Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Pediatric Radiology
Published in: Pediatric Radiology 6/2017

01-05-2017 | Review

Magnetic resonance imaging patterns of treatment-related toxicity in the pediatric brain: an update and review of the literature

Authors: Maria Camilla Rossi Espagnet, Luca Pasquini, Antonio Napolitano, Antonella Cacchione, Angela Mastronuzzi, Roberta Caruso, Paolo Tomà, Daniela Longo

Published in: Pediatric Radiology | Issue 6/2017

Login to get access

Abstract

Treatment-related neurotoxicity is a potentially life-threatening clinical condition that can represent a diagnostic challenge. Differentiating diagnoses between therapy-associated brain injury and recurrent disease can be difficult, and the immediate recognition of neurotoxicity is crucial to providing correct therapeutic management, ensuring damage reversibility. For these purposes, the knowledge of clinical timing and specific treatment protocols is extremely important for interpreting MRI patterns. Neuroradiologic findings are heterogeneous and sometimes overlapping, representing the compounding effect of the different treatments. Moreover, MRI patterns can be acute, subacute or delayed and involve different brain regions, depending on (1) the mechanism of action of the specific medication and (2) which brain regions are selectively vulnerable to specific toxic effects. This review illustrates the most common radiologic appearance of radiotherapy, chemotherapy and medication-associated brain injury in children, with special focus on the application of advanced MRI techniques (diffusion, perfusion and proton spectroscopy) in the diagnosis of the underlying processes leading to brain toxicity.
Literature
1.
Pružincová Ľ, Šteňo J, Srbecký M et al (2009) MR imaging of late radiation therapy- and chemotherapy-induced injury: a pictorial essay. Eur Radiol 19:2716–2727CrossRefPubMed
2.
Ball WS Jr, Prenger EC, Ballard ET (1992) Neurotoxicity of radio/chemotherapy in children: pathologic and MR correlation. AJNR Am J Neuroradiol 13:761–776PubMed
3.
Iyer RS, Chaturvedi A, Pruthiet S et al (2011) Medication neurotoxicity in children. Pediatr Radiol 41:1455–1464CrossRefPubMed
4.
Vázquez E, Lucaya J, Castellote A et al (2002) Neuroimaging in pediatric leukemia and lymphoma: differential diagnosis. Radiographics 22:1411–1428CrossRefPubMed
5.
Vázquez E, Delgado I, Sánchez-Montañez A et al (2011) Side effects of oncologic therapies in the pediatric central nervous system: update on neuroimaging findings. Radiographics 31:1123–1139CrossRefPubMed
6.
Valk J, Van der Knaap S (1992) Toxic encephalopathy. AJNR Am J Neuroradiol 13:747–760PubMed
7.
Reddick WE, Taghipour DJ, Glass JO et al (2014) Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers. Pediatr Blood Cancer 61:1074–1079CrossRefPubMedPubMedCentral
8.
Oeffinger K, Mertens A, Sklar C et al (2006) Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355:1572–1582CrossRefPubMed
9.
10.
Quattrocchi CC, Errante Y, Rossi Espagnet MC (2016) Magnetic resonance imaging differential diagnosis of brainstem lesions in children. World J Radiol 8:1–20CrossRefPubMedPubMedCentral
11.
Greene-Schloesser D, Robbins ME, Peiffer AM et al (2012) Radiation-induced brain injury: a review. Front Oncol 19:2–73
12.
Perry A, Schmidt RE (2006) Cancer therapy-associated CNS neuropathology: an update and review of the literature. Acta Neuropathol 111:197–212CrossRefPubMed
13.
O’Brien BJ, Colen RR (2014) Post-treatment imaging changes in primary brain tumors. Curr Oncol Rep 16:397CrossRefPubMed
14.
Murphy ES, Merchant TE, Wu S et al (2012) Necrosis after craniospinal irradiation: results from a prospective series of children with central nervous system embryonal tumors. Int J Radiat Oncol Biol Phys 83:e655–e660CrossRefPubMedPubMedCentral
15.
Kumar AJ, Leeds NE, Fuller GN et al (2000) Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 217:377–384CrossRefPubMed
16.
Poussaint TY, Rodriguez D (2006) Advanced neuroimaging of pediatric brain tumors: MR diffusion, MR perfusion, and MR spectroscopy. Neuroimaging Clin N Am 16:169–192CrossRefPubMed
17.
Ball WS, Holland SK (2001) Perfusion imaging in the pediatric patient. Magn Reson Imaging Clin N Am 9:207–230PubMed
18.
Bangiyev L, Rossi Espagnet MC, Young R (2014) Adult brain tumor imaging: state of the art. Semin Roentgenol 49:39–52CrossRefPubMed
19.
Sugahara T, Korogi Y, Tomiguchi S et al (2000) Post-therapeutic intraaxial brain tumor: the value of perfusion-sensitive contrast-enhanced MR imaging for differentiating tumor recurrence from nonneoplastic contrast-enhancing tissue. AJNR Am J Neuroradiol 21:901–909PubMed
20.
Hu LS, Baxter LC, Smith KA et al (2009) Relative cerebral blood volume values to differentiate high-grade glioma recurrence from post-treatment radiation effect: direct correlation between image-guided tissue histopathology and localized dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging measurements. AJNR Am J Neuroradiol 30:552–558CrossRefPubMed
21.
Verma N, Cowperthwaite MC, Burnett MG et al (2013) Differentiating tumor recurrence from treatment necrosis: a review of neuro-oncologic imaging strategies. Neuro Oncol 15:515–534CrossRefPubMedPubMedCentral
22.
Merchant T, Farr JB (2014) Proton beam therapy: a fad or a new standard of care. Curr Opin Pediatr 26:3–8CrossRefPubMed
23.
Faraci M, Morana G, Bagnasco F et al (2011) Magnetic resonance imaging in childhood leukemia survivors treated with cranial radiotherapy: a cross sectional, single center study. Pediatr Blood Cancer 57:240–246CrossRefPubMed
24.
Koike T, Yanagimachi N, Ishiguro H et al (2012) High incidence of radiation-induced cavernous hemangioma in long-term survivors who underwent hematopoietic stem cell transplantation with radiation therapy during childhood or adolescence. Biol Blood Marrow Transplant 18:1090–1098CrossRefPubMed
25.
Huisman TAGM, Singhi S, Pinto PS (2010) Non-invasive imaging of intracranial pediatric vascular lesions. Childs Nerv Syst 26:1275–1295CrossRefPubMed
26.
Di Giannatale A, Morana G, Rossi A et al (2014) Natural history of cavernous malformations in children with brain tumors treated with radiotherapy and chemotherapy. J Neuro Oncol 117:311–320CrossRef
27.
Nimjee SM, Powers CJ, Bulsara KR (2004) Review of the literature on de novo formation of cavernous malformations of the central nervous system after radiation therapy. Neurosurg Focus 21:e4
28.
Acciarri N, Galassi E, Giulioni M et al (2009) Cavernous malformations of the central nervous system in the pediatric age group. Pediatr Neurosurg 45:81–104CrossRefPubMed
29.
Chen CY, Zimmerman RA, Faro S et al (1996) Childhood leukemia: central nervous system abnormalities during and after treatment. AJNR Am J Neuroradiol 17:295–310PubMed
30.
Löning L, Zimmermann M, Reiter A et al (2000) Secondary neoplasms subsequent to Berlin-Frankfurt-Münster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy. Blood 95:2770–2775PubMed
31.
Hijiya N, Hudson MM, Lensing S et al (2007) Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA 297:1207–1215CrossRefPubMed
32.
Bartynski WS (2008) Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 29:1036–1042CrossRefPubMed
33.
Morris EB, Laningham FH, Sandlund JT et al (2007) Posterior reversible encephalopathy syndrome in children with cancer. Pediatr Blood Cancer 48:152–159CrossRefPubMed
34.
Bartynski WS (2008) Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol 29:1043–1049CrossRefPubMed
35.
Patel AJ, Fox BD, Fulkerson DH et al (2010) Posterior reversible encephalopathy syndrome during posterior fossa tumor resection in a child. J Neurosurg Pediatr 6:377–380CrossRefPubMed
36.
Hodnett P, Coyle J, O’Regan K et al (2009) PRES (posterior reversible encephalopathy syndrome), a rare complication of tacrolimus therapy. Emerg Radiol 16:493–496CrossRefPubMed
37.
Donmez FY, Guleryuz P, Agildere M (2014) MRI findings in childhood PRES: what is different than the adults? Clin Neuroradiol 26:209–213CrossRefPubMed
38.
McKinney AM, Short J, Truwit CL et al (2007) Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol 189:904–912CrossRefPubMed
39.
McKinney AM, Kieffer SA, Paylor RT et al (2009) Acute toxic leukoencephalopathy: potential for reversibility clinically and on MRI with diffusion-weighted and FLAIR imaging. AJR Am J Roentgenol 193:192–206CrossRefPubMed
40.
41.
Akiba T, Okeda R, Tajima T (1996) Metabolites of 5-fluorouracil, alpha-fluoro-beta-alanine and fluoroacetic acid, directly injure myelinated fibers in tissue culture. Acta Neuropathol 92:8–13CrossRefPubMed
42.
43.
Beitinjaneh A, McKinney AM, Cao Q et al (2011) Toxic leukoencephalopathy following fludarabine-associated hematopoietic cell transplantation. Biol Blood Marrow Transplant 17:300–308CrossRefPubMed
44.
Gandola L, Massimino M, Cefalo G et al (2009) Hyperfractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma. J Clin Oncol 27:566–571CrossRefPubMed
45.
Vivekanandan S, Breene R, Ramanujachar R et al (2015) The UK experience of a treatment strategy for pediatric metastatic medulloblastoma comprising intensive induction chemotherapy, hyperfractionated accelerated radiotherapy and response directed high dose myeloablative chemotherapy or maintenance chemotherapy (Milan strategy). Pediatr Blood Cancer 62:2132–2139CrossRefPubMed
46.
Spreafico F, Gandola L, Marchianò A et al (2008) Brain magnetic resonance imaging after high-dose chemotherapy and radiotherapy for childhood brain. Int J Radiat Oncol Biol Phys 70:1011–1019CrossRefPubMed
47.
Thust SC, Blanco E, Michalski AJ et al (2014) MRI abnormalities in children following sequential chemotherapy, hyperfractionated accelerated radiotherapy and high-dose thiotepa for high-risk primitive neuroectodermal tumours of the central nervous system. J Med Imaging Radiat Oncol 58:683–690CrossRefPubMed
48.
Fouladi M, Chintaqumpala M, Laningham FH et al (2004) White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor. J Clin Oncol 22:4551–4560CrossRefPubMed
49.
Dietrich U, Wanke I, Mueller T et al (2001) White matter disease in children treated for malignant brain tumors. Childs Nerv Syst 17:731–738CrossRefPubMed
50.
Edelmann MN, Krull KR, Liu W et al (2014) Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia. Brain 137:2973–2983CrossRefPubMedPubMedCentral
51.
Khong PL, Leung LH, Chan GC et al (2005) White matter anisotropy in childhood medulloblastoma survivors: association with neurotoxicity risk factors. Radiology 236:647–652CrossRefPubMed
52.
Khong PL, Leung LH, Fung AS et al (2006) White matter anisotropy in post-treatment childhood cancer survivors: preliminary evidence of association with neurocognitive function. J Clin Oncol 24:884–890CrossRefPubMed
53.
Palmer SL, Reddick WE, Glass JO et al (2010) Regional white matter anisotropy and reading ability in patients treated for pediatric embryonal tumors. Brain Imaging Behav 4:132–140CrossRefPubMedPubMedCentral
54.
Massimino M, Spreafico F, Pignoli E et al (2016) Comment on: The UK experience of a treatment strategy for pediatric metastatic medulloblastoma comprising intensive induction chemotherapy, hyperfractionated accelerated radiotherapy and response directed high-dose myeloablative chemotherapy or maintenance chemotherapy (Milan strategy). Pediatr Blood Cancer 63:1123–1124CrossRefPubMed
55.
Vivekanandan S (2016) Reply to comment on: The UK experience of a treatment strategy for pediatric metastatic medulloblastoma comprising intensive induction chemotherapy, hyperfractionated accelerated radiotherapy, and response-directed high-dose myeloablative chemotherapy or maintenance chemotherapy (Milan strategy). Pediatr Blood Cancer 63:1125–1126CrossRefPubMed
56.
Fisher MJ, Khademian ZP, Simon EM et al (2005) Diffusion-weighted MR imaging of early methotrexate-related neurotoxicity in children. AJNR Am J Neuroradiol 26:1686–1689PubMed
57.
Rollins N, Winick N, Bash R et al (2004) Acute methotrexate neurotoxicity: findings on diffusion-weighted imaging and correlation with clinical outcome. AJNR Am J Neuroradiol 25:1688–1695PubMed
58.
Reddick WE, Glass JO, Helton KJ et al (2005) Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol 26:1263–1269PubMedPubMedCentral
59.
Reddick WE, Glass JO, Helton KJ et al (2005) A quantitative MR imaging assessment of leukoencephalopathy in children treated for acute lymphoblastic leukemia without irradiation. AJNR Am J Neuroradiol 26:2371–2377PubMedPubMedCentral
60.
Sandoval C, Kutscher M, Jayabose S et al (2003) Neurotoxicity of intrathecal methotrexate: MR imaging findings. AJNR Am J Neuroradiol 24:1887–1890PubMed
61.
Schulz U, Mann G, Zoubek A et al (1994) Venous thrombosis of cranial sinuses in asparaginase therapy: a case report. Klin Padiatr 206:342–345CrossRefPubMed
62.
63.
Boukobza M, Crassard I, Bousser MG et al (2009) MR imaging features of isolated cortical vein thrombosis: diagnosis and follow-up. AJNR Am J Neuroradiol 30:344–348CrossRefPubMed
64.
Wheless JW, Carmant L, Bebin M et al (2009) Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy. Epilepsia 50:195–205CrossRefPubMed
65.
Pearl PL, Vezina LG, Saneto RP et al (2009) Cerebral MRI abnormalities associated with vigabatrin therapy. Epilepsia 50:184–194CrossRefPubMed
66.
Milh M, Villeneuve N, Chapon F et al (2009) Transient brain magnetic resonance imaging hyperintensity in basal ganglia and brain stem of epileptic infants treated with vigabatrin. J Child Neurol 24:305–315CrossRefPubMed
67.
Frytak S, Moertel CH (1978) Childs DS neurologic toxicity associated with high-dose metronidazole therapy. Ann Intern Med 88:361–362CrossRefPubMed
68.
Heaney CJ, Campeau NG, Lindell EP (2003) MR imaging and diffusion-weighted imaging changes in metronidazole (Flagyl)-induced cerebellar toxicity. AJNR Am J Neuroradiol 24:1615–1617PubMed
69.
Kim E, Na DG, Kim EY et al (2007) MR imaging of metronidazole-induced encephalopathy: lesion distribution and diffusion-weighted imaging findings. AJNR Am J Neuroradiol 28:1652–1658CrossRefPubMed
70.
McErlean A, Abdalia K, Donoghue V et al (2010) The dentate nucleus in children: normal development and patterns of disease. Pediatr Radiol 40:326–339CrossRefPubMed
71.
Rovira A, Alonso J, Córdoba J (2008) MR imaging findings in hepatic encephalopathy. AJNR Am J Neuroradiol 29:1612–1621CrossRefPubMed
72.
Aschner J, Anderson A, Slaughter J et al (2015) Neuroimaging identifies increased manganese deposition in infants receiving parenteral nutrition. Am J Clin Nutr 102:1482–1489CrossRefPubMedPubMedCentral
73.
Jiang J, Shi S, Zhou Q et al (2014) Downregulation of the Wnt/β-catenin signaling pathway is involved in manganese-induced neurotoxicity in rat striatum and PC12 cells. J Neurosci Res 92:783–794CrossRefPubMed
Metadata
Title
Magnetic resonance imaging patterns of treatment-related toxicity in the pediatric brain: an update and review of the literature
Authors
Maria Camilla Rossi Espagnet
Luca Pasquini
Antonio Napolitano
Antonella Cacchione
Angela Mastronuzzi
Roberta Caruso
Paolo Tomà
Daniela Longo
Publication date
01-05-2017
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Radiology / Issue 6/2017
Print ISSN: 0301-0449
Electronic ISSN: 1432-1998
DOI
https://doi.org/10.1007/s00247-016-3750-4

Other articles of this Issue 6/2017

Pediatric Radiology 6/2017 Go to the issue

Original Article

The imaging appearance of crayons

Erratum

Erratum to: External validation of clinical decision rules for children with wrist trauma

Case Report

Lumbar translaminar fenestration for insertion of intrathecal baclofen catheter: a novel technique

Original Article

Radiation dose associated with CT-guided drain placement for pediatric patients

Original Article

Use of gadolinium-based magnetic resonance imaging contrast agents and awareness of brain gadolinium deposition among pediatric providers in North America

Pictorial Essay

Muscle MRI in pediatrics: clinical, pathological and genetic correlation