A prospective study of corpus callosum regional volumes and neurocognitive outcomes following cranial radiation for pediatric brain tumors

Arif Rashid, Ashwin N. Ram, Wendy R. Kates, Kristin J. Redmond, Moody Wharam, E. Mark Mahone, Alena Horska, Stephanie Terezakis

Research output: Contribution to journalArticle

Abstract

Purpose/objective(s): Cranial radiation therapy (CRT) may disrupt the corpus callosum (CC), which plays an important role in basic motor and cognitive functions. The aim of this prospective longitudinal study was to assess changes in CC mid-sagittal areas, CC volumes, and performance on neuropsychological (NP) tests related to the CC in children following CRT. Materials/methods: Twelve pediatric patients were treated with CRT for primary brain malignancies. Thirteen age-matched healthy volunteers served as controls. Brain MRIs and NP assessment emphasizing motor dexterity, processing speed, visuomotor integration, and working memory (visual and verbal) were performed at baseline and at 6, 15, and 27 months following completion of CRT. Linear mixed effects (LME) analyses were used to evaluate patient NP performance and changes in regional CC volumes (genu, anterior body, mid-body, posterior body, and splenium) and mid-sagittal areas over time and with radiation doses, correcting for age at CRT start. Results: The mean age at CRT was 9.41 (range 1.2–15.7) years. The median prescription dose was 54 (range 18–59.4) Gy. LME analysis revealed a significant decrease in overall CC volumes over time (p < 0.00001), with no overall effect of radiation dose. Analysis of individual CC regions demonstrated a significant decrease in all regional volumes over time (p < 0.00001) in patients, with no effect of radiation dose. Only in the splenium was there a trend toward a dose-dependent effect (p = 0.093). Patients had significantly reduced NP performance across visits—most notably in motor dexterity and visual working memory (both p < 0.0001). Conclusions: These prospective data demonstrate a significant decrease in CC regional volumes after CRT, with associated decline in neurocognitive function, most notably in manual dexterity, attention, and working memory. Further prospective study of larger cohorts of patients is needed to establish the relationship between CRT dose, neuroanatomical, and functional changes in the CC.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalChild's Nervous System
DOIs
StateAccepted/In press - Apr 28 2017

Fingerprint

Corpus Callosum
Brain Neoplasms
Prospective Studies
Radiation
Pediatrics
Short-Term Memory
Radiation Effects
Brain
Neuropsychological Tests
Prescriptions
Longitudinal Studies
Healthy Volunteers

Keywords

  • CNS tumors
  • Neurocognitive side effects
  • Neurotoxicity of therapy
  • Radiation therapy
  • Volumetric MRI

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

@article{f986529f331049dd9acc9a15b18d1526,
title = "A prospective study of corpus callosum regional volumes and neurocognitive outcomes following cranial radiation for pediatric brain tumors",
abstract = "Purpose/objective(s): Cranial radiation therapy (CRT) may disrupt the corpus callosum (CC), which plays an important role in basic motor and cognitive functions. The aim of this prospective longitudinal study was to assess changes in CC mid-sagittal areas, CC volumes, and performance on neuropsychological (NP) tests related to the CC in children following CRT. Materials/methods: Twelve pediatric patients were treated with CRT for primary brain malignancies. Thirteen age-matched healthy volunteers served as controls. Brain MRIs and NP assessment emphasizing motor dexterity, processing speed, visuomotor integration, and working memory (visual and verbal) were performed at baseline and at 6, 15, and 27 months following completion of CRT. Linear mixed effects (LME) analyses were used to evaluate patient NP performance and changes in regional CC volumes (genu, anterior body, mid-body, posterior body, and splenium) and mid-sagittal areas over time and with radiation doses, correcting for age at CRT start. Results: The mean age at CRT was 9.41 (range 1.2–15.7) years. The median prescription dose was 54 (range 18–59.4) Gy. LME analysis revealed a significant decrease in overall CC volumes over time (p < 0.00001), with no overall effect of radiation dose. Analysis of individual CC regions demonstrated a significant decrease in all regional volumes over time (p < 0.00001) in patients, with no effect of radiation dose. Only in the splenium was there a trend toward a dose-dependent effect (p = 0.093). Patients had significantly reduced NP performance across visits—most notably in motor dexterity and visual working memory (both p < 0.0001). Conclusions: These prospective data demonstrate a significant decrease in CC regional volumes after CRT, with associated decline in neurocognitive function, most notably in manual dexterity, attention, and working memory. Further prospective study of larger cohorts of patients is needed to establish the relationship between CRT dose, neuroanatomical, and functional changes in the CC.",
keywords = "CNS tumors, Neurocognitive side effects, Neurotoxicity of therapy, Radiation therapy, Volumetric MRI",
author = "Arif Rashid and Ram, {Ashwin N.} and Kates, {Wendy R.} and Redmond, {Kristin J.} and Moody Wharam and {Mark Mahone}, E. and Alena Horska and Stephanie Terezakis",
year = "2017",
month = "4",
doi = "10.1007/s00381-017-3412-3",
pages = "1--8",
journal = "Child's Nervous System",
issn = "0256-7040",
publisher = "Springer Verlag",

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T1 - A prospective study of corpus callosum regional volumes and neurocognitive outcomes following cranial radiation for pediatric brain tumors

AU - Rashid,Arif

AU - Ram,Ashwin N.

AU - Kates,Wendy R.

AU - Redmond,Kristin J.

AU - Wharam,Moody

AU - Mark Mahone,E.

AU - Horska,Alena

AU - Terezakis,Stephanie

PY - 2017/4/28

Y1 - 2017/4/28

N2 - Purpose/objective(s): Cranial radiation therapy (CRT) may disrupt the corpus callosum (CC), which plays an important role in basic motor and cognitive functions. The aim of this prospective longitudinal study was to assess changes in CC mid-sagittal areas, CC volumes, and performance on neuropsychological (NP) tests related to the CC in children following CRT. Materials/methods: Twelve pediatric patients were treated with CRT for primary brain malignancies. Thirteen age-matched healthy volunteers served as controls. Brain MRIs and NP assessment emphasizing motor dexterity, processing speed, visuomotor integration, and working memory (visual and verbal) were performed at baseline and at 6, 15, and 27 months following completion of CRT. Linear mixed effects (LME) analyses were used to evaluate patient NP performance and changes in regional CC volumes (genu, anterior body, mid-body, posterior body, and splenium) and mid-sagittal areas over time and with radiation doses, correcting for age at CRT start. Results: The mean age at CRT was 9.41 (range 1.2–15.7) years. The median prescription dose was 54 (range 18–59.4) Gy. LME analysis revealed a significant decrease in overall CC volumes over time (p < 0.00001), with no overall effect of radiation dose. Analysis of individual CC regions demonstrated a significant decrease in all regional volumes over time (p < 0.00001) in patients, with no effect of radiation dose. Only in the splenium was there a trend toward a dose-dependent effect (p = 0.093). Patients had significantly reduced NP performance across visits—most notably in motor dexterity and visual working memory (both p < 0.0001). Conclusions: These prospective data demonstrate a significant decrease in CC regional volumes after CRT, with associated decline in neurocognitive function, most notably in manual dexterity, attention, and working memory. Further prospective study of larger cohorts of patients is needed to establish the relationship between CRT dose, neuroanatomical, and functional changes in the CC.

AB - Purpose/objective(s): Cranial radiation therapy (CRT) may disrupt the corpus callosum (CC), which plays an important role in basic motor and cognitive functions. The aim of this prospective longitudinal study was to assess changes in CC mid-sagittal areas, CC volumes, and performance on neuropsychological (NP) tests related to the CC in children following CRT. Materials/methods: Twelve pediatric patients were treated with CRT for primary brain malignancies. Thirteen age-matched healthy volunteers served as controls. Brain MRIs and NP assessment emphasizing motor dexterity, processing speed, visuomotor integration, and working memory (visual and verbal) were performed at baseline and at 6, 15, and 27 months following completion of CRT. Linear mixed effects (LME) analyses were used to evaluate patient NP performance and changes in regional CC volumes (genu, anterior body, mid-body, posterior body, and splenium) and mid-sagittal areas over time and with radiation doses, correcting for age at CRT start. Results: The mean age at CRT was 9.41 (range 1.2–15.7) years. The median prescription dose was 54 (range 18–59.4) Gy. LME analysis revealed a significant decrease in overall CC volumes over time (p < 0.00001), with no overall effect of radiation dose. Analysis of individual CC regions demonstrated a significant decrease in all regional volumes over time (p < 0.00001) in patients, with no effect of radiation dose. Only in the splenium was there a trend toward a dose-dependent effect (p = 0.093). Patients had significantly reduced NP performance across visits—most notably in motor dexterity and visual working memory (both p < 0.0001). Conclusions: These prospective data demonstrate a significant decrease in CC regional volumes after CRT, with associated decline in neurocognitive function, most notably in manual dexterity, attention, and working memory. Further prospective study of larger cohorts of patients is needed to establish the relationship between CRT dose, neuroanatomical, and functional changes in the CC.

KW - CNS tumors

KW - Neurocognitive side effects

KW - Neurotoxicity of therapy

KW - Radiation therapy

KW - Volumetric MRI

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