Cognitive Implications of Ototoxicity in Pediatric Patients With Embryonal Brain Tumors.

Purpose: Sensorineural hearing loss (SNHL) is associated with intellectual and academic declines in children treated for embryonal brain tumors. This study expands upon existing research by examining core neurocognitive processes that may result in reading difficulties in children with treatment-related ototoxicity.

Patients And Methods: Prospectively gathered, serial, neuropsychological and audiology data for 260 children and young adults age 3 to 21 years (mean, 9.

Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1.

Objective: To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1).

Methods: A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8-15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70).

Neuroplastic Response After Radiation Therapy for Pediatric Brain Tumors: A Pilot Study.

Purpose: Clinically effective measurement of cognitive toxicity from photon radiation therapy (XRT) should be accurate, sensitive, and specific. This pilot study tested translational findings on phasic changes in children's memory systems that are sensitive and insensitive to toxic XRT effects to identify a possible neuroplastic effect.

Methods And Materials: Memory processes were prospectively tested before XRT and at 3 later time points up to 2 years in 35 children with mixed primary brain tumors who had not experienced recurrence.

Zebrin II / aldolase C expression in the cerebellum of the western diamondback rattlesnake (Crotalus atrox).

Aldolase C, also known as Zebrin II (ZII), is a glycolytic enzyme that is expressed in cerebellar Purkinje cells of the vertebrate cerebellum. In both mammals and birds, ZII is expressed heterogeneously, such that there are sagittal stripes of Purkinje cells with high ZII expression (ZII+), alternating with stripes of Purkinje cells with little or no expression (ZII-). The patterns of ZII+ and ZII- stripes in the cerebellum of birds and mammals are strikingly similar, suggesting that it may have first evolved in the stem reptiles.

Working memory abilities among children treated for medulloblastoma: parent report and child performance.

Objective: We investigated the 5-year postsurgical developmental trajectory of working memory (WM) in children with medulloblastoma using parent and performance-based measures.

Method: This study included 167 patients treated for medulloblastoma. Serial assessments of WM occurred at predetermined time points for 5 years.

Examination of risk factors for intellectual and academic outcomes following treatment for pediatric medulloblastoma.

Background: The aim of this study was to prospectively examine the effects of hearing loss and posterior fossa syndrome (PFS), in addition to age at diagnosis and disease risk status, on change in intellectual and academic outcomes following diagnosis and treatment in a large sample of medulloblastoma patients.

Methods: Data from at least 2 cognitive and academic assessments were available from 165 patients (ages 3-21 years) treated with surgery, risk-adapted craniospinal irradiation, and 4 courses of chemotherapy with stem cell support. Patients underwent serial evaluation of cognitive and academic functioning from baseline up to 5 years post diagnosis.

Processing speed, attention, and working memory after treatment for medulloblastoma: an international, prospective, and longitudinal study.

Purpose: The current study prospectively examined processing speed (PS), broad attention (BA), and working memory (WM) ability of patients diagnosed with medulloblastoma over a 5-year period.

Patients And Methods: The study included 126 patients, ages 3 to 21 years at diagnosis, enrolled onto a collaborative protocol for medulloblastoma. Patients were treated with postsurgical risk-adapted craniospinal irradiation (n = 36 high risk [HR]; n = 90 average risk) followed by four cycles of high-dose chemotherapy with stem-cell support.

Neural substrates for heightened anxiety in children with brain tumors.

This study investigated anxiety symptoms' associations with cognitive functioning and tumor locus in pediatric brain tumor patients. Data from 91 patients were collected as part of a neuropsychological assessment. Significant relationships were found between anxiety symptoms and mental set shifting (Wisconsin Card Sorting).

Parent-reported social outcomes after treatment for pediatric embryonal tumors: a prospective longitudinal study.

Purpose: To examine longitudinal parent-reported social outcomes for children treated for pediatric embryonal brain tumors.

Patients And Methods: Patients (N=220) were enrolled onto a multisite clinical treatment protocol. Parents completed the Child Behavior Checklist/6-18 at the time of their child's diagnosis and yearly thereafter.

Phase measurement of cognitive impairment specific to radiotherapy.

Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs.

Brain region white matter associations with visual selective attention.

To understand how normal variations in white matter relate to cognition, magnetization transfer imaging ratios (MTR) of a hypothesized neural network were associated with a test of visual selective attention (VST). Healthy adults (N = 16) without abnormal signal on brain scans viewed a version of DeSchepper and Treisman's test of VST (1996) with two levels of processing (novel shape matching with and without distractors, contingency feedback). A hypothesized neural network and component regions was significantly associated with accuracy and response times when distractors were present, with betas predicting 55% of variance in accuracy, and 59% of response times.

Mechanisms of compartmental purkinje cell death and survival in the lurcher mutant mouse.

The Lurcher mutant mouse is characterized by its ataxic gait and loss of cerebellar Purkinje cells and their afferents, granule cells and olivary neurons, during the first weeks of postnatal development. For the 50 years since its discovery, the heterozygous Lurcher mutant has served as an important model system for studying neuron-target interactions in the developing cerebellum and cerebellar function. The identification of the Lurcher (Lc) gene over 10 years ago as a gain-of-function mutation in the δ2 glutamate receptor (GluRδ2) led to extensive studies of cell death mechanisms in the Lc/+ cerebellum.

Tumor locus moderates anxiety symptoms in a pediatric neuro-oncologic sample.

Despite the prevalence of pediatric Central Nervous System (CNS) solid tumors, little is understood about patients' disease-related anxiety experience. Data from 25 remitted pediatric CNS tumor patients posttreatment were collected. Significant symptoms of anxiety were reported by 32% of patients.

Development of Hsp25 expression compartments is not constrained by Purkinje cell defects in the Lurcher mouse mutant.

Four transverse zones can be distinguished in the adult mouse cerebellar cortex based on differential expression of cell-specific antigens, termination patterns of mossy fiber afferents, and phenotypes of mouse mutants with cerebellar defects: the anterior zone (AZ), central zone (CZ), posterior zone (PZ), and nodular zone (NZ). In the heterozygous Lurcher (Lc/+) mouse a zonally restricted abnormality in Purkinje cell development is seen. The Purkinje cell-specific antigen zebrin II is normally differentially expressed in all four zones of the adult cerebellum, but in the Lc/+ mutant is confined to the PZ and NZ, caudal to a transverse boundary in the dorsal aspect of lobule VIII.

MRI changes due to early-delayed conformal radiotherapy and postsurgical effects in patients with brain tumors.

Purpose: Discernment of radiotherapy (XRT) effects vs. tumor activity is difficult in brain tumor patients during the months after XRT when white matter hyperintensities sometimes emerge. We examined brain scans in XRT-treated vs.

The impact of low-grade brain tumors on verbal fluency performance.

Verbal fluency has traditionally represented left hemispheric function, based on large acquired lesion studies. However, recent functional imaging studies have demonstrated bilateral hemispheric activation during phonemic and semantic word generation tasks. We examined 25 left hemisphere (LH) and 26 right hemisphere (RH) low-grade brain tumor patients on semantic and phonemic fluency.

A critical review of the clinical effects of therapeutic irradiation damage to the brain: the roots of controversy.

We critically examined the damaging affects of therapeutic irradiation by comparing results from cross-disciplinary studies of early- and late-delayed radiotherapy effects. Focus is attained by concentrating on clinical treatment issues (volume of brain, dose, timing of effects, age, modality types, and stereotactic treatment techniques), rather than on methodological means or problems, which is necessary to understand the mechanisms and characteristics of radiotherapy-induced behavioral dysfunction including cognition. We make observations and hypotheses about the actual risks from radiotherapy that could be informative in the treatment decision process, and which may lessen the concerns of some patients and their families about the risks they take when receiving radiation.

Age-related, regional, hemispheric, and medial-lateral differences in myelin integrity in vivo in the normal adult brain.

Background And Purpose: Clinical validation of magnetization transfer (MT) imaging is important for investigating clinical disease and organization of normal brain function. We determined whether an in vivo quantitative measure sensitive to white matter is distributed in functionally important ways.

Methods: Axial 1.

The impact of frontal and non-frontal brain tumor lesions on Wisconsin Card Sorting Test performance.

Several lesion and imaging studies have suggested that the Wisconsin Card Sorting Test (WCST) is a measure of executive dysfunction. However, some studies have reported that this measure has poor anatomical specificity because patients with either frontal or non-frontal focal lesions exhibit similar performance. This study examined 25 frontal, 20 non-frontal low-grade brain tumor patients, and 63 normal controls (NC) on the WCST.

The impact of left and right intracranial tumors on picture and word recognition memory.

This study investigated the effects of left and right intracranial tumors on picture and word recognition memory. We hypothesized that left hemispheric (LH) patients would exhibit greater word recognition memory impairment than right hemispheric (RH) patients, with no significant hemispheric group picture recognition memory differences. The LH patient group obtained a significantly slower mean picture recognition reaction time than the RH group.

Attention in adult intracranial tumors patients.

This study investigated the neuropsychological effects of intracranial tumors on attention, prior to irradiation and chemotherapy. Subjects (n = 55) being treated for low-grade, supratentorial brain tumors were administered tests of attention and working memory. We divided the tumor patients into a "superficial" regional group (e.

The predictive value of longitudinal neuropsychologic assessment in the early detection of brain tumor recurrence.

Background: Neuropsychologic tests are widely used to predict the course of progressive neurologic diseases, and recent research has demonstrated the specificity of cognitive measures, even in relatively diffuse diseases. However, the cognitive effects of brain tumors of similar histology and location are known to be highly variable. The authors used the specificity of cognitive function principle to compare two models for the early detection of low-grade brain tumor recurrence prior to detection with clinically scheduled neuroimaging.