Levels In Multiple Sclerosis Patients Research Articles

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.

BDNF AS A POTENTIAL BIOMARKER OF DISEASE ACTIVITY IN PATIENTS WITH MULTIPLE SCLEROSIS

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is expressed by immune cells directly in demyelinated areas of brain lesions in multiple sclerosis (MS). Also, BDNF plays an important role in the processes of neuroplasticity and prevents damage to axons and neurons after pathological lesions. In recent studies, more and more data are appearing on the possibility of using BDNF as a promising biomarker for the diagnosis of MS [1, 2, 3]. Determination of serum BDNF levels in MS patients may be an indicator of disease activity, which may allow early identification of patients with a more severe course of the disease.

Dysregulated autotaxin expression by T cells in multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease characterized by infiltration of autoreactive T cells into the central nervous system (CNS). In order to understand how activated, autoreactive T cells are able to cross the blood brain barrier, the unique molecular characteristics of pathogenic T cells need to be more thoroughly examined. In previous work, our laboratory found autotaxin (ATX) to be upregulated by activated autoreactive T cells in the mouse model of MS. ATX is a secreted glycoprotein that promotes T cell chemokinesis and transmigration through catalysis of lysophoshphatidic acid (LPA). ATX is elevated in the serum of MS patients during active disease phases, and we previously found that inhibiting ATX decreases severity of neurological deficits in the mouse model. In this study, ATX expression was found to be lower in MS patient immune cells during rest, but significantly increased during early activation in a manner not seen in healthy controls. The ribosomal binding protein HuR, which stabilizes ATX mRNA, was also increased in MS patients in a similar pattern to that of ATX, suggesting it may be helping regulate ATX levels after activation. The proinflammatory cytokine interleukin-23 (IL-23) was shown to induce prolonged ATX expression in MS patient Th1 and Th17 cells. Finally, through ChIP, re-ChIP analysis, we show that IL-23 may be signaling through pSTAT3/pSTAT4 heterodimers to induce expression of ATX. Taken together, these findings elucidate cell types that may be contributing to elevated serum ATX levels in MS patients and identify potential drivers of sustained expression in encephalitogenic T cells.

Immunological outcomes of autologous hematopoietic stem cell transplantation for multiple sclerosis: a systematic review.

Autologous hematopoietic stem cell transplantation (AHSCT) is an extensive procedure that allows for the depletion of the immune system and its restoration from hemopoietic stem cells. The approach has been modified for the treatment of severe immune-mediated illnesses, including multiple sclerosis (MS), after being initially devised for the treatment of hematological malignancies. This systematic review aims to determine and consolidate the information on the short-term and long-term immunological effects of AHSCT on the cellular level in MS patients. The PubMed, Scopus, and Web of Science servers were used to conduct a systematic search in compliance with the PRISMA guidelines. The results were tabulated and analyzed. A total of 17 studies (10 clinical trials, 6 cohort studies, and 1 case-control study) were included in the final analysis, and 383 MS patients were analyzed. A significant decline in the cell count of CD4 T cells was reported when compared to the CD8 T cells, B cells, and NK cells. B cell count returned to baseline in 71.4% of the studies at the end of 6 months. The NK cell count was found to be above the baseline in 62.5% of studies. AHSCT has been proven to be one of the most effective treatment modalities for MS in recent studies. However, debilitating complications due to immunological outcomes of the procedure have led to increased morbidity. Further research into this domain will help boost the success rate and efficacy of AHSCT.

Insulin-like growth factor-1 (IGF-1) levels in multiple sclerosis patients: A systematic review and meta-analysis.

Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

Role of Serum Zinc, Urinary Sodium and Urinary Uric Acid in Multiple Sclerosis in Egypt

Background Studies have suggested that zinc (Zn), sodium (Na) and uric acid (UA) have a role in multiple sclerosis (MS). Objectives Aim of study is to measure serum Zn, urinary Na and urinary UA levels in MS patients compared to healthy control (HC) subjects, and investigate the difference between the MS subtypes and correlate it with disease activity and disability. Patients and Methods It is a case control study was carried on 60 clinically definite MS patients, 30 Relapsing Remitting MS (RRMS) and 30 secondary progressive MS (SPMS), recruited from MS unit at Ain Shams University Hospitals, and 30 HC subjects. Results Regarding Zn level, there was no significance between MS and HC groups. However, significant higher level in SPMS group. There was significant higher Zn level in males of HC group only. Regarding Na level, there was significant higher level in MS group and higher level in SPMS group. There were positive correlations with duration of illness, number of relapses per year and EDSS. Regarding UA level, there was significant higher level in MS group and higher level in RRMS group. There was negative correlation with relapses rate. Conclusion The role of Zn level in MS is linked to disability, not its diagnosis nor its activity, due to its disturbed metabolism in CNS diseases. In addition, the role of Na level in MS is linked to higher disease activity and disability. However, the lower UA level in MS is linked to higher relapse rate, but its higher level may be a cause of disease or a consequence to effect of DMTs.

Efficacy of vitamin D in multiple sclerosis: a review

Introduction: Multiple sclerosis (MS) is a chronic, multifocal, inflammatory disease of the central nervous system (CNS) with an autoimmune basis. There is a strong correlation between vitamin D deficiency and the onset of multiple sclerosis and a more severe course of the disease and more severe comorbid symptoms. Many studies have investigated vitamin D supplementation to compensate for low 25(OH)D levels in MS patients. &#x0D; Methods of research: A literature review was conducted based on PubMed, Google Scholar databese. Articles were researched using following keywords: multiple sclerosis; vitamin D; multiple sclerosis prevention; vitamin D deficiency. &#x0D; The results: The results of these studies have provided important information on the safety and efficacy of vitamin D therapy in MS. Dietary vitamin D supplementation can therefore serve as a prevention of MS and as an adjunct to traditional MS therapy. However, it is important to emphasize the need to assess the risks and benefits individually for each patient.

A Comparison of Two Analytical Approaches for the Quantification of Neurofilament Light Chain, a Biomarker of Axonal Damage in Multiple Sclerosis.

Neurofilament light chain (NfL), is a neuron-specific cytoskeletal protein detected in extracellular fluid following axonal damage. Extensive research has focused on NfL quantification in CSF, establishing it as a prognostic biomarker of disability progression in Multiple Sclerosis (MS). Our study used a new commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit and Single Molecular Array (Simoa) advanced technology to assess serum NfL levels in MS patients and Healthy Controls (HC). Verifying the most accurate, cost-effective methodology will benefit its application in clinical settings. Blood samples were collected from 54 MS patients and 30 HC. Protocols accompanying the kits were followed. The ELISA thershold was set as 3 S.D. above the mean of the HC. For Simoa, the Z-score calculation created by Jens Kuhle's group was applied (with permission). Samples exceeding the threshold or z-score ≥1.5 indicated subclinical disease activity. To our knowledge, this is the first study to find strong-positive correlation between ELISA and Simoa for the quantification of NfL in serum (r = 0.919). Despite the strong correlation, Simoa has better analytical sensitivity and can detect small changes in samples making it valuable in clinical settings. Further research is required to evaluate whether serum NfL quantification using ELISA could be utilized to predict disability progression.

The CYP24A1 gene variant rs2762943 is associated with low serum 1,25-dihydroxyvitamin D levels in multiple sclerosis patients.

Vitamin D is considered to play a role in multiple sclerosis (MS) etiopathogenesis. A polymorphism in the CYP24A1 gene, rs2762943, was recently identified that was associated with an increased MS risk. CYP24A1 encodes a protein involved in the catabolism of the active form of vitamin D. The immunological effects of carrying the rs2762943 risk allele were investigated, as well as its role as genetic modifier. Serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D (1,25(OH)2 D) were measured in a cohort of 167 MS patients. In a subgroup of patients, expression levels of major histocompatibility complex class II and co-stimulatory molecules were determined by flow cytometry, and serum levels of pro-inflammatory (interferon gamma, granulocyte macrophage colony-stimulating factor, C-X-C motif chemokine ligand 13) and anti-inflammatory (interleukin 10) cytokines and neurofilament light chain were measured by single-molecule array assays. The effect of the rs2762943 polymorphism on disease activity and disability measures was evaluated in 340 MS patients. Compared to non-carriers, carriers of the rs2762943 risk allele were characterized by reduced levels of 1,25(OH)2 D (p = 0.0001) and elevated levels of interferon gamma (p = 0.03) and granulocyte macrophage colony-stimulating factor (p = 0.008), whereas no significant differences were observed for the other markers. The presence of the rs2762943 risk allele had no significant impact on disease activity and disability outcomes during follow-up. However, risk allele carriers were younger at disease onset (p = 0.04). These findings suggest that the CYP24A1 rs2762943 polymorphism plays a more important role in MS susceptibility than in disease prognosis and is associated with lower 1,25(OH)2 D levels and a heightened pro-inflammatory environment in MS patients.

Investigating the Effect of Cigarette Smoking on Serum Uric Acid Levels in Multiple Sclerosis Patients: A Cross Sectional Study.

The present study is aimed at determining the effect of cigarette smoking (CS) on serum uric acid (UA) levels quantitatively before and after smoking cessation among people with MS (pwMS). Additionally, a possible correlation between UA levels and both disability progression and disease severity was also investigated. A retrospective cross-sectional study was conducted using the Nottingham University Hospitals MS Clinics database. It involves 127 people with definite MS recorded when reporting the latest smoking status and the clinical diagnosis. All necessary demographics and clinical characteristics were collected. We found that smoker pwMS had significantly lower serum UA levels than non-smoker pwMS (p-value = 0.0475), and this reduction was recovered after smoking cessation (p-value = 0.0216). However, the levels of disability or disease severity were not correlated with the levels of serum UA in current smoker pwMS, measured by the expanded disability status scale (EDSS; r = -0.24; p-value = 0.38), multiple sclerosis impact scale 29 (MSIS-29; r = 0.01; p-value = 0.97) and MS severity score (MSSS; r = -0.16; p-value = 0.58), respectively. Our result suggests that the reduction in UA levels is more likely a consequence of oxidative stress triggered by many risk factors, including CS, and could be considered a potential indicator of smoking cessation. In addition, the absence of a correlation between UA levels and disease severity and disability suggests that UA is not an optimal biomarker for disease severity and disability prediction among current smoker, ex-smoker or non-smoker pwMS.

Prognostic significance of neurofilament light in Fingolimod therapy for Multiple Sclerosis: A systemic review and meta-analysis based on randomized control trials

This research was conducted to assess Neurofilament light chain (NfL) as prognostic factor for Multiple Sclerosis and effect of Fingolimod on plasma levels of NfL. A systemic search was conducted from electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to 7th September 2022. All statistical analyses were conducted in Review Manager 5.4.1. Studies meeting inclusion criteria were selected. Only those studies that involved Multiple sclerosis patients in which plasma levels of NfL was provided and Fingolimod was used in the treatment group. Fixed-effect model was used to pool the studies to assess NfL as prognostic factor, which was reported in the Hazards ratio (HR) and their corresponding 95% confidence interval (CI). Moreover, effect of Fingolimod on NfL levels was analysed qualitatively. Five Randomized Controlled Trials were used in the study. Four studies were used in quantitative analysis which showed increased NfL was related to significant increase in cognitive disability worsening (HR= 1.66 [1.35, 2.05]; p< 0.00001; I2= 0%). The qualitative analysis method was employed to evaluate the factors correlating with increased NfL levels in Multiple Sclerosis patients. Five studies evaluated that there was significant decrease in NfL levels when Fingolimod was used as compared to placebo. 4 studies were included to correlated NfL levels with clinical and MRI parameters and association was found between increasing NfL levels and relapses, active/new T2 lesions and percentage of brain volume change. The results of our meta-analysis and systematic review demonstrated statistically significant effect of NfL as a prognostic marker with its level being decreased significantly when Fingolimod was used for treating Multiple Sclerosis.

Lower cerebral arterial blood flow is associated with greater serum neurofilament light chain levels in multiple sclerosis patients

Background: Hypoperfusion, vascular pathology, and cardiovascular risk factors are associated with disease severity in multiple sclerosis (MS).1,2 In particular, the total cerebral arterial blood flow (CABF), measured as a sum of all arterial flow in the neck, was associated with the cognitive performance of MS patients.3&#x0D; Objective: To assess relationships between CABF and serum neurofilament light chain (sNfL), as neuronal damage biomarker with good prognostic value and treatment responsiveness.4 If the cerebrovascular changes are an independent pathophysiological factor in MS, a relationship should remain significant after controlling for common MS-based disease measures (i.e., T2 lesion volume and brain volume).&#x0D; Materials and methods: Total CABF was measured in 137 patients (86 clinically isolated syndrome (CIS)/relapsing-remitting (RR) and 51 progressive MS (PMS)) and 48 healthy controls (HCs) using Doppler ultrasound. sNfL was quantitated using a single molecule assay (Simoa). Three point zero T magnetic resonance imaging (MRI) examination allowed quantification of T2 lesion and whole-brain volume (WBV). Multiple linear regression models determined the sNfL associated with CABF after correction for demographic and MRI-derived variables.&#x0D; Results: After adjustment for age, sex and body mass index (BMI), total CABF remained statistically significant and model comparisons showed that CABF explained additional 2.6% of the sNfL variance (β=-0.167, p=0.044). (Table 1) CABF also remained significant in a step-wise regression model (β=0.18, p=0.034) upon the inclusion of T2 lesion burden and WBV effects. The explained sNfL variance improved from 17.4%, 22.7% with the presence of at least 2 CVD variable and 25.8% with both CVD and CABF predictors. Lastly, the disease-modifying therapy was not kept in the final model as an independent predictor of sNfL. Patients in the lowest CABF quartile (CABF≤761 mL/min) had significantly higher sNfL (34.6 pg/mL versus 23.9 pg/mL, adjusted-p=0.042) when compared to the highest quartile (CABF≥1130 mL/min).&#x0D; Conclusions: Lower CABF is associated with increased sNfL in MS patients, highlighting direct and independent relationship between cerebral hypoperfusion and axonal pathology. This relationship remained significant in the CIS/RRMS after adjusting for age, sex, and BMI effects.

Comparison of Serum Mitochondrial Open Reading Frame of the 12S rRNA-c (MOTS-c) Levels in Patients With Multiple Sclerosis and Healthy Controls.

BackgroundMultiple sclerosis (MS) is a major global problem, and as its pathogenesis is understood more clearly, therapeutic options expand accordingly. The mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a novel mitochondria-derived protein acting on metabolic homeostasis. In this study, we aimed to investigate the role of serum MOTS-c in the pathophysiology of the disease in MS patients and to discuss the mechanism of MOTS-c.MethodologyIn total, 43 patients diagnosed with relapsing-remitting MS and 41 healthy controls were enrolled in the study. MOTS-c, fasting blood glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipid panel, and body mass index levels were assessed.ResultsThe participants’ MOTS-c levels remained significantly lower than that of the control group, while their fasting blood glucose and HOMA-IR values were higher. The multivariate logistic regression analysis established that increased MOTS-c levels could be a protective factor against the development of MS disease. The area under the receiver operating characteristic curve for MOTS-c was calculated as 0.782 (95% confidence interval = 0.684-0.879, p = 0.0001).ConclusionsThis study is the first to scrutinize MOTS-c levels in MS patients. We tried to provide clinical evidence that MOTS-c could act as a highly discriminative biomarker between MS patients and control groups, which may hold great promise for future therapeutic options.

Investigation of serum adropin levels and its relationship with hypothalamic atrophy in patients with multiple sclerosis

ObjectiveAdropin is expressed in vascular endothelial cells and regulates nitric oxide (NO) bioavailability by upregulating nitric oxide. In recent years, some studies have revealed its relationship with the pathogenesis of multiple sclerosis (MS). Our aim in this study is to determine serum adropin levels in MS patients and to investigate adropin levels's relationship with hypothalamic atrophy. MethodsA total of 80 people, 40 of whom had MS and 40 of whom were healthy volunteers, were included in the study. Serum samples were taken from all participants. Hypothalamus and pituitary diameters were calculated from magnetic resonance imaging of MS patients. The relationship between serum adropin levels and demographic characteristics, Expanded Disability Status Scale (EDSS), and hypothalamic atrophy were evaluated. ResultsThe levels of adropin were 848,282±139,229 ng/L in patients with MS and 2957,108±284,034 ng/L in the healthy controls. MS patients had significantly lower levels of adropin than the healthy controls (p = 0.003). Adropin has the highest diagnostic value (AUC=0.874, (95% CI, 0,800–0,947) as cut-off value (838.00), sensitivity (80.43%) and specificity (70.64%) in the MS group. In the study, serum adropin levels were not significantly correlated with 3 ventricle diameter (3VD) and pituitary diameter (PD) size (p = 0,968) and no significant relationships were determined between adropin and other clinical parameters. ConclusionAs a potential diagnostic marker, adropin levels were significantly lower in MS patients than in those without. Comprehensive studies are needed to verify this entity.

Cytokine Profile in Patients with Multiple Sclerosis Following Exercise: A Systematic Review of Randomized Clinical Trials.

Multiple sclerosis (MS) is one of the most prevalent causes of nontraumatic neurological impairment in young adults. This review aims to determine the impact of exercise on cytokine and adipokine profile levels as inflammatory markers in MS patients across various exercise paradigms. We used specific keywords in PubMed, Web of Science, The Cochrane Library, and Scopus to find randomized clinical trials addressing the effects of physical activity and exercise training on inflammatory markers levels in MS patients. The majority of the research showed no considerable changes in IL-6 levels, while three studies reported declining levels after the intervention. Approximately half of the trials observed a change in TNF-α and IL-10 levels after exercise interventions, while the other half showed no meaningful changes. Other markers such as IL-17, IL-4, IL-12, adipokines, and BDNF showed fluctuations in levels. We found no universal agreement on the effects of different exercise training protocols on the serum level of inflammatory markers in patients with MS. More research is needed to fully identify the effects of exercise on cytokines in MS patients.

Investigation of serum adropin levels and its relationship with hypothalamic atrophy in patients with multiple sclerosis

Objective Adropin is expressed in vascular endothelial cells and regulates nitric oxide (NO) bioavailability by upregulating nitric oxide. In recent years, some studies have revealed its relationship with the pathogenesis of multiple sclerosis (MS). Our aim in this study is to determine serum adropin levels in MS patients and to investigate adropin levels's relationship with hypothalamic atrophy.Methods A total of 80 people, 40 of whom had MS and 40 of whom were healthy volunteers, were included in the study. Serum samples were taken from all participants. Hypothalamus and pituitary diameters were calculated from magnetic resonance imaging of MS patients. The relationship between serum adropin levels and demographic characteristics, Expanded Disability Status Scale (EDSS), and hypothalamic atrophy were evaluated.Results The levels of adropin were 0.85±0.14 ng/mL in patients with MS and 2.96 ng/mL±0.285 ng/mL in the healthy controls. MS patients had significantly lower levels of adropin than the healthy controls (p = 0.003). Adropin has the highest diagnostic value (AUC=0.874, (95% CI, 0,800–0,947) as cut-off value (838.00), sensitivity (80.43%) and specificity (70.64%) in the MS group. In the study, serum adropin levels were not significantly correlated with 3 ventricle diameter (3VD) and pituitary diameter (PD) size (p = 0,968) and no significant relationships were determined between adropin and other clinical parameters.Conclusion As a potential diagnostic marker, adropin levels were significantly lower in MS patients than in those without. Comprehensive studies are needed to verify this entity.

Lower cerebral arterial blood flow is associated with greater serum neurofilament light chain levels in multiple sclerosis patients.

Hypoperfusion, vascular pathology, and cardiovascular risk factors are associated with disease severity in multiple sclerosis (MS). We aimed to assess relationships between cerebral arterial blood flow (CABF) and serum neurofilament light chain (sNfL) as neuronal damage biomarkers. Total CABF was measured in 137 patients (86 with clinically isolated syndrome/relapsing-remitting (RR) MS and 51 with progressive MS [PMS]) and 48 healthy controls using Doppler ultrasonography. sNfL was quantitated using a single-molecule assay (Simoa). Examination using 3.0-T magnetic resonance imaging (MRI) allowed quantification of T2 lesions and whole-brain volume (WBV). Multiple linear regression models determined the sNfL association with CABF after correction for demographic and MRI-derived variables. After adjustment for age, sex and body mass index (BMI), total CABF remained statistically significant and model comparisons showed that CABF explained an additional 2.6% of the sNfL variance (β=-0.167, p=0.044). CABF also remained significant in a stepwise regression model (β=0.18, p=0.034) upon the inclusion of T2 lesion burden and WBV effects. Patients in the lowest CABF quartile (CABF≤761ml/min) had significantly higher sNfL levels (34.6 vs. 23.9pg/ml, age and BMI-adjusted-p=0.042) when compared to the highest quartile (CABF≥1130ml/min). Lower CABF is associated with increased sNfL in MS patients, highlighting the relationship between cerebral hypoperfusion and axonal pathology.

TSPO-PET-measurable Microglial Activation Associates with Serum 3-hydroxykynurenine Levels in Multiple Sclerosis Patients (P14-4.007)

TSPO-PET-measurable Microglial Activation Associates with Serum 3-hydroxykynurenine Levels in Multiple Sclerosis Patients (P14-4.007)

Lower Cerebral Arterial Blood Flow is Associated with Greater Serum Neurofilament Light Chain Levels in Multiple Sclerosis Patients (S19.006)

Lower Cerebral Arterial Blood Flow is Associated with Greater Serum Neurofilament Light Chain Levels in Multiple Sclerosis Patients (S19.006)

Nitrosative Stress Molecules in Multiple Sclerosis: A Meta-Analysis.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system of unknown etiology. As it is still a diagnosis of exclusion, there is an urgent need for biomarkers supporting its diagnosis. Increasing evidence suggests that nitrosative stress may play a pivotal role in the pathogenesis of MS. However, previous reports supporting the role of nitrosative stress molecules as disease biomarkers are inconsistent overall. We therefore systematically analyzed the existing literature to compare the serum and cerebrospinal fluid (CSF) levels of nitrite/nitrate in MS patients with those in patients with noninflammatory other neurological diseases (NIOND) and healthy controls (HC), respectively. We searched the PubMed database and included original articles investigating nitrite/nitrate levels in MS patients and NIOND patients or HC based on predefined selection criteria. Effect sizes were estimated by the standardized mean difference using a random effects model. Our results suggest that MS is associated with higher nitrite/nitrate levels within the CSF compared with patients with NIOND (SMD of 1.51; 95% CI: 0.72, 2.30; p = 0.0008). Likewise, nitrite/nitrate in the CSF of MS patients trends towards increased levels compared with those of HC but does not reach statistical significance (SMD of 3.35; 95% CI: −0.48, 7.19; p = 0.07). Measurement of nitrite/nitrate in the CSF might be a valuable tool facilitating the differentiation of MS and NIOND. Further studies with more homogeneous study criteria are needed to corroborate this hypothesis.