Q J Med 2003; 96: 643-648
© 2003 Association of Physicians
Clinical relevance of hydrocephalus as a presenting feature of tuberculous meningitis
From the Division of Neurology, University Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong
Received 25 February 2003 and in revised form 19 May 2003
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Summary |
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Background: Hydrocephalus is a common complication of tuberculous meningitis (TBM).
Aim: To study the incidence, associated clinical features, and impact on outcome of hydrocephalus at presentation in TBM.
Design: Observational study.
Setting: Regional hospital serving 500 000 people.
Methods: Adult patients with TBM were studied over 57 months. Those with hydrocephalus on initial CT scan were assessed by neurosurgeons. Clinical, neuroradiological, and biochemical features of patients with hydrocephalus upon presentation were compared to those without initial hydrocephalus.
Results: Of 31 TBM patients during the study period, nine (29.0%) had hydrocephalus at presentation, and eight of them (25.8% of all) underwent urgent neurosurgical intervention. Of the 22 patients without initial hydrocephalus, hydrocephalus developed after commencement of chemotherapy in one patient only. Hydrocephalus at presentation was associated with a longer duration of presenting symptoms (p = 0.01), ataxia (p = 0.001), later stages of TBM (p = 0.045), a longer delay before commencement of anti-tuberculous chemotherapy (p = 0.001), stroke (p = 0.012), and a poor outcome at 1 year (p = 0.001).
Discussion: Hydrocephalus upon presentation is common in our TBM patients. This may be a poor prognostic marker associated with severe TBM and a higher risk of stroke.
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Introduction |
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Tuberculous meningitis (TBM) is a serious neurological disease with significant morbidity and mortality.1–3 Diagnosis may be difficult when the presentation is atypical.1,4–6 In addition, neurological complications, such as cerebral infarct and hydrocephalus, are common and may worsen the prognosis.7–10 Previous studies have shown an association between poor outcome and an advanced stage of TBM on presentation,11 and emphasized the importance of prompt diagnosis and early treatment with anti-tuberculous drugs.1,7,12
Hydrocephalus, a common complication of TBM, can occur either early or late in the clinical course, as well as either before or after commencement of anti-tuberculous drugs.8,13,14 Paediatric TBM patients with hydrocephalus and decerebrate rigidity have a higher mortality rate and more severe sequelae.15 When hydrocephalus is the presenting feature, urgent neurosurgical decompression may be required; the underlying TBM should be promptly diagnosed to minimize any delay in the use of specific chemotherapy. The clinical implication of hydrocephalus upon presentation in adult patients with TBM is uncertain. Although shunting is recommended,16,17 surgical relief of hydrocephalus may not alter the neurological status or long-term outcome. The best treatment for hydrocephalus complicating TBM is unknown, as large randomized controlled trials are not available to confirm the benefit of systemic steroids18 and/or shunting. In this observational study, we analysed the incidence, associated clinical features, and impact on outcome of hydrocephalus as a presenting feature of TBM.
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Methods |
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Our regional hospital serves about 500 000 people living in the western part of Hong Kong Island, with more than 70 000 annual admissions. All adult patients diagnosed with TBM in our hospital during the period from January 1997 to September 2001 were included; TBM patients referred from other hospitals for management of hydrocephalus were excluded. Table 1 shows the diagnostic criteria.9 An urgent CT brain scan was done before the first lumbar puncture, and contrast-enhanced CT or MRI brain study was done at 3 months after commencement of anti-tuberculous drugs. Urgent CT brain studies were also repeated when neurological deterioration and/or new neurological features occurred. In addition to the clinical, neuroradiological and biochemical data, Medical Research Council staging was performed: stage 1 for a fully conscious and rational patient without focal neurological signs; stage 2 for confusion or isolated focal neurological signs such as hemiparesis or cranial nerve palsy; and stage 3 for coma, severe delirium, multiple cranial nerve palsy, dense hemiplegia, and/or paraplegia. A Glasgow Coma Scale (GCS) score
8 was taken to indicate coma. Lumbar puncture was withheld and urgent neurosurgical consultation instigated if the CT brain scan revealed radiological features of hydrocephalus: ventricular dilatation, sulcal effacement, and periventricular lucency. Severity of hydrocephalus was arbitrarily graded into mild or marked, according to the degree of hydrocephalus and clinical features of raised intracranial pressure. Neurosurgical interventions were offered to patients with hydrocephalus of marked severity, and cerebrospinal fluid (CSF) was collected for analyses during neurosurgical interventions, but opening pressure was not recorded.
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A standardized anti-tuberculous drug regimen was adopted (Table 2). 10,19 In addition, a 6-week course of systemic steroids was prescribed for patients with stage 2 or 3 disease (dexamethasone 16 mg daily for 1 week, gradually tailing off over 5 weeks).18 Clinical condition was assessed serially during hospitalization and monthly for 2 months after discharge, and then quarterly thereafter. Duration of follow-up ranged from 1 to 5 years. The modified Barthel Index at 1 year of therapy was used to assess the degree of disability: patients with a modified Barthel Index < 12 and those who died were classified as having a poor outcome. Statistical analyses were performed using
2 or Student’s t test, and a two-tailed p value 0.05 was taken to indicate statistical significance.
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Results |
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Of 31 patients with TBM during the study period, the initial CT brain scan revealed obstructive or communicating hydrocephalus in nine (two with definite TBM, three highly probable TBM, and four probable TBM). Eight patients had urgent neurosurgical interventions: seven underwent ventriculoperitoneal shunting; and one had ventriculostomy. The hydrocephalus in the remaining patient was mild and gradually resolved after commencement of anti-tuberculous treatment. Of twenty-two patients without initial hydrocephalus (three with definite TBM, five highly probable TBM, and 14 probable TBM), delayed hydrocephalus developed in one patient despite commencement of anti-tuberculous drugs. Antibody to human immunodeficiency virus (HIV) was checked in 28 patients, and one patient without hydrocephalus upon presentation had a positive test. Three patients refused the blood test for HIV antibody, but acquired immunodeficiency syndrome was not evident upon subsequent follow-up.
Table 3 summarizes the clinical, biochemical and radiological features. Two patients with hydrocephalus upon presentation had 4 weeks or more of symptoms before diagnosis: personality change for 4 months in one, and confusion for 2 months in another. Hydrocephalus upon presentation was associated with a longer duration of presenting symptoms, stage 2 or 3 disease, and cerebellar ataxia.
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Table 4 summarizes the CSF and neuroradiological findings. All CSF isolates of Mycobacterium tuberculosis were sensitive to the first-line anti-tuberculous drugs. Table 5 shows the delay between admission and commencement of anti-tuberculous chemotherapy, neurological complications, persistent deficits, and outcome at 1 year. There was a longer delay between admission and anti-tuberculous chemotherapy in patients with initial hydrocephalus. Two patients with initial hydrocephalus died from extensive cerebral infarcts within 2 months of treatment, but all patients without initial hydrocephalus were alive at 1 year of follow-up. Hydrocephalus at presentation was associated with cerebral infarcts on follow-up neuroimaging, symptomatic stroke, persistent hemiparesis and/or hemisensory deficits, and poor outcome at 1 year. All these complications occurred after commencement of anti-tuberculous chemotherapy, other supportive therapies, and neurosurgical intervention for significant hydrocephalus, if present. Cerebral infarcts on follow-up neuroimaging were asymptomatic in two patients, and one had hydrocephalus on initial CT brain scan. Hydrocephalus disappeared from follow-up neuroimaging at 3 months in all ten patients. Blockade of ventriculoperitoneal shunt occurred at 3 weeks after shunting, and required revision in one patient. Tuberculomata were seen on follow-up neuroimaging in three patients.
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Discussion |
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Formation of hydrocephalus in TBM is due to blockade of the CSF pathway and/or impaired CSF absorption.20 Typically, non-specific symptoms of chronic meningitis precede the recognition of hydrocephalus by weeks or months, and the clinical course is indolent. The reported frequency of hydrocephalus complicating TBM varies among different studies. In an earlier study of 58 patients with TBM, seven patients (12.1%) had hydrocephalus and only four of them (6.9% of all) required neurosurgical intervention.3 We had a much higher proportion of TBM patients with hydrocephalus upon presentation requiring urgent neurosurgical intervention, comparable to a published study of 48 patients with severe TBM receiving intensive care, in which 31% of patients had severe hydrocephalus requiring neurosurgical interventions.8 Although acute presentation of TBM is common in our locality,9 hydrocephalus upon presentation is associated with a longer duration of presenting symptoms and may be a feature of delayed presentation.
Focal neurological features upon presentation indicate stage 2 or 3 disease. Of all focal neurological features, the presence of cerebellar symptoms or signs may be useful in alerting the clinician about the existence of hydrocephalus. The association between hydrocephalus upon presentation and stage 2 or 3 TBM suggests that hydrocephalus is an indicator of more severe disease, with a higher frequency of focal neurological signs and/or impaired consciousness.15 Pathological adhesions formed around the skull base can obstruct CSF flow, constrict cranial nerves and cause cerebral infarcts. Hydrocephalus upon presentation may indicate a higher risk of symptomatic cerebral infarcts complicating TBM. Cerebral infarcts probably account for higher percentages of persistent hemiparesis and/or hemisensory loss, as well as poor outcome at 1 year. Apparently, neurosurgical intervention, anti-tuberculous chemotherapy, and systemic steroids may not effectively prevent symptomatic cerebral infarcts.10 Randomized controlled trials are needed to identify the effective treatment of hydrocephalus complicating TBM. There is no published information on the role of inflammation and/or thromboembolism of small and medium-sized cerebral arteries in cerebral infarcts complicating TBM, and further clinical studies are warranted.
Our results reveal that the delay in initiation of anti-tuberculous chemotherapy may be longer when hydrocephalus is a presenting feature. The probable explanations are greater difficulty in arriving at the diagnosis, inability to perform an early lumbar puncture, and/or delay due to performance of emergency neurosurgical interventions. Thus, TBM must be considered in endemic regions when patients present with hydrocephalus, even in the absence of meningism and despite initial improvement after neurosurgical decompression. Prompt CSF analysis and early initiation of anti-TB drugs are important when the CSF abnormalities are compatible with TBM.
In conclusion, hydrocephalus is a common presenting feature of TBM in Hong Kong. TBM patients with initial hydrocephalus tend to have a delayed presentation. Recognizing this feature may help making an early diagnosis and minimizing any additional delay in commencement of anti-tuberculous chemotherapy. Further studies are required to confirm whether TBM with initial hydrocephalus is a predictor of severe disease with a higher risk of stroke and/or poor outcome, and whether more aggressive treatment is warranted in such patients.
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Footnotes |
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Address correspondence to Dr R.T.F. Cheung, Division of Neurology, University Department of Medicine, 4th Floor Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong. e-mail: rtcheung{at}hkucc.hku.hk
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References |
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