Diagnostic Considerations

Differential Diagnoses

Workup

Lai R, Abrey LE, Rosenblum MK, DeAngelis LM. Treatment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study. Neurology. 2004 Feb 10. 62(3):451-6. [QxMD MEDLINE Link].
Liu AK, Macy ME, Foreman NK. Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys. 2009 Nov 15. 75(4):1148-54. [QxMD MEDLINE Link].
Barajas RF Jr, Chang JS, Segal MR, Parsa AT, McDermott MW, Berger MS, et al. Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology. 2009 Nov. 253(2):486-96. [QxMD MEDLINE Link]. [Full Text].
Levin VA, Bidaut L, Hou P, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys. 2011 Apr 1. 79(5):1487-95. [QxMD MEDLINE Link]. [Full Text].
Plimpton SR, Stence N, Hemenway M, Hankinson TC, Foreman N, Liu AK. Cerebral Radiation Necrosis in Pediatric Patients. Pediatr Hematol Oncol. 2013 May 7. [QxMD MEDLINE Link].
Kureshi SA, Hofman FM, Schneider JH, Chin LS, Apuzzo ML, Hinton DR. Cytokine expression in radiation-induced delayed cerebral injury. Neurosurgery. 1994 Nov. 35(5):822-9; discussion 829-30. [QxMD MEDLINE Link].
Langleben DD, Segall GM. PET in differentiation of recurrent brain tumor from radiation injury. J Nucl Med. 2000 Nov. 41(11):1861-7. [QxMD MEDLINE Link].
Cheng KM, Chan CM, Fu YT, Ho LC, Cheung FC, Law CK. Acute hemorrhage in late radiation necrosis of the temporal lobe: report of five cases and review of the literature. J Neurooncol. 2001 Jan. 51(2):143-50. [QxMD MEDLINE Link].
Ali FS, Arevalo O, Zorofchian S, Patrizz A, Riascos R, Tandon N, et al. Cerebral Radiation Necrosis: Incidence, Pathogenesis, Diagnostic Challenges, and Future Opportunities. Curr Oncol Rep. 2019 Jun 19. 21 (8):66. [QxMD MEDLINE Link].
Ruben JD, Dally M, Bailey M, Smith R, McLean CA, Fedele P. Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys. 2006 Jun 1. 65(2):499-508. [QxMD MEDLINE Link].
Kim IH. Appraisal of re-irradiation for the recurrent glioblastoma in the era of MGMT promotor methylation. Radiat Oncol J. 2019 Mar. 37 (1):1-12. [QxMD MEDLINE Link].
Korytko T, Radivoyevitch T, Colussi V, Wessels BW, Pillai K, Maciunas RJ, et al. 12 Gy gamma knife radiosurgical volume is a predictor for radiation necrosis in non-AVM intracranial tumors. Int J Radiat Oncol Biol Phys. 2006 Feb 1. 64 (2):419-24. [QxMD MEDLINE Link].
Maranzano E, Trippa F, Loreti F. Tumor relapse or radionecrosis after radiosurgery: single-photon emission computed tomography for differential diagnosis. In regard to Blonigen et al. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. (Int J Radiat Oncol Biol Phys 2010;77:996-1001). Int J Radiat Oncol Biol Phys. 2010 Nov 15. 78 (4):1279. [QxMD MEDLINE Link].
Mayer R, Sminia P. Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys. 2008 Apr 1. 70 (5):1350-60. [QxMD MEDLINE Link].
Patel KR, Chowdhary M, Switchenko JM, Kudchadkar R, Lawson DH, Cassidy RJ, et al. BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis. Melanoma Res. 2016 Aug. 26 (4):387-94. [QxMD MEDLINE Link].
Miller JA, Bennett EE, Xiao R, Kotecha R, Chao ST, Vogelbaum MA, et al. Association Between Radiation Necrosis and Tumor Biology After Stereotactic Radiosurgery for Brain Metastasis. Int J Radiat Oncol Biol Phys. 2016 Dec 1. 96 (5):1060-1069. [QxMD MEDLINE Link].
Wang TM, Shen GP, Chen MY, Zhang JB, Sun Y, He J, et al. Genome-Wide Association Study of Susceptibility Loci for Radiation-Induced Brain Injury. J Natl Cancer Inst. 2019 Jun 1. 111 (6):620-628. [QxMD MEDLINE Link].
Eisele SC, Dietrich J. Cerebral radiation necrosis: diagnostic challenge and clinical management. Rev Neurol. 2015 Sep 1. 61 (5):225-32. [QxMD MEDLINE Link].
Shah R, Vattoth S, Jacob R, Manzil FF, O'Malley JP, Borghei P, et al. Radiation necrosis in the brain: imaging features and differentiation from tumor recurrence. Radiographics. 2012 Sep-Oct. 32(5):1343-59. [QxMD MEDLINE Link].
Asao C, Korogi Y, Kitajima M, et al. Diffusion-weighted imaging of radiation-induced brain injury for differentiation from tumor recurrence. AJNR Am J Neuroradiol. 2005 Jun-Jul. 26(6):1455-60. [QxMD MEDLINE Link].
Dequesada IM, Quisling RG, Yachnis A, Friedman WA. Can standard magnetic resonance imaging reliably distinguish recurrent tumor from radiation necrosis after radiosurgery for brain metastases? A radiographic-pathological study. Neurosurgery. 2008 Nov. 63(5):898-903; discussion 904. [QxMD MEDLINE Link].
Reddy K, Westerly D, Chen C. MRI patterns of T1 enhancing radiation necrosis versus tumour recurrence in high-grade gliomas. J Med Imaging Radiat Oncol. 2013 Jun. 57(3):349-55. [QxMD MEDLINE Link].
Jahng GH, Li KL, Ostergaard L, Calamante F. Perfusion magnetic resonance imaging: a comprehensive update on principles and techniques. Korean J Radiol. 2014 Sep-Oct. 15 (5):554-77. [QxMD MEDLINE Link].
Strauss SB, Meng A, Ebani EJ, Chiang GC. Imaging Glioblastoma Posttreatment: Progression, Pseudoprogression, Pseudoresponse, Radiation Necrosis. Radiol Clin North Am. 2019 Nov. 57 (6):1199-1216. [QxMD MEDLINE Link].
Hyare H, Thust S, Rees J. Advanced MRI Techniques in the Monitoring of Treatment of Gliomas. Curr Treat Options Neurol. 2017 Mar. 19 (3):11. [QxMD MEDLINE Link].
Hein PA, Eskey CJ, Dunn JF, Hug EB. Diffusion-weighted imaging in the follow-up of treated high-grade gliomas: tumor recurrence versus radiation injury. AJNR Am J Neuroradiol. 2004 Feb. 25 (2):201-9. [QxMD MEDLINE Link].
Rock JP, Hearshen D, Scarpace L, et al. Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis. Neurosurgery. 2002 Oct. 51(4):912-9; discussion 919-20. [QxMD MEDLINE Link].
Sawlani V, Davies N, Patel M, Flintham R, Fong C, Heyes G, et al. Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature. Clin Oncol (R Coll Radiol). 2019 Jan. 31 (1):41-49. [QxMD MEDLINE Link].
Miyashita M, Miyatake S, Imahori Y, Yokoyama K, Kawabata S, Kajimoto Y, et al. Evaluation of fluoride-labeled boronophenylalanine-PET imaging for the study of radiation effects in patients with glioblastomas. J Neurooncol. 2008 Sep. 89(2):239-46. [QxMD MEDLINE Link].
Xiangsong Z, Weian C. Differentiation of recurrent astrocytoma from radiation necrosis: a pilot study with 13N-NH3 PET. J Neurooncol. 2007 May. 82(3):305-11. [QxMD MEDLINE Link].
Mogard J, Kihlstrom L, Ericson K, Karlsson B, Guo WY, Stone-Elander S. Recurrent tumor vs radiation effects after gamma knife radiosurgery of intracerebral metastases: diagnosis with PET-FDG. J Comput Assist Tomogr. 1994 Mar-Apr. 18(2):177-81. [QxMD MEDLINE Link].
Kahn D, Follett KA, Bushnell DL, et al. Diagnosis of recurrent brain tumor: value of 201Tl SPECT vs 18F-fluorodeoxyglucose PET. AJR Am J Roentgenol. 1994 Dec. 163(6):1459-65. [QxMD MEDLINE Link].
Chung JK, Kim YK, Kim SK, et al. Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET. Eur J Nucl Med Mol Imaging. 2002 Feb. 29(2):176-82. [QxMD MEDLINE Link].
Monteris AXiiiS Stereotactic Miniframe for Intracranial Biopsy: Precision, Feasibility, and Ease of Use: Erratum. Oper Neurosurg (Hagerstown). 2016 Jun 1. 12 (2):198. [QxMD MEDLINE Link].
Koch CJ, Lustig RA, Yang XY, Jenkins WT, Wolf RL, Martinez-Lage M, et al. Microvesicles as a Biomarker for Tumor Progression versus Treatment Effect in Radiation/Temozolomide-Treated Glioblastoma Patients. Transl Oncol. 2014 Dec. 7 (6):752-8. [QxMD MEDLINE Link]. [Full Text].
Soler DC, Young AB, Cooper KD, Kerstetter-Fogle A, Barnholtz-Sloan JS, Gittleman H, et al. The ratio of HLA-DR and VNN2⁺ expression on CD14⁺ myeloid derived suppressor cells can distinguish glioblastoma from radiation necrosis patients. J Neurooncol. 2017 Aug. 134 (1):189-196. [QxMD MEDLINE Link].
Chuba PJ, Aronin P, Bhambhani K, et al. Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer. 1997 Nov 15. 80(10):2005-12. [QxMD MEDLINE Link].
Ashamalla HL, Thom SR, Goldwein JW. Hyperbaric oxygen therapy for the treatment of radiation-induced sequelae in children. The University of Pennsylvania experience. Cancer. 1996 Jun 1. 77(11):2407-12. [QxMD MEDLINE Link].
Co J, De Moraes MV, Katznelson R, Evans AW, Shultz D, Laperriere N, et al. Hyperbaric oxygen for radiation necrosis of the brain. Can J Neurol Sci. 2019 Aug 30. 1-34. [QxMD MEDLINE Link].
Levin VA, Bidaut L, Hou P, Kumar AJ, Wefel JS, Bekele BN, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys. 2011 Apr 1. 79 (5):1487-95. [QxMD MEDLINE Link].
Boothe D, Young R, Yamada Y, Prager A, Chan T, Beal K. Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro Oncol. 2013 Sep. 15 (9):1257-63. [QxMD MEDLINE Link].
Hong CS, Beckta JM, Kundishora AJ, Elsamadicy AA, Chiang VL. Laser interstitial thermal therapy for treatment of cerebral radiation necrosis. Int J Hyperthermia. 2020 Jul. 37 (2):68-76. [QxMD MEDLINE Link].
Hong CS, Deng D, Vera A, Chiang VL. Laser-interstitial thermal therapy compared to craniotomy for treatment of radiation necrosis or recurrent tumor in brain metastases failing radiosurgery. J Neurooncol. 2019 Apr. 142 (2):309-317. [QxMD MEDLINE Link].
Sujijantarat N, Hong CS, Owusu KA, Elsamadicy AA, Antonios JP, Koo AB, et al. Laser interstitial thermal therapy (LITT) vs. bevacizumab for radiation necrosis in previously irradiated brain metastases. J Neurooncol. 2020 Jul. 148 (3):641-649. [QxMD MEDLINE Link].
Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW, Schold SC Jr. Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology. 1994 Nov. 44(11):2020-7. [QxMD MEDLINE Link].
Wong ET, Huberman M, Lu XQ, Mahadevan A. Bevacizumab reverses cerebral radiation necrosis. J Clin Oncol. 2008 Dec 1. 26(34):5649-50. [QxMD MEDLINE Link].
Gonzalez J, Kumar AJ, Conrad CA, Levin VA. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys. 2007 Feb 1. 67(2):323-6. [QxMD MEDLINE Link].
Buchpiguel CA, Alavi JB, Alavi A, Kenyon LC. PET versus SPECT in distinguishing radiation necrosis from tumor recurrence in the brain. J Nucl Med. 1995 Jan. 36(1):159-64. [QxMD MEDLINE Link].
Cerghet M, Redman B, Junck L, Forman J, Rogers LR. Prolonged survival after multifocal brain radiation necrosis associated with whole brain radiation for brain metastases: case report. J Neurooncol. 2008 Oct. 90(1):85-8. [QxMD MEDLINE Link].
Chen W. Clinical applications of PET in brain tumors. J Nucl Med. 2007 Sep. 48(9):1468-81. [QxMD MEDLINE Link].
de Vries B, Taphoorn MJ, van Isselt JW, Terhaard CH, Jansen GH, Elsenburg PH. Bilateral temporal lobe necrosis after radiotherapy: confounding SPECT results. Neurology. 1998 Oct. 51(4):1183-4. [QxMD MEDLINE Link].
Deshmukh A, Scott JA, Palmer EL, Hochberg FH, Gruber M, Fischman AJ. Impact of fluorodeoxyglucose positron emission tomography on the clinical management of patients with glioma. Clin Nucl Med. 1996 Sep. 21(9):720-5. [QxMD MEDLINE Link].
Ishikawa M, Kikuchi H, Miyatake S, Oda Y, Yonekura Y, Nishizawa S. Glucose consumption in recurrent gliomas. Neurosurgery. 1993 Jul. 33(1):28-33. [QxMD MEDLINE Link].
Kumar AJ, Leeds NE, Fuller GN, et al. Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology. 2000 Nov. 217(2):377-84. [QxMD MEDLINE Link].
Lee AW, Foo W, Chappell R, et al. Effect of time, dose, and fractionation on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1998 Jan 1. 40(1):35-42. [QxMD MEDLINE Link].
McPherson CM, Warnick RE. Results of contemporary surgical management of radiation necrosis using frameless stereotaxis and intraoperative magnetic resonance imaging. J Neurooncol. 2004 May. 68(1):41-7. [QxMD MEDLINE Link].
Nelson MD Jr, Soni D, Baram TZ. Necrosis in pontine gliomas: radiation induced or natural history?. Radiology. 1994 Apr. 191(1):279-82. [QxMD MEDLINE Link].
Nelson SJ, Huhn S, Vigneron DB, et al. Volume MRI and MRSI techniques for the quantitation of treatment response in brain tumors: presentation of a detailed case study. J Magn Reson Imaging. 1997 Nov-Dec. 7(6):1146-52. [QxMD MEDLINE Link].
Olivero WC, Dulebohn SC, Lister JR. The use of PET in evaluating patients with primary brain tumours: is it useful?. J Neurol Neurosurg Psychiatry. 1995 Feb. 58(2):250-2. [QxMD MEDLINE Link].
Omuro AM, Leite CC, Mokhtari K, Delattre JY. Pitfalls in the diagnosis of brain tumours. Lancet Neurol. 2006 Nov. 5(11):937-48. [QxMD MEDLINE Link].
Packer RJ, Zimmerman RA, Kaplan A, et al. Early cystic/necrotic changes after hyperfractionated radiation therapy in children with brain stem gliomas. Data from the Childrens Cancer Group. Cancer. 1993 Apr 15. 71(8):2666-74. [QxMD MEDLINE Link].
Peterson K, Clark HB, Hall WA, Truwit CL. Multifocal enhancing magnetic resonance imaging lesions following cranial irradiation. Ann Neurol. 1995 Aug. 38(2):237-44. [QxMD MEDLINE Link].
Posner JB. Side effects of radiation therapy. Neurologic Complications of Cancer. No. 54. Philadelphia, Pa: FA Davis; 1995. 311-37.
Rizzoli HV, Pagnanelli DM. Treatment of delayed radiation necrosis of the brain. A clinical observation. J Neurosurg. 1984 Mar. 60(3):589-94. [QxMD MEDLINE Link].
Slizofski WJ, Krishna L, Katsetos CD, et al. Thallium imaging for brain tumors with results measured by a semiquantitative index and correlated with histopathology. Cancer. 1994 Dec 15. 74(12):3190-7. [QxMD MEDLINE Link].

Media Gallery

MRI of a patient with symptoms of gait unsteadiness 1 year after being diagnosed with a posterior fossa primitive neuroectodermal tumor (PNET). Treatment during the 1-year interval prior to this MRI consisted of surgical resection, craniospinal radiation of 2340 cGy, boost dose given to the posterior fossa for a total of 5500 cGy, chemotherapy (vincristine, cis-platinum, and cyclohexylchloroethylnitrosurea [CCNU]), and dexamethasone therapy.
Positron emission tomography with [18F]-labeled fluorodeoxyglucose (PET-FDG) performed following the MRI of a patient with symptoms of gait unsteadiness 1 year after being diagnosed with a posterior fossa primitive neuroectodermal tumor (PNET). Treatment during the 1-year interval prior to these studies consisted of surgical resection, craniospinal radiation of 2340 cGy, boost dose given to the posterior fossa for a total of 5500 cGy, chemotherapy (vincristine, cis-platinum, and cyclohexylchloroethylnitrosurea [CCNU]), and dexamethasone therapy. PET-FDG demonstrates hypometabolism consistent with probable radiation necrosis. Four years later, the patient is stable and without evidence of tumor progression.
T1-weighted contrast imaging shows left frontoparietal enhancing mass lesion with significant perilesional edema and midline shift. Peripheral wavy frond-like enhancement is typical of radiation necrosis.
T1-weighted contrast imaging after the corticosteroid administration showing a significant reduction in enhancement, swelling, and mass effect with reversal of midline shift.

of 4

Author

Gaurav Gupta, MD, FAANS, FACS Associate Professor of Neurosurgery, System Co-Director, Cerebrovascular and Endovascular Neurosurgery, Fellowship Director, Endovascular Neurosurgery Fellowship (Site), Department of Surgery, Division of Neurosurgery, Rutgers RWJ Barnabas Healthcare, Rutgers Robert Wood Johnson Medical School

Gaurav Gupta, MD, FAANS, FACS is a member of the following medical societies: American Academy of Neurology, American Association for the Advancement of Science, American Association of Neurological Surgeons, American College of Surgeons, American Heart Association, American Medical Association, Congress of Neurological Surgeons, Facial Pain Association, Society for Neuroscience, Society of NeuroInterventional Surgery

Disclosure: Nothing to disclose.

Coauthor(s)

Fareed R Jumah, MBBS Postdoctoral Research Fellow, Department of Neurosurgery, RWJ University Hospital, Rutgers Robert Wood Johnson Medical School

Disclosure: Nothing to disclose.

Bharath Raju, MBBS, MCh Postdoctoral Research Fellow, Department of Neurosurgery, RWJ University Hospital, Rutgers Robert Wood Johnson Medical School

Bharath Raju, MBBS, MCh is a member of the following medical societies: AOSpine, Bangalore Neurological Society, European Association of Neurosurgical Societies, Neurological Society of India, Neurotrauma Society of India

Disclosure: Nothing to disclose.

Sudipta Roychowdhury, MD Clinical Associate Professor of Radiology, Department of Radiology, Rutgers Robert Wood Johnson Medical School; Attending Radiologist/Neuroradiologist, University Radiology Group, PC

Sudipta Roychowdhury, MD is a member of the following medical societies: American College of Radiology, American Medical Association, American Society of Neuroradiology, Medical Society of New Jersey, Radiological Society of New Jersey, Radiological Society of North America, Society of NeuroInterventional Surgery

Disclosure: Nothing to disclose.

Anil Nanda, MD, MPH, FACS Professor and Chairman, Department of Neurosurgery, Rutgers University Robert Wood Johnson Medical School and Rutgers New Jersey Medical School; Peter W Carmel, MD, Endowed Chair of Neurological Surgery, Senior Vice President of Neurosurgical Services, RWJBarnabas Health

Anil Nanda, MD, MPH, FACS is a member of the following medical societies: American Academy of Neurological Surgery, American Association of Neurological Surgeons, American Medical Association, Brain Attack Coalition, Congress of Neurological Surgeons, John C McDonald Surgical Society, Louisiana Neurosurgical Society, Louisiana State Medical Society, North American Skull Base Society, Shreveport Medical Society, Society of Neurological Surgeons, Society of University Neurosurgeons, Southern Neurosurgical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jorge C Kattah, MD Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria

Jorge C Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA Professor of Pediatrics, Neurology, Neurosurgery, and Psychiatry, Medical Director, Tulane Center for Autism and Related Disorders, Tulane University School of Medicine; Pediatric Neurologist and Epileptologist, Ochsner Hospital for Children; Professor of Neurology, Louisiana State University School of Medicine

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association, American Neurological Association, Association of Military Surgeons of the US, Child Neurology Society, Southern Pediatric Neurology Society

Disclosure: Nothing to disclose.

Additional Contributors

Michael J Schneck, MD, MBA Vice Chair and Professor, Departments of Neurology and Neurosurgery, Loyola University, Chicago Stritch School of Medicine; Associate Director, Stroke Program, Director, Neurology Intensive Care Program, Medical Director, Neurosciences ICU, Loyola University Medical Center

Michael J Schneck, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Society of Neuroimaging, Neurocritical Care Society, Stroke Council of the American Heart Association

Disclosure: Nothing to disclose.

Frederick M Vincent, Sr, MD Clinical Professor, Department of Neurology and Ophthalmology, Michigan State University Colleges of Human and Osteopathic Medicine

Frederick M Vincent, Sr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Forensic Examiners Institute, American College of Legal Medicine, American College of Physicians

Disclosure: Nothing to disclose.

Anna Janss, MD, PhD Associate Professor of Pediatric Neuro-oncology, Emory University School of Medicine; Consulting Neuro-oncologist, Children's Healthcare of Atlanta

Anna Janss, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Association for Cancer Research, American Medical Association, International Association for the Study of Pain, Pennsylvania Medical Society, Society for Neuroscience, Children's Oncology Group, Society for Neuro-Oncology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Robert Wilson, MD to the development and writing of this article.