Whole Brain Volume Loss, Higher Thalamic and Hippocampal Atrophy Rate Identified in MOGAD

Itay Lotan, MD

Recently, a cross-sectional analysis showed significantly lower age-adjusted whole brain (WB) volume loss in healthy controls (HC) than in patients in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), and multiple sclerosis (MS). In addition, the longitudinal analyses showed a significantly higher rate of thalamic volume loss over time in patients with MOGAD compared with both MS and NMOSD patient groups, and a significantly higher rate of hippocampal volume loss in MOGAD compared with MS.¹ These findings provided new data on volumetric brain shifts in MOGAD and show a possibility of the subclinical disease process being operative in MOGAD.

The cross-sectional analyses included 24 patients with MOGAD, 47 with NMOSD, 40 with MS, and 37 HCs. The age-adjusted WB volume was significantly lower in patients with MOGAD (P = .0002), NMOSD (P = .042), and MS (P = .01) in comparison with HC. The longitudinal analyses, which included 8 patients with MOGAD, 22 with NMOSD, and 34 with MS, showed a greater loss of thalamic volume in the MOGAD group compared with the MS (P = .028) and NMOSD (P = .023) groups and a greater loss of hippocampal volumes compared with the MS (P = .007) group.

“We report a similar rate of WB volume loss in MS, but a somewhat lower rate of WB volume loss in NMOSD compared to previous reports,” lead author Itay Lotan, MD, professor of neurology, Rabin Medical Center, Petah-Tikva, Israel, and colleagues wrote.¹ “The difference observed in the NMOSD group may again be related to the small sample sizes, and/or to differences in baseline demographic and clinical characteristics that were not adjusted for, such as ethnicity, immunotherapy, disability status and disease duration.”

Patients, 18 years of age or older, diagnosed with relapsing MOGAD and NMOSD were recruited from the NYU MS Comprehensive Care Center clinical database. Clinical and paraclinical data taken from the patients’ medical charts included sex; age; disease onset; race/ethnicity; dates of relapses; current and prior immunotherapies; Expanded Disability Status Scale (EDSS) score at the last follow-up; AQP4-IgG antibody serostatus, MOG-IgG antibody serostatus, and brain MRI. Investigators reviewed all the patients’ brain MRI data and compared them with patients with MS and HC. Following the analysis, volumetric parameters were assessed with FDA-approved icobrain software which was adjusted for age and sex.

The cross-sectional analysis observed significantly lower parietal GM volume in MOGAD, NMOSD, and MS compared with HC (MOGAD vs. HC, P = .019; NMOSD vs., P = .0051; MS vs. HC, P = .0062). the global CGM volume and the occipital GM volume was only significantly lower in MOGAD relative to controls (P = 0.012 and P = 0.0016, respectively). Notably, the lateral ventricles volume was significantly higher in all disease groups compared with HC (MS vs. HC, P = .0027; MOGAD vs. HC, P = .012; NMOSD vs. HC, P = .0090).

Patients with MS and NMOSD showed a significantly higher total T2-hyperintense lesion volume mean than in the HC group (MS vs. HC, P <.001; NMOSD vs. HC, P = .046), with no significant difference shown between the MOGAD and HC groups (P = .99). The total T2-hyperintense lesion volume in MS patients was significantly higher compared with patients with MOGAD (p=0.0024). In addition, the MS group was significantly higher in the volume of T1-hypointense lesions compared with HC (P <.001), MOGAD (P <.001), and NMOSD (P =.0062).

Study limitations included the design, as it was a small sample of patient referrals hence, protocols were not completely standardized. Additionally, a small number of patients from the MOGAD were included in the longitudinal analysis. This study only focused on brain MRI and did not have clinical data on the patient's cognitive status.

“In cross-sectional analysis, WB volume, parietal lobe volume, global CGM, occipital GM and thalamus volumes were significantly lower in MOGAD patients compared to HC. The longitudinal analysis suggests a possible distinct pattern of brain tissue loss in MOGAD, predominantly affecting the thalamus and hippocampus. Further prospective studies on larger cohorts are warranted to validate our findings and investigate their clinical implications,” Lotan et al noted.¹

REFERENCES
1. Lotan I, Billiet T, Ribbens A, et al. Volumetric brain changes in MOGAD: A cross-sectional and longitudinal comparative analysis. Mult Scler Relat Disord. 2022;69:104436. doi:10.1016/j.msard.2022.104436