A randomized controlled trial of oral antipyretic treatment to reduce overheating during exercise in adults with multiple sclerosis.

BACKGROUND: Some people with multiple sclerosis (pwMS) avoid exercise due to overheating. Evidence from a variety of cooling treatments shows benefits for pwMS. OBJECTIVE: Conduct a randomized controlled trial of antipyretic treatment before exercise in pwMS. METHODS: Adults over age 18 diagnosed with relapsing-remitting MS reporting heat sensitivity during exercise were randomly assigned to one of six sequences counterbalancing aspirin, acetaminophen, placebo. At each of three study visits separated by ≥ one week, participants received 650-millograms of aspirin, acetaminophen, or placebo before completing a maximal exercise test. Primary outcomes were body temperature change and total time-to-exhaustion (TTE), secondary outcomes were physiological and patient-reported outcomes (PROs). RESULTS: Sixty participants were enrolled and assigned to treatment sequence; 37 completed ≥ one study visit. After controlling for order effects, we found that body temperature increase was reduced after aspirin (+ 0.006 ± 0.32 degrees Fahrenheit, p < 0.001) and after acetaminophen (+ 0.31 ± 0.35; p = 0.004) compared to placebo (+ 0.68 ± 0.35). TTE after aspirin (331.6 ± 76.6 s) and acetaminophen (578.2 ± 82.1) did not differ significantly from placebo (551.0 ± 78.4; p's > 0.05). Aspirin benefited all secondary outcomes compared to placebo (all p's < 0.001); acetaminophen showed broadly consistent benefits. CONCLUSION: These results support antipyretic treatment as effective for reducing overheating during exercise in pwMS and failed to support antipyretics for increasing TTE in the context of a maximal exercise test. Benefits were shown for physiological markers of exercise productivity and PROs of fatigue, pain, and perceived exertion.

Inflammatory vaginitis in four B-cell suppressed women with Multiple Sclerosis.

B-cell depleting therapies are effective in multiple sclerosis (MS) and are widely used (Hauser et al., 2017). Inflammatory vaginitis (IV), characterized by unexplained vaginal symptoms including mucopurulent discharge, pain, irritation, and dyspareunia, has been reported in one MS patient on ocrelizumab (Filikci and Jensen, 2022), and to be present in 3.5 % of women on rituximab for autoimmune diseases (Yockey et al., 2021). We report here four cases of IV in B cell depleted women with MS. B-cell reconstitution was temporally associated with improvement of IV symptoms. Further investigation and vigilance for this potential treatment emergent adverse event affecting sexual and reproductive health of women with MS is needed.

Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions.

OBJECTIVE: Postpartum, patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have increased risk for disease activity. Anti-CD20 IgG1 monoclonal antibodies (mAb) are increasingly used as disease-modifying therapies (DMTs). Patients may wish to both breastfeed and resume DMT postpartum. This study aimed to determine the transfer of anti-CD20 IgG1 mAbs, ocrelizumab, and rituximab (OCR/RTX), into mature breastmilk and describe maternal and infant outcomes. METHODS: Fifty-seven cis-women receiving OCR/RTX after 59 pregnancies and their infants were enrolled and followed up to 12M postpartum or 90 days post-infusion. Breastmilk was collected pre-infusion and serially up to 90 days and assayed for mAb concentration. Medical records and patients' questionnaire responses were obtained to assess neurologic, breastfeeding, and infant development outcomes. RESULTS: The median average concentration of mAb in breastmilk was low (OCR: 0.08 µg/mL, range 0.05-0.4; RTX: 0.03 µg/mL, range 0.005-0.3). Concentration peaked 1-7 days post-infusion in most (77%) and was nearly undetectable after 90 days. Median average relative infant dose was <1% (OCR: 0.1%, range 0.07-0.7; RTX: 0.04%, range 0.005-0.3). Forty-three participants continued to breastfeed post-infusion. At 8-12 months, the proportion of infants' growth between the 3rd and 97th World Health Organization percentiles did not differ for breastfed (36/40) and non-breastfed (14/16, p > 0.05) infants; neither did the proportion with normal development (breastfed: 37/41, non-breastfed: 11/13; p > 0.05). After postpartum infusion, two mothers experienced a clinical relapse. INTERPRETATION: These confirm minimal transfer of mAb into breastmilk. Anti-CD20 mAb therapy stabilizes MS activity before conception to the postpartum period, and postpartum treatments appears to be safe and well-tolerated for both mother and infant.

Depression symptoms and cognition in multiple sclerosis: Longitudinal evidence of a specific link to executive control.

BACKGROUND: Depression symptoms are prevalent in multiple sclerosis (MS) and associated with poorer cognition in cross-sectional studies; it is unknown whether changes in depression symptoms track with cognitive changes longitudinally. OBJECTIVE: Investigate whether changes in depression symptoms correspond with cognitive changes over time in MS, and identify specific cognitive functions related to depression symptoms. METHOD: Persons with early relapse-onset MS (n = 165) completed a depression questionnaire (Beck Depression Inventory FastScreen) and tests of cognitive speed, executive control, and memory at baseline and 3-year follow-up. One-way ANOVAs assessed differences in cognitive change across participants with worsened, stable, or improved depression symptoms from baseline to year 3. RESULTS: Change in depression symptoms was related to change in executive control (p = 0.001, ηp2 = 0.08; worsened mood with worsened executive control; improved mood with improved executive control), even when adjusting for cognitive speed (p = 0.002, ηp2 = 0.08). There were no links to cognitive speed (p = 0.826) or memory (p = 0.243). Regarding individual depression symptoms, executive control was related to loss of pleasure and suicidal thoughts. CONCLUSIONS: Executive control tracks with depression symptoms, raising hope that management of mood may improve executive control. The specific link between executive control and anhedonia implicates dysfunctional reward processing as a key component of MS depression.

A structured evaluation of cryopreservation in generating single-cell transcriptomes from cerebrospinal fluid.

Single-cell transcriptomics allows characterization of cerebrospinal fluid (CSF) cells at an unprecedented level. Here, we report a robust cryopreservation protocol adapted for the characterization of fragile CSF cells by single-cell RNA sequencing (RNA-seq) in moderate- to large-scale studies. Fresh CSF was collected from twenty-one participants at two independent sites. Each CSF sample was split into two fractions: one was processed fresh, while the second was cryopreserved for months and profiled after thawing. B and T cell receptor sequencing was also performed. Our comparison of fresh and cryopreserved data from the same individuals demonstrates highly efficient recovery of all known CSF cell types. We find no significant difference in cell type proportions and cellular transcriptomes between fresh and cryopreserved cells. Results were comparable at both sites and with different single-cell sequencing chemistries. Cryopreservation did not affect recovery of T and B cell clonotype diversity. Our CSF cell cryopreservation protocol provides an important alternative to fresh processing of fragile CSF cells.

Two cases of MT-ND5-related mitochondrial disorder misdiagnosed as seronegative neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease primarily affecting the optic nerves and spinal cord, which is usually associated with anti-aquaporin-4 antibodies. Here, we present two individuals who were negative for anti-aquaporin-4 antibodies and were initially diagnosed with seronegative NMOSD. Each patient's clinical course and radiographic features raised suspicion for an alternative disease process. Both individuals were found to have pathogenic variants of MT-ND5, encoding subunit 5 of mitochondrial complex I, ultimately leading to a revised diagnosis of a primary mitochondrial disorder. These cases illustrate the importance of biochemical and genetic testing in atypical cases of NMOSD.

Impact of the COVID-19 Pandemic on Personal Networks and Neurological Outcomes of People with Multiple Sclerosis: A Case-Control Cross-sectional and Longitudinal Analysis.

Background: The COVID-19 pandemic has negatively impacted the social fabric of people with multiple sclerosis (pwMS). Objective: To evaluate the associations between personal social network environment and neurological function in pwMS and controls during the COVID-19 pandemic and compare with the pre-pandemic baseline. Methods: We first analyzed data collected from 8 cohorts of pwMS and control participants during the COVID-19 pandemic (March-December 2020). We then leveraged data collected between 2017-2019 in 3 of the 8 cohorts for longitudinal comparison. Participants completed a questionnaire that quantified the structure and composition of their personal social network, including the health behaviors of network members. We assessed neurological disability using three interrelated patient-reported outcomes: Patient Determined Disease Steps (PDDS), Multiple Sclerosis Rating Scale â€" Revised (MSRS-R), and Patient Reported Outcomes Measurement Information System (PROMIS)-Physical Function. We identified the network features associated with neurologic disability using paired t-tests and covariate-adjusted regressions. Results: In the cross-sectional analysis of the pandemic data from 1130 pwMS and 1250 control participants, higher percent of network members with a perceived negative health influence was associated with greater neurological symptom burden in pwMS (MSRS-R: Beta[95% CI]=2.181[1.082, 3.279], p<.001) and worse physical function in controls (PROMIS-Physical Function: Beta[95% CI]=-5.707[-7.405, -4.010], p<.001). In the longitudinal analysis of 230 pwMS and 136 control participants, the networks of both pwMS and controls experienced an increase in constraint (pwMS p=.006, control p=.001) as well as a decrease in network size (pwMS p=.003, control p<.001), effective size (pwMS p=.007, control p=.013), maximum degree (pwMS p=.01, control p<.001), and percent contacted weekly or less (pwMS p<.001, control p<.001), suggesting overall network contraction during the COVID-19 pandemic. There was also an increase in percentage of kin (p=.003) in the networks of pwMS but not controls during the COVID-19 pandemic when compared to the pre-pandemic baseline. These changes in personal social network due to the pandemic were not associated with worsening neurological disability during the pandemic. Conclusions: Our findings suggest that perceived negative health influences in personal social networks are associated with worse disability in all participants during the COVID-19 pandemic. Despite the perturbation in social environment and connections during the pandemic, the stability in neurological function among pwMS suggests potential resilience.

Brain volumetric correlates of remotely versus in-person administered symbol digit modalities test in multiple sclerosis.

BACKGROUND: Prior studies in multiple sclerosis (MS) support reliability of telehealth-delivered cognitive batteries, although, to date, none have reported relationships of cognitive test performance to neural correlates across administration modalities. In this study we aimed to compare brain-behavior relationships, using the Symbol Digit Modalities Test (SDMT), the most reliable and sensitive cognitive measure in MS, measured from patients seen via telehealth versus in-person. METHODS: SDMT was administered to individuals with MS either in-person (N=60, mean age=39.7) or remotely via video conference (N=51, mean age=47.4). Magnetic resonance imaging (MRI) data was collected in 3-Tesla scanners. Using 3-dimensional T1 images cerebral, cortical, deep gray, cerebral white matter and thalamic nuclei volumes were calculated. Using a meta-analysis approach with an interaction term for participant group, individual regression models were run for each MRI measure having SDMT scores as the outcome variable in each model. In addition, the correlation and average difference between In-person and Remote group associations across the MRI measures were calculated. Finally, for each MRI variable I2 score was quantified to test the heterogeneity between the groups. RESULTS: Administration modality did not affect the association of SDMT performance with MRI measures. Brain tissue volumes showing high associations with the SDMT scores in one group also showed high associations in the other (r = 0.83; 95% CI = [0.07, 0.86]). The average difference between the In-person and the Remote group associations was not significant (ßRemote - ßIn-person = 0.14, 95% CI = [-0.04, 0.34]). Across MRI measures, the average I2 value was 14%, reflecting very little heterogeneity in the relationship of SDMT performance to brain volume. CONCLUSION: We found consistent relationships to neural correlates across in-person and remote SDMT administration modalities. Hence, our study extended the findings of the previous studies demonstrating the feasibility of remote administration of the SDMT.

Impact of resilience, social support, and personality traits in patients with neuroinflammatory diseases during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic negatively impacted the well-being of persons with neuroinflammatory diseases (pwNID). Identifying factors that influence the response to challenging conditions could guide supportive care. METHODS: 2185 pwNID and 1079 healthy controls (HCs) from five US centers completed an online survey regarding the effects of the COVID-19 pandemic on physical and psychological well-being. Survey instruments included resilience (Connor-Davidson Resilience Scale, CD-RISC), loneliness (UCLA Loneliness Scale), social support (modified social support survey, MSSS-5), personality traits (NEO-Five Factor Inventory, NEO-FFI), and disability (Patient-Determined Disability Steps (PDDS). Step-wise regression models and mediation analyses assessed whether the level of self-reported resilience, size of the social support, and specific personality traits (study predictors) were associated with self-reported disability and/or loneliness (study outcomes). RESULTS: The response rate varied significantly between the questionnaires. While, all pwNID completed the demographic questionnaire, 78.8% completed the loneliness questionnaire and 49.7% completed the NEO-FFI. Based on 787 responses, greater neuroticism (standardized ß = 0.312, p < 0.001), less social support (standardized ß = -0.242, p < 0.001), lower extraversion (standardized ß = -0.083, p=0.017), lower agreeableness (standardized ß = -0.119, p < 0.001), and lower resilience (standardized ß = -0.125, p = 0.002) were associated with the feeling of loneliness. Social support and resilience modestly but significantly mediated the association between personality traits and loneliness. Older age (standardized ß = 0.165, p < 0.001) and lower conscientiousness (standardized ß = -0.094, p = 0.007) were associated with worse disability (higher PDDS scores). There were no differences in outcomes between pwNID and HCs. CONCLUSION: Greater social support potentially attenuates the association between neuroticism and the feeling of loneliness in pwNID during the COVID-19 pandemic. Assessment of personality traits may identify pwNID that are in greater need of social support and guide targeted interventions.

Feasibility trial of a telehealth support group intervention to reduce anxiety in multiple sclerosis.

OBJECTIVE: Anxiety is common among persons with MS (PwMS), but widely accepted treatments are lacking. Group-based interventions delivered via telehealth are an accessible treatment option requiring clinical trial evidence to support feasibility and initial efficacy. We conducted a pilot feasibility trial of an online support group intervention to reduce anxiety in PwMS. METHODS: A non-randomized, parallel arm clinical trial was conducted. A total of 31 PwMS were enrolled: 20 completed a 12-week telehealth-delivered support group intervention and 11 were assigned to a survey-only control group. Primary feasibility outcomes were adherence and completion rates. Primary efficacy outcome was anxiety, secondary outcomes were depression, loneliness, distress, self-efficacy, stress, and quality of life. RESULTS: Twenty-six participants completed the study. Intervention group adherence (75%) and completion (85%) rates were acceptable. Results indicated a medium size between-group effect, suggesting a greater reduction in anxiety in the intervention group compared to the control group [U = 39.50, p = 0.045, r = 0.39]. No group differences in other outcomes were observed. CONCLUSION: A telehealth-delivered support group intervention appears feasible for further study and shows initial efficacy for the reduction of anxiety in PwMS.

Summary metrics of memory subnetwork functional connectivity alterations in multiple sclerosis.

BACKGROUND: Memory dysfunction is common in multiple sclerosis (MS); mechanistic understanding of its causes is lacking. Large-scale network resting-state functional connectivity (RSFC) is sensitive to memory dysfunction. OBJECTIVE: We derived and tested summary metrics of memory network RSFC. METHODS: Cognitive data and 3T magnetic resonance imaging (MRI) scans were collected from 235 MS patients and 35 healthy controls (HCs). Index scores were calculated as RSFC within (anteriority index, AntI) and between (integration index, IntI) dorsomedial anterior temporal and medial temporal memory subnetworks. Group differences in index expression were evaluated. Associations between index scores and memory/non-memory cognition were evaluated; relationships between T2 lesion volume (T2LV) and index scores were assessed. RESULTS: Index scores were related to memory and T2LV in MS patients, who showed marginally elevated AntI relative to HC (p = 0.06); no group differences were found for IntI. Better memory was associated with higher AntI (ß = 0.15, p = 0.018) and IntI (ß = 0.16, p = 0.014). No associations were found for non-memory cognition. Higher T2LV was associated with higher AntI and IntI; exploratory mediation analysis revealed significant inconsistent mediation, that is, higher index scores partially suppressed the negative association between T2LV and memory. CONCLUSION: Summary, within-subject metrics permit replication and circumvent challenges of traditional (incommensurate) RSFC variables to advance development of mechanistic models of memory dysfunction in MS.

Association of personality traits with physical function, cognition, and mood in multiple sclerosis.

BACKGROUND: Growing literature supports the hypothesis that personality influences health outcomes. Few studies have examined the association between personality traits and key clinical manifestations in persons with multiple sclerosis (pwMS). OBJECTIVE: To investigate whether personality traits are associated with physical function, cognition, and depression in persons with MS. METHODS: In this cross-sectional study, we analyzed data from two cohorts (UPMC, n = 365 and CUIMC, n = 129). Participants completed a personality scale (assessing neuroticism, extraversion, openness, agreeableness, and conscientiousness) and validated surveys measuring physical function, cognition, and depression. Stepwise linear regressions were used to evaluate associations between personality traits and outcome measures. RESULTS: Consistently across cohorts, higher extraversion was associated with better physical function, whereas higher neuroticism was associated with worse depression. In the first cohort, higher extraversion was associated with better cognition, while higher neuroticism was associated with greater risk for memory impairment in the second cohort. Relationships were independent of age and disease duration. CONCLUSION: Findings suggest a potentially protective role of extraversion, and a harmful role of neuroticism, in MS-specific patient-reported clinical outcomes. Increased understanding of the interplay between personality and health outcomes may inform risk models for physical decline, cognitive impairment, and depression in pwMS.

Diagnosis concealment is associated with psychosocial outcomes in persons with multiple sclerosis.

Persons with multiple sclerosis (pwMS) frequently conceal their diagnosis, fearing professional and personal repercussions of disclosing. Associations of concealment behavior and expected consequences of disclosure with psychosocial outcomes were examined in 90 pwMS who completed validated self-report measures of diagnosis concealment, loneliness, social support, and self-efficacy. More frequent concealment was related to worse loneliness (rp = 0.213, p = 0.045) and lower social support (rp = -0.211, p = 0.047), controlling for depression. Higher anticipated negative consequences of disclosure were associated with worse loneliness (rp = 0.263, p = 0.013), lower social support (rp = -0.338, p < 0.001), and lower self-efficacy (rp = -0.350, p < 0.001). Findings hold implications for the development of psychological support strategies addressing concealment/disclosure issues and their psychosocial consequences.

Compassionate-use pocapavir and immunoglobulin therapy for treatment of rituximab-associated enterovirus meningoencephalitis.

A 71-year-old woman previously on rituximab treatment for rheumatoid arthritis presented with 2 years of progressive neurologic symptoms. She was found to have persistent hypogammaglobulinemia and B cell depletion despite rituximab discontinuation a year prior. MRI revealed diffuse meningeal enhancement along the entire neuroaxis. LP showed a CSF lymphocytic pleocytosis, elevated protein, and presence of enterovirus by PCR. The patient was hospitalized several times for progressive clinical and radiologic decline, though she had transient improvements following treatment with immunoglobulin therapy. Her CSF remained positive for enterovirus PCR for at least 12 months. Though two brain biopsies were non-diagnostic, pan-Enterovirus was ultimately identified using a high-throughput next-generation sequencing technique. She was treated with compassionate-use pocapavir with clinical stabilization at 4-month follow-up; however, she expired 8 months later from a bacterial pneumonia.

Associations of social network structure with cognition and amygdala volume in multiple sclerosis: An exploratory investigation.

BACKGROUND: Humans are inherently social, biologically programmed to connect with others. Social connections are known to impact mental and physical health. OBJECTIVE: The aim of this study was to test whether social network structure is linked to cognition, mood, fatigue, and regional brain volumes in persons with multiple sclerosis (MS). METHODS: A questionnaire quantifying individual-level social network structure (size, density, effective size, and constraint), a comprehensive battery of neuropsychological tests, and magnetic resonance imaging (MRI) was administered to 51 persons with relapsing-remitting MS. Linear regressions assessed associations of network variables to cognition, depression, fatigue, and structural brain volumes. RESULTS: Higher network density and constraint, indicating stronger connections among network members, were associated with worse language functions. Conversely, larger network effective size, a measure of non-redundant network members, was associated with better language functions. No relationships of network structure to depression or fatigue were found. Larger network size was related to larger amygdala volume. CONCLUSION: Findings suggest that social network structure is linked to language function and amygdala volume in persons with MS. Patients with close-knit networks showed worse language function than those with open networks. Longitudinal studies with larger samples are warranted to evaluate potential causal links between social network structure and MS-related cognitive impairment.

Machine learning to investigate superficial white matter integrity in early multiple sclerosis.

BACKGROUND AND PURPOSE: This study aims todetermine the sensitivity of superficial white matter (SWM) integrity as a metric to distinguish early multiple sclerosis (MS) patients from healthy controls (HC). METHODS: Fractional anisotropy and mean diffusivity (MD) values from SWM bundles across the cortex and major deep white matter (DWM) tracts were extracted from 29 early MS patients and 31 age- and sex-matched HC. Thickness of 68 cortical regions and resting-state functional-connectivity (RSFC) among them were calculated. The distribution of structural and functional metrics between groups were compared using Wilcoxon rank-sum test. Utilizing a machine learning method (adaptive boosting), 6 models were built based on: 1-SWM, 2-DWM, 3-SWM and DWM, 4-cortical thickness, or 5-RSFC measures. In model 6, all features from previous models were incorporated. The models were trained with nested 5-folds cross-validation. Area under the receiver operating characteristic curve (AUCroc ) values were calculated to evaluate classification performance of each model. Permutation tests were used to compare the AUCroc values. RESULTS: Patients had higher MD in SWM bundles including insula, inferior frontal, orbitofrontal, superior and medial temporal, and pre- and post-central cortices (p < .05). No group differences were found for any other MRI metric. The model incorporating SWM and DWM features provided the best classification (AUCroc = 0.75). The SWM model provided higher AUCroc (0.74), compared to DWM (0.63), cortical thickness (0.67), RSFC (0.63), and all-features (0.68) models (p < .001 for all). CONCLUSION: Our results reveal a non-random pattern of SWM abnormalities at early stages of MS even before pronounced structural and functional alterations emerge.

Vaccination Against SARS-CoV-2 in Neuroinflammatory Disease: Early Safety/Tolerability Data.

BACKGROUND: Patients with autoimmune disease and on immunotherapy were largely excluded from seminal anti-SARS-CoV-2 vaccine trials. This has led to significant vaccine hesitancy in patients with neuroinflammatory diseases (NID); including, but not limited to: multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), neurosarcoidosis and myelin oligodendrocyte antibody-mediated disease (MOG-AD). Data is urgently needed to help guide clinical care in the NID population. METHODS: This was a cross-sectional observational study evaluating adults with a neurologist-confirmed diagnosis of a neuroinflammatory disease (NID) and a neurologically asymptomatic control population. Participants were recruited from multiple academic centers participating in the MS Resilience to COVID-19 Collaborative study. We analyzed participant responses from a vaccine-specific questionnaire collected between February and May 2021. RESULTS: 1164 participants with NID and 595 controls completed the vaccine survey. Hesitancy rates were similar between NID and control groups (n = 134, 32.7% NID vs. n = 56, 30.6% control; p = 0.82). The most common reasons for hesitancy in NID participants were lack of testing in the autoimmune population and fear of demyelinating/neurologic events. Unvaccinated patients who had discussed vaccination with their doctor were less likely to be hesitant (n=184, 73.6% vs. n=83, 59.7%; p = 0.007). 634 NID patients and 332 controls had received at least one dose of a vaccine against SARS-CoV-2 at the time of survey completion. After adjusting for age, BMI, and comorbidities, there was no difference in self-reported side effects (SE) between groups with the first dose (n = 256, 42.2% NID vs. 141, 45.3% control; p = 0.20) or second dose (n = 246, 67.0% NID vs. n = 114, 64.8% control, p = 0.85) of the mRNA vaccines nor with the viral-vector vaccines (n = 6, 46% NID vs. n = 8, 66% control; p = 0.39). All reported SEs fell into the expected SE profile. There was no difference in report of new/recurrent neurologic symptoms (n = 110, 16.2% vaccinated vs. 71, 18.2% unvaccinated; p = 0.44) nor radiologic disease activity (n = 40, 5.9% vaccinated vs. n = 30, 7.6% unvaccinated) between vaccinated and unvaccinated NID participants. CONCLUSIONS: We found no difference in patient-reported vaccine side effects and no evidence of NID worsening after vaccination. Large-scale real-world evidence is needed for further validation.

RCT of a Telehealth Group-Based Intervention to Increase Physical Activity in Multiple Sclerosis: eFIT.

OBJECTIVE: To conduct a pilot randomized controlled trial to determine whether participation in a group-based structured telehealth intervention increases physical activity in people with multiple sclerosis (MS). METHODS: In this parallel-arms trial, all study procedures were administered remotely. Adults diagnosed with MS (any subtype) were randomized to one of two 12-week (1 h/wk) active conditions: eFIT, online moderated structured groups; or eJournal, online independent journaling. For comparison, a treatment-as-usual (TAU; i.e., no eFIT/eJournal) group was enrolled. The primary outcome was feasibility (completion and adherence). The secondary efficacy outcomes included self-reported physical activity level (International Physical Activity Questionnaire, IPAQ). RESULTS: Participants were 37 adults with MS. The sample was diverse: 66.7% female; age range 23-64 years; 17.5% Hispanic, 12.5% Black; and progressive and relapsing-remitting disease subtypes. Regarding feasibility, 70.7% completed; average adherence was 74.9%. Physical activity in active groups increased by 34.2% (baseline IPAQ = 2,406.8 ± 1,959.7, follow-up = 3,229.4 ± 2,575.2) and decreased in the TAU group by 17.4% (baseline = 2,519.9 ± 1,500.1, follow-up = 2,081.2 ± 1,814.9); group × time interaction was not statistically significant [F(2,25) = 1.467, p = 0.250; partial η2 = 0.105]. CONCLUSIONS: Telehealth represents an accessible, acceptable vehicle to deliver targeted behavioral treatments to a neurologic population. eFIT may be an effective intervention for increasing physical activity, a historically intractable treatment target, in individuals with MS. In addition, these results provide evidence for feasibility of conducting fully remote clinical trial research. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for people with MS, participation in a group-based structured telehealth intervention compared with TAU resulted in a (non-significant) increase in self-reported physical activity level. The percentage of participants who completed follow-up questionnaires did not differ between groups. The trial was registered at ClinicalTrials.gov (NCT03829267).

Neurologic Safety Monitoring of COVID-19 Vaccines: Lessons From the Past to Inform the Present.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global effort to rapidly develop and deploy effective and safe coronavirus disease 2019 (COVID-19) vaccinations. Vaccination has been one of the most effective medical interventions in human history, although potential safety risks of novel vaccines must be monitored, identified, and quantified. Adverse events must be carefully assessed to define whether they are causally associated with vaccination or coincidence. Neurologic adverse events following immunizations are overall rare but with significant morbidity and mortality when they occur. Here, we review neurologic conditions seen in the context of prior vaccinations and the current data to date on select COVID-19 vaccines including mRNA vaccines and the adenovirus-vector COVID-19 vaccines, ChAdOx1 nCOV-19 (AstraZeneca) and Ad26.COV2.S Johnson & Johnson (Janssen/J&J).