Anti-Myelin Oligodendrocyte Glycoprotein and Human Leukocyte Antigens as Markers in Pediatric and Adolescent Multiple Sclerosis: on Diagnosis, Clinical Phenotypes, and Therapeutic Responses

Early-onset (pediatric and adolescent) multiple sclerosis (MS) is a well-established demyelinating disease that accounts for approximately 3-5% of all MS cases. Thus, identifying potential biomarkers that can reflect the pathogenic mechanisms, disease course and prognosis, and therapeutic response in such patients is of paramount importance. Myelin oligodendrocyte glycoprotein (MOG) has been regarded as a putative autoantigen and autoantibody target in patientswith demyelinating diseases for almost three decades. However, recent studies have suggested that antibodies against MOG represent a distinct clinical entity of dominantly humoral profile, with a range of clinical phenotypes closely related to the age of onset, specific patterns of disease course, and responses to treatment. Furthermore, the major histocompatibility complex (MHC)-which has been regarded as the “gold standard” for attributing genetic burden in adult MS since the early 1970s-has also emerged as the primary genetic locus in early-onsetMS, particularly with regard to the human leukocyte antigen (HLA) alleles DRB1*1501 and DRB1*0401. Recent studies have investigated the potential interactions among HLA, MOG, and environmental factors, demonstrating that early-onset MS is characterized by genetic, immunogenetic, immunological, and familial trait correlations. In this paper, we review recent evidence regarding HLA-genotyping and MOG antibodies-the two most important candidate biomarkers for early-onset MS-as well as their potential application in the diagnosis and treatment of MS

Anti-Myelin Oligodendrocyte Glycoprotein and Human Leukocyte Antigens as Markers in Pediatric and Adolescent Multiple Sclerosis: on Diagnosis, Clinical Phenotypes, and Therapeutic Responses

Early-onset (pediatric and adolescent) multiple sclerosis (MS) is a well-established demyelinating disease that accounts for approximately 3-5% of all MS cases. Thus, identifying potential biomarkers that can reflect the pathogenic mechanisms, disease course and prognosis, and therapeutic response in such patients is of paramount importance. Myelin oligodendrocyte glycoprotein (MOG) has been regarded as a putative autoantigen and autoantibody target in patients with demyelinating diseases for almost three decades. However, recent studies have suggested that antibodies against MOG represent a distinct clinical entity of dominantly humoral profile, with a range of clinical phenotypes closely related to the age of onset, specific patterns of disease course, and responses to treatment. Furthermore, the major histocompatibility complex (MHC)—which has been regarded as the “gold standard” for attributing genetic burden in adult MS since the early 1970s—has also emerged as the primary genetic locus in early-onset MS, particularly with regard to the human leukocyte antigen (HLA) alleles DRB1⁎1501 and DRB1⁎0401. Recent studies have investigated the potential interactions among HLA, MOG, and environmental factors, demonstrating that early-onset MS is characterized by genetic, immunogenetic, immunological, and familial trait correlations. In this paper, we review recent evidence regarding HLA-genotyping and MOG antibodies—the two most important candidate biomarkers for early-onset MS—as well as their potential application in the diagnosis and treatment of MS

Apoptosis of Oligodendrocytes and Post-Translational Modifications of Myelin Basic Protein in Multiple Sclerosis: Possible Role for the Early Stages of Multiple Sclerosis

Recent studies outline apoptosis of oligodendrocytes (OLDs) as an early event prior to the formation of the demyelinated plaque and post-translational modifications (PTMs) of myelin basic protein as characteristic processes of normal-appearing white matter in multiple sclerosis (MS). We reviewed reports using the following keywords: apoptosis, PTMs, autoimmunity and multiple sclerosis in all possible combinations. Introductory basic scientific information is included for the non-experts. Given the standard and ongoing studies, we raise the hypothesis that, at least in some cases, defective apoptosis of OLDs, early in the course of the disease, and post-translationally modified molecules lead to the activation of immune responses and eventually to autoimmunity. Autoimmune reactions and epitope spreading that take place in the course of the disease might obscure the initial events and leave most investigators blind to etiopathogenesis. Our paper outlines the need for studies at the very early stages of the disease, as well as sequential ones, in order to give us a valuable hint about the clarification of the cause(s) of the different clinical subtypes of MS. Copyright (C) 2010 S. Karger AG, Base

Apoptosis of Oligodendrocytes and Post-Translational Modifications of Myelin Basic Protein in Multiple Sclerosis: Possible Role for the Early Stages of Multiple Sclerosis

Recent studies outline apoptosis of oligodendrocytes (OLDs) as an early event prior to the formation of the demyelinated plaque and post-translational modifications (PTMs) of myelin basic protein as characteristic processes of normal-appearing white matter in multiple sclerosis (MS). We reviewed reports using the following keywords: apoptosis, PTMs, autoimmunity and multiple sclerosis in all possible combinations. Introductory basic scientific information is included for the non-experts. Given the standard and ongoing studies, we raise the hypothesis that, at least in some cases, defective apoptosis of OLDs, early in the course of the disease, and post-translationally modified molecules lead to the activation of immune responses and eventually to autoimmunity. Autoimmune reactions and epitope spreading that take place in the course of the disease might obscure the initial events and leave most investigators blind to etiopathogenesis. Our paper outlines the need for studies at the very early stages of the disease, as well as sequential ones, in order to give us a valuable hint about the clarification of the cause(s) of the different clinical subtypes of MS.</jats:p

Stress as a Risk Factor for Multiple Sclerosis Onset or Relapse: A Systematic Review

&lt;i&gt;Background:&lt;/i&gt; Stress has been considered a triggering factor for multiple sclerosis (MS) since the description of the disease by Jean-Martin Charcot. Until our times, many published studies have supported that both MS onset and relapse could be predisposed by psychological stress. This review aims to synthesize existing knowledge of the relationship between psychological stress and MS onset and relapse, focusing mainly on the quality of observational studies. &lt;i&gt;Methods:&lt;/i&gt; We hand-searched MEDLINE with the terms ‘stress and multiple sclerosis’, using English language restrictions, from January 1980 to November 2010. We included only observational longitudinal studies. The Newcastle-Ottawa scale proposed by the Cochrane Collaboration was used for assessing the quality of the observational studies. &lt;i&gt;Results:&lt;/i&gt; Seventeen publications were analyzed, 5 for MS onset (1 cohort and 4 case-control studies) and 12 for MS relapse (9 cohort and 3 case-control studies). We found a marked heterogeneity in stress measurement that mostly targeted the environmental approach to stress. Only 2 publications used radiological criteria for MS relapse. Quality issues were identified mainly for comparability, meaning that studies failed to control adequately for various triggering and psychosocial factors in the stress-MS relationship. Also, selection and blinding problems were identified in most case-control studies. All studies, with only 2 exceptions, resulted in favor of the stress-MS relationship, but due to marked stress measurement heterogeneity, no secure conclusions could be drawn. &lt;i&gt;Conclusions:&lt;/i&gt; Future studies should incorporate a multidisciplinary approach to stress measurement and radiological criteria for MS. We further encourage researchers to test the effect of early life stress and stress management techniques on the clinical course of the disease.</jats:p

Pythagorean Self-Awareness Intervention for Multiple Sclerosis Patients: A Quasi-Experimental Pragmatic Trial

Abstract Objective Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system affecting patients’ well-being and quality of life. Pythagorean Self-Awareness Intervention (PSAI) is a novel non-pharmaceutical intervention with significant benefits both in MS and other chronic diseases. In this study, the longstanding effectiveness of PSAI was investigated. Method This was a two-arm quasi-experimental pragmatic trial in relapsing–remitting MS patients (23 in the PSAI and 21 in the control group). PSAI patients received an 8-week training period and then they performed PSAI at home for another 16 weeks. Assessments took place at baseline, 8 weeks, and 24 weeks. These included cognition, fatigue, perceived stress, and hair cortisol. Results Significant group × time interactions favoring PSAI were found during the first 8-week period for information processing speed, fatigue, and perceived stress. However, only verbal memory was found to be significantly improved in the PSAI group during the 24-week follow-up period. There were no significant group × time differences with respect to hair cortisol. No side effects were noted and compliance was excellent. Conclusions PSAI was mostly effective during the first 8-week training period. Its benefits worn out during the non-training period, albeit we observed a delayed significant improvement of verbal memory. Our findings will help to further refine the technique, either by extending the training period and/or by including booster sessions, throughout the PSAI treatment. This study provided Class III evidence for PSAI. </jats:sec