Should we irradiate a brain tumor in a patient with parkinsonism? A case report and literature review

Abstract Purpose Parkinson's disease (PD) is the second most common neurodegenerative disorder; the safety and effects of radiation therapy on PD are not well established. We report a patient with PD and a brain tumor referred for radiation therapy and review the literature on this topic focusing on the incidence of cancer and brain tumors in PD, brain tumors and radiation therapy as independent causes of PD, and the safety and effect of radiation therapy, including functional radiosurgery, in patients with PD. Methods and materials A PubMed literature review focusing on all English language publications from 1940 to 2014 identified 146 relevant articles, of which 91 discussed functional radiosurgery for PD, 49 discussed "neoplastic parkinsonism," 4 discussed radiation-induced parkinsonism, and 2 discussed the safety of fractionated radiation therapy in patients with PD. Results Odds ratios of 0.4 to 0.88 have been reported for the development of cancer in general among patients with PD, whereas the incidence ratios of PD patients developing a brain tumor relative to the general population range from 0.9 to 1.61. Parkinsonian symptoms thought to arise as a sequelae of tumor growth have been described in 49 papers dating to 1953. We identified 4 reports of parkinsonian syndromes that arose after radiation therapy, comprising a total of 7 patients, including 5 adults and 2 pediatric patients. Pediatric patients showed a mixed response to dopamine agonist therapy, whereas adults had little symptom improvement. Reports of PD patients irradiated in conventional fractionation for a variety of indications do not appear to indicate increased sensitivity to radiation therapy or exacerbated PD symptoms after irradiation. Radiosurgery performed for management of refractory tremor in PD patients results in up to an 88% favorable outcome, with the onset of symptom improvement ranging from 3 days to 1 year and minimal toxicity (not exceeding the toxicities observed for the same stereotactic radiosurgery procedure performed for essential tremor in nonparkinsonian patients). Conclusions Patients with PD do not harbor an increased risk for the development of cancer in general and have similar incidence of brain tumors as the general population. Tumor-induced parkinsonism is a rare entity. Parkinsonism as a side effect of brain radiation is an uncommon phenomenon, even after high doses, but is associated with limited response to medical management. Rare cases in children, typically associated with bilateral imaging changes, have been described, which suggests possible uncommon genetic predisposition. There are no convincing reports that suggest that pre-existing parkinsonism is worsened by radiation therapy, although a mechanistic possibility for this exists. Functional radiosurgery for management of refractory tremor in PD patients is safe and effective. Radiation therapy, either fractionated or stereotactic radiosurgery, appears to be safe when used judiciously for patients with PD, for the treatment of either tumors or PD itself.