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The temporal and clinical course of multiple sclerosis is heterogeneous, varying among patients as well as over time in the same individual. Greater specificity in describing disease classification and course is important for conduct of clinical trials as well as prognosis for individual patients. This chapter reviews the results of recent consensus panels that have further defined the relapsing and progressive forms of multiple sclerosis through clarification of clinical relapse, subclinical relapse, active disease, and progressive disease. Clinical characteristics, conventional and nonconventional magnetic resonance imaging metrics, and immunologic and genetic biomarkers that can be used to predict disease severity and course are also discussed.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the CNS. Its sequelae include both physical and cognitive disability. Advances in neuropsychological testing and screening have led to increased recognition of cognitive impairment in MS; more than half of MS patients have been found to have some degree of cognitive impairment. Strong correlations have been found between neuropsychological testing, brain atrophy and other brain imaging techniques. These tools can aid in the comprehensive evaluation of MS patients. Genetic markers, such as ApoE and brain-derived neurotrophic factor polymorphisms, may also correlate with cognitive impairment in MS. This review details advances in recognizing and predicting cognitive dysfunction in MS. Increased understanding and better evaluation and monitoring of cognitive status in MS may improve the sensitivity of studies designed to test new disease-modifying therapies and interventions for cognitive impairment.

Objectives To compare serum levels of the receptor for advanced glycation end products (sRAGE) between multiple sclerosis (MS) patients and healthy control subjects, and to investigate whether serum sRAGE levels correlate with MS disease severity as indicated by the Kurtzke Expanded Disability Status Scale (EDSS). Method 37 patients with clinical diagnosis of MS and 22 healthy control subjects were investigated in a cross-sectional study using enzyme-linked immunosorbent assays (ELISA). Results Serum levels of sRAGE were found to be significantly lower in MS patients compared to levels in healthy controls ( p = 0.005). A trend toward lower levels of serum sRAGE was observed in female MS patients compared to their male counterparts ( p = 0.05). A relationship between sRAGE and EDSS, and sRAGE and rate of clinical relapse was observed ( p = 0.012). Conclusion The significant reduction of sRAGE in MS patients relative to healthy controls supports the potential role for RAGE axis in MS clinical pathology. Lower levels of sRAGE may be associated with enhanced inflammatory responses. Based on these observations, further investigations into the role of sRAGE in MS clinical pathology is warranted.

The study is aimed to determine the role of quercetin (3,3'4',5,7-pentahydroxy flavone), alone and in combination with human interferon-beta (IFN-beta), in modulating the immune response(s) of peripheral blood mononuclear cells (PBMC) isolated from multiple sclerosis (MS) patients and from normal healthy subjects. PBMC proliferation in the presence or absence of these drugs was determined and the production of proinflammatory cytokines (IL-1beta, TNF-alpha), and the ratio of cell migration mediator MMP-9, and its inhibitor, TIMP-1 were assessed in the culture supernatants. Quercetin reduced, in a dose-dependent manner, the proliferation of PBMC and modulated the level of IL-1beta and TNF-alpha released by PBMC in the culture supernatants. Quercetin reduced the MMP-9/TIMP-1 ratio via lowering MMP-9 production. Quercetin, when combined with IFN-beta, had additive effects in modulating TNF-alpha and MMP-9. These immunomodulatory responses to quercetin were similar between MS patients and healthy control (HC) subjects.

Multiple sclerosis is characterized by the dual pathological processes of inflammation and neurodegeneration. Conventional MRI techniques are considered the best tools for assessing and monitoring lesion burden and inflammation but are limited in their ability to assess axonal loss. Optical coherence tomography (OCT) is a simple high-resolution technique that uses near infrared light to quantify the thickness of the retinal nerve fiber layer (RNFL), which contains only non-myelinated axons. RNFL thickness (RNFLT) was measured using OCT on thirty consecutive MS patients (60 eyes). Eighteen patients underwent quantitative MRI analysis including T1- and T2-lesion volumes (LV), normalized brain volume (NBV), normalized cortical, white and gray matter volumes (NCV, NWMV, and NGMV), and mean whole brain diffusivity (MD). There was a strong association between NBV and average RNFL thickness (p