Familial Nasopharyngeal Carcinoma 6

Long-Term Complication in the Treatment of Nasopharyngeal Carcinoma 283postural techniques, sensory techniques, motor exercise,swallowing maneuvers, and change in diet(Murphy and Gilbert 2009).With modern radiotherapy technology such asIMRT, it is possible to decrease the risk of radiationfibrosis. The temporomandibular joints can be contouredas avoidance structures and they can potentiallybe spared using IMRT. Since there is adose–response relationship between dysphagia andthe radiation dose delivered to the superior and middlepharyngeal constrictors, if those structures canbe spared using IMRT without risking a geographicmiss of disease, the risk of dysphagia can be reduced(Murphy and Gilbert 2009).22.5Cranial NeuropathyAmong all long-term complications, radiationinducedcranial neuropathy (CNP) is one of the leaststudied and understood entities. Although the biologicbasis of radiation-induced nerve damage is notwell understood, there is a notion that peripheralnerve is relatively resistant to radiation damage(Janzen and Warren 1942). However, once occurred,peripheral nerve damage can be debilitating andeven life-threatening. The low incidence of cranialneuropathy after the completion of radiation, as wellas the long latent of the onset of the condition, makeprospective studies of the topic not possible.22.5.1PathogenesisCranial nerves are a special group of the peripheralnerves in the cranium. It is generally accepted thatperipheral nerve is highly resistant to radiation damage(Janzen and Warren 1942). However, the mechanismsof radiation-induced neuropathy are not wellstudied and understood. Like other types of peripheralnerves, cranial nerve trunks are composed ofnumerous nerve fascicles. The nerve fascicle containsindividual nerve fibers. The cranial nerve trunks aresurrounded by a fibrous connective tissue epineurium;the nerve fascicles are surrounded by a fibrousperineurium; and the nerve fibers are embedded infibrous endoneurium. Each nerve fiber consists of anaxon, which is surrounded by a myelin sheath orunmyelinated depending on its size. The cell bodiesof the axon may be in the brainstem or peripheralganglia. The epineurium carries major blood supplyto the nerve trunk, and the arteries become arteriolesin the perineurium; the arterioles then become capillariesin the endoneurium.When damage to a peripheral nerve occurs, thedeath of an axonal cell body will cause the death ofthe nerve fiber. However, if only a portion of axonwas damaged, it may form sprouts and regenerate.Schwann cells, the composing cells of the myelinsheath, can regenerate after damage including radiation-induceddamage.The knowledge of anatomy of the peripheral nervesis important in the understanding of radiation-induceddamage. Peripheral neuropathy induced by high-doseirradiation may occur in two phases. Radiation mayhave early and direct effect on nerve fibers that maycause changes in electrophysiology and histochemistry.However, the later phase of radiation damage tothe nerve may be caused by the changes in the surroundingfibrotic structures and its embedded bloodsupply to nerve fibers (Mendes et al. 1991).Radiation-induced fibrosis of neck muscle may bea secondary cause of cranial neuropathy. Lin et al.(2002) reported 19 cases of radiation-induced cranialnerve palsy and found that the most frequentlyinvolved nerves were the hypoglossal nerve, thevagus nerve, and the recurrent laryngeal nerve. Allthree cranial nerves pass through the high-dose irradiatedneck regions. Results of other retrospectiveseries also supported that muscle fibrosis after irradiationmight be the cause of cranial nerve palsy(Huang and Chu 1981; Saunders and Hodgson1979; Marks et al. 1982; Mesic et al. 1981). In a morerecently completed cross-sectional study, Kong andLu et al. (2009 , unpublished data) studied 98 NPCpatients who experienced cranial nerve palsy afterdefinitive radiation therapy, and discovered that theprobability of involvement of lower group of cranialnerves (i.e., CN IX–XII) was significantly higher thanthat of the anterior group. In addition, muscle fibrosiswas a significant predictive factor for cranialnerve palsy.Radiation-induced fibrosis of skeletal muscle maycause nerve entrapment with secondary demyelination.Furthermore, the fibrotic process of muscle,epineurium, perineurium, and endoneurium may alsoinduce damage of the vasculature of the nerve (Mendeset al. 1991; Stryker et al. 1990). The significantlyhigher probability of neuropathy in the posterior groupof cranial nerves suggests that the radiation-inducedchanges particularly fibrosis in the surrounding tissue