RESUMO
OBJECTIVE: To investigate chitotriosidase (CTTS) activity in serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS) patients in relation to disease course and CSF markers for immune activation or inflammation. MATERIALS AND METHODS: We studied 80 patients with relapsing-remitting MS (RRMS), 24 with secondary progressive MS (SPMS), 20 with primary progressive MS (PPMS) and 29 patients with other neurological disorders (OND). We measured CTTS activity and studied the correlation with CSF mononuclear cell count (MNC) and intrathecal IgG production. RESULTS: CTTS activity was significantly higher in CSF, but not in serum, from the total MS group compared with OND and controls. In RRMS and SPMS CTTS, index was increased compared with controls (RRMS, 0.10 +/- 0.21; SPMS, 0.10 +/- 0.15; controls, 0.021 +/- 0.020), but not in PPMS (0.061 +/- 0.052). CTTS index was higher in MS patients with elevated MNC or CSF-restricted oligoclonal IgG bands than in MS patients without these CSF findings. CONCLUSIONS: CTTS index is elevated in RRMS and SPMS. The CTTS index is related to CSF markers of inflammation or immune activation.
Assuntos
Hexosaminidases/líquido cefalorraquidiano , Esclerose Múltipla Crônica Progressiva/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Adulto , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Contagem de Células , Hexosaminidases/sangue , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Leucócitos Mononucleares , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/sangue , Esclerose Múltipla Crônica Progressiva/enzimologia , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/enzimologia , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/enzimologia , Bandas Oligoclonais/líquido cefalorraquidianoAssuntos
Terapia por Acupuntura , Eletroacupuntura , Esclerose Múltipla/complicações , Esclerose Múltipla/terapia , Doenças da Bexiga Urinária/etiologia , Doenças da Bexiga Urinária/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Qualidade de Vida , Doenças da Bexiga Urinária/psicologia , Adulto JovemRESUMO
Diagnostic criteria for neuromyelitis optica (NMO) state that there should be no active disease outside the optic nerves and spinal cord. However, several cases have been described with symptomatic brain involvement. We describe an autopsy case of a patient with NMO and symptomatic involvement of the brain. The histopathology of the brain lesions is typical for NMO, with extensive macrophage infiltration, including perivascular accumulation of large numbers of eosinophils. This is the first case that clearly shows that in NMO, the histopathology of the brain lesions is identical to that of the lesions in the optic nerves and spinal cord.
Assuntos
Encéfalo/patologia , Neuromielite Óptica/patologia , Adulto , Encéfalo/imunologia , Eosinófilos/patologia , Evolução Fatal , Feminino , Humanos , Macrófagos/patologia , Neuromielite Óptica/imunologia , Medula Espinal/imunologia , Medula Espinal/patologiaRESUMO
Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) disease activity and improving disability scores. However, the mechanism by which this beneficial effect is achieved remains unclear. An effect of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role in the disease process - has been postulated in a number of animal and ex vivo studies. Hence, we performed a study on 34 patients with secondary progressive (SP) MS being treated with monthly IVIG or placebo for two years according to the protocol of the ESIMS study. Clinical outcome measures and cytokine production (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were recorded in all patients and compared with respect to the treatment group. Against our expectations, IVIG did not reduce the relapse rate or the progression of disability or cytokine production. Our data argue against an enduring immunomodulating effect of IVIG, at least in SPMS.
Assuntos
Citocinas/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Linfócitos/imunologia , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Crônica Progressiva/imunologia , Adulto , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/sangue , RecidivaRESUMO
The aim of this study was to test, in patients with multiple sclerosis (MS), whether the concept of helplessness might improve the understanding of the relationship between disease severity (neurological impairment) and personality characteristics (emotional instability) on one hand, and depressive mood and fatigue severity on the other hand. Data pertain to 89 patients with a definite diagnosis of MS (Expanded Disability Status Scale [EDSS] ratings: 1-8). Helplessness, fatigue severity, depressive mood and emotional instability were rated with validated questionnaires. Model testing revealed that more neurological impairment and more emotional instability were associated with more helplessness, while higher levels of helplessness were associated with more fatigue and depressive mood. The initially observed direct relationship between EDSS and fatigue disappeared. Emotional instability also had a direct significant relationship with depressive mood, and depressive mood had only a small relationship with fatigue severity. The results indicated that helplessness affected both depressive mood and fatigue severity and that fatigue was not merely a symptom of depressive mood. The correlation between neurological impairment and fatigue severity was largely explained by the mediating effect of helplessness. These findings suggest that MS patients troubled by disabling fatigue might benefit from a psychological intervention targeting unfavourable illness cognitions.
Assuntos
Depressão/psicologia , Fadiga/psicologia , Desamparo Aprendido , Esclerose Múltipla Crônica Progressiva/psicologia , Esclerose Múltipla Recidivante-Remitente/psicologia , Adulto , Sintomas Afetivos/etiologia , Sintomas Afetivos/psicologia , Idoso , Coleta de Dados , Depressão/etiologia , Avaliação da Deficiência , Pessoas com Deficiência/psicologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Papel do DoenteRESUMO
Abnormalities in T-cell-derived cytokine production are a well-known phenomenon in multiple sclerosis (MS). An association between disability and the production of interferon gamma has been demonstrated recently. The present study investigated associations between disability, cytokine production in stimulated blood lymphocytes and magnetic resonance imaging data in 37 patients with the secondary progressive course in the stable phase of the disease. Patients with high interleukin-10 (IL-10) production had significantly lower disability scores (p=0.009) and lower T2 lesion load (p=0.03). Interleukin-10 might not only play a role in the pathological process of multiple sclerosis but has an impact on disease outcome as well.
Assuntos
Interleucina-10/metabolismo , Esclerose Múltipla Crônica Progressiva/diagnóstico , Adulto , Biomarcadores/análise , Análise Química do Sangue , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-4/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/metabolismo , Prognóstico , Estatística como Assunto , Subpopulações de Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Several studies have reported a defective Fas function in patients with multiple sclerosis (MS). We were interested whether this could result from a genetically altered Fas regulation. We examined the FAS-670 polymorphism in 382 patients with MS and 206 controls, and found that the carriership of allele FAS-670*G was significantly less frequent in patients than in controls. We found no association between the carriership of FAS-670*G and clinical features. For a subgroup of patients, longitudinal MRI data were available. We observed similar brain and lesion volumes in carriers and noncarriers of FAS-670*G. These data suggest that FAS-670*G decreases the risk of developing MS, but does not affect the course of disease.
Assuntos
Predisposição Genética para Doença/genética , Glicoproteínas de Membrana/genética , Esclerose Múltipla/genética , Polimorfismo Genético/genética , Receptor fas/genética , Adulto , Idade de Início , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Análise Mutacional de DNA , Proteína Ligante Fas , Feminino , Frequência do Gene , Testes Genéticos , Humanos , Interferon beta/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/fisiopatologia , Polimorfismo Genético/imunologia , Fatores Sexuais , Receptor fas/imunologiaRESUMO
The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of systemic diseases that include the familiar disease entities of dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM). A subset of patients has unique autoantibodies which are specific for IIM (myositis specific autoantibodies; MSAs). We studied the clinical and serological characteristics of IIM in 125 Dutch patients. Sera were analysed by immunoblotting, enzyme-linked immunosorbent assay, and immunoprecipitation. The most frequently encountered MSA was the anti-Jo-1 autoantibody (20%), followed by anti-tRNAHis (6%), anti-Mi-2 (6%), and anti-SRP (4%). The presence of certain MSAs was clearly associated with specific clinical characteristics. Anti-Jo-1 and anti-tRNAHis were associated with the anti-synthetase syndrome, anti-SRP with PM with severe myalgia and arthralgia and a moderate response to immunosuppressive treatment. A novel finding was the presence of anti-Mi-2, not only in DM, but also in PM. MSAs were frequently present in DM/PM sera, but were hardly ever detected in the sera of IBM patients. The few IBM patients with MSAs demonstrated a significant response to immunosuppressive treatment. It can be concluded that MSAs define specific clinical syndromes within the spectrum of IIM and that they can assist in the differential diagnosis and treatment plan of these enigmatic disorders by virtually excluding IBM by their presence, and by potentially identifying a subgroup of steroid-responsive IBM patients.