10 Nov 21. Featured Paper

Link to paper on Brain Communications

 

Authors

Elizabeth N York, Sarah-Jane Martin, Rozanna Meijboom, Michael J Thrippleton, Mark E Bastin, Edwin Carter, James Overell, Peter Connick, Siddharthan Chandran, Adam D Waldman, David P J Hunt, the Future-MS consortium

 

Abstract

Myelin loss is associated with axonal damage in established multiple sclerosis.

This relationship is challenging to study in vivo in early disease.

Here, we ask whether myelin loss is associated with axonal damage at diagnosis, by combining non-invasive neuroimaging & blood biomarkers.

We performed quantitative microstructural MRI & single molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis.

Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation (MTsat) & neurite orientation dispersion & density imaging (NODDI) diffusion data.

We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 vs 0.57, difference 0.036, 95% CI 0.029 to 0.043, p < 0.001).

Lesion volume (Spearman’s rho rs= 0.38, p < 0.001) & g-ratio (rs= 0.24 p < 0.05) correlated independently with plasma neurofilament.

In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) (11/23 [48%] versus 2/15 [13%] p < 0.05).

These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage.

MRI-derived g-ratio may provide useful additional information regarding lesion severity, & help to identify individuals with a high degree of axonal damage at disease onset.

York, Martin et al. simultaneously measured g-ratio & plasma neurofilament in 73 relapsing-remitting multiple sclerosis patients at diagnosis using advanced MRI & single molecule ELISA.

They demonstrate that g-ratio of cerebral white matter lesions varies at diagnosis, & show that high g-ratio of lesions is associated with elevated plasma neurofilament.

 

Keywords

• G-ratio
• MRI
• Multiple Sclerosis
• Myelin
• Neurofilament