Intensive short course chemotherapy in the management of tuberculous meningitis.

SETTING: Short course chemotherapy for tuberculous meningitis (TBM) is advocated by several groups, but relatively few children have been so treated and followed up. METHODS: A prospective, observational study of isoniazid (INH), rifampicin (RMP) and ethionamide (ETH) in a dosage of 20 mg/kg, and pyrazinamide (PZA) 40 mg/kg, all given once daily in hospital for 6 months. Surviving children were followed up for a year after discharge. RESULTS: Ninety five children, 39 (41%) at stage III, 52 (55%) at stage II and 4 (4%) at stage I TBM were studied. Ten (26%) at stage III and 3 (6%) at stage II died before completion of therapy. Five surviving children (6%) moved on discharge and were untraceable; seven children (9%) were lost during follow up and three were inadvertently restarted on antituberculosis therapy. Two children with severe stage III disease died after discharge. One child experienced a probable disease recrudescence 1 month after discharge. Eighteen children (20%) developed a mildly elevated serum bilirubin concentration during the first month of treatment. In five of these children INH, RMP, ETH and PZA were stopped and streptomycin (SM) and ethambutol substituted. In all cases the original treatment was restarted without incident. One child developed overt jaundice after 5 months of treatment due to hepatitis A infection. CONCLUSIONS: Our experience suggests that young children with TBM can be safely treated for 6 months with high doses of antituberculosis agents without overt hepatotoxicity and with a low risk of relapse.

Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis.

OBJECTIVE: To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM). STUDY DESIGN: Prospective, controlled, randomized study. METHODS: Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment. RESULTS: No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness. CONCLUSIONS: Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly.

Serial CT scanning in childhood tuberculous meningitis: prognostic features in 198 cases.

Serial cranial computed tomographic (CT) scanning and intracranial pressure monitoring were performed on 198 children with stage II and III tuberculous meningitis. The aims of the study were to document the course of tuberculous hydrocephalus during medical and surgical treatment, as well as the prognostic significance of parenchymal changes in the brain as demonstrated by CT. Lumbar cerebrospinal fluid pressure was monitored continuously for a 1-hour period in all patients on admission and at weekly intervals in patients with communicating hydrocephalus for the 1st month of treatment. Cranial CT scanning was done on admission and repeated in survivors after 1 month and again after 6 months of antituberculous therapy. The raised intracranial pressure of 112 children with communicating hydrocephalus, as demonstrated by air-encephalography, was treated medically (with daily acetazolamide and furosemide) for 1 month. Thirty-one children with noncommunicating hydrocephalus were referred for immediate ventriculoperitoneal shunting. No significant difference was found in the eventual ventricular size or clinical outcome between the two treatment groups. Lumbar cerebrospinal fluid pressure changes in the children with communicating hydrocephalus closely followed changes in the degree of hydrocephalus during the course of treatment. The main cause of permanent neurologic disability was basal ganglia infarction, which occurred unilaterally in 21% and bilaterally in 10% of patients on admission and developed in a further 22% of children during treatment. A prominent subarachnoid space, which was seen on the CT scan of 36% of patients after the 1st month of treatment and which reverted to normal, probably relates to the poor nutritional state of these patients on admission.(ABSTRACT TRUNCATED AT 250 WORDS)

BCG vaccination status of children with tuberculous meningitis and the use of unsupervised isoniazid prophylaxis.

From 1985 to 1992, 193 children with tuberculous meningitis (TBM) with a median age of 26 months were admitted to the Department of Paediatrics and Child Health, Tygerberg Hospital. Of these children 143 (74%) were documented to have received BCG, either by reference to 'Road to Health' cards or by contact with local authority clinic staff. In a further 18 children a BCG scar was visible. Therefore at least 161 of the children (83%) had received BCG vaccination. As the Western Cape has also been shown to have the highest incidence of TBM in South Africa, there is concern that BCG as currently used does not have a significant protective effect against disseminated tuberculosis. Seventy-seven children (40%) were also reported to have a close household contact who had been treated for pulmonary tuberculosis within the previous 24 months. Only 17 of these children (22%), however, were prescribed prophylactic isoniazid and only 7 of these completed 3 months or more prophylaxis.

Raised intracranial pressure, the syndrome of inappropriate antidiuretic hormone secretion, and arginine vasopressin in tuberculous meningitis.

Intracranial pressure (ICP) monitored shortly after admission over a period of 1 h in 31 children with tuberculous meningitis (TBM) was significantly higher (median 22.5 mmHg, range 8.4-50.9 mmHg) in 19 children with laboratory evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) than in 12 children without such evidence (median 16.2 mmHg, range 5.8-42.5 mmHg; P = 0.027). Neither plasma nor cerebrospinal fluid arginine vasopressin (AVP) was related to ICP (r = 0.33 and 0.13 respectively). Mean arterial pressure (MAP) was measured in 23 children and a moderate correlation was found with plasma AVP (r = 0.62; P = 0.0019). In TBM, plasma AVP may be secreted as a response to raised ICP in an effort to raise MAP and maintain cerebral perfusion pressure. In this setting excess fluid may be inappropriately retained, leading to hyponatremia and hypo-osmolemia.

Plasma arginine vasopressin and the syndrome of inappropriate antidiuretic hormone secretion in tuberculous meningitis.

Biochemical evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was documented in 17 of 24 (71%) children with tuberculous meningitis. Plasma arginine vasopressin concentrations in patients with signs of SIADH were significantly higher (median, 15.44 (range, 1.62 to greater than 24.52) pg/ml; n = 14) than those without (median, 1.91 (range, 0.44 to 4.91) pg/ml; n = 6) (P less than 0.002). Patients who developed evidence of SIADH were older than those who did not (median, 34 (range, 6 to 101) months vs. 10 (range, 6 to 38) months; P less than 0.007). Five patients with and none without died. In 9 patients evidence of SIADH developed only after hospitalization. These patients received a median of 58 (range, 28 to 109) ml/kg/day fluids (n = 7) before developing evidence of SIADH compared with 107 (range, 58 to 146) ml/kg/day received by patients who did not develop SIADH (n = 6) (P = 0.035). SIADH occurs commonly and its presence appears to influence the outcome of tuberculous meningitis in children.

Cerebrospinal fluid investigations in tuberculous meningitis.

The results of conventional cerebrospinal fluid (CSF) investigations (CSF cell count, protein and glucose concentrations and Pandy's test for CSF globulin) obtained on admission and sequentially from weekly follow-up lumbar punctures for 4 weeks were evaluated in 99 children (median age 28 months) with stage II (50 children) and stage III (49 children) tuberculous meningitis. On admission, six children (6%) had a CSF cell count greater than 500 x 10(6)/l and nine (9%) a polymorphonuclear predominance. A CSF protein less than 0.8 g/l was found in 17 children (18%) of 97 in whom CSF protein was evaluated. Globulin was either absent or present as a trace only in 26 children (27%). CSF glucose was less than 2.2 mmol/l in 58 cases (60%) and less than 2.5 mmol/l in 67 (69%). In 63 children weekly CSF specimens obtained for the 1st 4 weeks of therapy showed an uninterrupted decline in cell count in 23 (37%), a fluctuating downward trend in 27 (43%) and a fluctuating upward trend in 13 (21%). Sequential CSF protein values in 57 children showed an uninterrupted rise in three (5%), a fluctuating upward course in 19 (33%), an uninterrupted downward trend in seven (12%), and a fluctuating downward course in 28 (49%). Of the 61 children in whom sequential CSF glucose concentrations were available, 11 (18%) experienced fluctuating concentrations, values falling to less than 2.2 mmol/l after being greater than 2.2 mmol/l on admission or after having risen to greater than 2.2 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Meningococcal disease at Tygerberg Hospital.

From June 1978 to November 1979, 298 patients with meningococcal disease were seen at Tygerberg Hospital, Parowvallei, CP. The manner of presentation, the diagnosis and some of the clinical features of these patients are reviewed and certain aspects discussed.