Fatigue and depression are common conditions diagnosed in people with multiple sclerosis (MS). Fatigue defined as subjective lack of physical and/or mental energy is present in 35–97% of people with MS, who classify it as one of the most serious symptoms interfering with daily activities and influencing the quality of life. Depression is diagnosed in about 50% of people with MS. Since fatigue and depression frequently coexists, it may be quite hard to differentiate them. Primary fatigue and primary depression in MS are caused by inflammatory, oxidative/nitrosative, and neurodegenerative processes leading to demyelination, axonal damage, and brain atrophy. In people with MS and comorbid fatigue and/or depression there is reported increased serum and cerebrospinal fluid concentration of inflammatory mediators such as tumor necrosis factor, interleukins (IL-1a, IL-1b, IL-6), interferon γ and neopterin. Moreover, the brain atrophy of prefrontal, frontal, parietotemporal regions, thalamus, and basal ganglia was observed in people with MS with fatigue and/or depression. The secondary fatigue and secondary depression in people with MS may be caused by emotional factors, sleep disorders, pain, the coexistence of other diseases, and the use of medications. In some studies, the use of disease-modifying therapies positively influenced fatigue, probably by reducing the inflammatory response, which proves that fatigue and depression are closely related to immunological factors. In this mini-review, the pathogenesis, methods of evaluation and differentiation, and possible therapies for fatigue and depression in MS are discussed.

The aim of the study was to verify the association of clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments in Poland. Disability progression was defined as relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and progression independent of relapses and brain MRI Activity (PIRMA). Data from the Therapeutic Program Monitoring System were analyzed. Three panels of patients were identified: R0, no relapse during treatment, and R1 and R2 with the occurrence of relapse during the first and the second year of treatment, respectively. In the R0 panel, we detected 4.6% PIRA patients at 24 months (p < 0.001, 5.0% at 36 months, 5.6% at 48 months, 6.1% at 60 months). When restricting this panel to patients without brain MRI activity, we detected 3.0% PIRMA patients at 12 months, 4.5% at 24 months, and varying from 5.3% to 6.2% between 36 and 60 months of treatment, respectively. In the R1 panel, RAW was detected in 15.6% patients at 12 months and, in the absence of further relapses, 9.7% at 24 months and 6.8% at 36 months of treatment. The R2 group was associated with RAW significantly more frequently at 24 months compared to the R1 at 12 months (20.7%; p < 0.05), but without a statistical difference later on. In our work, we confirmed that disability progression was independent of relapses and brain MRI activity.

The FOXP3 gene encodes a transcription factor and is predominantly expressed in the CD4⁺CD25⁺ regulatory T cells which plays a pivotal role in the maintenance of immune homeostasis. The defect of FOXP3 gene may provide a critical link between autoimmunity and immune deficiency. The purpose of our study was to evaluate the association of chosen polymorphisms of FOXP3 gene (rs3761549, rs3761548, rs3761547) with different clinical multiple sclerosis (MS) data of our relapsing-remitting groups of patients and in control group. The study was performed on a group consisting of 174 relapsing-remitting MS patients, diagnosed under 40 years of life, and 174 healthy volunteers. Genotyping was performed using a real-time PCR-based method by TaqMan Assays. Significant differences in distribution of allele C rs3761547 were found in male MS patients in comparison to the male healthy group (p = 0.046, OR 1.95, CI 95%). No association between MS and the other two polymorphisms was observed in males and females of both studied groups. Our data may suggest that FOXP3 rs3761547 gene polymorphism are related notably with the increased risk of MS development in males patients. To our knowledge this is the first study which indicates gender-specific relation between rs3761547 FOXP3 gene polymorphism and multiple sclerosis.

Background: It is well known that the cerebrospinal fluid (CSF) concentrations of free light chains (FLC) and immunoglobulin G (IgG) are elevated in multiple sclerosis patients (MS). Therefore, in this study we aimed to develop a model based on the concentrations of free light chains and IgG to predict multiple sclerosis. We tried to evaluate the diagnostic usefulness of the novel κIgG index and λIgG index, here presented for the first time, and compare them with the κFLC index and the λFLC index in multiple sclerosis patients. Methods: CSF and serum samples were obtained from 76 subjects who underwent lumbar puncture for diagnostic purposes and, as a result, were divided into two groups: patients with multiple sclerosis (n = 34) and patients with other neurological disorders (control group; n = 42). The samples were analyzed using turbidimetry and isoelectric focusing. The κIgG index, λIgG index, κFLC index, and λFLC index were calculated using specific formulas. Results: The concentrations of CSF κFLC, CSF λFLC, and serum κFLC and the values of κFLC index, λFLC index, and κIgG index were significantly higher in patients with multiple sclerosis compared to controls. CSF κFLC concentration and the values of κFLC index, λFLC index, and κIgG index differed in patients depending on their pattern type of oligoclonal bands. κFLC concentration was significantly higher in patients with pattern type 2 and type 3 in comparison to those with pattern type 1 and type 4. The κFLC index, λFLC index, and κIgG index were significantly higher in patients with pattern type 2 in comparison to those with pattern type 4. The κFLC index and κIgG index were significantly higher in patients with pattern type 2 in comparison to those with pattern type 1, and in patients with pattern type 3 compared to those with pattern type 4. The κIgG index was markedly elevated in patients with pattern type 3 compared to those with pattern type 1. In the total study group, κFLC, λFLC, κFLC index, λFLC index, κIgG index, and λIgG index correlated with each other. The κIgG index showed the highest diagnostic power (area under the curve, AUC) in the detection of multiple sclerosis. The κFLC index and κIgG index showed the highest diagnostic sensitivity, and the κIgG index presented the highest ability to exclude multiple sclerosis. Conclusion: This study provides novel information about the diagnostic significance of four markers combined in the κIgG index. More investigations in larger study groups are needed to confirm that the κIgG index can reflect the intrathecal synthesis of immunoglobulins and may improve the diagnosis of multiple sclerosis.