Original Article

Characteristics of in Tuberculous Patients with Hydrocephalus Astrid Tamara Maajid Budiman,1 Nida Suraya,2 Ahmad Faried,3 Ida Parwati2

1Faculty of Medicine, Universitas Padjadjaran 2Department of Clinical , Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin General Hospital, Bandung 3Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin General Hospital, Bandung

Abstract Objective: meningitis (TBM) with hydrocephalus patients as diagnostic criteria of TBM. To describe cerebrospinal fluid (CSF) characteristics in tuberculous Methods: A cross-sectional using retrospective method was applied in this study by obtaining medical records of TBM with hydrocephalus patients that were treated at Department of Neurosurgery Dr. Hasan Sadikin General Hospital, Bandung from January 2014–September 2016.

Results: Sixty one records were included in the study. Patient characteristics and differential count, , and were recorded and descriptively such as age, gender, and CSF laboratory features such as color and clarity, cells 3 with analyzed.lymphocyte The predominance majority of CSF (median: macroscopic 76%). appearance Increased protein was seen from to benormal clear (88%) and colorless (88%). Median for CSF cell count was 25 cells/mm value range was seen in CSF (median: 50 mg/dL) while the mean for CSF glucose in this study remained in its normal value range (mean: 58.9±26.68 mg/dL)Conclusions: with lower CSF to blood glucose ratio (mean: 0.41±0.27). Received: November 2, 2017 Clear CSF with colorless appearance, lymphocyte pleocytosis, highNeurosurgery, protein level, Dr. Hasanand low Sadikin CSF glucose General as Hospital, well as blood Bandung. glucose ratio remain Revised: typical CSF characteristics of TBM patients found at the Department of Keywords: MayAccepted: 15, 2018 pISSN: 2302-1381; eISSN: 2338-4506; http://doi.org/10.15850/ijihs.v6n2.1129 IJIHS. 2018;6(2):57–62Cerebrospinal fluid, hydrocephalus, tuberculous meningitis

September 5, 2018

Introduction Early diagnosis and proper management Tuberculosis (TB) currently remains a major global health issue. Indonesia is currently in of TBM is an important factor that influences the top three in terms of TB cases where 10% mortality and morbidity. Cerebrospinal fluid of the total TB population in the world is found includes macroscopic, microscopic, chemical, 1 (CSF) examination is an important parameter in this country. One of extrapulmonary TB inand the microbiological diagnosis of TBM examinations. . This CSF examinations Bacterial with high mortality and morbidity, esepcially in children, is tuberculosis meningitis (TBM).2 Hydrocephalus is the most frequently found culturediagnosis. or2,3 acid-fast A previous bacilli study (AFB) has observation reported complication of TB and one of the predictors inthat CSF the are ratio used of positive to establish culture TBM results definitive were of mortality and morbidity.2 13% among TBM patients.4 In several cases, Correspondence: Astrid Tamara Maajid Budiman Universitas Padjadjaran lowobserve results the ofmacroscopic, bacterial culture microscopic, and AFB and on Jl. Raya Bandung-Sumedang KM, Faculty21 Jatinangor, of Medicine, Indonesia CSFchemical may characteristic be seen. Hence as a it reference is important for the to e-mail: [email protected] laboratory-based diagnosis of TBM.4

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This study aimed to observe the chemical, macroscopic, and microscopic characteristics color, clarity, leukocyte cell numbers, cell countVariables percentage, used inprotein this study level, were and age,glucose CSF the Department of Neurosurgery Dr. Hasan level. Data were then analyzed descriptively by ofSadikin CSF in General TBM patients Hospital, with Bandung. hydrocephalus at counting the number and percentage for the results of macroscopic examination while for microscopic and chemical examination results, Methods mean and standard deviations or median and range were used based on the distribution of This design used in this study was retrospective the data. cross-sectional descriptive study. TBM patients with hydrocephalus treated at the Department of Neurosurgery, Dr. Hasan Sadikin General Results Hospital, Bandung who met the inclusion and exclusion criteria were included. The inclusion There were 477 patients with TBM in Dr. Hasan criteria in this study were inpatients during Sadikin General Hospital Bandung from 2014 the period of January 2014–September 2016, treated at the Department of Neurosurgery results that suggested hydrocephalus who toDr. 2016. Hasan A Sadikintotal of 170General (35.6%) Hospital, patients Bandung were with a computerized tomography (CT) scan TBM with hydrocephalus. Sixty six cases had undergo CSF examination with specimens with 149 cases (31.2%) were diagnosed as derivedGeneral fromHospital, ventricular Bandung, drainage with macroscopic,at the Clinical them must be excluded, resulting a total of Pathologymicroscopic, Laboratory and chemical of characteristic Dr. Hasan Sadikin result, (44.3) met the inclusion criteria but five of including protein and glucose levels. Exclusion criteria included congenital hydrocephalus, 61patients (40.9%) were cases. taken Allfrom were ventricular included drainage in the meningitis caused by other than study. All CSF samples collected from these 61 Mycobacterium tuberculosis, positive Human suchThe as number extra ventricular of male patients drainage was (EVD) higher or incomplete medical record. Samples were ventriculoperitonealthan the number of female (VP) shunt. patients (Table 1). Immunodeficiencyselected using the total Virus sampling (HIV) method. status, and Age categorization of children and adults in this study referred to the existing consensus in Dr. Hasan Sadikin General Hospital, Bandung Approval from the Ethics Committee of the with 0–14 years categorized as children, and Faculty of Medicine, Universitas Padjadjaran underwas conducted the ethical from clearanceAugust to December No. 102/UN6. 2016 pediatric patients was higher when compared C1.3.2/KEPK/PN/2016by collecting data from thewas medical gained. Thisrecords study of >14to adults years patients. classified Median as adults. age wasThe 6number years old of TBM inpatients with hydrocephalus i who were treated at the Department of Neurosurgery, Dr. Hasan Sadikin General Hospital, Bandung. withpatients a range with of hydrocephalus 6 months–58 years. and the results wereExamination compared ofto CSF normal was performedvalues and on criteria TBM from Marais et al.3 CSFhospital. of these patients were examined at the Laboratory of Clinical Pathology of the same (Table 2). Cerebrospinal fluid color in TBM patients with hydrocephalus Table 1 Distribution of Tuberculous Meningitis with Hydrocephalus Patients Based on Age and Gender Gender Children Adults Total (%) Male 20 7 27 (44) 15 34 (56) Total 22 61 (100) Female 19 39

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:57–62 Astrid Tamara Maajid Budiman, Nida Suraya, et al. in this study was generally colorless. Similarly, could only be calculated in 11 patients (mean: showed a clear result. the clarity level of CSF in this study generally 0.41±0.27). 3 3). Discussion TheThe differential median ofcell the count CSF ofleukocyte the cerebrospinal cells was 25 cells/mm (range was 1-613 cells/mm This study reveals that the prevalence of TBM of mononuclear (MN) and polymorphonuclear with hydrocephalus is predominated by males. fluidcells (PMN).was presented Mononuclear in the cellsform were of percentage shown to of previous studies.4–6 A study found that the percentage for both PMN and MN was 0% to Thisprevalence finding of is pediatric in agreement patient with with the TBM results with be100%. the dominantThere were cell two in thecases CSF. which The scopeshowed of hydrocephalus as complication is 71% while the same prevalence for adults is 12%.7 This 3 in both. study also shows that more children has TBM the percentage of PMN of 100%, with a CSF with hydrocephalus compared to adult. leukocytethe normal cell value count but of not 1 cell/mm as high as the one in Macroscopic examination on the color and MaraisThe et median al.3 CSF protein was higher than

criteria. The mean CSF glucose clarityclear and of CSF colorless. was performed. This is Thein line macroscopic with the was 58.9±26.68 mg/dL which was still in the appearance of CSF in this study was generally normal limit. The CSF to blood glucose ratio Table 2 Cerebrospinal Fluid Examination in Tuberculous Meningitis Patients with Hydrocephalus Marais et al.3 Variable Normal value Criteria for TBM Result Macroscopic appearance

CSF color* Colorless Yellowish, n(%) 4 (7) Colorless, n(%) 54 (88 Yellow, n(%)

3 (5) Clarity Clear Clear 6 (10) Clear, n(%) 54 (88) Turbid, n(%) 1 (2) Cloudy, n(%) Microscopic examination 3 3 3 25 (1–613) Differential count, median (range) CSF cells, median (range) <5 cells/mm 10-500 cells/mm cells/mm 24 (0–100) MN (%)# 76 (0-100) PMN (%)** <50% Chemistry >50% >50% Protein, median (range)

deviation 10–40 mg/dL >100 mg/dL 50 (5–977) mg/dL Absolute CSF glucose, mean±std 50–800.6 mg/dL <40 mg/dL 58.9±26.68 mg/dL

CSF to blood glucose ratio##, <0.5 0.41±0.27 mean±std deviation

Note: *CSF = Cerebrospinal fluid; **PMN = polymorphonuclear; #MN = mononuclear; ##Could only be done in 11 patients

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:57–62 Characteristics of Cerebrospinal Fluid in Tuberculous Meningitis with Hydrocephalus Patients diagnosis criteria of TBM according to Marais for TBM.4,14 The previous studies showed that et al.3 Tuberculous meningitis is a chronic On the really high leukocyte count and is dominated theother sensivity hand, previous of the low studies absolute also showedCSF12,15 glucose that diseaseby lymphocytes. characterized by clear CSF with not was low, that is 68% and 69,5%. of T cell as TBM 3,8,9pathogenesis is demonstrated This explains why the normal through the predominance The inflammation of lymphocytes response the sensitivity 15 of low CSF to blood glucose ratiopossibility was 90%. of infection and it had also been previous studies and this study. absolutesuggested CSF that glucose considerations level cannot should rule be out given the 3 in microscopicMarais et al. examination stated that a ofdiagnosis CSF,5,10–13 as criteriaseen in information for diagnosis of TBM. to use CSF to blood glucose ratio as15 additional of chemical examination of CSF includes an compared to Marais et al.3 criteria might be increase in CSF protein (>100 mg/dL). This The difference of CSF content in16 thisPrevious study studycriteria shows diagnosis the amountby Marais of CSFet al protein.3 However, was not greater than 100 mg/dL as stated in the caused by the CSF source itself. studybe caused had byshown the ’sdifference . CSF composition16 the median CSF protein was in accordance with betweenThe impaired ventricular blood-brain and spinal barrier CSF leads that mayto a previous studies stating that the mean CSF higher protein composition which may slow proteincompared was to not the more normal than 100value. mg/dL6 As thedespite top thereferral increase hospital of in the West CSF Java, protein Dr. Hasan value Sadikin when General Hospital, Bandung, in particular the downthat causes the circulation hydrocephalus of CSF after and aggregation may impair CSF absorption or obstruct the CSF pathway16 The median of age in this study (median: hospital’s Clinical Pathology Laboratory, has of CSF protein and leukocytes caudally. theirwhich own is supposed normal CSF to beprotein increased range according standard children below 6 years old. Several previous ofto the 10–40 pathogenesis mg/dL. The of TBM CSF is protein considered in TBM as 6studies years) have reflects shown a higher age-related distribution variations among in the result from the increased permeability of 8,17 It is shown here that blood brain barrier or decreased reabsorption in the arachnoidalis villi.8,13 CSFwhen protein compared content. to adults and this might result there is a lower protein CSF value in children the Marais et al.3 criteria.8,17 The normal 8,13value As alreadyof glucose explained in CSF isin 2/3the in lower protein CSF in this study compared to of the plasma glucose, or approximately 50 ti=o 80 mg/dL. proteinFurthermore, and glucose the content.use of antimicrobial18 Time of interval agent criteria for TBM diagnosis, the CSF glucose beforemedian ventricular between the drainage occurence may of also tuberculosis affect CSF should be less than 40 mg/dL3 This (2.2 decrease mmol/L) in to hydrocephalus development was 21 days orglucose the ratio is resulted between from CSF anaerobicglucose and plasma (range: 3–180 days). In between, patients glucosecaused byis lowerbacteria than or 50%.disturbance in glucose consumed antituberculous drugs. A previous transport mechanism.8,13 The mean glucose

studyafter thehas shownuse of thatantibiotic, CSF glucose especially will increase in the levelis in contrast in this studywith wasthe diagnostic >40 mg/dL criteria and waby andperiod CSF of >12 protein hours will postantibiotics. decrease significantly18 stillMarais in theet al normal.3 and somerange previous of CSF glucose. studies. This A There are several limitations in the study previous study presented that the number6,9 of including the small sample size, i.e. 61 samples. This is due to the limited time and rejection 48% or less than a half of all patients and that from some TBM patients with hydrocephalus patientsthe glucose with level glucose had a levelwide <40 range mg/dL between was to undergo ventricular drainage that includes 11 There are only 11 patients patient records and archives creates another 12.1–156.7 mg/dL as also shown in this study both EVD and VP shunts. In addition, incomplete (2–135 mg/dL). patient who underwent ventricular drainage is whoseis in line CSF with glucose the diagnostic to blood criteriaglucose by ratio Marais can limitation,missing. Another especially reason when is thethat result blood of glucose CSF in beet almeasured.3 (median: 0.41±0.27). This result ventricular drainage was not done in almost all Most which previous stated studies that CSF that glucose have discussed to blood measurement done 15–30 minutes prior to the glucose ratio is <50%. glucose ratio cannot be performed in almost samples.all patients. This Specimen makes the was calculation also taken of CSF from to the CSF characteristics in TBM use CSF to blood glucose ratio <0.5 as one ofdiagnostic criteria 60 International Journal of Integrated Health Sciences. 2018;6(2)

:57–62 Astrid Tamara Maajid Budiman, Nida Suraya, et al. ventricular drainage that may also affect the are still the typical characteristics found in results compared to those of previous studies TBM with hydrocephalus in Dr. Hasan Sadikin In conclusion, the diagnosis of tuberculous in TBM may be done in every level of health thatmeningitis mostly is used still lumbar problematic, fluid as especially specimens. with Generalfacilities Hospital, as it is theBandung. easiest Examination way to diagnose of CSF the high number of the hydrocephalus seen. to blood glucose ratio as a routine examination thisto in disease. TBM diagnosis. This study suggests the use of CSF CSF presentations such as clear and colorless CSF, lymphocyte pleocytosis, increased protein level, and lower CSF to blood glucose ratio References

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