The accuracy of distinguishing relapsing–remitting multiple sclerosis from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease can be achieved with high precision using cortical lesions, central vein sign, and optic nerve markers.
When serologic testing for relapsing-remitting multiple sclerosis (RRMS), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is unavailable or inconclusive, it is difficult to differentiate between them due to overlapping clinical features. This study, published in the journal Neurology, reports Class II evidence that certain conventional and advanced MRI and OCT markers of the brain, spinal cord, and optic nerve can accurately distinguish between RRMS, AQP4-NMOSD, and MOGAD in adult patients, which can be useful in clinical practice.
The cross-sectional study included 91 patients (31 RRMS, 30 AQP4-NMOSD, and 30 MOGAD) and 34 healthy controls. The participants were recruited from a single center in China. All patients fulfilled the revised McDonald criteria for MS diagnosis, while AQP4-NMOSD and MOGAD were diagnosed based on the 2015 diagnostic criteria.
Differences in MRI and OCT Measures Between MS, AQP4-NMOSD, and MOGAD Patients
The study found significant differences in MRI and OCT measures between the three groups of patients. Brain white matter lesions were detected in 100% of patients with RRMS, 83% of patients with AQP4-NMOSD, and 27% of patients with MOGAD. The mean number and volume of lesions were higher in RRMS than AQP4-NMOSD and MOGAD. There was no difference in the number or volume of brain lesions between AQP4-NMOSD and MOGAD. The presence of at least one cervical cord lesion was more common in RRMS (55%) than AQP4-NMOSD (40%) and MOGAD (4%).
Brain Structure Differences Found Between MS, AQP4-NMOSD, and MOGAD Patients
Patients with RRMS had lower brain parenchymal fraction, white matter fraction, and deep gray matter fraction than healthy individuals. In addition, RRMS patients had lower brain parenchymal fraction and deep gray matter fraction than AQP4-NMOSD and lower deep gray matter fraction than MOGAD. However, patients with MOGAD did not differ from healthy controls and AQP4-NMOSD.
Cortical Lesions: A Differentiator Between MS, AQP4-NMOSD, and MOGAD
Cortical lesions were found in a majority of patients with MS (73%), while only a small percentage of patients with AQP4-NMOSD (4%) and MOGAD (3%) had them. The number of cortical lesions was found to be significantly higher in RRMS patients (with a total of 74 lesions, including 40 leukocortical and 34 intracortical lesions, and a median of 2 lesions per patient) compared to those with AQP4-NMOSD (only one leukocortical lesion in one patient) and MOGAD (only one intracortical lesion in one patient). These findings suggest that cortical lesions could serve as a distinguishing feature between
MRI and OCT Can Differentiate Between MS Subtypes
MRI studies have revealed that patients with RRMS have 100% occurrence of central vein sign (CVS) within white matter lesions on SWI, while this number is lower in patients with AQP4-NMOSD and MOGAD. Patients with RRMS and AQP4-NMOSD had smaller cervical cord cross-sectional areas than healthy individuals, while patients with MOGAD did not show cervical cord atrophy. Patients with AQP4-NMOSD and MOGAD also had lower average magnetization transfer ratio (MTR) of the whole optic nerve and the intraorbital segment compared with RRMS and healthy controls, with MOGAD showing lower MTR of the intracranial segments. All patient groups also observed lower retinal nerve fiber layer thickness and ganglion cell-inner plexiform layer thickness. These results indicate that MRI and OCT measures can aid in distinguishing between patients with RRMS, AQP4-NMOSD, and MOGAD.
Relationship Between Clinical Measures and Imaging Measures
In patients with RRMS a worse 9-HPT z-score was associated with lower brain white matter fraction and lower cross-sectional area (CSA). Furthermore, worse high-contrast VA was associated with reduced RNFL thickness. In AQP4-NMOSD, worse EDSS score and TWT z-score were associated with lower cord CSA. Additionally, worse 9-HPT and greater vibration dysfunction were associated with lower cervical cord FA. Worse high-contrast VA was associated with lower average MTR of the whole optic nerve and the intraorbital segment. In MOGAD, worse high-contrast VA was associated with reduced RNFL thickness, reduced GCIPL thickness, and lower average MTR of the optic nerve and the intraorbital segment.
MRI and OCT Discriminators Between the Three Diseases
A higher proportion of lesions with the CVS accurately distinguished RRMS from AQP4-NMOSD, while a higher number of brain white matter lesions predicted RRMS over MOGAD. At least one cervical cord lesion was the only MRI marker that predicted AQP4-NMOSD over MOGAD.
Cortese, R., Prados Carrasco, F., Tur, C., Bianchi, A., Brownlee, W., De Angelis, F., De La Paz, I., Grussu, F., Haider, L., Jacob, A., Kanber, B., Magnollay, L., Nicholas, R. S., Trip, A., Yiannakas, M., Toosy, A. T., Hacohen, Y., Barkhof, F., & Ciccarelli, O. (2023). Differentiating Multiple Sclerosis From AQP4-Neuromyelitis Optica Spectrum Disorder and MOG-Antibody Disease With Imaging. Neurology, 100(3), e308-e323. https://doi.org/10.1212/wnl.0000000000201465