Cytokines regulate immune responses and are crucial to MS pathogenesis. This study evaluated pro-inflammatory and anti-inflammatory cytokine concentrations in the CSF of de novo diagnosed RRMS patients compared to healthy controls. We assessed cytokine levels in the CSF of 118 de novo diagnosed RRMS patients and 112 controls, analyzing relationships with time from symptom onset to diagnosis, MRI lesions, and serum vitamin D levels. Elevated levels of IL-2, IL-4, IL-6, IL-13, FGF-basic, and GM-CSF, and lower levels of IL-1β, IL-1RA, IL-5, IL-7, IL-9, IL-10, IL-12p70, IL-15, G-CSF, PDGF-bb, and VEGF were observed in RRMS patients compared to controls. IL-2, IL-4, IL-12p70, PDGF, G-CSF, GM-CSF, and FGF-basic levels increased over time, while IL-10 decreased. IL-1β, IL-1RA, IL-6, TNF-α, and PDGF-bb levels negatively correlated with serum vitamin D. TNF-α levels positively correlated with post-contrast-enhancing brain lesions. IL-15 levels negatively correlated with T2 and Gd(+) lesions in C-spine MRI, while TNF-α, PDGF-bb, and FGF-basic correlated positively with T2 lesions in C-spine MRI. IL-6 levels positively correlated with post-contrast-enhancing lesions in Th-spine MRI. Distinct cytokine profiles in the CSF of de novo diagnosed MS patients provide insights into MS pathogenesis and guide immunomodulatory therapy strategies.

Background/Objectives: Developments in eye-tracking technology are opening up new possibilities for diagnosing patients in a state of minimal consciousness because they can provide information on visual behavior, and the movements of the eyeballs are correlated with the patients’ level of consciousness. The purpose of this study was to provide validation of a tool, based on eye tracking by comparing the results obtained with the assessment obtained using the Coma Recovery Scale-Revised (CRS-R). Methods: The mul-ti-center clinical trial was conducted in Poland in 2022–2023. The results of 46 patients who were not able to communicate verbally due to severe brain injury were analyzed in this study. The state of consciousness of patients was assessed using the Minimally Conscious State Detection test (MCSD), installed on an eye tracker and compared to CRS-R. The examinations consisted of performing the MCSD test on patients five times (T1–T5) within 14 days. Collected data were processed based on the FDA and GCP’s regulatory requirements. Depending on the nature of the data, the mean and standard deviation, median and lower and upper quartiles, and maximum and minimum values were calculated. Passing–Bablok regression analysis was used to assess the measurement equiva-lence of the methods used. Results: There was no difference between the MCSD and CRS-R in the raw change between T5 and T1 time points, as well as in the total % of points from all time points. The MCSD results from each time point show that at least the first two measurements serve to famil-iarize and adapt the patient to the measurement process, and the third and next measurement should be considered reliable. Conclusions: The results indicated a significant relationship be-tween the scores obtained with MCSD and CRS-R. The results suggest that it seems reasonable to introduce an assessment of the patient’s state of consciousness based on eye-tracking technology. The use of modern technology to assess a patient’s state of consciousness opens up the opportunity for greater objectivity, as well as a reduction in the workload of qualified personnel.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by autoimmune-mediated damage to oligodendrocytes and subsequent myelin destruction. Clinical implications: Clinically, the disease presents with many symptoms, often evolving over time. The insidious onset of MS often manifests with non-specific symptoms (prodromal phase), which may precede a clinical diagnosis by several years. Among them, headache is a prominent early indicator, affecting a significant number of MS patients (50–60%). Results: Headache manifests as migraine or tension-type headache with a clear female predilection (female-male ratio 2-3:1). Additionally, some disease-modifying therapies in MS can also induce headache. For instance, teriflunomide, interferons, ponesimod, alemtuzumab and cladribine are associated with an increased incidence of headache. Conclusions: The present review analyzed the literature data on the relationship between headache and MS to provide clinicians with valuable insights for optimized patient management and the therapeutic decision-making process.

Studies suggest that vitamin D (VitD) may reduce oxidative stress (OS) in multiple sclerosis (MS) patients. This study aimed to compare the effects of various VitD doses on OS in relapsing–remitting MS (RRMS). A 6-month supplementation was introduced using two doses of VitD: 2000 IU/day in the high-dose group (HD, n = 23) and 15,960 IU/month in the low-dose group (LD, n = 29). Significant differences in body weight, height, and age were found between groups. A significant increase in the level of VitD (25(OH)D) was noted in both groups (p < 0.01). A significant increase was observed in the levels of LF and MDA (p < 0.01) and a significant decrease in the concentrations of PSH (p < 0.01), CuZnSOD (p = 0.02), and TOS (p < 0.01). A significant positive correlation was observed between serum VitD and SOD (R = 0.38, p < 0.01) and MnSOD (R = 0.31, p < 0.05), as well as a significant negative correlation between serum VitD and MDA (R = −0.31, p = 0.05) at the beginning of the study. At the end of the study, a significant positive correlation was observed between serum VitD and SOD (R = 0.34, p < 0.05) and CuZnSOD (R = 0.51, p < 0.01). In RRMS patients, the VitD doses are probably insufficient to induce a beneficial effect on the pro- and antioxidant balance.

Background: Uhthoff’s phenomenon (UP) is a transient, fully reversible exacerbation of pre-existing neurological deficits in multiple sclerosis (MS) patients, triggered by minor elevations in core body temperature. In clinical practice, UP is a frequent source of distress, often misidentified as an acute inflammatory disease relapse. Objectives: This narrative review provides a critical analysis of UP, addressing the methodological heterogeneity in its epidemiological estimates, its clinical presentation, and its differential diagnosis from true relapses. Methods: Mechanistically, we synthesize traditional concepts of temperature-dependent conduction block with modern insights into neuroenergetic failure, mitochondrial dysfunction, inflammatory mediators, and autonomic dysregulation. Results: Furthermore, this work delineates current management strategies, establishing a clear distinction between robust evidence-based interventions and expert-informed practical guidance for patient education, physical rehabilitation planning, targeted active/passive cooling, and pharmacological approaches. Conclusion: Characterized as a pseudo-relapse, UP occurs independently of novel focal neuroinflammation. Although it does not inflict permanent structural damage to axons, the transient neuroenergetic crises and accompanying psychological burdens constitute a genuine threat to patient quality of life and functional autonomy, requiring systematic, interdisciplinary care.

Uhthoff’s phenomenon (UP) is a transient, fully reversible exacerbation of pre-existing neurological deficits in multiple sclerosis (MS) patients, triggered by minor elevations in core body temperature. In clinical practice, UP is a frequent source of distress, often misidentified as an acute inflammatory disease relapse. This narrative review provides a critical analysis of UP, addressing methodological heterogeneity in its epidemiological estimates, its clinical presentation, and its differential diagnosis from true relapses. Mechanistically, we synthesize traditional concepts of temperature-dependent conduction block with modern insights into neuroenergetic failure, mitochondrial dysfunction, inflammatory mediators, and autonomic dysregulation. Furthermore, this work delineates current management strategies, establishing a clear distinction between robust evidence-based interventions and expert-informed practical guidance for patient education, physical rehabilitation planning, targeted active/passive cooling, and pharmacological approaches. Characterized as a pseudo-relapse, UP occurs independently of novel focal neuroinflammation. In conclusion, an isolated episode of Uhthoff’s phenomenon (UP) represents a transient, functional conduction block and does not inflict acute, permanent structural damage to the axon. However, emerging frameworks suggest that frequent, repeated episodes subject the already demyelinated axon to recurrent metabolic strain. Over time, these successive neuroenergetic crises do not directly destroy the fiber, but they may gradually exhaust the cell’s metabolic reserve. This cumulative stress potentially increases long-term secondary axonal vulnerability, making the axon more susceptible to the progressive neurodegenerative processes inherent to multiple sclerosis.