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1.
Biochem Biophys Rep ; 7: 45-51, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29114578

RESUMO

BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory disease caused by the aquaporin (AQP)-4-antibody. Pathological studies on NMO have revealed extensive astrocytic damage, as evidenced by the loss of AQP4 and glial fibrillary acidic protein (GFAP), specifically in perivascular regions with immunoglobulin and complement depositions, although other pathological patterns, such as a loss of AQP4 without astrocyte destruction and clasmatodendrosis, have also been observed. Previous studies have shown that complement-dependent antibody-mediated astrocyte lysis is likely a major pathomechanism in NMO. However, there are also data to suggest antibody-mediated astrocyte dysfunction in the absence of complement. Thus, the importance of complement inhibitory proteins in complement-dependent AQP4-antibody-mediated astrocyte lysis in NMO is unclear. In most of the previous studies, the complement and target cells (astrocytes or AQP4-transfected cells) were derived from different species; however, the complement inhibitory proteins that are expressed on the cell surface cannot protect themselves against complement-dependent cytolysis unless the complements and complement inhibitory proteins are from the same species. To resolve these issues, we studied human astrocytes in primary culture treated with AQP4-antibody in the presence or absence of human complement and examined the effect of complement inhibitory proteins using small interfering RNA (siRNA). METHODS: Purified IgG (10 mg/mL) was obtained from 5 patients with AQP4-antibody-positive NMO, 3 patients with multiple sclerosis (MS), and 3 healthy controls. Confluent human astrocytes transfected with Venus-M1-AQP4-cDNA were incubated with IgG (5% volume). After washing, we cultured the cells with human complements with or without heat inactivation. We observed time-lapse morphological and immunohistochemical changes using a fluorescence microscope. We also evaluated cytotoxicity using a propidium iodide (PI) kit and the lactate dehydrogenase (LDH) assay. RESULT: AQP4-antibody alone caused clustering and degradation followed by endocytosis of membraneous AQP4, thereby resulting in decreased cellular adherence and the shrinkage of astrocytic processes. However, these changes were partially reversed by the removal of IgG in culture. In contrast, following the application of AQP4-antibody and non-heated human complements, the cell bodies and nuclei started to swell. At 3 h, most of the astrocytes had lost mobility and adherence and were eventually destroyed or had swollen and were then destroyed. In addition, the remaining adherent cells were mostly PI-positive, indicating necrosis. Astrocyte lysis caused by rabbit complement occurred much faster than did cell lysis with human complement. However, the cell lysis was significantly enhanced by the transfection of astrocytes with siRNA against human CD55 and CD59, which are major complement inhibitory proteins on the astrocyte membrane. AQP4-antibody-negative IgG in MS or control did not induce such changes. CONCLUSION: Taken together, these findings suggest that both complement-dependent and complement-independent AQP4-antibody-mediated astrocytopathies may operate in NMO, potentially contributing to diverse pathological patterns. Our results also suggest that the effect of complement inhibitory proteins should be considered when evaluating AQP4-antibody-mediated cytotoxicity in AQP4-expressing cells.

2.
J Neurol ; 262(4): 831-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25605435

RESUMO

Multiple sclerosis (MS) is relatively common in the West, but rare in Japan. In the literature, there are few comparative data regarding disease severity throughout the world. The objective of this study was to compare disability in patients from a UK and a Japanese MS cohort. We retrospectively analysed the clinical features of patients with MS from a UK and Japanese MS centre. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Expanded Disability Status Scale score according to disease duration, was used as a marker of disease severity. One thousand one hundred forty-eight UK patients and 104 Japanese patient were identified representing the relative national prevalence. Demographics and disease duration did not differ between the groups. Median MSSS was significantly different between the two groups (Japan 3.34 vs. UK 5.87, p < 0.001). Primary progressive MS was more common in the UK (12.9%) than in the Japanese cohort (3%, p = 0.044). The majority of Japanese patients (83.7% vs. UK 17%) had been exposed to disease modifying treatments (DMTs). Exposure to DMTs did not show a significant effect on disability. In conclusion, this study suggests that MS in Japan may be associated with less disability than in UK. More Japanese patients were treated with DMTs. Differences in treatments do not seem to explain the disparity in disability severity. This suggests either genetic or environmental influences on disease severity.


Assuntos
Esclerose Múltipla/epidemiologia , Índice de Gravidade de Doença , Adulto , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapia , Reino Unido/epidemiologia , Adulto Jovem
3.
Neurology ; 77(7): 652-8, 2011 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-21813781

RESUMO

OBJECTIVE: To assess the features of pain and its impact on the health-related quality of life (HRQOL) in neuromyelitis optica (NMO). METHODS: We analyzed 37 patients with NMO or NMO spectrum disorders seen at the Department of Neurology, Tohoku University Hospital, Sendai, Japan, during the period from November 2008 to February 2009. A total of 35 of them were aquaporin-4 antibody-positive. We used Short Form Brief Pain Inventory (BPI) to assess pain and Short Form 36-item (SF-36) health survey to evaluate the HRQOL. Fifty-one patients with multiple sclerosis (MS) were also studied for comparison. RESULTS: Pain in NMO (83.8%) was far more common than in MS (47.1%). The Pain Severity Index score in BPI was significantly higher in NMO than in MS, and patients' daily life assessed by BPI was highly interfered by pain in NMO as compared with MS. Pain involving the trunk and both legs was much more frequent in NMO than in MS. SF-36 scores in NMO were lower than MS, especially in bodily pain. CONCLUSION: Our study showed that pain in NMO is more frequent and severe than in MS and that pain has a grave impact on NMO patients' daily life and HRQOL. Therapy to relieve pain is expected to improve their HRQOL.


Assuntos
Neuromielite Óptica/psicologia , Dor/psicologia , Qualidade de Vida/psicologia , Adulto , Estudos Transversais , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/psicologia , Neuromielite Óptica/complicações , Neuromielite Óptica/fisiopatologia , Dor/complicações , Dor/fisiopatologia , Medição da Dor , Índice de Gravidade de Doença , Inquéritos e Questionários
4.
Neurology ; 75(3): 208-16, 2010 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-20644148

RESUMO

INTRODUCTION: Loss of aquaporin 4 and glial fibrillary acidic protein (GFAP) with necrosis and demyelination is a prominent pathologic feature of neuromyelitis optica (NMO). However, the clinicopathologic significance of astrocytic damage and its relation with demyelination are unknown. OBJECTIVE: To analyze clinical and pathologic values of a CSF biomarker of astrocytic damage in NMO. METHODS: We measured the levels of GFAP, S100B, myelin basic protein (MBP), and neurofilament H (NF-H) in CSF obtained from patients with NMO (n = 33), multiple sclerosis (MS) (n = 27), acute disseminated encephalomyelitis (ADEM), ischemia, meningitis, and other neurologic disease controls (OND). RESULTS: The CSF-GFAP levels during relapse in NMO (2,476.6 +/- 8,815.0 ng/mL) were significantly higher than those in MS (0.8 +/- 0.4 ng/mL) and OND (0.7 +/- 0.5 ng/mL), and much beyond those in ADEM (14.1 +/- 27.4 ng/mL). The sensitivity and specificity of CSF-GFAP for NMO was 90.9% and 76.9% in all, but the specificity improved above 90% in cases limited to demyelinating diseases. CSF-S100B showed a similar trend but was less remarkable. In contrast, MBP and NF-H are not different between NMO and MS. Following treatments, the CSF-GFAP rapidly decreased to a normal level, but CSF-MBP remained high. There were strong correlations between the CSF-GFAP, CSF-S100B, or CSF-MBP levels and Expanded Disability Status Scale (EDSS) or spinal lesion length in the acute phase (r > 0.6). Only CSF-GFAP correlated with EDSS at 6-month follow-up (r = 0.51) in NMO. CONCLUSIONS: Astrocytic damage reflected by elevated CSF glial fibrillary acidic protein is a clinically relevant, primary pathologic process in neuromyelitis optica, and is far more severe than demyelination.


Assuntos
Astrócitos/patologia , Sistema Nervoso Central/patologia , Proteína Glial Fibrilar Ácida/sangue , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Neuromielite Óptica/líquido cefalorraquidiano , Neuromielite Óptica/patologia , Adulto , Idoso , Anticorpos/sangue , Aquaporina 4/imunologia , Astrócitos/metabolismo , Biomarcadores/líquido cefalorraquidiano , Sistema Nervoso Central/imunologia , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/líquido cefalorraquidiano , Doenças Desmielinizantes/tratamento farmacológico , Avaliação da Deficiência , Encefalomielite Aguda Disseminada/líquido cefalorraquidiano , Encefalomielite Aguda Disseminada/tratamento farmacológico , Encefalomielite Aguda Disseminada/patologia , Feminino , Seguimentos , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/patologia , Proteína Básica da Mielina/líquido cefalorraquidiano , Fatores de Crescimento Neural/líquido cefalorraquidiano , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/patologia , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Neuromielite Óptica/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/líquido cefalorraquidiano , Estatísticas não Paramétricas
5.
Neurology ; 74(19): 1543-5, 2010 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-20458072

RESUMO

BACKGROUND: Neuromyelitis optica (NMO) is a disease of the CNS characterized by severe optic neuritis and longitudinally extended transverse myelitis. Recent studies suggest that anti-aquaporin-4 (AQP4) antibodies, NMO-specific biomarkers, are pathogenic and target AQP4-expressing astrocytes in NMO, although an additional event (T-cell response or infection) should occur for anti-AQP4 antibodies and complements to pass through the blood-brain barrier and cause the CNS lesions. AQP4 is the major water channel in the CNS, but it is also expressed in fast-twitch skeletal muscle fibers. However, muscle diseases have not been described in NMO. METHODS: We retrospectively examined the serologic database of 733 cases of NMO with anti-AQP4 antibody at the Department of Neurology, Tohoku University School of Medicine. The serum samples were sent to our laboratory for testing anti-AQP4 antibody from around the country during the period from 2006 to 2009. RESULTS: We found 3 anti-AQP4 antibody-positive female patients (7, 34, and 67 years old) with NMO who had episodes of prominent hyperCKemia (12,520, 19,415, and 59,660 IU/L) with general fatigue some weeks before the onset of optic neuritis. HyperCKemia was transient without any treatment in all patients, but recurred once in one of them. CONCLUSIONS: These cases suggest that hyperCKemia may be involved in the pathogenesis of neuromyelitis optica (NMO) in a fraction of patients. The causes of transient hyperCKemia are unknown. Further studies are needed to know the frequency of hyperCKemia in NMO and clarify its pathogenic role.


Assuntos
Creatina Quinase/sangue , Doenças Musculares/sangue , Doenças Musculares/epidemiologia , Neuromielite Óptica/epidemiologia , Adulto , Idoso , Aquaporina 4/imunologia , Autoanticorpos/análise , Autoanticorpos/sangue , Biomarcadores/análise , Biomarcadores/sangue , Criança , Comorbidade , Creatina Quinase/análise , Feminino , Humanos , Fadiga Muscular/imunologia , Debilidade Muscular/sangue , Debilidade Muscular/enzimologia , Debilidade Muscular/epidemiologia , Músculo Esquelético/enzimologia , Músculo Esquelético/imunologia , Músculo Esquelético/fisiopatologia , Doenças Musculares/enzimologia , Neuromielite Óptica/imunologia , Neuromielite Óptica/fisiopatologia , Estudos Retrospectivos , Regulação para Cima/fisiologia
7.
Mult Scler ; 15(6): 695-700, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19435750

RESUMO

BACKGROUND: The corpus callosum is commonly involved in multiple sclerosis (MS), but the characteristics of callosal lesions in neuromyelitis optica (NMO) are unknown.ObjectiveTo reveal the features of callosal lesions in NMO in comparison to MS. METHODS: We retrospectively reviewed the medical records and the brain magnetic resonance imaging films of 56 patients with MS and 22 patients with NMO. RESULTS: In MS, 36 (64.3%) of 56 patients had callosal lesions, but only four patients had acute lesions. All such acute lesions were small, isolated and non-edematous, and the intensity was homotonic. Chronic lesions were observed in 34 patients with MS, and 32 (94%) of them presented small lesions located at the callosal lower margin ("hemi-oval pattern"). Meanwhile, four (18.2%) patients with NMO had callosal lesions, and three of them had acute lesions. Those acute lesions were multiple, large edematous ones with heterogeneous intensity ("marbled pattern"). In the chronic stage, the lesions shrank or disappeared. CONCLUSIONS: Acute large, edematous callosal lesions occasionally occur in NMO. Similar to longitudinally extensive transverse myelitis, such callosal lesions may reflect severe edematous inflammation in NMO, and may provide additional evidence that the pathogenesis in NMO is different from that in MS.


Assuntos
Edema Encefálico/patologia , Corpo Caloso/patologia , Imageamento por Ressonância Magnética , Esclerose Múltipla/patologia , Neuromielite Óptica/patologia , Doença Aguda , Adulto , Edema Encefálico/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Neuromielite Óptica/imunologia , Estudos Retrospectivos , Índice de Gravidade de Doença
8.
J Neurol Neurosurg Psychiatry ; 80(5): 575-7, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19372295

RESUMO

BACKGROUND: Neuromyelitis optica (NMO) is a neurological inflammatory disease associated with autoimmunity to aquaporin 4, predominantly localised in astrocytic foot processes. Recent studies have revealed that loss of aquaporin 4 and glial fibrillar acidic protein (GFAP) is a prominent feature of NMO lesions, suggesting astrocytic impairment. OBJECTIVE: To reveal a useful clinical biomarker of NMO. METHODS: Enzyme-linked immunosorbent assays were carried out for astrocytic markers GFAP and S100B in CSFs, obtained from the patients with NMO (n = 10) and multiple sclerosis (MS) (n = 10) manifesting acute myelitis, acute disseminated encephalomyelitis (ADEM) (n = 3), spinal infarction (n = 3), and other neurological diseases (OND) (n = 5). RESULTS: The CSF-GFAP levels during relapse in NMO (7666.0 (SD 15 266.5) ng/ml) were significantly over several thousand times higher than those in MS (0.7 (1.5)) or OND (0.6 (0.3)), and considerably higher than those in spinal infarction (354.7 (459.0)) and ADEM (0.4 (0.2)). They returned close to normal levels along with clinical improvement soon after corticosteroid therapy in NMO. There were strong correlations between the CSF-GFAP or S100B levels and expanded disability status scales or spinal lesion length in NMO (r>0.9). CONCLUSIONS: CSF-GFAP and S100B may be clinically useful biomarkers in NMO, and astrocytic damage is strongly suggested in the acute phase of NMO.


Assuntos
Astrócitos/patologia , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Neuromielite Óptica/líquido cefalorraquidiano , Adulto , Idoso , Aquaporina 4/genética , Biomarcadores , Encefalomielite Aguda Disseminada/líquido cefalorraquidiano , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas S100/líquido cefalorraquidiano , Medula Espinal/patologia
10.
J Neurol Neurosurg Psychiatry ; 79(9): 1075-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18420727

RESUMO

BACKGROUND: Intractable hiccup and nausea (IHN) are unique symptoms in neuromyelitis optica (NMO). Recent studies have strongly suggested that the pathogenesis of NMO is closely associated with anti-aquaporin-4 (AQP4) antibody. However, clinical implications of IHN and the relationship with anti-AQP4 antibody remain unknown. METHODS: The past medical records of 35 patients with seropositivity for anti-AQP4 antibody were reviewed. We also followed the titres of anti-AQP4 antibody in a patient with NMO, who had newly developed IHN. RESULTS: Of the 35 patients, 15 patients (43%) had episodes of IHN. There was a total of 35 episodes of IHN in these 15 patients and, of the 35 episodes, hiccup was seen in 23 episodes (66%) and nausea was seen in 28 episodes (80%). The IHN frequently preceded (54%) or accompanied (29%) myelitis or optic neuritis. The IHN was often preceded by an episode of viral infection. The titres of anti-AQP4 antibody were remarkably increased when the intractable hiccup appeared in a case. CONCLUSIONS: IHN could be a clinical marker for the early phase of an exacerbation. Careful observation may be needed when INH is seen in patients with NMO, and the early initiation of the treatment could prevent subsequent neurological damage.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Aquaporina 4/imunologia , Soluço/diagnóstico , Soluço/epidemiologia , Náusea/diagnóstico , Náusea/epidemiologia , Neuromielite Óptica , Doença Aguda , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/imunologia , Prevalência
11.
J Neurol ; 255(2): 163-70, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18231705

RESUMO

OBJECTIVE: To delineate the MRI features that distinguish neuromyelitis optica (NMO) from multiple sclerosis (MS). METHODS: We compared the distribution of the spinal cord lesions by analyzing 1) lesion area, 2) lesion density (by superimposing the lesions onto the standard sections of the cervical and thoracic cord with appropriate transparencies using computer software), and 3) T1-hypointensity in axial sections of MRI in NMO and MS. RESULTS: In NMO, 60-70% of the cervical and thoracic cord MRI lesions occupied more than half of the cord area and mainly involved the central gray matter in the acute stage. In the chronic stage, half or more of the lesions were localized at the central gray matter region. The lesion superimposition analysis also revealed much higher densities in the central gray matter region than in the peripheral white matter regions. Two patients with NMO had T1-hypointense lesions in the central region. In contrast, over 80% of the lesions in MS were localized in the lateral and posterior white matter regions of the cord in the chronic as well as acute stage. Lesion densities were much higher in the lateral and posterior white matter regions than in the central gray matter region. None of the lesions in MS were T1-hypointense. CONCLUSIONS: These MRI findings strongly suggest a preferential involvement in the spinal central gray matter in NMO which is distinct from MS.


Assuntos
Neuromielite Óptica/patologia , Medula Espinal/patologia , Adulto , Idoso , Feminino , Humanos , Imunoglobulina G/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Clin Exp Immunol ; 150(3): 397-406, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17900307

RESUMO

Intravenous immunoglobulin (IVIg) preparations are reportedly effective in inhibiting the relapse of multiple sclerosis (MS), but few reports have investigated the effect of IVIg on dendritic cells (DCs), which are thought to be involved in such relapses. In the system that uses monokines to differentiate DCs from peripheral blood monocytes (Mo-DCs), we investigated the effect of immunoglobulin G (IgG) on these antigen-presenting cells. Using monocytes derived from healthy volunteers, IgG partially inhibited the expression of CD1a, a marker of immature DCs (imDCs), and CD40 and CD80, which are markers associated with T cell activation. In contrast, IgG enhanced the expression of CD83, a marker of mature DCs (mDCs). Furthermore, IgG markedly inhibited the expression of CD49d [very late activation antigen (VLA)-4 alpha4-integrin], the adhesion molecule required for mDCs to cross the blood-brain barrier. We obtained similar results on all the aforementioned cell surface molecules investigated in both healthy controls and MS patients. In addition, IgG treatment of cells from both healthy controls and MS patients inhibited the production of interleukin (IL)-12, a cytokine associated with mDC differentiation, but did not inhibit the production of IL-10. These results suggested the possibility that IgG treatment, apart from its known ability to regulate inflammation, may help to prevent relapses of MS by controlling DC maturation, consequently inhibiting invasion of immune cells into the central nervous system and affecting the cytokine profile.


Assuntos
Células Dendríticas/imunologia , Imunoglobulina G/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Adulto , Antígenos CD/metabolismo , Diferenciação Celular/imunologia , Células Cultivadas , Células Dendríticas/citologia , Feminino , Humanos , Imunoglobulinas Intravenosas/imunologia , Integrina alfa4/metabolismo , Interleucina-10/biossíntese , Interleucina-12/biossíntese , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/imunologia
13.
Mult Scler ; 13(8): 968-74, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17623727

RESUMO

Neuromyelitis optica (NMO) is a relapsing neurologic disease characterized by severe optic neuritis and transverse myelitis. A disease-modifying therapy for NMO has not been established. We retrospectively analysed the effect of low-dose corticosteroid (CS) monotherapy on the annual relapse rate in nine patients with NMO. We divided the clinical course in each patient into two periods; the CS Period in which CS was administered, and the No CS Period in which CS was not administered. Periods related to other immunological therapies, such as high-dose methylprednisolone, immunosuppressants, interferon-beta, and plasma exchange, were excluded. As a result, the annual relapse rate during the CS Periods [median, 0.49 (range, 0-1.31)] was found to be significantly lower than that during the No CS Periods [1.48 (0.65-5.54)]. As for the dose of CS, relapses occurred significantly more frequently with ;10 mg/day or less' than with ;over 10 mg/day' (odds ratio: 8.75). The results of the present study suggest a beneficial effect of low-dose CS monotherapy in reducing relapses in NMO.


Assuntos
Corticosteroides/uso terapêutico , Neuromielite Óptica/prevenção & controle , Adulto , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos
14.
Brain ; 130(Pt 5): 1224-34, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17405762

RESUMO

Neuromyelitis optica (NMO) is an inflammatory and necrotizing disease clinically characterized by selective involvement of the optic nerves and spinal cord. There has been a long controversy as to whether NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recently, an NMO-specific antibody (NMO-IgG) was found in the sera from patients with NMO, and its target antigen was identified as aquaporin 4 (AQP4) water channel protein, mainly expressed in astroglial foot processes. However, the pathogenetic role of the AQP4 in NMO remains unknown. We did an immunohistopathological study on the distribution of AQP4, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), activated complement C9neo and immunoglobulins in the spinal cord lesions and medulla oblongata of NMO (n = 12), MS (n = 6), brain and spinal infarction (n = 7) and normal control (n = 8). The most striking finding was that AQP4 immunoreactivity was lost in 60 out of a total of 67 acute and chronic NMO lesions (90%), but not in MS plaques. The extensive loss of AQP4 accompanied by decreased GFAP staining was evident, especially in the active perivascular lesions, where immunoglobulins and activated complements were deposited. Interestingly, in those NMO lesions, MBP-stained myelinated fibres were relatively preserved despite the loss of AQP4 and GFAP staining. The areas surrounding the lesions in NMO had enhanced expression of AQP4 and GFAP, which reflected reactive gliosis. In contrast, AQP4 immunoreactivity was well preserved and rather strongly stained in the demyelinating MS plaques, and infarcts were also stained for AQP4 from the very acute phase of necrosis to the chronic stage of astrogliosis. In normal controls, AQP4 was diffusely expressed in the entire tissue sections, but the staining in the spinal cord was stronger in the central grey matter than in the white matter. The present study demonstrated that the immunoreactivities of AQP4 and GFAP were consistently lost from the early stage of the lesions in NMO, notably in the perivascular regions with complement and immunoglobulin deposition. These features in NMO were distinct from those of MS and infarction as well as normal controls, and suggest that astrocytic impairment associated with the loss of AQP4 and humoral immunity may be important in the pathogenesis of NMO lesions.


Assuntos
Aquaporina 4/análise , Bulbo/química , Esclerose Múltipla/metabolismo , Neuromielite Óptica/metabolismo , Medula Espinal/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrócitos/química , Astrócitos/patologia , Infarto Encefálico/metabolismo , Estudos de Casos e Controles , Ativação do Complemento , Complemento C9/análise , Progressão da Doença , Feminino , Proteína Glial Fibrilar Ácida/análise , Humanos , Imunoglobulina G/análise , Imuno-Histoquímica , Infarto/metabolismo , Masculino , Bulbo/patologia , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Proteína Básica da Mielina/análise , Neuromielite Óptica/patologia , Nervo Óptico/química , Nervo Óptico/patologia , Medula Espinal/irrigação sanguínea , Medula Espinal/patologia
15.
Mult Scler ; 13(1): 128-32, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17294622

RESUMO

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS) with a poor prognosis in terms of the optic-spinal function. Recently, a serum autoantibody (NMO-IgG) binding to the blood-brain barrier region was detected exclusively in patients with NMO and its high risk group. We treated six NMO-IgG-positive patients (all female; age 21-67 years old, median 41; three with optic neuritis and three with myelitis) who were unresponsive to high-dose intravenous methylprednisolone (HIMP), with plasma exchange (PE) (three to five exchanges, 2-3 L each). Three of the patients (one with optic neuritis and two with myelitis) showed definite functional improvement following PE. The clinical improvement started to appear after one or two exchanges, while there was little or no improvement in the other three patients. Such quick clinical responses to PE suggest a pathogenetic role of humoral immune factors in NMO, although delayed responses to the corticosteroid therapy might have contributed to the therapeutic efficacy, in part. Further clinical and in vitro studies are needed to determine whether the removal of NMO-IgG is directly relevant to the therapeutic efficacy. PE may hasten the functional recovery from corticosteroid-resistant relapses in some NMO-IgG-positive patients with NMO.


Assuntos
Neuromielite Óptica/imunologia , Neuromielite Óptica/terapia , Troca Plasmática , Adulto , Anti-Inflamatórios/administração & dosagem , Autoanticorpos/sangue , Barreira Hematoencefálica/imunologia , Terapia Combinada , Resistência a Medicamentos , Feminino , Humanos , Imunoglobulina G/sangue , Injeções Intravenosas , Imageamento por Ressonância Magnética , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Neuromielite Óptica/patologia , Recidiva , Medula Espinal/patologia
16.
J Neurol Neurosurg Psychiatry ; 77(9): 1073-5, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16505005

RESUMO

This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic-spinal form of multiple sclerosis (OSMS), three with the spinal form of multiple sclerosis (SMS), and 13 with the conventional form of multiple sclerosis (CMS), which affects the brain. NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (> 3 vertebral segments) spinal cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS. The two patients having CMS with NMO-IgG had unusual brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS. This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic-spinal disease.


Assuntos
Imunoglobulina G/sangue , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Neuromielite Óptica/imunologia , Neuromielite Óptica/patologia , Adulto , Autoanticorpos , Cegueira/etiologia , Encéfalo/patologia , Feminino , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/complicações , Neuromielite Óptica/sangue , Neuromielite Óptica/complicações , Medula Espinal/patologia
17.
Acta Neurol Scand ; 113(2): 125-31, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16411974

RESUMO

OBJECTIVES: To evaluate the association between callosal or periventricular lesions, and the presence of oligoclonal IgG bands (OB) or the IgG index in Japanese patients with multiple sclerosis (MS). MATERIALS AND METHODS: Brain magnetic resonance imaging (MRI) was studied in 34 Japanese clinically definite MS cases. Sagittal 2-mm fast fluid-attenuated inversion-recovery (FLAIR) imaging was added to the routine MRI studies. RESULTS: Among the 34 patients, 20 (59%) were OB positive. Among the 20 patients with OB-positive MS, 17 (85%) had callosal lesions, although only two (14%) of 14 OB-negative MS patients had callosal lesions. The periventricular lesion area was significantly larger in the OB-positive patients compared with the OB-negative patients. CONCLUSIONS: The present study clearly demonstrated a strong association between the periventricular lesions and OB in Japanese MS. Certain OB-related immune mechanisms may contribute to the development of callosal and periventricular lesions in MS. OB may be an important factor to understand the pathomechanisms of MS lesions.


Assuntos
Ventrículos Cerebrais/patologia , Corpo Caloso/patologia , Imunoglobulina G/metabolismo , Esclerose Múltipla Recidivante-Remitente/metabolismo , Esclerose Múltipla Recidivante-Remitente/patologia , Bandas Oligoclonais/metabolismo , Adulto , Povo Asiático , Atrofia/etiologia , Atrofia/metabolismo , Atrofia/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/etnologia
18.
Neurology ; 65(9): 1479-82, 2005 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-16275842
19.
Neurology ; 62(1): 144-6, 2004 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-14718720

RESUMO

The authors studied immunoglobulin (Ig) G subclasses in the CSF and sera of patients with relapsing neuromyelitis optica (RNMO) and typical multiple sclerosis (MS). Although the total IgG concentrations were elevated in the CSF of patients with RNMO and MS, IgG1% and IgG1 index were significantly elevated only in patients with MS. The absence of the CSF IgG1 responses in the patients with RNMO may suggest less Th1 immunity and may also explain the rarity of oligoclonal IgG bands in patients with this disease.


Assuntos
Imunoglobulina G/líquido cefalorraquidiano , Neuromielite Óptica/líquido cefalorraquidiano , Neuromielite Óptica/imunologia , Adulto , Idade de Início , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/imunologia , Recidiva , Valores de Referência , Células Th1/imunologia
20.
Mult Scler ; 8(6): 459-62, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12474983

RESUMO

The cerebrospinal fluid oligodonal IgG bands (OB) are less frequently observed in Japanese multiple sclerosis (MS) patients compared with Caucasian patients. We studied 40 consecutive Japanese MS patients to investigate the differences in the clinical and magnetic resonance imaging (MRI) features of MS between OB-positive patients and OB-negative ones. Among the 40 patients, 22 (55%) patients were OB-positive by either agarose gel electrophoresis (AGE) or isoelectric focusing (IEF), and 18 (45%) patients were OB-negative by both AGE and IEF. There were differences between the two groups only in the clincal forms of MS, but not in terms of gender, onset age, disease duration, or disease severity. In the OB-negative group, nine (50%) of the patients had the optic-spinal form of MS (OS-MS), but only one patient (4.5%) in the OB-positive group had OS-MS. Although most OB-positive patients showed brain MRI lesions typical of MS, 13 (72%) of the OB-negative patients showed no or few brain MRI lesions and the rest of the OB-negative patients showed atypical MS lesions, such as diffuse white matter lesions or large ring-enhanced lesions. Our results suggest that the majority of OB-negative Japanese MS patents show either no or few brain MRI lesions or atypical brain MRI lesions.


Assuntos
Imunoglobulinas/análise , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Adulto , Encéfalo/patologia , Criança , Eletroforese em Gel de Ágar , Feminino , Humanos , Focalização Isoelétrica , Japão , Imageamento por Ressonância Magnética , Masculino , Fibras Nervosas/patologia , Bandas Oligoclonais
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