Background and Objectives:Neurosarcoidosis poses a diagnostic and management challenge due to its rarity, phenotypic variability, and lack of randomized controlled studies to guide treatment selection. Recommendations for management based on expert opinion are useful in clinical practice and provide a framework for designing prospective studies. Methods:In this Delphi survey study, specialists with experience in managing patients with neurosarcoidosis were invited to anonymously complete 2 surveys about key elements of evaluation, diagnosis, treatment, monitoring, and long-term management of neurosarcoidosis. Expert consensus recommendations were adopted if >80% threshold of agreement was reached. Results:Of the 41 invited expert clinicians across the United States, 32 (78%) participated in the study. All round 1 respondents self-identified as neuroimmunologists (except for 1 pulmonologist). Consensus was reached regarding the need to consider neurosarcoidosis phenotype and severity to guide the choice of initial immunosuppression in both the acute (relapse) and maintenance phases. Experts endorsed the use of TNF-α inhibitors as first-line agents in selected phenotypes with poor prognosis. Neuroimaging was recommended to complement clinical surveillance for treatment response. Discussion:There was agreement on several key issues, most importantly on the need to consider neurosarcoidosis phenotype and severity when deciding initial treatment. No consensus was achieved on the dosing and duration of specific immunosuppressants, nor regarding the management of the peripheral nervous system manifestation of neurosarcoidosis. These topics warrant further investigation.

AimsTo describe the 12-month effectiveness, persistence, tolerability, and safety of ofatumumab (OMB), a highly effective disease-modifying therapy (DMT) for relapsing multiple sclerosis (MS), in a real-world MS population.Patients & methodsElectronic medical records of patients starting OMB from October 2020 to August 2022 at two comprehensive MS centers were reviewed. Demographics and disease characteristics and 6- and 12-month clinical, patient-reported, and radiologic outcome measures were analyzed.ResultsA total of 175 patients started OMB with mean age 44.9 (SD 10.4) and disease duration 13.6 (SD 9.6) years. The cohort was 74% female, included 81% White and 13% Black American patients, and consisted of 80% relapsing-remitting MS or clinically isolated syndrome. Most (87%) had prior DMT exposure with 38% switching from high efficacy DMT. Over 12 months, 9.7% discontinued OMB (mean 117 days, SD 99.2), with tolerability issues being the most common reason. Thirty-nine (22%) had relapses in the year before starting OMB. By 12 months, only 1 relapse had occurred after approximately 4 months post-treatment initiation.DiscussionThis real-world study demonstrated that OMB is highly effective with robust persistence and good safety and tolerability by 12-month follow-up. Further analyses are planned to examine longer-term outcomes.

Clinically overt granulomatous involvement of the nervous system, or neurosarcoidosis, occurs in up to 5% of patients with sarcoidosis. Diagnosing neurosarcoidosis is often challenging due to its highly heterogeneous and frequently nonspecific clinical presentations, as well as the difficulty in obtaining tissue confirmation. In practice, the diagnosis of neurosarcoidosis is typically made based on supportive findings from ancillary tests — such as magnetic resonance imaging and cerebrospinal fluid analysis — in conjunction with the exclusion of alternative diagnoses in patients with known extraneural sarcoidosis. Current treatment recommendations are largely based on expert opinion and retrospective studies. Several factors should guide the initial treatment strategy, including disease extent, severity, functional impairment, comorbidities, and patient preferences. Glucocorticoids remain the cornerstone of therapy, with steroid-sparing agents and biologics frequently required in more severe cases.

Neurosarcoidosis poses a diagnostic and management challenge due to its rarity, phenotypic variability, and lack of randomized controlled studies to guide treatment selection. Recommendations for management based on expert opinion are useful in clinical practice and provide a framework for designing prospective studies. In this Delphi survey study, specialists with experience in managing patients with neurosarcoidosis were invited to anonymously complete 2 surveys about key elements of evaluation, diagnosis, treatment, monitoring, and long-term management of neurosarcoidosis. Expert consensus recommendations were adopted if >80% threshold of agreement was reached. Of the 41 invited expert clinicians across the United States, 32 (78%) participated in the study. All round 1 respondents self-identified as neuroimmunologists (except for 1 pulmonologist). Consensus was reached regarding the need to consider neurosarcoidosis phenotype and severity to guide the choice of initial immunosuppression in both the acute (relapse) and maintenance phases. Experts endorsed the use of TNF-α inhibitors as first-line agents in selected phenotypes with poor prognosis. Neuroimaging was recommended to complement clinical surveillance for treatment response. There was agreement on several key issues, most importantly on the need to consider neurosarcoidosis phenotype and severity when deciding initial treatment. No consensus was achieved on the dosing and duration of specific immunosuppressants, nor regarding the management of the peripheral nervous system manifestation of neurosarcoidosis. These topics warrant further investigation.

Aim: Anti-CD20 monoclonal antibodies and fumarates are common multiple sclerosis (MS) diseasemodifying therapies (DMTs). Data on switching from anti-CD20s to other DMTs are limited. This retrospective, observational study of the US Komodo Health Sentinel claims database aimed to evaluate a de-escalation strategy in a real-world cohort, comparing clinical characteristics, relapses, healthcare encounters (HCEs) and healthcare costs (HCCs) between patients aged ≥18 years with stable MS who switched from anti-CD20s to fumarates (‘Switchers’) versus patients who stayed on anti-CD20s (‘Stayers’). Materials & methods: Patients withMS (diagnosed 1 January 2015–31 August 2022) were propensity score matched 5:1 (Stayers:Switchers) and followed from index to end of study; end of insurance eligibility; >45- day gap in index DMT; or DMT switch. Primary outcomes were clinical characteristics and claims-based annualized relapse rate (ARR). Rates of HCEs and HCCs were estimated. Results: Baseline characteristics were well balanced between cohorts (Stayers, n = 540; Switchers, n = 108). Mean (SD) duration of postindex follow-up was 341.4 (250.0) days for both cohorts. Mean (SD) ARR was 0.08 (0.41; Stayers) versus 0.14 (0.5; Switchers; p = 0.3). Twenty-one Stayers (3.9%) and 1 Switcher (0.9%) were hospitalized for infections, with mean stays of 9.9 and 1 day, respectively. Mean annualized all-cause HCEs were similar between cohorts; annualized inpatient infection-related HCEs were higher for Stayers versus Switchers (mean difference: -0.05; p = 0.005). Annualized all-cause HCCs were similar between cohorts; Switchers had lower annualized infection-related HCCs overall (mean difference: -$2412; p = 0.002) and in the inpatient setting (mean difference: -$2325; p = 0.002). Conclusion: After 1 year, no significant differences in ARR emerged between cohorts. Switchers experienced lower inpatient infection-related HCEs, shorter inpatient infection-related hospital stays and lower overall infection-related HCCs.

Objective: Evaluate NIH Toolbox motor battery (NIHTB-M), a multidimensional set of measures used to track motor impairment, for use in people with neurosarcoidosis (PwNS). Background: Despite its profound impact on quality of life, there are no validated measures of neurologic impairment in NS to track disability progression or treatment response. Design/Methods: Cross-sectional study of adults with NS recruited from a tertiary referral center for sarcoidosis. All participants were adults meeting NS Consortium diagnostic criteria for NS. NIHTB-M measures were compared to age-, education-, sex-, and race/ethnicity-matched peers using neurologically healthy individuals from the NIHTB norming project. NIHTB-M measures were compared to patient-reported assessments of mobility and fine motor control using Quality of Life in Neurological Disorders (Neuro-QoL) and clinician-assessed functional impairment using Barthel Index (BI). Results: 41 PwNS were enrolled, 62% female, 29% African American, 71% Caucasian, 86% with biopsy-proven sarcoidosis. 7% had severe, 27% moderate, 7% slight, and 56% no functional dependence by BI. Compared to propensity-matched healthy controls, impairment (≥ 1 standard deviation worse than normative mean) was more common in PwNS on 9-Hole Peg Test (9-HPT) (81% vs. 14%, OR: 19.53, 95%CI [6.51, 67.56]) and 4-Meter Walk Test (4-MWT) (77% vs. 15%, OR: 18.89, 95% CI [6.41, 64.41]). There were moderate correlations between 9-HPT and Neuro-QoL fine motor scores (r = 0.39, 95% CI [0.03, 0.66]) and strong correlations between 4-MWT and 2-Minute Walk Test (2-MWT) and Neuro-QoL mobility scores (r = −0.69, 95% CI [−0.84, −0.44]; 0.66, 95% CI [0.44, 0.78], respectively). Scores on 9-HPT (P=0.008), 4-MWT (P=0.007), 2-MWT (P=0.032), and select measures of Standing Balance Test (SBT) (P < 0.001) were significantly different between subjects who were functionally dependent versus independent by BI. Conclusions: We provide preliminary evidence for validity of 9-HPT as a measure of fine motor control and 4-MWT, 2-MWT, and SBT as measures of mobility in PwNS. Disclosure: Dr. Moss has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. An immediate family member of Dr. Moss has stock in Pfizer. The institution of Dr. Moss has received research support from Novartis. The institution of Dr. Moss has received research support from Genentech. Nicholas Thompson has nothing to disclose. Daniel Culver has nothing to disclose.

Cerebrovascular involvement of neurosarcoidosis is a rare albeit increasingly recognized disorder requiring a multidisciplinary approach to diagnosis and management. We present a case of systemic sarcoidosis with neurological involvement of brain parenchyma and intracranial vasculature, and discuss a step-wise approach to the diagnostic evaluation. An inflammatory vasculitis should be considered in a patient with confirmed or highly suspected sarcoidosis with ischemic stroke. MR angiography with vessel-wall imaging should be pursued early in the evaluation to support this diagnosis. Cerebrovascular complications of sarcoidosis are often responsive to sarcoid-related immunotherapies.

Patients with immune-mediated inflammatory diseases (IMIDs) receiving B cell–depleting therapy (BCDT) are among the most vulnerable to severe COVID-19, as well as the most likely to suboptimally respond to SARS–CoV-2 vaccines. However, little is known about the frequency or severity of breakthrough infection in this population. We retrospectively analyzed a large group of vaccinated IMID patients undergoing BCDT in order to identify breakthrough COVID-19 infections and assess their outcomes. In this retrospective cohort study, the pharmacy records and COVID-19 registry at the Cleveland Clinic were searched using specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes to identify IMIDs patients who 1) received treatment with BCDT, 2) were vaccinated against SARS–CoV-2, and 3) experienced breakthrough infections. Each electronic medical record was reviewed to extract clinical data and outcomes. Univariate and multivariable logistic/proportional odds regression models were used to examine the risk factors for severe outcomes. Of 1,696 IMID patients receiving BCDT, 74 developed breakthrough COVID-19 prior to December 16, 2021. Outcomes were severe, with 29 patients hospitalized (39.2%), 11 patients requiring critical care (14.9%), and 6 deaths (8.1%). Outpatient anti–SARS–CoV-2 monoclonal antibodies were used to treat 21 patients, with 1 hospitalization and no deaths. A comparator analysis examining 1,437 unvaccinated IMID patients receiving BCDT over the same time period identified 57 COVID-19 cases (4.0%), with 28 requiring hospitalization (49.1%), including 7 deaths (12.3%). IMID patients receiving BCDT regardless of vaccine status appear to be vulnerable to infection with SARS–CoV-2, and use of BCDT is frequently associated with severe outcomes. Outpatient use of anti–SARS–CoV-2 monoclonal antibody therapy appears to be associated with enhanced clinical outcomes.

Background: There are no validated clinical outcome assessments (COAs) used in neumsarcoidosis. Objective: We surveyed clinicians who treat patients with neumsarcoidosis to determine: 1) current approaches to assessment of neurologic impairment, and 2) clinicians' needs regarding future COA development. Methods: Physician contacts from the Foundation for Sarcoidosis Research and Neurosarcoidosis Consortium Group were sent an online survey. Results: For 43/143 responders, COAs were used in a minority of settings. Apart from time for administration, the biggest barriers to implementation were lack of validated, disease-specific measures. Conclusions: Lack of validated, disease-specific measures is a barrier to monitoring neurological impairment in neurosarcoidosis.

© Author(s) (or their employer(s)) 2022. Reuse permitted under CC BYNC. No commercial reuse. See rights and permissions. Published by BMJ. Among immunocompromised patients, those with immunemediated inflammatory diseases (IMIDs) treated with B cell depleting therapies (BCDTs) and those with inborn errors of humoral immunity (IEI) are among the poorest responders to vaccination against SARSCoV2. These patients are also more likely to experience severe COVID19 outcomes, regardless of vaccination status. Although vaccination has not proven to be as efficacious as hoped in this population, the December 2021 emergency use authorisation of tixagevimab/cilgavimab has been greeted with cautious optimism by those providing care for immunocompromised patients. Tixagevimab/cilgavimab consists of two Fcmodified fully human monoclonal antibodies administered by intramuscular injection; it is effective for the prevention of COVID19 in patients with moderatetosevere immune compromise who are unlikely to mount an adequate immune response to COVID19 vaccination (Levin et al #2781). In the pivotal trial, however, only 3.3% of patients were receiving immunosuppressive drugs at baseline and no details as to class of agents were provided. It is becoming more and more evident that multiple strategies are required to prevent and treat outpatient COVID19 in immunosuppressed patients; this includes the use of monoclonal antibodies and antiviral therapies when prevention strategies fail. The practical effectiveness of this multipronged approach in terms of safety, tolerability and effectiveness has yet to be described. To date, there exist only limited reports of experience with tixagevimab/cilgavimab in patients with compromised humoral immunity and none describing tolerability or clinical outcomes in a realworld setting. Starting 18 January 2022, the Cleveland Clinic has made tixagevimab/cilgavimab available to select highrisk patients including those on BCDT and humoral IEI. Here we report out initial realworld experience with breakthrough infections in combination with standard of care outpatient management of COVID19.

Especially early in the disease course, people with multiple sclerosis (PwMS) may be able to choose whether to reveal their diagnosis to their employer, colleagues, and friends. Concealment might prevent discrimination but can also be stressful, resulting in the fear of being discovered, the need for continual self-monitoring to avoid disclosing too much, and a sense of detachment from one’s true self. A few studies have addressed this topic in multiple sclerosis (MS), in part because the field lacks a formal, validated measurement tool assessing diagnosis and disclosure and concealment behavior in PwMS.

This case series describes 9 patients diagnosed with myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorder (MOGAD) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients developed neurological symptoms between 4 days and 5 weeks following SARS-CoV-2 infection. Myelitis was observed in 4 patients; 4 presented with optic neuritis; and encephalopathy was observed in 3. Serum MOG-IgG cell-based assay was medium or high positive in each case. The majority of patients had near-complete recovery following acute immunosuppression. This series adds to the growing number of cases of central nervous system demyelination following SARS-CoV-2 infection and highlights a potential role of infection in the immunopathogenesis of MOGAD.

Background People with MS may have unique perspectives on COVID-19 vaccines due to their condition and/or medications. Objective Assess perspectives and experiences with COVID-19 vaccination, and quantify variables impacting COVID-19 vaccine willingness in people with MS. Methods A survey captured demographics, MS characteristics, and COVID-19 infection and exposures data; opinions on COVID-19 vaccine safety, side effects, and efficacy; and experiences following vaccination. Chi-square tests and a logistic regression model were used to denote between-group differences and variables predicting vaccine willingness, respectively. Results Most (87.8%) of the 237 participants were willing to receive the vaccine. Fifteen percent held or delayed a DMT dose for vaccination. MS symptoms worsened in a minority (7.6% first/only dose; 14.7% second dose), and most side effects were mild (80.0%; 55.3%). Those not planning to receive the vaccine were primarily concerned with long-term safety (70.4%). Medical comorbidities (adjusted odds ratio [aOR]=5.222; p=0.04) and following infection prevention precautions (aOR=6.330; p=0.008) were associated with vaccine willingness. Conclusion Most individuals with MS surveyed plan to receive the COVID-19 vaccine. People with MS experience similar side effects to the general population, and few experience transient MS symptom worsening. These results can inform conversations on vaccination between providers and people with MS.

INTRODUCTION:Clinically overt granulomatous involvement of the nervous system (i.e. neurosarcoidosis) can be seen in up to 10% of patients with sarcoidosis. Establishing a diagnosis of neurosarcoidosis is often challenging due to the heterogeneity of clinical presentations that are sometimes nonspecific, and inaccessibility of tissue confirmation. Recommended treatments are based on expert opinions that are derived from clinical experience and limited data from retrospective studies, as data from randomized controlled studies are limited.AREA COVERED:In this article, we comprehensively review all available literature on epidemiology, clinical presentations, diagnosis, treatment, and outcomes of neurosarcoidosis. We also offer our opinions on diagnostic approach and treatment strategy.EXPERT OPINION:Given the invasive nature and the limited sensitivity of biopsy of the nervous system, diagnosis of neurosarcoidosis is usually made when ancillary tests (such as magnetic resonance imaging and cerebrospinal fluid analysis) are compatible, and alternative diagnoses are reasonably excluded in patients with established extraneural sarcoidosis. Several factors must be taken into consideration to formulate the initial treatment strategy, including the extent of the disease, severity, functional impairment, comorbidities, and patient's preference. In addition, treatment regimen of neurosarcoidosis should be formulated with an emphasis on long-term strategy.

Abstract Objectives: Immunocompromised patients with immune mediated inflammatory diseases (IMIDs), undergoing therapy with B cell depleting agents are among the most vulnerable to experience severe COVID-19 disease as well as respond sub-optimally to SARS CoV-2 vaccines yet little is known about the frequency or severity of breakthrough infection in this population. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes. Methods: Utilizing specific ICD codes the pharmacy records and COVID-19 registry at the Cleveland clinic were used to identify all patients with IMIDS treated with B cell depleting monoclonal antibodies who were vaccinated against SARs CoV-2 and experienced breakthrough infections. Each EMR record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, other therapies, details of B cell depleting therapy, and outcomes. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes. Results: Of 1696 IMIDS patients on B cell depleting therapies 74 developed breakthrough COVID-19. Outcomes were severe with 24 (35%) hospitalized, 11 (15%) patients requiring critical care and 6 (8 %) deaths. Monoclonal antibodies were used on an outpatient basis to treat 21 with only a single patient requiring hospitalization without oxygen support and no deaths. Conclusions: In IMIDS patients on B cell depleting therapies breakthrough infections are frequent and associated with severe outcomes. Outpatient use of monoclonal antibody therapy was associated with enhanced clinical outcomes.