Episodic and semantic memory in children with mesial temporal sclerosis

Epilepsy & Behavior 21 (2011) 242–247

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Episodic and semantic memory in children with mesial temporal sclerosis

Patricia Rzezak a,⁎, Catarina Guimarães b, Daniel Fuentes c, MarilisaM. Guerreiro b, Kette Dualibi Ramos Valente a,d

a LIM-21, Laboratory for Medical Research 21—Neuroimaging Laboratory, Department of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazilb Neurology Department, University of Campinas, Campinas, Brazilc Division of Psychology and Neuropsychology, Department of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazild Laboratory of Clinical Neurophysiology, Department of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil

⁎ Corresponding author at: Rua Abdo Ambuba, 75/31 SFax: +55 11 30314196.

E-mail address: [email protected] (P. Rzeza

1525-5050/$ – see front matter © 2011 Elsevier Inc. Aldoi:10.1016/j.yebeh.2011.03.032

a b s t r a c t

Article history:Received 21 January 2011Revised 22 February 2011Accepted 27 March 2011Available online 2 May 2011

Keywords:Mesial temporal sclerosisTemporal lobe epilepsyChildrenAdolescentsEpisodic memorySemantic memoryNeuropsychological evaluation

The aim of this study was to analyze semantic and episodic memory deficits in children with mesial temporalsclerosis (MTS) and their correlation with clinical epilepsy variables. For this purpose, 19 consecutive childrenand adolescents with MTS (8 to 16 years old) were evaluated and their performance on five episodic memorytests (short- and long-term memory and learning) and four semantic memory tests was compared with thatof 28 healthy volunteers. Patients performed worse on tests of immediate and delayed verbal episodicmemory, visual episodic memory, verbal and visual learning, mental scanning for semantic clues, objectnaming, word definition, and repetition of sentences. Clinical variables such as early age at seizure onset,severity of epilepsy, and polytherapy impaired distinct types of memory. These data confirm that childrenwith MTS have episodic memory deficits and add new information on semantic memory. The data alsodemonstrate that clinical variables contribute differently to episodic and semantic memory performance.

ão Paulo–SP, Brazil, 05725–030.

k).

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© 2011 Elsevier Inc. All rights reserved.

1. Introduction

There are several ways of describing and categorizing memoryfunctions, although most concepts are mostly theoretical, because theborders among different types of memory are unclear. One theoryholds that episodic and semantic memories are two of the five majorhuman memory systems, whereas the other three systems areprocedural, perceptual representation, and short-term memory [1].

Taken in this sense, episodic memory could be explained as afunction that enables a person to remember personally experiencedevents, allowing an individual to be consciously aware of an earlierexperience in a certain situation at a certain time. Thus, theinformation of episodic memory could be said to concern the self'sexperiences in subjective space and time [1], whereas semanticmemory registers and stores knowledge about the world in itsbroadest sense, making it available for retrieval. Thus, semanticmemory enables individuals to represent and mentally operate onsituations, objects, and relations in the world that are not available tothe senses: the owner of a semantic memory system can think aboutthings that are not here now. Therefore, the information of semanticmemory processes concerns objects and their relations in the world atlarge [1]. Nevertheless, semantic memory comprises stored knowl-

edge about concepts, facts, and attributes that are acquired from, butno longer defined by, particular episodes [2].

Semantic memory has been widely investigated in patients withmemory impairments caused by degenerative disorders such asAlzheimer's disease and vascular dementias [3–6]. These studies havedemonstrated the importance of temporal lobe structures, as well asfrontal lobe structures, to the semantic system [7]. This systemincludes anterior temporal lobe components [8], lateral posterior(superior andmiddle) temporal gyri [9], and ventral occipitotemporalregions [10]. Moreover, there is some evidence that medial temporallobe structures, which are reciprocally connected to most neocorticalareas, are also involved in semantic memory [11].

Despite the involvement of mesial temporal structures, there arefew studies on semantic memory in patients with mesial temporalsclerosis (MTS), even though these patients may represent a specialgroup because of well-delineated lesions, restricted to the mesialtemporal lobes, thus offering a unique scenario to understand the roleof the hippocampus in this type of memory [12].

Another relevant issue is that patients with MTS are younger thanpatients with dementia, as the first seizure usually occurs between theages of 3 months and 15 years [13]. It should also be emphasized thatthe few studies on semanticmemory and temporal lobe epilepsywereconducted mostly in adults, and to date, there is only one study onsemantic memory in children [14].

Children represent a particular group for the study of cognitivefunctions, as previously demonstrated in a study of episodic memoryand executive functions in children [15,16], because the impact of the

243P. Rzezak et al. / Epilepsy & Behavior 21 (2011) 242–247

hippocampal lesion and epileptogenic activity on semantic memorymay be better evaluated in children with MTS as they do not yet havethe effects of long-lasting epilepsy in contrast to adults, as well as theimpact of many years of polytherapy.

There are many studies on memory deficits, especially of verbaland visual episodic memory, in children with temporal lobe epilepsy(TLE) [17–19]. Although memory deficits do not represent a majorcomplaint in children with TLE, contrary to adults, children withepilepsy have major learning disabilities, which may representindirect evidence of the impact of memory impairment on dailyactivities [20].

The objective of the present study was to analyze the presence ofsemantic and episodic memory deficits in a population of childrenwith MTS and their correlation with clinical epilepsy variables.

Table 1Clinical description of the patients with mesial temporal sclerosis.

Age at onset (years) 4.20±3.20Epilepsy duration (years) 6.49±3.22Lesion lateralitya

2. Methods

2.1. Participants

Consecutive patients with TLE were recruited from amongchildren and adolescents under treatment at a tertiary care centerfor the treatment of epilepsy. The control group was composed ofhealthy volunteers, matched to the patients with respect to age,sociodemographic profile, and educational background.

Patients were evaluated by a multidisciplinary team comprising achild neurologist, child psychiatrist, and neuropsychologist. Thepsychiatric assessment was characterized by clinical anamnesesfollowed by an interview with a version of the KIDDE-SADS validatedfor Portuguese [21]. Psychiatric disorders were classified in accor-dance with the DSM-IV-TR [22]. For the purpose of the present study,controls were screened with a Brazilian validated tool screening forchildhood psychiatric illnesses [23] followed by the same protocolapplied for patients.

The following exclusion criteria were applied to patients andcontrols: an estimated IQ b80; clinical signs of drug intoxication or ofany other condition that could lead to cognitive impairment; previousor current psychiatric disorder; alcohol or drug abuse; previousneurosurgical procedure; and not currently attending school. Patientswith TLE with major psychiatric disorders and severe/moderatelearning disabilities that might impair neuropsychological perfor-mance were excluded. In addition, we excluded patients with ADHDand patients using psychoactive drugs. According to these criteria,seven patients and two controls were excluded.

Right 14 (73.7%)Left 5 (26.3%)

Status epilepticusPresent 6 (31.6%)Absent 13 (68.4%)

Family historyPresent 11 (57.9%)Absent 8 (42.1%)

Febrile seizuresPresent 8 (42.1%)Absent 11 (57.9%)

Seizure frequencyNo seizures 7 (36.8%)Daily 7 (36.8%)Weekly 4 (21.1%)Monthly 1 (5.3%)

Number of AEDsMonotherapy 12 (63.2%)Polytherapy 7 (38.8%)

Seizure typeSimple partial 2 (10.5%)Complex partial 4 (21.1%)Simple partial, complex partial 8 (42.2%)Complex partial, generalized tonic–clonic 2 (10.6%)Simple partial, complex partial, generalized tonic–clonic 3 (15.9%)

a Laterality defined through neuroimaging and neurophysiological data.

2.2. Patients

Between 2005 and 2009, we prospectively evaluated 19 consec-utive children and adolescents with unilateral MTS (14with rightMTSand 5 with left MTS), defined by MRI and corroborated by EEG andVEEG studies, followed in a tertiary center for epilepsy from 2005to 2009. Patients with other lesions, such as patients with dualpathology, were not included in the present study.

The study group comprised 11 boys (57.89%) with a mean age of11.46 years (range: 8–16, SD:±2.06) andameanestimated IntelligenceQuotient (IQ), based on Block Design and Vocabulary subtests ofWechsler Intelligence Scale for Children III (WISC-III) [24], of 97.79(range: 80–135, SD: 13.16). Mean age at epilepsy onset was 4.20 years(SD: ±3.20), and duration of epilepsy, 6.49 years (SD: ±3.22). Twelve(63.16%) patients had refractory epilepsy, and 7 (36.84%) were well-controlled at the time of evaluation. The criterion to define seizurecontrol in these 7 patients was at least 6 months of seizure freedomprior to cognitive assessment. Twelve patients (63.16%) were onmonotherapy and 7 (36.84%) on polytherapy. Demographic and clinicalinformation is summarized in Table 1.

2.3. Controls

Healthy volunteers were recruited among students from a publicstate-sponsored school located in the neighborhood of the Universityof São Paulo. These children were matched to the patients withrespect to age, sociodemographic status, and educational background,and had neither psychiatric diagnoses, according to the DSM-IV-TR[22], nor previous or current history of neurological disorders. Thecontrol group comprised 28 healthy children (9 boys) with a meanage of 11.96 (range: 9–16, SD: ±2.30). Mean estimated IQ, based onBlock Design and Vocabulary subtests of the WISC-III [24] was 109.39(range: 83–135, SD: ±13.95).

No statistical differences were observed between patients andcontrols with respect to gender (χ2=4.07, P=0.080), age (t=−0.75,P=0.459) and years of formal education (t=−1.58, P=0.120).However, patients had lower IQ than controls (t=−2.86, P=0.006).

2.4. Procedures

All procedures were approved by the Research Ethics Committeesof the University of São Paulo and of the University of Campinas inaccordance with the Declaration of Helsinki. A written informedconsent was obtained.

Neuropsychological evaluations were performed at least 48 hoursafter the last seizure. Three patients had seizures during testingand were reevaluated 1 week later. Tests were administered by twotrained neuropsychologists, in a quiet laboratory setting and in astandardized sequence. Evaluations were conducted over the courseof two sessions, in which a battery of episodic and semantic memorytests was administered (for a review see [25–27]):

2.5. Episodic memory

1. Story Memory subtest of the WRAML: Recall of two short butdetailed stories immediately after hearing them (Story Memory I)

244 P. Rzezak et al. / Epilepsy & Behavior 21 (2011) 242–247

and 30 minutes later (Story Memory II), as well as with a multiple-choice questionnaire (Story Memory III).

2. Picture Memory subtest of theWRAML: Identification of items thathave been altered when a picture is compared with a very similarpicture shown immediately before.

3. Design Memory subtest of the WRAML: The drawing of four cardsdesigns from memory.

4. Verbal Learning subtest of the WRAML: Performance on a word listrecall task with four lists of 16 words each, considering the sum ofthe correct answers of the four trials (Verbal Learning I) and recallafter 30 minutes (Verbal Learning II).

5. Visual Learning subtest of the WRAML: Visuospatial learning of 14simple designs, considering the sum of the correct answers of thefour trials (Visual Learning I) and recall after 30 minutes (VisualLearning II).

2.6. Semantic memory

1. Sentence Memory subtest of the WRAML: Performance on asentence repetition task with sentences of increasing length andcomplexity.

2. WISC-III Vocabulary: Patients were instructed to provide as manyattributes as possible to a given word.

3. Verbal Fluency (animals and foods): Subjects were instructed toorally generate a list of animals and a list of foods in a 60-secondperiod for each category.

4. Boston Naming Test: Measure of object naming from 60 linedrawings.

2.7. Data analysis

Descriptive analysis consisted of the mean and SD of each variable.For this study, we performed two analyses:

1. Performance of patients with MTS and controls on (i) episodic and(ii) semantic memory tests was compared with analysis ofcovariance (ANCOVA) using IQ as a covariate.

2. The impact of age at epilepsy onset (“early” [b4 years] vs “late”[≥4 years]), epilepsy duration (b7 years vs ≥7 years), occurrenceof status epilepticus, seizure frequency (“frequent” daily or weeklyvs “infrequent” monthly and no seizures), seizure control,occurrence of generalized seizures, number of antiepileptic drugs

Table 2Comparison of performance of patients with MTS and controls on semantic and episodic m

Test Patients with MTS Con

Mean (SD) Adjusted mean (SD) Me

Episodic memoryScene Memory 20.63 (4.72) 21.27 (1.30) 23.Design Memory 30.37 (9.59) 30.90 (2.19) 38.Story Memory I 20.42 (6.67) 21.42 (2.01) 29.Story Memory II 16.56 (7.28) 17.63 (2.34) 25.Story Memory III 9.76 (4.04) 10.23 (0.72) 11.Verbal Learning I 33.58 (6.38) 33.30 (2.14) 38.Verbal Learning II 2.06 (3.13) 1.91 (0.60) 0.Visual Learning I 20.33 (11.36) 21.42 (2.49) 28.Visual Learning II 0.53 (1.46) 0.63 (0.35) 0.

Semantic memoryVerbal Fluency animals 12.26 (3.60) 12.32 (1.14) 14.Verbal Fluency foods 10.16 (3.75) 10.53 (1.04) 13.Boston Naming Test 40.13 (6.78) 40.97 (2.08) 46.Vocabulary 23.21 (6.21) 24.66 (1.64) 32.Sentence Memory 13.78 (5.08) 14.12 (1.46) 20.

(“monotherapy” vs “polytherapy”), and lateralization (left vs right)was verified using Student's t test.

3. Results

3.1. Episodic memory

The patients performed worse on the following episodic memorytests, all with high effect size: visual episodic memory—DesignMemory(F[2]=6.17, P=0.009); immediate verbal episodic memory—StoryMemory I (F[2]=7.77, P=0.004); delayed verbal episodic memory—StoryMemory II (F[2]=4.91, P=0.016); Learning—Verbal Learning I(F[2]=3.69, P=0.031) and Visual Learning I (F[2]=3.23, P=0.040)(Table 2).

3.2. Semantic memory

Regarding semantic memory, patients with MTS performed worseonmental scanning for semantic clues (Verbal Fluency for foods, F[2]=4.88, P=0.016); object naming (Boston Naming Test, F[2]=3.02,P=0.046); word definition (Vocabulary, (F[2]=9.76, P=0.002); andrepetition of sentences (Sentence Memory, F[2]=9.59, P=0.002)(Table 2).

3.3. Influence of clinical variables on memory functions

Regarding episodic memory, patients with a history of at least oneepisode of status epilepticus had worse visual episodic memory (SceneMemory, t[1]=−2.306, P=0.034), whereas patients whose seizureswere not controlled andhad daily andweekly seizures hadworse verballearning (Verbal Learning I, t[1]=2.216, P=0.041, and t[1]=−2.194,P=0.042, respectively). Finally, patients on polytherapy were moreimpaired in visual learning (Visual Learning I, t[1]=2.387, P=0.030)(Table 3). The only clinical variable of epilepsy that showed a significantimpact on semantic memory tests (Boston Naming Test) was early ageat onset (t[1]=−2.933, P=0.012) (Table 3).

Concerning laterality, after the normality of residuals was verified,a t test was conducted to compare performance of patients with leftTLE with that of patients with right TLE on episodic and semanticmemory tests. Patients with left TLE performed worse on the BostonNaming Test (t[18]=2.977, P=0.011) than patients with right TLE.There were no differences between patients with left and those withright TLE in any other episodic or semantic memory test (Table 4).

emory tests (ANCOVA).

trols F P Cohen's d

an (SD) Adjusted mean (SE)

32 (5.91) 22.89 (1.05) 0.87 0.178 1.3754 (8.64) 38.18 (1.78) 6.17 0.009 0.9061 (9.49) 28.93 (1.63) 7.77 0.004 1.2018 (10.65) 24.49 (1.84) 4.91 0.016 0.9443 (1.99) 11.15 (0.55) 0.95 0.168 0.5261 (10.06) 38.80 (1.73) 3.69 0.031 0.6086 (1.74) 0.95 (0.46) 1.50 0.115 0.4711 (9.20) 27.40 (2.00) 3.23 0.040 0.7515 (1.32) 0.08 (0.27) 1.40 0.122 0.27

61 (5.29) 14.57 (0.93) 2.17 0.074 0.5286 (4.66) 13.60 (0.84) 4.88 0.016 0.8720 (8.07) 45.70 (1.58) 3.02 0.046 0.8150 (7.94) 31.51 (1.33) 9.76 0.002 1.3032 (6.25) 20.10 (1.15) 9.58 0.002 1.15

Table 3Mesial temporal sclerosis clinical variables impact performance on episodic and semantic memory tests.

Age at onset Duration Status epilepticus Seizure frequency Seizure control Generalization Number of AEDs

b4 years ≥4 years b7 years ≥7 years Yes No Frequent Infrequent Yes No Yes No Monotherapy Poytherapy(n=11) (n=8) (n=8) (n=11) (n=6) (n=13) (n=5) (n=14) (n=7) (n=12) (n=5) (n=14) (n=12) (n=7)

Scene Memory 20.91 20.25 19.38 21.55 17.33a 22.15 18.64 23.38 23.29 19.08 18.00 21.57 21.67 18.86(5.61) (3.45) (6.30) (3.17) (1.51) (4.98) (4.72) (3.25) (3.50) (4.76) (6.32) (3.86) (3.98) (5.64)

Design Memory 27.64 34.13 27.00 32.82 26.67 32.08 29.09 33.50 31.43 29.75 30.60 30.29 29.33 32.14(7.78) (11.05) (8.45) (9.74) (6.62) (10.47) (8.01) (11.20) (10.31) (9.55) (10.88) (9.53) (8.62) (11.57)

Story Memory Ib 19.45 21.75 17.75 22.36 19.00 21.08 19.18 22.13 22.57 19.17 17.40 21.50 21.42 18.71(7.74) (5.04) (6.58) (6.31) (3.35) (7.78) (6.98) (6.24) (6.60) (6.66) (7.23) (6.38) (6.82) (6.55)

Story Memory II 16.60 16.50 16.71 16.45 16.83 16.42 15.40 18.00 18.71 15.18 11.50 18.00 18.08 13.50(7.17) (7.91) (7.43) (7.54) (2.86) (8.34) (7.60) (7.07) (7.32) (7.25) (9.61) (6.15) (6.40) (8.55)

Story Memory III 10.78 8.63 10.33 9.45 11.17 9.00 9.00 10.63 11.29 8.70 6.00 10.57 10.50 8.00(3.90) (4.14) (3.88) (4.27) (4.54) (3.74) (4.12) (4.03) (3.86) (4.00) (3.61) (3.76) (3.48) (5.15)

Verbal Learning I 32.64 34.88 31.50 35.09 32.00 34.31 31.09a 37.00 37.43a 31.33 30.60 34.64 34.75 31.57(6.39) (6.56) (6.46) (6.17) (5.55) (6.81) (5.91) (5.63) (5.94) (5.69) (7.02) (6.05) (6.57) (5.97)

Verbal Learning II 2.00 2.13 0.67 2.82 0.17 3.09 1.67 2.50 2.00 2.10 3.00 1.77 1.36 3.33(2.24) (4.09) (1.75) (3.52) (1.83) (3.27) (3.57) (2.73) (2.52) (3.63) (5.10) (2.49) (2.34) (4.18)

Visual Learning I 22.60 17.50 21.71 19.45 17.33 21.83 16.40 25.20 26.57 16.36 13.50 22.29 24.33a 12.33e

(10.38) (12.58) (11.54) (11.72) (10.03) (12.10) (10.01) (11.61) (11.87) (9.50) (9.04) (11.47) (10.81) (8.16)Visual Learning II 0.33 0.75 0.67 0.45 0.83 0.36 0.89 0.13 0.14 0.80 0.67 0.50 0.50 0.60

(1.80) (1.04) (0.82) (1.76) (0.75) (1.75) (0.93) (1.89) (2.04) (0.92) (1.53) (1.51) (1.62) (1.14)Verbal Fluencyanimals

12.09 12.50 11.38 12.91 12.00 12.38 12.09 12.50 12.14 12.33 14.20 11.57 11.42 13.71(3.51) (3.96) (4.24) (3.11) (4.15) (3.50) (3.89) (3.42) (3.53) (3.80) (3.96) (3.45) (3.45) (3.64)

Verbal Fluencyfoods

9.91 10.50 10.38 10.00 9.33 10.54 11.27 8.62 8.86 10.92 11.60 9.64 9.58 11.14(4.30) (3.07) (4.69) (3.13) (4.97) (3.21) (3.41) (3.85) (4.10) (3.48) (2.30) (4.09) (4.25) (2.67)

Boston NamingTest

35.71a 44.00 36.50 42.56 42.00 39.20 39.44 41.17 41.20 39.60 38.25 40.82 39.56 41.00(5.50) (5.43) (6.09) (6.39) (5.70) (7.36) (7.16) (6.68) (7.46) (6.77) (8.22) (6.49) (5.94) (8.14)

Vocabulary 21.55 25.50 22.25 23.91 23.50 23.08 23.45 22.88 22.29 23.75 22.80 23.36 23.08 23.42(6.30) (5.68) (5.23) (7.01) (4.14) (7.12) (5.11) (7.86) (8.30) (4.98) (5.45) (6.65) (7.14) (4.72)

Sentence Memory 12.30 15.63 12.43 14.64 13.83 13.75 13.00 14.75 14.43 13.36 12.50 14.14 13.83 13.67(5.44) (4.21) (5.71) (4.72) (4.26) (5.63) (4.71) (5.68) (6.05) (4.63) (7.05) (4.66) (4.97) (5.79)

a pb0.05.b I, immediate recall; II, delayed recall; III, recognition.

245P. Rzezak et al. / Epilepsy & Behavior 21 (2011) 242–247

4. Discussion

This study demonstrated semantic and episodic memory impair-ment in children with temporal lobe epilepsy caused by mesialtemporal sclerosis. It is the first study of semantic memory in childrenfrom a homogenous group of patients with TLE, meaning exclusivelychildren with unilateral mesial temporal sclerosis. The study ofchildren with a temporal lobe lesion involving mesial temporalstructures, in this case unilateral, provides a unique opportunity totrace the relationship between the presence of a brain lesion andcognition, in this case memory functions. Additionally, the study ofchildren is of significant relevance as it involves patients without the

Table 4Comparison of performance on episodic and semantic memory tests between patientswith left TLE and those with right TLE (t test).

Test Mean (SD) t P Cohen's d

Left TLE Right TLE

Episodic memoryScene Memory 19.80 (6.57) 20.93 (4.14) 0.449 0.659 0.21Design Memory 23.60 (4.72) 32.79 (9.82) 1.983 0.064 1.19Story Memory Ia 18.20 (8.58) 21.21 (6.03) 0.861 0.401 0.41Story Memory II 15.50 (7.59) 16.86 (7.45) 0.320 0.753 0.18Story Memory III 11.67 (6.11) 9.36 (3.65) –0.893 0.386 0.46Verbal Learning I 30.20 (6.72) 34.79 (6.04) 1.418 0.174 0.72Verbal Learning II 1.00 (1.73) 2.29 (3.36) 0.633 0.536 0.48Visual Learning I 23.25 (10.21) 19.50 (11.89) –0.571 0.576 0.34Visual Learning II 0.67 (0.58) 0.50 (1.61) –0.174 0.865 0.14

Semantic memoryVerbal Fluencyanimals

12.00 (4.06) 12.00 (3.55) –0.522 0.609 0.00

Verbal Fluency foods 11.00 (4.18) 9.86 (3.70) –0.575 0.573 0.29Boston Naming Test 29.50 (4.95) 41.77 (5.46) 2.977 0.011 2.35Vocabulary 21.60 (5.32) 23.79 (6.59) 0.665 0.515 0.37Sentence Memory 14.00 (7.75) 13.71 (4.46) –0.096 0.925 0.05

a I, immediate recall; II, delayed recall; III, recognition.

long-lasting effects of epilepsy, thus excluding possible confusingconcomitant factors.

In the last decades, several studies have consistently demonstratedthe presence of episodic memory impairment in patients with MTS.We corroborated previous studies showing deficits in verbal andvisual [14,28] episodic memory as well as in learning [28]. Thehippocampus plays a pivotal role in storing events and contextualizedmemories [29]. For this reason, the emphasis of such studies inpatients with MTS is not surprising, given the possibility of anassociation between a well-localized lesion and memory function.Despite this, cognitive functions remain less investigated in childrenwith MTS than in adults.

In adults with TLE, previous research demonstrated that lefthippocampal lesions are related to verbal memory decline [30,31],and right lesions to visual memory deficits [32,33]. Nevertheless,some authors suggest that the relationship between laterality of thehippocampal pathology and memory deficit is more straightforwardin patients with left TLE (verbal memory deficit) than in patients withright TLE [31,34].

In childhood TLE, because of the great clinical, electrographic, andetiological diversity [35], the relationship between memory deficitand lateralization remains unknown [36,37]. Some authors havefound that verbal memory deficit is correlated with left TLE and visualmemory deficit is correlated with right TLE [17,18], whereas othershave observed an unexpected correlation between visual memorydeficit and right TLE [17,19].

In our study, a specific memory deficit was not observed, which isin agreement with studies demonstrating no correlation betweenlesion laterality and memory deficits in children with TLE [38,39]. Inthe present study, we must consider that our sample had an unequaldistribution of patients with right (n=14) and left (n=5) TLE,limiting the relevance of laterality in episodic memory. Our patientsshowed impairments in both verbal and visual episodic and learningtests. Although a more emphatic conclusion cannot be drawn from

246 P. Rzezak et al. / Epilepsy & Behavior 21 (2011) 242–247

our data, this pattern of impairment seems to favor a non-material-specific pattern of memory impairment in children with TLE.

Although dysfunctions of episodic memory have been extensivelystudied, much less attention has been devoted to semantic memory inTLE, even though investigation of this type of memory in patients withAlzheimer's disease and semantic dementia continues to make asubstantial contribution to the understanding of its relationship withthe temporal lobes [40,41]. In this scenario, we demonstrated thatchildren with TLE have impairments in category fluency, objectnaming; word definition, and sentence repetition, all of thesecognitive functions are related to semantic memory. This relationshiphas been previously demonstrated in adults with TLE in tasks of objectnaming [12,42,43], category fluency [44,45], word definition [46], andattribute knowledge [43]. Davies et al. [47] found significant namingdeficits in adults with hippocampal sclerosis compared with patientswithout hippocampal damage and suggested a role for the hippo-campus or its connections in retrieving names from the lexicon held incortical areas.

Interestingly, most studies aiming to evaluate semantic memory inpatients with TLE have focused on laterality (right or left) and itsrelevance to the severity of memory dysfunction. Some of thesestudies have demonstrated material-specific semantic memorydeficits involving the classification of figures and names after lefttemporal lobectomy [48], and studies of nonoperated patients withleft TLE have revealed impairments in verbal recall on semantic cuesand the verbal production of categories [49], picture naming andsemantic judgment [43], and semantic knowledge [42]. Nevertheless,there is evidence that patients with right TLE also have impairedsemantic memory when compared with healthy adults [50,52],although they are less compromised than those with left TLE.

In our study, children with left MTS had worse naming ability thanthose with right MTS, which is probably correlated to the majorparticipation of the left hemisphere in abilities related to languageevaluated with the Boston Naming Test. It is worthwhile noting thatnaming was compromised in our children with MTS as well in thosewith TLE with distinct etiologies (hippocampal sclerosis, temporallobe tumors, cortical dysplasias, and ischemias) studied by Jambaqueet al. [14]. This finding corroborates data in adults, except for the factthat adults with long-duration left TLE seem to be more compromisedthan children.

The search for material-specific memory deficits in patients withTLE is common when considering episodic memory, and for thatreason, application of the same rationale to semantic memory isunderstandable. However, the lateralized impairment in verbal andnonverbal episodic memory in adults with TLE, seems to be related tothe involvement of the hippocampus in episodic memory, and thus, itis important to consider the structures and networking involved insemantic memory to transpose the episodic memory rationale to thesemantic domain.

Semantic memory impairments in TLE are related to the integrityof the lateral temporal lobe cortex, as demonstrated by clinical,neuropathological, and neuroimaging data [5,10,51,52]. However,considering the brain network involved in semantic memory, a linkbetween hippocampal integrity and semantic performance has beenreported [47]. Patients with mesial temporal lobe epilepsy have ahippocampal lesion, and in addition, PET and SPECT studiesdemonstrate that these patients exhibit interictal temporal lobehypometabolism beyond mesial structures [53,54], temporal lobemetabolic abnormalities consistent with myelin alterations [55], oratrophy of the lateral temporal lobe as well as of other cortical areas[56,57].

Presence of a focal lesion in mesial structures has a determinantrole in mnestic dysfunction. However, clinical variables of epilepsymay contribute to this deficit, as previously demonstrated by others[58–60]. In our group of children with MTS, we observed that episodicmemorywas related to the severity of epilepsy (seizure frequency and

control and history of status epilepticus) as well as polytherapy,whereas semantic memory was related to age at onset and laterality.The effect of antiepileptic drugs (AEDs) on cognition is wellestablished. Therefore, it is not surprising that patients under AEDpolytherapy have worse episodic memory. On the other hand, it is notpossible to exclude an overlap between polytherapy and seizurecontrol. Patientswithworse seizure control—more refractory epilepsy—receive polytherapy. In opposition to other studies [61], long duration ofepilepsy was not relevant for episodic or semantic memory. Thiscorroborates the importance of studying children with epilepsy.Interestingly, age at onset had no impact on episodic memory, but astrong relation with semantic memory. This finding reinforces interestin a detailed study ofmemory, consideringdifferent types ofmemory. Inadults, Giavagnoli et al. [43] suggested that the earlier the epilepsyonset, the more severe the compromise of semantic memory. Semanticknowledge is acquired early in life,mainly during school. In linewith theearly acquisition of many semantic abilities, the relationship of thesemantic factor to age at seizure onset suggests that the earlier theepilepsy onset, the more severe the compromise of semantic memory[62,63].

Considering the robust finding of episodic and semantic memoryimpairment in this particular sample, one may pose the question ofwhether this group of patients is impaired on any cognitive domainother than memory functions. Children included in this study had amean IQ of 97.79, which, although lower than controls, is considered anormal intelligence level. In addition, this group of patients is notimpaired in all cognitive domains, as previously demonstrated by ourgroup [60,64]. The authors have shown that these children havedeficits in mental flexibility and set shifting, word generation inresponse to certain semantic cues, and maintenance of attention, butnot in mental control and processing speed.

In conclusion, children with mesial temporal lobe epilepsy havesemantic and episodic memory deficits despite their shorter durationof epilepsy as compared with adults. The study of distinct domains ofmemory seems necessary to establish more adequate rehabilitationprograms.

Acknowledgments

This work was supported by FAPESP (03/06025-3 and 05/03489-4).We are grateful to the staff members of the Clinical NeurophysiologyLaboratory and thePsychologyandNeuropsychologyUnit, especially LiaArno Fiore, Juliana Góis, Sylvie Paes, and Pedro Zuccolo, for theirconstant assistance.

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