Destruction of a proximal spinal motor root results in a gradual dissolution of the distal motor nerve and its myelin sheath (a form of wallerian degeneration). The neuronal motor cell body that gives rise to the motor fiber undergoes characteristic retrograde morphologic changes described below but does not die. Similar destruction of the dorsal spinal root produces secondary wallerian degeneration of the posterior columns of the spinal cord, but not of the peripheral sensory nerve because the dorsal root ganglion cell maintains the integrity of the distal axon. In other words, destruction of axons results within several days in wallerian degeneration of the myelin distal to the point of injury but not transgressing the neuronal cell body. The myelin breaks down into blocks or ovoids in which lie fragments of axons (digestion chambers of Cajal). The myelin fragments are then converted, through the action of macrophages, into neutral fats and cholesterol esters and carried by these cells to the bloodstream.
Certain diseases affect the neuron primarily rather than the axon and cause either a motor or sensory neuronopathy. In the former case, more properly considered a myelopathy, the anterior horn cell is affected by a disease process (motor neuron disease, or motor neuronopathy) and in the latter, the sensory ganglion cell (ganglionopathy) is destroyed. A type of wallerian distal degeneration of the respective nerve fibers follows.
Some of these pathologic reactions are more easily understood if one considers certain features of cytoskeletal structure and function of nerve cells and their axons. The axon contains longitudinally oriented neurofilaments and microtubules, which are separated but interconnected by cross-bridges. Their main function involves the transport of substances from nerve cell body to axon terminal (anterograde transport) and from the distal axon back to the cell body (retrograde transport). Thus, when the axon is severed, organelles cannot be transmitted to the distal axon for the purpose of renewing membrane and neurotransmitter systems. By means of retrograde axonal transport, the cell bodies receive signals to increase their metabolic activity and to produce growth factors and other materials needed for axonal regeneration. In an incompletely defined way, the axon also creates a local environment that allows the Schwann cell to maintain the integrity of the adjacent myelin sheath. Loss of this trophic influence leads to dissolution of the myelin sheath, but not of the Schwann cell itself.
There are also highly characteristic histopathologic changes in the nerve cell body termed chromatolysis as a secondary consequence of axonal interruption. These retrograde changes consist of swelling of the cell cytoplasm and marginalization and dissolution of the Nissl substance. The important point again is that despite the destructive changes in the nerve fibers, the nerve cells, while altered in histologic appearance, are left intact with preservation of the apparatus required for recovery.
In segmental demyelination, recovery of function may be rapid because the intact but denuded axon needs only become remyelinated. The newly formed internodal segments are initially thinner than normal and of variable length. By contrast, recovery is much slower with wallerian or axonal degeneration, often requiring months to a year or more because the axon must first regenerate and then reinnervate the muscle, sensory organ, or blood vessel before function returns. When the regenerating axon first becomes myelinated, the internodal myelin segments are short, the length of one normal internode being replaced by 3 or 4 shorter new ones. Recurrent demyelination and remyelination lead to “onion bulb” formations and enlargement of nerves, the result of proliferating Schwann cells and fibroblasts that encircle the axon and its thin myelin sheath. If nerve cells are destroyed, no recovery of function is possible except by collateral regeneration of axons from intact nerve cells. Interruption of a nerve fiber by severing or by crude destruction usually prevents continuity from being reestablished. Regenerating axon filaments take aberrant courses and, with fibroblastic scar formation, they may form a disorganized clump of tissue termed pseudoneuroma.