White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma

Liu, Fang; Scantlebury, Nadia; Tabori, Uri; Bouffet, Éric; Laughlin, Suzanne; Strother, Douglas; McConnell, Dina; Hukin, Juliette; Fryer, Chris; Brière, Marie-Eve; Montour-Proulx, Isabelle; Keene, Daniel; Wang, Frank; Mabbott, Donald

doi:10.1093/neuonc/nou306

Cited by 39 publications

(48 citation statements)

References 49 publications

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“…Previous studies corroborate that therapies other than radiation may cause white matter tract damage, which results in cognitive deficits. In a recent study of children with NF1 and non‐NF1 low‐grade gliomas unexposed to radiation, white matter integrity mediated the effect of therapy (chemotherapy and/or surgery) on decreased IQ . The magnitude of difference in FA that was found in our study ( Δ FA = –4.5% [corpus callosum] and –5.5% [cerebellothalamic tracts]) was similar to that found in prior studies that correlated cognitive impairment with lower FA of the corpus callosum ( Δ FA = –4.1%[17] and –4.8%[13]) and the cerebello‐thalamocortical tracts ( Δ FA = –1% to –6%[10]) .…”

Section: Discussionsupporting

confidence: 87%

“…Although prior studies have investigated the effect of brain tumors and their therapies on white matter tract integrity, none have been able to isolate the effect of systemic chemotherapy separate from surgery, radiation, or tumor infiltration. Further, prior studies have not investigated the effect of radiation‐sparing therapy specifically in individuals with NF1, who are at additional risk for cognitive deficits.…”

Section: Discussionmentioning

confidence: 99%

“…Our study found that exposure to systemic chemotherapy is associated with reduced FA, specifically in tracts associated with cognition. Previous studies have used a data‐driven voxel‐based analysis to examine changes in DTI measures across the whole brain . Our approach is hypothesis based and focused on tracts associated with cognition described in previous studies of brain tumor survivors .…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies have demonstrated a connection between microstructural damage to white matter and cognitive function in subjects with brain tumors . Surgery, radiation, and chemotherapy are associated with decreased white matter integrity, measured by FA .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Systemic Chemotherapy and White Matter Integrity in Tracts Associated with Cognition Among Children With Neurofibromatosis Type 1

Blank

Berman

Fisher

2016

Pediatr Blood Cancer

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Exposure to low-intensity chemotherapy in NF1 is associated with changes in white matter microstructure in tracts associated with cognition. Future studies should determine whether these changes are associated with cognitive decline. While chemotherapy may spare cognition relative to radiation and surgery, children with NF1 exposed to chemotherapy may benefit from early cognitive testing to allow for earlier intervention.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Systemic Chemotherapy and White Matter Integrity in Tracts Associated with Cognition Among Children With Neurofibromatosis Type 1

Blank

Berman

Fisher

2016

Pediatr Blood Cancer

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“…Among 32 children with low grade glioma treated without radiation, compromise of supratentorial white matter mediated the effect of treatment on intelligence quotient (IQ), suggesting that brain tumor therapies affect cognition by damaging white matter. Greater white matter damage was seen in five children with NF1 (Liu et al, 2015). However, exercise may help moderate the neurotoxic effect of cranial radiation.…”

Section: Present and Future Impact Of Novel Imaging In The Managementmentioning

confidence: 98%

2016 Children's Tumor Foundation conference on neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis

Fisher

Belzberg

Blank

et al. 2018

American J of Med Genetics Pt A

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Organized and hosted by the Children's Tumor Foundation (CTF), the Neurofibromatosis (NF) conference is the premier annual gathering for clinicians and researchers interested in neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). The 2016 edition constituted a blend of clinical and basic aspects of NF research that helped in clarifying different advances in the field. The incorporation of next generation sequencing is changing the way genetic diagnostics is performed for NF and related disorders, providing solutions to problems like genetic heterogeneity, overlapping clinical manifestations, or the presence of mosaicism. The transformation from plexiform neurofibroma (PNF) to malignant peripheral nerve sheath tumor (MPNST) is being clarified, along with new management and treatments for benign and premalignant tumors. Promising new cellular and in vivo models for understanding the musculoskeletal abnormalities in NF1, the development of NF2 or SWN associated schwannomas, and clarifying the cells that give rise to NF1-associated optic pathway glioma were presented. The interaction of neurofibromin and SPRED1 was described comprehensively, providing functional insight that will help in the interpretation of pathogenicity of certain missense variants identified in NF1 and Legius syndrome patients. Novel promising imaging techniques are being developed, as well as new integrative and holistic management models for patients that take into account psychological, social, and biological factors. Importantly, new therapeutic approaches for schwannomas, meningiomas, ependymomas, PNF, and MPNST are being pursued. This report highlights the major advances that were presented at the 2016 CTF NF conference.

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Predictors of neuropsychological late effects and white matter correlates in children treated for a brain tumor without radiation therapy

Peterson

Tabori

Bouffet

et al. 2019

Pediatric Blood & Cancer

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Background:Little is known about cognition and predictors of neuropsychological outcomes in pediatric low-grade glioma (PLGG) survivors treated without radiation therapy. This research expands upon our previous work by further identifying the cognitive profile of PLGG patients treated without radiation therapy, investigating the specific medical and demographic variables that predict functioning, and examining white matter structure and its relationship to neuropsychological performance.Procedure: Nineteen PLGG patients (11-19 years) were administered the Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale, and subtests from the Woodcock-Johnson Tests of Cognition (visual matching, rapid picture naming, and pair cancellation) and Cambridge Neuropsychological Test Automated Battery (pattern recognition memory, delayed matching to sample, intra-extra dimensional set shift, motor screening task, rapid visual information processing, and spatial span). Results:The sample had normative weaknesses in verbal working memory, brief attention/vigilance, psychomotor speeded output, visual perception and matching, overall cognition, working memory, and processing speed. Increased surgeries or subtotal resections, hydrocephalus, shunting procedures, chemotherapy, NF1, and supratentorial location were predictive of cognitive deficits. Broad white matter involvement of the frontal, temporal, parietal, and occipital lobes as well as the cerebellum, as inferred from diffusion tensor imaging indices of decreased fiber orientation and increased water diffusion, was related to many cognitive difficulties. Conclusions:This study comprehensively examines cognitive functioning in PLGG patients treated without radiation therapy, predictors of cognition, and its relation to white matter structure. Our findings indicate that medical and demographic variables other than radiation therapy can lead to cognitive late effects with diffuse white matter involvement. K E Y W O R D S

show abstract

White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma

Cited by 39 publications

References 49 publications

Systemic Chemotherapy and White Matter Integrity in Tracts Associated with Cognition Among Children With Neurofibromatosis Type 1

Systemic Chemotherapy and White Matter Integrity in Tracts Associated with Cognition Among Children With Neurofibromatosis Type 1

2016 Children's Tumor Foundation conference on neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis

Predictors of neuropsychological late effects and white matter correlates in children treated for a brain tumor without radiation therapy

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