The Early Diagnosis And Dynamic Observation After Therapy In Cryptococcal Meningitis

Objective:The incidence of fungal meningitis, especially cryptococcal meningitis(CM), has increased in recent years. A number of factors have contributed to this increase; these include the increasing prevalence of AIDS, the use of corticosteroids in autoimmune diseases, the use of radio- and chemotherapy for cancer therapy, and the long-term use of immunosuppressants after organ transplantation. CM is still the most common fungal meningitis seen.CM is a common opportunistic infection in AIDS patients,particularly in Southeast Asia and Africa. But in China, CM ofen occur in patients with other forms of immunosupression individuals.In recent years,cases also occur in patients with HIV postive and in apparently immunocompetent individuals. We should improve the recognization on CM and investigate the early diagnosis method and effective treatment.A great quantitiy of investigations have indicateded that the prognosis of CM is largely dependent on the early diagnosis. Since the clinical manifestations and the results of cerebrospinal fluid(CSF) routine and biochemistry examinations for CM are similar to those of tuberculous meningitis, viral meningitis, and atypical purulent meningitis, CM has high misdiagnosis rate.The finding of Cryptococcus in cerebrospinal fluid and brain biopsy should be the golden standard diagnosis.Only 54%-74% of microscopic CSF examination with orthodox India ink were postitive at the first time for the detection of Cryptococcus.Many people have ingressesed the advanced stage of the disease and lost the opportunity of the treatment when they get the final diagnosis.Therefor CM has high case fatality rate,and bring galactic detriment to the family and society. It will be a problem urged to solve that can prolong the patients'life and improve their survival quality by searching the early diagnosis methods and effective treatment. Our research tries to find the powerful evidence of the early diagnose and the monitoring of the therapeutic effect for CM.It will improve the prognosis and decrease the case fatality rate of the patients with CM.Methods:All patients are from department of Neurology of the second hospital of Hebei Medical University.These 132 patients were divided into two groups. One group include 42 patients with CM. The other group include 90 patients with other diseases of central nervous system. All patients'CSF were collected in 24 to 48 hours. They were undertaken the routine test and CSF cytologic(CSFC) examinations (including CSFC May-Grunwald-Giemsa(MGG) staining, CSFC aricine blue staining, India ink staining).Some of the patients'CSF were made India ink staining after centrifugalization.In some patients,the latex agglutination test(LAT) were used to detect the cryptococcal antigen and antibody in CSF and serum. Then compare the sensitivity and specificity of the different methods. Otherwise, from these 42 cases, 17 cases were selected in which there was documentation of the titration changes in the LAT before and after therapy. These 17 cases were analyzed to evaluate the significance of LAT for cryptococcal antigen in the diagnosis of CM and therapy monitoring.Results:1 The morbidity rate and case fatality rate of CM:The hospitalization number of CM was in the September 1988--December 1998 10-year period was 12,the case fatality of CM was 50%. The hospitalization number of CM was in the Janury 1999-- December 2006 8-year period was 30, the case fatality of CM was 20%.2 The misdiagnosis of CM:32 cases were misdiagnosed and 22 cases were misdiagnosed as tubercular meningitis.3 The detection of etiology:50.00%(20/40) of microscopic cerebrospinal fluid(CSF) examination with India ink were positive,81.08%(30/37) with CSFC MGG staining were positive,83.3%(21/24) with CSFC aricine blue staining were positive,80.00%(13/15) with India ink after centrifugalization were positive. The specificity of these methods is 100%.The result demonstrated that the positive rate of CSFC MGG staining, CSFC aricine blue staining,and India ink staining after centrifugalization is higher than orthodox India ink staining.(P<0.05)4 The detection of cryptococcal antigen:100%(35/35) of the detection of cryptococcal antigen in CSF with LAT were positive. The specificity of the method was 98.89%(89/90). The result demonstrated that the positive rate of the detection of cryptococcal antigen in CSF with LAT is higher than CSFC MGG staining, CSFC aricine blue staining,India ink staining after centrifugalization and orthodox India ink staining.Among the 42 cases with CM,17 cases were carried out dynamic staste observation with the detection of the cryptococcal antigen in CSF.The cryptococcal antigen latex agglutination tests in CSF were positive before therapy, with the titers ranging from 1:16 to 1 : 67536,average titles was 1070.02±6.65. 15 cases showed cryptococcal antigen titer decrease after antifungal therapy with the titers ranging from1:8 to 1:1024,average titles was 108.97±3.87.The result demonstrated that there was a remarkable decrease in cryptococcal antigen titers before and after therapy.(P<0.05)Among the 42 cases with CM,15 cases were carried out the detection of the cryptococcal antigen in serum,14 cases were positive with the titers ranging from 1:8 to 1:16784,average titles was 345.74±7.38. The specificity of the method was 96.67%(29/30). There was no significant difference in positive rate and titles between the detection of the cryptococcal antigen in CSF and serum. (P>0.05) 5 The detection of cryptococcal antibody:Among the 42 cases with CM,15 cases were carried out the detection of the cryptococcal antibody in serum,8 cases were positive. The specificity of the method was 100%(30/30). The result demonstrated that the positive rate of the detection of cryptococcal antigen is higher than the detection of cryptococcal antibody in serum. (P<0.05)Conclusions:1 In recent years,the incidence of CM has risen markedly and cases ofen occur in patients with HIV postive in our country, so we should improve our vigilance on CM.2 CM has high misdiagnosis rate and case fatality rate,so the important turning point is early diagnosis and effective treatment.3 The use of CSFC MGG staining, CSFC aricine blue staining and India ink staining should be united in order to improve the positive detection rate of the Cryptococcus.4 The detection of cryptococcal capsular antigen in serum and CSF by latex agglutination is rapid and has been documented to be both sensitive and specific, but its significance for monitoring therapy is limited.5 The value of the detection of cryptococcal antibody in serum is limited in the early diagnosis of CM,but it can help us to judge the prognosis of the patients.