[Show abstract][Hide abstract] ABSTRACT: Purpose: Cognitive impairment is observed commonly in children with a history of infantile spasms (IS). The goal of this study was to prospectively examine the effect on cognitive outcome of a neuroprotective agent used as adjunctive therapy during treatment of the spasms.
Methods: In a randomized controlled trial, patients received a standardized therapy plus flunarizine or placebo. The standardized treatment consisted of vigabatrin as first-line therapy. Nonresponders were switched to intramuscular synthetic adrenocorticotropic hormone (sACTH depot) after 2 weeks and, if necessary, to topiramate after two additional weeks. The Vineland Adaptive Behavior Scale (VABS) and Bayley Scales of Infant Development (BSID) were used as outcome measures 24 months after the intervention.
Key Findings: Sixty-eight of 101 children diagnosed over 3 years in seven centers in Canada received either adjunctive flunarizine or placebo. Sixty-five of the 68 children (96%) became spasm-free within 8 weeks and no late relapse occurred. Bayley and Vineland results were available at baseline and at 24 months in 45 children. There was no significant difference in the BSID developmental quotient between the flunarizine- and placebo-treated children at baseline (44.3 ± 35.5 vs. 30.9 ± 29.8; p = 0.18) or 24 months later (56.9 ± 33.3 vs. 46 ± 34.2; p = 0.29). However, the 10 flunarizine-treated children with no identified etiology had a better outcome than the eight controls at 24 months on both the Vineland Scale (84.1 ± 11.3 vs. 72.3 ± 9.8; p = 0.03) and the Bayley Scale (87.6 ± 14.7 vs. 69.9 ± 25.3; p = 0.07).
Significance: Our study failed to demonstrate a protective effect of flunarizine on cognitive outcome in a cohort of children with IS. An analysis of subgroups suggested that flunarizine may further improve cognitive outcome in children with no identified etiology.
[Show abstract][Hide abstract] ABSTRACT: Consequences of status epilepticus (SE) on psychomotor development and the specific impact of the convulsive event on emerging executive functions remain controversial. Infants treated for a single episode of SE, those treated for a single febrile seizure, and healthy infants were tested with respect to motor development, language, personal, and social skills and self-regulation. The children were divided into two age groups to investigate the impact of the convulsive event at different windows of brain maturation. We found that infants who had had SE were inferior to healthy controls on the development scales. Age differentiated SE impact on visuomotor development versus sociolinguistic development. Children who had been treated for SE had significantly more difficulties delaying a response to an attractive stimulus in one of the long-delay conditions. A single episode of SE can interfere with psychomotor and cognitive development in children without previous developmental delay, and it seems that the functions that are emerging at the time of insult are most vulnerable.
[Show abstract][Hide abstract] ABSTRACT: We investigated the development of the magnitude and phase alignment of steady-state visual evoked potentials induced by 5 Hz intermittent photic stimulation in 46 children (3 to 16 years) and 8 adults, as a function of age. We found that, over the occipital region, magnitude values were the highest in 8-11-year old children, but decreased with age over all other cerebral regions. Phase alignment values increased with age over the occipital, parietal and frontal cerebral regions. We interpret these findings in terms of the development of functional interactions between different cortical areas involved in the processing of visual stimuli.
International journal of psychophysiology: official journal of the International Organization of Psychophysiology 12/2010; 78(3):295-8. DOI:10.1016/j.ijpsycho.2010.09.003 · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epilepsy is one of the most frequent childhood disorders. While most cases are well controlled, approximately 30-50% are resistant to medical treatment. In these cases, neurosurgery may be an option. Since 1979, our team at the Sainte-Justine Hospital in Montreal has studied the impact of epilepsy on the psycho-motor and cognitive development of the affected children. The aim of a first series of studies was to explore the extent and limits of cerebral plasticity by investigating the neuropsychological sequelae of early versus late callosotomy and hemispherectomy. In keeping with the plasticity hypothesis, the results revealed that the children who were operated before puberty showed fewer deficits than those operated during adolescence or adulthood. However, the compensatory mechanisms available to them appeared to be limited with respect to the nature and complexity of the information they can process. For instance, young children having undergone section of the corpus callosum resembled individuals born without a corpus callosum (callosal agenesis) in that there did not show the typical disconnection deficits seen in adult ''split-brain'' patients. However, they exhibited deficits on tasks requiring interhemispheric integration of motor and visuo-motor information. By the same token, hemispherectomy patients were still able to make visual judgements in their ''blind'' visual field but they were found to be impaired on a variety of visual and auditory tasks (localization of a sound sources in space) requiring the participation of both hemispheres. In a second series of studies, carried out in collaboration with a Parisian team, we intended to describe the neuropsychological profile of focal epilepsies, specifically frontal and temporal epilepsy. Contrary to the common belief that childhood epilepsy would result in diffuse impairments, we were able to demonstrate that children manifest the same localized deficits as adult patients. In studies presently underway in our laboratories, we make use of functional neuroimaging techniques such as high density electrophysiology, optical imaging and magnetoencephalography to investigate pre-and postoperative language and memory functions and to study the impact of epilepsy on brain maturation.
Medecine sciences: M/S 12/2007; 23(11):923-8. · 0.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: L'épilepsie est l'affection neurologique la plus commune après la migraine : elle touche près de 2 % de la population. Elle apparaît le plus souvent durant la première année de vie et dans 75 % des cas avant l'âge de 18 ans. Parmi les enfants atteints, après quelques années de traitement, la moitié connaîtra un développement neurologique normal, l'autre moitié fera face à un pronostic sombre, tant sur les plans clinique que social et professionnel. Compte tenu des séquelles cognitives, neurologiques et sociales que les épilepsies chroniques entraînent chez l'enfant, une inter-vention chirurgicale est fréquemment envisagée. La callosotomie Très tôt, le service de neurologie du Centre hospitalier universitaire Sainte-Justine s'est fait connaî-tre par son approche avant-gardiste dans le traitement de l'épilepsie infantile. En effet, en 1979 et à l'initiative de feu Dr Guy Geoffroy, neurologue, l'hôpital Sainte-Justine est devenu le premier établissement hospitalier à effectuer chez l'enfant une callosotomie -opération qui n'avait jusqu'alors été pratiquée que chez l'adulte épileptique dans quelques centres spécialisés aux États-Unis . Cette option thérapeutique chirurgicale a pour but d'abolir la propagation de la décharge épileptique d'un hémisphère à un autre par les voies de communi-cation inter-hémisphérique (soit le corps calleux). Elle est pratiquée pour traiter les cas d'épilepsies sévères et pharmaco-résistantes, notamment le syndrome de Len-nox et Gastaut, les crises atoniques et toniques, les crises tonico-cloniques et l'épilepsie multifocale 1 . Les premières études neuropsychologiques que nous avons effectuées auprès des enfants callosotomisés, ou split-brain, ont d'abord eu pour objet de vérifier que la chirurgie pouvait être accomplie sans perturber leurs fonctions cognitives [1, 2]. Au contraire, comme l'intervention chirurgicale entraînait une atténuation des crises et une diminution de la médication chez plus des deux tiers d'entre eux, ces enfants manifestaient, 1 Bien que la section du corps calleux soit encore effectuée dans plusieurs centres, notamment dans le traitement des crises akinétiques, elle a été progressivement remplacée par d'autres approches telle la stimulation du nerf vague dans certains centres d'épilepsie.
Medecine sciences: M/S 11/2007; 23(11). DOI:10.1051/medsci/20072311923 · 0.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The intracarotid amobarbital test (IAT) is the most widely used procedure for pre-surgical evaluation of language lateralization in epileptic patients. However, apart from being invasive, this technique is not applicable in young children or patients who present mental retardation and/or language deficits. Functional magnetic resonance imaging (fMRI) is increasingly employed as a non-invasive alternative. Again, this method is more difficult to use with young children, especially hyperactive ones, since they have to remain motionless during data acquisition. The aim of this study was to determine whether near-infrared spectroscopy (NIRS) can be used as an alternative technique to investigate language lateralization in children and special populations. Unlike Wada test, NIRS is non-invasive, and it is more tolerant to movement artefacts than fMRI. In the present study, NIRS data were acquired in four epileptic children, a 12-year-old boy with pervasive developmental disorder and a 3-year-old, healthy child, as well as three healthy and two epileptic adults, while they performed a verbal fluency task and a control task. When applicable, the results were compared to the subjects' fMRI and/or IAT findings. Clear laterality of speech was obtained in all participants, including the two non-epileptic children, and NIRS results matched fMRI and IAT findings. These results, if replicable in larger samples, are encouraging and suggest that NIRS has the potential to become a viable, non-invasive alternative to IAT and fMRI in the determination of speech lateralization in children and clinical populations that cannot be submitted to more invasive techniques.
Epileptic disorders: international epilepsy journal with videotape 10/2007; 9(3):241-55. DOI:10.1684/epd.2007.0118 · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The cognitive outcome of the surgical removal of an epileptic focus depends on the assessment of the localisation and functional capacity of language and memory areas which need to be spared by the neurosurgeon. Traditionally, presurgical evaluation of epileptic patients has been achieved by means of the intracarotid amobarbital test assisted by neuropsychological measures. However, the advent of neuroimaging techniques has provided new ways of assessing these functions by means of non-invasive or minimally invasive methods, such as anatomical and functional magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, transcranial magnetic stimulation, functional transcranial Doppler monitoring, magnetoencephalography and near infrared spectroscopy. This paper aims at comparing and evaluating the traditional and recent preoperative approaches from a neuropsychological perspective.
Epileptic disorders: international epilepsy journal with videotape 07/2007; 9(2):111-26. DOI:10.1684/epd.2007.0109 · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epilepsy is frequently associated with cognitive impairments which result from various interacting factors. The present paper deals with the contribution of neuropsychology to the characterization of the type of epilepsy and the possible mechanisms underlying idiopathic epileptic syndromes. The non-lesional, so-called idiopathic epilepsies, constitute an interesting model for assessing the relationship between epileptiform EEG discharges and cognition. Among the idiopathic generalized epilepsies, disorders of social integration and personality have been frequently reported in juvenile myoclonic epilepsy (JME). Since similar disturbances are observed in frontal-lobe-lesioned patients, impairments in other frontal lobe functions (e.g. executive functions) might be expected in JME. This gives rise to speculation about the possible underlying pathophysiological mechanisms in JME. With regard to partial idiopathic epilepsies, benign childhood epilepsy with centrotemporal spikes (BCECTS) may provide a useful model for the study of the relationship between epileptiform EEG discharges in the peri-sylvian region and language functions. Furthermore, the description of mild cognitive dysfunctions in BCECTS, and their persistence into adulthood, can provide information about compensatory mechanisms and may allow for the generation of remedial strategies. Thus, 'lesional' neuropsychology has given way to 'dynamic' neuropsychology based on specific postulates. By using the cognitive profile to specify the mechanism underlying the behavioral disturbances observed in different types of epilepsy, neuropsychology may eventually contribute to a revision of the present classification of epileptic syndromes. In addition, the neuropsychological data may help predict the extent and limits of functional recovery and cerebral plasticity.
[Show abstract][Hide abstract] ABSTRACT: The neuropsychological assessment is an integral part of the clinical investigation of patients suffering from epilepsy. The aim of the evaluation is to determine disease-related and treatment-related effects on cognition and behavior in order to orient therapeutic interventions, by taking into account the compensatory mechanisms that are available to the patient. Examples of the tests best illustrating the classical neuropsychological protocol are presented. Neuropsychology also plays an important role in the assessment of language lateralization in patients slated for epilepsy surgery. Traditionally, this has been achieved by means of the rather invasive Wada procedure. However, with the advent of new neuroimaging techniques, this procedure is gradually being replaced by minimally invasive or noninvasive methods, such as functional magnetic resonance imaging, positron emission tomography, and optical imaging. In the present paper, we discuss some of the newer techniques that are available to the neuropsychologist for the study of the impact of epilepsy on cerebral functioning.
[Show abstract][Hide abstract] ABSTRACT: We evaluated somatosensory and motor interhemispheric integration in four patients who underwent transection of different portions of the anterior corpus callosum (CC) for removal of an intraventricular cyst. The study goal was to relate their performances to the topographical organization of the CC.
Experimental tasks included bimanual coordination, tactile cross-localization, and intermanual and interfield comparisons of somesthetic information. Response accuracy and response times were measured. In addition, interhemispheric transmission times were obtained in the somesthetic modality.
Section of the middle portion of the genu caused a deficit in motor coordination, which was absent in patients with more posteriorly located lesions, whereas section of more rostral portions of the genu seemed to interfere with motor planning. The most posterior section in our sample, including the anterior portion of the body of the corpus, abolished interhemispheric transfer of simple somesthetic information (perception of touch) but not tactile discrimination (intermanual comparisons of shapes). We speculate that more complex somesthetic information is transferred through the caudal region of the body of the CC, which was spared in all patients. Thus, it seems that section of different portions of the anterior CC (genu and anterior body) produces specific deficits in interhemispheric integration in the motor and somesthetic modalities. These deficits are consistent with the anteroposterior topography of anterior callosal fibers.
The specific disconnections deficits observed in this study may provide the surgeon with information regarding the consequences of anterior callosotomy and allow for remedial measures to be implemented if required.
[Show abstract][Hide abstract] ABSTRACT: To explore whether attention, memory, and behavior would be more affected in children with frontal lobe epilepsy than in children with other types of epilepsy, we compared 16 children with frontal lobe epilepsy (FLE), 8 with temporal lobe epilepsy (TLE), and 8 with generalized absence (GEA) seizures on the Performance Speed (PS) and Freedom of Distraction (FD) indices of the WISC-III, the Continuous Performance Test (CPT), the California Verbal Learning Test (CVLT), and Rey-Osterrieth Complex Figure (ROCF). Parents completed Achenbach's Child Behavior Check List. Children with FLE scored significantly lower than the other two groups on the PS and CPT. On the CVLT they made more intrusion errors and were more prone to interference. Furthermore, they had more difficulties copying and recalling the ROCF. Behavior profiles revealed greater attention problems in this group. This may put children with FLE at greater risk of developing school problems than children with TLE and GEA.
[Show abstract][Hide abstract] ABSTRACT: To explore whether attention, memory, and behavior would be more affected in children with frontal lobe epilepsy than in children with other types of epilepsy, we compared 16 children with frontal lobe epilepsy (FLE), 8 with temporal lobe epilepsy (TLE), and 8 with generalized absence (GEA) seizures on the Performance Speed (PS) and Freedom of Distraction (FD) indices of the WISC-III, the Continuous Performance Test (CPT), the California Verbal Learning Test (CVLT), and Rey–Osterrieth Complex Figure (ROCF). Parents completed Achenbach’s Child Behavior Check List. Children with FLE scored significantly lower than the other two groups on the PS and CPT. On the CVLT they made more intrusion errors and were more prone to interference. Furthermore, they had more difficulties copying and recalling the ROCF. Behavior profiles revealed greater attention problems in this group. This may put children with FLE at greater risk of developing school problems than children with TLE and GEA.
[Show abstract][Hide abstract] ABSTRACT: The Canadian Pediatric Epilepsy Network is a network of scientists and health care professionals in partnership with organizations which provide education and support to children with epilepsy. The objective of the network is to gain a better understanding of childhood epilepsy through collaborative research conducted with doctors, psychologists, nurses, social workers, educators and scientists across Canada. The network was launched at a meeting in Ottawa in the spring of 2000 where several oral presentations addressed the issues of the fundamental questions of epilepsy, the economic impact and the neuropsychology of childhood epilepsy. The intent was to provoke discussion on future areas of research for the network.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 12/2002; 29(4):364-71. · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Frontal lobe dysfunction in adults has been associated with impairments of planning abilities, working memory, impulse control, attention and certain aspects of motor coordination. However, very few studies have attempted to assess these functions in children suffering from frontal lobe epilepsy. The aim of the present study was to determine whether some or all of the components of the frontal lobe syndrome are present in children with this disorder. For this purpose, a neuropsychological test battery was administered to 32 unresected epileptic children, aged 8-16 years: 16 with frontal lobe epilepsy (FLE), eight with temporal lobe epilepsy (TLE) and eight with generalized epilepsy whose principal manifestations were typical absences (GEA). The performances of the three epileptic groups were further compared to normative data derived from 200 French-speaking, healthy children aged 7-16 years, except for standardized tests for which the norms provided in the manual were used. The three epilepsy groups did not differ with respect to conceptual shift and recency memory. However, the FLE children showed deficits in planning and impulse control. Furthermore, they had significantly more coordination problems and exhibited greater rigidity than the other epilepsy groups on the motor tests. These problems were more marked in younger FLE children (8-12 years). The latter were also more impaired on verbal fluency measures. No differences were observed with respect to gender, localization of the epileptic abnormality (unilateral versus bilateral) or medication (monotherapy versus polytherapy). The findings reveal similarities between the neuropsychological profiles of FLE children and adults with frontal lobe lesions.
[Show abstract][Hide abstract] ABSTRACT: Neuropsychological problems have frequently been reported following treatment of Acute Lymphoblastic Leukemia (ALL), however, partly because of the heterogeneity of the previously studied samples, the specific nature of these deficits is still a matter of debate. These problems, however, appear to be related more to the combination of cranial radiation therapy (CRT) and intrathecal chemotherapy (ITC) than to ITC alone. In this study, we evaluated a homogenous group of 19 girls between the ages of 7 and 11 years, 30 months after the completion of treatment. Nine received cranial radiation and chemotherapy and 10 were treated with chemotherapy alone. The patients were compared to 10 normal healthy controls. Neuropsychological tests included the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), the California Verbal Learning Test-Children's Version (CVLT-C), and the Calculation and Passage Comprehension subtests of the Woodcock-Johnson Psycho-Educational Battery-Revised. Results confirmed the presence ofa verbal learning deficit in ALL girls treated with the combination of ITC and CRT. The ITC and CRT group scored significantly lower than the healthy controls on the Passage Comprehension subtest and on 5 of the 6 verbal subtests of the WISC-III. Furthermore, compared to nonirradiated patients and healthy normal controls, the ITC and CRT group was impaired on the Freedom from Distractibility index of the WISC-III, indicating an auditory-verbal attention deficit. On the CVLT-C, the ITC and CRT group was particularly impaired on the second half of the learning trials compared to the other two groups, showing a plateau in their performance. The ITC group was not different from the healthy control group, suggesting a less detrimental effect of the ITC alone on verbal abilities. Globally, these results indicate a deficit affecting auditory attention and verbal learning in girls who receive ITC and CRT, which may suggest the necessity for special educational assistance for these children.
[Show abstract][Hide abstract] ABSTRACT: Frontal lobe dysfunction in adults has been associated with impairments of planning abilities, working memory, impulse control, attention and certain aspects of motor coordination. However, very few studies have attempted to assess these functions in children suffering from frontal lobe epilepsy. The aim of the present study was to determine whether some or all of the components of the frontal lobe syndrome are present in children with this disorder. For this purpose, a neuropsychological test battery was administered to 32 unresected epileptic children, aged 8–16 years: 16 with frontal lobe epilepsy (FLE), eight with temporal lobe epilepsy (TLE) and eight with generalized epilepsy whose principal manifestations were typical absences (GEA). The performances of the three epileptic groups were further compared to normative data derived from 200 French-speaking, healthy children aged 7–16 years, except for standardized tests for which the norms provided in the manual were used. The three epilepsy groups did not differ with respect to conceptual shift and recency memory. However, the FLE children showed deficits in planning and impulse control. Furthermore, they had significantly more coordination problems and exhibited greater rigidity than the other epilepsy groups on the motor tests. These problems were more marked in younger FLE children (8–12 years). The latter were also more impaired on verbal fluency measures. No differences were observed with respect to gender, localization of the epileptic abnormality (unilateral versus bilateral) or medication (monotherapy versus polytherapy). The findings reveal similarities between the neuropsychological profiles of FLE children and adults with frontal lobe lesions.
[Show abstract][Hide abstract] ABSTRACT: Childhood epilepsy is one of the most prevalent forms of chronic and disabling childhood disorders. Because it disrupts brain maturation, it has long been thought to produce non-specific consequences such as mental deficiency and behavioral problems. However, advances in medical knowledge have shown that childhood epilepsy should not be considered as a single disorder, and it is now becoming apparent that various clinical entities have different cognitive expressions that yet need to be specified. The purpose of this paper is to provide an up-to-date analysis of this multi-faceted pathology. The first section is devoted to the characterization of the neuropsychological profile that accompanies focal epilepsies, as defined by the site of the epileptic process. We report the first group study of children with frontal lobe epilepsy. The results indicate that frontal lobe epilepsy produces symptoms (deficits of planning, attention and motor dexterity) that are akin to those found in frontal-lesioned adults. Similarly, like in adults, temporal lobe epilepsy produces memory impairment in children as well as behavioral and academic disturbances. Occipito-parietal lobe epilepsy is rare in children and its effects still need to be specified. The second section deals with the neuropsychological techniques used in presurgical evaluation. Finally, the various neurosurgical procedures that are increasingly being used as part of the arsenal of epilepsy treatment are described along with the neuropsychological findings that are associated with these interventions. It can be concluded that the beneficial effects of epilepsy surgery (callosotomy, hemispherectomy, temporal and extra-temporal resections) by far outweigh the few cognitive deficits that are occasionally reported following these interventions.
Epileptic disorders: international epilepsy journal with videotape 04/2000; 2(1):3-13. · 0.95 Impact Factor