have a tendency toward involving specific venous sinuses and is associated with a higher rate of ICH but similar overall prognosis.

The pivotal role of timing of intravenous thrombolysis bridging treatment prior to endovascular thrombectomy.

Background: The role of intravenous thrombolysis (IVT) as bridging treatment prior to endovascular thrombectomy (EVT) is under debate and better patient selection is needed. Objectives: As the efficacy and safety of IVT diminish with time, we aimed to examine the impact of bridging treatment within different time frames from symptom onset. Design: A retrospective registry study. Methods: Data were extracted from ongoing prospective EVT registries in two large tertiary centers. The current study included IVT-eligible patients with onset to door (OTD) < 4 h. We examined the efficacy and safety of bridging treatment through a comparison of the IVT + EVT group with the direct-EVT group by different time frames. Results: In all, 408 patients (age 71.1 ± 14.6, 50.6% males) were included, among them 195 received IVT + EVT and 213 underwent direct EVT. Both groups had similar characteristics. In the IVT + EVT group only, longer OTD was associated with lower rates of favorable outcome (p = 0.021) and higher rates of hemorrhagic transformation (HT; p = 0.001). In patients with OTD ⩽ 2 h, IVT + EVT compared to direct EVT had higher rates of TICI 2b-3 (86.2% versus 80.7%, p = 0.038). In patients with OTD > 2 h, IVT + EVT had lower rates of favorable outcome (33.3% versus 56.9%, p = 0.021), worse discharge National Institutes of Health Stroke Scale [7 (2-13) versus 3 (1-8), p = 0.024], and higher rates of HT (34.0% versus 8.5%, p < 0.001). Discussion: In this study, we found OTD times to have a significant effect on the impact of IVT bridging treatment. Our study shows that among patients with OTD < 2 h bridging treatment may be associated with higher rates of successful recanalization. By contrast, in patients with OTD > 2 h, bridging treatment was associated with worse outcomes. Further time-sensitive randomized trials are needed.