BACKGROUND: Neurofilaments are promising biomarkers in multiple sclerosis (MS) 
and increased levels in cerebrospinal fluid (CSF) indicate axonal damage or 
degeneration. In a previous study, neurofilament light chain (NfL) levels in CSF 
of relapsing remitting (RR) patients with MS were normalized by natalizumab 
treatment.
AIMS OF THE STUDY: We compared the coherence between NfL and neurofilament heavy 
chain (NfH(SMI) (35) ) levels in longitudinal CSF samples in a subset of these 
patients.
METHODS: In 30 patients with RRMS, CSF was obtained prior to and following 
12 months of natalizumab treatment. NfH(SMI) (35) was measured by an 
electrochemiluminescence-based immunoassay. NfL levels were determined 
previously by the UmanDiagnostics NF-light(®) assay.
RESULTS: NfH(SMI) (35) decreased in 73.3% and NfL in 90% of the patients 
following natalizumab treatment (32.4 vs 27.4 pg/ml, P = 0.002 and 820 vs 
375 pg/ml, P < 0.0001). Patients experiencing a relapse showed higher NfH(SMI) 
(35) levels compared with patients in remission (47.7 vs 27.6 pg/ml, n = 8, 
P = 0.001). This difference was less obvious for NfL (1055 vs 725 pg/ml, 
P = 0.256). In patients in remission, NfL levels were lower following 
natalizumab treatment (830 vs 365 pg/ml, n = 20, P = 0.0002), whereas the same 
comparison failed significance for NfH(SMI) (35) (28.3 vs 26.9 pg/ml, 
P = 0.086).
CONCLUSIONS: We confirm previous findings, indicating reduced axonal damage 
under natalizumab treatment by measuring NfH(SMI) (35) , using an assay with 
independent methodology. In comparison with NfH(SMI) (35) , NfL changes were 
more pronounced and the treatment effect also included patients in remission. 
Our results suggest that NfL is superior over NfH(SMI) (35) as therapeutic 
biomarker and is a promising candidate to measure neuroaxonal damage in MS 
treatment trials.