Neurosurgery of the Peripheral Nervous System: Injuries, Degeneration, and Regeneration of the Peripheral Nerves

Abstract

Increased knowledge is shedding new light on our understanding of the biologic processes involved in nerve regeneration and degeneration. Regeneration is a multistep event that seems to be controlled by neurotrophic factors. Following traumatic, agerelated, or disease-related nerve injuries, these molecules can be expressed and released by target cells, Schwann cells, neuron ensheathing glial cells, or neural somata themselves. The success of nerve regeneration depends on the survival of axotomized neurons, the efficacy of axonal outgrowth from the neurons, and the specificity of peripheral target reinnervation by the regenerating axons. Specific molecules help the injured neurons to survive. Trophic factors, such as nerve growth factors, are taken from either the terminal target tissue or cells such as Schwann cells by the axon and transported retrogradely to the neuronal cell body where they support gene regulation and promote survival of the neuron. A peripheral nerve, regardless of the mechanism of the lesion (e.g., compression, laceration, transection), responds to injury in a predictable way. After peripheral nerve sectioning, changes occur at the level of the proximal and distal axon stumps, their parent neuronal cell bodies, and peripheral nerve targets. Changes in the neuronal cell body consist of chromatolysis, swelling, and displacement of the Nissl substance to the periphery. During chromatolysis, the lipids and proteins necessary for axonal regeneration are synthesized and transferred along the proximal axon stump by so-called “axonal transport.” Axonal elongation begins with emerging axonal sprouts. In the distal axon stump, wallerian degeneration occurs. The axon and myelin degenerate and their debris is removed by phagocytic cells. Empty endoneurial tubes remain within the perineurium and epineurium of the distal nerve stump. Then, in such tubes, the residual Schwann cells proliferate, forming the Bungner’s bands that are ready to receive regenerating axons from the proximal nerve stump. Here, the emerging sprouts, in the appropriate environment, can grow across the area of damage and enter and regenerate along the endoneurial tubes in the distal nerve stump. Chemotactic factors are believed to guide the growing axonal sprouts to reinnervate their original peripheral targets. Only when regenerating axons reach a diameter of two microns do the Schwann cells start remyelination. If the regenerating axons do not reach a distal endoneurial tube or the tube has been replaced by fibrosis, they will form a local tangle or neuroma. A peripheral nerve lesion also leads to pathologic changes in the end organs. For example, by 3 weeks after nerve injury, the denervated muscle undergoes fibrosis. The fibrosis will gradually replace the muscle fibers and after 2 years often only scar tissue is present. Therefore, the muscle should be reinnervated within 18 months after nerve injury to eventually provide a functional outcome. Proximal nerve lesions are therefore, more at risk for poor outcome because of the longer time required for the regenerated axons to reach the target muscles. Turning our attention to the principal kinds of lesions that occur in the peripheral nerves and referring to the classification of Seddon, the following types of nerve injuries can be outlined: Address reprint requests to: Eduardo Fernandez, M.D., Department of Neurosurgery, Catholic University School of Medicine, 00168 Rome, Italy.