Acute Carotid Artery Thrombosis After Neck Irradiation Rob Reed, MD, Shahzad Sadiq, MD Over the past several decades radiation therapy has become an important modality in the treatment of numerous malignant diseases. Although its benefits and efficacy are undeniable, tumor irradiation has significant side effects that must be considered. These include central nervous system damage, myelosuppression, gastrointestinal toxicity, skin changes, and pneumonitis. Most of these changes are mediated by small vessel damage and occlusion. Larger vessels also can be affected, and several case reports in the literature describe delayed arterial occlusive disease or embolic disease involving the aorta and the carotid, subclavian, and iliac arteries (Table 1). Nearly all of these cases occurred years after completion of the radiation therapy. The most acute cases reported occurred between 6 months and 3 years after completion of therapy. In this case report we describe acute left carotid arterial thrombosis causing neurologic symptoms that occurred during the course of radiation treatment for Hodgkin's disease. ABBREVIATIONS CT, Computed tomography; PlT, Partial thromboplastin time; PT, Prothrombin time; WBC, White blood cells Received December 21, 1993, from the Department of Radiology, St. Joseph Mercy Hospital, Pontiac, Michigan. Revised manuscript accepted for publication April6, 1994. Address correspondence and reprint requests to S. Sadiq, MD, Dept. of Radiology, St. Joseph Mercy Hospital, 900 N. Woodward, Pontiac, Ml 48341 . CASE REPORT The patient, a 60 year old woman, developed left cervical lymphadenopathy in October 1991. She was diagnosed as having Hodgkin's disease and underwent staging laparotomy and splenectomy in November 1991. Radiation therapy via a standard anteroposterior and posteroanterior mantle port was performed in 20 fractions over 32 days with 6 MV photons. The total dose to the left neck was 4680 rad. On December 30, 1991, the patient developed sudden onset of right facial droop and right hemiparesis. Laboratory values on admission were as follows: PTf, 23.5 sec; PT, 12.9 sec; WBC, 8100 per cu mm; hemoglobin, 12.9 g/ dl; hematocrit, 38.5 ml/ dl; platelets, 463 per cu mm.The initial CT scan of the brain was negative. Duplex and color Doppler ultrasonography of the carotid arteries revealed soft thrombus in the left internal carotid artery with a tail (Fig. 1). The patient underwent anticoagulation therapy with gradual resolution of the neurologic symptoms. A second CT scan of the brain on January 4, 1992 revealed ischemic changes in the distribution of the left middle cerebral artery. A second sonogram of the carotid arteries on January 27, 1992, demonstrated complete resolution of the intraluminal thrombus with no evidence of significant underlying atherosclerotic disease (Fig. 2). The patient also had a normal echocardiogram. Given the history of recent irradiation to the neck and the absence of significant atherosclerosis within the left carotid artery, this case suggests an acute radiation-induced thrombosis of the left common carotid artery with embolism to the middle cerebral artery. DISCUSSION Radiation effects on biologic tissues have been studied extensively. In 1899, only 4years after the discovery of x-rays, Gassman described radiation-induced © 1994 by the American Institute of Ultrasound in Medicine •J Ultrasound Med 13:641-644, 1994 • 0278-4297/94/$3.50 642 JUltrasound Med 13:641-644, 1994 CAROTID ARTERY THROMBOSIS Table 1: Comparison of Radiation-related Vascular Complications Author(s) Type of Neoplasm or Disease Anatomic site Glick2 Vocal cord Carotid arteries (bilateral) Haywardl Thyroid Left carotid artery 27 years Kearsley and Tattersall4 Vocal cord Breast Right carotid artery Right carotid artery 17 years 11.5 years Larynx Parotid Hyperthyroidism Left carotid artery Right carotid artery Right carotid artery 25 years 34 years 32 years Nasopharynx Right carotid artery 15 years Breast Breast Breast Hodgkin's disease Uterus Cervix Cervix Right subclavian artery Left axillary artery Left subclavian artery Left anterior descending artery Iliac·femoral arteries Left femoral artery Iliac arteries (bilateral) 19 years Call et al 10 Hodgkin's disease Hodgkin's diseilse Rhabdomyosarcoma Left carotid artery Left carotid artery Right mrotid artery 2.5 years 2.5 years 2 years Conomyand Kellermeyer11 Hodgkin's disease Left carotid artery 8 months Kagan et al 12 Hodgkin's disease Multifocal 6 months Levinson et al ~ Osgood et aJf> Peters et aJ1 Time Interval• 16 years 36 years 7 1 3 years year years •Interval between cessation of therapy and onset of symptoms. vascular changes consisting of intimal thickening and vacuolization with medial changes.1 Further work by Fajardo and Berthrong1 and others characterized the vascular damage caused by radiation. The endothelial cell is injured initially and subsequently undergoes intimal damage. This is followed by formation of mural thrombus and myointimal proliferation. The most sensitive segments are the smallest arterioles and capillaries, and occlusion of these vascu1ar channels is an important precipitating factor in radiation damage of the skin, lung, kidneys, heart, gastrointestinal tract, and the central nervous system. Larger arteries are affected less commonly because of their strong supporting walls and large lumen diameter. The majority of the reported cases in the literature are of delayed large artery stenosis or occlusion occurring years after completion of radiation thera- py. 2-7 The pathogenesis of delayed vascular occlusion is thought to be accelerated atherosclerotic disease at the site of arterial wall damage. The histologic changes that occur were well documented in animal models by Gold8 and Kirkpatrick.9 Several other authors report vascular complications occurring between 6 months and 3 years after radiation therapy7·10·11·12 In the majority of these instances, as in our case, thrombotic occlusion occurred in an irradiated segment of the vascular system that was free of significant underlying atherosclerotic disease. The biologic effects of radiation and the potential complications of brachytherapy are well known. Radiation-induced disease affects the smallest segments of the vascular system, resulting in endothelial damage and thrombotic occlusion. The endothelium of larger arteries is affected similarly. However, because of the larger lumen and stiffer walls, clinical J Ultrasound Med 13:641-644, 1994 REED AND SADIQ 643 8 A Figure I Transverse (A) and longitudinal (8) color Doppler sonograms of the left internal carotid artery obtained on December 31, 1991. The images demonstrate intraluminal thrombus with a freely moving tail located within the proxi~ mal internal carotid artery. A Figure 2 Transverse (A) and longitudinal (8) color Doppler sonograms of the left internal carotid artery obtained on january, 27, 1992. Complete resolution of the intraluminal thrombus has occurred, and there is no evidence of underly~ ing atherosclerotic disease. 8 644 signs and symptoms often are delayed by months or years and are mediated by accelerated atherosclerosis. The case presented here is an exception to this rule in that acute large artery thrombosis occurred in the absence of significant atherosclerotic change in a patient with a normal coagulation profile. The presence of neurologic or ischemic symptoms in a patient who is undergoing or has previously had radiation therapy should initiate the appropriate diagnostic tests so that therapy can be started without delay. REFERENCES 1. 2. JUltrasound Med 13:641-644, 1994 CAROTID ARTERY THROMBOSIS Fajardo LF, Berthrong M: Vascular lesions following radiation. Pathol Annu 23:297, 1988 Glick 8: Bilateral carotid occlusive disease following irradiation for carcinoma of the vocal cords. Arch Pathol 93:352, 1972 5. Levinson SA, Close MB, Ehrenfeld WK, et a!: Carotid artery ocdusive disease following external cervical irradiation. Arch Surg 107:395, 1973 6. Osgood CP, Karumaratre ER, Sandler R, et al: Carotid occlusion in a 27 year old man: A case report. Neurosurgery 18:459,1986 7. Peters WR, Schlicke CP, Schmutz DO: Peripheral vascu· Jar disease following radiation therapy. Am Surg 45:700, 1979 8. Gold H: Production of Atherosclerosis in the Rat. Arch Pathol71:268, 1961 9. Kirkpatrick JB: Pathogenesis of foam cell lesions in irradiated arteries. Am J Path 50:291, 1967 10. Call GK, Bray PF, Smoker WR et al: Carotid thrombosis foDowing neck irradiation. Int J Radial Onco118:635, 1990 11. Conomy JP, Kellermeyer RW: Delayed cerebrovascular consequences of therapeutic radiation. Cancer 36:1702, 1975 3. Hayward RH: Arteriosclerosis produced by radiation. Surg Clin North Am 52:359, 1972 12. Kagan AR, Bruce OW, diChiro G: Fatal foam cell arteritis of the brain after irradiation for Hodgkin's diseaseangiography and pathology. Stroke 2:232,1971 4. Kearsely JH, Tattersall MHN: Cerebral embolism in cancer patients. Q JMedl203:279, 1982 13. Silverberg GO. Britt RH, Goffinet DR: Radiation induced carotid artery disease. Cancer 41:130, 1978