Subject(s)
Antitubercular Agents/therapeutic use , HIV Infections/complications , Immune Reconstitution Inflammatory Syndrome/drug therapy , Immunosuppressive Agents/therapeutic use , Nervous System Diseases/etiology , Thalidomide/therapeutic use , Tuberculosis/complications , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/immunology , Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Female , HIV Infections/drug therapy , HIV Infections/psychology , Humans , Immune Reconstitution Inflammatory Syndrome/complications , Immune Reconstitution Inflammatory Syndrome/psychology , Magnetic Resonance Imaging , Middle Aged , Mycobacterium tuberculosis/immunology , Mycobacterium tuberculosis/isolation & purification , Nervous System Diseases/drug therapy , Nervous System Diseases/psychology , Neurologic Examination , Paresis/etiology , Treatment Outcome , Tuberculosis/drug therapyABSTRACT
INTRODUCTION: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a potentially life-threatening complication in HIV infected children with tuberculosis (TB) of the central nervous system. HIV-associated TB-IRIS has not been previously described in children with neurotuberculosis. OBJECTIVE: To describe the neurological and neuro-radiological features of 4 consecutive cases of TB-IRIS in children with neurotuberculosis and to discuss possible management strategies. RESULTS: Three patients treated for tuberculosis of the central nervous system experienced paradoxical worsening of neurological symptoms when combination antiretroviral therapy (cART) was initiated. Intracranial tuberculomas were unmasked in the 4th patient. All patients developed new neurological signs within 10 days of cART initiation. Neurological symptoms and signs included headache, seizures, meningeal irritation, decreased level of consciousness, ataxia and focal motor deficit. Interventions included the temporary discontinuation of cART and the use of corticosteroids in all patients. Three patients received thalidomide and 1 chloroquine and mycophenolate mofetil. One patient died and the others experienced prolonged hospitalization. CONCLUSION: TB-IRIS should be considered when new neurological signs develop shortly after initiation of cART in children. There is little data to guide the timing of initiation of cART and the management of complications in children.
Subject(s)
HIV Infections/complications , Immune Reconstitution Inflammatory Syndrome/complications , Nervous System Diseases/etiology , Tuberculosis/complications , Adolescent , Adrenal Cortex Hormones/therapeutic use , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Child , Enzyme-Linked Immunosorbent Assay , Female , Glasgow Coma Scale , HIV Infections/drug therapy , HIV Infections/psychology , Humans , Hydrocephalus/etiology , Immune Reconstitution Inflammatory Syndrome/drug therapy , Immune Reconstitution Inflammatory Syndrome/psychology , Immunologic Factors/therapeutic use , Infant , Lymphatic Diseases/pathology , Magnetic Resonance Imaging , Male , Nervous System Diseases/drug therapy , Nervous System Diseases/psychology , Neurologic Examination , Paresis/etiology , Seizures/etiology , Tomography, X-Ray Computed , Tuberculosis/drug therapy , Tuberculosis/psychologyABSTRACT
OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) has become much more common with monoclonal antibody treatment for multiple sclerosis and other immune-mediated disorders. METHODS: We report 2 patients with severe psoriasis and fatal PML treated for ≥3 years with efalizumab, a neutralizing antibody to αLß2-leukointegrin (LFA-1). In one patient, we conducted serial studies of peripheral blood and CSF including analyses of leukocyte phenotypes, migration ex vivo, and CDR3 spectratypes with controls coming from HIV-infected patients with PML. Extensive pathologic and histologic analysis was done on autopsy CNS tissue of both patients. RESULTS: Both patients developed progressive cognitive and motor deficits, and JC virus was identified in CSF. Despite treatment including plasma exchange (PE) and signs of immune reconstitution, both died of PML 2 and 6 months after disease onset. Neuropathologic examination confirmed PML. Efalizumab treatment was associated with reduced transendothelial migration by peripheral T cells in vitro. As expression levels of LFA-1 on peripheral T cells gradually rose after PE, in vitro migration increased. Peripheral and CSF T-cell spectratyping showed CD8+ T-cell clonal expansion but blunted activation, which was restored after PE. CONCLUSIONS: From these data we propose that inhibition of peripheral and intrathecal T-cell activation and suppression of CNS effector-phase migration both characterize efalizumab-associated PML. LFA-1 may be a crucial factor in homeostatic JC virus control.
