Radiation: CNS complications

Puyao Li MD (

Dr. Li of Massachusetts General Hospital has no relevant financial relationships to disclose.

Maximilian Niyazi MD MSc (

Dr. Niyazi of Ludwig Maximilians University of Munich has no relevant financial relationships to disclose.

Helen A Shih MD MPH MS (

Dr. Shih of Massachusetts General Hospital has no relevant financial relationships to disclose.

Rimas V Lukas MD, editor. (

Dr. Lukas of Northwestern University Feinberg School of Medicine received honorariums from Novocure for speaking engagements, honorariums from Novocure for advisory board membership, and research support from BMS.

Originally released March 24, 1999; last updated August 3, 2020; expires August 3, 2023


Radiation therapy is an effective therapy for many malignancies and benign conditions. However, risks of radiation therapy include both potential early and late associated complications to the nervous system. They include radiation necrosis, cerebrovascular disease, cognitive deficits, endocrinopathies, encephalopathy, myelopathy, plexopathy, radiculopathy, neuropathy, and secondary tumors. This article discusses in detail the various radiation complications and therapeutic options.

The authors have updated content on potential strategies to mitigate the risk of radiation injury, including the recently published results of NRG Oncology CC001 on hippocampal-sparing radiotherapy, and added data on proton therapy. The authors have added laser interstitial thermotherapy (LITT) as an alternative to craniotomy for management of radiation necrosis.

Key points


• When radiation therapy is used to treat primary or metastatic central nervous system (CNS) diseases, or non-CNS targets located close to neural structures, side effects to the normal neural tissues can occur.


• When practicing within accepted constraints, the acute and subacute complications of radiation therapy are generally mild, transient, or treatable with corticosteroids.


• In contrast, the late complications of radiation therapy are generally progressive and may be permanent.


• The incidence and severity of radiation-induced CNS complications varies with the radiation dose, volume of tissue irradiated, fractionation scheme, and potentially target radiotherapy location; degree of edema; patient age; underlying diseases (malignant and nonmalignant); concomitant treatments; comorbidities; and length of survival after completion of radiation treatment.


• In general, the risks of radiation-related CNS side effects are balanced with the risk of progressive or recurrent disease.

Historical note and terminology

Most historic cancer therapies are nonspecifically cytotoxic. This is especially true of radiation therapy. As a result, when radiation therapy is used to treat primary or metastatic nervous system diseases, or non-CNS indications located adjacent to neural structures, side effects to the normal nervous system can occur. The most dramatic example of this type of injury, brain radiation necrosis, was first recognized in 1930, soon after radiation was first used therapeutically for brain tumors (Fisher and Holfelder 1930). Since that time, a spectrum of injuries throughout the central and peripheral nervous system has been identified, and some of the details of specific syndromes have been elucidated. Despite this heightened awareness, the neurologic complications of radiation therapy continue to occur because individual tolerances to radiation are variable, safe radiation thresholds are not precisely known, latency to development of injury range between days to years, and risks are altered by use of chemotherapy, other systemic therapies, or preexisting disease. The incidence of radiation-related nervous system side effects appears to be increasing as conventional radiation therapy techniques are being applied more aggressively, new radiation delivery approaches such as stereotactic radiotherapy, intensity modulated radiation therapy (IMRT), volumetric modulated arc radiation therapy (VMAT) or particle therapy are becoming commonplace, and patients are surviving longer.

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