RESUMO
Defect of metallothionein-III (MT-III) has been reported to be a contributor to the progression of amyotrophic lateral sclerosis (ALS). We explored the expression and effects of MT-III on the motor neurons of spinal cords of ALS model mice (G93A Cu/Zn superoxide dismutase (SOD-1) mutant-transgenic (Tg) mice) using a retrograde viral delivery system. Once-weekly injection of the adenovirus encoding LacZ or MT-III gene was started at the age of 20 weeks, which was the mean age of ALS onset. Gene expression was detected in the motor neurons of the lumbar spinal cord. At 160 days of age (14 days after injection), the mean numbers of Nissl-stained α neurons were 15.42±5.32, 16.50±1.35, and 24.75±4.01 in 5-µm sections of the lumbar hemispinal cord from the untreated group, LacZ group, and MT-III group, respectively. The mean durations of illness were 15.20±5.30 days, 10.33±4.27 days, and 25.71±7.67 days in the untreated group, LacZ group, and MT-III group, respectively. The mean life spans were 163.20±7.72 days, 159.50±3.27 days, and 178.14±12.97 days in the untreated group, LacZ group, and MT-III group, respectively. We demonstrated that MT-III prevents the loss of motor neurons of ALS model mice and prolongs the life span, even when the administration is started at the time of onset.
Assuntos
Esclerose Lateral Amiotrófica/terapia , Neurônios Motores/patologia , Proteínas do Tecido Nervoso/genética , Adenoviridae/genética , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Animais , Morte Celular , Sobrevivência Celular , Terapia Genética , Vetores Genéticos , Metalotioneína 3 , Camundongos , Camundongos Mutantes Neurológicos , Camundongos Transgênicos , Neurônios Motores/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia , Análise de SobrevidaRESUMO
OBJECTIVE: To investigate a target for antibodies in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). BACKGROUND: Pathogenesis of NPSLE may be related to autoantibody-mediated neural dysfunction, vasculopathy, and coagulopathy. However, very few autoantibodies are sensitive and specific to NPSLE because the neuropsychiatric syndromes associated with SLE are diverse in cause and presentation. METHODS: We identified antibodies against brain antigens in the sera of 7 patients with NPSLE and 12 healthy controls by 2-dimensional electrophoresis, followed by Western blotting and liquid chromatography-tandem mass spectrometry (LC-MS/MS), using rat brain proteins as the antigen source. RESULTS: Six antibodies were detected in patients with NPSLE. One of these 6 antibodies was found in antibodies against Rab guanosine diphosphate dissociation inhibitor alpha (alphaGDI) (which is specifically abundant in neurons and regulates synaptic vesicle exocytosis) in patients with NPSLE with psychosis. We tested more samples by 1-dimensional immunoblotting of human recombinant alphaGDI. Positivity of the anti-alphaGDI antibody was significantly higher in patients with NPSLE with psychosis (80%, 4 of 5) than in patients with NPSLE without psychosis (0%, 0 of 13), patients with systemic lupus erythematosus without neuropsychiatric symptoms (5.3%, 1 of 19), patients with multiple sclerosis (0%, 0 of 12), patients with infectious meningoencephalitis (0%, 0 of 13), patients with polyneuropathy (0%, 0 of 10), patients with psychotic syndromes (0%, 0 of 10), and healthy controls (0%, 0 of 12). CONCLUSIONS: We propose that the anti-Rab guanosine diphosphate dissociation inhibitor alpha antibody is a candidate for further exploration as diagnostic marker of psychosis associated with neuropsychiatric systemic lupus erythematosus.
Assuntos
Autoanticorpos/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Transtornos Psicóticos/imunologia , Adolescente , Adulto , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Biomarcadores , Western Blotting , Eletroforese em Gel Bidimensional , Exocitose/imunologia , Feminino , Inibidores de Dissociação do Nucleotídeo Guanina/imunologia , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Masculino , Pessoa de Meia-Idade , Neurônios/imunologia , Transtornos Psicóticos/sangue , Transtornos Psicóticos/etiologia , Vesículas Sinápticas/imunologia , Espectrometria de Massas em TandemRESUMO
We identified the autoantibody against phosphoglycerate mutase 1 (PGAM1), which is a glycolytic enzyme, in sera from multiple sclerosis (MS) patients by proteomics-based analysis. We further searched this autoantibody in sera from patients with other neurological diseases. The prevalence of the anti-PGAM1 antibody is much higher in patients with MS and neuromyelitis optica (NMO) than in those with other neurological diseases and in healthy controls. It was reported that the anti-PGAM1 antibody is frequently detected in patients with autoimmune hepatitis (AIH). Results of our study suggest that the anti-PGAM1 antibody is not only a marker of AIH but also a nonspecific marker of central nervous system autoimmune diseases.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/sangue , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Fosfoglicerato Mutase/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/classificação , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/epidemiologia , Eletroforese em Gel Bidimensional/métodos , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/imunologia , Ratos , Adulto JovemRESUMO
Regular exercise has displayed a beneficial effect on the progression of amyotrophic lateral sclerosis (ALS). However, the mechanism is poorly understood. We here present that regular exercise on a treadmill induces metallothioneins (MTs: MT-1, MT-2, and MT-3) in spinal cords of mice. As MTs are strong scavengers of reactive oxygen species and have some neurotrophic activities, exercise may have some beneficial effects on spinal motor neurons in patients with ALS owing to the induction of MTs. The running exercise on a treadmill for 30 min/day increased the mRNA expression levels of MT-1, MT-2, and MT-3 up to 193%, 298%, and 196%, respectively, of the control value 12 h after the start of exercise. After two weeks of daily exercise, Western blotting of the MTs proteins showed that the expression levels of MT-1/2 and MT-3 reached 173% and 146%, respectively, compared with those in sedentary mice. Running exercise on a treadmill for 2 weeks led to the gradual accumulation of MT proteins in the spinal cords of the mice. In addition, MT-1/2 and MT-3 immunoreactivities were enhanced in astrocytes particularly in the gray matter of the spinal cord. We revealed that regular exercise induced transient increases in the expression levels of MT mRNAs and resulted in accumulation of MT proteins in the spinal cords of the normal mice.
Assuntos
Astrócitos/metabolismo , Terapia por Exercício/métodos , Metalotioneína/metabolismo , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/fisiologia , Medula Espinal/metabolismo , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/terapia , Animais , Astrócitos/citologia , Sobrevivência Celular/fisiologia , Citoproteção/fisiologia , Teste de Esforço , Sequestradores de Radicais Livres/metabolismo , Masculino , Metalotioneína/genética , Metalotioneína 3 , Camundongos , Camundongos Endogâmicos C57BL , Neurônios Motores/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Medula Espinal/citologia , Regulação para Cima/fisiologiaRESUMO
Cerebral ischemia induces Ca(2+) influx into neuronal cells, and activates several proteases including calpains. Since calpains play important roles in neuronal cell death, calpain inhibitors may have potential as drugs for cerebral infarction. ((1S)-1((((1S)-1-Benzyl-3- cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945) is a novel calpain inhibitor that has good membrane permeability and water solubility. We evaluated the effect of SNJ-1945 on the focal brain ischemia induced by middle cerebral artery occlusion (MCAO) in mice. Brain damage was evaluated by assessing neurological deficits at 24 h or 72 h after MCAO and also by examining 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining of brain sections. When injected at 1 h after MCAO, SNJ-1945 at 30 and 100 mg/kg, i.p. decreased the infarction volume and improved the neurological deficits each assessed at 24 h. SNJ-1945 at 100 mg/kg, i.p. also showed neuroprotective effects at 72 h and reduced the number of TUNEL-positive cells at 24 h. SNJ-1945 was able to prevent neuronal cell death even when it was injected at up to 6 h, but not at 8 h, after MCAO. In addition, SNJ-1945 decreased cleaved alpha-spectrin at 6 h and 12 h, and active caspase-3 at 12 h and 24 h in ischemic brain hemisphere. These findings indicate that SNJ-1945 inhibits the activation of calpain, and offers neuroprotection against the effects of acute cerebral ischemia in mice even when given up to 6 h after MCAO. SNJ-1945 may therefore be a potential drug for stroke.
Assuntos
Carbamatos/uso terapêutico , Infarto Cerebral/patologia , Infarto Cerebral/prevenção & controle , Ácidos Docosa-Hexaenoicos/uso terapêutico , Análise de Variância , Animais , Isquemia Encefálica/complicações , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Infarto Cerebral/etiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Marcação In Situ das Extremidades Cortadas/métodos , Masculino , Camundongos , Exame Neurológico , Espectrina/metabolismo , Sais de Tetrazólio , Fatores de TempoRESUMO
The pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) may be related to autoantibody-mediated neural dysfunction, vasculopathy and coagulopathy. We encountered an NPSLE patient whose brain showed characteristic diffuse symmetrical hyperintensity lesions in the cerebral white matter, cerebellum and middle cerebellar peduncles on T2-weighted magnetic resonance (MR) images. In this study, we investigated all the antigens that reacted strongly with autoantibodies in this patient's serum by two-dimensional electrophoresis (2DE), followed by western blotting (WB) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) using rat brain proteins as the antigen source. As a result, we identified four antigens as beta-actin, alpha-internexin, 60 kDa heat-shock protein (Hsp60) and glial fibrillary acidic protein (GFAP). There are several reports on the detection of anti-endothelial cell antibodies (AECAs) in an SLE patients. Recently, one of the antigens reacting with AECAs in SLE patient's sera has been identified as human Hsp60. We speculated that the abnormal findings on brain MR images of our patient may be due to impairment of microcirculation associated with vascular endothelial cell injury mediated by the antibody against Hsp60. This proteomic analysis is a useful tool for identifying autoantigens in autoimmune diseases involving autoantibodies.
Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Encéfalo/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Imageamento por Ressonância Magnética , Proteômica , Actinas/imunologia , Idoso , Animais , Western Blotting , Encéfalo/imunologia , Chaperonina 60 , Cromatografia Líquida , Eletroforese em Gel Bidimensional , Proteína Glial Fibrilar Ácida/imunologia , Humanos , Proteínas de Filamentos Intermediários/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Masculino , Proteômica/métodos , Ratos , Espectrometria de Massas em TandemRESUMO
Metallothioneins (MTs) are small cysteine-rich proteins found widely throughout the mammalian body, including the CNS. MT-1 and -2 protect against reactive oxygen species and free radicals. We investigated the role of MT-1 and -2 using MT-1,-2 knockout (KO) mice. MT-1,-2 KO mice exhibited greater neuronal damage after permanent middle cerebral artery occlusion (MCAO) than wild-type mice. MT-2 mRNA was significantly increased at 6, 12, and 24 h after MCAO in the wild-type mouse brain [as detected by real-time reverse-transcription polymerase chain reaction (RT-PCR)], while MT-1 and MT-3 were decreased at 12 and 24 h. In an immunohistochemical study, MT expression displayed colocalization with glial fibrillary acidic protein (GFAP)-positive cells (astrocytes) in the penumbra area in wild-type mice. Since erythropoietin (EPO) has been reported to induce MT-1 and -2 gene expression in vitro, we examined its effect after permanent MCAO, and explored the possible underlying mechanism by examining MT-1 and -2 induction in vivo. In wild-type mice, EPO significantly reduced both infarct area and volume at 24 h after the ischemic insult. However, in MT-1,-2 KO mice EPO-treatment did not alter infarct volume (vs. vehicle-treatment). In wild-type mice at 6 h after EPO administration, real-time RT-PCR revealed increased MT-1 and -2 mRNA expression in the cerebral cortex (without MCAO). Further, MT-1 and -2 immunoreactivity was increased in the cortex of EPO-treated mice. These findings indicate that MTs are induced, and may be neuroprotective against neuronal damage, after MCAO. Furthermore, EPO is neuroprotective in vivo during permanent MCAO, and this may be at least partly mediated by MTs.
Assuntos
Infarto Encefálico/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Eritropoetina/farmacologia , Metalotioneína/genética , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Infarto Encefálico/metabolismo , Infarto Encefálico/fisiopatologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Citoproteção/efeitos dos fármacos , Citoproteção/fisiologia , Eritropoetina/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Proteína Glial Fibrilar Ácida/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Metalotioneína/metabolismo , Metalotioneína 3 , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Degeneração Neural/tratamento farmacológico , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Regulação para Cima/genéticaRESUMO
We investigated the presence of autoantibodies against glutamate receptor (GluR) epsilon2 in serum and cerebrospinal fluid (CSF) samples from 12 consecutive patients with acute encephalitis/encephalopathy by immunoblotting using recombinant GluR epsilon2 as antigen. In 4 patients, IgM autoantibodies against GluR epsilon2 were detected in CSF in the early phase of the disease but were not detectable after several months. Seizures and psychiatric symptoms were noted during the acute phase of the disease in these 4 patients, who showed various degrees of residual amnesia. Immunotherapy was performed on 3 patients (patients 1, 3 and 4), and they showed marked improvements. Immunohistochemistry using these patients' sera showed that immunoreactivity is specifically detected in the cytoplasm of rat hippocampal and cortical neurons. The clinical features and neuroimaging findings of patients with IgM autoantibodies against GluR epsilon2 in CSF resemble those of patients with reversible autoimmune limbic encephalitis.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Encefalite Límbica/sangue , Encefalite Límbica/imunologia , Receptores de Glutamato/imunologia , Adolescente , Adulto , Idoso , Autoanticorpos/líquido cefalorraquidiano , Doenças Autoimunes/sangue , Doenças Autoimunes/líquido cefalorraquidiano , Doenças Autoimunes/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Humanos , Imunoglobulina M/sangue , Encefalite Límbica/líquido cefalorraquidiano , Encefalite Límbica/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Estudos RetrospectivosRESUMO
The neuroprotective effect of cilostazol, an antiplatelet drug, was examined after 24 h permanent middle cerebral artery (MCA) occlusion in mice, and explored the possible underlying mechanism by examining metallothionein (MT)-1 and -2 induction in vivo. Cilostazol (30 mg/kg) was intraperitoneally administered at 12 h before, 1 h before, and just after MCA occlusion. Mice were euthanized at 24 h after the occlusion, and the neuronal damage was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cilostazol significantly reduced the infarct area and volume, especially in the cortex. Real-time RT-PCR revealed increased mRNA expressions for MT-1 and -2 in the cortex of normal brains at 6 h after cilostazol treatment without MCA occlusion. MT-1 and -2 immunoreactivity was also increased in the cortex of such mice, and this immunoreactivity was observed in the ischemic hemisphere at 24 h after MCA occlusion (without cilostazol treatment). The strongest MT-1 and -2 immunoreactivity was detected in MCA-occlused mice treated with cilostazol [in the peri-infarct zone of the cortex (penumbral zone)]. These findings indicate that cilostazol has neuroprotective effects in vivo against permanent focal cerebral ischemia, especially in the penumbral zone in the cortex, and that MT-1 and -2 may be partly responsible for these neuroprotective effects.
Assuntos
Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Metalotioneína/biossíntese , Fármacos Neuroprotetores/farmacologia , Tetrazóis/farmacologia , Animais , Córtex Cerebral/patologia , Cilostazol , Indução Enzimática/efeitos dos fármacos , Imuno-Histoquímica , Infarto da Artéria Cerebral Anterior/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Artéria Cerebral Média/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We report on an autopsy case of a 62-year-old Japanese woman with a 2.5-year history of axial dystonia. She presented with a form of axial dystonia reminiscent of Pisa syndrome. The pathophysiological mechanism underlying forms of axial dystonia remains to be elucidated. We report here the histopathological findings of a multiple system atrophy of parkinsonian predominance (MSA-P) patient with Pisa syndrome.
Assuntos
Transtornos Parkinsonianos/diagnóstico , Putamen , Atrofia/patologia , Distonia/complicações , Distonia/diagnóstico , Evolução Fatal , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/patologia , Transtornos Parkinsonianos/complicações , Putamen/diagnóstico por imagem , Putamen/patologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
In a previously described case of Waldenstrom's Macroglobulinemia, complicated by polyneuropathy, the IgM/lambda monoclonal antibody (mAb) was highly reactive with myelin basic protein (MBP). Given our demonstration that V lambda x, a recently described murine lambda variable region gene product, can itself bind MBP as well as confer MBP reactivity to an Ab, the possibility of a shared idiotypy between murine V lambda x and this human IgM/lambda anti-MBP was investigated. We characterized the epitope specificity of the macroglobulinemia patient's MBP-reactive IgM/lambda using indirect ELISA procedures with MBP, a citrullinated isomer of MBP termed C8, or peptide fragments of MBP as the coating antigens and monospecific Ab to V lambda x as the secondary Ab. The patient's MBP-reactive IgM/lambda was recognized by Ab specific for V lambda x and, like murine mAb containing V lambda x bound human MBP but not MBP-C8 nor other common autoantigens such as DNA, thyroglobulin, or actin. The anti-MBP reactivity was selective for MBP peptide 90-170 and preferentially recognized MBP peptide 84-96. Thus, the patient's macroglobulin and perhaps certain other human Ab with a 'V lambda x idiotype' bind to MBP peptide residues 84-96, an immunodominant peptide in multiple sclerosis patients. Such binding may be involved in the pathogenesis of neural damage in patients with neuroimmunologic disorders related to plasma cell dyscrasias or autoimmunity.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Epitopos Imunodominantes/imunologia , Imunoglobulina M/sangue , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Polineuropatias/imunologia , Macroglobulinemia de Waldenstrom/imunologia , Animais , Autoanticorpos/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Macroglobulinas/imunologia , Fragmentos de Peptídeos/imunologia , CoelhosAssuntos
Rigidez Muscular Espasmódica , Autoanticorpos , Diagnóstico Diferencial , Glutamato Descarboxilase/imunologia , Humanos , Proteínas do Tecido Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso , Prognóstico , Rigidez Muscular Espasmódica/etiologia , Ácido gama-Aminobutírico/fisiologiaRESUMO
Paraneoplastic neurological syndrome is a rare disorder caused by the secondary effects of cancer and is thought to be immune-mediated. A high titer of autoantibodies in the patient's serum and cerebrospinal fluid, directed against both neurons and tumor, have been detected in some forms of this syndrome. These autoantibodies are considered the result of an immunological response to tumor and may cross-react with cells of the nervous system, causing neuronal damage. Specific forms of this syndrome are often associated with specific antineuronal antibodies and tumors. The onset of neurological symptoms and detection of these antibodies often precede the diagnosis of the tumor; therefore, detection of these antibodies greatly assists the diagnosis of this syndrome and prompts investigations for the underlying tumor. The pathogenicity of these antineuronal antibodies has been proven in only a few cases, such as that of anti-voltage gated calcium-channel antibodies in Lambert-Eaton myasthenic syndrome. The selective involvement of specific types of neurons has not been fully elucidated. The target spectrum of some of these antineuronal antibodies correlates well with the neurological symptoms, but that of others is wider than expected from the symptoms. Interesting evidence has suggested that these antionconeuronal antibodies can suppress tumor growth. The discovery of new antibodies and characterization of target molecules have been reported with advances in the field of molecular biology. A more detailed understanding of the relationship between the cancer and the neural involvement from the molecular biological standpoint may lead to rational tumor therapy and elucidation of the mechanism of neuronal death. Here, major clinical forms with well-known antineuronal antibodies and specific tumors are reviewed; for each antineuronal antibody, the target antigens and its putative role in the pathogenesis of this syndrome are described.
Assuntos
Anticorpos Antineoplásicos/imunologia , Antígenos de Neoplasias/imunologia , Autoanticorpos/metabolismo , Neurônios/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Autoanticorpos/sangue , Carcinoma de Células Pequenas/imunologia , Morte Celular , Humanos , Neoplasias Pulmonares/imunologiaAssuntos
Neoplasias/complicações , Doenças do Sistema Nervoso/etiologia , Polineuropatia Paraneoplásica/etiologia , Autoanticorpos/análise , Humanos , Neoplasias/imunologia , Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/imunologia , Polineuropatia Paraneoplásica/imunologia , Linfócitos T Citotóxicos/imunologiaAssuntos
Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Antineoplásicos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/fisiopatologia , Troca Plasmática , Prognóstico , Esteroides/uso terapêuticoAssuntos
Antígenos de Neoplasias , Proteínas do Tecido Nervoso , Síndromes Paraneoplásicas do Sistema Nervoso , Autoanticorpos , Diagnóstico Diferencial , Humanos , Imunoglobulina G , Antígeno Neuro-Oncológico Ventral , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/fisiopatologia , Prognóstico , Proteínas de Ligação a RNA/imunologia , Ribonucleoproteínas/imunologiaRESUMO
OBJECTIVE: To report neuropathologic features of argyrophilic inclusions in the anterior horn cells, motor cortex Betz cells, and neurons of the medullary reticular formation, spinal posterior horn, and Clarke column in a Japanese case of familial amyotrophic lateral sclerosis with I113T substitution in exon 4 of the copper-zinc superoxide dismutase (SOD1) gene. METHODS AND RESULTS: These inclusions were stained pale pink on the hematoxylin-eosin stain and dark on the Bielschowsky stain. They were positive for antibodies to phosphorylated neurofilaments, ubiquitin, and SOD1. On electron microscopy, they consisted of abundant intermediate filaments of 10 to 20 nm in diameter with disordered array indicating neurofilaments. CONCLUSION: These findings suggest that the I113T mutation induces accumulation of neurofilaments and SOD1 in the central nervous system neurons.
Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Corpos de Inclusão/patologia , Proteínas de Neurofilamentos/análise , Superóxido Dismutase/genética , Idoso , Esclerose Lateral Amiotrófica/enzimologia , Saúde da Família , Evolução Fatal , Humanos , Corpos de Inclusão/enzimologia , Corpos de Inclusão/ultraestrutura , Masculino , Microscopia Eletrônica , Neurônios Motores/química , Neurônios Motores/enzimologia , Neurônios Motores/patologia , Degeneração Neural/enzimologia , Degeneração Neural/patologia , Mutação Puntual , Superóxido Dismutase/análiseRESUMO
We report the case of 5-year-old girl with acute disseminated encephalomyelitis (ADEM), whose MRI showed bilateral thalamic lesions. She suffered from left optic neuritis and generalized convulsion. Examination of cerebrospinal fluid revealed elevation of mononuclear cells and myelin basic protein (MBP). MRI showed the swelling of left optic nerve and high intensity areas of bilateral thalamus. After methylprednisolone pulse therapy, her visual acuity was dramatically improved and bilateral thalamic lesions were decreased. In childhood, bilateral thalamic lesions were observed in several diseases, such as viral encephalitis. Reye syndrome, Leigh syndrome and acute necrotizing encephalopathy. Demyelinating diseases involving the grey matter were very rare, but we must consider the presence of symmetrical thalamic involvement in patients with ADEM.
Assuntos
Encefalomielite Aguda Disseminada/diagnóstico , Imageamento por Ressonância Magnética , Neurite Óptica/etiologia , Tálamo/patologia , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Nervo Óptico/patologia , Resultado do TratamentoRESUMO
To determine whether the nocturnal decrease in arginine vasopressin (AVP) secretion into the plasma, found in a patient with multiple system atrophy (MSA) reported previously, is a usual finding in MSA, the plasma AVP concentrations in 13 patients with MSA were measured every 4 hours during a 24 hour period. The plasma AVP concentrations in these patients showed significant daily variations and were the lowest during the night. This finding indicates that patients with MSA often exhibit nocturnal decrease in AVP secretion into the plasma. The results suggest the possibility that the system responsible for the daily variations in AVP secretion is involved in MSA.