Annotated Abstracts of Journal Articles
2014, 2nd Quarter
Annotations by Audrey Walker, MD, FAPM
Reddick WE, Taghipour DJ, Glass JO, et al
Pediatr Blood Cancer 2014 Jun; 61(6):1074-9
ANNOTATION (Audrey Walker)
The Finding: BT survivors had lower WMV than ALL survivors, who had less than the control group. Increased CNS treatment intensity, younger age at treatment, and greater time since treatment were significantly associated with lower WMV. Additionally, cancer survivors did not perform as well as the control group on neurocognitive measures of intelligence, attention, and academic achievement. Reduced WMV had a greater impact on estimated IQ among females and children treated at younger ages.
Strengths and Weaknesses: The large number of participants from multiple institutions was a strength of this study.
A limitation of this study is the cross-sectional design, which does not allow for temporal evaluation of WMV development or neurocognitive performance.
Relevance: Young children with common childhood cancers are experiencing very high 5-year-event-free survival rates following treatment. As a result, there is a growing population of patients with neurocognitive disabilities. This study adds important data on the extent and specifics of these disabilities, strengthening the support for early assessment and intervention in these vulnerable children.
Objective: In children, CNS-directed cancer therapy is thought to result in decreased cerebral white matter volumes (WMV) and subsequent neurocognitive deficits. This study was designed as a prospective validation of the purported reduction in WMV, associated influential factors, and its relationship to neurocognitive deficits in a very large cohort of both acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT) survivors in comparison to an age similar cohort of healthy sibling controls.
Procedures: The effects of host characteristics and CNS treatment intensity on WMV were investigated in 383 childhood cancer survivors (199 ALL, 184 BT) at least 12 months post-completion of therapy and 67 healthy siblings that served as a control group. t-Tests and multiple variable linear models were used to assess cross-sectional WMV and its relation with neurocognitive function.
Results: BT survivors had lower WMV than ALL survivors, who had less than the control group. Increased CNS treatment intensity, younger age at treatment, and greater time since treatment were significantly associated with lower WMV. Additionally, cancer survivors did not perform as well as the control group on neurocognitive measures of intelligence, attention, and academic achievement. Reduced WMV had a larger impact on estimated IQ among females and children treated at a younger age.
Conclusions: Survivors of childhood cancer that have undergone higher intensity therapy at a younger age have significantly less WMV than their peers and this difference increases with time since therapy. Decreased WMV is associated with significantly lower scores in intelligence, attention, and academic performance in survivors.
Reilly C, Atkinson P, Das KB, et al
Pediatrics 2014; 133(6):e1586-e1593
ANNOTATION (Audrey Walker)
The Finding: In this community-based study, 85 children with active epilepsy (74% of the eligible population) were enrolled. 80% of subjects had a DSM-IV-TR behavioral disorder or cognitive impairment. Intellectual disability (40%), attention deficit hyperactivity disorder (33%), and autism spectrum disorders (21%) were the most common diagnoses in this population. Independent predictors of having a comorbid diagnosis of intellectual disability were: first seizures before 24 months of age and polytherapy. The presence of intellectual disability independently predicted that a child would have a comorbid diagnosis of autism spectrum disorder. Epilepsy-related factors were not strong predictors of psychopathology in this population.
Given the high rate of intellectual disability, autism spectrum disorders and comorbid behavioral disorders in children with childhood epilepsy, the authors believe that early screening of this population for behavioral and cognitive difficulties is warranted, as has been previously recommended.
Strengths and Weaknesses: This study included a comprehensive screening for intellectual disability and behavioral disorders including multiple informants and standardized, well-validated instruments. The participation rate (74 % of the eligible population) was robust.
A weakness of the study is the small sample size taken from a limited geographical region in the UK. In addition, no assessment of family functioning or family environment was included in the assessment; therefore, no conclusions regarding the role of family stress or poor family adaptation in the development of behavioral disorders could be made.
Relevance: The high rates of intellectual disability, autism spectrum disorder, and behavioral disorders in this population of children with active epilepsy strengthens the case that has been made by previous authors that these patients should receive early assessment and intervention.
Background: In addition to recurrent epileptic seizures, children with epilepsy can have coexisting cognitive and behavioral difficulties but the spectrum and prevalence of such difficulties are uncertain.
Methods: The Children with Epilepsy in Sussex Schools study is a prospective, community-based study involving school-aged children (5-15 years) with active epilepsy in a defined geographical area in the United Kingdom. Participants underwent comprehensive psychological assessment, including measures of cognition, behavior, and motor functioning. Consensus neurobehavioral diagnoses were made with respect to Diagnostic and Statistical Manual, Fourth Edition-Text Revision (DSM-IV-TR) criteria.
Results: A total of 85 children (74% of eligible population) were enrolled; 80% of children with active epilepsy had a DSM-IV-TR behavioral disorder and/or cognitive impairment (IQ <85). Intellectual disability (ID) (IQ <70) (40%), attention-deficit/hyperactivity disorder (ADHD) (33%), and autism spectrum disorder (ASD) (21%) were the most common neurobehavioral diagnoses. Of those who met criteria for a DSM-IV-TR behavioral disorder, only one-third had previously been diagnosed. Logistic regression revealed that seizures in the first 24 months compared with first seizures at 24 to 60 or 61+ months (odds ratio [OR] 13, 95% confidence interval 2.2-76.9; OR 21.3, 3.2-148.9) and polytherapy (OR 7.7, 1.6-36.3) were independently associated with ID and the presence of ID was associated with a diagnosis of ASD (OR 14.1, 2.3-87.1) after Bonferroni adjustment. Epilepsy-related factors did not independently predict the presence of behavioral disorders.
Conclusions: Screening for neurobehavioral comorbidities should be an integral part of management in children with “active” epilepsy. There is a need for research to identify neurobiological mechanisms underpinning neurobehavioral impairments and studies to evaluate possible treatments.