The aim of this study was to assess whether the heart rate variability (HRV) could predict a favorable or unfavorable stroke outcome. The endpoint was based on the National Institutes of Health Stroke Scale (NIHSS). The patient’s health condition was assessed upon discharge from the hospital. An unfavorable stroke outcome was defined as death or NIHSS ≥ 9, while NIHSS < 9 meant a favorable stroke outcome. The studied group consisted of 59 patients with acute ischemic stroke AIS (mean age of 65.6 ± 13.2; 58% were females). An original and innovative non-linear measure was used to analyze HRV. It was based on symbolic dynamics consisting of comparing the “length of the longest words” in the night recording of HRV. “The length of the longest word” meant the longest sequence of identical adjacent symbols possible for a patient. An unfavorable stroke outcome occurred in 22 patients, whereas the majority of patients (37) had a favorable stroke outcome. The average hospitalization time of patients with clinical progression was 29 ± 14 days, and with favorable outcomes was 10 ± 3 days. Patients with long words (more than 150 adjacent RR intervals having the same symbol) were hospitalized no longer than 14 days and they had no clinical progression. The patients with a favorable stroke outcome were characterized by longer words. Our pilot study may be the beginning of work on the development of a non-linear, symbolic method as a predictor of prolonged hospitalization and increased risk of clinical progression in patients with AIS.

Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease with demyelinating inflammatory characteristics. It is the most common nontraumatic and disabling disease affecting young adults. The incidence and prevalence of MS have been increasing. However, its exact cause remains unclear. The main tests used to support the diagnosis are magnetic resonance imaging (MRI) examination and cerebrospinal fluid (CSF) analysis. Nonetheless, to date, no sensitive or specific marker has been identified for the detection of the disease at its initial stage. In recent years, researchers have focused on the fact that the number of natural killer cell group 2 member D (NKG2D) family of C-type lectin-like receptor + (NKG2D+) T cells in the peripheral blood, CSF, and brain tissue has been shown to be higher in patients with MS than in controls. The activating receptor belonging to the NKG2D is stimulated by specific ligands: in humans these are major histocompatibility complex (MHC) class I polypeptide–related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB) proteins and UL16 binding 1–6 proteins (ULBP1-6). Under physiological conditions, the aforementioned ligands are expressed at low or undetectable levels but can be induced in response to stress factors. NKG2D ligands (NKG2DLs) are involved in epigenetic regulation of their expression. To date, studies in cell cultures, animal models, and brain tissues have revealed elevated expression of MICA/B, ULPB4, and its mouse homolog murine UL16 binding protein-like transcript (MULT1), in oligodendrocytes and astrocytes from patients with MS. Furthermore, soluble forms of NKG2DLs were elevated in the plasma and CSF of patients with MS compared to controls. In this review, we aim to describe the role of NKG2D and NKG2DLs, and their interactions in the pathogenesis of MS, as well as in other autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and celiac disease (CeD). We also assess the potential of these proteins as diagnostic markers and consider future perspectives for targeting NKG2D ligands and their pathways as therapeutic targets in MS.

Introduction: Cladribine tablets (CladT) are a high-efficacy disease-modifying therapy recommended for the treatment of relapsing–remitting multiple sclerosis (RRMS) particularly in early disease. This study is aimed to evaluate the long-term efficacy of CladT in population of Polish RRMS patients, with more advanced disease.Methods: This retrospective observational study included patients with RRMS who started CladT treatment between December 2019 and November 2023. Collected data included prior treatments, annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS) score, no evidence of disease activity (NEDA-3), lymphocyte counts, and safety outcomes were collected.Results: Of the 230 patients (8.3% treatment-naïve, mean disease duration 9.2 years), follow-up data were available up to year 1 for 222 patients, year 2 for 154 patients, year 3 for 87 patients and year 4 for 31 patients. The ARR decreased from 1.42 at baseline to 0.26, 0.22, and 0.36 in years 1, 2, and 3, respectively. The proportion of relapse-free patients increased from 13.9% at baseline to 76.8% in year 1, 82% in year 2 and 75.4% in year 3 with no relapses reported in year 4. The proportion of patients with active MRI lesions declined from 90.4% at baseline to 36.3% in year 1, 25.2% in year 2, 45.9% in year 3 and 8.3% in year 4. Stable or improved EDSS was observed in 85.9% of patients in year 1, 80.8% in year 2, 73.7% in year 3 and 88.9% in year 4. NEDA-3 status was achieved in 47.4% of patients in year 1, 51.0% in year 2, 40.4% in year 3 and 71.4% in year 4. Adverse events were reported in 16.7% of patients in years 1–2 and in 6.3% of patients in year 3.Discussion: The results indicate that CladT is effective and safe in Polish patients with RRMS, characterized by high disease activity, delayed treatment initiation, and multiple number of prior therapies.

Introduction: Immune reconstitution therapies (IRT) are highly effective therapies for multiple sclerosis (MS). Among IRT, we can distinguish partially selective therapies such as cladribine in tablets (CLAD) and non-selective therapies, which include alemtuzumab (ALEM). Today, it is known that these therapies are effective in controlling the relapse activity of the disease and the progression of clinical disability, which has been proven both in clinical trials and in real world evidence (RWE). However, there is a lack of data assessing the effect of IRT on the neurodegenerative process, which is intensified in patients with MS. The aim of the study was to assess the effect of IRT treatment on the degree and pattern of brain atrophy in patients with MS during 3 years of observation.Methods: Patients with relapsing-remitting MS (RRMS) treated with CLAD and ALEM were retrospectively recruited for the study. Demographic, clinical, and magnetic resonance imaging (MRI) data were collected at 4 time points: before the treatment and one, two, and three years after the treatment. MRI examinations were analyzed volumetrically using Freesurfer software. Global and regional changes in atrophy were assessed by calculating percentage changes in volume between time points. Results of drug groups were compared with each other.Results: After 3 years of follow-up, statistically significant differences between groups were observed in hippocampus [p < 0.01] and amygdala volume changes [p < 0.01]. Ventral diencephalon atrophy was noted in both groups. On the other hand, in both groups, no significant atrophy of white and grey matter was noted. In addition, an increase in the thalamus volume was observed.Discussion: In the studied groups, IRT therapies were shown to slow down the atrophy process in MS patients to a similar extent. These therapies may play a neuroprotective role by increasing the volume of the thalamus and hippocampus. The study was limited by the small number of both groups. Therefore, further studies are needed to fully assess the effect of reconstitution therapies on neurodegenerative processes in patients with RRMS.

Introduction: The measurement of brain atrophy in patients with relapsing–remitting multiple sclerosis (RRMS) may be a marker of the disease activity. However, currently this method is not widely used in clinical practice. In the presented study, the relationship between lesions (T2) in magnetic resonance imaging (MRI), including contrast-enhancing (Gd+), clinical relapses and no evidence of disease activity (NEDA-3) with volumetric changes was investigated.Methods: Clinical and MRI data from RRMS patients treated with cladribine tablets (CLAD) and alemtuzumab (ALEM) were retrospectively analyzed at 4 time points (pretreatment and 3 years of follow-up). Volumetric data were obtained using the FreeSurfer. Annual volumetric changes and new T2/Gd + lesions were pooled together to assess short-term relationships, baseline T2/Gd + lesions were correlated with 3-year volume changes and years with NEDA-3 and without NEDA-3 were compared.Results: The study included 33 patients treated with CLAD and 19 patients treated with ALEM. In the year-to-year analysis (n_CLAD = 59, n_ALEM = 36) within the CLAD group, new T2 lesions were significantly associated with a decrease in thalamic (p = 0.02), cerebellum (p = 0.05) and deep grey matter (p = 0.05) volume. When analyzing the correlation between baseline T2 lesions and overall 3-year volume changes (N_CLAD = 9, N_ALEM = 7), in the CLAD group, strong associations were found with whole brain (p = 0.001, ꞵ = −0.89), cerebellum (p = 0.002, ꞵ = −0.20), cerebellar cortex (p = 0.003, ꞵ = −0.19) and DGM (p = 0.015, ꞵ = −0.04) atrophy, as well as with lateral ventricular volume increase (p = 0.00001, ꞵ = 0.1). A similar situation occurred when only the first year of treatment was analyzed (N_CLAD = 29, N_ALEM = 13). It was not observed in the ALEM group. Interestingly, no correlation was noted between Gd + lesions and volumetric changes. Remarkably, no statistically significant differences between years with and without relapses were observed. However, years without NEDA-3 (n = 31) were characterized by greater atrophy in white matter (p = 0.04), thalamus (p = 0.02), and putamen (p = 0.04).Conclusion: The results of the presented study suggested an association of increased brain atrophy with radiological activity rather than with relapsing disease activity. However, further studies with larger numbers of patients are needed to verify these associations more precisely.

Introduction. Prior research regarding multiple sclerosis (MS) has extensively examined the inflammatory processes, while the mechanisms of neurodegeneration, particularly cerebral atrophy, remain less understood. The purpose of this systematic review was to summarize the current knowledge about the degree and pattern of atrophy in various types of MS, and its relationship with the clinical progression of the disease and the impact of treatment on brain volume loss. Material and methods. A systematic review was performed in accordance with the PRISMA guidelines. Relevant articles published between 1 January 2018 and 1 July 2024 available in the PubMed and Cochrane Library databases were obtained using a systematic search strategy. The following keywords were used to screen the publications: ’multiple sclerosis’ and/or ’MS’ and ’atrophy’. The eligibility criteria that identified and described outcomes were pre-established by the authors. Studies constituting clinical research protocols, theoretical inspections, articles describing other measurement methods or comparing measuring methods, conference abstracts and articles in a language other than English were excluded. Results. Of the 1,911 records obtained from the systematic search based on keywords, 26 were included in the final review. Publications enabled the analysis of atrophy in patients compared to the healthy population, the evaluation of atrophy concerning different MS subtypes, its correlation with disability progression, the patterns of atrophy and the impact of disease-modifying therapies. Moreover, clinical trials involving atrophy measurements in MS patients were also collected. Discussion. This systematic review confirmed the role of assessing volumetric changes in brain regions as a useful tool in the diagnosis of MS, assessment of its progression, and response to treatment. Given the relatively small number of new reports in the last six years, it also indicated the need for further research, especially using atrophy to assess the efficacy of therapy. Keywords: multiple sclerosis atrophy pattern degree systematic review