Advertisement

Neuropsychological Problems in Neuro-oncology

  • Carol L. Armstrong
  • Cynthia J. Schmus
  • Jean B. Belasco
Chapter

Abstract

Neuropsychological studies in the field of oncology are related to neuro-oncology: (1) brain tumors – which arise from neurons and other brain tissues, cranial nerves, leptomeninges, neuroendocrine glands, skull, and blood vessels and (2) treatment effects. The neurocognitive effects of brain tumors themselves are variable and require close examination of the cognitive underpinnings of composite test scores. Other cases present fascinating modular deficits when tumors occur in eloquent brain loci. After providing basic biomedical background on tumors in children and adults, the questions of tumor site and metastatic spread as well as treatment effects on brain and cognitive and emotional function will be examined in this chapter. Information will also be presented on the techniques for diagnosing and treating tumors and on issues to be considered in doing research in neuro-oncology. Finally, this chapter will discuss how disorders and syndromes that result from brain tumors and their treatments differ from more classical or traditionally understood forms of the disorders.

Keywords

Autism Spectrum Disorder Autism Spectrum Disorder Brain Tumor Malignant Peripheral Nerve Sheath Tumor White Matter Abnormality 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The research from the neuropsychological laboratory at the University of Pennsylvania and the Children’s Hospital of Philadelphia was funded by Dr. Carol Armstrong’s grant from the National Cancer Institute, #RO1 CA 65438.

Many thanks to Mark Goodman for his invaluable editing of the manuscript.

References

  1. 1.
    Jarquin-Valdivia AA. Psychiatric symptoms and brain tumors: a brief historical overview. Arch Neurol. 2004;61:1800–04.PubMedCrossRefGoogle Scholar
  2. 2.
    Fisher M, Phillips P. PET imaging of brain tumors. In: Charron M, editor. Practical pediatric PET imaging. New York, NY: Springer; 2006. pp. 175–219.Google Scholar
  3. 3.
    Simpson JR, Scott CB, Rotman M, et al. Race and prognosis of brain tumor patients entering multicenter clinical trials. Am J Clin Oncol (CCT). 1996;19:114–20.CrossRefGoogle Scholar
  4. 4.
    Louis DN, Cavenee WK. Molecular biology of central nervous system tumors. Boston, MA: Massachusetts General Hospital, MGH Neurosurgical Service, Brain Tumor Center, 2005:http://brain.mgh.harvard.edu/MolecularGenetics.htm
  5. 5.
    Wechsler-Reya R, Scott MP. The developmental biology of brain tumors. Annu Rev Neurosci. 2001;24:385–428.PubMedCrossRefGoogle Scholar
  6. 6.
    Filley CM, Kleinschmidt-DeMasters BK, Lillehei KO, et al. Gliomatosis cerebri: neurobehavioral and neuropathological observations. Cogn Behav Neurol. 2003;16:149–59.PubMedCrossRefGoogle Scholar
  7. 7.
    Wen PY, Loeffler JS. Management of brain metastases. Oncology. 1999;13:941–54; 957–61.Google Scholar
  8. 8.
    Posner J. Management of brain metastases. Rev Neurol. 1992;148:477–87.PubMedGoogle Scholar
  9. 9.
    Armstrong CL. Neurofibromatosis type 1. In: Kreutzer J, DeLuca J, Caplan B, editors. Encyclopedia of clinical neuropsychology. New York, NY: Springer; 2010.Google Scholar
  10. 10.
    Armstrong CL. Neurofibromatosis type 2. In: Kreutzer J, DeLuca J, Caplan B, editors. Encyclopedia of clinical neuropsychology. New York, NY: Springer; 2010.Google Scholar
  11. 11.
    Zoller ME, Rembeck B, Backman L. Neuropsychological deficits in adults with neurofibromatosis type 1. Acta Neurol Scand. 1997;95:225–32.PubMedCrossRefGoogle Scholar
  12. 12.
    Moore BD, Denckla MB. Neurofibromatosis. In: Yeates KO, Ris MD, Taylor HG, editors. Pediatric neuropsychology: research, theory and practice. New York, NY: The Guilford Press; 2000.Google Scholar
  13. 13.
    Rosser TL, Packer RJ. Neurocognitive dysfunction in children with neurofibromatosis type 1. Curr Neurol Neurosci Rep. 2003;3:129–36.PubMedCrossRefGoogle Scholar
  14. 14.
    Barton B, North K. Social skills of children with neurofibromatosis type 1. Dev Med Child Neurol. 2004;46:553–63.PubMedCrossRefGoogle Scholar
  15. 15.
    Mautner VF, Kluwe L, Thakker SD, Leark RA. Treatment of ADHD in neurofibromatosis type 1. Dev Med Child Neurol. 2002;44:164–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Krab LC, Aarsen FK, de Goede-Bolder A, et al. Impact of neurofibromatosis type 1 on school performance. J Child Neurol. 2008;23:1002–20.PubMedGoogle Scholar
  17. 17.
    Hyman SL, Gill DS, Shores EA, et al. Natural history of cognitive deficits and their relationship to MRI T2-hyperintensities in NF1. Neurology. 2003;60: 1139–45.PubMedCrossRefGoogle Scholar
  18. 18.
    Hyman SL, Shores EA, North KN. Learning disabilities in children with neurofibromatosis type 1: subtypes, cognitive profile, and attention-deficit-hyperactivity disorder. Dev Med Child Neurol. 2006;48:973–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Dalmau J, Gultekin HD, Posner J. Paraneoplastic neurologic syndromes: pathogenesis and physiopathology. Brain Pathol. 1999;9:275–84.PubMedCrossRefGoogle Scholar
  20. 20.
    Honnorat J, Cartalat-Carel S, Ricard D, et al. Onco-neural antibodies and tumour type determine survival and neurological syndromes in paraneoplastic neurological syndromes with Hu or CV2/CRMP5 antibodies. J Neurol Neurosurg Psychiatr. 2009;80:412–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Franz DN, Leonard J, Tudor C, et al. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol. 2006;59:490–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Tee AR, Fingar DC, Manning BD, et al. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci USA. 2002;99:13571–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Inskip PD, Heineman EL. New malignancies following cancer of the brain and central nervous system. In: (SEER) SEaER, ed. Brain and Other CNS, 2008: 363–373Google Scholar
  24. 24.
    Paulino AC, Mai WY, Chintagumpala M, et al. Radiation-induced malignant gliomas: is there a role for reirradiation?. Int J Rad Onc Bio Phys. 2008;71:1381–7.CrossRefGoogle Scholar
  25. 25.
    Thierry-Chef I, Simon SL, Land CE, Miller DL. Radiation dose to the brain and subsequent risk of developing brain tumors in pediatric patients undergoing interventional neuroradiology procedures. Radiat Res. 2008;170:553–65.PubMedCrossRefGoogle Scholar
  26. 26.
    Zacharatou JC, Paganetti H. Risk of developing second cancer from neutron dose in proton therapy as function of field characteristics, organ, and patient age. Int J Rad Onc Bio Phys. 2008;72:228–35.CrossRefGoogle Scholar
  27. 27.
    NRC NRCUS. Radiation-induced cancer: mechanisms, quantitative experimental studies, and the role of genetic factors. Health risks from exposure to low levels of ionizing radiation: BEIR VII phase 2. Washington, DC: National Academies Press; 2006Google Scholar
  28. 28.
    Preston-Martin S, Mack W, Henderson BE. Risk factors for gliomas and meningiomas in males in Los Angeles County. Cancer Res. 1989;49:6137–43.PubMedGoogle Scholar
  29. 29.
    Wrensch M, Minn Y, Chew T, et al. Epidemiology of primary brain tumors: current concepts and review of the literature. Neurooncology. 2002;4:278–99.Google Scholar
  30. 30.
    Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.PubMedCrossRefGoogle Scholar
  31. 31.
    American Joint Commission on Cancer. AJCC cancer staging manual. 6th ed. New York, NY: Springer; 2002.Google Scholar
  32. 32.
    Kayl AE, Meyers CA. Does brain tumor histology influence cognitive function? Neurooncology. 2003;5: 255–60.Google Scholar
  33. 33.
    Bosma I, Douw L, Bartolomei F, et al. Synchronized brain activity and neurocognitive function in patients with low-grade glioma: a magnetoencephalography study. Neurooncology. 2008;10:734–44.Google Scholar
  34. 34.
    Sands S, Van Gorp W, Finlay J. A dramatic loss of non-verbal intelligence following a right parietal ependymoma: a brief case report. Psycho Oncol. 2000;9: 259–66.CrossRefGoogle Scholar
  35. 35.
    Sahadevan S, Pang WS, Tan NJL, et al. Neuroimaging guidelines in cognitive impairment: lessons from 3 cases of meningiomas presented as isolated dementia. Singapore Med J. 1997;38:339–43.PubMedGoogle Scholar
  36. 36.
    Skirboll SS, Ojemann GA, Berger MS, et al. Functional cortex and subcortical white matter located within gliomas. Neurosurgery. 1996;38:678–85.PubMedCrossRefGoogle Scholar
  37. 37.
    Anderson S, Damasio H, Tranel D. Neuropsychological impairments associated with lesions caused by tumor or stroke. Arch Neurol. 1990;47:397–405.PubMedCrossRefGoogle Scholar
  38. 38.
    Scheibel R, Meyers C, Levin V. Cognitive dysfunction following surgery for intracerebral glioma: influence of histopathology, lesion location and treatment. J Neurooncol. 1996;30:61–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Riva D, Giorgi D. The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumours. Brain. 2000;123:1051–61.PubMedCrossRefGoogle Scholar
  40. 40.
    Goldstein B, Obrzut JE, John C, Hunter JV, Armstrong CL. The impact of low-grade brain tumors on verbal fluency performance. J Clin Exp Neuropsychol. 2004;26:750–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Gourovitch ML, Kirkby BS, Goldberg TE, et al. A comparison of rCBF patterns during letter and semantic fluency. J Int Neuropsychol Soc. 2000;14:353–60.Google Scholar
  42. 42.
    Stuss DT, Alexander MP, Hamer L, et al. The effects of focal anterior and posterior brain lesions on verbal fluency. J Int Neuropsychol Soc. 1998;4:265–78.PubMedGoogle Scholar
  43. 43.
    Goldstein B, Obrzut JE, John D, Ledakis G, Armstrong CL. The impact of frontal and non-frontal brain tumor lesions on Wisconsin card sorting test performance. Brain Cogn. 2004;54:110–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Goldstein B, Armstrong CL, Modestino E, et al. Picture and word recognition memory in adult intracranial tumor patients. Brain Cogn. 2004;54:1–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Snodgrass JG, Vanderwart M. A standardized set of 260 pictures: norms for name agreement, image agreement, familiarity, and visual complexity. J Exp Psychol Hum Learn. 1980;6:174–215.PubMedCrossRefGoogle Scholar
  46. 46.
    Goldstein B, Armstrong CL, John C. Neuropsychological effects of intracranial tumors on attention. J Clin Exp Neuropsychol. 2003;25:66–78.PubMedCrossRefGoogle Scholar
  47. 47.
    Tulving E, Kapur S, Craik F, et al. Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings. Proc Natl Acad Sci. 1994;91:2016–20.PubMedCrossRefGoogle Scholar
  48. 48.
    Meyers C, Hess K, Yung W, Levin V. Cognitive function as a predictor of survival in patients with recurrent malignant glioma. J Clin Oncol. 2000;18:646–50.PubMedGoogle Scholar
  49. 49.
    Armstrong CL, Goldstein B, Shera D, et al. The predictive value of longitudinal neuropsychological assessment in the early detection of brain tumor recurrence. Cancer. 2003;97:649–56.PubMedCrossRefGoogle Scholar
  50. 50.
    Armstrong CL, Hunter JV, Ledakis GE, et al. Late cognitive and radiographic changes related to radiotherapy: initial prospective findings. Neurology. 2002;59:40–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Newport DJ, Nemeroff CB. Assessment and treatment of depression in the cancer patient. J Psychosom Res. 1998;45:215–37.PubMedCrossRefGoogle Scholar
  52. 52.
    Pringle AM, Taylor R, Whittle IR. Anxiety and depression in patients with an intracranial neoplasm before and after tumour surgery. Br J Neurosurg. 1999;13:46–51.PubMedCrossRefGoogle Scholar
  53. 53.
    Giovagnoli AR. Quality of life in patients with stable disease after surgery, radiotherapy, and chemotherapy for malignant brain tumour. J Neurol Neurosurg Psychiatr. 1999;67:358–63.PubMedCrossRefGoogle Scholar
  54. 54.
    Radcliffe J, Bennett D, Kazak AE, et al. Adjustment in childhood brain tumor survival: child, mother, and teacher report. J Pediatr Psychol. 1996;21:529–39.PubMedCrossRefGoogle Scholar
  55. 55.
    Suzuki R, Hirao M, Miyo T, et al. Changes in QOL in patients with brain tumors measured by mood changes during and after treatment. No Shinkei Geka. 1998;26:795–801.PubMedGoogle Scholar
  56. 56.
    Osteraker A-L, Kihlgren M, Melin L. Long-term psychosocial consequences for families with children treated for brain-tumor and other malignancies. J Int Neuropsychol Soc. 1999;5:108.Google Scholar
  57. 57.
    Armstrong C, Goldstein B, Cohen B, et al. Clinical predictors of depression in patients with low-grade brain tumors: consideration of a neurologic versus a psychogenic model. J Clin Psychol Med Settings. 2002;9:97–107.CrossRefGoogle Scholar
  58. 58.
    Weitzner M, Meyers C, Byrne K. Psychosocial functioning and quality of life in patients with primary brain tumors. J Neurosurg. 1996;84:29–34.PubMedCrossRefGoogle Scholar
  59. 59.
    Kaplan CP, Miner ME. Relationships: importance for patients with cerebral tumours. Brain Inj. 2000;14:251–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Irle E, Peper M, Wowra B, Kunze S. Mood changes after surgery for tumors of the cerebral cortex. Arch Neurol. 1994;51:164–74.PubMedCrossRefGoogle Scholar
  61. 61.
    Wellisch DK, Kaleita TA, Freeman D, et al. Predicting major depression in brain tumor patients. Psychooncology. 2002;11:230–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Habermeyer B, Weiland M, Mager R, et al. A clinical lesson: Glioblastoma multiforme masquerading as depression in a chronic alcoholic. Alcohol Alcohol. 2008;43:31–3.PubMedGoogle Scholar
  63. 63.
    Butler JM Jr., Case LD, Atkins J, et al. A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation. Int J Rad Oncol Biol Phys. 2007;69:1496–501.CrossRefGoogle Scholar
  64. 64.
    Thompson SJ, Leigh L, Christensen R, et al. Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer. J Clin Oncol. 2001;19:1802–08.PubMedGoogle Scholar
  65. 65.
    Mulhern RK, Khan RB, Kaplan S, et al. Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer. J Clin Oncol. 2005;22:4795–803.CrossRefGoogle Scholar
  66. 66.
    Kaleita TA, Wellisch DK, Graham CA, et al. Pilot study of modafinil for treatment of neurobehavioral dysfunction and fatigue in adult patients with brain tumors. J Clin Oncol. 2006;24:1503.Google Scholar
  67. 67.
    Kohli S, Fisher SG, Tra Y, et al. The effect of modafinil on cognitive function in breast cancer survivors. Cancer. 2009;115:2605–16.PubMedCrossRefGoogle Scholar
  68. 68.
    Redd WH, Silberfarb PM, Andersen BL, et al. Physiologic and psychobehavioral research in oncology. Cancer. 1991;67:813–22.PubMedCrossRefGoogle Scholar
  69. 69.
    Mulhern R, Crisco J, Kun L. Neuropsychological sequelae of childhood brain tumors: a review. J Clin Child Psychol. 1983;12:66–73.CrossRefGoogle Scholar
  70. 70.
    Kazak AE, Barakat LP, Meeske K, et al. Posttraumatic stress, family functioning, and social support in survivors of childhood leukemia and their mothers and fathers. J Consult Clin Psychol. 1997;65:120–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Pelcovitz D, Libov BG, Mandel F, et al. Posttraumatic stress disorder and family functioning in adolescent cancer. J Trauma Stress. 1998;11:205–21.PubMedCrossRefGoogle Scholar
  72. 72.
    Libov BG, Nevid JS, Pelcovitz D, Carmony TM. Posttraumatic stress symptomatology in mothers of pediatric cancer survivors. Psychol Health. 2002;17:501–511.CrossRefGoogle Scholar
  73. 73.
    Birmaher B, Brent D, Chiappetta L, et al. Psychometric properties of the screen for child anxiety related emotional disorders (SCARED): a replication study. J Am Acad Child Adolesc Psychiatry. 1999;38:545–53.CrossRefGoogle Scholar
  74. 74.
    Moitra E, Armstrong CL. Tumor locus moderates anxiety symptoms in a pediatric neuro-oncologic sample. Child Neuropsychol. 2009;15:460.PubMedCrossRefGoogle Scholar
  75. 75.
    Williams PG, Hersh JH. Brief report: the association of neurofibromatosis type 1 and autism. J Autism Dev Disord. 1998;28:567–71.PubMedCrossRefGoogle Scholar
  76. 76.
    Mouridsen SE, Andersen LB, Sorensen SA, et al. Neurofibromatosis in infantile autism and other types of childhood psychoses. Acta Paedopsychiatr. 1992;55:15–8.PubMedGoogle Scholar
  77. 77.
    Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiat Clin Neurosci. 2004;16:367–78.CrossRefGoogle Scholar
  78. 78.
    Schmahmann JD. Therapeutic and research implications. Int Rev Neurobiol. 1997;41:637–47.PubMedCrossRefGoogle Scholar
  79. 79.
    VanDeinse D, Hornyak J. Linguistic and cognitive deficits associated with cerebellar mutism. Pediatr Rehabil. 1997;1:41–4.PubMedGoogle Scholar
  80. 80.
    Pollack IF, Polinko P, Albright AL, et al. Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology. Neurosurgery. 1995;37:885–93.PubMedCrossRefGoogle Scholar
  81. 81.
    Ferrante L, Mastronardi L, Acqui M, Fortuna A. Mutism after posterior fossa surgery in children. J Neurosurg. 1990;72:959–63.PubMedCrossRefGoogle Scholar
  82. 82.
    Ersahin Y, Mutluer S, Caglil S, Duman Y. Cerebellar mutism: report of seven cases and review of the literature. Neurosurgery. 1996;38:60–66.PubMedCrossRefGoogle Scholar
  83. 83.
    Miyakita Y, Taguchi Y, Sakakibara Y, et al. Transient mutism resolving into cerebellar speech after brain stem infarction following a traumatic injury of the vertebral artery in a child. Acta Neurochir. 1999;141:209–13.CrossRefGoogle Scholar
  84. 84.
    Tavano A, Grasso R, Gagliardi C, et al. Disorders of cognitive and affective development in cerebellar malformations. Brain. 2007;130:2646–60.PubMedCrossRefGoogle Scholar
  85. 85.
    Mainio A, Hakko H, Niemelä A, et al. Level of obsessionality among neurosurgical patients with a primary brain tumor. J Neuropsychiat Clin Neurosci. 2005;17:399–404.CrossRefGoogle Scholar
  86. 86.
    Price TRP, Goetz KL, Lovell MR. Neuropsychiatric aspects of brain tumors. In: Yudofsky SC, Hales RE, editors. Essentials of neuropsychiatry and clinical neurosciences. Arlington, VA: American Psychiatric Publishing, Inc.; 2004. pp. 373–98.Google Scholar
  87. 87.
    Weissenberger AA, Dell ML, Liow K, et al. Aggression and psychiatric comorbidity in children with hypothalamic hamartomas and their unaffected siblings. J Am Acad Child Adolesc Psychiatry. 2001;40:696–703.PubMedCrossRefGoogle Scholar
  88. 88.
    Merchant TE, Hua CH, Shukla H, et al. Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive dysfunction. Pediatr Blood Cancer. 2008;51:110–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Klein M, Heimans J, Aaronson N, et al. Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study. Lancet. 2002;360:1361–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Armstrong C, Corn B, Ruffer J, et al. Radiotherapeutic effects on brain function: double dissociation of memory systems. Neuropsychiatry Neuropsychol Behav Neurol. 2000;13:101–11.PubMedGoogle Scholar
  91. 91.
    Armstrong C, Ruffer J, Corn B, et al. Biphasic patterns of memory deficits following moderate dose/partial brain irradiation: neuropsychologic outcome and proposed mechanisms. J Clin Oncol. 1995;13:2263–71.PubMedGoogle Scholar
  92. 92.
    Lee P, Hung B, Woo E, et al. Effects of radiation therapy on neuropsychological functioning in patients with nasopharyngeal carcinoma. J Neurol Neurosurg Psychiat. 1989;52:488–92.PubMedCrossRefGoogle Scholar
  93. 93.
    Reimers TS, Mortensen EL, Schmiegelow K. Memory deficits in long-term survivors of childhood brain tumors may primarily reflect general cognitive dysfunctions. Pediatr Blood Cancer. 2007;48:205–12.PubMedCrossRefGoogle Scholar
  94. 94.
    Llanes S, Torres IJ, Roeske A, et al. Temporal lobe radiation and memory in adult brain tumor patients. J Int Neuropsychol Soc. 2004;10(S1):185.Google Scholar
  95. 95.
    Armstrong C, Stern C, Ruffer J, Corn B. Memory performance used to detect radiation effects on cognitive functioning. Appl Neuropsychol. 2001;8:129–39.PubMedCrossRefGoogle Scholar
  96. 96.
    Mulhern R, Palmer S, Merchant TE, et al. Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma. J Clin Oncol. 2005;23:5511–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Palmer S, Gajjar A, Reddick W, et al. Predicting intellectual outcome among children treated with 35–40 Gy craniospinal irradiation for medulloblastoma. Neuropsychology. 2003;17:548–55.PubMedCrossRefGoogle Scholar
  98. 98.
    Palmer S, Reddick W, Glass J, et al. Decline in corpus callosum volume among pediatric patients with medulloblastoma: longitudinal MR imaging study. Am J Neuroradiol. 2002;23:1088–94.PubMedGoogle Scholar
  99. 99.
    Mulhern R, Palmer S, Reddick W, et al. Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. J Clin Oncol. 2001;19:472–9.PubMedGoogle Scholar
  100. 100.
    Shaw EG, Rosdhal R, D‘Agostino RBJ, et al. Phase II study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life. J Clin Oncol. 2006;24:1415–20.PubMedCrossRefGoogle Scholar
  101. 101.
    Armstrong C, Gyato K, Awadalla A, et al. A critical review of the clinical effects of therapeutic irradiation damage to the brain: the roots of controversy. Neuropsychol Rev. 2004;14:65–86.PubMedCrossRefGoogle Scholar
  102. 102.
    Welzel G, Fleckenstein K, Mai SK, et al. Acute neurocognitive impairment during cranial radiation therapy in patients with intracranial tumors. Strahlenther Onkol. 2008;184:647–54.PubMedCrossRefGoogle Scholar
  103. 103.
    Merchant TE, Kiehna EN, Miles MA, et al. Acute effects of irradiation on cognition: changes in attention on a computerized continuous performance test during radiotherapy in pediatric patients with localized primary brain tumors. Int J Rad Onc Biol Phys. 2002;53:1271–8.CrossRefGoogle Scholar
  104. 104.
    Berg R, Ch’ien L, Lancaster W, et al. Neuropsychological sequelae of postradiation somnolence syndrome. Dev Behav Pediatr. 1983;4:103–07.CrossRefGoogle Scholar
  105. 105.
    Armstrong CL, Guglielmi L, Seiler CB. Early delayed radiotherapy damage affects widespread semantic memory networks. J Int Neuropsychol Soc (abstr.). 2004;10(S1):97–8.Google Scholar
  106. 106.
    Mettler F, Upton A. Medical effects of ionizing radiation. 2nd ed. Philadelphia, PA: W.B. Saunders; 1995.Google Scholar
  107. 107.
    Viner K. Cognitive changes in response to treatment of brain tumors: the late-delayed effects of radiation therapy. (Psy.D. Dissertation). Chester, PA: Widener University; 2008.Google Scholar
  108. 108.
    Bleyer A, Geyer J, Taylor E, Hubbard B. The susceptibility of the cerebral subependymal zone (SEZ) to chemotherapy (CT) and radiotherapy (RT): mechanism of clinical neurotoxicity caused by CT and RT (Abstr.). Proc Am Soc Clin Oncol. 1989;8:84.Google Scholar
  109. 109.
    Monje ML, Mizumatsu S, Fike S, Palmer TD. Irradiation induces neural precursor-cell dysfunction. Nat Med. 2002;8:955–62.PubMedCrossRefGoogle Scholar
  110. 110.
    Monje ML, Palmer T. Radiation injury and neurogenesis. Curr Opin Neurol. 2003;16:129–34.PubMedCrossRefGoogle Scholar
  111. 111.
    Shaw EG, Robbins ME. Biological bases of radiation injury to the brain. In: Meyers CA, Perry JR, editors. Cognition and cancer. Cambridge, UK: Cambridge University Press; 2008. pp. 83–96.CrossRefGoogle Scholar
  112. 112.
    Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science. 2003;302:1760–65.PubMedCrossRefGoogle Scholar
  113. 113.
    Armstrong CL, Hunter JV, Hackney D, et al. MRI changes during the early-delayed phase of radiotherapy effects. Int J Rad Oncol Biol Phys. 2005;63:56–63.CrossRefGoogle Scholar
  114. 114.
    Nagel BJ, Palmer SL, Reddick WE, et al. Abnormal hippocampal development in children with medulloblastoma treated with risk-adapted irradiation. Am J Neuroradiol. 2004;25:1575–82.PubMedGoogle Scholar
  115. 115.
    Armstrong CL, Hampstead B, Guglielmi L. Hippocampal response to neuro-oncological stressors [abstract]. J Int Neuropsychol Soc. 2004;10(S1):65.Google Scholar
  116. 116.
    Cao Y, Tsien CI, Sundgren PC, et al. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for prediction of radiation-induced neurocognitive dysfunction. Clin Cancer Res. 2009;15:1747–54.PubMedCrossRefGoogle Scholar
  117. 117.
    Hahn CA, Zhou SM, Raynor R, et al. Dose-dependent effects of radiation therapy on cerebral blood flow, metabolism, and neurocognitive dysfunction. Int J Rad Oncol Biol Phys. 2009;73:1082–7.CrossRefGoogle Scholar
  118. 118.
    Sato K, Kameyama M, Kayama T, et al. Serial positron emission tomography imaging of changes in amino acid metabolism in low grade astrocytoma after radio- and chemotherapy. Neurol Med Chir (Tokyo). 1995;35:808–12.CrossRefGoogle Scholar
  119. 119.
    Walter A, Mulhern R, Grajjar A, et al. Survival and neurodevelopmental outcome of young children with medulloblastoma at St. Jude Children’s Research Hospital. J Clin Oncol. 1999;17:3720–8.PubMedGoogle Scholar
  120. 120.
    Radcliffe J, Bunin G, Sutton L, et al. Cognitive deficits in long-term survivors of childhood medulloblastoma and other noncortical tumors: age-dependent effects of whole brain radiation. Int J Dev Neurosci. 1994;12:327–34.PubMedCrossRefGoogle Scholar
  121. 121.
    Blowers E, Hall K. Adverse events in bevacizumab and chemotherapy: patient management. Br J Nurs. 2009;18:424–8.PubMedGoogle Scholar
  122. 122.
    Shiminski-Maher T, Cullen P, Sansalone M. Childhood brain and spinal cord tumors: a guide for families, friends, and caregivers. Sebastopol, CA: O‘Reilly and Associates; 2002.Google Scholar
  123. 123.
    Fischer D, Knobf MT. The cancer chemotherapy handbook. St. Louis, MO: Mosby Year Book; 1989.Google Scholar
  124. 124.
    Erbetta A, Salmaggi A, Sghirlanzoni A, et al. Clinical and radiological features of brain neurotoxicity caused by antitumor and immunosuppressant treatments. Neurol Sci. 2008;29:131–7.PubMedCrossRefGoogle Scholar
  125. 125.
    Perry A, Schmidt RE. Cancer therapy-associated CNS neuropathology: an update and review of the literature. Acta Neuropathol. 2006;111:197–212.PubMedCrossRefGoogle Scholar
  126. 126.
    Meyers CA. How chemotherapy damages the nervous system. J Biol. 2008;7:II.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Carol L. Armstrong
    • 1
  • Cynthia J. Schmus
    • 2
  • Jean B. Belasco
    • 2
    • 3
  1. 1.Division of Oncology/Neuro-OncologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Division of OncologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  3. 3.Department of Pediatrics, School of MedicineThe University of PennsylvaniaPhiladelphiaUSA

Personalised recommendations