Solomon, Andrew

Importance Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) lacks proven relapse-preventive therapies. While clinical trials are ongoing, safety data may be limited and approved drugs are costly. Studies of interleukin 6 receptor blocker (IL-6RB) in MOGAD are limited by small numbers and no comparative studies, contributing to low use. Objective To evaluate the impact of IL-6RB therapy on relapse rates in MOGAD and compare relapse frequency with intravenous immunoglobulin (IVIG). Design, Setting, and Participants This international, multicenter, retrospective cohort study (January 1, 2015, through December 31, 2025) included a historical IVIG-treated cohort of varying doses. The study took place across sites in North and South America (US, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). Patients with MOGAD (n = 116, no excluded patients) who received at least 1 dose of an IL-6RB were included. These data were analyzed in January 2026. Exposures Tocilizumab or satralizumab. Main Outcomes and Measures Annualized relapse rate (ARR) during IL-6RB therapy, time to next relapse after treatment initiation, and adverse events. Outcomes were compared with the IVIG cohort using inverse probability of treatment weighting (IPTW) adjusted for age, sex, prior ARR, and concomitant therapies. Results A total of 116 patients with MOGAD (89% relapsing) receiving IL-6RB (tocilizumab, 104 [90%] and satralizumab, 12 [10%]) were included; overall, 60.3% were female, 39.7% were male, and 18% were younger than 18 years. The median (IQR) IL-6RB treatment follow-up was 1.4 (0.7-2.5) years and 23 relapses occurred during 241.8 person-years of IL-6RB therapy. The ARR decreased from 0.64 (95% CI, 0.58-0.70) for relapsing MOGAD before IL-6RB to 0.09 (95% CI, 0.06-0.14) during IL-6RB treatment (incidence rate ratio, 0.08; 95% CI, 0.04-0.16). Adverse events occurred in 58 patients (50%), most commonly mild infections, although 10 (9%) had severe infections. In the IVIG cohort (n = 59), 30 relapses occurred over 133.8 person-years (ARR, 0.22; 95% CI, 0.15-0.32). After IPTW, IL-6RB was associated with a lower hazard ratio (HR) than the group who underwent IVIG therapy less than 1 g/kg every 4 weeks (HR, 4.5; 95% CI, 2.0-9.8), with no significant difference vs the group who underwent IVIG 1 g/kg or more every 4 weeks (HR, 2.0; 95% CI, 0.8-4.5). Conclusions and Relevance In this multicenter observational cohort, IL-6RB use in MOGAD was associated with low relapse rates and a favorable safety profile, though severe infections occurred occasionally. Relapse rates were lower than the group who underwent IVIG less than 1 g/kg every 4 weeks but not significantly different from the group who underwent IVIG 1 g/kg or more every 4 weeks. This supports IL-6RB as a potential relapse-prevention therapy in MOGAD; the wide availability and relative affordability of tocilizumab may enable broad global use.

Importance While the typical onset of multiple sclerosis (MS) occurs in early adulthood, 2% to 10% of cases initially present prior to age 18 years, and approximately 5% after age 50 years. Guidance on approaches to differential diagnosis in suspected MS specific to these 2 age groups is needed. Observations There are unique biological factors in children younger than 18 years and in adults older than age 50 years compared to typical adult-onset MS. These biological differences, particularly immunological and hormonal, may influence the clinical presentation of MS, resilience to neuronal injury, and differential diagnosis. While mimics of MS at the typical age at onset have been described, a comprehensive approach focused on the younger and older ends of the age spectrum has not been previously published. Conclusions and Relevance An international committee of MS experts in pediatric and adult MS was formed to provide consensus guidance on diagnostic approaches and key clinical and paraclinical red flags for non-MS diagnosis in children and older adults.

ImportanceAutoimmune encephalitis misdiagnosis can lead to harm.ObjectiveTo determine the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis.Design, Setting, and ParticipantsThis retrospective multicenter study took place from January 1, 2014, to December 31, 2020, at autoimmune encephalitis subspecialty outpatient clinics including Mayo Clinic (n = 44), University of Oxford (n = 18), University of Texas Southwestern (n = 18), University of California, San Francisco (n = 17), Washington University in St Louis (n = 6), and University of Utah (n = 4). Inclusion criteria were adults (age ≥18 years) with a prior autoimmune encephalitis diagnosis at a participating center or other medical facility and a subsequent alternative diagnosis at a participating center. A total of 393 patients were referred with an autoimmune encephalitis diagnosis, and of those, 286 patients with true autoimmune encephalitis were excluded.Main Outcomes and MeasuresData were collected on clinical features, investigations, fulfillment of autoimmune encephalitis criteria, alternative diagnoses, potential contributors to misdiagnosis, and immunotherapy adverse reactions.ResultsA total of 107 patients were misdiagnosed with autoimmune encephalitis, and 77 (72%) did not fulfill diagnostic criteria for autoimmune encephalitis. The median (IQR) age was 48 (35.5-60.5) years and 65 (61%) were female. Correct diagnoses included functional neurologic disorder (27 [25%]), neurodegenerative disease (22 [20.5%]), primary psychiatric disease (19 [18%]), cognitive deficits from comorbidities (11 [10%]), cerebral neoplasm (10 [9.5%]), and other (18 [17%]). Onset was acute/subacute in 56 (52%) or insidious (>3 months) in 51 (48%). Magnetic resonance imaging of the brain was suggestive of encephalitis in 19 of 104 patients (18%) and cerebrospinal fluid (CSF) pleocytosis occurred in 16 of 84 patients (19%). Thyroid peroxidase antibodies were elevated in 24 of 62 patients (39%). Positive neural autoantibodies were more frequent in serum than CSF (48 of 105 [46%] vs 7 of 91 [8%]) and included 1 or more of GAD65 (n = 14), voltage-gated potassium channel complex (LGI1 and CASPR2 negative) (n = 10), N-methyl-d-aspartate receptor by cell-based assay only (n = 10; 6 negative in CSF), and other (n = 18). Adverse reactions from immunotherapies occurred in 17 of 84 patients (20%). Potential contributors to misdiagnosis included overinterpretation of positive serum antibodies (53 [50%]), misinterpretation of functional/psychiatric, or nonspecific cognitive dysfunction as encephalopathy (41 [38%]).Conclusions and RelevanceWhen evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered and misdiagnosis occurs in many settings including at specialized centers. In this study, red flags suggesting alternative diagnoses included an insidious onset, positive nonspecific serum antibody, and failure to fulfill autoimmune encephalitis diagnostic criteria. Autoimmune encephalitis misdiagnosis leads to morbidity from unnecessary immunotherapies and delayed treatment of the correct diagnosis.

Background: Few studies have addressed the results of educational efforts concerning proper use of McDonald criteria (MC) revisions outside multiple sclerosis (MS) subspecialty centers. Neurology residents and MS subspecialist neurologists demonstrated knowledge gaps for core elements of the MC in a recent prior study. Objective: To assess comprehension and application of MC core elements by non-MS specialist neurologists in the United States who routinely diagnose MS. Methods: Through a cross-sectional study design, a previously developed survey instrument was distributed online. Results: A total of 222 neurologists completed the study survey. Syndromes atypical for MS were frequently incorrectly considered “typical” MS presentations. Fourteen percent correctly identified definitions of both “periventricular” and “juxtacortical” lesions and 2% correctly applied these terms to 9/9 images. Twenty-four percent correctly identified all four central nervous system (CNS) regions for satisfaction of magnetic resonance imaging (MRI) dissemination in space. In two presented cases, 61% and 71% correctly identified dissemination in time (DIT) was not fulfilled, and 85% and 86% subsequently accepted nonspecific historical symptoms without objective evidence for DIT fulfillment. Conclusion: The high rate of knowledge deficiencies and application errors of core elements of the MC demonstrated by participants in this study raise pressing questions concerning adequacy of dissemination and educational efforts upon publication of revisions to MC.

Objective: To assess comprehension and application of the McDonald criteria. Background: Studies suggest that knowledge gaps for specific core elements of the McDonald criteria may contribute to multiple sclerosis (MS) misdiagnosis. Methods: Neurology residents (NR) and multiple sclerosis specialists (MSS) in North America completed a web-based survey. Results: A total of 160 participants were included: 72 NR and 88 MSS. Syndromes incorrectly identified as typical of MS included: complete transverse myelopathy (35% NR and 15% MSS), intractable vomiting/nausea/hiccoughs (20% NR and 5% MSS), and bilateral optic neuritis/unilateral optic neuritis with poor visual recovery (17% NR and 10% MSS). Periventricular magnetic resonance imaging (MRI) lesions were correctly identified by 39% NR and 52% MSS, and juxtacortical lesions were correctly identified by 28% NR and 53% MSS. The correct definition of “periventricular” was chosen by 38% NR and 61% MSS, and that of “juxtacortical” was chosen by 19% NR and 54% MSS. Regions incorrectly identified for MRI dissemination in space fulfillment included the optic nerve (31% NR and 26% MSS) and the subcortical white matter (11% NR and 18% MSS). The majority of participants assessed previous non-specific neurological symptoms without objective evidence of a central nervous system (CNS) lesion as sufficient for clinical dissemination in time. Conclusion: The McDonald criteria are often misunderstood and misapplied. Concerted educational efforts may prevent MS misdiagnosis.

Medication reconciliation (MedRec) is a mission-critical process which can serve to reduce adverse drug events (ADEs) in surgical settings. However, providing quality care is limited by current health information technology (IT), which is often inefficient and unintuitive due to poor usability, resulting in high cognitive burden. We have been characterizing EHR mediated workflow in the Mayo Clinic enterprise prior to a system-wide electronic health records (EHR) conversion in order to harmonize workflows. We compared and evaluated MedRec processes in pre-operative nursing assessments across two different EHRs in place in different locales at baseline. The interfaces differed both in their modes of interaction and cognitive support. Analyses surfaced interface elements that were unintuitive and inefficient, creating unnecessary complexities in clinicians’ interactive behavior. Keystroke level models (KLM), a modeling tool for predicting task completion time, showed that to access medication lists required a different series of operations across the two systems. Different designs can differentially mediate task performance, which can aid in the mitigation of errors for complex cognitive tasks. Identification of barriers in EHR-mediated workflow and barriers to interface usability could lead to system redesigns that minimize cognitive load while improving patient safety and efficiency.