Neurocognitive deficits in medulloblastoma survivors and white matter loss

Abstract

Although previous studies have documented a significant risk of intellectual loss after treatment for childhood medulloblastoma (MED), the pathophysiology underlying this process is poorly understood. The purpose of this study was to test the hypotheses that (1) patients treated for MED in childhood have reduced volumes of normal white matter (NWM) related to their treatment with craniospinal irradiation with or without chemotherapy, and (2) deficits in NWM among patients surviving MED can at least partially explain deficits in their intellectual performance. Eighteen pediatric patients previously treated for MED were matched on the basis of age at the time of evaluation to 18 patients previously treated for low‐grade posterior fossa tumors with surgery alone (mean difference, 3.7 months). Evaluations were conducted with age‐appropriate neurocognitive testing and quantitative magnetic resonance imaging by using a novel automated segmentation and classification algorithm constructed from a hybrid neural network. Patients treated for MED had significantly less NWM (p < 0.01) and significantly lower Full‐Scale IQ values than those treated for low‐grade tumors (mean, 82.1 vs 92.9). In addition, NWM had a positive and statistically significant association with Full‐Scale IQ among the patients treated for MED. We conclude that irradiation‐ or chemotherapy‐induced destruction of NWM can at least partially explain intellectual and academic achievement deficits among MED survivors.

Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies

“…A few days following administration, some patients have developed a toxic leukoencephalopathy with altered mental status and multifocal deficits. Within days to weeks, a transverse myelopathy with pain, sensory loss, paraplegia, and bladder dysfunction can [11][12][13] Treatment with low doses of purine analogs such as fludarabine (used in Case 1), cytarabine (used in Case 3), and 5-fluorouracil (used in Case 4) has also previously been known to result in at least rare white matter changes. These effects have generally been mild and reversible.…”

Brain structural abnormalities in survivors of pediatric posterior fossa brain tumors: A voxel-based morphometry study using free-form deformation

“…Long-term survivors of pediatric brain tumors suffer a variety of cognitive deficits in intelligence, memory, attention, and fine-motor functions (Copeland et al, 1985;Konczak et al, 2005;Mulhern et al, 1988;Mulhern et al, 1999;Mulhern et al, 2004;Palmer et al, 2001;Reeves et al, 2006;Steinlin et al, 2003). Cognitive deficits may be caused by brain tumors located in the central nervous system (CNS) or by treatments directed at the CNS such as chemotherapy and cranial radiation therapy (CRT).…”

“…Many studies have investigated the association between CNS-directed treatment and structural damage of the brain. Brain structural changes such as atrophy from gray and white matter loss or developmental deficits in the corpus callosum that are known to occur after CNS-directed treatments have been correlated with cognitive deficits (Macedoni-Luksic et al, 2003;Mulhern et al, 1999;Mulhern et al, 2001;Palmer et al, 2002;Reddick et al, 2003;Reddick et al, 2005;Steen et al, 2001), but the specific neural substrates of those deficits are largely unknown. Neuroimaging techniques, including functional MRI (fMRI) and diffusion tensor imaging (DTI), are promising new tools to investigate brain structure and function in such patients Phillips et al, 2005;Ries et al, 2004;Zou et al, 2005).…”

Changes in Cerebral Cortex of Children Treated for Medulloblastoma

“…The decrease in the amount of normalappearing white matter also correlated with the craniospinal radiation dose (24). Decreased amounts of normalappearing white matter correlated with decreases in fullscale intelligence quotient (IQ), factual knowledge, verbal thinking, nonverbal thinking, attention, and academic achievement (22,23,25).…”