Internuclear Ophthalmoplegia Characterizes Multiple Sclerosis Rather Than Neuromyelitis Optica Spectrum Disease

Neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS) share clinical presentations including optic neuritis and brainstem syndromes. Internuclear ophthalmoplegia (INO) is characterized by slowed ipsilateral adduction saccades and results from a lesion in the medial longitudinal fasciculus (MLF). Although INO is a common clinical finding in MS, its prevalence in NMOSD is unknown. The objective of this work is to determine the comparative frequencies of INO in patients with NMOSD and MS and compare clinical features of both disease processes.

This is a retrospective study of patients 18 years and older who have an established diagnosis of NMOSD or MS and were evaluated by both neuro-ophthalmology and neuro-immunology specialists between 2014 and 2020. Electronic medical records were screened for documentation of an acute INO at any time during follow-up. Incidence rates were calculated from number of cases of new-onset INO and patient years observed. Logistic regression was used to evaluate the likelihood of developing an INO at any time point for NMOSD vs MS patients. Multivariable analysis was performed by adjusting for age, race, gender, and length of follow-up.

Two hundred eighty patients (80 NMOSD, 200 MS) were included. Age range was 18-79 years with a mean age of 35.14 (SD ± 12.41 years). Average length of follow-up in MS and NMOSD patients was 4.18 years vs 3.79 years, respectively (P > 0.05), and disease duration before the start of the study in MS and NMOSD was 8.76 years vs 4.65 years, respectively (P < 0.01). Mean disease duration and follow-up time of both groups was 7.58 years and 4.07 ± 2.51 years, respectively. NMOSD patients were predominantly seropositive for AQP4 antibody (61.25%, n = 49). Individuals who had MOG antibody but also met NMOSD criteria were also included (18.75%, n = 15). The frequency of INO at any time point was 1.25% (n = 1) in NMOSD compared with 16% (n = 32) in MS. The incidence rate of new-onset INO in NMOSD (excluding MOGAD) was 3.8/1,000 person years and 23.9/1,000 person years in MS. Adjusted analysis showed that NMOSD patients were 13.89 times (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.01-0.598, P = 0.015) less likely to develop an INO compared with those with MS when including MOGAD patients, 12.5 times less likely (OR 0.08, 95% CI: 0.10-0.67, P = 0.02) when excluding MOGAD patients and 9.62 times less likely (OR 0.10, 95% CI: 0.01-0.87, P = 0.036) for AQP4+ patients.

Our study shows that the incidence of new INO (3.8 vs 23.9 per 1,000 person years), and the odds of having INO at any time point are significantly lower in NMOSD than MS. This suggests that INO and consequently MLF lesions are less common in NMOSD. The presence of an INO may help in the differentiation of NMOSD from MS and may aid in earlier implementation of disease appropriate therapy.