Transcranial magnetic stimulation (TMS) is a noninvasive technique mainly used for the assessment of corticospinal tract integrity and excitability of the primary motor cortices. Motor evoked potentials (MEPs) play a pivotal role in TMS studies. TMS clinical guidelines, concerning the use and interpretation of MEPs in diagnosing and monitoring corticospinal tract integrity in people with multiple sclerosis (pwMS), were established almost ten years ago and refer mainly to the use of TMS implementation; this comprises the magnetic stimulator connected to a standard EMG unit, with the positioning of the coil performed by using the external landmarks on the head. The aim of the present work was to conduct a narrative literature review on the MEP assessment and outcome measures in clinical and research settings, assessed by TMS Methodological characteristics of different TMS system implementations (TMS without navigation, line-navigated TMS and e-field-navigated TMS); these were discussed in the context of mapping the corticospinal tract integrity in MS. An MEP assessment of two case reports, by using an e-field-navigated TMS, was presented; the results of the correspondence between the e-field-navigated TMS with MRI, and the EDSS classifications were presented. Practical and technical guiding principles for the improvement of TMS studies in MEP assessment for MS are discussed, suggesting the use of e-field TMS assessment in the sense that it can improve the accuracy of corticospinal tract integrity testing by providing a more objective correspondence of the neurophysiological (e-field-navigated TMS) and clinical (Expanded Disability Status Scale—EDSS) classifications.

The aim of the retrospective study was to compare the immunophenotyping of T-lymphocytes, B-lymphocytes, and natural killer cells before the administration of the first and the second dose of ocrelizumab in 22 patients with multiple sclerosis in a three-year period (2019–2021) at the Department of Neurology of the University Hospital of Split. The values of cell immunophenotyping and protein electrophoresis, as well as laboratory parameters, were investigated. There was no significant decrease in serum albumin and globulins before the second dose of ocrelizumab (p > 0,05). A decrease in the number of T-lymphocytes before administration of the second dose of ocrelizumab was observed, but without statistical significance (p = 0.274). Significant depletion occurred in median CD19+ B-lymphocytes (p < 0.001) before the intake of the second dose of ocrelizumab confirming the primary action of ocrelizumab on the B cell lineage.

Expression of CD40 and CD192 markers in different monocyte subpopulations has been reported to be altered in people with MS (pwMS). Also, functional connectivity of the corticospinal motor system pathway alterations has been proved by transcranial magnetic stimulation (TMS). The study objective was to investigate the expression of CD40 and CD192 in classical (CD14⁺⁺CD16⁻), intermediate CD14⁺⁺CD16⁺ and non-classical (CD14⁺CD16⁺⁺) blood monocyte subpopulations in pwMS, undergoing neurophysiological TMS assessment of the corticospinal tract integrity by recording motor-evoked potentials (MEPs). Radiological examination on lesion detection with MRI was performed for 23 patients with relapsing–remitting MS treated with teriflunomide. Then, immunological analysis was conducted on peripheral blood samples collected from the patients and 10 healthy controls (HC). The blood samples were incubated with anti-human CD14, CD16, CD40 and CD192 antibodies. Next, pwMS underwent neurological testing of functional disability (EDSS) and TMS assessment with recording MEPs from upper and lower extremity muscles. The results show that in comparison to HC subjects, both pwMS with normal and altered MEP findings (prolonged MEP latency or absent MEP response) had significantly decreased surface receptor expression measured (MFIs) of CD192 and increased CD40 MFI in classical monocytes, and significantly increased percentages of classical and total monocytes positive for CD40. Knowing CD40’s pro-inflammatory action, and CD192 as a molecule that enables the passing of monocytes into the brain, decreased CD192 in classical monocytes could represent a beneficial anti-inflammatory parameter.

The objective of this study was to investigate regulatory T cells (Tregs) and monocytes; specifically, the expression of CTLA-4 (CD152) and FOXP3⁺ in CD4⁺CD25⁺ Tregs and the expression of CD40+ and CD192+ monocyte subpopulations in subjects with primary progressive multiple sclerosis (PPMS). Immunological analysis was conducted on peripheral blood samples collected from the 28 PPMS subjects (15 treated with ocrelizumab and 13 untreated PPMS subjects) and 10 healthy control subjects (HCs). The blood samples were incubated with antihuman CD14, CD16, CD40, and CD192 antibodies for monocytes and antihuman CD4, CD25, FOXP3, and CTLA-4 antibodies for lymphocytes. The study results showed that in comparison to HCs both ocrelizumab treated (N = 15) and untreated (N = 13) PPMS subjects had significantly increased percentages of CTLA-4⁺ and FOXP3⁺ in CD4⁺CD25⁺ Tregs. Further, ocrelizumab treated PPMS subjects, compared to the untreated ones, had significantly decreased percentages of CD192+ and CD40+ nonclassical monocytes. Increased percentages of CTLA-4⁺ and FOXP3⁺ in CD4⁺CD25⁺ Tregs in both ocrelizumab treated and untreated PPMS subjects indicates the suppressive (inhibitory) role of Tregs in abnormal immune responses in PPMS subjects. Decreased percentages of CD40+ and CD192+ non-classical CD14⁺CD16⁺⁺ monocytes for treated compared to untreated PPMS subjects suggest a possible role for ocrelizumab in dampening CNS inflammation.

Background/Objectives: Visual evoked potential (VEP) P100 maximum latency is known to predict fatigue and cognition in multiple sclerosis (MS). However, the relationship between VEP and neurological (impairment)/neuropsychological status is not well understood in MS. Therefore, the aim of the present prospective cross-sectional study was to investigate associations among VEP, neurological impairment, and neuropsychological status in MS. Methods: The study included 25 subjects with primary progressive MS (PPMS), with a median EDSS score of 4.5, and 30 control subjects. Neurological status of PPMS subjects was evaluated with the Expanded Disability Status Scale (EDSS), while neuropsychological assessment included the Symbol Digit Modalities Test (SDMT), Nine-Hole Peg Test (9HPT), Fatigue Severity Scale (FSS), Depression, Anxiety and Stress Scale (DASS-21), and Multiple Sclerosis Impact Scale (MSIS-29). Statistical analysis included group comparisons, Spearman correlations, multivariable linear regression analyses, bidirectional stepwise selection, and a parsimonious multivariable model. Results: PPMS subjects had significantly prolonged P100 maximum latencies (p < 0.01) compared to control subjects, as well as significantly poorer performance on the 9HPT (p < 0.01) and higher fatigue scores (FSS; p < 0.01). In multivariable analyses within the PPMS group, disease duration was independently associated with the EDSS (p = 0.009), whereas neuropsychological measures were intercorrelated (ρ > 0.45) and associated with the EDSS at intermediate stages of model selection. P100 maximum latency showed a positive but non-significant association after adjustment for sex and disease duration in the parsimonious model, which explained approximately 49% of the variance in the EDSS. Conclusions: The findings provide insight into the complex interplay among neurophysiological (VEP), neuropsychological and neurological status in MS.