Multiple Sclerosis Samples Research Articles

Coping strategies: Seeking personalized care in relapsing-remitting multiple sclerosis. A patient reported measure–coping responses inventory

BackgroundCoping is defined as a set of cognitive and behavioral efforts made to master stressful specific demands. Adaptation to chronic diseases, such as Multiple Sclerosis (MS), depends on the effectiveness of coping.Objective: To assess the psychometric properties of the Coping Responses Inventory (CRI-A) in persons with MS (PwMS), verifying the transferability of the measure, already validated in the Argentine general population, and to describe the types of coping strategies available for PwMS.Methods: 90 PwMS were included.Outcome measures: CRI-A Inventory, Expanded Disability Status Scale (EDSS), Beck Depression Inventory, Fatigue Severity Scale and MS International Quality of Life questionnaire.Results: Descriptive data is as follows: mean age (years): 40.97 ± 12.85; years of education: 13.46 ± 3.93; EDSS: 2.48 ± 1.79; disease evolution (years): 10.76 ± 9.72; depression: 13.92 ± 10.45; fatigue 3.77 ± 1.72. The psychometric properties of the CRI-A Inventory observed in the Argentine general population are present in the MS sample as well, with adequate validity and reliability. The respondents most frequently utilized a problem-focused coping style.Conclusions: Results showed the CRI-A has good transferability properties from the Argentine general population to the MS population.

Using data science for medical decision making case: role of gut microbiome in multiple sclerosis

BackgroundA decade ago, the advancements in the microbiome data sequencing techniques initiated the development of research of the microbiome and its relationship with the host organism. The development of sophisticated bioinformatics and data science tools for the analysis of large amounts of data followed. Since then, the analyzed gut microbiome data, where microbiome is defined as a network of microorganisms inhabiting the human intestinal system, has been associated with several conditions such as irritable bowel syndrome - IBS, colorectal cancer, diabetes, obesity, and metabolic syndrome, and lately in the study of Parkinson’s and Alzheimer’s diseases as well. This paper aims to provide an understanding of differences between microbial data of individuals who have been diagnosed with multiple sclerosis and those who were not by exploiting data science techniques on publicly available data.MethodsThis study examines the relationship between multiple sclerosis (MS), an autoimmune central nervous system disease, and gut microbial community composition, using the samples acquired by 16s rRNA sequencing technique. We have used three different sets of MS samples sequenced during three independent studies (Jangi et al, Nat Commun 7:1–11, 2016), (Miyake et al, PLoS ONE 10:0137429, 2015), (McDonald et al, Msystems 3:00031–18, 2018) and this approach strengthens our results. Analyzed sequences were from healthy control and MS groups of sequences. The extracted set of statistically significant bacteria from the (Jangi et al, Nat Commun 7:1–11, 2016) dataset samples and their statistically significant predictive functions were used to develop a Random Forest classifier. In total, 8 models based on two criteria: bacteria abundance (at six taxonomic levels) and predictive functions (at two levels), were constructed and evaluated. These include using taxa abundances at different taxonomy levels as well as predictive function analysis at different hierarchical levels of KEGG pathways.ResultsThe highest accuracy of the classification model was obtained at the genus level of taxonomy (76.82%) and the third hierarchical level of KEGG pathways (70.95%). The second dataset’s 18 MS samples (Miyake et al, PLoS ONE 10:0137429, 2015) and 18 self-reported healthy samples from the (McDonald et al, Msystems 3:00031–18, 2018) dataset were used to validate the developed classification model. The significance of this step is to show that the model is not overtrained for a specific dataset but can also be used on other independent datasets. Again, the highest classification model accuracy for both validating datasets combined was obtained at the genus level of taxonomy (70.98%) and third hierarchical level of KEGG pathways (67.24%). The accuracy of the independent set remained very relevant.ConclusionsOur results demonstrate that the developed classification model provides a good tool that can be used to suggest the presence or absence of MS condition by collecting and analyzing gut microbiome samples. The accuracy of the model can be further increased by using sequencing methods that allow higher taxa resolution (i.e. shotgun metagenomic sequencing).

A Scoring Algorithm for Deriving Utility Values from the Neuro-QoL for Patients with Multiple Sclerosis.

The Neuro-QoL is a standardized approach to assessing health-related quality of life in people with neurological conditions, including multiple sclerosis (MS). Item banks were developed with item response theory (IRT) methodology so items are calibrated along a continuum of each construct. The purpose of this study was to develop a preference-based scoring algorithm for the Neuro-QoL to derive utilities that could be used in economic modeling. With input from neurologists, 6 Neuro-QoL domains were selected based on relevance to MS and used to define health states for a utility elicitation study in the United Kingdom. General population participants and individuals with MS valued the health states and completed questionnaires (including Neuro-QoL short forms). The Neuro-QoL Utility Scoring System (NQU) was derived based on multi-attribute utility theory using data from the general population sample. Single-attribute disutility functions for 6 Neuro-QoL domains were estimated using isotonic regression with linear interpolation and then combined with a multiplicative model. NQU validity was assessed using MS participant data. Interviews were completed with 203 general population participants (50.2% female; mean age = 45.0 years) and 62 participants with MS (62.9% female; mean age = 46.1 years). Mean (SD) NQU scores were 0.94 (0.06) and 0.82 (0.13) for the general population and MS samples, respectively. The NQU demonstrated known-groups validity by differentiating among subgroups categorized based on level of disability. The NQU demonstrated convergent validity via correlations with generic measures (0.66 and 0.63 with EQ-5D-5L and Health Utilities Index Mark 3, respectively; both P < 0.001). With the NQU, utilities can be derived from any MS treatment group, subgroup, or patient sample who completes items from 6 Neuro-QoL domains. Because the Neuro-QoL is frequently used with MS patients, the NQU greatly expands the options for quantifying outcomes in cost-utility analyses conducted to inform allocation of resources for MS treatment.

Are Established Embedded Performance Validity Test Cut-Offs Generalizable to Patients With Multiple Sclerosis?

Data for the use of embedded performance validity tests (ePVTs) with multiple sclerosis (MS) patients are limited. The purpose of the current study was to determine whether ePVTs previously validated in other neurological samples perform similarly in an MS sample. In this retrospective study, the prevalence of below-criterion responding at different cut-off scores was calculated for each ePVT of interest among patients with MS who passed a stand-alone PVT. Previously established PVT cut-offs generally demonstrated acceptable specificity when applied to our sample. However, the overall cognitive burden of the sample was limited relative to that observed in prior large-scale MS studies. The current study provides initial data regarding the performance of select ePVTs among an MS sample. Results indicate most previously validated cut-offs avoid excessive false positive errors in a predominantly relapsing remitting MS sample. Further validation among MS patients with more advanced disease is warranted.

Propriedades psicométricas da Frontal Assessment Battery na esclerose múltipla

Contexto: A Esclerose Múltipla (EM) é uma doença desmielinizante crónica que pode envolver alterações cognitivas e executivas. As alterações executivas, relacionadas essencialmente com o lobo frontal, podem ser subdiagnosticadas, uma vez que os instrumentos utilizados na EM são extensos e complexos, podendo os seus resultados ser comprometidos pelos níveis de fadiga que poderão daí decorrer. A Bateria de Avaliação Frontal (FAB) é de aplicação rápida e simples e avalia as funções do lobo frontal. Objetivo: Explorar as propriedades psicométricas da FAB numa amostra de doentes com EM. Métodos: No estudo avaliaram-se 68 doentes com EM e 81 indivíduos sem diagnóstico de doença neurológica (amostra de controlo) com a FAB, a Subescala executiva do Montreal Cognitive Assessment/MoCA-E e o Teste de Fluências Verbais Fonéticas/TFVF. Vinte e nove doentes foram reavaliados com a FAB (intervalo 4-8 semanas). Resultados: Na amostra com EM, a consistência interna revelou-se adequada e a estabilidade temporal situou-se entre moderada a alta nas subescalas Semelhanças, FluênciasLexicais, Séries Motoras de Luria e Go-no-Go. A FAB correlacionou-se de forma elevada com o MoCA-E e TFVF, atestando a sua validade convergente, e a sua estabilidade temporal teste-reteste revelou-se adequada. A amostra com EM teve pontuações significativamente inferiores nas subescalas Fluências Lexicaise Séries Motoras de Luria comparativamente com a amostra de controlo(p &lt; 0,05). Na EM, a FAB discriminou os níveis de escolaridade (p &lt; 0,001) e a subescala Séries Motoras de Luria diferenciou os padrões de EM (p &lt; 0,05). Conclusões: A FAB apresenta propriedades psicométricas adequadas para avaliar as funções do lobo frontal em doentes com EM, devendo integrar a sua avaliação neuropsicológica para auxiliar no correto encaminhamento terapêutico. Adicionalmente, a subescala das Fluências Lexicais parece ser importante para avaliar estes doentes, tendo potencial para o nível I do rastreio da disfunção frontal na EM.

Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder.

Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD).Methods: Blood samples were collected from 20 patients with NMOSD and 17 patients with MS, as well as from 15 patients with Systemic Lupus Erythematosus (SLE) and 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) with density gradient separation and stained the cells with antibodies against CD14, CD15, CD16, and CD45, and analyzed the cells by flow cytometry or imaging flow cytometry. We defined LDGs as CD14−CD15high and calculated their share in total PBMC leukocytes (CD45+) as well as the share of CD16hi LDGs. Clinical data on disease course, medication, and antibody status were obtained.Results: LDGs were significantly more common in MS and NMOSD than in HDs, comparable to SLE samples (median values HD 0.2%, MS 0.9%, NMOSD 2.1%, SLE 4.3%). 0/23 of the HDs, but 17/20 NMOSD and 11/17 MS samples as well as 13/15 SLE samples had at least 0.7 % LDGs. NMOSD patients without continuous immunosuppressive treatment had significantly more LDGs compared to their treated counterparts. LDG nuclear morphology ranged from segmented to rounded, suggesting a heterogeneity within the group.Conclusion: LDGs are a feature of the immunophenotype in some patients with MS and NMOSD.

Patient-reported outcomes in multiple sclerosis: Validation of the Quality of Life in Neurological Disorders (Neuro-QoL™) short forms.

BackgroundPatient-reported outcome (PRO) measures have been shown to be effective for tracking treatment outcomes in multiple sclerosis (MS). However, collecting PROs as part of the clinical standard of care can be time-consuming and examination of their validity for use in an MS sample has been limited.ObjectiveTo determine the discriminant validity of the Quality of Life in Neurological Disorders (Neuro-QoL™) short forms in a real-world MS clinic population.Design/MethodsNeuro-QoL is a series of questionnaires for tracking physical function, emotional/cognitive health, and social abilities in clinical populations. Neuro-QoL data from 902 MS patients were analyzed for psychometric properties and factor structure.ResultsNeuro-QoL demonstrated acceptable reliability in the moderate-to-good ranges. Moderate support for convergent validity was observed with other measures of MS quality of life, disease severity, and symptoms. However, results from a confirmatory factor analysis suggested poor model fit for most of the 12 domains tested.ConclusionsThese findings support the utility of some of the Neuro-QoL questionnaires in evaluating MS-related PROs. However, additional research may help abridge and strengthen these measures for use in this population.

Astrocytes in the Pathogenesis of Multiple Sclerosis: An In Situ MicroRNA Study

Astrocytes are increasingly recognized as active contributors to the disease process in multiple sclerosis (MS), rather than being merely reactive. We investigated the expression of a selected microRNA (miRNA) panel that could contribute both to the injury and to the recovery phases of the disease. Individual astrocytes were laser microdissected from brain sections. We then compared the miRNAs' expressions in MS and control brain samples at different lesional stages in white versus grey matter regions. In active MS lesions, we found upregulation of ischemia-related miRNAs in white but not grey matter, often with reversion to the normal state in inactive lesions. In contrast to our previous findings on MS macrophages, expression of 2 classical inflammatory-related miRNAs, miRNA-155 and miRNA-146a, was reduced in astrocytes from active and chronic active MS lesions in white and grey matter, suggesting a lesser direct pathogenetic role for these miRNAs in astrocytes. miRNAs within the categories regulating aquaporin4 (-100, -145, -320) and glutamate transport/apoptosis/neuroprotection (-124a, -181a, and -29a) showed some contrasting responses. The regional and lesion-stage differences of expression of these miRNAs indicate the remarkable ability of astrocytes to show a wide range of selective responses in the face of differing insults and phases of resolution.

Serum Neurofilament Light Chain Levels in Patients With Presymptomatic Multiple Sclerosis

Unrecognized demyelinating events often precede the clinical onset of multiple sclerosis (MS). Identification of these events at the time of occurrence would have implications for early diagnosis and the search of causal factors for the disease. To assess whether serum neurofilament light chain (sNfL) levels are elevated before the clinical MS onset. Nested case-control study among US military personnel who have serum samples stored in the US Department of Defense Serum Repository. Serum samples were collected from 2000 to 2011; sNfL assays and data analyses were performed from 2018 to 2019. We selected 60 case patients with MS who either had 2 samples collected before onset (mean follow-up, 6.3 years) or 1 sample collected before and 1 after onset (mean follow-up, 1.3 years), among 245 previously identified case patients. For each case, we randomly selected 1 of 2 previously identified control individuals matched by age, sex, race/ethnicity, and dates of sample collection. The sample size was chosen based on the available funding. Serum NfL concentrations measured using an ultrasensitive single-molecule array assay (Simoa). Log-transformed sNfL concentrations in case patients and control individuals compared using conditional logistic regression and linear mixed models. Mean age at baseline was 27.5 years, and 92 of 120 participants (76.7%) were men. Serum NfL levels were higher in case patients with MS compared with their matched control individuals in samples drawn a median of 6 years (range, 4-10 years) before the clinical onset (median, 16.7 pg/mL; interquartile range [IQR], 12.6-23.1 pg/mL vs 15.2 pg/m; IQR, 10.3-19.9 pg/mL; P = .04). This difference increased with decreasing time to the case clinical onset (estimated coefficient for interaction with time = 0.063; P = .008). A within-person increase in presymptomatic sNfL levels was associated with higher MS risk (rate ratio for ≥5 pg/mL increase, 7.50; 95% CI, 1.72-32.80). The clinical onset was associated with a marked increase in sNfL levels (median, 25.0; IQR, 17.1-41.3 vs 45.1; IQR, 27.0-102.7 pg/mL for presymptomatic and postonset MS samples; P = .009). The levels of sNfL were increased 6 years before the clinical MS onset, indicating that MS may have a prodromal phase lasting several years and that neuroaxonal damage occurs already during this phase.

High openness and high extroversion are linked with better time-based prospective memory in multiple sclerosis.

Prospective memory (PM) deficits are often reported in multiple sclerosis (MS), but their relationship with neuropsychological characteristics and personality traits remains to be explored. To systematically investigate both time-based and event-based PM abilities in a sample of MS without clinically relevant disability or global cognitive decline and to explore cognitive, neuropsychiatric characteristics and personality traits associated with PM deficits. Thirty-three patients with MS and 33 healthy individuals were enrolled in the study. All participants underwent a standardized measure of PM to evaluate both time-based and event-based PM. Moreover, patients with MS completed the Brief Repeatable Battery to assess cognitive functioning, the Beck Depression Inventory-II and the Dimensional Apathy Scale to assess neuropsychiatric characteristics, and the NEO Personality Inventory-3 to assess personality traits. Individuals with MS demonstrated impaired time-based PM compared to healthy individuals. The regression analysis showed that poor performance in time-based PM was significantly related to lower extroversion and openness traits, whereas poor performance in event-based PM was significantly related to lower visuospatial memory abilities. Low levels of openness and extroversion traits are associated with a greater risk of developing time-based PM deficit. Therefore, personality assessment and behavioural interventions should be encouraged in MS clinical practice.

Limb apraxia profiles in different clinical samples

Objective: Limb apraxia is a motor cognitive disorder that has been mainly studied in patients with dementia or left hemisphere stroke (LHS). However, limb apraxia has also been reported in patients with right hemisphere stroke (RHS), multiple sclerosis (MS) or traumatic brain injury (TBI). This study’s aim was to report detailed praxis performance profiles in samples suffering from these different neurological disorders by use of the Diagnostic Instrument for Limb Apraxia (DILA-S).Method: 44 LHS patients, 36 RHS patients, 27 patients with dementia, 26 MS and 44 TBI patients participated. The diagnostics included the imitation of meaningless and meaningful hand gestures, pantomime of tool-use, single real tool-use as well as a multistep naturalistic action task (preparing breakfast).Results: Apraxia occurred in all tested samples but to a varying degree and with dissimilar profiles. LHS patients demonstrated most severe deficits in pantomime, but they were also vulnerable to deficits in real tool-use. Dementia patients showed high incidence rates of apraxia in almost all subscales of the DILA-S. RHS patients demonstrated difficulties in imitation and pantomime of tool-use, but they did not show severe difficulties with real tool-use. TBI patients appeared challenged by multistep naturalistic actions. The tested MS sample did not show clinically relevant symptoms in the DILA-S.Conclusion: Different types of patients display varying limb apraxic symptoms detectable by the DILA-S. In these limb apraxia susceptible populations, testing should be warranted as standard. Prospectively, individual error profiles may be helpful for shaping motor cognitive training.

Acid sensing ion channel 2: A new potential player in the pathophysiology of multiple sclerosis.

Acid‐sensing ion channels (ASICs) are proton‐gated channels involved in multiple biological functions such as: pain modulation, mechanosensation, neurotransmission, and neurodegeneration. Earlier, we described the genetic association, within the Nuoro population, between Multiple Sclerosis (MS) and rs28936, located in ASIC2 3′UTR. Here we investigated the potential involvement of ASIC2 in MS inflammatory process. We induced experimental autoimmune encephalomyelitis (EAE) in wild‐type (WT), knockout Asic1−/− and Asic2−/− mice and observed a significant reduction of clinical score in Asic1−/− mice and a significant reduction in the clinical score in Asic2−/− mice in a limited time window (i.e., at days 20–23 after immunization). Immunohistochemistry confirmed the reduction in adaptive immune cell infiltrates in the spinal cord of EAE Asic1−/− mice. Analysis of mechanical allodynia, showed a significant higher pain threshold in Asic2−/− mice under physiological conditions, before immunization, as compared to WT mice and Asic1−/−. A significant reduction in pain threshold was observed in all three strains of mice after immunization. More importantly, analysis of human autoptic brain tissue in MS and control samples showed an increase of ASIC2 mRNA in MS samples. Subsequently, in vitro luciferase reporter gene assays, showed that ASIC2 expression is under possible miRNA regulation, in a rs28936 allele‐specific manner. Taken together, these findings suggest a potential role of ASIC2 in the pathophysiology of MS.

Spectrum of Microbial Sequences and a Bacterial Cell Wall Antigen in Primary Demyelination Brain Specimens Obtained from Living Patients

Multiple sclerosis (MS) is an autoimmune disease characterized by multiple lesions in the brain and spinal cord. We used RNA sequencing to identify microbial sequences and characterize human gene expression patterns in 30 human brain biopsy specimens. RNAs which aligned to known microbial taxa, were significantly enriched in 10 of 12 primary demyelination (MS) brain specimens compared to a group of 15 epilepsy controls, leading to a list of 29 MS microbial candidate genera from 11 different phyla. Most of the candidate MS microbes are anaerobic bacteria. While there were some shared candidates, each of the 10 MS samples with significant microbial RNA enrichment had a distinct set microbial candidates. The fraction of microbial sequencing reads was greater for the MS group (128.8 PPM) compared to the controls (77.4 PPM, p = 0.016). Bacterial peptidoglycan was demonstrated in brain tissue sections from several MS subjects. Human gene expression analysis showed increased expression of inflammation-related pathways in the MS group. This data shows that demyelinating brain lesions are associated with the presence of microbial RNA sequences and bacterial antigen. This suggests that MS is triggered by the presence of a diverse set of microbes within a lesion.

Generalizing remotely supervised transcranial direct current stimulation (tDCS): feasibility and benefit in Parkinson\u2019s disease

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown to improve common symptoms of neurological disorders like depressed mood, fatigue, motor deficits and cognitive dysfunction. tDCS requires daily treatment sessions in order to be effective. We developed a remotely supervised tDCS (RS-tDCS) protocol for participants with multiple sclerosis (MS) to increase accessibility of tDCS, reducing clinician, patient, and caregiver burden. The goal of this protocol is to facilitate home use for larger trials with extended treatment periods. In this study we determine the generalizability of RS-tDCS paired with cognitive training (CT) by testing its feasibility in participants with Parkinson’s disease (PD).MethodsFollowing the methods in our MS protocol development, we enrolled sixteen participants (n = 12 male, n = 4 female; mean age 66 years) with PD to complete ten open-label sessions of RS-tDCS paired with CT (2.0 mA × 20 min) at home under the remote supervision of a trained study technician. Tolerability data were collected before, during, and after each individual session. Baseline and follow-up measures included symptom inventories (fatigue and sleep) and cognitive assessments.ResultsRS-tDCS was feasible and tolerable for patients with PD, with at-home access leading to high protocol compliance. Side effects were mostly limited to mild sensations of transient itching and burning under the electrode sites. Similar to prior finding sin MS, we found preliminary efficacy for improvement of fatigue and cognitive processing speed in PD.ConclusionsRS-tDCS paired with CT is feasible for participants with PD to receive at home treatment. Signals of benefit for reduced fatigue and improved cognitive processing speed are consistent across the PD and MS samples. RS-tDCS can be generalized to provide tDCS to a range of patients with neurologic disorders for at-home rehabilitation.Trial registrationClinicalTrials.gov Identifier: NCT02746705. Registered April 21st 2016.

BP180 Autoantibodies Target Different Epitopes in Multiple Sclerosis or Alzheimer’s Disease than in Bullous Pemphigoid

Neurologic patients have an increased risk for bullous pemphigoid (BP), in which autoantibodies target BP180, a cutaneous basement membrane protein also expressed in the brain. Here we show that 53.6% of sera from patients with multiple sclerosis (MS) (n= 56) had IgG reactivity against full-length BP180 in immunoblotting, while in BP180 non-collagenous 16A ELISA (n= 143), only 7.7% of MS samples studied were positive. Epitope mapping with 13 fusion proteins covering the entire BP180 polypeptide revealed that in MS and Alzheimer's disease (AD) patients, IgG autoantibodies target regions located in the intracellular and mid-extracellular parts of BP180, but not the well-known BP epitopes located in the non-collagenous 16A domain and the distal partofextracellular domain. In indirect immunofluorescence analysis, 8.1% of MS sera recognized the cutaneous basement membrane and in full-length BP180 ELISA analysis, 7.5% MS and AD sera were positive, indicating thatthese autoantibodies rarely recognize BP180 in its native conformation. Thus, in MS and ADpatients,BP180autoantibodies have a different epitope profile than in patients with BP, and seldom bindtonative BP180.This explains the inability of these autoantibodies to cause skin symptoms. Our resultssuggest that the autoantibodies against BP180 alone are not sufficient to induce BP in MS and AD patients.

Moral Cognition and Multiple Sclerosis: A Neuropsychological Study

Recent literature proved that social cognition impairments may characterize the neuropsychological profile of Multiple Sclerosis (MS) patients. However, little is still known about moral cognition in MS. In this study, we evaluated non-social, social, and moral cognitive performances in 45 relapsing-remitting MS patients. Patients underwent the Brief International Cognitive Assessment for Multiple Sclerosis battery, the Cognitive Estimation and Stroop tasks, the Ekman-60 Faces test, the Reading the Mind in the Eye and Story-based Empathy task. Additionally, a task of moral dilemmas including both "instrumental" and "incidental" conditions was administered to patients. Forty-five age-, gender- and education-matched healthy control subjects (HC) were enrolled for comparisons. The majority of patients (i.e., 77.6%) showed deficits at non-social tasks, particularly in the executive domains. A subset of MS sample (i.e., 24%) presented with emotion recognition and socio-affective processing impairments. Overall, MS patients showed comparable levels of moral judgment with respect to HC. The rate of yes/no response in resolution of moral dilemmas and scores of attribution of emotional valence were comparable between groups. Nevertheless, lower moral permissibility and emotional arousal, particularly for the instrumental dilemmas, characterized the MS profile. Significant correlations between the attribution of emotional valence to moral actions and mentalizing scores emerged. Our findings expand current literature on MS supporting not only deficits in executive and socio-emotional domains but also low levels of permissibility of immoral actions and emotional detachment in the moral judgment process.

IFNAR1 expression level in Iranian multiple sclerosis patients treated with IFN-B.

Multiple sclerosis (MS) as an auto-immune disease is an inflammatory, demyelinating disease of the central nervous system. Certain genes have shown to be involved in the initiation of MS but the specific role of some of them, e.g. IFNAR1 has not been identified in certain populations yet. The IFNAR1 as a type I membrane protein shapes one of the two chains of a receptor for interferons alpha and beta. To find out how IFNAR1 functions in the Iranian population, the researchers compared the expression level of this gene in relapsing-remitting MS (RR-MS) samples with normal individuals. RNA from the whole blood of 50 RR-MS patients and 50 normal controls were extracted. All patients were HLA-DRB1*15 negative and were responders to interferon-beta with a normal vitamin D level. The level of IFNAR1 gene expression was measured using quantitative RT-PCR. According to the results the RR-MS patients manifested a statistically higher expression level of IFNAR1 than their normal counterparts (p= 0.012). Age-wise, females between the ages, 30 to 40 had a significant increase (p= 0.046) but males under 30 showed a statistically meaningful decrease in the expression level (p= 0.04). In terms of sex, only the female patients manifested a statistically significant increase in IFNAR1 (p= 0.004). The overall results show an increase in IFNAR1 level in MS patients treated with IFN-B.

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis.

Multiple sclerosis (MS) is an immune mediated, inflammatory and demyelinating disease of the central nervous system (CNS). Substantial evidence points toward monocytes and macrophages playing prominent roles early in disease, mediating both pro‐ and anti‐inflammatory responses. Monocytes are subdivided into three subsets depending on the expression of CD14 and CD16, representing different stages of inflammatory activation. To investigate their involvement in MS, peripheral blood mononuclear cells from 40 patients with incipient or progressed MS and 20 healthy controls were characterized ex vivo. In MS samples, we demonstrate a highly significant increase in nonclassical monocytes (CD14+CD16++), with a concomitant significant reduction in classical monocytes (CD14++CD16−) compared with healthy controls. Also, a significant reduction in the surface expression of CD40, CD163, and CD192 was found, attributable to the upregulation of the nonclassical monocytes. In addition, significantly increased levels of human endogenous retrovirus (HERV) envelope (Env) epitopes, encoded by both HERV‐H/F and HERV‐W, were specifically found on nonclassical monocytes from patients with MS; emphasizing their involvement in MS disease. In parallel, serum and cerebrospinal fluid (CSF) samples were analyzed for soluble biomarkers of inflammation and neurodegeneration. For sCD163 versus CD163, no significant correlations were found, whereas highly significant correlations between levels of soluble neopterine and the intermediate monocyte (CD14++CD16+) population was found, as were correlations between levels of soluble osteopontin and the HERV Env expression on nonclassical monocytes. The results from this study emphasize the relevance of further focus on monocyte subsets, particularly the nonclassical monocytes in monitoring of inflammatory diseases.

Validation and cross-cultural adaptation of the COMPASS-31 in Croatian and Serbian patients with multiple sclerosis.

To validate and cross-culturally adapt Croatian and Serbian versions of composite autonomic symptom score-31 (COMPASS-31) for the detection of dysautonomia in patients with multiple sclerosis (MS). A total of 179 patients, 67 with clinically isolated syndrome (CIS) and 112 with MS, completed the COMPASS-31 at two MS centers in Zagreb and Belgrade between April 1 and October 31, 2016. Demographic and clinical data including age, gender, MS phenotypes, and the Expanded Disability Status Scale (EDSS) score were collected. The Cronbach's alpha coefficient of COMPASS-31 total score was 0.844 for the Croatian MS sample and 0.779 for the Serbian MS sample. A joint analysis yielded Cronbach's alpha coefficients ranging from 0.394 to 0.796, with values in four domains higher than 0.700. In Croatian and Serbian samples and the total study sample, the Cronbach's alpha coefficient of COMPASS-31 was 0.785. Reproducibility measured by intra-class correlation coefficient (ICC) was acceptable (ICC=0.795). With regard to the clinical validity, significant correlation was found between EDSS and the COMPASS-31 total score (P<0.001). Furthermore, significant differences between MS phenotypes were detected for bladder and gastrointestinal domains and for the COMPASS-31 total score (PP<0.001, P=0.005, and P=0.027, respectively). Finally, significant differences between MS phenotypes in patients with score >0, which implies the existence of at least one of the symptoms investigated in each domain, were detected for secretomotor and bladder domains (P=0.015 and PP<0.001, respectively). COMPASS-31 represents a valid and acceptable self-assessment instrument for the detection of dysautonomia in MS patients.

Monitoring disease activity in multiple sclerosis using serum neurofilament light protein.

Objective:To examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS).Methods:NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months. The CSF NFL concentration was measured with the UmanDiagnostics NF-light enzyme-linked immunosorbent assay. The serum NFL concentration was measured with an in-house ultrasensitive single-molecule array assay.Results:In MS, the correlation between serum and CSF NFL was r = 0.62 (p < 0.001). Serum concentrations were significantly higher in patients with relapsing-remitting MS (16.9 ng/L) and in patients with progressive MS (23 ng/L) than in HCs (10.5 ng/L, p < 0.001 and p < 0.001, respectively). Treatment with DMT reduced median serum NFL levels from 18.6 (interquartile range [IQR] 12.6–32.7) ng/L to 15.7 (IQR 9.6–22.7) ng/L (p < 0.001). Patients with relapse or with radiologic activity had significantly higher serum NFL levels than those in remission (p < 0.001) or those without new lesions on MRI (p < 0.001).Conclusions:Serum and CSF NFL levels were highly correlated, indicating that blood sampling can replace CSF taps for this particular marker. Disease activity and DMT had similar effects on serum and CSF NFL concentrations. Repeated NFL determinations in peripheral blood for detecting axonal damage may represent new possibilities in MS monitoring.