Side effects of radiotherapy on the brain

Abstract

Neželeni učinki radioterapije na možgane so številni in pogosto nepredvidljivi. Lahko gre za neposredno ali posredno okvaro možganov. Okvara se lahko pojavi akutno ali več tednov, mesecev ali celo let po končani radioterapiji. Ločevanje med temi oblikami je pomembno, saj so zgodnji zapleti navadno reverzibilni, pozni pa se večinoma ne popravijo. Incidenco neželenih učinkov radioterapije na možgane je težko oceniti. Razlogi za to so v različnih opredelitvah in metodoloških razlikah v raziskavah ter v klinični sliki, ki se pogosto prekriva z napredovanjem osnovne maligne bolezni. Med mehanizmi radiacijske okvare možganov je v ospredju okvara celic glije in možganskih endotelijskih celic. Za radiacijsko okvaro je zlasti občutljiv hipokampus. Obseg okvare možganov je odvisen od številnih dejavnikov. Dodatna sistemska ali intratekalna kemoterapija pomembno poveča nevrotoksičnost. Diagnosticiranje neželenih učinkov radioterapije na možgane je težavno, saj je časovni interval med radioterapijo in pojavom nevroloških simptomov precej variabilen, klinična slika pa lahko posnema metastatsko, paraneoplastično ali drugo nevrološko bolezen. Zavedati se je treba, da klinično sliko lahko pripišemo neželenim učinkom radioterapije na možgane šele po izključitvi drugih vzrokov. V članku opisujeva različne klinične oblike neposredne in posredne radiacijske okvare možganov. Pri akutni encefalopatiji ima pomembno vlogo okvara krvno-možganske pregrade. Pri zgodnji odloženi encefalopatiji je pomembna demielinizacija, pri pozni odloženi encefalopatiji pa radiacijska nekroza. O kognitivnem upadu kot posledici radioterapije so mnenja še vedno deljena.There are numerous and often unpredictable side effects of radiotherapy on the brain. The damage can be direct or indirect, and becomes apparent acutely or even many years thereafter. The distinction between these forms is important since early side effects are predominantly reversible whereas late ones usually are not. The incidence of radiotherapy-induced side effects is hard to estimate due to the differing definitions and methodologies used in clinical studies. Nevertheless, the clinical picture often resembles the progression of pre-existent malignant disease. The mechanism underlying side effects of radiotherapy is mainly injury to glial cells and cerebral endothelial cells. The hippocampus is especially prone to radiation damage. The burden of radiation damage in a given individual is dependent upon many factors. Concomitant systemic and intrathecal chemotherapy adds significantly to neurotoxicity. Diagnosing side effects of radiotherapy can be a daunting task since the time interval between radiotherapy and the occurrence of neurological side effects is variable. What is more, the clinical picture can resemble metastatic, paraneoplastic or other neurological disease. It is therefore of crucial importance to be aware of the fact that the clinical picture can be ascribed to side effects of radiotherapy only after other possible reasons (mainly tumor progression) have been effectively ruled out. The article entails a broad spectrum of direct and indirect radiotherapyinduced consequences on the brain. Acute encephalopathy is connected to blood-brain barrier disruption. Early-delayed encephalopathy is caused by demyelination. Late-delayed encephalopathy is represented mainly by radiation necrosis. Cognitive decline as a consequence of radiotherapy is still a matter of hot debate

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