Clinical Outcome Measures Following Peripheral Nerve Repair

Abstract

The hope of translational medicine is to identify treatments that improve the rate and quality of neuronal recovery following peripheral nerve injuries (PNI). A major obstacle to the trial of new treatments for PNI is the absence of sensitive and responsive measures of clinical function, which are the ultimate outcome of the biological events of nerve regeneration. The development of objective clinical measures of nerve regeneration that are sensitive, responsive, and valid is challenging for a number of reasons. The Peripheral Nervous System (PNS) allows us to have complex interactions with our surroundings (for example, the perception of pain, touch, and temperature). Developing objective measures that reflect the multimodal function of the PNS and separate it from psychological influences on that experience is difficult. Secondly, the recovery of function following PNI is dependent upon a number of biological processes at multiple levels including the end organ, the damaged nerve segments, as well as the Central Nervous System (CNS). Clinical measures that quantify these changes and relate them to the recovery of function are not well documented. The biological process of neural regeneration is often assessed in the research arena through postmortem tissue assessment. However, the harvesting of vital nerve tissue for assessment of neural regeneration often risks the function that has been recovered. Therefore, this is not feasible when studying the biological process of regeneration in humans. This has necessitated the development of noninvasive methods to attain the same degree of assessment of biological regeneration. In order to assess the biological mechanisms of tissue and cellular regeneration, the relationship of these processes with human clinical experiences needs to be explained. Correlating these new areas of human assessment will help establish the influence of the complex biological processes that underpin nerve regeneration on the lived experience of nerve injury. This chapter provides an overview of the clinical, neurophysiological, and imaging assessments that can provide pre-, intra-, and postoperative measures of nerve regeneration. This will inform the development of outcome measures that have the capacity to detect a meaningful cinical response in clinical trials which aim to detemine the efficacy of new therapies for PNI.