RESUMO
BACKGROUND AND PURPOSE: Oral or intravenous methylprednisolone (≥500 mg/day for 5 days) is recommended for multiple sclerosis (MS) relapses. Nonetheless, the optimal dose remains uncertain. We compared clinical and radiological effectiveness, safety and quality of life (QoL) of oral methylprednisolone [1250 mg/day (standard high dose)] versus 625 mg/day (lesser high dose), both for 3 days] in MS relapses. METHODS: A total of 49 patients with moderate to severe MS relapse within the previous 15 days were randomized in a pilot, double-blind, multicentre, non-inferiority trial (ClinicalTrial.gov, NCT01986998). The primary endpoint was non-inferiority of the lesser high dose by Expanded Disability Status Scale (EDSS) score improvement on day 30 (non-inferiority margin, 1 point). The secondary endpoints were EDSS score change on days 7 and 90, changes in T1 gadolinium-enhanced and new/enlarged T2 lesions on days 7 and 30, and safety and QoL results. RESULTS: The primary outcome was achieved [mean (95% confidence interval) EDSS score difference, -0.26 (-0.7 to 0.18) at 30 days (P = 0.246)]. The standard high dose yielded a superior EDSS score improvement on day 7 (P = 0.028). No differences were observed in EDSS score on day 90 (P = 0.352) or in the number of T1 gadolinium-enhanced or new/enlarged T2 lesions on day 7 (P = 0.401, 0.347) or day 30 (P = 0.349, 0.529). Safety and QoL were good at both doses. CONCLUSIONS: A lesser high-dose oral methylprednisolone regimen may not be inferior to the standard high dose in terms of clinical and radiological response.
Assuntos
Glucocorticoides/administração & dosagem , Metilprednisolona/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Adulto , Método Duplo-Cego , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de VidaRESUMO
BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. RESULTS: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2-5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6-1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7-1.6, P = 0.69). CONCLUSION: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.
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Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Adulto , Estudos de Coortes , Avaliação da Deficiência , Pessoas com Deficiência , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/patologiaRESUMO
BACKGROUND: Myelitis can appear as an initial symptom in the context of demyelinating diseases, systemic inflammatory diseases, and infectious diseases. We aim to analyse the differences between myelitis associated with multiple sclerosis (MS) and myelitis resulting from other aetiologies. METHODS: Single-centre, retrospective analysis of patients with initial myelitis (2000-2013). Demographic, aetiological, clinical, radiological and prognostic variables were analysed and compared between patients with myelitis from MS and those with myelitis due to other aetiologies. RESULTS: We included 91 patients; mean follow-up was 7 years. Diagnoses were as follows: MS 57 (63%), idiopathic transverse myelitis 22 (24%), associated systemic diseases 6 (7%), and other diagnoses (6%). Myelitis due to MS was associated with younger age of onset (35 ± 11 vs. 41 ± 13; P = .02), more pronounced sphincter involvement (40.4 vs. 27.3%; P=.05), greater multifocal involvement in spinal MRI (77.2 vs. 26.5%; P=.001), shorter lesion extension (2.4 vs. 1.4 vertebral segments; P=.001), cervical location (82.5 vs. 64.7%; P=.05) and posterior location (89.5 vs. 41.2%; P=.001). Myelitis due to other aetiologies more frequently showed anterior location (47.1 vs. 24.6%; P=.02), and central cord involvement (47.1 vs. 14.1%; P=.001), with better recovery at one year of follow up (EDSS 2.0 vs. 1.5; P=.01). Multivariate analysis showed that multifocal spinal cord involvement (OR 9.38, 95% CI: 2.04-43.1) and posterior cord involvement (OR 2.16, 95% CI: 2.04-2.67) were independently associated with the diagnosis of MS. CONCLUSIONS: A high percentage of patients with an initial myelitis event will be diagnosed with MS. The presence of multifocal and posterior spinal cord lesions was significantly associated with the diagnosis of MS.
Assuntos
Esclerose Múltipla/complicações , Mielite/etiologia , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/epidemiologia , Mielite/diagnóstico por imagem , Mielite/epidemiologia , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
UNLABELLED: Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 (p = 0.05 / p = 0.03) and at week 4 (p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00753792.
Assuntos
Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Citocinas/metabolismo , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/metabolismo , Esclerose Múltipla/prevenção & controle , Recidiva , Adulto JovemRESUMO
BACKGROUND: Steroids improve multiple sclerosis (MS) relapses but therapeutic window and dose, frequency and administration route remain uncertain. OBJECTIVE: The objective of this paper is to compare the clinical and radiologic efficacy, tolerability and safety of intravenous methylprednisolone (ivMP) vs oral methylprednisolone (oMP), at equivalent high doses, for MS relapse. METHODS: Forty-nine patients with moderate or severe relapse within the previous 15 days were randomized in a double-blind, noninferiority, multicenter trial to receive ivMP or oMP and their matching placebos. Expanded Disability Status Scale (EDSS) scores were determined at baseline and weeks 1, 4 and 12. Brain MRI were assessed at baseline and at weeks 1 and 4. Primary endpoint was a noninferiority assessment of EDSS improvement at four weeks (noninferiority margin of one point), with further key efficacy assessments of number and volume of T1 gadolinium-enhancing (Gd+), and new or enlarged T2 lesions at four weeks' post-treatment initiation. Secondary outcomes were safety and tolerability. RESULTS: The study achieved the main outcome of noninferiority at four weeks for improved EDSS score. No differences were found between ivMP and oMP in the number of Gd+ lesions (0 (0-1) vs 0 (0-0.5), p = 0.630), volume of Gd+ lesions (0 (0-88.0) vs 0 (0-32.9) mm(3), p = 0.735), or new or enlarged T2 lesions (0 (0-194) vs 0 (0-123), p = 0.769). MP was well tolerated, and no serious adverse events were reported. CONCLUSIONS: This study provides confirmatory evidence that oMP is not inferior to ivMP in reducing EDSS, similar in MRI lesions at four weeks for MS relapses and is equally well tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00753792.
Assuntos
Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adulto , Idoso , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Recidiva , Resultado do TratamentoAssuntos
Aloe/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Interferon beta/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Feminino , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversosRESUMO
OBJECTIVE: To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. METHODS: We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. RESULTS: Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0-4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p=0.002). CONCLUSION: Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario.
Assuntos
Gadolínio , Esclerose Múltipla , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Gadolínio/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Metilprednisolona/uso terapêutico , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , RecidivaRESUMO
BACKGROUND: The use of tolerogenic DCs is a promising therapeutic strategy for transplantation and autoimmune disorders. Immunomodulatory DCs are primarily generated from monocytes (MDDCs) for in vitro experiments following protocols that fail to fulfil the strict regulatory rules of clinically applicable products. Here, we compared the efficacy of three different tolerance-inducing agents, dexamethasone, rapamycin and vitamin D3, on DC biology using GMP (Good Manufacturing Practice) or clinical grade reagents with the aim of defining their use for human cell therapy. METHODS: Tolerogenic MDDCs were generated by adding tolerogenic agents prior to the induction of maturation using TNF-α, IL-ß and PGE2. We evaluated the effects of each agent on viability, efficiency of differentiation, phenotype, cytokine secretion and stability, the stimulatory capacity of tol-DCs and the T-cell profiles induced. RESULTS: Differences relevant to therapeutic applicability were observed with the cellular products that were obtained. VitD3-induced tol-DCs exhibited a slightly reduced viability and yield compared to Dexa-and Rapa-tol-DCs. Phenotypically, while Dexa-and VitD3-tol-DCs were similar to immature DCs, Rapa-tol-DCs were not distinguishable from mature DCs. In addition, only Dexa-and moderately VitD3-tol-DCs exhibited IL-10 production. Interestingly, in all cases, the cytokine secretion profiles of tol-DCs were not modified by a subsequent TLR stimulation with LPS, indicating that all products had stable phenotypes. Functionally, clearly reduced alloantigen T cell proliferation was induced by tol-DCs obtained using any of these agent. Also, total interferon-gamma (IFN-γ) secretion by T cells stimulated with allogeneic tol-DCs was reduced in all three cases, but only T cells co-cultured with Rapa-tol-DCs showed impaired intracellular IFN-γ production. In addition, Rapa-DCs promoted CD4+ CD127 low/negative CD25high and Foxp3+ T cells. CONCLUSIONS: Our results demonstrate contrasting influences of different clinical-grade pharmacological agents on human tol-DC generation. This should be taken into account for decisions on the use of a specific agent for the appropriate cellular therapy in the context of a particular disease.
Assuntos
Células Dendríticas/imunologia , Tolerância Imunológica/imunologia , Anti-Inflamatórios/metabolismo , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colecalciferol/farmacologia , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Dexametasona/farmacologia , Fatores de Transcrição Forkhead/metabolismo , Humanos , Tolerância Imunológica/efeitos dos fármacos , Interferon gama/metabolismo , Interleucina-10/biossíntese , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Fenótipo , Sirolimo/farmacologia , Células Th1/citologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismoRESUMO
BACKGROUND: The identification of major immunogenic peptides in multiple sclerosis (MS) is of great importance for the development of antigen-specific therapies. Cellular reactivity against a selected mix of seven myelin peptides was evaluated in vitro. The evolution of this reactivity over time and its correlation with clinical variables was also analysed. MATERIAL AND METHODS: Forty-two patients with MS, 15 with other demyelinating diseases and 40 healthy donors (HD) were studied. Cell proliferation was measured by 3[H] thymidine incorporation into samples obtained at 0, 3, 6 and 12months of MS patient follow-up. RESULTS: A positive reaction to the peptide mix was detected in 31 of the 42 patients (74%), 12 of the 40 HD (30%) and 6 of the 15 (40%) patients with other demyelinating diseases. Patients with positive proliferation had greater disability (EDSS score, 3 [1-5.5] vs. 1.0[1-2], P=0.021), higher number of relapses (7±4.1 vs. 3±1.2, P<0.001) and shorter time since the last relapse (9±7.5 vs. 32±12.3months, P=0.036). After 12months of follow-up, cell reactivity was maintained in 33 patients (78%). CONCLUSION: A high percentage of patients exhibit a significant and maintained reactivity to myelin peptides over time. Therefore, this mix may be useful as a source of antigen in the development of protocols aimed at inducing specific tolerance in MS.
Assuntos
Proliferação de Células , Epitopos de Linfócito T/imunologia , Imunoterapia/métodos , Ativação Linfocitária/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Proteínas da Mielina/uso terapêutico , Fragmentos de Peptídeos/fisiologia , Adulto , Modulação Antigênica/imunologia , Feminino , Humanos , Tolerância Imunológica , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/terapia , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
BACKGROUND: most disease-modifying therapies (DMTs) for multiple sclerosis (MS) are self-injectable medications that must be taken on an ongoing basis to reduce disease activity. Thus, adherence to therapy becomes an important challenge that must be addressed to maximize benefits of therapy. This study evaluated rates of adherence to prescribed treatment and explored factors affecting adherence amongst patients with relapsing-remitting MS. METHODS: this was an observational, multicenter, multinational, phase 4 study. Patients and physicians received paper questionnaires regarding adherence to DMTs approved at the time of the study, including intramuscular interferon beta-1a (IFNß-1a), subcutaneous IFNß-1a, IFNß-1b, and glatiramer acetate. Quality of life and cognition data also were collected. Multivariate analysis was conducted to identify factors associated with adherence to long-term DMTs. RESULTS: two thousand six hundred and forty-eight patients were studied, revealing an average treatment duration of 31 months. Seventy-five percent of patients (n = 1923) were adherent to therapy. The most common reasons for non-adherence were forgetting to administer the injection (50.2%) and other injection-related reasons (32.0%). Adherent patients reported better quality of life (P < 0.05) and fewer neuropsychological issues (P < 0.001) than non-adherent patients. Adherent patients had significantly shorter duration of disease (P < 0.001) and shorter duration of therapy (P = 0.005) than non-adherent patients. Women were more likely than men to adhere to treatment. CONCLUSION: identifying factors that affect adherence to prescribed treatments is the first step in improving adherence of patients with MS to therapy, thereby helping maximize the benefits of long-term DMTs.
Assuntos
Interferon beta/uso terapêutico , Adesão à Medicação , Esclerose Múltipla Recidivante-Remitente/terapia , Peptídeos/uso terapêutico , Feminino , Acetato de Glatiramer , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
The post-marketing international Global Adherence Project investigated adherence to disease-modifying therapy for relapsing-remitting multiple sclerosis. We report adherence data from the first 2 years in the Spanish subset of patients (n = 254 at baseline). The overall adherence rate was 85.4%. Patients taking intramuscular (IM) interferon-ß (IFNß)-1a were significantly more adherent (96.4%) compared with patients taking subcutaneous (SC) IFNß-1a 22 µg (79.1%; p = 0.0064), SC IFNß-1a 44 µg (79.6%; p = 0.0064) and glatiramer acetate (82.7%; p = 0.0184). At year 1 (n = 142), the overall adherence rate was 86.6%. Patients on IM IFNß-1a were significantly more adherent than patients on SC IFNß-1a 22 µg (93.9 vs. 66.7%; p = 0.0251). At year 2 (n = 131), the overall adherence rate was 82% (87.5% for IM IFNß-1a, 80.0% for SC IFNß-1a 22 µg, 77.8% for SC IFNß-1a 44 µg, 85.2% for IFNß-1b, and 80.0% for glatiramer acetate). In conclusion, adherence remained high among all disease-modifying therapies over the first 2 years of the study and was significantly higher for IM IFNß-1a, at visit 1, compared with SC IFNß-1a.
Assuntos
Fatores Imunológicos/administração & dosagem , Interferon beta/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Estudos Transversais , Progressão da Doença , Feminino , Acetato de Glatiramer , Humanos , Fatores Imunológicos/uso terapêutico , Injeções Intramusculares , Injeções Subcutâneas , Interferon beta/uso terapêutico , Masculino , Peptídeos , Estudos Retrospectivos , EspanhaRESUMO
INTRODUCTION: Despite pain being a disabling symptom in patients with multiple sclerosis (MS), its prevalence and characteristics are not well established. The aim of this study is to describe the characteristics and prevalence of pain in patients with MS, and to assess the associated clinical variables and radiological findings. METHODS: We prospectively studied patients with MS. A structured questionnaire which evaluated depression symptoms, type of pain, location, intensity (defined according to a visual analogue scale (VAS) as severe (VAS 7-10), moderate (VAS 4-6) and mild (VAS 0-4), and pain therapy was recorded in patients who referred to pain at the time of interview. Protocol variables were demographic data, MS clinical forms (remitting-relapsing, progressive-secondary and progressive-primary), neurological dysfunction (defined according to EDSS scale), symptoms at onset, attack frequency, illness duration, disease modifying treatment, fatigue, spasticity, oligoclonal bands in CSF, visual evoked potentials, depression symptoms (Hamilton test) and presence of lesions in spinal cord MRI. RESULTS: A total of 134 MS patients were included, and MRI was performed on 105 of them. Pain was reported by 74 (55%) patients and was most frequently neuropathic, located in limbs, severe and burning/spiky. Of these 28 (38%) received therapy for their pain, based predominantly in anti-inflammatory drugs. Patients with pain had a worse functional state (EDSS score, 4.5 [3-6] vs 1.5 [1-2], p<0.001), higher number of relapses (7.13±3.4 vs 3.75±2.9, p<0.001), progressive forms of MS (86.7% vs 13.3%, p<0.001), depression (91.9% vs 8.1%, p<0.001), spinal cord involvement at onset (79.2% vs 20.8%, p=0.009), spinal cord lesions by MRI (84.3% vs 15.7%, p<0.001) and longer duration of disease (14.6±7.8 vs 8.43±5.9 months, p<0.001). In a logistic regression model, the presence of lesions in spinal cord MRI (OR 3.5 [1.5-24.5]) and higher EDSS score (OR 1.7 [1.1-2.7]) were independently associated with pain. CONCLUSIONS: Pain is a frequent disabling symptom in MS and is associated with disability and spinal cord lesions.
Assuntos
Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Dor/etiologia , Dor/fisiopatologia , Adulto , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Medição da Dor , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatments as well as different cell-based therapies that have been proposed to restore homeostasis in MS patients (tolerogenic dendritic cells, regulatory T cells, mesenchymal stem cells, and vaccination with T cells). Data collected from preclinical studies performed in the experimental autoimmune encephalomyelitis (EAE) model of MS in animals, in vitro cultures of cells from MS patients and the initial results of phase I/II clinical trials are analyzed to better understand which parameters are relevant for obtaining an efficient cell-based therapy for MS.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Esclerose Múltipla/terapia , Animais , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Tolerância Imunológica , Modelos Biológicos , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologiaRESUMO
We report on a Spanish family with cooccurrence of manic-depression and a form of hereditary cerebellar ataxia. All affected individuals in the second generation showed cerebellar ataxia and manic-depression simultaneously. Since anticipation has been described in both disorders and the pattern of segregation may be autosomal as well as X-linked, we have searched for a possible involvement of two candidate genes which are located either on an autosome (SCA1) or on the X-chromosome (GABRA3). We concluded that expansion of trinucleotide repeats at SCA1 gene cannot be considered as a disease-causing mutation, and this gene should be initially discarded.
Assuntos
Transtorno Bipolar/genética , Ataxia Cerebelar/genética , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Cromossomo X , Adolescente , Adulto , Ataxina-1 , Ataxinas , Biomarcadores , Transtorno Bipolar/complicações , Ataxia Cerebelar/complicações , Ataxia Cerebelar/diagnóstico por imagem , Mapeamento Cromossômico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Mutação , Linhagem , Radiografia , EspanhaRESUMO
OBJECTIVE: This communication aims to describe an approach suitable for the general neurologist or neurologist specialized in treating other disorders, to the current treatment of multiple sclerosis. DEVELOPMENT AND CONCLUSIONS: We discuss the treatments for recovery from the symptoms of an acute attack and those which modify the natural course of the illness (reduce the frequency and severity of attacks and/or prevent their progression). The attacks are treated with corticosteroids or ACTH. Both treatments have been shown on clinical trials to cause rapid improvement of the acute symptoms of an attack. In the progressive forms, the usefulness of high doses of corticosteroids has not been shown. Nor is there evidence that long term corticosteroid treatment, either daily or monthly, is of use in reducing the number of attacks or progression of the disease, although serious side-effects have been seen. At the moment, the interferons are the most popular treatment for multiple sclerosis. They have been the first drugs to modify the course of the disorder. Finally, we describe some of the most generally used treatments and some under investigation, although they are not widely used since it is still not clear exactly how they affect the course of the disease.
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Anti-Inflamatórios/uso terapêutico , Glucocorticoides/uso terapêutico , Interferons/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Doença Aguda , Humanos , EsteroidesRESUMO
INTRODUCTION: The existence of antibodies to aquaporin-4 (AQP-4-ab) has identified neuromyelitis optica (NMO) and multiple sclerosis (MS) as different diseases. Although HLA-DRB1 alleles contribute to MS risk, recent studies suggest that HLA back-ground differs between patients with NMO or MS in non-Caucasians populations. Our study was aimed to analyze HLA-DRB1 distribution in Caucasians NMO patients. SUBJECTS AND METHODS: We recruited a cohort of 22 NMO patients (73% were AQP-4-ab positive), 228 MS patients and 225 healthy controls from Spain and we genotyped the HLA-DRB1 locus. Then, we performed a pool analysis using reported data from 45 NMO patients (53% were AQP-4-ab positive), 156 MS patients and 310 healthy controls from Caucasian French population. RESULTS: In the Spanish cohort, NMO was associated with increased frequency of DRB1*10 allele compared with MS (odds ratio, OR = 15.1; 95% confidence interval, 95% CI = 3.26-69.84; p = 0.012). In the pooled analysis, by comparison with healthy controls, NMO was associated with increased frequency of DRB1*03 allele (OR = 2.27; 95% CI = 1.44-3.58; p < 0.0008) which was related to AQP-4-ab seropositivity (OR = 2.74; 95% CI = 1.58-4.77; p < 0.0008). By contrast, MS was associated with increased frequency of DRB1*15 allele (OR = 2.09; 95% CI = 1.62-2.68; p < 0.0008) and decreased frequency of DRB1*07 allele (OR = 0.58; 95% CI = 0.44-0.78; p < 0.0008). CONCLUSIONS: Caucasian patients with NMO and MS have a different HLA-DRB1 allelic distribution. DRB1*03 allele seems to contribute to NMO seropositivity. Multicenter collaborative efforts are needed to adequately address the genetic contribution to NMO susceptibility.