Itay Lotan

Background: The potential link between myasthenia gravis (MG) and COVID‐19 infection or vaccination remains unclear. This study aimed to evaluate the relationship between these factors and new‐onset MG. Methods: A case–control study was conducted using Clalit Health Services' database. We applied a ML algorithm to reduce diagnostic misclassification. The study examined adults with new onset MG, aged 18 or older, between January 2020 and December 2022 for COVID‐19 infection (Cohort I) and between January 2021 and December 2022 for Pfizer‐BioNTech COVID‐19 vaccine (Cohort II). For each new MG case, three controls matched by age, sex, and index date were selected. Prior exposure to either infection or vaccination was assessed within 90 and 180 days for cases and controls. Results: In cohort I, 253 new MG cases were identified. A multivariate logistic regression model showed an odds ratio (OR) of 1.44 (95% CI 0.708–2.92) within 90 days post‐infection and 1.67 (95% CI 0.98–2.84) within 180 days. In cohort II, 177 new MG cases were detected, with an OR of 1.76 (95% CI 1.049–2.95) within 90 days post‐vaccination and 2.45 (95% CI 1.51–3.95) within 180 days. Conclusion: This study suggests no significant increased risk of new‐onset MG following COVID‐19 infection, but the Pfizer‐BioNTech vaccine appears to be associated with a higher risk of developing MG, particularly within 180 days of vaccination.

Introduction/Aims: Myasthenia gravis (MG) is associated with thymic neoplasms. However, an increased prevalence of extrathymic neoplasms has also been reported. This study aimed to evaluate the rates of malignancy in MG patients while accounting for risk factors such as disease characteristics and immunomodulatory treatments. Methods: We conducted a case–control study using the Clalit Health Services database, applying a machine learning (ML) algorithm to minimize diagnosis misclassification. We included MG patients aged 18 years and older, with a sex‐ and age‐matched control group in a 1:3 ratio. We compared the prevalence and hazard ratios of extrathymic neoplasms between the groups. Results: A total of 1558 patients with a high probability of MG, according to our ML model, were included in the cohort, alongside a control group of 4674 individuals. MG patients had a higher prevalence of malignancy prior to MG diagnosis, with an odds ratio of 1.95 (95% CI, 1.65–2.08), and a higher incidence of malignancy after MG diagnosis, with a hazard ratio of 1.56 (95% CI, 1.38–1.77). The most prevalent extrathymic neoplasms after MG diagnosis were respiratory, intrathoracic, skin (specifically non‐melanoma), urinary tract, soft tissue, and myelodysplastic syndrome. Risk factors for malignancy included age, male sex, and thymoma. Immunosuppressive treatment did not increase the risk of malignancy. Discussion: MG patients have a higher prevalence of both solid and hematologic neoplasms compared to non‐myasthenic controls, regardless of immunosuppressive treatment. This supports the notion that malignancy is related to MG disease itself rather than external factors.

Cell-based therapies, particularly transplanted human oligodendrocyte progenitor cells (OPCs), are being explored for neuroprotection and remyelination in demyelinating diseases of the central nervous system (CNS). In this study, we investigated the potential of OPC transplantation into the optic nerve of dark agouti (DA) rats with experimental autoimmune encephalomyelitis (EAE). Human OPCs were transplanted 30 days after EAE induction in one optic nerve, while the contralateral nerve was injected with a vehicle. FTY720 (fingolimod) was administered starting from day 25 post-EAE to prevent graft rejection. Rats were monitored clinically and electrophysiologically using visually evoked potentials (VEPs) for up to 90 days post-transplant. Histological analysis of OPC viability, myelin, and axonal integrity was performed on days 30, 60, and 90 post-transplant. At days 30 and 60, sparse OPCs were detected in the injected optic nerve. However, no live cells were detected on day 90. There were no significant differences in myelin or axonal integrity between the OPC- and vehicle-injected nerves. The VEP traces were severely distorted throughout the 90-day follow-up. This approach did not show long-term viability following direct injection of OPCs in the optic nerve of EAE rats. Challenges related to graft rejection and cell transplantation are discussed, with implications for future research in cell-based therapies.

Data on the plasma exchange (PLEX) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are limited. Herein, we evaluate outcomes after PLEX in MOGAD. This international multicenter retrospective cohort study included patients from 18 tertiary care centers in 6 countries. Inclusion criteria included fulfillment of the 2023 International MOGAD panel criteria, receipt of at least 3 sessions of PLEX, and follow-up of ≥3 months after PLEX. Patients with coexisting neuroinflammatory disorders were excluded. We assessed the frequency of complete recovery (CR), clinically significant improvement (CSI), visual acuity (VA), and Expanded Disability Status Scale (EDSS). Logistic regression analyses were performed to identify predictors of CR and CSI. Of 234 patients, 135 (58%) were female. The median (interquartile range [IQR]) age at attack was 34 (IQR 22-49) years, and 42 (17%) were children. In 165 of 243 (68%), the attack treated with PLEX was the first attack. Attack phenotypes included 161 optic neuritis (235 eyes), 77 myelitis, 24 acute disseminated encephalomyelitis, 15 brainstem/cerebellar, 3 cerebral-cortical encephalitis attack, and 1 cerebral polyfocal deficit-36 with >1 core phenotypes. A total of 239 (99%) attacks were also treated with corticosteroids and 32 (13%) with IV immunoglobulins. VA in optic neuritis improved from 20/400 (20/70-hand motion) to 20/20 (20/20-20/30), p < 0.001, and EDSS decreased from a median of 4.0 (3.0-6.5) to 1.0 (0.0-2.5), p < 0.001. Of 229 attacks without subsequent attacks within 3 months, 100 (44%) achieved CR and 213 (93%) CSI. The probability of CR was decreased with advanced age (adjusted odd ratio [95% CI] 0.97 [0.96-0.99] per year), higher EDSS worsening from baseline (0.66 [0.54-0.81] per 0.5 increment) and delayed PLEX (0.98 [0.96-0.99] per day). Advanced age (0.97 [0.96-0.99] per year) and delayed PLEX (0.95 [0.94-0.96] per day) decreased the probability of CSI. We observed favorable outcomes after PLEX in MOGAD attacks. However, advanced age and delayed initiation of PLEX were associated with a reduced probability of improvement. The absence of a control group limits our ability to differentiate PLEX effects from spontaneous recovery, prior corticosteroid response, or long-term immunotherapy. Future prospective studies are needed to assess the impact of PLEX on improvement. This study provides Class IV evidence that PLEX is associated with favorable clinical outcomes in patients with MOGAD.

Background Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction, most commonly associated with autoantibodies against the acetylcholine receptor (AChR). While familial clustering of autoimmune MG (fMG) has been described, its prevalence and clinical characteristics remain uncertain. This study aimed to characterize autoimmune fMG cases in an Israeli cohort and describe global data through a systematic literature review. Methods We retrospectively analyzed the medical records of MG patients treated at Rabin Medical Center from 2000 to 2022. The clinical and demographic features of autoimmune fMG cases—defined by compatible clinical, serological, and electrophysiological features—were compared to those of sporadic MG. Additionally, a systematic review of published autoimmune fMG cases was performed according to PRISMA guidelines. Results Among 281 MG patients, 16 patients (5.7%) from eight families met criteria for autoimmune fMG. Compared to sporadic MG, fMG cases had a significantly younger age of onset (median 44.5 vs. 58 years, p = 0.04) and more frequently presented with severe generalized disease (MGFA class IV–V, 43.8% vs. 15%, p = 0.008). The antibody profiles, sex distribution, ocular involvement, and comorbid autoimmune diseases did not differ significantly. All fMG patients responded to immunotherapy. The systematic review identified 73 additional fMG cases, with similar trends toward earlier onset and generalized presentation. Patients with fMG in our cohort had higher rates of severe initial presentation (43.8% vs. 16.4%, p = 0.03) and underwent thymectomy less frequently (19% vs. 49.3%, p = 0.03). Conclusions Autoimmune familial MG occurs in 5–6% of MG cases and is associated with a younger onset and more severe initial presentation compared to sporadic MG, but shows similar long-term treatment response. These findings suggest that genetic factors may contribute to disease susceptibility and phenotypic expression in familial MG, highlighting the need for further research into the underlying genetic and immunological mechanisms.

Background and ObjectivesSusac syndrome (SuS) is a rare disorder characterized by encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss, often accompanied by vertigo. Recent updates to diagnostic criteria and treatment guidelines ...

Large, international, real-world MRI assessments showed high heterogeneity in the data collected from patients with aquaporin-4 immunoglobulin G–seropositive neuromyelitis optica spectrum disorder and frequent cerebral and lower spinal cord abnormalities.

Objective: The first international consensus criteria for optic neuritis (ICON) were published in 2022. We applied these criteria to a prospective, global observational study of acute optic neuritis (ON).Methods: We included 160 patients with a first‐ever acute ON suggestive of a demyelinating CNS disease from the Acute Optic Neuritis Network (ACON). We applied the 2022 ICON to all participants and subsequently adjusted the ICON by replacing a missing relative afferent pupillary defect (RAPD) or dyschromatopsia if magnetic resonance imaging pathology of the optical nerve plus optical coherence tomography abnormalities or certain biomarkers are present.Results: According to the 2022 ICON, 80 (50%) patients were classified as definite ON, 12 (7%) patients were classified as possible ON, and 68 (43%) as not ON (NON). The main reasons for classification as NON were absent RAPD (52 patients, 76%) or dyschromatopsia (49 patients, 72%). Distribution of underlying ON etiologies was as follows: 78 (49%) patients had a single isolated ON, 41 (26%) patients were diagnosed with multiple sclerosis, 25 (16%) patients with myelin oligodendrocyte glycoprotein antibody‐associated disease, and 15 (9%) with neuromyelitis optica spectrum disorder. The application of the adjusted ON criteria yielded a higher proportion of patients classified as ON (126 patients, 79%).Interpretation: According to the 2022 ICON, almost half of the included patients in ACON did not fulfill the requirements for classification of definite or possible ON, particularly due to missing RAPD and dyschromatopsia. Thorough RAPD examination and formal color vision testing are critical to the application of the 2022 ICON.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM). Immunotherapy is often used for relapsing disease, but there is variability in treatment decisions. Objective: The objective was to determine the annualized relapse rates (ARRs) and incidence rate ratios (IRRs) compared to pre-treatment and relapse-freedom probabilities among patients receiving steroids, B-cell depletion (BCD), intravenous immunoglobulin (IVIG), and mycophenolate mofetil (MMF). Methods: Retrospective cohort study of patients with relapsing MOGAD treated at Mass General Brigham. ARRs and IRRs compared to pre-treatment, and relapse-freedom probability and odds ratio for relapse-freedom compared to prednisone were calculated. Results: A total of 88 patients met the inclusion criteria. The ARR on IVIG was 0.13 (95% confidence interval (CI) = 0.06–0.27) and the relapse-freedom probability after at least 6 months of therapy was 72%. The ARR on BCD was 0.51 (95% CI = 0.34–0.77), and the relapse-freedom probability was 33%. The ARR on MMF was 0.32 (95% CI = 0.19–0.53) and the relapse-freedom probability was 49%. In pediatric-onset disease, MMF had the lowest ARRs (0.15, 95% CI = 0.07–0.33). Conclusion: IVIG had the lowest ARRs and IRRs compared to pre-treatment and the highest relapse-freedom odds ratio compared to prednisone, while BCD had the lowest. In pediatric-onset MOGAD, MMF had the lowest ARRs.

Acute optic neuritis treatment lacks standardized protocols. The value of oral prednisone taper (OPT) following intravenous methylprednisolone (IVMP) on visual outcome parameters in optic neuritis (ON) has never been explored. In the present retrospective study, we investigated whether OPT after IVMP affects the structural and functional visual outcomes of inaugural clinically isolated syndrome (CIS)- or multiple sclerosis (MS)-ON. Adult patients with acute, inaugural, unilateral CIS- or MS-ON, treated with IVMP in Germany and Israel were stratified into patients treated with IVMP alone—versus IVMP and OPT. Inclusion criteria were age ≥18, CIS or MS diagnosis according to McDonald criteria 2017, available visual acuity (VA) at nadir before treatment initiation and at follow-up ≥5 months, as well as a spectral domain optic coherence tomography (OCT) data scan at follow-up. Exclusion criteria included recurrent ON, concomitant ophthalmological comorbidities, optical coherence tomography (OCT) of insufficient quality and ON-related escalation therapy after IVMP. The structural outcome was defined as the average retinal nerve fiber layer (RNFL) difference between the ON-affected and the unaffected eye, while the functional outcome was defined as the final high-contrast best-corrected VA (HC-BCVA) at follow-up compared to nadir. The comparative analysis was performed using linear regression analysis, adjusted for sex, age, and days-to-treatment. Fifty-one patients met the inclusion criteria (25% male). The mean age was 33.9 (±10.23) years. Twenty-six patients (51%) received OPT following IVMP. There was no difference in nadir HC-BCVA between the groups (0.39 No OPT; 0.49 With OPT, P = 0.36). Adjusted linear regression analysis did not indicate an influence of OPT on RNFL thickness or on HC-BCVA (beta coefficient for RNFL difference in percentages: 0.51, 95%-CI: [-4.58, 5.59], beta coefficient for logMAR: 0.11, 95%; CI [-0.12, 0.35] at follow-up. In conclusion, the addition of OPT to IVMP did not affect RNFL thickness or the final VA in a retrospective cohort of 51 patients with inaugural acute CIS- or MS-ON. The results of this exploratory study are currently being re-examined in a large-scale, demographically diverse, prospective study.