Publications (5)12.5 Total impact
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Article: The role of aspirin in childhood tuberculous meningitis.
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ABSTRACT: 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.Journal of child neurology 05/2011; 26(8):956-62. · 1.59 Impact Factor -
Article: Cerebral infarction and neurodevelopmental outcome in childhood tuberculous meningitis.
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ABSTRACT: Cerebral infarction is an important cause of neurological sequelae in childhood tuberculous meningitis (TBM). To investigate neurodevelopmental outcome and development of motor sequelae in TBM-related cerebral infarction. A group of 64 children with TBM and computerized tomographic (CT) evidence of infarction were compared with regard to motor sequelae and neurodevelopmental outcome, with 54 children with TBM but no radiological evidence of infarction. The association between infarct number, size, location and outcome was investigated in the infarct group. Selected covariates were entered into a multivariate model to better understand the independent contribution of each factor on neurodevelopmental outcome. An association was found between the presence, number and size of hemispheric infarcts and motor handicap on follow-up. Location of single basal ganglia infarcts, however, did not correlate with motor outcome. The Griffiths general developmental quotient (GQ) was significantly lower in children with bilateral (p<0001) and unilateral multiple infarcts (p=0.0239) compared to those without infarcts. The GQ of children with unilateral single infarcts was not significantly lower than those without infarction (p=0.2282). Infarct characteristics should be taken into account when neurodevelopmental outcome is prognosticated in TBM. Young age, unilateral multiple or bilateral infarction on CT at 1 month, advanced stage of TBM and the interaction term stage x Glasgow coma score are the best predictors of neurodevelopmental outcome at 6 months.European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 09/2008; 13(4):343-9. · 2.01 Impact Factor -
Article: Coagulant and fibrinolytic status in tuberculous meningitis.
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ABSTRACT: The long-term neurologic sequelae of childhood tuberculous meningitis (TBM) mainly result from ischemia owing to cerebral vasculitis. Deep vein thrombosis occurs in adults with pulmonary tuberculosis owing to hypercoaguability. The present study aimed to investigate coagulation status during acute childhood TBM. Coagulation status, including the natural anticoagulants, antithrombin, protein C and protein S; procoagulant FVIII; fibrinolytic factors, tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) as well as anticardiolipin antibodies (ACA), was determined in 16 children with TBM before and during treatment. A prothrombotic profile was found as expressed by a decrease of anticoagulant (protein S) and increase of the procoagulant (factor VIII) activity. Raised PAI-1 and normal tissue plasminogen activator values indicated deficient fibrinolysis. This hypercoagulable state was more pronounced in stage 3 patients than in stage 2 patients. The bleeding time on admission ranged from 1.2 to 10 minutes [mean 4.2 minutes]. The mean platelet count on admission was 577.9 +/- 188.6 x 10/L and increased further during the course of the treatment. The hypercoagulable state in childhood TBM is comparable to that described in adults with pulmonary tuberculosis and may further increase the risk for infarction. Therapeutic measures that reduce the risk for thrombosis could therefore be potentially beneficial in childhood TBM.The Pediatric Infectious Disease Journal 06/2007; 26(5):428-31. · 3.58 Impact Factor -
Article: Vascular endothelial growth factor and blood-brain barrier disruption in tuberculous meningitis.
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ABSTRACT: Tuberculous meningitis (TBM) is characterized by disruption of the blood-brain barrier (BBB), cerebral edema and increased intracranial pressure (ICP). Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To investigate whether in children with TBM disruption of the BBB relates to VEGF production and to assess the effect of corticosteroids on Mycobacterium tuberculosis-induced VEGF production by mononuclear leukocytes. Blood and CSF samples were collected from 26 children with stage 2-3 TBM and 20 controls. All patients received antituberculous and adjuvant corticosteroid therapy. Children were evaluated by ICP recording, computerized tomography scanning and outcome assessment at 6 months follow-up. BBB disruption was quantified by cerebrospinal fluid (CSF)-serum albumin ratios. VEGF concentrations were measured by enzyme-linked immunosorbent assay. In vitro human monocytic THP-1 cells were stimulated with M. tuberculosis sonicate or culture supernatant, and VEGF production was measured in the presence or absence of corticosteroids. CSF VEGF concentrations were significantly higher in TBM patients than in the controls and correlated with mononuclear cell counts (r = 0.64; P = 0.001) and CSF-serum albumin ratio (r = 0.49; P = 0.015). CSF VEGF did not significantly correlate with elevated ICP. In vitro induction of VEGF production by M. tuberculosis sonicate or culture supernatant could be completely abrogated by corticosteroid treatment. Inflammatory cells secrete VEGF during TBM. CSF VEGF correlates with BBB disruption. Inhibition of VEGF may explain part of the clinical effect of adjuvant corticosteroid therapy in TBM.The Pediatric Infectious Disease Journal 08/2004; 23(7):608-13. · 3.58 Impact Factor -
Article: Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a randomized study.
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ABSTRACT: 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 alpha 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.Journal of Child Neurology 05/2004; 19(4):250-7. · 1.75 Impact Factor
