Obesity is associated with myelin oligodendrocyte glycoprotein antibody-associated disease in acute optic neuritis

Abstract

Optic neuritis (ON) is a frequent presentation at onset of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The pathophysiology underlying these diseases, especially MOGAD, is still being elucidated. While obesity has been reported to potentially be a risk factor for MS, this has not been explored in NMOSD or MOGAD. We aimed to investigate a possible association between obesity (body mass index [BMI] > 30 kg/m²) in patients with MOGAD, aquaporin 4-IgG positive NMOSD (AQP4-IgG+ NMOSD) or MS. In this multicenter non-interventional retrospective study, data was collected from patients with a first ever demyelinating attack of ON subsequently diagnosed with MOGAD (n = 44), AQP4-IgG+ NMOSD (n = 49) or MS (n = 90) between 2005 and 2020. The following data was collected: age, sex, ethnicity, BMI (documented before corticosteroid treatment), and the ON etiology after diagnostic work-up. A mixed model analysis was performed to assess the potential of obesity or BMI to predict MOGAD-ON, and to distinguish MOGAD-ON from AQP4-IgG+ NMOSD-ON and MS-ON. Main outcome measures included BMI in patients with acute ON and subsequent diagnosis of MOGAD, AQP4-IgG+ NMOSD or MS. A higher BMI was significantly associated with a diagnosis of MOGAD-ON (p < 0.001); in MOGAD patients the mean BMI was 31.6 kg/m² (standard deviation (SD) 7.2), while the mean BMI was 24.7 kg/m² (SD 5.3) in AQP4-IgG+ NMOSD patients, and 26.9 kg/m² (SD 6.2) in MS patients. Mixed-effects multinomial logistic regression, adjusted for age and sex, with obesity as a binary variable, revealed that obesity was associated with a higher odds ratio (OR) of a subsequent MOGAD diagnosis (OR 5.466, 95% CI [2.039, 14.650], p = 0.001) in contradistinction with AQP4-IgG+ NMOSD. This study suggests an association between obesity and MOGAD. Our findings require further exploration, but could have significant pathophysiologic implications if confirmed in larger prospective studies.

Figure 1

Patient selection and study design flowchart.

Figure 2

Infographic of body mass index (BMI) at presentation of first-ever acute optic neuritis in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), and multiple sclerosis (MS). Legends: Plots demonstrating the distribution of BMI by group. The boxplot lines correspond to the 25th, 50th and 75th percentiles. The male symbol represents the percentage of male patients in each group.

Figure 3

Body mass index (BMI) at presentation of 183 patients with first-ever acute optic neuritis is similar within the respective disease categories across the cohorts from Israel, the USA and Germany. Legends: Plots demonstrating the distribution of BMI by group. The boxplot lines correspond to the 25th, 50th and 75th percentiles.