R Raftopoulos1, J Kuhle2, D Grant1, S J Hickman3, D R Altmann4, D Leppert2, K Blennow5,6, H Zetterberg5,6,7,8, R Kapoor1, G Giovannoni9, S Gnanapavan9. 1. University College London Institute of Neurology, London, UK. 2. Department of Neurology, University Hospital Basel, Basel, Switzerland. 3. Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK. 4. Medical Statistics Department, London School of Hygiene & Tropical Medicine, London, UK. 5. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 6. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 7. Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK. 8. UK Dementia Research Institute at UCL, London, UK. 9. Department of Neuroscience & Trauma, QMUL, London, UK.
Abstract
BACKGROUND: 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. METHODS:Eighty-six acute ON cases were randomized 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 neurofilament light chain (NfL). RESULTS: Sixty-four patients 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). CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: 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. METHODS: Eighty-six acute ON cases were randomized 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 neurofilament light chain (NfL). RESULTS: Sixty-four patients 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). CONCLUSIONS: 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.
Authors: Thomas E Williams; Katherine P Holdsworth; Jennifer M Nicholas; Arman Eshaghi; Theodora Katsanouli; Henrietta Wellington; Amanda Heslegrave; Henrik Zetterberg; Chris Frost; Jeremy Chataway Journal: Neurol Neuroimmunol Neuroinflamm Date: 2022-01-14
Authors: Adam Anad; Miriam K Barker; Jessica A Katanga; Konstantinos Arfanakis; Leslie R Bridges; Margaret M Esiri; Jeremy D Isaacs; Sonja Prpar Mihevc; Anthony C Pereira; Julie A Schneider; Atticus H Hainsworth Journal: J Neuropathol Exp Neurol Date: 2022-02-24 Impact factor: 3.685