adiation therapy is used to treat a host of dif- ferent diseases, although the most frequent use revolves around the treatment of cancer. Although effective—sufficient doses are able to effect virtually 100% cellular death of neoplastic cells—the toxicity of such therapy precludes adminis- tration of such high amounts to patients. The nervous system is particularly sensitive to radiotherapy and is affected either directly or indirectly during the treat- ment of cancer. Both central and peripheral nervous system structures can be affected, leading to different syndromes, and may be complicated by involvement of blood vessels and endocrine organs. This review dis- cusses the various effects of radiation on the nervous system, with emphasis on the different areas of nervous system involvement. CELLULAR DAMAGE TO THE NERVOUS SYSTEM The most sensitive structures to radiation within the nervous system are thought to be primarily oligo- dendroglial and Schwann’s cells, with the neurons being less affected because of their postmitotic state. 1 However, any central or nervous system cell can be af- fected by radiation, depending on several factors, including the dose per fraction, the volume of tissue irradiated, the total dose given, and the energy of the radiation. 2 Host factors are also important in the cel- lular response to radiation: age 3 , sex, 4 the presence of concurrent diseases, 5 and previous therapy (ie, chem- otherapy) 6 are thought to be influential in the ner- vous system response to radiotherapy. Other factors that are putatively involved in the nervous system response to radiation include the vascular endotheli- um, which may result in ischemia and necrosis (as ad- dressed later in this discussion), and the immune sys- tem, leading to a hypothesized sensitivity reaction. 7 Clearly, the etiology of radiation damage on a cellular basis is multifactorial and most likely represents a combination of factors involving both the radiation itself, which affects different structures within the ner- vous system, as well as host factors, which either pre- dispose to toxicity or modify response within the ner- vous system. CLINICAL APPROACH TO DIAGNOSIS The diagnosis of radiation-induced damage of the nervous system may at times be difficult and perhaps require pathologic confirmation. Although formulas exist to calculate the relative energy deposited to ner- vous system structures, these formulas are at best approximations and do not consider other aspects of the mechanism of cellular injury, including concomi- tant therapy or host factors. 6 Retrospective reviews have attempted to document the clinical factors that are as- sociated with radiation injury; 8 the patients who appear to be more affected by radiation are male patients, 9 younger patients, 10 and patients who receive higher doses 1 and fractions. 11 However, radiation-induced toxi- city should be considered in the differential diagnosis for any patient who has had previous radiotherapy and complains of neurologic symptoms. The physician should be aware as well that a vasculopathy or endo- crinopathy caused by radiation injury can also be re- sponsible for neurologic symptoms. 6 Classification of Radiation Toxicity Radiation toxicity can be conveniently classified ac- cording to the time of presentation: acute reactions, early delayed reactions, late delayed reactions. 12 Acute reactions. Acute reactions occur during the course of treatment and consist of symptoms of in- creased intracranial pressure or worsening of existing neurologic symptoms. These symptoms are usually mild and transient and are thought to be caused by radiation-induced edema. Occasionally, the use of corticosteroids or an increase in the dose of cortico- steroids is temporarily required. Early delayed reactions. Early delayed reactions occur several weeks to months after finishing radiation treatment. Early delayed reactions may also present with worsening symptoms or manifest by increasing somnolence and fatigue. These symptoms are believed R Dr. Liang is Adjunct Associate Professor of Medicine and Neurology, University of Vermont, College of Medicine, Burlington, VT, and a mem- ber of the Hospital Physician Editorial Board. 54 Hospital Physician April 1999 Practice Strategies Radiation-Associated Neurotoxicity Bertrand C. Liang, MD