High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We ...aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (
p
= 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (
p
= 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.
Background:
Studies including patients with well-established multiple sclerosis (MS) have shown a significant and disability-related reduction in the cervical spinal cord (SC) magnetisation transfer ...ratio (MTR).
Objectives:
The objectives are to (1) assess whether MTR reduction is already measurable in the SC of patients with early relapsing–remitting multiple sclerosis (RRMS) and (2) describe its spatial distribution.
Methods:
We included 60 patients with RRMS <12 months and 34 age-matched controls at five centres. Axial T2*w, sagittal T2w, sagittal phase-sensitive inversion recovery (PSIR), 3DT1w, and axial magnetisation transfer (MT) images were acquired from C1 to C7. Lesions were manually labelled and mean MTR values computed both for the whole SC and for normal-appearing SC in different regions of interest.
Results:
Mean whole SC MTR was significantly lower in patients than controls (33.7 vs 34.9 pu, p = 0.00005), even after excluding lesions (33.9 pu, p = 0.0003). We observed a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2–C4). In the axial plane, we observed a greater mean MTR reduction at the SC periphery and barycentre.
Conclusion:
Cervical SC tissue damage measured using MTR is not restricted to macroscopic lesions in patients with early RRMS and is not homogeneously distributed.
Multiple sclerosis (MS) is a severe autoimmune disease characterized by inflammatory, demyelinating and neurodegenerative components causing motor, sensory, visual and/or cognitive symptoms. The ...relapsing-remitting MS affecting 85% of patients is reliably mimicked by the proteolipid-protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE) SJL/J-mouse model. Significant progress was made for MS treatment but the development of effective therapies devoid of severe side-effects remains a great challenge. Here, we combine clinical, behavioral, histopathological, biochemical and molecular approaches to demonstrate that low and well tolerated doses (10–20mg/kg) of TSPO ligand XBD173 (Emapunil) efficiently ameliorate clinical signs and neuropathology of PLP-EAE mice. In addition to the conventional clinical scoring of symptoms, we applied the robust behavioral Catwalk-method to confirm that XBD173 (10mg/kg) increases the maximum contact area parameter at EAE-disease peak, indicating an improvement/recovery of motor functions. Consistently, histopathological studies coupled with microscope-cellSens quantification and RT-qPCR analyzes showed that XBD173 prevented demyelination by restoring normal protein and mRNA levels of myelin basic protein that was significantly repressed in PLP-EAE mice spinal cord and brain. Interestingly, ELISA-based measurement revealed that XBD173 increased allopregnanolone concentrations in PLP-EAE mice spinal and brain tissues. Furthermore, flow cytometry assessment demonstrated that XBD173 therapy decreased serum level of pro-inflammatory cytokines, including interleukin-17A, Interleukin-6 and tumor-necrosis-factor alpha in PLP-EAE mice. As the optimal XBD173 dosing exerting the maximal beneficial action in EAE mice is the lower 10mg/kg dose, the paper opens interesting perspectives for the development of efficient and safe therapies against MS with slight or no side-effects.
•Low-dose XBD173 treatment is beneficial in a mouse model of relapsing-remitting MS.•XBD173 efficiently improves clinical scores in SJL/J mouse model of MS.•Catwalk behavior study shows that XBD173 restores normal motor function in MS mice.•XBD173 prevents myelin basic protein repression in MS mice spinal cord and brain.•XBD173 therapy reduced serum level of pro-inflammatory cytokines in MS mice.
La crise sanitaire a contraint au développement de prises ne charge dématérialisées. Le réseau AlSacEP a organisé des groupes de paroles en visioconférence sur 5 thématiques des troubles invisibles ...de la SEP.
Maintenir et améliorer l’accompagnement psychologique des patients adultes atteints de sclérose en plaques sur le territoire alsacien durant la période de confinement.
Organisation de 5 groupes de parole en visioconférence, animés par une psychologue, dédiés aux troubles invisibles de la sclérose en plaques : troubles de l’humeur, fatigue, troubles vésicosphinctériens et sexuels et douleurs. Utilisation de Google Meet, accessible gratuitement pour les patients depuis leur ordinateur, tablette ou téléphone et testé préalablement par la psychologue. Participation du réseau AlSacEP pour la constitution des groupes et l’attribution des créneaux horaires.
Succès important, obligeant à proposer 3 créneaux horaires de 1 h 30 aux dates initialement prévues. Inscription de 11 à 26 patients par thématique avec un total de 107 patients sur les 5 séances.
Cette prise en charge a contribué à la prise en charge psychologique pour les personnes handicapées, isolées et ayant des difficultés de déplacement dans un contexte de confinement partiel et a permis l’organisation de réunions en toute sécurité sanitaire, ainsi que le maintien et la poursuite de la prise en charge psychologique. Le taux de satisfaction était de 100 % avec un impact important sur la qualité de vie des patients.
L’organisation de groupes de parole en visioconférence est une alternative intéressante pour la prise en charge des patients isolés ou ayant de difficultés à se déplacer. L’expérience imposée par les circonstance sanitaires s’avère très concluante.
Introduction:
Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if ...COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry.
Case series:
We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild.
Discussion:
These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.
The 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.
Background:
Data are needed on long-term effect of natalizumab (NTZ) in relapsing-remitting multiple sclerosis (RRMS).
Objectives:
To evaluate the time of onset of secondary progressive phase in ...patients with an RRMS treated with NTZ and to investigate predictive factors.
Methods:
TYSTEN is an observational study. Patients starting NTZ between 2007 and 2012 were included and followed up until October 2018. Relapses, Expanded Disability Status Scale (EDSS) scores, and results of brain magnetic resonance imaging (MRI) were collected each year. Data were used to estimate the cumulative probability of several poor outcomes such as secondary progressive multiple sclerosis (SPMS) conversion, EDSS worsening, EDSS 4.0, and EDSS 6.0.
Results:
770 patients were included. The mean follow-up duration was 97 months and the mean time exposure to NTZ was 66 months. At 10 years, the cumulative probability of SPMS was 27.7%. Predictive factors for poor outcomes were a ⩾1-point increase in EDSS score from baseline, new T2 lesion or T1 gadolinium-enhancing lesion, the occurrence of relapse at 1 or 2 years and No Evidence of Disease Activity (NEDA-3; no relapse, no new T2 or T1 gadolinium-enhancing lesions, no progression) was a protective factor.
Conclusion:
In our cohort of patients treated with NTZ, poor outcomes were infrequent and are driven by disease activity.
To compare natalizumab and fingolimod on both clinical and MRI outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) from 27 multiple sclerosis centers participating in the French ...follow-up cohort Observatoire of Multiple Sclerosis.
Patients with RRMS included in the study were aged from 18 to 65 years with an Expanded Disability Status Scale score of 0-5.5 and an available brain MRI performed within the year before treatment initiation. The data were collected for 326 patients treated with natalizumab and 303 with fingolimod. The statistical analysis was performed using 2 different methods: logistic regression and propensity scores (inverse probability treatment weighting).
The confounder-adjusted proportion of patients with at least one relapse within the first and second year of treatment was lower in natalizumab-treated patients compared to the fingolimod group (21.1% vs 30.4% at first year, p = 0.0092; and 30.9% vs 41.7% at second year, p = 0.0059) and supported the trend observed in nonadjusted analysis (21.2% vs 27.1% at 1 year, p = 0.0775). Such statistically significant associations were also observed for gadolinium (Gd)-enhancing lesions and new T2 lesions at both 1 year (Gd-enhancing lesions: 9.3% vs 29.8%, p < 0.0001; new T2 lesions: 10.6% vs 29.6%, p < 0.0001) and 2 years (Gd-enhancing lesions: 9.1% vs 22.1%, p = 0.0025; new T2 lesions: 16.9% vs 34.1%, p = 0.0010) post treatment initiation.
Taken together, these results suggest the superiority of natalizumab over fingolimod to prevent relapses and new T2 and Gd-enhancing lesions at 1 and 2 years.
This study provides Class IV evidence that for patients with RRMS, natalizumab decreases the proportion of patients with at least one relapse within the first year of treatment compared to fingolimod.
Objectives
To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection.
Materials and methods
In this ...retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement.
Results
The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response.
Conclusion
Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML.
Key Points
• Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies.
• Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution “the milky way,” and more cortex involvement than rituximab- and HIV-associated PML.
• MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.
We compared SimoaTM and EllaTM immunoassays to assess serum neurofilament‐light chain levels in 203 multiple sclerosis patients from the OFSEP HD study. There was a strong correlation (ρ = 0.86, ...p < 0.0001) between both platforms. The EllaTM instrument overestimated values by 17%, but as the data were linear (p = 0.57), it was possible to apply a correction factor to EllaTM results. As for SimoaTM, serum neurofilament‐light chain levels measured by EllaTM were correlated with age and EDSS and were significantly higher in active multiple sclerosis, suggesting that these assays are equivalent and can be used in routine clinical practice.
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