Neuromyelitis Optica Spectrum Disorders Lower Cognitive Performance for Some

Approximately 40% of patients with neuromyelitis optica spectrum disorders have nondeteriorating below-average visual processing speed and semantic fluency.

Some patients with neuromyelitis optica spectrum disorders (NMOSD) have stable, but impaired visual processing speed and semantic fluency, according to the results of the CogniNMO Study published in Multiple Sclerosis Journal. However, this research, the largest NMOSD sample reported to date, shows a lower prevalence of cognitive impairment than has been previously shown.

Neuromyelitis optica spectrum disorders are inflammatory autoimmune diseases that affect the optic nerve, spinal cord, or area postrema. Previous studies report inconsistent findings about the relationship of NMOSD and cognitive impairment and research has uncovered little about the influence of antibody status. Thus, the CogniNMSO Study sought to evaluate longitudinal cognitive changes in patients with NMOSD-defined antibody status. 

The prospective, longitudinal study evaluated 217 patients who were diagnosed with NMOSD according to the International Panel for Neuromyelitis Optica Diagnosis (IPND) 2015 criteria and had a median disease duration of 6 years. Of these patients, 174 were seropositive for aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies and 43 were double seronegative for AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG).

At baseline, 40% of patients with NMOSD performed below the fifth percentile. This prevalence is lower than what previous studies have reported, which may be related to differences in the definition of impairment. Patients with neuromyelitis optica spectrum disorders performed worse on the Symbol Digit Modalities Test (SDMT; mean=-0.37; 95% CI, -0.63 to -0.10), Multiple Sclerosis Inventory Cognition (MuSIC) semantic fluency (mean=-0.42; 95% CI, -0.62 to -0.22), and MuSIC congruent speed (mean=-1.71; 95% CI, -2.36 to -1.06). Researchers report no significant differences between AQP4_IgG seropositive and double-seronegative patients. Additionally, they report no significant changes in cognitive performance at 1- and 2-year follow-up visits.

“Compared to normative data of healthy controls, NMOSD patients showed below-average visual processing speed and semantic fluency,” the researchers report. “In contrast to what has been suggested in some studies, however, we found no impairment with regard to immediate and delayed recall of verbal material presented in the auditory modality.”

Based on these data, the authors propose to “develop a standard change-sensitive test battery adapted to NMOSD patients for use in future longitudinal studies to examine cognitive performance independently of visual and motor disabilities.”

SDMT score correlated with physical and visual disability, which suggests that this assessment may not be appropriate to evaluate cognitive ability in patients with neuromyelitis optica spectrum disorders. Additionally, the follow-up interval was short and potential cognitive deterioration could be skewed by learning effects as patients become familiar with the testing.


Hümmert MW, Stern C, Paul F, et al. Cognition in patients with neuromyelitis optica spectrum disorders: A prospective multicentre study of 217 patients (CogniNMO-Study)Mult Scler. 2023;29(7):819-831. doi:10.1177/13524585231151212