Mother knows best or does she? Perceptions of the memory abilities of pediatric patients with epilepsy as reported by patients and their parents across time.

PURPOSE: This study compared the self-reported and parent-reported memory of children with epilepsy across time and explored the relationships between these measures of subjective memory and the children's actual performance on objective neuropsychological tests. METHOD: One-hundred and nineteen children with epilepsy who were surgical candidates underwent comprehensive neuropsychological testing that included the Everyday Verbal Memory Questionnaire (EVMQ). Each child's parent and 82 of the children themselves completed the appropriate version of this subjective memory measure. After 9 months, the children returned for a second neuropsychological evaluation with 71 parents and 39 children completing the same questionnaire. Approximately one-third of the children in the study underwent surgery between the two evaluations. Standardized regression-based norms were used to quantify change in cognitive abilities across assessments. RESULTS: Results revealed significant relationships between parent reports and child reports of the children's memory abilities. Parent reports, but not child reports, correlated with the children's objective test scores at baseline. In contrast, children were more attuned to changes in their memory across time. CONCLUSIONS: These findings demonstrate the importance of considering both parent and child perceptions of everyday cognitive functioning when evaluating cognition and cognitive changes over time in pediatric patients with epilepsy.

Cognitive outcomes following frontal lobe resection for treatment of epilepsy in children and adolescents.

OBJECTIVE: To use reliable change indices (RCIs) developed specifically for pediatric patients with epilepsy to examine cognitive outcomes after frontal lobe resection for pharmacoresistant epilepsy. METHODS: Forty-one pediatric patients (25 male, Mage = 10 years) completed comprehensive neuropsychological evaluations before and an average of 6.5 months after frontal lobe resections for treatment of epilepsy. Evaluations included tests of intelligence, attention/working memory, processing speed, language, visuospatial skills, executive function, and episodic memory. Practice effect-adjusted RCIs were used to determine clinically significant postoperative cognitive change. Demographic, disease, and surgical variables were examined to identify factors associated with postoperative cognitive decline or improvement. RESULTS: Within each cognitive domain, there was a large proportion of patients (51-84%) who did not exhibit significant cognitive change. In terms of overall cognitive profile, 44% demonstrated improvement in at least one domain and 69% declined in at least one domain. Postoperative cognitive improvement occurred most commonly in the domain of processing speed, whereas postoperative cognitive decline occurred most frequently in the domain of visuospatial skills. Younger age at surgery was associated with cognitive improvement. Older age at seizure onset and higher baseline cognitive performance were associated with cognitive decline. SIGNIFICANCE: Approximately 6.5 months after frontal lobe resection, only 15% of our sample showed stable performance across all cognitive domains. Seventeen percent of patients showed improvements without declines, 42% showed declines without improvements, and 27% showed a mix of improvements and declines across different cognitive domains. Age and baseline abilities were associated with postoperative cognitive change on multiple measures. With 1 in 8 children demonstrating postoperative decline across three or more domains, further research is needed to identify factors associated with cognitive decline in order to inform clinical decision-making and patient/family counseling.

Reliable change indices and standardized regression-based change score norms for evaluating neuropsychological change in children with epilepsy.

Reliable change indices (RCIs) and standardized regression-based (SRB) change score norms permit evaluation of meaningful changes in test scores following treatment interventions, like epilepsy surgery, while accounting for test-retest reliability, practice effects, score fluctuations due to error, and relevant clinical and demographic factors. Although these methods are frequently used to assess cognitive change after epilepsy surgery in adults, they have not been widely applied to examine cognitive change in children with epilepsy. The goal of the current study was to develop RCIs and SRB change score norms for use in children with epilepsy. Sixty-three children with epilepsy (age range: 6-16; M=10.19, SD=2.58) underwent comprehensive neuropsychological evaluations at two time points an average of 12 months apart. Practice effect-adjusted RCIs and SRB change score norms were calculated for all cognitive measures in the battery. Practice effects were quite variable across the neuropsychological measures, with the greatest differences observed among older children, particularly on the Children's Memory Scale and Wisconsin Card Sorting Test. There was also notable variability in test-retest reliabilities across measures in the battery, with coefficients ranging from 0.14 to 0.92. Reliable change indices and SRB change score norms for use in assessing meaningful cognitive change in children following epilepsy surgery are provided for measures with reliability coefficients above 0.50. This is the first study to provide RCIs and SRB change score norms for a comprehensive neuropsychological battery based on a large sample of children with epilepsy. Tables to aid in evaluating cognitive changes in children who have undergone epilepsy surgery are provided for clinical use. An Excel sheet to perform all relevant calculations is also available to interested clinicians or researchers.

Cognitive characteristics of PTEN hamartoma tumor syndromes.

PURPOSE: We sought to characterize cognition in individuals with germline PTEN mutations (n = 23) as well as in PTEN mutation-negative individuals with classic Cowden syndrome or Bannayan-Riley-Ruvalcaba syndrome (n = 2). METHODS: Twenty-five individuals completed a comprehensive neuropsychological evaluation. One sample t-tests and effect sizes were used to examine differences in participant test scores compared with normal controls. Composite scores were created for each patient within each of the cognitive domains assessed and classified as above average, average, or below average according to normative standards. χ(2) analyses compared these classifications to expected proportions in normal control samples. RESULTS: The mean intelligence quotient was in the average range, and the range of intellectual functioning was very wide (from extremely low to very superior). However, in a large subset of patients, scores were lower than expected on measures of motor functioning, executive functioning, and memory recall, suggesting disruption of frontal circuits in these participants. CONCLUSION: This is the first study to characterize cognition in individuals with PTEN mutations and associated syndromes using a comprehensive neuropsychological battery. Contrary to previous reports suggesting an association with intellectual disability, the mean intelligence quotient was average, and there was a broad range of intellectual abilities. Specific evidence of disruption of frontal circuits may have implications for treatment compliance and cancer surveillance, and further investigation is warranted.

Word-finding difficulties confound performance on verbal cognitive measures in adults with intractable left temporal lobe epilepsy.

This study sought to determine if word-finding difficulties (WFDs), which are common in adults with dominant temporal lobe epilepsy (TLE), are related to performance on verbal cognitive measures, including memory. One hundred six individuals with left TLE and pathologically confirmed mesial temporal sclerosis completed comprehensive preoperative neuropsychological evaluations. Patients were divided into two groups based on the degree of benefit received from phonemic cueing on a confrontation naming task. Cognitive performance was then compared between patients with greater and fewer WFDs. Patients with greater WFDs demonstrated poorer performance on many verbal cognitive measures compared to those with fewer WFDs. In contrast, there were no significant differences between groups on any of the nonverbal cognitive measures. Chi-square analyses indicated that below average verbal memory performance occurred at a significantly higher rate for patients with greater WFDs (42-46%) as compared to patients with fewer WFDs (18-24%). Results showed that WFDs confound performance on verbal cognitive measures in adult patients with left TLE, particularly on measures with high demands for lexical retrieval. This suggests that when patients have word-retrieval difficulties, measures of verbal memory and verbal intelligence may be underestimated and potentially lead to misinterpretation of test performance and misinformation regarding risk of declines after surgical resection.

Cognitive outcomes following pediatric epilepsy surgery.

OBJECTIVES: To characterize outcomes following pediatric epilepsy surgery across a broad range of cognitive domains using empirical methods (i.e., reliable change indices: RCIs), compare these outcomes with those based on traditional methods (i.e., standard deviation: SD), and identify factors associated with postoperative cognitive declines and/or improvements. METHODS: This retrospective cohort study included 186 children who underwent surgical resection for treatment of pharmacoresistant epilepsy and who completed pre- and postoperative neuropsychological assessments. Postoperative testing occurred approximately 6.5 months after surgery and included measures of intelligence, attention/working memory, processing speed, language, executive functioning, visuospatial skills, memory, and academic achievement. Change scores for each patient were classified as decline, no change, or improvement using epilepsy-specific RCIs. Chi-square goodness of fit tests were used to compare the distribution of outcomes as classified with RCIs to those obtained using a traditional one SD cutoff. Multinomial regression analyses were conducted to identify factors associated with cognitive decline and/or improvement. RESULTS: While 18% of children demonstrated no postoperative declines or improvements in any cognitive domain, the majority demonstrated relatively focal changes (declines and/or improvements in 1-2 cognitive domains). Rates of postoperative decline and improvement across individual cognitive domains were variable and ranged from 4-35% and 2-31%, respectively. Compared to RCIs, SD methodology often overestimated postoperative improvements and varied with respect to declines. Factors associated with RCI decline or improvement included preoperative performance, age at surgery, surgery site, and postoperative seizures. SIGNIFICANCE: Results suggest substantial variability in individual cognitive outcomes approximately 6.5 months following pediatric epilepsy surgery. The differences in change distributions obtained using epilepsy-specific RCIs versus SDs highlight the need for studies using empiric methodology to study postoperative cognitive change. Variables associated with postoperative cognitive change may be used to develop multivariable prediction models in future studies to aid clinical decision-making and patient counseling.

[Formula: see text] Reliable change in pediatric brain tumor: A preliminary investigation.

Children treated for brain tumor show evidence of declines in general intellectual abilities (i.e., IQ). Group-level data indicate subtle declines over time on average, but no study has utilized a clinical criterion to identify and describe a reliable change in survivors of pediatric brain tumor (PBT). In this study, we discuss the utility of reliable change index (RCI) methodology to supplement group-level analysis (e.g., repeated measures ANOVA). This pilot sample consisted of 22 children (M age = 10.47 years) treated for PBT who completed initial and follow-up assessments (M interval = 23.58 months). Cognitive data included composite scores from the WISC-IV. An RCI z-score was calculated for each participant on each composite score based on two different test-retest reliability coefficients. As a group, survivors of PBT did not demonstrate a statistically significant change from initial to follow-up on any WISC-IV composite score. When RCI was calculated based on reliability coefficients with shorter test-retest intervals provided by the test publisher, 77% of survivors demonstrated a reliable change in performance on at least one measure. The frequency of RCI decreases in working memory was significantly higher than expected. In contrast, only 32% of survivors showed reliable changes on at least one measure when RCI was based on a reliability coefficient derived from a clinical sample with a longer retest interval. This study demonstrates that highly divergent results may be obtained with RCI and the importance of the source of reliability estimates.

Longer duration of epilepsy and earlier age at epilepsy onset correlate with impaired cognitive development in infancy.

We assessed the impact of age at onset of epilepsy and duration and frequency of seizures on cognitive development in children less than 3 years old. Retrospective analysis was conducted on clinical data and neuropsychological testing of 33 infants with epilepsy. Developmental quotients were calculated and were correlated with age at epilepsy onset, duration of epilepsy, seizure frequency, brain pathology, and types of seizures (with/without spasms) as potential predictors. Infants with longer duration and earlier onset of epilepsy performed worse on developmental neuropsychological testing. Regression analyses showed that age at epilepsy onset and percentage of life with epilepsy were both strongly associated (regression model P<0.0001) with developmental quotient. There was no correlation with seizure frequency. Infants with spasms had worse developmental quotients than infants without spasms (P<0.001). These results suggest that duration of epilepsy and age at onset may be the best developmental predictors during the first years of life in patients with epilepsy. Early aggressive intervention should be considered.

Memory functioning following traumatic brain injury in children with premorbid learning problems.

This study examines the memory functioning of 25 children who sustained a traumatic brain injury (TBI) and who had prior learning problems, 48 children with TBI who did not have prior learning problems, and 23 noninjured controls. The children with TBI and prior learning problems displayed significantly worse memory abilities than both the control participants and the children with TBI and no prior learning problems. They differed significantly from these 2 groups on measures of general memory, verbal memory, sound-symbol learning, and attention. The results suggest that children with premorbid learning problems who sustain TBI have less cognitive reserve and a lower threshold for the expression of cognitive impairments in areas that reflect preexisting learning and language problems, compared to children without premorbid learning problems.

Effects of surgical side and site on mood and behavior outcome in children with pharmacoresistant epilepsy.

Children with epilepsy have a high rate of mood and behavior problems; yet few studies consider the emotional and behavioral impact of surgery. No study to date has been sufficiently powered to investigate effects of both side (left/right) and site (temporal/frontal) of surgery. One hundred patients (aged 6-16) and their families completed measures of depression, anxiety, and behavioral function as part of neuropsychological evaluations before and after surgery for pharmacoresistant epilepsy. Among children who had left-sided surgeries (frontal = 16; temporal = 38), there were significant interactions between time (pre to post-operative neuropsychological assessment) and resection site (frontal/temporal) on anhedonia, social anxiety, and withdrawn/depressed scales. Patients with frontal lobe epilepsy (FLE) endorsed greater pre-surgical anhedonia and social anxiety than patients with temporal lobe epilepsy (TLE) with scores normalizing following surgery. While scores on the withdrawn/depressed scale were similar between groups before surgery, the FLE group showed greater symptom improvement after surgery. In children who underwent right-sided surgeries (FLE = 20; TLE = 26), main effects of time (patients in both groups improved) and resection site (caregivers of FLE patients endorsed greater symptoms than those with TLE) were observed primarily on behavior scales. Individual data revealed that a greater proportion of children with left FLE demonstrated clinically significant improvements in anhedonia, social anxiety, and aggressive behavior than children with TLE. This is the first study to demonstrate differential effects of both side and site of surgery in children with epilepsy at group and individual levels. Results suggest that children with FLE have greater emotional and behavioral dysfunction before surgery, but show marked improvement after surgery. Overall, most children had good emotional and behavioral outcomes, with most scores remaining stable or improving.

Epilepsy surgery in children with electrical status epilepticus in sleep.

OBJECTIVE: Pediatric epilepsy surgery candidates with unilateral congenital or early-acquired brain lesions may present with refractory seizures and generalized electroencephalographic features such as electrical status epilepticus in sleep (ESES). The purpose of our study was to review the clinical presentation, neuroimaging findings, and outcome in a series of children with unilateral brain lesions and ESES undergoing resective surgery for refractory epilepsy. METHODS: A total of 415 consecutive patients younger than 18 years of age undergoing video electroencephalographic evaluation and epilepsy surgery at Cleveland Clinic were reviewed for ESES, an underlying pathological lesion, and outcome after surgery. RESULTS: Eight patients were included. All patients presented with medically refractory epilepsy, hemiparesis, and developmental delay. The pathogenesis was perinatal infarction in 7 patients and malformation of cortical development in 1 patient. Preoperative electroencephalography demonstrated generalized interictal spikes, electroencephalographic seizures, and ESES in all cases. Age at the time of surgery ranged from 3 to 14 years. Six patients underwent hemispherectomy, and 2 patients underwent focal resection. Six patients became seizure-free after resection. Two patients with functional hemispherectomy continued to have rare seizures, but were much improved. These patients also had perinatal infarctions in the hemisphere contralateral to the resection, possibly indicating a less beneficial outcome. Postoperative electroencephalography demonstrated resolution of generalized interictal discharges and ESES in all. Formal pre- and postoperative neuropsychological testing showed overall improvement of age-equivalent scores. CONCLUSION: Children with unilateral brain lesions and seizures may become seizure-free after epilepsy surgery, even if the preoperative electroencephalogram shows generalized ESES. The lesion occurring early in life and the location of the lesion may play a role in the development of ESES. Cognitive impairment may be aggravated by the persistence of ESES. Preliminary developmental data in this small sample suggest that termination of seizures and possibly of ESES by epilepsy surgery may have developmental benefits.