Structural and physiological properties of peripheral nerves after intraoperative irradiation

Peripheral nerve appears to be a dose-limiting normal tissue in the clinical application of intraoperative radiation therapy (IORT). The objectives of this review are to study structural and physiological changes peripheral nerves undergo after intraoperative irradiation through the evaluation of clinical and experimental studies. Clinically significant peripheral nerve injury will most likely occur if the dose of IORT exceeds 20 Gy. Tolerance of peripheral nerve will also depend on the volume of irradiated nerve and surrounding tissues, such as muscle and vasculature, or the combination of IORT with other therapeutic modalities, such as hyperthermia and chemotherapy. Evaluation of the histomorphometric findings showed a significant decrease in nerve fiber density, particularly in the central portion of the nerve and especially affecting large nerve fibers after doses higher than 20 Gy. Electron microscopic analysis have shown an increase in microtubule density and neurofilament accumulation in axons of irradiated nerves while changes in myelin were not present. These findings are suggestive of radiation induced hypoxia (damage to the vasculature) resulting in axon damage and subsequent nerve fiber loss as a mechanism of late radiation injury to the peripheral nerve.