Multiple Sclerosis Disease Duration Research Articles

Diffuse white matter pathology in multiple sclerosis during treatment with dimethyl fumarate-An observational study of changes in normal-appearing white matter using proton magnetic resonance spectroscopy.

Multiple sclerosis (MS) is an inflammatory demyelinating disease with neurodegenerative features causing risk for neurologic irreversible disability over time. Examination of normal-appearing white matter (NAWM) changes in MS by proton magnetic resonance spectroscopy (1H-MRS), may detect diffuse white matter pathology that is associated with neurodegeneration. In this observational study of in total twenty-six patients with MS, starting treatment with dimethyl fumarate (DMF), we measured the absolute concentration of metabolites in periventricular NAWM using 1H-MRS at baseline and after one and three years of treatment. Metabolite concentrations were analyzed both cross-sectionally, in relation to 10 controls and longitudinally in relation to disease activity. Patients with MS had higher concentrations of myo-inositol (mIns) in NAWM at baseline compared with controls (mean 5.98 ± 1.37 (SD) and 4.32 ± 1.16 (SD), p<0.01, independent samples t-test). The disease duration was inversely correlated with concentrations of total N-acetylaspartate and N-acetylaspartylglutamate (tNA) (r = -0.62, p<0.01) in NAWM as well as positively to the ratio of mIns and tNA (r = 0.51, p = 0.03). Metabolite concentrations during one-year (n = 19) and three-years (n = 11) follow-up were generally stable. The dropouts were caused by treatment switch after one year, mainly due to new MRI activity. Cross-sectional analyses showed that there was an inverse correlation between concentrations of tNA and mIns at both baseline and at 1 and 3-years follow-up (r = -0.44 to -0.65, p = 0.04 to 0.004). Metabolite concentrations were stable during 1-year follow-up independently of disease activity. Higher concentrations of the astrogliosis marker mIns in MS compared to controls, the inverse relation between MS disease duration and the neuroaxonal integrity marker tNA, as well as the consistent inverse relation between these two metabolites during follow-up, showed that non-lesional white matter pathology is present in this cohort of MS patients in early disease stages. However, metabolite concentrations during follow-up were generally stable and did not reflect differences in disease activity among patients.

Hospitalisations and humoral COVID-19 vaccine response in vaccinated rituximab-treated multiple sclerosis patients

BackgroundPatients with multiple sclerosis (MS) treated with anti-CD20 therapies such as rituximab may have increased risk of severe COVID-19 disease. Vaccination induces protective immunity, but humoral vaccine response is known to be attenuated in rituximab-treated MS-patients-patients, which has indicated a need for real world data on severe morbidity and mortality from COVID-19 after vaccination. MethodsRituximab-treated patients treated at Haukeland University Hospital were identified through the National MS Registry and invited to participate in the study by giving a consent and providing a blood sample 3 weeks or later after ordinary COVID-19- vaccination, i.e. 2 doses given with a standard interval of 3 weeks. Blood samples were analysed with Enzyme-Linked Immunosorbent assay (ELISA) to evaluate humoral vaccine response with screening test against receptor-binding domain (RBD) and confirmatory Spike IgG-specific ELISA. A haemagglutination test (HAT) was performed as a marker of neutralizing antibodies. Patient serum concentration of rituximab were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS). Registry data from the Norwegian MS registry and information on hospitalization from patient records were collected and linked to laboratory results. Results111 patients were included in the study. A total of 7 (6.3%) were hospitalized due to COVID-19 disease during the observation period. No patient was admitted to ICU and there were no deaths. 34.2% did not have detectable titre of SARS CoV-2 Spike IgG antibodies, 72.1% did not have a detectable titre of SARS CoV-2 RBD antibodies, and 88.2% did not have a detectable HAT titre. There was a correlation between hospitalisation and the absence of SARS CoV-2 Spike IgG antibody titre, and between hospitalisation and MS disease duration, as well as between spike IgG antibody titre and CD19 B-cell count, time since last rituximab infusion, cumulative rituximab treatment time and total IgG level in the patients. ConclusionA substantial proportion of rituximab-treated MS-patients-patients did not have detectable humoral vaccine responses after 2 doses of COVID-19 vaccination. Despite this, the cumulative percentage of patients hospitalized with COVID-19 disease throughout the observation period of 22 months was low, and no patients required ICU treatment. The results support that vaccinated MS-patients treated with rituximab have a protective effect against serious Covid-19 infection.

Clinical utility of the Lumipulse™ immunoassay for plasma neurofilament light chain in multiple sclerosis

ObjectiveBlood neurofilament light chain (NfL) is robustly associated with disease worsening in multiple sclerosis (MS), though potentially affected by concomitant factors also determining neuro-axonal loss. We investigated the association between plasma NfL (pNfL) measured with Lumipulse™ immunoassay and demographic and clinical variables in MS. MethodsThis cross-sectional study included 685 people with MS (age 49.7 ± 12.4 years; sex 65.55% females). On the same day, we collected plasma samples, along with demographics, comorbidities, and clinical variables (MS disease duration, expanded disability status scale (EDSS), Symbol Digit Modalities Test (SDMT), descriptor of disease progression, current disease modifying treatment (DMT), number of previous DMTs, evidence of disease activity in the past year (i.e. relapse or MRI new lesions), EDSS progression). pNfL was evaluated using Lumipulse™ fully automated chemiluminescent enzyme immunoassay. ResultsOn multivariable linear regression model, higher pNfL was associated with higher EDSS (Coeff = 1.73; 95%CI 0.78, 2.68; p < 0.01), recent disease activity (Coeff = 15.70; 95%CI = 5.35, 26.06; p < 0.01), and presence of cardiovascular comorbidity (Coeff = 3.84; 95%CI 0.48, 7.20; p = 0.025). Lower pNfL was found in patients on DMT treatment (Coeff = −10.23; 95%CI -18.42, −2.04; p = 0.015), when compared with no DMT (reference). For 77.81% of our population there was correspondence between pNfL levels and two previously-validated cutoffs. ConclusionspNfL measured using Lumipulse™ confirms known associations with MS activity, disability and treatments, and related confounding (e.g., cardiovascular comorbidity), thus granting further utilization in research and clinical practice.

Biological variation in cervical spinal cord MRI morphometry in healthy individuals and people with multiple sclerosis.

Conclusions from prior literature regarding the impact of sex, age, and height on spinal cord (SC) MRI morphometrics are conflicting, while the effect of body weight on SC morphometrics has been found to be nonsignificant. The purpose of this case-control study is to assess the associations between cervical SC MRI morphometric parameters and age, sex, height, and weight to establish their potential role as confounding variables in a clinical study of people with multiple sclerosis (MS) compared to a cohort of healthy volunteers. Sixty-nine healthy volunteers and 31 people with MS underwent cervical SC MRI at 3 Tesla field strength. Images were centered at the C3/C4 intervertebral disc and processed using Spinal Cord Toolbox v.4.0.2. Mixed-effects linear regression models were used to evaluate the effects of biological variables and disease status on morphometric parameters. Sex, age, and height had significant effects on cord and gray matter (GM) cross-sectional area (CSA) as well as the GM:cord CSA ratio. There were no significant effects of body weight on morphometric parameters. The effect of MS disease duration on cord CSA in the C4 level was significant when controlling for all other variables. Studies of disease-related changes in SC morphometry should control for sex, age, and height to account for physiological variation.

Alpha Calcitonin Gene-related Peptide, Neuropeptide Y, and Substance P as Biomarkers for Diagnosis and Disease Activity and Severity in Multiple Sclerosis.

Alpha calcitonin gene-related peptide (aCGRP), neuropeptide Y (NPY), and substance P (SP) are neuropeptides that have emerged recently as potent immunomodulatory factors with potential as novel biomarkers and therapeutic targets in multiple sclerosis (MS). The study aimed to detect serum levels of aCGRP, NPY, and SP in MS patients versus healthy controls and their association with disease activity and severity. Serum levels were measured in MS patients and age and sex-matched healthy controls using ELISA. We included 67 MS patients: 61 relapsing-remitting MS (RR-MS) and 6 progressive MS (PR-MS), and 67 healthy controls. Serum NPY level was found to be lower in MS patients than in healthy controls (p < 0.001). Serum aCGRP level was higher in PR-MS compared to RR-MS (p = 0.007) and healthy controls (p = 0.001), and it positively correlated with EDSS (r = 0.270, p = 0.028). Serum NPY level was significantly higher in RR-MS and PR-MS than in healthy controls (p < 0.001 and p = 0.001, respectively), and it was lower in patients with mild or moderate/severe disease than in healthy controls (p < 0.001). Significant inverse correlations were found between SP level and MS disease duration (r = -0.279, p = 0.022) and duration of current DMT (r = -0.315, p = 0.042). Lower serum levels of NPY were revealed in MS patients compared to healthy controls. Since serum levels of aCGRP are significantly associated with disease activity and severity, it is a potential disease progression marker.

Sirtuin-1 level and gene polymorphisms in multiple sclerosis

BackgroundSirtuin-1 (SIRT1) may affect multiple sclerosis (MS) disease. This study aimed to investigate the level of serum SIRT1, mRNA expression and genetic polymorphisms in Egyptian MS sufferers. Also, to assess its role as a possible biomarker in predicting the risk of MS and to evaluate the association between its levels and disability of MS. Measurement of SIRT1, serum level, mRNA expression level and genotyping for sirtuin-1 gene polymorphisms in 240 Egyptian subjects; 120 MS sufferers and 120 healthy control subjects.ResultsThere was a significant diminishment of level of serum sirtuin-1, and sirtuin-1 mRNA expression in MS sufferers compared to control subjects. Different sirtuin-1 single nucleotide polymorphism frequencies were statistically significant in MS sufferers compared to the control subjects. Moreover, a negative correlation of serum level of sirtuin-1 in MS sufferers with MS disease duration, disability according to Expanded Disability Status Scale (EDSS) score, cholesterol, and triglyceride serum levels. Regarding the sirtuin-1 gene polymorphisms in MS sufferers, the rs7895833 GG genotype had significant higher cholesterol, and low-density lipoprotein (LDL) levels than the GA and AA genotypes and that the rs7069102 GG genotype had a higher LDL level than the CG and CC genotypes while the rs2273773 TT genotype was significantly associated with cholesterol, and LDL levels than the TC and CC genotypes. No significant difference was detected in EDSS score comparing different sirtuin-1 genotypes among MS sufferers. In MS sufferers, rs7895833 G allele can be independently associated with cholesterol, triglycerides, and LDL levels. rs7069102 C allele can be independently associated with LDL level. With regard to rs2273773, T allele, it can be independently associated with cholesterol and LDL levels.ConclusionThere was a significant association between different sirtuin-1 gene polymorphisms and dyslipidemia which may modulate the course of MS disease. Furthermore, serum sirtuin-1 level can be considered as a possible predictor of disability in multiple sclerosis sufferers.

Investigating the Impact of Polypharmacy and Anticholinergic Medication Burden on Objective Cognitive Performance in Adults With Multiple Sclerosis.

Polypharmacy, or the use of 5 or more daily medications, is common in adults with multiple sclerosis (MS), and is often due to various physical, cognitive, and emotional symptoms. However, research regarding the association between polypharmacy and cognitive outcomes in MS is sparse. Furthermore, individuals with MS often use medications with anticholinergic properties, which are commonly associated with cognitive impairment and other central nervous system adverse effects. Currently, the utility of scales measuring anticholinergic burden in MS is unknown. This study aims to investigate the relationship between polypharmacy, anticholinergic burden, and objective cognitive performance in MS. We recruited 90 individuals with MS during routine visits at an MS specialty clinic in Kansas City. Participants completed a brief, virtual cognitive assessment and answered questions about their health. Participants provided their medication lists from which we determined polypharmacy and scores on several anticholinergic burden scales. Statistical analyses included Spearman correlations and linear regression models. Approximately 44% of the individuals surveyed met the criteria for polypharmacy. The number of daily medications was negatively correlated with cognitive performance (rs = -0.45, P < .001). Further, the Drug Burden Index accounted for additional variance in cognitive performance beyond that explained by age, education, MS disease duration, and comorbidities [ΔR2 = .12, F(5, 84) = 7.84, P < .001.]. Clinicians should consider the possible negative consequences of polypharmacy when addressing cognitive concerns in MS. Anticholinergic burden scales may be valuable in this regard. Future investigations could explore behavioral and pharmacological interventions aimed at reducing polypharmacy in MS.

Social Cognitive Theory Variables as Correlates of Physical Activity Behavior Among Hispanics With Multiple Sclerosis

ObjectiveTo examine the association between social cognitive theory (SCT) variables and physical activity (PA) behavior in Hispanic adults with multiple sclerosis (MS). DesignObservational, survey study. SettingGeneral community. ParticipantsInclusion criteria: (a) age 18 years or older, (b) self-identify as Hispanic or Latino, (c) diagnosis of MS, and (d) English or Spanish as primary language. Two hundred forty-three individuals opened the survey, 24 individuals did not meet inclusion criteria, and 66 individuals were excluded due to not completing any of the SCT variable measures (N=153). InterventionsNot applicable. Main Outcome Measure(s)PA was measured using the Godin Leisure Time Exercise Questionnaire (GLTEQ) total and Health Contribution Scores (HCS). SCT variables included standard measures of exercise self-efficacy, planning, goal setting, outcome expectations, social support, and functional impairment. ResultsThe final sample included 153 participants with a mean (SD) age of 43 (11) years, 78% identified as women, 57% were employed, and 63% had a college degree or higher. The mean (SD) MS disease duration was 11 (9) years, 74% of participants reported relapsing remitting MS, and median (interquartile range) Patient Determined Disease Steps (PDDS) score was 3.0 (3.0). Significant correlations were observed between all SCT variables and both GLTEQ total and GLTEQ HCS scores (P<.001). Forward stepwise regression with Akaike's Information Criterion (AICC) identified PDDS, age, exercise planning, exercise self-efficacy, and exercise goal setting as the most appropriate covariates and SCT variables to include in a multivariable model examining independent contributions on GLTEQ HCS scores. The multivariable, linear regression analysis indicated that PDDS (Standardized B=-.280, P<.001), exercise planning (Standardized B=.214, P<.05), and exercise self-efficacy (Standardized B=.183, P<.05) explained 42.4% of variance in GLTEQ HCS scores. ConclusionsThis study provides a contribution to the literature by identifying SCT variables that correlate with PA behavior among Hispanics with MS that may guide the creation of culturally appropriate PA programs.

Progression risk stratification with six-minute walk gait speed trajectory in multiple sclerosis.

Multiple Sclerosis (MS) disease progression has notable heterogeneity among patients and over time. There is no available single method to predict the risk of progression, which represents a significant and unmet need in MS. MS and healthy control (HC) participants were recruited for a 2-year observational study. A latent-variable growth mixture model (GMM) was applied to cluster baseline 6-min walk gait speed trajectories (6MWGST). MS patients within different 6 MWGST clusters were identified and stratified. The group membership of these MS patients was compared against 2-year confirmed-disease progression (CDP). Clinical and patient-reported outcome (PRO) measures were compared between HC and MS subgroups over 2 years. 62 MS and 41 HC participants completed the 2-year study. Within the MS cohort, 90% were relapsing MS. Two distinct patterns of baseline 6 MWGST emerged, with one cluster displaying a faster gait speed and a typical "U" shape, and the other showing a slower gait speed and a "flattened" 6 MWGST curve. We stratified MS participants in each cluster as low- and high-risk progressors (LRP and HRP, respectively). When compared against 2-year CDP, our 6 MWGST approach had 71% accuracy and 60% positive predictive value. Compared to the LRP group, those MS participants stratified as HRP (15 out of 62 MS participants), were on average 3.8 years older, had longer MS disease duration and poorer baseline performance on clinical outcomes and PROs scores. Over the subsequent 2 years, only the HRP subgroup showed a significant worsened performance on 6 MW, clinical measures and PROs from baseline. Baseline 6 MWGST was useful for stratifying MS participants with high or low risks for progression over the subsequent 2 years. Findings represent the first reported single measure to predict MS disease progression with important potential applications in both clinical trials and care in MS.

Hippocampal volume in cases of relapsing remitting multiple sclerosis and its correlation with cognitive impairment

Background. Multiple sclerosis (MS) is a chronic inflammatory immune-mediated disease, distinguished by demyelination and oligodendropathy in the central nervous system. Cognitive impairment (CI) can impact patients at any stage of MS, including those with clinically isolated syndrome (CIS). Patients and methods. This is a prospective cross-sectional study which enrolled 60 patients with RRMS. They were subjected to cognitive scale assessment, routine brain MRI study and volumetric assessment of hippocampus. Results. This study found a significant positive correlation between duration of disease and Subjective memory complaints questionnaire (r=0.525, p=0.001). A significant negative correlation existed between disease duration and MMSE score (r=-0.404, p=0.001) and between disease duration and MoCA score (r=-0.310, p=0.016). No significant difference between both groups regarding the relative hippocampal volume. Mean relative right hippocampal volume is 0.0026 for cases versus 0.0027 among control group and mean relative left hippocampal volume is 0.0025 for cases versus 0.0026 among control group. Conclusion. Multiple sclerosis disease duration had an impact on cognitive state. However, hippocampal volume assessment did not predict the cognitive affection in patient with RRMS.

Physical activity as a correlate of symptoms, quality of life, comorbidity, and disability status in Hispanics with multiple sclerosis

BackgroundHispanics with multiple sclerosis (MS) experience disproportionate rates of mobility disability compared to non-Hispanic Whites with MS. Physical activity (PA) is highlighted as a potential adjuvant therapy for improving MS symptoms and disease progression, however less than 30% of Hispanics with MS report sufficient levels of PA. ObjectivesThe current study aimed to examine the correlates of PA behavior among Hispanics with MS in the North American Research Committee on Multiple Sclerosis Registry (NARCOMS). MethodsIn Spring 2015, 136 NARCOMS participants identified as Hispanic and completed the International Physical Activity Questionnaire (IPAQ). IPAQ scores were converted to Health Contribution Scores (HCS) for estimating PA. The association between the HCS scores and MS symptoms (i.e., mobility, cognition, fatigue, spasticity, hand function, bowel/bladder, sensory, tremors, depression, and pain), quality of life (QOL), comorbid conditions, and disability status were evaluated using Pearson or Spearman correlation coefficients with follow-up multivariable regression analyses. ResultsThe mean age among participants was 58 years and 79% identified as female. The mean MS disease duration was 20 years and 68% reported relapsing disease course. The mean HCS score among participants was 15.6 ± 20.9. HCS was moderately associated with disability status (rs = −0.39), mobility (rs = −0.37), bowel/bladder function (rs = −0.33), and physical health related QOL (r = 0.32). There were small associations between HCS and hand function (rs = −0.29), fatigue (rs = −0.20), and tremor (rs = −0.25). Multivariable regression analyses indicated that disability status, mobility, bowel/bladder function, and physical health related QOL were all associated with HCS but did not independently contribute to the models when controlling for age, sex, and employment. ConclusionsThis study highlights correlates of PA behavior among Hispanics with MS. Researchers and clinicians may consider disability status, mobility, and physical health related QOL in future studies examining PA among Hispanics with MS.

Effect of Vascular Comorbidity on Visual and Disability Outcomes in a Secondary Progressive Multiple Sclerosis Clinical Trial Cohort.

Vascular comorbidity (VC) is associated with multiple sclerosis (MS) disease progression and visual dysfunction. The longitudinal effect of VC in people with secondary progressive MS (SPMS) is unclear. This study explored the impact of VC on standard clinical, MRI, and visual outcomes in people with SPMS enrolled in a clinical trial. Data were extracted from a 2-year randomized controlled trial (N = 51) testing the supplement lipoic acid in people with SPMS who underwent annual Expanded Disability Status Scales, Timed 25-Foot Walk tests, MRIs, visual acuity testing, and retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCIPL) thicknesses per optical coherence tomography (OCT). Post hoc linear mixed-effects regression analysis compared baseline and annualized outcomes between participants without VC (VC-) and with 1 or more VCs (VC+) (hypertension, dyslipidemia, obesity, diabetes, peripheral or cardiovascular disease, tobacco use). The VC- (n = 19) and VC+ (n = 28) participants were similar in age, sex, and MS disease duration and had comparable MS disability, mobility, and brain atrophy at baseline and throughout the 2-year parent study. The VC+ participants had worse baseline visual acuity than those in the VC- group by 0.13 logMAR (P = .041). No significant differences were detected in RNFL or GCIPL baseline thickness or atrophy between groups. In an SPMS cohort, VC had an inconsistent effect on standard clinical, MRI, and exploratory OCT outcomes, suggesting that the effect of VC may not be evident in smaller cohort studies. Using a more refined definition of VC in future, adequately powered investigations may help effectively elucidate and account for the interaction between vascular risk burden and MS disability.

Diagnostic utility of 3D DIR MRI in the estimation of MS lesions overall load with special emphasis on cortical subtypes

BackgroundA number of magnetic resonance imaging studies have shown that a significant proportion of multiple sclerosis (MS) lesions are located in the cerebral cortex and correlate with the patient's disability level. Double inversion recovery (DIR) has a higher sensitivity to detect cortical lesions and their different types. The aim of our study was to assess the superiority of 3D DIR as compared to FLAIR in detecting the different cortical subtypes and to enhance its role as a test for the clinical disability of the patient.ResultsThe current study included 82 MS patients (60 female and 22 male with mean age of 34.5 ± 8.2 years); 59 cases having relapsing–remitting MS, 5 having secondary progressive MS, and 4 having primary progressive MS, as well as eight clinically isolated syndrome cases, and six radiologically isolated syndrome cases. DIR was superior to FLAIR in MS plaque number detection of cortical plaque-types 1, 2, 3 and 4 with a p value < 0.001. DIR was superior to FLAIR for detection of overall cortical types, juxtacortical and juxtacortical extended MS plaques with p = < 0.001, 0.010 and < 0.001, respectively. DIR was significantly better than FLAIR for MS plaque number detection in the periventricular white matter, subcortical white matter, infratentorial region and the overall MS plaques burden with a p < 0.001, 0.038, < 0.001, < 0.001, respectively. No significant difference was noted between both sequences for plaques number detection in deep white matter and deep gray matter. A significant correlation between MS disease duration, number of attacks and EDSS and the overall cortical MS plaques types and the overall MS plaque burden.Conclusion3D DIR is a reliable tool and provides superior delineation in detecting cortical subtypes. In addition, DIR is of value in assessing the degree of clinical and cognitive impairment of MS affected patients.

Significance of serum VIP and PACAP in multiple sclerosis: an exploratory case-control study.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. Vasoactive and intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are neuropeptides that play roles in anti-inflammation and neuroprotection in MS. In this study, we aimed to determine the serum levels of VIP and PACAP in MS patients versus healthy controls and to correlate them with demographics and clinical characteristics. Serum samples were collected from MS patients (n = 145) and healthy controls (n = 73) to measure serum levels VIP and PACAP. VIP serum levels were lower in MS patients than healthy controls (p < 0.001). Serum PACAP levels were the same among the two groups. Gender-based analysis showed that VIP levels were lower in healthy females (1238.840pg/ml) than healthy males (3300.105pg/ml; p < 0.001), and PACAP serum levels were significantly lower in male MS patients (48,516.214fg/ml) than female MS patients (62,466.400fg/ml; p = 0.029). ROC curve suggested that serum VIP level can discriminate patients with MS from healthy controls. Relapsing-remitting MS, progressive-MS, and clinically isolated syndrome groups were different in age, MS disease duration, EDSS score, and VIP levels (p < 0.05). MS disease type and history of previous relapses in the preceding 24months predicted serum VIP levels, while gender predicted PACAP levels. VIP serum levels are decreased in MS patients and can be used to differentiate between MS patients and healthy controls. Further studies with larger sample sizes are required to investigate VIP as a marker to reflect MS disease progression.

Evaluation of short-term safety of COVID-19 vaccines in patients with multiple sclerosis from Latin America.

BackgroundTo date, there are no data available on the safety of COVID-19 vaccines in Latin American patients with Multiple Sclerosis (MS).ObjectiveCharacterize safety of COVID-19 vaccines in Latin American (LATAM) patients with Multiple Sclerosis (pwMS).MethodsA cross-sectional study between February 1, 2021, and April 30, 2021. Individuals with MS from LATAM countries were invited to participate in a self-administered web-based survey, through MS patient organizations from the region.Results393 vaccinated pwMS from 10 different Latin American countries were included. The vaccines administered were: inactivated virus vaccines (IVV) in 38.2% of patients, adenovirus vector vaccines (AdV) in 48.8% and mRNA vaccines 13%. All patients received at least one dose of any of the COVID-19 vaccines and 123 (31.3%) declared receiving a second dose. Mean (SD) age 41.5 (11.8) years, 82.4% female, MS disease duration: 8.4 (8.2) years. No serious adverse events were reported with any of the COVID-19 vaccines after either the first or second dose. A lower frequency of adverse events was found with IVV (22%) in comparison with AdV (46.4%) and mRNA (35.3%) (p < 0.01). Five participants reported having an MS relapse after IVV first dose.ConclusionCOVID-19 vaccines applied in LATAM proved safe for MS patients.

Demographic, clinical, and symptomatic correlates of subjective sleep quality in adults with multiple sclerosis

BackgroundThis study examined a comprehensive set of demographic, clinical, and symptomatic variables as correlates of subjective sleep quality in adults with multiple sclerosis (MS). MethodsParticipants with MS(N=485) completed the Pittsburgh Sleep Quality Index(PSQI), a demographics and clinical characteristics questionnaire, the Patient Determined Disease Steps Scale(PDDS), the Fatigue Severity Scale, and the Hospital Anxiety and Depression Scale. We conducted bivariate Spearman's rho (ρ) correlation analyses and multiple linear regression analysis for identifying variables associated with PSQI scores. ResultsParticipants had a mean (standard deviation) age of 55.4 (12.6) years and were mostly female (78%) with a median [interquartile range] PDDS of 2.0[3.0]. Higher levels of fatigue (ρ=0.32), more symptoms of anxiety (ρ=0.39) and depression (ρ=0.36), younger age (ρ=−0.12), lower income status (ρ=−0.13), shorter MS disease duration (ρ=−0.11), being in a minority group (ρ=0.09), and being unemployed (ρ=−0.10) were associated with worse sleep quality. There were no significant associations between gender, marital status, parental status, education level, disability status, or MS disease type and sleep quality. The overall regression model accounted for 26.3% of variance in sleep quality (F[8,229.8]=20.25) and there were significant coefficients for anxiety(β=0.25), fatigue(β=0.18), depression(β=0.16), and employment status(β=−0.12), but not disease duration, age, race, or income level. DiscussionParticipants with higher levels of anxiety, fatigue, and depression and who were unemployed reported worse sleep quality in our sample of adults with MS. These results may identify specific subgroups of the MS population that experience more sleep problems, and therefore are in greatest need for interventions designed to improve sleep impairment.

Differences in correlates of fatigue between relapsing and progressive forms of multiple sclerosis

BackgroundFatigue is one of the most prevalent and impactful symptoms for people with multiple sclerosis (MS). Yet, fatigue is less understood in progressive forms of MS, and few studies have explored the extent to which MS disease course is associated with fatigue. The current study aimed to (1) describe fatigue severity and fatigue interference (the extent to which fatigue interferes with individuals’ physical, mental, and social activities) in people with progressive MS (primary progressive MS and secondary progressive MS); (2) compare fatigue severity and fatigue interference in people with progressive forms of MS to people with relapsing-remitting MS (RRMS); and (3) identify factors associated with fatigue severity and fatigue interference in people with progressive forms of MS and RRMS. MethodsSecondary analysis of baseline data from participants with MS (N = 573; progressive forms of MS n = 142; RRMS n = 431) in a survey-based longitudinal study on healthy aging in people with a physical disability. Primary outcomes were average fatigue severity (0–10 Numerical Rating Scale), and fatigue interference (PROMIS Fatigue Short Form). Correlates were variables across the demographic and biopsychosocial domains, collected with validated self-reported measures. Statistical methods included t-test and chi-square analyses to compare fatigue severity and fatigue interference in people with progressive MS to those with RRMS, and multiple regression analyses to examine the association of variables with fatigue severity and fatigue interference. ResultsParticipants with progressive forms of MS reported moderate to severe levels of average fatigue severity (5.9 ± 2.8) and elevated levels of fatigue interference (T-Score of 58.2 ± 7.9). There were no group differences between people with progressive MS and RRMS in average fatigue severity or fatigue interference. Common factors associated with greater fatigue severity were lower income, being unemployed, shorter disease duration, greater disability, and greater sleep disturbance. Common factors associated with fatigue interference were younger age, lower income, being unemployed, greater disability, lower alcohol consumption, being a smoker, and greater sleep disturbance. For those with progressive forms of MS, longer MS disease duration was associated with lower average fatigue severity (b = -0.08, t(532) = -3.69, p < .001) and having a college degree or higher was associated with higher fatigue interference (b = 2.84, t(520) = 2.23, p = .026). ConclusionIn this sample, fatigue severity and fatigue interference were similar for progressive forms of MS and RRMS. Future research should consider if interventions that work for fatigue management in people with relapsing forms of MS work similarly for people with progressive forms of MS.

Registry of patients with multiple sclerosis and COVID-19 infection in Saudi Arabia

BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread and developed as a pandemic threatening global health. Patients with multiple sclerosis (MS)–an autoimmune demyelinating inflammatory disease of the central nervous system (CNS)–are predominantly treated with immunomodulatory/immunosuppressive disease-modifying therapies (DMTs), which can increase the risk of infection. Therefore, there is concern that these patients may have a higher risk of COVID-19. In response to growing concerns of neurologists and patients, this study aimed to determine the prevalence, severity, and possible complications of COVID-19 infection in patients with MS in Saudi Arabia (SA). MethodsIn this prospective cohort study, demographic and clinical data were obtained from patients residing in SA with MS who had a positive result for COVID-19 per reverse transcription-polymerase chain reaction test or viral gene sequencing, using respiratory or plasma samples. Comparison of COVID-19 severity groups was performed using one-way ANOVA or Kruskal-Wallis test for numerical variables and Chi-squared test for categorical variables. ResultsSeventy patients with MS and COVID-19 (71% female) were included in this analysis. Of the 53 (75.7%) patients receiving a DMT at the time of COVID-19 infection, the most frequently used DMTs were fingolimod (25%) and interferon-beta (25%). Nine (13%) patients had MS relapse and were treated with intravenous methylprednisolone in the four weeks before COVID-19 infection. The most common symptoms at the peak of COVID-19 infection were fever (46%), fatigue (37%), and headache (36%). Symptoms lasted for a mean duration of 8.7 days; all symptomatic patients recovered and no deaths were reported. COVID-19 severity was categorized in three groups: asymptomatic (n = 12), mild–not requiring hospitalization (n = 48), and requiring hospitalization (n = 10; two of whom were admitted to the intensive care unit [ICU]). Between the three groups, comparison of age, body mass index , Expanded Disability Severity Score , MS disease duration, and DMT use at the time of infection showed no significant differences. A higher percentage of patients who were admitted to hospital or the ICU (40%; p = 0.026) presented with an MS relapse within the prior four weeks compared with those who were asymptomatic or had a mild infection (both 8.3%). ConclusionThese findings present a reassuring picture regarding COVID-19 infection in patients with MS. However, patients with MS who have had a relapse in the preceding four weeks (requiring glucocorticoid treatment) may have an increased risk of severe COVID-19.

Predicting Infection Risk in Multiple Sclerosis Patients Treated with Ocrelizumab: A Retrospective Cohort Study.

BackgroundOcrelizumab safety outcomes have been well evaluated in clinical trials and open-label extension (OLE) studies. However, risk factors for infection in patients with multiple sclerosis (MS) receiving ocrelizumab have not been extensively studied in the real-world setting.ObjectiveThe aim of this study was to examine factors determining risk of self-reported infections and antimicrobial use in patients receiving ocrelizumab for MS.MethodsA retrospective, observational cohort study was conducted in patients receiving ocrelizumab at the Royal Melbourne Hospital. Infection type and number were reported by patients, and the associations of potential clinical and laboratory risk factors with self-reported infection and antimicrobial use were estimated using univariate and multivariable logistic regression models.ResultsA total of 185 patients were included in the study; a total of 176 infections were reported in 89 patients (46.1%), and antimicrobial use was identified in 47 patients (25.3%). In univariate analyses, a higher serum IgA was associated with reduced odds of infection (OR 0.44, 95% CI 0.25–0.76). In multivariable analyses, older age (OR 0.94, 95% CI 0.88–0.99), higher serum IgA (OR 0.37, 95% CI 0.17–0.80) and higher serum IgG (OR 0.81, 95% CI 0.67–0.99) were associated with reduced odds of infection. Older age (OR 0.85, 95% CI 0.75–0.96) and higher serum IgA (OR 0.23, 95% CI 0.07–0.79) were associated with reduced odds of antimicrobial use, whilst longer MS disease duration (OR 1.22, 95% CI 1.06–1.41) and higher Expanded Disability Status Scale (EDSS) score (OR 1.99, 95% CI 1.02–3.86) were associated with increased odds of antimicrobial use.ConclusionsHigher serum IgA and IgG and older age were associated with reduced odds of infection. Our findings highlight that infection risk is not uniform in patients with MS receiving ocrelizumab and substantiate the need to monitor immunoglobulin levels pre-treatment and whilst on therapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-021-00810-3.

Operationalization of a frailty index in patients with multiple sclerosis: A cross-sectional investigation

Background: Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical complexity of patients with multiple sclerosis (MS). Objective: To investigate the relationship between frailty and the clinical manifestations of MS. Methods: Patients with MS were consecutively enrolled at five tertiary dedicated services. Disability and fatigue were assessed. The phenotypes of MS were also identified. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits. Results: Overall, 745 MS patients (mean age = 48.2 years, standard deviation = 11.7 years; women 68%) were considered. The median FI value was 0.12 (interquartile range = 0.05–0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype. Conclusion: Frailty is significantly associated with major characteristics of MS. The findings of the present cross-sectional investigation should be explored in future longitudinal studies.