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Objective: To review the available scientific literature about the effects of nutritional status on the multiple sclerosis disease., Methods: A systematic review of the scientific literature in the Medline (PubMed), Scopus, Cochrane Library and Web of Science databases through November 2016. Search equation: ("Multiple Sclerosis"[Mesh] OR "Multiple Sclerosis"[Title/Abstract] OR "Disseminated Sclerosis"[Title/Abstract] OR "Multiple Sclerosis Acute Fulminating"[Title/Abstract]) AND ("Nutritional Status"[Mesh] OR "Nutritional Status"[Title/Abstract] OR "Nutrition Status"[Title/Abstract]). The quality of the selected articles was discussed using the STROBE questionnaire. The search was completed through experts inquiry and additional review of the bibliographic references included in the selected papers. The concordance between authors (Kappa index) had to be higher than 80% for inclusion in this review., Results: Of the 160 references recovered, after applying inclusion and exclusion criteria, 29 articles were selected for review. Concordance between evaluators was 100.00%. The most studies established vitamin D levels. Others focused their research on finding out which nutrient deficits might be related to the multiple sclerosis development., Conclusions: Vitamin D may influence multiple sclerosis improvement. Sunlight and physical activity would be important factors, with nutritional status, in the course of this disease. It is necessary to produce new specific works that will delve into the subject to find out more about the relationship between nutritional status and multiple sclerosis.

Multiple sclerosis is the most frequent disabling neurological disease in young adults. Its development includes independent processes of inflammation, demyelination, neurodegeneration, gliosis and repair, which are responsible for the heterogeneity and individual variability in the expression of the disease, its prognosis and response to treatment. As part of personalised medicine, the progress made in the search for new biomarkers has identified promising candidates that may be useful for the early diagnosis of the disease, for detecting prognostic and developmental profiles of the disease, and for monitoring the response to treatment. Unfortunately, few of them have been validated adequately, which prevents them from being applied in clinical practice. In view of the latest findings, the experts recommend orienting research in another direction, not so much towards the discovery of new molecules or imaging techniques, but instead towards a clinical validation of these markers, with the aim of fostering translational research. This review offers an update on the information about the biomarkers in multiple sclerosis that have currently been validated and are thus potential candidates, as well as looking at their value in the diagnosis, prognosis, evaluation of the development of the disability caused by the disease and the response to therapy.

The concept of multiple sclerosis (MS) as a demyelinating disease is deeply ingrained. Although the existence of a neurodegenerative component has always been apparent, it has only recently become emphasized. Thus, in recent years several studies have identified axonal degeneration as the major determinant of irreversible neurological disability in patients with MS. Axonal injury begins at disease onset and remains clinically silent for many years; irreversible neurological disability develops when a threshold of axonal loss is reached and CNS compensatory mechanisms are exhausted. The precise mechanisms of axonal loss are poorly understood, and three hypotheses have been proposed: 1) The damage is caused by an inflammatory process, 2) There is an excessive accumulation of intra-axonal Ca2+, 3) Demyelinated axons undergo degeneration due to lack of trophic support by myelin, or myelin forming cells. Although MS has traditionally been regarded as a disease of white matter, demyelination can also occur in the cerebral cortex. Cortical lesions exhibit neuronal injury represented by dendritic and axonal transection as well as neuronal apoptosis. Because conventional nuclear magnetic resonance (NMR) is limited in its ability to provide specific information about axonal pathology in MS, new techniques such as, diffusion-weighted MRI, proton magnetic resonance spectroscopy, functional MRI, as well as novel techniques designed to measure atrophy have been developed to monitor MS evolution. Recognition that MS is in part a neurodegenerative disease should trigger critical rethinking on the pathogenic mechanisms of this disease and provides new targets for a rational treatment.

Introduction: It has been recently suggested that total cholesterol and low density lipoproteins (LDL) levels can behave as biological markers of activity in demyelinating diseases. Thus, our aim has been to describe the modifications of the plasma levels of total cholesterol and triglyceride due to treatment with interferon-beta in multiple sclerosis (MS) patients and to determine their relationship with the disease activity., Patients and Methods: Study of the follow-up of MS patients under treatment with interferon-beta. Clinical and analytical controls were performed before initiating treatment and than at 1, 3, 6, 12, 18 and 24 months of its initiation., Results: Fifty six patients have been studied, 41 of them women. Mean age was 37.4 years. Fifty were relapsing- remitting forms and the rest secondary progressive forms. The mean plasma levels of triglyceride increased and total cholesterol levels diminished during the 24 months of treatment with interferon, mainly in the first 3 months. No statistically significant relationship was found between disease activity and mean plasma levels of triglyceride and total cholesterol before the beginning of the treatment and during the period of follow-up., Conclusions: Treatment with interferon-beta in the MS patients originates changes in the plasma lipid profile, but neither these changes nor the plasma lipid levels before the treatment behave as biological markers of disease activity.

Introduction: During recent years, different studies have proposed that apolipoprotein E e4 can be a predictor of progression in multiple sclerosis. We aim to evaluate these findings in our country., Patients and Methods: We studied 42 patients with relapsing remitting or secondary progressive multiple sclerosis, and a disease duration of at least 2 years. We correlated the presence or absence of e4 allele with markers of progression such as age of onset and diagnosis, disease duration, number of relapses, EDSS at 1, 2, 5 and 10 years, progression index and relapse rate., Results: None of the parameters evaluated significantly correlate with e4 allele of the APOE., Conclusions: In spite of the limitation due to the small number of patients studied, we cannot confirm that APOE e4 allele is a predictor of progression of disability in multiple sclerosis.

Introduction: Pentoxifylline (PTX) is a phosphodiesterase inhibitor which has been found in studies in vitro to inhibit the production of Th-1 cytokines. It has been postulated that it might be used as a possible coadjuvant treatment for interferon in patients with multiple sclerosis. This would also reduce the potential side effects of interferon. OBJECTIVE. To show the efficacy of PTX in reducing the side effects of interferon, and in the functional improvement of these patients., Patients and Methods: We studied 18 patients with remitting-relapsing multiple sclerosis over a period of 18 months; nine patients were given PTX and interferon 800 mg/day simultaneously, and nine patients were treated with interferon alone. The clinical condition was evaluated every three months using the Expanded Disability Status Scale (EDSS) and the Neurological Score (NRS) scales., Results: We found no statistical improvement in the clinical course of EDSS and NRS in either group of patients after treatment for 18 months. The patients treated with PTX have fewer secondary effects due to interferon (fever and myalgia) during the first three months, but these differences between the groups subsequently disappear. In two patients PTX caused transient gastralgias and nauseas., Conclusions: PTX may be useful as a coadjuvant drug with interferon during the first three months of treatment since some of the side effects of interferon may thus be reduced. However, there seems no justification for using PTX for a longer period since there is no functional improvement.

Introduction: Multiple sclerosis (MS) is characterized by the presence in the central nervous system (CNS) of perivascular inflammatory infiltrates containing auto-reactive T and B cells and activated macrophages thus indicating that MS is a T cell-mediated CNS-confined chronic inflammatory demyelinating disease in which the ultimate effector cell is the activated macrophage., Development: The inflammatory process, leading to patchy demyelination and axonal loss, is mainly sustained by pro-inflammatory cytokines that modulate at different levels the pathogenic process underlying MS. Cytokines can 1. Sustain the 'putative' CNS-confined inflammatory process leading to the development of myelin-specific T cells; 2. Activate circulating myelin-specific T cells and shape their repertoire (Th1 versus Th2 pattern); 3. Induce the CNS recruitment of non antigen specific T cells and myelinotoxic effector cells (monocyte/macrophages) from the periphery, and 4. Cause direct oligodendrotoxicity (TNF alpha) or induce the secretion of myelinotoxic substances. The present chapter will focus on the mechanisms sustaining the activity of pro-inflammatory cytokines in MS pathogenesis.

Introduction: At what stage in the pathogenesis of multiple sclerosis (MS) does the damage to axons occur, and why should there be any axon loss at all in what is thought to be principally an axon sparing demyelinating disease? A recently described new technique for investigating axon damage depends for its ability on the immunoreactivity of amiloid precursor protein (APP), which has been shown to be more sensitive than silver stains for detecting damaged axons., Development: We used APP immunoreactivity as a method to investigate whether axon damage occurs in acute MS lesions. The results of our APP staining showed that the expression of APP in MS lesions is associated with acute MS lesions and the active border of less acute lesions. There was little, if any, APP expression in the chronic lesions. If we accept that the APP staining represents irreversible damage to some axons, the next question is what factors are responsible for mediating damage to axons in MS? Matrix metalloproteinases (MMP) are expressed by macrophages in acute MS lesions and in the active borders of active chronic lesions. The injection of highly-purified MMP into the brain results in demyelination, blood-brain barrier breakdown, and axonal loss. Moreover, the inhibition of the MMP activity reduces the severity of MS-like lesions in experimental models. Thus the properties and distribution of these enzymes make them rational targets for therapeutic intervention., Conclusion: Whatever mechanism proves to be responsible for axonal damage in MS, it is clear that this disease should, perhaps, be more appropriately recognized as a primary demyelinating entity with associated primary axonal loss.

Patients and Methods: We studied five biological fluids which were easily accessible to immunological examination (cerebrospinal fluid, plasma, tears, saliva and urine) in 25 patients with multiple sclerosis, clinically definite according to the criteria of Cleveland, Ohio (1991) and tabulated according to the Kurztke's expanded disability status scale. The samples were obtained simultaneously during a clinical bout of the disease before any pharmacological or immunosuppressive treatment had been given., Results: The soluble interleukin-2 levels were significantly raised in at least three of these fluids--always absent from the urine--when compared with normal controls. The sensitivity and specificity of this determination for diagnosis of the condition was greater than that of other immunochemical parameters--oligoclonal distribution of immunoglobulins (specifically of IgG), imbalance of the light Kappa and Lambda chains--and physiological studies (evoked potentials). The dosification and quantification of basic myelin protein of the central nervous system, rich in citruline in the urine, may be a parameter of progressiveness., Conclusion: This methodology (five humours test) may be used to establish an earlier, more certain diagnosis of multiple sclerosis and also monitor its biological activity together with nuclear magnetic resonance with intravenous contrast.

Introduction: Axon pathology in multiple sclerosis is an emerging concept, not because it is unknown but because it has been forgotten. However, clinical, functional and pathological aspects have clearly shown that it is damaged at a very early stage in development of the plaque of demyelination. There is sufficient clinical, radiological and pathological evidence to permit definition of axonal damage as the central element of the pathology and clinical features of multiple sclerosis., Development and Conclusions: Throughout this article we will see how the axon is affected in multiple sclerosis, how this affects the inflammatory response and which parameters allow us to measure axonal damage and its relation to disability. Finally we will see how a new physiopathogenic concept of multiple sclerosis appears, based on the axonal lesion, and how this fits current clinico-pathological concepts better.

Introduction and Development: Multiple sclerosis (ME) is an inflammatory disease of the myelin of the central nervous system, the origin of which is still unknown. Genetic, infectious, immunological and environmental factors have all been blamed, but none of these factors on their own can explain the whole spectrum of this disease. Of the environmental factors, fat in the diet has given rise to most discussion. At the present time, it is known that polyunsaturated essential fatty acids form a part of biological membranes. A relationship has been found between the dietary fat consumed and the plasma levels and cell membrane content., Conclusions: The possible immuno-modulation function of these fatty acids justify rigorous evaluation of this hypothesis.

The production of interferon-tau (IFN-tau), interleukin-2 (IL-2) and prostaglandin-E2 (PGE2) in peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA) and the repercussion which these cytokines have on the growth and activity of the 2', 3' and cyclonucleotide-3'-phosphohydrolase (CNP) of cultures of rat oligodendrocytes were analyzed. The study was carried out in a group of patients (20 with active disease, 23 in remission) with defined multiple sclerosis (MS), a group of subjects with other central nervous system diseases (OCNSD) and a group of 20 healthy (HS). Increases in PGE2 were found in PBMC cultures of patients with MS (p < 0.0005, ANOVA test) and the production of PGE2 in patients with active MS correlated positively (R2 = 0.743, p = 0.02) with CNP activity in the oligodendroglial cultures. These results suggest that PGE2 may influence in the re-myelinization process.