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1.
J Clin Oncol ; 37(18): 1566-1575, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31046551

RESUMO

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, 9.15 years) enrolled in a multisite research and treatment protocol, which included surgery, risk-adapted craniospinal irradiation (average risk, n = 186; high risk, n = 74), and chemotherapy, were analyzed using linear mixed models. Participants were assessed at baseline and up to 5 years after diagnosis and grouped according to degree of SNHL. Included were 196 children with intact hearing or mild to moderate SNHL (Chang grade 0, 1a, 1b, or 2a) and 64 children with severe SNHL (Chang grade 2b or greater). Performance on eight neurocognitive variables targeting reading outcomes (eg, phonemics, fluency, comprehension) and contributory cognitive processes (eg, working memory, processing speed) was analyzed. RESULTS: Participants with severe SNHL performed significantly worse on all variables compared with children with normal or mild to moderate SNHL (P ≤ .05), except for tasks assessing awareness of sounds and working memory. Controlling for age at diagnosis and risk-adapted craniospinal irradiation dose, performance on the following four variables remained significantly lower for children with severe SNHL: phonemic skills, phonetic decoding, reading comprehension, and speed of information processing (P ≤ .05). CONCLUSION: Children with severe SNHL exhibit greater reading difficulties over time. Specifically, they seem to struggle most with phonological skills and processing speed, which affect higher level skills such as reading comprehension.


Assuntos
Neoplasias Encefálicas/complicações , Ototoxicidade/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
2.
Neurology ; 87(24): 2575-2584, 2016 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-27956565

RESUMO

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). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population. RESULTS: Lovastatin had no significant effect on primary outcomes after 16 weeks of treatment: visuospatial learning (Cohen d = -0.15, 95% confidence interval -0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval -0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo. CONCLUSIONS: Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population. CLINICALTRIALSGOV IDENTIFIER: This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493). CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.


Assuntos
Função Executiva/efeitos dos fármacos , Lovastatina/uso terapêutico , Neurofibromatose 1/tratamento farmacológico , Atenção/efeitos dos fármacos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Aprendizagem/efeitos dos fármacos , Masculino , Testes Neuropsicológicos , Qualidade de Vida
3.
Int J Radiat Oncol Biol Phys ; 95(3): 991-998, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27302514

RESUMO

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. Memory processes were verbal-semantic, visual-semantic, and visual-perceptual, including accuracy, speed to recall, encoding, retrieval, and recognition. The mixed-effects model included time (to estimate slope), covariates (age, tumor locus, XRT field, and medications) as fixed effects, and individual random intercepts. A sensitivity analysis examined the influence of XRT dose to the hippocampi on memory. RESULTS: Retrieval from long-term verbal-semantic memory declined 2 months after completing XRT, as seen in adults, and was lowest at 1 year, which was delayed in comparison with adults. Double dissociation from visual-perceptual memory at baseline and 2 months was found, consistent with adults. Recovery was demonstrated 2 years after XRT. Patterns were unchanged when dose to hippocampus was included in the model. CONCLUSIONS: Verbal and semantic long-term retrieval is specifically sensitive to XRT-related cognitive dysfunction, without effect on visual-perceptual memory. Children reached nadir in XRT-sensitive memory 1 year after XRT and recovered by 2 years, which is later than that observed in adults. The protracted period of post-XRT injury may represent the maturation of the human hippocampus and white matter into late adolescence.


Assuntos
Neoplasias Encefálicas/radioterapia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Irradiação Craniana/efeitos adversos , Plasticidade Neuronal/efeitos da radiação , Lesões por Radiação/fisiopatologia , Encéfalo/fisiopatologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/fisiopatologia , Criança , Disfunção Cognitiva/diagnóstico , Irradiação Craniana/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Projetos Piloto , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Recuperação de Função Fisiológica/efeitos da radiação , Resultado do Tratamento
4.
PLoS One ; 10(2): e0117539, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25692946

RESUMO

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. In this study, we examined the expression of ZII in the cerebellum of the western diamondback rattlesnake (Crotalus atrox). In contrast to birds and mammals, the cerebellum of the rattlesnake is much smaller and simpler, consisting of a small, unfoliated dome of cells. A pattern of alternating ZII+ and ZII- sagittal stripes cells was not observed: rather all Purkinje cells were ZII+. This suggests that ZII stripes have either been lost in snakes or that they evolved convergently in birds and mammals.


Assuntos
Cerebelo/metabolismo , Crotalus/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Células de Purkinje/metabolismo
5.
J Pediatr Psychol ; 39(5): 501-11, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24627465

RESUMO

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. RESULTS: There was a subtle, statistically significant increase in parental concern about WM, coupled with a statistically significant decrease in age-standardized scores on performance-based measures. However, whole-group mean scores on both parent and performance-based measures remained in the age-expected range. Posterior fossa syndrome was consistently associated with poorer WM. Younger age at treatment and higher treatment intensity were associated with greater negative change in WM performance only. CONCLUSIONS: Most children treated for medulloblastoma display WM within the age-appropriate range according to parent report and performance. However, the subtle negative changes over time and identified subgroups at increased risk highlight the need for ongoing monitoring of this population.


Assuntos
Neoplasias Cerebelares/psicologia , Meduloblastoma/psicologia , Memória de Curto Prazo , Adolescente , Fatores Etários , Neoplasias Cerebelares/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Meduloblastoma/cirurgia , Testes Neuropsicológicos , Pais , Adulto Jovem
6.
Neuro Oncol ; 16(8): 1129-36, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24497405

RESUMO

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. RESULTS: Serious hearing loss, PFS, younger age at diagnosis, and high-risk status were all significant risk factors for decline in intellectual and academic skills. Serious hearing loss and PFS independently predicted below-average estimated mean intellectual ability at 5 years post diagnosis. Patients with high-risk medulloblastoma and young age at diagnosis (<7 years) exhibited the largest drop in mean scores for intellectual and academic outcomes. CONCLUSIONS: Despite a significant decline over time, intellectual and academic outcomes remained within the average range at 5 years post diagnosis for the majority of patients. Future studies should determine if scores remain within the average range at time points further out from treatment. Patients at heightened risk should be closely monitored and provided with recommendations for appropriate interventions.


Assuntos
Neoplasias Cerebelares/terapia , Cognição/fisiologia , Radiação Cranioespinal , Perda Auditiva/terapia , Meduloblastoma/terapia , Adolescente , Animais , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/diagnóstico , Criança , Pré-Escolar , Terapia Combinada/métodos , Radiação Cranioespinal/métodos , Feminino , Perda Auditiva/etiologia , Humanos , Estudos Longitudinais , Masculino , Meduloblastoma/complicações , Meduloblastoma/diagnóstico , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
7.
Dev Neuropsychol ; 38(5): 337-51, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23862636

RESUMO

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). Analyses revealed patients with right cortical tumors or left cerebellar tumors had significantly greater anxiety than those with midline/bilateral tumor and those with left cortical or right cerebellar tumors. Results support the specific risk of anxiety with right cortical and left cerebellar tumors. Results highlight the association of anxiety and one important element of executive functioning.


Assuntos
Ansiedade/etiologia , Ansiedade/patologia , Mapeamento Encefálico , Neoplasias Encefálicas/complicações , Lateralidade Funcional/fisiologia , Adolescente , Criança , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Índice de Gravidade de Doença
8.
J Clin Oncol ; 30(33): 4134-40, 2012 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-23071220

RESUMO

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. A generalized linear mixed effects model regression approach was used to examine longitudinal changes in parent ratings of social competence, social problems, and withdrawn/depressed behaviors with demographic and treatment factors as covariates. RESULTS: During the 5-year period following diagnosis and treatment, few patients were reported to have clinically elevated scores on measures of social functioning. Mean scores differed significantly from population norms, yet remained within the average range. Several factors associated with unfavorable patterns of change in social functioning were identified. Patients with high-risk treatment status had a greater increase in parent-reported social problems (P=.001) and withdrawn/depressed behaviors (P=.01) over time compared with average-risk patients. Patients with posterior fossa syndrome had greater parent-reported social problems over time (P=.03). Female patients showed higher withdrawn/depressed scores over time compared with male patients (P<.001). Patient intelligence, age at diagnosis, and parent education level also contributed to parent report of social functioning. CONCLUSION: Results of this study largely suggest positive social adjustment several years after diagnosis and treatment of a pediatric embryonal tumor. However, several factors, including treatment risk status and posterior fossa syndrome, may be important precursors of long-term social outcomes. Future research is needed to elucidate the trajectory of social functioning as these patients transition into adulthood.


Assuntos
Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/terapia , Neoplasias Embrionárias de Células Germinativas/psicologia , Neoplasias Embrionárias de Células Germinativas/terapia , Pais/psicologia , Estresse Psicológico/psicologia , Adaptação Psicológica , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Comportamento Social , Estresse Psicológico/etiologia , Resultado do Tratamento , Adulto Jovem
9.
Int J Radiat Oncol Biol Phys ; 83(3): e319-24, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22420968

RESUMO

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. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. METHODS AND MATERIALS: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29 nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. RESULTS: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. CONCLUSIONS: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos da Memória/diagnóstico , Memória/efeitos da radiação , Radioterapia Conformacional/efeitos adversos , Neoplasias Supratentoriais/radioterapia , Adulto , Idoso , Transtornos Cognitivos/etiologia , Humanos , Estudos Longitudinais , Memória/fisiologia , Transtornos da Memória/etiologia , Rememoração Mental/efeitos da radiação , Pessoa de Meia-Idade , Testes Neuropsicológicos , Lesões por Radiação/complicações , Radioterapia Conformacional/métodos , Neoplasias Supratentoriais/patologia , Adulto Jovem
10.
Brain Imaging Behav ; 5(4): 262-73, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21720733

RESUMO

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. MTR for anterior and posterior cingulate, prefrontal region, and thalami comprised a model predicting 55% of accuracy when distractors were present, and the anterior cingulate accounted for the majority of this effect. Prefrontal MTR predicted longer response times which was associated with increased accuracy. Distal neural areas involved in complex, processing-driven tasks (error processing, response selection, and variable response competition and processing load) may be dependent on white matter fibers to connect distal brain regions/nuclei of a macronetwork, including prefrontal executive functions.


Assuntos
Atenção/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Idoso , Envelhecimento/fisiologia , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Cognição/fisiologia , Feminino , Percepção de Forma/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Testes Neuropsicológicos , Lobo Parietal/anatomia & histologia , Lobo Parietal/fisiologia , Desempenho Psicomotor/fisiologia , Análise de Regressão , Tálamo/fisiologia , Adulto Jovem
11.
J Neurooncol ; 105(2): 253-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21499990

RESUMO

The current study reports longitudinal coping responses among parents of children diagnosed with an embryonal brain tumor. Patients (n = 219) were enrolled on a treatment protocol for a pediatric embryonal brain tumor. Their parents (n = 251) completed the Coping Response Inventory at time of their child's diagnosis and yearly thereafter, resulting in 502 observations. Outcomes were examined with patient and parent age at diagnosis, patient risk, parent gender and education as covariates. At the time of diagnosis, the highest observed coping method was seeking guidance with well above average scores (T = 61.6). Over time, younger parents were found to seek guidance at a significantly higher rate than older parents (P = .016) and the use of acceptance resignation and seeking alternative results by all parents significantly increased (P = .011 and P < .0001 respectively). The use of emotional discharge was also observed above average at time of diagnosis (T = 55.4) with younger fathers being more likely to exhibit emotional discharge than older fathers (P = .002). Differences in coping according to age of the patient and parent education level are also discussed. Results show a high need for guidance, and above average emotional discharge, especially among younger parents. It is imperative for the healthcare team to lead with accurate information so that these parents may make informed decisions about the care of their child. This need remains high years after diagnosis. Therefore it is critical to continue a consistent level of effective communication and support, even following treatment.


Assuntos
Adaptação Psicológica , Neoplasias Encefálicas/psicologia , Neoplasias Embrionárias de Células Germinativas/psicologia , Pais/psicologia , Estresse Psicológico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Prognóstico , Estudos Prospectivos , Inquéritos e Questionários
12.
Cerebellum ; 10(3): 504-14, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21104177

RESUMO

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. The advantage of this model system is that GluRδ2(+) receptors and GluRδ2(Lc) channels are expressed predominantly in Purkinje cells, making it possible to study the effects of a well-characterized leak current in a well-defined cell type during a critical phase of neuronal development. Yet there is still controversy surrounding the mechanisms of neuronal death in Lc/+ Purkinje cells with competing hypotheses for necrotic, apoptotic, and autophagic cell death pathways as a consequence of the excitotoxic stress caused by the GluRδ2(Lc) leak current. The goal of this review is to summarize recent studies that critically test the role of various cell death pathways in Lc/+ Purkinje cell degeneration with respect to evidence for the molecular heterogeneity of Purkinje cells. We propose that the expression of putative survival factors, such as heat shock proteins, in a subset of cerebellar Purkinje cells may affect cell death pathways and account for the pattern and diverse mechanisms of Lc/+ Purkinje degeneration.


Assuntos
Apoptose/genética , Cerebelo/patologia , Camundongos Mutantes Neurológicos , Células de Purkinje/patologia , Células de Purkinje/fisiologia , Animais , Animais Recém-Nascidos , Sobrevivência Celular/genética , Cerebelo/crescimento & desenvolvimento , Proteínas de Choque Térmico/metabolismo , Camundongos , Modelos Neurológicos , Chaperonas Moleculares , Proteínas de Neoplasias/metabolismo
13.
Child Neuropsychol ; 15(5): 460-70, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19177254

RESUMO

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. MRI studies showed all anxious patients had right cortical tumors or left cerebellar tumors. Confound analyses suggest these results are not better accounted for by demographic, disease, or treatment variables. These results evidence the risk some pediatric neuro-oncologic patients face for developing significant anxiety symptoms.


Assuntos
Ansiedade/psicologia , Neoplasias Encefálicas/psicologia , Cerebelo/patologia , Córtex Cerebral/patologia , Adolescente , Ansiedade/patologia , Neoplasias Encefálicas/patologia , Criança , Feminino , Humanos , Masculino
14.
Int J Radiat Oncol Biol Phys ; 63(1): 56-63, 2005 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-16111572

RESUMO

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. untreated patients for early-delayed post-XRT effects. METHODS AND MATERIALS: Brain regions susceptible to XRT injury were examined on magnetic resonance imaging (MRI) for T2-weighted hyperintensities and atrophy in 37 adults with low-grade primary brain tumors (13 nonirradiated and 24 irradiated). Cases evidencing recurrence/growth over the study period were censored. Interactions with age, mood, fatigue, medications, tumor type and grade, extent of resection, and laterality of MRI changes were examined. RESULTS: Hyperintensity and atrophy ratings over time for the treated and untreated groups were not significantly different. White matter atrophy increased unrelated to XRT. In all patients combined, white matter atrophy and hyperintensities were greater at all time points and more lateralized in surgically treated patients. CONCLUSIONS: Radiotherapy status was not related to changes in MRI ratings during the weeks/months after XRT. Findings contradict assumptions about radiographically evidenced early-delayed XRT effects. Increases in T2-weighted hyperintensities during the 1-6-month period post-conformal radiotherapy for low-grade tumors are likely not related to early-delayed XRT effects.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/efeitos da radiação , Imageamento por Ressonância Magnética , Lesões por Radiação/patologia , Radioterapia Conformacional , Adolescente , Adulto , Idoso , Atrofia/patologia , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
15.
J Comp Neurol ; 491(1): 69-78, 2005 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-16127699

RESUMO

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. In this study we wanted to understand why zebrin II expression is arrested at this boundary and whether the Lc mutation affects the differentiation of additional Purkinje cell antigens in a similar manner. To determine this, we took advantage of the dynamic developmental timetable of another Purkinje cell antigen, the small heat shock protein Hsp25. Using immunohistochemistry we demonstrate that cerebellar maturation anterior to the CZ/PZ transverse boundary appears to be unaffected by the Lc allele, in that initial progression of Hsp25 expression in the Lc/+ cerebellum was similar to controls. Double-labeling experiments with anti-Hsp25 and anti-calbindin suggest that characteristic banding patterns of Hsp25 in Lc/+ cerebellum develop and are preserved despite cell loss. Thus, since simple temporal or spatial models cannot account for the zonal restriction seen during Lc/+ cerebellar development, the abnormality may be zebrin II-specific.


Assuntos
Cerebelo/crescimento & desenvolvimento , Proteínas de Choque Térmico/metabolismo , Camundongos Mutantes Neurológicos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células de Purkinje/metabolismo , Animais , Calbindinas , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Cerebelo/citologia , Cerebelo/metabolismo , Heterozigoto , Imuno-Histoquímica , Camundongos , Chaperonas Moleculares , Células de Purkinje/citologia , Proteína G de Ligação ao Cálcio S100/metabolismo
16.
J Clin Exp Neuropsychol ; 26(6): 750-8, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15370373

RESUMO

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. Patients were also assigned to a combined posterior (left and right) group (n = 26) or a combined posterior (left and right) group (n = 20) and compared with normal controls (NC; n = 57). We hypothesized that there would be greater left than right hemispheric phonemic and semantic fluency impairments. We also hypothesized that there would be greater anterior, specifically left anterior, than posterior impairments on phonemic fluency given their respective retrieval and initiation requirements. Finally, it was predicted that the LH patients, particularly the left posterior group, would exhibit the greatest semantic fluency impairments. Results indicated that on semantic fluency, the LH group produced significantly fewer semantic fluency responses compared to the RH group, but the expected left posterior and left frontal group differences were not found. There were no significant patient group differences associated with phonemic fluency. While we encountered semantic fluency impairments in this brain tumor population, we did not find the extensive deficits associated with the distinct or localized brain regions previously reported in the literature.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Comportamento Verbal/fisiologia , Aprendizagem Verbal/fisiologia , Adulto , Estudos de Casos e Controles , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiopatologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Testes de Linguagem , Linguística , Masculino , Pessoa de Meia-Idade , Testes de Associação de Palavras
17.
Neuropsychol Rev ; 14(1): 65-86, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15260139

RESUMO

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. Conditions that predispose to radiation injury are reviewed: (1) higher doses even to part of the brain versus lower doses to the whole brain, (2) combined treatment modalities, (3) malignancy itself, (4) radiation early during postnatal brain development, and (5) late-delayed effects (more than 3 years posttreatment). Current neurocognitive frameworks for understanding cognitive change over time in children and adults are summarized, along with the literature on effects of brain tumors and treatment on depression. No studies have as yet identified candidate brain regions that are more sensitive to radiotherapy. Two studies have provided early, preliminary evidence for a specific vulnerability of visual attention/memory to the early stage of late radiation damage. Furthermore, radiation effects appear severe only in a minority of patients. Risk is related to direct and indirect effects of cancer type, concurrent clinical factors, and premorbid risk factors.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/efeitos da radiação , Radioterapia/efeitos adversos , Acidente Vascular Cerebral/radioterapia , Adulto , Encéfalo/cirurgia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Criança , Transtornos Cognitivos/etiologia , Humanos , Doses de Radiação , Radiocirurgia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Fatores de Tempo
18.
AJNR Am J Neuroradiol ; 25(6): 977-84, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15205135

RESUMO

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 1.5-T MR images with and those without MT were obtained. MT ratios (MTRs) were computed for 33 regions of interest (ROIs) in 27 healthy adults (aged 18-69 years) without evidence of cognitive or radiographic abnormalities. Three tests of reliability yielded coefficients above 0.97. MTRs for the whole brain, groups of structures, and individual ROIs were calculated. Low standard errors confirmed the consistency of the technique. RESULTS: Age, education, sex, and hand dominance were not correlated with whole-brain MTR (mean = 37.35, SD = 1.25), but age was associated with the cerebellum and some lobes at a trend level. MTRs were as follows, in descending order: corpus callosum, cingulate, white matter, brain stem, subcortical nuclei, and cerebellum. MTRs were selectively higher in the prefrontal lobe versus the posterior frontal lobe and in the lateral temporal lobe versus medial temporal lobe. MTR was higher in the left hemisphere than in the right hemisphere for the whole brain, frontal and temporal lobes, and lenticular nuclei. CONCLUSION: MT imaging showed selective age, medial-lateral, and hemispheric differences, giving evidence of normal aging effects on the white matter in the absence of T2- weighted hyperintensities. These differences support neurocognitive theories of the organization of brain function. MT imaging appears to be a robust technique for use in cognitive neuroscience.


Assuntos
Encéfalo/anatomia & histologia , Bainha de Mielina , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Brain Cogn ; 54(2): 110-6, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14980451

RESUMO

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 frontal patients were also assigned to either a left frontal (n=10) group or a right frontal group (n=15) and compared with the non-frontal group and NC. It was hypothesized that the frontal brain tumor patients would display greater deficits on categories achieved and a higher number of perseverative errors than non-frontal brain tumor patients on the WCST. Finally, it was predicted that right frontal brain tumors would result in greater executive functioning deficits than left frontal or non-frontal brain tumors. Results indicated that the left frontal group achieved the fewest categories and committed the most perseverative errors compared to the other patient and normal control groups. In addition, the left frontal group committed significantly more perseverative errors than the right frontal group. These results suggest that the WCST is sensitive to the effects of low-grade brain tumors on executive functioning.


Assuntos
Neoplasias Encefálicas/complicações , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Lobo Frontal , Testes Neuropsicológicos , Lobo Occipital , Lobo Parietal , Lobo Temporal , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/patologia , Feminino , Lobo Frontal/patologia , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/patologia , Lobo Parietal/patologia , Índice de Gravidade de Doença , Lobo Temporal/patologia
20.
Brain Cogn ; 54(1): 1-6, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14733894

RESUMO

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. The LH group had a higher proportion of tumors extending into the temporal lobes, possibly accounting for their greater pictorial processing impairments. Dual coding and enhanced visual imagery may have contributed to the patient groups' similar performance on the remainder of the measures.


Assuntos
Neoplasias Encefálicas/complicações , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Reconhecimento Psicológico/fisiologia , Percepção Visual , Vocabulário , Adulto , Feminino , Lateralidade Funcional , Humanos , Masculino , Tempo de Reação , Índice de Gravidade de Doença
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