Familial Nasopharyngeal Carcinoma 6

286 S. S. Lo, J. J. Lu, and L. Kongradiotherapy. Injury to the brainstem and/or spinalcord can result in spastic paraparesis or quadraparesisand more than half of those patients progressrapidly to a debilitated state with a significant proportioneventually dying of the complication (Leeet al. 1992). Fortunately, this complication mainlyoccurred in the old radiotherapy era where twodimensionaltechniques were used, in which shieldingwas based on bony landmarks without the actualstructures volumetrically contoured. Furthermore,without the advantage of three-dimensional computerplanning, the radiation doses delivered to thebrainstem and cervical spinal cord might be underestimated.In cases where matching fields were used,suboptimal treatment set-up accuracy might result inoverdosing of the spinal cord. In a study from HongKong, all the patients who developed brainstem and/or spinal cord injury were patients treated before 1983(Lee et al. 1992). With the utilization of more sophisticatedradiation therapy technology, it is possible toaccurately estimate the radiation doses delivered tothe brainstem and spinal cord and to protect thosestructures without compromising target coverage. Inmost modern series, the occurrence of brainstem andspinal cord injury is extremely rare (Lee et al. 2009,2002, 2005; Sultanem et al. 2000; Kam et al. 2004).22.6.1PathogenesisThe mechanisms of injury to the brainstem and spinalcord are likely similar. According to Schultheiss et al.,the main morphologic features of radiation-inducedmyelopathy are demyelination and necrosis of the spinalcord, although they are not pathognomomic ofradiation injury. Vasculopathies and glial reactioncan also be seen in radiation-induced myelopathy(Schultheiss et al. 1995). Damage to the microvasculaturehas been implicated as one of the mechanisms ofradiation-induced myelopathy. Cytokine network inthe central nervous system may also have a role on thedevelopment of radiation myelopathy (Schultheisset al. 1995).22.6.2Clinical Manifestation and DiagnosisPatients may present with slowly progressive spasticparaparesis or quadraparesis and in patients withbrainstem injury, multiple cranial nerve deficits maycoexist (Lee 1999). Since the posterior parts of thebrainstem and cervical spinal cord are farther awayfrom the target volume, when injury occurs in thebrainstem or the cervical spinal cord, the anteriorlylocated corticospinal tracts are at the highest risk. Asa result, on clinical examination, the predominantdeficits are motor with mild or absent associatedsensory deficits. The majority of patients will progressand develop severe motor debilitation. In oneseries from Hong Kong, 59% of patients with encephalomyelopathybecame debilitated and 34% eventuallysuccumbed to the complication (Lee et al. 1992).To make a definite diagnosis of radiation-inducedbrainstem and spinal cord injury (encephalomyelopathy),it is crucial that certain criteria are fulfilled. Firstof all, the localization of the neurologic findings mustmatch the anatomic region of the brainstem or spinalcord treated with radiation therapy. It is important torule out other causes of encephalomyelopathy such astumor progression as well. In addition, the latent periodbetween the occurrence of the neurologic deficits andthe completion of radiotherapy has to be considered. Inthe classical radiation oncology teaching, a latencyperiod of less than 6 months is rare. In a study by Leeet al. from Hong Kong, the median latent period was3 years (Lee et al. 1992). On MRI, the regions affectedtypically show increased signal intensity on T2-weightedimages and decreased signal intensity on T1-weightedimages. Brainstem auditory evoked potentials mayreveal brainstem dysfunction (Lee 1999).22.6.3ManagementNo effective treatment is currently available for radiation-inducedbrainstem and/or spinal cord injury.Corticosteroid therapy has been used and may beable to temporarily delay progression of the injuriesand symptomatic progression (St Clair et al. 2003).Clinical and radiographic improvement of radiationinducedmyelopathy has been reported after treatmentwith heparin and coumadin (Glantz et al.1994). Hyperbaric oxygen has also been used withoutsubstantial success although clinical improvementhas been reported in a case report where a patientwith radiation myelopathy who was not respondingto steroid therapy was treated with 20 dives of hyperbaricoxygen (Calabro and Jinkins 2000).Because of the lack of effective treatment forbrainstem injury and myelopathy, the best strategyof prevention cannot be overemphasized. With the