Papers by Brenda Spiegler
Journal of the International Neuropsychological Society, Sep 1, 2000
We examined short duration perception (400 ms), long duration estimation (30 and 60 min), and spa... more We examined short duration perception (400 ms), long duration estimation (30 and 60 min), and spatiotemporal estimation in long-term survivors of childhood cerebellar tumors with a mean time since diagnosis of 14.2 years. Groups of individuals with tumors treated with surgery only (astrocytoma, N = 20) were compared to those with tumors treated with surgery, focal radiation, and craniospinal radiation (medulloblastoma, N = 20), and to age-matched controls (N = 40). Childhood lesions of the cerebellum produced enduring deficits in short-duration perception, but spared the ability to functionally estimate long durations, regardless of the pathology or treatment of the tumor. Evidence did not support any functional recovery over time of the cerebellar system that underlies short-duration perception. Younger age at treatment was not a protective factor. Although no group differences were present in the functional measures of long-duration estimation, tumor-related prospective memory deficits interfered with the ability to produce long-duration prospective estimates. The utilization of sensory and somatomotor information to refine real-world spatiotemporal estimates was compromised in the medulloblastoma group only.
Describes the use of behavioral assays for exploring the issue of age-based functional plasticity... more Describes the use of behavioral assays for exploring the issue of age-based functional plasticity in response to developmental dysmorphologies and childhood lesions of the cerebellum. The methodologies used here have some heuristic value for understanding age-based functional plasticity. The importance of specifying hypotheses is stressed, as is the need to adduce long-term observations in support or disconfirmation of these hypotheses. The data considered were from the chronic phase of brain lesions: By middle childhood, lesions sustained during gestation are by definition chronic and all the tumor cases were long-term survivors. Cerebellar lesions in the immature brain produce deficits rather than lags. Generally, the data support the view of stable, long-lasting deficits rather than developmental lags following congenital or childhood-acquired cerebellar lesions. To suggest that skills compromised by congenital malformations and acquired lesions of the cerebellum produce deficits...
Pediatric blood & cancer, Jan 25, 2015
Not all children with acute lymphoblastic leukemia (ALL) were developing in a typical manner prio... more Not all children with acute lymphoblastic leukemia (ALL) were developing in a typical manner prior to diagnosis. Pre-existing developmental vulnerabilities (DV) may be related to long-term neuropsychological sequelae following ALL treatment, yet little is known about the prevalence or nature of prior DV in this population. Children with newly diagnosed ALL aged 2-18 years (n = 115) were screened for DV by asking parents about the child's prior developmental history and with the Developmental Profile-3 (DP-3). Twenty-six participants (23% of total sample) screened positive for prior DV, with one or more of the following: delayed early motor and/or language milestones that required intervention (n = 17), prior diagnosis of Down syndrome (n = 3), prior diagnosis of autism spectrum disorder (n = 1), prior diagnosis of attention-deficit/hyperactivity disorder and/or learning disability (n = 6), or prior neurological conditions (n = 5). A sizable proportion of children with newly diag...
Supportive Care in Cancer, 2014
Supportive Care in Cancer, 2014
Pediatric Blood & Cancer, 2004
Prophylactic use of cranial radiation therapy (CRT) in young children with acute lymphoblastic le... more Prophylactic use of cranial radiation therapy (CRT) in young children with acute lymphoblastic leukemia (ALL) is associated with significant long-term morbidity. Therefore, current treatment protocols for pediatric B-precursor ALL have abandoned prophylactic CRT in favor of intrathecal chemotherapy, combined with either high-dose methotrexate infusions (HD-MTX) or intensive systemic chemotherapy. In contrast, prophylactic CRT continues to be used in children with T-lineage ALL (T-ALL), who historically have had an inferior prognosis. We conducted a retrospective cohort study to determine the effect on survival of substituting HD-MTX for CRT in young children with T-ALL, a group that faces a high risk of long-term sequelae from CRT. Twenty-six children, diagnosed with T-ALL between the ages of 1 and 5 years, were treated on the same high-risk leukemia protocol. Central nervous system (CNS) directed therapy consisted of either CRT (1,800 cGy) or HD-MTX (three doses of 8 g/m2), depending on the treatment era in which patients were diagnosed. Of the 24 patients who entered remission, 12 received CRT and 12 received HD-MTX. Five-year event-free survival (EFS) (+/-SE) was 92 +/- 8% in the HD-MTX group versus 75 +/- 13% in the CRT group (P=0.23). Five-year overall survival (OS) was 100% in the HD-MTX group versus 75 +/- 13% in the CRT group (P=0.07). There were no CNS recurrences in the HD-MTX group. One patient treated with CRT developed a brain tumor. The use of HD-MTX instead of CRT as CNS-directed therapy in very young children with T-ALL does not compromise survival, while avoiding the adverse long-term effects of cranial irradiation.
Medical and Pediatric Oncology, 1998
As the survival rates for children with brain tumors have increased, attention has been directed ... more As the survival rates for children with brain tumors have increased, attention has been directed to treatment-related sequelae and their effects on quality of life [1,2]. Follow-up studies of children treated for brain tumors often depend on length of survival or global indices of quality of ...
Neuroscience & Biobehavioral Reviews, 2013
It has been widely accepted that the younger the age and/or immaturity of the organism, the great... more It has been widely accepted that the younger the age and/or immaturity of the organism, the greater the brain plasticity, the young age plasticity privilege. This paper examines the relation of a young age to plasticity, reviewing human pediatric brain disorders, as well as selected animal models, human developmental and adult brain disorder studies. As well, we review developmental and childhood acquired disorders that involve a failure of regulatory homeostasis. Our core arguments are as follows:
Neuropsychology Review, 2014
At every point in the lifespan, the brain balances malleable processes representing neural plasti... more At every point in the lifespan, the brain balances malleable processes representing neural plasticity that promote change with homeostatic processes that promote stability. Whether a child develops typically or with brain injury, his or her neural and behavioral outcome is constructed through transactions between plastic and homeostatic processes and the environment. In clinical research with children in whom the developing brain has been malformed or injured, behavioral outcomes provide an index of the result of plasticity, homeostasis, and environmental transactions. When should we assess outcome in relation to age at brain insult, time since brain insult, and age of the child at testing? What should we measure? Functions involving reacting to the past and predicting the future, as well as social-affective skills, are important. How should we assess outcome? Information from performance variability, direct measures and informants, overt and covert measures, and laboratory and ecological measures should be considered. In whom are we assessing outcome? Assessment should be cognizant of individual differences in gene, socio-economic status (SES), parenting, nutrition, and interpersonal supports, which are moderators that interact with other factors influencing functional outcome.
Neuropsychologia, 1991
The neuroanatomy of memory deficits was studied in 46 children and adolescents with brain tumors.... more The neuroanatomy of memory deficits was studied in 46 children and adolescents with brain tumors. CT-scan reconstructions of 88 brain regions were coded with respect to tumor and related damage, and multiple regression procedures established patterns of brain damage predictive of memory deficits. Two forms of memory revealed non-overlapping focal neuroanatomical substrates: memory for the serial order of pictures that corresponded to heard words involved structures in the limbic system and hypothalamic-pituitary axis; whereas working memory, in which each of a succession of heard words is stored in temporary memory long enough to be compared to or contrasted with incoming words, involved the pineal-habenular region and the anterior and medial thalamic nuclei. Memory for semantically-based word-picture associations, in contrast, was unaffected by tumors in several subcortical brain regions. These data bear on current analyses of the neural substrates of associative and representational memory.
Neuropsychologia, 1991
Memory impairment was demonstrated in a sample of 46 children and adolescents with brain tumors. ... more Memory impairment was demonstrated in a sample of 46 children and adolescents with brain tumors. The overall distribution of memory scores was skewed positively; over half of the total number of test measures were in the lowest quarter of the score distribution; and more than three-quarters of the individual subjects had at least one memory score in the impaired range. Verbal intelligence accounted for less than one-quarter of the variance in memory scores. The type of memory impairment was analyzed in relation to various demographic and medical variables: age at onset of tumor symptoms, age or duration of tumor, sex, pre-tumor developmental disturbances, pre-tumor closed head injury, post-tumor anticonvulsant treatment and post-tumor epileptic seizures. The working memory task, in which each in a succession of heard words is stored in temporary memory long enough to be compared to or contrasted with incoming words, was unaffected by these variables, as was memory for semantically-based word-picture associations. Memory for the serial order of pictures that corresponded to heard words varied inversely with the age at tumor onset such that the later the onset, the lower the memory test performance.
Neuropsychologia, 1992
The effects on intelligence and memory of two post-surgical conditions (radiation treatment, horm... more The effects on intelligence and memory of two post-surgical conditions (radiation treatment, hormone deficiency and supplementation) were explored in 46 children and adolescents with tumors in a variety of brain sites.
Neuro-Oncology, 2011
Treatment for medulloblastoma during childhood impairs neurocognitive function in survivors. Whil... more Treatment for medulloblastoma during childhood impairs neurocognitive function in survivors. While those diagnosed at younger ages are most vulnerable, little is known about the long-term neurocognitive, functional, and physical outcomes in survivors as they approach middle age. In this retrospective cohort study, we assessed 20 adults who were treated with surgery and radiotherapy for medulloblastoma during childhood (median age at assessment, 21.9 years [range, 18 -47 years]; median time since diagnosis, 15.5 years [range, 6.5 -42.2 years]). Nine patients also underwent chemotherapy. Cross-sectional analyses of current neurocognitive, functional, and physical status were conducted. Data from prior neuropsychological assessments were available for 18 subjects; longitudinal analyses were used to model individual change over time for those subjects. The group was well below average across multiple neurocognitive domains, and 90% had required accommodations at school for learning disorders. Longer time since diagnosis, but not age at diagnosis, was associated with continued decline in working memory, a common sign of aging. Younger age at diagnosis was associated with lower intelligence quotient and academic achievement scores, even many years after treatment had been completed. The most common health complications in survivors were hearing impairment, second cancers, diabetes, hypertension, and endocrine deficiencies. Adult survivors of childhood medulloblastoma exhibit signs of early aging regardless of how young they were at diagnosis. As survival rates for brain tumors continue to improve, these neurocognitive and physical sequelae may become evident in survivors diagnosed at different ages across the lifespan. It will become increasingly important to identify factors that contribute to risk and resilience in this growing population.
Journal of the International Neuropsychological Society, 2000
We examined short duration perception (400 ms), long duration estimation (30 and 60 min), and spa... more We examined short duration perception (400 ms), long duration estimation (30 and 60 min), and spatiotemporal estimation in long-term survivors of childhood cerebellar tumors with a mean time since diagnosis of 14.2 years. Groups of individuals with tumors treated with surgery only (astrocytoma, N = 20) were compared to those with tumors treated with surgery, focal radiation, and craniospinal radiation (medulloblastoma, N = 20), and to age-matched controls (N = 40). Childhood lesions of the cerebellum produced enduring deficits in short-duration perception, but spared the ability to functionally estimate long durations, regardless of the pathology or treatment of the tumor. Evidence did not support any functional recovery over time of the cerebellar system that underlies short-duration perception. Younger age at treatment was not a protective factor. Although no group differences were present in the functional measures of long-duration estimation, tumor-related prospective memory deficits interfered with the ability to produce long-duration prospective estimates. The utilization of sensory and somatomotor information to refine real-world spatiotemporal estimates was compromised in the medulloblastoma group only.
Journal of the International Neuropsychological Society, 2007
The consequences of congenital brain disorders for adult cognitive function are poorly understood... more The consequences of congenital brain disorders for adult cognitive function are poorly understood. We studied different forms of memory in 29 young adults with spina bifida meningomyelocele (SBM), a common and severely disabling neural tube defect. Nondeclarative and semantic memory functions were intact. Working memory was intact with low maintenance and manipulation requirements, but impaired on tasks demanding high information maintenance or manipulation load. Prospective memory for intentions to be executed in the future was impaired. Immediate and delayed episodic memory were poor. Memory deficits were exacerbated by an increased number of lifetime shunt revisions, a marker for unstable hydrocephalus. Memory status was positively correlated with functional independence, an important component of quality of life.
Journal of Pediatric Oncology Nursing, 2008
Multimodal therapy for the treatment of childhood cancer has resulted in increased survival rates... more Multimodal therapy for the treatment of childhood cancer has resulted in increased survival rates, yet as growing cohorts of children mature, late effects are becoming apparent. Specifically, brain tumor survivors tend to have poor social skills, peer relationship problems, academic difficulties, and delayed college entry. This article addresses findings specific to the unique experience of childhood cancer survivors as they transition from adolescence to adulthood. Qualitative methods involving focus groups and in-depth interviews with 14 childhood cancer survivors and 22 family members were used. The dialectic of incompetence/competence pervaded all narratives. Contradictory concepts of integration/ isolation, realistic/unrealistic goals, and the need for special help/no help were underscored by respondents. The struggle to deal with these contradictory factors led to the simultaneous resistance and acceptance of feelings of competence.
Journal of Pediatric Hematology/Oncology, 2011
Five-year survival rates of childhood acute lymphoblastic leukemia (ALL) exceed 80% due to centra... more Five-year survival rates of childhood acute lymphoblastic leukemia (ALL) exceed 80% due to central nervous system-directed treatment including cranial radiation (CRT) and chemotherapy. However, these treatments are associated with neurocognitive compromise, the extent of which is correlated with higher dose and younger age at treatment. The aims of this study were to explore long-term neurocognitive outcomes in adult survivors of childhood ALL, and to identify measures sensitive to neurotoxicity in long-term survivors. We examined 24 adults who received 18 Gy CRT and chemotherapy for treatment of ALL between ages 2 and 15 years (median, 5.5). Time since diagnosis ranged from 6 to 26 years (median, 16.6). Younger age at diagnosis and longer time since diagnosis were associated with lower scores on a computerized battery that requires speed and accuracy across a number of domains (MicroCog), and other standardized neurocognitive tests. When compared with population norms, MicroCog indices were below average in survivors diagnosed with ALL before age 5, but only the reasoning/calculation index was below average in survivors diagnosed with ALL after age 5. In contrast, intelligence quotient (IQ) scores were average. In addition to confirming earlier studies showing that younger children are more vulnerable to treatment-related neurotoxicity, here we show that deficits exist many years post treatment even with a relatively lower dose of CRT, and that these deficits are especially evident on tasks involving rapid processing of information.
Journal of Neuro-Oncology, 1996
When a malignant tumor invades the child's cerebellum, the cost of successful treatment is often ... more When a malignant tumor invades the child's cerebellum, the cost of successful treatment is often significant cognitive morbidity. A review of neuropsychological outcome revealed that survivors of childhood medulloblastoma (MB) have long-term deficits in intelligence, memory, language, attention, academic skills, psychosocial function, and a compromised quality of life. These deficits varied with chronological age at tumor diagnosis and/or adjuvant treatment, type and duration of presenting symptoms, tumor extension beyond the cerebellum, a history of adjuvant radiation treatment, and time since treatment. The effects on neuropsychological outcome of other factors, such as post-surgical hydrocephalus, were less clear. To understand the interaction between two factors predictive of outcome, age at diagnosis and time since treatment, we analyzed IQ results for a new sample of 25 surgically-treated and radiated MB survivors, and found that age at diagnosis and time since treatment made separable contributions to intellectual morbidity. PIQ appeared to measure some general effects of diffuse cerebral insult because it varied with chronological age of the child at tumor diagnosis but was relatively constant in magnitude, once established. VIQ, in contrast, was somewhat less sensitive to age at diagnosis in treated MB survivors, but declined with time since treatment. These results are important for understanding the academic attainments and continuing rehabilitation needs of childhood MB survivors, because they suggest that these children progressively fail to assimilate new verbally-based knowledge at a developmentally-appropriate rate.
Journal of Clinical Oncology, 2005
To evaluate academic and behavioral outcome in radiated survivors of posterior fossa (PF) tumors.
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Papers by Brenda Spiegler