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

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.

Figure 1.. Magnetic Resonance Imaging (MRI) of the Brain and Spinal Cord, Cases 1 and 2

A, Axial T2-weighted fluid-attenuated inversion recovery image of the brain shows bilateral hemispheric lesions. B, Sagittal T2-weighted MRI of the spinal cord shows long myelitis. C, Axial T2-weighted MRI shows involvement of the frontal and occipital cortex and transcallosal lesion. D, An extensive occipital lesion can be seen.

Figure 2.. Magnetic Resonance Imaging of the Brain, Case 3

A and B, A lesion extends from the cortex to deep white matter. C, A lesion can be seen in the brainstem.

Figure 3.. Magnetic Resonance Imaging of the Brain, Cases 4 and 5

A, Coronal T2-weighted fluid-attenuated inversion recovery (FLAIR) image shows an extensive lesion affecting both the left temporal and parietal lobes. B, Coronal T2-weighted FLAIR image shows bilateral hemispheric white matter changes. C, Axial T2-weighted magnetic resonance imaging illustrates cortical involvement.