1,720,965 research outputs found
Integration of advanced molecular analyses and magnetic resonance imaging for the identification of biomarkers of disease progression in multiple sclerosis
Full text linkBackground. In the last 15 years, it has become increasingly accepted that cerebral grey matter (GM) damage in MS is evident since early MS stages and provides the best correlate of the rate of clinical progression since early disease stages. The lack of substantial inflammatory infiltrates, complement deposition and blood brain barrier damage in MS cortical lesions led to the initial suggestion that the mechanisms underlying GM and white matter (WM) pathology substantially differ and that activated microglia are the dominant effector cell population causing GM damage. Furthermore, in the last decade, post-mortem studies have revealed that the extent of meningeal inflammation associates positively with subpial cortical demyelination and disease progression, suggesting that chronic immune activity in the subarachnoid compartment plays a key role in mediating damage in the adjacent cerebral cortex of affected patients. Factors released by immune cells circulating in the CSF and/or colonizing the subarachnoid space may diffuse across the pial membrane, inducing a gradient of glia and neuronal pathological alterations, directly and/or indirectly through activated microglia.
Aim of the study. To combine CSF molecular and protein analyses with advanced MRI imaging techniques, able to better identify cortical grey matter demyelination, in order to identify potential early biomarkers of GM pathology and disease progression with prognostic and predictive value and to obtain information on the biological and immunological mechanisms that link the inflammatory process of the GM and the progressive neurodegeneration
Methods. Two independent cohorts of MS patients have been recruited and followed by the MS Centre of Padova. The first cohort of MS patients, composed of 35 patients and 5 controls was recruited retrospectively between February 2009 and September 2011 and followed by a detailed neurological and clinical follow-up. The second cohort of 31 patients and 13 controls was collected prospectively from January 2014 to May 2015. The patients, at their disease onset or in the very early phase of the disease, underwent a complete diagnostic work-up comprehensive of clinical evaluation, lumbar puncture and MRI evaluation inclusive of non-conventional sequences. By using the immuno-assay Bio-Plex System technique (Biorad - Bio-Plex Pro Human Chemokine panel 40-plex) we performed a protein analysis of the presence and levels of inflammatory molecules in both cohorts. In the second cohort we carried out also a gene expression analysis of the matched cellular fraction (using pre amplification real-time PCR for a panel of genes of interest).
Results. CSF protein analysis of the first cohort of MS patients reveal higher levels of proinflammatory cytokines CXCL13 (p=0,00006), CCL19 (p=0,0019), CCL1 (p=0,00018), and CCL22 (0.0009) compared to controls. Protein analysis on our second cohort pointed out an important increase of CXCL13, CXCL10, CXCL11 and CCL2 in MS population compared to controls. After stratification according to GM pathology we reported an increase of CXCL13 protein levels in the MS subgroup with higher cortical demyelination. Gene expression analysis reveals a significant increase in MS patients for CD20, CD138 and LTa compared to controls supporting the hypothesis of a key role of a B-cell response and lymphoid neogenesis in MS pathology
Conclusions. Combined CSF analysis and MRI analysis suggested that B cell immune response may play an important role in MS since the disease onset and correlates with the level of intrathecal inflammation and cortical pathology. A more detailed analysis of the CSF biomarkers suggested in the current study might provide, in addition to MRI optimization, a better indication of severity of disease process that characterized GM pathology and important tools in predicting/monitoring the evolution of the disease
Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: clinical and magnetic resonance imaging findings.
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Disease-modifying drugs reduce cortical lesion accumulation and atrophy progression in relapsing-remitting multiple sclerosis: results from a 48-month extension study
Full text linkCortical lesions (CLs) and atrophy are pivotal in multiple sclerosis (MS) pathology. This study determined the effect of disease modifying drugs (DMDs) on CL development and cortical atrophy progression in patients with relapsing-remitting MS (RRMS) over 48 months. Patients (n = 165) were randomized to sc IFN β-1a 44 μg, im IFN β-1a 30 μg, or glatiramer acetate 20 mg. The reference population comprised 50 DMD-untreated patients with RRMS. After 24 months, 43 of the untreated patients switched to DMDs. The four groups of patients were followed up for an additional 24 months. At 48 months the mean standard deviation number of new CLs was significantly lower in patients treated with sc IFN β-1a (1.4 ± 1.0, range 0-5) compared with im IFN β-1a (2.3 ± 1.3, range 0-6, P = 0.004) and glatiramer acetate (2.2 ± 1.5, range 0-7, P = 0.03). Significant reductions in CL accumulation and new white matter and gadolinium-enhancing lesions were also observed in the 43 patients who switched to DMDs after 24 months, compared with the 24 months of no treatment. Concluding, this study confirms that DMDs significantly reduce CL development and cortical atrophy progression compared with no treatment
Cerebrospinal fluid IL-1β correlates with cortical pathology load in multiple sclerosis at clinical onset
No full textGray matter pathology in MS: A 3-year longitudinal study in a pediatric population
Full text linkBACKGROUND AND PURPOSE: GM pathology is considered a major determinant of disability in MS, but the comprehension of its origin and progression rate is limited by the uncertainty of dating the biologic disease onset. Thus, we planned a longitudinal study aimed at analyzing and comparing cortical pathology in pediatric and adult MS patients at clinical onset. MATERIALS AND METHODS: Within 12 months from clinical onset, 35 patients with cMS and 57 with aMS were included in a longitudinal study. At T0, GMf and CL number and volume were analyzed. Percentages of Δ-GMf and number of new CLs were assessed every year for 3 years (T1-T3). Twenty-eight age- and sex-matched NCs constituted the reference population. RESULTS: At T0, GMf did not differ between cMS and NC (P = .18), while it was lower in patients with aMS compared with both NCs (P < .001) and patients with cMS (P < .001). The number of patients with CLs, as well as CL number and volume, were higher in patients with aMS than in those with cMS (P < .001). At T3, Δ-GMf was higher in both patients with cMS (1.6% ± 0.5%; range 0.7%-3.4%; P < .001) and aMS (1.6% ± 0.6%; range 0.6%-3.4%; P < .001) compared with NCs (0.7% ± 0.2%; range 0.4%-1.1%), whereas no difference was observed between patients with cMS and aMS (P = .93). Δ-GMf significantly correlated with increased CL volume (cMS: r = 0.46; aMS: r = 0.48) and with the appearance of new CLs (cMS: r = 0.51; aMS: r = 0.49). CONCLUSIONS: Our findings suggest that focal (CLs) and diffuse (atrophy) GM damage are strictly associated with the biologic onset of MS, and proceed linearly and partly independently of WM pathology
Increased incidence of multiple sclerosis in the Veneto region, Italy.
No full textBackground: To what extent the progressive increase in the incidence of multiple sclerosis (MS) observed in the province of Padova over the period 1970–1999 was an expression of a real increased risk of developing MS remained unclear.
Objective: The objective of this paper is to update the epidemiological figures of MS and probe whether the risk of having MS has increased in the province of Padova during the decade 2000–2009.
Methods: All patients born in Italy and having a diagnosis of MS or possible MS identified through analysis of all available sources of information were included in the study. The incidence and prevalence rates between 2000 and 2009 were obtained and compared with our previously published data.
Results: On 31 December 2009, the overall prevalence was 139.5/100,000, 192.0±9.5 for females and 83.9±6.3 for males. During the decade 2000–2009, the overall incidence rate of MS was 5.5±0.5, 7.4±0.8 for females and 3.5±0.6 for males. The onset-diagnosis delay, the female/male ratio and the mean age at onset did not significantly change compared to the prior period of observation.
Conclusion: Our findings support the hypothesis of a real increased risk of developing MS in the province of Padova. Moreover, the actual prevalence of 1.4/1000 makes our region a high-risk geographical area for MS. The role played by exogenous factors in determining susceptibility to MS needs to be thoroughly investigated
Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis.
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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