Radiation Vasculopathy

Introduction

Radiation-induced arterial damage was described shortly after the advent of the X-ray by Roentgen in the late 1800s . In the setting of radiation therapy for malignancy, this arterial change has been described in multiple vessels throughout the body, from the capillary bed to the aorta. Pertinent to stroke, radiation therapy to the neck may result in steno-occlusive disease of the carotid and vertebral arteries in patterns atypical for standard atherosclerosis. Furthermore, radiation delivered to cranial targets may result in moyamoya syndrome, cavernomas, arteriovenous malformations (AVMs), and hemorrhage. Radiation injury to cerebral vessels may also be pursued as a therapeutic intervention, for instance, to treat vascular malformations. This chapter discusses the pathophysiology, incidence, monitoring, and treatment of radiation vasculopathy relevant to cerebrovascular disease.

Pathophysiology

Radiation-induced damage to cerebral blood vessels may be divided grossly into acute, subacute, and chronic time periods. Endothelial cells are particularly radiosensitive and are among the first to succumb to radiation damage. In a study of irradiated canine femoral arteries by Fonkalsrud et al., endothelial cell disruption and fibrin deposition was seen within 48 h of radiation exposure. After the 1st week, this initial luminal injury was followed by progressive cellularity, fibrosis, and necrosis of the media, along with hemorrhage and inflammation of the adventitia . Other subacute changes include dilation of the blood vessel lumen, vessel wall thickening, endothelial cell nuclear enlargement, and astrocyte hypertrophy. Within the brain, these vascular changes lead to blood–brain barrier breakdown and accompany perivascular inflammation, edema, necrosis, and demyelination seen in the surrounding brain tissues . Advances in radiation dosage optimization and cotreatment with steroids have reduced the incidence of these acute and subacute complications of radiation.

Of increasing prevalence are the chronic effects of radiation to large vessels, both intracranially and extracranially. Histological sections of chronic large vessel radiation vasculopathy show connective tissue proliferation, dense hyalinization of the vessel wall, including thickening of the intima, internal elastic lamina, and adventitia . There are several pathological features that separate radiation vasculopathy from other forms of vascular disease ( Fig. 113.1 ). For instance, in studies of coronary arteries affected by radiation vasculopathy, medial thinning, and adventitial fibrosis distinguished these vessels from standard coronary atherosclerosis . Furthermore, the severe atherosclerotic change was limited to vessels within the field of irradiation.

Another distinguishing feature unique to radiation vasculopathy is the direct damage to the vascular endothelium. Endothelial cells are exquisitely sensitive to the effects of radiation, and this initial insult may provide the inflammatory nidus for further atherosclerosis. Additionally, endothelial cell loss in the vasa vasorum leads to progressive dysfunction of the vessel’s own blood supply, gradually choking the arterial wall of circulation and leading to further stenosis . The prominent damage to the vasa vasorum also separates radiation vasculopathy from traditional atherosclerosis. Interestingly, it is often noted that large vessels with significant stenosis due to radiation are associated with abundant collateral vasculature . Formation of these collaterals is a testament to the slow progressive nature of radiation vasculopathy and may allude to the angiogenic nature of radiation as well.

As for additional similarities to traditional atherosclerosis, risk factors such as diabetes, smoking, hyperlipidemia, and hypertension have an additive effect on irradiated vessels. Although these comorbid genetic and environmental pressures may hasten the development of stenosis in irradiated vessels, the progression is still relatively slow. Studies of the prevalence of radiation vasculopathy have established that these long-term pathological changes occur over years to decades.