title: Tuberculous meningitis: protracted course and clinical response to interferon-gamma.
abstract: A 12-year-old girl with protracted tuberculous meningitis received standard chemotherapy and dexamethasone and had a progressive cerebrospinal fluid neutrophilia, raised protein and depressed glucose levels. Her temperature was raised for 5 months until a second course of dexamethasone was given. At week 15, multiple tuberculomas and hydrocephalus were detected followed by acute hydrocephalus (week 58), which required a ventricular-peritoneal shunt. Tuberculomas resolved after a second course of dexamethasone but recurred 15 months later. Immunological investigations were normal including integrity of the type 1 cytokine pathway. From month 24, interferon-gamma was given subcutaneously (initially 50 microg/m(2)) and continued for 19 months. Within 2 weeks she responded clinically followed by a reduction in inflammatory signs on magnetic resonance imaging scan (but not in the tuberculomas). At month 44, when chemotherapy was stopped, the cerebrospinal fluid/serum albumin quotient was 57x10(-3) (normal <6.0x10(-3)), which supports continuing major impairment of the blood-brain barrier. Gene expression in peripheral blood mononuclear cells before and during treatment with interferon-gamma, assessed by gene array analysis, showed reduction in a number of cytokine and chemokine genes. The response to interferon-gamma might have been secondary to downregulation of certain cytokine and chemokine genes.
authors.affiliation: Royal Liverpool Children's NHS Trust, Liverpool, UK. coulters@fulwood11.wanadoo.co.uk
authors.forename: J Brian S
authors.initials: JB
authors.lastname: Coulter
authors.forename: Richard L
authors.initials: RL
authors.lastname: Baretto
authors.forename: Connor L
authors.initials: CL
authors.lastname: Mallucci
authors.forename: Maria I
authors.initials: MI
authors.lastname: Romano
authors.forename: Laurance J
authors.initials: LJ
authors.lastname: Abernethy
authors.forename: David M
authors.initials: DM
authors.lastname: Isherwood
authors.forename: Dinakantha S
authors.initials: DS
authors.lastname: Kumararatne
authors.forename: David A
authors.initials: DA
authors.lastname: Lammas
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000166:cytology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D002648:Child; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D005334:Fever; D015870:Gene Expression; D005947:Glucose / Q000134:cerebrospinal fluid; D006801:Humans; D006849:Hydrocephalus / Q000601:surgery; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009503:Neutropenia; D014375:Tuberculoma; D014390:Tuberculosis, Meningeal / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D000893:Anti-Inflammatory Agents; D000995:Antitubercular Agents; D018925:Chemokines; D003907:Dexamethasone; D007371:Interferon-gamma; D005947:Glucose