O’Carroll, Cumara B.

Background and Purpose Stroke is a frequent manifestation of non-bacterial thrombotic endocarditis (NBTE), yet current knowledge largely stems from case reports and small case series. This systematic review summarizes stroke presentation, imaging features, management, and outcomes in patients with NBTE-related stroke. Methods We conducted a patient-level systematic review of published case reports and case series. PubMed, MEDLINE, Embase, Web of Science, and PsycINFO were searched from inception through August 2025 for studies reporting individual patients with NBTE-related stroke. Extracted data included demographics, vascular risk factors, stroke presentation, imaging features, NBTE etiology, treatment (unfractionated heparin/low-molecular-weight heparin [UFH/LMWH], vitamin K antagonists [VKA], direct oral anticoagulants [DOACs], and/or valvular surgery), and outcomes. Multivariable regression was used to explore factors associated with recurrent stroke and mortality. Results We included 236 patients with NBTE and stroke from 218 studies (median age 56 years [IQR: 43–63], 63% female). Left hemispheric stroke syndromes predominated among clinical presentations (27%), and multi-vessel territory ischemic infarcts (>2 territories) were observed in 65%. Conventional vascular risk factors were infrequent (0%−21%), whereas deep vein thrombosis (43%) and systemic embolism (41%) frequently preceded or coincided with stroke onset. Malignancy (70%) and autoimmune disease (25%) were the main NBTE etiologies. Anticoagulation was initiated in 70%, and 21% underwent valvular surgery. Over a median follow-up of 2.0 months, stroke recurred in 43% and death occurred in 49% of patients. Malignant etiology (aOR 10.3, P < 0.001) and metastases (aOR 3.9, P < 0.001) were associated with increased mortality, while VKA use (aOR 0.08, P < 0.001) and autoimmune etiology (aOR 0.1, P < 0.001) were associated with lower mortality. Malignancy (aOR 2.8, P < 0.001) and DOAC use (aOR 5.2, P = 0.012) were associated with increased risk of recurrent stroke. Conclusion NBTE should be considered in stroke patients lacking conventional vascular risk factors, particularly those with malignancy or autoimmune disease. Malignancy and DOAC use were associated with higher recurrent stroke risk, while VKA use was associated with lower mortality; however, these anticoagulant-class findings should be considered hypothesis-generating and interpreted cautiously given the case-report evidence base, small treatment subgroups, potential confounding, and limited follow-up. What this study adds By synthesizing patient-level data from published case reports and case series, this review provides a stroke-focused characterization of NBTE, including clinical presentation, infarct topography, underlying etiologies, management strategies, recurrent cerebrovascular events, and mortality. The findings highlight multifocal infarction, malignancy-associated NBTE, and recurrent stroke despite anticoagulation as key clinical concerns, while emphasizing that observed associations with anticoagulant class should be viewed as hypothesis-generating rather than definitive treatment guidance

Background: Stroke is a frequent manifestation of non-bacterial thrombotic endocarditis (NBTE), yet current knowledge largely stems from case reports and small series. This systematic review aimed to comprehensively describe stroke presentation, imaging features, management, and outcomes in NBTE patients. Methods: A comprehensive search of EMBASE, PubMed, MEDLINE, Web of Science and PsycINFO databases was conducted through September 2023. Studies reporting individual cases or case series of NBTE-related stroke were included. Extracted data included demographics, vascular risk factors, stroke presentation, imaging features, NBTE etiology, treatment modalities (unfractionated heparin/low molecular weight heparin (UFH/LMWH), warfarin, direct oral anticoagulants (DOACs), and valvular intervention), stroke recurrence, and mortality. Multivariate regression was performed to identify predictors of recurrent stroke and mortality. Results: A total of 129 patients from 118 studies were included (median age 56 [IQR:44-64], 62% females). Right (28%) and left (26%) hemispheric stroke syndromes accounted for the majority of clinical presentation, and multivessel ischemic infarcts (>2 territories) were observed in 66%. Conventional vascular risk factors were infrequent (1%-21%), while deep vein thrombosis and systemic embolism occurred in 59% and 38% of patients, respectively, either preceding or coinciding with stroke onset. Malignancy and autoimmune diseases were identified in 72% and 22%, respectively. Anticoagulation was initiated in 66% and 21% underwent valvular treatment. Over a median follow-up of 1.3 months, stroke recurrence and death occurred in 48% and 50%, respectively. Malignancy significantly increased mortality risk (OR 16.8, P<0.001), while autoimmune-related NBTE (OR 0.2, P=0.029), and anticoagulation with UFH/LMWH (OR 0.3, P=0.011) and VKA (OR 0.09, P=0.002) reduced mortality. Recurrent stroke was more likely in patients with malignancy (OR 16.8, P=0.001) and those receiving DOACs (OR 6.2, P=0.057) Conclusion: NBTE should be considered in stroke patients lacking conventional risk factors, particularly with underlying malignancy or autoimmune disease. Malignancy and DOAC use may increase the risk of recurrent strokes in this patient population.

Introduction Hypoplastic left heart syndrome and Fontan procedure predispose to cardiac thrombus formation in the venous pathways due to the unique hemodynamic and hematologic disturbances inherent to the Fontan circulation. Systemic venous blood is routed passively to the pulmonary arteries without a subpulmonary pump, resulting in chronic low‐velocity flow, elevated central venous pressure, and venous stasis—all elements of Virchow's triad that favor clot formation 1 . Additionally, these patients exhibit reduced levels of protein C, coagulation factors II, V, VII, and X, plasminogen, and antithrombin III, along with increased levels of factor VIII 2,3 . Once a thrombotic event occurs, the rationale for lifelong anticoagulation is compelling. We report a case of an adult man that underwent Fontan palliation in infancy, with acute cerebral and renal infarcts, and discuss stroke and systemic embolism prevention. Case presentation A 22‐year‐old male with history of hypoplastic left heart syndrome status post Fontan procedure in infancy with congestive splenomegaly and liver disease presented with acute abdominal pain and was found to have bilateral renal infarcts. Anticoagulation was not initiated acutely and within 24 hours he developed left face and arm weakness, dysarthria and mild aphasia. Intravenous Tenecteplase was administered within 1 hour of symptom onset and was followed by symptoms’ complete resolution within 30 minutes of administration. Brain MRI confirmed scattered cerebral infarcts in the bilateral middle cerebral artery territories. Transthoracic echocardiogram showed atrial level shunting, expected due to fenestrated IVC to left atrium from prior Fontan procedure, and no evidence of atrial or ventricular thrombus. Due to the patient having evidence of multiple infarcts in multiple vascular beds within the brain and kidneys, an extensive hypercoagulable workup was undertaken which was unremarkable. The patient's stroke etiology was presumed to be cardioembolic from his altered cardiac anatomy with susceptibility to form venous thrombi and known surgically‐induced atrial level shunt. Low intensity heparin drip without bolus was started initially, and was transitioned to therapeutic apixaban upon discharge with proposed life long anticoagulation. Conclusions Subjects with hypoplastic heart syndrome display persistent unfavorable hemodynamics and procoagulant state after Fontan procedure. Either antiplatelet or anticoagulants are recommended after performing risk stratification. In high‐risk patients (recent thromboembolic event or stent, recurrent atrial arrhythmias, mechanical valve), therapeutic anticoagulation with either warfarin or direct oral anticoagulant is indicated, given increased vulnerability to recurrent events 1 . In intermediate‐risk subjects, antiplatelet or prophylactic doses of anticoagulation is indicated, whereas in low‐risk patients, antiplatelet agent is preferred.

Background: Radiologically Isolated Syndrome (RIS) is defined as incidentally found MRI abnormalities that are radiographically indistinguishable from multiple sclerosis (MS) and is considered a presymptomatic disease state of MS. Age <37 years, infratentorial or spinal cord lesions, gadolinium-enhancing lesions on index imaging, and positive cerebrospinal fluid oligoclonal bands have been identified as risk factors for conversion to MS. There are no existing guidelines regarding the role of disease-modifying therapy (DMT) in RIS patients. Objective: The objective of this study was to critically assess the current evidence regarding the impact of initiating DMT for patients with RIS on the time to first clinical attack of MS. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, medical librarian, and content experts in the field of neuroimmunology. Results: A multicenter, prospective, randomized, double-blind, placebo-controlled trial was chosen for critical appraisal. This trial examined the impact of treatment with dimethyl fumarate (DMF) versus placebo on the risk of conversion from RIS to MS over a 96-week study period. Patients in the DMF arm were found to have an 82% reduction in risk of clinical attack. DMF patients also had a smaller number of new/newly enlarging T2 hyperintense lesions compared with placebo. No subgroup analyses were performed to elucidate risk factors for conversion. Conclusions: While initiation of DMT in RIS does appear to reduce the time to first clinical attack of MS, the risk factors that should prompt initiation of DMT in this patient population require further study.

Background Patients with atrial fibrillation (AF) are at increased risk of ischemic cerebrovascular events despite anticoagulants (AC). We aim to evaluate whether changing AC or adding antiplatelet therapy to anticoagulants (AP + AC) in patients with AF presenting with acute ischemic stroke (AIS) or transient ischemic attack (TIA) despite AC, decreases the risk of recurrent AIS/TIA compared to patients continued on same AC regimen. Methods Patients with AF on AC presenting with AIS or TIA at our center between 2011- 2021 were included. Data on Demographics, index event, antithrombotic therapy before and after index event, recurrent AIS/TIA, or major bleeding events (MBE) were extracted. Cox proportional hazards models were used to compare outcomes between AC unchange vs AC change, and AP + AC vs AC only groups. Results One hundred eighty-five patients were included (mean age 78.3 years; 62% males, median follow-up 9 months (IQR 1-34)). Seventeen patients (9%) had AC change, 100 (54%) received AP + AC, 39 (21%) had recurrent AIS/TIA, and 27 (15%) had MBE following index event. No difference was observed between AC unchange vs AC change and AP + AC vs AC only groups regarding recurrent AIS/TIA (HR 1.72 [.65-4.57], P = .27 and HR 1.02 [.53- 1.98], P = .95, respectively) or MBE (HR .85 [.19-3.67], P = .83 and HR 1.49 [.67-3.33)], P = .33, respectively). Fourteen vascular neurologists treated this cohort and 9(64%) implemented AC changes. Conclusion In this single center retrospective study of 185 patients with AF and AIS/TIA despite AC, changing AC or adding AP agents did not decrease the risk of ischemic cerebrovascular events.