Volumetric Brain Loss Correlates With a Relapsing MOGAD Disease Course

Abstract

Background: Myelin oligodendrocyte glycoprotein antibody disorders (MOGAD) have evolved as a distinct group of inflammatory, demyelinating diseases of the CNS. MOGAD can present with a monophasic or relapsing disease course with distinct clinical manifestations.However, data on the disease course and disability outcomes of these patients are scarce. We aim to compare brain volumetric changes for MOGAD patients with different disease phenotypes and HCs.

Methods: Brain magnetic resonance imaging (MRI) scans and clinical data were obtained for 22 MOGAD patients and 22 HCs. Volumetric brain information was determined using volBrain and MDbrain platforms.

Results: We found decreased brain volume in MOGAD patients compared to HCs, as identified in volume of total brain, gray matter, white matter and deep gray matter (DGM) structures. In addition, we found significantly different volumetric changes between patients with relapsing and monophasic disease course, with significantly decreased volume of total brain and DGM, cerebellum and hippocampus in relapsing patients during the first year of diagnosis. A significant negative correlation was found between EDSS and volume of thalamus.

Conclusions: Brain MRI analyses revealed volumetric differences between MOGAD patients and HCs, and between patients with different disease phenotypes. Decreased gray matter volume during the first year of diagnosis, especially in the cerebrum and hippocampus of MOGAD patients was associated with relapsing disease course.

Keywords: MOGAD; brain MRI; brain atrophy; brain volume; relapsing MOGAD.

Figure 1

Decreased brain volume in MOGAD patients compare to HCs. Brain volume of HCs (n = 22) and MOGAD patients (n = 22) analyzed by Volbrain software. (A) Volume of white matter (512.56 ± 57.33 vs. 458.68 ± 89.60, p = 0.018), gray matter (699.97 ± 59.45 vs. 681.66 ± 106.70, p = 0.476) and total brain (1,214.14 ± 105.65 vs. 1,139.91 ± 135.15, p = 0.048), and volume of (B) cerebellum (134.64 ± 10.28 vs. 124.17 ± 12.42, p = 0.007), (C) brainstem (23.96 ± 2.55 vs. 21.61 ± 2.45, p = 0.003), (D) caudate (7.46 ± 0.79 vs. 6.56 ± 1.03, p = 0.001), (E) thalamus (11.97 ± 0.98 vs. 10.74 ± 1.72, p = 0.008), (F) hippocampus (7.78 ± 0.83 vs. 6.86 ± 1.27, p = 0.011), and (G) amygdala (1.60 ± 0.27 vs. 1.37 ± 0.36, p = 0.024) of MOGAD patients and HCs. MOGAD, Myelin oligodendrocyte glycoprotein antibody disorders; HCs, healthy controls. p * ≤ 0.05, ** ≤ 0.01.

Figure 2

Decrease brain volume of MOGAD patients during the first year of diagnosis. Brain volume of HCs (n = 22) and MOGAD patients during the first year of diagnosis (n = 15) analyzed by Volbrain software. (A) Volume of brainstem (23.96 ± 2.49 vs. 22.13 ± 2.48, p = 0.035), (B) caudate (7.46 ± 0.79 vs. 6.68 ± 1.03, p = 0.010), (C) thalamus (11.92 ± 0.99 vs. 10.99 ± 1.67, p = 0.040), (D) hippocampus 7.78 ± 0.83 vs. 6.82 ± 1.41, p = 0.021), and (E) amygdala (1.60 ± 0.27 vs. 1.32 ± 0.41, p = 0.021) of MOGAD patients during the first year of diagnosis and HCs. MOGAD, Myelin oligodendrocyte glycoprotein antibody disorders; HCs, healthy controls. p * ≤ 0.05.

Figure 3

Decreased brain volume in relapsing compared to monophasic MOGAD patients. Brain volume of relapsing (n = 8) and monophasic MOGAD patients (n = 8) analyzed by Volbrain software. (A) White matter (413.63 ± 62.74 vs. 476.17 ± 74.35, p = 0.088), gray matter (620.94 ± 73.22 vs. 747.28 ± 68.61, p = 0.003) and whole brain volumes (1,034.07 ± 88.93 vs. 1,223.45 ± 86.84, p < 0.001), (B) cerebellum (114.95 ± 12.81 vs. 130.48 ± 7.08, p = 0.010), (C) cerebrum (899.04 ± 88.93 vs. 1,070.78 ± 86.84, p < 0.001), (D) Putamen (7.02 ± 0.94 vs. 8.04 ± 0.96, p = 0.051), (E) thalamus (9.88 ± 1.30 vs. 11.45 ± 1.19, p = 0.024), (F) hippocampus (6.72 ± 0.86 vs. 7.79 ± 0.68, p = 0.015), and (G) amygdala (1.33 ± 0.21 vs. 1.63 ± 0.15, p = 0.005) of monophasic and relapsing MOGAD patients. MOGAD, Myelin oligodendrocyte glycoprotein antibody disorders. p * ≤ 0.05, ** ≤ 0.01, *** ≤ 0.001.

Figure 4

Decreased brain volume in relapsing compared to monophasic MOGAD patients during the first year of diagnosis. Brain volume of relapsing (n = 5) and monophasic MOGAD patients (n = 5) during the first year of diagnosis analyzed by Volbrain software. Volume of (A) total brain (1,235.95 ± 64.17 vs. 1,041.76 ± 105.77, p = 0.010), (B) gray matter volume (724.63 ± 61.14 vs. 598.34 ± 83.82, p = 0.038), (C) cerebrum (1,080.29 ± 61.15 vs. 907.26 ± 92.98, p = 0.010), and (D) hippocampus (7.83 ± 0.70 vs. 6.87 ± 0.96, p = 0.044) of monophasic and relapsing course MOGAD patients during the first year of diagnosis. MOGAD, Myelin oligodendrocyte glycoprotein antibody disorders. p * ≤ 0.05.

Figure 5

Decrease volume of cerebellar lobules at MOGAD patients compared to HCs and decreased volume of cerebellar lobules at relapsing MOGAD patients compared to monophasic MOGAD patients. (A–D) Volume of cerebellar lobules of HCs (n = 22) and MOGAD patients (n = 20) analyzed by CERES pipeline of Volbrain software. Volume of (A) total cerebellum gray matter (96.23 ± 6.89 vs. 90.66 ± 10.43, p = 0.050), (B) cerebellar lobules I.II (0.12 ± 0.03 vs. 0.09 ± 0.05, p = 0.009), (C) Crus II (17.33 ± 2.18 vs. 14.39 ± 1.75, p < 0.001), and (D) VIIB (9.70 ± 1.24 vs. 8.26 ± 1.09, p < 0.001) of MOGAD patients and HCs. (E,F) Volume of cerebellar lobules of monophasic (n = 6) and relapsing (n = 6) MOGAD patients analyzed by CERES pipeline of Volbrain software. Volume of (E) total cerebellum gray matter (83.14 ± 10.78 vs. 95.34 ± 8.52, p = 0.047) and (F) cerebellar lobule VIIIA (9.87 ± 0.97 vs. 12.09 ± 1.03, p = 0.002) of monophasic and relapsing MOGAD patients. MOGAD, Myelin oligodendrocyte glycoprotein antibody disorders; HCs, healthy controls. p * ≤ 0.05, ** ≤ 0.01, *** ≤ 0.001, **** ≤ 0.0001.

Figure 6

Decreased Volume of CA4/DG at MOGAD patients compare to HCs. (A,B) Volume of hippocampal subfields of HCs (n = 21) and MOGAD patients (n = 18) analyzed by HIPS pipeline of Volbrain software. (A) Volumes of CA/DG4 (1.31 ± 0.18 vs. 1.14 ± 0.21, p = 0.009) and (B) SR/SL/SM (0.98 ± 0.14 vs. 0.82 ± 0.22, p = 0.008). (C) Volume of hippocampal subfields of monophasic (n = 6) and relapsing patients (n = 6), analyzed by HIPS pipeline of Volbrain software. (C) CA4/DG (0.98 ± 0.24 vs. 1.23 ± 0.14, p = 0.03) volume of MOGAD monophasic and relapsing course patients. MOGAD, Myelin oligodendrocyte glycoprotein antibody disorders; HCs, healthy controls. p * ≤ 0.05, ** ≤ 0.01.

Figure 7

There is a significant correlation between EDSS and decrease volume of thalamus of MOGAD patients. Correlation between EDSS and brain volumes. Correlation between EDSS and volumes of (A) white matter (r = −0.051, p = 0.021), (B) cerebellum (r = −0.389, p = 0.082), (C) brainstem (r = −0.393, p = 0.078), and (D) thalamus (r = −0.476, p = 0.029) in MOGAD patients (n = 22). MOGAD, Myelin oligodendrocyte glycoprotein antibody disorders.