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. 2012 Jun;14(Suppl 1):i111–i115. doi: 10.1093/neuonc/nos103

NEUROPSYCHOLOGY

PMCID: PMC3483349
Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-01. SHUNT PLACEMENT PREDICTS NEUROCOGNITIVE IMPAIRMENT IN LONG-TERM SURVIVORS OF CNS TUMORS: A REPORT FROM THE ST. JUDE LIFETIME COHORT (SJLIFE)

Tara Brinkman 1, Wei Liu 1, Gregory Armstrong 1, Amar Gajjar 1, Thomas Merchant 1, Cara Kimberg 1, Larry Kun 1, Deo Kumar Srivastava 1, James Gurney 1, Leslie Robison 1, Melissa Hudson 1, Kevin Krull 1

Abstract

BACKGROUND: Ventriculoperitonal shunt placement has been identified as a risk factor for poor neurocognitive outcomes; yet the specific contribution of shunt placement on long-term outcomes has not been investigated in a large number of adult survivors of pediatric brain tumors. METHODS: Neurocognitive functions were evaluated in 130 adult survivors of pediatric brain tumors (50 shunt and 80 without shunt, mean [SD] current age = 27.4 years [5.2], age at diagnosis = 8.6 years [4.6], and time since diagnosis = 18.8 years [4.8]) participating in the SJLIFE long-term follow-up protocol. Age-adjusted standard scores for neurocognitive measures were calculated, with clinical impairment defined as scores <10th percentile. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression models to examine associations between neurocognitive impairment and treatment variables. RESULTS: Fifty-two percent of survivors with a history of shunt placement had impaired global intelligence compared to 23% without a shunt (p < 0.001), mean IQs of 81.6 and 91.9, respectively. After adjusting for sex, age at diagnosis, tumor location (infratentorial/supratentorial), and cranial radiation therapy (yes/no), shunt placement was associated with impaired performance on tasks of focused attention (OR = 3.50, 95% CI = 1.50-8.16), cognitive fluency (OR = 2.68, 95% CI = 1.21-5.93), short-term memory (OR = 6.99, 95% CI = 2.30-21.2), working memory (OR = 3.69, 95% CI = 1.20-11.3), long-term memory (OR = 2.85, 95% CI = 1.31-6.19), and processing speed (OR = 4.10, 95% CI = 1.63-10.3). Shunt placement was also associated with impaired performance on measures of reading (OR = 4.21, 95% CI = 1.50-11.8) and math (OR = 2.78, 95% CI = 1.15-6.69). Demographics and length of follow-up did not differ by shunt placement (all p-values >0.1). CONCLUSIONS: Placement of a ventriculoperitonal shunt was associated with long-term neurocognitive impairment, independent of established risk factors including cranial radiation therapy and younger age at diagnosis. To further examine the impact of shunt placement on neurocognitive functioning, future studies will examine factors including number of shunt revisions/infections and degree of hydrocephalus.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-02. A PILOT STUDY EVALUATING LONG-TERM IMPACT OF POSTERIOR FOSSA SYNDROME ON QUALITY OF LIFE IN SURVIVORS OF CHILDHOOD MEDULLOBLASTOMA

Jeffrey Rubens 1, Rishi R Lulla 1, Jin-Shei Lai 2, Jason Fangusaro 1

Abstract

INTRODUCTION: Posterior fossa syndrome (PFS) after resection of childhood medulloblastoma (MB) results in significant long-term complications including speech difficulties, intellectual delays and learning disabilities. Few studies have considered the impact of PFS on quality of life (QOL) among survivors of childhood MB. METHODS: Survivors of childhood MB (≥ 8 years of age) with and without evidence of PFS were enrolled and administered a Pediatric Neuro-QOL measurement system (pedsNeuro-QOL). The survey is optimized for pediatric patients with neurological conditions and measures patients' perception of their QOL in 7 domains (anxiety, depression, anger, friendships, fatigue, pain, and stigma). Survey results for patients with PFS were compared to risk-matched controls without PFS. Additionally, we performed a retrospective analysis assessing patients' long-term neurologic impairments as documented by clinicians in survivors of MB with and without PFS treated at our institution between 1990 and 2010. RESULTS: Four patients with PFS and 4 controls completed the pedsNeuro-QOL. There were no significant differences in QOL in any of the 7 domains. In selected domains (friendships, anger and depression) there was a trend toward improved QOL in the patients with PFS (p = 0.059; 0.24; 0.27 respectively). Our retrospective analysis identified 38 survivors of MB (15 with PFS and 23 without PFS) with follow-up a median of 49.6 months after their initial surgery. Patients with PFS had significantly lower performance scores (p < 0.01), a greater number of documented neurologic abnormalities (p < 0.01) and required more rehabilitative services (p < 0.01). CONCLUSION: Our results suggest that there are no significant differences in perceived QOL in survivors of childhood MB with PFS as compared to those without PFS despite significant persistent neurologic impairment. Prospective studies on additional patients as well as evaluation of parental perception of QOL are required to more completely understand the impact of PFS on patient's QOL.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-03. AN fMRI INVESTIGATION OF WORKING MEMORY AND ITS RELATIONSHIP WITH CARDIORESPIRATORY FITNESS IN PEDIATRIC POSTERIOR FOSSA TUMOR SURVIVORS

Kelly Wolfe 1, Avi Madan-Swain 1, Alyssa Reddy 1, Gary Hunter 1, James Banos 1, Rajesh Kana 1

Abstract

INTRODUCTION: Posterior fossa tumors are the most common brain tumors in children. As multimodal treatment has greatly increased survival rates, morbidities in survivorship have become increasingly important, particularly deficits in executive functions (e.g., working memory). Attempts to address these deficits through cognitive and pharmacological intervention have yielded mixed results. A relationship between cardiorespiratory fitness and better cognitive skills has been shown in aging adults, young adults, adolescents, and children. This suggests exercise as an as-yet-unexplored potential intervention for working memory deficits in survivors of pediatric brain tumor. METHODS: Ten survivors of pediatric posterior fossa tumor, age 11-18 years, at least 2 years off-treatment, with IQ > 70, who received cranial irradiation, were recruited from Children's Hospital of Alabama. Caregivers completed demographic and executive function questionnaires. Subjects completed a working memory task during a functional MRI scan, and cardiorespiratory fitness testing on a cycle ergometer. Data were analyzed using SPSS and statistical parametric mapping. RESULTS: Neuroimaging findings indicated normal activation patterns specific to working memory: frontal-parietal connections among right inferior frontal gyrus, supplementary motor areas, bilateral insula, bilateral inferior parietal lobule, and right middle occipital gyrus. More efficient neural functioning was related to higher cardiorespiratory fitness across indices of behavioral performance (reaction time), parent-report executive functions, neural activation (voxel counts, percent signal change), and functional connectivity. CONCLUSIONS: This is the first study to utilize fMRI techniques to study neural activation patterns in response to a working memory task in pediatric brain tumor survivors. We provide insight into the brain regions recruited for working memory, an area of commonly-noted deficits in these survivors, which can be used in future studies as targets for intervention or as indicators of treatment efficacy. In addition, we provide preliminary evidence that exercise may be an effective intervention for working memory deficits in pediatric brain tumor survivors.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-04. NEUROPSYCHOLOGICAL OUTCOME IN PEDIATRIC BRAIN TUMOR PATIENTS: FIRST RESULTS FOR PATIENTS OLDER THAN 4 YEARS TREATED WITHIN THE HIT 2000 TRIAL

Anika Resch 1, Katja von Hoff 1, André O von Büren 1, Carsten Friedrich 1, Wiebke Treulieb 1, Christine Lindow 1, Robert Kwiecien 2, Holger Ottensmeier 3, Stefan Rutkowski 1

Abstract

PURPOSE: Brain tumour patients are at high risk to develop treatment related neuropsychological impairments. Knowing the severity of neuropsychological impairments is important for the individual care of the patient and for the design of future trials. PATIENTS AND METHODS: Patients aged 4 years and older at diagnosis with malignant brain tumours (medulloblastoma/ependymoma/CNS-PNET) treated within the multicenter HIT 2000 study were tested in a cross-sectional study with the neuropsychological basic diagnostic tool including the matrices by Raven (fluid intelligence), the “Developmental Test of Visual-Motor-Integration” (visual-spatial processing), K-ABC Number Recall (short term memory), a vocabulary test (i.e. K-ABC riddle, HAWIK IV, WIE; crystallized intelligence), the “Purdue Pegboard”(fine motor skills) and the “Continuous Performance test-short version” (cognitive processing speed). Total average testing time was 1 hour. After the test, a semi-structured interview was conducted with patients and parents. RESULTS: Between 2007 and 2011 192 patients without tumour recurrence (male, n = 118) from 47 centers were tested. Median age at diagnosis was 8.8 years (range, 4-17.7 years). Median time to test was 5.4 years since diagnosis (range, 1.5-10.1 years). Histopathological diagnoses included medulloblastoma (n = 140, 49 metastatic), CNS-PNET (n = 13) and ependymoma (n = 39). Mean scores for fluid intelligence according to therapy group were: ependymoma 97 (±14), CNS-PNET 88 (±20), non-metastatic medulloblastoma 89 (±17), metastatic medulloblastoma 86 (±21). Therapy group also influenced short term memory and fine motor skills. In this cross-sectional study there was no association of age at diagnosis and neuropsychological outcome. In the interviews, 23% of parents reported that their child attends a special school, 32% of adult patients were engaged in special occupations. CONCLUSIONS: The basic diagnostic tool can be used as a direct screening tool in a multicenter setting. Longitudinal follow-up examinations are ongoing. Supported by Fördergemeinschaft Kinderkrebszentrum Hamburg e.V.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-05. LONGITUDINAL PHASE MEASUREMENT OF RADIATION-SPECIFIC COGNITIVE IMPAIRMENT IN CHILDREN WITH BRAIN TUMORS

Carol L Armstrong 1, Peter C Phillips 1, Robert A Lustig 2, Cynthia Stamos 1, Yimei Li 1, Jean Belasco 1, Jane E Minturn 1, Michael J Fisher 1

Abstract

The late cognitive effects of therapeutic irradiation (XRT) in children have been predominantly measured as IQ. However, a consensus in the adult literature is that it is critical to measure memory function, as memory and the hippocampus are selectively vulnerable to the late effects. There is a thrust by the NIH to transfer adult therapeutics to pediatrics, and thus the impetus for the current study. Children with primary brain tumors (n = 35) who received involved field and/or cranial XRT were prospectively tested four times from baseline (pre-XRT) to two years with tests of memory shown in longitudinal adult studies to be most sensitive to late phasic effects of XRT. The mean/median age at baseline was 10 years. Secondary analyses examined possible differential memory patterns between patients receiving dose to the cerebellum or posterior fossa (CB/PF; n = 14) versus supratentorial loci (n = 21). A mixed model included longitudinal pattern, individual random effects, age, and locus of treatment. Tests were visual memory (immediate and delayed recall), verbal memory (learning, post-interference retrieval, delayed retrieval), and a classic hippocampal paradigm of visual recognition. Patients' decline in memory retrieval (but not learning) was not followed by recovery as in adults, but this was not significant (p = 0.183). When treatment fields were analyzed separately, results were significant in the CB/PF group (p < 0.05), while supratentorial patients showed an earlier non-significant recovery (consistent with adults). Visual memory was insensitive to XRT, consistent with adults. Recognition memory changed significantly over time, with improving accuracy concurrent with slowing of recognition. Tests of cognition that are linked with the mechanisms of radiation damage to neural structures can be used effectively in children. Phasic patterns were similar to adults except that children with XRT to the CB/PF had a more protracted recovery, and all children showed greater slowing of memory process over time.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-06. COGNITIVE FUNCTIONING IN CHILDREN WITH CANCER BEFORE AND AFTER MEDICAL INTERVENTION

Theda Heinks-Maldonado 1, Kevin Wingeier 1, Vanda Lory 1, Christina Schäfer 1, Martina Studer 1, Maja Steinlin 1, Kurt Leibundgut 2

Abstract

Extensive research has shown that survivors of childhood cancer often demonstrate a consistent pattern of neurocognitive deficits especially when the malignancies and/or the treatments (surgery, chemotherapy, radiation therapy) involve the CNS. Even without CNS involvement negative effects of chemo- and radiation therapy on cognitive functions have been shown in adults. So far mostly children who have been off treatment for one year or longer have been included in studies on cognitive outcome. Few studies have investigated the “baseline” of cognitive abilities before the start of any treatment. In the study presented here all children (ages 4-16; n = 43) hospitalized at the University Children's Hospital Berne for treatment of malignancies underwent their first extensive neuropsychological assessment in the days following initial diagnosis and before start of medical intervention. The second neuropsychological assessment was performed 8 weeks after the end of chemo- and/or radiation therapy. Results show that immediately after diagnosis children with brain tumors show significantly worse performance on tests of learning, long-term memory and attention compared to children with non-CNS malignancies. At this point the two groups did not differ, however, in other cognitive areas (FSIQ, performance speed, executive functions, short-term memory). After the end of medical treatment the differences between the two groups is extending to other cognitive functions. This shows that children with malignancies involving the CNS present with memory and attention deficits even before surgery. Chemo- and/or radiation therapy then further contribute to cognitive decline. Future steps of this study will include implementation and evaluation of a cognitive training program for the affected children.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-07. ATTENTION NETWORKS IN PEDIATRIC BRAIN TUMOR SURVIVORS

Marieke de Ruiter 1, Netteke Schouten 1, Juliette Greidanus 1, Martha Grootenhuis 1, Jaap Oosterlaan 2

Abstract

INTRODUCTION: Pediatric brain tumor survivors (PBTS) are at increased risk of impaired neurocognitive functioning. Attention seems to play an important role in acquiring new knowledge and skills. Posner and Peterson (1990) distinguish three independent attention networks in the brain that enable alerting, orienting, and executive attention, located in the thalamus, parietal lobe and anterior cingulated cortex, respectively. We aim to investigate the functioning of these networks in PBTS. METHODS: A sample of 55 PTBS, aged 8-18 years with attention or memory problems as reported by parents, was compared to a control group of 30 age-matched healthy siblings. Attention abilities were tested using a computerized version of the Attention Network Task (ANT). The ANT contained four types of trials: (1) no cue, (2) neutral cue, (3) orienting cue, and (4) conflicting cue trials. The functioning of the three networks was assessed by contrasting mean hit reaction times (MHRT) on the trial types: trial types (1) and (2) to assess alerting, trial types (2) and (3) to measure orienting, and trial types (3) and (4) to assess executive attention. RESULTS: Mean age of PBTS and healthy siblings did not differ (M = 13.2 and M = 13.6 year, respectively). Mean age at diagnosis of PBTS was 7.1 year. Compared to healthy siblings, PBTS had slower overall MHRT (F(1) = 9.18, P = .003). PBTS performance slowed to a greater extent than performance of healthy siblings on conflicting cue trials compared to orienting cue trials (F(1) = 6.10, P = .016), indicative of poor executive attention. No evidence was found for dysfunction in PBTS on the alerting and orienting networks. CONCLUSION: This is the first study that assessed attention abilities in PBTS distinguishing alerting, orienting, and executive attention. PBTS were shown to have a less efficient executive attention network compared to healthy siblings. Poor attention abilities may underlie the learning difficulties that many PBTS experience.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-08. NEUROPSYCHOLOGICAL ASSESSMENT IN CHILDREN AND ADOLESCENTS TREATED FOR FRONTAL LOBE TUMOURS

Audrey Longaud-Valès A 1, Jacques Grill 1, Stéphanie Puget 2, Christian Sainte-Rose 2, Christelle Dufour 1, Virginie Kieffer 3, Geoerges Dellatolas 4

Abstract

BACKGROUND: Acquired frontal lobe injury in children and adolescents has been mainly explored in traumatic brain injury. There is no available series with tumors. METHOD: Between September 2010 and September 2011, we explored 22 patients aged 8.3-27.1 years, all treated for frontal tumour at Necker Sick Children and/or Gustave Roussy Institute. Mean age at surgery was 8.06, range [0.16-21.9]. Neuropsychological assessment included IQ measure (WISC-IV or WAIS-III), executive function measures (Tower of London, Wisconsin, TMT, BADS), behaviour (BRIEF questionnaire), memory (CMS/MEM-III, Rey figure), attention and working memory tests (Tea-Ch, Mesulam test), gesture imitation (from NEPSY), and theory of mind/social cognition tests (facial emotional recognition test, false belief). Most tests were also performed by 44 age-matched control subjects. School/social situation and rehabilitations were also collected. RESULTS: Educational achievement (from specialized institution to University) and IQ (between 50 and 125) were variable. Classical “executive function” tests discriminate less patients from controls than facial emotional recognition or gesture imitation. Factors associated with overall outcome and specific deficits (type of tumour, treatment, age at surgery, lesion topography, etc.) were analysed. DISCUSSION: This is a first study with comprehensive neuropsychological assessment in a group children/adolescents treated for a tumour involving the frontal lobe. Findings have to be compared with classical studies of frontal lobe lesions in adults.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-09. THE CORRELATION BETWEEN DOSE OF FOLINIC ACID AND NEUROTOXICITY IN CHILDREN AND ADOLESCENTS TREATED FOR OSTEOSARCOMA WITH HIGH DOSE METHOTREXATE (HDMTX): A NEUROPSYCHOLOGICAL AND PSYCHOSOCIAL STUDY

Estie Boneda –Shkedi 1, Myriam Weyl Ben Arush 2, Haim Kaplinsky 3, Shifra Ash 1, Yaakov Goshen 1, Isaac Yaniv 1, Ian J Cohen 1

Abstract

BACKGROUND: This study has been performed to examine currently used doses of folinic acid and to determine the importance of the dose of folinic acid used in preventing subtle neurotoxicity. 30 Osteosarcoma patients were the appropriate population studied since they have no intrinsic neurological involvement. The neuropsychological and psychosocial status was tested in two group of patients treated with similar protocols containing repeated doses of HDMTX but different doses of folinic acid. The patients received 300-600mg/m2 or 120-250mg/m2 folinic acid in their protocols. METHODS: 18 equations of neuropsychological assessment was tested. RESULTS: 11 out of 18 equations in the neuropsychological assessment were found statistically significant, (P < 0.0025) favoring the group treated with high dose of folinic acid. There was no clear results in the psychosocial measures with only a single measure of self esteem (understanding) being significantly higher (p = 0.024) in the group treated with high dose of folinic acid, other measures had no statistical significance. CONCLUSIONS: A correlation between a higher dose of folinic acid after HDMTX and a better neuropsychological status was clearly shown. The doses of folinic acid used in the LFA group 120-250mg/m2 were similar to those used by several groups, some have used even lower doses report and have reported gross neurotoxicity.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-10. GENETIC PREDICTORS OF NEUROCOGNITIVE OUTCOMES IN SURVIVORS OF PEDIATRIC BRAIN TUMORS

Jean Mulcahy Levy 1, Tiffany Tello 2, Xian Lu 3, Dexiang Gao 3, Greta Wilkening 1, Andrew Donson 1, Nicholas Foreman 1, Arthur Liu 2

Abstract

BACKGROUND: There is increasing concern over the neurocognitive deficits that accompany treatment of pediatric brain tumors. A number of clinical factors predicting a risk for neurocognitive deficits have been identified including female gender, younger children and children with hydrocephalus. Unfortunately, there are very few predictive biologic markers. The use of single nucleotide polymorphism (SNP) analysis may be effective in identifying patients at risk for increased treatment toxicity and adverse neurocognitive outcomes. We hypothesize that SNPs in DNA repair genes will predict poor neurocognitive outcomes in children treated with radiation therapy for brain tumors. METHODS: 1048 SNP representing 59 DNA repair genes were evaluated by Human 660W-Quad v1.0 DNA BeadChip analysis (Illumina) in 41 subjects. IQ testing was measured by Wechler Intelligence Scale. Patients had no known neurocognitive deficits prior to initial diagnosis. Fisher's exact tests were used to evaluate the association between dichotomous IQ scores (high IQ: >= 90; low IQ: <90) and identified genotypes. P < 0.05 was considered statistically significant. RESULTS: Twenty-one patients had high IQ and 19 had low IQ. Patients were well matched for gender, age at diagnosis, diagnosis, tumor location, and treatment. Fifteen SNPs had genotypes significantly associated with increased odds of having a low IQ. Identified SNPs were associated with the following genes: BRIP1, BLM, ERCC4, ERCC5, ESR1, FANCA, FANCC, LIG4, RAD51B, XRCC3. CONCLUSIONS: This study suggests SNPs in these genes could be predictive for adverse neurocognitive outcomes in patients treated with radiation for a pediatric brain tumor. Identifying patients with the highest risk of neurocognitive toxicity would help to stratify patients to determine a radiation dose. It would also allow for identification of children who should be intensively followed for academic interventions at an earlier stage to prevent school delays.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-11. SPECIFIC BEHAVIORS IN DIFFERENT LOCALIZATIONS OF BRAIN TUMORS. ORGANIC NEUROPSYCHOLOGICAL CONSEQUENCES OR BEHAVIORAL PHENOTYPE?

Justyna Korzeniewska 1, Bozenna Dembowska Baginska 1, Danuta Perek 1

Abstract

BACKGROUND: Neuropsychological problems are commonly observed in childhood brain tumors survivors. Psychological functions are strictly connected with brain structures and symptomatology of brain tumors. AIM: The aim of the study was to describe behavioral phenotype of different brain tumors and attempt to explain the link between tumor and characteristic pattern of motor, cognitive, linguistic, emotional and social function. MATERIAL AND METHODS: Full psychological outcome in 350 pts was performed. Age at psychological diagnosis ranged from 2 to 26 years. We looked for broad spectrum of coexisting symptoms of brain damage. We also studied the specificity and dynamic of symptoms and to identified the mechanism of dysfunction. Organic damage, effects of treatment and hormone disturbances were analyzed. All hypotheses are reasonable but not sufficient to explain this phenomenon. RESULTS: In our patients we observed strong relation between particular tumor (location and tumor type) and cognitive problems, emotional functioning, behavior disturbances as well as psychological problems. It is more than just neuropsychological consequences of brain damage, it is closer to behavioral phenotype concept. Observation and repeated psychological testing showed specific physical, cognitive and affective problems strongly associated with particular brain tumors. Among others: GCT (55 pts) – emotional disturbances, depressed mood, decreased psychomotor activity; MB (100 pts) – emotional rigidity, slowness, interpersonal withdrawal; deep structures of right hemisphere (10 pts) – sensory integration problems, transitions difficulties and problems in making decisions connected with oppositional behavior. SUMMARY: The research allowed to put hypothesis about the probable causes and mechanisms of injury and decomposition of psychological functioning. Also it may be an important voice in the debate on behavioral phenotype and emotional brain. The project supported by grant NR13001106/2009, Ministry of Science, Poland

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-12. GAIT CHARACTERISTICS AND VISUO-SPATIAL SKILLS OF PATIENTS WITH POSTERIOR FOSSA TUMOR (PFT)

Susanna Staccioli 1, Daniela Chieffo 1, Maurizio Petrarca 1

Abstract

OBJECTIVE: The aim of this study is to analyze the link between gait characteristics and visuo-perceptual and visuo-spatial skills in children with PFT after surgery. METHODS: Seven patients (mean age 11.67 ± 1.89, M = 4, F = 3) with PFT (3 with Pylocitic Astrocitoma and 4 with Medulloblastoma) after surgery (1-3 months) were enrolled. All patients underwent to a neurological examination and an orthoptic evaluation. Gait analysis was assessed by an optoelectronic system having 8 cameras and two force plates. An EMG surface was administrated by a wireless system. A comprehensive neuropsychological evaluation was performed (visuo-spatial, visual-perceptual, attention). RESULTS: Gait analysis revealed reduction of gait velocities in children with PFT, with reduction of stride length, and preserved stride time (0.84 ± 0.37m/s, 1.14 ± 0.11m/s; 0.83 ± 0.3m, 1.16 ± 0.12m; 1.09 ± 0.32s, 1.03 ± 0.070s for PFT and healthy children, respectively). Kinematics analysis showed reduction of hip extension, increased knee flexion and increased dorsi-flexion of the ankle, highlighting in late stance a reduction of extensor moment of the knee and of ankle dorsal moment. EMG data showed co-contraction activity of the tibialis anterior and the triceps during late swing, increasing until the load response phase. During neurological examination all patients presented ataxia. Six patients out of eight presented abnormal orthoptic evaluation: ocular motility (5), nystagmus (4), acuity (4). IQ was normal in all patients. Specific neuropsychological disorders were observed. All patients reported visuo-spatial problems and a praxia imagery function. Visual perception abilities were abnormal in eight out of nine patients. CONCLUSION: Gait analysis, never been used in children with brain tumors before, represents an innovative outcome measure according to functional scales. Our results highlight the existence of abnormal internal representation of movement in children with PFT related to the link between motor impairment and visual spatial representation, not depending only on ataxia but also on dysfunction of movement imagination/prediction and praxia abilities.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-13. NEUROCOGNITIVE OUTCOME AS A FUNCTION OF GENOMIC SUBGROUP IN MEDULLOBLASTOMA PATIENTS

Iska Moxon-Emre 1, Michael Taylor 1, Eric Bouffet 1, David Malkin 1, Cynthia Hawkins 1, Nadia Scantlebury 1, Donald Mabbott 1

Abstract

BACKGROUND: Medulloblastoma is the most common malignant central nervous system (CNS) tumor in childhood. The craniospinal radiation (CSR) required to treat this disease results in long-term cognitive and neurologic impairments. Medulloblastoma has been categorized into four distinct genetic subgroups (Wnt, Shh, Group 3, and Group 4) that differ in demographic and clinical features. METHODS: Tumors from thirty-eight patients were classified based on RNA-nanostring; Wnt (n = 4; Age at diagnosis = 9.1 yrs), Shh (n = 6; 8.11 years), Group 3 (n = 11; 6.2 years), Group 4 (n = 17; 6.85 years). Serial neuro-cognitive assessment was conducted for all patients as standard of care. Mean time from first to last assessment was: Wnt = 0.45 yrs, Shh = 0.63 yrs, Group 3 = 2.25 yrs, and Group 4 =3.76 yrs. Change over time in intelligence scores was evaluated using growth curve analyses. RESULTS: For the sample of 38 patients, full scale IQ (FSIQ) was 85 at baseline and declined by 1.5 points per year over the modeled time period, p < .01. Based on qualitative evaluation, Shh and Group 3 patients presented with the highest FSIQ and experienced the most dramatic declines, while Wnt patients presented with the lowest FSIQ but experienced minimal decline. Group 4 patients fell in the middle of these two profiles. Similar patterns in verbal comprehension and working memory were observed. Only Group 3 and 4 patients showed declines in information processing speed. CONCLUSIONS: Medulloblastoma subgroups appear to have heterogeneous neurocognitive profiles. We are currently subgrouping 30 additional patients for whom we have neuro-cognitive data. Our plan is to compare the profiles of patients treated with standard vs. reduced dose CSR as a function of genetic subgroup. Such information is critical for informing the development of new protocols targeted at specific subgroups - where radiation may be reduced or removed altogether.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-14. AN EXERCISE PROGRAM TARGETED AT NEURO-RECOVERY IN PEDIATRIC BRAIN TUMOUR SURVIVORS TREATED WITH CRANIAL RADIATION

Todd Cunningham 1, Eric Bouffet 1, Nadia Scantlebury 1, Janine Piscione 1, Deirdre Igoe 1, Melanie Orfus 1, Ute Bartels 1, Suzanne Laughlin 1, Uri Tabori 1, Donald Mabbott 1

Abstract

BACKGROUND: Cranial radiation is associated with significant neurotoxicity, including white matter damage, disrupted hippocampal neurogenesis, and cognitive morbidity. Animal and human studies have shown that physical exercise can help the brain to recover from injury by fostering maturation and recruitment of cells from the endogenous neural stem cell compartment. We carried out a structured exercise program as a feasibility study to determine whether increases in cardio-respiratory fitness result in neural recovery in paediatric brain tumor patients treated with cranial radiation. METHODS: The exercise program consisted of three 1-hour sessions of aerobic games/activities per week, for a total of 12 weeks. Physical fitness (distance walked in 6 minutes), neuro-cognitive function, and neuro-imaging were assessed prior to and following the intervention. To date, 9 patients (7 exercise participants and 2 waitlist controls) have been evaluated. Participants were between 8.0 and 16.4 years old with a prior diagnosis of a hemispheric or posterior fossa brain tumour and treated with cranial spinal or focal radiation. RESULTS: The compliance rate of 90% suggested that children treated with cranial radiation are willing to participate in a regularly-scheduled exercise program. With one exception, all participants increased their 6-minute walk distances, with increases ranging between 11% and 49%. Cognitive scores of participants showed a pattern of stability and gain as opposed to decline over time. In particular, declarative memory measures showed improvement upon program completion. This finding is supported by imaging data that show an increase in hippocampal volume after participating in the exercise program, which was not seen in the waitlist controls. CONCLUSION: These preliminary data suggest that increased physical fitness following exercise may be associated with improved neuro-cognitive performance and neuro-recovery. We see this study as a first step toward development of an intervention program to remediate the long-term effects of cranial radiation.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-15. FEASIBILITY OF HOME-BASED COMPUTERIZED COGNITIVE TRAINING FOR CHILDREN WITH CENTRAL NERVOUS SYSTEM-IMPACTING CANCER

Kristina Hardy 1, Bonnie Carlson-Green 1, Heather Conklin 1

Abstract

OBJECTIVE: Neurocognitive sequelae among survivors of pediatric central nervous system (CNS)-impacting cancer are prevalent and impairing. Empirically-supported treatment approaches including pharmacotherapy and cognitive rehabilitation are promising, but are associated with limitations due to medical contraindications, limited availability, and high resource utilization. As such, there is a critical need for additional interventions to mitigate deficits in this population. Home-based computerized cognitive training (CT) is a novel approach that has shown efficacy in improving working memory in children with attention disorders and localized brain injury. The feasibility of this approach is currently being examined through several studies, including children both on and off treatment. METHODS: Data from six completed and ongoing studies at three institutions will be presented. Four studies focus on CT with children and adolescents exhibiting neurocognitive deficits in the survivorship period, and two are examining the feasibility of using CT shortly after diagnosis, before specific deficits emerge. All trials have utilized the Cogmed training program, a computerized intervention which targets visual and verbal working memory skills with repeated practice of success-adapted trials. Compliance statistics (e.g., time spent training) are tracked automatically by the program. In our trials, participants were asked to complete at least 25 training sessions (lasting approximately 30 minutes each) at home over a 2-3 month time period. RESULTS AND CONCLUSIONS: To date, 74 survivors and 10 on-therapy patients aged 6-18 have been enrolled across studies. Nearly 85% of enrolled survivors have completed at least 25 training sessions, and satisfaction associated with the intervention is high among families. In contrast, compliance among participants in the on-treatment studies is lower (60%). Based on these preliminary trials, it appears that home-based computerized CT for children with CNS-impacting cancer is feasible, particularly during the off-therapy period. Barriers to compliance and issues associated with evaluating treatment efficacy will be discussed.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-16. SLOWED BRAIN RHYTHMICITY PREDICTS NEUROPSYCHOLOGICAL IMPAIRMENT IN CHILDREN TREATED WITH CRANIAL-SPINAL RADIATION FOR BRAIN TUMOURS

Colleen Dockstader 1, Eric Bouffet 1, Frank Wang 1, Donald Mabbott 1

Abstract

INTRODUCTION: Children treated with cranial-spinal radiation (CSR) for brain tumours of the posterior fossa (PF) exhibit slowed information processing speed. However, the neuropathology underlying this neurocognitive deficit is currently unknown. The speed of cortical rhythms during resting state can predict neuropsychological task performance in other clinical populations. Therefore, we performed a power analysis of cortical brain rhythms, classified by the speed of their oscillations, in children treated with CSR for malignant brain tumours of the PF and healthy controls during resting state. We asked whether resting state measures would predict performance on neuropsychological tests of processing speed. MATERIALS AND METHODS: Neuromagnetic activity was recorded using a whole-head 151-channel CTF Magnetoencephalography (MEG) system. MEG recordings were obtained from 20 patients) and 19 matched controls during three minutes of eyes-open, at rest. Relative power of brain rhythmicity during rest was calculated for the delta (0.5-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-29 Hz), and lower (30-59 Hz) and higher (60-100 Hz) gamma frequency bandwidths. MEG indices were regressed onto composite index scores of neurocognitive function (WISC composite scores of processing speed, verbal comprehension, working memory, and perceptual reasoning). RESULTS: Patients exhibited significantly more slow-wave activity (theta waves) compared to healthy controls which was observed diffusely across the brain (p < 0.05). This increase predicted overall scores of processing speed in patients (r = -0.59, p < 0.05). There were no significant group differences in any other bandwidth. Nor did power within any other bandwidth predict performance on any other measures. CONCLUSION: Children treated with CSR for brain tumours exhibit significantly more slow cortical rhythms during resting state than healthy control children. This cortical slowing specifically predicts impaired information processing speed. Widespread changes in the strength and spatial organization of slow-wave cortical activities may underlie cognitive dysfunction in these patients.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-17. REDUCED WHITE MATTER INTEGRITY PREDICTS SLOWED BRAIN RHYTHMICITY IN CHILDREN TREATED WITH CRANIAL RADIATION FOR BRAIN TUMOURS

Stefan Bostan 1, Colleen Dockstader 1, Nadia Scantlebury 1, Eric Bouffet 1, Fang Liu 1, Frank Wang 1, Donald Mabbott 1

Abstract

INTRODUCTION: Children treated with cranial-spinal radiation (CSR) for brain tumours exhibit reduced white matter integrity in several brain regions following treatment. These children demonstrate a wide variety of cognitive impairments including slowed response times on visual-motor tasks. How white matter damage impedes neuronal function which ultimately leads to cognitive deficits is not yet known. We collected functional and structural data from children treated with CSR for brain tumours while they were at rest and also while they performed a visual-motor task. We asked whether Diffusion Tensor Imaging (DTI) measures of white matter integrity would predict measures of functional brain activity in these children. MATERIALS AND METHODS: Neuromagnetic activity was recorded from 10 patients treated with CSR for Posterior Fossa tumours using Magnetoencephalography (MEG) for two conditions: 1) at rest and 2) during visual-motor performance. Power of cortical rhythms was calculated for multiple frequency bandwidths during rest. Both strength and power of the visual and motor responses during visual-motor performance were calculated. DTI Tractography was conducted for the right Inferior Frontal Occipital Fasciculus (IFOF), a prominent tract implicated in visual-motor performance. We performed a regression analysis relating functional brain measures (speed, strength) to white matter integrity [fractional anisotropy (FA)] of the rIFOF. RESULTS: Reduced FA of the rIFOF predicted slower response times of the primary motor cortex (r = -0.57, p < 0.05) as well as slower cortical activities during resting state [increases in slow-wave, theta power (4-7 Hz)] (r = 0.75, p < 0.01). FA of the rIFOF did not predict any other MEG measures. CONCLUSION: Children treated with CSR for brain tumours show a predictive relationship between reduced rIFOF white matter integrity and slowed cortical rhythms at rest and during visual-motor performance. These predominant slow-wave motor activities may underlie impaired visual-motor performance in these patients.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-18. CHANGES IN BRAIN ACTIVITY AMONG CHILDHOOD CANCER SURVIVORS PARTICIPATING IN A COGNITIVE REMEDIATION PROGRAM

Ping Zou 1, Yimei Li 1, Heather M Conklin 1, Raymond K Mulhern 1, Robert W Butler 2, Robert J Ogg 1

Abstract

INTRODUCTION: Increased under-standing of cognitive remediation is needed to guide development of intervention strategies for childhood cancer survivors experiencing cognitive late effects. We conducted a pilot functional magnetic resonance imaging (fMRI) study to identify neural correlates of baseline attentions deficits and response to intervention in childhood cancer survivors who participated in the Cognitive Remediation Program (CRP) clinical trial. METHODS: The IRB-approved study included survivors of leukemia and brain tumor, aged 12.02 ± 0.09 years. Functional MRI in survivors was performed at 3 time points (baseline, CRP completion, and 6 months after CRP completion). The fMRI task was a continuous performance test (CPT) with visually presented single letter stimuli. Additionally, 28 age-matched healthy children (mean 12.7 ± 0.6 years) participated in the fMRI study as controls. RESULTS: Left and right ventral visual areas, left and right cerebellum, supplementary motor area, and left inferior frontal cortex were activated in healthy participants during the CPT task. In survivors, brain activation in these regions was diminished at baseline; then increased in some regions upon CRP completion and 6 months later. The fMRI activation index for each region of interest was inversely associated with the CPT clinical index (r ranged from -0.3 to -0.47, p < 0.01). CONCLUSIONS: Functional MRI is sensitive to changes in brain activation related to disease, therapy, and behavioral remediation in leukemia and brain tumor survivors. Changes in patterns of brain activity detected with fMRI were associated with performance improvements following CRP. Functional neuroimaging will be useful to identify target neural systems for remedial interventions, to identify patients most likely to benefit from a given intervention, and to evaluate the efficacy and mechanisms of action of interventions to improve brain function in the growing population of pediatric cancer survivors.

Neuro Oncol. 2012 Jun;14(Suppl 1):i111–i115.

NP-19. NEUROCOGNITIVE PREDICTORS OF ADAPTIVE FUNCTIONING IN CHILDREN/ADOLESCENTS TREATED FOR MEDULLOBLASTOMA

Tanya Diver 1, Peter' Manley 2, Mark Kieran 2, Christine Chordas 2, Cori Liptak 2, Brian Delaney 2, Sarah Brand 2, Celiane Rey-Casserly 1

Abstract

PURPOSE: To examine the predictive utility of neuropsychological measures beyond overall intellectual functioning in determining adaptive behavior in individuals who have been treated for childhood medulloblastoma. PATIENTS AND METHODS: Institutional Review Board approved retrospective study of neurocognitive and adaptive functioning in children diagnosed with medulloblastoma between 1986 and 2008 and followed clinically at DFCI/CHB. Seventy-six individuals (57% male) had completed neuropsychological assessment; the most recent evaluation was used for those with multiple assessments. Median age at assessment was 12.3 years. Children who did not receive CSI were excluded. Psychological measures examining intelligence (age appropriate Wechsler Scale), adaptive functioning (parent completed Adaptive Behavior Assessment System - Second Edition or Scales of Independent Behavior - Revised), memory (Children's/Wechsler Memory Scale; California Verbal Learning Test), executive functioning (parent completed Behavior Rating Inventory of Executive Function) and attentional processes (Conners' Continuous Performance Test) were evaluated. RESULTS: Hierarchical regression analyses performed. In the full overall model, Full Scale IQ and Behavioral Regulation and Metacognitive Indices from the BRIEF accounted for 46% of the variance in overall adaptive score, F(3,44 = 12.44, p < .001. The Full Scale IQ accounted for 32.5% of the variance in adaptive score, F(1,46) = 22.19, p < .001. The BRIEF Indices accounted for 13.3% of the unique variance in adaptive score, beyond the effects of IQ, F(2,44) = 5.43, p < .01. Of the BRIEF Indices, the Metacognitive Index contributed significant unique variance, β = -.827, p < .01. The regression equations for verbal memory and attentional processes were not significant. CONCLUSIONS: The BRIEF holds some promise in its predictive utility over IQ in determining overall adaptive scores. Clearly further research is necessary to identify additional factors that contribute to adaptive behavior to promote overall functioning and adjustment in survivors. Efforts might then focus on how to best intervene prophylactically.

Articles from Neuro-Oncology are provided here courtesy of Society for Neuro-Oncology and Oxford University Press

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