| Autor: |
Simon Thebault, Hyunwoo Lee, Gauruv Bose, Daniel Tessier, Mohammad Abdoli, Marjorie Bowman, Jason Berard, Lisa Walker, Carolina A. Rush, Heather MacLean, Ronald A. Booth, Sridar Narayanan, Douglas L. Arnold, Vincent Tabard‐Cossa, Harold L. Atkins, Amit Bar‐Or, Mark S. Freedman |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Annals of Clinical and Translational Neurology, Vol 7, Iss 5, Pp 767-775 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2328-9503 |
| DOI: |
10.1002/acn3.51045 |
| Popis: |
Abstract Objective Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as ‘pseudoatrophy’, related to reduced inflammation. Treatment‐related neurotoxicity may be contributory. We sought objective evidence of post‐IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. Methods Sera were collected from 22 MS patients pre‐ and post‐IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single‐molecule assay. Results Pre‐IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12‐month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). Interpretation There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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