Multiple sclerosis (MS) is the most common acquired demyelinating disorder of the central nervous system (CNS). Diagnosing MS can be very challenging owing to its variable clinical features and lack of specific tests. Magnetic resonance imaging (MRI) is a key measure in this process. Although white matter lesions on brain MRI are regarded as a hallmark of MS, they are a common radiological finding and their pattern may overlap in particular CNS inflammatory diseases. The increasing availability of therapies for MS and the knowledge of benefits associated with an early treatment underscore the importance of precise and quick diagnosis. Despite an extensive research, currently no fully specific diagnostic test is available to distinguish between CNS inflammatory disorders. In this review, we discuss characteristic findings and distinctive features of CNS inflammatory disorders, with particular focus on rheumatic diseases.

Plasmacytoid dendritic cells (pDCs) represent a DC subtype that exerts divergent functions in innate and adoptive immunity including the immediate reaction to microbial factors and the induction of immunoregulatory responses. It is thought that different DC subtypes may be critically involved in the pathogenesis of multiple sclerosis (MS). In our study we assessed the phenotype, maturation and functional properties of peripheral blood pDCs from 35 clinically stable, untreated multiple sclerosis patients, 30 healthy controls and 9 patients with pneumonia, which was used as a non-specific inflammatory condition (NIC). Ex vivo expression of CD86 and 4-1BBL was significantly lower on pDCs from multiple sclerosis patients than from controls and patients with NIC (22 versus 47 versus 41% and 12 versus 35 versus 32%, respectively). When stimulated with IL-3 and CD40L, pDCs of multiple sclerosis patients showed inefficient maturation as demonstrated by significantly lower or delayed upregulation of CD86, 4-1BBL, CD40 and CD83. Additionally, in multiple sclerosis, stimulation of pDCs by unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) resulted in a significantly lower interferon (IFN) alpha secretion than in controls. In multiple sclerosis, but not in controls, pDCs failed to upregulate proliferative responses and IFN-gamma secretion of autologous peripheral blood mononuclear cells (PBMC) in a co-culture system. Moreover, depletion of pDCs in multiple sclerosis patients, but not in controls, had no effect on generation of CD4⁺Foxp3⁺ regulatory T cells. We also provide data showing that glatiramer acetate (GA) treatment partially restores phenotype and function of pDCs in multiple sclerosis patients. These findings suggest functional abnormalities of pDCs in these patients, which might be of importance in the understanding of the development of immune dysregulation in this disease.

The dysfunction of oligodendrocytes (OLs) is regarded as one of the major causes of inefficient remyelination in multiple sclerosis, resulting gradually in disease progression. Oligodendrocytes are derived from oligodendrocyte progenitor cells (OPCs), which populate the adult central nervous system, but their physiological capability to myelin synthesis is limited. The low intake of essential lipids for sphingomyelin synthesis in the human diet may account for increased demyelination and the reduced efficiency of the remyelination process. In our study on lipid profiling in an experimental autoimmune encephalomyelitis brain, we revealed that during acute inflammation, nervonic acid synthesis is silenced, which is the effect of shifting the lipid metabolism pathway of common substrates into proinflammatory arachidonic acid production. In the experiments on the human model of maturating oligodendrocyte precursor cells (hOPCs) in vitro, we demonstrated that fish oil mixture (FOM) affected the function of hOPCs, resulting in the improved synthesis of myelin basic protein, myelin oligodendrocyte glycoprotein, and proteolipid protein, as well as sphingomyelin. Additionally, FOM reduces proinflammatory cytokines and chemokines, and enhances fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) synthesis by hOPCs was also demonstrated. Based on these observations, we propose that the intake of FOM rich in the nervonic acid ester may improve OL function, affecting OPC maturation and limiting inflammation.

Purpose of Review: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that mainly affects young adults and that is one of the leading causes of disability in this age group, with cognitive impairment occurring early in the course of the disease. This article summarizes the current knowledge about cognitive dysfunction in the early phase of MS, including biomarkers, MRI correlates, and its value as a prognostic marker. Recent Findings: New sets of neuropsychological tests have been established to screen for cognitive dysfunction more easily and accurately. Moreover, structural changes detected by brain MRI and several biomarkers found in cerebrospinal fluid and blood serum have been recently correlated with decreased cognitive performance. Additionally, factors influencing cognition in MS, such as disease-modifying therapy, mood disorders, and lifestyle, are better described. Summary: Cognitive impairment early in the course of MS is suggested as a prognostic factor for disease progression. However, clear-cut definitions of the early stage of MS as well as unified criteria for the diagnosis of cognitive impairment are still lacking. New and more reliable tools for evaluating cognition in MS patients should be developed and introduced into everyday practice to facilitate the implementation of effective disease-modifying therapy, cognitive rehabilitation, and lifestyle management.