High serum neurofilament light chain normalizes after hematopoietic stem cell transplantation for MS. Issue 5 (September 2019)

• Record Type: Journal Article
• Authors: Thebault, Simon; R. Tessier, Daniel; Lee, Hyunwoo; Bowman, Marjorie; Bar-Or, Amit; Arnold, Douglas L.; L. Atkins, Harold; Tabard-Cossa, Vincent; Freedman, Mark S.
• Is Part Of: Neurology. Volume 6:Issue 5(2019)
• Publication Date: 2019-09
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000000598
• Languages: English
• ISSNs: 2332-7812

Abstract

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.