ABSTRACT
BACKGROUND: Neurofilament Light (NfL) chain levels in both cerebrospinal fluid (CSF) and serum have been correlated with the reduction of axonal damage in multiple sclerosis (MS) patients treated with Natalizumab (NTZ). However, little is known about the function of plasmacytoid cells in NTZ-treated MS patients. OBJECTIVE: To evaluate CSF NfL, serum levels of soluble-HLA-G (sHLA-G), and eventual tolerogenic behavior of plasmacytoid dendritic cells (pDCs) in MS patients during NTZ treatment. METHODS: CSF NfL and serum sHLA-G levels were measured using an ELISA assay, while pDCs (BDCA-2+) were accessed through flow cytometry analyses. RESULTS: CSF levels of NfL were significantly reduced during NTZ treatment, while the serum levels of sHLA-G were increased. Moreover, NTZ treatment enhanced tolerogenic (HLA-G+, CD274+, and HLA-DR+) molecules and migratory (CCR7+) functions of pDCs in the peripheral blood. CONCLUSION: These findings suggest that NTZ stimulates the production of molecules with immunoregulatory function such as HLA-G and CD274 programmed death-ligand 1 (PD-L1) which may contribute to the reduction of axonal damage represented by the decrease of NfL levels in patients with MS.
ABSTRACT
Given the low detection rates of CSF IgG-Oligoclonal bands (IgG-OCB) in non-European Multiple Sclerosis (MS) patients and higher specificity of the MRZH-reaction, we evaluated whether associating MRZH-reaction to CSF IgG-OCB detection improved investigation of suspected MS. Paired CSF and sera were analyzed for IgG-OCB and polyspecific viral antibodies. IgG-OCB were detected in 72% of MS patients and an MRZH-reaction in 67%. Combining IgG-OCB and MRZH raised detection of IgG abnormalities to 97% of studied MS patients. Detection of IgG-OCB and/or ≥2 MRZH antibodies showed sensitivity of 88% and specificity of 92% for MS, versus 72% and 96% for IgG-OCB alone.
Subject(s)
Antibodies, Viral/cerebrospinal fluid , Immunoglobulin G/biosynthesis , Immunoglobulin G/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/diagnosis , Oligoclonal Bands/cerebrospinal fluid , Adolescent , Adult , Biomarkers/cerebrospinal fluid , Female , Herpesvirus 3, Human/metabolism , Humans , Male , Measles virus/metabolism , Middle Aged , Rubella virus/metabolism , Simplexvirus/metabolism , Young AdultABSTRACT
BACKGROUND: It is recognized that there is a particular geographic and ethnic distribution of neuromyelitis optica (NMO) among Caucasian and non-Caucasian populations. OBJECTIVE: To review the diagnoses of patients whom were enrolled in the South Atlantic Project, a Brazilian multiple sclerosis (MS) survey performed from 1995-1998, and to identify NMO and MS case frequencies. METHODS: We reviewed the data from a 10-year follow-up of MS patients. To apply the current diagnostic criteria, the neurologists were asked to collect clinical and laboratory data from the medical records of study patients treated from 1999-2009. RESULTS: The spectrum of inflammatory demyelinating disease in 322 patients (67% white; 33% African-Brazilian) was: 49 (15%) with NMO; 14 (4%) with NMO syndromes; 10 (3%) with acute disseminated encephalomyelitis (ADEM); one isolated tumefactive brain lesion; 249 (77%) with MS (151 with relapsing-remitting MS (RRMS), 70 with secondary progressive MS (SPMS) and 27 with primary progressive MS (PPMS)). Disability was more severe in NMO and PPMS. One-third of the NMO patients had died. CONCLUSIONS: The frequency of NMO was 6.8% in São Paulo and 20.5% in Rio de Janeiro, and mainly seen in persons of African descent, which strengthens the hypothesis of there being an ethnic association of this disease. We recommend that epidemiological studies on MS that were performed previously be reviewed again, to ensure more accurate diagnoses.
Subject(s)
Multiple Sclerosis/pathology , Neuromyelitis Optica/diagnosis , Adolescent , Adult , Child , Cross-Sectional Studies , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multiple Sclerosis/complications , Neuromyelitis Optica/etiology , Young AdultABSTRACT
Human endogenous retroviruses (HERVs) arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS), most of them from Xq22.3, 15q21.3, and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2) lack the 5' LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20 kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in central nervous system (CNS) of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG). Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS pathogenesis.
ABSTRACT
Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥ 1 AIIDL. We collected their demographic, clinical and magnetic resonance imaging data and obtained follow-up (FU) information on 77 of these patients over a mean duration of 4 years. The AIIDLs presented as a single lesion in 72 (80 %) patients and exhibited an infiltrative (n = 35), megacystic (n = 16), Baló (n = 10) or ring-like (n = 16) lesion appearance in 77 (86 %) patients. Additional multiple sclerosis (MS)-typical lesions existed in 48 (53 %) patients. During FU, a further clinical attack occurred rarely (23-35 % of patients) except for patients with ring-like AIIDLs (62 %). Further attacks were also significantly more often in patients with coexisting MS-typical lesions (41 vs. 10 %, p < 0.005). New AIIDLs developed in six (7 %), and new MS-typical lesions in 29 (42 %) patients. Our findings confirm the previously reported subtypes of AIIDLs. Most types confer a relatively low risk of further clinical attacks, except for ring-like lesions and the combination with MS-typical lesions.
Subject(s)
Multiple Sclerosis/pathology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/pathology , Adolescent , Adult , Age Factors , Brain/pathology , Databases, Factual , Disease Progression , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis/classification , Multiple Sclerosis/diagnosis , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/classification , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosis , Prognosis , Sex Factors , Young AdultABSTRACT
Fatigue is a common symptom in multiple sclerosis (MS). The objective of this study was to relate fatigue and autonomic disturbances in MS. Fifty patients with MS relapsing remitting clinical form participated in this study. Thirty three (66%) were women and 17 (34%) men. Score less or equal to 3.5 in the EDSS. Five non invasive cardiovascular tests were applied in all patients for the sympathetic and parasympathetic evaluation. The results obtained in the hand grip test were increased in the blood pressure of 14.62 +/- 9.13 mmHg for the group with fatigue and of 21.68 +/- 7.18 mmHg for the non fatigue group. This difference was statistically significant (p<0.05). Conclusion is that there is a loss in the capacity to increase blood pressure in patients with fatigue suggesting a sympathetic dysfunction.
Subject(s)
Autonomic Nervous System Diseases/physiopathology , Fatigue/physiopathology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Adult , Autonomic Nervous System Diseases/etiology , Blood Pressure/physiology , Chi-Square Distribution , Disability Evaluation , Disease Progression , Exercise/physiology , Fatigue/etiology , Female , Heart Rate/physiology , Humans , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/complications , Sickness Impact Profile , Statistics, NonparametricABSTRACT
A fadiga é sintoma comum na esclerose múltipla (EM). O objetivo deste estudo é relacionar a fadiga nos portadores de EM aos distúrbios autonômicos. Participaram deste estudo, 50 pacientes portadores de EM na forma clínica remitente recorrente. Trinta e três (66 por cento) eram mulheres e 17 (34 por cento) homens; pontuação menor ou igual a 3,5 na Escala de EDSS. Foram aplicados em todos os pacientes cinco testes cardiovasculares, já padronizados, para avaliação das funções simpáticas e parassimpáticas. Os resultados encontrados no teste do exercício isométrico foram elevações da pressão arterial de 14,62±9,13 mmHg para o grupo com fadiga e de 21,68±7,18 mmHg para o grupo sem fadiga, sendo estatisticamente significante (p<0,05) a diferença entre os grupos. Conclui-se que há prejuízo na capacidade de elevar a pressão arterial diante de um exercício físico nos portadores de fadiga desta casuística, sugerindo uma disfunção simpática.
Fatigue is a common symptom in multiple sclerosis (MS). The objective of this study was to relate fatigue and autonomic disturbances in MS. Fifty patients with MS relapsing remitting clinical form participated of this study. Thirty three (66 percent) were women and 17 (34 percent) men. Score less or equal to 3.5 in the EDSS. Five non invasive cardiovascular tests were applied in all patients for the sympathetic and parasympathetic evaluation. The results obtained in the hand grip test were increase in the blood pressure of 14.62±9.13 mmHg for the group with fatigue and of 21.68±7.18 mmHg for the non fatigue group. This difference was statistically significant (p<0.05). Conclusion is that there is a loss in the capacity to increase the blood pressure in patients with fatigue suggesting a sympathetic dysfunction.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Autonomic Nervous System Diseases/physiopathology , Fatigue/physiopathology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Autonomic Nervous System Diseases/etiology , Blood Pressure/physiology , Chi-Square Distribution , Disability Evaluation , Disease Progression , Exercise/physiology , Fatigue/etiology , Heart Rate/physiology , Multiple Sclerosis, Relapsing-Remitting/complications , Sickness Impact Profile , Statistics, NonparametricABSTRACT
The Multiple Sclerosis Functional Composite Measure (MSFC) is an outcome measure in multiple sclerosis developed by USA National Multiple Sclerosis Society (1994), a three-part composite clinical measure--9-Hole Peg Test, Timed 25-Foot Walk and PASAT. It should be multidimensional in order to reflect the principal ways MS affects an individual. The MSFC was applied in 91 Brazilian subjects and standardized to be use in MS centers.
Subject(s)
Multiple Sclerosis/diagnosis , Neurologic Examination/instrumentation , Adult , Age Distribution , Brazil , Educational Status , Female , Humans , Male , Middle Aged , Neurologic Examination/methods , Reproducibility of Results , TranslatingABSTRACT
A Multiple Sclerosis Functional Composite Measure (MSFC) é escala para avaliação dos pacientes portadores de esclerose múltipla, desenvolvida pela National Multiple Sclerosis Society dos EUA em 1994, que envolve uma composição de três testes - 9-Hole Peg Test, Timed 25-Foot Walk e PASAT - abrangendo de maneira multidimensional as principais funções neurológicas comprometidas nestes pacientes. A MSFC foi aplicada em 91 indivíduos sadios com o objetivo de padronizá-la na população brasileira para posterior uso nos diversos centros de tratamento e pesquisa no Brasil.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Multiple Sclerosis/diagnosis , Neurologic Examination/instrumentation , Age Distribution , Brazil , Educational Status , Neurologic Examination/methods , Reproducibility of Results , TranslatingABSTRACT
Relatamos os resultados de estudo com o interferon beta 1-a em 62 pacientes ambulatoriais com a forma remitente-recorrente da esclerose múltipla durante um ano. Os critérios de inclusão para este tratamento foram de escore do EDSS entre 0 e 5,5 e de pelo menos relato de dois surtos nos dois últimos anos. Administramos 3 milhões de unidades internacionais de interferon beta 1-a três vezes por semana. Os objetivos deste estudo foram verificar o efeito da medicação no número de surtos e avaliar a eficácia da droga na progressão da doença. O índice anual de surtos nos pacientes que não tomaram a medicação foi 1,32 e naqueles medicados 0,63. O escore do EDSS em pacientes não medicados foi 4,7 e naqueles com medicamento 2,0. O interferon beta 1-a foi bem tolerado e 85 por cento dos pacientes completaram um ano de tratamento.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Adjuvants, Immunologic/therapeutic use , Interferon-beta/therapeutic use , Multiple Sclerosis/drug therapy , Age of Onset , Disease Progression , Follow-Up Studies , Treatment OutcomeSubject(s)
Humans , Male , Female , Adult , Cerebrospinal Fluid , Lymphocyte Count , Multiple SclerosisABSTRACT
Em 26 pacientes com diagnóstico definido de esclerose múltipla foram colhidas amostras de sangue e pesquisados os receptores solúveis de interleucina-2 (RsIL-2). Para tal os pacientes foram dividios em dois grupos: um constituído de 14 pacientes emsurto da doença e o outro com 12 pacientes em remissäo da moléstia. Além destes, procedeu-se a colheita de material para a mesma pesquisa em 8 pacientes com outras doenças neurológicas. Os resultados demonstraram aumento dos RsIL-2 em 50 por cento dos casos do grupo de pacientes em surto da doença, fato näo observado nos demais pacientes dos demais grupos. Estes resultados confirmam a hipótese da ativaçäo de células T em pacientes em surto de esclerose múltipla, corroborando a hipótese da existência de um desiquilíbrio imunológico na doença
Subject(s)
Adolescent , Adult , Middle Aged , Humans , Male , Female , Multiple Sclerosis/blood , Receptors, Interleukin/analysis , Receptors, Interleukin/physiology , Lymphocyte ActivationABSTRACT
Apresentamos um caso com diagnóstico definido de esclerose múltipla confirmado pelos achados necroscópicos. Os aspectos anatompatológicos nessa doença säo bem conhecidos e têm sido referidos por vários autores. O objetivo desta apresentaçäo é a divulgaçäo do primeiro caso de esclerose múltipla autopsiado na Santa Casa de Säo Paulo, onde já foram realizadas cerca de 30500 autópsias. Os achados macro e microscópicos observados no sistema nervoso central, com placas de desmielinizaçäo em fases diferentes de atividade, säo características da doença. A detecçäo de imunoglobulinas nessas placas, pelo método de imunohistoquímica, adicionou aos achados morfológicos a hipótese patogênica de uma doença imunologicamente mediada
Subject(s)
Humans , Male , Central Nervous System/pathology , Multiple Sclerosis/pathology , Multiple Sclerosis/immunology , Immunoglobulin G/analysisABSTRACT
O estudo histoquímico do músculo esquelético em 10 pacientes com esclerose múltipla e atrofia muscular revelou comprometimento em todos eles. As alteraçöes histológicas observadas mostraram padräo histológico homogênio, näo se observando diferenças entre as formas clássica e progressiva. Foram observadas; vasculite do tipo linfoplasmocitário, aumento da porcentagem de fibras do Tipo IIB, alteraçöes inflamatórias ao nível dos ramos nervosos periféricos terminais, acúmulo lipídico intrassarcoplasmática e presença de fibras 'moth-eaten'. As características a hipótese etipatogênica de uma lesäo autoimune na esclerose múltipla
