RESUMEN
The emergence of immune-based treatments for cancer has led to a growing field dedicated to understanding and managing iatrogenic immunotoxicities that arise from these agents. Immune-related adverse events (irAEs) can develop as isolated events or as toxicities affecting multiple body systems. In particular, this review details the neurological irAEs from immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell immunotherapies. The recognition and treatment of neurological irAEs has variable success, depending on the severity and nature of the neurological involvement. Understanding the involved mechanisms, predicting those at higher risk for irAEs, and establishing safety parameters for resuming cancer immunotherapies after irAEs are all important fields of ongoing research.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/terapia , Biomarcadores Farmacológicos/análisis , Biomarcadores de Tumor/análisis , Antígeno CTLA-4/antagonistas & inhibidores , Encefalitis/inducido químicamente , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia Adoptiva/métodos , Meningitis Aséptica/inducido químicamente , Meningitis Aséptica/inmunología , Neoplasias/inmunología , Síndromes Paraneoplásicos/inducido químicamente , Receptores Quiméricos de Antígenos/uso terapéutico , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Aseptic meningitis can be caused by autoimmune diseases, such as lupus and sarcoidosis. Aseptic meningitis with leptomeningeal enhancement can be the initial presentation of a neuroinflammatory syndrome associated with antibodies to myelin oligodendrocyte glycoprotein (MOG-abs). MOG-abs is a serum biomarker for MOG-associated disorder (MOG-AD), an acquired demyelinating syndrome that includes features of neuromyelitis optica, multiple sclerosis, optic neuritis, and acute disseminated encephalomyelitis. The purpose of this study is to review cases of aseptic meningitis and leptomeningeal enhancement associated with MOG-abs. METHODS: Systematic review using PubMed, Embase, Ovid MEDLINE, Web of Science Core Collection, and Google Scholar up to December 2020 was performed. Cases of MOG-AD were included if they met the following criteria: 1) Initial clinical presentation of aseptic meningitis; 2) positive leptomeningeal enhancement and 3) MOG-Ab seropositivity. Descriptive statistics were used. This analysis was limited to the cases available in the literature. RESULTS: 11 total cases of aseptic meningitis and leptomeningeal enhancement in setting of MOG-ab were identified. Demyelinating type T2 lesions were also present at time of presentation in 6/11; however, 5/11 of patients had leptomeningeal enhancement alone without demyelinating lesions. All 5 patients required immunotherapy for improvement, including one patient with symptoms for 28 days, with 4/5 receiving steroids and 1/5 receiving intravenous immunoglobulin (IVIG). CONCLUSIONS: Aseptic meningitis with leptomeningeal enhancement can be the initial presenting symptom of MOG-AD. MOG-ab testing should be considered in a patient presenting with aseptic meningitis and leptomeningeal enhancement of unknown etiology.
Asunto(s)
Autoanticuerpos/sangre , Meningitis Aséptica/sangre , Meningitis Aséptica/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/sangre , Autoanticuerpos/inmunología , Enfermedades Autoinmunes Desmielinizantes SNC/sangre , Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico por imagen , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Humanos , Meningitis Aséptica/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuromielitis Óptica/sangre , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/inmunologíaRESUMEN
BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelinating disorders (MOGAD) are increasingly being recognized in the pediatric age group. Over time, unusual presentations have expanded the clinical presentation. We report 12 cases of MOGAD where prolonged fever (PF) was an important part of the symptom complex during the course of the illness. METHODS: After initial recognition of this atypical clinical presentation, more patients were recruited over 2 years and followed up prospectively. RESULTS: Eight of twelve patients had no clinical/imaging evidence of demyelination until much later in the course. Three clinical presentations recognized were fever of unknown origin (4 of 12), aseptic meningitis (4 of 12), and PF seen concurrently with established acute demyelination syndrome (4 of 12). Leukocytosis, raised inflammatory markers, and cerebrospinal fluid pleocytosis were almost universal. The first two presentations frequently caused diagnostic confusion, as MOGAD was not considered until several weeks after disease onset. The third group was more a therapeutic conundrum on how to manage the PF. Early seizures without encephalopathy were not uncommon and were probably independent of the later-appearing demyelination. CONCLUSIONS: This case series highlights PF as an important component of the pediatric MOGAD symptom complex. MOGAD could be considered in the differential diagnosis of these clinical presentations.
Asunto(s)
Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico , Fiebre/diagnóstico , Meningitis Aséptica/diagnóstico , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos , Niño , Enfermedades Autoinmunes Desmielinizantes SNC/sangre , Enfermedades Autoinmunes Desmielinizantes SNC/líquido cefalorraquídeo , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Diagnóstico Diferencial , Femenino , Fiebre/sangre , Fiebre/líquido cefalorraquídeo , Fiebre/inmunología , Estudios de Seguimiento , Humanos , Masculino , Meningitis Aséptica/sangre , Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Aséptica/inmunologíaRESUMEN
For those surviving encephalitis, the influence on daily life of patients and their relatives may be substantial. In contrast, the prognosis after aseptic meningitis (ASM) is considered good. In this prospective study in patients with encephalitis (n = 20) and ASM (n = 46), we show that both groups experienced reduced Health Related Quality of Life (HRQoL) at two months after discharge, and that workability was reduced in 37% of the patients with ASM. However, 12 months after discharge no neuropsychological deficits were detected in the ASM group, whereas patients with encephalitis had lower scores on tests of fine motor and psychomotor skills as well as on learning and memory. We also found that for patients with encephalitis, neopterin, as a marker of Th1 cell induced macrophage activation, and a putatively neurotoxic ratio of the kynurenine pathway (KP) measured during the acute phase was associated with lower HRQoL. Our data show that not only encephalitis, but also ASM has substantial short-term influence on HRQoL and workability. For patients with encephalitis we suggest a link between immune activation and activation of the KP during the acute phase with impaired HRQoL.
Asunto(s)
Encefalitis/psicología , Meningitis Aséptica/psicología , Calidad de Vida , Sobrevivientes/psicología , Adulto , Anciano , Biomarcadores , Daño Encefálico Crónico/etiología , Daño Encefálico Crónico/psicología , Encefalitis/complicaciones , Encefalitis/inmunología , Encefalitis/terapia , Femenino , Estudios de Seguimiento , Humanos , Quinurenina/metabolismo , Discapacidades para el Aprendizaje/etiología , Discapacidades para el Aprendizaje/psicología , Activación de Macrófagos , Masculino , Trastornos de la Memoria/etiología , Trastornos de la Memoria/psicología , Meningitis Aséptica/complicaciones , Meningitis Aséptica/inmunología , Meningitis Aséptica/terapia , Persona de Mediana Edad , Neopterin/sangre , Pruebas Neuropsicológicas , Pronóstico , Estudios Prospectivos , Desempeño Psicomotor , Células TH1/inmunología , Resultado del TratamientoRESUMEN
The spectrum of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) associated demyelination is evolving. Our case report describes a unique clinical presentation of aseptic meningitis with demyelinating lesions of the brain resembling acute disseminated encephalomyelitis and MOG-Ab seropositivity. A 22-year-old lady presented with history of fever of one week duration followed by headache, vomiting and neck stiffness. She had bilateral papilledema and signs of meningeal irritation. Neuroimaging revealed T2 and FLAIR hyperintense lesions in the right caudate, temporal lobe and left insula with enhancement on gadolinium contrast along with leptomeningeal enhancement. An extensive search for infectious and inflammatory etiology was negative while serum was positive for MOG-Abs tested twice at an interval of 12â¯days. She showed remarkable clinical-radiological resolution with steroids and has remained symptom free on follow up.
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Autoanticuerpos/inmunología , Autoantígenos/inmunología , Enfermedades Desmielinizantes/inmunología , Meningitis Aséptica/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Enfermedades Desmielinizantes/sangre , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Enfermedades Desmielinizantes/diagnóstico por imagen , Potenciales Evocados Visuales , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Imagen por Resonancia Magnética , Meninges/diagnóstico por imagen , Meninges/patología , Meningitis Aséptica/sangre , Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Aséptica/diagnóstico por imagen , Neuroimagen , Papiledema/etiología , Adulto JovenRESUMEN
Viral meningitis is an inflammation of the meninges associated with acute onset of meningeal symptoms and fever, pleocytosis of the cerebrospinal fluid, and no growth on routine bacterial culture. It is sometimes associated with viral encephalitis and meningoencephalitis. Viruses reach the central nervous system (CNS) hematogenously or in a retrograde manner from nerve endings. The viral etiology varies according to age and country. Molecular diagnostics technology has helped improve the rate of pathogen detection reducing unnecessary antibiotic use and length of hospitalization. Most of the viral infections detailed in this article have no specific treatment other than supportive care. Many of the viruses discussed are preventable by vaccination and proper skin protection against transmitting vectors.
Asunto(s)
Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Aséptica/diagnóstico , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/diagnóstico , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/diagnóstico , Encefalitis Viral/inmunología , Humanos , Meningitis Aséptica/inmunología , Meningitis Viral/inmunologíaAsunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Cefalea/inducido químicamente , Meningitis Aséptica/inducido químicamente , Mieloma Múltiple/tratamiento farmacológico , Progresión de la Enfermedad , Resultado Fatal , Femenino , Cefalea/diagnóstico , Humanos , Meningitis Aséptica/diagnóstico , Meningitis Aséptica/inmunología , Meningitis Aséptica/terapia , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/inmunología , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To investigate the nature of prodromal headache in anti-NMDA receptor (NMDAR) encephalitis. METHODS: Retrospective review of the clinical information of 39 patients with anti-NMDAR encephalitis admitted between January 1999 and September 2017. Five patients with an atypical presentation were excluded. Thus, in 34 patients (median 27 years [range, 12-47 years]; 28 [82%] female), the clinical features were compared between patients who initially reported headache and those who did not report. RESULTS: Twenty-two patients (65%) reported headache either transiently (n = 5) or continuously (n = 17). Encephalitic symptoms (psychobehavioral memory alterations, seizure, dyskinesias, or altered level of consciousness) developed in 20 patients with median 5.5 days (range, 1-29 days) after headache onset. In one patient, NMDAR antibodies were detected in CSF 3 days after headache onset. Patients with headache had more frequently fever (14/22 [64%] vs. 2/12 [17%] p = 0.013) and higher CSF pleocytosis (median white blood cells 79/µl [range, 6-311/µl] vs. 30/µl [range, 2-69/µl], p = 0.035) than those without headache, but there was no difference in gender, age at onset, seizure, migraine, CSF oligoclonal band detection, elevated IgG index, tumor association, or brain MRI abnormalities between them. CONCLUSIONS: Headache often developed with fever and pleocytosis, but it was rapidly replaced by psychiatric symptoms. Based on current knowledge on the antibody-mediated mechanisms that cause a decrease of synaptic NMDAR through crosslinking and internalization leading to a state mimicking "dissociative anesthesia," we speculated that prodromal headache is not likely caused by direct effect of the autoantibodies but rather meningeal inflammation (noninfectious aseptic meningitis) that occurs in parallel to intrathecal antibody synthesis as an epiphenomenon of NMDAR autoimmunity. Psychobehavioral alterations following headache is an important clue to the diagnosis.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Trastornos de Cefalalgia/etiología , Adolescente , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Autoanticuerpos/inmunología , Autoinmunidad/fisiología , Niño , Discinesias/etiología , Discinesias/inmunología , Femenino , Fiebre/etiología , Fiebre/inmunología , Trastornos de Cefalalgia/inmunología , Humanos , Masculino , Meningitis Aséptica/etiología , Meningitis Aséptica/inmunología , Persona de Mediana Edad , Receptores de N-Metil-D-Aspartato , Estudios Retrospectivos , Convulsiones/etiología , Convulsiones/inmunología , Adulto JovenAsunto(s)
Encefalitis por Varicela Zóster/diagnóstico , Inmunocompetencia , Meningitis Aséptica/virología , Infección por el Virus de la Varicela-Zóster/complicaciones , Preescolar , Encefalitis por Varicela Zóster/inmunología , Femenino , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/aislamiento & purificación , Humanos , Meningitis Aséptica/diagnóstico , Meningitis Aséptica/inmunología , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/inmunologíaRESUMEN
We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in an immunocompromised patient with acute lymphocytic leukemia who was initially diagnosed with aseptic meningitis. Isolation of Sabin-like type 1 poliovirus from the patient's cerebrospinal fluid made this a case of vaccine-related poliovirus (VRPV) infection. The patient developed paralysis and respiratory distress and deceased a few months after onset of paralysis with respiratory failure. This tragic case report highlights the emergence of VAPP and indicates the importance of timely diagnosis of VRPV infections to improve clinical management of VRPV-infected patients and to prevent the devastating consequences of silent introduction of VRPVs in treatment wards and eventually in the society.
Asunto(s)
Huésped Inmunocomprometido , Meningitis Aséptica/diagnóstico , Poliomielitis/diagnóstico , Vacuna Antipolio Oral/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adulto , Errores Diagnósticos , Resultado Fatal , Humanos , Masculino , Meningitis Aséptica/inmunología , Meningitis Aséptica/patología , Meningitis Aséptica/virología , Parálisis/diagnóstico , Parálisis/inmunología , Parálisis/patología , Parálisis/virología , Poliomielitis/etiología , Poliomielitis/inmunología , Poliomielitis/virología , Vacuna Antipolio Oral/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/virologíaRESUMEN
BACKGROUND: Although aseptic meningitis associated with echovirus type 30 has emerged as a global public health concern, no data have been reported on Children's immune status against echovirus type 30. The current study aimed to investigate the seropositivity among Korean children for antibodies against echovirus 30. METHODS: Two hundred and fifty residual serum samples were collected at St. Paul's Hospital. Individuals were categorized by age into four groups: group 1 (3 months-2 years), group 2 (3-6 years), group 3 (7-10 years) and group 4 (11-15 years). Neutralizing antibodies against echovirus 30 were measured. RESULTS: Seroprotective neutralizing antibodies against echovirus 30 were detected in 129 (49%) individuals. Seropositivity rates were 23%, 48%, 55% and 73% in groups 1-4, respectively. For antibody titers, 1:256-1:512 was the highest neutralizing antibody titer range in group 2, while 1:1024-1:2048 in group 3 and 4. Among the seropositive individuals in group 3 and 4, 6% and 12% had neutralizing antibody titers of 1:2048, respectively. CONCLUSIONS: The seropositivity rate increased significantly with age. The distribution of neutralizing antibody titers varied by age group, and higher ranges of neutralizing antibody titers were observed in higher age groups. These findings suggest high susceptibility to echovirus 30 infection in children younger than 2 years old. Echovirus 30 infection in childhood may have contributed to increased neutralizing antibody titers with age.
Asunto(s)
Brotes de Enfermedades , Infecciones por Echovirus/epidemiología , Enterovirus Humano B/clasificación , Meningitis Aséptica/epidemiología , Meningitis Aséptica/inmunología , Adolescente , Distribución por Edad , Distribución de Chi-Cuadrado , Niño , Preescolar , China/epidemiología , Intervalos de Confianza , Infecciones por Echovirus/diagnóstico , Infecciones por Echovirus/inmunología , Enterovirus Humano B/aislamiento & purificación , Femenino , Encuestas Epidemiológicas , Humanos , Incidencia , Lactante , Masculino , Meningitis Aséptica/diagnóstico , Salud Pública , Medición de Riesgo , Estudios Seroepidemiológicos , Distribución por SexoRESUMEN
Interleukin-10 (IL-10) delivered by intrathecal (i.t.) gene vectors is a candidate investigational new drug (IND) for several chronic neurological disorders such as neuropathic pain. We performed a preclinical safety study of IL-10. A syngeneic large animal model was used delivering porcine IL-10 (pIL-10) to the i.t. space in swine by adeno-associated virus serotype 8 (AAV8), a gene vector that was previously found to be nontoxic in the i.t. space. Unexpectedly, animals became ill, developing ataxia, seizures, and an inability to feed and drink, and required euthanasia. Necropsy demonstrated lymphocytic meningitis without evidence of infection in the presence of normal laboratory findings for body fluids and normal histopathology of peripheral organs. Results were replicated in a second animal cohort by a team of independent experimenters. An extensive infectious disease and neuropathology workup consisting of comprehensive testing of tissues and body fluids in a specialized research veterinary pathology environment did not identify a pathogen. These observations raise the concern that i.t. IL-10 therapy may not be benign, that previously used xenogeneic models testing the human homolog of IL-10 may not have been sensitive enough to detect toxicity, and that additional preclinical studies may be needed before clinical testing of IL-10 can be considered.
Asunto(s)
Ataxia/inmunología , Dependovirus/inmunología , Vectores Genéticos/administración & dosificación , Meningitis Aséptica/inmunología , Convulsiones/inmunología , Animales , Ataxia/inducido químicamente , Ataxia/mortalidad , Ataxia/patología , Dependovirus/genética , Evaluación Preclínica de Medicamentos , Drogas en Investigación , Femenino , Terapia Genética/métodos , Vectores Genéticos/química , Vectores Genéticos/inmunología , Inyecciones Espinales , Interleucina-10/genética , Interleucina-10/inmunología , Masculino , Meningitis Aséptica/inducido químicamente , Meningitis Aséptica/mortalidad , Meningitis Aséptica/patología , Convulsiones/inducido químicamente , Convulsiones/mortalidad , Convulsiones/patología , Análisis de Supervivencia , PorcinosRESUMEN
Autoantibodies to triosephosphate isomerase (TPI), which is an important glycolytic enzyme in red blood cells and neuronal cells, have been reported to be associated with neuropsychiatric systemic lupus erythematosus (NPSLE) pathogenesis. However, the clinical features regarding anti-TPI antibody (anti-TPI)-positive NPSLE are not yet known. The aim of this study is to investigate the clinical features of anti-TPI-positive NPSLE patients using anti-TPI index values determined by enzyme-linked immunosorbent assay (ELISA). Thirty-one NPSLE patients treated in our department were included in this study. Serum samples were collected, and serum anti-TPI titers were measured by ELISA. The anti-TPI index values were defined as follows: (OD405 of samples - OD405 of negative control)/(OD405 of positive control - OD405 of negative control) × 100. Anti-TPI index values greater than 2 standard deviations above the mean of healthy controls were regarded as positive. The clinical features of anti-TPI-positive and anti-TPI-negative NPSLE were compared. Ten of the 31 NPSLE patients had anti-TPI positivity (32.3%). The clinical features of anti-TPI-positive NPSLE were comparable with those of anti-TPI-negative NPSLE, except for a higher frequency of aseptic meningitis (p = 0.027) and a lower frequency of acute confusional state (P = 0.026). Laboratory data in patients with anti-TPI-positive NPSLE showed significantly higher serum IgG levels. Furthermore, anti-TPI index values positively correlated with serum IgG levels. Our study indicates that serum anti-TPI increases in the presence of elevated IgG levels and can be associated with the pathogenesis of aseptic meningitis in NPSLE.
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Autoanticuerpos/sangre , Vasculitis por Lupus del Sistema Nervioso Central/inmunología , Meningitis Aséptica/inmunología , Triosa-Fosfato Isomerasa/inmunología , Adolescente , Adulto , Femenino , Humanos , Vasculitis por Lupus del Sistema Nervioso Central/sangre , Vasculitis por Lupus del Sistema Nervioso Central/complicaciones , Masculino , Meningitis Aséptica/sangre , Meningitis Aséptica/complicaciones , Adulto JovenAsunto(s)
Fiebre/genética , Meningitis Aséptica/genética , Mutación , Mielitis/genética , Neutrófilos/inmunología , Pirina/genética , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad Crónica , Análisis Mutacional de ADN , Femenino , Fiebre/diagnóstico , Fiebre/tratamiento farmacológico , Fiebre/inmunología , Predisposición Genética a la Enfermedad , Herencia , Humanos , Inmunosupresores/uso terapéutico , Masculino , Meningitis Aséptica/diagnóstico , Meningitis Aséptica/tratamiento farmacológico , Meningitis Aséptica/inmunología , Persona de Mediana Edad , Mielitis/diagnóstico , Mielitis/tratamiento farmacológico , Mielitis/inmunología , Neutrófilos/efectos de los fármacos , Linaje , Fenotipo , Recurrencia , Inducción de Remisión , Resultado del TratamientoAsunto(s)
Antiinfecciosos Urinarios/efectos adversos , Hipersensibilidad a las Drogas/etiología , Meningitis Aséptica/inducido químicamente , Trimetoprim/efectos adversos , Anciano de 80 o más Años , Hipersensibilidad a las Drogas/sangre , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/inmunología , Femenino , Humanos , Meningitis Aséptica/sangre , Meningitis Aséptica/diagnóstico , Meningitis Aséptica/inmunologíaRESUMEN
BACKGROUND: Human parechovirus (HPeV) and enterovirus (EV) cause a range of human diseases including serious CNS infections. Little is known regarding the immune response to HPeV meningitis compared to EV meningitis or how the immune response to HPeV reflects its pathogenesis. OBJECTIVE: To characterize the innate immune response to HPeV CNS infection in order to increase our understanding of HPeV pathogenesis and possibly help identify HPeV in the clinical setting. STUDY DESIGN: CSF samples from 13 patients with HPeV meningitis, 7 patients with EV meningitis, and 11 patients negative for CNS infections were analyzed for chemokines/cytokines using multiplex ELISA assays. RESULTS: CSF levels of the majority of cytokines/chemokines analyzed were significantly higher in patients with EV meningitis (EV group) compared to patients with HPeV meningitis (HPeV group) and controls. In the HPeV group, a small number of cytokine/chemokine levels were higher than controls; however, these levels were either significantly lower or not significantly different compared to the EV group. IL-6 levels were lower in HPeV than in both EV and controls. CONCLUSIONS: The immune response to HPeV CNS infection differs from that of EV. Distinct patterns of cytokine/chemokine expression in HPeV infections suggest HPeV-mediated modulation of the immune response. HPeV disrupts the interferon cascade and seems to interfere with early inflammatory signaling. Although HPeV elicits a predominantly muted immune reaction, a partial, general infectious-type cytokine/chemokine response does occur. Beyond providing insight into HPeV pathogenesis, the identified cytokine/chemokine profile may aid in early detection of HPeV infection.
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Enterovirus/inmunología , Inmunidad Innata , Meningitis Aséptica/inmunología , Meningitis Aséptica/virología , Parechovirus/inmunología , Adolescente , Niño , Preescolar , Citocinas/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios RetrospectivosAsunto(s)
Anticuerpos Monoclonales/efectos adversos , Meningitis Aséptica/inmunología , Meningoencefalitis/inmunología , Neoplasias del Ojo/patología , Humanos , Ipilimumab , Neoplasias Hepáticas/secundario , Masculino , Melanoma/terapia , Meningitis Aséptica/diagnóstico , Meningitis Aséptica/terapia , Meningoencefalitis/diagnóstico , Meningoencefalitis/terapia , Persona de Mediana EdadRESUMEN
Blood-brain barrier (BBB) dysfunction seen in neuroinflammation contributes to mortality and morbidity in multiple sclerosis, encephalitis, traumatic brain injury, and stroke. Identification of molecular targets maintaining barrier function is of clinical relevance. We used a novel in vivo model of localized aseptic meningitis where tumor necrosis factor alpha (TNFα) was introduced intracerebrally and surveyed cerebral vascular changes and leukocyte-endothelium interactions by intravital videomicroscopy. Poly(ADP-ribose) polymerase-1 (PARP) inhibition significantly reduced leukocyte adhesion to and migration across brain endothelium in cortical microvessels. PARP inactivation diminished BBB permeability in an in vivo model of systemic inflammation. PARP suppression in primary human brain microvascular endothelial cells (BMVEC), an in vitro model of BBB, enhanced barrier integrity and augmented expression of tight junction proteins. PARP inhibition in BMVEC diminished human monocyte adhesion to TNFα-activated BMVEC (up to 65%) and migration (80-100%) across BBB models. PARP suppression decreased expression of adhesion molecules and decreased activity of GTPases (controlling BBB integrity and monocyte migration across the BBB). PARP inhibitors down-regulated expression of inflammatory genes and dampened secretion of pro-inflammatory factors increased by TNFα in BMVEC. These results point to PARP suppression as a novel approach to BBB protection in the setting of endothelial dysfunction caused by inflammation.
Asunto(s)
Barrera Hematoencefálica/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Meningitis Aséptica/fisiopatología , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/fisiología , Barrera Hematoencefálica/fisiopatología , Western Blotting , Permeabilidad Capilar/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Células Cultivadas , Citocinas/inmunología , Células Endoteliales , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiología , Endotelio Vascular/fisiopatología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Citometría de Flujo , Humanos , Leucocitos/citología , Masculino , Meningitis Aséptica/inmunología , Meningitis Aséptica/metabolismo , Ratones Endogámicos C57BL , Microscopía por Video , Poli(ADP-Ribosa) Polimerasa-1 , Proteínas de Uniones Estrechas/metabolismo , Migración Transendotelial y Transepitelial/efectos de los fármacosRESUMEN
OBJECTIVE: To review the literature on trimethoprim-sulfamethoxazole (TMP-SMX)-induced aseptic meningitis (TSIAM) and discuss the features, possible mechanisms, evaluation, and treatment options relevant for the allergist. DATA SOURCES: A MEDLINE search was performed using the terms aseptic meningitis, trimethoprim-sulfamethoxazole, trimethoprim, and sulfamethoxazole. STUDY SELECTIONS: Cases were included that fit the case definition of headache, neck pain, or change in mental status with elevated cerebrospinal fluid white blood cell count or protein attributable to TMP-SMX or either medication alone. RESULTS: Forty-one patient cases were reviewed. There was a predominance of female patients and patients with autoimmune disease reported. Fever, headache, neck pain, and altered mental status were the most common findings reported in TSIAM reactions. Severe reactions ranged from hypotension to seizure and unconsciousness or coma. Typical cerebrospinal fluid findings included elevated white blood cell count with neutrophil predominance, elevated protein, and normal glucose. Symptoms quickly remitted with withdrawal of TMP-SMX, typically over 48 to 72 hours. Full recovery was typically experienced, although permanent paraplegia was reported in 1 case. The mechanism of reaction is unknown, although an IgE-mediated reaction is unlikely. Many patients experienced multiple TSIAM reactions before the diagnosis was made. Diagnosis can be confirmed with drug challenge or graded test dosing when necessary. Patients with TSIAM subsequently reacted to TMP and SMX alone and therefore should be advised to avoid these 2 classes of medication after diagnosis. CONCLUSION: TMP-SMX is the most common antibiotic to cause drug-induced aseptic meningitis. By being aware of this reaction, allergists are well poised to diagnose TSIAM and prevent future reoccurrences for the patient.
Asunto(s)
Antiinfecciosos/efectos adversos , Hipersensibilidad a las Drogas/etiología , Meningitis Aséptica/inducido químicamente , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Hipersensibilidad a las Drogas/líquido cefalorraquídeo , Hipersensibilidad a las Drogas/inmunología , Femenino , Humanos , Masculino , Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Aséptica/inmunología , Persona de Mediana Edad , Adulto JovenRESUMEN
We investigated the extent of lymphocytic choriomeningitis virus (LCMV) infection in employees and rodents at 3 commercial breeding facilities. Of 97 employees tested, 31 (32%) had IgM and/or IgG to LCMV, and aseptic meningitis was diagnosed in 4 employees. Of 1,820 rodents tested in 1 facility, 382 (21%) mice (Mus musculus) had detectable IgG, and 13 (0.7%) were positive by reverse transcription PCR; LCMV was isolated from 8. Rats (Rattus norvegicus) were not found to be infected. S-segment RNA sequence was similar to strains previously isolated in North America. Contact by wild mice with colony mice was the likely source for LCMV, and shipments of infected mice among facilities spread the infection. The breeding colonies were depopulated to prevent further human infections. Future outbreaks can be prevented with monitoring and management, and employees should be made aware of LCMV risks and prevention.