The 2013 clinical course descriptors for multiple sclerosis: A clarification

The clinical courses of multiple sclerosis were defined in 1996 and refined in 2013 to provide a time-based assessment of the current status of the individual. These definitions have been successfully used by clinicians, clinical trialists, and regulatory authorities. Recent regulatory decisions produced variations and discrepancies in the use of the clinical course descriptions. We provide here a clarification of the concepts underlying these descriptions and restate the principles used in their development. Importantly, we highlight the critical importance of time framing the disease course modifiers activity and progression and clarify the difference between the terms worsening and progressing

Unified understanding of MS course is required for drug development

The treatment of multiple sclerosis (MS) has evolved remarkably over the past 25 years. This progress has been enabled by advances in research, drug development and active engagement of the scientific community with regulatory authorities. However, an inconsistent approach to MS disease courses could have a negative impact on the drug development process

Coenzyme Q10 and the exclusive club of diseases that show a limited response to treatment

Introduction: Coenzyme Q10 (CoQ10) is a ubiquitous organic molecule with a significant role in the mitochondrial electron transport chain (ETC). As a result of its role in such an important biological process, CoQ10 deficiency has been implicated in the pathogenesis of numerous diseases such as Parkinson’s disease (PD) and multiple sclerosis (MS). This has led to multiple attempts to use CoQ10 supplementation as a treatment or pre-treatment with varying degrees of success. Areas covered: The present review will identify evidence of mitochondrial dysfunction in MS, PD and mitochondrial ETC disorders. In addition, the inability of Co10 supplementation to elicit significant clinical outcome in these disorders and possible flaws in these studies will be discussed. The databases utilized for this review were the Web of science and PubMed, with inclusive dates (1957–2021). Expert opinion: A lack of improved neurological outcome in these disorders post treatment with CoQ10 may be attributable to the limited ability of CoQ10 to cross the blood–brain barrier. Thus, CoQ10 alternatives should also be considered. Other factors including time of disease diagnosis, dosage, administration, and duration of CoQ10 therapy may have a significant influence on the efficacy of this treatment

A composite measure to explore visual disability in primary progressive multiple sclerosis

Background: Optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can provide complementary information on visual system damage in multiple sclerosis (MS). Objectives: The objective of this paper is to determine whether a composite OCT/MRI score, reflecting cumulative damage along the entire visual pathway, can predict visual deficits in primary progressive multiple sclerosis (PPMS). Methods: Twenty-five PPMS patients and 20 age-matched controls underwent neuro-ophthalmologic evaluation, spectral-domain OCT, and 3T brain MRI. Differences between groups were assessed by univariate general linear model and principal component analysis (PCA) grouped instrumental variables into main components. Linear regression analysis was used to assess the relationship between low-contrast visual acuity (LCVA), OCT/MRI-derived metrics and PCA-derived composite scores. Results: PCA identified four main components explaining 80.69% of data variance. Considering each variable independently, LCVA 1.25% was significantly predicted by ganglion cell-inner plexiform layer (GCIPL) thickness, thalamic volume and optic radiation (OR) lesion volume (adjusted R2 0.328, p = 0.00004; adjusted R2 0.187, p = 0.002 and adjusted R2 0.180, p = 0.002). The PCA composite score of global visual pathway damage independently predicted both LCVA 1.25% (adjusted R2 value 0.361, p = 0.00001) and LCVA 2.50% (adjusted R2 value 0.323, p = 0.00003). Conclusion: A multiparametric score represents a more comprehensive and effective tool to explain visual disability than a single instrumental metric in PPMS

Prognosis of the individual course of disease - steps in developing a decision support tool for Multiple Sclerosis

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis is a chronic disease of uncertain aetiology. Variations in its disease course make it difficult to impossible to accurately determine the prognosis of individual patients. The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) developed an "online analytical processing (OLAP)" tool that takes advantage of extant clinical trials data and allows one to model the near term future course of this chronic disease for an individual patient.</p> <p>Results</p> <p>For a given patient the most similar patients of the SLCMSR database are intelligently selected by a model-based matching algorithm integrated into an OLAP-tool to enable real time, web-based statistical analyses. The underlying database (last update April 2005) contains 1,059 patients derived from 30 placebo arms of controlled clinical trials. Demographic information on the entire database and the portion selected for comparison are displayed. The result of the statistical comparison is provided as a display of the course of Expanded Disability Status Scale (EDSS) for individuals in the database with regions of probable progression over time, along with their mean relapse rate. Kaplan-Meier curves for time to sustained progression in the EDSS and time to requirement of constant assistance to walk (EDSS 6) are also displayed. The software-application OLAP anticipates the input MS patient's course on the basis of baseline values and the known course of disease for similar patients who have been followed in clinical trials.</p> <p>Conclusion</p> <p>This simulation could be useful for physicians, researchers and other professionals who counsel patients on therapeutic options. The application can be modified for studying the natural history of other chronic diseases, if and when similar datasets on which the OLAP operates exist.</p

Reproducibility over a 1-month period of 1H-MR spectroscopic imaging NAA/Cr ratios in clinically stable multiple sclerosis patients

N-acetylaspartate/creatine (NAA/Cr) ratios, assessed with proton magnetic resonance spectroscopy, are increasingly used as a surrogate marker for axonal dysfunction and degeneration in multiple sclerosis (MS). The purpose of this study was to test short-time reproducibility of NAA/Cr ratios in patients with clinically stable MS. In 35 MS patients we analysed NAA/Cr ratios obtained with 1H-MR spectroscopic imaging at the centrum semiovale either with lateral ventricles partially included (group 1; n=15) or more cranially with no ventricles included (group 2; n=20). To test short-term reproducibility of the NAA/Cr measurements, patients were scanned twice 4 weeks apart. We determined mean NAA/Cr and Cho/Cr ratios of 12 grey matter and 24 white matter voxels. Mean NAA/Cr ratios of both the white and grey matter did not change after 4 weeks. Overall 4-week reproducibility of the NAA/Cr ratio, expressed as coefficient of variation, was 4.8% for grey matter and 3.5% for white matter. Reproducibility of cranial scanning of the ventricles was slightly better than with cerebrospinal fluid included. Our study shows good short-term reproducibility of NAA/Cr ratio measurements in the centrum semiovale, which supports the reliability of this technique for longitudinal studies