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Delayed complications of cranial irradiation

Jorg Dietrich, MD, PhD
Vinai Gondi, MD
Minesh Mehta, MD
Section Editor
Lisa M DeAngelis, MD, FAAN, FANA
Deputy Editor
April F Eichler, MD, MPH


Cranial irradiation is used to treat patients with primary or metastatic brain tumors and as prophylaxis for selected patients at high risk of neoplastic involvement of the nervous system. A full understanding of the potential consequences associated with cranial irradiation is needed both to manage potential complications and to properly counsel patients and families prior to treatment.

The complications of radiation therapy are usually divided into acute effects that can occur during radiation or up to six weeks afterwards, early-delayed effects that appear up to six months after radiation, and late effects that can develop six months or more after the completion of radiation. Unlike acute and early-delayed reactions that are usually reversible, late reactions are generally irreversible.

The late complications of fractionated cranial irradiation will be reviewed here. Early complications of brain radiation therapy and complications of spinal cord and peripheral nerve irradiation are discussed elsewhere. (See "Acute complications of cranial irradiation" and "Complications of spinal cord irradiation" and "Brachial plexus syndromes", section on 'Neoplastic and radiation-induced brachial plexopathy' and "Lumbosacral plexus syndromes", section on 'Radiation plexopathy'.)


The effects of radiation can be divided into the effects on the vasculature of the brain as well as the direct effects on neuroglial cells and their precursors, including stem cells [1]. In addition, inflammation and blood-brain barrier disruption, induced by radiation, may also cause direct or indirect cellular damage [2].

In preclinical studies, endothelial damage occurs within the first 24 hours after a large single dose of radiation [3]. The exact mechanism is not known, but endothelial cell apoptosis appears to play a major role. Preclinical studies suggest that radiation may act directly on the plasma membrane of several cell types, activating acid sphingomyelinase and generating ceramide that initiates apoptosis [4]. Endothelial damage can lead to subsequent disruption of the blood-brain barrier and other late vascular effects, such as telangiectasias, microvascular dilatation, and thickening and hyalinization of the vessel wall. As a result, ischemic strokes or brain hemorrhage, such as microbleeds, may occur months to years after brain radiation. (See 'Cerebrovascular effects' below.).


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