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Seizures and Encephalitis in Myelin Oligodendrocyte Glycoprotein IgG Disease vs Aquaporin 4 IgG Disease

Educational Objective
To evaluate whether seizures and encephalopathy occur more commonly in myelin oligodendrocyte glycoprotein IgG disease than in aquaporin 4 IgG disease.
1 Credit CME
Key Points

Question  Do seizures and encephalopathy occur more commonly in myelin oligodendrocyte glycoprotein IgG disease than in aquaporin 4 IgG disease?

Findings  In this case series, 5 of 34 patients (14.7%) with myelin oligodendrocyte glycoprotein IgG disease had seizures compared with 1 of 100 patients with aquaporin 4 IgG neuromyelitis optica spectrum disorder. All 5 patients with myelin oligodendrocyte glycoprotein IgG disease had inflammatory cortical brain lesions associated with the seizures.

Meaning  Myelin oligodendrocyte glycoprotein IgG disease may be the cause for a proportion of autoimmune encephalitis-like presentations with seizures.

Abstract

Importance  Antibodies to myelin oligodendrocyte glycoprotein IgG (MOG-IgG) are increasingly detected in patients with non–multiple sclerosis–related demyelination, some of whom manifest a neuromyelitis optica (NMO) phenotype. Cortical involvement, encephalopathy, and seizures are rare in aquaporin 4 antibody (AQP4-IgG)–related NMO in the white European population. However, the authors encountered several patients with seizures associated with MOG-IgG disease.

Objective  To compare incidence of seizures and encephalitis-like presentation, or both between AQP4-IgG–positive and MOG-IgG–positive patients.

Design, Setting, and Participants  Retrospective case series of all patients who were seropositive for MOG-IgG (n = 34) and the last 100 patients with AQP4-IgG disease (NMO spectrum disorder) seen in the NMO service between January 2013 and December 2016, and analysis was completed January 4, 2017. All patients were seen in a tertiary neurological center, The Walton Centre NHS Foundation Trust in Liverpool, England.

Main Outcomes and Measures  The difference in seizure frequency between the AQP4-IgG–positive and MOG-IgG–positive patient groups was determined.

Results  Thirty-four patients with MOG-IgG disease (20 female) with a median age at analysis of 30.5 years (interquartile range [IQR], 15-69 years), and 100 AQP4-IgG–positive patients (86 female) with a median age at analysis of 54 years (IQR, 12-91 years) were studied. Most patients were of white race. Five of the 34 patients with MOG-IgG (14.7%) had seizures compared with 1 patient with AQP4-IgG (2-sided P < .008, Fisher test). On magnetic resonance imaging, all 5 MOG-IgG–positive patients had inflammatory cortical brain lesions associated with the seizures. In 3 of the 5 MOG-IgG–positive patients, seizures occurred as part of the index event. Four of the 5 presented with encephalopathy and seizures, and disease relapsed in all 5 patients. Four of these patients were receiving immunosuppressant medication at last follow-up, and 3 continued to take antiepileptic medication. In contrast, the only AQP4-IgG–positive patient with seizures had a diagnosis of complex partial epilepsy preceding the onset of NMO by several years and experienced no encephalitic illness; her magnetic resonance imaging results demonstrated no cortical, subcortical, or basal ganglia involvement.

Conclusions and Relevance  Patients with MOG-IgG–associated disease were more likely to have seizures and encephalitis-like presentation than patients with AQP4-IgG–associated disease.

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Article Information

Corresponding Author: Anu Jacob, DM, FRCP, The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerley, Liverpool L9 7LJ, England (anujacob@nhs.net).

Accepted for Publication: July 8, 2017.

Published Online: November 13, 2017. doi:10.1001/jamaneurol.2017.3196

Author Contributions: Drs Hamid and Jacob 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.

Study concept and design: Hamid, Bhojak, Jacob.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Hamid, Whittam, Saviour, Alorainy, Bhojak, Appleton, Jacob.

Critical revision of the manuscript for important intellectual content: Hamid, Mutch, Linaker, Solomon, Bhojak, Woodhall, Waters, Duddy, Jacob.

Statistical analysis: Hamid.

Administrative, technical, or material support: Hamid, Saviour, Alorainy, Mutch, Linaker, Solomon, Woodhall, Appleton.

Study supervision: Bhojak, Jacob.

Conflict of Interest Disclosures: Dr Waters and the University of Oxford hold patents and receive royalties for antibody assays (LGI1, CASPR2, TAG-1, and GABAAR). Dr Waters reported receiving speaker honoraria from Biogen Idec and EUROIMMUN AG, travel grants from the Guthy-Jackson Charitable Foundation, and speaker honoraria from MedImmune, Mereo BioPharma Group, and Retrogenix. No other disclosures were reported.

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