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.

Seizure specificities in patients with antibody‐mediated autoimmune encephalitis

“…Many patients develop relapsing disease, with relapses typically occurring during corticosteroid weaning or cessation. The fact that myelinated oligodendrocytes are also present in the cortical gray matter permits to explain the pathophysiology of the recently described cases of MOG‐Ab‐associated cortical syndromes …”

“…In young adults, MOG‐associated encephalitis commonly manifests as bilateral tonic‐clonic seizures, preceded or followed by ON or, less frequently, by other demyelinating events . CSF analysis demonstrates pleocytosis and brain MRI often shows a peculiar pattern characterized by unilateral, cortical, FLAIR hyperintense and swollen lesions .…”

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease: practical considerations

“…MR scan of the brain in the acute phase usually shows unilateral mildly oedematous cortical lesion(s) best seen on fluid-attenuated inversion recovery images (figure 3). The prognosis is typically good, with the seizures and MRI brain lesions resolving,14 although there are exceptions 15…”

Isolated seizures during the first episode of relapsing myelin oligodendrocyte glycoprotein antibody‐associated demyelination in children

“…Myelin oligodendrocyte glycoprotein (MOG) antibodies have a strong association with acute disseminated encephalomyelitis (ADEM) in children, and bilateral and recurrent optic neuritis in children and adults . Recent reports in adults suggest that seizures and encephalopathy may be an emerging clinical phenotype with MOG antibodies, either concurrent with or remote from demyelination . In some cases, these patients had unilateral cortical fluid‐attenuated inversion recovery hyperintensities on magnetic resonance imaging (MRI) with resolution of these lesions after clinical remission .…”

“…In some cases, these patients had unilateral cortical fluid‐attenuated inversion recovery hyperintensities on magnetic resonance imaging (MRI) with resolution of these lesions after clinical remission . Seizures have been found to be more common in adults with MOG antibody‐associated demyelination compared to those with aquaporin‐4 antibody‐associated demyelination …”