Cerebral thrombus analysis as a useful diagnostic tool for infective endocarditis in ischemic stroke patients

Introduction: Infective endocarditis (IE) is a life-threatening condition and a rare cause of ischemic stroke (IS). This study aimed to evaluate the utility of analyzing cerebral thrombi, obtained through endovascular thrombectomy in IS, for the pathological diagnosis of IE. Patients and methods: Cerebral thrombi from three groups of IS patients were compared: definite IE (n = 10), cardioembolic stroke without and with concomitant infection (CE-I$^{-}$: n = 30, CE-I$^{+}$: n = 10). We performed histological examination, molecular biology, and microbiological tests on cerebral thrombi, to detect microorganisms and assess their composition. Results: Median age of included patients was 73 years and 50% were females. Hematoxylin & Eosin and Grocott-Gomori Methenamine Silver stains detected microorganisms in all IE cerebral thrombi, and none in the control groups. Thrombus PCR detected relevant microorganism in n = 2/7 IE. Compared to control groups, IE thrombi were characterized by significant lower content of red blood cells (median [IQR]: IE = 7.4 [4.2-26.7], CE-I$^{-}$ = 49.3 [17-62.6], CE-I$^{+}$ = 57.5 [40.7-60.8], % over thrombus section area [%TSA], p = 0.001), increased von Willebrand Factor (IE = 23.9 [19.1-32], CE-I$^{-}$ = 11.2 [8.2-12.8], CE-I$^{+}$ = 12.9 [10.7-18.3], %TSA, p = 0.001), cell-dominant pattern of Neutrophil Extracellular Traps (IE = 100%, CE-I$^{-}$ = 69%, CE-I$^{+}$ = 70%, p ⩽ 0.001), and more frequent sub-acute or chronic thrombus age classification (p ⩽ 0.001). These latter thrombus features displayed good discriminative ability between IE and controls, with AUC values between 0.84 and 0.95. Discussion: Multimodal analysis of cerebral thrombi in IS with suspected IE supports early and definite pathological diagnosis by detecting pathogens and assessing changes in thrombus composition.