MS Disease Progression Research Articles

Neurofilaments light chains as a diagnostic and predictive biomarker for Tunisian Multiple Sclerosis patients

BackgroundMultiple Sclerosis (MS) course was shown to be more severe among North Africans compared to Caucasians. Validation of prognostic biomarkers of disease activity and severity is a priority in our practice. ObjectiveWe aimed to investigate the association between baseline cerebrospinal fluid (CSF) and serum NfL (sNFL) levels and disease activity and disability accrual in a cohort of Tunisian patients with MS. MethodsA cross-sectional study was conducted, in the department of Neurology of Razi Hospital, including patients diagnosed with MS. Patient's data were retrieved from our local MS database. Blood and CSF sampling were performed at the first visit. sNFL levels were measured using the Enzyme-Linked Immuno-Sorbent Assay (ELISA) sandwich technique. ResultsThree hundred MS patients were enrolled (sex-ratio= 3.05; mean age at MS onset=28.83 years+9.55, mean MS course = 10.21 years+8.96). MS phenotype was predominately relapsing (73%). CSF NfL levels were significantly correlated to the serum ones. NfL concentrations were significantly associated with MS activity (p = 0.012), disease progression (p = 0.001), and higher Multiple Sclerosis Severity Scores (MSSS) (p = 0.0017, r = 0.28). ConclusionsThese results support the value of NfL as a sensitive and clinically meaningful CSF and blood biomarker to evaluate MS activity and outcomes among Tunisian MS patients.

Identification of brain-enriched proteins in CSF as biomarkers of relapsing remitting multiple sclerosis

BackgroundMultiple sclerosis (MS) is a clinically and biologically heterogenous disease with currently unpredictable progression and relapse. After the development and success of neurofilament as a cerebrospinal fluid (CSF) biomarker, there is reinvigorated interest in identifying other markers of or contributors to disease. The objective of this study is to probe the predictive potential of a panel of brain-enriched proteins on MS disease progression and subtype.MethodsThis study includes 40 individuals with MS and 14 headache controls. The MS cohort consists of 20 relapsing remitting (RR) and 20 primary progressive (PP) patients. The CSF of all individuals was analyzed for 63 brain enriched proteins using a method of liquid-chromatography tandem mass spectrometry. Wilcoxon rank sum test, Kruskal-Wallis one-way ANOVA, logistic regression, and Pearson correlation were used to refine the list of candidates by comparing relative protein concentrations as well as relation to known imaging and molecular biomarkers.ResultsWe report 30 proteins with some relevance to disease, clinical subtype, or severity. Strikingly, we observed widespread protein depletion in the disease CSF as compared to control. We identified numerous markers of relapsing disease, including KLK6 (kallikrein 6, OR = 0.367, p < 0.05), which may be driven by active disease as defined by MRI enhancing lesions. Other oligodendrocyte-enriched proteins also appeared at reduced levels in relapsing disease, namely CNDP1 (carnosine dipeptidase 1), LINGO1 (leucine rich repeat and Immunoglobin-like domain-containing protein 1), MAG (myelin associated glycoprotein), and MOG (myelin oligodendrocyte glycoprotein). Finally, we identified three proteins—CNDP1, APLP1 (amyloid beta precursor like protein 1), and OLFM1 (olfactomedin 1)—that were statistically different in relapsing vs. progressive disease raising the potential for use as an early biomarker to discriminate clinical subtype.ConclusionsWe illustrate the utility of targeted mass spectrometry in generating potential targets for future biomarker studies and highlight reductions in brain-enriched proteins as markers of the relapsing remitting disease stage.

Holistic, Long-Term Management of People with Relapsing Multiple Sclerosis with Cladribine Tablets: Expert Opinion from France.

Cladribine tablets (CladT) has been available for therapeutic use in France since March 2021 for the management of highly active relapsing multiple sclerosis (RMS). This high-efficacy disease-modifying therapy (DMT) acts as an immune reconstitution therapy. In contrast to most high-efficacy DMTs, which act via continuous immunosuppression, two short courses of oral treatment with CladT at the beginning of years 1 and 2 of treatment provide long-term control of MS disease activity in responders to treatment, without the need for any further pharmacological treatment for several years. Although the labelling for CladT does not provide guidance beyond the initial treatment courses, real-world data on the therapeutic use of CladT from registries of previous clinical trial participants and patients treated in routine practice indicate that MS disease activity is controlled for a period of years beyond this time for a substantial proportion of patients. Moreover, this clinical experience has provided useful information on how to initiate and manage treatment with CladT. In this article we, a group of expert neurologists from France, provide recommendations on the initiation of CladT in DMT-naïve patients, how to switch from existing DMTs to CladT for patients with continuing MS disease activity, how to manage patients during the first 2years of treatment and finally, how to manage patients with or without MS disease activity in years 3, 4 and beyond after initiating treatment with CladT. We believe that optimisation of the use of CladT beyond its initial courses of treatment will maximise the benefits of this treatment, especially early in the course of MS when suppression of focal inflammation in the CNS is a clinical priority to limit MS disease progression.

Potential beneficial effect of IFN-β1a and ocrelizumab in people with MS during the COVID-19 pandemic.

Disease-modifying therapy (DMT) has led to added challenges in the management of people with multiple sclerosis (pwMS) during the COVID-19 era. It can reduce relapse in MS or slow down disease progression, but some DMTs can increased risk of infection. The aim of study was to evaluate risk and severity of COVID-19 in pwMS. The examined group of pwMS were divided in group treated with IFN-β1a, group treated with ocrelizumab and untreated group. The examination included impact of age, gender, duration of MS, type of MS, vaccination status and Expanded Disability Status Scale (EDSS) on the risk and severity of COVID-19 infection. A diagnosis of COVID-19 in pwMS was confirmed by positive polymerase-chain-reaction (PCR) or antigen test. Out of 207 pwMS, 82 patients were treated with ocrelizumab, 63 with IFN-β1a, while 62 patients were untreated pwMS. The average duration of the MS was longer in the group of patients treated with ocrelizumab than in the group treated with IFN-β1a (p < 0.05). EDSS was higher in the ocrelizumab group compared to the other two groups (p < 0.001). Untreated (more often unvaccinated) had the same COVID frequency as ocrelizumab-treated (more vaccinated, but higher EDSS). The multivariate logistic regression model indicated that administration of IFN-β1a reduces the risk of COVID-19 infection (p = 0.001, OR = 0.381, 95% CI 0.602-0.160). The use of both DMTs, driven mainly by the IFN-β1a effect, reduces the risk of moderate and severe COVID-19 (p < 0.05, OR = 0.105, 95% CI 0.011-0.968). This study provides evidence that IFN-β1a can reduce the frequency of COVID-19 infection and that two DMTs, driven mainly by the IFN-β1a effect, do not increase the risk of moderate/severe COVID-19.

Vascular disease risk factors in multiple sclerosis: Effect on metabolism and brain volumes.

Vascular disease risk factors (VDRF) such as hypertension, hyperlipidemia, obesity, diabetes and heart disease likely play a role in disease progression in people with multiple sclerosis (PwMS) (Marrie, Rudick etal. 2010). Studies exploring the mechanistic connection between vascular disease and MS disease progression are scant. We hypothesized that phosphate energy metabolism impairment in PwMS with VDRFs (VDRF+) will be greater compared to PwMS without VDRFs (VDRF-) and is related to increased brain atrophy in VDRF+. To test this hypothesis, we planned to study the differences in the high energy phosphate (HEP) metabolites in cerebral gray matter as assessed by 31P magnetic resonance spectroscopic imaging (MRSI) and MRI brain volumetric in the VDRF+ and VDRF- PwMS at four different timepoints over a 3 yearlong period using a 7T MR system. We present here the results from the cross-sectional evaluation of HEP metabolites and brain volumes. We also evaluated the differences in clinical impairment, blood metabolic biomarkers and quality of life in VDRF+ and VDRF- PwMS in this cohort. Group differences in high energy phosphate metabolites were assessed from a volume of interest in the occipital region using linear mixed models. Brain parenchymal and white matter lesion volumes were determined from MR anatomic images. We present here the cross-sectional analysis of the baseline data collected as part of a longitudinal 3 yearlong study where we obtained baseline and subsequent 6-monthly clinical and laboratory data and annual 7T MRI volumetric and 31P MR spectroscopic imaging (MRSI) data on 52 PwMS with and without VDRF. Key clinical and laboratory outcomes included: body mass index (BMI), waist and thigh circumferences and disability [Expanded Disability Status Scale (EDSS)], safety (complete blood count with differential, complete metabolic), lipid panel including total cholesterol and HbA1C. We analyzed clinical and laboratory data for the group differences using student's t or χ2 test. We investigated relationship between phosphate metabolites and VDRF using mixed effect linear regression. Complete MRI data were available for 29 VDRF+, age 56.3 (6.8) years [mean (SD)] (83% female), and 23 VDRF-, age 52.5 (7.5) years (57% female) individuals with MS. The mean value of normalized adenosine triphosphate (ATP) (calculated as the ratio of ATP to total phosphate signal in a voxel) was decreased by 4.5% (p < .05) in VDRF+ compared to VDRF- MS group. White matter lesion (WML) volume fraction in VDRF+ individuals {0.007 (0.007)} was more than doubled compared to VDRF- participants {0.003 (0.006), p= .02}. We found significantly lower brain ATP and higher inorganic phosphate (Pi) in those PwMS with VDRFs compared to those without. ATP depletion may reflect mitochondrial dysfunction. Ongoing longitudinal data analysis from this study, not presented here, will evaluate the relationship of phosphate metabolites, brain atrophy and disease progression in PwMS with and without vascular disease.

Genetic Variants in Iron Metabolism impact Disease Progression in MS through HIF1A (S9.006)

Genetic Variants in Iron Metabolism impact Disease Progression in MS through HIF1A (S9.006)

Assessment of cognitive performance in multiple sclerosis using smartphone-based training games: a feasibility study

BackgroundCognitive impairment occurs in up to 70% of people with MS (pwMS) and has a large impact on quality of life and working capacity. As part of the development of a smartphone-app (dreaMS) for monitoring MS disease activity and progression, we assessed the feasibility and acceptance of using cognitive games as assessment tools for cognitive domains.MethodsWe integrated ten cognitive games in the dreaMS app. Participants were asked to play these games twice a week for 5 weeks. All subjects underwent a battery of established neuropsychological tests. User feedback on acceptance was obtained via a five-point Likert-scale questionnaire. We correlated game performance measures with predetermined reference tests (Spearman’s rho) and analyzed differences between pwMS and Healthy Controls (rank biserial correlation).ResultsWe included 31 pwMS (mean age 43.4 ± 12.0 years; 68% females; median Expanded Disability Status Scale score 3.0, range 1.0–6.0) and 31 age- and sex-matched HC. All but one game showed moderate–strong correlations with their reference tests, (|rs|= 0.34–0.77). Performance improved in both groups over the 5 weeks. Average ratings for overall impression and meaningfulness were 4.6 (range 4.2–4.9) and 4.7 (range 4.5–4.8), respectively.ConclusionModerate–strong correlations with reference tests suggest that adaptive cognitive games may be used as measures of cognitive domains. The practice effects observed suggest that game-derived measures may capture change over time. All games were perceived as enjoyable and meaningful, features crucial for long-term adherence. Our results encourage further validation of adaptive cognitive games as monitoring tools for cognition in larger studies of longer duration.Study RegisterClinicalTrials.gov: NCT04413032.

Therapeutic Effects of Physical Exercise and the Mesenchymal Stem Cell Secretome by Modulating Neuroinflammatory Response in Multiple Sclerosis.

Multiple Sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by Central Nervous System (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.

The Impact of Vitamin D on The Development of Multiple Sclerosis (Review article)

Multiple Sclerosis is a harmful disease causes severe and painful symptoms. In the recent period, researchers have tended to study the effect of vitamin D deficiency on general health. Several studies have reported that there is a relation between vitamin D levels and MS disease progression. Epidemiological testimony&#x0D; and reports have recorded that there are an association between the decrement in plasma vitamin D levels and the incidence of MS also with the disease development; and it has seen that when take vitamin D as supplement may protect the MS patients against disease development. Despite clear evidence of the correlation between disease progression and vitamin D deficiency but the mechanism yet unclear.

Retinal nerve fiber layer thickness in multiple sclerosis with and without optic neuritis: a four-year follow-up study from Oman

BackgroundMultiple sclerosis (MS) is an autoimmune disease that attacks the central nervous system, with optic neuritis (ON) being a common early manifestation. Retinal nerve fiber layer (RNFL) thickness may be a biomarker of neuroaxonal damage in MS patients. We sought to evaluate changes in RNFL thickness over 4 years in Omani MS patients with or without ON in comparison to a healthy control group.MethodsThis retrospective case-control study involved 27 MS patients and 25 healthy controls. Optical coherence tomography was performed upon first diagnosis and at a four-year follow-up. Differences in mean RNFL thickness were calculated.ResultsA total of 51 eyes from the MS group and 50 eyes from the control group were evaluated. There was a significant reduction in mean RNFL thickness among MS patients with ON at follow-up (81.21 versus 72.14 μm; P = .003), whereas no significant RNFL thinning was observed among MS patients without ON. However, there was a significant reduction in RNFL thickness among MS patients compared to healthy controls (76.79 versus 93.72 μm; P = .009), regardless of ON presence/absence.ConclusionsAxonal damage was seen in the optic nerves of Omani MS patients. Moreover, there was a significant reduction in RNFL thickness among MS patients with ON as the disease progressed; however, while there was evidence of RNFL thinning in MS patients without ON, this difference lacked statistical significance. Evaluation of RNFL thickness may represent a useful biomarker for monitoring disease progression in MS and its association with ON.

CSF neurofilament light chain predicts 10-year clinical and radiologic worsening in multiple sclerosis.

BackgroundNeurofilament light chain (NfL) is an attractive biomarker of disease activity and progression in MS, but there is a lack in long-term prognostic data.ObjectiveTo test the long-term clinical and radiological prognostic value of cerebrospinal fluid (CSF)-NfL among newly diagnosed patients with MS.MethodsNewly diagnosed MS patients where followed prospectively with baseline CSF-NfL and repeated MRI and clinical assessments for up to 10 years. Associations between baseline CSF-NfL and longitudinal MRI and clinical assessments were found by Generalized Estimating Equations analysis.ResultsForty-two participants were included. CSF-NfL at baseline was significantly associated with the rate of atrophy in globus pallidus (p = 0.009) and hippocampus (p = 0.001) as evaluated by MRI. Baseline volumes of thalamus (β −0.33; 95% CI −0.57 to −0.10, p = 0.006), T1 (β 0.28; 95% CI 0.11 to 0.44, p = 0.001) and T2 (β 0.16; 95% CI 0.04 to 0.27, p = 0.008) lesions and baseline levels of CSF-NfL (β 0.9; 95% CI 0.3 to 1.5, p = 0.002) significantly predicted EDSS worsening over 10 years. Baseline CSF-NfL gave a comparable prediction to the best MRI volumetric predictors.ConclusionCSF-NfL predicted the clinical and radiological course of newly diagnosed patients with MS over a 10-year period, underlining its prognostic role.

An internet-based survey of synesthesia in multiple sclerosis: Incidence, characteristics and implications

Objective Prior work raises the interesting possibility that both multiple sclerosis and synesthesia share a common etiology, that being immune system dysfunction, as well as neuroanatomical and neurochemical abnormalities, including those involving white matter and serotonergic pathways, respectively. Given these links between these two syndromes, we examined the possibility that prevalence of synesthesia would be elevated in a population of individuals with MS, relative to what is thought to be the prevalence in the neurotypical population. It was not known whether synesthesia might be a marker for subsequent development of MS, or if synesthesia might reflect neurological damage resulting from MS disease progression. Method Individuals with self- reported clinically definite MS were recruited online via the internet and social media using sites specifically relevant to the MS community. Data from 147 individuals who completed several questionnaires related to synesthesia were analyzed. Results Depending on criteria, between approximately 7 and 16% of individuals with MS reported synesthesia here. This is an estimated 1.57 to 3.55 times increased incidence of synesthesia here relative to previous findings in neurotypical samples. Limitations of the study include that this was an internet survey, and that synesthesia was not directly assessed in this sample. Conclusions Results suggest a link between the syndromes, primarily indicating that synesthesia may be a marker for subsequent MS development, and the implications and directions for future study are discussed.

Fear of COVID-19, problems accessing medical appointments, and subjective experience of disease progression, predict anxiety and depression reactions in patients with Multiple Sclerosis

BackgroundDuring the current COVID-19 pandemic there are studies that have suggested a negative impact of the pandemic on the mental health of patients with multiple sclerosis (PwMS). In this sense, several factors may be related to the increase in experiences of anxiety and depression in PwMS during the current pandemic. ObjectiveIn this study we first explored the reactions of anxiety, depression and fear to COVID-19 in a group of PwMS that belong to the Ibero-American region. Besides, we explored whether having been positive to COVID-19, fear of COVID-19, the obstacles to attend medical appointments during the outbreak and subjective experience of MS progression, could predict the anxiety and depression reactions in our PwMS sample. Materials and methodsAn online cross-sectional survey was conducted on 202 MS patients from six countries (Argentina, Mexico, Spain, Dominican Republic, Venezuela and Cuba). For comparisons between variables an independent-samples t-test and one-way analysis of variance were used. Multiple linear regression was used to evaluate the effects of potential predictor variables over emotional reactions. ResultsOur results showed that PwMS who were positive for COVID-19 reported higher levels of fear of COVID-19 (p<.001) and also higher levels of anxiety (p<.001) compared to non-positive patients. Those patients who had difficulties attending their medical appointments during the outbreak showed higher levels of depression (p=.03) and anxiety (p=.019). Levels of anxiety (p<.001) and depression (p=.006) were also higher among patients with the subjective experience of MS disease progression. The reactions of fear of COVID-19, having been positive to COVID-19, problems attending medical appointments, and subjective experience of MS disease progression showed a high association with the negative impact of the pandemic on mental health of PwMS. ConclusionsOur results show that the situation generated by the COVID-19 pandemic has had a negative impact on the mental health of PwMS in our sample. Our results also alert to the importance of offering psychological care to patients with multiple sclerosis during the current outbreak, regardless of whether they have been positive for COVID-19.

A Unique Multiplex Assay to Identify Th1/Th2 Cytokine Profile in MS Patients

Abstract Multiple Sclerosis (MS) is a chronic neuroinflammatory, demyelinating autoimmune disease of the central nervous system (CNS). There are diverse views on the paradigm that disease pathogenesis of MS is due to an imbalance in the proinflammatory T helper 1 (Th1)-type cytokines and anti-inflammatory Th2-type cytokines. Several factors play a crucial role in Th1/Th2 polarization that contributes towards disease activation or progression and this is dependent on MS disease sub-type. The goal of our research study is to investigate a unique and robust multiplex assay for identification of Th1 versus Th2 cytokine expression pattern as applicable to samples derived from MS patients. Towards this end, a sandwich ELISA-based multiplex assay method in a 96-well plate format is designed for establishing Th1/Th2 cytokine profile. Cerebrospinal fluid (CSF) samples derived from MS patients diagnosed with either Relapsing-Remitting MS (RRMS, N = 10) or Secondary progressive MS (SPMS, N = 10) and two unaffected control CSF samples derived from the otherwise healthy human subjects are included in the study. Multiplex ELISA analysis in a 96-well format included TNF, IFN-gamma, IL-4, IL-13 and IL-17E cytokines. Each well is imprinted in a 3*3 format with a capture antibody against a given cytokine of interest. The colorimetric read-outs from multiplex assay are analyzed by ImageJ. Preliminary results identify the multiplex assay to be robust, unique and cost-effective for establishing Th1/Th2 cytokine profiles in two different sub-types of MS. Th1/Th2 cytokine pattern could help predict the course of MS disease progression and remission.

Comparing HCP and Patient Perceptions of Conversations about Disease Progression in MS (4304)

Comparing HCP and Patient Perceptions of Conversations about Disease Progression in MS (4304)

Alcohol consumption leads to sex-specific amelioration of disability in a mouse model of multiple sclerosis

Abstract Multiple sclerosis (MS) is a neuroinflammatory autoimmune disorder and the leading cause of neurological disability in young people. Alcohol consumption is known to have both neuroinflammatory and immunosuppressive effects, yet despite high rates of alcohol abuse among MS patients, its effects on MS disease progression have not been well studied. The few studies on alcohol consumption during MS have produced conflicting results and suggest opposing clinical outcomes at different alcohol doses. In this study, we hypothesized that low-dose daily alcohol consumption could ameliorate the clinical course of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male and female C57BL/6 mice were fed a 2.6% ABV Lieber-deCarli diet or isocaloric control prior to MOG35–55-mediated EAE induction and monitored for 40 days. Male alcohol consumers (AC) experienced significantly greater remission compared to controls or AC females. Histological analysis revealed significantly fewer Iba1+ cells in the dorsal horns and lateral columns of AC male cervical and thoracic spinal cords compared to the other groups. 16S rRNA gut microbiome sequencing revealed distinct flora patterns during EAE onset and remission, and showed increased abundance of immunoregulatory species A. muciniphila and A. equolifaciens in AC males. These results demonstrate that moderate alcohol consumption can ameliorate EAE by modulating male microglial activation while simultaneously promoting an anti-inflammatory gut microbiome.

Vascular Disease Risk Factors (VDRF) in MS is Associated with Brain ATP Abnormalities: Dysmetabolism May Drive MS Disease Progression. (S55.001)

Vascular Disease Risk Factors (VDRF) in MS is Associated with Brain ATP Abnormalities: Dysmetabolism May Drive MS Disease Progression. (S55.001)

No evidence of disease activity status over 3 years in a real-world cohort of relapsing remitting MS patients in Germany

BackgroundOver the last decade, therapy of relapsing remitting multiple sclerosis (RRMS) has evolved with the approval of several new treatment concepts. Thus, treatment goals have become more ambitious aiming at “no evidence of disease activity” (NEDA). As NEDA-3, this concept comprises freedom of clinical disease progression and relapses as well as inflammatory MRI activity. So far, data on NEDA status mainly stem from post-hoc analyses of drug approval studies. Yet, less is known about the significance of NEDA in “real-world” clinical settings. Hence, our study aims at investigation of NEDA in a heterogeneous cohort of relapsing MS patients. MethodsThis is a retrospective single-center study at the Department of Neurology of the University Hospital Erlangen, Germany, including data of 306 patients with relapsing forms of MS (RMS) or clinical isolated syndrome (CIS) from 2009 to 2016. Inclusion required sufficient clinical information and in house cranial MRI follow-up data sets at baseline and at follow-up after one year with a potential extension to two and three year follow-up, if possible. NEDA-3 status, its correlation to clinical features, associated medication and NEDA failure (EDA) were analyzed. ResultsIn a cohort of RMS patients at the early stages of the disease (median EDSS 1.5, mean disease duration 30 months) at baseline, 45% retained NEDA-3 status after one year. This percentage decreased in year two (29%) and three (21%) of follow-up. MRI criteria were responsible for loss of NEDA status in 64% of cases and CIS patients were more likely to sustain NEDA status. Therapy with monoclonal antibodies appeared superior in sustaining NEDA status as compared to injectables or oral treatment options. DiscussionIn our real-world analysis, we confirm the potential of NEDA for the evaluation and surveillance of MS disease activity, progression and therapy efficacy. Despite highly efficient immunomodulatory treatment, NEDA-3 was only preserved in a minority of patients. Monoclonal antibodies may yield best NEDA rates. Further studies are warranted to evaluate the value of the NEDA concept in real-world settings beyond standardized clinical studies.

Quantitative spinal cord MRI in radiologically isolated syndrome.

ObjectivesTo assess whether quantitative spinal cord MRI (SC-MRI) measures, including atrophy, and diffusion tensor imaging (DTI) and magnetization transfer imaging metrics were different in radiologically isolated syndrome (RIS) vs healthy controls (HCs).MethodsTwenty-four participants with RIS and 14 HCs underwent cervical SC-MRI on a 3T magnet. Manually segmented regions of interest circumscribing the spinal cord cross-sectional area (SC-CSA) between C3 and C4 were used to extract SC-CSA, fractional anisotropy, mean, perpendicular, and parallel diffusivity (MD, λ⊥, and λ||) and magnetization transfer ratio (MTR). Spinal cord (SC) lesions, SC gray matter (GM), and SC white matter (WM) areas were also manually segmented. Multivariable linear regression was performed to evaluate differences in SC-MRI measures in RIS vs HCs, while controlling for age and sex.ResultsIn this cross-sectional study of participants with RIS, 71% had lesions in the cervical SC. Of quantitative SC-MRI metrics, spinal cord MTR showed a trend toward being lower in RIS vs HCs (p = 0.06), and there was already evidence of brain atrophy (p = 0.05). There were no significant differences in SC-DTI metrics, GM, WM, or CSA between RIS and HCs.ConclusionThe SC demonstrates minimal microstructural changes suggestive of demyelination and inflammation in RIS. These findings are in contrast to established MS and raise the possibility that the SC may play an important role in triggering clinical symptomatology in MS. Prospective follow-up of this cohort will provide additional insights into the role the SC plays in the complex sequence of events related to MS disease initiation and progression.

Association of CYP2R1 rs10766197 with MS risk and disease progression.

MS is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Among these, vitamin D and genetic variants associated with vitamin D-metabolism gain great attention. The aim of our study was to assess five SNPs in NADSYN1 and CYP2R1 genes in relation to serum 25-OH-vitamin D3 levels in MS patients and controls. 25-OH-vitamin D3 levels and genotyping of CYP2R1- and NADSYN1-SNPs were investigated both in MS patients and in healthy controls. The analysis revealed lower 25-OH-vitamin D3 concentrations in MS patients than in controls and an association of rs10766197 CYP2R1 SNP with MS risk. After stratifying MS patients according to gender, we found that the minor allele A of rs10766197 had a higher frequency in men in comparison to women affected by MS. Additionally, the presence of allele A in men was associated with disease progression, assessed by EDSS and MSSS scores. The findings of our study open new perspectives for a role of CYP2R1 in both risk and progression of MS, with sex-related differences.