The consequences of uncontrolled epilepsy

The consequences of epilepsy can be quite severe and include shortened lifespan, excessive bodily injury, neuropsychological and psychiatric impairment, and social disability. There is evidence that seizures cause brain injury, including neuronal death and physiological dysfunction. Mortality rates are 4-7 times higher in people with medically refractory seizures, and injury rates are substantial, ranging from one per 20 person-years to as much as one per 3 person-years. Quality of life is impaired in epilepsy, and relates to seizure control. Psychosocial disabilities, including lower social interaction with reduced marriage rates and reduced employment levels, are more common in people with refractory seizures. Complete seizure control is desirable, since seizures potentially constitute a serious threat to health and well-being. Therefore, satisfactory seizure control should be defined as having no seizures. Treatment should be directed to preventing seizures whenever possible and achieving control early in the course of illness. The risks of uncontrolled seizures outweigh the risks of aggressive medical or surgical therapy.     

Effects of early seizures on later behavior and epileptogenicity

Both clinical and laboratory studies demonstrate that seizures early in life can result in permanent behavioral abnormalities and enhance epileptogenicity. Understanding the critical periods of vulnerability of the developing nervous system to seizure-induced changes may provide insights into parallel or divergent processes in the development of autism. In experimental rodent models, the consequences of seizures are dependent on age, etiology, seizure duration, and frequency. Recurring seizures in immature rats result in long-term adverse effects on learning and memory. These behavioral changes are paralleled by changes in brain connectivity, changes in excitatory neurotransmitter receptor distribution, and decreased neurogenesis. These changes occur in the absence of cell loss. Although impaired cognitive function and brain changes have been well-documented following early-onset seizures, the mechanisms of seizure-induced dysfunction remain unclear.     

The role of neuropsychology in the assessment and treatment of persons with epilepsy.

Several areas of current interest in the neuropsychology of epilepsy are briefly reviewed in this article. These include variables pertaining to seizures, seizure history, antiepileptic drugs, and methods of neuropsychological evaluation. It is apparent that epilepsy is a multifaceted area: Psychologists not only can be of great assistance to patients with this condition, but may also learn a great deal from this complex disorder.     

Frontal lobe epilepsy presenting as a psychotic disorder with delusions and hallucinations: a case study

Although psychotic symptoms are a recognized manifestation of epilepsy, these are more often associated with seizures of the temporal lobe type. While 10% of children with temporal lobe epilepsy develop a psychotic disorder by adulthood, the literature does not report any cases of psychotic disorders associated with frontal lobe seizures in children. This article presents a unique case of a girl whose frontal lobe seizures were associated with delusional psychotic symptoms. Once her seizure disorder was identified through electroencephalography (EEG) and appropriate anticonvulsant therapy was initiated, her associated psychotic symptoms resolved.     

Cellular abnormalities and synaptic plasticity in seizure disorders of the immature nervous system

The nervous system has an enhanced capacity to generate seizures during a restricted phase of postnatal development. Studies in animals and particularly in in vitro brain slices from hippocampus and neocortex have been instrumental in furthering an understanding of the underlying processes. Developmental alterations in glutaminergic excitatory synaptic transmission appear to play a key role in the enhanced seizure susceptible of rodents during the second and third week of life. Prior to this period, the number of excitatory synapses is relatively low. The scarcity of connections and the inability of the existing synapses to release glutamate when activated at high frequencies likely contribute importantly to the resistance of neonates to seizures. However, at the beginning of week 2, a dramatic outgrowth of excitatory synapses occurs, and these synapses are able to faithfully follow activation at high frequencies. These changes, coupled with the prolonged nature of synaptic potentials in early life, likely contribute to the ease of seizure generation. After this time, seizure susceptibility declines, patterns of local synaptic connectivity remodel, and some synapses are pruned. Concurrently, the duration of excitatory postsynaptic potentials shortens due at least in part to a switch in the subunit composition of postsynaptic receptors. Other studies have examined the mechanisms underlying chronic epilepsy initiated in early life. Models of both cortical dysplasia and recurrent early-life seizures suggest that alterations in the normal development of excitatory synaptic transmission can contribute importantly to chronic epileptic conditions. In the recurrent early-life seizure model, abnormal use-dependent selection of subpopulations of excitatory synapses may play a role. In experimental cortical dysplasia, alterations in the molecular composition of postsynaptic receptor are observed that favor subunit combinations characteristic of infancy.     

Behandlung von Epilepsie bei Menschen mit Intelligenzminderung

People with intellectual disability frequently suffer from epilepsy. Management of epilepsy in this population is particularly challenging because of the different ways of communicating, cognitive impairment, changes in behavior which can be disruptive, the severity of the epilepsy syndrome, the seizure types, and the seizure frequency. Treatment of epilepsy is complicated due to the interaction of the intellectual disability and the behavior as well as behavioral changes caused by the antiepileptic drugs or the change of seizure types or frequency. This article provides the reader with a guidance for managing epilepsy in this particular population and raises important open questions.     

Structural and functional imaging in children with partial epilepsy

Imaging plays an increasingly important role in the evaluation of children with complex partial seizures. Most partial epilepsy, especially of temporal lobe origin, begins during childhood. Structural imaging with high-resolution MRI can help identify the etiology of partial seizure disorders in many children. MRI studies also show the more widespread effect of seizures on brain structure. Progressive volume loss of the hippocampal formation in some patients with temporal lobe epilepsy provides evidence that continued seizures may be associated with progressive neuronal injury. FDG-PET studies show regional decreases in glucose consumption in the cortical zone from which seizures arise. Functional abnormalities often are more extensive than the seizure focus. Studies in children with recent-onset epilepsy show that metabolic abnormalities are considerably less common than in adults with partial epilepsy, supporting the notion that in some patients there may be progressive metabolic changes that occur with continued seizures. Functional MRI may be used to identify language areas in children with partial epilepsy. fMRI language tasks reliably identify the dominant hemisphere for language dominance when compared to the intracarotid amytal procedure. Tests of verbal fluency and semantic decision identify frontal lobe language areas, while reading text paradigms and auditory passage paradigms are better for identifying temporal language areas. A panel of paradigms is best used to identify language areas in children being considered for epilepsy surgery. fMRI is a valuable tool for elucidating the impact of chronic neurologic disease states on the functional organization of language networks during development.     

Age-dependent consequences of seizures: relationship to seizure frequency, brain damage, and circuitry reorganization

Seizures in the developing brain pose a challenge to the clinician. In addition to the acute effects of the seizure, there are questions regarding the impact of severe or recurrent seizures on the developing brain. Whether provoked seizures cause brain damage, synaptic reorganization, or epilepsy is of paramount importance to patients and physicians. Such questions are especially relevant in the decision to treat or not treat febrile seizures, a common occurrence in childhood. These clinical questions have been addressed using clinical and animal research. The largest prospective studies do not find a causal connection between febrile seizures and later temporal lobe epilepsy. The immature brain seems relatively resistant to the seizure-induced neuronal loss and new synapse formation seen in the mature brain. Laboratory investigations using a developmental rat model corresponding to human febrile seizures find that even though structural changes do not result from hyperthermic seizures, synaptic function may be chronically altered. The increased understanding of the cellular and synaptic mechanisms of seizure-induced damage may benefit patients and clinicians in the form of improved therapies to attenuate damage and changes induced by seizures and to prevent the development of epilepsy.     

Classroom performance and adaptive skills in children with epilepsy

The relationships of age at onset, seizure syndrome, seizure type, and seizure frequency, respectively, to the classroom performance and adaptive skills of 131 children with epilepsy were studied. The Teacher Report Form of the Child Behavior Checklist was completed by the children's teachers. Hierarchical multiple regression analyses were conducted on ratings of academic subject areas and overall adaptive skills. Significant results were obtained for English/Language, Reading, Mathematics, overall School Performance, Learning, Happy, and Total Adaptive skills. Epilepsy syndrome and frequency of seizures were significantly related to some of these analyses, with amounts of variance accounted for ranging from 11% to 23%. Children with secondary generalized epilepsy performed significantly worse than children with other epilepsy syndromes. The results suggest that a seizure disorder associated with a diffuse or multifocal brain insult can produce problems in achievement and school adaptation as manifested on a day-to-day basis. Suggestions for future research are presented.     

Assessment of executive functioning in childhood epilepsy: the Tower of London and BRIEF

Children and adolescents with epilepsy are known to demonstrate executive function dysfunction, including working memory deficits and planning deficits. Accordingly, assessing specific executive function skills is important when evaluating these individuals. The present investigation examined the utility of two measures of executive functions-the Tower of London and the Behavioral Rating Inventory of Executive Functioning (BRIEF)-in a pediatric epilepsy sample. Ninety clinically referred children and adolescents with seizures were included. Both the Tower of London and BRIEF identified executive dysfunction in these individuals, but only the Tower of London variables showed significant relations with epilepsy severity variables such as age of epilepsy onset, seizure frequency, number of antiepileptic medications, etc. Further, the Tower of London and BRIEF variables were uncorrelated. Results indicate that objective measures of executive function deficits are more closely related to epilepsy severity but may not predict observable deficits, as reported by parents. Comprehensive evaluation of such deficits, therefore, should include both objective measures as well as subjective ratings from caregivers.     

Assessment of executive functioning in childhood epilepsy: The Tower of London and BRIEF

Children and adolescents with epilepsy are known to demonstrate executive function dysfunction, including working memory deficits and planning deficits. Accordingly, assessing specific executive function skills is important when evaluating these individuals. The present investigation examined the utility of two measures of executive functions—the Tower of London and the Behavioral Rating Inventory of Executive Functioning (BRIEF)—in a pediatric epilepsy sample. Ninety clinically referred children and adolescents with seizures were included. Both the Tower of London and BRIEF identified executive dysfunction in these individuals, but only the Tower of London variables showed significant relations with epilepsy severity variables such as age of epilepsy onset, seizure frequency, number of antiepileptic medications, etc. Further, the Tower of London and BRIEF variables were uncorrelated. Results indicate that objective measures of executive function deficits are more closely related to epilepsy severity but may not predict observable deficits, as reported by parents. Comprehensive evaluation of such deficits, therefore, should include both objective measures as well as subjective ratings from caregivers.     

Differential effect of lesion side on intra-individual variability in children with focal lateralized epilepsy

A differential impact of hemispheric side (left vs right) on cognitive measures, specifically Verbal and Performance IQ, has been described previously for both focal onset seizures and lateralized brain lesions. This study revealed a differential effect on intra-individual variability, measured as subtest scaled-score range, on the Dutch WISC-R and WISC-III, in children with epilepsy. The presence of documented brain lesion was associated with elevated variability on the Verbal Scale for the left hemisphere seizure group and with decreased variability on the Verbal and Full Scales for the right hemisphere seizure group.     

Neuropsychological Features of Lesion-related Epilepsy in Adults: An Overview

Lesional epilepsy is thought to be a direct consequence of focal brain lesions of dysgenetic, neoplastic, vascular, or traumatic origin. It has been estimated that at least half of all epilepsies are the result of such lesions. The current discussion includes an overview of the cognitive and behavioral presentations in adults with epilepsy secondary to focal pathology. The neuropsychological presentation in this population is influenced by many factors, including the location and nature of the underlying lesion, seizure characteristics, the effects of treatment, and patient variables. Few studies attempt to disentangle the specific contributions of these variables to cognitive performance. However, where available studies examining the separable effects of seizure-related variables on cognitive functioning in individuals with lesional epilepsy are also reviewed. This overview includes a discussion of focal malformations of cortical and vascular development and select foreign tissue and acquired lesions.     

Neuropsychological profile of children with cryptogenic localization related epilepsy.

Up to one third of the epilepsy population consists of children with cryptogenic localization related epilepsy (CLRE). Unfortunately, the effect of CLRE on the development is still unclear. Behavioral and academic problems have been reported, but no conclusive study concerning the impact of CLRE on neuropsychological functioning is yet published. This study was a systematic cross-sectional open clinical and nonrandomized investigation, which included 68 children with CLRE. Several neuropsychological tests were analyzed and age-related normative values were used as reference. Differences between CLRE and reference values were tested with Paired-Samples t-tests. Z scores were computed to compare the different neuropsychological tests and to inspect whether a characteristic neuropsychological profile exists for CLRE. The Independent-Samples t-test was used to explore which epilepsy factors (seizure type, seizure frequency, age at onset, duration of epilepsy, and drug load) were influencing the cognitive profile of CLRE. There seems to be a characteristic cognitive profile for children with CLRE; children with CLRE experience cognitive difficulties on a wide range of areas-in particular, alertness, mental speed, and memory. Seizure type, seizure frequency, duration of epilepsy, and drug load do not influence this neuropsychological profile. Age at onset was an important risk factor; the earlier the age at onset, the worse the cognitive performance. In spite of the influence of age at onset, the revealed profile can be seen as a stable, independent of temporary factors, neuropsychological profile for children with CLRE.     

Contents

Up to one third of the epilepsy population consists of children with cryptogenic localization related epilepsy (CLRE). Unfortunately, the effect of CLRE on the development is still unclear. Behavioral and academic problems have been reported, but no conclusive study concerning the impact of CLRE on neuropsychological functioning is yet published.

This study was a systematic cross-sectional open clinical and nonrandomized investigation, which included 68 children with CLRE. Several neuropsychological tests were analyzed and age-related normative values were used as reference. Differences between CLRE and reference values were tested with Paired-Samples t-tests. Z scores were computed to compare the different neuropsychological tests and to inspect whether a characteristic neuropsychological profile exists for CLRE. The Independent-Samples t-test was used to explore which epilepsy factors (seizure type, seizure frequency, age at onset, duration of epilepsy, and drug load) were influencing the cognitive profile of CLRE.

There seems to be a characteristic cognitive profile for children with CLRE; children with CLRE experience cognitive difficulties on a wide range of areas—in particular, alertness, mental speed, and memory. Seizure type, seizure frequency, duration of epilepsy, and drug load do not influence this neuropsychological profile. Age at onset was an important risk factor; the earlier the age at onset, the worse the cognitive performance. In spite of the influence of age at onset, the revealed profile can be seen as a stable, independent of temporary factors, neuropsychological profile for children with CLRE.     

Sleep and arousal mechanisms in experimental epilepsy: epileptic components of NREM and antiepileptic components of REM sleep

Neural generators related to different sleep components have different effects on seizure discharge. These sleep-related systems can provoke seizure discharge propagation during nonrapid eye movement (NREM) sleep and can suppress propagation during REM sleep. Experimental manipulations of discrete physiological components were conducted in feline epilepsy models, mostly in the systemic penicillin epilepsy model of primary generalized epilepsy and the amygdala kindling model of the localization-related seizure disorder, temporal lobe epilepsy. The sleep-wake state distribution of seizures was quantified before and after discrete lesions, systemic and localized drug administration, and/or photic stimulation, as well as in relation to microdialysis of norepinephrine. We found that (1) neural generators of synchronous EEG oscillations--including tonic background slow waves and phasic "arousal" events (sleep EEG transients such as sleep spindles and k-complexes)--combine to promote electrographic seizure propagation during NREM and drowsiness, and antigravity muscle tone permits seizure-related movement; (2) neural generators of asynchronous neuronal discharge patterns reduce electrographic seizures during alert waking and REM sleep, and skeletal motor paralysis blocks seizure-related movement during REM; (3) there are a number of similarities between amygdala-kindled kittens and children with Landau-Kleffner Syndrome (LKS) that suggest a link among seizures, sleep disorders, and behavioral abnormalities/regression.     

Cognitive estimations as a measure of executive dysfunction in childhood epilepsy

Children and adolescents with epilepsy are known to demonstrate executive function deficits. Despite prior work that has shown that cognitive estimation tasks are sensitive to executive dysfunction in children, such tasks have not been studied in children with epilepsy. This is particularly important given the fact that executive tasks have heretofore shown poor ecological validity, and it has been speculated that estimation tasks may show stronger ecological validity than other executive tests. One hundred and thirteen clinically referred children and adolescents with epilepsy were included. The Biber Cognitive Estimations Test was sensitive to cognitive dysfunction, with about half showing impairments on this task in comparison to age-matched normative data; the most frequently impaired subscales were quantity estimation and time estimation. Moreover, the Biber Cognitive Estimation Test showed moderate correlations with not only overall intellectual functions and academic achievement but also other commonly administered tests of executive functions, including digit span, Trailmaking, and the Tower of London but not with the contingency naming test. Cognitive estimations were also modestly correlated with age of epilepsy onset but not other epilepsy-severity variables such as number of antiepilepsy drugs (AEDs) or seizure frequency. Unfortunately, the hypothesis that the Biber Cognitive Estimation Test would show strong ecological validity was not supported, as it showed weak relations with parent-reported executive function deficits. The significance and limitations of this investigation are discussed.     

Speech abnormalities in seizures: a comparison of absence and partial complex seizures

In order to determine whether speech changes are useful in differentiating seizure types, a study was done in which speech abnormalities during two distinct seizure types, partial complex and absence seizures, were compared. Speech changes noted during prolonged electroencephalographic and video monitoring were compared in 16 patients with 47 partial complex seizures and 19 patients with 95 absence seizures. Speech changes were common during both seizure types. Although some significant differences in speech patterns were noted in the two seizure types, the degree of overlap was such to preclude using speech changes alone as the sole clinical criteria in differentiating the seizures.