| Objective:Infectious encephalitis/meningitis is a kind of nervous system disease with high mortality and high disability rate.It is usually treated on the basis of experience without a clear etiology.The existing detection methods often lead to missed diagnosis and misdiagnosis.As a new and accurate detection method,cerebrospinal fluid metagenomic next-generation sequencing(mNGS)is playing a more and more important role.The purpose of this study is to explore the application value of cerebrospinal fluid mNGS in the diagnosis of infective encephalitis/meningitis.By analyzing the positive detection rate of mNGS in cerebrospinal fluid,the pathogen spectrum and the results of conventional detection methods,the sensitivity of mNGS and traditional etiological detection methods in the diagnosis of infective encephalitis/meningitis was compared,so as to guide clinical early diagnosis,early identification,early treatment and improve prognosis.It can reduce mortality and disability rate,benefit the majority of patients,and can be widely used in clinical.Method:Using single center retrospective analysis in this study,36 cases of infectious encephalitis/meningitis diagnosed by Department of Neurology of affiliated Hospital of Hebei University from December 2018 to January 2021 were examined by mNGS,including16 cases of viral encephalitis/meningitis,10 cases of suppurative meningitis,1 case of tuberculous meningitis,1 case of cryptococcal meningitis and 1 case of cerebral cysticercosis.There were 7 cases of infectious encephalitis/meningitis with unknown pathogen.The basic information and past medical history of each patient were recorded.After admission,lumbar puncture was performed to collect and analyze the mNGS results of cerebrospinal fluid,cerebrospinal fluid routine,biochemistry,cytology,cerebrospinal fluid culture/blood culture,neuroimaging clinical data and detection of specific antibody.Paired four-grid table chi-square test(Mc Nemar test)was used to compare the difference between mNGS and traditional etiological detection in the diagnosis of infective encephalitis/meningitis.Results:1.A total of 36 patients with infectious encephalitis/meningitis were included in this study,including 26 males and 10 females,at the age of(42.25±17.59)years old.The major clinical symptoms were headache,fever,disturbance of consciousness,nausea and vomiting and seizures.The first symptoms were headache and fever.2.The specific DNA sequences of the following pathogens were detected in 36 cases of infectious encephalitis/meningitis: virus in 10 cases(27.78%),including 5 cases of VZV,2cases of HSV-1,1 case of EBV,1 case of HHV-6 and 1 case of HHV-7.Bacteria in 9 cases(25.00%),including 4 cases of Streptococcus,2 cases of Listeria monocytogenes,1 case of Escherichia coli,1 case of Klebsiella pneumoniae,1 case of Mycobacterium tuberculosis complex,1 case of fungus 1(1 in 36,2.78%),which was Cryptococcus neoformans,and parasite 1(1 in 36,2.78%),was Streptococcus suis.The results of mNGS pathogen test were positive and consistent with clinical diagnosis in 21 cases,with a true positive rate of 58.33%(21 in 36),false positive in 3 cases(3 in 36,8.33%)and fungus in 1 case(2.78%).There were12 cases of infectious encephalitis/meningitis clinically diagnosed as infectious encephalitis/meningitis without pathogens detected by mNGS.3.Among the 36 cases of infectious encephalitis/meningitis submitted for mNGS,34 cases had background bacteria contamination.Among all the background bacteria detected,propionibacterium acne was detected in 25 cases(73.53%),human staphylococci in 24 cases(70.59%),and so on.Propionibacterium acne(7 cases)was the most positive bacteria in the background bacteria,and Ralston dangerous bacteria(6 cases)was the most G-bacteria in the background bacteria.The background bacteria detected are mainly bacteria,and these pathogens have not yet reached the standard for the diagnosis of positive infection.4.10 cases of virus infection were detected by mNGS,in the results of physical examination and clinical verification of mNGS pathogen in cerebrospinal fluid,including 1case of HSV-1,2 cases of VZV and 1 case of H;H6A viral encephalitis/meningitis,and the specific antibodies of 1 case of human herpesvirus 3 and 1 case of human herpesvirus 4 were positive to assist in the diagnosis of herpesvirus infection.Herpes was found in the intercostal and posterior waist of patients with viral encephalitis/meningitis of HH6 A,which helps to diagnose herpesvirus infection.9 cases of bacterial infection were detected by mNGS,including 2 cases of streptococcal infection,2 cases of Listeria monocytogenes,1 case of Klebsiella pneumoniae,1 case of tuberculosis meningitis,and 1 case of Cryptococcus neoformans infection,and one case of Cryptococcus neoformans was positive for cytological ink staining in the patient’s cerebrospinal fluid cytology.The culture of cerebrospinal fluid was positive in 2 cases of streptococcal infection,2 cases of Listeria monocytogenes infection,1 case of Klebsiella pneumoniae cerebrospinal fluid and 1 case of tuberculous meningitis.5.Based on clinical diagnosis,the sensitivity of traditional etiological detection methods for the diagnosis of infectious encephalitis/meningitis was 25.00%.The sensitivity of mNGS for the diagnosis of infectious encephalitis/meningitis was 58.33%.There was a significant difference in the sensitivity between cerebrospinal fluid mNGS and traditional etiological detection methods in the diagnosis of infective encephalitis/meningitis,and the difference was statistically significant(Mc Nemar test,p=0.002),mNGS was significantly higher than that of traditional etiological detection methods.Conclusion:1.Cerebrospinal fluid mNGS is more sensitive than traditional etiological diagnosis methods in the diagnosis of infectious encephalitis/meningitis,and can play an accurate role in diagnosis and treatment,so as to improve the clinical cure rate,improve the prognosis and reduce the mortality and disability rate.2.The spectrum of pathogenic bacteria detected by cerebrospinal fluid mNGS in the diagnosis of infectious encephalitis/meningitis is mainly virus and bacteria,which has a certain advantage in the diagnosis of viral encephalitis/meningitis and bacterial meningitis,but the presence of background bacteria should be paid attention to when reading the results of pathogens so as not to interfere with the final diagnosis. |
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