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.

Complex left appendage morphology is associated with Embolic Stroke of Undetermined Source.

INTRODUCTION: Variations in the left atrial appendage (LAA) morphology are associated with different embolic risk in patients with atrial fibrillation (AF). Data are scarce regarding the association between LAA morphology and Embolic stroke of undetermined source (ESUS). PATIENTS AND METHODS: Using cardiac computed tomography (CCT) scans, LAA morphology was categorized as either chicken wing (CW), cactus, windsock, or cauliflower. Furthermore, we examined the presence of large secondary lobes arising from the main lobe, considering their existence as indicative of a complex LAA morphology. LAA morphologies were compared between ESUS (n = 134) and AF patients (n = 120); and between ESUS patients with (n = 24) and without (n = 110) subsequent AF diagnosis during long-term follow-up. RESULTS: ESUS patients had a significantly higher prevalence of cauliflower morphology compared to AF group (52% vs 34%, respectively, p = 0.01); however, no significant difference was found between the groups when categorizing LAA morphology to either CW or non-CW. ESUS patients had significantly higher prevalence of large secondary lobes compared with AF patients (50% vs 29%, respectively, p = 0.001). When comparing ESUS patients with and without AF diagnosis during follow-up (20-48 months of follow-up, median 31 months), there were no significant differences in the prevalence of the "classical" morphologies, but large secondary lobes were significantly more prevalent among those without subsequent AF diagnosis. CONCLUSION: ESUS patients have a high prevalence of complex LAA morphology, which might be associated with an increased risk for thrombus formation even in the absence of AF.

Impact of dementia status on intravenous thrombolysis and endovascular treatment for acute ischemic stroke: Retrospective study.

INTRODUCTION: Individuals with dementia are underrepresented in interventional studies for acute ischemic stroke (AIS). This research gap creates a bias against their treatment in clinical practice. Our goal was to compare the safety and efficacy of intravenous-thrombolysis (t-PA) and endovascular treatment (EVT) in individuals with or without pre-AIS dementia. METHOD: A retrospective study of AIS patients receiving t-PA or EVT between 2019 and 2022. Patients were classified as dementia on a case-by-case review of baseline assessment. Additional variables included demographic, vascular risk factors, AIS severity and treatment. Outcomes of interest were intracerebral hemorrhage, mortality in 90-days, and the difference in modified rankin scale (mRS) before AIS and in 90-days follow-up. Outcomes were compared across non-matched groups and following propensity-score matching. RESULTS: Altogether, 628 patients were included, of which 68 had pre-AIS dementia. Compared to non-dementia group, dementia group were older, had a higher rate of vascular risk factors, higher pre-stroke mRS and higher baseline NIHSS. Individuals with dementia had higher rates of mortality (25% vs.11%,p < 0.01) on non-matched comparison. All cohort and restricted t-PA EVT matched analysis showed no difference in any outcome. Regression analysis confirmed that AIS severity at presentation and its treatment, not dementia, were the chief contributors to patients' outcomes. DISCUSSION: Our results indicate that pre-AIS dementia does not impact the efficacy or safety of EVT or t-PA for AIS. We thus call for more inclusive research on stroke therapy with regards to baseline cognitive status. Such studies are urgently required to inform stroke guidelines and enhance care.

Association between clinical characteristics, acute steroid treatment and oligoclonal bands result in multiple sclerosis: A retrospective study.

BACKGROUND: Detection of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) is important for diagnosis of multiple sclerosis (MS). Previous studies reported that treatment with intravenous methylprednisolone (IVMP) before lumber puncture (LP) could suppress OCBs production. The aim of this study was to assess whether IVMP initiation prior to CSF collection affects OCBs results in patients with an acute demyelinating event. Additionally, we examined which clinical characteristics are associated with the presence of OCBs in the CSF. METHODS: We retrospectively evaluated patients admitted to the neurology department at rabin medical center (RMC) between 2010 and 2022 who underwent LP with OCBs analysis as part of their demyelinating attack workup. Patients were divided into OCB-positive and OCB-negative groups and demographical and clinical characteristics (including timing and duration of acute steroid treatment and history of prior demyelinating attacks) were analyzed for association with OCBs results. RESULTS: A total of 342 patients were included with a median age of 35 years (IQR, 27-46). Two hundred thirty-eight (69.6 %) were OCB-positive. Initiation of IVMP before LP was not associated with negative OCBs (11.8 % Vs. 13.5 %, P = 0.721), nor was it correlated with OCBs positivity (OR=0.86, P = 0.66). CSF cell count was higher in OCB-positive patients (5 Vs. 3, P = 0.001), and a history of prior demyelinating attacks was associated with- (33.6 % Vs. 20.2 %, P = 0.014) and predictive of OCBs positivity (OR=2, P = 0.013). CONCLUSIONS: Timing of steroids was not associated with OCB positivity. However, pleocytosis and a prior attack were associated with OCB positivity in this cohort. Our results suggest that steroid treatment is unlikely to affect OCBs results. Ideally, larger prospective studies would be needed to confirm our observations.

The Impact of Cerebral Embolic Protection Devices on Characteristics and Outcomes of Stroke Complicating TAVR.

BACKGROUND: Acute ischemic stroke remains a serious complication of transcatheter aortic valve replacement (TAVR). Cerebral embolic protection devices (CEPD) were developed to mitigate the risk of acute ischemic stroke complicating TAVR (AISCT). However, the existing body of evidence does not clearly support CEPD efficacy in AISCT prevention. OBJECTIVES: In a cohort of patients with AISCT, we aimed to compare the characteristics and outcomes of patients who have had unprotected TAVR (CEPD-) vs CEPD-protected TAVR (CEPD+). METHODS: Data were derived from an international multicenter registry focusing on AISCT. We included all patients who experienced ischemic stroke within 72 hours of TAVR. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Primary outcomes were neurologic disability status according to the modified Rankin Score at 30 days, and 6-month all-cause death. Propensity score matched analysis was used to control for differences between groups. RESULTS: In 18,725 TAVR procedures, 416 AISCT (2.2%) within 72 hours were documented, of which 376 were in the CEPD- TAVR group and 40 in the CEPD+ TAVR group. Although the middle cerebral artery stroke rate was similar in both groups (29.7% CEPD- vs 33.3% CEPD+; P = 0.71), AISCT in the CEPD+ group was characterized by a lower rate of internal carotid artery occlusion (0% vs 4.7%) and higher rate of vertebrobasilar system strokes (15.4% vs 5.7%; P = 0.04). AISCT was severe (NIHSS ≥15) in 21.6% CEPD- and 23.3% CEPD+ AISCT (P = 0.20). Disabling stroke rates (modified Rankin Score >1 at 30 days) were 47.3% vs 42.5% (P = 0.62), and 6-month mortality was 31.3% vs 23.3% (P = 0.61), in the CEPD- and CEPD+ groups, respectively. In the propensity score matched cohort, disabling stroke rates were 56.5% vs 41.6% (P = 0.16), and 6-month mortality was 33% vs 19.5% (P = 0.35), in the CEPD- and CEPD+ groups, respectively. CONCLUSIONS: In a large cohort of patients with AISCT, the use of CEPD had little effect on stroke distribution, severity, and outcomes.

Lung cancer is associated with acute ongoing cerebral ischemia: A population-based study.

BACKGROUND AND OBJECTIVES: Cerebral microinfarcts (CMIs) are the most common type of brain ischemia; however, they are extremely rare in the general population. CMIs can be detected by magnetic resonance diffusion-weighted imaging (MRI-DWI) only for a very short period of approximately 2 weeks after their formation and are associated with an increased stroke risk and cognitive impairment. We aimed to examine CMI detection rate in patients with lung cancer (LC), which is strongly associated with ischemic stroke risk relative to other cancer types. METHODS: We used the Clalit Health Services record (representing more than 5 million patients) to identify adults with LC and breast, pancreatic, or colon cancer (non-lung cancer, NLC) who underwent brain magnetic resonance diffusion (MRI) scan within 5 years following cancer diagnosis. All brain MRI scans were reviewed, and CMIs were documented, as well as cardiovascular risk factors. RESULTS: Our cohort contained a total of 2056 MRI scans of LC patients and 1598 of NLC patients. A total of 143 CMI were found in 73/2056 (3.5%) MRI scans of LC group compared to a total of 29 CMI in 22/1598 (1.4%) MRI scans of NLC (p < 0.01). Cancer type (e.g. LC vs NLC) was the only associated factor with CMI incidence on multivariate analysis. After calculating accumulated risk, we found an incidence of 2.5 CMI per year in LC patients and 0.5 in NLC. DISCUSSION: CMIs are common findings in cancer patients, especially in LC patients and therefore might serve as a marker for occult brain ischemia, cognitive decline, and cancer-related stroke (CRS) risk.

Association Between Guillain-Barré Syndrome and COVID-19 Infection and Vaccination: A Population-Based Nested Case-Control Study.

BACKGROUND AND OBJECTIVES: Existing data regarding occurrence of Guillain-Barré syndrome (GBS) after coronavirus disease 2019 (COVID-19) infection and vaccination are inconclusive. We aimed to assess the association between GBS and both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 vaccine. METHODS: We conducted a nested case-control study in a cohort of 3,193,951 patients aged 16 years or older, without a diagnosis of prior GBS, from the largest health care provider in Israel. Participants were followed from January 1, 2021, until June 30, 2022, for the occurrence of GBS. Ten randomly selected controls were matched to each case of GBS on age and sex. We assessed both SARS-CoV-2 infection and COVID-19 vaccine administration in the prior 6 weeks in cases and controls. RESULTS: Overall, 76 patients were diagnosed with GBS during follow-up and were matched to 760 controls. A positive test for SARS-CoV-2 was detected in 9 (11.8%) cases and 18 (2.4%) controls. An administration of COVID-19 vaccine was detected in 8 (10.5%) cases (all Pfizer-BioNTech [BNT162b2] vaccine) and 136 (17.9%) controls (134 Pfizer-BioNTech vaccine). Multivariable conditional logistic regression models showed that the odds ratio for GBS associated with SARS-CoV-2 infection and COVID-19 vaccine administration was 6.30 (95% CI 2.55-15.56) and 0.41 (95% CI 0.17-0.96), respectively. The results were similar when exposure to SARS-CoV-2 infection or COVID-19 vaccine administration was ascertained in the prior 4 and 8 weeks, although did not reach statistical significance for COVID-19 vaccine at 4 weeks. DISCUSSION: Our study suggests that SARS-CoV-2 infection is associated with increased risk of GBS, whereas Pfizer-BioNTech COVID-19 vaccine is associated with decreased risk of GBS.

Association between COVID-19 vaccination and myasthenia gravis: A population-based, nested case-control study.

BACKGROUND: Existing data regarding the link between COVID-19 vaccine and myasthenia gravis (MG) are scarce. We aimed to assess the association between Pfizer-BioNTech vaccine with both new-onset MG and MG exacerbation. METHODS: For the first aim, we conducted a nested case-control study in a cohort of 3,052,467 adults, without a diagnosis of MG, from the largest healthcare provider in Israel. Subjects were followed from January 1, 2021 until June 30, 2022 for the occurrence of MG. Ten randomly selected controls were matched to each case of new-onset MG on age and sex. For the second aim, a nested case-control study was conducted in a cohort of 1446 MG patients. Four randomly selected MG patients (controls) were matched to each case of MG exacerbation. Exposure to COVID-19 vaccine in the prior 4 weeks was assessed in cases and controls. RESULTS: Overall, 332 patients had new-onset MG and were matched with 3320 controls. Multivariable conditional logistic regression models showed that the odds ratio (OR) for new-onset MG, associated with COVID-19 vaccine, was 1.14 (95% CI 0.73-1.78). The results were consistent in sensitivity analysis that used more stringent criteria to define MG. Overall, 62 patients with MG exacerbation were matched to 248 MG controls. The multivariable OR for MG exacerbation, associated with COVID-19 vaccine, was 1.35 (95% CI 0.37-4.89). All results were similar when the prior exposure to COVID-19 vaccine was extended to 8 weeks. CONCLUSION: This study suggests that Pfizer-BioNTech vaccine is not associated with increased risk of new-onset nor exacerbation of MG.

Clinicoradiologic Criteria for the Diagnosis of Stroke-like Episodes in MELAS.

Background and Objectives: Stroke-like episodes (SLEs) in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome are often misdiagnosed as acute ischemic stroke (AIS). We aimed to determine unique clinical and neuroimaging features for SLEs and formulate diagnostic criteria. Methods: We retrospectively identified patients with MELAS admitted for SLEs between January 2012 and December 2021. Clinical features and imaging findings were compared with a cohort of patients who presented with AIS and similar lesion topography. A set of criteria was formulated and then tested by a blinded rater to evaluate diagnostic performance. Results: Eleven MELAS patients with 17 SLE and 21 AISs were included. Patients with SLEs were younger (median 45 [37-60] vs 77 [68-82] years, p < 0.01) and had a lower body mass index (18 ± 2.6 vs 29 ± 4, p < 0.01), more commonly reported hearing loss (91% vs 5%, p < 0.01), and more commonly presented with headache and/or seizures (41% vs 0%, p < 0.01). The earliest neuroimaging test performed at presentation was uniformly a noncontrast CT. Two main patterns of lesion topography with a stereotypical spatiotemporal evolution were identified-an anterior pattern (7/21, 41%) starting at the temporal operculum and spreading to the peripheral frontal cortex and a posterior pattern (10/21, 59%) starting at the cuneus/precuneus and spreading to the lateral occipital and parietal cortex. Other distinguishing features for SLEs vs AIS were cerebellar atrophy (91% vs 19%, p < 0.01), previous cortical lesions with typical SLE distribution (46% vs 9%, p = 0.03), acute lesion tissue hyperemia and venous engorgement on CT angiography (CTA) (45% vs 0%, p < 0.01), and no large vessel occlusion on CTA (0% vs 100%, p < 0.01). Based on these clinicoradiologic features, a set of diagnostic criteria were constructed for possible SLE (sensitivity 100%, specificity 81%, AUC 0.905) and probable SLE (sensitivity 88%, specificity 95%, AUC 0.917). Discussion: Clinicoradiologic criteria based on simple anamnesis and a CT scan at presentation can accurately diagnose SLE and lead to early administration of appropriate therapy. Classification of Evidence: This study provides Class III evidence that an algorithm using clinical and imaging features can differentiate stroke-like episodes due to MELAS from acute ischemic strokes.

Intracranial stenting for large vessel intracranial atherosclerotic disease: Retrospective study.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a common cause for stroke and can be defined as symptomatic (stroke) or asymptomatic. Current guidelines recommend against intracranial stenting (ICS) for patients with ICAD; treatment of patients who failed the best medical therapy is still debatable. METHODS: We introduce a preliminary retrospective analysis of our tertiary stroke center during 2018-2022 of patients that were treated with ICS either in acute phase or elective (eICS). Study endpoints were stroke, functional outcome (modified Rankin Score [mRS] at 3 months), and serious adverse events. RESULTS: Thirty-three stents were implanted, 21 in acute group and 12 in the eICS group. Most patients (75%) were treated with a new generation self-expandible stent. One patient had peri-procedural stroke and four patients had transient ischemic event or stroke during follow-up. There were eight cases of death (all acute group patients, seven of which occurred in the posterior circulation). Fifteen patients (62%) had favorable clinical outcomes (mRS 0-2 for pre-stroke), of which 10/10 (100%) in the eICS, the other two eICS patients had pre-morbid mRS 3 with no clinical change. CONCLUSIONS: The evolution of new devices for ICS and the accumulating interventional experience might open a new era. As no other effective alternative treatment options exist for preventing recurrent stroke, stenting is still common practice in many tertiary centers either urgently or as elective procedure for refractory cases.

Clinical score for early diagnosis and treatment of stroke-like episodes in MELAS syndrome.

BACKGROUND AND OBJECTIVES: Stroke-like episodes (SLEs) in patients with MELAS syndrome are often initially misdiagnosed as acute ischemic stroke (AIS), resulting in treatment delay. We aimed to determine clinical features that may distinguish SLEs from AISs and explore the benefit of early L-arginine treatment on patient outcomes. METHODS: We looked retrospectively for MELAS patients admitted between January 2005 and January 2022 and compared them to an AIS cohort with similar lesion topography. MELAS patients who received L-arginine within 40 days of their first SLE were defined as the early treatment group and the remaining as late or no treatment group. RESULTS: Twenty-three SLEs in 10 MELAS patients and 21 AISs were included. SLE patients had significantly different features: they were younger, more commonly reported hearing loss, lower body mass index, had more commonly a combination of headache and/or seizures at presentation, serum lactate was higher, and hemiparesis was less common. An SLE Early Clinical Score (SLEECS) was constructed by designating one point to each above features. SLEECS ≥ 4 had 80% sensitivity and 100% specificity for SLE diagnosis. Compared to late or no treatment, early treatment group patients (n = 5) had less recurrent SLEs (total 2 vs. 11), less seizures (14% vs. 25%, p = 0.048), lower degree of disability at first and last follow-up (modified ranking scale, mRS 2 ± 0.7 vs. 4.2 ± 1, p = 0.005; 2 ± 0.7 vs. 5.8 ± 0.5, p < 0.001, respectively), and a lower mortality (0% vs. 80% p = 0.048). CONCLUSIONS: The SLEECS model may aid in the early diagnosis and treatment of SLEs and lead to improved clinical outcomes.

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.

Effect of time delay in inter-hospital transfer on outcomes of endovascular treatment of acute ischemic stroke.

Background: Endovascular treatment (EVT) with mechanical thrombectomy is the standard of care for large vessel occlusion (LVO) in acute ischemic stroke (AIS). The most common approach today is to perform EVT in a comprehensive stroke center (CSC) and transfer relevant patients for EVT from a primary stroke center (PSC). Rapid and efficient treatment of LVO is a key factor in achieving a good clinical outcome. Methods: We present our retrospective cohort of patients who underwent EVT between 2018 and 2021, including direct admissions and patients transferred from PSC. Primary endpoints were time intervals (door-to-puncture, onset-to-puncture, door-to-door) and favorable outcome (mRS ≤ 2) at 90 days. Secondary outcomes were successful recanalization, mortality rate, and symptomatic intracranial hemorrhage (sICH). Additional analysis was performed for transferred patients not treated with EVT; endpoints were time intervals, favorable outcomes, and reason for exclusion of EVT. Results: Among a total of 405 patients, 272 were admitted directly to our EVT center and 133 were transferred; there was no significant difference between groups in the occluded vascular territory, baseline NIHSS, wake-up strokes, or thrombolysis rate. Directly admitted patients had a shorter door-to-puncture time than transferred patients (190 min vs. 293 min, p < 0.001). The median door-to-door shift time was 204 min. We found no significant difference in functional independence, successful recanalization rates, or sICH rates. The most common reason to exclude transferred patients from EVT was clinical or angiographic improvement (55.6% of patients). Conclusion: Our results show that transferring patients to the EVT center does not affect clinical outcomes, despite the expected delay in EVT. Reassessment of patients upon arrival at the CSC is crucial, and patient selection should be done based on both time and tissue window.

Management and Outcome of Acute Ischemic Stroke Complicating Transcatheter Aortic Valve Replacement.

BACKGROUND: Despite advances in transcatheter aortic valve replacement (TAVR), periprocedural acute ischemic stroke remains a concern. OBJECTIVES: The aims of this study were to investigate acute ischemic stroke complicating TAVR (AISCT) and to describe the indications and outcomes of interventions to treat AISCT. METHODS: An international multicenter registry was established focusing on AISCT within 30 days of TAVR. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Primary outcomes were 1-year all-cause death and neurologic disability status at 90 days according to modified Rankin scale score. RESULTS: Of 16,615 TAVR procedures, 387 patients with AISCT were included (2.3%). Rates of 1-year death were 28.9%, 35.9%, and 77.5% in patients with mild, moderate, and severe stroke, respectively (P < 0.001). Although 348 patients were managed conservatively, 39 patients (10.1%) underwent neurointervention (NI) with either mechanical thrombectomy (n = 26) or thrombolytic therapy (n = 13). In a subanalysis excluding patients with mild stroke, there was no clear 1-year survival benefit for NI compared with conservative management (47.6% vs 41.1%, respectively; P = 0.78). In a logistic regression model controlling for stroke severity, NI was associated with 2.9-fold odds (95% CI: 1.2-7.0; P = 0.016) of independent survival at 90 days. CONCLUSIONS: AISCT carries significant morbidity and mortality, which is correlated with stroke severity. The present findings suggest that neurologic disability for patients with moderate or worse stroke could potentially be improved by timely intervention and highlight the importance of collaboration between cardiologists and neurologists to optimize AISCT outcomes.

Cardiac CT for intra-cardiac thrombus detection in embolic stroke of undetermined source (ESUS).

Introduction: Embolic stroke of undetermined source (ESUS) is a common medical challenge regarding secondary prevention strategy. Cardiac imaging is the cornerstone of embolic stroke workup, in an effort to diagnose high risk cardio-embolic sources. Cardiac computed tomography angiography (CCTA) is an emerging imaging modality with high diagnostic performance for intra-cardiac thrombus detection. The yield of CCTA implementation in addition to standard care in ESUS workup is unknown. Thus, the aim of this study was to assess the utility of CCTA in detecting intra-cardiac thrombi in the routine ESUS workup. Patients and methods: This is a retrospective observational analysis of ESUS cases managed in vascular neurology unit between 2019 and 2021. Within this ESUS registry, consecutive patients undergoing CCTA were included and carefully analyzed. Results: During the study period 1066 Ischemic stroke (IS) cases were treated and evaluated. 266/1066 (25%) met ESUS criteria and 129/266 (48%) underwent CCTA. Intra-cardiac thrombus was detected by CCTA in 22/129 (17%; 95% CI, 11.5%-23.5%) patients: left ventricular thrombus (LVT) in 13 (10.1%) patients, left atrial appendage (LAA) thrombus in 8 (6.2%) patients, and left atrial (LA) thrombus in 1 (0.8%) patient. Only 5/22 (23%) of these thrombi were suspected, but could not be confirmed, in trans-thoracic echocardiogram (TTE). Among CCTA-undergoing patients, 27/129 (21%; 95% CI, 14%-28%) were found to have an indication (including pulmonary embolism) for commencing anticoagulation (AC) treatment, rather than anti-platelets. In favor of CCTA implementation, 22/266 (8.2%; 95% CI, 4.9%-11.5%) patients within the entire ESUS cohort were diagnosed with intra-cardiac thrombus, otherwise missed. Conclusion: CCTA improves the detection of intra-cardiac thrombi in addition to standard care in ESUS patients. The implementation of CCTA in routine ESUS workup can change secondary prevention strategy in a considerable proportion of patients.

Clinical improvement of a toddler with COVID-19 focal cerebral arteriopathy possibly due to intra-arterial nimodipine.

Pediatric stroke is considered an infrequent complication of COVID-19. Focal cerebral arteriopathy (FCA) is one of the most common causes of arterial ischemic stroke in a previously healthy child. The present report describes a toddler with FCA most likely induced by SARS-CoV-2 infection who showed significant clinical improvement that may be related to injection of intra-arterial nimodipine. To our knowledge, this is the first reported use of nimodipine in this setting.

A Novel Rodent Model of Hypertensive Cerebral Small Vessel Disease with White Matter Hyperintensities and Peripheral Oxidative Stress.

Cerebral small vessel disease (CSVD) is the second most common cause of stroke and a major contributor to dementia. Manifestations of CSVD include cerebral microbleeds, intracerebral hemorrhages (ICH), lacunar infarcts, white matter hyperintensities (WMH) and enlarged perivascular spaces. Chronic hypertensive models have been found to reproduce most key features of the disease. Nevertheless, no animal models have been identified to reflect all different aspects of the human disease. Here, we described a novel model for CSVD using salt-sensitive 'Sabra' hypertension-prone rats (SBH/y), which display chronic hypertension and enhanced peripheral oxidative stress. SBH/y rats were either administered deoxycorticosteroid acetate (DOCA) (referred to as SBH/y-DOCA rats) or sham-operated and provided with 1% NaCl in drinking water. Rats underwent neurological assessment and behavioral testing, followed by ex vivo MRI and biochemical and histological analyses. SBH/y-DOCA rats show a neurological decline and cognitive impairment and present multiple cerebrovascular pathologies associated with CSVD, such as ICH, lacunes, enlarged perivascular spaces, blood vessel stenosis, BBB permeability and inflammation. Remarkably, SBH/y-DOCA rats show severe white matter pathology as well as WMH, which are rarely reported in commonly used models. Our model may serve as a novel platform for further understanding the mechanisms underlying CSVD and for testing novel therapeutics.

Characteristics of Cerebral Sinus Venous Thrombosis Patients Presenting with Intracerebral Hemorrhage.

Patients with cerebral venous sinus thrombosis (CVST) occasionally present with intracerebral hemorrhage (ICH). In this study, we aimed to identify predictors for ICH in CVST patients. Prospective CVST databases from three academic centers were retrospectively analyzed. CVST patients with and without ICH upon presentation were compared. Among the 404 included patients (mean age 41.8 years, 33% male), 74 (18.3%) had an ICH. The patients with ICH were older (45 ± 20.6 vs. 41.1 ± 18 years, p = 0.045), and were more often pregnant or postpartum women (15% vs. 6%, p = 0.011), or chronically hypertensive (15% vs. 5%, p = 0.001). The ICH patients had higher rates of seizures (60% vs. 15%, p < 0.001), and focal neurological deficits (53% vs. 23%, p < 0.001). The ICH group had lower rates of excellent outcome measured by 90-day mRS 0 (56.7% vs. 80.3%, p < 0.001) and higher rates of 90-day mortality (8% vs. 3%, p = 0.041). Radiological variables associated with ICH included superior sagittal sinus (SSS) thrombosis (63% vs. 36%), isolated cortical vein thrombosis (38% vs. 8%), and presence of venous infarction (34% vs. 7%) (p < 0.001 for all). Upon multivariate analysis, chronic hypertension (OR 3.7, p = 0.027), being either pregnant or postpartum (OR 4.3, p = 0.006), isolated cortical thrombosis (OR 3.5, p = 0.007), and SSS involvement (OR 3.4, p < 0.001) were independently associated with ICH upon admission. In conclusion, among CVST patients, the following present higher for ICH: pregnant or postpartum women, and individuals with chronic hypertension, cortical vein, or SSS involvement.

The Association between Low Levels of Low Density Lipoprotein Cholesterol and Intracerebral Hemorrhage: Cause for Concern?

Excessive levels of low-density lipoprotein cholesterol (LDL-C) in the blood are a known risk factor for atherosclerosis, and a common target of treatment for primary and secondary prevention of cerebrocardiovascular disease. As lipid lowering agents including statins, ezetimibe and anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown good therapeutic results, the guidelines are constantly lowering the "optimal" LDL-C goals. However, old and new data point towards an association between low LDL-C and total cholesterol and intracerebral hemorrhage (ICH). In this review we aimed to shed light on this troubling association and identify the potential risk factors of such a potential adverse reaction. With respect to the data presented, we concluded that in patients with high risk of ICH, a cautious approach and individualized therapy strategy are advised when considering aggressive LDL reduction.