RESUMO
PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating illnesses primarily characterized by chronic symptoms of fatigue and musculoskeletal pain, respectively. Some investigators have observed an elevated sense of effort in these patient groups; however, this effect has not been substantiated via quantitative review. As such, we conducted a meta-analysis of RPE responses to aerobic exercise in ME/CFS and FM compared with healthy adults. METHODS: Case-control studies involving adults with ME/CFS or FM that measured RPE and heart rate responses to acute aerobic exercise were included. Data sources included PubMed, Scopus/Embase, CINAHL, CENTRAL, and Google Scholar. Risk of bias was assessed by evaluating each study's description of participant characteristics, matching procedures, and administration of RPE scales. Hedges' d effect sizes for RPE were calculated and aggregated using random-effects models, and potential moderators were explored with meta-regression analysis. RESULTS: Forty-one effects were extracted from 37 studies involving 1016 patients and 686 healthy controls. We observed a large (Hedges' d = 0.85, 95% confidence interval = 0.62-1.08) effect indicating higher RPE in patients than controls. The mean effect size was significantly moderated (P < 0.001, R = 0.38) by whether RPE data were analyzed at a peak or submaximal intensity (b = 0.60, z = 4.6, P < 0.001) and the type of patient group that was studied (b = 0.25, z = 2.08, P = 0.04). CONCLUSIONS: People with ME/CFS and FM perceive aerobic exercise as more effortful than healthy adults, but the exact causes are unclear. The large magnitude of this effect merits further exploration of underlying mechanisms that could provide insight into the pathophysiology of ME/CFS and FM or the broader debate about the nature of central and/or peripheral signals that influence RPE.
Assuntos
Encefalomielite/fisiopatologia , Exercício Físico/fisiologia , Síndrome de Fadiga Crônica/fisiopatologia , Fibromialgia/fisiopatologia , Mialgia/fisiopatologia , Esforço Físico/fisiologia , Adulto , Viés , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Medidas de Resultados Relatados pelo Paciente , Análise de Regressão , AutorrelatoRESUMO
BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition with no reliable diagnostic biomarkers. Studies have shown evidence of autonomic dysfunction in patients with ME/CFS, but results have been equivocal. Heart rate (HR) parameters can reflect changes in autonomic function in healthy individuals; however, this has not been thoroughly evaluated in ME/CFS. METHODS: A systematic database search for case-control literature was performed. Meta-analysis was performed to determine differences in HR parameters between ME/CFS patients and controls. RESULTS: Sixty-four articles were included in the systematic review. HR parameters assessed in ME/CFS patients and controls were grouped into ten categories: resting HR (RHR), maximal HR (HRmax), HR during submaximal exercise, HR response to head-up tilt testing (HRtilt), resting HR variability (HRVrest), HR variability during head-up tilt testing (HRVtilt), orthostatic HR response (HROR), HR during mental task(s) (HRmentaltask), daily average HR (HRdailyaverage), and HR recovery (HRR) Meta-analysis revealed RHR (MDâ±â95% CIâ=â4.14â±â1.38, Pâ<â.001), HRtilt (SMDâ±â95% CIâ=â0.92â±â0.24, Pâ<â.001), HROR (0.50â±â0.27, Pâ<â.001), and the ratio of low frequency power to high frequency power of HRVrest (0.39â±â0.22, Pâ<â.001) were higher in ME/CFS patients compared to controls, while HRmax (MDâ±â95% CIâ=â-13.81â±â4.15, Pâ<â.001), HR at anaerobic threshold (SMDâ±â95% CIâ=â-0.44â±â0.30, Pâ=â0.005) and the high frequency portion of HRVrest (-0.34â±â0.22, Pâ=â.002) were lower in ME/CFS patients. CONCLUSIONS: The differences in HR parameters identified by the meta-analysis indicate that ME/CFS patients have altered autonomic cardiac regulation when compared to healthy controls. These alterations in HR parameters may be symptomatic of the condition.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Encefalomielite/fisiopatologia , Síndrome de Fadiga Crônica/fisiopatologia , Coração/fisiopatologia , Adulto , Idoso , Exercício Físico/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome , Teste da Mesa InclinadaRESUMO
Interferon (IFN) regulatory factors (IRFs) are important determinants of the innate response to infection. We evaluated the role(s) of combined and individual IRF deficiencies in the outcome of infection of C57BL/6 mice with Sindbis virus, an alphavirus that infects neurons and causes encephalomyelitis. The brain and spinal cord levels of Irf7, but not Irf3 mRNAs, were increased after infection. IRF3/5/7-/- and IRF3/7-/- mice died within 3-4 days with uncontrolled virus replication, similar to IFNα receptor-deficient mice, while all wild-type (WT) mice recovered. IRF3-/- and IRF7-/- mice had brain levels of IFNα that were lower, but brain and spinal cord levels of IFNß and IFN-stimulated gene mRNAs that were similar to or higher than WT mice without detectable serum IFN or increases in Ifna or Ifnb mRNAs in the lymph nodes, indicating that the differences in outcome were not due to deficiencies in the central nervous system (CNS) type I IFN response. IRF3-/- mice developed persistent neurological deficits and had more spinal cord inflammation and higher CNS levels of Il1b and Ifnγ mRNAs than WT mice, but all mice survived. IRF7-/- mice died 5-8 days after infection with rapidly progressive paralysis and differed from both WT and IRF3-/- mice in the induction of higher CNS levels of IFNß, tumour necrosis factor (TNF) α and Cxcl13 mRNA, delayed virus clearance and more extensive cell death. Therefore, fatal disease in IRF7-/- mice is likely due to immune-mediated neurotoxicity associated with failure to regulate the production of inflammatory cytokines such as TNFα in the CNS.
Assuntos
Infecções por Alphavirus/fisiopatologia , Encefalomielite/fisiopatologia , Interações Hospedeiro-Patógeno , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 7 de Interferon/metabolismo , Sindbis virus/crescimento & desenvolvimento , Animais , Encéfalo/patologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Fator Regulador 3 de Interferon/deficiência , Fator Regulador 7 de Interferon/deficiência , Camundongos Endogâmicos C57BL , Camundongos Knockout , Medula Espinal/patologia , Análise de SobrevidaRESUMO
OBJECTIVE: To report the clinical and immunological characteristics of 22 new patients with glial fibrillar acidic protein (GFAP) autoantibodies. METHODS: From January 2012 to March 2017, we recruited 451 patients with suspected neurological autoimmune disease at the Catholic University of Rome. Patients' serum and cerebrospinal fluid (CSF) samples were tested for neural autoantibodies by immunohistochemistry on mouse and rat brain sections, by cell-based assays (CBA) and immunoblot. GFAP autoantibodies were detected by immunohistochemistry and their specificity confirmed by CBA using cells expressing human GFAPα and GFAPδ proteins, by immunoblot and immunohistochemistry on GFAP-/- mouse brain sections. RESULTS: Serum and/or CSF IgG of 22/451 (5%) patients bound to human GFAP, of which 22/22 bound to GFAPα, 14/22 to both GFAPα and GFAPδ and none to the GFAPδ isoform only. The neurological presentation was: meningoencephalomyelitis or encephalitis in 10, movement disorder (choreoathetosis or myoclonus) in 3, anti-epileptic drugs (AED)-resistant epilepsy in 3, cerebellar ataxia in 3, myelitis in 2, optic neuritis in 1 patient. Coexisting neural autoantibodies were detected in five patients. Six patients had other autoimmune diseases. Tumours were found in 3/22 patients (breast carcinoma, 1; ovarian carcinoma, 1; thymoma, 1). Nineteen patients were treated with immunotherapy and 16 patients (84%) improved. Histopathology analysis of the leptomeningeal biopsy specimen from one patient revealed a mononuclear infiltrate with macrophages and CD8+ T cells. CONCLUSIONS: GFAP autoimmunity is not rare. The clinical spectrum encompasses meningoencephalitis, myelitis, movement disorders, epilepsy and cerebellar ataxia. Coexisting neurological and systemic autoimmunity are relatively common. Immunotherapy is beneficial in most cases.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Proteína Glial Fibrilar Ácida/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Doenças Autoimunes do Sistema Nervoso/complicações , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/terapia , Encéfalo/diagnóstico por imagem , Neoplasias da Mama/complicações , Carcinoma/complicações , Ataxia Cerebelar/complicações , Ataxia Cerebelar/imunologia , Ataxia Cerebelar/fisiopatologia , Ataxia Cerebelar/terapia , Criança , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/imunologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/terapia , Encefalomielite/complicações , Encefalomielite/imunologia , Encefalomielite/fisiopatologia , Encefalomielite/terapia , Feminino , Proteína Glial Fibrilar Ácida/genética , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia , Imageamento por Ressonância Magnética , Masculino , Meningoencefalite/complicações , Meningoencefalite/imunologia , Meningoencefalite/fisiopatologia , Meningoencefalite/terapia , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Transtornos dos Movimentos/complicações , Transtornos dos Movimentos/imunologia , Transtornos dos Movimentos/fisiopatologia , Transtornos dos Movimentos/terapia , Mielite/complicações , Mielite/imunologia , Mielite/fisiopatologia , Mielite/terapia , Mioclonia/complicações , Mioclonia/imunologiaAssuntos
Potenciais de Ação/fisiologia , Proteínas ELAV , Encefalomielite/diagnóstico , Células Receptoras Sensoriais/fisiologia , Encefalomielite/complicações , Encefalomielite/fisiopatologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/fisiopatologiaRESUMO
The clinical associations of glycine receptor antibodies have not yet been described fully. We identified prospectively 52 antibody-positive patients and collated their clinical features, investigations and immunotherapy responses. Serum glycine receptor antibody endpoint titres ranged from 1:20 to 1:60 000. In 11 paired samples, serum levels were higher than (n = 10) or equal to (n = 1) cerebrospinal fluid levels; there was intrathecal synthesis of glycine receptor antibodies in each of the six pairs available for detailed study. Four patients also had high glutamic acid decarboxylase antibodies (>1000 U/ml), and one had high voltage-gated potassium channel-complex antibody (2442 pM). Seven patients with very low titres (<1:50) and unknown or alternative diagnoses were excluded from further study. Three of the remaining 45 patients had newly-identified thymomas and one had a lymphoma. Thirty-three patients were classified as progressive encephalomyelitis with rigidity and myoclonus, and two as stiff person syndrome; five had a limbic encephalitis or epileptic encephalopathy, two had brainstem features mainly, two had demyelinating optic neuropathies and one had an unclear diagnosis. Four patients (9%) died during the acute disease, but most showed marked improvement with immunotherapies. At most recent follow-up, (2-7 years, median 3 years, since first antibody detection), the median modified Rankin scale scores (excluding the four deaths) decreased from 5 at maximal severity to 1 (P < 0.0001), but relapses have occurred in five patients and a proportion are on reducing steroids or other maintenance immunotherapies as well as symptomatic treatments. The glycine receptor antibodies activated complement on glycine receptor-transfected human embryonic kidney cells at room temperature, and caused internalization and lysosomal degradation of the glycine receptors at 37°C. Immunoglobulin G antibodies bound to rodent spinal cord and brainstem co-localizing with monoclonal antibodies to glycine receptor-α1. Ten glycine receptor antibody positive samples were also identified in a retrospective cohort of 56 patients with stiff person syndrome and related syndromes. Glycine receptor antibodies are strongly associated with spinal and brainstem disorders, and the majority of patients have progressive encephalomyelitis with rigidity and myoclonus. The antibodies demonstrate in vitro evidence of pathogenicity and the patients respond well to immunotherapies, contrasting with earlier studies of this syndrome, which indicated a poor prognosis. The presence of glycine receptor antibodies should help to identify a disease that responds to immunotherapies, but these treatments may need to be sustained, relapses can occur and maintenance immunosuppression may be required.
Assuntos
Anticorpos/sangue , Encefalomielite/imunologia , Rigidez Muscular/imunologia , Mioclonia/imunologia , Receptores de Glicina/imunologia , Rigidez Muscular Espasmódica/imunologia , Adolescente , Adulto , Idoso , Animais , Anticorpos/líquido cefalorraquidiano , Criança , Pré-Escolar , Comorbidade , Encefalomielite/tratamento farmacológico , Encefalomielite/epidemiologia , Encefalomielite/fisiopatologia , Epilepsias Mioclônicas/epidemiologia , Feminino , Glutamato Descarboxilase/imunologia , Células HEK293 , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Rigidez Muscular/tratamento farmacológico , Rigidez Muscular/epidemiologia , Rigidez Muscular/fisiopatologia , Mioclonia/tratamento farmacológico , Mioclonia/epidemiologia , Mioclonia/fisiopatologia , Neoplasias/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Estudos Prospectivos , Ratos , Rigidez Muscular Espasmódica/tratamento farmacológico , Rigidez Muscular Espasmódica/epidemiologia , Rigidez Muscular Espasmódica/fisiopatologia , Síndrome , Adulto JovemRESUMO
Sindbis virus (SINV), the prototype alphavirus, contains a macro domain in the highly conserved N-terminal region of nonstructural protein 3 (nsP3). However, the biological role of the macro domain is unclear. Mutations of amino acids 10 and 24 from asparagine to alanine in the ADP-ribose binding region of the macro domain impaired SINV replication and viral RNA synthesis particularly in neurons, but did not alter binding of poly(ADP-ribose). Mutation at position 10 had the greatest effect and caused nsP3 instability in neurons, decreased SINV-induced death of mature, but not immature neurons, and attenuated virulence in 2 week-old, but not 5 day-old mice. A compensatory mutation at amino acid 31 in the macro domain of nsP3, as well as reversion of mutated amino acid 10, occurred during replication of double mutant SINV in vitro and in vivo. The nsP3 macro domain is important for SINV replication and age-dependent susceptibility to encephalomyelitis.
Assuntos
Neurônios/virologia , Sindbis virus/fisiologia , Sindbis virus/patogenicidade , Proteínas não Estruturais Virais/química , Virulência/genética , Replicação Viral/fisiologia , Animais , Sítios de Ligação/genética , Linhagem Celular , Encefalomielite/genética , Encefalomielite/fisiopatologia , Encefalomielite/virologia , Camundongos , Mutação , Neurônios/metabolismo , Poli Adenosina Difosfato Ribose/genética , Estrutura Terciária de Proteína/genética , Ratos , Sindbis virus/genética , Relação Estrutura-Atividade , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/genéticaRESUMO
BACKGROUND: Hepatitis C virus (HCV) infection is a common and chronic disorder with numerous extrahepatic manifestations. We review the neurologic complications in this article. REVIEW SUMMARY: Neurologic complications can involve the peripheral or the central nervous system. The most frequently reported complication is a subacute, distal, symmetric, sensorimotor polyneuropathy in the presence of mixed cryoglobulinemia (MC). HCV infection is the most common cause of MC. In HCV-infected patients without MC, mononeuropathy or mononeuropathy multiplex is more common. Both ischemic and hemorrhagic strokes, probably related to MC and vasculitis, have been described. More recently, transverse myelopathy and cognitive impairment have been linked to HCV infection, but the association is less certain and needs to be confirmed in larger studies. HCV has also been reported as a possible cause of encephalomyelitis in some cases. Although there are no definite treatment guidelines, immunomodulating agents and antiviral therapy are most often used with favorable outcomes. CONCLUSIONS: HCV infection should be considered in the differential diagnosis of a variety of neurologic disorders. Further studies are necessary to establish the full spectrum of the neurologic complications, identify specific pathophysiologic mechanisms, and provide clear guidelines for management.
Assuntos
Crioglobulinemia/virologia , Hepatite C/complicações , Mielite Transversa/induzido quimicamente , Doenças do Sistema Nervoso Periférico/virologia , Acidente Vascular Cerebral/virologia , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/virologia , Crioglobulinemia/complicações , Encefalomielite/fisiopatologia , Encefalomielite/virologia , Humanos , Mielite Transversa/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Vasculite do Sistema Nervoso Central/fisiopatologia , Vasculite do Sistema Nervoso Central/virologiaRESUMO
Sensory ganglionopathies have a frequent association with neoplastic disorders (paraneoplastic subacute sensory neuronopathy, or SSN) or dysimmune disorders, with drugs, such as cisplatin or pyridoxine, and with inherited disorders with degeneration of dorsal root ganglion cells. Unsteady gait and pseudoathetoid movements of the hand are the distinctive signs encountered in these disorders. The chronic disorders are characterized by non-length-dependent abnormalities of sensory nerve action potentials (SNAPs) and differ from other sensory neuropathies in showing a global, rather than distal, decrease in SNAP amplitudes. This review focuses on recent advances in defining the mechanisms involved in sensory ganglionopathies, and describes the differential diagnosis including the rarely encountered hereditary neuronopathies and the infectious causes.
Assuntos
Gânglios Sensitivos/fisiopatologia , Polineuropatia Paraneoplásica/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Potenciais de Ação , Encéfalo/patologia , Diagnóstico Diferencial , Encefalomielite/diagnóstico , Encefalomielite/patologia , Encefalomielite/fisiopatologia , Humanos , Doença Iatrogênica , Imageamento por Ressonância Magnética , Neurônios Aferentes/fisiologia , Polineuropatia Paraneoplásica/diagnóstico , Doenças do Sistema Nervoso Periférico/terapiaRESUMO
OBJECTIVE: The objective is to report the clinical, electrophysiological, and histopathological features of 16 patients with anti-Hu antibody neuropathy. METHODS: Clinical and electrophysiological data in 16 patients (11 females and 5 males) with positive anti-Hu antibody and nerve biopsy data in 9 cases were analyzed. RESULTS: Cancer was detected in 11 patients, including 9 with small-cell lung cancer. Classical paraneoplastic subacute sensory neuronopathy (SSN) and/or encephalomyelitis (EM) was observed in 7 patients (44%), including 5 with SSN. The most common clinical feature was sensory-motor neuropathy (SMN), accounting for 50% of cases. Though sensory nerve conduction abnormality was the prominent feature in 14 (88%) cases, sensory and motor nerve conduction was abnormal in all cases. Motor nerve conduction findings were typical of axonal degeneration. The most common nerve conduction pattern was that of SMN, with a sensory neuronopathy pattern being observed in only 3 cases. Sural nerve biopsy in 9 patients showed axonal degeneration in all cases and inflammatory cells in 4 cases. CONCLUSIONS: Classical sensory neuronopathy is rarer than expected, both clinically and electrophysiologically. Motor involvement is not uncommon and motor nerve conduction abnormality is frequently seen. A diverse clinical and electrophysiological, and histopathological spectrum was observed in this neuropathy. SIGNIFICANCE: New guidelines for the selection of patients for anti-Hu antibody test are recommended.
Assuntos
Carcinoma de Células Pequenas/patologia , Encefalomielite/fisiopatologia , Proteínas do Tecido Nervoso/imunologia , Polineuropatia Paraneoplásica/fisiopatologia , Proteínas de Ligação a RNA/imunologia , Potenciais de Ação/fisiologia , Potenciais de Ação/efeitos da radiação , Idoso , Anticorpos Anti-Idiotípicos/líquido cefalorraquidiano , Carcinoma de Células Pequenas/metabolismo , Doenças Desmielinizantes/fisiopatologia , Proteínas ELAV , Estimulação Elétrica/métodos , Encefalomielite/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Degeneração Neural/fisiopatologia , Condução Nervosa/fisiologia , Polineuropatia Paraneoplásica/metabolismo , Tempo de Reação/fisiologia , Tempo de Reação/efeitos da radiação , Estudos RetrospectivosAssuntos
Barorreflexo/fisiologia , Encefalomielite/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Neuroblastoma/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Reflexo Anormal/fisiologia , Adolescente , Sistema Nervoso Autônomo/fisiopatologia , Diagnóstico Diferencial , Encefalomielite/fisiopatologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/fisiopatologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Neuroblastoma/fisiopatologia , Neuroblastoma/terapia , Exame Neurológico , Síndromes Paraneoplásicas/fisiopatologiaRESUMO
A 40-year-old Hispanic man with acute lymphoblastic leukemia was treated with a single dose of intrathecal methotrexate 12 mg for prophylaxis against leptomeningeal spread of tumor. The day after methotrexate administration, the patient complained of severe back pain and urinary retention. The diagnosis of encephalomyelitis was made on day 3 after methotrexate administration, and by day 6 mechanical ventilation was begun secondary to ascending paralysis. By day 8 the patient was comatose, with minimal signs of brain activity and little hope for recovery; on day 12 he died. Although neurotoxicity is a frequent complication of methotrexate therapy, fatal acute neurotoxicity is extremely uncommon, especially in adults. The mechanisms of methotrexate toxicity remain unclear, and no effective treatment exists to prevent its occurrence. This patient rapidly progressed from mild neurotoxicity to fatal encephalopathy after one dose of intrathecal methotrexate during his third cycle of chemotherapy. Clinicians should be aware of the signs and symptoms of neurotoxicity during treatment, as well as predisposing factors that put patients receiving methotrexate at risk for neurotoxic effects.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Encefalomielite/induzido quimicamente , Metotrexato/efeitos adversos , Adulto , Antimetabólitos Antineoplásicos/administração & dosagem , Encefalomielite/fisiopatologia , Evolução Fatal , Humanos , Injeções Espinhais , Masculino , Metotrexato/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
Central nervous system demyelination has been described in adults but not in children with chronic inflammatory demyelinating polyneuropathy. We describe a patient with clinical and electrophysiological features consistent with chronic inflammatory demyelinating polyneuropathy who presented at age 5 with an intramedullary spinal cord tumor-like lesion and at age 8, represented with cerebral and spinal demyelinating lesions. Her clinical course and magnetic resonance imaging features were atypical for multiphasic disseminated encephalomyelitis and indistinguishable from multiple sclerosis. To our knowledge, this association has not been previously described in the English literature in childhood.
Assuntos
Doenças do Sistema Nervoso Central/complicações , Esclerose Múltipla/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Encéfalo/patologia , Pré-Escolar , Eletrofisiologia , Encefalomielite/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Tempo de Reação/fisiologia , Medula Espinal/patologiaRESUMO
Paraneoplastic disorders may affect any part of the central or peripheral nervous systems. Although relatively uncommon, these disorders are a significant cause of neurologic morbidity for cancer patients. At least some paraneoplastic syndromes are believed to be caused by an autoimmune reaction against shared tumor-neural antigens. This article summarizes the clinical features of paraneoplastic disorders, the current evidence for autoimmunity, and guidelines for diagnosis and treatment.
Assuntos
Encéfalo/fisiopatologia , Encefalomielite/fisiopatologia , Neoplasias/fisiopatologia , Autoanticorpos/imunologia , Cerebelo/patologia , Doenças Desmielinizantes/patologia , Glicoproteínas/imunologia , Humanos , Síndrome Miastênica de Lambert-Eaton/imunologia , Sistema Límbico/fisiopatologia , Doença dos Neurônios Motores/fisiopatologia , Neoplasias/imunologia , Degeneração Neural/patologiaAssuntos
Encéfalo/patologia , Regiões Determinantes de Complementaridade/genética , Encefalomielite/patologia , Glicoproteínas de Membrana/genética , Vírus da Hepatite Murina/patogenicidade , Proteínas do Envelope Viral/genética , Animais , Encéfalo/virologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Encefalomielite/fisiopatologia , Encefalomielite/virologia , Humanos , Glicoproteínas de Membrana/metabolismo , Camundongos , Vírus da Hepatite Murina/genética , Mutação , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Glicoproteína da Espícula de Coronavírus , Proteínas do Envelope Viral/metabolismo , Replicação ViralAssuntos
Epitopos de Linfócito T/genética , Epitopos Imunodominantes/genética , Glicoproteínas de Membrana/genética , Vírus da Hepatite Murina/patogenicidade , Mutação , Proteínas do Envelope Viral/genética , Animais , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Encefalomielite/imunologia , Encefalomielite/fisiopatologia , Encefalomielite/virologia , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina/genética , Vírus da Hepatite Murina/imunologia , Recombinação Genética , Glicoproteína da Espícula de Coronavírus , Proteínas do Envelope Viral/imunologiaRESUMO
A series of recently published articles by a group of Austrian, German and American neuropathologists have proposed the existence of several different pathogenetic pathways in multiple sclerosis (MS). These studies were based on both biopsy and autopsy material. A review of the available published clinical, imaging and cerebrospinal fluid data suggest that some the cases used in those studies were more probably instances of disseminated encephalomyelitis rather than MS. This has serious implications regarding the specificity and significance of the findings in regard to MS pathogenesis. The specific myelinoclastic sequence and the variable clinical course of MS are determined by the individual's genetic endowment and immunologic history. Regardless of pathogenetic pathway and clinical course, the final pathologic picture of MS is always the same. The MS brain is genetically programmed to produce a unique, pathognomonic change, the plaque with sharply demarcated borders.
Assuntos
Encéfalo/patologia , Esclerose Múltipla/fisiopatologia , Progressão da Doença , Encefalomielite/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Reprodutibilidade dos TestesRESUMO
Interleukin 10 (IL-10) is an important anti-inflammatory cytokine. To examine its role in virus-induced encephalomyelitis, IL-10-deficient (IL-10 -/-) mice were infected with a neurotropic strain of mouse hepatitis virus (JHMV). JHMV-infected IL-10 -/- mice, compared to IL-4 -/- and syngeneic C57BL/6 mice, exhibited increased morbidity and mortality. Virus was cleared from the CNS of all groups of mice with equal kinetics by day 9 postinfection and the lack of either IL-4 or IL-10 did not alter the distribution of viral antigen, suggesting a lack of correlation between viral replication and the increased clinical disease in IL-10 -/- mice. In moribund IL-10 -/- mice, a moderate increase in mononuclear cell infiltration was correlated with increased expression of tumor necrosis factor-alpha, interferon-gamma, and inducible nitric oxide synthase mRNAs. In the small percentage of IL-10 -/- mice that survived, no differences in either demyelination or inflammation were observed. Together, these results suggest that IL-10 is not required for viral clearance, and although it appears to be one of the mechanisms responsible for inhibiting the extent of inflammation in the CNS during acute JHMV infection, it has little role in the eventual resolution of CNS inflammatory responses.
Assuntos
Infecções por Coronavirus/fisiopatologia , Encefalomielite/fisiopatologia , Encefalomielite/virologia , Interleucina-10/fisiologia , Vírus da Hepatite Murina , Animais , Infecções por Coronavirus/mortalidade , Encefalomielite/mortalidade , Interferon gama/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase/fisiologia , Óxido Nítrico Sintase Tipo II , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
Paraneoplastic neurological diseases are a group of neurological disorders associated with neoplastic tumors but not due to tumoral extension, metabolic, infectious, vascular or toxic complications of these tumors or their treatment. In the majority of paraneoplastic neurological disorders, circulating autoantibodies directed against neurons have been found in the serum and/or the CSF suggesting, and in some cases implicating, autoimmunity in the pathophysiology of these diseases. The finding of autoimmune phenomena during the course of paraneoplastic neurological disorders is of importance: from a practical point of view, since the detection of anti-neuronal autoantibodies is of great diagnostic help and should lead to the thorough search of the associated tumor often at an early stage of its development; from a theoretical point of view, these disorders represent a peculiar type of molecular mimicry. Tumoral neontigens having structural homology or identity with neuronal autoantigens elicit autoreactivity. The immunological effector mechanisms involved in the pathophysiology of paraneoplastic syndromes appear to differ according to the disease: autoantibodies are pathogenic in Lambert-Eaton syndrome whereas, in paraneoplastic cerebellar degeneration and in the Hu syndrome, the cellular immune response might play a greater role.
Assuntos
Doenças do Sistema Nervoso/fisiopatologia , Síndromes Paraneoplásicas/fisiopatologia , Encefalomielite/etiologia , Encefalomielite/fisiopatologia , Humanos , Síndrome Miastênica de Lambert-Eaton/etiologia , Síndrome Miastênica de Lambert-Eaton/fisiopatologia , Doenças do Sistema Nervoso/etiologia , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/fisiopatologia , Degenerações Espinocerebelares/etiologia , Degenerações Espinocerebelares/fisiopatologia , Rigidez Muscular Espasmódica/etiologia , Rigidez Muscular Espasmódica/fisiopatologiaRESUMO
Human herpesvirus 6 (HHV-6), the etiologic agent of roseola in young children, has been reported to be detectable in the brain of many neurologically normal adults, although regional localization to plaques of multiple sclerosis has also been demonstrated. Large amounts of this virus were present in multifocal demyelinating white matter lesions of fulminant encephalomyelitis with seizures in a 21-year-old woman with normal immune parameters. Brain biopsy after 3 weeks of neurologic deterioration revealed a viral etiology by light and electron microscopy; the virus was identified as HHV-6 by immunohistochemistry and by polymerase chain reaction (PCR) amplification in biopsy and autopsy specimens.