Clinical Study On The Characteristics And Pathogenesis Of Pulmonary Tuberculosis-associated Ischemic Stroke

Part1 Study on the Characteristics,Risk Factors and Identification Model of Pulmonary Tuberculosis-associated Ischemic StrokeObjective:To provide a reliable basis of prevention and treatment of pulmonary tuberculosis-associated ischemic stroke,we summarized the patients’ clinical characteristics and the independent risk factors were analyzed by the clinical data,laboratory and imaging findings of patientswith pulmonary tuberculosis-associated ischemic stroke.Inorder to improve the ability of predicting pulmonary tuberculosis-associated ischemic stroke,we combined the independent risk factors to establish a combing model which named identification model.Methods:This retrospective study was conducted on pulmonary tuberculosis-associated ischemic stroke patients and age,gender and living condition-matched acute pulmonary tuberculosis patients without ischemic stroke.The definition of pulmonary tuberculosis-associated ischemic stroke in the study was patients with acute ischemic stroke and pulmonary tuberculosis without conventional stroke risk factors such as hypertension,hyperlipidemia,diabetes,smoking and drinking,atrial fibrillation,rheumatic heart valve disease,etc.The pulmonary tuberculosis-associated ischemic stroke patients were registered at the First Affiliated Hospital of Guangxi Medical University,the Second Affiliated Hospital of Guangxi Medical University,the Fourth People’s Hospital of Nanning,Wu-Ming Hospital affiliated to Guangxi Medical Universityand Guangxi People’s Hospital five centers between January 2011 and October 2020.Clinical data was collected and logistic regression analysis was used to analyze the independent risk factors of pulmonary tuberculosis-associated ischemic stroke,and the ROC curve was constructed to assess the ability of a combined model based on single independent risk factors to predict pulmonary tuberculosis-associated ischemic stroke.Results:197 pulmonary tuberculosis-associated ischemic stroke patients and 197 pulmonary tuberculosis patients without ischemic stroke were enrolled in this study.Most(143/197,72.58%)of pulmonary tuberculosis-associated ischemic stroke occurred within 3 months after diagnosis of tuberculosis and initiation of anti-tuberculosis treatment.Most(168/197,85.28%)of the patients had 2 or more lesions,and most of them(126/197,63.96%)showed scattered patches or patches of lesions distributed in 2 or more cerebral vessels supply areas which without structural or functional abnormalities.Compared to pulmonary tuberculosis patients,significantly higher levels of WBC count,neutrophil count,neutrophil percentage,lymphocyte percentage,monocyte count,monocyte percentage,mean platelet volume,D-dimer,C-reactive protein and serum ferritin levels and lower level of hemoglobin were found in pulmonary tuberculosis-associated ischemic stroke patients(all P<0.05).Logistic regression analysis showed that elevated D-dimer,mean platelet volume,C-reactive protein,serum ferritin,and monocyte percentage were independent risk factors of tuberculosis-associated ischemic stroke.Compared to the single independent risk factor,the combing model based on the single independent risk factor had the greatest predicting ability for pulmonary tuberculosis-associated ischemic stroke(AUC=0.762,sensitivity 64.60%,specificity 78.92%).Conclusion:We found in the present study,the ischemic lesions of pulmonary tuberculosis-associated ischemic stroke were characterized by multiple infarcts in multiple responsible vascular territories.Elevated plasma D-dimer,C-reactive protein,serum ferritin levels,mean platelet volume,and monocyte percentage were independent risk factors of pulmonary tuberculosis-associated ischemic stroke.The identification model which established by the combination of the independent risk factors of pulmonary tuberculosis-associated ischemic stroke had better ability to predict it.Part2 Clinical Study on the Pathogenesis of Pulmonary Tuberculosis-associated Ischemic StrokeObjective:Based on the first part of the retrospective study,this part aimed to further explore the specific pathogenesis of pulmonary tuberculosis-associated ischemic stroke by prospectively collecting blood biochemical and clinical data.Methods:This prospective study was conducted on 48 pulmonarytuberculosis-associated ischemic stroke patients and age,gender and living condition-matched54 acute pulmonary tuberculosis patients without ischemic stroke(control group 1)and 54 acute ischemic stroke patients with conventional stroke risk factors(control group 2).The definition of pulmonary tuberculosis-associated ischemic stroke in the study was patients with acute ischemic stroke and pulmonary tuberculosis without conventional stroke risk factors such as hypertension,hyperlipidemia,diabetes,smoking and drinking,atrial fibrillation,rheumatic heart valve disease,etc.All the patientswere hospitalized in 4 centers in Guangxi from November 2018 to January 2021.Clinical data of 3 groups were collected and compared.The peripheral blood biochemistry and routinedata,inflammatory factors,sP-selectin,sCD40L,CitH3 and vWF were detected and compared in 3 groups too.All patients with ischemic stroke were followed up for 28 days and the NIHSS and mRS scores were recorded on the first,14th and 28th days after enrollment.Results:Compared to control group 2,the absolute value of percentage change of NIHSS and MRS score[(W14d/28d-Wld)/W1d×100%]in pulmonary tuberculosis-associated ischemic stroke group at 14d and 28d versus 1d was significantly higher(P<0.05).The levels of D-dimer,C-reactive protein,serum ferritin,erythrocyte sedimentation rate,monocyte percentage,neutrophilic granulocyte percentage,sP-selectin and CitH3(CitH3,a specific bio-marker of NETs,and the significantly elevated of CitH3 indicates a large amount of NETs formation)were significantly high in pulmonary tuberculosis-associated ischemic stroke patients than that of control group 2(P<0.05).Compared with control group 1,the levels of mean platelet volume,sP-selectin and vWF significantly elevated in pulmonary tuberculosis-associated ischemic stroke patients(P<0.05).In addition,in pulmonary tuberculosis-associated ischemic stroke group,the high expression of CitH3 and vWF was positively correlated with sP-selectin respectively.Conclusion:The occurrence of pulmonary tuberculosis-associated ischemic strokemay be related to the fact that Mycobacterium tuberculosis infection induces the blood system to generate a large number of NETs.NETs directly act on platelets or indirectly act on platelets by vWF secreted and released by damaged vascular endothelium,by these two ways platelets were activated,adhered and aggregatedrepeatedly and finallytriggered intravascular microthrombosisto cause ischemic stroke.