Choroid plexus volume differentiates MS from its mimics.

This study aimed to determine whether choroid plexus volume (CPV) could differentiate multiple sclerosis (MS) from its mimics. A secondary analysis of two previously enrolled studies, 50 participants with MS and 64 with alternative diagnoses were included. CPV was automatically segmented from 3T magnetic resonance imaging (MRI), followed by manual review to remove misclassified tissue. Mean normalized choroid plexus volume (nCPV) to intracranial volume demonstrated relatively high specificity for MS participants in each cohort (0.80 and 0.76) with an area under the receiver-operator characteristic curve of 0.71 (95% confidence interval (CI) = 0.55-0.87) and 0.65 (95% CI = 0.52-0.77). In this preliminary study, nCPV differentiated MS from its mimics.

Impact of the COVID-19 Pandemic on the Personal Networks and Neurological Outcomes of People With Multiple Sclerosis: Cross-Sectional and Longitudinal Case-Control Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has negatively affected the social fabric. OBJECTIVE: We evaluated the associations between personal social networks and neurological function in people with multiple sclerosis (pwMS) and controls in the prepandemic and pandemic periods. METHODS: During the early pandemic (March-December 2020), 8 cohorts of pwMS and controls completed a questionnaire quantifying the structure and composition of their personal social networks, including the health behaviors of network members. Participants from 3 of the 8 cohorts had additionally completed the questionnaire before the pandemic (2017-2019). We assessed neurological function using 3 interrelated patient-reported outcomes: Patient Determined Disease Steps (PDDS), Multiple Sclerosis Rating Scale-Revised (MSRS-R), and Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function. We identified the network features associated with neurological function using paired 2-tailed t tests and covariate-adjusted regressions. RESULTS: In the cross-sectional analysis of the pandemic data from 1130 pwMS and 1250 controls during the pandemic, having a higher percentage of network members with a perceived negative health influence was associated with worse disability in pwMS (MSRS-R: ß=2.181, 95% CI 1.082-3.279; P<.001) and poor physical function in controls (PROMIS Physical Function: ß=-5.707, 95% CI -7.405 to -4.010; P<.001). In the longitudinal analysis of 230 pwMS and 136 controls, the networks of all participants contracted, given an increase in constraint (pwMS-prepandemic: mean 52.24, SD 15.81; pwMS-pandemic: mean 56.77, SD 18.91; P=.006. Controls-prepandemic: mean 48.07, SD 13.36; controls-pandemic: mean 53.99, SD 16.31; P=.001) and a decrease in network size (pwMS-prepandemic: mean 8.02, SD 5.70; pwMS-pandemic: mean 6.63, SD 4.16; P=.003. Controls-prepandemic: mean 8.18, SD 4.05; controls-pandemic: mean 6.44, SD 3.92; P<.001), effective size (pwMS-prepandemic: mean 3.30, SD 1.59; pwMS-pandemic: mean 2.90, SD 1.50; P=.007. Controls-prepandemic: mean 3.85, SD 1.56; controls-pandemic: mean 3.40, SD 1.55; P=.01), and maximum degree (pwMS-prepandemic: mean 4.78, SD 1.86; pwMS-pandemic: mean 4.32, SD 1.92; P=.01. Controls-prepandemic: mean 5.38, SD 1.94; controls-pandemic: mean 4.55, SD 2.06; P<.001). These network changes were not associated with worsening function. The percentage of kin in the networks of pwMS increased (mean 46.06%, SD 29.34% to mean 54.36%, SD 30.16%; P=.003) during the pandemic, a change that was not seen in controls. CONCLUSIONS: Our findings suggest that high perceived negative health influence in the network was associated with worse function in all participants during the pandemic. The networks of all participants became tighter knit, and the percentage of kin in the networks of pwMS increased during the pandemic. Despite these perturbations in social connections, network changes from the prepandemic to the pandemic period were not associated with worsening function in all participants, suggesting possible resilience.

Pearls & Oy-sters: Homozygous Complement Factor I Deficiency Presenting as Fulminant Relapsing Complement-Mediated CNS Vasculitis.

A 36-year-old man presented multiple times with fever, headache, alteration of mental status, and focal neurologic deficits. MRI revealed extensive white matter lesions that were partially reversed between episodes. Workup revealed persistently low complement factor C3, low factor B, and absent alternative complement pathway activity. Biopsy revealed neutrophilic vasculitis. Genetic testing revealed a homozygous variant in complement factor I (CFI), which was thought to be pathogenic. CFI regulates complement-mediated inflammation, and deficiency in this factor leads to unchecked alternative pathway activity and decrease in C3 and factor B through consumption. The patient has remained stable since starting IL-1ß inhibition. Complement factor I is a rare disorder that should be considered in patients with atypical relapsing neurologic disease associated with neutrophilic pleocytosis.

A retrospective evaluation of seroconversion after COVID-19 during the early Omicron wave in fully vaccinated multiple sclerosis patients receiving anti-CD20 therapies.

BACKGROUND: Patients with multiple sclerosis (MS) are commonly treated with anti-CD20 therapies. Reduced seroconversion following COVID-19 vaccination in patients receiving certain anti-CD20 therapies has been reported; however, the immune response following natural infection is poorly characterised. This study aimed to retrospectively evaluate COVID-19 antibody responses after vaccination and natural infection in patients treated with anti-CD20 therapies. METHODS: We performed a retrospective review evaluating COVID-19 seroconversion and anti-spike glycoprotein antibody titres in double-vaccinated patients with MS, or related neuroinflammatory conditions, treated with anti-CD20 therapies (N = 30) with a confirmed history of natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (n = 14) or without infection (control; n = 16). This single-centre study was performed at the Yale Multiple Sclerosis Center, where patients treated with anti-CD20 therapies (ocrelizumab, n = 21; rituximab, n = 5; ofatumumab, n = 4) were systematically checked for SARS-CoV-2 anti-spike antibody levels throughout the pandemic. Data were collected from March 2020 to March 2022. All patients had received at least two doses of a Food and Drug Administration (FDA)-approved COVID-19 vaccine. Qualitative anti-spike antibody seropositivity was determined based on test-specific laboratory reference ranges. For a subset of patients (n = 18), quantitative anti-spike antibody levels were assessed via DiaSorin LIAISON® chemiluminescence immunoassay (positive titre was defined as ≥ 13). Vaccination and infection dates were also recorded, and patients were monitored for adverse COVID-19-related health effects. RESULTS: Overall, 15/30 (50.0%) patients seroconverted following double vaccination. After infection, 13/14 (92.9%) seroconverted, while 6/16 (37.5%) uninfected patients seroconverted after vaccination. For the 18 patients with quantitative anti-spike antibody titres, mean titre post-vaccination was 37.4. Mean antibody titres were significantly higher after infection: 540.3 versus 20.1 in the control group (p < 0.05). Of the 14 infected patients, 13 had mild COVID-19 symptoms and one was asymptomatic. No hospitalisations or deaths were reported. CONCLUSIONS: This study reports that SARS-CoV-2 anti-spike antibody titres in double-vaccinated MS patients treated with anti-CD20 therapies were significantly increased post-infection compared with the control group. Patients treated with anti-CD20 therapy who had confirmed infections displayed mild or asymptomatic infection. These results provide reassurance that anti-CD20 therapies in double-vaccinated patients do not preclude an appropriate SARS-CoV-2 antibody response post-infection.

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.

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.

Seroconversion after COVID-19 vaccination for multiple sclerosis patients on high efficacy disease modifying medications.

The impaired ability to mount an effective immune response to vaccination leaves immunosuppressed patients at higher risk of severe COVID-19 infection. This retrospective study aimed to evaluate COVID-19 seroconversion and antibody titers for patients on immune modulating therapies compared to those not on disease modifying therapy (DMT). As expected, individuals on B-cell depletion therapies (BCDT) and those on sphingosine 1-phosphate (S1P) modulators had an impaired humoral response to mRNA vaccination. We observed variable seroconversion depending on the type of B-cell depleting medication, with a smaller percentage of seroconversion in patients on infused BCDT (iBCDT, ocrelizumab and rituximab) compared to ofatumumab. The humoral response to vaccination was not impaired for individuals on natalizumab or for untreated MS patients. These observations may influence DMT selection during the COVID-19 era.

Worsening physical functioning in patients with neuroinflammatory disease during the COVID-19 pandemic.

OBJECTIVE: To quantify changes in psychological wellbeing and physical function as reported by people with neurological inflammatory disease (PwNID) during the COVID-19 pandemic. METHODS: 1134 PwNID and 868 control participants were recruited through five major academic medical centers in the Northeast/Mid-Atlantic U.S. beginning in April 2020. Participants completed serial surveys throughout the COVID-19 pandemic that aimed to quantify mood symptoms and physical function, analyzed cross-sectionally with a smaller cohort analyzed longitudinally. RESULTS: Throughout the pandemic, depression scores were not significantly different between PwNID and controls, although a higher proportion of PwNID reported clinically significant depression at study entry. Depression scores did not worsen over time for either group. Loneliness was the strongest predictor of worse depression, along with older age, male gender in both PwNID and controls, as well as lack of disease modifying therapy use, and disease duration in PwNID only. In contrast, physical disability worsened significantly over time for both PwNID and controls. Age, DMT status and comorbid health conditions emerged as significant predictors of physical function. CONCLUSIONS: Depressive symptoms remained consistent for both PwNID and controls throughout the COVID-19 pandemic, but physical function worsened significantly over time for both groups. This is particularly impactful for PwNID, who have higher baseline levels of physical disability, and underscores the importance of reinstituting services and interventions that facilitate exercise and reconditioning for this population.

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.

A New England COVID-19 Registry of Patients With CNS Demyelinating Disease: A Pilot Analysis.

BACKGROUND AND OBJECTIVES: We sought to define the risk of severe coronavirus disease 2019 (COVID-19) infection requiring hospitalization in patients with CNS demyelinating diseases such as MS and the factors that increase the risk for severe infection to guide decisions regarding patient care during the COVID-19 pandemic. METHODS: A pilot cohort of 91 patients with confirmed or suspected COVID-19 infection from the Northeastern United States was analyzed to characterize patient risk factors and factors associated with an increased severity of COVID-19 infection. Univariate analysis of variance was performed using the Mann-Whitney U test or analysis of variance for continuous variables and the χ2 or Fisher exact test for nominal variables. Univariate and stepwise multivariate logistic regression identified clinical characteristics or symptoms associated with hospitalization. RESULTS: Our cohort demonstrated a 27.5% hospitalization rate and a 4.4% case fatality rate. Performance on Timed 25-Foot Walk before COVID-19 infection, age, number of comorbidities, and presenting symptoms of nausea/vomiting and neurologic symptoms (e.g., paresthesia or weakness) were independent risk factors for hospitalization, whereas headache predicted a milder course without hospitalization. An absolute lymphocyte count was lower in hospitalized patients during COVID-19 infection. Use of disease-modifying therapy did not increase the risk of hospitalization but was associated with an increased need for respiratory support. DISCUSSION: The case fatality and hospitalization rates in our cohort were similar to those found in MS and general population COVID-19 cohorts within the region. Hospitalization was associated with increased disability, age, and comorbidities but not disease-modifying therapy use.

Brainstem lesions are associated with sleep apnea in multiple sclerosis.

BACKGROUND: Studies linking MRI findings in MS patients with obstructive sleep apnea severity are limited. OBJECTIVE: We conducted a retrospective study to assess MRI abnormalities associated with obstructive sleep apnea (OSA) in patients with multiple sclerosis (MS). METHODS: We performed retrospective chart review of 65 patients with multiple sclerosis who had undergone polysomnography (PSG) for fatigue as well as brain MRI. We measured the number of lesions in the brainstem and calculated the standardized third ventricular width (sTVW) as a measure of brain atrophy, and subsequently performed correlation analyses of the apnea-hypopnea index (AHI) with brainstem lesion location, sTVW, and Expanded Disability Status Scale (EDSS). RESULTS: MS Patients with OSA were significantly older and had a higher body mass index (BMI) and higher AHI measures than patients without OSA. After adjustment for covariates, significant associations were found between AHI and lesion burden in the midbrain (p < 0.01) and pons (p = 0.05), but not medulla. CONCLUSIONS: Midbrain and pontine lesions burden correlated with AHI, suggesting MS lesion location could contribute to development of OSA.