Thalamic atrophy and dysconnectivity are associated with cognitive impairment in a multi-center, clinical routine, real-word study of people with relapsing-remitting multiple sclerosis.

BACKGROUND: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient. OBJECTIVE: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting. METHODS: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed. RESULTS: 332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized ß = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized ß = -0.14, p = 0.028) in a linear regression model. CONCLUSIONS: PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting.

Agreement Between Published Reference Resources for Neurofilament Light Chain Levels in People With Multiple Sclerosis.

OBJECTIVES: To examine the agreement between published reference resources for neurofilament light chain (NfL) applied to a large population of people with multiple sclerosis (MS). METHODS: Six published reference resources were used to classify NfL in participants in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network as elevated or normal and to derive age-specific NfL Z-scores. NfL values were classified as elevated if they exceeded the >95th percentile (i.e., Z-score >1.645) of the age-specific reference range. Furthermore, age-specific NfL Z-scores could be derived for 4 of 6 reference resources. RESULTS: NfL measurements were assessed from 12,855 visits of 6,687 people with MS (median 2 samples per individual [range 1-7]). The mean ± SD age was 47.1 ± 11.7 years, 72.1% of participants were female, disease duration was 15.0 ± 10.6 years, body mass index was 28.6 ± 6.9 kg/m2, and serum NfL was 12.87 ± 12.86 pg/mL. Depending on the selection of the reference resource, the proportion of NfL measurements classified as elevated varied from 3.7% to 30.9%. The kappa coefficient across the 6 reference resources used was 0.576 (95% CI 0.571-0.580) indicating moderate agreement. Spearman correlations between Z-scores derived from the various reference resources exceeded 0.90; however, concordance coefficients were lower, ranging from 0.72 to 0.89. DISCUSSION: Interpretation of blood NfL values may vary markedly depending on the selection of the reference resource. Borderline elevated values should be interpreted with caution, and future studies should focus on standardizing NfL measurement and reporting across laboratories/platforms, better characterizing the effects of confounding/influencing factors, and defining the performance of NfL (including as part of multimodal predictive algorithms) for prediction of disease-specific outcomes.

Accelerometry measures of physical activity and sedentary behavior: Associations with cognitive functioning in MS.

BACKGROUND: Cognitive dysfunction is a pervasive symptom of multiple sclerosis (MS). Correlational evidence on the relationships between physical activity, sedentary behavior, and cognition has been mixed and limited to a few activity measures. The collinearity of accelerometry-based metrics has precluded an assessment of the full activity spectrum. Here, we aimed to examine the rich set of activity measures using analytic approaches suitable for collinear metrics. We investigated the combination of physical activity, sedentary, and clinicodemographic measures that explain the most variance in composite scores of working memory/processing speed, visual memory, and verbal memory. METHODS: We analyzed baseline accelerometry and neuropsychological data (n = 80) from a randomized controlled trial of pedometer tracking. Using partial least squares regression (PLSR), we built three models to predict latent scores on the three domains of cognition using 12 activity metrics, sex, education, and Expanded Disability Status Scale (EDSS) scores. Significance was assessed using linear regression models with model component scores as predictors and cognitive composites as outcomes. RESULTS: The latent component was significant for working memory/processing speed but was not significant for visual memory and verbal memory after Bonferroni correction. Working memory/processing speed was positively associated with average kilocalories, moderate-to-vigorous physical activity (MVPA), steps, and sex (i.e., higher scores in males) and negatively related to duration of long sedentary bouts and EDSS. CONCLUSIONS: These findings suggest that increasing overall energy expenditure through walking and MVPA, while decreasing prolonged sedentary time may positively benefit working memory/processing speed in people with MS. TRIAL REGISTRATION: This RCT #NCT03244696 was registered on Clinicaltrials.gov (https://www. CLINICALTRIALS: gov/ct2/show/NCT03244696).

Associations of sNfL with clinico-radiological measures in a large MS population.

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice. METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay. RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with sNfL-E included male sex, younger age, progressive disease subtype, diabetes mellitus, impaired renal function, and active smoking. Higher body mass index (BMI) was associated with lower odds of elevated sNfL. Active treatment with disease-modifying therapy was associated with lower odds of sNfL-E. MS participants with sNfL-E exhibited worse neurological function (patient-reported disability, walking speed, manual dexterity, and cognitive processing speed), lower brain parenchymal fraction, and higher T2 lesion volume. Longitudinal analyses revealed accelerated short-term rates of whole brain atrophy in sNfL-E participants and higher odds of new T2 lesion development, although both MS participants with or without sNfL-E exhibited faster rates of whole brain atrophy compared to HC. Findings were consistent in analyses examining age-normative sNfL Z-scores as a continuous variable. INTERPRETATION: Elevated sNfL is associated with clinical disability, inflammatory disease activity, and whole brain atrophy in MS, but interpretation needs to account for comorbidities including impaired renal function, diabetes, and smoking.

Satisfaction with alemtuzumab in relapsing multiple sclerosis patients: Results from the real-world PRO-ACT study.

Background: Patient-reported outcomes are increasingly used in the management of patients with multiple sclerosis to understand the patient's perspective of disease and treatment. These measures provide insights into important factors including treatment satisfaction, physical and psychological function, and quality of life. Objective: To present results from the real-world PRO-ACT study in patients with multiple sclerosis who switched to alemtuzumab from another disease-modifying therapy. Methods: This 24-month, prospective, multicenter, observational study had a primary endpoint of change in overall satisfaction, measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4. Secondary endpoints included the Multiple Sclerosis Impact Scale-29 (MSIS-29), Modified Fatigue Impact Scale-5 (MFIS-5), and the Patient-Determined Disease Steps (PDDS). Safety was monitored with adverse events (AEs). Results: Of 199 enrolled patients, improvements were observed in mean TSQM scores for overall satisfaction (baseline, 50.3; year 2, + 13.2; p < 0.0001), effectiveness (49.3 and + 12.2; p < 0.0001), and side effects (77.6 and + 4.5; p = 0.04). Improvements were also observed in MSIS-29 physical (52.4 and -6.0; p < 0.0001), MSIS-29 psychological (53.4 and -7.0; p = 0.0003), and MFIS-5 (12.8 and -1.7; p < 0.0001). Most (95.0%) patients experienced ≥ 1 AE (88.4% mild, 67.8% moderate). Conclusions: The primary endpoint was met; the safety of alemtuzumab was consistent with pivotal studies.

Impact of mindfulness training on emotion regulation in multiple sclerosis: Secondary analysis of a pilot randomized controlled trial.

Purpose/Objective Research: This secondary analysis of a pilot randomized controlled trial in people with multiple sclerosis (PwMS) aimed to compare mindfulness-based training (MBT), adaptive cognitive training (aCT), and a waitlist control (WL) on the use of emotion regulation strategies during daily worries and ruminations. Further, we examined cognitive functioning as a moderator of training effects. RESEARCH METHOD/DESIGN: Sixty-one PwMS were randomized into an MBT, aCT, or a WL control group for four weeks. Participants completed daily diaries assessing their use of emotion regulation strategies and measures of cognitive functioning at pre- and posttraining. The frequency of acceptance use, maladaptive strategies, and cognitive reappraisal, as well as the success of acceptance use, were the primary outcomes of interest. We also examined whether a cognitive composite score moderated treatment gains. RESULTS: Relative to pretraining, at posttraining, participants in the MBT group used acceptance more frequently, and this change was significantly greater compared to the change in aCT and WL groups. Training did not have differential effects on the frequency of maladaptive strategy and cognitive reappraisal use or on the success of acceptance use. Cognitive functioning did not moderate observed treatment gains. CONCLUSION/IMPLICATIONS: Our findings, based on this pilot study, suggest that after brief training in mindfulness meditation, PwMS used more acceptance strategies to regulate their emotions. Future studies with larger sample sizes, longer duration of treatment, and longitudinal follow-up are needed to better understand the efficacy of mindfulness mediation for promoting affective and cognitive health in PwMS. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Static and group-based trajectory analyses of factors associated with non-adherence in patients with multiple sclerosis newly-initiating once- or twice-daily oral disease-modifying therapy.

Background: Increased understanding of adherence may facilitate optimal targeting of interventions. Objective: To utilize group-based trajectory modeling (GBTM) to understand longitudinal patterns of adherence and factors associated with non-adherence in patients with multiple sclerosis (MS) newly-initiating once-/twice-daily oral disease-modifying therapy (DMT) (fingolimod, dimethyl fumarate, or teriflunomide). Methods: Commercial plan data were analyzed using proportion of days covered (PDC) to evaluate factors associated with non-adherence. GBTM clustered patient subgroups with similar longitudinal patterns of adherence measured by monthly PDC (≥80%) and multinomial logistic regression identified factors associated with adherence trajectory subgroups. Results: Among 7689 patients, 39.5% were non-adherent to once-/twice-daily oral DMTs. Characteristics associated with non-adherence (PDC<80%) included younger age, female, depression or migraine, switching during follow-up, more frequent dosing, relapse, and absence of magnetic resonance imaging. GBTM elucidated three adherence subgroups: Immediately Non-Adherent (14.9%); Gradually Non-Adherent (19.5%), and Adherent (65.6%). Additional factors associated with adherence (i.e. region, chronic lung disease) were identified and factors differed among trajectory subgroups. Conclusion: These analyses confirmed that a significant proportion of patients with MS are non-adherent to once-/twice-daily oral DMTs. Unique patterns of non-adherence and factors associated with patterns of adherence emerged. The approach demonstrated how quantitative trajectories can help clinicians develop tailored interventions.

Dimethyl fumarate is associated with lower rates of infection and lower infection-related healthcare costs when compared with ocrelizumab.

BACKGROUND: Infections in people with multiple sclerosis (PwMS) may have a detrimental effect on disease progression, risk of hospitalization, and healthcare resource utilization (HRU). The infection risk and HRU costs may vary between disease-modifying therapies (DMTs); however, the individual risks and differences associated with DMTs are not well characterized. Some DMTs may increase the risk for infections in PwMS; however, previous studies have reported an intact humoral immune response in dimethyl fumarate (DMF)-treated patients. The objective was to compare infection-related HRU and healthcare costs (HCCs) between PwMS treated with DMF or ocrelizumab (OCR). METHODS: Eligible patients were identified from the Optum US claims database between April 2017 and September 2020 (DMF n = 1429; OCR n = 3170). Patients were followed from index date to first occurrence of: (1) end of study, (2) end of insurance eligibility, (3) discontinuation of index DMT, or (4) switch from index DMT to another DMT. Outcomes were annualized rate of infection encounters (defined as infection encounters [n] during follow-up window / days followed [n] × 365); annualized infection-related HCCs (defined as aggregated costs of infection encounters during follow-up window / days followed [n] × 365); location-specific infections, and overall infection-related events. Propensity score matching (PSM) 1:1 method was used; PS was calculated via logistic regression for probability of DMF treatment conditional on demographics and comorbidities. Mean differences (MD) were reported for infection encounter measures. RESULTS: After PSM, DMF and OCR cohorts (n = 1094 in each cohort) were balanced based on baseline characteristics (standardized MD of adjusted baseline characteristics <0.1). Mean (standard deviation) follow-up was 296 (244) days for DMF patients and 297 (243) for OCR patients. DMF patients experienced lower annualized rates of overall infection encounters vs OCR patients (MD -0.51 [95% confidence interval (CI): -0.92 to -0.11], p = 0.01). When stratified by type of infection encounter, DMF patients experienced significantly lower annualized rates of outpatient (MD [95% CI]: -0.44 [-0.80 to -0.08], p = 0.02) and inpatient/hospitalization infection encounters (-0.08 [-0.14 to -0.02], p<0.01) vs OCR patients. A trend towards a shorter duration of infection-related hospitalization in the DMF vs the OCR group was observed (MD [95% CI]: -2.20 [-4.73 to 0.26] days, p = 0.08). The most common infection types in both DMT groups were urinary tract infections, sepsis, and pneumonia. DMF patients experienced lower annualized infection-related HCCs (MD [95% CI]: -$3642 [-$6380 to -$904], p < 0.01) vs OCR patients, which were driven largely by infection-related hospitalization costs (-$3639 [-$6019 to -$1259], p < 0.01). CONCLUSION: DMF-treated patients PS-matched with OCR patients experienced lower annualized rates of infection encounters and lower infection-related HCCs.

A promising cognitive screener in multiple sclerosis: The NIH toolbox cognition battery concords with gold standard neuropsychological measures.

BACKGROUND: Routine cognitive screening is a priority in MS clinical care. The National Institutes of Health Toolbox (NIHTB) Cognition Battery is a 30-min instrument validated in neurological populations excluding MS. OBJECTIVES: To assess construct validity of NIHTB tests and compare classification of cognitive impairment with gold-standard tests. To evaluate relationships between fluid cognition and clinical measures. METHODS: Eighty-seven individuals, aged 30-59 years, completed the NIHTB, Minimal Assessment of Cognitive Function in MS (MACFIMS), Wechsler Adult Intelligence Scale-IV subtests, and measures of disease severity, depression, and fatigue. RESULTS: The NIHTB showed adequate convergent validity for processing speed, working memory, and episodic memory. Although fluid cognition scores from the NIHTB and MACFIMS classified a similar proportion of participants as cognitively impaired, the two batteries differed in which individuals were classified as impaired versus preserved. NIHTB fluid cognition was inversely correlated with disease severity but not related to depression or fatigue. CONCLUSIONS: The NIHTB concords with gold-standard measures, and classifies cognitive impairment at similar rates to the MACFIMS. Adjusted NIHTB fluid cognition was negatively associated with disease severity suggesting clinical utility. Psychometric validation of the NIHTB in clinical practice will elucidate its promise as a cognitive screener in MS.

Trait mindfulness, emotion dysregulation, and depression in individuals with multiple sclerosis.

OBJECTIVES: Emotion dysregulation plays a role in the development and maintenance of psychopathology. Given the higher rates of mood disturbances in people with multiple sclerosis (PwMS), there is a need to explore the relationships between metrics of emotion dysregulation and potential protective traits. Mindfulness, a multi-faceted trait characteristic reflecting present moment awareness, is one such trait showing promise for positive associations with affective health. The current project assessed the relationship between trait mindfulness, the use of emotion regulation strategies during an emotionally evocative task, and depression in PwMS. METHODS: Sixty-one PwMS completed a worry/rumination induction task that examined emotion regulation strategy use in response to emotionally evocative stimuli. RESULTS: Higher trait mindfulness was associated with both lower symptoms of depression and greater employment of acceptance-based strategies following worry and rumination inductions. Acceptance use mediated the relationship between trait mindfulness and symptoms of depression. CONCLUSIONS: Our results suggest that the association between trait mindfulness and emotion dysregulation extends to the use of emotion regulation strategies during an emotionally evocative task. Additionally, emotion regulation strategy use, and acceptance in particular, may play a role in the relationship between trait mindfulness and depression. These findings suggest that increasing levels of mindfulness through clinical interventions may present a path toward improving emotion regulation, and by extension, reducing the symptoms of depression in PwMS.

Employing Connectome-Based Models to Predict Working Memory in Multiple Sclerosis.

Introduction: Individuals with multiple sclerosis (MS) are vulnerable to deficits in working memory (WM), but the search for neural correlates of WM within circumscribed areas has been inconclusive. Given the widespread neural alterations observed in MS, predictive modeling approaches that capitalize on whole-brain connectivity may better capture individual differences in WM. Materials and Methods: We applied connectome-based predictive modeling to functional magnetic resonance imaging data from WM tasks in two independent samples with relapsing-remitting MS. In the internal sample (ninternal = 36), cross-validation was used to train a model to predict accuracy on the Paced Visual Serial Addition Test from functional connectivity. We hypothesized that this MS-specific model would successfully predict performance on the N-back task in the validation cohort (nvalidation = 36). In addition, we assessed the generalizability of existing WM networks derived in healthy young adults to these samples, and we explored anatomical differences between the healthy and MS networks. Results: We successfully derived an MS-specific predictive model of WM in the internal sample (full: rs = 0.47, permuted p = 0.011), but the predictions were not significant in the validation cohort (rs = -0.047; p = 0.78, mean squared error [MSE] = 0.006, R2 = -2.21%). In contrast, the healthy networks successfully predicted WM in both MS samples (internal: rs = 0.33 p = 0.049, MSE = 0.009, R2 = 13.4%; validation cohort: rs = 0.46, p = 0.005, MSE = 0.005, R2 = 16.9%), demonstrating their translational potential. Discussion: Functional networks identified in a large sample of healthy individuals predicted significant variance in WM in MS. Networks derived in small samples of people with MS may have limited generalizability, potentially due to disease-related heterogeneity. The robustness of models derived in large clinical samples warrants further investigation. ClinicalTrials.gov ID: NCT03244696.

Balancing Potential Benefits and Risks of Bruton Tyrosine Kinase Inhibitor Therapies in Multiple Sclerosis During the COVID-19 Pandemic.

Bruton tyrosine kinase inhibitors (BTKis) encompass a new class of therapeutics currently being evaluated for the treatment of multiple sclerosis (MS). Whether BTKis affect COVID-19 risk or severity or reduce vaccine efficacy are important but unanswered questions. Here, we provide an overview on BTKi mechanisms relevant to COVID-19 infection and vaccination and review preliminary data on BTKi use in patients with COVID-19. BTKis block B-cell receptor- and myeloid fragment crystallizable receptor-mediated signaling, thereby dampening B-cell activation, antibody class-switching, expansion, and cytokine production. Beyond antibodies, COVID-19 severity and vaccine efficacy appear largely linked to T-cell responses and interferon induction, processes not directly affected by BTKis. Given that B cells have clear roles in antigen presentation to T cells, however, it is possible that BTKis may indirectly interfere with beneficial or detrimental T-cell responses during COVID-19 infection or vaccination. In addition to these possible effects on generating a protective immune response, BTKis may attenuate the hyperinflammatory dysregulation often seen in severe cases of COVID-19 that evolves as a key risk factor in this disease. Currently available outcomes from BTKi-treated patients with COVID-19 are discussed. Clinical trials are currently underway to evaluate the safety and efficacy of BTKis in individuals with MS. Although limited data suggest a potential benefit of BTKis on outcomes for some COVID-19 patients, data from adequately powered, prospective and randomized clinical trials are lacking. Likewise, the specific effect of BTKis on the safety and efficacy of COVID-19 vaccines remains to be determined. Any potential unknown risks that BTKi therapy may present to the patient relative to COVID-19 infection, severity, and vaccine efficacy must be balanced with the importance of timely intervention to prevent or minimize MS progression.

Harnessing Real-World Data to Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS).

Background: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial implementation of MS PATHS and initial patient characteristics. Methods: MS PATHS is an ongoing initiative conducted in 10 healthcare institutions in three countries, each contributing standardized information acquired during routine care. Institutional participation required the following: active MS patient census of ≥500, at least one Siemens 3T magnetic resonance imaging scanner, and willingness to standardize patient assessments, share standardized data for research, and offer universal enrolment to capture a representative sample. The eligible participants have diagnosis of MS, including clinically isolated syndrome, and consent for sharing pseudonymized data for research. MS PATHS incorporates a self-administered patient assessment tool, the Multiple Sclerosis Performance Test, to collect a structured history, patient-reported outcomes, and quantitative testing of cognition, vision, dexterity, and walking speed. Brain magnetic resonance imaging is acquired using standardized acquisition sequences on Siemens 3T scanners. Quantitative measures of brain volume and lesion load are obtained. Using a separate consent, the patients contribute DNA, RNA, and serum for future research. The clinicians retain complete autonomy in using MS PATHS data in patient care. A shared governance model ensures transparent data and sample access for research. Results: As of August 5, 2019, MS PATHS enrolment included participants (n = 16,568) with broad ranges of disease subtypes, duration, and severity. Overall, 14,643 (88.4%) participants contributed data at one or more time points. The average patient contributed 15.6 person-months of follow-up (95% CI: 15.5-15.8); overall, 166,158 person-months of follow-up have been accumulated. Those with relapsing-remitting MS demonstrated more demographic heterogeneity than the participants in six randomized phase 3 MS treatment trials. Across sites, a significant variation was observed in the follow-up frequency and the patterns of disease-modifying therapy use. Conclusions: Through digital health technology, it is feasible to collect standardized, quantitative, and interpretable data from each patient in busy MS practices, facilitating the merger of research and patient care. This approach holds promise for data-driven clinical decisions and accelerated systematic learning.

Real-world adherence to, and persistence with, once- and twice-daily oral disease-modifying drugs in patients with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Nonadherence to disease-modifying drugs (DMDs) for multiple sclerosis (MS) is associated with poorer clinical outcomes, including higher rates of relapse and disease progression, and higher medical resource use. A systematic review and quantification of adherence and persistence with oral DMDs would help clarify the extent of nonadherence and nonpersistence in patients with MS to help prescribers make informed treatment plans and optimize patient care. The objectives were to: 1) conduct a systematic literature review to assess the availability and variability of oral DMD adherence and/or persistence rates across 'real-world' data sources; and 2) conduct meta-analyses of the rates of adherence and persistence for once- and twice-daily oral DMDs in patients with MS using real-world data. METHODS: A systematic review of studies published between January 2010 and April 2018 in the PubMed database was performed. Only studies assessing once- and twice-daily oral DMDs were available for inclusion in the analysis. Study quality was evaluated using a modified version of the Newcastle-Ottawa Scale, a tool for assessing quality of observational studies. The random effects model evaluated pooled summary estimates of nonadherence. RESULTS: From 510 abstracts, 31 studies comprising 16,398 patients with MS treated with daily oral DMDs were included. Overall 1-year mean medication possession ratio (MPR; n = 4 studies) was 83.3% (95% confidence interval [CI] 74.5-92.1%) and proportion of days covered (PDC; n = 4 studies) was 76.5% (95% CI 72.0-81.1%). Pooled 1-year MPR ≥80% adherence (n = 6) was 78.5% (95% CI 63.5-88.5%) and PDC ≥80% (n = 5 studies) was 71.8% (95% CI 59.1-81.9%). Pooled 1-year discontinuation (n = 20) was 25.4% (95% CI 21.6-29.7%). CONCLUSIONS: Approximately one in five patients with MS do not adhere to, and one in four discontinue, daily oral DMDs before 1 year. Opportunities to improve adherence and ultimately patient outcomes, such as patient education, medication support/reminders, simplified dosing regimens, and reducing administration or monitoring requirements, remain. Implementation of efforts to improve adherence are essential to improving care of patients with MS.

Effects of 4-week mindfulness training versus adaptive cognitive training on processing speed and working memory in multiple sclerosis.

OBJECTIVE: The aim of this preregistered, secondary analysis of a pilot randomized controlled trial (NCT02717429) was to compare the impact of 4-week mindfulness-based training and adaptive cognitive training, with a waitlist control condition, on processing speed and working memory in people with multiple sclerosis (PwMS). METHOD: Sixty-one PwMS were randomized to mindfulness-based training (MBT), adaptive computerized cognitive training (aCT), or a waitlist (WL) control group and completed the Brief Repeatable Battery of Neuropsychological Tests at pre- and posttraining. Training-related changes on the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) were the primary outcomes of interest. Baseline cognitive status was examined as a moderator of treatment gains. Practice time, change in aCT game difficulty, and rate of change in state awareness across MBT were assessed as correlates of cognitive gains. FINDINGS: Compared with aCT and WL, mindfulness training significantly improved processing speed (ηp² = .14). Baseline cognitive status did not moderate change in processing speed (ηp² = .005) or working memory (ηp² = .014). Practice time and change in game difficulty were not significantly correlated with cognitive gains (all ps > .49). In the MBT group, rate of change in awareness was significantly associated with improvement in working memory (ρ = .52, p = .04). CONCLUSIONS: In PwMS, 4 weeks of mindfulness meditation training improved processing speed above and beyond aCT and WL. More rapid change in awareness during mindfulness training may be associated with greater gains in working memory. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Burden of relapsing-remitting multiple sclerosis on workers in the US: a cross-sectional analysis of survey data.

BACKGROUND: Multiple sclerosis (MS) is prevalent among working age individuals (20-60 years), leading to high burden on work productivity. Few data are available about the absenteeism and presenteeism in employed individuals with MS in comparison to non-MS personnel. This study aimed to quantify the burden of illness of employed US adults with relapsing-remitting multiple sclerosis (RRMS) and examine burden by levels of work impairment. METHODS: A retrospective cross-sectional analysis was conducted using patient-reported responses from the US National Health and Wellness Survey (NHWS). Data from NHWS 2015-2016 were analyzed from 196 employed RRMS respondents who were matched 1:4 to employed respondents without MS based on demographic and general health characteristics. Demographic and general health characteristics for employed RRMS individuals were analyzed by levels of work impairment (none, 1-30%; 31-68%; 69-100%). Work productivity (absenteeism, presenteeism, and work impairment), decrements in health-related quality of life (HRQoL) (short form-36, EQ-5D), and healthcare resource utilization (HCRU) were compared to determine the burden of RRMS. RESULTS: After propensity score matching, the levels of absenteeism and presenteeism were 2 and 1.8 times higher in the employed RRMS population than the employed non-MS population, respectively (P < 0.001 for both). HRQoL was significantly lower in employed respondents with RRMS than those without MS (P < 0.001 for all). Employed respondents with RRMS had significantly more HCRU over 6 months compared to those without MS (P < 0.001). Furthermore, among employed RRMS respondents, greater levels of impairment were associated with increasing disease severity, greater healthcare resource use, fatigue, and cognitive impairment and inversely associated with mental and physical HRQoL (P < 0.0001 for all). CONCLUSIONS: Among employed individuals, respondents with RRMS had lower, work productivity, HRQoL, and higher HCRU as compared with those without MS. Given the large impact RRMS has on work impairment, a need exists to manage individuals on therapies that improve HRQoL, reduce symptoms, and improve their ability to perform in the workforce.

Examining trait mindfulness, emotion dysregulation, and quality of life in multiple sclerosis.

OBJECTIVE: Dispositional mindfulness exhibits a positive association with quality of life (QoL). One potential mechanism for this association is enhanced emotion regulation abilities. Individuals with multiple sclerosis (MS) experience a range of physical, cognitive, and affective impairments, thus reducing overall QoL. The current cross-sectional study examines the relation between trait mindfulness and QoL, mediated by emotion dysregulation in individuals with MS. METHOD: Ninety-five participants with self-reported MS completed an online survey that incorporated self-report measures of trait mindfulness, emotion dysregulation, and QoL. Although clinically significant depression was exclusionary, we observed a wide range of depressive symptoms in our sample. These scores were thus entered as a moderator in the mediation analysis. RESULTS: Dispositional mindfulness correlated positively with QoL, with lower emotion dysregulation partially mediating the correlation. Depression scores moderated the observed mediation, such that the effect was stronger in those with higher symptoms of depression. CONCLUSIONS: Trait mindfulness is positively associated with QoL in individuals with MS. Reduced emotion dysregulation may be a critical pathway linking mindfulness and QoL in MS, especially in those with higher symptoms of depression.

Concise review: modeling multiple sclerosis with stem cell biological platforms: toward functional validation of cellular and molecular phenotypes in inflammation-induced neurodegeneration.

In recent years, tremendous progress has been made in identifying novel mechanisms and new medications that regulate immune cell function in multiple sclerosis (MS). However, a significant unmet need is the identification of the mechanisms underlying neurodegeneration, because patients continue to manifest brain atrophy and disability despite current therapies. Neural and mesenchymal stem cells have received considerable attention as therapeutic candidates to ameliorate the disease in preclinical and phase I clinical trials. More recently, progress in somatic cell reprogramming and induced pluripotent stem cell technology has allowed the generation of human "diseased" neurons in a patient-specific setting and has provided a unique biological tool that can be used to understand the cellular and molecular mechanisms of neurodegeneration. In the present review, we discuss the application and challenges of these technologies, including the generation of neurons, oligodendrocytes, and oligodendrocyte progenitor cells (OPCs) from patients and novel stem cell and OPC cellular arrays, in the discovery of new mechanistic insights and the future development of MS reparative therapies.

Reproductive issues in women with multiple sclerosis: ethical considerations.

Addressing the reproductive concerns of women with multiple sclerosis (MS) is vital for comprehensive care. Contraception, conception, pregnancy, and breast-feeding present many vexing questions to the woman with MS. The risks and benefits of using disease-modifying therapy during the various stages of a woman's reproductive life are topics that need to be discussed. The physician's primary duty is to the patient; however, the physician must also consider the fetus and later the child. In helping guide the patient in making medical decisions, the physician must take into account the patient's motivation for those decisions, including family obligations, cultural norms, and patient values. The physician is instrumental in providing the patient with sound, nonjudgmental information and advice so that she may make a well-informed, autonomous decision about her health and her disease.