Serum neurofilament light chain measurements following nerve injury

Abstract

BACKGROUND: Functional outcomes following peripheral nerve injury (PNI) are dependent upon early recognition and prompt referral to specialist centres for appropriate surgical intervention. Technologies which facilitate the early detection of PNI would allow faster referral rates and encourage improvements in functional outcome. Serum Neurofilament Light chain (NfL) measurements are cheaper to perform, easier to access and interpret than many conventional methods used for nerve injury diagnosis such as electromyography (EMG) and/or MRI assessments, but changes in serum NfL levels following PNI have not been investigated in detail. This pre-clinical study aimed to determine whether the serum Neurofilament Light chain (NfL) levels can: 1) detect the presence of a nerve injury and 2) delineate between different severities of nerve injury. METHODS: A rat sciatic nerve crush and common peroneal nerve crush were implemented as controlled animal models of nerve injury. At 1, 3, 7 and 21 days post-injury, serum samples were retrieved for analysis using the SIMOA® NfL analyser kit. Nerve samples were also retrieved for histological analysis. Static sciatic index (SSI) was measured at regular time intervals following injury. RESULTS: Significant 45-fold and 20-fold increases in NfL serum levels were seen one day post-injury following sciatic and common peroneal nerve injury respectively. This corresponded with an 8-fold higher volume of axons injured in the sciatic compared to the common peroneal nerve (p<0.001). SSI measurements post-injury revealed greater reduction in function in the sciatic crush group compared with the common peroneal crush group. CONCLUSIONS: NfL serum measurements represent a promising method for detecting nerve injuries and identifying their severity. Clinical translation of these findings could provide a powerful tool to improve surgical management of nerve injured patients. This article is protected by copyright. All rights reserved