Metabolic counterparts of sodium accumulation in multiple sclerosis: A whole brain 23Na-MRI and fast 1H-MRSI study

Increase of brain total sodium concentrations (TSC) is present in multiple sclerosis (MS), but its pathological involvement has not been assessed yet. To determine in vivo the metabolic counterpart of brain sodium accumulation. Whole brain Na-MR imaging and 3D- H-EPSI data were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and 20 volunteers. Metabolites and sodium levels were extracted from several regions of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM) T lesions. Metabolic and ionic levels expressed as Z-scores have been averaged over the different compartments and used to explain sodium accumulations through stepwise regression models. MS patients showed significant Na accumulations with lower choline and glutamate-glutamine (Glx) levels in GM; Na accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo-Inositol (m-Ins) in NAWM; and higher Na, m-Ins levels with lower NAA in WM T lesions. Regression models showed associations of TSC increase with reduced NAA in GM, NAWM and T lesions, as well as higher total-creatine, and smaller decrease of m-Ins in T lesions. GM Glx levels were associated with clinical scores. Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

From inflammation to neurodegeneration : what we can learn about MS pathology from MRI ?

La sclérose en plaques est une maladie chronique. Elle se caractérise par une inflammation focale et diffuse, une démyélinisation, une souffrance axonale et une dégénérescence neuronale. L’apparition d’une incapacité progressive et irréversible en est la principale morbidité. Mieux comprendre les liens entre les différents mécanismes impliqués dans la SEP et la part de chacun dans la genèse du handicap est fondamental.L’inflammation dans la SEP est polymorphe. Une famille de produits de contraste, l’USPIO, permet le marquage des macrophages et leur suivi en IRM. Ainsi, 35 patients ont été inclus. Le rehaussement par l’USPIO était spatialement et temporellement différent de celui observé après injection de gadolinium. Les lésions caractérisées par une activité macrophagique induisent localement une déstructuration tissulaire plus importante sur l’IRM initiale et après 1 an.À cette inflammation aiguë s’ajoutent l’inflammation et la démyélinisation chroniques, qui entraînent une accumulation de sodium. La deuxième étude a permis de montrer cette accumulation en IRM chez 20 patients souffrant de la forme progressive, où prédominent l’inflammation et la démyélinisation chroniques.L'importance de l’accumulation corticale de sodium chez ces patients nous a conduit à entreprendre une troisième étude chez des patients souffrant de troubles cognitifs. Ainsi 58 patients rémittents ont été inclus dans cette étude. Une accumulation de sodium a été mise en évidence chez les patients présentant une atteinte cognitive. Cette accumulation touche le néocortex, en particulier préfrontal, cingulaire et le precuneus. De plus, cette accumulation survient avant l’atrophie.Multiple sclerosis (MS) is a chronic disease leading to permanent disability. Demyelination, inflammation and diffuse axonal and neuronal loss are histological hallmarks of MS. Better understand the links between these different mechanisms and their role in the genesis of disability is fundamental. Inflammation in MS is polymorphic. A family of recent contrast agents, the USPIO, allows the labelling and monitoring of macrophages. 35 patients were included. Enhancement by USPIO was spatially and temporally different from gadolinium. Lesions characterized by macrophage activity locally induce a more significant tissue destructuration at baseline and at one year.Moreover, chronic inflammation and chronic demyelination lead to intra-neuronal sodium accumulation. Because of the physical properties of 23Na and technical improvements, sodium MRI imaging is to date possible. Thus in the second study, sodium accumulation was demonstrated in 20 patients at a progressive phase, particularly susceptible to chronic inflammation and demyelination. Then, the discovery of the importance of cortical sodium accumulation in this study led us to undertake a third study in patients prone to cognitive disorders, were cortical involvement seems to be more pronounced. 58 remitting patients were enrolled. Sodium accumulation was demonstrated in patients with cognitive impairment. This accumulation affects the neocortex (prefrontal cortices, cingulate and the precuneus). This accumulation occurs before atrophy

Rôle de l'activité macrophagique dans l'atteinte tissulaire de la sclerose en plaques (étude longitudinale en RMN de 35 patients)

REIMS-BU Santé (514542104) / SudocSudocFranceF

Maintenance of natalizumab during the first trimester of pregnancy in active multiple sclerosis

International audienceBackground: Planning pregnancy in patients with active multiple sclerosis (MS) is highly challenging because treatment withdrawn may be associated with dramatic disease reactivation. Objective: To compare two strategies for women with active MS who were planning pregnancy: stopping natalizumab (1) at the end of the first trimester and (2) at conception. Methods: Standardized strategy for women with active MS was initiated in our department. Maintenance of natalizumab until the end of first trimester was recommended (“secured first trimester” (SFT)). When patients refused, they were advised to continue until conception (“secured conception” (SC)). Predictors of disease activity during pregnancy were assessed. Results: Forty-six pregnancies were prospectively followed (30 with SFT and 16 with SC). One congenital anomaly occurred in the SC group. The proportions of patients with relapse and disability progression during pregnancy were lower in the SFT than in the SC group (3.6% vs 38.5%, p < 0.005 and 3.6% vs 30.8%, p < 0.05, respectively). Predictors of relapse and disability progression during pregnancy were the time when natalizumab was stopped (conception vs end of first trimester) and the number of relapses during the year before natalizumab. Conclusion: Maintaining natalizumab during the first trimester may reduce the risk of disease reactivation during pregnancy in patients with active MS

Multiple Sclerosis Lesions Evolution in Patients with Clinically Isolated Syndrome

International audienceMultiple sclerosis (MS) is a disease with heterogeneous evolution among the patients. Some classifications have been carried out according to either the clinical course or the immunopathological profiles. Epidemiological data and imaging are showing that MS is a two-phase neurodegenerative inflammatory disease. At the early stage it is dominated by focal inflammation of the white matter (WM), and at a latter stage it is dominated by diffuse lesions of the grey matter and spinal cord. A Clinically Isolated Syndrome (CIS) is a first neurological episode caused by inflammation/demyelination in the central nervous system which may lead to MS. Few studies have been carried out so far about this initial stage. Better understanding of the disease at its onset will lead to a better discovery of pathogenic mechanisms, allowing suitable therapies at an early stage. We propose a new data processing framework able to provide an early characterization of CIS patients according to lesion patterns, and more specifically according to the nature of the inflammatory patterns of these lesions. The method is based on a two layers classification. Initially, the spatio-temporal lesion patterns are classified using a tensor-like representation. The discovered lesion patterns are then used to identify group of patients and their correlation to 15 months follow-up total lesion loads (TLL), which is so far the only image-based figure that can potentially infer future evolution of the pathology. We expect that the proposed framework can infer new prospective figures from the earliest imaging sign of MS since it can provide a classification of different types of lesion across patients

Extending rituximab dosing intervals in patients with MS during the COVID-19 pandemic and beyond?

International audienceObjective To evaluate disease activity in patients with relapsing-remitting MS (RRMS) receiving rituximab with an extended dosing interval. Methods In the context of COVID-19 pandemic, this was an interim analysis of an ongoing prospective observational study of patients who were stable on rituximab for at least 6 months and who had a planned extended dosing interval of 24 months. Only data for patients with active RRMS before rituximab were analyzed. Results Among 177 patients receiving rituximab, 33 had RRMS and MRI activity before rituximab and at least 8 months of follow-up after the last infusion. The mean (SD) age was 40 (14) years, 25 were females, the mean disease duration was 10 (6.8) years, the mean annual relapse rate (ARR) before rituximab was 1.7 (1.3), and the median Expanded Disability Status Scale (EDSS) score before rituximab was 4.5 (1–7). Before extended dosing, when rituximab was infused every 6 months, the mean (SD) ARR decreased to 0.04 (0.1) ( p 1% for 10 of 25 patients at the last count (median time 8 [6–25] months). Conclusions An extended dosing interval for rituximab for patients with stable MS during the COVID-19 pandemic may be associated with a low risk of disease activity

Diffusion MRI abnormalities detection with orientation distribution functions: A multiple sclerosis longitudinal study

International audienceWe propose a new algorithm for the voxelwise analysis of orientation distribution functions between one image and a group of reference images. It relies on a generic framework for the comparison of diffusion probabilities on the sphere, sampled from the underlying models. We demonstrate that this method, combined to dimensionality reduction through a principal component analysis, allows for more robust detection of lesions on simulated data when compared to classical tensor-based analysis. We then demonstrate the efficiency of this pipeline on the longitudinal comparison of multiple sclerosis patients at an early stage of the disease: right after their first clinically isolated syndrome (CIS) and three months later. We demonstrate the pre-dictive value of ODF-based scores for the early detection of lesions that will appear or heal

Le risque du cancer dans la SEP : une étude de cohorte nationale (2012–2021)

National audienceObjectifs :Comparer le risque de cancer entre les pSEP et la population générale entre 2012 et 2021 à partir du Système national des données en santé (SNDS ; 99 % population française)