Publications & Posters

Neurofilament Results For The Phase II Neuroprotection Study Of Phenytoin In Optic Neuritis


Raftopoulos R, Kuhle J, Grant D, Hickman SJ, Altmann DR, Leppert D, Blennow K, Zetterberg H, Kapoor R, Giovannoni G and Gnanapavan S

Eur J Neurol. 2020 Oct 14


This study was peformed using a Simoa® Homebrew assay.



A randomized trial of phenytoin in acute optic neuritis (ON) demonstrated a 30% reduction in retinal nerve fiber layer (RNFL) loss with phenytoin versus placebo. Here we present the corresponding serum neurofilament analyses.


Eighty‐six acute ON cases were randomised to receive phenytoin (4‐6 mg/kg/day) or placebo for 3 months, and followed up for 6 months. Serum was collected at baseline, 3, and 6 months for analysis of neurofilament heavy chain (NfH) and light chain (NfL).


Sixty‐four had blood sampling. Of these, 58 and 56 were available at 3 months, and 55 and 54 were available at 6 months for NfH and NfL, respectively. There was no significant correlation between serum NfH and NfL at the time points tested. For NfH, the difference in mean placebo – phenytoin was ‐44 pg/ml at 3 months (p=0.019), and ‐27 pg/ml at 6 months (p=0.234). For NfL, the difference was 1.4 pg/ml at 3 months (p=0.726), and ‐1.6 pg/ml at 6 months (p=0.766).


At 3 months, there was a reduction in NfH, but not NFL in the phenytoin versus placebo group, while differences at 6 months were not statistically significant. This suggests a potential neuroprotective role for phenytoin in acute ON, with the lower NfH at 3 months, when levels secondary to degeneration of the anterior visual pathway are still elevated, but not at 6 months, when levels have normalized.