The Significance Of Anti-LAM Antibody, HBHA And S-100B Protein Determination During The Diagnosis Of Tuberculous Meningitis

Objective: Tuberculous meningitis is a non-purulent meningitis caused byMycobacterium tuberculosis. As it is known to be the most severemanifestation of extrapulmonary tuberculosis with a high mortality rate and ahigh rate of sequelae among survivors, it gives us a huge challenge in thediagnosis and treatment. Delaying therapy in patients with TBM will increasemortality, wheras the diagnosis is often difficult to confirm. Smear microscopyhas a dismal yield (25%), culture results are delayed for several weeks and theyields are variable (18%–83%). These are limited factors of quick clinicaldecision-making. Besides it is hard to distinct tuberculous meningitis (TBM)from other subacute or chronic meningoenchephalitides (SACM). It has beenreported that highly specific M. tuberculosis serological help early diagnosis.In this study we examined the anti-LAM antibody, HBHA and S-100B proteinlevels in the cerebrospinal fluid of TBM patients to further evaluate their valuein the diagnosis of tuberculous meningitis.Methods:All these patients were from either department of neurology andpediatric inpatients or outpatients in the Second Hospital of Hebei MedicalUniversity during2010September-2011October. Tuberculous meningitisgroup included35patients clinically diagnosed with tuberculous meningitis.Of these35participants,3,16and16patients had been termed as definite,probable and possible, respectively. Of the3definite tuberculous meningitissamples, one was PCR positive for M.tuberculosis DNA and the other twocases were cerebrospinal fluid acid-fast stain positive. Of the16probabletuberculous meningitis cases, there was an HIV positive sample. Classificationby symptoms of patients:15,12,8patients were classified as grade Ⅰ, Ⅱ andⅢ respectively. In the Control group, of45cases,15,15and15cases had purulent meningitis, viral meningitis and other non-central nervous systeminfection, respectively (including six cases with hemopathy, five cases withperipheral neuropathy, and one case with spinal arachnoiditis, one case withvenous sinus thrombosis, one case with multiple sclerosis and one case withidiopathic epilepsy).All the cases were conducted lumbar puncture after they were hospitalized.The specimens were submitted to test cerebrospinal fluid routine, biochemicaland cytology series examination (MGG pigmentation, alcian bluepigmentation). The levels of anti-LAM antibody, HBHA and S-100B proteinin cerebrospinal fluid were determined under the ELISA theorem.Results:1Cerebrospinal fluid routine, biochemical examination resultsTuberculous meningitis group, the average number of the total cells was502.00±575.00×10⁶/L;the average number of white blood cells was116.00±260.00×10⁶/L;the average glucose was2.40±1.15mmol/L; the averageprotein was1.25±1.39g/L; the average chloride was118.00±14.90mmol/L; theaverage pressure of lumbar puncture was275.89±90.47mmH₂O. In thecontrol group, the average numbers respectively were total cells89.50±238.50×10⁶/L; white blood cells89.50±238.50×10⁶/L; glucose3.47±1.15mmol/L; protein0.47±0.78g/L; chloride123.00±11.15mmol/L; thepressure of lumbar puncture163.50±77.50mmH₂O.The total cells, white blood cells count, pressure of lumbar puncture andprotein content in the TMB group were obviously higher than the controlgroup, P﹤0.05, there were statistical significances. The content of glucoseand chloride in the case group were lower compared with the control group, P﹤0.05, differences were statistically significant.2The performance of cerebrospinal fluid cytologyOf the35patients of TBM group,10,17and18patients had mixed-cellreaction, neutrophil reaction and lymphocytes response respectively. Amongthe control group, of the15patients of Purulent meningitis,12,2and1caseshad neutrophil reaction, lymphocytes response and mixed-cell reaction, respectively; of the15cases of viral meningitis,11cases showed lymphocytereaction, four cases showed less cell count;15cases of non-encephalitis groupshowed normal cytology. It can be observed that tuberculous meningitis groupcytology analyses were not characterized by a single cellular reaction. Mixedcellular responses of the tuberculous meningitis group accounted for28.57%.Neutrophil reaction accounted for20%, lymphocyte reactions accounted for51.43%. Although a variety of cellular responses were detected, lymphocytereaction was mainly observed. Changes in the dynamic observation ofcerebrospinal fluid cytology can provide some value to the treatment andprognosis of tuberculous meningitis.3The content determination of anti-LAM antibody in cerebrospinal fluidTuberculous meningitis group: the range of anti-LAM antibody levels incerebrospinal fluid was (38.94-87.38) ng/ml, average content72.12±8.07ng/ml; while in the control group, purulent meningitis group: therange of anti-LAM antibody levels was (55.24-74.62)ng/ml, average content67.07±6.00ng/ml; Viral meningitis group: the range of the anti-LAM antibodylevels was (59.91-78.92) ng/ml, the average content68.47±4.86ng/ml;Non-encephalitis group: the range of anti-LAM antibody levels was(58.09-76.92) ng/ml, the average content63.75±4.97ng/ml; By comparingtuberculous meningitis group with purulent meningitis group, viral meningitisgroup and non-encephalitis group in control group, differences werestatistically significant.Of the35tuberculous meningitis cases, grade I group: the range ofanti-LAM antibody levels in the cerebrospinal fluid was (38.94-87.38)ng/ml,average content70.45±8.86ng/ml；grade II group: the range of anti-LAMantibody levels in the cerebrospinal fluid was (63.35-82.88)ng/ml, averagecontent72.22±6.63ng/ml；grade III group: the range of anti-LAM antibodylevels in the cerebrospinal fluid was (68.71-82.14)ng/ml, average content75.34±4.14ng/ml. No significant differences were detected within these threegroups.4The content determination of HBHA in cerebrospinal fluid Tuberculous meningitis group: the range of HBHA levels in thecerebrospinal fluid was (7.25-28.76)ng/ml, average content value18.45±2.61ng/ml; while in the control group, purulent meningitis group: therange of HBHA levels was (9.57-27.01) ng/ml, average content16.78±4.16ng/ml; viral meningitis group: the range of HBHA levels of was(13.29-19.89) ng/ml, average content17.20±1.76ng/ml; non-encephalitisgroup: the range of HBHA levels was (13.09-19.76)ng/ml, average content17.14±1.71ng/ml. Differences were statistically significant, comparingtuberculous meningitis group with purulent meningitis group, viral meningitisgroup and non-encephalitis group in control group.Of the35tuberculous meningitis cases, grade I group: the range of HBHAlevels in the cerebrospinal fluid was (7.25-28.76)ng/ml, average content17.49±4.57ng/ml； grade II group: the range of HBHA levels in thecerebrospinal fluid was (15.34-24.04) ng/ml, average content19.15±2.42ng/ml； grade III group: the range of HBHA levels in thecerebrospinal fluid was (17.84-21.11)ng/ml, average content19.42±1.33ng/ml.No significant differences were detected within these three groups.5The content determination of S-100B protein in cerebrospinal fluidTuberculous meningitis group: the range of S-100B protein levels incerebrospinal fluid was (237.80-1346.35)pg/ml, average content985.67±168.38pg/ml; while in the control group, purulent meningitis group:the range of S-100B protein levels was (713.01-10⁶7.72)pg/ml, averagecontent881.96±112.18pg/ml; Viral meningitis group: the range of the S-100Bprotein levels was (674.78-1052.41)pg/ml, average content955.54±127.35pg/ml; Non-encephalitis group: the range of S-100B proteinlevels was (632.16-1228.40)pg/ml, average content848.03±140.28pg/ml. Bycomparing tuberculous meningitis group with purulent meningitis group andnon-encephalitis group in control group, differences were statisticallysignificant, but no significant difference was detected between tuberculousmeningitis group and viral meningitis group.In35cases of tuberculous meningitis, grade I group: the range of S-100B protein levels in the cerebrospinal fluid was (237.80-1141.22)pg/ml, averagecontent924.98±306.84pg／ml； grade II group: the range of S-100B proteinlevels in the cerebrospinal fluid was(755.75-1275.41)pg/ml, average content986.95±135.63pg/ml；grade III group: the range of S-100B protein levels inthe cerebrospinal fluid was (946.35-1346.35) pg/ml, average content1094.75±141.45pg/ml. By comparison, there were significant differencesamong the three groups.Conclusions:1Anti-LAM antibody and HBHA levels in the cerebrospinal fluid of patientswith tuberculous meningitis were higher than those in purulent meningitisgroup, viral meningitis group and non-encephalitis group. There weresignificant differences in statistics. They might provide certain referencevalue to distinct tuberculous meningitis from purulent meningitis and viralmeningitis.2S-100B protein levels in Cerebrospinal fluid of patients with tuberculousmeningitis was higher than those in purulent meningitis group andnon-encephalitis group. The difference was statistically significant, wheras nosignificant difference was detected between tuberculous meningitis group andviral meningitis group.3In patients with tuberculous meningitis, anti-LAM antibody and HBHAcontent in grade I, grade II and grade III group had no statistical significance.4In patients with tuberculous meningitis, the differences of S-100B proteincontent in mild symptoms group, moderate symptoms group and heavysymptoms group were statistically significant.