Correlation between cerebral cortex changes and clinical features in patients with neuromyelitis optica spectrum disorder with normal-appearing brain tissue: a case-control study

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system. However, whether and how cortical changes occur in NMOSD with normal-appearing brain tissue, or whether any cortical changes correlate with clinical characteristics, is not completely clear. The current study recruited 43 patients with NMOSD who had normal-appearing brain tissue and 45 healthy controls matched for age, sex, and educational background from December 2020 to February 2022. A surface-based morphological analysis of high-resolution T1-weighted structural magnetic resonance images was used to calculate the cortical thickness, sulcal depth, and gyrification index. Analysis showed that cortical thickness in the bilateral rostral middle frontal gyrus and left superior frontal gyrus was lower in the patients with NMOSD than in the control participants. Subgroup analysis of the patients with NMOSD indicated that compared with those who did not have any optic neuritis episodes, those who did have such episodes exhibited noticeably thinner cortex in the bilateral cuneus, superior parietal cortex, and pericalcarine cortex. Correlation analysis indicated that cortical thickness in the bilateral rostral middle frontal gyrus was positively correlated with scores on the Digit Symbol Substitution Test and negatively correlated with scores on the Trail Making Test and the Expanded Disability Status Scale. These results are evidence that cortical thinning of the bilateral regional frontal cortex occurs in patients with NMOSD who have normal-appearing brain tissue, and that the degree of thinning is correlated with clinical disability and cognitive function. These findings will help improve our understanding of the imaging characteristics in NMOSD and their potential clinical significance.

Keywords: Expanded Disability Status Scale; cognitive function; cortical thickness; gyrification; magnetic resonance imaging; neuromyelitis optica spectrum disorder; normal-appearing brain tissue; rostral middle frontal gyrus; sulcal depth; superior frontal gyrus.

Figure 1

Flow chart of the selection process for included participants. AQP4: Aquaporin-4; HC: healthy control; MOG: myelin oligodendrocyte glycoprotein; MRI: magnetic resonance imaging; NMOSD: neuromyelitis optica spectrum disorder.

Figure 2

Brain regions with cortical thicknesses that differed significantly between the patients with NMOSD who had normal-appearing brain tissue and the healthy controls. (A) The NMOSD group showed significantly thinner cortex in the bilateral rostral middle frontal gyri (rMFG_L and rMFG_R) and left superior frontal gyrus (SFG_L) compared with the HC group (P < 0.001, false discovery rate-corrected at the cluster level). These brain regions were defined as ROIs. (B) Mean cortical thicknesses for each group and each ROI. *P < 0.05, ***P < 0.001 (two-sample t-test). HC: Healthy control; L: left; LH: left hemisphere; NMOSD: neuromyelitis optica spectrum disorder; R: right; RH: right hemisphere; rMFG: rostral middle frontal gyrus; SFG: superior frontal gyrus.

Figure 3

Brain regions with cortical thicknesses that differed significantly between the NMOSD-ON group and the non-NMOSD-ON group. The NMOSD-ON group exhibited significantly thinner cortex in the bilateral cuneus, superior parietal cortex, and pericalcarine cortex compared with the non-NMOSD-ON group (P < 0.01, false discovery rate-corrected at the cluster level). LH: Left hemisphere; NMOSD: neuromyelitis optica spectrum disorder; NMOSD-ON: NMOSD patients who experienced at least one clinical episode of optic neuritis; non-NMOSD-ON: NMOSD patients without clinical episodes of optic neuritis; RH: right hemisphere.

Figure 4

Correlation analyses between the mean cortical thickness and clinical parameters, including disease durations, EDSS, and cognitive scale scores. (A) Heatmap of the correlational r-values between the mean cortical thickness in the brain regions showing significant differences from controls, and clinical parameters including disease durations, the EDSS scores, and cognitive scale scores (i.e., DSST, TMT-A, TMT-B). (B, C) In the left rMFG, mean cortical thickness positively correlated with DSST scores and negatively correlated with TMT-A and EDSS scores. (D, E) In the right rMFG, mean cortical thickness positively correlated with the DSST scores and negatively correlated with TMT-A, TMT-B, and EDSS scores. Pearson’s (ROI-based surface values vs. TMT-B scores) and Spearman’s (ROI-based surface values vs. disease durations, EDSS, DSST, and TMT-A scores) correlation analyses were applied. *P < 0.05, **P < 0.01. DSST: Digit Symbol Substitution Test; EDSS: Expanded Disability Status Scale; L: left; R: right; rMFG: rostral middle frontal gyrus; SFG: superior frontal gyrus; TMT-A: Trail Making Test (subscale A); TMT-B: Trail Making Test (subscale B).