Journal of Infection (2011) 62, 404e405

www.elsevierhealth.com/journals/jinf

LETTER TO THE EDITOR

Tuberculous meningitis with positive cell-count inlumbar puncture CSF though negative cell-count fromventricular drainage CSF

Early diagnosis and treatment is crucial for survival intuberculous meningitis (TM), an aggressive infection that isfatal or disabling in more than half of those affected. Thediagnosis is suggested by clinical assessment and history oftuberculosis exposition and is strongly aided by a chestradiograph positive for tuberculosis.1 The cerebrospinalfluid (CSF) typically shows mononuclear pleocytosis with in-creased protein and decreased glucose levels. Direct mi-croscopy of the CSF, mycobacterial culture and PCR arethe cornerstones of diagnosis. However, both direct exam-ination of CSF and PCR can yield false negative results andculture takes several weeks. Computer tomography (CT)and magnetic resonance imaging (MRI) of the brain couldsupport the diagnosis but are not diagnostic.2 In the currentarticle, a case of TM where diagnosis was postponed due todifficulties in interpreting CSF samples from different com-partments is reported. Hopefully this can serve as a peda-gogic example of this type of diagnostic pitfalls and thusfacilitate correct assessments of similar future cases.

A 33 year old Burundian male, who had lived in Swedenfor the past two years, presented to the Emergency de-partment of a local hospital. He suffered from urinaryretention and received a urinary catheter after which hewas discharged. Two days later he returned with a fever(38.0 �C), impaired consciousness and altered personality.His initial blood tests showed elevated C-reactive protein(CRP) concentrations of 120 mg/L, but an almost normalwhite cell-count of 9.3 � 109/L, and a non-contrast-en-hanced CT head was normal. The patient was subsequentlyadmitted to the department for internal medicine for obser-vation. The following day, a cerebrospinal fluid (CSF) sampleobtained by lumbar puncture (LP) contained 542.0 � 106/Lleucocytes (total leucocyte count, TLC) with 530.0 � 106/Lmononuclear leucocytes (MLs) and 12.0 � 106/L polymor-phonuclear leucocytes (PMN; Table 1). A chest X-ray showedsigns of previous tuberculosis in the apical part of the rightlung, and thus TM was suspected and treatment was initi-ated. At this time, the patient refused oral medication,why the treatment was restricted to intravenous amikacin(1000 mg once daily), rifampicin (600 mg once daily) andmoxifloxacin (400 mg once daily). Since the aetiology was

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not definitely established, intravenous aciclovir (750 mgthree times daily) and meropenem (2000 mg three timesdaily) were added. Further, intravenous betametason(6 mg twice daily) was given due to impaired consciousness(GCS 12). On the third day the patient deteriorated, becamenearly unconscious (GCS 10) and developed facial palsy. Hewas referred to the neuro intensive care unit (NICU) at thenearby University Hospital, where he received an externalventricular drain (EVD) due to hydrocephalus and brain oe-dema. New CSF samples and cultures were taken during sur-gery through the EVD, and the CSF TLC was e surprisingly ealmost normal, 4.2 � 106/L. Therefore, new CSF samplesthrough the EVD were collected the following day with thesame result; TLC 1.0 � 106/L (Table 1). Thus, the patient’scondition had deteriorated but his leukocyte count had ap-parently normalised. Because of this discrepancy, the diag-nosis of TM was strongly in doubt and the tuberculosismedications were cancelled.

The next day, MRI of the head and spinal column wasperformed as the patient suffered from increasing para-paresis. It showedmarked contrast enhancement in the basalmeninges of the brain and upper cervical column consistentwith TM. Therefore the tuberculostatics were reinstated,approximately 24 h after they had been cancelled. Since thedistribution of the central nervous tuberculosis affected thebasal parts of the brain it was discussed whether the CSFsamples from the lateral ventricles were representativeaccording to normal CSF production and circulation. Toinvestigate this, a new LP was performed which showedCSF pleocytosis, TLC 597.0� 106/L, all monocytes, increasedlactate (8.4 mmol/L) and albumin (976 mg/L) (Table 1). Fur-ther, PCR analysis of the CSF was positive for Mycobacteria,which confirmed the diagnosis. The patient improved gradu-ally andwas transferred to the department for infectious dis-eases after 12 days of intensive care. At this timepoint,sputumculture obtained at the NICU showed growth ofMyco-bacterium tuberculosis, sensitive to isoniazid, rifampicin,myambutol and pyrazinamide, which after another six weekswas confirmed by a CSF culture. At discharge, 4.5 months af-ter he was admitted, the patient was unable to walk, had re-duced strength in his arms and he suffered from dysphasiaand urinary and faecal incontinence.

This case underscores the importance of the site of CSFsampling e lumbar or cerebroventricular e in TM. Adequateand vital treatment was discontinued because of misinter-pretation of CSF analysis results. The reason was an explicit

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Table 1 Laboratory investigation of CSF from lumbarpunctures (LP) and ventricular drainage (EVD). Note thelarge discrepancy in total and mononuclear leukocytecounts between CSF collected from LP or EVD. N/A, NotAnalysed.

Days afterhospital admission

0 (LP) 2 (EVD) 3 (EVD) 4 (LP)

Total leukocytecount [�106/L]

542.0 4.2 1.0 597.0

Mononuclear leukocytecount [�106/L]

530.0 0.5 0.9 597.0

Polymorphonuclearleukocytecount [�106/L]

12.0 3.7 0.1 0.0

Erythrocytecount [�106/L]

42.6 432.0 297.0 2.0

Lactate [mmol/L N/A 2.2 1.8 8.4Albumine [mg/L] N/A 106 56.9 N/AImmunoglobin [mg/L] N/A 45 N/A N/A

Tuberculous meningitis with positive cell-count 405

discrepancy in leukocyte count between the ventricular(1.0 � 106/L) and lumbar (597 � 106/L) CSF samples, whichpossibly could be explained by the fact that the CSF drawnfrom the EVD was collected from an area not engaged bythe infection. The ventricular system is situated deep inthe brain, far upstream from the infected meninges, andnew CSF is synthesized in the ventricular system, whichmay dilute the local concentration of any inflammatorycells. In support of this hypothesis, the MRI of our patientshowed intense contrast enhancement in the meninges,both around the brain and the spinal cord, but no contrastenhancement in or adjacent to the ventricular system.There are no previous studies specifically comparing thecomposition of ventricular and lumbar CSF in TM. However,there are a few studies on patients with other communityacquired or post-operative CNS infections that have foundhigher lumbar than ventricular leukocyte counts.3e5 Inter-estingly, this difference was not observed in a study wherethe majority of patients suffered from cerebral haemor-rhage and only a few suffered from central nervous infec-tions.6 This could be in line with our findings in thecurrent case, where the location of the inflammation or in-fection in relation to the site of CSF sampling was crucial.A haemorrhage may occur in a variety of cerebral locationswhereas bacterial meningitis rarely involves the ventricles.Thus, the potential diagnostic pitfalls of CSF samples fromdifferent sites are probably restricted to CNS infections,perhaps only bacterial meningitis.

In conclusion, our case highlights the importance ofobtaining adequate CSF samples from LP, and not only fromEVD, to enable proper diagnosis and treatment of TM.

References

1. Girgis NI, Sultan Y, Farid Z, Mansour MM, Erian MW, Hanna LS,et al. Tuberculosis meningitis, Abbassia fever Hospital-NavalMedical Research unit No. 3-Cairo, Egypt, from 1976 to 1996.Am J Trop Med Hyg 1998 Jan;58(1):28e34.

2. Thwaites GE, Tran TH. Tuberculous meningitis: many questions,too few answers. Lancet Neurol 2005 Mar;4(3):160e70.

3. Gerber J, Tumani H, Kolenda H, Nau R. Lumbar and ventricularCSF protein, leukocytes, and lactate in suspected bacterial CNSinfections. Neurology 1998 Dec;51(6):1710e4.

4. Naija W, Mateo J, Raskine L, Timsit JF, Lukascewicz AC,George B, et al. Case report: greater meningeal inflammationin lumbar than in ventricular region in human bacterial meningi-tis. Crit Care 2004 Dec;8(6):RR491e4.

5. Torres-Corzo JG, Tapia-Perez JH, Sanchez-Aguilar M, DellaVecchia RR, Chalita Williams JC, Cerda-Gutierrez R. Comparisonof cerebrospinal fluid obtained by ventricular endoscopy and bylumbar puncture in patients with hydrocephalus secondary toneurocysticercosis. Surg Neurol 2009 Mar;71(3):376e9.

6. Sommer JB, Gaul C, Heckmann J, Neundorfer B, Erbguth FJ.Does lumbar cerebrospinal fluid reflect ventricular cerebrospi-nal fluid? A prospective study in patients with external ventric-ular drainage. Eur Neurol 2002;47(4):224e32.

Jakob PauesDepartment of Infectious Diseases,

Institution of Clinical and Experimental Medicine,University Hospital, Link€oping University,

Sweden

Jakob O Str€omDepartment of Clinical Chemistry,

Institution of Clinical and Experimental Medicine,University Hospital, Link€oping University,

Sweden

Lars ErikssonDepartment of Infectious Diseases,

Institution of Clinical and Experimental Medicine,University Hospital, Link€oping University,

Sweden

Annette Theodorsson*E-mail address: Annette.Theodorsson@liu.se

Accepted 24 February 2011Available online 8 March 2011

* Corresponding author. Department of Neurosurgery, Institution ofClinical and Experimental Medicine, University Hospital, Link€opingUniversity, 581 85 Link€oping, Sweden. Tel.: þ46 101037585;fax:þ46 101034275.