CSF neurofilament and N-acetylaspartate related brain changes in clinically isolated syndrome

Abstract

Background: Axonal damage is considered a major cause of disability in multiple sclerosis (MS) and may start early in the disease. Specific biomarkers for this process are of great interest.

Objective: To study if cerebrospinal fluid (CSF) biomarkers for axonal damage reflect and predict disease progression already in the earliest stages of the disease, that is, in clinically isolated syndrome (CIS).

Methods: We assessed CSF levels of neurofilament heavy (NFH), neurofilament light (NFL) and N-acetylaspartate (NAA) in 67 patients with CIS and 18 controls with neuropsychiatric diseases of non-inflammatory aetiology (NC). Patients with CIS underwent baseline magnetic resonance imaging (MRI) at 3T, and a follow-up MRI after 1 year was obtained in 28 of them.

Results: Compared with NC, patients with CIS had higher NFH (p=0.05) and NFL (p<0.001) levels. No significant group differences were found for NAA. Patients' NFH levels correlated with physical disability (r=0.304, p<0.05) and with change in brain volume over 1 year of follow-up (r=-0.518, p<0.01) but not with change in T2 lesion load.

Conclusion: Our results confirm increased neurofilament levels already in CIS being related to the level of physical disability. The association of NFH levels with brain volume but not lesion volume changes supports the association of these markers with axonal damage.

Figures 1A-C.

Group differences of CSF NFH, NFL and NAA between patients with CIS and controls. Patients with CIS had higher levels of NFH (A) and NFL (B). No significant group difference was observed regarding NAA levels (C). CIS: clinically isolated syndrome, CO: control, CSF: cerebrospinal fluid, NAA: N-acetylaspartate; NFH: neurofilament heavy, NFL: neurofilament light, ns: not significant.

Figure 2.

Correlation of CSF NFH levels (ranked variable) with the change of normalized brain tissue volume over time. Higher NFH levels are associated with increased brain tissue loss over time (r=-0.518, p<0.01; Pearson partial correlation corrected for age). CSF: cerebrospinal fluid, NFH: neurofilament heavy.

Figure 3.

Scatter plot of CSF NFL levels and CSF white cell count variables (unranked and not corrected for age). NFL levels were significantly correlated with white cell count (r=0.646, p<0.001, Pearson partial correlation corrected for age). CSF: cerebrospinal fluid, NFL: neurofilament light.