Quantitative MRI findings indicate diffuse white matter damage in Susac Syndrome

Abstract

Background: Susac Syndrome (SuS) is an autoimmune endotheliopathy impacting the brain, retina and cochlea that can clinically mimic multiple sclerosis (MS).

Objective: To evaluate non-lesional white matter demyelination changes in SuS compared to MS and healthy controls (HC) using quantitative MRI.

Methods: 3T MRI including myelin water imaging and diffusion basis spectrum imaging were acquired for 7 SuS, 10 MS and 10 HC participants. Non-lesional white matter was analyzed in the corpus callosum (CC) and normal appearing white matter (NAWM). Groups were compared using ANCOVA with Tukey correction.

Results: SuS CC myelin water fraction (mean 0.092) was lower than MS(0.11, p = 0.01) and HC(0.11, p = 0.04). Another myelin marker, radial diffusivity, was increased in SuS CC(0.27μm2/ms) compared to HC(0.21μm2/ms, p = 0.008) and MS(0.23μm2/ms, p = 0.05). Fractional anisotropy was lower in SuS CC(0.82) than HC(0.86, p = 0.04). Fiber fraction (reflecting axons) did not differ from HC or MS. In NAWM, radial diffusivity and apparent diffusion coefficient were significantly increased in SuS compared to HC(p < 0.001 for both measures) and MS(p = 0.003, p < 0.001 respectively).

Conclusions: Our results provided evidence of myelin damage in SuS, particularly in the CC, and more extensive microstructural injury in NAWM, supporting the hypothesis that there are widespread microstructural changes in SuS syndrome including diffuse demyelination.

Keywords: MRI; Susac syndrome; demyelination; diffusion basis spectrum imaging; multiple sclerosis; myelin water imaging; neuroimaging.

Figure 1.

Representative MRI from susac syndrome, multiple sclerosis (MS) and a healthy control (HC). The 3DT1 is used as an anatomical image. The myelin water fraction (MWF) image reflects myelin content (hotter for more myelin). The apparent diffusion coefficient (ADC) is a measure extracted from diffusion basis spectrum imaging measuring overall diffusion and is indicative of non-specific overall tissue damage.

Figure 2.

Advanced imaging results for the corpus callosum (CC) for controls (HC), multiple sclerosis (MS) and susac syndrome (SuS) participants. Significant results are a) Myelin water fraction (MWF). MWF of the CC of SuS (0.092 ± 0.01) was significantly lower than HC (0.11 ± 0.02) (p = 0.04) MS (0.11 ± 0.02) (p = 0.01). b) Radial diffusivity (RD). RD in SuS (0.27 ± 0.03) was significantly higher compared to HC (0.21 ± 0.01) (p = 0.008) and MS (0.23 ± 0.05) (p = 0.05). c) Fractional anisotropy (FA). FA of SuS (0.82 ± 0.02) was significantly lower than HC (0.86 ± 0.02) (p = 0.04). d) Apparent diffusion coefficient (ADC). ADC in the CC of SuS (0.84 ± 0.08) was significantly increased compared to MS (0.73 ± 0.04) and controls (0.71 ± 0.04) (p < 0.001 for both). * p < 0.01, ** p < 0.001.

Figure 3.

Advanced MRI results for white matter of the whole brain for controls (HC), multiple sclerosis (MS) and susac syndrome (SuS) participants. Significant results are a) Myelin water fraction of white matter. SuS is lower than MS (0.11 ± 0.02) (p = 0.02) b) Radial diffusivity (RD) of white matter. RD is higher in SuS (0.33 ± 0.02) compared to HC (0.29 ± 0.01) (p < 0.001) and MS (0.30 ± 0.01) (p = 0.003). d) The apparent diffusion coefficient (ADC) of white matter. SuS (0.74 ± 0.04) ADC is higher than HC (0.68 ± 0.01) (p < 0.001) and MS (0.69 ± 0.02) (p < 0.001). g) Restricted isotropic fraction (RIF) of white matter. SuS (0.046 ± 0.006) RIF is lower compared to HC (0.054 ± 0.004) (p = 0.01). * p < 0.01, ** p < 0.001.