Cognitive proficiency in pediatric epilepsy

Epilepsy & Behavior 23 (2012) 146–151

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Cognitive proficiency in pediatric epilepsy Lev Gottlieb a, Frank A. Zelko a,⁎, Deok Soo Kim b, Douglas R. Nordli c a b c

Department of Child and Adolescent Psychiatry, Children's Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Epilepsy Center, Children's Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

a r t i c l e

i n f o

Article history: Received 1 September 2011 Revised 20 October 2011 Accepted 24 October 2011 Available online 9 January 2012 Keywords: Cognitive proficiency Intelligence Pediatric epilepsy Frontal Temporal Lateralized

a b s t r a c t Cognitive proficiency (CP) is a sensitive gauge of neurological status, but it is not typically viewed in relation to focal cerebral function. We examined CP and its relationship to general intellectual ability and seizure focus in 90 patients with pediatric epilepsy. CP was significantly lower than general ability (GA) in the overall sample. In particular, it was more deficient than GA in patients with right- than left-lateralized epilepsy onset, and in patients with frontal- than temporal-onset epilepsy. The discrepancy between CP and GA varied with participants’ overall intelligence, being more pronounced (i.e., GA–CP difference larger) in individuals of lower overall ability. Deficits in CP are a defining characteristic of pediatric epilepsy and serve as an important marker of neurocognitive status, especially when seizures originate from a primary epileptogenic focus within the right hemisphere or the frontal lobe. © 2011 Elsevier Inc. All rights reserved.

1. Introduction Working memory (WM) and processing speed (PS) are facets of cognitive ability that are known to be sensitive indicators of neurological functioning in epilepsy [1–9] and other patient populations [10–17]. WM and PS both depend upon the integrity of the prefrontal cortex (PFC) and its connections to posterior brain regions [15,18–21]. The term cognitive proficiency (CP) has been used to refer to the functional domain encompassing these two overlapping mental faculties [22]. WM provides maintenance and manipulation of information in short-term storage, whereas PS determines information throughput, including the amount of information that can be used effectively in WM before it decays [23–25]. Together, they support critical abilities that evolve with age such as learning and problem solving [23,24], and they are key components of fluid reasoning for novel or higherorder cognitive tasks [22]. It is therefore not surprising that CP makes a major contribution to cognitive aptitude [17,26]. Although deficits of WM [5,9] and PS [1–8] have been independently documented in epilepsy, prior research has not considered them together as an integrated component of mental ability. A focus on CP is particularly relevant to pediatric populations, as WM and PS constitute a critical substrate for the development of intelligence [23,24]. Some studies have suggested that right-lateralized

⁎ Corresponding author at: Department of Child and Adolescent Psychiatry, Children's Memorial Hospital #10, 2300 Children's Plaza, Chicago, IL 60614, USA. Fax: + 1 773 880 8110. E-mail address: [email protected] (F.A. Zelko). 1525-5050/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2011.10.024

seizures differentially affect this cognitive substrate [9,27], whereas others have implicated left hemisphere disruption [28,29]. Though much research has been conducted on seizure lateralization and cognitive abilities [30], the impact of right- versus leftlateralized seizure onset on cognition remains unclear [31]. This is especially true in children, likely because of the immature brain's potential to reorganize [32–34]. There is greater, though still limited, consensus on the impact of seizure localization (anterior–posterior) on cognitive function. Frontal lobe epilepsy and temporal lobe epilepsy are two localization-based syndromes that have undergone particular scrutiny. Executive functions (EFs) such as CP are generally attributed to frontal cortex structures, whereas mnestic functions are classically associated with the temporal lobe [35,36]. Most direct comparisons indicate greater EF deficits in frontal than temporal lobe epilepsy [37–41]. Nevertheless, impaired EFs have been reported in temporal lobe epilepsy as well, suggesting adverse effects of epileptogenic temporal cortex on extratemporal neurocognitive functioning, partly through its impact on PFC connections to posterior association areas [1–5,8,42–44] and on the PFC itself [9,27,45–48]. The Wechsler Intelligence Scale for Children—Fourth Edition (WISC-IV) offers the opportunity to easily examine CP in isolation and also in comparison with another overarching intellectual subcomponent, general ability (GA) [17,49,50]. Dumont and Willis [49] defined the Cognitive Proficiency Index (CPI) based on the WISC-IV Working Memory (WM) and Processing Speed (PS) indices, which is distinct from a clustering of subscales called the General Ability Index (GAI) [17,50]. The GAI comprises the WISC-IV Verbal Comprehension (VC) and Perceptual Reasoning (PR) subscale indices. GAI and CPI provide more comprehensive and reliable cognitive estimates

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2. Methods

Table 1 Epilepsy diagnoses. Diagnosis

n

Childhood Childhood absence epilepsy Benign childhood epilepsy with centrotemporal spikes Epilepsy with myoclonic astatic seizures Epileptic encephalopathy with continuous spike-and-wave discharges during sleep Panayiotopoulos syndrome Lennox–Gastaut syndrome Adolescence Juvenile myoclonic epilepsy Juvenile absence epilepsy Distinctive constellations Mesial temporal lobe epilepsy with hippocampal sclerosis Rasmussen syndrome Epilepsy associated with identified structural or metabolic disorder not otherwise specified Epilepsy with no identified cause (structural–metabolic–idiopathic) not otherwise specified

11 5 4 3 2 1 2 1 6 3 35 17

than their subcomponents [51,52]. The GAI–CPI conceptualization of Wechsler Full Scale IQ (FSIQ) constitutes a substantial departure from the traditional Verbal IQ–Performance IQ framework, which was abandoned with the fourth edition of the WISC. This new framework may be particularly useful for clinical research, as it allows for intraindividual comparisons of CP with GA. The relationship between the GAI–CPI analytic framework and other models of intelligence such as Cattell–Horn theory is not straightforward [53]. Although subscales of the WISC-IV that make up the CPI clearly tap fluid abilities, the conceptual rationale for pooling the WISC-IV VC and PR indices is admittedly more tenuous. To an extent, both VC and PR tap crystallized abilities. However, some PR subtests (e.g., Matrix Reasoning) also tap fluid ability, so the GAI– CPI analytical framework is probably not factorially pure with respect to Cattell–Horn theory. Clinical experience with children who have epilepsy suggests that the combination of VC and PR to form the GAI provides a more stable and valid estimate of a child's “core” learning potential, apart from the deleterious impact of disease- and treatment-related factors on fluid abilities. In designing this project, we suspected that the GAI–CPI framework would be a promising one for intraindividual comparison in childhood epilepsy. The current study examines CP and GA in relation to seizure lateralization (right vs left) and seizure localization (frontal vs temporal) in a sample of children with epilepsy. On the basis of previous research, we hypothesized that CP would be deficient relative to GA across the overall sample, but particularly in those with a primary epileptic focus in the right hemisphere or the frontal lobe. We also hypothesized that the relationship between CP and GA might vary depending on subjects’ overall intellectual level.

2.1. Procedure This study was based on a retrospective chart review of patients who had been referred by a tertiary-care pediatric epilepsy center for neuropsychological testing to assist in clinical care or surgical planning. All participants had also received clinical evaluations consisting of a comprehensive neurological examination, video/EEG monitoring, and, in most cases (80%), MRI. In addition to neuropsychological testing results, demographic (age, gender) and clinical diagnostic (epilepsy diagnosis/syndrome, age at onset, duration of epilepsy, lateralization, localization, and current number of antiepileptic drugs) data were collected. In this study, lateralization refers to identified onset of seizures in one hemisphere, whereas localization refers to identified onset of seizures in either the frontal or temporal lobe. Duration of epilepsy refers to the time between epilepsy diagnosis and neuropsychological evaluation. All data were reviewed by a neurologist (D.S.K.) and neuropsychologist (F.A.Z.). This study was approved by the institutional review board of the Children's Memorial Research Center and is in accordance with the ethical standards established in the 1964 Declaration of Helsinki. 2.2. Participants Participants were 90 children and adolescents (aged 6–18 years) with either focal- or generalized-onset epilepsy who had been referred for clinical neuropsychological evaluation between November 2003 and June 2010. Fifteen participants had received repeat neuropsychological evaluations; for those individuals, only the last evaluation was considered. Age at epilepsy onset ranged from b1 to 15 years, and diagnoses of participants included a wide variety of epilepsy syndromes (Table 1). Additional descriptive characteristics of participants are summarized in Table 2. On the basis of clinical diagnostic information including clinical neurological exam, video/EEG monitoring, and structural MRI results, subgroups were defined consisting of participants with epilepsy that was determined to be of (1) unilateral right hemisphere onset (n = 28), (2) unilateral left hemisphere onset (n = 22), (3) frontal lobe onset (n = 10), and (4) temporal lobe onset (n = 24). Lateralization/localization group membership was not mutually exclusive; that is, a participant assigned to the frontal or temporal localization subgroup could also be assigned to a right or left hemisphere onset group. Forty participants (44%), including those with multifocal onset, were not assigned to either of these lateralization or localization subgroups. Subjects were also divided into three IQ range subgroups based on the sample mean Full Scale Intelligence Quotient (FSIQ) ± 1 SD (low: FSIQ b63; middle: FSIQ 63–100; high: FSIQ >100). FSIQ scores for the overall sample ranged from 40 to 129 (M = 81.2, SD = 19.1).

Table 2 Descriptive statistics. Group

n

Male

Age at neuropsychological evaluation

Age at onset

Duration of illness

Current number of AEDs

Overall Lateralization Right Left Localization Frontal Temporal IQ range Low Middle High

90

48%

11.7 (3.21)

7.44 (3.83)

3.97 (3.68)

1.28 (0.89)

28 22

50% 45%

12.3 (3.18) 12.3 (3.41)

7.23 (3.80) 7.58 (4.59)

4.85 (4.20) 4.21 (5.06)

1.29 (0.71) 1.55 (0.91)

10 24

50% 46%

12.6 (3.60) 12.9 (3.25)

7.11 (3.95) 7.95 (4.39)

5.00 (4.12) 4.68 (4.89)

1.40 (0.70) 1.38 (0.77)

17 59 14

47% 44% 64%

12.6 (3.34) 11.2 (3.18) 12.4 (3.03)

7.14 (4.91) 6.92 (3.32) 9.85 (3.87)

5.50 (5.43) 3.85 (3.38) 2.85 (1.77)

1.59 (0.80) 1.25 (0.96) 1.00 (0.56)

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Patients with epilepsy who had been referred for neuropsychological evaluation over the period retrospectively reviewed were excluded from participation if they had not been administered the full WISC-IV or if they had not undergone video/EEG monitoring. The WISC-IV was typically omitted from an evaluation of an age-eligible patient only when the patient (typically 6 or 7 years of age) was incapable of obtaining valid basal-level subtest scores or when the patient's primary language was not English. Patients were not excluded from participation on the basis of a performance criterion such as below-average intelligence. 2.3. Measure: Wechsler Intelligence Scale for Children—Fourth Edition The WISC-IV [54] is a measure for children aged 6–16 that provides estimates of FSIQ and four subcomposite factors—Verbal Comprehension (VC), Perceptual Reasoning (PR), Working Memory (WM), and Processing Speed (PS)—all with excellent reliability and validity [55]. These four indices sample the following functional domains: VC—verbal reasoning, comprehension, and conceptualization; PR—perceptual reasoning and organization; WM—maintenance and manipulation of verbal material in working memory; and PS—speed of visual scanning, tracking, sequencing, discrimination, and mental processing [26]. These indices were used to generate broader estimates of the GAI [17,50] and the CPI [22,49] for each participant (Fig. 1). All indices have a mean of 100 and a SD of 15. 2.4. Statistical analysis A paired-sample t test was used to compare mean GAI and CPI scores in the overall sample. GAI–CPI difference scores for patients with right- versus left-lateralized onset of seizures and frontal versus temporal localization were then examined using independent sample t tests. Independent sample t tests were also used to compare GAI–CPI differences for subjects with generalized-onset versus focal-onset of

Vocabulary

VC

Similarities

Comprehension GAI Block Design PR

Picture Concepts

seizures and to compare GAI–CPI differences in the generalizedonset group against, separately, the right lateralized-onset and frontal-onset groups. Finally, a one-way ANOVA was used to explore the impact of overall intellectual level (FSIQ) on GAI–CPI difference scores, with subjects divided into low-, middle-, and high-IQ groups, as described above. We decided on a three IQ group comparison because inspection of the distribution of scores suggested that patients clustered into these three groups in a fairly normal manner. Post hoc comparisons were conducted for significant overall group effects using Tukey HSD. Groups were compared on demographic and epilepsy diagnosis-related variables, with η 2 statistics used to estimate effect sizes. 3. Results In the overall sample, CPI scores (M = 80.6, SD = 19.8) were significantly lower than GAI scores [M = 84.9, SD = 18.1, t(89) = 3.19, P = 0.002], with η 2 (0.10) indicating a moderate to large effect size. Subjects with right- versus left-lateralized seizures and frontal versus temporal localization did not differ significantly on demographic or epilepsy diagnosis-related variables (Table 2), though lateralization was confounded with localization: The percentage of patients with right-lateralized seizures was greater in those with frontal than temporal localization [χ²(1, N = 34) = 4.01, P = 0.05]. GAI > CPI differences were significantly greater in the right- (M = 8.89, SD = 11.9) than left- (M = 0.41, SD = 15.4) lateralized group [t(48) = 2.20, P = 0.03] (Fig. 2) and also greater for the frontal (M = 11.5, SD = 10.5) than temporal (M = 0.42, SD = 15.7) group [t(32) = 2.05, P = 0.05] (Fig. 3), with η 2 statistics (0.09 and 0.12, respectively) indicating moderate to large effect sizes. Of note, GAI scores were essentially equivalent across these groups. Thus, CP was selectively compromised in those with seizures lateralized to the right hemisphere or localized to the frontal lobe. Because lateralization was confounded with localization, additional analyses were conducted in an attempt to clarify the impact of right lateralization versus frontal localization. Exploratory analyses within the temporal group identified significantly greater GAI > CPI differences in the right temporal (M = 7.18, SD = 12.1) than left temporal (M = −5.31, SD = 16.4] group [t(22) = 2.08, P = 0.05]. Numerically greater but nonsignificant GAI > CPI differences were observed in patients with right frontal (M = 11.4, SD = 11.1) than right temporal (M = 7.18, SD = 12.1) onset of seizures. Comparisons of participants with left frontal seizure onset (n = 1) with other groups were not possible because of insufficient sample size. These data suggest that right lateralization and frontal localization independently impact CP. GAI > CPI discrepancies did not differ significantly between the focal-onset group overall (M = 5.16, SD = 14.1) and the generalizedonset group overall (M = 2.31, SD = 10.0) [t(80) = 0.99, P = 0.32]. However, GAI > CPI differences were significantly greater in the

Matrix Reasoning

FSIQ

Digit Span WM Letter-Number Sequencing CPI Coding PS Symbol Search Fig. 1. Wechsler Intelligence Scale for Children—Fourth Edition factor structure. FSIQ, Full Scale Intelligence Quotient; GAI, General Abilities Index; CPI, Cognitive Proficiency Index; VC, Verbal Comprehension; PR, Perceptual Reasoning; WM, Working Memory; PS, Processing Speed.

Fig. 2. Mean GAI (General Ability Index) and CPI (Cognitive Proficiency Index) scores for right- and left-lateralized onset groups. Error bars span 1 SD of the mean.

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Fig. 3. Mean GAI (General Ability Index) and CPI (Cognitive Proficiency Index) scores for frontal and temporal localization groups. Error bars span 1 SD of the mean.

right-lateralized group than the generalized group [t(58) = 2.33, P = 0.02] and in the frontal-localized group than the generalized group [t(40) = 2.50, P = 0.02]. IQ-range subgroups did not differ significantly on demographic or epilepsy diagnosis-related variables, with the exception of age at epilepsy onset, which was significantly greater in the high- than mid-IQ subgroup [F(2,76) = 3.26, P = 0.04] (Table 2). GAI > CPI difference scores varied significantly among the three IQ-range subgroups [F(2,87) = 4.16, P = 0.02] (Fig. 4). Post hoc Tukey HSD comparisons showed the mean difference score for the mid-IQ subgroup (M = 6.81, SD = 12.9) to be significantly greater than that for the high-IQ subgroup (M = −2.79, SD = 11.3). The low-IQ subgroup mean difference score (M = 1.18, SD = 10.3) did not vary significantly from those of the other subgroups. 4. Discussion To our knowledge, this constitutes the first study of cognitive proficiency in pediatric epilepsy as a construct encompassing the functional subdomains of working memory and processing speed. The current data indicate that deficits in CP are a defining neurocognitive characteristic of pediatric epilepsy, among individuals with both focal and generalized onset. This is particularly true through the center of the IQ distribution of clinically referred children with epilepsy (i.e., mid-IQ subgroup), a range that is itself displaced below the general population mean. This finding is consistent with a large epidemiological study of epilepsy that documented PS deficits in children with relatively intact cognitive abilities [7], as well as more circumscribed studies reporting WM deficits [4,9]. It also coincides with recent research documenting white matter abnormalities in epilepsy [1–6,8,9,56]. Although other neurological insults affecting white matter pathways can also impair components of CP [13–16], deficient CP is not

Fig. 4. Mean GAI (General Ability Index) and CPI (Cognitive Proficiency Index) scores for low-, mid-, and high-IQ-range groups. Error bars span 1 SD of the mean.

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synonymous with compromised mental status. In fact, as FSIQ decreases in the general population, CP appears to be relatively spared [17]. CP, then, seems to be a particularly sensitive marker of neurocognitive dysfunction in neurological conditions affecting connectivity, such as epilepsy. Cognitive proficiency appears to be most notably depressed relative to GA when seizures originate from a primary epileptogenic focus within the right hemisphere or the frontal lobe. Our study indicates that CP was especially impacted in these groups, even in the context of relatively intact GA. Within our sample, right versus left hemisphere-onset group comparisons and frontal- versus temporalonset group comparisons failed to reveal differences on demographic, seizure-related, and other cognitive variables, including the GAI. Thus, deficient CP in individuals with right-lateralized or frontal lobe seizures cannot be explained by these external factors. Consistent with our findings, right(vs left)-lateralized seizures have been associated with greater cognitive dysfunction in general [57] and deficits in WM [9,27] and fluid abilities [57] in particular. Likewise, our results coincide with the preponderance of evidence documenting greater executive function deficits in frontal (than temporal) lobe epilepsy [37–41]. Contrary to what might be expected based on prior neurocognitive [28] and neuroimaging research on connectivity [28,29,42,58], we did not observe CP deficits in those with seizures lateralized to the left temporal lobe. Several factors may account for this discrepancy: small sample-size [29,58], confounding lateralization with age at onset [28,42], and studying adults rather than children [28,29,42]. Unfortunately, the one prior study of temporal lobe epilepsy, lateralization, and connectivity in children [58] examined only youth with left temporal lobe epilepsy, limiting comparisons of seizure lateralization (i.e., right vs left) on neurocognition. Although our study addresses some of these limitations, it would have benefited from an increased sample size. Our results nevertheless indicate that right temporal lobe seizures impact CP, consistent with evidence suggesting adverse effects of the epileptogenic temporal cortex on extratemporal neurocognitive functioning [4,9,27,45–48], at least when seizures are lateralized to the right hemisphere. Proficient processing relies on prefrontal cortex (PFC) structures and white matter connectivity to posterior association areas [15,19,20]. Our findings suggest greater disruption of these pathways when seizures originate in the right hemisphere or frontal lobe. The finding that frontal lobe seizures affect PFC functions like CP is not surprising, but reasons for the differential impact of right-lateralized seizures are less obvious. Long-standing theory on hemispheric asymmetries has posited that the right hemisphere contains a disproportionate share of the brain's multimodal association areas and relatively more white matter than the left hemisphere [59–61]. Under this view, white matter insults would be expected to have a greater disruptive effect on right hemisphere-mediated cognitive functions and also on cerebral connectivity critical to CP [27]. Recent technological advances in neuroimaging (e.g., diffusion tensor imaging) have made it possible to examine white matter tracts in finer detail, and emerging evidence [62–65] suggests a more complex and nuanced cerebral architecture than that posited by Goldberg and Costa [59]. Future studies will help clarify the nature of these hemispheric differences. Researchers have already begun to elucidate the neuroanatomical correlates of CP. Owen [18] and Petrides [19] document that independent of the domain of presentation (verbal, visual, spatial), the midventrolateral PFC subserves maintenance of information in WM, whereas monitoring and manipulation of such information are governed by the mid-dorsolateral PFC. WM also depends on PFC connections to multimodal posterior association areas involved in polysensory processing and encoding, such as parietal, parahippocampal, and superior temporal regions [19,21,66] and, thus, depends on both the PFC and its connectivity to posterior regions. PS also relies

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on white matter connectivity [15,66–70] and PFC executive functions such as energization [20] independent of domain. It is worth noting that a component of proficient processing—WM —is verbally mediated; hence, our findings of greater deficits from right (than left)-lateralized seizures contradict classic assumptions of verbal–nonverbal domain specificity and instead support models of process specificity. In light of recent challenges to the material specificity of cognition [71,72], some have argued that neuropsychological assessment has limited lateralizing value [30]. Still, the identified right and frontal process-specific impact of seizures on CP may inform epilepsy surgery planning by corroborating localization information from other sources such as structural and functional imaging, electroencephalography, and seizure semiology. 4.1. Limitations and future directions Interpretation of the current study's results is limited by considerations that stem largely from its retrospective, single-site design. In light of the following limitations, these findings should be considered preliminary and in need of corroboration. As already noted, a larger sample drawn from multiple study sites would have enhanced the power of our analyses and our ability to examine CP and GA within clinical subgroups defined by lateralization, localization, and epilepsy diagnosis. Second, our subjects’ clinical records did not consistently include reliable quantitative estimates of seizure frequency. Most of our subjects with focal onset had been referred for neuropsychological evaluation because of intractability, in consideration for epilepsy surgery. We know that similar proportions of cases with right (64%), left (86%), frontal (70%), and temporal (79%) onset were surgery candidates, and we can safely conclude that seizure control was not optimal in any of these cases. However, we cannot conclude that seizure frequency was the same in these groups. Likewise, our retrospective method limited our ability to establish with certainty the presence or absence of comorbid psychiatric conditions. Third, in the current sample, lateralization was confounded with localization: The proportion of patients with right (vs left)-lateralized seizures was greater in those with frontal (than temporal) localization. We attempted to tease apart the impact of right lateralization from frontal localization, but could not do so completely. Within a circumscribed sample of children with temporal lobe seizures, we demonstrated that right-lateralized seizures impact CP independent of frontal localization. Thus, our results suggest an independent effect of frontal (vs temporal) localization, but interpretation of those analyses is limited by the modest size of our left frontal group. Fourth, a potential confound in our analyses is the fact that age at epilepsy onset was greater in the high- than mid-IQ group. Earlier age at epilepsy onset has been clearly associated with greater neurocognitive dysfunction [1,2]. One could argue, then, that deficient CP simply reflects neurocognitive disruption by early onset of seizures. Though this may be partly true, age at onset does not tell the whole story, as the aforementioned groups differed in onset by less than 3 years on average, and age at onset/epilepsy duration was not significantly associated with CP deficits across the entire sample. These data reinforce the point that factors other than early onset, such as seizure localization, severity, and frequency must also be considered as contributors to CP deficits. Fifth, all children with frontal or temporal lobe seizures had underlying structural lesions, making it impossible to distinguish the neurocognitive impact of lesions from that of seizures themselves. Still, we examined a large and diverse sample of children with epilepsy representative of those presenting to tertiary-care facilities, and groups defined in our analyses were strikingly similar across most potentially confounding demographic and seizure-related variables. Finally, CP is partly derived from PS subtests of the WISC-IV, which require quick motor responses. Thus, low CP in those with frontal

lobe seizures may be partly attributable to compromised integrity of the motor cortex. However, motor dysfunction cannot account for the (deficient) WM loadings on CP, nor our right-lateralized findings. Moreover, psychometric studies have demonstrated that PS tasks rely more on cognitive fluency than speeded-motor execution [67]. Neurocognitive deficits in pediatric epilepsy have received increasing empirical scrutiny over recent years as investigators have attempted to understand the cognitive sequelae of recurrent seizures over the course of development. We now know that white matter pathways are damaged by the epileptic process [1–5]. Consistent with this neuroanatomical disruption, our preliminary data indicate that CP is selectively compromised by epileptogenic activity, especially in individuals with seizures originating from the right hemisphere or frontal lobe. Deficient CP can be detrimental to children who depend on this cognitive substrate to learn and reason. In light of the importance of CP, neuropsychological assessment of children with epilepsy should routinely examine this facet of cognitive ability. Future research should consider within broader samples the relationship between CP and more detailed parameters of epilepsy such as specific diagnoses, other localizations (e.g., parietal), and degree of seizure control. Efforts are also needed to identify interventions and accommodations that can effectively remediate CP deficits. Ethical approval We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Conflict of interest statement None of the authors has any conflict of interest to disclose. Acknowledgment This work was supported in part by a Shaw Nursing & Allied Health Research Grant sponsored by the Walden W. and Jean Young Shaw Foundation. References [1] Hermann B, Seidenberg M, Bell B, et al. The neurodevelopmental impact of childhood-onset temporal lobe epilepsy on brain structure and function. Epilepsia 2002;43:1062–71. [2] Hermann B, Hansen R, Seidenberg M, Magnotta V, O'Leary D. Neurodevelopmental vulnerability of the corpus callosum to childhood onset localization-related epilepsy. Neuroimage 2003;18:284–92. [3] Hermann B, Seidenberg M, Bell B, et al. Extratemporal quantitative MR volumetrics and neuropsychological status in temporal lobe epilepsy. J Int Neuropsychol Soc 2003;9:353–62. [4] Dow C, Seidenberg M, Hermann B. Relationship between information processing speed in temporal lobe epilepsy and white matter volume. Epilepsy Behav 2004;5:919–25. [5] Oyegbile TO, Dow C, Jones J, et al. The nature and course of neuropsychological morbidity in chronic temporal lobe epilepsy. Neurology 2004;62:1736–42. [6] Hermann B, Jones J, Sheth R, Dow C, Koehn M, Seidenberg M. Children with newonset epilepsy: neuropsychological status and brain structure. Brain 2006;129: 2609–19. [7] Berg AT, Langfitt JT, Testa FM, et al. Residual cognitive effects of uncomplicated idiopathic and cryptogenic epilepsy. Epilepsy Behav 2008;13:614–9. [8] Dabbs K, Jones J, Seidenberg M, Hermann B. Neuroanatomical correlates of cognitive phenotypes in temporal lobe epilepsy. Epilepsy Behav 2009;15:445–51. [9] Keller SS, Baker G, Downes JJ, Roberts N. Quantitative MRI of the prefrontal cortex and executive function in patients with temporal lobe epilepsy. Epilepsy Behav 2009;15:186–95. [10] Sperling RA, Guttmann CR, Hohol MJ, et al. Regional magnetic resonance imaging lesion burden and cognitive function in multiple sclerosis: a longitudinal study. Arch Neurol 2001;58:115–21. [11] Verger K, Junque C, Levin HS, et al. Correlation of atrophy measures on MRI with neuropsychological sequelae in children and adolescents with traumatic brain injury. Brain Inj 2001;15:211–21. [12] Van der HP, Donders J. WAIS-III factor index score patterns after traumatic brain injury. Assessment 2003;10:115–22.

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