| ObjectiveThrough retrospective case analysis,the disease spectrum of immunocompetent patients with positive EB virus（Epstein-Barr virus,EBV）DNA detection in cerebrospinal fluid（CSF）was summarized.The clinical characteristics of patients with infectious encephalitis/meningitis were analyzed separately to explore the key factors affecting their prognosis.MethodsThe medical record system was used to collect adult patients with a normal immune function who were examined by lumbar puncture and positive for EBV DNA in cerebrospinal fluid from December 2016 to June 2021 in the Department of Neurology,Qilu Hospital of Shandong University.Patients with infectious encephalitis/meningitis were divided into groups according to the types of pathogens and the level of EBV load in cerebrospinal fluid.The basic information,clinical symptoms and signs,laboratory examination,imaging data,and treatment plans were collected and analyzed retrospectively to explore the factors affecting prognosis.ResultsBy the end of follow-up on August 31,2021,a total of 137 patients who met the criteria and had relatively complete and reliable clinical data were included in this study.The most common diseases were infectious encephalitis/meningitis（87 cases,63.5%）,followed by acute myelitis（12 cases,8.8%）.Optic neuromyelitis pedigree disease（7 cases,5.1%）,autoimmune encephalitis（7 cases,5.1%）,peripheral neuropathy（5 cases,3.6%）.The overall age range of the patients was 19-78 years old,the median age was 53 years old,and the quartile interval was 39-62 years old.The overall age peak is 51-60 years old.The age peak of male patients was 61-70 years old,while there were two age peaks of 31-40 years old and 51-60 years old in female patients.There were 87 male patients（63.5%）and 50 female patients（36.5%）.The ratio of males to females was 1.74:1.There were 76 patients with infectious encephalitis/meningitis with complete data,including 36 cases of simple EBV infection（47.4%）and 40 cases of other pathogen infection（52.6%）,including 12 cases of viral infection（30.0%）,20 cases of bacterial infection（50.0%）,3 cases of viral-bacterial dual infection（7.5%）,3 cases of fungal infection（7.5%）and 1 case of parasite infection（2.5%）.One case（2.5%）was complicated with spirochete infection.The age of the coinfection group（52.45±14.03）was higher than that of the simple EBV infection group（44.31 ± 14.25）,and the difference was statistically significant（P=0.014）.There was no significant difference between the two groups in terms of gender distribution（P=0.524）,seasonal distribution of the disease（P=0.913）,and predisposing factors（P=0.812）.The most common clinical manifestations of the two groups were fever,headache,digestive tract symptoms,mental and behavioral disorders,varying degrees of disturbance of consciousness,cone system involvement.Headache（32 cases,88.9%）was the most common clinical manifestation in the simple EBV infection group,and fever（31 cases,80.0%）was the most common clinical manifestation in the combined infection group.The incidence of pyramidal system involvement in the co-infection group（42.5%）was significantly higher than that in the simple EBV infection group（13.9%）,and the difference was statistically significant（P=0.006）.There was no significant correlation between cerebrospinal fluid EBV load and cerebrospinal fluid white blood cell count in all patients with encephalitis/meningitis and patients with simple EBV infection.All 8 patients with perfect serum EBV-related antibody tests showed the previous infection.The cerebrospinal fluid protein content（P=0.005）,IgG（P=0.005）,IgA（P=0.009）,IgM（P=0.005）,and lactic acid（P=0.001）in the co-infection group were significantly higher than those in the simple infection group,and the difference was statistically significant.There was a significant difference in the distribution of cerebrospinal fluid cytology between the two groups（P=0.003）.The results corrected by the Bonferroni method showed that the difference in distribution between the two groups was mainly caused by "neutrophil reaction".The results of craniocerebral MRI showed that the most frequently involved sites in both groups were cerebral lobes（12 cases in the simple infection group and 10 cases in the co-infection group）.The most common type of lesion in the simple infection group was inflammatory lesions of the brain parenchyma（9 cases,26.5%）,and the most common type of lesion in the co-infection group was meningeal enhancement（7 cases,18.4%）.There was no significant difference in the abnormal rate,involved site,and lesion type of craniocerebral MRI between the two groups.There was no significant difference in the abnormal rate of EEG between the two groups.The prognosis of the simple EB V infection group was better than that of the co-infection group,and the difference was statistically significant（P=0.032）.Patients with infectious encephalitis/meningitis were divided into the high load group（31 cases,40.8%）and low load group（45 cases,59.2%）according to the dividing line of cerebrospinal fluid EBV copy number<1000copies/ml.The age of the high load group（53.39±13.93）was higher than that of the low load group（45.29±14.31）,and the difference was statistically significant（P=0.017）.The most common clinical manifestations of the two groups were fever,headache,abnormal mental behavior,disturbance of consciousness,and involvement of the pyramidal system.The incidence of fever in the low load group（93.5%）was higher than that in the high load group（75.6%）,and the difference was statistically significant（P=0.041）.The incidence of dizziness in the low load group（40.0%）was significantly higher than that in the high load group（9.7%）,and the difference was statistically significant（P=0.004）.The probability of abnormal mental behavior in the high load group（32.3%）was higher than that in the low load group（13.3%）,and the difference was statistically significant（P=0.047）.The probability of cone system involvement in the high load group（41.9%）was higher than that in the low load group（20.0%）,and the difference was statistically significant（P=0.038）.There was no significant difference in routine blood examination,cerebrospinal fluid examination,craniocerebral MRI,EEG,and prognosis between the two groups.Conclusion1.When the immune function is normal,cerebrospinal fluid EBV DNA can be detected in a variety of nervous system diseases.Infectious encephalitis/meningitis is the most common disease,and other diseases with high proportion include acute transverse myelitis,NMOSD,autoimmune encephalitis and so on.2.In patients with infectious encephalitis/meningitis,older ages tend to become coinfected and their cerebrospinal fluid EBV load is higher.3.The most common clinical manifestations of infectious encephalitis/meningitis are headache,fever,vary ing degrees of disturbance of consciousness,abnormal mental behavior and involvement of cone system.The types of pathogens and EBV load in cerebrospinal fluid are related to different clinical manifestations.4.Compared with the simple EBV infection group,the results of cerebrospinal fluid test in the co-infection group showed intrathecal synthesis and inflammatory reaction.5.The factors affecting the prognosis of patients with infectious encephalitis/meningitis were age,symptoms of digestive tract,cranial nerve involvement and IgG in cerebrospinal fluid.The cut-off value of age was 47.5 years old,and the cut-off value of IgG in cerebrospinal fluid was 164.5mg/L. |
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