Neurofilament light chain levels in pregnant multiple sclerosis patients: a prospective cohort study

Abstract

Background and purpose Neurofilament light chain is a cytoskeletal protein of neurons. Its levels are increasingly recognized as measures of neuroaxonal damage. The aim of this study was to explore serum neurofilament light chain (sNfL) levels in multiple sclerosis (MS) patients and healthy controls during pregnancy and puerperium. Methods This was a prospective, longitudinal, single‐center study. sNfL concentration was assessed using a highly sensitive single‐molecule array during pregnancy and in puerperium, in a cohort of 39 pregnant patients with relapsing multiple sclerosis (P‐MS). Twenty‐one healthy pregnant women (HPW) served as a control group. Eight P‐MS suffered relapses during pregnancy (P‐MS‐R) in the first or second trimesters. Results No differences in pregnancy and delivery data were observed between P‐MS and HPW. P‐MS showed higher sNfL values than HPW in the first trimester, independently of the presence (P = 0.002) or not (P = 0.02) of relapses during pregnancy. However, in the third trimester, only P‐MS‐R showed higher sNfL values than HPW (P = 0.001). These differences extended to the puerperium, where P‐MS‐R showed higher sNfL values than those with no relapses during gestation (P = 0.02). Conclusion These data strongly suggest that sNfL levels reflect MS activity during pregnancy. Additionally, the absence of relapses during pregnancy may have a beneficial effect on neurodegeneration during puerperium.

Blood neurofilament light: a critical review of its application to neurologic disease

“…In initial studies of blood NfL using ECL technology showed an association between serum NfL and brain atrophy over 2 years and number of MRI lesions, 64 though it had a poor prognostic value for patients with clinically isolated syndrome later converting to MS. 65 These studies on a small group of patients were limited by the sensitivity of the assay. 11 The high sensitivity of the SIMOA â technology provided the reliable quantification of blood NfL in MS. 11 On the group level, blood NfL in MS was higher than in healthy controls 32,44,62,66 with progressive MS having higher levels of blood NfL than relapsing MS. 16,32 The increased levels of blood NfL in progressive versus relapsing MS was unexpected and contrasted with lower levels of NfL in the CSF in progressive versus relapsing MS. 67 This remains unexplained but could be related to a breakdown of the BBB in progressive MS linked to aging and/or a contribution from the peripheral nervous system. Ascherio's group reported that in a military cohort, blood NfL was able to identify neuronal damage 6 years prior to the clinical disease onset, 68 thus neurodegeneration was already present at the prodromal stage of MS. A number of studies have found that disease activity as measured by clinical or MRI assessment is associated with an increase in blood NfL levels in both adult 16,32,66,[69][70][71][72][73] and pediatric patients.…”

“…16,69,70 The known reduction in disease activity during pregnancy 77 was reflected by similar blood NfL levels among pregnant healthy women and MS patients. 62 It is not known whether this was related to the physiological increase in blood volume that occurs during pregnancy. 60 With a better understanding of the role of NfL and the development of sensitive and reproducible assays, a fertile ground has developed for the use of blood NfL in clinical studies.…”

“…During pregnancy, there is an increase in blood volume (approximately 45%) though this may vary between individuals 60 . Paradoxically, in both women at risk that did not develop preeclampsia 61 and in healthy pregnant women 62 blood NfL levels progressively increased during pregnancy until delivery, perhaps due to the developing brain of the fetus. It may be appropriate to consider BMI and pregnancy as a confounder when measuring NfL.…”

“…The high sensitivity of the SIMOA ® technology provided the reliable quantification of blood NfL in MS 11 . On the group level, blood NfL in MS was higher than in healthy controls 32,44,62,66 with progressive MS having higher levels of blood NfL than relapsing MS 16,32 . The increased levels of blood NfL in progressive versus relapsing MS was unexpected and contrasted with lower levels of NfL in the CSF in progressive versus relapsing MS 67 .…”

“…Observational studies suggested a prognostic value of NfL in being able to predict brain and spinal cord atrophy over 2, 5, and 10 years 16,69,70 . The known reduction in disease activity during pregnancy 77 was reflected by similar blood NfL levels among pregnant healthy women and MS patients 62 . It is not known whether this was related to the physiological increase in blood volume that occurs during pregnancy 60 …”