Abstract
Background and Objectives
Data on the plasma exchange (PLEX) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are limited. Herein, we evaluate outcomes after PLEX in MOGAD.
Methods
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.
Results
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.
Discussion
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.
Classification of Evidence
This study provides Class IV evidence that PLEX is associated with favorable clinical outcomes in patients with MOGAD.
Introduction
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disease of the CNS, distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).1 MOGAD attacks are usually severe,2 and disability accumulation in MOGAD primarily results from attacks.3,4 Although immunotherapies can reduce attacks in MOGAD, many patients continued to relapse and accumulate disability.5 Approximately 40%–50% of patients experience permanent disability after poor recovery from relapse.6,7 Therefore, effective acute treatment is crucial for managing and mitigating long-term disability in MOGAD.
High-dose corticosteroids are commonly used as the first-line treatment for acute attacks of CNS inflammatory disorders including MOGAD.8,9 However, severe attacks may necessitate additional acute immunotherapies, most commonly plasma exchange (PLEX). Multiple studies have shown PLEX effectiveness in severe acute attacks in CNS inflammatory diseases including MS and NMOSD.10-13 However, studies on PLEX in MOGAD remain limited.
In this study, we use data from 18 neuroimmunology referral centers across 6 countries to investigate the outcome after PLEX in acute MOGAD attacks and to identify outcome predictors that could help refine therapeutic strategies and patient outcomes. The primary research question addressed by this study is what are the outcomes and factors associated with recovery after PLEX?
Methods
Standard Protocol Approvals, Registrations, and Patient Consents
This international multicenter retrospective cohort study was approved by the Mayo Clinic Institutional Review Board (08-006647). Medical records of patients at Mayo Clinic, who consented to research review, were included. For other centers, respective institutional review boards granted approval, and owing to the retrospective nature of the study, informed consent was waived. All data were transferred to the lead site in a deidentified format using Microsoft Excel spreadsheets. The reporting of this study was done in conjunction with the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline for observational studies.14
Patient Identification, Inclusion, and Exclusion Criteria
Medical records of patients from 18 tertiary neuroimmunology referral centers from 6 countries including 7 centers from the United States, 4 centers from France, 3 centers from the United Kingdom, 2 centers from Thailand, 1 center from Israel, and 1 Center from New Zealand, who underwent PLEX from July 2001 to June 2023, were reviewed. Inclusion criteria were as follows: (1) fulfillment of 2023 International MOGAD panel proposed criteria,1 (2) received PLEX as an acute attack therapy at least 3 sessions, and (3) had a follow-up at least 3 months after PLEX. Patients with coexisting neuroinflammatory disorders (e.g., anti-NMDA receptor encephalitis) were excluded.
Data Collection
The data collection encompassed demographic and clinical parameters including age at attack, sex, clinical phenotype, acute immunotherapies during the attack, and chronic immunotherapy before and after the attack. PLEX was performed according to the protocol of each institution. Prolonged steroid therapy was defined as a treatment with steroids extending beyond 3 months after attack. In addition, Expanded Disability Status Scale (EDSS) scores and visual acuity (VA) were recorded at baseline, attack nadir, before PLEX, and last follow-up before any subsequent attack at least 3 months after PLEX. Adverse events during PLEX and residual symptoms, including visual impairment, gait impairment, and bladder and bowel dysfunctions 3 months after PLEX, were also extracted.
Outcomes
The outcomes included EDSS, VA (for optic neuritis attack), and residual symptoms after PLEX (at the last follow-up before any subsequent attack), the rates of early subsequent attacks, complete recovery (CR), and clinically significant improvement (CSI). An early subsequent attack was defined as a new or worsening of an existing neurologic symptom that lasted at least 24 hours,1 occurring more than 30 days after the previous attack,1 and within 3 months after PLEX. CR is characterized by the absence of residual neurologic deficits or the return of the EDSS and VA to the baseline level before the attack that was treated with PLEX. A patient was considered to achieved CSI if they reached confirmed disability improvement—defined as a sustained decrease of EDSS by at least 1.0 after PLEX if the EDSS before PLEX was 5.0 or less, or by at least 0.5 after PLEX if the EDSS before PLEX was greater than 5.0, adapted from previously used in criteria MS clinical trials15,16—or demonstrate a sustained improvement in VA of 3 lines or more for optic neuritis attacks.17 Sustained improvement was determined retrospectively from clinician-documented assessment. For patients with first attack, baseline was relied on patient-reported history, estimating EDSS from self-reported disability.18 The outcomes were assessed at follow-up visits occurring at or beyond 3 months, with the evaluation time point closest to 3 months being prioritized.
Statistical Analysis
All VA were converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis and then converted back to standard VA for reporting results. Non-numeric VA values were converted as follows: count fingers (CFs) at 1.7, hand motion (HM) at 2.0, light perception at 2.3, and no light perception at 3.0.19
Descriptive statistics were used. Categorical variables were analyzed using frequency and percentage, whereas continuous variables were described using median and interquartile range. Comparisons of EDSS and logMAR from the attack nadir, before PLEX, and after PLEX were conducted using the Friedman test with the Bonferroni correction. Binary logistic regression was used to evaluate factors associated with CR and CSI. In addition to factors that were likely influencing CR and CSI including age, optic neuritis and myelitis phenotype, pre-PLEX EDSS and time to PLEX, factors found to be significant from univariate analysis were included in the multivariate analysis to further account for potential confounders. Age, time to first acute immunotherapy, time to PLEX, and EDSS were analyzed as continuous variables. When variables were highly correlated, only the one with the strongest association with the outcomes were included in multivariate analysis to avoid multicollinearity. To address imbalanced categorical data, class weights were assigned inversely proportional to the frequencies of each class during the multivariate analysis. Odds ratios and 95% CI were used to quantify the strength of the associations. The p value was 2-sided, and a p value of less than 0.05 was considered significant. To generate probability curves of CR and CSI, the outcome-specific predicted probabilities were derived for each case via multivariate logistic regression. These predicted probabilities were subsequently plotted against the independent variables using quadratic spline fitting to illustrate the mean probability and 95% CI. Statistical analyses were performed using IBM SPSS Statistics version 28 (IBM Corp., Armonk, NY).
Data Availability
Anonymized data used for this study may be available on request depending on the local consent.
Results
Cohort Demographic and Clinical Characteristics
This international multicenter cohort study encompassed 243 attacks treated with PLEX involving 234 patients. The number of patients from each center is detailed in eTable 1. Demographic and clinical characteristics of the cohort are summarized in Table 1. Of the 234 patients, 135 (58%) were female. Of the 243 attacks, 42 (17%) occurred in pediatric patients (age <18 years), and 165 (68%) were the first attack. Before the attack, 45 (19%) were on baseline chronic immunotherapy. The most frequent attack presentation was optic neuritis in 161 attacks (66%) (involving 235 eyes). This was followed by myelitis in 77 attacks (31%), acute disseminated encephalomyelitis in 24 (10%), brainstem or cerebellar deficits in 15 (6%), cerebral-cortical encephalitis in 3 (1%), and cerebral polyfocal deficits in 1 (0.4%). Of note, 36 attacks (15%) presented with more than 1 core clinical syndrome. Of 243, 188 (77%) attacks underwent 5 cycles, with the total number of cycles ranging from 3 to 14.
Table 1.
Demographic and Clinical Characteristics of the Cohort
| Total cohort (N = 234 patients, 243 attacks) | |
| Female, n (%) | 135/234 (58) |
| Age at attack onset, y, median (IQR) | 34 (22–49) |
| Age ≤18 y, n (%) | 42 (17) |
| Ethnicity, n (%) | |
| Non-Hispanic White | 171 (73) |
| Black | 20 (9) |
| Hispanic | 14 (6) |
| Asian or Pacific islander | 13 (6) |
| Others | 15 (6) |
| First attack, n (%) | 165 (68) |
| Chronic immunotherapy before PLEX, n (%) | 45 (19) |
| Prolonged steroids | 10 (4) |
| Azathioprine | 5 (2) |
| Mycophenolate mofetil | 10 (4) |
| B-cell depleting therapies | 14 (6) |
| Othersa | 12 (5) |
| Clinical presentation, n (%) | |
| Optic neuritis | 161 (66) |
| Myelitis | 77 (32) |
| ADEM | 24 (10) |
| Cerebral monofocal or polyfocal deficit | 1 (0.4) |
| Brainstem or cerebellar deficit | 15 (6) |
| Cerebral cortical encephalitis | 3 (1) |
| >1 core clinical syndrome | 36 (15) |
| VA and logMAR at nadir, median (IQR)b | CF (20/100–HM) 1.70 (0.70–2.00) |
| EDSS at attack nadir, median (IQR) | 4.0 (3.0–7.0) |
| EDSS worsening from pre-attack baseline at attack nadir, median (IQR) | 4.0 (3.0–6.5) |
Abbreviations: ADEM = acute disseminated encephalomyelitis; CF = count finger; EDSS = Expanded Disability Status Scale; HM = hand motion; IQR = interquartile range; IVIG = IV immunoglobulin; logMAR = logarithm of the minimum angle of resolution; PLEX = plasma exchange; VA = visual acuity.
Methotrexate 4, adalimumab 1, cyclophosphamide 1, cyclosporine 1, dimethyl fumarate 1, fingolimod 1, glatiramer acetate 1, mitoxantrone 1, maintenance IVIG 1.
Data included all 235 involved eyes from patients with optic neuritis only.
Attack Severity and Treatment
Detailed attack severity is presented in Table 1. At the attack nadir, the median EDSS was 4.0 (3.0–7.0). For the 235 eyes affected by optic neuritis, the median VA was CF (20/100–HM) at nadir. The median time from attack onset to the first acute immunotherapy was 7 days (2–14 days). Before PLEX, the EDSS remained at 4.0 (3.0–6.5) without significant change from the attack nadir (p = 0.890). However, VA before PLEX had improved to 20/400 (20/70–HM) from the attack nadir (p = 0.009).
Treatment profile is detailed in Table 2. In addition to PLEX, other acute immunotherapies given included high-dose systemic corticosteroids in 239 (99%) and IV immunoglobulin (IVIG) in 32 (13%). PLEX was administered as the first-line therapy in 40 (17%). All other patients received PLEX as a second-line treatment after receiving high-dose systemic corticosteroids as first-line therapy, and 1 of 203 (<1%) received both high-dose systemic corticosteroids and IVIG before PLEX. The primary reasons for PLEX included 1 or more of lack of improvement or worsening after steroid therapy in 163 (67%), severe disability at presentation in 81 (33%), and a history of positive response to prior PLEX in 8 (3%). The median time from attack onset to the initiation of PLEX was 13 (7–24) days.
Table 2.
Treatment Profile
| Total cohort (N = 234 patients, 243 attacks) | |
| Time from attack onset to the first acute immunotherapy, d, median (IQR) | 7 (2–14) |
| VA and logMAR before PLEX, median (IQR) | 20/400 (20/70–HM) 1.30 (0.54–2.00) |
| EDSS before PLEX, median (IQR) | 4.0 (3.0–6.5) |
| EDSS worsening from pre-attack baseline before PLEX, median (IQR) | 4.0 (3.0–6.5) |
| PLEX as the first-line therapy, n (%) | 40 (17) |
| PLEX indication, n (%) | |
| No or suboptimal improvement or worsening after steroid | 163 (67) |
| Severe disability at presentation | 81 (33) |
| History of prior PLEX responsiveness | 8 (3) |
| Time from attack onset to PLEX, d, median (IQR) | 13 (7–24) |
| Additional acute immunotherapy, n (%) | 243 (100) |
| High-dose systemic corticosteroids | 239 (99) |
| IVIG | 32 (13) |
| Long-term immunotherapy after attack, n (%) | 162 (67) |
| Prolonged steroids | 41 (17) |
| Azathioprine | 28 (12) |
| Mycophenolate mofetil | 32 (13) |
| Maintenance IVIG | 23 (10) |
| B-cell depleting therapies | 56 (23) |
| Othersa | 11 (5) |
Abbreviations: EDSS = Expanded Disability Status Scale; IVIG = IV immunoglobulin; IQR = interquartile range; logMAR = logarithm of the minimum angle of resolution; PLEX = plasma exchange; VA = visual acuity.
Methotrexate 4, maintenance PLEX 3, cyclophosphamide 2, adalimumab 1, cyclosporine 1.
After PLEX, 162 (67%) continued or commenced long-term immunotherapy. Prolonged steroids were given in 41 patients (17%). Other therapies included B-cell depleting therapy in 56 (23%), mycophenolate mofetil in 32 (13%), azathioprine in 28 (12%), maintenance IVIG in 23 (10%), methotrexate in 4 (2%), maintenance PLEX in 3 (1%), and cyclophosphamide in 2 (1%). In addition, 1 patient each received adalimumab and cyclosporine.
Outcomes After PLEX
Outcomes after PLEX are summarized in Table 3. The outcomes of patients treated in different years are shown in eTable 2. Within 3 months after PLEX, early subsequent attacks occurred in 14 (6%). Recovery outcomes were assessed in the remaining 229 patients. The median time to outcome assessment was 7 (4–11) months. The changes of EDSS from attack nadir, before PLEX, and the last follow-up are illustrated in Figure 1. Before PLEX, none of the patients had achieved CR, and 24 (10%) had experienced CSI. The EDSS decreased significantly from before PLEX 4.0 (3.0–6.5) to 1.0 (0–2.5) at last follow-up (p < 0.001). VA also increased from 20/400 before PLEX (20/70–HM) to 20/20 (20/20–20/30), at last follow-up (p < 0.001). After PLEX, CR was achieved in 100 (44%), and CSI was observed in 213 (93%) attacks.
Table 3.
Outcomes
| Total cohort (n = 234 patients, 243 attacks) | |
| Subsequent relapse within 3 mo after PLEX, n (%) | 14 (6) |
| Final VA and logMAR, median (IQR) | 20/20 (20/20–20/30) 0 (0–0.18) |
| Final EDSS, median (IQR) | 1.0 (0–2.5) |
| Complete recovery, n/N (%) | 100/229 (44) |
| Clinically significant improvement, n/N (%) | 213/229 (93) |
| Time to outcome assessment, mo, median (IQR) | 7 (4–11) |
| Follow-up length, mo, median (IQR) | 31 (12–55) |
Abbreviations: EDSS = Expanded Disability Status Scale; IQR = interquartile range; logMAR = logarithm of the minimum angle of resolution; PLEX = plasma exchange; VA = visual acuity.
Figure 1. Outcomes After Plasma Exchange.
Changes in (A) expanded disability status scale and (B) visual acuity from attack nadir, before plasma exchange and last follow-up (at least 3 months from plasma exchange). CF = count finger; HM = hand motion; LP = light perception; NLP = no light perception.
Residual symptoms were also assessed in patients without a subsequent attack within 3 months after PLEX. Patients with baseline deficits before the attack were excluded from this assessment: 42 eyes with VA worse than 20/40, 16 patients with gait impairment or bowel dysfunction, and 21 patients with bladder dysfunction. The frequencies of symptoms at the attack nadir, before PLEX, and after PLEX are detailed in eTable 3. The frequencies of symptoms at the attack nadir and before PLEX were similar. Among the 193 eyes with VA worse than 20/40 at attack nadir, 26 (13%) had a VA worse than 20/40 after PLEX, with only 5 (3%) having VA worse than 20/200. Gait impairment was observed in 95 patients at attack nadir (28 wheelchair dependent). After PLEX, 27 (28%) still had gait impairment with 13 (14%) requiring unilateral assistance, 7 (7%) needing bilateral assistance, and 7 (7%) wheelchair dependence. Of the 75 patients experiencing bladder dysfunction at nadir (66 required intermittent or constant catheterization), 35 (47%) continued to have bladder dysfunction after PLEX. Mild bladder dysfunction (not requiring catheterization) was observed in 12 (16%), but 18 (24%) required intermittent catheterization, and 5 (7%) needed continuous catheterization. In addition, of the 61 patients with bowel dysfunction at nadir (40 required stool evacuation), 24 (39%) had residual bowel dysfunction after PLEX. Nineteen (31%) did not require any form of evacuation, whereas 5 (8%) needed intermittent stool evacuation.
Factors Associated With Improvement After PLEX
The univariate analyses of factors associated with CR and CSI are presented in eTables 4 and 5, respectively. The results of the multivariate analysis are detailed in Table 4. Factors associated with a lower likelihood of CR from multivariate analysis include advanced age, with an adjusted odd ratio (aOR) of 0.97 (0.96–0.99) per additional year of age (p = 0.005), a higher EDSS worsening from preattack baseline before PLEX 0.66 (0.54–0.81) per 0.5 increment of EDSS (p < 0.001), and delayed PLEX 0.98 (0.96–0.99) per 1 additional day of delay (p = 0.024). The factors associated with a lower likelihood of CSI were age and the time from onset to PLEX. Advanced age (aOR 0.97 [0.96–0.99] per additional year of age, p < 0.001) and delayed PLEX (aOR 0.95 [0.94–0.96] per 1 additional day of delay, p < 0.001) decreased the likelihood of CSI. However, there was no difference in outcomes in children (younger than 18 years) and adults (eTable 5), and there was not a particular cutoff of timing to PLEX treatment that clearly delineated improved chances of recovery.
Table 4.
Multivariate Analyses for Factors Associated With Complete Recovery and Clinically Significant Improvement After PLEX
| Odds ratio (95% CI) | p Value | |
| Complete recovery | ||
| Age at attack onset | 0.97 (0.96–0.99)a | 0.005 |
| First attack | 0.48 (0.20–1.14) | 0.096 |
| Chronic immunotherapy before PLEX | 0.79 (0.28–2.19) | 0.646 |
| Optic neuritis | 0.87 (0.34–2.25) | 0.775 |
| Myelitis | 0.90 (0.40–1.99) | 0.790 |
| Higher EDSS worsening from preattack baseline before PLEX | 0.66 (0.54–0.81)b | <0.001 |
| Time from onset to PLEX | 0.98 (0.96–0.99)c | 0.024 |
| Clinically significant improvement | ||
| Age at attack onset | 0.97 (0.96–0.99)a | <0.001 |
| Optic neuritis | 2.04 (0.90–4.62) | 0.088 |
| Myelitis | 1.09 (0.60–1.99) | 0.784 |
| Higher EDSS worsening from pre-attack baseline before PLEXa | 1.05 (0.90–1.21)b | 0.555 |
| Time from onset to PLEX | 0.95 (0.94–0.96)c | <0.001 |
Abbreviations: EDSS = Expanded Disability Status Scale; PLEX = plasma exchange.
Odds ratio per each additional year of age.
Odds ratio per 0.5 increment of EDSS.
Odds ratio per each additional day of delay.
The predicted probability of CR and CSI in relation to EDSS worsening from baseline and time from onset to PLEX is illustrated in Figure 2. The predicted probability of CR decreases with age, higher EDSS worsening from baseline before PLEX, and increased delays in initiating PLEX (Figure 2, A–C). Conversely, the predicted probability of achieving CSI was decreased with age (Figure 2D) while irrespective of EDSS worsening from baseline (Figure 2E). Similar to CR, the predicted probability for CSI also decreased with delayed initiation of PLEX (Figure 2F). Individual centers did not differ in outcome, and including centers to the multivaraite model did not alter the associations of the other factors (data not shown).
Figure 2. Factors Associated With Outcomes After Plasma Exchange.
The predicted probabilities of complete recovery and clinically significant improvement in relation to age at the attack onset, Expanded Disability Status Scale worsening from preattack baseline before plasma exchange, and time from attack onset to plasma exchange.
Adverse Events After PLEX
Adverse effects were reported in 16 (7%) patients. The most common complications were hypotension and hypofibrinogenemia, each occurring in 4 cases. Other adverse effects are listed in Table 5. Only 1 patient stopped the PLEX before the intended number of treatments because of adverse effects (received 4 cycles PLEX and stopped because of FFP transfusion reaction; VA improved to 20/25 at that time).
Table 5.
Complications From Plasma Exchange Reported in 16 Cases
| Complication | No. of cases |
| Hypotension | 4 |
| Hypofibrinogenemia | 4 |
| Nausea | 3 |
| Central line thrombosis | 2 |
| Diaphoresis | 2 |
| Malaise | 2 |
| Shortness of breath | 2 |
| Hypocalcemia | 2 |
| Chest pain | 1 |
| Dizziness | 1 |
| Fresh frozen plasma infusion reaction | 1 |
| Pulmonary embolism tachycardia | 1 |
| Tachycardia | 1 |
Classification of Evidence
This study provides Class IV evidence that PLEX is associated with favorable clinical outcomes in patients with MOGAD.
Discussion
Our international collaborative study described outcomes in patients treated with PLEX in acute MOGAD attack. This study also reveals a few critical points for PLEX in MOGAD attack. First, delays in initiating PLEX were associated with a reduction in the likelihood of achieving both CR and CSI. Second, although CSI was observed in more than 90% of patients, CR was achieved in only 44%. Bowel and bladder dysfunction remain the most common residual deficit, persisting in 40%–50% of patients. This is important for counseling regarding treatment expectations and underscores the need for postattack symptomatic treatment and future neuroregenerative therapy.
Our study suggests the principle “time is brain (as well as optic nerve and spinal cord)” remains crucial in managing MOGAD, mirroring insights from studies on other acute immunotherapies in MOGAD8,9 and PLEX in MOGAD20 as well as other CNS inflammatory diseases,11,12,21 where timely treatment is essential. Similar to previous studies, we demonstrated that delayed overall acute treatment was associated with a decreased likelihood of CR, but the stronger statistical significance was observed with an association of delayed PLEX and CR. For CSI, only delayed PLEX was associated with a decreased likelihood of CSI while delayed overall acute treatment was not significantly associated. This highlights the importance of early treatment, as earlier PLEX initiation was observed in patients with favorable outcomes. The necessity for prompt PLEX treatment in MOGAD attacks can be explained by the pathogenicity of MOG antibodies and inflammatory cytokines. Similar to the damage caused by aquaporin-4 antibodies in NMOSD, MOG antibodies may cause neuronal injury through complement activation and antibody-dependent cytotoxicity.22,23 Recent evidence also suggested that several inflammatory cytokines may contribute to pathogenesis of MOGAD.24-26 Consequently, early removal of MOG antibodies and inflammatory cytokines with PLEX may lessen cellular damage and significantly improve clinical outcomes, paralleling findings from NMOSD.11,12
In addition, our study demonstrated that age was associated with both CR and CSI after PLEX, similar to a previous study.6 This is likely due to age-dependent neural plasticity. In an independent international multicenter cohort, children demonstrated better visual outcomes than adults despite similar levels of neuroaxonal atrophy after MOGAD attack.27 However, there was no statistically significant difference in outcomes in children (younger than 18 years) and adults in our study. Additional research is needed to determine whether the responsiveness to PLEX is age-dependent.6
In our study, CR and CSI rates were higher than those reported for NMOSD.11,12 This distinction in outcomes may reflect greater complement activation in NMOSD than MOGAD,22,28,29 and differences in the primary cellular targets of each disease. In NMOSD, aquaporin-4 antibodies target astrocyte foot processes, leading to astrocytic injury.30 This astrocytic damage disrupts CNS homeostasis and affects the structural and metabolic support of neurons and glial cells, leading to not only neuronal damage but also secondary demyelination because of oligodendrocyte injury.31,32 By contrast, MOG antibodies primarily target oligodendrocytes, leading predominantly to demyelination with sparing of astrocytes. Moreover, over 70% of MOGAD T2-lesions resolve over time when compared with 10%–15% in NMOSD.33 This suggests less widespread damage compared with NMOSD and greater capacity for healing, potentially explaining the higher recovery rates in MOGAD.34,35
This study is not designed to demonstrate the superiority of PLEX to other acute immunotherapies, but rather to describe its outcome in acute treatment of MOGAD. Our findings demonstrate the potential of PLEX as an adjunctive therapy in acute MOGAD attack. The patients in our study typically exhibited more severe initial symptoms than those in general MOGAD cohorts because PLEX is typically reserved for severe or corticosteroid refractory attacks. The outcomes related to the EDSS in our cohort are comparable with those of previous studies encompassing all severity levels at presentation.3,6,7,36-41 Our study also reported similar or lower frequencies of residual bowel and bladder dysfunction, which are the most common residual deficits, compared with other cohorts.6,39 The rate of gait dependence was comparable with the previous studies.38 Visual recovery was favorable as well, with only 3% in our study experiencing VA of 20/200 or worse among patients with a normal baseline VA, compared with 5%–14% reported in other MOGAD studies, which included various acute treatments,7-9,42 despite our cohort having a bias toward very severe optic neuritis that providers felt required PLEX therapy.
Several limitations of our study should be acknowledged. First, the retrospective design may lead to recall bias, particularly the adverse events which could be underreported. In addition, the multicenter and international design could introduce variability in treatment administration and potential differences because of regional practices, affecting the uniformity of the data. Moreover, the absence of a control group limits our ability to rule out spontaneous improvement, the delayed effect of prior high-dose corticosteroids, the effect of long-term immunotherapy and determine the superiority of PLEX over other escalation treatments. Although the EDSS measures a broad range of neurologic disability, it is less sensitive for visual and brain or brainstem-related disabilities. Although including VA in outcome evaluation can address the gap in visual outcome, better measurements (e.g., formal cognitive testing, seizure outcomes, speech and swallowing measurement) are still needed for future studies. Moreover, inter-rater variability of EDSS may also affect outcomes. Sustained improvement was also determined retrospectively from clinician-documented assessments in medical records rather than a predefined third time point. Additional studies with standardized prospective follow-up assessments may provide additional validation. In addition, incorporating formal visual field evaluation, and optical coherence tomography will further improve visual outcome evaluation. Moreover, patients in our cohort may represent more severe cases of MOGAD because clinicians often reserve PLEX for particularly severe or refractory attacks. In the absence of a control group with comparable demographics, phenotype, and disease severity, our study could not determine a specific cutoff period for the optimal initiation of PLEX in MOGAD attacks. Further prospective controlled studies are necessary to establish precise guidelines for PLEX timing, taking into account the additive benefits beyond natural recovery and steroid therapy, as well as the potential risks of adverse events. The ongoing study, Treatment of Inflammatory Myelitis and Optic Neuritis with Early Plasma Exchange,43 is expected to provide critical prospective data on the efficacy and safety of early PLEX in inflammatory myelitis and optic neuritis and may help define future treatment guidelines in MOGAD and other inflammatory demyelinating conditions. Owing to a limited number of pediatric patients, the generalizability of the findings in this age group may be limited. Because all participating centers in this study are tertiary referral centers, they are likely to encounter a higher proportion of severe or refractory cases. This could influence the generalizability of our findings to the broader MOGAD population.
In conclusion, this international collaborative study provides insights into outcomes in patients treated with PLEX for acute MOGAD attack and demonstrates better outcomes in patients with earlier PLEX. Additional studies, including prospective randomized controlled trials, are essential to validate these results and explore the comparative effectiveness of PLEX against other treatments. These efforts will pave the way for refined guidelines for using PLEX in acute MOGAD treatment.
Glossary
- aOR
adjusted odd ratio
- CA
complete recovery
- CF
count finger
- CSI
clinically significant improvement
- EDSS
Expanded Disability Status Scale
- HM
hand motion
- IVIG
IV immunoglobulin
- logMAR
logarithm of the minimum angle of resolution
- MOGAD
myelin oligodendrocyte glycoprotein antibody-associated disease
- MS
multiple sclerosis
- NMOSD
neuromyelitis optica spectrum disorder
- PLEX
plasma exchange
- VA
visual acuity
Footnotes
Editorial, page e214114
Author Contributions
S. Thakolwiboon: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data. V. Redenbaugh: major role in the acquisition of data; analysis or interpretation of data. B. Chen: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; analysis or interpretation of data. S. Hewitt: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. S. Shah: drafting/revision of the manuscript for content, including medical writing for content. I. Lotan: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. M. Levy: drafting/revision of the manuscript for content, including medical writing for content. M. Forcadela: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. S. Huda: drafting/revision of the manuscript for content, including medical writing for content. J. Pique: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. R. Marignier: drafting/revision of the manuscript for content, including medical writing for content. C. Boutiere: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. B. Audoin: drafting/revision of the manuscript for content, including medical writing for content. P. Poullin: drafting/revision of the manuscript for content, including medical writing for content. D. Champsas: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. D. Choi: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. H.V. Danesh-Meyer: drafting/revision of the manuscript for content, including medical writing for content. E. Vasileiou: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. E.S. Sotirchos: drafting/revision of the manuscript for content, including medical writing for content. J.B. Davis: drafting/revision of the manuscript for content, including medical writing for content. A.D. Henderson: drafting/revision of the manuscript for content, including medical writing for content. A. Wilf-Yarkoni: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. H. Stiebel-Kalish: drafting/revision of the manuscript for content, including medical writing for content. E. Maillart: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. L. Bonelli: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. A.C. Arnold: drafting/revision of the manuscript for content, including medical writing for content. M. Boudot De La Motte: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. R. Deschamps: drafting/revision of the manuscript for content, including medical writing for content. J. Jitprapaikulsan: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. H.E. Moss: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. S.E. Villarreal Navarro: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. Y. Mao-Draayer: drafting/revision of the manuscript for content, including medical writing for content. M. Mishra: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. N. Vorasoot: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. L. Cacciaguerra: drafting/revision of the manuscript for content, including medical writing for content. N. Tisavipat: drafting/revision of the manuscript for content, including medical writing for content. D.A. Tajfirouz: drafting/revision of the manuscript for content, including medical writing for content. J.-M. Tillema: drafting/revision of the manuscript for content, including medical writing for content. S.A. Lopez-Chiriboga: drafting/revision of the manuscript for content, including medical writing for content. J. Palace: drafting/revision of the manuscript for content, including medical writing for content; analysis or interpretation of data. Y. Hacohen: drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data. S.J. Pittock: drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data. E.P. Flanagan: drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data. J.J. Chen: drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data.
Study Funding
The authors report no targeted funding.
Disclosure
S. Shah has served as a consultant for Alexion, Amgen, and Genentech. M. Levy has received personal compensation for advising the following companies: Alexion, Horizon, Genentech/Roche, UCB, Sanofi and Mitsubishi through Massachusetts General Hospital; and has also received grants from Alexion, Horizon, Genentech, Roche, UCB, and Sanofi for research projects. A.D. Henderson has served on advisory boards for Horizon Therapeutics and receives compensation from Springer Nature for authorship and editorial services. E. Maillart reports research support from Biogen and personal fees for lectures and advisory boards from Alexion, Biogen, Horizon, Janssen, Merck, Novartis, Roche, Sanofi, and Teva. M. Boudot de la Motte has served on scientific advisory boards for Alexion and Sanofi and received personal fees and travel honoraria from Alexion and Novartis. H.V. Moss reports funding from NIH p30 026877 and an unrestricted grant from research to prevent blindness that supported this work. S.E. Villarreal Navarro reports funding from NIH p30 026877 and an unrestricted grant from research to prevent blindness that supported this work. Y. Mao-Draayer has consulted for and/or received grant support from: Acorda, Bayer Pharmaceutical, Biogen Idec, EMD Serono, Sanofi-Genzyme, Novartis, Questor, Roche-Genentech, Horizon/Amgen, and Teva Neuroscience. L. Cacciaguerra received speaker and consultant honoraria from ACCMED, Roche, BMS Celgene, and Sanofi; and travel support for conferences by Merck Serono. N. Tisavipat reports no disclosure relevant to this study. A.S. Lopez-Chiriboga has received personal compensation for participating in scientific advisory boards for Genentech and Horizon. S.J. Pittock reports grants, personal fees, and nonfinancial support from Alexion Pharmaceuticals, Amgen (previously MedImmune/Viela Bio/Horizon) Genentech, and Roche; grants from Adimune; and personal fees for consulting from UCB, Astellas and Arialys, and Sage Therapeutics; has 2 patents issued (8889102; application 12-678350; Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia; and 9891219B2; application 12-573942; Methods for Treating Neuromyelitis Optica [NMO] by Administration of Eculizumab to an individual that is Aquaporin-4 [AQP4]-IgG Autoantibody positive) for which he has received royalties; has patents pending for IgGs to the following proteins as biomarkers of autoimmune neurologic disorders: septin-5, kelch-like protein 11, GFAP, PDE10A, and MAP1B; works at Mayo Clinic, which offers commercial MOG-IgG and AQP4-IgG testing; and receives no royalties from the sale of tests done at the neuroimmunology Laboratory at Mayo Clinic. E.P. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB; has received research support from UCB; has received speaker honoraria from Pharmacy Times; received royalties from UpToDate; was a site primary investigator in a randomized clinical trial on inebilizumab in neuromyelitis optica spectrum disorder run by Medimmune/Viela-Bio/Horizon Therapeutics; has received funding from the NIH (R01NS113828); is a member of the medical advisory board of the MOG project; is an editorial board member of the Journal of the Neurological Sciences and Neuroimmunology Reports; and has a submitted patent on DACH1-IgG as a biomarker of paraneoplastic autoimmunity. J.J. Chen has served as a consultant for UCB and Horizon. All other authors report no disclosure relevant to this study. Go to Neurology.org/N for full disclosures.
References
- 1.Banwell B, Bennett JL, Marignier R, et al. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurol. 2023;22(3):268-282. doi: 10.1016/S1474-4422(22)00431-8 [DOI] [PubMed] [Google Scholar]
- 2.Jitprapaikulsan J, Chen JJ, Flanagan EP, et al. Aquaporin-4 and myelin oligodendrocyte glycoprotein autoantibody status predict outcome of recurrent optic neuritis. Ophthalmology. 2018;125(10):1628-1637. doi: 10.1016/j.ophtha.2018.03.041 [DOI] [PubMed] [Google Scholar]
- 3.Lopez-Chiriboga AS, Sechi E, Buciuc M, et al. Long-term outcomes in patients with myelin oligodendrocyte glycoprotein immunoglobulin G–associated disorder. JAMA Neurol. 2020;77(12):1575-1577. doi: 10.1001/jamaneurol.2020.3115 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Akaishi T, Misu T, Takahashi T, et al. Progression pattern of neurological disability with respect to clinical attacks in anti-MOG antibody-associated disorders. J Neuroimmunol. 2021;351:577467. doi: 10.1016/j.jneuroim.2020.577467 [DOI] [PubMed] [Google Scholar]
- 5.Thakolwiboon S, Zhao-Fleming H, Karukote A, Mao-Draayer Y, Flanagan EP, Avila M. Meta-analysis of effectiveness of steroid-sparing attack prevention in MOG-IgG-associated disorder. Mult Scler Relat Disord. 2021;56:103310. doi: 10.1016/j.msard.2021.103310 [DOI] [PubMed] [Google Scholar]
- 6.Jurynczyk M, Messina S, Woodhall MR, et al. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain. 2017;140(12):3128-3138. doi: 10.1093/brain/awx276 [DOI] [PubMed] [Google Scholar]
- 7.Deschamps R, Pique J, Ayrignac X, et al. The long-term outcome of MOGAD: an observational national cohort study of 61 patients. Eur J Neurol. 2021;28(5):1659-1664. doi: 10.1111/ene.14746 [DOI] [PubMed] [Google Scholar]
- 8.Min YG, Moon Y, Kwon YN, et al. Prognostic factors of first-onset optic neuritis based on diagnostic criteria and antibody status: a multicentre analysis of 427 eyes. J Neurol Neurosurg Psychiatry. 2024;95(8):753-760. doi: 10.1136/jnnp-2023-333133 [DOI] [PubMed] [Google Scholar]
- 9.Rode J, Pique J, Maarouf A, et al. Time to steroids impacts visual outcome of optic neuritis in MOGAD. J Neurol Neurosurg Psychiatry. 2023;94(4):309-313. doi: 10.1136/jnnp-2022-330360 [DOI] [PubMed] [Google Scholar]
- 10.Weinshenker BG, O'Brien PC, Petterson TM, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol. 1999;46(6):878-886. doi: 10.1002/1531-8249(199912)46:6<878::aid-ana10>3.0.co;2-q [DOI] [PubMed] [Google Scholar]
- 11.Bonnan M, Valentino R, Debeugny S, et al. Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurol Neurosurg Psychiatry. 2018;89(4):346-351. doi: 10.1136/jnnp-2017-316286 [DOI] [PubMed] [Google Scholar]
- 12.Kleiter I, Gahlen A, Borisow N, et al. Apheresis therapies for NMOSD attacks: a retrospective study of 207 therapeutic interventions. Neurol Neuroimmunol Neuroinflamm. 2018;5(6):e504. doi: 10.1212/NXI.0000000000000504 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Jacob S, Mazibrada G, Irani SR, Jacob A, Yudina A. The role of plasma exchange in the treatment of refractory autoimmune neurological diseases: a narrative review. J Neuroimmune Pharmacol. 2021;16(4):806-817. doi: 10.1007/s11481-021-10004-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344-349. doi: 10.1016/j.jclinepi.2007.11.008 [DOI] [PubMed] [Google Scholar]
- 15.Phillips JT, Giovannoni G, Lublin FD, et al. Sustained improvement in Expanded Disability Status Scale as a new efficacy measure of neurological change in multiple sclerosis: treatment effects with natalizumab in patients with relapsing multiple sclerosis. Mult Scler. 2011;17(8):970-979. doi: 10.1177/1352458511399611 [DOI] [PubMed] [Google Scholar]
- 16.Cree BA, Cohen JA, Reder AT, et al. Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis. Mult Scler. 2021;27(14):2219-2231. doi: 10.1177/13524585211000280 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Joussen AM, Lehmacher W, Hilgers RD, Kirchhof B. Is significant relevant? Validity and patient benefit of randomized controlled clinical trials on age-related macular degeneration. Surv Ophthalmol. 2007;52(3):266-278. doi: 10.1016/j.survophthal.2007.02.010 [DOI] [PubMed] [Google Scholar]
- 18.Kaufmann M, Salmen A, Barin L, et al. Development and validation of the self-reported disability status scale (SRDSS) to estimate EDSS-categories. Mult Scler Relat Disord. 2020;42:102148. doi: 10.1016/j.msard.2020.102148 [DOI] [PubMed] [Google Scholar]
- 19.Chen JJ, Flanagan EP, Pittock SJ, et al. Visual outcomes following plasma exchange for optic neuritis: an international multicenter retrospective analysis of 395 optic neuritis attacks. Am J Ophthalmol. 2023;252:213-224. doi: 10.1016/j.ajo.2023.02.013 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Schwake C, Ladopoulos T, Häußler V, et al. Apheresis therapies in MOGAD: a retrospective study of 117 therapeutic interventions in 571 attacks. J Neurol Neurosurg Psychiatry. 2024;96(7):639-646. doi: 10.1136/jnnp-2024-334863 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Magaña SM, Keegan BM, Weinshenker BG, et al. Beneficial plasma exchange response in central nervous system inflammatory demyelination. Arch Neurol. 2011;68(7):870-878. doi: 10.1001/archneurol.2011.34 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Yandamuri SS, Filipek B, Obaid AH, et al. MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity. JCI Insight. 2023;8(11):e165373. doi: 10.1172/jci.insight.165373 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Kaneko K, Kuroda H, Matsumoto Y, et al. Different complement activation patterns following C5 cleavage in MOGAD and AQP4-IgG+NMOSD. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200293. doi: 10.1212/NXI.0000000000200293 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Cacciaguerra L, Flanagan EP. Updates in NMOSD and MOGAD diagnosis and treatment: a tale of two central nervous system autoimmune inflammatory disorders. Neurol Clin. 2024;42(1):77-114. doi: 10.1016/j.ncl.2023.06.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Kothur K, Wienholt L, Tantsis EM, et al. B cell, Th17, and neutrophil related cerebrospinal fluid cytokine/chemokines are elevated in MOG antibody associated demyelination. PLoS One. 2016;11(2):e0149411. doi: 10.1371/journal.pone.0149411 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Kwon YN, Kim B, Ahn S, et al. Serum level of IL-1β in patients with inflammatory demyelinating disease: marked upregulation in the early acute phase of MOG antibody associated disease (MOGAD). J Neuroimmunol. 2020;348:577361. doi: 10.1016/j.jneuroim.2020.577361 [DOI] [PubMed] [Google Scholar]
- 27.Havla J, Pakeerathan T, Schwake C, et al. Age-dependent favorable visual recovery despite significant retinal atrophy in pediatric MOGAD: how much retina do you really need to see well? J Neuroinflammation. 2021;18(1):121. doi: 10.1186/s12974-021-02160-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Jitprapaikulsan J, Fryer JP, Majed M, et al. Clinical utility of AQP4-IgG titers and measures of complement-mediated cell killing in NMOSD. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e727. doi: 10.1212/NXI.0000000000000727 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Mader S, Ho S, Wong HK, et al. Dissection of complement and Fc-receptor-mediated pathomechanisms of autoantibodies to myelin oligodendrocyte glycoprotein. Proc Natl Acad Sci USA. 2023;120(13):e2300648120. doi: 10.1073/pnas.2300648120 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Hinson SR, Pittock SJ, Lucchinetti CF, et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology. 2007;69(24):2221-2231. doi: 10.1212/01.WNL.0000289761.64862.ce [DOI] [PubMed] [Google Scholar]
- 31.Marignier R, Nicolle A, Watrin C, et al. Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury. Brain. 2010;133(9):2578-2591. doi: 10.1093/brain/awq177 [DOI] [PubMed] [Google Scholar]
- 32.Lucchinetti CF, Guo Y, Popescu BF, Fujihara K, Itoyama Y, Misu T. The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol. 2014;24(1):83-97. doi: 10.1111/bpa.12099 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Sechi E, Krecke KN, Messina SA, et al. Comparison of MRI lesion evolution in different central nervous system demyelinating disorders. Neurology. 2021;97(11):e1097-e1109. doi: 10.1212/WNL.0000000000012467 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Höftberger R, Guo Y, Flanagan EP, et al. The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody. Acta Neuropathol. 2020;139(5):875-892. doi: 10.1007/s00401-020-02132-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Spadaro M, Gerdes LA, Mayer MC, et al. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Ann Clin Transl Neurol. 2015;2(3):295-301. doi: 10.1002/acn3.164 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Höftberger R, Sepulveda M, Armangue T, et al. Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease. Mult Scler. 2015;21(7):866-874. doi: 10.1177/1352458514555785 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.van Pelt ED, Wong YY, Ketelslegers IA, Hamann D, Hintzen RQ. Neuromyelitis optica spectrum disorders: comparison of clinical and magnetic resonance imaging characteristics of AQP4-IgG versus MOG-IgG seropositive cases in the Netherlands. Eur J Neurol. 2016;23(3):580-587. doi: 10.1111/ene.12898 [DOI] [PubMed] [Google Scholar]
- 38.Cobo-Calvo A, Ruiz A, Maillart E, et al. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology. 2018;90(21):e1858-e1869. doi: 10.1212/WNL.0000000000005560 [DOI] [PubMed] [Google Scholar]
- 39.Ramanathan S, Mohammad S, Tantsis E, et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry. 2018;89(2):127-137. doi: 10.1136/jnnp-2017-316880 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Shor N, Aboab J, Maillart E, et al. Clinical, imaging and follow-up study of optic neuritis associated with myelin oligodendrocyte glycoprotein antibody: a multicentre study of 62 adult patients. Eur J Neurol. 2020;27(2):384-391. doi: 10.1111/ene.14089 [DOI] [PubMed] [Google Scholar]
- 41.Sepúlveda M, Armangue T, Martinez-Hernandez E, et al. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes. J Neurol. 2016;263(7):1349-1360. doi: 10.1007/s00415-016-8147-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Tajfirouz DA, Bhatti MT, Chen JJ. Clinical characteristics and treatment of MOG-IgG-associated optic neuritis. Curr Neurol Neurosci Rep. 2019;19(12):100. doi: 10.1007/s11910-019-1014-z [DOI] [PubMed] [Google Scholar]
- 43.Treatment of Inflammatory Myelitis and Optic Neuritis with Early Plasma Exchange (TIMELY-PLEX). Patient-Centered Outcomes Research Institute; Accessed April 21, 2025. pcori.org/research-results/2024/treatment-inflammatory-myelitis-and-optic-neuritis-early-plasma-exchange-timely-plex. [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Anonymized data used for this study may be available on request depending on the local consent.