Relapsing-remitting Multiple Sclerosis Group Research Articles

Can Selected Parameters of Brain Injury Reflect Neuronal Damage in Smoldering Multiple Sclerosis?

Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neurodegeneration and disease progression. A single-center prospective observational study was performed. The median age of the patients was 40 (31-52) years. Women comprised 64% of the study population. We evaluated the concentrations of the parameters of brain injury (NF-H, GFAP, S100B and UCHL1) in the cerebrospinal fluid (CSF) and the selected interleukins (ILs) in serum of 123 relapsing-remitting MS (RRMS) and 88 progressive MS (PMS) patients. The levels of GFAP, S100B and UCHL were higher in the PMS group than the RRMS group, in contrast to the levels of NF-H. We observed a positive correlation between the selected pro-inflammatory cytokines and the parameters of brain injury. The Expanded Disability Status Scale (EDSS) score increased with GFAP and NF-H levels and was correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.

The multidimensional assessment of body representation and interoception in multiple sclerosis

BackgroundThe mental representation of the body (or body representation, BR) derives from the processing of multiple sensory and motor inputs and plays a crucial role in guiding our actions and in how we perceive our body. Fundamental inputs for BR construction come also from the interoceptive systems which refer to the whole bidirectional processes between the brain and the body. People with Multiple sclerosis (MS) show an abnormal multisensory integration which may compromise BR and interoception integrity. However, no study has evaluated possible deficits on distinct and dissociable dimensions of body representation (i.e., action-oriented, aBR; and a nonaction-oriented body representation, NaBR) and interoception (i.e., interoceptive accuracy, interoceptive sensibility, and interoceptive awareness) in MS. ObjectiveIn the present study, we aimed to determine whether participants with MS present changes in BR and interoceptive dimensions. MethodsWe performed comparison analyses on tasks and questionnaires tapping all BR and interoceptive dimensions between 36 people with relapsing-remitting MS (RRMS) and 42 healthy controls, and between 23 people with progressive MS (PMS) and 33 healthy controls. ResultsOverall, patients with MS exhibited lower interoceptive accuracy than matched controls. The RRMS group also showed higher visceral interoceptive sensibility levels. No differences were found in BR accuracy measures, but the PMS reported longer response times when performing the aBR task. ConclusionThese findings open a new issue on the role of inner‐signal monitoring in the body symptomatology of MS and highlight the need for an accurate BR and interoceptive assessment in a clinical setting.

Choroid plexus enlargement is associated with future periventricular neurodegeneration in multiple sclerosis

BackgroundThe choroid plexus (CP), located within the ventricles of the brain and the primary producer of cerebrospinal fluid, has been shown to be enlarged in patients with multiple sclerosis (MS) and linked to periventricular remyelination failure. Atrophied T2-lesion volume (aT2-LV), a promising neurodegenerative imaging marker in progressive MS (PMS), reflects the volume of periventricular lesions subsumed into cerebrospinal fluid over the follow-up. MethodsIn a cohort of 143 people with relapsing-remitting MS (RRMS) and 53 with PMS, we used 3T magnetic resonance imaging (MRI) to quantify CP volume (CPV) at baseline and aT2-LV over an average of 5.4 years of follow-up. Partial correlations, adjusting for age and sex, and linear regression analyses were used to assess the relationships between imaging measures. ResultsIn both cohorts, CPV was associated with aT2-LV in both the RRMS group (r = 0.329, p < 0.001) as well as the PMS group (r = 0.522, p < 0.001). In regression analyses predicting aT2-LV, ventricular volume (final adjusted R2 = 0.407, p < 0.001) explained additional variance beyond age, sex, and T2-lesion volume in the RRMS group while CPV (final adjusted R2 = 0.446, p = 0.009) was retained in the PMS group. ConclusionFindings from this study suggest that the CP enlargement is associated with future neurodegeneration, with a particularly relevant role in PMS.

Assessment of serum inflammatory parameters in RRMS and SPMS patients

ABSTRACT 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.

Transcranial ultrasonography as a predictor of disease progression in multiple sclerosis

BackgroundDevelopment of novel biomarkers for multiple sclerosis (MS) is of utmost importance to improve the capability to predict disease progression and disability. Transcranial ultrasonography (TCS) is a noninvasive imaging technique that allows the visualization of major parenchymal structures. This study aimed to evaluate the role of parenchymal transcranial sonography as a predictor for disease severity and progression in MS patients. Sixty patients with clinically definite Multiple sclerosis divided into two groups, relapsing–remitting MS (RRMS) group and chronic progressive MS (CPMS) group were included.ResultsThere was a statistically significant increase in the mean diameters of the third ventricle, both frontal horns of lateral ventricle in RRMS and CPMS group compared to control values, and in CPMS group compared to RRMS group. Expanded Disability Status Scale (EDSS) score was significantly positively correlated with the diameter of right frontal horn of lateral ventricle in CPMS group. Linear regression analysis revealed that diameters of right frontal horn of lateral ventricle and third ventricle were independent predictors for MS severity.ConclusionsTCS can be used as a simple noninvasive tool for prediction of disease severity and progression in MS patients.

The significance of miRNA-191-5P and miRNA-24-3P as novel biomarkers for multiple sclerosis: a case–control study

BackgroundMultiple sclerosis (MS) is a long-term disease that can lead to disability. microRNAs (miRNA) can provide noninvasive markers allowing more frequent and easy testing in MS. Treatment methods based on manipulating miRNA activity can be innovative. The purpose of this work is to measure the serum expression of miRNA-191-5P and miRNA-24-3P in MS patients. The investigation was carried out on 80 patients with MS (68 patients with Relapsing–remitting multiple sclerosis (RRMS), 12 patients with Progressive MS) and 40 healthy controls. The serum expression of miRNA-191-5P and miRNA-24-3P was measured using real-time quantitative PCR. The expression of the studied miRNAs was relatively calculated using the Eq. 2−ΔΔCt.ResultsSerum levels of miRNA-191 and miRNA-24 showed no difference between MS patients and healthy controls, and neither between RRMS and progressive MS groups. A negative correlation was detected between miRNA-191 and disease duration. Also, a positive correlation was detected between miRNA-191 and miRNA-24 expression. RRMS patients were significantly different from progressive MS patients regarding disease duration (p value 0.001) as well as expanded disability status scale score (p value < 0.001).ConclusionThe study uniquely analyzed the correlation between the miRNA-191 and miRNA-24, being expressed in all MS patients, and being positively correlated means they are influenced by the same factors and they can be therapeutically targeted in the same way, so further studies are required. The impact of disease duration on miRNA-191 expression encourages regular monitoring of miRNA-191.

Predictors of progression of multiple sclerosis in a sample of Egyptian patients

BackgroundMultiple sclerosis (MS) is a multifactorial neurodegenerative autoimmune disease with a varied clinical course and presentation, which is more frequent than ever in the Middle East. The aim of this work is to investigate potential predictors of MS progression in order to help in early diagnose and predict progressive course of the disease.ResultsThis is a retrospective case–control study conducted on a group of multiple sclerosis (MS) patients who developed secondary progression of the disease course (SPMS). The cases were matched with control MS patients who did not develop any disease progression (relapsing remitting MS (RRMS)). The matching was done for sex, and age with a ratio 1:1, total of 150 patients were included as cases and were matched with 150 control patients. Significant associations between MS progression and smoking, vitamin D deficiency, disease duration, delay in MS diagnosis, unemployment, site and number of lesions, and number of black holes were reported. About half of SPMS patients (53.3%) had 3 or more spinal lesions compared to only 1.4% of RRMS patients (p < 0.001). Moreover, about 76% of RRMS patients had no black holes in their radiological finding, while it was found that 35.3% of the SPMS patients had more than 5 black holes, compared to 8% of RRMS patients. Additionally, juxta-cortical site lesions were more frequent in SPMS than that in RRMS in a percentage 72.7 and 46%, respectively. Also, infra-tentorial lesions were found to be more frequent in SPMS group rather than RRMS group 92% and 78.7%, respectively.On the other hand, a lower SDMT scale was associated with a shorter time to SPMS diagnosis in the multivariate Cox regression analysis adjusted to baseline factors and 25-FWT (HR: 0.928, 95% CI: 0.906–0.95).ConclusionsMS secondary progression can be predicted among MS patients in routine practice comprising exposure history, clinical assessment, laboratory findings, and radiological examinations.

Baseline serum neurofilament light chain levels differentiate aggressive from benign forms of relapsing–remitting multiple sclerosis: a 20-year follow-up cohort

Background and objectivesSerum biomarkers are emerging as useful prognostic tools for multiple sclerosis (MS); however, long-term studies are lacking. We aimed to evaluate the long-term prognostic value of the serum levels of neurofilament light chain (NfL), total tau, glial fibrillary acidic protein (GFAP), and chitinase 3-like-1 (CHI3L1) measured close to the time of MS onset.MethodsIn this retrospective, exploratory, observational, case and controls study, patients with relapsing–remitting MS (RRMS) with available baseline serum samples and prospectively follow-up in our MS unit for a long time were selected based on their clinical evolution to form two groups: (1) a benign RRMS (bRRMS) group, defined as patients with an Expanded Disability Status Scale (EDSS) score of ≤ 3 at ≥ 10 years of follow-up; (2) an aggressive RRMS (aRRMS) group, defined as patients with an EDSS score of ≥ 6 at ≤ 15 years of follow-up. An age-matched healthy control (HC) group was selected. NfL, total tau, and GFAP serum levels were quantified using a single-molecule array (SIMOA), and CHI3L1 was quantified using ELISA.ResultsThirty-one patients with bRRMS, 19 with aRRMS, and 10 HC were included. The median follow-up time from sample collection was 17.74 years (interquartile range, 14.60–20.37). Bivariate and multivariate analyses revealed significantly higher NfL and GFAP levels in the aRRMS group than in the bRRMS group. A receiver operating characteristic curve analysis identified serum NfL level as the most efficient marker for distinguishing aRRMS from bRRMS.DiscussionThis proof-of-concept study comparing benign and aggressive RRMS groups reinforces the potential role of baseline NfL serum levels as a promising long-term disability prognostic marker. In contrast, serum GFAP, total tau, and CHI3L1 levels demonstrated a lower or no ability to differentiate between the long-term outcomes of RRMS.

Expression analysis of vitamin D receptor-associated long noncoding RNAs in patients with relapsing-remittingmultiple sclerosis.

Vitamin D is a neuroactive steroid that carries out its biological functions through the vitamin D receptor (VDR). The VDR gene interacts with certain long noncoding RNAs (lncRNAs). The present study is aimed at evaluating the expression levels of the VDR gene as well as those of HOTAIR, H19, MALAT1, and P21 lncRNAs in patients with relapsing-remitting multiple sclerosis (RRMS). This research was conducted on 38 RRMS patients and 38 healthy individuals. The expression levels of VDR and selected lncRNAs in peripheral blood as well as those of vitamin D in the plasma were measured. The results revealed a significant increase in the expression of lncRNA H19 in the RRMS group compared to the control group. The analysis of the receiver operating characteristic (ROC) curve for H19 gene expression demonstrated a diagnostic value of 0.699 (95% CI: 0.575-0.823). Positive correlations were detected between VDR and lncRNA HOTAIR (r = 0.446, p = 0.008), H19 (r = 0.351, p = 0.042), MALAT1 (r = 0.464, p = 0.006), and P21 (r = 0.512, p = 0.002) in MS patients. The findings of this study suggest that lncRNA H19 could serve as a potential biomarker for MS diagnosis (Tab. 4, Fig. 1, Ref. 34).

Relationship of tryptophan metabolites with the type and severity of multiple sclerosis.

Tryptophan is an essential amino acid primarily metabolized by the kynurenine pathway in mammals. Intermediate metabolites emerging in this pathway have been associated with many neurogenerative diseases. This study aimed to compare tryptophan pathway metabolite levels in patients with multiple sclerosis (MS) and healthy controls and reveal the relationship of tryptophan metabolites with disease subtype and the Expanded Disability Status Scale (EDSS) score. The study included a total of 80 MS cases [53 with relapsing remitting MS (RRMS) and 27 with secondary progressive MS (SPMS)] and 41 healthy volunteers. The patients with RRMS were further divided into relapse (RRMS-attack) and non-attack (RRMS-stable) groups. Using liquid chromatography mass spectrometry, tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid levels were measured. The serum metabolite levels of the patient and control groups were compared. In addition, the link and relationship between the EDSS score and disease duration of the patients and their plasma tryptophan metabolite levels were examined. The tryptophan level of the patient group was significantly lower than that of the healthy controls (p<0.05). The kynurenine (105.38±65.43), quinolinic acid (10.42±3.56), kynurenine/tryptophan ratio (0.0218±0.019), and quinolinic acid/kynurenic acid ratio (1.7054±0.96141) of the patients with MS were significantly higher compared to the controls (p<0.05). In the receiver operating characteristic analysis of the power of kynurenine/tryptophan and quinolinic acid/kynurenic acid ratios in predicting the disease, both ratios predicted the diagnosis of MS (area under the curve: 0.793 and 0.645, respectively; p<0.05), albeit at low sensitivity and specificity. The parameters were similar between the RRMS-attack and RRMS-stable patient groups (p>0.05). There was also no significant difference between the RRMS and SPMS patient groups in terms of tryptophan metabolites (p>0.05). Lastly, no significant relationship was observed between tryptophan metabolites and MS subtype and the EDSS score. Our findings revealed that the kynurenine pathway involved in the tryptophan metabolism differed between the patients with MS and healthy controls, and this difference may be a limited guide in the diagnosis of MS, due to major overlaps in values for MS versus Controls, and is insufficient to determine the disease subtype.

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.

Metabolomic profiles in relapsing-remitting and progressive multiple sclerosis compared to healthy controls: a five-year follow-up study.

Multiple sclerosis (MS) is a disease of the central nervous system associated with immune dysfunction, demyelination, and neurodegeneration. The disease has heterogeneous clinical phenotypes such as relapsing-remitting MS (RRMS) and progressive multiple sclerosis (PMS), each with unique pathogenesis. Metabolomics research has shown promise in understanding the etiologies of MS disease. However, there is a paucity of clinical studies with follow-up metabolomics analyses. This 5-year follow-up (5YFU) cohort study aimed to investigate the metabolomics alterations over time between different courses of MS patients and healthy controls and provide insights into metabolic and physiological mechanisms of MS disease progression. A cohort containing 108 MS patients (37 PMS and 71 RRMS) and 42 controls were followed up for a median of 5years. Liquid chromatography-mass spectrometry (LC-MS) was applied for untargeted metabolomics profiling of serum samples of the cohort at both baseline and 5YFU. Univariate analyses with mixed-effect ANCOVA models, clustering, and pathway enrichment analyses were performed to identify patterns of metabolites and pathway changes across the time effects and patient groups. Out of 592 identified metabolites, the PMS group exhibited the most changes, with 219 (37%) metabolites changed over time and 132 (22%) changed within the RRMS group (Bonferroni adjusted P < 0.05). Compared to the baseline, there were more significant metabolite differences detected between PMS and RRMS classes at 5YFU. Pathway enrichment analysis detected seven pathways perturbed significantly during 5YFU in MS groups compared to controls. PMS showed more pathway changes compared to the RRMS group.

Choroid plexus volume is enlarged in clinically isolated syndrome patients with optic neuritis

Objectives: We investigated choroid plexus (CP) volume in patients presenting with optic neuritis (ON) as a clinically isolated syndrome (CIS), compared to a cohort with established relapsing–remitting multiple sclerosis (RRMS) and healthy controls (HCs). Methods: Three-dimensional (3D) T1, T2-FLAIR and diffusion-weighted sequences were acquired from 44 ON CIS patients at baseline, 1, 3, 6 and 12 months after the onset of ON. Fifty RRMS patients and 50 HCs were also included for comparison. Results: CP volumes was larger in both ON CIS and RRMS groups compared to HCs, but not significantly different between ON CIS and RRMS patients (analysis of covariance (ANCOVA) adjusted for multiple comparisons). Twenty-three ON CIS patients who converted to clinically definite MS (MS) demonstrated CP volume similar to RRMS patients, but significantly larger compared to HCs. In this sub-group, CP volume was not associated with the severity of optic nerve inflammation or long-term axonal loss, not with brain lesion load. A transient increase of CP volume was observed following an occurrence of new MS lesions on brain magnetic resonance imaging (MRI). Interpretation: Enlarged CP can be observed very early in a disease. It transiently reacts to acute inflammation, but not associated with the degree of tissue destruction.

Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (p = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, p = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, p = 0.0018, cut-off < 3.0875 Kb, sensitivity = 75%, specificity = 62%), whereas the prediction is improved with a logistic regression model including LTL plus age (AUC = 0.762, p = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients.

Plasma 24-hydroxycholesterol is associated with narrower common carotid artery and greater flow velocities in relapsing multiple sclerosis

Background: Multiple sclerosis (MS) studies suggest greater cardiovascular disease burden and disturbances in the cholesterol pathways1,2 The potential impact of oxidized cholesterol molecules (oxysterols) on MS is emerging (Figure 1).3&#x0D; Objective: To determine the relationship between multiple oxysterol molecules and atherosclerosis burden in MS patients.&#x0D; Materials and methods: A total of 99 MS patients (61 relapsing-remitting MS (RRMS) and 38 progressive MS (PMS)) patients and 38 healthy controls (HCs) underwent magnetic resonance angiography (MRA) and the cross-sectional area (CSA) of the common carotid artery (CCA) was determined at three different levels before the bifurcation (C7, C6 and C5). Additionally, an echo-color Doppler ultrasound was performed and measures of blood flow velocities were derived. Blood samples acquired at the time of the imaging examinations were analyzed and 24-, 25-, 27-hydroxycholesterol (24HC, 25HC, 27HC) and 7-ketocholesterol (7KC) were quantified in ng/mL.&#x0D; Results: In the MS patients, higher levels of 24HC were significantly associated with smaller CCA CSA measured at all three cervical levels (r=-0.201, p=0.046; r=-0.228, p=0.023, and r=-0.215, p=0.032, for C7, C6 and C5, respectively). These associations were driven by the RRMS group only (r=-0.407, p=0.002 for C7; r=-0.414, p=0.002, for C6; and r=-0.368, p=0.006 for C5). No associations were seen in the HCs. Despite adjusting for the significant age effect (B=0.445, p=0.004), higher 24HC levels were independently associated with smaller CCA CSA (B=-0.20, p=0.045). 24HC was additionally associated with greater time-averaged and peak diastolic CCA velocities. RRMS patients treated with potent anti-inflammatory therapies had lower oxysterol levels (p=0.019). RRMS patients in the lower 24HC quartiles had significantly higher expanded disability status scale (EDSS) scores when compared to RRMS patients in the higher two 24HC quartiles (2.5 (IQR 1.9-3.1) vs 2.0 (1.5-2.5), p=0.038).&#x0D; Conclusions: Greater 24HC levels are associated with smaller CSA CCA and greater flow velocities in RRMS patients. The higher inflammatory activity in RRMS patients may contribute to the production of highly reactive oxysterols and worsen the atherosclerotic burden in the MS population. Potent anti-inflammatory medications can significantly decrease oxysterol levels.

Oral health-related quality of life is more strongly correlated with mental health than with oral health in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a leading cause of neurological disability in young and middle-aged populations, associated with substantial burden of illness. Because a growing literature now shows that this burden extends to poorer oral health, oral health-related quality of life (OHRQoL) may be reduced as well. To test whether people with relapsing-remitting MS (RRMS) have poorer OHRQoL than demographically matched controls, and to establish which variables are associated with worse OHRQoL. In total, 64 people with RRMS and 69 demographically matched controls participated. Both groups completed the Oral Health Impact Profile (OHIP-14), a validated measure of OHRQoL, as well as an objective oral health examination performed by a qualified dentist, a measure of dental-related functionality and a measure of mental health. OHRQoL was significantly poorer in the RRMS relative to the control group. However, although poorer OHRQoL in the RRMS group was moderately associated with objectively assessed oral health (r=.30), it was more strongly associated with mental health (r=.61). For the control group, the reverse pattern of association was evident, with OHRQoL more strongly associated with oral health (r=.48) relative to mental health (r=.20). People with RRMS report poorer OHRQoL than demographically matched controls, but these appraisals are more strongly linked to mental health than to objective oral health indicators.

Resting-State Functional Connectivity in Relapsing-Remitting Multiple Sclerosis with Mild Disability: A Data-Driven, Whole-Brain Multivoxel Pattern Analysis Study.

Background: Multivoxel pattern analysis (MVPA) has emerged as a powerful unbiased approach for generating seed regions of interest (ROIs) in resting-state functional connectivity (RSFC) analysis in a data-driven manner. Studies exploring RSFC in multiple sclerosis have produced diverse and often incongruent results. Objectives: The aim of the present study was to investigate RSFC differences between people with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC). Methods: We performed a whole-brain connectome-wide MVPA in 50 RRMS patients with expanded disability status scale ≤4 and 50 age and gender-matched HCs. Results: Significant group differences were noted in RSFC in three clusters distributed in the following regions: anterior cingulate gyrus, right middle frontal gyrus, and frontal medial cortex. Whole-brain seed-to-voxel RSFC characterization of these clusters as seed ROIs revealed network-specific abnormalities, specifically in the anterior cingulate cortex and the default mode network. Conclusions: The network-wide RSFC abnormalities we report agree with the previous findings in RRMS, the cognitive and clinical implications of which are discussed herein. Impact statement This study investigated resting-state functional connectivity (RSFC) in relapsing-remitting multiple sclerosis (RRMS) people with mild disability (expanded disability status scale ≤4). Whole-brain connectome-wide multivoxel pattern analysis was used for assessing RSFC. Compared with healthy controls, we were able to identify three regions of interest for significant differences in connectivity patterns, which were then extracted as a mask for whole-brain seed-to-voxel analysis. A reduced connectivity was noted in the RRMS group, particularly in the anterior cingulate cortex and the default mode network regions, providing insights into the RSFC abnormalities in RRMS.

Relapses after SARS-CoV-2 vaccination in patients with neuromyelitis optica spectrum disorder and multiple sclerosis

BackgroundThe COVID-19 pandemic outbreak raises the question of whether immunization is recommended for patients with CNS demyelinating diseases. On the one hand, existing studies suggested that SARS-CoV-2 vaccinations are not associated with increased risk of relapse activity. On the other hand, case reports with acute CNS demyelinating disease post vaccination were emerging and raising clinicians’ attention. MethodsIn this longitudinal observational study, we included 556 patients with neuromyelitis optica spectrum disorder (NMOSD) and 280 patients with relapsing-remitting multiple sclerosis (RRMS). Each vaccinated patient was matched to two unvaccinated patients according to age, gender, ARR and immunotherapy status, based on propensity score matching model (PSM). The primary outcome is the short- and medium-term risk of relapse, which were evaluated by Kaplan–Meier analysis between groups. ResultsIn our cohort, 649 patients (77.6%) have not yet been vaccinated, mainly due to their concerns about relapse. After PSM, 109 vaccinated patients with NMOSD, 218 PS-matched unvaccinated patients with NMOSD, 78 vaccinated patients with RRMS, and 156 PS-matched unvaccinated patients with RRMS were included in the survival analysis to explore the safety of vaccines, with a median of 9-month follow-up. Following the first vaccination dose, 10 patients with NMOSD (9.2%) and four with RRMS (5.1%) experienced an acute relapse. Meanwhile, in the PS-matched unvaccinated group, 15 patients with NMOSD (6.9%) and 12 patients with RRMS (7.7%) presented with an acute relapse. There was no significant difference between the two curves in both NMOSD and RRMS groups over the course of the observation period. There were no significant differences in demographic characteristics, clinical characteristics, and symptoms of relapses between the vaccinated and PS-matched unvaccinated groups. Post vaccination adverse events (ADE) were reported in 39 individuals (20.9%). ConclusionOur results indicate that inactivated SARS-CoV-2 vaccines appear safe for patients with CNS demyelinating diseases.

Cytokine Secretion Dynamics of Isolated PBMC after Cladribine Exposure in RRMS Patients.

Cladribine (CLD) treats multiple sclerosis (MS) by selectively and transiently depleting B and T cells with a secondary long-term reconstruction of the immune system. This study provides evidence of CLD’s immunomodulatory role in peripheral blood mononuclear cells (PBMCs) harvested from 40 patients with untreated relapsing-remitting MS (RRMS) exposed to CLD. We quantified cytokine secretion from PBMCs isolated by density gradient centrifugation with Ficoll–Paque using xMAP technology on a FlexMap 3D analyzer with a highly sensitive multiplex immunoassay kit. The PBMC secretory profile was evaluated with and without CLD exposure. PBMCs isolated from patients with RRMS for ≤12 months had significantly higher IL-4 but significantly lower IFN-γ and TNF-α secretion after CLD exposure. PBMCs isolated from patients with RRMS for >12 months had altered inflammatory ratios toward an anti-inflammatory profile and increased IL-4 but decreased TNF-α secretion after CLD exposure. CLD induced nonsignificant changes in IL-17 secretion in both RRMS groups. Our findings reaffirm CLD’s immunomodulatory effect that induces an anti-inflammatory phenotype.

Inner and outer retina findings determined by optical coherence tomography in different subtypes of multiple sclerosis.

Integrity of outer retinal bands among multiple sclerosis (MS) subtypes remains unclear, however alterations of thickness in retinal layers is well described. The objective of the study was to determine the alterations in the thickness of the inner and outer layers of the retina and the findings in both layers detected by optical coherence tomography (OCT) among patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). A total of 132 eyes from 66 patients with multiple sclerosis (MS) (70 eyes from 35 patients with RRMS and 62 eyes from 31 patients with SPMS) and 72 eyes from 36 healthy controls were included in the study. The external structures of the retina, including the outer limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ), were examined using OCT in RRMS, SPMS, and healthy control groups. The correlation of neurological disability expressed by the Expanded Disability Study Scale (EDSS) score, best-corrected visual acuity, and duration of disease among OCT parameters was also analyzed. In eyes, with no history of previous optic neuritis (ON), the macular nerve fiber layer, the internal plexiform layer of ganglion cells (GCIPL), and the total thickness of the retinal layer were thinner in the SPMS group than in the RRMS group (P < 0.05, in each comparison). EZ was more vulnerable among the three hyperreflective external retinal zones in the retina of patients with SPMS than in patients with RRMS (P = 0.016). Alterations in retinal thickness in MS are not limited to the inner layers of the retina and also occur in the outer structures of the retina.