Assessment of serum inflammatory parameters in RRMS and SPMS patients.

OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) differ in their responses to treatment; therefore, the correct diagnosis of the particular type of MS is crucial, and biomarkers that can differentiate between the forms of MS need to be identified. The aim of this study was to compare the levels of inflammatory parameters in serum samples from patients with RRMS and SPMS. METHODS: The study group consisted of 60 patients with diagnosed MS. The patients were divided into RRMS and SPMS groups. In the RRMS patients, the usage of disease-modifying treatment was included in our analysis. The serum levels of inflammatory parameters were evaluated. RESULTS: The serum levels of BAFF, gp130 and osteopontin were significantly higher in SPMS patients than in RRMS patients. The serum levels of BAFF correlated with age in both RRMS and SPMS patients. The serum levels of MMP-2 were significantly higher in RRMS patients than in SPMS patients and correlated with the number of past relapses. The serum levels of IL-32 were significantly higher in RRMS treatment-naïve patients than in RRMS patients treated with disease-modifying therapy. DISCUSSION: Significant differences were found in BAFF, gp130, MMP-2 and osteopontin levels between RRMS and SPMS patients. Serum IL-32 levels were statistically lower in RRMS patients treated with disease-modifying therapy than in treatment-naïve patients.

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.

A comparison of serum inflammatory parameters in progressive forms of multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system. Primary progressive MS (PPMS) is diagnosed in approximately 10-15 % of MS patients. Disease-modifying therapies (DMT) are less effective in modifying the course of progressive types of MS. It seems that inflammatory processes differ in the MS subtypes. OBJECTIVES: The objective of this study was to assess differences in the inflammatory parameters between PPMS and other courses of MS. MATERIALS AND METHODS: A total of 84 subjects were included in the study. The study group was divided according to the course of MS into the following categories: PPMS (n = 24); SPMS-secondary progressive multiple sclerosis (n = 14); RRMS-relapsing-remitting multiple sclerosis (n = 46). PPMS patients were further divided into treated with ocrelizumab and treatment-naive groups. The concentrations of serum inflammatory parameters were evaluated. RESULTS: PPMS and SPMS significantly differed in the serum levels of sCD30, gp130, sIL-6R alpha, osteopontin, pentraxin-3 and sTNF-R1. The serum concentrations of IFN-alpha2, IL-10, IL-20, IL-29 and osteopontin significantly differed between PPMS and RRMS. The serum levels of BAFF, IL-19, IL-20, pentraxin-3, s-TNF-R1 and s-TNF-R2 significantly differed between PPMS treated with ocrelizumab and treatment-naive. CONCLUSION: Although inflammatory processes take part in the pathogenesis of all types of MS, they differ between MS courses. Serum inflammatory parameters seem to be promising biomarkers in helping to differentiate courses of MS, and in assessing reactions to DMT treatment. Further investigations on their usage are required.

Multiple sclerosis immunomodulatory therapies tested for effectiveness in COVID-19.

INTRODUCTION: The global pandemic of COVID-19 began in Wuhan, China in December 2019. Research into effective therapies has been conducted worldwide. Currently, there is no antiviral treatment and many patients develop a severe course of the disease, including severe respiratory failure. Due to similar pathomechanisms of inflammation in multiple sclerosis (MS) and COVID-19, immunomodulatory drugs that are registered for the treatment of MS are under study in the SARS-CoV-2 infection in clinical trials. MATERIALS AND METHODS: Using clinicaltrials.gov, we found information related to ongoing clinical studies on potential drugs for COVID-19 which are also used in MS therapy. The outcomes of several trials were published on pubmed.ncbi.nlm.nih.gov. RESULTS: There were 18 clinical trials evaluating the effectiveness and safety of interferon-ß, fingolimod, or leflunomide in COVID-19. Some trial outcomes available at pubmed.ncbi.nlm.nih.gov suggested an association of these drug treatments with improvements in signs and symptoms, and the disease course. CONCLUSION: The administration of immunomodulatory drugs in COVID-19 may result in potential beneficial effects probably associated with their anti-inflammatory and antiviral properties. Further research is warranted to confirm the long-term effects of immunomodulatory therapies in patients with COVID-19.

The course of COVID-19 infection in patients with multiple sclerosis-The experience of one center based on the population of Upper Silesia.

BACKGROUND: It is suspected that patients with multiple sclerosis (MS) are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to disability and immunotherapy. The relationship between MS and coronavirus disease 2019 (COVID-19) is uncertain. The aim of the study was to collect and analyze this relationship. METHODS: All MS patients of the Neurological Outpatient Clinic in Zabrze, Poland, were regularly questioned for the symptoms of COVID-19 and contact with an infected person. Patients that presented with COVID-19 symptoms or confirmed contact with an infected person were referred for the COVID-19 test. All patients with confirmed SARS-CoV-2 infection (n = 41) were included in the analysis. Medical records of the study group were analyzed. Patient condition was monitored in the outpatient clinic after recovery. In 26 subjects, additional examinations, including brain magnetic resonance imaging (MRI), electroneurography (ENG), electroencephalography (EEG), color duplex Doppler (CDD), visual evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs) and psychological assessment were performed following recovery. RESULTS: Only one patient required hospitalization during COVID-19 infection, whereas 87.80% of patients did not require treatment for COVID-19. In all patients, C-reactive protein (CRP) levels were below 10 mg/L. In 2.44% of patients, oxygen partial pressure was below 95%. In most MS patients, the results of further examinations after COVID-19 infection were similar to those prior to infection. Psychological assessment revealed that anxiety was found in 42.31% of patients. CONCLUSIONS: A mild course of COVID-19 in MS patients seems common despite disease-modifying drug treatment and disability. Self-isolation is recommended to reduce the number of infected patients. COVID-19 infection did not worsen the course of MS in most subjects. Patients with MS may require additional psychological support during the pandemic due to their susceptibility to anxiety.

Plasma Interleukin-33 level in relapsing-remitting multiple sclerosis. Is it negatively correlated with central nervous system lesions in patients with mild disability?

BACKGROUND: Cytokines and chemokines are undoubtedly involved in the pathogenesis of multiple sclerosis (MS). There are many reports that suggest a significant role for Interleukin-33 (IL-33) in the course of MS development, but it is not clear whether negative or positive. We therefore investigated plasma IL-33 levels in patients with relapsing-remitting MS (RRMS). METHODS: The study consisted of RRMS patients (n = 73) and healthy subjects (n = 54). Blood samples were taken from all and plasma IL-33 levels were then determined using an enzyme-linked immunosorbent assay method. Patients also underwent laboratory and imaging tests and their disability status was assessed. RESULTS: Plasma IL-33 levels were marginally significantly higher in patients with RRMS (p = 0.07). Higher IL-33 levels are significantly associated with higher age (p = 0.01). There was also a statistically significant negative correlation between plasma IL-33 levels and the number of high signal intensity lesions in T2-weighted MRI (p = 0.03). After dividing the number of lesions into groups < 9 and ≥ 9 T2-weighted lesions, the Student's t-test for unrelated variables showed a negative correlation, but not statistically significant (p = 0.22), while the Spearman's correlation showed a marginally significant correlation (p = 0.06) between IL-33 level and number of T2-weighted lesions. IL-33 was also shown to have a significant ability to differentiate RRMS patients from healthy subjects with a sensitivity of 99% and specificity of 70% (p = 0.00). CONCLUSIONS: Patients with RRMS have elevated plasma IL-33 levels. In RRMS patients with mild disability, high plasma levels of IL-33 may have neuroprotective effects potentially by stimulating remyelination and/or suppressing autoimmune inflammation and damage. Further studies on this matter on a larger number of patients are needed.

The Combined Effect of Neuromuscular Electrical Stimulation and Insulin Therapy on Glycated Hemoglobin Concentrations, Lipid Profiles and Hemodynamic Parameters in Patients with Type-2-Diabetes and Hemiplegia Related to Ischemic Stroke: A Pilot Study.

Type-2-diabetes mellitus (T2DM) is a global problem of medical, social and economic consequences. Physical activity is a vital therapy in patients with T2DM, but some of them cannot exercise for various reasons. The purpose of our pilot study was to determine whether a combination of neuromuscular electrostimulation (NMES) and insulin therapy could improve the management of T2DM patients with hemiplegia caused by an ischemic stroke. Fifteen immobile patients with T2DM on insulin therapy were enrolled in the study. NMES was applied to their lower limbs for 60 min, 5 days a week, over a period of 12 weeks. The intervention caused statistically significant reductions in the blood concentrations of glycated hemoglobin, total cholesterol and low-density cholesterol in the participants. Furthermore, systolic and diastolic blood pressure levels were significantly lower. More randomized clinical trials are needed to accurately measure the effect of NMES on T2DM treatment and to determine whether it can be an alternative for physical activity for immobile patients with T2DM.

Neurological symptoms as a clinical manifestation of coronavirus disease 2019: implications for internists.

Numerous experimental and clinical studies have proven that the new severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) has a tropism for the nervous system. The infection of the nervous system by SARS­CoV­2 can occur via the nasal route through trans­synaptic pathways. Coronaviruses can infect neurons and glial cells through angiotensin­converting enzyme 2 receptors or by endocytosis. The infection of the central nervous system accompanied by coronavirus disease 2019-related systemic inflammation leads to the impairment of the blood-brain barrier and triggers a neuroinflammatory response with reactive astrogliosis and microglial activation. In addition, brain stem cells are being damaged, which results in respiratory distress. Apart from typical symptoms of COVID­19 associated with the involvement of the respiratory system, neurological manifestations such as headache, dizziness, myalgia, anosmia, ageusia, encephalopathy, encephalitis, stroke, epileptic seizures, rhabdomyolysis, and Guillain-Barré syndrome are related to SARS­CoV­2 infection. In this review, we focused on the currently known neurological manifestations of COVID­19, which could be considered mainly in asymptomatic patients with COVID­19 and, if noted, may limit the transmission of coronavirus infection.

Evaluation of serum human epididymis protein 4 in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: So far, little is known about the properties of human epididymis protein 4 (HE4) in multiple sclerosis (MS). This type 4 glycoprotein belongs to a family of genes encoding proteins whose expression is associated with the process of spermatogenesis in the epididymis. The biological function of HE4 is not fully understood. Overexpression of HE4 has been found in several malignant tumors, particularly in ovarian cancer, as well as in mesothelioma, lung, endometrial, breast, and kidney cancers. OBJECTIVES: To evaluate serum HE4 in patients with relapsing-remitting multiple sclerosis (RRMS) as compared to healthy controls. MATERIAL AND METHODS: Fifty patients with RRMS undergoing first-line immunomodulatory treatment were enrolled in the prospective study. We analyzed correlations between serum HE4 levels and gender, age, disease duration, the Expanded Disability Status Scale (EDSS), annualized relapse rate (ARR), and magnetic resonance imaging (MRI) lesions. RESULTS: The patients from the study group had higher concentrations of HE4 than the subjects from the control group. Patients with EDSS > 2 had significantly higher concentrations of HE4. Positive correlations were found between HE4 concentrations and age as well as between HE4 concentrations and disease duration. No significant correlations were found between HE4 concentrations and EDSS or between HE4 concentrations and ARR. CONCLUSIONS: The results of the study indicate a novel aspect of the HE4 protein in the pathomechanisms of MS.

Assessment of the manifestations of atrial fibrillation in patients with acute cerebral stroke - a single-center study based on 998 patients.

Aim of the Study: Cardioembolic stroke accounts for approximately 15-25% of ischemic strokes and is characterized by a poor prognosis. Atrial fibrillation (AF) is more commonly diagnosed in the elderly.The aim of the study was the assessment of the manifestations of AF in patients hospitalized due to cerebral stroke, with particular attention paid to newly diagnosed AF.Methods: A retrospective analysis was performed on 998 cerebral stroke patients. The data were analyzed for sex, age, cerebral stroke risk factors, drugs, NIHSS, RANKIN scores and ECG recordings on admission and at discharge.Results: The mean age of disease onset was 73 ± 16 years. Women accounted for 50.8% of patients. AF prior to hospital admission was diagnosed in 20.1% of patients, while de novo AF in 26.3% of patients during hospitalization. Hypercholesterolemia, hypertriglyceridemia and smoking were more commonly reported in ischemic stroke patients without AF compared to patients with ischemic stroke and AF. Ischemic heart disease, more frequent deaths, and a worse prognosis were more frequently observed in patients with ischemic stroke and AF compared to patients without AF. The first manifestation of AF in 25% of stroke patients was related to the period of the first 10 days of hospitalization.Discussion: The above data should prompt neurologists, cardiologists and family doctors to try to detect AF as a risk factor for ischemic stroke which worsens patient prognosis, prolongs hospital stay and contributes to increase in mortality, especially when more effective drug treatment is currently possible.

Does the nutritional status of acute stroke patients affect the neurological status in the early post-stroke period?

According to recent reports, malnutrition may be associated with a worse prognosis in stroke patients. The aim of this study was to determine the nutritional status of stroke patients and its impact on neurological and functional status of patients in the early post-stroke period. Our prospective study included a total of 128 patients admitted to the Stroke Unit. The assessment was made in the patients within the first week after the onset of stroke symptoms. Groups of patients with abnormal body mass index (BMI <20kg/m2 or >25kg/m2) were compared to the group of normal BMI, serum albumin, total cholesterol, HDL and LDL levels were determined in each patient within 24h following admission. The analysis showed that the patients with lower levels of serum albumin and triglycerides had higher scores in the National Institutes of Health Stroke Scale (NIHSS) on admission. Patients with a higher risk of malnutrition, confirmed by the Subjective Global Assessment scale, had higher NIHSS scores. The study showed a positive relationship between the nutritional status and worse neurological status of patients in the early post-stroke period.Abbreviation: NIHSS; Rankin scale.

The viability and intestinal epithelial cell adhesion of probiotic strain combination--in vitro study.

To be effective, probiotic bacteria must exhibit a number of functional characteristics, including the resistance to gastric acidity and the ability to adhere to the intestinal epithelium. In this study, we examined in vitro the viability of lactic acid bacteria (LAB) combination after exposure to low pH, and the adhesion of LAB to Caco-2 cells during coincubation of 9 bacterial strains. To test bacterial viability, 6 commercially available products were incubated in 0.1 N HCl at pH 1.2 for 60 min. The greatest growth inhibition was noted for the non-capsulated product containing the Lactobacillus rhamnosus strain (log reduction of CFU = 6.4), and the best survival observed for the product containing 9 bacterial strains, equipped with a modern capsule made according to the Multi-Resistant Encapsulation technology (log reduction of CFU = 0.1). In the adhesion experiment, the combination of 9 bacterial strains was added to 17-day-old Caco-2 cell culture for 90 min. The greatest efficiency of adhesion was observed for the inoculum containing 5.5x10(8) CFU/mL/9.6 cm(2) of Caco-2 and the dose of probiotic bacteria of 190 cells per one Caco-2 cell. As a result, approximately 157 bacterial cells adhered to one Caco-2 cell. The results indicate that the combination of 9 bacterial strains in the examined product is characterized as highly adhesive.

Wernicke-Korsakoff syndrome in the course of thyrotoxicosis - a case report.

Wernicke-Korsakoff syndrome (also called Wernicke's encephalopathy) is a potentially fatal, neuropsychiatric syndrome caused most frequently by thiamine deficiency. The three classic symptoms found together are confusion, ataxia and eyeball manifestations. Memory disturbances can also be symptoms. Wernicke's encephalopathy mainly results from alcohol abuse, but also from malnutrition, cancer, chronic dialysis, thyrotoxicosis and, in well-founded cases, encephalopathy associated with autoimmune thyroid disease (EAATD). The coexistence of many factors makes a proper diagnosis difficult, delays appropriate treatment and consequently reduces the chance of complete recovery. We present the case of a 53 year-old female with Wernicke's encephalopathy caused by chronic malnutrition, surgical operation, as well as thyrotoxicosis. She received treatment with intravenous thiamine administration and also anti-thyroid treatment which caused satisfactory regression of her neurological symptoms.