Phosphorylated Neurofilament Heavy Chain Correlations to Visual Function, Optical Coherence Tomography, and Treatment

Abstract

Objective. To correlate visual and neurologic clinical scores and treatment of optic neuritis and multiple sclerosis (MS) patients with assays of serum phosphorylated neurofilament heavy chain (pNF-H) and optical coherence tomography (OCT) measurements of axonal loss. Design/Methods. The Optic Neuritis Treatment Trial (ONTT) randomized 457 patients with acute optic neuritis to intravenous methylprednisolone (IVMP) followed by oral prednisone, oral prednisone or placebo treatment arms. We quantified serum pNF-H levels in 175 ONTT patients 5 years after study entry. We performed OCT measurements of macular volume and the retinal nerve fiber layer (RNFL) in a subset of 51 patients at year 15. Results. Elevated pNF-H levels at year 5 correlated to poorer visual function at study entry. Lower 15 year macular volumes and RNFL thickness correlated better with follow-up than with baseline visual function measures. With IVMP treatment, 15 year RNFL differences of the fellow eye (FE) minus the affected eye (SE) RNFLFEmSE correlated with five-year pNF-H levels. PNF-H was reduced by half with IVMP relative to placebo or by 40% relative to prednisone. Conclusions/Relevance. Acute optic neuritis patients who have more severe visual loss during initial presentation have a higher incidence of axonal loss that was slightly suppressed with IVMP treatment.

The Diagnostic and Prognostic Value of Neurofilament Heavy Chain Levels in Immune-Mediated Optic Neuropathies

“…This is consistent with the clinical observation of more server loss of visual function and retinal nerve fibres in patients with NMO [20]. Interestingly, loss of retinal nerve fibres as quantified by OCT was correlated to serum pNfH levels in patients participating in the Optic Neuritis Treatment Trial [11]. …”

“…Blood Nf heavy chain (NfH) levels have been shown to be elevated in patients with acute optic neuritis compared with control subjects, and its level correlates inversely with visual loss and the retinal nerve fibre thickness as assessed by retinal optical coherence tomography (OCT) [9–11]. …”

Biomarker Report from the Phase II Lamotrigine Trial in Secondary Progressive MS – Neurofilament as a Surrogate of Disease Progression

“…Interestingly, performance in the 9-HPT and its relationship with NfH levels was found predominantly in the non-dominant hand which may be related to the loss in manual dexterity that may be more obvious with the non-dominant hand as the test is normally performed faster using the dominant hand [13]. Others have also shown that high NfH levels correlate with poor visual outcome [14], [15]. Neuropsychological test scores from the PASAT and MSIS-29 appeared to be also responsive to changes in NfH, with patients with higher NfH having lower PASAT scores and higher MSIS-29 psychological scores, possibly related to the significant neurodegenerative changes observed in grey matter disease [16] or in relation to EDSS deterioration, respectively; McGuigan et al .…”

Plasma neurofilament heavy chain is not a useful biomarker in Charcot-Marie-Tooth disease

“…To date, plasma neurofilament heavy chain (NfH) levels have been shown to be raised in several central nervous system diseases, including amyotrophic lateral sclerosis (ALS) and optic neuritis . Neurofilaments are the most abundant neuronal cytoskeletal protein in peripheral nerves, and their concentration in blood likely reflects axonal breakdown and provides a biomarker of peripheral nerve disease .…”