Intrathecal administration of mesenchymal stem cells in patients with adrenomyeloneuropathy.

Background and objectives: X-linked adrenomyeloneuropathy (AMN) is an inherited neurodegenerative disorder associated with mutations in the ABCD1 gene and the accumulation of very long-chain fatty acids (VLFCAs) in plasma and tissues. Currently, there is no effective treatment for AMN. We have aimed to evaluate the therapeutic effects of mesenchymal stem cell (MSC) transplantation in patients with AMN. Methods: This is a small cohort open-label study with patients with AMN diagnosed and treated at the University Hospital in Olsztyn, Poland. All patients met clinical, biochemical, MRI, and neuropsychological criteria for AMN. MSCs derived from Wharton jelly, 20 × 106 cells, were administered intrathecally three times every 2 months, and patients were followed up for an additional 3 months. The primary outcome measures included a blinded assessment of lower limb muscle strength with the Medical Research Council Manual Muscle Testing scale at baseline and on every month visits until the end of the study. Additional outcomes included measurements of the timed 25-feet walk (T25FW) and VLFCA serum ratio. Results: Three male patients with AMN with an age range of 26-37 years participated in this study. All patients experienced increased muscle strength in the lower limbs at the end of the study versus baseline. The power grade increased by 25-43% at the baseline. In addition, all patients showed an improvement trend in walking speed measured with the T25FW test. Treatment with MSCs in patients with AMN appeared to be safe and well tolerated. Discussion: The results of this study demonstrated that intrathecal administration of WJ-MSC improves motor symptoms in patients with AMN. The current findings lend support to the safety and feasibility of MSC therapy as a potentially viable treatment option for patients with AMN.

Analysis of seroconversion following COVID-19 vaccination among multiple sclerosis patients treated with disease-modifying therapies in Poland.

CLINICAL RATIONALE FOR THE STUDY: The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to control the pandemic and to protect people at risk for severe disease courses. Disease-modifying therapies (DMT) in multiple sclerosis (MS), whether immunomodulatory or immunosuppressive, may affect the immune response. Therefore, the question arose as to whether these vaccinations would be effective. AIM OF THE STUDY: We planned a study to assess the immune response to SARS-CoV-2 vaccines by type of therapy. MATERIAL AND METHODS: Participants were recruited from 14 Polish MS centres. The data was obtained by neurologists using a questionnaire. We collected data on 353 MS patients (269 females, 84 males) who received complete primary SARS-CoV-2 vaccination. All persons with MS (PwMS) were treated with disease-modifying therapies. RESULTS: 305 out of 353 PwMS (86.4%) were positive for IgG Abs against SARS-CoV-2 S domain S1 Ag after vaccination. A strong immune response was noted in 129 PwMS (36.5%). The rate of seroconversion after SARS-CoV-2 vaccination in PwMS who received immunomodulatory DMTs (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab) was 91.5%, in PwMS receiving immune reconstruction therapy (alemtuzumab, cladribine) was 92%, and in immunosuppressive DMTs (fingolimod, ocrelizumab), the seroconversion rate was 59%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study shows that, in PwMS receiving immunomodulatory therapy, the immune response to vaccination is generally excellent. Even in immunosuppressive patients, seroconversion is satisfactory.

Predicting Short- and Long-Term Functional Outcomes Based on Serum S100B Protein Levels in Patients with Ischemic Stroke.

BACKGROUND: Ischemic stroke is one of the leading causes of mortality and disability. The neuroimaging methods are the gold standard for diagnostics. Biomarkers of cerebral ischemia are considered to be potentially helpful in the determination of the etiology and prognosis of patients with ischemic stroke. AIM: This study aimed to investigate the usefulness of serum S100B protein levels as a short- and long-term prognostic factor in patients with ischemic stroke. STUDY DESIGN AND METHODS: The study group comprised 65 patients with ischemic stroke. S100B protein levels were measured by immunoenzymatic assay. Short-term functional outcome was determined by the NIHSS score on day 1 and the difference in the NIHSS scores between day 1 and day 9 (delta NIHSS). Long-term outcome was assessed by the modified Rankin Scale (MRS) at 3 months after the stroke. At the end of the study, patients were divided into groups based on the NIHSS score on day 9 (0-8 "good" and >8 "poor"), the delta NIHSS ("no improvement" ≤0 and >0 "improvement"), and the MRS ("good" 0-2 and >2 "poor"). Differences in S100B levels between groups were analyzed with the ROC curve to establish the optimal cut-off point for S100B. The odds ratio was calculated to determine the strength of association. Correlations between S100B levels at three time points and these variables were evaluated. RESULTS: We revealed a statistically significant correlation between S100B levels at each measurement point (<24 h, 24-48 H, 48-72 h) and the NIHSS score on day 9 (R Spearman 0.534, 0.631, and 0.517, respectively) and the MRS score after 3 months (R Spearman 0.620, 0.657, and 0.617, respectively). No statistically significant correlation was found between S100B levels and the delta NIHSS. Analysis of the ROC curve confirmed a high sensitivity and specificity for S100B. The calculated AUC for the NIHSS on day 9 were 90.2%, 95.0%, and 82.2%, respectively, and for the MRS, 83.5%, 83.4%, and 84.0%, respectively. After determining the S100B cut-off, the odds ratio for beneficial effect (NIHSS ≤ 8 at day 9 or MRS 0-2 after 3 months) was determined for each sampling point. CONCLUSION: S100B is a useful marker for predicting short- and long-term functional outcomes in patients with ischemic stroke.

Analysis of Side Effects Following Vaccination Against COVID-19 Among Individuals With Multiple Sclerosis Treated With DMTs in Poland.

Background and Objectives: Since vaccination against COVID-19 is available for over a year and the population of immunized individuals with autoimmune disorders is higher than several months before, an evaluation of safety and registered adverse events can be made. We conducted a large study of side effects following the COVID-19 vaccine among patients with multiple (MS) sclerosis treated with disease-modifying therapies (DMTs) and analyzed factors predisposing for particular adverse events. Methods: We gathered data of individuals with MS treated with DMTs from 19 Polish MS Centers, who reported at least one adverse event following COVID-19 vaccination. The information was obtained by neurologists using a questionnaire. The same questionnaire was used at all MS Centers. To assess the relevance of reported adverse events, we used Fisher's exact test, t-test, and U-Menn-Whutney test. Results: A total of 1,668 patients with MS and reports of adverse events after COVID-19 vaccination were finally included in the study. Besides one case marked as "red flag", all adverse events were classified as mild. Pain at the injection site was the most common adverse event, with a greater frequency after the first dose. Pain at the injection site was significantly more frequent after the first dose among individuals with a lower disability (EDSS ≤2). The reported adverse events following immunization did not differ over sex. According to age, pain at the injection site was more common among individuals between 30 and 40 years old, only after the first vaccination dose. None of the DMTs predisposed for particular side effects. Conclusions: According to our findings, vaccination against COVID-19 among patients with MS treated with DMTs is safe. Our study can contribute to reducing hesitancy toward vaccination among patients with MS.

Safety of Vaccines against SARS-CoV-2 among Polish Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies.

(1) Background: The present study aims to report the side effects of vaccination against coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) who were being treated with disease-modifying therapies (DMTs) in Poland. (2) Methods: The study included 2261 patients with MS who were being treated with DMTs, and who were vaccinated against COVID-19 in 16 Polish MS centers. The data collected were demographic information, specific MS characteristics, current DMTs, type of vaccine, side effects after vaccination, time of side-effect symptom onset and resolution, applied treatment, relapse occurrence, and incidence of COVID-19 after vaccination. The results were presented using maximum likelihood estimates of the odds ratio, t-test, Pearson's chi-squared test, Fisher's exact p, and logistic regression. The statistical analyses were performed using STATA 15 software. (3) Of the 2261 sampled patients, 1862 (82.4%) were vaccinated with nucleoside-modified messenger RNA (mRNA) vaccines. Mild symptoms after immunization, often after the first dose, were reported in 70.6% of individuals. Symptoms included arm pain (47.5% after the first dose and 38.7% after the second dose), fever/chills/flu-like symptoms (17.1% after the first dose and 20.5% after the second dose), and fatigue (10.3% after the first dose and 11.3% after the second dose). Only one individual presented with severe side effects (pro-thrombotic complications) after vaccination. None of the DMTs in the presented cohort were predisposed to the development of side effects. Nine patients (0.4%) had a SARS-CoV-2 infection confirmed despite vaccination. (4) Conclusions: Vaccination against SARS-CoV-2 is safe for people with MS who are being treated with DMTs. Most adverse events following vaccination are mild and the acute relapse incidence is low.

Symptoms after COVID-19 Infection in Individuals with Multiple Sclerosis in Poland.

(1) Background: To report and analyze the presence of residual symptoms after SARS-CoV-2 infection among Polish patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs). (2) Methods: The study included 426 individuals with MS treated with DMTs and confirmed SARS-CoV-2 infection from 12 Polish MS centers. The data were collected through to 31 May 2021. The information included demographics, specific MS characteristics, course of SARS-CoV-2 infection, and residual (general and neurological) symptoms lasting more than four and 12 weeks after the initial infection. The results were obtained using maximum likelihood estimates for odds ratio and logistic regression. (3) Results: A total of 44.84% patients with MS reported symptoms lasting between four and 12 weeks after the initial infection; 24.41% people had symptoms that resolved up to 12 weeks, and 20.42% patients had symptoms that lasted over 12 weeks. The most common symptoms were: fatigue, disturbance of concentration, attention, and memory, cognitive complaints, and headache. None of the DMTs were predisposed to the development of residual symptoms after the initial infection. A total of 11.97% of patients had relapse three months prior or after SARS-CoV-2 infection. (4) Conclusion: Almost half of individuals with MS treated with different DMTs had residual symptoms after SARS-CoV-2 infection. None of the DMTs raised the probability of developing post-acute COVID symptoms.

Therapeutic applicability of helminths in autoimmune diseases - literature overview.

This paper presents an overview of published studies conducted on helminths - parasites of the human gastrointestinal tract. Making use of their ability for immunomodulation may lead to the introduction of effective therapies for autoimmune diseases. This paper presents chronologically attempts to treat autoimmune diseases not only of the gastrointestinal tract, but also of the nervous and endocrine systems, which have been undertaken for decades. The overview of analysed reports demonstrates that as medical knowledge on the cells and mediators participating actively in inflammatory processes accumulates, clinical trials focus on ever more specific areas concerning the pathomechanisms of autoimmune diseases. The outcomes of clinical trials conducted both on animals and humans give reasons to assume that the modification of the human intestinal microflora may be the key to fighting against these diseases.