PT  - JOURNAL ARTICLE
AU  - Saraste, Maija
AU  - Bezukladova, Svetlana
AU  - Matilainen, Markus
AU  - Tuisku, Jouni
AU  - Rissanen, Eero
AU  - Sucksdorff, Marcus
AU  - Laaksonen, Sini
AU  - Vuorimaa, Anna
AU  - Kuhle, Jens
AU  - Leppert, David
AU  - Airas, Laura
TI  - High serum neurofilament associates with diffuse white matter damage in MS
AID  - 10.1212/NXI.0000000000000926
DP  - 2021 Jan 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e926
VI  - 8
IP  - 1
4099  - http://nn.neurology.org/content/8/1/e926.short
4100  - http://nn.neurology.org/content/8/1/e926.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 Jan 01; 8
AB  - Objective To evaluate to which extent serum neurofilament light chain (NfL) increase is related to diffusion tensor imaging–MRI measurable diffuse normal-appearing white matter (NAWM) damage in MS.Methods Seventy-nine patients with MS and 10 healthy controls underwent MRI including diffusion tensor sequences and serum NfL determination by single molecule array (Simoa). Fractional anisotropy and mean, axial, and radial diffusivities were calculated within the whole and segmented (frontal, parietal, temporal, occipital, cingulate, and deep) NAWM. Spearman correlations and multiple regression models were used to assess the associations between diffusion tensor imaging, volumetric MRI data, and NfL.Results Elevated NfL correlated with decreased fractional anisotropy and increased mean, axial, and radial diffusivities in the entire and segmented NAWM (for entire NAWM ρ = −0.49, p = 0.005; ρ = 0.49, p = 0.005; ρ = 0.43, p = 0.018; and ρ = 0.48, p = 0.006, respectively). A multiple regression model examining the effect of diffusion tensor indices on NfL showed significant associations when adjusted for sex, age, disease type, the expanded disability status scale, treatment, and presence of relapses. In the same model, T2 lesion volume was similarly associated with NfL.Conclusions Our findings suggest that elevated serum NfL in MS results from neuroaxonal damage both within the NAWM and focal T2 lesions. This pathologic heterogeneity ought to be taken into account when interpreting NfL findings at the individual patient level.DTI=diffusion tensor imaging; EDSS=Expanded Disability Status Scale; FLAIR=fluid-attenuated inversion recovery; IQR=interquartile range; NAWM=normal-appearing white matter; NfL=neurofilament light chain; RRMS=relapsing-remitting MS; SPMS=secondary progressive MS