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The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18-70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4-554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD (p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant.

Recognition of multiple sclerosis (MS) attacks relies mostly on clinical assessment. However, their definition based on McDonald criteria refers mostly to timing and when dealing with clinical features is rather ambiguous: "...of the kind seen in multiple sclerosis." This is heightened in clinically isolated syndromes of the brainstem/cerebellum (CISB), where clinical manifestations can be manifold. This study aimed to describe the clinical features of patients with CISB to improve clinical recognition of patients with brainstem manifestations at the onset of their MS. To this end, we conducted a retrospective analysis of case notes of consecutively recruited patients with CISB assessed within 3 months of symptoms onset. Seventy-five patients were included. Most common brainstem-specific symptoms were: diplopia (68%), facial sensory symptoms (32%) and gait disturbance (31%). Adjusting for follow-up times, total number of symptoms and presence of other brainstem-specific symptoms, only the presence of facial sensory symptoms was predictive of (a lower risk of) conversion to clinically definite (CD) MS (Odds ratio: 0.086; p = 0.007). Neither the total number of brainstem-specific, non brainstem-specific nor the sum of both predicted conversion to CDMS. Results indicate that diplopia, facial sensory symptoms and gait disturbance occur in more than 30% of patients with CISB. Facial sensory symptoms are less associated with conversion to CDMS.

Background: Cytokine inhibitors, such as soluble tumor necrosis factor receptor II (sTNFRII) and interleukin-1 receptor antagonist (IL-1ra) are possible regulators of proinflammatory cytokine activity. Although previous studies have shown induction of sTNF-RII and IL-1ra by interferon-beta (IFNbeta) in patients with relapse-onset forms of multiple sclerosis (MS), to date no studies of these cytokine inhibitors have been performed in patients with essentially progressive forms of MS., Objective: To address the effects of IFNbeta on serum levels of sTNF-RII and IL-1ra in a cohort of progressive MS patients and to assess the relationship between levels and changes of sTNF-RII and IL-1ra and clinical and radiological variables. Methods Serial blood samples were obtained from a cohort of 73 patients with progressive MS who participated in a placebo-controlled clinical trial with IFNbeta-1b. Serum levels of sTNF-RII and IL-1ra were measured by multiplex enzyme-linked immunosorbent assay at baseline and after 3, 6, 12, and 24 months. EDSS and MSFC scores were recorded at the time of blood sampling, and MR scans were obtained at baseline and after 12 and 24 months., Results: Treatment with IFNbeta was associated with significant increases of sTNF-RII and IL-1ra serum levels during the followup period. A strong correlation at 24 months was observed between levels of sTNF-RII and EDSS scores in the placebo group. Finally, a trend for negative association was found between changes in sTNFRII and percentage change in T2-weighted lesion load at 24 months in the IFNbeta treated group., Conclusions: sTNF-RII and IL-1ra levels are increased in the serum of progressive MS patients during IFNbeta therapy and may be one mechanism by which IFNbeta mediates its effects in the treatment of MS.

Background and Objective: Observational studies may provide additional information about the behaviour of different drugs in the post-marketing period. We present the data from a cohort of secondary progressive multiple sclerosis (SPMS) patients treated with interferon beta (IFNbeta-1b) at our MS clinic., Methods: This was an independent, open-label, non-randomised, observational study. Within the period 1998 to 2005, all patients with SPMS who started therapy with IFNbeta-1b at our centre were studied. Each patient was included in a follow-up protocol collecting demographic and baseline clinical data., Results: We studied 146 SPMS patients with a median follow-up of 60 months. Over the total study period, 62.2% of patients had confirmed progression. The analysis of the time to con- firmed progression showed that patients with two or more relapses in the 2 years before IFNbeta initiation, had a higher risk of disability increase than those patients with less than two relapses (p = 0.002). Multiple regression analysis showed disease activity in terms of relapses as the only factor to predict increase of disability during the follow-up period. A significant proportion of patients (36%) stopped treatment during the follow-up period. IFNbeta was safe, although some unexpected adverse events were observed., Conclusions: A higher disease activity before the beginning of treatment with IFNbeta in SPMS patients with a given EDSS rank could identify those with faster disability progression after treatment initiation.

Background and Objective: Fatigue is one of the most frequent symptoms in multiple sclerosis (MS) but there is a lack of knowledge about its behaviour over time. The aim of our study was to investigate changes in fatigue in a large cohort of MS patients and to determine the relationship between changes in disability and depression with changes in fatigue severity., Methods: We studied fatigue in 227 MS consecutive patients and again after one year. During the clinical interview, we recorded the patient's degree of disability using the Expanded Disability Status Scale and relapses; fatigue was measured by means of the Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) and depression was measured by the Beck Depression Inventory (BDI)., Results: After a mean follow-up of 18 months, 86.8% of patients who were fatigued at study onset remained in a fatigued status, whereas 25% of those without fatigue at onset had become fatigued at the end of follow-up. We observed that only variations on BDI scores positively correlate with variations on fatigue scales, mainly with MFIS (r = 0.49, p < 0.0001). An increase of BDI score was the factor that best predicted the increase of fatigue over time. No differences in the increase of fatigue were found between patients with and without progression of disability during the follow-up period, or between patients with or without relapses., Conclusions: Fatigue in MS persists over time. Changes in mood status but not in disability are related to changes in fatigue in MS patients.

Background and Objective: Long-term observational studies may provide additional information about the behaviour of different drugs in the post-marketing period. We present the data of our cohort of relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon beta (IFNbeta)., Methods: We analysed RRMS patients followed for at least 2 years. From 1995, we initiated therapy with IFNbeta. As they became available, patients were allocated to one of the IFNs at standard doses (IFNbeta-1b, IFNbeta-1a i.m. or IFNbeta-1a s.c.). Each patient was included in a follow-up protocol containing demographic and baseline clinical data., Results: Between 1995 and 2004, 382 patients have completed at least 2 years of follow-up. Significant differences at entry were observed. Patients on IFNbeta-1b had a higher disease activity and disability at baseline than those on IFNbeta-1a i.m. or IFNbeta-1a s.c. A significant reduction in the relapse rate was observed for the three drugs (70% for IFNbeta-1b, 64% for IFNbeta-1a i.m. and 74% for IFNbeta-1a s.c.). We observed a sustained progression of disability in 11% of patients on IFNbeta-1b, 17% on IFNbeta-1a i.m. and 19% on IFNbeta-1a s.c.; and at four years of follow-up in 24% of patients on IFNbeta-1b, 23% on IFNbeta-1a i.m. and 35% on IFNbeta-1a s.c. No unexpected major adverse events were observed with any of the drugs., Conclusions: Interferon beta is safe and well tolerated. The various registered interferon beta drugs provide a comparable efficacy in a large non-selected cohort of RRMS patients.