CXCL12 Gene Polymorphisms and Serum Levels: Associations with Multiple Sclerosis Prevalence and Clinical Parameters in Lithuania.

Our study aimed to investigate the associations between CXCL12 rs1029153, rs1801157, and rs2297630 single-nucleotide polymorphisms (SNPs), CXCL12 protein levels, MS prevalence, and clinical parameters. This study included 250 individuals diagnosed with MS and 250 sex- and age-matched healthy control individuals from Lithuania. The SNPs were genotyped with real-time PCR-based assays. The CXCL12 protein concentration was evaluated in serum using the ELISA method. Of the studied CXCL12 SNPs, we found that the rs1801157 CT genotype in the males was associated with 2.3 times reduced MS odds when compared with the CC genotype according to the overdominant and codominant models (p = 0.011 and p = 0.012, respectively). There was a tendency, which did not reach adjusted statistical significance, for a lower CXCL12 protein concentration in the healthy individuals with the rs1801157 CT genotype (p = 0.028). Sensory symptoms were rarer in the women with the rs1801157 TT genotype (p = 0.004); however, this genotype was also associated with a shorter MS disease duration (p = 0.007). CXCL12 rs1801157 was associated with reduced odds of MS occurrence in the male individuals. In women, rs1801157 was associated with a sensory symptom prevalence.

Exploring the Spectrum of Visual Illusions and Other Minor Hallucinations in Patients with Parkinson's Disease in Lithuania.

Background and Objectives: Parkinson's disease (PD) is associated with various non-motor symptoms, including minor hallucinations, comprising visual illusions and presence and passage hallucinations. Despite their occurrence, even in newly diagnosed PD patients, data regarding the prevalence and characteristics of minor hallucinations, visual illusions in particular, remain limited. The aim of this study was to address this knowledge gap by assessing the prevalence of minor hallucinations in PD patients, with a focus on visual illusions. Materials and Methods: In this prospective pilot study, we enrolled 35 PD patients without dementia and 35 age- and gender-matched PD-unaffected individuals. Cognitive function was assessed using the Montreal Cognitive Assessment, clinical data were collected, and all subjects were assessed via questionnaires regarding 20 types of visual illusions and other minor hallucinations. Results: The prevalence of minor hallucinations was significantly higher among PD patients compared to controls (45.7% vs. 11.4%, p = 0.003). PD patients reported visual illusions and presence hallucinations more frequently than the controls (37.1% vs. 8.6% and 22.9% vs. 2.9%, p = 0.009 and p = 0.028, respectively), with no significant difference in passage hallucinations (20% vs. 8.6%, p = 0.306). In the PD group, the most frequently observed visual illusions were complex visual illusions, kinetopsia, and pelopsia; the latter was also the most common visual illusion in the control group. PD patients experiencing visual illusions were more likely to report presence hallucinations compared to patients without visual illusions (53.8% vs. 4.5%, p = 0.002); no significant differences in other clinical characteristics were found. Conclusions: Minor hallucinations are a common phenomenon among PD patients without dementia, with a higher prevalence than among healthy controls. Visual illusions are the most prevalent type of minor hallucinations, affecting more than a third of PD patients, with complex visual illusions, kinetopsia, and pelopsia being the most frequently reported types.

Pilot Study of the Total and Phosphorylated Tau Proteins in Early-Stage Multiple Sclerosis.

Background and Objectives: Recent findings suggest that neurodegeneration starts early in the course of multiple sclerosis (MS) and significantly contributes to the progression of patients' disability. Tau is a microtubule-binding protein that is known to play a role in the pathophysiology of many neurodegenerative disorders. Newly emerging data on tau protein-induced neurodegenerative processes and its possible involvement in MS suggest that it may be involved in the pathology of early-stage MS. Therefore, this study aimed to test this hypothesis in patients with newly diagnosed MS. Materials and Methods: Cerebrospinal fluid (CSF) was collected from 19 patients with newly diagnosed MS and 19 control subjects. All MS patients underwent neurological examination, lumbar punction, and brain magnetic resonance imaging (MRI). CSF concentrations of total and phosphorylated tau (phospho-tau-181) protein were measured using commercial enzyme-linked immunosorbent assay kits. Results: The total tau concentration was significantly higher in the CSF of MS patients compared to controls (141.67 pg/mL, IQR 77.79-189.17 and 68.77 pg/mL, IQR 31.24-109.17, p = 0.025). In MS patients, the total tau protein positively correlated with total CSF protein (r = 0.471, p = 0.048). Significantly higher total tau concentration was measured in MS patients with higher lesion load in brain MRI (≥9 versus <9 lesions; 168.33 pg/mL, IQR 111.67-222.32 and 73.33 pg/mL, IQR -32.13-139.29-, p = 0.021). The CSF concentration of phospho-tau-181 protein was below the detection limit in both MS and control subjects. Conclusions: The concentration of total tau protein level is elevated, whereas phospho-tau-181 is undetectable in the CSF of patients with early-stage MS.

Characteristics of the Manifestation of Multiple Sclerosis in Children in Lithuania.

Background and Objectives: Multiple sclerosis (MS) starts quite rarely in childhood, comprising just 3-10% of all diagnosed cases of MS population. The age of onset of the disease may be related to the initial phenotype and the prognosis of MS. The aim of the study is to assess the characteristics of the manifestation of MS in children. Materials and Methods: Two groups of patients were analyzed: those diagnosed with MS in childhood (0 < 18 years of age) and who developed MS in 2005-2021, and those diagnosed in adulthood (≥18 years old). The data were collected from the database of the Lithuanian University of Health Sciences Kauno Klinikos. Results: For the analysis, 105 patients were selected: 35 children (group A) and 70 adults (group B). At the onset of the disease, 62.9% of children and 70.0% of adults experienced visual disturbances (p > 0.05). Isolated symptoms were more common in children (65.7%) as compared to adults (28.6%), p < 0.001. Sensory disorders were more common in adults than in children (p < 0.001). Optic nerve and cerebral hemispheres were the most affected in group A (p < 0.05). During the first year after diagnosis, the median number of relapses in group A was higher (3, range 1-5) as compared to group B (1, range 1-2) (p < 0.001). Recovery time after a relapse was shorter in children as compared to adults (p < 0.001). Oligoclonal bands were found in 85.7% of children and in 98.6% of adults. Oligoclonal bands were less common in the childhood-onset than in the adult-onset group (p = 0.007). Conclusions: The initial symptoms of multiple sclerosis in pediatric patients usually appeared around the age of 16, with a similar frequency in boys and girls, and in most of the childhood cases the initial symptoms were limited to the dysfunction of a single part of the nervous system children usually started with visual disorders, while sensory, coordination and motor disorders were less common. The course of the disease in juvenile patients with MS was more aggressive in the first year as there were more relapses, but the functional impairment recovered faster as compared to adults.

Sonographic Phrenic Nerve Changes in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects both the upper and lower motor neurons in the nervous system, causing muscle weakness and severe disability. The progressive course of the disease reduces the functional capacity of the affected patients, limits daily activities, and leads to complete dependence on caregivers, ultimately resulting in a fatal outcome. Respiratory dysfunction mostly occurs later in the disease and is associated with a worse prognosis. Forty-six participants were included in our study, with 23 patients in the ALS group and 23 individuals in the control group. The ultrasound examination of the phrenic nerve (PN) was performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine with a linear 4-18 MHz transducer. Our study revealed that the phrenic nerve is significantly smaller on both sides in ALS patients compared to the control group (p < 0.001). Only one significant study on PN ultrasound in ALS, conducted in Japan, also showed significant results (p < 0.00001). These small studies are particularly promising, as they suggest that ultrasound findings could serve as an additional diagnostic tool for ALS.

Oligoclonal Band Status and Features of Radiological and Clinical Findings in Patients with Multiple Sclerosis in Lithuania.

Background and Objectives: Multiple sclerosis (MS) is a widely spread and debilitating disease with 2.8 million people worldwide currently affected. However, the exact pathogenesis of the disease and its progression remains incompletely understood. According to the revised McDonald criteria, cerebrospinal fluid oligoclonal bands (CSF OCBs) magnetic resonance imaging (MRI) results, in conjunction with clinical presentation, remain the gold standard of MS diagnostics. Therefore, this study aims to evaluate the association between CSF OCB status and features of radiological and clinical findings in patients with multiple sclerosis in Lithuania. Materials and Methods: The selection of 200 MS patients was performed in order to find associations between CSF OCB status, MRI data and various disease features. The data were acquired from outpatient records and a retrospective analysis was performed. Results: OCB positive patients were diagnosed with MS earlier and had spinal cord lesions more frequently than OCB negative patients. Patients with lesions in the corpus callosum had a greater increase in the Expanded Disability Status Scale (EDSS) score between their first and last visit. Patients with brainstem lesions had higher EDSS scores during their first and last visit. Even so, the progression of the EDSS score was not greater. The time between the first symptoms and diagnosis was shorter for patients who had juxtacortical lesions than patients who did not. Conclusions: CSF OCBs and MRI data remain irreplaceable tools when diagnosing multiple sclerosis as well as prognosing the development of the disease and disability.

GAD65 Antibody-Associated Epilepsy.

Autoimmune processes are an increasingly recognized cause of seizures. Antibodies against neuronal surface antigens are implicated in the development of acute symptomatic seizures secondary to autoimmune encephalitis, whereas antibodies against intracellular antigens (anti-glutamic acid decarboxylase (GAD) and onconeural antibodies) are found in cases of autoimmune-associated epilepsy (AAE). AAE is described as isolated drug-resistant epilepsy without any specific magnetic resonance imaging (MRI) or cerebrospinal fluid changes and with a very limited response to immunotherapy. We present a clinical case and a literature review on autoimmune-associated epilepsy to increase awareness of this disease and illustrate its complexity. This is a clinical case of a female with a history of refractory focal epilepsy. The patient had been given several trials of multiple antiepileptic drugs and their combinations without any clear effect. Multiple evaluations including brain MRI, PET, and interictal and ictal electroencephalograms were performed. An APE2 score was calculated with a result of 4 and, in the presence of anti-GAD65 antibodies in the serum, the diagnosis of AAE was confirmed. There was no effect after five sessions of plasma exchange; however, after a course of intravenous immunoglobulin, a positive but temporary clinical effect was noticed: anti-GAD65 levels initially decreased but rebounded to previous levels 6 months later.

Factors Related to the Progression of Clinically Isolated Syndrome to Multiple Sclerosis: A Retrospective Study in Lithuania.

Background and Objectives: Multiple sclerosis (MS) is a demyelinating disease which usually manifests as clinically isolated syndrome (CIS). Approximately 70% of patients with CIS progress to MS. Therefore, there is a pressing need to identify the most accurate predictive factors of CIS developing into MS, some of which could be a clear clinical phenotype of early MS as well as lesions in magnetic resonance imaging (MRI), pathological findings in cerebrospinal fluid (CSF) and evoked potentials (EP) tests. The problem is of outstanding importance since early MS diagnosis and treatment prevents long-term disability. The aim of our study is to analyze the factors that could influence the progression of CIS to MS. Materials and Methods: This study is a retrospective data analysis which included patients with their primary CIS diagnosis between 1st January 2015 and 1st January 2020. The prevalence and predictive value of clinical symptoms, MRI lesions, pathological CSF and EP findings were evaluated in accordance with the final diagnosis and compared between the sexes and age groups. Results: Out of 138 CIS patients, 49 (35.5%) patients progressed to MS. MS patients were more likely to have a diminished sense of vibration and proprioception (χ2 = 9.033, p = 0.003) as well as spinal cord MRI lesions (χ2 = 7.209, p = 0.007) in comparison with the non-MS group. Positive oligoclonal bands (OCBs) in CSF (χ2 = 34.859, p ≤ 0.001) and pathological brainstem auditory evoked potential (BAEP) test findings (χ2 = 10.924, p ≤ 0.001) were more prevalent in the MS group. Diminished sense of vibration and proprioception increased the risk for developing MS by 13 times (p = 0.028), whereas positive OCBs in CSF increased the risk by 100 times (p < 0.001). MS patients that were older than 50 years were more likely to exhibit positive Babinski's reflex (χ2 = 6.993, p = 0.03), decreased muscle strength (χ2 = 13.481, p = 0.001), ataxia (χ2 = 8.135, p = 0.017), and diminished sense of vibration and proprioception (χ2 = 7.918, p = 0.019) in comparison with both younger age groups. Conclusions: Diminished sense of vibration and proprioception, spinal cord MRI lesions, positive OCBs and pathological BAEP test findings were more common among patients that developed MS. Diminished sense of vibration and proprioception along with positive CSF OCBs are predictors of CIS progressing to MS. Older patients that develop MS have more symptoms in general, such as positive Babinski's reflex, decreased muscle strength, ataxia, and diminished sense of vibration and proprioception.

Pain Characteristics and Associations with Quality of Life in Patients with Multiple Sclerosis in Lithuania.

BACKGROUND AND OBJECTIVES: Even though pain in multiple sclerosis (MS) patients is common and possibly associated with reduced quality of life, its exact prevalence and characteristics remain vaguely understood. We aimed to estimate the true extent of pain and its associations with quality of life in Lithuanian MS patients and to compare this data with that of a control group. MATERIALS AND METHODS: Data were collected prospectively at the Department of Neurology, Lithuanian University of Health Sciences Kaunas Clinics. A face-to-face structured interview and a questionnaire were used to collect demographic and clinical data of the MS (n = 120) and control (n = 120) groups. The Expanded Disability Status Scale (EDSS) was used to quantify disability in the MS group. Scores ≥4/10 in the Douleur Neuropathique 4 questionnaire were classified as neuropathic pain. Patients were evaluated using the anxiety and depression subsets of the Hospital Anxiety and Depression Scale (HADS-A and HADS-D), the physical and mental component subsets of the Short Form-12 questionnaire (PSC-12 and MSC-12). RESULTS: The MS and control groups did not differ in pain prevalence (76.7% vs. 65.9%, p = 0.064) or intensity. Lhermitte sign, lower limb, and face pain were more common in the MS group, whereas subjects in the control group were more often affected by lower back, neck, and joint pain. Neuropathic pain and pain lasting longer than 2 years were more common among pain-affected MS patients than among controls. MS patients with pain had higher EDSS, HADS-D, and HADS-A and lower PSC-12 scores than those without pain; however, no difference was found regarding the duration of MS or age. Males with MS and pain had higher MSC-12 and HADS-D scores in comparison to the same subset of females. CONCLUSIONS: Pain affects approximately three out of four patients with MS in Lithuania and is negatively associated with the mental and physical aspects of quality of life.

Absolute blood eosinophil count could be a potential biomarker for predicting haemorrhagic transformation after intravenous thrombolysis for acute ischaemic stroke.

BACKGROUND: Immune cells are involved in all stages of acute ischaemic stroke (AIS) and possess both neuroprotective and neurodamaging properties. It has been suggested that immune system activation after stroke may be associated with the development of haemorrhagic transformation (HT), which is the main complication limiting the clinical use of intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) for AIS. The purpose of our study was to analyse the association between absolute eosinophil count (AEC) at admission and the occurrence of HT after intravenous rtPA therapy for AIS. METHODS: In this retrospective study we enrolled AIS patients who were treated with rtPA within 4.5 h of symptom onset. Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Patients underwent head computed tomography scans at admission which were repeated 24 h after treatment with rtPA or promptly in case of clinical deterioration. HT was defined as blood at any site in the brain on follow-up head computed tomography scans. Spearman's rank correlation test was used to analyse the correlation between AEC and NIHSS scores. The optimal AEC cut-off value for predicting HT was calculated using the area under the receiver operating characteristic curve. Multiple logistic regression was used to determine the association between AEC included as a binary variable and the incidence of HT. RESULTS: The data of 201 patients was analysed (59.7% females; median age 77 years); 23 (11.4%) of them developed HT. The median of AEC was 62.5% greater in the non-HT group compared to the HT group (0.13 ×  109/l and 0.08 × 109/l, respectively, p = 0.026). No correlation was found between AEC and baseline NIHSS scores (r = 0.061, p = 0.393). AEC ≥ 0.11 × 109/l predicted the occurrence of HT with 69.6% sensitivity and 60.7% specificity. AEC ≥ 0.11 × 109/l was independently associated with a 78% reduction in the odds of developing HT (adjusted odds ratio = 0.223, 95% confidence interval = 0.069-0.723, p = 0.012). CONCLUSION: Higher values of AEC were associated with lower odds of developing HT, thus, AEC at admission could be considered an independent predictive marker of HT after treatment with rtPA for AIS.

The Effect of Three Different Strategies Based on Motor Task Performance on Neuromuscular Fatigue in Healthy Men and Men with Multiple Sclerosis.

Background and objectives: Fatigue during physical activity occurs because of decreased neuromuscular function. The aim of this study was to evaluate the effect of three different strategies based on motor task performance on neuromuscular fatigue in healthy men and men with multiple sclerosis (MS). Materials and Methods: We studied age-matched (18⁻43 years of age) healthy men (n = 15) and men with MS (n = 9). The inclusion criteria for MS subjects were a Kurtzke Expanded Disability Status Score <4 and a Fatigue Severity Scale Score >5. Both groups performed one of three exercise trials (with at least a 1-week interval between them) of 100 intermittent isometric knee extensions with flexion of 60°. The three different experimental conditions (ECs) were intermittent isometric contraction tasks with constant, predictable, and unpredictable torque target sequences. The variation of maximal voluntary contraction contractions (MVCs) within the strategies was 25%, 50%, and 75%, with a set average of 50%. All of them had a 5 s contraction and a 20 s rest period. The variables were measured: before exercise, after 100 repetitions (100-Reps), and 1 h after exercise. Results: In all EC tasks, the central activation ratio values of healthy and MS subjects were significantly different; however, no significant differences were observed among the EC tasks. No significant differences were seen in electrically induced torque, MVC torque, muscle temperature, subjective sensation of effort, coefficient of variation, or constant and absolute error after 100-Reps and 1 h after exercise between the two groups and in all EC tasks. Conclusions: Men with MS experienced higher central motor fatigue than did healthy men, but this had no effect on the variability, accuracy, or force sensation of the movements performed.

Characteristics of headache in relation to the manifestation of Susac syndrome.

Susac syndrome is characterized by a clinical triad of encephalopathy, branch retinal artery occlusion, and hearing loss. Due to the absence of the whole complex of the triad in the majority of cases at disease presentation, the syndrome often remains underdiagnosed and untreated. Headache is estimated to affect up to 80% of Susac syndrome patients, but the relevance of headache characteristics and profile is not yet clear. The proposed diagnostic criteria of the European Susac Consortium acknowledge headache as a possible brain manifestation if it is new, described as migrainous or oppressive, and precedes the other symptoms by not more than 6 months. Herein, a case series of different migraine-like headache associations attributed to Susac syndrome is presented and discussed in relevance with previously published literature. Our patients experienced different presentations of migraine-like headache related with Susac syndrome: exacerbation and chronification of headache just before the manifestation of the first symptoms of Susac syndrome, the manifestation of headache during the first episode of the syndrome, and an increasing frequency of headache during the course of the disease. The diagnosis of Susac syndrome in all three cases was confirmed by typical clinical symptoms and findings in retinal fluorescein angiography, audiometry, and brain magnetic resonance imaging, based on the diagnostic criteria of the European Susac Consortium. Based on the analysis of our presented cases, we conclude that headache attributed to Susac's syndrome is of migraine-like type but could be of different presentations in relation to the onset of the syndrome.

Sporadic Creutzfeldt-Jakob disease with unusual initial presentation as posterior reversible encephalopathy syndrome: a case report.

BACKGROUND: Creutzfeldt - Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative prion disease. MRI findings are included in diagnostic criteria for probable CJD, giving a sensitivity and specificity more than 90%, but the atypical radiological presentations in the early stage of the disease could cause the diagnostic difficulties. CJD can be definitively diagnosed by histopathological confirmation, brain biopsy or at autopsy. CASE PRESENTATION: We present a case of 53-year-old woman with a history of a rapidly progressive dementia with symptoms of visual impairment, increased extrapyramidal type muscle tonus, stereotypical movements and ataxic gait resulting in the patient's death after13 months. The clinical symptoms deteriorated progressively to myoclonus and akinetic mutism already on the 14th week. The series of diagnostic examinations were done to exclude the possible causes of dementia. Initial MRI evaluation as posterior reversible encephalopathy syndrome (PRES) on the 9th week after the onset of symptoms created us a diagnostic conundrum. Subsequent MRI findings of symmetrical lesions in the basal ganglia (nucleus caudatus, putamen) on the 13th week and EEG with periodic sharp wave complexes (PSWC) in frontal regions on the 18th week allowed us to diagnose the probable sCJD. The histopathological findings after brain biopsy on the 14th week demonstrated the presence of the abnormal prion protein deposits in the grey matter by immunohistochemistry with ICSM35, KG9 and 12 F10 antibodies and confirmed the diagnosis of sCJD. CONCLUSIONS: In this article we focus our attention on a rare association between radiological PRES syndrome and early clinical stage of sCJD. Although concurrent manifestation of these conditions can be accidental, but the immunogenic or neuropeptide mechanisms could explain such radiological MRI findings. A thorough knowledge of differential diagnostic of PRES may be especially useful in earlier diagnosis of sCJD.

Associations of HLA DRB1 alleles with IgG oligoclonal bands and their influence on multiple sclerosis course and disability status.

BACKGROUND AND AIM: Oligoclonal bands (OCB) may be associated with the genes of HLA complex, which allows to consider the possible interaction of genetic and immunological factors and its importance in the development and progression of multiple sclerosis (MS). The aim of this study was to evaluate the associations between HLA DRB1 alleles and oligoclonal bands (OCBs) in the disease course and disability of multiple sclerosis (MS) patients. MATERIALS AND METHODS: This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. Matched cerebrospinal fluid (CSF) and plasma samples were analyzed using isoelectric focusing and IgG specific immunofixation to test for the presence of intrathecal specific OCB. RESULTS: HLA DRB1*08 allele was related to a lower degree of disability. Oligoclonal bands were an independent and significant factor that influenced disability status irrespective of HLA DRB1* 04, *07, *08, *13, *15 and *16 alleles. Age at the onset and duration of the disease were independent and significant factors for MS progression in all logistic regression models with each newly added HLA DRB1 allele. HLA DRB1*08 allele was related to 75% lower odds that relapsing remitting (RR) MS will change to a progressive course MS irrespective of the other factors investigated. Detection of OCBs in the CSF was associated with the higher possibility of RR MS progression in all cases, except when the *08 allele was present. CONCLUSIONS: OCBs had an influence on disability status, while HLA DRB1*08 allele was significantly associated with lower possibility that RR MS will change to progressive course MS.

Reliability and validity of the Lithuanian Tinnitus Handicap Inventory.

OBJECTIVE: The aim of this study was to determine the reliability and validity of the Lithuanian version of the Tinnitus Handicap Inventory (THI), a self-report measure of perceived tinnitus handicap. MATERIALS AND METHODS: A cross-sectional psychometric validation study was performed in the University Hospital. A total of 248 subjects reporting chronic tinnitus as their primary complaint or secondary to hearing loss were encluded in the study and filled in the Lithuanian version of THI. For assessment of construct validity a subgroup of 55 participants completed the Lithuanian version of the Hospital Anxiety and Depression Scale as a measure of self-perceived levels of anxiety and depression. Test-retest and internal consistency reliability as well as construct validity were calculated. RESULTS: The Lithuanian version of the THI and its subscales showed a robust internal consistency reliability (Cronbach's alpha=0.93) comparable to the original version. Statistically significant correlations were observed between the Lithuanian translation of the THI and the measures of self-perceived levels of anxiety and depression using HADS. Confirmatory factor analysis demonstrated that the three subscales of the THI Lithuanian version corresponded to three different factors, which strongly correlated between themselves. CONCLUSIONS: The results suggest that the Lithuanian version of THI maintains its original validity and may serve as reliable and valid measure of general tinnitus related distress that can be used in a clinical setting to quantify the impact of tinnitus on daily living.

TNF-alfa Gene Polymorphism Associations with Multiple Sclerosis.

Background:TNF-α has a dual role in multiple sclerosis (MS), contributing to both protective and harmful effects. It activates immune cells, promotes the formation of inflammatory lesions in the central nervous system, and stimulates the production of other pro-inflammatory cytokines and chemokines, leading to myelin destruction and neuronal damage. Our research focused on investigating the relationship between TNF-alpha (rs1800630, rs1800629, and rs361525) gene polymorphisms and MS. Methods: 250 healthy controls and 250 multiple sclerosis (MS) patients were included in the study. DNA was extracted from leucocytes from peripheral venous blood by salt precipitation. Single nucleotide polymorphisms (SNPs) were tested using RT-PCR. Statistical analysis of the data was performed using IBM SPSS Statistics 29.0 data analysis software. Results: The analysis revealed that the rs361525 AG genotype was significantly less frequent in the MS group compared to the control group (4.0% vs. 7.2%, p = 0.042). Sex-specific analysis showed a significant difference in genotype distribution (GG, AG, AA) among males between the MS group and the control group (97.7%, 0%, 2.3% vs. 90.6%, 9.4%, 0%, p = 0.005). For the rs1800629 polymorphism, significant results were also found. In subjects younger than 39 years, the A allele was significantly less frequent in the MS group than in the control group (8.6% vs. 15.0%, p = 0.030). The most robust model indicated that the AA genotype reduced the odds of MS by approximately 2 fold compared to the AG + GG genotype (p = 0.044), and each A allele reduced the odds of MS by approximately 2 fold (p = 0.028). The rs1800630 A allele was significantly more common in males in the MS group than in the control group (21.0% vs. 12.9%, p = 0.046). Conclusions: In conclusion, our study identifies significant associations between TNF-alpha gene variants and MS. Specifically, the rs631525 AG genotype was less common in the MS group, with notable sex-specific differences observed. The rs1800629 A allele was statistically significantly less frequent in the MS group than in the control group, and the AA genotype reduced the odds of MS occurrence by ~2 fold compared with the AG + GG genotypes. Additionally, each A allele of rs1800629 was linked to a 2-fold decreased odds of MS occurrence. In males, the rs1800630 A allele was more frequent in the MS group. These findings highlight the relevance of TNF-alpha genetic variations in MS susceptibility, suggesting potential avenues for further research and therapeutic exploration.

Investigating the Potential Influence of TAS2R16 Genetic Variants and Protein Levels on Multiple Sclerosis Development.

The study aimed to investigate the association between the TAS2R16 gene (rs860170, rs978739, rs1357949), TAS2R16 serum levels, and multiple sclerosis (MS). A total of 265 healthy control subjects and 218 MS patients were included in the study. Single nucleotide polymorphisms (SNPs) were tested by real-time polymerase chain reaction (RT-PCR). The serum concentration of TAS2R16 was measured using the ELISA method. Analyses revealed that the TAS2R16 rs860170 TT genotype was statistically significantly less frequent in the MS group than in the control group (p = 0.041), and the CC genotype was statistically significantly more frequent in the MS group than in the control group (p < 0.001). In the most robust (codominant) model, the CC genotype was found to increase the odds of MS by ~27-fold (p = 0.002), and each C allele increased the odds of MS by 1.8-fold (p < 0.001). Haplotype analysis of the rs860170, rs978739, and rs1357949 polymorphisms showed that the C-C-A haplotype was associated with a ~12-fold increased odds of MS occurrence (p = 0.02). Serum TAS2R16 levels were elevated in the MS group compared to control subjects (p = 0.014). Conclusions: The rs860170, rs978739, and rs1357949 polymorphisms demonstrated that the C-C-A haplotype and elevated TAS2R16 serum levels can promote the development of MS. These preliminary findings underscore the importance of specific genetic variants, such as rs860170, rs978739, and rs1357949, in MS risk. Additionally, elevated TAS2R16 serum levels in MS patients suggest a potential role in MS pathogenesis. These findings provide insights into the genetic and molecular mechanisms underlying MS and pave the way for personalized diagnostic and therapeutic strategies. Integrating genetic and serum biomarker data in MS research offers promising avenues for improving clinical outcomes and advancing precision medicine approaches in the future.

Influence of STAT4 Genetic Variants and Serum Levels on Multiple Sclerosis Occurrence in the Lithuanian Population.

Background: Multiple sclerosis (MS) is an autoimmune disease involving demyelination, inflammation, gliosis, and the loss of neurons. MS is a growing global health problem most likely caused by genetic, immunological, and environmental factors. However, the exact etiology of the disease is still unknown. Since MS is related to a dysregulation of the immune system, it could be linked to signal transducer and activator of transcription 4 (STAT4). To fully comprehend the significance of the STAT4 gene and STAT4 serum levels in MS, further research is required. Methods: A total of 200 MS patients and 200 healthy controls participated in the study. Deoxyribonucleic acid (DNA) was extracted using silica-based membrane technology. Polymerase chain reaction was used in real time for genotyping. Using the ELISA technique, serum levels were measured. Results:STAT4 rs7601754 AA genotype and the A allele were statistically significantly less frequent in MS patients (p = 0.003). Also, rs7601754 was associated with 1.9-fold increased odds of MS occurrence (p = 0.004). The rs7601754 AG genotype was more common in males with MS (p = 0.011) and was associated with 2.5-fold increased odds of MS occurrence in males (p = 0.012). STAT4 serum levels were statistically significantly lower in MS patients compared to the control group (p = 0.007). Conclusions:STAT4 rs7601754 increases the odds of MS occurrence. STAT4 serum levels were statistically significantly lower in MS patients compared to the control group.

The importance of HLA DRB1 gene allele to clinical features and disability in patients with multiple sclerosis in Lithuania.

BACKGROUND: The association of HLA DRB1 alleles with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical features and disability is still unclear probably due to diversity in ethnicity and geographic location of the studied populations. The aim of the present study was to investigate the influence of HLA DRB1 alleles on the clinical features and disability of the patients with MS in Lithuania. METHODS: This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. RESULTS: The first symptoms of MS in patients with HLA DRB1*15 allele manifested at younger age than in those without this allele (28.32 +/- 5.49 yrs vs. 30.94 +/- 8.43 yrs, respectively, p = 0.043). HLA DRB1*08 allele was more prevalent among relapsing-remitting (RR) MS patients than among patients with progressive course of MS (25.0% vs. 8.3%, respectively, chi^2 = 6.000, p = 0.05). MS patients with this allele had lower relapse rate than those without this allele (1.00 +/- 0.97 and 1.44 +/- 0.85, respectively, p = 0.043). Degree of disability during the last visit was lower among the patients with HLA DRB1*08 allele (EDSS score 3.15 +/- 1.95 vs. 4.49 +/- 1.96, p = 0.006), and higher among those with HLA DRB1*15 allele (EDSS score 4.60 +/- 2.10 vs.4.05 +/- 1.94, p = 0.047) compared to patients without these alleles but there were no significant associations between these alleles and the duration of the disease to disability. HLA DRB1*08 allele (OR = 0.18, 95% CI 0,039-0,8, p = 0.029) was demonstradet to be independent factor to take a longer time to reach an EDSS of 6, while HLA DRB1*01 allele (OR = 5.92, 95% CI 1,30-26,8, p = 0.021) was related in a shorter time to reach and EDSS of 6. Patients with HLA DRB1*08 allele had lower IgG index compared to patients without this allele (0.58 +/- 0.17 and 0.73 +/- 0.31, respectively, p = 0.04), and HLA DRB1*15 allele was more often found among MS patients with oligoclonal bands (OCBs) in cerebrospinal fluid than among those without OCBs (OR 2.3, CI 95% 1.017-5.301; p = 0.043). CONCLUSIONS: HLA DRB1*15 allele was related with an earlier manifestation of the first MS symptoms, progressive course of the disease and higher degree of disability. HLA DRB1*08 allele was more prevalent among the RR MS patients and was associated with the lower rate of relapse, degree of disability and IgG index.

The Influence of TEP1 and TERC Genetic Variants on the Susceptibility to Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. According to recent studies, cellular senescence caused by telomere shortening may contribute to the development of MS. AIM OF THE STUDY: Our aim was to determine the associations of TEP1 rs1760904, rs1713418, TERC rs12696304, rs35073794 gene polymorphisms with the occurrence of MS. METHODS: The study included 200 patients with MS and 230 healthy controls. Genotyping of TEP1 rs1760904, rs1713418 and TERC rs12696304, rs35073794 was performed using RT-PCR. The obtained data were analysed using the program "IBM SPSS Statistics 29.0". Haplotype analysis was performed using the online program "SNPStats". RESULTS: The TERC rs12696304 G allele of this SNP is associated with 1.4-fold lower odds of developing MS (p = 0.035). TERC rs35073794 is associated with approximately 2.4-fold reduced odds of MS occurrence in the codominant, dominant, overdominant, and additive models (p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). Haplotype analysis shows that the rs1760904-G-rs1713418-A haplotype is statistically significantly associated with 1.75-fold increased odds of developing MS (p = 0.006). The rs12696304-C-rs35073794-A haplotype is statistically significantly associated with twofold decreased odds of developing MS (p = 0.008). In addition, the rs12696304-G-rs35073794-A haplotype was found to be statistically significantly associated with 5.3-fold decreased odds of developing MS (p < 0.001). CONCLUSION: The current evidence may suggest a protective role of TERC SNP in the occurrence of MS, while TEP1 has the opposite effect.