Nerve compression, nerve injury, and nerve regeneration: An overview

Major peripheral nerves consist of motor, sensory, and autonomic axons of varying diameter and myelination that are grouped into fascicles enveloped in a connective tissue matrix with a nourishing vascular supply. A detailed understanding of neural anatomy and physiology provides the basis for our understanding of various mechanisms and patterns of nerve injury as well as potential for recovery. Fascicles within major nerves have a degree of somatotopic organization that increases distally, and knowledge of this organization can be helpful in diagnosis and localizing injuries. Sunderland classified nerve injuries into five grades based on the severity of damage to axons and their surrounding connective tissue framework, and the degree of injury carries prognostic significance for recovery. Diagnosis of nerve injuries relies on a careful physical exam and is aided by ultrasound, magnetic resonance imaging (MRI), and electrodiagnostic studies. Nerve compression causes ischemia that over time results in demyelination, axonal loss, and progressive fibrosis. This can be exacerbated by excessive strain on the nerve. Nerve transection initiates a predictable process of Wallerian degeneration that consists of a series of molecular changes resulting fundamentally from changes in nicotinamide adenine dinucleotide (NAD+) homeostasis and with well-described downstream effects on muscle histology. Techniques for nerve repair include a tension-free, primary end-to-end coaptation, autologous nerve grafting, or the use of nerve conduits and processed nerve allograft. Future directions include use of the immune modulator FK506 and the promise of polyethylene glycol (PEG) fusion to achieve plasmalemmal sealing prior to the initiation of Wallerian degeneration.