RESUMO
Tumor necrosis factor-a (TNF-a) inhibition, used in the treatment of rheumatoid arthritis (RA), is associated with central nervous system (CNS) events including new onset and/or exacerbations of pre-existing demyelinating neurological diseases. We describe a patient with refractory RA where adalimumab, a fully humanized IgG1 monoclonal antibody against TNF-a, may have contributed to the development of meningoencephalitis, with brain biopsy suggestive of hypertrophic pachymeningitis, a rare complication of this disease. The patient had recurrence of neurological symptoms upon repeated administration of adalimumab, and resolution of symptoms after withdrawal.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Meningite/induzido quimicamente , Adalimumab , Idoso , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais Humanizados , Histocitoquímica , Humanos , Imageamento por Ressonância Magnética , Masculino , Meningite/diagnóstico , Meningite/tratamento farmacológico , Prednisona/administração & dosagemRESUMO
Benign neurofibromas and malignant peripheral nerve sheath tumors are serious complications of neurofibromatosis type 1. The epidermal growth factor receptor is not expressed by normal Schwann cells, yet is overexpressed in subpopulations of Nf1 mutant Schwann cells. We evaluated the role of EGFR in Schwann cell tumorigenesis. Expression of EGFR in transgenic mouse Schwann cells elicited features of neurofibromas: Schwann cell hyperplasia, excess collagen, mast cell accumulation, and progressive dissociation of non-myelin-forming Schwann cells from axons. Mating EGFR transgenic mice to Nf1 hemizygotes did not enhance this phenotype. Genetic reduction of EGFR in Nf1(+/-);p53(+/-) mice that develop sarcomas significantly improved survival. Thus, gain- and loss-of-function experiments support the relevance of EGFR to peripheral nerve tumor formation.
Assuntos
Receptores ErbB/metabolismo , Neurofibroma/metabolismo , Neurofibromatose 1/metabolismo , Neurofibromatose 1/patologia , Nervos Periféricos/metabolismo , Nervos Periféricos/patologia , Células de Schwann/fisiologia , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/genética , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo , Animais , Células Cultivadas , Receptores ErbB/genética , Fibrose , Humanos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias de Tecido Nervoso/genética , Neoplasias de Tecido Nervoso/metabolismo , Neoplasias de Tecido Nervoso/patologia , Neurofibroma/genética , Neurofibroma/patologia , Neurofibromatose 1/genética , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Nervos Periféricos/ultraestrutura , Células de Schwann/citologia , Transdução de Sinais/fisiologia , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVE: To evaluate the use of dexamethasone in a model of meningitis-induced brain injury. Changes in neurobehavioral performance were the primary outcome variables. Changes in caspase activation and markers of neuronal injury were the secondary outcome variables. DESIGN: Randomized, prospective animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Animals underwent a basilar cistern injection of either placebo or a suspension of Group B Streptococcus. Sixteen hours after inoculation, animals were randomized and received either dexamethasone or placebo in addition to antibiotics. Neurobehavioral performance and biological markers of brain injury were assessed at 3 days and 9 days after randomization. In a second experiment, caspase 1 and 3 were evaluated at 6 h, 24 h, and 72 h after dexamethasone administration. MEASUREMENTS AND MAIN RESULTS: Neurobehavioral performance at 3 days and 9 days was significantly improved in the dexamethasone group. Serum C-tau and cerebral edema were decreased after 3 days of dexamethasone treatment. Dexamethasone decreased Caspase 3 activation in meningitic animals. CONCLUSION: These findings demonstrate that dexamethasone decreases acute brain injury in a rat model of bacterial meningitis as measured by preservation of neurobehavioral performance.
Assuntos
Lesões Encefálicas/enzimologia , Caspases/metabolismo , Dexametasona/farmacologia , Meningites Bacterianas/enzimologia , Atividade Motora/efeitos dos fármacos , Infecções Estreptocócicas/enzimologia , Animais , Antibacterianos/uso terapêutico , Lesões Encefálicas/microbiologia , Ativação Enzimática/efeitos dos fármacos , Masculino , Meningites Bacterianas/tratamento farmacológico , Ratos , Ratos Wistar , Streptococcus agalactiaeRESUMO
This report documents the hospital course and autopsy findings of a 43-year-old man with a renal allograft who died of West Nile virus (WNV) encephalitis. Central nervous system (CNS) findings were those of severe necrotizing and hemorrhagic encephalitis affecting gray matter regions limited to the diencepahlon, rhombencephalon, spinal cord, and limbic system. The bilateral process exhibited preferential involvement of motor neurons. Brain imaging obtained 6 days before death demonstrated an unusual pattern of involvement corresponding with the autopsy findings, confirming that imaging may be a specific diagnostic guide in WNV encephalitis. Extra-CNS findings include myositis with T-lymphocyte infiltration of nerve fibers, suggesting that the virus may reach the CNS via peripheral nerves. Orchitis with dense T-lymphocyte infiltration and syncytial cell formation thought to be due to WNV were also noted.
