A Value Of Measurement Of Notch1and DLL1for Diagnosis Of Diseases With Central Nervous System Infection

Background&ObjectiveTuberculous meningitis (TM) is one of the most common infectious diseases of central nervous system, there exists an increasing trend of morbidity in recent years,the correct diagnosis and early treatment are important factors in determining the prognosis. However, the widespread use of clinical antibiotics,the atypical and changeable meningitis clinical manifestations, the long bacteriological examination cycle and the not high sensitivity, the difficult pathogen detection always make it hard for early diagnosis, which leads misdiagnosis and missed diagnosis.Notch signaling is evolutionarily conserved transduction pathways involved in embryonic development and self-renewal,as well as the regulation of cell fate,which is essential pathway in biological development. Moreover, the pathway involves a complex interaction between respective signals and is associated with pathophysiological process in many diseases. The DLL1is one of the ligands of Notch receptor, the loss of function of DLL1may result in the death of the embryo, but there is little finding about the the role of changed DLL protein levels in diseases.Through previous work,we found that DLL1levels were significantly increased in TM patients’ serum and cerebrospinal fluid (CSF),which has important diagnostic significance.In order to explore new diagnostic methods for TM, the subject will continue to use the enzyme linked immunosorbent assays (ELISA) and Western Blot method to detect the levels of soluble Notch1and DLL1in patients’ CSF with infectious diseases in central nervous system.Object and methodsWe selected289cases with lumbar puncture from July2008to March2012in the Department of Neurology, the First Affiliated Hospital of Zhengzhou University and divided them into groups according to clinical diagnosis.127cases were set as TM group,while90cases were set as non-TM infectious encephalitis(meningitis) group including10cases of purulent meningitis,65cases of viral meningitis and15cases of cryptococcal meningitis.72cases of non-infectious nervous system diseases were set as control group which includes20cases of Guillain-Barre syndrome,25cases of Multiple sclerosis,8cases of Alzheimer disease,10cases of hypotensive cranial pressure headache and9cases of tension headache. The subject was approved by the medical ethics committee of the First Affiliated Hospital of Zhengzhou University, and all patients have signed an informed consent. We employed ELISA and Western Blot methods to detect the levels of Notch1, DLL1in CSF of different groups.ResultThe level of soluble Notch1in the TM group was significantly higher than the other groups (P<0.01); Notch1≥8.50pg/ml was set as judgment value of TM, the sensitivity was86.8%and the specificity was85.2%, but this standard was poor for distinguishing cryptococcal encephalitis, there was no significantly differentce between the other groups (P>0.05).The level of soluble DLL1in the cerebrospinal fluid of TM group was significantly higher than the other groups (P<0.01).DLL1≥0.77ng/ml was set as judgment value of TM, the sensitivity was100%and the specificity was96.9%, and there were no significant differences among other groups (P>0.05). The CSF level of soluble Notchl in TM groups with high triglycerides and TM groups with the normal triglyceride were respectively6.85±2.32pg/ml and7.30±1.35pg/ml, and the CSF level of soluble DLL1in TM groups with high triglycerides and TM groups with normal triglyceride were respectively3.18±2.92ng/ml and3.62±1.79ng/ml.There were no significant differences in the CSF levels of soluble Notchl and DLL1between these two groups(P>0.05). There were also no significant differences in the CSF levels of soluble Notchl and DLL1among TM groups and other other groups (P>0.05).Western Blot results showed that there were higher expression of Notchl and DLL-1in the CSF of TM patients than the other groups. And little expression of Notchl and DLL-1were detected in other groups.39cases of tuberculous meningitis patients were followed up for12weeks. The results showed that the CSF soluble Notchl, DLL1levels in37cases receiving4-week effective chemotherapy decreased significantly (5.78±2.87pg/ml and1.89±0.58ng/ml; P<0.05), After12-week treatment, the CSF soluble Notchl, DLL1levels decreased to normal levels (0.85±0.62pg/ml, and2.05±1.21ng/ml; P<0.05). While the CSF soluble Notchl, DLL1levels didn’t decrease in the2cases with poor effect after treatment.ConclusionThis study showed that the CSF levels of soluble Notchl and DLL1in TM patients increased significantly, while the CSF levels of soluble Notchl and DLL1in patients with viral meningitis, purulent meningitis, cryptococcal meningitis, and non-infectious diseases of the nervous system is too low or undetectable. So our findings indicate that the levels of Notchl and DLL1in CSF are reliable markers for the diagnosis of tuberculous meningitis.