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The following is a summary of “Comorbidities Are Associated With Unfavorable Outcome in Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Exploratory Study From the CROCTINO Cohort,” published in the June 2025 issue of European Journal of Neurology by Samadzadeh et al. 

The presence of comorbidities in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and double seronegative NMOSD (DN-NMOSD) has been linked to a potentially more aggressive disease course, highlighting their relevance in disease characterization and management. 

Researchers conducted a retrospective study to characterize comorbidities in AQP4-NMOSD, MOGAD, and DN-NMOSD and to examine their association with optic neuritis (ON) outcomes using optical coherence tomography (OCT) in AQP4-NMOSD.  

They evaluated 442 participants from the Collaborative Retrospective Study of Retinal Optical Coherence Tomography in Neuromyelitis optica (CROCTINO) cohort for comorbidities which included 515 individuals—369 with AQP4-NMOSD, 54 with MOGAD, and 58 with DN-NMOSD—meeting the 2006 and 2015 diagnostic criteria for NMOSD. Data was collected from 22 centers across North and South America, Asia, and Europe, following STROBE reporting guidelines. The dataset, acquired between 2000 and 2018, comprised OCT and clinical metadata. Since comorbidities were not the original focus, 73 participants (14%) were excluded due to missing comorbidity, OCT, or antibody data, resulting in 442 eligible cases. Collected variables included the Expanded Disability Status Scale (EDSS), age at onset, disease duration, number of ON attacks, visual acuity, and OCT metrics.  

The results showed that among individuals with AQP4-NMOSD (n = 360), 43.5% (n = 161) had comorbidities split evenly between single and multiple conditions. In MOGAD (n = 49), 40.8% had comorbidities, with 75% (n = 15) being single and 25% (n = 5) having multiple. In DN-NMOSD (n = 33), 36.4% (n = 12) had comorbidities, also evenly split, AQP4-NMOSD had a higher proportion of multiple comorbidities (50%, n = 81/161) than MOGAD (25%, n = 5/20, P= 0.03), and more autoimmune disorders (AID) at 40.4% (n = 65) compared to MOGAD (20%, n = 4, P= 0.09) and DN-NMOSD (none, P= 0.004). Cardiovascular comorbidities and related risk factors (CVC/RF) occurred in 34.8% (n = 56) of AQP4-NMOSD, 50% (n = 10) of MOGAD, and 33.3% (n = 4) of DN-NMOSD. EDSS scores were higher in MOGAD (3.0 vs 2.0, P= 0.006) and DN-NMOSD (5.0 vs 2.0, P= 0.008) with comorbidities. The AQP4-NMOSD individuals with CVC/RF had higher ON relapse rates than those with AID (1.06 ± 3.33 vs 0.49 ± 0.98, P< 0.001). The OCT showed reduced inner nuclear layer thickness in AQP4-NMOSD with comorbidities (B = −1.52, P= 0.047), more marked in those with CVC/RF (B = −2.96, P= 0.009).  

Investigators concluded that comorbidities were common in AQP4-NMOSD and MOGAD and were related to higher ON frequency and greater disability.   

Source: onlinelibrary.wiley.com/doi/10.1111/ene.70214