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Frontal Lobe Dysfunction in Children WithTemporal Lobe Epilepsy

Patrícia Rzezak, BSc*, Daniel Fuentes, PhD*, Catarina A. Guimarães, PhD†,Sigride Thome-Souza, MD‡§, Evelyn Kuczynski, MD, PhD§, Li M. Li, MD, PhD†,

Renata C. Franzon, MD, PhD†, Claudia C. Leite, MD, PhD¶, Marilisa Guerreiro, MD, PhD†,and Kette D. Valente, MD, PhD‡§

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here is evidence that adults with temporal lobepilepsy present executive impairments. However,here is limited information in children, especiallyhen using a comprehensive neuropsychologic bat-

ery. We aimed to: 1) investigate the presence andeverity of executive dysfunctions in children withemporal lobe epilepsy, and 2) determine the impli-ations of clinical variables (including etiology) inhe occurrence and severity of executive dysfunction,sing eight paradigms. Thirty-one children withemporal lobe epilepsy were evaluated and com-ared with 21 age-matched controls. Patients withemporal lobe epilepsy had significantly worse per-ormance than controls. Intragroup analysis indi-ated that patients with symptomatic epilepsy wereore impaired than those with cryptogenic epilepsy.

n the former group, patients with mesial lesionserformed worse than those with lateral lesions.egarding the severity of executive dysfunction,3.87% manifested severe to moderate executivempairment. Early age of onset, longer duration ofpilepsy, and use of polytherapy were correlated withorse executive dysfunction. These findings indicated

he presence of frontal lobe dysfunction in childrenith temporal lobe epilepsy, with worse performance

n those with mesial temporal lobe epilepsy, earlynset, longer duration of disease, and use of polythe-apy. Our study corroborates the hypothesis that tem-oral lobe epileptogenic activity affects the extratem-oral regions that mediate attentional and executiveunctions. © 2007 by Elsevier Inc. All rights reserved.

rom the *Psychology and Neuropsychology Unit, Institute ofsychiatry, Clinical Hospital, Medical School, University of Sãoaulo, São Paulo, Brazil; †Department of Neurology, University ofampinas, Campinas, Brazil; and ‡Laboratory of Clinicaleurophysiology, Institute of Psychiatry and Department ofsychiatry, §Project for the Study of Psychiatric Disorders in Childrennd Adolescents with Epilepsy, Institute of Psychiatry, and ¶Institute

nd Department of Radiology, Clinical Hospital, Medical School,niversity of São Paulo, São Paulo, Brazil.

76 PEDIATRIC NEUROLOGY Vol. 37 No. 3doi:1

zezak P, Fuentes D, Guimarães CA, Thome-Souza S,uczynski E, Li LM, Franzon RC, Leite CC, Guerreiro M,alente KD. Frontal lobe dysfunction in children with

emporal lobe epilepsy. Pediatr Neurol 2007;37:176-185.

ntroduction

In temporal lobe epilepsy, the presence of specificognitive deficits, such as learning and memory impair-ents (functions known to be associated with the temporal

obes), are fully recognized as part of the typical clinicalicture [1-3].In addition, some studies demonstrated the occurrence

f frontal lobe dysfunction, characterized by executivealfunctioning, in adults with temporal lobe epilepsy.hese patients show perseverative responding and impair-ents in abstraction and problem-solving abilities [4-7].Two hypotheses were postulated to explain this execu-

ive dysfunction in patients with temporal lobe epilepsy.ccording to Corcoran and Upton [8], perseverative re-

ponding could be explained by an impairment of workingemory, determined by the involvement of the hippocam-

us per se. In their study, patients with hippocampalclerosis performed poorly in a modified version of the

isconsin Card Sorting Test compared with patients withither temporal neocortical lesions or frontal lobe lesions.n the other hand, Hermann and Seidenberg [5] proposed

hat temporal lobe epileptogenic activity might disrupt thextratemporal lobe connections responsible for executive

ommunications should be addressed to:r. Valente; Rua Jesuíno Arruda 901/51; São Paulo,4532-082 São Paulo, Brazil.-mail: kettevalente@msn.comeceived July 31, 2006; accepted May 25, 2007.

© 2007 by Elsevier Inc. All rights reserved.0.1016/j.pediatrneurol.2007.05.009 ● 0887-8994/07/$—see front matter

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kills, based on a correlation between performance andeizure control, but not with etiology.

In children with temporal lobe epilepsy, many neuro-sychologic aspects are unclear, even when consideringxtensively studied temporal lobe functions, such as mem-ry. For instance, there is evidence of memory deficitshen these patients are compared with normal controls

9-14]. However, whether children and adolescents withemporal lobe epilepsy do [15-18] or do not [19,20] haveemispheric specialization for verbal and visual memoryemains controversial.

Hernandez et al. [21] analyzed frontal lobe dysfunctionplanning abilities, working memory, impulse control,ttention, and certain aspects of motor coordination) inhildren with frontal lobe epilepsy by using children withemporal lobe epilepsy, with idiopathic generalized epi-epsy (typical absences) and normal controls for compar-son. Children with frontal lobe epilepsy exhibited deficitsn planning and impulse control, and more coordinationroblems than the others. A further study [22], withimilar characteristics, corroborated these findings, i.e.,hildren with frontal lobe epilepsy had worse performancen executive function tests, whereas temporal lobe epilepsynly showed impairments in memory tests.These findings, revealing worse performance in executive

ests in children with frontal lobe epilepsy compared withhildren with temporal lobe epilepsy, were expected, but doot exclude subtle executive dysfunctions in temporal lobepilepsy that could impair children’s daily-life performance.herefore, the importance of studying executive functions in

emporal lobe epilepsy is crucial, because these executiveeficits may remain undervalued in these children.

The only study that specifically addressed frontal lobeysfunction in children with temporal lobe epilepsy [23]ound poor performance in executing and planning tasks inhildren with hippocampal sclerosis compared with lateralemporal lobe or frontal lobe lesions, when using onearadigm: the Wisconsin Card Sorting Test.To date, no studies have used a comprehensive neuro-

sychologic battery to evaluate executive functions inhildren with temporal lobe epilepsy compared with age-atched, normal controls. For this reason, we aimed to:

) investigate the presence and severity of executiveysfunctions in children with temporal lobe epilepsy, and) determine the implications of clinical variables ofpilepsy and etiology on the occurrence and severity ofxecutive dysfunction, by using an extensive neuropsy-hologic evaluation consisting of eight paradigms.

ethods

atients

We prospectively evaluated 31 consecutive children and adolescentsith temporal lobe epilepsy, followed in the Ambulatory of Epilepsy in

he Clinics Hospital of the University of São Paulo from 2005 to 2007. a

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The group was made up of 17 boys (54.84%) with a mean age of 11.84ears (range, 8 to 16 years old; standard deviation, 4.59 years), and aean estimated intelligence quotient (IQ), based on the Block Design

nd Vocabulary subtests of the Wechsler Intelligence Scale for Children-II [24], of 95.78 (range, 71 to 135; standard deviation, 12.57).

Twenty-four patients (77.42%) had symptomatic temporal lobe epi-epsy. Symptomatic temporal lobe epilepsy was defined as a lesionestricted to the temporal lobe region (mesial or lateral), and demon-trated with a 1.5T magnetic resonance image.

We also included seven patients (22.58%) with cryptogenic temporalobe epilepsy determined by ictal and interictal electroencephalogramindings. Patients with extratemporal epileptic activity were excludedrom this group. Demographic and clinical information for each individ-al is presented in Table 1.

emporal Lobe Epilepsy Groups

The symptomatic temporal lobe epilepsy groups included:

1) Mesial temporal lobe epilepsy group: composed of 18 patients(75%), including 13 boys (72.22%), 15 with hippocampal sclerosis,two with a mesial temporal tumor, and one with gliosis of theparahippocampal gyrus, at a mean age of 12.35 years (standarddeviation, 2.29 years) and mean estimated intelligence quotient of95.36 (standard deviation, 14.25).

2) Lateral temporal lobe epilepsy group: composed of six patients(25%), including two boys (33.33%), three with temporal dysplasia,one with temporal cysts, one with a temporal tuber, and one with atemporal cavernoma, at a mean age of 11.57 years (standarddeviation, 2.57) and mean estimated intelligence quotient of 93.18(standard deviation, 12.11).

The cryptogenic temporal lobe epilepsy group: Seven patients, includ-ng two boys (28.57%), with a mean age of 11.86 years (standardeviation, 2.03), and mean estimated intelligence quotient of 98.92standard deviation, 9.64).

ontrols

Healthy volunteers were recruited among students from a publicchool. These children were matched to study subjects in terms of age,nd socio-demographic and educational background, had neither psychi-tric diagnosis according to the Diagnostic and Statistical Manual ofental Disorders-IV [25], nor previous or current history of neurologic

isorders.Twenty-one healthy children (7 boys), at a mean age of 11.8 years

range, 9-16 years old; standard deviation, 2.4), were selected. Meanstimated intelligence quotient, based on the Block Design and Vocab-lary subtests of the Wechsler Intelligence Scale for Children-III [24],as 108 (range, 83 to 135; standard deviation, 15.0).The exclusion criteria for patients and controls included: an estimated

ntelligence quotient below 70; clinical signs of drug intoxication or anyther condition that could lead to cognitive impairment; diagnosis ofsychiatric illness; alcohol or drug abuse; any brain-related surgicalntervention; and not being in school.

The elapsed time between last seizure and the moment of neuropsy-hologic evaluation was at least 48 hours. Three patients who experi-nced seizures during testing were reevaluated 1 week later.

erformance in Attention and Executive Tests

Evaluation was completed during the course of two sessions, duringhich a battery of attention and executive tests was performed with each

hild. Tests were administered by a trained neuropsychologist in a quietaboratory and in a standard sequence. Applied tests and cognitive

ssessed functions included:

177zezak et al: Executive Dysfunction and Temporal Lobe Epilepsy

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1) Auditory attention and short-term retention capacity (Digit Span,Wechsler Intelligence Scale for Children-III [24], and Number andLetter, Wide Range Assessment of Memory and Learning [26]);

2) Visual attention and short-term retention capacity (Finger Windows,Wide Range Assessment of Memory and Learning [26]);

3) Complex visual scanning, visual attention, mental flexibility, andinhibitory control (Trail Making Test, Children’s Version [27]);

4) Semantic naming, response initiation, verbal search, and productionof individual words under restrictive search conditions (WordFluency, Animals and Foods) [27];

5) Abstract behavior, set shifting, response inhibition, and mentalflexibility at the cognitive level (Wisconsin Card Sorting Test [28]);and

6) Impulse control (Matching Familiar Figures Test-20 [29]).

orrelation With Clinical Variables

Clinical variables included: etiology (symptomatic versus crypto-enic), location (mesial temporal lobe epilepsy and lateral temporal lobepilepsy in the symptomatic group), laterality (right versus left), age ofnset, duration of epilepsy, seizure type, presence of secondary general-zation, frequency of seizures, history of status epilepticus, history of

able 1. Demographic description of patients with temporal lobe e

Patient Sex Age (yr) IQ Subgroup

1 F 15 83 Cryptogenic2 M 15 122 Lateral3 F 10 80 Lateral4 M 15 71 Mesial5 M 12 80 Mesial6 F 14 109 Cryptogenic7 M 15 103 Mesial8 F 12 85 Lateral9 F 11 103 Cryptogenic0 F 12 97 Mesial1 F 12 85 Mesial2 M 11 94 Mesial3 M 9 135 Mesial4 M 14 77 Mesial5 F 11 106 Cryptogenic6 F 11 103 Cryptogenic7 M 9 85 Cryptogenic8 F 10 109 Mesial9 M 15 103 Mesial0 M 9 94 Mesial1 F 13 86 Mesial2 M 12 106 Cryptogenic3 F 8 100 Mesial4 M 13 117 Mesial5 M 9 100 Lateral6 M 15 91 Mesial7 M 13 103 Mesial8 M 14 85 Mesial9 F 9 94 Lateral0 F 11 91 Lateral1 M 15 94 Mesial

bbreviations:PS � Complex partial seizureNET � Dysembryoplastic neuroepithelial tumor

� FemaleH � Familiar history of epilepsyS � Febrile seizuresTCS � Generalized tonic-clonic seizureA � Hippocampal atrophy

revious neurological insult, family history of epilepsy, use of mono- b

78 PEDIATRIC NEUROLOGY Vol. 37 No. 3

herapy and polytherapy, and seizure control status at the moment ofeuropsychologic evaluation.

everity of Executive Dysfunction

We adopted clinical criteria to measure the severity of executiveysfunction in our patients with temporal lobe epilepsy. We consideredn executive function to be impaired when the patient had a baderformance (lower than 1 standard deviation) in at least two executivearadigms compared with controls.Degrees of severity for the comprehensive battery of eight executive

aradigms were classified as mild when deficits occurred in twoxecutive tests, moderate if impairment occurred in 3 to 4 executive tests,nd severe when there was failure in 5 out of 8 executive paradigms.

tatistical Analysis

Descriptive analysis consisted of means and standard deviations ofach variable. Demographic variables (age, sex, and education) ofatients and controls were compared using the chi-square test to verify if

Lesion Education (yr) Age of Onset (yr)

n 6 6r temporal dysplasia 8 6mpal dysplasia, R 4 1

5 15 1

n 8 9L 10 7

dysplasia, R 3 2n 5 3teral 6 7

6 86 24 35 5

n 5 2n 2 2n 4 2

3 2pocampal gyrus lesion 5 1mpal rotation 4 2

4 5n 7 10

2 27 6

al cavernoma, L 3 79 45 107 3

al cyst, R 3 2al tubers bilateral 4 1ala tumor, R 6 6

pilepsy

No lesioPosterioHippocaMTS, RMTS, LNo lesioDNET,WernickNo lesioHA bilaMTS, RMTS, LMTS, LMTS, RNo lesioNo lesioNo lesioMTS, RParahipHippocaMTS, RNo lesioMTS, RMTS, LTemporMTS, LHA, RMTSRTemporTemporAmygd

oth groups could be matched.

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Regarding neuropsychologic performance, patients and controls wereompared by t test. A nonparametric Mann-Whitney test was used toompare groups (symptomatic, cryptogenic, and controls) because of themall number of subjects in each group.

Finally, analysis of variance was used to evaluate the influence oflinical variables on executive functions. Significance was set at P �.05. For statistical analysis, the SPSS 11.0 software package was used.

esults

No statistical difference was found between the tempo-al lobe epilepsy groups and controls regarding sex (F �.596, P � 0.087), and years of education (F � 0.466,� 0.335). However, differences were observed regard-

ng chronological age (F � 0.051, P � 0.035), withontrols being younger.

erformances in Attention and Executive Tests

Patients with temporal lobe epilepsy had a worse perfor-

able 1. Continued

Duration (yr) SE FH FS

9 No Yes No9 Yes Yes No9 No Yes No

14 Yes Yes Yes12 No Yes Yes5 No Yes No8 Yes No No

10 No Yes No8 No Yes No5 No Yes Yes4 Yes Yes No9 Yes No Yes6 No Yes No9 No No No9 No No No8 No Yes No7 No Yes No8 Yes Yes Yes

14 Yes No No7 No Yes No8 Yes No Yes2 No Yes No6 No Yes No7 No Yes No2 Yes No Yes

11 No No Yes3 Yes No No9 No Yes Yes6 No Yes No9 No No No9 No No No

Q � Intelligence quotient� Left� Male

TS � Mesial temporal sclerosis� Right

E � Status epilepticusPS � Simple partial seizure

ance compared with controls in the following tests: Wis- a

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onsin Card Sorting Test (number of categories achieved,� 0.002, number of perseverative errors, P � 0.035; and

umber of perseverative responses, P � 0.045); Digit For-ard (Wechsler Intelligence Scale for Children-III, P �.003); Matching Familiar Figures Test (number of errors,� 0.033; and total index, P � 0.042); Trail Making Test

numbers of errors in trial A, P � 0.040; time to accomplishn trial B, P � 0.038; and number of errors in trial B, P �.006); Word Fluency (animals, P � 0.035); Finger WindowWide Range Assessment of Memory and Learning, P �.014); and Number and Letter (Wide Range Assessment ofemory and Learning, P � 0.007) (Table 2).There were no differences between patients with tem-

oral lobe epilepsy and controls in the Wisconsin Cardorting Test (number of nonperseverative errors, andailure to maintain set); Digit Back-Forward (Wechslerntelligence Scale for Children-III); Matching Familiarigures Test (latency time); Trail Making Test (time to

equency Number of AEDs Seizure Type

ly 1 CPSut seizures 1 CPS, GTCSut seizures 2 CPSkly 2 SPS, CPS, GTCSly 1 CPSut seizures 0 CPSly 0 SPS, CPS, GTCSut seizures 1 CPSly 1 SPS

ly 2 SPS, CPS, GTCS2 SPS

ut seizures 2 SPS, CPS1 SPS

ly 2 SPSut seizures 1 SPS, CPS, GTCSut seizures 0 CPSut seizures 1 SPS, CPS

1 SPS, CPS1 SPS, CPS

ut seizures 1 SPS, CPS1 SPS, CPS

ut sizures 1 CPSut seizures 1 CPSut seizures 1 SPS, CPSly 1 SPS, CPSly 2 CPS

ly 2 SPS, CPS, GTCSut seizures 1 SPS, CPSut seizures 1 SPS, CPSut seizures 1 CPS, GTCSly 1 SPS, CPS

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WeekWithoWithoBiweeWeekWithoWeekWithoMonthWeekDailyWithoDailyWeekWithoWithoWithoDailyDailyWithoDailyWithoWithoWithoMonthMonthWeekWithoWithoWithoWeek

ccomplish trial A); and Word Fluency (foods) (Table 2).

179zezak et al: Executive Dysfunction and Temporal Lobe Epilepsy

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orrelation With Clinical Variables

We observed that the existence of a temporal lobe lesionin the mesial or lateral structures), as visualized onagnetic resonance imaging, determined a worse perfor-ance of children with symptomatic temporal lobe epi-

epsy in executive functions tests compared with patientsith cryptogenic temporal lobe epilepsy and controls

Table 3). In addition, patients with lesions in mesialemporal lobe structures had a worse performance in aigher number of tests than those with lateral temporalobe lesions (Table 3).

Patients with an early age of epilepsy onset, longeruration of epilepsy, and polytherapy had a statisticallyignificantly worse performance in a large number ofubtests (Table 4). History of status epilepticus, familyistory of epilepsy, seizure control, frequency of seizures,nd presence of secondary generalization had a smallernfluence on executive performance, considering the num-er of subtests (�2 subtests) (Table 4).

everity of Executive Dysfunction

Based on the adopted clinical criteria, 28 (90.32%) of

able 2. Means, standard deviations, and P values of the differencxecutive functions tests (t test)

TestsTemporal LobeEpilepsy, Mean

Temporal Lobe EpilepsyStandard Deviation

CST (categ.) 4.07 2.82CST (PE) 29.77 21.16CST (NPE) 25.13 16.95CST (PR) 36.43 29.13CST (MS) 0.93 1.01F (WISC-III) 6.73 2.15B (WISC-III) 4.53 2.01FFT errors 20.00 11.28FFT time 216.31 129.71FFT total 3178.86 1936.81

M A time 37.73 38.61M A errors 0.23 0.50M B time 63.00 26.33M B errors 0.55 0.87F foods 10.61 4.26F animals 12.71 4.87

inger Windows 13.07 5.16umber-Letter 7.80 3.12

bbreviations:B � Digit Back-ForwardF � Digit ForwardFFT � Matching Familiar Figures Test

M � Trail Making TestCST � Wisconsin Card Sorting TestCST (categ.) � Wisconsin Card Sorting Test (number of categoriesCST (MS) � Wisconsin Card Sorting Test (failure in maintenanceCST (NPE) � Wisconsin Card Sorting Test (nonperseverative errorCST (PE) � Wisconsin Card Sorting Test (perseverative errors)CST (PR) � Wisconsin Card Sorting Test (perseverative responseF � Word Fluency

oldface indicates statistical significance.

1 patients with temporal lobe epilepsy exhibited an c

80 PEDIATRIC NEUROLOGY Vol. 37 No. 3

xecutive dysfunction. In terms of the severity of thisysfunction, we estimated that:

2 patients (7.14%) had a mild executive dysfunction(two with cryptogenic temporal lobe epilepsy);11 patients (39.28%) had a moderate executive dysfunc-tion (seven with mesial temporal lobe epilepsy, one withlateral temporal lobe epilepsy, and three with crypto-genic temporal lobe epilepsy); and15 patients (53.57%) had a severe executive dysfunction(nine with mesial temporal lobe epilepsy, four withlateral temporal lobe epilepsy, and two with cryptogenictemporal lobe epilepsy).

herefore, 28 patients (90.32%) had some degree ofxecutive dysfunction, and 26 (83.87%) of 31 evaluatedatients had an executive dysfunction classified as mod-rate or severe.

iscussion

Frontal lobe dysfunction includes difficulties in antici-ating, planning and organizing, initiating action plans,nhibiting distractions and interference, monitoring a pro-

mporal lobe epilepsy patients’ and controls’ performance in

ontrols, MeanControls, Standard

Deviation t P Value

6.35 2.35 �2.997 0.02020.25 10.74 1.854 0.03519.55 10.74 1.314 0.09724.40 13.04 1.731 0.0450.85 0.88 0.30 0.3807.90 1.70 �2.853 0.0034.81 1.25 �0.557 0.290

14.15 8.39 1.876 0.033227.00 148.97 �0.235 0.407

2339.05 1094.82 1.757 0.04228.19 13.20 1.086 0.141

0.05 0.22 1.792 0.04049.14 27.09 1.815 0.038

0.10 0.30 2.619 0.00614.14 4.61 �1.064 0.14614.48 5.18 �2.836 0.03515.71 3.32 �2.248 0.01410.62 4.91 �2.543 0.007

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nd working memory. These abilities are attributed toxecutive functioning [6,7,30].

This study is the first to analyze executive functions inhildren with temporal lobe epilepsy by means of a broadeuropsychologic battery. The absence of significant dif-erences between performances in several tests in ourtudy underscores their complementary nature, and rein-orces the concept of executive functions as a multidimen-ional phenomenon comprising a wide spectrum of abili-ies, not all of which are measured by the same tests.

oreover, groups of subjects with impairments of theseunctions are heterogeneous, and neuropsychologic mea-ures address independent and complementary compo-ents.The Wisconsin Card Sorting Test is the most frequently

sed test to examine executive functions in patients withpilepsy [23,31-33]. For patients with frontal lobe lesionsnd severe executive impairment, there is a consensus thathis test is as sensitive as any other [23,34-36]. However,here are many controversies regarding the degree ofxecutive impairment in patients with subtle executiveysfunctions, such as in temporal lobe patients. It wasostulated [1,6,37] that these controversies may be theesult of a widespread use of the Wisconsin Card Sortingest, which may be insufficient to evaluate all of theseeficits.In studies of children, the prefrontal region became fully

unctional only in late childhood or preadolescence [38-0]. Developmental changes were described in a cross-ectional study by Igarashi and Kato [41], using the

isconsin Card Sorting Test on normal children. Theseuthors found that the adult pattern was achieved after 12ears of age. Our results with the Wisconsin Cardorting Test, in children with temporal lobe epilepsy,orroborate those observed in adults [5,8,31], demon-trating that, even in children, some of the executiveunctions measured by the Wisconsin Card Sorting Testre compromised, despite the presence of mechanismsf neural plasticity.In our series, using a more comprehensive battery for

xecutive functions, we observed that children and ado-escents with temporal lobe epilepsy had impairments notompletely measured by the Wisconsin Card Sorting Testn mental flexibility and set shifting, perseveration, inhib-tory control, verbal fluency, and maintenance of attention,einforcing our hypothesis that a more comprehensive andxtensive neuropsychologic battery is necessary to assesshese complex cognitive functions.

The importance of studying children and adolescentsas emphasized by Martin et al. [31]. Although children

nd adults with temporal lobe epilepsy have the samenderlying pathology, children and adolescents have notet undergone the effects of long-lasting epilepsy, andave substantially fewer years of seizure activity. Ouresults suggest that temporal lobe involvement per se ismportant, because this pattern of extensive cognitive

mpairment, as reported elsewhere [1,5,8,31] in adults, can d

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lso be observed in early stages of life. Patients with earlypilepsy onset had a worse performance, corroborating theecent study of Cormack et al. [42], which demonstratedhat age of onset was the best predictor of intellectualysfunction, suggesting that the first year of life representscritical period for the development of intellectual abili-

ies. However, it must be emphasized that our patientsith a longer duration of epilepsy had more extensive

ognitive impairment, corroborating the idea that earlyntervention is necessary.

In terms of etiology, patients with symptomatic tempo-al lobe epilepsy had a worse performance in tests ofxecutive function than those with cryptogenic temporalobe epilepsy and controls. Moreover, patients with lesionsn mesial structures had a worse performance in a higherumber of tests compared with patients with lateral tem-oral lesions. However, the number of children in thisroup was low (six patients), which could represent aimiting factor to this analysis.

Based on our findings, we partially agree with Corcorannd Upton [8] that the hippocampus acts like a comparatorf actions, wherein lesions determine the existence of arefrontal lobe dysfunction. Nevertheless, it is importanto emphasize that patients with lateral temporal lobepilepsy also displayed executive dysfunction. For thateason, we believe in a wide anatomical and functionaletwork connecting temporal and frontal lobes, and allow-ng the temporal epileptogenic zone to affect the frontalnd prefrontal regions [23,31,32].

In accordance with this hypothesis, recent functionaleuroimaging studies demonstrated hypometabolism inhe prefrontal regions of patients with temporal lobepilepsy [43,44]. Nelissen et al. [43], using single-photonmission computed tomography and positron emissionomography, found interictal hypometabolism in the fron-al lobe cortex of adults with temporal lobe epilepsy. Theuthors suggested a dynamic process of frontal lobeunction inhibition, which could represent a process ofrotection against epileptiform-discharge propagation, buthich could also be responsible for the functional deficitsresented by these patients. In a structural imaging study,sing voxel-based morphometry, Cormack et al. [45]ound a reduction in grey-matter density ipsilateral to theeizure focus in the hippocampus, lateral temporal lobe,nd extratemporal regions, including the thalamus, poste-ior cingulate cortex, cerebellum, and frontal and parietalpercular cortex, which, according to these authors, couldeflect a structural change determined by the disruption ofortical development by recurrent seizures and by a loss ofunctional input from the sclerotic hippocampus. Thisinding suggests more than a functional intermittenthange [43], and would explain our findings of worseerformance in earlier and longer-duration epilepsy.The severity of executive dysfunction in temporal lobe

pilepsy patients was not previously evaluated. Here, welaborate upon clinical criteria with which we could

etermine that 83.87% of those children and adolescents

181zezak et al: Executive Dysfunction and Temporal Lobe Epilepsy

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able 3. Differences in executive performance of temporal lobe epilepsy patients (mesial, lateral, and cryptogenic) and controls (Z and Palues) (Mann-Whitney test)

TestsMesial Lateral

� (SD) Z P � (SD) Z P

CST (categ.) 3.67 (2.56) �2.282 0.002 3.5 (2.88) �2.180 0.014CST (PE) 32.89 (24.10) �1.639 0.050 30.50 (11.40) �1.768 0.038CST (NPE) 26.06 (19.36) �0.585 0.279 28.00 (11.90) �1.615 0.053CST (PR) 40.72 (33.73) �1.434 0.076 36.67 (12.52) �1.951 0.025CST (MS) 0.72 (0.89) �0.520 0.301 1.17 (0.41) �1.160 0.123F (WISC-III) 7.00 (2.17) �2.410 0.008 6.67 (1.97) �1.677 0.047B (WISC-III) 4.39 (1.54) �1.091 0.137 4.00 (3.10) �1.071 0.142FFT errors 18.82 (11.17) �1.444 0.126 20.17 (11.65) �1.251 0.100FFT time 228.22 (140.80) 0.000 0.500 247.67 (105.66) �0.292 0.385FFT total 2943.12 (1081.29) �0.412 0.340 4576.50 (3463.55) �2.313 0.010

M A 31.38 (16.36) �0.412 0.340 66.17 (79.76) �1.343 0.089imeM A errors 0.24 (0.42) �1.679 0.046 0.33 (0.82) �1.027 0.152M B 65.06 (27.56) �1.718 0.043 70.40 (37.42) �1.204 0.114imeM B errors 0.76 (1.00) �2.664 0.004 0.00 (0.00) �0.704 0.240F 12.67 (4.47) �2.675 0.003 10.00 (5.33) �1.961 0.028

oodsF animals 10.39 (3.87) �1.202 0.114 9.67 (3.98) �1.908 0.025

inger Windows 12.67 (4.57) �1.982 0.023 10.50 (6.35) �2.495 0.006umber Letter 7.39 (2.66) �2.557 0.005 7.00 (3.58) �2.208 0.013

bbreviations:B � Digit Back-ForwardF � Digit ForwardFFT � Matching Familiar Figures Test

� MeanD � Standard deviationM � Trail Making Test

oldface indicates statistical significance.

able 4. Influence of clinical variables in temporal lobe epilepsy on executive function tests (analysis of variance)

Test/Variable (P Value) Lesion Laterality Age of Onset (yr) Duration (yr) SE FH FS

CST (categ.) 0.933 0.281 0.680 0.392 0.142 0.462 0.435CST (PE) 0.731 0.729 0.925 0.260 0.010 0.045 0.626CST (NPE) 0.525 0.184 0.827 0.437 0.812 0.114 0.877CST (PR) 0.746 0.644 0.806 0.273 0.090 0.044 0.525CST (MS) 0.248 0.001 0.302 0.128 0.282 0.805 0.758F (WISC-III) 0.860 0.099 0.953 0.016 0.993 0.501 0.482B (WISC-III) 0.891 0.700 0.025 0.266 0.171 0.027 0.107FFT errors 0.832 0.069 0.609 0.750 0.714 0.979 0.223FFT time 0.939 0.323 0.976 0.988 0.403 0.899 0.348FFT total 0.268 0.286 0.494 0.995 0.851 0.347 0.826

M A time 0.968 0.449 0.438 0.801 0.629 0.689 0.680M A errors 0.528 0.168 0.574 0.614 0.610 0.339 0.323M B time 0.493 0.582 0.311 0.161 0.534 0.376 0.964M B errors 0.225 0.939 0.781 0.527 0.151 0.902 0.283F foods 0.666 0.183 0.164 0.494 0.827 0.289 0.478F animals 0.272 0.383 0.278 0.582 0.614 0.262 0.933

inger Windows 0.070 0.289 0.153 0.871 0.049 0.641 0.839umber-Letter 0.117 0.002 0.866 0.352 0.336 0.819 0.366

bbreviations:B � Digit Back-ForwardF � Digit ForwardH � Familiar history of epilepsyS � Febrile seizuresFFT � Matching Familiar Figures Test

E � Status epilepticusM � Trail Making Test

oldface indicates statistical significance.

82 PEDIATRIC NEUROLOGY Vol. 37 No. 3

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able 3. Continued

Cryptogenic Controls� (SD) Z P � (SD)

5.83 (2.99) �0.308 0.379 6.35 (2.35)19.67 (10.48) �0.305 0.380 20.25 (10.74)19.50 (10.52) �0.061 0.475 19.55 (10.74)23.33 (13.94) �0.518 0.302 24.40 (13.04)1.33 (1.63) �0.452 0.325 0.85 (0.88)6.00 (2.10) �1.944 0.026 7.90 (1.70)5.50 (2.17) �0.537 0.295 4.81 (1.25)

21.67 (10.65) �1.524 0.064 14.15 (8.39)157.00 (70.59) �0.700 0.242 227.00 (148.97)401.50 (973.90) �0.122 0.451 2339.05 (1094.82)27.57 (12.07) �0.133 0.447 28.19 (13.20)

0.14 (0.38) �0.832 0.202 0.05 (0.22)52.71 (22.31) �0.451 0.326 49.14 (27.09)

0.43 (0.53) �1.958 0.025 0.10 (0.3)15.14 (5.52) �0.772 0.440 14.14 (4.61)

12.00 (5.97) �0.133 0.894 14.48 (5.18)16.43 (4.58) �0.641 0.261 15.71 (3.32)9.57 (3.36) �0.134 0.447 10.62 (4.91)

CST � Wisconsin Card Sorting TestCST (categ.) � Wisconsin Card Sorting Test (number of categories achieved)CST (MS) � Wisconsin Card Sorting Test (failure in maintenance of set)CST (NPE) � Wisconsin Card Sorting Test (nonperseverative errors)CST (PE) � Wisconsin Card Sorting Test (perseverative errors)CST (PR) � Wisconsin Card Sorting Test (perseverative responses)

F � Word Fluency

able 4. Continued

Frequency Frequent Versus Infrequent Seizure Control Number of AEDs Seizure Type Secondary Generalization

0.228 0.219 0.419 0.036 0.533 0.9920.255 0.191 0.073 0.538 0.570 0.8150.296 0.836 0.576 0.983 0.844 0.7990.227 0.184 0.065 0.593 0.672 0.8810.085 0.013 0.003 0.825 0.452 0.4770.642 0.501 0.668 0.290 0.761 0.7230.222 0.914 0.691 0.179 0.496 0.5910.606 0.410 0.089 0.936 0.596 0.0070.664 0.593 0.954 0.444 0.649 0.0390.249 0.493 0.409 0.310 0.760 0.9440.466 0.196 0.108 0.279 0.919 0.4120.171 0.441 0.836 0.701 0.832 0.3020.514 0.162 0.300 0.692 0.906 0.2660.283 0.357 0.493 0.368 0.342 0.6060.469 0.253 0.296 0.711 0.783 0.9850.771 0.683 0.941 0.915 0.045 0.0580.309 0.480 0.682 0.336 0.339 0.1560.945 0.773 0.980 0.363 0.270 0.619

CST � Wisconsin Card Sorting TestCST (categ.) � Wisconsin Card Sorting Test (number of categories achieved)CST (MS) � Wisconsin Card Sorting Test (failure in maintenance of set)CST (NPE) � Wisconsin Card Sorting Test (nonperseverative errors)CST (PE) � Wisconsin Card Sorting Test (perseverative errors)CST (PR) � Wisconsin Card Sorting Test (perseverative responses)

F � Word Fluency

183Rzezak et al: Executive Dysfunction and Temporal Lobe Epilepsy

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ith temporal lobe epilepsy exhibited a moderate orevere executive dysfunction, with an undeniable effect onheir quality of life, because these children were stilleceiving their education.

It is common to assume that memory impairments areesponsible for the poor performance of those childrenn cognitive tests. Even so, the influence of attentionalkills in memory functions is well-known [46]. Thus,e believe that memory deficits, widely described in

he literature, could be partially explained by executiveysfunctions.Furthermore, it is important to keep in mind the influ-

nce of clinical variables of epilepsy on cognitive func-ioning. In our study, we observed the important roles ofhe existence of a lesion, early age of onset, longeruration of epilepsy, and use of polytherapy. These find-ngs corroborate those of Hermann et al. [32] regarding thenfluence of age of onset of epilepsy on executive func-ioning. Therefore, our data suggest that temporal lobenvolvement per se is an important variable that couldetermine the presence of an executive dysfunction, andhat early interventions are necessary, because the exten-ive cognitive impairment pattern observed by Hermannnd Seidenberg [5] in adults can already be seen in the firsttages of life, and could be aggravated by longer durationf epilepsy and the use of polytherapy.In conclusion, our data indicate the need for compre-

ensive batteries to assess executive functions, and forlinical criteria to classify degrees of executive dysfunc-ion in children and adolescents, because some of the mostidely used executive-function tests are not sensitive

nough to detect minor impairments. Our study alsoonfirms that children and adolescents with temporal lobeesions have extratemporal cognitive deficits, despite theirhorter duration of epilepsy. In addition, we corroboratehe notion that the abnormal epileptogenic activity of theemporal lobe affects extratemporal areas of the frontalobe, responsible for executive functions, emphasizing thexistence of a neural network linking both the temporalnd frontal lobes. We also think that the existence ofrontal lobe dysfunction in patients with lateral lesionsould be related to the great number of patients withortical dysplasia, suggesting the existence of a microdys-enesis not visualized by routine extratemporal neuroim-ging examinations. Moreover, the hypothesis of a neuraletwork and the existence of invisible structural abnor-alities in the frontal cortex are not mutually exclusive,

ut could be coexistent and correlated.

e are grateful to the staff members of the Clinical Neurophysiologyaboratory and the Psychology and Neuropsychology Unit, and espe-ially Bernardo Moreira, MD, Lia Arno Fiore, MD, Flavio Alóe, MD,uliana Góis, BSc, Sylvie Paes, BSc, and Pedro Zuccolo, BSc, for theirngoing assistance. This work was supported by Fundação de Amparo à

esquisa do Estado de São Paulo grants 03/06025-3 and 05/03489-4.

I

84 PEDIATRIC NEUROLOGY Vol. 37 No. 3

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