Short-term treatments were undertaken within 6 weeks and included 1 or more of corticosteroids (oral/intravenous [IV]), intravenous immunoglobulin (IVIg), or plasma exchange. Maintenance treatments with multiple sclerosis (MS) medications included any current or prior approved MS medications except rituximab and ocrelizumab. Oral immunosuppressants included azathioprine, cyclophosphamide, methotrexate, or mycophenolate mofetil. Twenty-three patients received 1 or more maintenance attack-prevention treatments, including MS medications excluding rituximab/ocrelizumab (n = 6); IVIg (n = 3); oral/intermittent IV steroids (n = 5); rituximab (n = 1); oral immunosuppressants (n = 6); or a combination (n = 14). Of 14 patients who received combination treatment, the combinations included steroids and oral immunosuppressant, 13; steroids and rituximab, 5; steroids and IVIg, 4; rituximab and oral immunosuppressant, 1; and steroids and plasma exchange, 1. Triple combinations were also used: steroids, rituximab, and IVIg, 2; steroids, rituximab, and oral immunosuppressant, 1 (7%). EDSS indicates Expanded Disability Status Scale; NMO, neuromyelitis optica; ON, optic neuritis; TM, transverse myelitis; VFS, visual functional system.
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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
Data on long-term outcomes of patients with myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG)–associated disorder (MOGAD) are scarce.1,2 We report outcomes in a single-institution cohort with long-term follow-up.
We retrospectively identified 11 adult and 18 pediatric (onset age younger than 18 years) Mayo Clinic patients from January 1, 2000, through May 31, 2019, with (1) MOGAD clinical phenotype3; (2) MOG-IgG 1 seropositivity (median titer, 1:100; range, 1:20-1:1000; 8 of 13 serial samples persistently positive)3; and (3) 9 or more years’ follow-up from onset. The study was approved by the Mayo Foundation Institutional Review Board (IRB No. 08.006647). Written informed consent was provided by patients or parents.
The annualized relapse rate, Expanded Disability Status Scale (EDSS) score, ophthalmology evaluation (including visual acuity evaluation), and magnetic resonance imaging (MRI) scans were assessed at last follow-up (S.L., M.B., J.J.C.). Persistent visual field defects were defined by confrontation testing or mean deviation greater than −3 dB on Humphrey testing, and funduscopic examination was used to assess for optic atrophy.
A total of 29 patients were included (Table, Figure). The temporal distribution and types of attacks (total attacks, 172; median [range] per patient, 5 [1-16]) and short-term and maintenance immunotherapy are illustrated in the Figure. The median (range) follow-up duration was 14 (9-31) years; 4 patients (14%) were monophasic. The median (range) annualized relapse rate was 0.33 (0.06-1.47). Eight of 15 (53%) with brain/spinal cord involvement required a wheelchair at initial attack nadir. The median (range) EDSS score at last follow-up was 2 (0-10), and 2 patients (7%) had an EDSS score of 6 or greater (1 died of MOGAD). No patients had secondary progression. Seven patients had residual bowel/bladder dysfunction. In patients with relapsing disease, the postrecovery median (range) EDSS score after the first attack was lower than at last follow-up (0 [0-3] vs 2 [0-10]; P = .001; paired t test).
Optic neuritis occurred in 28 patients (97%; multiple episodes, 21; single episode, 7) (Figure, Table). At last follow-up, the median (range) visual acuity was 20/20 (20/20 to count fingers), and 26 of 29 patients (90%) had visual acuity of 20/40 or better bilaterally. Persistent visual field deficit occurred in 8 of 26 patients (31%), and optic atrophy was noted in 24 of 25 patients (96%; 8 with unilateral and 16 with bilateral atrophy).
Follow-up brain MRI (median [range] time from onset, 6 [1-11] years) was available in 25 patients and revealed no residual demyelination in 18 patients (72%) and residual demyelinating T2 hyperintensities in 7 patients (28%; 3 with atrophy). All 6 follow-up spine MRI scans were normal.
We found that most patients with MOGAD had a favorable long-term outcome without secondary progression despite frequent relapses, differing from that reported with multiple sclerosis (MS) and aquaporin-4–IgG neuromyelitis optica spectrum disorders (NMOSDs).
Our finding of just 7% having an EDSS score of 6 or greater and 7% unilaterally blind or worse after a median of 14 years of follow-up is similar to outcomes in previous studies with shorter follow-up.1,2,4 While some long-term deficit was accumulated from the presenting attack (similar to prior reports),1 additional attack-related EDSS score worsening in most patients suggests that attack prevention may be associated with lower long-term disability in relapsing MOGAD. Disability is less than with aquaporin-4–IgG NMOSD, with 65% being unilaterally blind or worse and 30% having an EDSS score of 6 or greater after a median of 8.3 years in a prior study.5 These contrasting outcomes support biomarker-based over syndromic-based diagnostic criteria, as NMOSD prognosis with MOG IgG differs markedly from prognosis with aquaporin-4 IgG.
A normal MRI (brain/spine) despite multiple radiologically confirmed relapses favors MOGAD over MS where residual T2 lesions are almost universal. No patients with MOGAD developed secondary progression, and a previous study of 200 patients with progressive MS found no MOG IgG seropositives,6 but younger age and frequent immunosuppressant use in this study could be associated with longer time to progression. Thus, more studies with longer follow-up are needed.
Our limitations include risk of acquisition bias from irregular follow-up, overrepresentation of severe cases from referral bias, and underrepresentation of monophasic or milder cases less likely to undergo follow-up. Nonetheless, the inclusion of additional patients with milder disease would support our conclusion that outcomes are good.
Accepted for Publication: July 3, 2020.
Published Online: August 31, 2020. doi:10.1001/jamaneurol.2020.3115
Correction: This article was corrected on April 5, 2021, to correct an error in the first author’s name.
Corresponding Author: Eoin P. Flanagan, MD, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (email@example.com).
Author Contributions: Drs Lopez and Flanagan had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Lopez and Sechi contributed equally to the manuscript.
Study concept and design: Lopez, Pittock, Flanagan.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Lopez, Sechi, Buciuc, Flanagan.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Sechi, Buciuc, Lucchinetti.
Obtained funding: Pittock.
Administrative, technical, or material support: Lopez.
Study supervision: Lopez, Flanagan.
Conflict of Interest Disclosures: Dr Pittock reported receiving grants, personal fees, and nonfinancial support from Alexion Pharmaceuticals; grants from Grifols and the Autoimmune Encephalitis Alliance; grants, personal fees, nonfinancial support, and other from MedImmune; other support from Astellas; and personal fees from UCB; and having Patent No. 8,889,102 (Application No. 12-678350)—Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia—issued; and Patent No. 9,891,219B2 (Application No. 12-573942)—Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an Individual That Is Aquaporin-4 (AQP4)-IgG Autoantibody Positive—issued. Dr Lucchinetti reported receiving grants from Biogen, National Multiple Sclerosis Society, Kingsland Foundation, and National Institute of Neurological Disorders and Stroke during the conduct of the study. Dr Flanagan reported serving as a site principal investigator for a clinical trial of inebilizumab in neuromyelitis optica spectrum disorder and receiving funding to support the research work from Viela Bio during the conduct of the study. No other disclosures were reported.
Funding/Support: This work was supported by funding from the National Institutes of Health (R01NS113828).
Role of the Funder/Sponsor: The National Institutes of Health had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: The authors thank Katie Dunlay, BA, Jessica Sagen, MS, and John Schmeling, BA, for technical support, Mary Curtis, BA, for secretarial assistance, The Mayo Clinic Center for MS and Autoimmune Neurology for funding support, and Brian G. Weinshenker, MD, Dean M. Wingerchuk, MD, Divyanshu Dubey, MD, Vanessa Marin-Collazo, MD, Eric Eggenberger, DO, Amy Kunchok, MD, and Jan-Mendelt Tillema, MD, for their critical revision of the manuscript. We thank Grant Spears, BS, and Sarah Jenkins, MS, for their assistance with creation of the figure. The individuals were not compensated for their contributions.