Correlation of Diffusion and Metabolic Alterations in Different Clinical Forms of Multiple Sclerosis

Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients

Magnetic resonance imaging outcomes from a phase III trial of teriflunomide

Objective: The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis (MS) pathology inferred by magnetic resonance imaging (MRI). Methods: Patients ( n=1088) with relapsing MS were randomized to once-daily teriflunomide 7 mg or 14 mg, or placebo, for 108 weeks. MRI was recorded at baseline, 24, 48, 72 and 108 weeks. Annualized relapse rate and confirmed progression of disability (sustained ≥12 weeks) were the primary and key secondary outcomes. The principal MRI outcome was change in total lesion volume. Results: After 108 weeks, increase in total lesion volume was 67.4% ( p=0.0003) and 39.4% ( p=0.0317) lower in the 14 and 7 mg dose groups versus placebo. Other measures favoring teriflunomide were accumulated enhanced lesions, combined unique activity, T2-hyperintense and T1-hypointense component lesion volumes, white matter volume, and a composite MRI score; all were significant for teriflunomide 14 mg and most significant for 7 mg versus placebo. Conclusions: Teriflunomide provided benefits on brain MRI activity across multiple measures, with a dose effect evident on several markers. These effects were also consistent across selected subgroups of the study population. These findings complement clinical data showing significant teriflunomide-related reductions in relapse rate and disease progression, and demonstrate containment of MRI-defined disease progression

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients

A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia

We have identified a novel gene in a genome-wide, double-strand break DNA repair RNAi screen and show that is involved in the neurological disease hereditary spastic paraplegia

THROMBOPHLEBITE CEREBRALE AU DECOURS D'UN FLASH DE CORTICOIDES POUR UN PREMIER EPISODE DE TYPE DEMYELINISANT APRES REALISATION D'UNE PONCTION LOMBAIRE (A PROPOS DE 4 CAS)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mitoxantrone et sclérose en plaques (efficacité et tolérance chez 123 patients)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Atteintes démyélinisantes aigües inflammatoies du système nerveux central chez l'enfant (facteurs pronostiques d'évolution vers la sclérose en plaques et le handicap)

Notre objectif était de préciser les facteurs pronostiques cliniques et en imagerie IRM de rechute (qualifiant pour le diagnostic de sclérose en plaques) et de handicap sévère après un premier épisode démyélinisant aigû inflammatoire du système nerveux central avant 16 ans. Nous avons mis en place d'une cohorte incluant tout patient avec ces critères d'inclusion dans les centres neuropédiatriques français à partir de 1985 et étudié des variables standardisées avec des modèles d'analyse de survie. Selon l'analyse multivariée, le risque de rechute (50% des patients à 3 ans de suivi) était plus élevé chez les patients ayant débuté après 10 ans et si l'IRM montrait des lésions perpendiculaires au corps calleux ou exclusivement bien limitées. Il était plus bas en cas de myélite ou de troubles de conscience. Le risque d'atteindre un handicap sévère (10% des patients à 3 ans de suivi) était plus élevé en cas de début polysymptomatique, de séquelles du premier épisode, de rechutes ou d'une évolution progressive.LYON1-BU.Sciences (692662101) / SudocSudocFranceF