Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome

We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS). The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation. A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation. In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation

Etude de la dégénérescence axonale rétinienne dans les différentes formes de sclérose en plaques

La tomographie par cohérence optique (OCT) permet de mesurer l épaisseur de la couche rétinienne des fibres optiques péripapillaires. L absence de myélinisation de ces fibres dans leur trajet intra-oculaire en fait un indicateur potentiel de la perte axonale dans la SEP. Un examen OCT et ophtalmologique a été effectué chez 58 patients atteints de SEP définie sans antécédent de névrite optique clinique et chez 32 sujets témoins. Les patients atteints de SEP présentaient un amincissement significatif de la couche rétinienne des fibres optiques par rapport aux sujets témoins. La sévérité de la perte axonale rétinienne était corrélée avec le handicap et avec la durée d évolution de la maladie. Ces résultats confortent l existence de mécanismes neurodégénératifs dans la SEP et soulignent l intérêt de la mesure de la perte axonale rétinienne par l OCT comme indicateur de suivi de la dégénérescence axonale cérébrale.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Revisiting Vision Rehabilitation

Low vision is a condition caused by eye or brain disease, in which visual acuity is 20/70 (3/10 or 6/18) or poorer in the better-seeing eye and cannot be corrected or improved with regular eyeglasses. It impacts personal ability to perform vision-dependent tasks as activities of daily living, walking, reading or using a computer. Rehabilitation is a multidisciplinary training dedicated to improve patients’ functional abilities and quality of life. It has to be personalized to every individual situation, whatever the underlying pathology

Neither the patient nor the physician could see anything: Atypical Bing-Neel syndrome

International audienc

Neither the patient nor the physician could see anything: Atypical Bing-Neel syndrome

International audienc

COGEVIS: A New Scale to Evaluate Cognition in Patients with Visual Deficiency

International audienceWe evaluated the cognitive status of visually impaired patients referred to low vision rehabilitation (LVR) based on a standard cognitive battery and a new evaluation tool, named the COGEVIS, which can be used to assess patients with severe visual deficits. We studied patients aged 60 and above, referred to the LVR Hospital in Paris. Neurological and cognitive evaluations were performed in an expert memory center. Thirty-eight individuals, 17 women and 21 men with a mean age of 70.3 ± 1.3 years and a mean visual acuity of 0.12 ± 0.02, were recruited over a one-year period. Sixty-three percent of participants had normal cognitive status. Cognitive impairment was diagnosed in 37.5% of participants. The COGEVIS score cutoff point to screen for cognitive impairment was 24 (maximum score of 30) with a sensitivity of 66.7% and a specificity of 95%. Evaluation following 4 months of visual rehabilitation showed an improvement of Instrumental Activities of Daily Living (p = 0 004), National Eye Institute Visual Functioning Questionnaire (p = 0 035), and Montgomery-Åsberg Depression Rating Scale (p = 0 037). This study introduces a new short test to screen for cognitive impairment in visually impaired patients

Interactions between NS1 and NS2 proteins and human host factors.

<p>(A) Yeast two-hybrid array. The 33 NS1-specific interactors are indicated in blue, 28 NS2-specific interactors in grey and shared interactors in yellow. The 11 NS1 and the single NS2 interactors described earlier are highlighted with bold letters. DRBD-containing proteins (DRBPs) are indicated with a star. (B) Frequency of interactions between individual host cell factors and NS1 and/or NS2 proteins of the 9 different influenza virus strains. (C) Degree distribution of human proteins and human proteins targeted by NS1 and/or NS2 proteins in the human interactome. P(k) is the probability of a node to connect k other nodes in the network. Solid lines represent linear regression fits. Vertical dashed lines indicate the mean degree of each distribution. (D) Betweenness distribution of human proteins and human proteins targeted by NS1 and/or NS2 proteins in the human interactome. P(b) is the probability for a node to have a betweenness value of b in the network. Solid lines represent linear regression fits. Vertical dashed lines indicate the mean betweenness value for each distribution.</p

Impact of silencing of NS1 and NS2 interactors on influenza A virus replication.

<p>A549 cells were transfected with indicated siRNAs, infected at a MOI of 0.5 with A/H1N1/Puerto Rico/8/34 virus strain (A) or A/H1N1/New Caledonia/2006 virus strain (B) and the neuraminidase activity (NA) was measured in the supernatant 48 h post infection. Values are normalized to neuraminidase activity measured in supernatants of control siRNA-transfected cells and represent the mean +/− standard deviation (triplicates). ATP6V1G1 is a host dependency factor, CSNK2B is an anti-viral host factor. Both served as controls.</p

Dengue virus NS3 protein also interacts with ADAR1.

<p>(A) Pairwise Yeast diploids co-expressing dengue virus type 2 NS3 helicase fused to Gal4 DNA-binding domain and ADAR1 fused to Gal4 transactivation domain were plated onto a selective medium lacking histidine to determine interaction-dependent transactivation of the HIS3 reporter gene. Negative controls are vectors without insert (pPC97 and pPC86 for bait and prey respectively). (B) HEK293T cells were co-transfected with 3×Flag-tagged ADAR1 and GST-tagged full-length NS3 of dengue virus (GST-DV-NS3) or its helicase domain (GST-DV-NS3 helicase) or GST-tagged full-length NS1 of influenza virus (GST-FLUAV-NS1) as a positive control. Proteins bound to glutathione sepharose beads were analyzed by western blot using antibodies against GST or 3×Flag. (C) ADAR1 expression in Huh-7 cells upon interferon treatment or dengue virus infection. Huh-7 cells were incubated with 0, 100 or 1000 IU/ml of interferon- (IFN)-α2b or infected with dengue virus and analyzed 24 h later for expression of ADAR1, NS3 and GAPDH. (D) Impact of ADAR1 silencing on dengue virus replication in Huh-7. Data are expressed as the percentage of virus titer obtained with control siRNA-transfected cells. A siRNA targeting dengue virus NS1-coding region (siDV-NS1) was used as positive control for the silencing. (E) ADAR editing activity in Huh-7 cells infected with dengue virus. (F) Dengue virus NS3 contribution to ADAR1 editing activity. The NS1 effector domain of influenza virus, full-length NS3 of dengue virus or its helicase domain were co-expressed with ADAR1 and the editing reporter in HEK293T cells. Luminescence reflecting Firefly and Renilla luciferase activities was measured 48 h post-transfection. The influenza virus NS1 effector domain does not interact with ADAR1 and was used as negative control. Data are normalized to the values obtained with the NS1 effector domain. RLU, relative light unit.</p