Harahsheh, Ehab

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.

Abstract INTRODUCTION Leptomeningeal disease (LMD) represents a serious neurological complication of systemic malignancies. Once diagnosed, LMD has been associated with limited life-expectancy. Herein, we report a patient with non-small cell lung cancer (NSCLC) with LMD who achieved almost 7-year overall survival (OS) from her LMD diagnosis. CASE REPORT A 60-year-old female developed worsening dry cough at age of 52. A 3-cm FDG-avid right lower lobe lung mass was found. Biopsy revealed NSCLC with EGFR exon 19 deletion. Surveillance imaging was implemented given early-stage disease. Two years later, she was found to have focal LMD along with parenchymal brain metastases. She underwent surgical resection with concomitant placement of Ommaya Reservoir. She was initiated on Osimertinib. This resulted in improvement of her focal LMD, and control of extracranial disease for 33 months when neuroimaging revealed evidence of recurrent LMD over right lateral temporal lobe. Osimertinib dose was then increased from 80 mg to 160 mg daily. At 42 months, she developed LMD progression. Despite treatment with stereotactic radiosurgery, she had further LMD progression, and another surgical resection was performed at 55 months, yet LMD recurred at 62 months, and she was enrolled in phase-2 WSD0922 clinical trial utilizing an oral brain-penetrant non-competitive reversible EGFR inhibitor with complete radiological resolution of LMD. At 73 months, she had LMD relapse and was initiated on intrathecal pemetrexed and intravenous amivantamab, and has thus far received 11 doses of intrathecal pemetrexed and amivantamab every two weeks with complete radiological response. At last follow-up, the patient is alive 82 months from her LMD diagnosis with excellent functional status. DISCUSSION our case highlights that leveraging different mechanisms of action to target EGFR mutation in sequential fashion along with consideration of intrathecal chemotherapy in patients with LMD related to metastatic EGFR-mutated NSCLC can potentially help control LMD and prolong OS.

This cohort study examines the oncological, neurological, and serological profiles of adult male patients with testicular germ cell tumors and paraneoplastic neurologic syndromes.

Objective To determine the frequency and accuracy of diffusion restriction (DR) of the retina and/or optic nerve (ON) detection on standard brain magnetic resonance diffusion-weighted imaging (DWI-MRI) in patients presenting with acute non-arteritic central retinal artery occlusion (CRAO). Methods This is a retrospective case-control study that includes all consecutive patients presenting to our tertiary academic center from 2013-2021 with acute non-arteritic CRAO (cases) or acute ischemic stroke syndrome (controls, age and gender-matched) that had brain MRI performed within 14 days from symptom onset. Two neurology residents (junior and senior), a vascular neurologist, and two neuroradiologists, blinded to the site of CRAO, independently reviewed the brain MRIs to assess for the presence of retina and ON DR. The consensus agreement between the two neuroradiologists was used to perform sensitivity and specificity analyses and calculate inter-rater reliability (prevalence-adjusted bias-adjusted kappa coefficient). Results A total of 128 patients with acute non-arteritic CRAO (mean (SD) age 69 (14) years; 50% female; median time from CRAO to DW-MRI 2 days (IQR 1-5)) and 128 age and gender-matched controls with acute cerebral ischemia were included. After the neuroradiologist consensus, DR was correctly identified in the retina or ON in 51/128 (39.8%) CRAO cases, retina alone 27.3%, ON alone 24.2%, and both retina and ON 11.7%, with almost perfect neuroradiologists’ inter-rater reliability for retina (K = 0.91) and ON (K = 0.83). Among controls, the retina DR was identified in 1/128 (0.8%) and ON DR in 5/128 (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value were 28.1%, 99.2%, 97.3%, and 58.0% for retina DR, and 27.3%, 96.1%, 87.5%, and 56.9% for ON DR. Conclusions Though experienced neuroradiologists identified retina and ON DR with excellent inter-rater reliability, these are infrequent findings in real world CRAO practice, with excellent specificity but limited sensitivity. Prospective studies with larger cohort of patients, optimization of standardized orbit DWI-MRI protocols are needed to facilitate a more accurate and reliable identification of retina and ON DR in acute CRAO.