Klinička serija slučajeva kod devet bolesnika s tuberkuloznim meningitisom u Kliničkom centru...

8/11/2019 Klinika serija sluajeva kod devet bolesnika s tuberkuloznim meningitisom u Klinikom centru Vojvodine

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ORIGINAL ARTICLE

Clinical case series of nine patients with tuberculousmeningitisin the Clinical Centre of Vojvodina, Novi Sad, AP Vojvodina,Serbia 2001-2010

Radoslava Doder 1,2, Grozdana anak 1,2, Sandra Stefan Miki1,2, Sinia Sevi1,2, Aleksandar Potkonjak 3,Dragan Doder4, Vuk Vraar3

1School of Medicine, University of Novi Sad,2Department of Infectious Diseases, Clinical Centre of Vojvodina,3Department of Veteri-nary Medicine, Faculty of Agriculture, University of Novi Sad,4Provincial Institute of Sports Medicine and Sports; Novi Sad, Serbia

Corresponding author:

Radoslava Doder

School of Medicine, University of Novi Sad;

Department of Infectious Diseases,

Clinical Centre ofVojvodina

Hajduk Veljkova 1-9,

21000 Novi Sad, Serbia.

Phone: +381 21 484 3859;

Fax:+381 21 480 062;

E mail: [email protected]

Original submission :

05 February 2014;

Revised submission:

14 April 2014;

Accepted:

21 May 2014.

Med Glas (Zenica) 2014; 11(2):

ABSTRACT

Aim To determine immediate risk factors of developing tubercu-lous meningitis, to assess the practical importance of clinical signsand ndings in the cerebrospinal uid (CSF) when opting for thespeci c therapy, and to predict the outcome of disease in relationto the beginning of treatment.

Methods A retrospective clinical case series of nine patients withtuberculous meningitis who were treated from April 2001 until

November 2010 at the Department of Infectious Diseases in NoviSad, Serbia was presented. Data of patients medical records and

presentation of clinical and laboratory features, neuroradiological -ndings and outcome were used.

Results The factors of immediate risk/predisposition for the deve-lopment of tuberculous meningitis were found in two (22.2%) pa -tients. The duration of symptoms prior to admission was 9 days onaverage (from 3 to 20 days). The most frequent symptoms on ad -mission were headache and fever in eight (88.9%) patients, whe -reas two patients (22.2%) were presented with stiff neck and pho -tophobia. Consciousness was preserved in six patients (66.7%),two patients were somnolent and one was in coma. Two(22.2%)

patients had concurrent pulmonary tuberculosis. Neuroradiologi -cal signs of the disease were present in two patients.

Conclusion The duration of symptoms before admission, clinicalexamination and CSF analysis can be helpful in identifying pati -ents who are at high risk of developing tuberculous meningitis.

Key words: meningitis, tuberculosis, clinical features, complica-tions, outcome


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INTRODUCTION

Tuberculosis of the central nervous system(CNS) is expected in about 1% of all patients

having active tuberculosis (1). It is caused byhematogenous dissemination of Mycobacteriumtuberculosis (MBT) from the primary infection inthe lungs and the formation of small andsubepen-dimal foci in the brain or spinal cord (1). Ruptureof the tubercula on the surface of the brain leadsto the direct penetration of MBT into the subara -chnoid space and development of meningitis (2).The process of merging of multiple small foci lo-cated deep in the parenchyma of the brain or spi -nal cord results in tuberculomas (rarely abscess),without meningitis (1).

Early diagnosis and promptly indicated treatmentare essential for the favorable course and out-come of tuberculous meningitis (TBM)(2). Thisdisease begins gradually with uncharacteristicsymptoms such as headache, fever, vomiting andanorexia. The stiff neck and paralysis of cranialnerves occur in 40-80% and 30-50% of patients,respectively (2). The analysis of cerebrospinal

uid (CSF) is necessary and it usually revealstypical, moderately intensive pleocytosis (10-1000x10 3, with the dominance of lymphocytes),elevated protein level (0.5-3.0 g/L) and decreasedconcentration of glucose (sugar ratio in the CSF:

blood sugar


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presented.This study was approved by the EthicsCommittee of Clinical Centre of Vojvodina.

Risk factors

The risk factors included a close contact with the person having a similar disease, previous pulmo-nary tuberculosis, the use of corticosteroid drugs,malignant disease, head trauma, HIV co-infecti -on as well as the social status.

Diagnostic criteria

The de nite diagnosis of TBM was made in three patients when MBT was isolated from the CSF,orother body uids or tissues. In all other patients,the diagnosis of probable TBM was based onthe clinical features and analysis of changes inthe CSF obtained by lumbar puncture on admi -ssion, and favorable response to the applicationof anti-tuberculosis drugs (ATD).

Clinical data

Clinical data included the duration of symptoms before admission, presenting symptoms and

ndings, CSF analysis results, basic hematolo -gical analyses and microbiological cultures onadmission, additional diagnostic procedures and

applied therapy. The following inclusion criteriawereused:fever >38.0 C, headache, meningealirritation, and neurological nding (examinationof consciousness, cerebral nerves, presence of

physiological and/or pathological re exes andabnormal movements), as well as CSF pleocyto -sis, protein and glucose level and the reductionin CSF/blood glucose ratio. Cytological-bioche -mical analysis of CSF was performed at the La -

boratory Diagnostics Center, Clinical Center ofVojvodina. Blood culture, CSF culture, urine cul -

ture for bacteria and fungi, and microbiologicalanalysis of nasal and throat swabs were carriedout at the Department of Microbiology, Institu -te for Public Health of Vojvodina in Novi Sad.Directmicroscopy and MBT culture in the CSF,sputum and urine samples were performedin theCentre for Microbiology, Virusology and Immu -nology at the Institute for Pulmonary Diseasesof Vojvodina in Sremska Kamenica.All patientsunderwent lung radiography, CT scan or MRI ofthe head, electroencephalogram (EEG), and otherdiagnostic methods as needed (abdominal ultra -sonography, chest CT scan, fundus examination).

Statistical analysis

The methods of descriptive statistics were usedfor statistical analysis. Pearsons Chi square test

was applied to determine the statistically signi -cant correlation between the two subgroups (withthe con rmatory diagnosis and with a presump -tive diagnosis).

RESULTS

Risk factors

Epidemiological data regarding the contact with a person having a similar disease were negative.Nocommon risk factors for TBM (previous pulmo -

nary tuberculosis, use of corticosteroid drugs, ma -lignant disease, and head trauma) were found. Halfof the patients were testedfor HIV status, and all ofthem were seronegative. Two patients (one fromeach subgroup) had data on alcohol consumption.Eight of nine patients lived in the cityarea.

Demographic and clinical characteristics

The average age of patients was 47.3 years, ran -ging from 19 to 65 years; females were more pre -valent (F:M=66.5%:33.4%). The length of symp -toms before admission for treatment was 9 dayson average, ranging from 3 to 20 days (8.6 daysand 9.1 days in the subgroup with the con rma -tory diagnosis and the subgroup with presumpti -ve diagnosis, respectively (p=0.904).

On admission, eight (88.9%) patients had headacheand fever, stiff neck and photophobia were obser -ved in two (22.2%) patients. Consciousness was

preserved in six (66.7%) patients: two patients had preserved consciousness and one female patientwas drowsy with dysarthria in the subgroup withthe con rmatory diagnosis,whereasin the subgroupwith the presumptive diagnosis, four patients wereconscious, one patient was somnolent and one wasin coma.Nystagmus and hemiparesis were foundin one, and tremor in two patients in the subgroupwith the presumptive diagnosis (Table 1).

The CSF analysis on admission showed whi -te blood cell count of 331.8193.5 x 10 6 with61.2% lymphocytes (in the subgroup with thecon rmatory diagnosis it was 255.6166.6x 10 6 with 74.6% lymphocytes; in the subgroup withthe presumptive diagnosis it was 370 208.6 x

10 6 with 54.5% lymphocytes) (p=0.440). The le -


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vel of proteins in CSF was 1.91.2 g/L (2.21.5and1.8 1.2 in the subgroup with the con rma -tory and presumptive diagnosis, respectively)(p=0.675); the glucose concentration in CSF was

1.90.7 mmol/L (1.5 0.5 and 2.1 0.8, in thesubgroup with the con rmatory and presumptivediagnosis, respectively)(p=0.291) (Table 2).

Diagnostic data

All patients had intracranial meningitis exceptone female patient who had spinal form of menin -gitis. Only three patients had positive CSF cultu -re. The active form of tuberculosis was identi edin two patients with the con rmatory diagnosisof TBM. In younger patients, the disease had mi -

liary, bronchiolitic and nodular form. The pati -ents underwent lymph node biopsy due to severelymphadenomegaly three months before admi -ssion for treatment.According to Ziehl-Neelsenstain results no acid alcohol resistant bacilli were

presented.Magnetic resonance imaging of the brain revealed speci c changes intwo cases. Co -mmunicant decompensated hydrocephalus wasdetected in one patient with the presumptive di -agnosis. In another case, post-contrast enhancednodular lesions in leptomeninges were found in afemale patient with the con rmatory diagnosis.

Treatment

Initial antituberculosis therapy with three drugs(isoniazid, rifampicin, pyrazinamide) was ad -ministered in four patients; other patients weregiven four drugs (isoniazid, rifampicin, pyrazi -namide and ethambutol or streptomycin) for twomonths. The therapy was introduced during the

rst week of hospitalization in one patient andat the beginning of the second week in another.Intermittent phase was continued with two drugs(isoniazid and rifampicin) for 9 months in total.Side effects during the treatment were reported intwo patients in the form of toxic hepatitis. Fourof the patients received the adjuvant therapy ofcorticosteroids (dexamethasone) together with

antituberculosis drugs (ATD).Outcome

Seven (77.7%) patients were discharged withoutany consequences of the disease. One patient withthe presumptive diagnosis was discharged with se -vere neurological de cit, and another one with thecon rmatory diagnosis was transferred to anotherfacility due to exacerbated pulmonary infection.

DISCUSSION

The duration of symptoms in tuberculous meningi -

tis ranges from a few days to a month. The shorter

Patient Age (years) Gender Residence Symptoms* Duration (days) Neurological signs*

1 65 F urban headache, fever, photophobia 14 preserved consciousness, disorientation2 30 F urban headache, fever, photophobia 3 preserved consciousness, stiff neck

3 19 F rural thoracic pain 20 preserved consciousness4 63 F urban headache, fever 5 preserved consciousness, stiff neck 5 54 M / headache, fever 10 drowsiness, nystagmus, tremor 6 52 F / headache, fever 7 drowsiness, dysarthria7 63 M urban headache, fever 10 coma, tremors8 60 F urban headache, fever 7 preserved consciousness, left hemiparesis9 20 M urban headache, fever 5 preserved consciousness, stiff neck

Table 1. Clinical characteristics on admission of patients with tuberculous meningitis

*Clinical symptoms and neurological sings on admission; Duration of symptoms before admission; Patients with con rmed diagnosis of tuber -culous meningitis s

PatientNo

WBC inblood

(x 106)

PMN(%)

SR FibrinogenGlucose

(mmol/L)Blood

culture

WBC inCSF

(x 106)

PMNin CSF

(%)

Proteinlevel in

CSF (g/L)

Glucoselevel in CSF

(mmol/L)

CSFculture

MT inCSF

culture

MT insputumculture

1* 7.4 78 62/110 5.5 7.3 negative 156 95 3.36 2.1 negative positive negative2 7.9 85 30/61 2.31 5.3 negative 121 99 1.55 3.3 negative negative negative3 7.2 80 139/144 6.6 3.80 negative 624 30 1.37 2.21 negative negative negative4 21.5 84 40/45 2.25 6.3 negative 576 95 1.62 1.62 negative negative not done5 7.4 75 22/48 5.1 6.2 negative 347 15 0,55 2.8 negative negative not done6* 9.83 92 43/64 4.8 5.7 negative 163 99 0.54 1.2 negative positive positive7 4,14 93 40/40 4.38 6.2 negative 152 53 4.2 1.3 negative negative negative8 5.47 75 66/105 4.7 3.6 negative 400 35 1.81 1.6 negative negative negative9* 7.52 93 22/44 2.89 5.0 negative 448 30 2.87 1.4 negative positive positive

Table 2. Diagnostic data in patients with tuberculous meningitis

*Patients with con rmed diagnosis of tuberculous meningitis; WBC, white blood cell count; PMN,polymorphonuclear cells; SR, erytrocyte sedi -mentation rate; CSF, cerebrospinal uid; MT, Mycobacterium tuberculosis

Doder et al. Tuberculous meningitis


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course of illness (


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Klinika serija sluajeva kod devet bolesnika s tuberkuloznimmeningitisom u Klinikom centru Vojvodine (AP Vojvodina,Srbija) u periodu od 2001. do 2010. godineRadoslava Doder 1,2, Grozdana anak 1,2, Sandra Stefan Miki1,2, Sinia Sevi1,2, Aleksandar Potkonjak 3,Dragan Doder4, Vuk Vraar31Medicinski fakultet, Univerzitet u Novom Sadu,2Klinika za infektivne bolesti, Kliniki centar Vojvodine,3Departman za veterinarskumedicinu, Poljoprivredni fakultet, Univerzitet u Novom Sadu,4Pokrajinski zavod za sport i medicinu sporta; Novi Sad, Srbija

SAETAK

Cilj Utvrditi faktore neposrednog rizika za razvoj tuberkuloznog meningitisa, ispitati praktini znaajklinikih znakova i nalaza u likvoru u donoenju odluke za otpoinjanje speci ne terapije, kao i usta -noviti ishod bolesti u odnosu na poetak leenja.

Metode Prikazana je retrospektivna serija devet bolesnika koji su pod dijagnozom tuberkuloznogmeningitsa leeni u periodu od aprila 2001. do novembra 2010. godine u Klinici za infektivne bolesti u

Novom Sadu, Srbija. Podaci dobijeni iz istorij bolesti odnosili su se na klinike, laboratorijske i demo -grafske karakteristike pacijenata, rezultate neuroradiolokih ispitivanja i ishod bolesti.

Rezultati Faktori neposrednog rizika/predispozicije za razvoj tuberkuloznog meningitsa naeni su koddva (22,2%) bolesnika. Trajanje simptoma bolesti pre prijema na leenje, iznosilo je u proseku 9 dana(od 3 do 20). Najei simptomi i znaci pri prijemu na leenje bili su glavobolja i poviena temperaturakod osam (88,9%), te ukoen vrat i fotofobija kod dva (22,2%) bolesnika. Svest je bila ouvana kod est(66,7%), dok su dva bolesnika bila somnolentna, a jedan u komi. Nistagmus, dizartrija i tremor registro -vani su u pojedinanim sluajevima. Istovremena pluna tuberkuloza registrovana je kod dva (22,2%)

bolesnika. Neuroradioloke znake bolesti imala su dva bolesnika. Kultura likvora bila je pozitivna kodtri (33,3%) pacijenta.

Zakljuak Duina simptoma pre prijema na leenje, klinika slika i analiza likvora, mogu biti od po -moi u identi kaciji bolesnika koji su u visokom riziku za tuberkulozni meningitis.

Kljune rei: meningitis, tuberkulozni, klinika slika, komplikacije, ishod

Doder et al. Tuberculous meningitis

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