Johan F. Schoeman

Arterial stroke is the main cause of poor outcome in childhood tuberculous meningitis. Aspirin has an antithrombotic action at low dose and anti-ischemic and anti-inflammatory properties, which are dose-related. The aim of the study was to explore the possible benefits of aspirin in children with tuberculous meningitis. A total of 146 consecutive children with a diagnosis of probable tuberculous meningitis were studied. Patients were randomized into 3 groups: (1) placebo group, (2) low-dose aspirin group, and (3) high-dose aspirin group. Twenty-nine additional patients who received aspirin before admission were excluded from the randomized study, but continued on low-dose aspirin. Aspirin, irrespective of dose, did not show any significant benefit regarding morbidity (hemiparesis and developmental outcome) and mortality. Aspirin was well tolerated, but 1 death was probably related to aspirin. The fact that the outcome of the high-dose aspirin group compared favorably with the other treatment groups despite younger age and more severe neurological involvement at baseline needs further investigation.

Blindness is an uncommon but devastating complication of tuberculosis meningitis. The main causes are chronically raised intracranial pressure (hydrocephalus and/or tuberculomas) or direct involvement of the optic chiasm or optic nerves by the basal arachnoiditis (inflammation and/or compression). Antituberculosis therapy combined with corticosteroids and control of intracranial pressure constitutes the mainstay of therapy for tuberculous meningitis. Despite these treatment measures, some patients develop blindness, mainly as a result of progressive optochiasmatic arachnoiditis. This led us to explore the role of adjuvant thalidomide therapy, and we describe the dramatic recovery of vision in 4 consecutive cases. Clinical recovery was accompanied by marked radiological improvement on magnetic resonance imaging (MRI) of the brain.

The purpose of the study was to investigate child behaviour in children who recovered from tuberculous meningitis (TBM) and to compare behaviour profiles of stage II and stage III patients. The mean age of the cohort of 74 children at the time of evaluation was 10 years and 7 months. At follow-up all patients underwent a thorough neurological examination and a psychometric test battery, which included intellectual assessment and evaluation of behaviour by means of the CBCL/6–18. Results indicated elevated mean scores (T > 60) on CBCL/6–18 scales which measure problems with anxiety, depression, attention, social relationships, disruptive and rule-breaking behaviour. Mean CBCL scores of stage III patients were significantly higher than the mean scores of stage II patients on scales which measure social problems, disruptive and rule-breaking behaviour. In addition, problems with conduct, attention, attention-deficit/hyperactivity problems, affective problems as well as the total problem scores were more pronounced in the patients with stage III TBM. We conclude that general behavioural disinhibitions as well as internalized emotional disorder probably are long-term complications in more than 10% of the survivors of TBM.

Paradoxical enlargement and development of new intracranial tuberculomas and tuberculous brain abscesses on adequate antituberculosis treatment are well recognized and supposedly cytokine mediated. These lesions are often unresponsive to conventional antituberculosis treatment, corticosteroids, and surgery. We therefore assessed the effect of adjunctive thalidomide, a tumor necrosis factor α—modulating drug, in intractable intracranial tuberculosis that did not respond to standard medical and surgical therapy. Four consecutive children (three children with bacteriologic proof and one child with clinical evidence of intracranial tuberculosis) were studied. Three patients each had a giant tuberculous abscess, and the fourth had chronic basal arachnoiditis with progressive loss of vision. Three of the four patients had relentless neurologic deterioration, and all showed disease progression on neuroimaging despite full medical and appropriate surgical treatment. Marked clinical and neuroradiologic improvement occurred after thalidomide was added to the antituberculosis treatment regimen of these four patients. Adjunctive thalidomide might have a role in the management of intractable intracranial tuberculosis and needs further investigation in this regard. (J Child Neurol 2 0 0 6; 2 1: 3 0 1 — 3 0 8; DOI 10.2310/7010.2006.00071).

Childhood tuberculous meningitis is associated with serious long-term sequelae, including mental retardation, behavior disturbances, and motor handicap. Brain damage in tuberculous meningitis results from a cytokine-mediated inflammatory response, which causes vasculitis and obstructive hydrocephalus. Thalidomide, a potent tumor necrosis factor α inhibitor, was well tolerated and possibly showed some clinical benefit in children with tuberculous meningitis during a pilot study. The purpose of the present study was to assess the effect of adjunctive thalidomide in addition to standard antituberculosis and corticosteroid therapy on the outcome of tuberculous meningitis. Thalidomide (24 mg/kg/day orally) or placebo was administered in a double-blind randomized fashion for 1 month to patients with stage 2 or 3 tuberculous meningitis. The study was terminated early because all adverse events and deaths occurred in one arm of the study (thalidomide group). Thirty of the 47 children enrolled received adjunctive thalidomide, of whom 6 (20%) developed a skin rash, 8 (26%) hepatitis, and 2 (6%) neutropenia or thrombocytopenia. Four deaths (13%) occurred in patients with very severe neurologic compromise at baseline; two deaths were associated with a rash. Motor outcome after 6 months of antituberculosis therapy was similar in the two groups, even though the thalidomide group showed greater neurologic compromise on admission. In addition, the mean IQ of the two treatment groups did not differ significantly (mean IQ thalidomide group 57.8 versus mean IQ control group 67.5; P = 16). These results do not support the use of adjunctive high-dose thalidomide therapy in the treatment of tuberculous meningitis. (J Child Neurol 2004;19:250-257).

Treatment of obstructive hydrocephalus in children with tuberculous meningitis (TBM) depends on the level of the cerebrospinal fluid (CSF) block. Air-encephalography is regarded as the gold standard for differentiating communicating and non-communicating hydrocephalus. Since air-encephalography involves a lumbar puncture, it carries the risk of cerebral herniation. The aim of this study was to determine whether communicating and non-communicating hydrocephalus in TBM can be differentiated by means of cranial computerised tomography (CT). A number of CT indices were measured in 50 children with communicating and 34 children with non-communicating hydrocephalus according to air-encephalographic findings. The only CT finding that correlated with the type of hydrocephalus was the shape of the third ventricle. Significantly more children with non-communicating hydrocephalus had a rounded third ventricle than those with communicating hydrocephalus. CT is therefore not useful in determining the level of CSF block in TBM. Air-encephalography remains the most reliable way of determining the level of CSF obstruction.

Summary: Objectives  To document the clinical and diagnostic features of tuberculous meningitis (TBM) in young children with and without concomitant miliary tuberculosis (TB).Methods  A retrospective comparative study.Results  Of 104 children with TBM, 32 (31%), median age 17.0 months, had a miliary appearance on chest radiograph; 72 (69%), median age 30.5 months, had TBM only (P = 0.04). Mediastinal adenopathy was noted in 27 (84%) of the children with miliary TB and 33 (46%) of those with TBM only (P = 0.0005). The mean cerebrospinal fluid (CSF) lymphocyte and polymorphonuclear counts of all children (no significant differences between groups) were 137 × 10⁶/l and 38 × 10⁶/l and the mean protein and glucose concentrations were 1.45 g/l and 0.72 mmol/l, respectively. Polymorphonuclear leukocytes were predominant in the CSF of 17% of children, in 16% the CSF glucose was >2.2 mmol/l and in 26% the CSF protein was P = 0.23). Ten children (10%) died, five (7%) who had TBM only and five (16%) who had TBM and miliary TB.Conclusion  Children with TBM and miliary TB were younger and more likely to have mediastinal adenopathy on chest radiography than those with TBM only. Diagnostic features and investigations in both groups may be misleading at times.