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ID PMID Title PublicationDate abstract
17122966 Superoxide production and NADPH oxidase expression in human rheumatoid synovial cells: reg 2006 Nov OBJECTIVES: to evaluate the rheumatoid synovial cell capacity to produce superoxide anion in response to interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha), and to study the NADPH oxidase involvement in this production. MATERIAL AND METHODS: Synovial cells obtained from 7 rheumatoid arthritis (RA), 5 osteoarthritic (OA) patients, and dermal fibroblasts, were stimulated (i) with IL-1beta and TNF-alpha, or (ii) with specific oxidase activators and inhibitors, before studying superoxide production; we also studied NADPH oxidase mRNAs and protein expression, and p47-phox phosphorylation. RESULTS: Constitutive superoxide production by RA cells was increased in comparison to OA cells and dermal fibroblasts, and was stimulated by PMA and ionomycin. This production was increased after cytokine treatment of RA synovial cells. Cytokine-induced superoxide production by RA cells was inhibited by iodonium diphenyl or apocynin, suggesting the involvement of NADPH oxidase. RT-PCR and western blot analysis revealed the presence of p47-phox, gp91-phox and Nox4 in RA and OA cells, and in dermal fibroblasts. P47-phox phosphorylation was enhanced after cytokine-treatment in RA and OA cells, suggesting a PKC-mediated up-regulation of NADPH oxidase. CONCLUSIONS: NADPH oxidase is involved in the superoxide release by RA synovial cells, constitutively and after cytokine up-regulation. These cells express two different homologues (gp91-phox and Nox4).
16508942 Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis 2006 Mar OBJECTIVE: To examine the promoter activity and protein expression of the death receptor 3 gene DR3, a member of the apoptosis-inducing Fas gene family, with particular reference to the methylation status of its promoter region in rheumatoid arthritis (RA). METHODS: Genomic DNA was prepared from peripheral blood mononuclear cells obtained from healthy individuals and from patients with RA and synovial cells obtained from patients with RA and osteoarthritis. The methylation status of the DR3 promoter was analyzed by bisulfite genomic sequencing and methylation-specific polymerase chain reaction techniques. Gene promoter activity and protein expression were examined using the luciferase reporter and Western blotting techniques. RESULTS: The promoter region of the DR3 gene contained many CpG motifs, including one CpG island that was specifically hypermethylated in synovial cells from patients with RA. Promoter assays showed that the promoter CpG island was essential for the transactivation of the DR3 gene and that forced hypermethylation of the CpG island with the bacterial methylase Sss I in vitro resulted in inhibition of the DR3 gene expression. Furthermore, the expression of DR-3 protein was down-modulated in association with methylation of the promoter CpG island in RA synovial cells. CONCLUSION: The CpG island in the DR3 gene promoter was specifically methylated to down-modulate the expression of DR-3 protein in rheumatoid synovial cells, which may provide resistance to apoptosis in RA synovial cells.
17660625 [Pathologic condition of osteoporosis in rheumatoid arthritis]. 2007 Aug Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis which causes osteoporosis and joint destruction. Recently, it has been well understood that pro-inflammatory cytokine plays a pivotal role in disease progression. These pro-inflammatory cytokine induces activation of osteoclasts, resulting in paraarticular osteoporosis and joint destruction. While systemic osteoporosis caused by several factors is often seen in patients with RA. This article reviews the pathologic condition of osteoporosis in RA.
16309927 Raised chondroitin sulfate epitopes and hyaluronan in serum from rheumatoid arthritis and 2006 Mar OBJECTIVES: Serum hyaluronan (HA) and chondroitin sulfate (CS) epitopes WF6 and 3B3 (+) were determined to investigate disease association in patients with osteoarthritis (OA), rheumatoid arthritis (RA) and healthy controls. METHODS: Specific assays for HA and CS epitopes WF6 and 3B3 (+) were established and applied to a cross-sectional study of serum samples from patients (96 OA, 57 RA and 50 healthy controls). RESULTS: Both CS epitopes were increased in serum of many OA and RA patients and average levels were significantly above in healthy controls. In contrast serum HA was increased in RA, but only in few OA patients. CONCLUSIONS: CS epitopes WF6 and 3B3 (+) are raised in serum of patients with both OA and RA and were thus distinct from serum HA. The results suggest that OA may be detected systemically as well as RA. The range of levels of CS epitopes detected in OA and RA was wide and correlation with any aspect of disease activity is yet to be determined.
18591855 An autopsy case of Mycobacterium abscessus pulmonary infection complicated with rheumatoid 2008 We present the case of a 70-year-old man diagnosed with Mycobacterium abscessus pulmonary infection complicated with rheumatoid arthritis who was treated with corticosteroids. He died despite treatment according to the recommended regimen of imipenem, clarithromycin, and amikacin. Autopsy revealed granulomatous lesions throughout the bilateral lungs. We conclude that M. abscessus infection may have a fatal outcome because of the drug resistance of the pathogen. This case suggests that rheumatoid arthritis might be a risk factor for M. abscessus pulmonary infection, but further studies are necessary for clarification.
18718877 Co-stimulatory modulation in rheumatoid arthritis: the role of (CTLA4-Ig) abatacept. 2008 Oct Associations between rheumatoid arthritis (RA) susceptibility and polymorphism in multiple immunoregulatory genes suggest a role of altered T cell function in the disease. The growing relevance of the oxidative stress in RA synovitis, which results in a number of T cell signalling abnormalities, is reinforced by the demonstration of a direct NO inducing activity through the shared epitope of the HLA class II molecules HLA-DRbeta1, with secondary lymphocytes oxidative damage. Direct T cell/macrophage contact-dependent activation, one of the driving mechanisms of synovitis, is mediated by co-stimulatory molecules as well as cell membrane cytokines and may also result in an impaired suppressive function of T regulatory cells (Treg) in RA joints. The fusion of CTLA4 extracellular binding domain to the Fcgamma1 allows to obtain a soluble CTLA4 receptor, the dimeric recombinant human fusion protein abatacept (CTLA4-Ig). The improved knowledge of the CTLA4-B7 co-stimulation regulatory mechanisms by signals delivered into DCs and Tregs provides multiple potential targets for the abatacept treatment. CTLA4-Ig shows the capacity, either ex vivo or in vivo, to interrupt at multiple steps the ongoing inflammatory and destructive process, and to concur in restoring the immunoregulatory balance in RA.
16368734 Limited VH gene usage in B-cell clones established with nurse-like cells from patients wit 2006 May OBJECTIVES: Nurse-like stromal cells (NLC) in synovia and bone marrow of patients with rheumatoid arthritis (RA) can support pseudoemperipolesis, protect from apoptosis and enhance immunoglobulin production of peripheral blood B cells isolated from healthy individuals, suggesting the profound contribution of hyperactivation of B cells in RA. In the course of establishing RA-NLC from RA patients, we observed the growth of B cells in the presence of RA-NLC. METHODS: We cloned B cells from the synovium or bone marrow of RA patients using the limiting dilution technique. For established clones, nucleotide sequences of immunoglobulin and surface antigens were investigated. To investigate the dependence of these clones on NLC, differences in the proliferation and the amount of immunoglobulin produced in the presence or absence of NLC were compared. Immunocytochemical staining of various cells was performed using the antibody these clones produced. RESULTS: Nine B-cell clones established from RA patients showed RA-NLC-dependent growth. These B-cell clones expressed CD19, CD20, CD38, CD39 and CD40, suggesting that the cloned cells were mature and activated. All clones secreted immunoglobulins in culture media, which were specific for intracellular components of various cell lines, including RA-NLC. Interestingly, we found limited usage of immunoglobulin heavy-chain variable regions (VH) among B-cell clones from RA patients. These repertoires were reported to be detected preferentially in fetal livers. CONCLUSION: The present study provides a novel insight into the involvement of RA-NLC in the immunopathogenesis of RA via an autoreactive B cell development and/or activation mechanism.
18283490 Computer-assisted validation of the synovitis score. 2008 Jun Histopathological examination of synovial specimens can contribute to the diagnosis of chronic joint diseases. A so-called synovitis score has been introduced as a standardised grading system, based on the semi-quantitative evaluation of the three determining features of chronic synovitis: enlargement of synovial lining, density of synovial stroma and inflammatory infiltrate, giving a score between 0 and 9. The present study examines the reliability of this procedure by comparison with exact measurements using computer-assisted image analysis (CAIA). Seventy-one synovial specimens from patients with osteoarthritis (OA, n=22), psoriatic arthritis (PsA, n=7), rheumatoid arthritis (RA, n=35) and from a control group (Co, n=7) were evaluated using both the synovitis score and CAIA. The measurements were transformed to semi-quantitative values analogous to the synovitis score. The differences between the transformed CAIA scores and the pathologist's scores were 0 or +/-1 in 40 cases, whereas in 31 cases the difference was greater than 1 (correlation coefficient r=0.725). The CAIA scores differed significantly between Co and RA cases (p=0.000) as well as between OA and RA (p=0.000). We conclude that the synovitis score was validated by CAIA and can be regarded a reliable grading system that contributes to the diagnostic procedure of chronic joint inflammation.
18587633 Impact of three anti-TNFalpha biologics on existing and emergent autoimmunity in rheumatoi 2008 Sep OBJECTIVE: The objective of this study was to analyze the effects of 3 anti-TNFalpha agents on markers of autoimmunity in rheumatoid arthritis (RA) and spondylarthropathy (SPA) patients. METHODS: First-time anti-TNFalpha biologics (infliximab, etanercept, or adalimumab) were prescribed to 156 RA and 95 SPA (58 ankylosing spondylarthritides, 37 psoriatic arthritides). During 1-2 years of follow-up, clinical, biological [antinuclear (ANA) and anti-double-stranded (dsDNA) antibodies, rheumatoid factors (RF), and anti-cyclic citrullinated peptide (CCP) for RA], and therapeutic data were collected biannually. RESULTS: ANA appeared or ANA and anti-dsDNA titers increased significantly (P < 0.001) more under infliximab than etanercept in both rheumatisms and than adalimumab in RA patients. During the 2-year follow-up, ANA appeared more in RA patients taking adalimumab than etanercept (P = 0.003), but independently of the anti-TNFalpha used; anti-dsDNA titers rarely became positive. Under etanercept or infliximab, ANA and anti-dsDNA were not influenced by the underlying pathology nor were they affected by infliximab intensification over 18 months. Only one case of cutaneous lupus was observed in a patient having IgG anti-dsDNA. The therapeutic responses were independent of ANA and anti-dsDNA titers for all rheumatisms and biologics. In RA patients, RF titers, but not anti-CCP levels, declined with the therapeutic response for all biologics. CONCLUSION: This is the first study that has evaluated the impact of three TNFalpha blockers on ANA and anti-dsDNA antibodies in RA and SPA patients. Autoimmunity was more induced with infliximab than etanercept and to a lesser degree to adalimumab but, more importantly, this emergent autoimmunity was exceptionally associated to clinical manifestations of lupus.
18587545 [Biological therapy for the treatment of rheumatic diseases]. 2008 Aug The analysis of cytokines (i.e. interleukins, interferons and colony-stimulating factors) has only flourished in the last 25 years subsequently revealing new insights into the pathogenesis of rheumatic diseases that revolutionised the management of patients with chronic rheumatic disorders. Tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6) have been found to play a pivotal role in rheumatic inflammation. As early as in 1992 the first proof of concept study with a monoclonal antibody against TNF was able to demonstrate positive effects in rheumatoid arthritis. Since the approval of the first anti-TNF-alpha therapy, further agents against TNF and other proinflammatory cytokines were approved and even more biological drugs are under development aimed at modulating the disturbed immune system in patients with rheumatic diseases. To date the following biologics are approved for therapy of chronic rheumatic diseases: the TNF antagonists Etanercept, Infliximab and Adalimumab; Anakinra as an IL-1 receptor antagonist; the anti-CD20 monoclonal antibody Rituximab and the anti-CD80/86 fusion protein Abatacept. In the present article, we report on biological therapy modalities in rheumatic diseases as well as the recommendations for initiation of these agents.
16414972 Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfati 2006 Sep BACKGROUND: Rheumatoid arthritis is a chronic autoimmune inflammatory condition characterised by polyarthritis and severe change in body mass and neuroendocrine environment. OBJECTIVES: To investigate plasma levels of adipocytokines (leptin, adiponectin, visfatin and resistin) in patients with rheumatoid arthritis and to compare them with levels in healthy controls. METHODS: Adiponectin, resistin, visfatin and leptin concentrations were measured in 31 patients with rheumatoid arthritis and 18 healthy controls by using specific enzyme-linked immunosorbent assays. RESULTS: Patients with rheumatoid arthritis showed considerably higher plasma levels of leptin, adiponectin and visfatin than healthy controls. No marked difference was observed in resistin levels between patients and controls. CONCLUSION: A marked increase in plasma levels of leptin, adiponectin and visfatin was noted in patients with rheumatoid arthritis, whereas resistin levels were similar to those observed in healthy controls. Coordinated roles for adiponectin, leptin and visfatin are suggested in the modulation of the inflammatory environment in patients with rheumatoid arthritis, whereas the lack of modulation in resistin levels is predictive of an irrelevant role for this peptide, suggesting that resistin level is probably not one of the main signals associated with the pathogenesis of this disease.
18412224 Photodynamic treatment as a novel approach in the therapy of arthritic joints. 2008 Apr BACKGROUND AND OBJECTIVE: Minimal invasive local treatment of joints is a desirable option in the therapy of rheumatoid arthritis (RA). Aim of this study was to evaluate the effects of photodynamic treatment (PDT) with different doses of the photosensitizer meta-tetra(hydroxyphenyl)chlorin (m-THPC; or temoporfin) in a murine model of RA (antigen-induced arthritis, AIA). METHODS IN VIVO DISTRIBUTION: The distribution of native and liposomal m-THPC (including a formulation with polyethylene glycol [PEG] coating) was assessed by fluorescence spectrometry in arthritic joints, normal joints, and skin. TREATMENT: AIA mice received different concentrations of pegylated liposomal m-THPC (0.1, 0.05, 0.01, or 0.005 mg/kg body weight; n = 5 per group) and subjected to PDT with a laser system 12 hours post-injection of the photosensitizer. Treatment effects were evaluated histologically in comparison to untreated AIA (n = 5). RESULTS: Pegylated liposomal m-THPC showed the most favorable accumulation in arthritic joints compared to native m-THPC and to non-peg-liposomal m-THPC, therefore it was selected as photosensitizer for PDT treatment. In comparison to untreated AIA, PDT reduced the arthritic score with all doses of pegylated liposomal m-THPC; statistical significant effects were obtained with doses of 0.05 and 0.01 mg/kg. CONCLUSION: Our study demonstrated that local PDT of arthritic joints is feasible. Application of pegylated liposomal m-THPC for PDT resulted in significant reduction of arthritis scores.
17665477 Antioxidants and other novel cardiovascular risk factors in subjects with rheumatoid arthr 2007 Aug 15 OBJECTIVE: To compare antioxidants and other novel and traditional cardiovascular disease (CVD) risk factors in participants with rheumatoid arthritis (RA) and non-RA controls in a large population sample. METHODS: The Third National Health and Nutrition Examination Survey (NHANES-III) was a cross-sectional population survey in which subjects ages >or=60 underwent a musculoskeletal examination. RA subjects were defined as those who met >or=3 of 6 available 1987 American College of Rheumatology (ACR) criteria. Non-RA subjects were defined as those who met no ACR criteria. We performed univariate and multivariate analyses of the association between RA and each novel and traditional CVD risk factor in RA versus non-RA subjects. RESULTS: The sample included 5,302 subjects ages >or=60, with 131 (2.5%) RA and 4,444 (84%) non-RA participants. A total of 727 subjects were excluded. Plasma levels of antioxidants alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene were significantly lower in RA subjects compared with non-RA subjects in multivariate analysis adjusting for potential confounders. Compared with non-RA participants, RA subjects were more likely to have increased C-reactive protein (CRP) levels in multivariate analysis adjusting for potential confounders. RA and non-RA participants had similar prevalence of traditional CVD risk factors and previous CVD. CONCLUSION: In this large population study, RA subjects had similar prevalence of previous CVD and traditional CVD risk factors as controls. Among novel CVD risk factors, plasma carotenoid levels were significantly lower and CRP level was significantly higher in RA compared with non-RA subjects after adjustment for potential confounders. Further research should evaluate whether these differences account for the observed increased incidence of CVD in individuals with RA.
16001180 Comparison of modern marker proteins in serum and synovial fluid in patients with advanced 2006 Mar Numerous studies have focused on the significance of modern marker proteins in the synovial fluid of the knee joint and in the serum both, for osteoarthritis (OA) and rheumatoid arthritis (RA). The relationship between the serum concentrations and the concentrations in the synovial fluid is still unclear. Synovial fluid and serum samples were obtained from 13 patients with advanced OA and from 8 patients with severe RA and concentrations of MMP-1, MMP-3, MMP-13, TIMP-1, COMP and MIA/CD-RAP were determined. All values were normalized against the total protein concentrations. Serum concentrations of MMP-13 in the RA-group were statistically higher than the synovial values (P<0.05). MMP-13 was the only marker protein that revealed distinct higher levels in the serum than in the synovial fluid. The study design allows only conclusions about advanced stages of RA and OA. Longitudinal investigations may provide further information about the value of MMP-13 as a potential marker to monitor the course of RA and OA.
19062243 [Pneumocystis pneumonia among patients with systemic diseases]. 2009 Feb The termPneumocystis carinii is now reserved for the animal form of the disease, for humans Pneumocystis jiroveci is appropriated. Incidence of pneumocystis pneumonia (PCP) among patients with systemic rheumatic diseases varies from 0.2% for rheumatoid arthritis to up 12% for Wegener's granulomatosis. Clinical and radiological presentation of pneumocystis pneumonia among non-VIH patients is often difficult to diagnose and the installation can be abrupt. Most of cases of PCP occur during the first 3 months following the beginning of immunosuppressant agents. Mortality during PCP is high with an average of 40% of death, rising 60% in case of mechanical ventilation. Prophylaxis of PCP is needed (without support by randomised studies) for patients with Wegener's granulomatosis, in case of cyclophosphamide or high-dose of methotrexate use except for rheumatoid patients, if a simultaneous treatment by corticosteroids and immunosuppressant agent is required, if a prolonged corticosteroid treatment (> 2 months) is used with dose of prednisone-equivalent > 16mg per day or > 20mg per day > 1month associated with one or more risk factors of PCP among advanced age, denutrition or deep lymphopenia. The best prophylaxis of PCP is cotrimoxazole.
17065120 Osteolysis after Sutter metacarpophalangeal arthroplasty: a prospective study of 282 impla 2006 Our aim was to evaluate the incidence and degree of osteolysis in a prospective series of patients with rheumatoid arthritis operated on with Sutter implants. Eighty-seven of the 110 operated hands (104 patients) with 282 implants were evaluated after a mean of 5.7 years (2.1-7.4). Osteolytic changes were present in 142 (50%) of the metacarpal and 152 (54%) of the phalangeal bones. Twenty-six of the metacarpal (9%) and 36 of the proximal phalangeal (13%) bones had osteolytic changes that did not affect the cortical bone. Cortical invasion was recorded in 100 (35%) of the metacarpal and 103 (37%) of the proximal phalangeal bones. The cortex was perforated in both bones in 14 (5%). Osteolytic changes were related to fractures of implants and to the dominant hand, but not to pain. Surgeons who operate on patients with rheumatoid diseases should note that silicone rubber implants often cause osteolytic changes.
17721706 [Conservative local therapy of inflammation of joints: local invasive forms of therapy]. 2007 Sep Local invasive procedures represent possibilities for the treatment of arthritic swollen joints without surgical interventions, when general measures alone are not successful and intra-articular injections are of utmost importance in this context. The differences between degenerative and rheumatologic diseases must be considered as well as possible specific adverse reactions, side effects and contraindications. The technical intervention is performed according to the guidelines of scientific societies such as the Scientific Medical Profession Society (AWMF). Cortisone and radiosynoviorthesis/chemosynoviorthesis are suitable for activated rheumatic and degenerative joints, low-grade radiation therapy or infiltration of hyaluronic acid is recommended for relief in cases of arthritic inflammation. The combination of arthroscopic synovectomy and subsequent radiosynoviorthesis in the early stages of rheumatically swollen joints show the best results with respect to regression prophylaxis and slowing the process of rapidly progressing destruction of chondral surfaces and distension of the capsules and ligaments.
16826439 Single-factor scoring validation for the Health Assessment Questionnaire-Disability Index 2006 Oct OBJECTIVE: Structural validity for the Health Assessment Questionnaire-Disability Index (HAQ-DI) has recently been provided for patients with rheumatoid arthritis (RA). The goal of the current study was to examine the structural validity of the HAQ-DI in patients with systemic sclerosis (SSc, scleroderma) and to compare its performance with that in patients with RA. METHODS: The HAQ-DI structural validity was first assessed in a sample of 100 scleroderma patients using confirmatory factor analysis. Second, the similarity of factor structures between SSc patients (n = 291) and RA patients (n = 278) was tested using a multigroup structural validity model to assure that comparison of scores between these two diagnostic groups is appropriate. RESULTS: Results yielded a single-factor HAQ-DI score which favored the current scoring system of the HAQ-DI (model fit was CFI = 0.99 and RMSEA = 0.04). Moreover, even the most stringent model of multigroup structural validity affirmed the similarity between SSc and RA patients on the HAQ-DI (model fit was CFI = 0.99 and RMSEA = 0.04) nor was it different from a model without any demands on group similarity: CFI difference = 0.007; chi(2) = 4.29, df = 26, p=0.99. CONCLUSION: The current results indicate that a single-factor HAQ-DI is appropriate for future clinical trials in scleroderma and, in addition, HAQ-DI scores among patients with SSc and early RA can be compared legitimately with one another.
16463408 Retrospective analysis of utilization patterns and cost implications of coxibs among senio 2006 Feb 15 OBJECTIVE: In September 2004, the manufacturer of rofecoxib announced a voluntary worldwide withdrawal of the drug. The impact of this withdrawal on drug budgets is unclear. This study evaluated average daily doses and costs of rofecoxib and celecoxib and concomitant use of gastroprotective agents (GPAs) in elderly patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in Quebec, prior to the rofecoxib withdrawal. METHODS: This retrospective cohort study used prescription drug and medical service data from the Quebec government health agency administrative database and included coxib users > or =66 years of age with OA or RA who filled > or =3 consecutive rofecoxib or celecoxib prescriptions in 2001-2002. Results were adjusted for gastrointestinal risk factors and other patient baseline characteristics. RESULTS: Data were analyzed for 11,975 rofecoxib and 12,480 celecoxib users. Mean daily dosages were 20.7 mg for rofecoxib and 231.3 mg for celecoxib. Rofecoxib users consumed a mean +/- SD of 0.95 +/- 0.43 pills per day, and celecoxib users took 1.34 +/- 0.65 pills per day. Mean +/- SD unadjusted daily acquisition costs were $1.18 +/- $0.53 (Canadian) for rofecoxib and $1.45 +/- $0.74 for celecoxib. After adjusting for patient baseline characteristics, the mean daily acquisition cost for rofecoxib was $0.25 lower than for celecoxib. Rofecoxib users were less likely than celecoxib users to fill a GPA coprescription (odds ratio 0.88; 95% confidence interval 0.81, 0.95). Subgroup analyses yielded comparable results. CONCLUSION: Celecoxib appears to be a more expensive therapeutic option than rofecoxib due to a relatively higher daily dose and tablet consumption.
17511276 [Apperceptive form visual agnosia caused by anti-TNFalpha therapy to rheumatoid arthritis] 2007 Feb TNFalpha plays an important role as an inflammatory mediator in both several autoimmune diseases and multiple sclerosis. Anti-TNFalpha antibody has been widely used to treat rheumatoid arthritis and Crohn's disease. On the. other hand, anti-TNFalpha antibody treatment increased recurrence rate in clinical trials for multiple sclerosis. We report a patient with rheumatoid arthritis without past history of any neurological disorders, who developed diplopia, ataxia, and visual agnosia specific to line drawing in the course of anti-TNFalpha antibody treatment. MRI studies detected multiple demyelinating lesions in the cerebral white matter and brainstem. The present case indicates that careful observation of neurological symptoms is important in the course of anti-TNFalpha antibody treatment, even in patients without past history of demyelinating diseases.