Acute axonal damage predicts clinical outcome in patients with multiple sclerosis

The objectives of this study were ( 1) to determine how cerebrospinal fluid (CSF) neurofilament heavy chain ( NfH(SMI34) and NfH(SMI35)) levels relate to clinical outcome in optic neuritis ( ON) and multiple sclerosis ( MS) relapse patients treated with high dose oral methylprednisolone; and ( 2) to correlate neurofilament and myelin basic protein (MBP) concentrations, particularly as the latter was previously associated with clinical disability. Fifty subjects participated in two double-blind, randomized, placebo-controlled clinical trials. Eight/18 patients in the ON trial and 15/32 subjects in the MS attack trial were treated with oral methylprednisolone. In the MS attack trial group, CSF NfH(SMI34) and NfH(SMI35) measured at week 3 and Delta CSF NfH(SMI34) levels from baseline to week 3 were predictive of clinical outcome at week 8 and 52. In the ON group, no such association was seen. When both groups were combined, baseline CSF NfH(SMI34) and NfH(SMI35) correlated positively with baseline enhancing lesion volume (ELV) (r(s) = 0.50, P < 0.01 and r(s) = 0.53, P < 0.01, respectively). Levels of NfH(SMI35) at baseline and week 3 also strongly correlated with the MBP concentration. This study supports the view that acute inflammation in ON and MS results in axonal pathology and that the latter has a role in determining functional impairment.