ATYPICAL PRESENTATION OF TUBERCULOSIS MENINGITIS: A CASE REPORT
SMJ 2002: 47(1): 14-15
R. D’Souza, D. Franklin, J. Simpson, F. Kerr
Medical Unit, Highland Acute Hospitals NHS Trust, Inverness
Abstract: A 19 year old woman presented with atypical symptoms of tuberculous meningitis. Meningitis is the most serious form of tuberculosis (TB) and it often presents with nonspecific signs and symptoms. Delayed diagnosis can result in rapid progression of neurological deficits and poor prognosis. Polymerase chain reaction and other nucleic acid amplification methods are becoming increasingly useful for the rapid detection of Mycobacterium tuberculosis in the cerebrospinal fluid. Early treatment reduces morbidity and mortality of this serious condition.
Key words: Tuberculosis; tuberculosis meningitis; anti-tuberculosis treatment; polymerase chain reaction; BCG vaccination
Introduction
The
incidence of tuberculosis (TB) has shown a resurgence
in many industrially developed countries due to the increased mobility of people
from areas endemic for TB. A further serious problem is the immunodeficiency
status related to the HIV/AIDS pandemic which facilitates the spread of
tuberculosis. This is further complicated by high levels of multidrug-resistant
tuberculosis. All these factors necessitate the early diagnosis and treatment of
TB in order to minimise complications and sequelae. We report an atypical
presentation of TB meningitis that highlights the diagnostic problems which can
arise.
Case report
A 19 year old woman presented to hospital in November 2000 with a cough productive of yellow sputum and a severe headache and nausea. She had been pyrexial for several days prior to her first admission. Examination was unremarkable. Her chest x-ray and white cell count were normal. Over the next few days her temperature settled without the use of an antibiotic. Subsequent viral serology was negative and she was discharged.
Two days later she was readmitted with vomiting and a recurrence of headache. Initial examination on this occasion, as on the previous admission, was hampered by her rather emotional state. She refused to co-operate with history taking, physical examination or investigation and insisted on going home. She then had a generalised tonic clonic seizure. This lasted for approximately 30 seconds and thereafter she became drowsy and irritable with a Glasgow Coma Score of 9/15 (eye-opening to speech, localising to pain, incomprehensible sounds). She was febrile with a temperature of 38.2oC and poor peripheral perfusion. Her heart rate was 86 beats/min, blood pressure 140/70 mmHg and capillary oxygen saturation 100% on 15 litres oxygen by Hudson mask. She was irritable when moved or examined. She had no signs of meningism or rash.
Cardiovascular, respiratory and abdominal examination were unremarkable as was neurological examination and fundoscopy. She was started on intravenous fluids and cefotoxime and catherised with a residual urine volume of 75ml . Soon after this it was noted that she had a copious brown vaginal discharge and intravenous gentamicin and flucloxacillin were added to her pre-existing treatment to cover toxic shock syndrome.
Apart from the discharge, vaginal examination was normal and there was no tampon in situ. A pregnancy test was negative and a subsequent vaginal swab grew lactobacilli. Her antibiotic regime was continued. A full blood count, urea and electrolytes, liver function tests, midstream specimen of urine and chest x-ray were all normal.
In order to simplify management it became necessary to sedate and ventilate her. A CT scan of her head and ultrasound of uterus and ovaries were normal. A lumbar puncture was performed and produced clear cerebrospinal fluid (CSF) with CSF pressure of 13.5 cm of H20. The biochemical and microbiological features revealed a CSF glucose of 1.0 mmol/1 ( blood glucose 6.5 mmol/1), CSF protein 0.93 g/l 46 white blood cells per microlitre ( 70% mononuclear) and organisms were absent on smear. CSF antigen tests were negative for Neisseria meningococcus type B, streptococcus pneumonia and Haemophilus influenzae. Quadruple anti-tuberculosis therapy consisting of isoniazid, rifampicin, ethambutol and pyrazinamide were added. A Mantoux test (dilution 10 units of purified protein derivative) was negative but the diagnosis was confirmed by detection of Mycobacterium tuberculosis in the CSF using the polymerase chain reaction. Her initial antibiotics were stopped and she was continued on the anti-TB medications.
Her case was notified and contact tracing performed. Over a period of four days her clinical condition improved and it was possible to discontinue her sedation and ventilation. Thereafter she mobilised quickly and appeared to make a complete recovery without adverse sequelae.
It subsequently transpired that she had been experiencing seizures for a number of years and had been concealing the fact. TB culture confirmed the diagnosis of TB meningitis and the organism was fully sensitive to the above treatment. She will continue on ethambutol for two months and rifampicin, pyrazinamide and isoniazid for twelve months.
An HIV test has been found to be negative and the contact tracing has discovered a possible source for her illness.
Discussion
The incidence of TB is on the increase and has been attributed to the following factors:- improved case notification, a rise in the elderly population, high rates of TB among new immigrants, increase in the prevalence of poverty and homelessness and the HIV epidemic.
TB meningitis is associated with high morbidity and mortality. Infection is always secondary to haematogenous spread or in some cases local extension of tubercle bacilli from a focus of infection. A tuberculoma in the cerebral cortex (arriving there by haematogenous spread) may enlarge and rupture with dissemination of bacilli and development of meningitis.
Retrospective studies confirm that at least 75% of individuals have a tuberculous infection at least twelve months before admission for meningitis.1 Early diagnosis can be difficult due to nonspecific early presentation and the disease is fatal if not treated early. The outcome of TB meningitis depends on the degree of neurological deterioration that has occurred by the time antituberculous therapy is started.2
A negative tuberculin test occurs with sufficient frequency in all forms of active tuberculosis. A negative Mantoux is therefore of no help in excluding the diagnosis of TB meningitis. Our patient had BCG as a child. BCG immunisation has been shown to offer about 70% protection from the more serious aspects of TB (miliary and TB meningitis) in UK teenagers.3 This may have afforded her some protection, resulting in the atypical presentation.
In the United Kingdom (UK) the BCG vaccination programme had to be interrupted in September 1999 due to a national shortage of vaccine. It started again in London in July 2000 and the rest of the country will catch up during the next school year. It is hoped that reintroduction of the BCG immunisation programme will contribute to a decline in TB in the UK. Tracing contacts of an infectious case, and their appropriate treatment is an integral part of TB control.
In bacterial meningitis previous antibiotic therapy can alter the results of the cerebrospinal fluid (CSF) examination. In these circumstances precise diagnosis may be difficult. Our patient had polymorphonuclear predominance in her CSF and this has been demonstrated in one study in the initial phase of the disease4 although lymphocyte predominance is the usual finding.
Early diagnosis and prompt treatment of tuberculosis is important to minimise complications and reduce mortality. Before the advent of the DNA/RNA polymerase chain reaction there could have been considerable delay awaiting the result of TB culture. Amplification of nucleic acids from body fluids has considerably improved the diagnosis of infectious diseases. The DNA/RNA polymerase chain reaction has become the method of choice for early diagnosis. However, the test is expensive and less sensitive than culture and there is the potential for false-negative results to occur in samples containing very few organisms (< 2 colony forming units/ml).
CT scan can also be an effective tool as a combination of basilar meningeal enhancement and any degree of hydrocephalus is strongly suggestive of the diagnosis of TB meningitis.5
There is a lack of evidence from controlled clinical trials but evidence suggests that rifampicin and isoniazid for nine to twelve months, supplemented by pyrizanamide and a fourth drug for at least the first two months will give good results.6
TB meningitis can often be a diagnostic challenge. When recognised early and treated promptly with appropriate antituberculous medication prognosis is good.
R E F E R E N C E S
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3Sutherland I, Springett VH. Effectiveness of KG vaccination in England and Wales in 1983. Tubercle 1987; 68: 81-92.
4Clark WC, Metcalf JC, Muhibauer MS, Dohan FC, Robertson JH. Mycobacterium tuberculosis meningitis: a report of 12 cases and literature review. Neurosurgery 1986:18; 604-610.
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6Humphries M. The management of tuberculous meningitis. Thorax 1992;47:577-581.