Snapshot A 32-year-old woman presents to her primary care physician with pain affecting the right hand. She states that the pain is worst in the thumb, index, middle, and part of the ring finger. The pain is worst at night and at times wakes her up from sleep. She tries to put her hand in running warm water and shakes her hand in order to improve the pain. Extending the right hand worsens the pain. Medical history is significant for type II diabetes mellitus and obesity. She works as a secretary. She has a positive Phalen test. When discussing surgical treatment for her carpal tunnel syndrome, she asks what can occur if the nerve compression is not relieved. The physician explains the possibility of Wallerian degeneration. Introduction Definition axonal degeneration distal to the site of transection and proximal axonal retraction When an axon is cut or crushed, it is divided into a proximal and distal segment the proximal segment is still attached to the cell body it may undergo a chromatolytic reaction, where there is swelling of the cell body and the nucleus is eccentricly positioned fragmentation of the rough endoplasmic reticulum the distal segment the neuronal membrane and cytoskeleton is impaired and subsequently degenerates Axotomy (axonal transection) of peripheral nerves results in Schwann cells breaking down myelin into small fragments and englufs it recruiting macrophages to dispose of the axonal debri producing growth factors to promote the regeneration of axons Wallerian degeneration occurs much more slowly in the central nervous system (CNS) than in the peripheral nervous system (PNS) oligodendrocytes do not have a robust system of removing myelin the blood-brain barrier impairs macrophages from entering and removing axonal debri this in turn makes microglia responsible for removing the debri