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

Devenir médico-social d'une cohorte de 81 sujets de plus de 65 ans hospitalisés à la phase aigüe d'un accident vasculaire cérébral

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Encéphalomyélite autoimmune expérimentale (expression neuronale du TNFalpha, expression du système FAS/FAS-L et apoptose des cellules immunes chez le rat DA)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Enquête auprès des centres spécialisés SEP en France et à l'étranger sur la prise en charge thérapeutique d'une maladie démyélinisante inaugurale idiopathique fulminante du système nerveux central

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mechanism of action of s1p receptor modulators in multiple sclerosis: The double requirement

International audienceThe ideal treatment for multiple sclerosis (MS) would target both the neuroinflammatory component of the disease (peripheral and central) and its neurodegenerative component, via modulation of a ubiquitous and pleiotropic common target. Sphingosine-1-phosphate (S1P), a product of sphingosine metabolism, regulates many biological functions (including cell proliferation and survival, cell migration, the immune response and cardiovascular function) via five subtypes of receptor. These receptors are expressed in all types of brain cells where they modulate a number of processes involved in neuronal plasticity, including myelination, neurogenesis and neuroprotection. This profile has aroused interest in modulation of S1P function as a therapeutic target in many brain diseases, particularly those in which the immune system plays a role in the development of brain lesions. Fingolimod, a S1P receptor modulator, exerts its beneficial effects in MS through its anti-inflammatory and anti-neurodegenerative effects. This review discusses recent evidence indicating that fingolimod may target both the inflammatory and neurodegenerative components of the disease process in MS

Deciphering Depressive Mood in Relapsing-Remitting and Progressive Multiple Sclerosis and Its Consequence on Quality of Life

<div><p>Background</p><p>Depressive mood and other emotional symptoms are common in multiple sclerosis (MS). The patient-reported outcome version of the “Echelle d’Humeur Dépressive” (EHD-PRO) aims to differentiate between two dimensions of depressive mood in people living with MS (PwMS).</p><p>Objectives</p><p>First, to compare EHD-PRO assessment and its two dimensions, lack of emotional control and emotional blunting, between a large sample of healthy controls (HCs) and two samples of PwMS, relapsing-remitting MS (RRMS) and primary progressive MS (PPMS); and second, to analyse the relationships between EHD-PRO scores with neurological disability, cognitive function, fatigue and health-related quality of life (HR-QOL).</p><p>Results</p><p>Regardless of their phenotype, PwMS had significantly higher EHD-PRO scores than HCs. EHD-PRO scores did not differ between the two MS groups. EHD-PRO scores did not correlate with disability and fatigue scores, disease duration or cognitive z scores. In RRMS, the lack of emotional control was independently associated with a decrease in HR-QOL.</p><p>Conclusion</p><p>The EHD-PRO is able to easily detect depressive mood and to differentiate between two clinical dimensions, emotional blunting and lack of emotional control. The scale is sensitive and seems robust to confounding factors. Lack of emotional control seems to contribute significantly to altered HR-QOL in RRMS.</p></div

Hemophagocytic Lymphohistiocytosis Gene Mutations in Adult Patients Presenting With CLIPPERS-Like Syndrome

International audienceObjective To determine whether adult cases of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) may be related to familial hemophagocytic lymphohistiocytosis (HLH) causes, we have screened patients with adult-onset CLIPPERS for mutations in primary HLH-associated genes.Methods In our cohort of 36 patients fulfilling the criteria for probable or definite CLIPPERS according to the CLIPPERS-2017 criteria, we conducted a first study on 12 patients who consented to genetic testing. In these 12 patients, systemic HLH criteria were searched, and genetic analysis of 8 genes involved in primary HLH was performed.Results Four definite and 8 probable CLIPPERS were enrolled (n = 12). Mutations involved in HLH were identified in 2 definite and 2 probable CLIPPERS (4/12). Three of them had biallelic PRF1 mutations with reduced perforin expression in natural killer cells. The remaining patient had biallelic UNC13D mutations with cytotoxic lymphocyte impaired degranulation. None of the mutated patients reached the criteria for systemic HLH. During follow-up, 3 of them displayed atypical findings for CLIPPERS, including emergence of systemic non-Hodgkin lymphoma (1/3) and confluent gadolinium-enhancing lesions on brain MRI (3/3).Conclusions In our patients presenting with adult-onset CLIPPERS, one-third have HLH gene mutations. This genetic treatable condition should be searched in patients with CLIPPERS, especially in those presenting with atypical findings

Linear regression models describing EHD scores in PwPPMS.

<p>^a variables significantly correlated with EHD scores in multivariate analyses.</p><p>^b variables with a p value <0.25 in univariate analyses. Age, gender, EDSS score were included in multivariate analyses.</p><p>PPMS: primary progressive multiple sclerosis. EDSS: Expanded Disability Status Scale; BDI-FS: Beck Depression Inventory-Fast Screen; S-Anxiety: State Anxiety scale of State-Trait Anxiety Inventory-State Form Y; EHD-EC-PRO: Echelle d’Humeur Dépressive lack of Emotional Control-Patient Reported Outcomes; EHD-EB-PRO: Echelle d’Humeur Dépressive Emotional Blunting-Patient Reported Outcomes; EHD-PRO: total score corresponding to an addition of EHD-EC and EHD-EB.</p><p>Linear regression models describing EHD scores in PwPPMS.</p

Clinical and PRO scores of PwMS.

<p>F: female; M: male. RRMS, relapsing–remitting multiple sclerosis; PPMS, primary progressive MS. For all clinical data, scores are expressed as the mean ± standard deviation (SD), except for EDSS, which are expressed as the median (range).</p><p>EDSS: Expanded Disability Status Scale; BDI: Beck Depression Inventory II; BDI-FS: Beck Depression Inventory-Fast screen; STAI-S: State Anxiety scale of State-Trait Anxiety Inventory-State Form Y; EHD-PRO: Echelle d’Humeur Dépressive-Patient-reported outcomes; EHD-EC: Echelle d’Humeur Dépressive lack of Emotional Control-Patient Reported Outcomes; EHD-EB: Echelle d’Humeur Dépressive Emotional Blunting-Patient Reported Outcomes; EHD-PRO: total score corresponding to an addition of EHD-EC and EHD-EB; PCS/SF-36 MCS/SF-36. p values from a chi-squared test comparing sex; p values from non-matched t-tests comparing means; p values between each MS group and matched controls, 60 PwRRMS and 310 matched controls, 41 PwPPMS and 263 matched controls: ^ns,non significant</p><p>*<0.05</p><p>**<0.01</p><p>***<0.001.</p><p>Clinical and PRO scores of PwMS.</p