Vitality, perceived social support and disease activity determine the performance of social roles in recently diagnosed multiple sclerosis: a longitudinal analysis.

OBJECTIVE: The aim of this study was to identify the principal determinants that are longitudinally associated with the performance of social roles in the first 3 years following a diagnosis of multiple sclerosis. DESIGN: Inception cohort with 5 measurements over 3 years. PATIENTS: A total of 156 patients recently diagnosed with multiple sclerosis. METHOD: Performance of social roles was measured using the 2 role functioning and the social sub-scales of the Medical Outcome Study Short Form 36. Potential determinants (n = 43) were divided into the following clusters: patient and disease characteristics (n = 12), psychosocial characteristics (n = 10), basic functions (n = 18) and basic activities (n = 3). Multivariate longitudinal regression analyses were performed with generalized estimating equations. A backwards selection procedure for every cluster per outcome reduced the large number of potential determinants. In order to determine whether longitudinal associations are present the selected determinants were entered into an overall regression model. RESULTS: Twenty-three candidate determinants were selected. Vitality, measured with the SF36 sub-scale vitality, the T2-weighted supratentorial lesion load and the perceived amount of social support, measured with the Social Support List Discrepancies, were longitudinally associated with the performance of social roles in 2 or 3 of the models. CONCLUSION: Vitality, the perceived amount of social support, and disease activity, i.e. the T2-weighted supratentorial lesion load, determine the performance of social roles in the early stages of multiple sclerosis.     

Magnetization transfer histogram parameters reflect all dimensions of MS pathology, including atrophy

INTRODUCTION: Magnetization transfer ratio (MTR) histogram analysis can be used as a method for quantifying overall disease burden in MS. We studied correlations between MTR histogram and clinical parameters in MS subgroups. Contrary to earlier studies we placed special emphasis on the lower MTR range, to explore the effect of partial volume averaging effects with CSF. METHODS: Seventy-nine patients with MS [26 primary progressive (PP), and 53 'relapse-onset', including 26 secondary progressive (SP)], and 23 healthy individuals were studied. MR imaging included 3 mm 2D gradient-echo images with and without an off-resonance MT pulse. According to the visually determined cut-off, histogram parameters were classified as parenchymal or CSF-related variables. Clinical measurements included the Expanded Disability Status Scale (EDSS) as a measure of global impairment/disability and the Paced Auditory Serial Addition Test (PASAT) as a measure of cognition. RESULTS: SP MS patients differed from the other subgroups on many MTR variables, originating from both the lower and the higher MTR range. CSF-related low MTRs were clearly over-represented in SP patients, and showed a significant distinction between the SP and PP MS group. In the total group, as well as in the relapse-onset patients, significant correlations were found between MTR parameters and clinical parameters. No associations were found in the PP group. CONCLUSION: This explorative study suggests that MTR histogram analysis can distinguish between MS patients and controls, and best identifies the SP phenotype, partly as a result of increased CSF volume (atrophy). In addition, we show that MTR histogram analysis gives information about the level of impairment and disability in patients with a 'relapse-onset' course of MS, and therefore provides a useful tool to monitor the evolution of the disease in these patients.     

Intrathecal CD4+ and CD8+ T‐cell responses to endogenously synthesized candidate disease‐associated human autoantigens in multiple sclerosis patients

MS pathology is potentially orchestrated by autoreactive T cells, but the antigens recognized remain unknown. A novel APC/T‐cell platform was developed to determine intrathecal CD4⁺ and CD8⁺ T‐cell responses to candidate MS‐associated autoantigens (cMSAg) in clinically isolated syndrome (CIS, n = 7) and MS (n = 6) patients. Human cMSAg encoding open reading frames (n = 8) were cloned into an Epstein–Barr virus (EBV)‐based vector to express cMSAg at high levels in EBV‐transformed B‐cells (BLCLs). Human cMSAg cloned were myelin‐associated and ‐oligodendrocyte glycoprotein, myelin basic protein, proteolipid protein, ATP‐dependent potassium channel ATP‐dependent inwards rectifying potassium channel 4.1, S100 calcium‐binding protein B, contactin‐2, and neurofascin. Transduced BLCLs were used as autologous APC in functional T‐cell assays to determine cMSAg‐specific T‐cell frequencies in cerebrospinal fluid derived T‐cell lines (CSF‐TCLs) by intracellular IFN‐γ flow cytometry. Whereas all CSF‐TCL responded strongly to mitogenic stimulation, no substantial T‐cell reactivity to cMSAg was observed. Contrastingly, measles virus fusion protein‐specific CD4⁺ and CD8⁺ T‐cell clones, used as control of the APC/T‐cell platform, efficiently recognized transduced BLCL expressing their cognate antigen. The inability to detect substantial T‐cell reactivity to eight human endogenously synthesized cMSAg in autologous APC do not support their role as prominent intrathecal T‐cell target antigens in CIS and MS patients early after onset of disease.     

Antibodies against aquaporin-4 in neuromyelitis optica: distinction between recurrent and monophasic patients

The detection of antibodies against aquaporin-4 (AQP4) has improved the diagnosis of neuromyelitis optica (NMO). We evaluated a recently established cell-based anti-AQP4 assay in 273 patients with inflammatory CNS demyelination. The assay had a specificity of 99% and a sensitivity of 56% to detect all NMO patients and of 74% to detect the recurrent NMO patients, similar to the initial studies reported. AQP4 antibodies were absent in monophasic NMO patients, while samples in recurrent cases remained positive during follow-up. We conclude that the pathogenesis of monophasic NMO may be different from that of relapsing NMO.     

Familial clustering of multiple sclerosis in a Dutch genetic isolate

Multiple sclerosis (MS) is a complex disease with a substantial, yet poorly identified, genetic influence. We estimated the pattern of familial aggregation of MS in a recent genetically isolated population in The Netherlands. Forty-eight MS patients were identified. Their relationship was evaluated by tracing extended pedigrees, making use of municipal and church records. Of the 48 MS patients, 24 could be linked to a common ancestor in 14 generations. However, multiple relationships exist between patients and, to take these into account, we calculated inbreeding and kinship coefficients. We found that MS patients from the isolate were significantly more often related to each other and significantly more often inbred than a non-MS control group, drawn from the same isolate. There was no clustering of Type 1 diabetes and autoimmune thyroid diseases in families of MS patients from this isolate. Finally, HLA typing was performed. Although there was a trend towards a higher prevalence of the HLA DRB1*15 allele in patients compared to controls, differences did not reach significance. This study suggests familial aggregation in the genetically isolated population. The high level of inbreeding makes this population valuable for finding novel genes involved in MS.     

A three-year study of brain atrophy after autologous hematopoietic stem cell transplantation in rapidly evolving secondary progressive multiple sclerosis

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), autologous hematopoietic stem cell transplantation (AHSCT) induces a profound suppression of clinical activity and MR imaging-detectable inflammation, but it may be associated with a rapid brain volume loss in the months subsequent to treatment. The aim of this study was to assess how AHSCT affects medium-term evolution of brain atrophy in MS. MATERIALS AND METHODS: MR imaging scans of the brain from 14 patients with rapidly evolving secondary-progressive MS obtained 3 months before and every year after AHSCT for 3 years were analyzed. Baseline normalized brain volumes and longitudinal percentage of brain volume changes (PBVCs) were assessed using the Structural Image Evaluation of Normalized Atrophy software. RESULTS: The median decrease of brain volume was 1.92% over the first year after AHSCT and then declined to 1.35% at the second year and to 0.69% at the third year. The number of enhancing lesions seen on the pretreatment scans was significantly correlated with the PBVCs between baseline and month 12 (r = -0.62; P = .02); no correlation was found with the PBVCs measured over the second and third years. CONCLUSIONS: After AHSCT, the rate of brain tissue loss in patients with MS declines dramatically after the first 2 years. The initial rapid development of brain atrophy may be a late consequence of the pretransplant disease activity and/or a transient result of the intense immunoablative conditioning procedure.     

Treatment of MOG antibody associated disorders: results of an international survey

Journal of Neurology - While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on...