Epilepsy & Behavior 44 (2015) 17–22

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Neuropsychological functioning in children with temporal lobe epilepsy and hippocampal atrophy without mesial temporal sclerosis: A distinct clinical entity? Charlotte S.M. Schmidt a,b,c, Maryse Lassonde a,b, Louise Gagnon a, Catherine H. Sauerwein a,b, Lionel Carmant a, Philippe Major a, Natacha Paquette a,b, Franco Lepore a,b, Anne Gallagher a,b,⁎ a b c

Centre de Recherche du CHU Sainte-Justine, 3175 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1C5, Canada Centre de Recherche en Neuropsychologie et Cognition (CERNEC), Département de Psychologie, Université de Montréal, 90 Avenue Vincent-d'Indy, Montréal, QC H2V 2S9, Canada Department of Neuropsychology, Maastricht University, Universiteitssingel 40, 6229 Maastricht, The Netherlands

a r t i c l e

i n f o

Article history: Received 4 November 2014 Revised 17 December 2014 Accepted 18 December 2014 Available online 16 January 2015 Keywords: Pediatric epilepsy Intelligence Memory Attention Executive functions Hippocampus Neuropsychological assessment Cognition

a b s t r a c t Unilateral hippocampal atrophy (HA) is considered as a precursor of mesial temporal sclerosis (MTS) in some patients with temporal lobe epilepsy. However, in other cases, it has been suggested that HA without MTS may constitute a distinct epileptic entity. Hippocampal atrophy without MTS was defined as HA without T2-weighted hyperintensity, loss of internal architecture, or associated lesion seen on the MRI data. To date, no study has focused on the cognitive pattern of children with epilepsy with HA without MTS. The objectives of the present study were to characterize the cognitive profile of these children and to investigate the presence (or the absence) of material-specific memory deficits in these young patients, as found in patients with MTS. Toward this end, 16 young patients with epilepsy with either left or right HA without MTS completed a set of neuropsychological tests, assessing overall intelligence, verbal memory and nonverbal memory, and some aspects of attention and executive functions. Results showed normal intellectual functioning without specific memory deficits in these patients. Furthermore, comparison between patients with left HA and patients with right HA failed to reveal a material-specific lateralized memory pattern. Instead, attention and executive functions were found to be impaired in most patients. These results suggest that HA may constitute a distinct epileptic entity, and this information may help health-care providers initiate appropriate and timely interventions. © 2014 Elsevier Inc. All rights reserved.

1. Introduction Mesial temporal sclerosis (MTS) is one of the most common neuropathological substrates of temporal lobe epilepsy (TLE) [1]. Mesial temporal sclerosis can be suspected on MRI when hippocampal atrophy is associated with loss of internal architecture and T2-weighted signal hyperintensity [2]. Most patients with unilateral MTS have intractable epilepsy [3] and poor neuropsychological prognosis [4–11]. In adult patients with MTS, most studies investigated memory function deficits [5,8,12,13], which further seem to be of a material-specific nature [1]. The notion of material-specific impairment proposes that the left and right temporal lobes process different types of material and that lateralized MTS leads to different memory profiles. Notably, left mesial temporal epilepsy and right mesial temporal epilepsy lead to verbal memory impairment and nonverbal memory impairment, respectively [14]. Pediatric studies have also shown memory dysfunctions in children with epilepsy with unilateral MTS [15–18]. However, compared with ⁎ Corresponding author at: Centre de Recherche du CHU Sainte-Justine, 3175, Chemin de la Côte-Sainte-Catherine, H3T 1C5 Montreal, QC, Canada. E-mail address: [email protected] (A. Gallagher).

http://dx.doi.org/10.1016/j.yebeh.2014.12.023 1525-5050/© 2014 Elsevier Inc. All rights reserved.

studies in adults, pediatric data could only partially confirm the notion of material-specific deficits in children with epilepsy with MTS [6,7,19, 20]. An association between left MTS and verbal memory problems has frequently been observed [18,21–23], but there are no consistent findings for right MTS and nonverbal memory deficits [9,14,24]. For instance, Gargaro and colleagues [7] found the typical memory profile (e.g., left MTS and verbal memory problems and right MTS and nonverbal memory problems) in only 25% of their pediatric cohort. The remaining children had atypical memory profiles, which included i) no memory impairments, ii) both verbal and nonverbal memory deficits, or iii) memory deficits that are typically found contralateral to the epileptic focus [7]. In contrast with MTS, unilateral hippocampal atrophy (HA) is a decrease in size or diminishing amount of tissue in the hippocampus without loss of internal architecture. It is still unclear whether epileptic seizures cause HA or whether HA causes epileptic seizures [3,25]. In some cases, hippocampal atrophy has been found to be a precursor of MTS [26], whereas, in other cases, HA does not evolve toward MTS. In a prior study [27], we were interested in clinical characteristics and evolution of 16 children with epilepsy with isolated HA. We found a distinct clinical presentation of unilateral HA compared with unilateral MTS,

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including an association with a positive family history of epilepsy, a lower incidence of febrile seizures, and a better seizure prognosis. These results suggest that unilateral HA might represent a distinct epileptic entity and that HA is not necessarily a precursor of MTS in children with epilepsy. To our knowledge, the cognitive profile of children with unilateral HA without MTS has not been specified. Therefore, the aim of the present study was to establish a comprehensive cognitive profile of children with epilepsy with unilateral HA without MTS, focusing not only on memory functions but also on other cognitive domains, including attention and executive functions. In addition, the presence of material-specific memory deficits (verbal versus nonverbal) in these young patients was investigated by comparing results of patients with left HA with those of patients with right HA. 2. Methods 2.1. Participants Sixteen children with epilepsy with left or right HA without MTS were recruited from the Comprehensive Epilepsy Clinic of the University of Montreal Hospital Center Sainte-Justine. Inclusion criteria included the following: 1) a diagnosis of childhood-onset epilepsy; 2) the presence of unilateral HA without MTS on MRI, defined by a pediatric neuroradiologist as HA without T2-weighted hippocampal hyperintensity, loss of internal architecture, or associated lesion; 3) fluency in French or English; and 4) between 6 years (minimal age for using standardized neuropsychological tests) and 19 years (maximal age of patients that have been followed at the clinic since childhoodonset epilepsy) of age. Patients who had undergone neurosurgery, had a tumor or a space-occupying lesion, or no clear lateralization of HA were excluded. The study was approved by the Sainte-Justine Hospital Ethics Committee, and informed written consent was obtained from all participants or their parents before they underwent a neuropsychological assessment. 2.2. Neuropsychological assessment The neuropsychological evaluation was performed by a qualified neuropsychologist who was blind to the hemispheric lateralization of HA. Testing was carried out in the morning for optimizing vigilance and attentional resources and lasted approximately 3 1/2 h including rest periods. The assessment included several standardized cognitive measures. An estimate of intellectual functioning was obtained using an ageappropriate intelligence scale: the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV), for children under 16 years of age [28] and the Wechsler Adult Intelligence Scale, third edition (WAISIII), for participants 16 years of age and older [29]. Memory functions were assessed by means of the Children Memory Scale (CMS) for patients below 16 years of age [30] and the Wechsler Memory Scale (WMS) for children 16 years of age and older [31]. In addition, the Rey–Osterrieth Complex Figure (ROCF; [32]) was administered to assess immediate visual memory and delayed visual memory as well as executive functions such as organizational skills and planning ability. Finally, the California Verbal Learning Tests, both the child version (CVLT-C) for children under 16 years of age [33] and the adult version (CVLT) for patients 16 years of age and older [34], were used to investigate different aspects of verbal memory such as learning strategies, short- and longdelay free recall, recognition memory, and susceptibility to interference (e.g., List B). 2.3. Data analyses The following results obtained from the WISC-IV or the WAIS-III were included for analysis: Full-Scale Intellectual Quotient (IQ), Verbal

Comprehension Index (VCI) or Verbal IQ, Perceptual Reasoning Index (PRI) or Nonverbal IQ, Working Memory Index (WMI), and Processing Speed Index (PSI). For the CMS or the WMS, the following results were used: nonverbal memory (nonverbal memory = immediate nonverbal memory index + delayed nonverbal memory index / 2), verbal memory (verbal memory = immediate verbal memory + delayed verbal memory / 2), global memory quotient (MQ), and attention/ concentration index (AC). Furthermore, copy, immediate, and delayed recall standard scores from the ROCF were compiled and used for group comparison. Standard scores of the total score for trials one to five (learning trials) and trial one and trial five separately were evaluated from the CVLT-C or the CVLT to determine differences between groups for immediate attention. The scores of List B (interference list) and List A (immediate recall) were analyzed to evaluate the effect of interference. Moreover, List A short-delayed free recall and List A long-delayed free recall were included for additional short- and longterm verbal memory functions. The scores from all participants were compared with normative data in order to obtain a neuropsychological profile of young patients with unilateral HA without MTS. Moreover, cognitive results from patients with left HA were compared with those from patients with right HA in order to investigate for material-specific lateralization patterns. 2.4. Statistical analyses The statistical analyses were performed using Statistic Package for the Social Sciences Version 20.0 (SPSS, IBM Corp., Armonk, NY). In order to characterize the global cognitive profile of children with unilateral HA (N = 15) with respect to normative data, a one-sample t-test using a test value of 100 ± 15, (which corresponds to the normative mean and standard deviation) was performed on overall IQ, verbal IQ, nonverbal IQ, MQ, verbal memory, nonverbal memory, WMI, AC index, and PSI. All t-tests were two-tailed. In order to lower the risk of type 1 error when computing multiple comparisons, the alpha level of significance was adjusted to p b 0.01. Finally, between-groups analysis (left HA versus right HA) consisted of a one-way analysis of variance (ANOVA), with the side of HA as an independent variable and with a significance level of p ≤ 0.05. 3. Results All datasets were normally distributed, except for the WMI of the group with left HA as shown using the Kolmogorov–Smirnov test (p = 0.04). In addition to parametric tests, nonparametric equivalents tests (Wilcoxon signed-rank test and Kruskal–Wallis test) were, thus, performed and provided similar results. In the interests of clarity, only parametric test results are presented here [35]. 3.1. Demographic and clinical characteristics of patients with epilepsy with unilateral HA Demographic and clinical data are provided in Table 1. From the initial 16 children, data from one patient with left HA were excluded after the neuropsychological assessment because of missing data and a suspected floor effect, which precluded a valid interpretation of the results. Data from the 15 remaining patients (8 girls) with a mean age (± standard deviation (SD)) of 13.1 ± 3.7 years (range: 9–19 years) were used for analyses. Ten patients had left HA (mean age ± SD of 12.6 ± 3.8 years, range: 9–19 years, 6 girls), and five had right HA (mean age ± SD of 14 ± 3.7 years, range: 9–17 years, 2 girls). Demographic characteristics of this sample showed no significant differences between groups (left HA versus right HA) with respect to gender, age at testing, age at onset of epilepsy, duration of the epilepsy, and presence or absence of anticonvulsant medication at testing and medically refractory epilepsy (see Table 2 for details).

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Table 1 Demographic and clinical data. Patient

Sex

Epilepsy syndrome

HA

Age at testing (yrs;mo)

Age at onset of epilepsy (yrs;mo)

Epilepsy duration (yrs;mo)

EEG

AED at testing

Medically refractory epilepsya

1 2 3 4 5 6

F F M M F F

L L R R L L

19;0 9;1 16;4 17;1 19;8 11;3

9;0 6;3 3;4 10;5 4;7 5;0

7;11 1;4 1;4 3;5 1;0 6;3

Bilateral frontotemporal spikes Left temporal spikes Normal Normal N/A 3-Hz spike and wave

Yes Yes No No Yes Yes

No No No No No Yes

7b 8 9 10 11 12 13 14 16 18

F F M F M F F M M M

Partial Partial Partial Partial Partial Generalized (absences) Partial Partial Partial Partial Partial Partial Partial Partial Partial Partial

L L L R L R L L R L

13;0 13;10 9;6 11;11 12;5 17;0 14;6 9;10 9;1 10;4

6;0 10;0 2;7 6;0 6;0 10;11 6;0 4;0 4;5 3;0

2;0 0;7 0;5 2;2 7;11 2;0 4;0 4;0 4;6 7;0

Normal Left temporal spikes Normal Normal Left frontocentrotemporal Right temporal slowing Normal Left hemispheric spikes Right frontotemporal spikes and slowing Left temporal spikes

Yes No No No No Yes Yes Yes Yes Yes

No No No No No No No No No Yes

Note. yrs;mo = years; months, AED = antiepileptic drug, HA = side of hippocampal atrophy. a No treatment or combination of treatments brought complete control of seizures at the time of testing. b Excluded patient.

3.2. Neuropsychological profile of patients with epilepsy with unilateral HA Neuropsychological data, as well as mean scores and standard deviations (SD), are presented in Table 3. Individual neuropsychological data for each patient are presented in Supplementary Table S1. Compared with normative data, patients showed normal intellectual and memory functioning (see Fig. 1, black square). However, one-sample t-tests revealed that patients had significantly lower scores on WMI (t(14) = −3.16, p = 0.007; 95% confidence interval of the difference (CI) = −25.19 to −4.81) compared with normative data and that patients tended to have significantly lower scores on AC index (t(14) = − 2.62, p = 0.02; 95% CI = − 25.84 to − 2.56) and PSI (t(14) = −2.42, p = 0.03; 95% CI = −20.01 to −1.19) compared with normative data. In addition, patients had significantly lower scores for the ROCF copy (t(14) = −3.27, p = 0.006; 95 %CI = −23.00 to − 4.8) and List B of the CVLT (t(14) = 3.01, p = 0.009; 95% CI = 3.16 to 18.84) compared with normative data.

3.3. Patients with left HA versus right HA Statistical results for the group comparisons are presented in Table 4. Overall, the cognitive profile of the group with right HA was superior to that of the group with left HA (see Fig. 1), except for intellectual functioning and processing speed index, which were comparable. The one-way ANOVA revealed significant differences between the two groups for MQ (F(1,13) = 11.45, p = 0.005), verbal memory (F(1,13) = 6.78, p = 0.022), nonverbal memory (F(1,13) = 6.33,

Table 2 Demographic and clinical data of each patient group. Characteristics

Left HA

Right HA

Number of patients Sex (male/female) Age at testing, yr (mean(SD)) Age at onset of epilepsy, yr (mean(SD)) Epilepsy duration, yr (mean(SD)) AED at testing (yes/no) Medically refractory epilepsy (yes/no)

10 4/6 13(4) 6(3) 4(3) 9/1 2/8

5 3/2 14(4) 7(3) 2(1) 2/3 0/5

p-Value (t-test) 0.500 n.s. 0.489 n.s. 0.468 n.s. 0.370 n.s. 0.113 n.s. 0.371 n.s.

Note. AED = antiepileptic drug, yr = years, SD = standard deviation, n.s. = not significant.

p = 0.026), WMI (F(1,13) = 8.49, p = 0.012), and AC index (F(1,13) = 6.06, p = 0.029) (Fig. 1). There was no significant difference between the two groups on scores of the ROCF and the CVLT (all p N 0.05, for all subcomponents). 4. Discussion The current study was designed to specify the cognitive profile of children with epilepsy and young adults with unilateral HA without MTS and to explore the nature of memory impairments in these children. Overall, the results showed normal intellectual functioning in our cohort. More importantly, no specific memory impairments were observed. Surprisingly, in patients with right HA, memory functions were even superior to intellectual functions in all domains. Taken together, these findings suggest that patients with epilepsy with unilateral HA have relatively favorable cognitive outcome without specific memory dysfunction. This profile differs from the neuropsychological profile of children with unilateral MTS, in whom memory dysfunctions have consistently been reported [15–18]. The absence of memory impairments may be explained by the specific nature of the hippocampal abnormality found in our participants. In contrast with patients with MTS, the hippocampus of patients with HA may be normally functioning or, at least, partially functioning [36], thus explaining the normal memory performance measured in this study. Furthermore, detailed analyses of our neuropsychological results revealed no significant differences between verbal memory and nonverbal memory in our patients, regardless of the laterality of HA. Although this subject is still a matter of debate, our results are in accordance with most previous studies in pediatric populations, which failed to detect a specific lateralized memory pattern in patients with unilateral HA compared with patients with MTS [14,15,23]. On the other hand, this absence of material-specific patterns in children may be attributable to greater cerebral plasticity and brain adaptation [37,38]. In this context, Helmstaedter and Elger [38] examined age-related regression of verbal learning and memory in patients with chronic TLE. Their results indicate that although chronic epilepsy may interfere with normal development of cognitive functions, laterality differences were only present in adolescent (age above 16 years) and adult patients, not in children. This may suggest that the maturing brain is able to compensate more effectively for one dysfunctional temporal lobe compared with the mature brain [38,39]. It may also explain the absence of

103 (15) 102 (15) 104 (16) 107 (14) 102 (18) 109 (21) 102 (14) 93 (8) 106 (15) 102 (17) 107 (21) 100 (14) 103 (18) 110 (11) 100 (20) 92 (14) 88 (5) 94 (16) 92 (17) 89 (5) 94 (21) 89 (17) 93 (17) 88 (18)

86 (16) 80 (20) 89 (15)

List B Del Imm T5 T1 T1–5

List A Copy

Imm

Del

86 (21) 102 (18) 78 (18) 85 (18) 101 (17) 77 (14) 101 (22) 122 (15) 90 (18) 101 (23) 119 (20) 92 (20) 101 (21) 118 (13) 92 (20) 93 (15) 98 (12) 90 (16) 99 (13) 100 (8) 98 (15)

Overall Nonverbal Verbal Nonverbal

Overall Verbal

93 (14) 96 (9) 91 (16) All patients Right HA Left HA

CVLT ROCF PSI AC WMI Memory IQ

Table 3 Neuropsychological data for all patients, patient group with right HA, and patient group with left HA (standardized scores; mean = 100, SD = 15).

Note. Cells contain means; standard deviations are shown in parentheses. HA = hippocampal atrophy; IQ = intelligence quotient; WMI = working memory index; AC = attention/concentration index; PSI = processing speed index; ROCF = Rey– Osterrieth Complex Figure; CVLT = California Verbal Learning Task; T1–5 = total of trials one to five of the CVLT; T1 = total of trial one; T5 = total of trial five; Imm = immediate recall; Del = delayed recall.

C.S.M. Schmidt et al. / Epilepsy & Behavior 44 (2015) 17–22 111 (14) 114 (17) 110 (13)

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material-specific patterns we found in our group, since most of our participants were 16 years old or younger. The hypothesis regarding brain plasticity has been studied by Gleissner and colleagues [40]. These authors compared the cognitive outcome in children and adults 3 and 12 months posttemporal lobe surgery. They found that children recovered more quickly and more completely compared with adults. In fact, the children were able to reach their preoperative level one year postsurgery, while most adults were still obtaining lower neuropsychological results compared with their presurgical assessment. In addition, greater improvements of attentional abilities and a better postsurgical seizure outcome were observed in children compared with adult patients, which points once more to a greater plasticity and compensational capacity of the developing brain [40]. This compensatory mechanism may also operate in our patients with epilepsy with unilateral HA, thereby providing an explanation for the absence of memory deficits in this pediatric cohort. In addition to memory, other cognitive functions have been assessed in the present study. The combined results of all participants revealed impairments in working memory and in organizational skills and planning ability as evidenced by low WMI index and low performance on the copy of the ROCF compared with delayed recall, respectively. Weaknesses in immediate and selective attention were also shown with low AC index and PSI (statistical tendency). These findings point to impairment of attention and executive functions in children with epilepsy and adolescents with unilateral (left or right) HA without MTS. These specific difficulties have also been reported in recent studies including children with TLE [17,41,42]. Several hypotheses can be offered to explain the impairments in attention and executive functions in patients with HA. Although the medial temporal lobe, including the hippocampus, is known to be essential for memory and learning [43], previous studies have shown that damage to the hippocampus results not only in learning and memory deficits but also in impairments of attention and executive functions, such as working memory [44,45]. The temporal lobe is known to have rich connections to the prefrontal cortex, which, together with other subcortical structures such as the hippocampus, the caudate nucleus, and the thalamus, have been implicated in working memory, executive function, and attention regulation [5,13,41,46]. In addition, connectivity through numerous pathways of the temporal lobes with the frontal lobes facilitates propagation of seizure activity, which might further explain why executive and attention impairments are found in children with temporal lobe epilepsy and unilateral HA [5,41,42,47,48]. In fact, HA has been associated with extratemporal epileptic discharges, which may explain the presence of extratemporal functional deficits, such as attention and executive impairments [20,27,42]. Regardless of the underlying mechanisms accounting for impairments in attention and executive function, these deficits may have significant clinical implications and should be investigated as part of the clinical management of patients with epilepsy with HA. Comparisons between groups (left HA versus right HA) did not reveal any differences in global intellectual functioning as reported in previous studies [7,40]. However, patients with right HA were superior to children with left HA with regard to memory, attention, and executive functions. This pattern of results is similar to that reported for patients with MTS [7,40,49]. Studies that investigated preoperative and postoperative cognitive functions in left or right hippocampal resection also indicate that patients with right resection tend to have a better outcome compared with those with left hippocampal resection [7,23,50]. To explain this discrepancy, it has been suggested that there is larger functional plasticity in the right temporal lobe than in the left temporal lobe [50]. This notion has gained support from studies comparing preoperative and postoperative cognitive functioning of children with either left or right temporal lobe resection, which have shown greater deterioration of cognitive functions after left resection than after right resection [39]. Finally, another factor that may explain the superior

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Fig. 1. Between-groups comparisons for specific cognitive functioning. The black square indicates the mean performance of all patients combined; the blue X indicates the mean performance of patients with left HA, and the red circle indicates the mean performance of patients with right HA for each cognitive domain. The straight horizontal dotted line indicates the mean of standardized scores; and the gray shaded area indicates the normal range based on normative data (range from ±1 SD to the mean 100 ± 15). IQ = intelligence quotient, MQ = memory quotient, WMI = working memory index, AC = attention/concentration index, PSI = processing speed index.

results of the group with right HA is our small sample size (10 patients with left HA versus 5 patients with right HA). The small sample size constitutes, indeed, the main limitation of this study. Therefore, results have to be interpreted with caution, and generalization of our data is limited. Furthermore, the small sample size did not allow exploration of the effect of demographic variables (e.g., age and sex) or epilepsy-related factors (e.g., age at onset, seizure frequency, and number of medication) on cognitive functioning that have been shown to influence neuropsychological data [48,51]. Nevertheless, no group differences were found regarding these factors. 5. Conclusion To our knowledge, this study is the first to specify the cognitive profile of children with epilepsy with HA without MTS. All patients showed favorable global intellectual outcome and no memory deficits or material-specific memory impairments but exhibited deficits in attention, working memory, and executive functions. This neuropsychological profile contrasts with that reported for children with MTS, who tend to have poor cognitive outcome including memory dysfunction [4–8]. Although generalization of our data is limited because of the small sample size, it is possible to speculate that HA may be a distinct clinical entity. Furthermore, our study points to the importance of performing a global cognitive assessment that includes the investigation of attention and executive functions, since deficits in these Table 4 Statistical group comparisons: left HA versus right HA. Cognitive function

Left HA

Right HA

p-Value (t-test, p ≤ 0.05)

Overall IQ Verbal IQ Nonverbal IQ MQ Verbal memory Nonverbal memory WMI AC PSI

90 (16) 91 (16) 98 (15) 90 (18) 92 (20) 92 (20) 77 (14) 78 (18) 88 (18)

98 (12) 96 (9) 100 (8) 122 (15) 118 (13) 119 (20) 101 (17) 102 (18) 93 (17)

0.323 n.s. 0.503 n.s. 0.812 n.s. 0.005a 0.022a 0.026a 0.012a 0.029a 0.624 n.s.

Note. Cells contain means; standard deviations are shown in parentheses. n.s. = not significant; IQ = intelligence quotient; MQ = memory index; WMI = working memory index; AC = attention/concentration index; PSI = processing speed index. a Significant difference.

cognitive domains may lead to other cognitive or behavioral problems in everyday life, academic, and professional activities [52,53]. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.yebeh.2014.12.023. Acknowledgments This work was funded (AG) by the Canadian Institutes of Health Research (MSH-131472) and the Fonds de la Recherche du Québec Santé (26804). CSM was supported by a scholarship fund from the TransAtlantic Neuroscience Teaching Network (TANTEN) from the University of Maastricht, The Netherlands. Conflict of interest We confirm that there are no known conflicts of interest associated with this publication and that there has been no significant financial support for this work that could have influenced its outcome. References [1] Hermann B, Seidenberg M. Neuropsychology and temporal lobe epilepsy. CNS Spectr 2002;7(5):343–8. [2] Jackson GD. The diagnosis of hippocampal sclerosis: other techniques. Magn Reson Imaging 1995;13(8):1081–93. [3] Cendes F, Andermann F, Dubeau F, Gloor P, Evans A, Jones-Gotman M, et al. Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy: an MRI volumetric study. Neurology 1993;43(6):1083–7. [4] Baxendale S, Heaney D, Thompson PJ, Duncan JS. Cognitive consequences of childhood-onset temporal lobe epilepsy across the adult lifespan. Neurology 2010; 75(8):705–11. [5] Campo P, Garrido MI, Moran RJ, Garcia-Morales I, Poch C, Toledano R, et al. Network reconfiguration and working memory impairment in mesial temporal lobe epilepsy. Neuroimage 2013;72:48–54. [6] Castro LH, Silva LC, Adda CC, Banaskiwitz NH, Xavier AB, Jorge CL, et al. Low prevalence but high specificity of material-specific memory impairment in epilepsy associated with hippocampal sclerosis. Epilepsia 2013;54(10):1735–42. [7] Gargaro AC, Sakamoto AC, Bianchin MM, GeraldiCde V, Scorsi-Rosset S, Coimbra ER, et al. Atypical neuropsychological profiles and cognitive outcome in mesial temporal lobe epilepsy. Epilepsy Behav 2013;27(3):461–9. [8] Hermann BP, Seidenberg M, Schoenfeld J, Davies K. Neuropsychological characteristics of the syndrome of mesial temporal lobe epilepsy. Arch Neurol 1997;54(4): 369–76. [9] Alessio A, Damasceno BP, Camargo CH, Kobayashi E, Guerreiro CA, Cendes F. Differences in memory performance and other clinical characteristics in patients with mesial temporal lobe epilepsy with and without hippocampal atrophy. Epilepsy Behav 2004;5(1):22–7.

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[10] Hermann B, Seidenberg M, Lee EJ, Chan F, Rutecki P. Cognitive phenotypes in temporal lobe epilepsy. J Int Neuropsychol Soc 2007;13(1):12–20. [11] Oddo S, Solis P, Consalvo D, Giagante B, Silva W, D'Alessio L, et al. Mesial temporal lobe epilepsy and hippocampal sclerosis: cognitive function assessment in Hispanic patients. Epilepsy Behav 2003;4(6):717–22. [12] Alessio A, Kobayashi E, Damasceno BP, Lopes-Cendes I, Cendes F. Evidence of memory impairment in asymptomatic individuals with hippocampal atrophy. Epilepsy Behav 2004;5(6):981–7. [13] Tudesco Ide S, Vaz LJ, Mantoan MA, Belzunces E, Noffs MH, Caboclo LO, et al. Assessment of working memory in patients with mesial temporal lobe epilepsy associated with unilateral hippocampal sclerosis. Epilepsy Behav 2010;18(3):223–8. [14] Saling MM. Verbal memory in mesial temporal lobe epilepsy: beyond material specificity. Brain 2009;132(Pt 3):570–82. [15] Engle JA, Smith ML. Attention and material-specific memory in children with lateralized epilepsy. Neuropsychologia 2010;48(1):38–42. [16] Gadian DG, Isaacs EB, Cross JH, Connelly A, Jackson GD, King MD, et al. Lateralization of brain function in childhood revealed by magnetic resonance spectroscopy. Neurology 1996;46(4):974–7. [17] Guimaraes CA, Rzezak P, Fuentes D, Franzon RC, Montenegro MA, Cendes F, et al. Memory in children with symptomatic temporal lobe epilepsy. Arq Neuropsiquiatr 2014;72(3):184–9. [18] Jambaque I, Dellatolas G, Dulac O, Ponsot G, Signoret JL. Verbal and visual memory impairment in children with epilepsy. Neuropsychologia 1993;31(12):1321–37. [19] Kar BR, Rao SL, Chandramouli BA, Thennarasu K, Satishchandra P. Neuropsychological lateralization of brain dysfunction in children with mesial temporal sclerosis: a presurgical evaluation. J Child Neurol 2010;25(6):705–14. [20] Alessio A, Bonilha L, Rorden C, Kobayashi E, Min LL, Damasceno BP, et al. Memory and language impairments and their relationships to hippocampal and perirhinal cortex damage in patients with medial temporal lobe epilepsy. Epilepsy Behav 2006;8(3):593–600. [21] Zamarian L, Trinka E, Bonatti E, Kuchukhidze G, Bodner T, Benke T, et al. Executive functions in chronic mesial temporal lobe epilepsy. Epilepsy Res Treat 2011;2011: 596174. [22] Cormack F, Vargha-Khadem F, Wood SJ, Cross JH, Baldeweg T. Memory in paediatric temporal lobe epilepsy: effects of lesion type and side. Epilepsy Res 2012;98(2–3): 255–9. [23] Lee TM, Yip JT, Jones-Gotman M. Memory deficits after resection from left or right anterior temporal lobe in humans: a meta-analytic review. Epilepsia 2002;43(3): 283–91. [24] Gonzalez LM, Anderson VA, Wood SJ, Mitchell LA, Harvey AS. The localization and lateralization of memory deficits in children with temporal lobe epilepsy. Epilepsia 2007;48(1):124–32. [25] Sloviter RS. The functional organization of the hippocampal dentate gyrus and its relevance to the pathogenesis of temporal lobe epilepsy. Ann Neurol 1994;35(6): 640–54. [26] Kalviainen R, Salmenpera T, Partanen K, Vainio P, Riekkinen P, Pitkanen A. Recurrent seizures may cause hippocampal damage in temporal lobe epilepsy. Neurology 1998;50(5):1377–82. [27] Major P, Decarie JC, Nadeau A, Diadori P, Lortie A, Nguyen D, et al. Clinical significance of isolated hippocampal volume asymmetry in childhood epilepsy. Neurology 2004;63(8):1503–6. [28] Wechsler D. The Wechsler Intelligence Scale for Children. 4th ed. London: Pearson Assessment; 2004. [29] Wechsler D. The Wechsler Adult Intelligence Scale. 3rd ed. London: Pearson Assessment; 1997. [30] Cohen M. Children's Memory Scale (CMS). London: Pearson Assessment; 1997. [31] Wechsler D. Wechsler Memory Scale. London: Pearson Assessment; 1945. [32] Rey A. Manuel du test de copie d'une figure complexe de A. Rey. Paris: Les Editions du Centre de Psychologie Appliquée; 1959.

[33] Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test. 2nd ed. San Antonio: Psychological Corporation; 2000. [34] Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test — Children's Version (CVLT-C). London: Pearson; 1994. [35] Tremblay E, Vannasing P, Roy MS, Lefebvre F, Kombate D, Lassonde M, et al. Delayed early primary visual pathway development in premature infants: high density electrophysiological evidence. PLoS One 2014;9(9):e107992. [36] Coan AC, Campos BM, Yasuda CL, Kubota BY, Bergo FP, Guerreiro CA, et al. Frequent seizures are associated with a network of gray matter atrophy in temporal lobe epilepsy with or without hippocampal sclerosis. PLoS One 2014;9(1):e85843. [37] Reminger SL, Kaszniak AW, Labiner DM, Littrell LD, David BT, Ryan L, et al. Bilateral hippocampal volume predicts verbal memory function in temporal lobe epilepsy. Epilepsy Behav 2004;5(5):687–95. [38] Helmstaedter C, Elger CE. Chronic temporal lobe epilepsy: a neurodevelopmental or progressively dementing disease? Brain 2009;132(Pt 10):2822–30. [39] Gleissner U, Sassen R, Lendt M, Clusmann H, Elger CE, Helmstaedter C. Pre- and postoperative verbal memory in pediatric patients with temporal lobe epilepsy. Epilepsy Res 2002;51(3):287–96. [40] Gleissner U, Sassen R, Schramm J, Elger CE, Helmstaedter C. Greater functional recovery after temporal lobe epilepsy surgery in children. Brain 2005;128(Pt 12): 2822–9. [41] Longo CA, Kerr EN, Smith ML. Executive functioning in children with intractable frontal lobe or temporal lobe epilepsy. Epilepsy Behav 2013;26(1):102–8. [42] Tuchscherer V, Seidenberg M, Pulsipher D, Lancaster M, Guidotti L, Hermann B. Extrahippocampal integrity in temporal lobe epilepsy and cognition: thalamus and executive functioning. Epilepsy Behav 2010;17(4):478–82. [43] Bear MF, Connors BW, Paradiso MA. Neuroscience exploring the brain. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. [44] Abrahams S, Morris RG, Polkey CE, Jarosz JM, Cox TC, Graves M, et al. Hippocampal involvement in spatial and working memory: a structural MRI analysis of patients with unilateral mesial temporal lobe sclerosis. Brain Cogn 1999;41(1):39–65. [45] Nagel BJ, Herting MM, Maxwell EC, Bruno R, Fair D. Hemispheric lateralization of verbal and spatial working memory during adolescence. Brain Cogn 2013;82(1): 58–68. [46] Hermann B, Seidenberg M, Bell B, Rutecki P, Sheth RD, Wendt G, et al. Extratemporal quantitative MR volumetrics and neuropsychological status in temporal lobe epilepsy. J Int Neuropsychol Soc 2003;9(3):353–62. [47] 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(2):186–95. [48] Marques CM, Caboclo LO, da Silva TI, Noffs MH, Carrete Jr H, Lin K, et al. Cognitive decline in temporal lobe epilepsy due to unilateral hippocampal sclerosis. Epilepsy Behav 2007;10(3):477–85. [49] Maher H, Pender N, Delanty N, Doherty C, Burke T. The nature and extent of cognitive disruption in mesial temporal lobe epilepsy relative to unaffected siblings and healthy controls. Paper presented at the 30th International Epilepsy Congress (IEC), Montreal, Canada, 23–27; June, 2013. [50] Gleissner U, Helmstaedter C, Elger CE. Right hippocampal contribution to visual memory: a presurgical and postsurgical study in patients with temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 1998;65(5):665–9. [51] Jokeit H, Ebner A. Long term effects of refractory temporal lobe epilepsy on cognitive abilities: a cross sectional study. J Neurol Neurosurg Psychiatry 1999;67(1):44–50. [52] Rzezak P, Guimaraes CA, Fuentes D, Guerreiro MM, Valente KD. Memory in children with temporal lobe epilepsy is at least partially explained by executive dysfunction. Epilepsy Behav 2012;25(4):577–84. [53] Cornaggia CM, Beghi M, Provenzi M, Beghi E. Correlation between cognition and behavior in epilepsy. Epilepsia 2006;47(Suppl. 2):34–9.

Neuropsychological functioning in children with temporal lobe epilepsy and hippocampal atrophy without mesial temporal sclerosis: a distinct clinical entity?

Unilateral hippocampal atrophy (HA) is considered as a precursor of mesial temporal sclerosis (MTS) in some patients with temporal lobe epilepsy. Howe...
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