Multiple sclerosis can follow very different patterns of evolution and variable rates of disability accumulation. This raises the issue whether it represents one or several distinct diseases. We ...assessed demographic and clinical characteristics in 1844 patients with multiple sclerosis that we categorized according to the classification of Lublin and Reingold (1996) into 1066 (58%) relapsing–remitting, 496 (27%) secondary progressive, 109 (6%) progressive relapsing and 173 (9%) primary progressive cases of multiple sclerosis. Relapsing–remitting and secondary progressive cases shared similar age at disease onset (median = 28.7 versus 29.5 years; P = 0.21), initial symptoms of the relapsing–remitting phase, degree of recovery from the first neurological episode, and time from the first to the second episode. By contrast, disease duration was twice as long in secondary progressive than in relapsing–remitting cases (mean ± SD = 17.6 ± 9.6 versus 8.7 ± 8.6 years; P < 0.001). Progressive relapsing and primary progressive cases were essentially similar in their clinical characteristics. In patients experiencing a progressive course, median age at onset of progressive phase was similar in secondary progressive cases and in cases who were progressive from onset (39.1 versus 40.1 years; P = 0.47). The proportion of cases with superimposed relapses during progression was ∼40% in both categories. Finally, the 1562 patients with an exacerbating–remitting initial course and the 282 patients with a progressive initial course of the disease were essentially similar with respect to the time course of disability accumulation from assignment to a given disability score, and the age at assignment of disability landmarks. These observational data suggest that the clinical phenotype and course of multiple sclerosis are age dependent. Relapsing–remitting disease can be regarded as multiple sclerosis in which insufficient time has elapsed for the conversion to secondary progression; secondary progressive forms as relapsing–remitting multiple sclerosis that has ‘grown older’; and progressive from onset cases as multiple sclerosis ‘amputated’ from the usual preceding relapsing–remitting phase. Times to reach disability milestones, and ages at which these landmarks are reached, follow a predefined schedule not obviously influenced by relapses, whenever they may occur, or by the initial course of the disease, whatever its phenotype. This leads to a unifying concept of the disease in which primary and secondary progression might be regarded as essentially similar. From the clinical and statistical positions, multiple sclerosis might be considered as one disease with different clinical phenotypes rather than an entity encompassing several distinct diseases—the position of complexity rather than true heterogeneity.
The clinical interest for auto-antibodies against myelin oligodendrocyte glycoprotein (MOG) has recently reemerged, with the use of more specific detection methods. Large national cohorts have ...allowed characterizing a more precise clinical spectrum delineated by the presence of human MOG-antibodies.
In adults with MOG-antibodies, optic neuritis is the most frequent clinical presentation, with features different from multiple sclerosis (MS), including bilateral involvement and predilection for the anterior part of the optic nerve. Myelitis and brainstem syndrome are also frequent, and may clinically mimic neuromyelitis optica spectrum disorders (NMOSD). Despite the frequently severe clinical presentation, most of patients recover quickly after steroids initiation. Other less typical presentations include encephalitis with seizures, cranial nerve involvement, and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids-like. Although the majority of adult patients follow a relapsing course, long-term prognosis differs from aquaporin-4-antibodies NMOSD, with only a small proportion of patients with a poor outcome.
MOG-antibodies-associated disease is a new entity in the spectrum of inflammatory demyelinating diseases, distinct from both MS and NMOSD. There is a crucial need to identify factors associated to the risk of relapse or poor outcome, to seek patient subgroups in which immunoactive treatments could be beneficial.
MRI plays a crucial role in multiple sclerosis diagnostic and patient follow-up. In particular, the delineation of T2-FLAIR hyperintense lesions is crucial although mostly performed manually - a ...tedious task. Many methods have thus been proposed to automate this task. However, sufficiently large datasets with a thorough expert manual segmentation are still lacking to evaluate these methods. We present a unique dataset for MS lesions segmentation evaluation. It consists of 53 patients acquired on 4 different scanners with a harmonized protocol. Hyperintense lesions on FLAIR were manually delineated on each patient by 7 experts with control on T2 sequence, and gathered in a consensus segmentation for evaluation. We provide raw and preprocessed data and a split of the dataset into training and testing data, the latter including data from a scanner not present in the training dataset. We strongly believe that this dataset will become a reference in MS lesions segmentation evaluation, allowing to evaluate many aspects: evaluation of performance on unseen scanner, comparison to individual experts performance, comparison to other challengers who already used this dataset, etc.
Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the ...response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease.
This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment.
Median age at onset was 34.1 years (range 18.0-67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval CI, 77.1-89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil MMF, rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20-0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab.
In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD.
In this work, we introduce a method to classify Multiple Sclerosis (MS) patients into four clinical profiles using structural connectivity information. For the first time, we try to solve this ...question in a fully automated way using a computer-based method. The main goal is to show how the combination of graph-derived metrics with machine learning techniques constitutes a powerful tool for a better characterization and classification of MS clinical profiles.
Sixty-four MS patients 12 Clinical Isolated Syndrome (CIS), 24 Relapsing Remitting (RR), 24 Secondary Progressive (SP), and 17 Primary Progressive (PP) along with 26 healthy controls (HC) underwent MR examination. T1 and diffusion tensor imaging (DTI) were used to obtain structural connectivity matrices for each subject. Global graph metrics, such as density and modularity, were estimated and compared between subjects' groups. These metrics were further used to classify patients using tuned Support Vector Machine (SVM) combined with Radial Basic Function (RBF) kernel.
When comparing MS patients to HC subjects, a greater assortativity, transitivity, and characteristic path length as well as a lower global efficiency were found. Using all graph metrics, the best
-Measures (91.8, 91.8, 75.6, and 70.6%) were obtained for binary (HC-CIS, CIS-RR, RR-PP) and multi-class (CIS-RR-SP) classification tasks, respectively. When using only one graph metric, the best
-Measures (83.6, 88.9, and 70.7%) were achieved for modularity with previous binary classification tasks.
Based on a simple DTI acquisition associated with structural brain connectivity analysis, this automatic method allowed an accurate classification of different MS patients' clinical profiles.
Objective:
To evaluate the effectiveness and tolerance of mycophenolate mofetil (MMF) as a first-line treatment in neuromyelitis optica spectrum disorder (NMOSD).
Methods:
In all, 67 NMOSD patients ...treated by MMF as first-line therapy, from the NOMADMUS cohort were included. A total of 65 fulfilled 2015 NMOSD criteria, and 5 were myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) positive. Effectiveness was evaluated on percentage of patients continuing MMF, percentage of patients free of relapse, pre- and post-treatment change in the annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS).
Results:
Among 67 patients, 40 (59.7%) continued treatment till last follow-up. A total of 33 (49.3%) were relapse-free. The median ARR decreased from one pre-treatment to zero post-treatment. Of 53 patients with complete EDSS data, the score improved or stabilized in 44 (83%; p < 0.05). Effectiveness was observed in aquaporin-4 (AQP4)-IgG (57.8% continued treatment, 46.7% relapse-free), MOG-IgG (3/5 continued treatment, 4/5 relapse-free), and seronegative NMOSD (64.7% continued treatment, 61.3% relapse-free). In 16 patients with associated steroids, 13 (81.2%) continued MMF till last follow-up versus 15 of 28 (53.6%) in the non-steroid group. Nine patients discontinued treatment for tolerability purpose.
Conclusion:
MMF showed effectiveness and good tolerability as a first-line therapy in NMOSD, whatever the AQP4-IgG status. Concomitant use of oral steroids at start could limit the risk of treatment failure.
Neuromyelitis optica spectrum disorder (NMOSD) attacks require an urgent probabilistic anti-inflammatory therapeutic strategy. As inadequately treated attacks result in disability, there is a need to ...identify the optimal attack-treatment regimen. Our study aimed to identify predictors of outcome after a first attack in patients with an NMOSD presentation and propose the best treatment strategy.
We performed a retrospective cohort study on the French national NMOSD registry (NOMADMUS), a nested cohort of the French multiple sclerosis observatory (OFSEP) recruiting patients with NMOSD presentations in France. We studied the first attack for any independent locations of clinical core characteristic of NMOSD, in treatment-naïve patients. The primary outcome was the evolution of the Expanded Disability Status Scale (EDSS) score at 6 months, stratified in two ways to account for recovery (return to baseline EDSS score) and treatment response (classified as "good" if the EDSS score decreased by ≥ 1 point after a nadir EDSS score ≤ 3, or by ≥ 2 points after a nadir EDSS score > 3). We used ordinal logistic regression to infer statistical associations with the outcome.
We included 211 attacks among 183 patients (104 with anti-AQP4 antibodies, 60 with anti-MOG antibodies, and 19 double seronegative). Attack treatment regimens comprised corticosteroids (n = 196), plasma exchanges (PE; n = 72) and intravenous immunoglobulins (n = 6). Complete recovery was reached in 40 attacks (19%) at 6 months. The treatment response was "good" in 134 attacks (63.5%). There was no improvement in EDSS score in 50 attacks (23.7%). MOG-antibody seropositivity and short delays to PE were significantly and independently associated with better recovery and treatment response.
We identified two prognostic factors: serostatus (with better outcomes among MOG-Ab-positive patients) and the delay to PE. We, therefore, argue for a more aggressive anti-inflammatory management of the first attacks suggesting an NMOSD presentation, with the early combination of PE with corticosteroids.
The influence of pregnancy in multiple sclerosis has been a matter of controversy for a long time. The Pregnancy in Multiple Sclerosis (PRIMS) study was the first large prospective study which aimed ...to assess the possible influence of pregnancy and delivery on the clinical course of multiple sclerosis. We report here the 2‐year post‐partum follow‐up and an analysis of clinical factors which might predict the likelihood of a relapse in the 3 months after delivery. The relapse rate in each trimester up to the end of the second year post‐partum was compared with that in the pre‐pregnancy year. Clinical predictors of the presence or absence of a post‐partum relapse were analysed by logistic regression analysis. Using the best multivariate model, women were classified as having or not having a post‐partum relapse predicted, and this was compared with the observed outcome. The results showed that, compared with the pre‐pregnancy year, there was a reduction in the relapse rate during pregnancy, most marked in the third trimester, and a marked increase in the first 3 months after delivery. Thereafter, from the second trimester onwards and for the following 21 months, the annualized relapse rate fell slightly but did not differ significantly from the relapse rate recorded in the pre‐pregnancy year. Despite the increased risk for the 3 months post‐partum, 72% of the women did not experience any relapse during this period. Confirmed disability continued to progress steadily during the study period. Three indices, an increased relapse rate in the pre‐pregnancy year, an increased relapse rate during pregnancy and a higher DSS (Kurtzke’s Disability Status Scale) score at pregnancy onset, significantly correlated with the occurrence of a post‐partum relapse. Neither epidural analgesia nor breast‐feeding was predictive. When comparing the predicted and observed status, however, only 72% of the women were correctly classified by the multivariate model. In conclusion, the results for the second year post‐partum confirm that the relapse rate remains similar to that of the pre‐pregnancy year, after an increase in the first trimester following delivery. Women with greater disease activity in the year before pregnancy and during pregnancy have a higher risk of relapse in the post‐ partum 3 months. This is, however, not sufficient to identify in advance women with multiple sclerosis who are more likely to relapse, especially for planning therapeutic trials aiming to prevent post‐partum relapses.
Neuromyelitis optica, a rare neuroinflammatory demyelinating disease of the CNS, is characterized by the presence of specific pathogenic autoantibodies directed against the astrocytic water channel ...aquaporin 4 (AQP4) and is now considered as an astrocytopathy associated either with complement-dependent astrocyte death or with astrocyte dysfunction. However, the link between astrocyte dysfunction and demyelination remains unclear. We propose glial intercellular communication, supported by connexin hemichannels and gap junctions, to be involved in demyelination process in neuromyelitis optica. Using mature myelinated cultures, we demonstrate that a treatment of 1 h to 48 h with immunoglobulins purified from patients with neuromyelitis optica (NMO-IgG) is responsible for a complement independent demyelination, compared to healthy donors' immunoglobulins (P < 0.001). In parallel, patients' immunoglobulins induce an alteration of connexin expression characterized by a rapid loss of astrocytic connexins at the membrane followed by an increased size of gap junction plaques (+60%; P < 0.01). This was co-observed with connexin dysfunction with gap junction disruption (-57%; P < 0.001) and increased hemichannel opening (+17%; P < 0.001), associated with glutamate release. Blocking connexin 43 hemichannels with a specific peptide was able to prevent demyelination in co-treatment with patients compared to healthy donors' immunoglobulins. By contrast, the blockade of connexin 43 gap junctions with another peptide was detrimental for myelin (myelin density -48%; P < 0.001). Overall, our results suggest that dysregulation of connexins would play a pathogenetic role in neuromyelitis optica. The further identification of mechanisms leading to connexin dysfunction and soluble factors implicated, would provide interesting therapeutic strategies for demyelinating disorders.
The purpose of this study was to examine antibacterial and antifungal activity of antibacterial finish based on Citric acid on cotton medical textiles. The ability to effectively reduce the number of ...gram-negative, gram-positive bacteria and yeast was evaluated, specifically comparing the antibacterial activity after two different drying/curing methods. Citric acid (CA) and diethyl–tetradecyl–3–(trimethoxysilyl)-propyl ammonium chloride (Quat) were used for hygiene and disinfection purposes of medical textiles in this study. It was applied by pad-dry process and its fixation to cellulose hydroxyls was enhanced either by high curing temperatures or microwaves (MW). Determination of antibacterial activity of finished products was performed according to ISO 20743:2007 standard before the washing and after the 10 washing cycles. Antibacterial activity was tested against gram-negative bacteria,
Escherichia coli
, gram-positive-
Staphylococcus aureus
and yeast,
Candida albicans
. Obtained results are confirming the possibility of eco-friendly CA application, for the purpose of antimicrobial finishing of cotton medical textiles. Prevention of nosocomial infections with the Citric acid is possible using both curing methods (convection and microwave) and furthermore, the treatment is durable up to 10 washing cycles. Citric acid, as one of the suitable active substances is crosslinked to the cellulose hydroxyls by the formation of ester linkages. Its antimicrobial effectiveness against the chosen microorganisms proved to be the best against
S. aureus
. Applied finish bath has additional crease proof effectiveness providing sufficient both antimicrobial and crease proof effectiveness, so as the durability against 10 washing cycles.
PDF
