Content area
Full Text
About the Authors:
Nieves Velez de Mendizabal
* E-mail: [email protected]
Affiliations Indiana University School of Medicine; Indianapolis, Indiana, United States of America, Indiana Clinical and Translational Sciences Institute (CTSI), Indianapolis, Indiana, United States of America
Matthew M. Hutmacher
Affiliation: Ann Arbor Pharmacometrics Group (A2PG), Ann Arbor, Michigan, United States of America
Iñaki F. Troconiz
Affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain
Joaquín Goñi
Affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States of America
Pablo Villoslada
Affiliation: Center for Neuroimmunology, Institute of Biomedical Research August Pi Sunyer (IDIBAPS), Hospital Clinic of Barcelona, Barcelona, Spain
Francesca Bagnato
Affiliations Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, United States of America, Department of Neurology, University of Maryland, Baltimore, Maryland, United States of America
Robert R. Bies
Affiliations Indiana University School of Medicine; Indianapolis, Indiana, United States of America, Indiana Clinical and Translational Sciences Institute (CTSI), Indianapolis, Indiana, United States of America
Introduction
Multiple sclerosis (MS) is a prototypic autoimmune disease that affects the central (CNS) with a relapsing-remitting (RR) disease progression [1]. Clinical relapses in MS, acute symptoms that appear in episodic periods, are considered to be the reflection of focal inflammatory events in the white matter that disrupts neural conduction by damaging axons [2]. Clinical relapses are used to categorize different forms of the disease, i.e. RR versus progressive MS, as a marker to define the disease's disease progression and to measure the success of new therapies [2].
Magnetic Resonance Image (MRI) is a useful tool for understanding and following the disease progression in patients with MS [3]–[5]. The focal inflammatory events of the CNS that accompany a clinical MS relapse are evident on MRI recordings as contrast enhancing lesions (CELs) on T1-weighted images [6]. This kind of MRIs shows CELs four to ten times more frequently compared with clinically defined relapses [7]. That is, clinical relapses may not occur even if a CEL is observed. Therefore, CELs are more informative biomarker for disease progression than the Expanded Disability Status Score (EDSS). The natural history of a CEL is highly variable both within and between patients (Figure 1). In MS, CELs and associated clinical relapses generally last for a month...