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Neurol Neuroimmunol Neuroinflamm. 2019 Aug 8;6(5):e598. doi: 10.1212/NXI.0000000000000598. eCollection 2019 Sep.

High serum neurofilament light chain normalizes after hematopoietic stem cell transplantation for MS.

Author information

1
The University of Ottawa and Ottawa Hospital Research Institute (S.T., M.B., H.L.A., M.S.F.); Department of Physics (D.R.T., V.T.-C.), University of Ottawa; Montreal Neurological Institute (H.L., D.L.A.); and Perelman School of Medicine and University of Pennsylvania (A.B.-O.).

Abstract

Objective:

To evaluate neurofilament light chain (NfL) levels in serum and CSF of patients with aggressive MS pre- and post-treatment with immunoablation followed by autologous hematopoietic stem cell transplantation (IAHSCT) and examine associations with clinical and MRI outcomes.

Methods:

Paired serum and CSF in addition to MRI and clinical measures were collected on 23 patients with MS at baseline and 1 and 3 years post-IAHSCT. An additional 33 sera and CSF pairs were taken from noninflammatory neurologic controls. NfL levels were quantitated using the Simoa platform (Quanterix).

Results:

Baseline MS NfL levels were significantly elevated relative to controls in serum (p = 0.001) and CSF (p = 0.001). Following IAHSCT, high pretreatment NfL levels significantly reduced in serum (p = 0.0023) and CSF (p = 0.0068) and were not significantly different from controls. Serum and CSF NfL levels highly correlated (r = 0.81, p < 0.0001). Baseline NfL levels were associated with worse pretreatment disease measures (Expanded Disability Status Scale [EDSS], relapses, MRI lesions, and MR spectroscopy (MRS) N-acetylaspartate/creatine). Elevated baseline NfL levels were associated with persistently worse indices of disease burden post-IAHSCT (sustained EDSS progression, cognition, quality of life, T1 and T2 lesion volumes, MRS, and brain atrophy).

Conclusion:

These data substantiate that serum and CSF NfL levels reflect disease severity and treatment response in patients with MS and may therefore be a useful biomarker. Baseline serum levels associated with markers of pretreatment disease severity and post-treatment outcomes.

Classification of evidence:

This study provides Class II evidence that for patients with aggressive MS, serum NfL levels are associated with disease severity.

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