Cognitive disorders in pediatric epilepsy.

Childhood epilepsy may cause cognitive disorders and the intellectual quotient is indeed not normally distributed in epileptic children, a fair proportion of whom show an IQ in the deficient range. Some epileptic syndromes happen during vulnerability periods of brain maturation and interfere with the development of specific cognitive functions. This is the case for the Landau-Kleffner syndrome, which generally appears during speech development and affects language. Similarly, West syndrome - or infantile spasms - is an epileptogenic encephalopathy appearing during the first years of life and induces a major delay in social and oculo-motor development. Specific impairments can also be identified in partial childhood epilepsies in relation with seizure focus localization. For instance, left temporal and frontal epilepsies are frequently associated with verbal impairments. Moreover, episodic memory disorders have been described in children suffering from temporal lobe epilepsy whereas executive deficits (planning, self-control, problem solving) have been reported in frontal lobe epilepsy. In most cases, including its mildest forms, childhood epilepsy induces attention deficits, which may affect academic achievement. These observations militate in favor of individual neuropsychological assessments as well as early interventions in order to provide the child with an optimal individualized treatment program.

The neuropsychology of the Klüver-Bucy syndrome in children.

The Klüver-Bucy syndrome (KBS) is characterized by a number of peculiar behavioral symptoms. The syndrome was first observed in 1939 by Heinrich Klüver and Paul Bucy in the rhesus monkey following removal of the greater portion of the monkey's temporal lobes and rhinencephalon. The animal showed (a) visual agnosia (inability to recognize objects without general loss of visual discrimination), (b) excessive oral tendency (oral exploration of objects), (c) hypermetamorphosis (excessive visual attentiveness), (d) placidity with loss of normal fear and anger responses, (e) altered sexual behavior manifesting mainly as marked and indiscriminate hypersexuality, and (f) changes in eating behavior. In humans, KBS can be complete or incomplete. It occurs as a consequence of neurological disorders that essentially cause destruction or dysfunction of bilateral mesial temporal lobe structures (i.e., Pick disease, Alzheimer disease, cerebral trauma, cerebrovascular accidents, temporal lobe epilepsy, herpetic encephalopathy, heat stroke). As for epilepsy, complete and incomplete KBS are well documented in temporal lobe epilepsy, temporal lobectomy, and partial status epilepticus. KBS can occur at any age. Children seem to show similar symptoms to adults, although some differences in the manifestations of symptoms may be related to the fact that children have not yet learned certain behaviors.

[Quality of life in children with epilepsy: a review]. / La qualité de vie chez l'enfant avec épilepsie: revue de la littérature.

Health-related quality of life (HRQOL) is a multidimensional construct, without general agreement on the number of domains and the content of each domain. In children with epilepsy, the HRQOL evaluation includes both nonspecific aspects, such as behavioral, psychological and cognitive difficulties and the impact of a chronic pediatric illness on the child and its family and specific aspects, such as the perception of the severity of the seizures and of the undesirable effects of the antiepileptic treatments, as well as the social impact of a negative attitude toward epilepsy. The present article presents a review of the methods proposed for the assessment of HRQOL in children with epilepsy. Most methods rely on parental reports; however, there is an increasing effort to develop tools taking the child's point of view into account. HRQOL tools have often been used in clinical trials and, especially, to evaluate the surgical treatments of epilepsy. For the clinician, HRQOL tools may be a preliminary approach to the patient's problems to be interpreted in relation to the patient's medical, psychological, cognitive, social and familial context. In France, few large-scale studies on HRQOL in children with epilepsy have been conducted. We present the preliminary results of a French study based on parental reports.

[The rapid development of child neuropsychology]. / L'essor de la neuropsychologie de l'enfant.

The past few years have seen important progress and new developments in the field of child neuropsychology. Children can exhibit acquired or learning disorders, but in all cases such deficits take place in a developmental trajectory that requires taking into account cerebral maturation and plasticity processes. Child neuropsychology finds its specificity in the perspective of developmental neuropsychology and has close connections with health and education. This article focuses on two pathologies - childhood epilepsies and developmental dyslexia - that highlight the recent progress in this specialty and its perspectives.

[Neuropsychological assessment in epilepsy surgery of children]. / Chirurgie de l'épilepsie: études neuropsychologiques chez l'enfant.

In children with epilepsy, surgical treatment has been recognized as a valuable therapeutic option that can improve the cognitive prognosis and facilitate schooling. Most of the earlier studies focused on general intellectual outcome and behavior. However, substantial progress and new developments in the neuropsychological evaluation of epileptic children treated with surgery have been made over the past few years. Several recent studies explored language, memory, executive functions and behavior in patients undergoing surgery, taking into account cerebral maturation and plasticity processes. Neuropsychological studies have demonstrated greater functional recovery after surgery in children than in adults. Notably, there is evidence of particular reorganization processes for language dominance. Other studies demonstrate that early surgery of temporal lobe epilepsy in children is associated with better memory than in adults. Longitudinal studies are still needed to describe developmental trajectories and optimize neuropsychological rehabilitation.

Do school-age children remember or know the personal past?

The aim of this study was to examine developmental differences in autobiographical memory using a novel test that assesses its semantic and episodic subcomponents. Forty-two children aged 7-13 years were asked to recall semantic information and episodic events from three different time periods (current school year, last school year, and previous school years). For the recalls of all events, sense of remembering or sense of just knowing was measured via the Remember/Know paradigm. Age-related differences were observed for episodic autobiographical memory whereas semantic autobiographical memory was characterized by a relative developmental invariance. The increase with age was also found in the number of "Remember" responses and their justification in terms of the actual contextual information retrieved-factual, spatial, and, more especially, temporal details. These findings highlight developmental differences between the episodic and semantic subcomponents of autobiographical memory and support the view that mental 'time travel' through subjective time, which allows one to re-experience the past through self-awareness, is the last feature of autobiographical memory to become fully operational.

Devastating epileptic encephalopathy in school-aged children (DESC): a pseudo encephalitis.

PURPOSE: To describe the characteristics of a previously overlooked devastating epileptic encephalopathy that presents as intractable bilateral perisylvian epilepsy starting with prolonged status epilepticus (SE) in normally developing school-aged children. METHODS: Retrospective study over 7 years of all normally developing children admitted in our institution for a prolonged SE following non-specific febrile illness with at least one seizure recorded on EEG. RESULTS: Fourteen children were included at a median age of 7.5 years (4-11) (median follow-up of 4 years (1-7)). Intractable SE lasted 4-60 days (median 30). CSF cell count was normal in five cases and moderately increased in the others. During SE, seizures were recorded in 11 patients and involved temporal lobes in 7; the other 4 patients exhibited perisylvian clinical features with secondary generalization. Intractable epilepsy followed SE in all cases without any latent period. Persisting seizures were recorded in 10 patients and involved temporo-perisylvian regions in 8, frontal regions in 2; 3 others had perisylvian ictal semiology. Spiking was bilateral in 10 cases. MRI showed bilateral hippocampal hypersignal and/or atrophy in 10 cases (extended to the neocortex in 3). All children had major cognitive sequelae. When feasible (six patients), detailed neuropsychology suggested fronto-temporal impairment. CONCLUSIONS: Among so called grey matter encephalitis patients, we identified a recognizable pattern we propose to call Devastating Epileptic encephalopathy in School-age Children (DESC) that begins with prolonged SE triggered by fever of unknown cause, and persists as intractable perisylvian epilepsy with severe cognitive deterioration.

Regional cerebral glucose metabolism in epilepsies with continuous spikes and waves during sleep.

BACKGROUND: Epileptic syndromes with continuous spikes and waves during sleep (CSWS) represent a wide spectrum of epileptic conditions associated with cognitive dysfunctions that have the EEG pattern of CSWS as a common feature. Reported are the results of voxel-based analyses of brain glucose metabolism performed in a group of 18 children with CSWS. METHODS: Voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (SPM). First, each patient was compared with a control group and the influence of age, epileptic activity, and corticosteroid treatment on metabolic abnormalities was studied. Also, disease-related changes in the contribution of a brain area to the level of metabolic activity in another brain area were investigated using pathophysiologic interactions in groups of patients compared with the control group. RESULTS: Individual SPM analyses identified three metabolic patterns: association of hypermetabolic and hypometabolic areas, hypometabolic areas only, and normal pattern. Age and intensity of awake interictal spiking did not significantly differ in patients showing focal hypermetabolism compared with the other ones. Treatment with corticosteroids was associated with absence of focal hypermetabolism. In the group of patients with hypermetabolic areas, analyses of pathophysiologic interactions showed disease-related altered functional connectivity between the parietal and frontal cortices. CONCLUSIONS: Cerebral metabolic patterns are heterogeneous among patients with CSWS. This metabolic heterogeneity could be related to the use of corticosteroid treatment before PET. The parietofrontal altered connectivity observed in patients with hypermetabolism is interpreted as a phenomenon of remote inhibition of the frontal lobes induced by highly epileptogenic and hypermetabolic posterior cortex.

Behavioural epileptic seizures: a clinical and intracranial EEG study in 8 children with frontal lobe epilepsy.

We report on eight children who underwent prolonged invasive video-EEG recording (IC-EEG) for intractable frontal lobe epilepsy and whose seizures consisted of behaviour changes. Seizures were recorded on a BMSI computer with 128 channels connected to the Gotman software of a stellate system; their identification was made both clinically and by automatic detection of paroxysmal electrical events. Behavioural epileptic seizures (BES) consisted of various clinical signs comprising mood change, sudden agitation, unexpected quietness, and subtle change of awareness or awakening. In 2 patients, seizures consisted in repetitive movements that we referred to as epileptic stereotypes. BES came from the prefrontal areas of the brain. Most of them were overlooked or misdiagnosed as behavioural manifestations, especially in children with mental deficiency and autistic features. Given the improvement of behaviour and mental functions following surgery, we assume that BES may contribute to generate mental and behavioural dysfunction.

Impact of temporal lobe epilepsy on phonological processing and reading: a case study of identical twins.

In order to evaluate the possible consequences of temporal lobe epilepsy on reading acquisition, we first compared the reading skills and phonological awareness abilities in a set of 13-year-old identical twins, one of whom is affected by temporal lobe epilepsy (LB). We then compared their performances to those of an age- and IQ-matched control group. Both siblings have an intellectual quotient above average as well as normal memory and linguistic abilities. Results showed that the reading age of LB (assessed by the Lefabvrais French reading test) was more than two years behind expectations whereas that of her sister was above average. Further, in contrast to her sister and healthy control subjects, LB exhibited specific deficits in elaborate metaphonological awareness abilities (non-word repetition, rhyme production, phonemic segmentation and syllabic inversion). These could be linked to temporal lobe dysfunction, thus confirming the important role of the temporal lobes in reading acquisition.

[Optic pathway gliomas in neurofibromatosis type I. Longitudinal study of 30 cases in two multidisciplinary practices]. / Les gliomes des voies optiques dans la neurofibromatose de type 1. Etude longitudinale de 30 cas suivis dans deux consultations multidisciplinaires.

UNLABELLED: The aim of this study was to analyse the outcome of optic pathway gliomas in 30 children with neurofibromatosis type 1, the indications of treatment, and the follow-up and screening protocol. PATIENTS AND METHODS: All patients with a minimal two years follow-up (median six years, range two to 19 years), in two multidisciplinary consultations of Saint-Vincent-de-Paul (Paris) and Purpan (Toulouse) hospitals, were included in the study. In our series, we practiced systematic screening MRI in children under six years' of age or with neuropsychological deficiency that may imply an unreliable ophthalmological examination. RESULTS: Thirty-seven percent (11 patients) had progressive ophthalmological signs and were treated, and 63% (19 patients) were not progressive. Our study confirmed that most of optic pathway gliomas were stable during evolution, but rare cases may have bad prognosis. CONCLUSION: Our study supported the importance of close ophthalmological follow-up during childhood for which screening methods are discussed. There is a consensus to limit treatment for patients with progressive ophthalmological symptoms.

Patterns of neuropsychological deficits in children with medulloblastoma according to craniospatial irradiation doses.

This study aimed to analyse the relationship between supratentorial irradiation dose and the intellectual outcome in 36 children (aged between 5 and 15 years) treated for medulloblastoma. The supratentorial radiation dose was reduced to 25 Gy in 23 children and given at the standard dose, 35 Gy, in 13 other children. Neuropsychological evaluation was performed at a mean of 4.3 years (SD 4.7 years) after radiotherapy. The supratentorial radiation dose was the principal risk factor associated with impaired intellectual outcome. Verbal fluency, immediate word list recall, block design, and fine motricity of the dominant hand were significantly lower in children irradiated at the standard doses than in those irradiated at reduced doses. These findings suggest that the dose of radiotherapy applied to the brain strongly influences later verbal and non-verbal skills in children with medulloblastoma. This should be taken into account in treatment planning and in rehabilitation programs.

Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy.

BACKGROUND: The childhood-onset cerebral form of X-linked adrenoleukodystrophy, a demyelinating disorder of the central nervous system, leads to a vegetative state and death within 3-5 years once clinical symptoms are detectable. The hypothesis to be tested was whether bone-marrow transplantation can over an extended period of time halt the inexorable progressive demyelination and neurological deterioration. METHODS: 12 patients with childhood onset of cerebral X-linked adrenoleukodystrophy have been followed for 5-10 years after bone-marrow transplantation. Magnetic resonance imaging (MRI), neurological, neuropsychological, electrophysiological, and plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of this treatment. FINDINGS: MRI showed complete reversal of abnormalities in two patients and improvement in one. One patient showed no change from baseline to last follow-up. All eight patients who showed an initial period of continued demyelination stabilised and remained unchanged thereafter. Motor function remained normal or improved after bone-marrow transplantation in ten patients. Verbal intelligence remained within the normal range for 11 patients. Performance (non-verbal) abilities were improved or were stable in seven patients. Decline in performance abilities followed by stability occurred in five patients. Plasma VLCFA concentrations decreased by 55% and remained slightly above the upper limits of normal. INTERPRETATION: 5-10-year follow-up of 12 patients with childhood-onset cerebral X-linked adrenoleukodystrophy shows the long-term beneficial effect of bone marrow transplantation when the procedure is done at an early stage of the disease.

Neuropsychology of childhood epilepsy: pre- and postsurgical assessment.

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 syndromes, cognitive assessment and school placement: a study of 251 children.

Two-hundred and fifty-one children (98 girls and 153 boys, aged from 3 to 17 years) with documented diagnosis of epileptic syndrome, IQ measurement, and information on school placement were included in this retrospective study. The relations between these three parameters as well as effects of age at onset and duration of epilepsy, seizure frequency, and number of antiepileptic drugs (AEDs) were analysed. Both IQ and schooling were univariately related to epileptic syndrome, age at onset and duration of epilepsy, and number of AEDs; seizure frequency was related to IQ but not to school placement. Multiple regression showed that IQ was independently related to epileptic syndrome and AED; multiple logistic regression showed that type of school (mainstream versus adapted or special) was independently related to IQ and AED. Children with idiopathic generalised or with localisation-related epilepsy had higher IQ scores and higher probability of mainstream schooling than those with symptomatic or cryptogenic generalised epilepsies or epileptic syndromes which were undetermined. Subtests profile of intelligence scale in localisation-related epilepsies showed different specific cognitive deficits, according to the location of the epileptic focus.

Mental and behavioural outcome of infantile epilepsy treated by vigabatrin in tuberous sclerosis patients.

Vigabatrin (VGB) has demonstrated high efficacy in infantile spasms (IS) due to tuberous sclerosis. Our first objective was to evaluate the cognitive long term effect outcome of children whose refractory spasms definitely disappeared when VGB was given as an add on drug. Our second objective was to determine the response of generalized epilepsy (infantile spasms) compared to partial epilepsy on cognitive impairment. A non selected series of 13 children underwent psychometric and behavioural evaluation before VGB initiation at a mean of 3 years on VGB treatment. Eight of them could perform detailed neuropsychological tests at follow-up. Seven had infantile spasms (Group I), they all were spasm free before 2 years of age and five remained with rare partial seizures (mean age, 5.5 years). Six others had partial epilepsy without spasms (Group II) and five remained with rare seizures (mean age, 7.5 years). Patients of Group I experienced dramatic changes. Developmental quotient (DQ) significantly rose in six out of seven by ten to more than 45 points (P = 0.03) and autistic behaviour disappeared in five out of the six who presented with. The four tested children had normal verbal level after 5 years and could integrate at school but they remained with marked visuospatial disabilities. By contrast, patients of Group II remained with an unchanged DQ of about 60 so that both groups had similar DQ levels on follow-up. The cessation of spasms with VGB is therefore associated with significant improvement of cognition and behaviour in children with tuberous sclerosis. Controlling secondary generalization induced by infantile spasms seems to be a key factor for mental development.