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The Study Of Cerebrospinal Fluid Markers In Sporadic Creutzfeldt-Jakob Disease

Posted on:2018-04-25Degree:MasterType:Thesis
Country:ChinaCandidate:J J JiangFull Text:PDF
GTID:2334330518951879Subject:Neurology
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Background: Sporadic Creutzfeldt-Jakob disease is one kind of central nervous system diseases and is characterized by low diagnostic rate, strong infectivity and 100% mortality.Its clinical diagnosis depends on clinical manifestation, imaging examination,electrophysiological examination and specific cerebrospinal fluid (CSF) biomarkers.Pathological examination of brain tissue can make a definite diagnosis. However, low specificity of the clinical manifestation, low sensitivity of imaging and electrophysiological examination, and the difficulty of pathological examination to implement make it difficult to diagnose sCJD in the early stage. However, the neurological disorders can significantly affect the variety of the CSF protein. So the CSF biomarkers can indirectly reflect brain lesions and can help to diagnose central nervous system diseases. As one of the central nervous system diseases, the examination of specific CSF biomarkers is also a simply, directly and rapidly diagnostic means of sCJD. Furthermore, it can be used to predict the progression of sCJD and to explore the pathogenesis and treatment methods of the disease.Objective: To explore the concentration of cystatin C (CysC), glial fibrillary acidic protein(GFAP), transferrin (Tf) and tau protein in CSF, in order to find highly sensitive and specific biomarkers for the early diagnosis and differential diagnosis of sCJD.Methods: We selected 24 patients with sCJD (case group, sCJD group), 24 patients with autoimmune encephalitis together with cognitive decline (control group 1, AE group) and 24 other patients with cognitive impairment (control group 2, DMs group) in our study.ELISA was used to detect the concentration of CysC, GFAP, tau protein and Tf in the CSF of the patients in the three groups. We compared the concentration difference of these proteins in the CSF of the three groups using Student's t test or the Mann-Whitney U test.We evaluated the diagnostic value of each index in the diagnosis of sCJD using receiver operating characteristic (ROC).Results: The content of CysC in CSF of sCJD patients was significantly higher than that of AE group, and the sensitivity, specificity, positive predictive value (PV+), negative predictive value (PV-) and the area under the ROC curve (AUC) were 70.8%, 66.7% , 68%,69.6% and 0.705 respectively. GFAP in the CSF of sCJD patients were significantly increased than the DMs patients, GFAP can discriminate sCJD from DMs patients with a sensitivity of 62.5%, a specificity of 75%, a PV+ of 71.4%, a PV- of 66.7% and a AUC value of 0.688. Tau protein in the CSF of sCJD patients was significantly increased than DMs patients. A diagnostic sensitivity of 66.7%, a diagnostic specificity of 87.5%, PV+ of 84.2%, a PV- of 72.4% and the AUC of 0.763 was achieved for tau protein to distinguish sCJD from DMs group. Tf level in the CSF of sCJD patients was significantly decreased than the AE group and DMs group. Tf can discriminate sCJD from AE patients with a sensitivity of 87.5%, a specificity of 54.2%, a PV+ of 65.6%, a PV- of 81.3% and the AUC of 0.707. And it can discriminate sCJD from DMs patients with a sensitivity of 83.3%, a specificity of 75%, a PV+ of 76.9%, a PV-of 81.8% and the AUC of 0.797.Conclusion: CysC in the CSF was significantly increased in sCJD patients than AE patients and it can be used as a specific biomarker for the differential diagnosis of sCJD and AE. The content of GFAP in the CSF of sCJD group was more than DMs group and it can be used as a specific biological marker to identify. sCJD from other patients with dementia. Tau protein in the CSF may be used as a specific biomarker for the differential diagnosis of sCJD and DMs. Tf in the CSF of sCJD group decreased markedly than other groups and it could be used as a specific biomarker for discriminating sCJD from AE and DMs. The diagnostic value of Tf in the CSF was tallest. The combination of more than one index may have an remarkably improved value for diagnosis of sCJD.
Keywords/Search Tags:sporadic Creutzfeldt-Jakob disease, cystatin C, glial fibrillary acidic protein, tau protein, transferrin
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