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.

Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases

“…If present, such a relationship would require age dependent cut-off values [7]. A major limitation to all studies in this field to date [6,7,11,32–34] is that they have not been powered to investigate this potential correlation in the CSF, due to lack of samples from a sufficiently large healthy control group across all age categories. Again, the availability of the present method to investigate this in readily available serum samples is highly relevant.…”

Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

“…Increased serum NfL and Nf heavy chain levels have been found in neurological conditions other than MS, such as amyotrophic lateral sclerosis and Guillain-Barré syndrome, and have also been used as a marker of neurotoxicity after chemotherapy 5 6 10 11. Results from previous studies in CIS have been controversial with one study showing slightly higher CSF NfL levels in patients with CIS converting to CDMS than in NC,4 while other studies have not 12 13. It should be noted that even in this cohort, serum NfL levels were to some extent higher in FC than NC and it is plausible that by increasing the sample size the difference may become statistically significant.…”

Cerebrospinal fluid neurofilament tracks fMRI correlates of attention at the first attack of multiple sclerosis

“…26 Several studies have suggested a relationship between cognitive dysfunction and MRI measure of axonal damage in MS. 12 However, this is the first study evaluating the relationship between cognitive processing and CSF NFL levels at the earliest stages of MS. Since NFL concentration in MS increases both in acute and in chronic axonal damage, 8,27 the possibility that the observed NFL changes are related to acute axonal dysfunction must be taken into account. In order to minimize this possibility, we included patients far from clinical exacerbation.…”