Transganglionic gracile response following limb amputation in man

Gracile neuroaxonal dystrophy (NAD) is an distinctive morphological alterat ion of central projecting axon terminals of dorsal root ganglion neurons. E xperimentally, lower limb amputation has been shown to accelerate the forma tion of gracile NAD, suggesting that the transganglionic response to periph eral axotomy may play a role in its development. To determine if a similar response occurs in the human sensory nervous system following peripheral ne rve injury, we have performed postmortem histopathological examinations of the dorsal column nuclei of three patients (aged 15, 55, and 77 years old); all of whom had undergone accidental or therapeutic unilateral limb amputa tion (1 year, 38 years, and 1 year 8 months prior to death, respectively). In a 15-year-old man who underwent therapeutic leg amputation, the gracile nuclei on the transected side revealed reactive gliosis and many small axon al spheroids. The spheroids and fine neurites were immunolabelled with anti bodies for growth-associated protein-43, ubiquitin and neuropeptide Y (NPY) . Neither routine histological nor immunohistochemical methods demonstrated comparable changes in the contralateral gracile nucleus. In a 77-year-old man who underwent leg amputation, the gracile nucleus on the amputated side was gliotic and showed several NPY and ubiquitin-immunoreactive spheroids, which were not seen in the contralateral non-transected side. A 55-year-ol d man with a history of accidental arm amputation showed well-developed NAD in the cuneate nucleus only on the transected side. This study clearly dem onstrates the occurrence of transganglionic response to limb amputation in human dorsal column nuclei. The extent of the regenerative and/or degenerat ive responses may vary depending on the age of the patient and the time int erval following the peripheral axotomy.