Effects of a Broad-Spectrum Behavior Modification Treatment Program on Children with Refractory Epileptic Seizures

A group of 18 children with refractory epileptic seizures was divided into three groups--behavior modification treatment, attention control, and control groups--with the purpose of investigating the effects of a learning-based broad-spectrum treatment program superimposed on a regular medical treatment program. The design consisted of a 10-week baseline, 6-week intervention, and 10-week and 1-year follow-ups. A combination of number of seizures and seizure duration--termed "seizure index"--was used as a dependent measure. There was a significant reduction in seizure index only for those children receiving the behavior modification treatment, at both follow-ups. The results indicate that this behavioral treatment program may be of substantial help to children with epilepsy who are resistant to conventional drug therapy.     

Effects of a Contingent Relaxation Treatment Program on Adults with Refractory Epileptic Seizures

A group of eighteen adults with refractory epileptic seizures were given psychological treatment in a two-phase experimental group study. In phase one, the experimental phase, the patients were divided into three groups--contingent relaxation (CR), attention control (ATC) treatment, and a no-treatment (NT) control group--with the purpose of investigating the effects of a learning-based contingent relaxation program compared with the effects of professional attention alone when superimposed on a regular medical treatment program. The design of the experimental phase was comprised of a 10-week baseline, 6-week intervention, and 10-week follow-up. Results of this phase at the end of follow-up showed a significant reduction only for those patients receiving the CR treatment. In the nonexperimental phase, the two control groups also received the CR treatment for a 6-week period, and subsequent seizure frequency measures for all three groups were analyzed after 10-week and 30-week follow-up periods. Results of this phase showed a significant reduction in seizure frequency for all three groups after receiving the CR treatment. Effects of the CR treatment were maintained at a 30-week follow-up. The results indicate that the CR treatment program may be of substantial help to adults whose seizures are resistant to conventional drug therapy.     

Effects of a Behavioral Intervention on Epileptic Seizure Behavior and Paroxysmal Activity: A Systematic Replication of Three Cases of Children with Intractable Epilepsy

Three children with very frequent refractory epileptic seizures underwent a behavioral intervention consisting of symptom discrimination, countermeasures, contingent relaxation, and positive reinforcement for correct responses in a systematic replication series. The studies involved a 6-h nonintervention base rate, a 6-h treatment phase, and a 6-h nonintervention follow-up under laboratory conditions for each child. Neurophysiologic and behavioral measures of the effects of treatment were made using electroencephalogram (EEG)-video equipment. Effects of treatment were assessed by using a random sample of EEG-video sequences in base rate and follow-up. Results showed that no significant reduction of either seizure behavior or paroxysmal EEG activity was found subsequent to training in discrimination of early paroxysmal activity and/or sensations preceding seizures. Both seizure behavior and paroxysmal activity were significantly reduced in all three cases following intervention with an adapted countermeasure technique. No additional effects could be noted subsequent to the application of either contingent relaxation or positive reinforcement for correct responses. Paroxysmal EEG changes and seizure behavior were highly correlated. Reduction of the clinical manifestation or seizure response by behavioral manipulation was accompanied by a reduction of the total amount of paroxysmal activity as measured by the EEG.     

Follow-Up of 146 Children with Epilepsy after Withdrawal of Antiepileptic Therapy

The relapse rate after discontinuation of antiepileptic drug treatment was investigated in 146 children with epilepsy, in whom medication was withdrawn according to a predesigned protocol, after a seizure-free period of at least 2 years and normalization of the EEG. The cumulative probability of remaining seizure-free in this series was 74.5%. Three-quarters of the relapses occurred during the withdrawal period and in the 2 years thereafter. From multivariate analysis, the factors indicating a significantly higher relapse risk were seizures with a known cause and female sex. In primary generalized epilepsy, no factor significantly increased the likelihood of a recurrence. In partial epilepsy, significant factors predictive of recurrence were the presence of a neurological deficit (focal neurological signs and/or mental retardation), female sex, a positive family history for epilepsy, and the number of drugs necessary for control of the seizures. The present results are compared with the available literature data. It is argued that using multivariate analysis after elimination of EEG variables uncovers significant clinical predictive factors that in other studies may have remained hidden. Finally, it is argued that statistical analysis may be used to enable the clinician to predict the likelihood of recurrence in individual children with a given set of relevant predictive factors.     

Efficacy and Tolerability of Vigabatrin in Children with Refractory Partial Seizures: A Single-Blind Dose-Increasing Study

Summary: The efficacy and tolerability of vigabatrin (VGB) in children with refractory partial epilepsy were assessed in a single-blind, add-on, fixed-sequence, placebo-controlled trial. After 1-month observation, the patients entered a 7-month treatment period that involved administration of placebo for 1 month followed by VGB at the initial dosage of 40 mg/kg/day, to be increased to 60 and 80 mg/kg/day at 2-month intervals if seizures persisted. Of the 46 children enrolled in the study, 7 dropped out prematurely due to lack of efficacy of the drug (n = 6) or increased seizure frequency (n = 1). In 11 patients who either became seizure-free (n = 3) or improved markedly (n = 8), treatment was completed at a dose <80 mg/kg/day. The average number of seizures per month in the 39 patients who completed the study decreased from 97 during placebo to 21,12, and 9 after 2, 4, and 6 months of VGB treatments respectively (p < 0.0001 at each time). Response to VGB remained statistically significant when dropouts were included in the evaluation. The number of patients who had <50% reduction in seizure frequency after 2, 4, and 6 months was 28, 33, and 35, respectively. Eight patients became seizure-free during the last 2 months of VGB treatment (3 at 40, 3 at 60, and 2 at 80 mg/kg/day, as compared with none during placebo treatment). Serum levels of associated antiepileptic drugs (AEDs) showed no signscant changes, except for serum phenytoin (PHT) concentration, which significantly (p < 0.01) decreased after VGB treatment. Increased appetite and sedation were observed in 17 and 11% of cases, respectively. VGB is effective in the management of refractory partial epilepsy in children, and in some patients a positive dose-response relationship appears to occur over the assessed dosing range.     

Hypnic Tonic Postural Seizures in Healthy Children Provide Evidence for a Partial Epileptic Syndrome of Frontal Lobe Origin

Summary: In the pediatric age period, three idiopathic partial epileptic syndromes are recognized: benign childhood epilepsy with centrotemporal spikes, childhood epilepsy with occipital paroxysms, and primary reading epilepsy. All other partial epilepsies are considered cryptogenic, and no other idiopathic partial epilepsies have been recognized. We observed 10 children with tonic partial postural seizures, mainly hypnic, coinciding with a recognizable ictal epileptiform EEG pattern. The children all had normal neuropsychological development before and after seizure onset. The seizures were tractable in all. Onset was in the early pediatric age period; no other type of seizure was recognized. The occurrence of a family history of epilepsy was high. The seizure pattern was typical of supplementary motor area origin. Because of the normal neuropsychological status, high familial incidence of epilepsy, and benign course of this partial epilepsy, we believe it should be considered idiopathic, using the criteria of the International Classification of Epilepsies and Epileptic Syndromes. We therefore suggest the existence of a partial idiopathic epileptic syndrome having onset with seizures of frontal lobe origin.     

Remission of Seizures in a Population-Based Adult Cohort with a Newly Diagnosed Unprovoked Epileptic Seizure

PURPOSE: To investigate the probability of achieving remission of seizures after a newly diagnosed unprovoked epileptic seizure in an adult population-based cohort. METHODS: 107 patients aged 17 years or older with a newly diagnosed unprovoked epileptic seizure (index seizure) in 1985 through 1987 were followed up until the date of death or to the end of 1996. The proportion of cases during follow-up that attained a 1-year, 3-year, 5-year remission was calculated by actuarial analyses. Variables for stratification were age at diagnosis, seizure type, etiology, EEG, and the occurrence of seizures within 1 year of initiation of antiepileptic drug (AED) therapy. RESULTS: Cumulative 1-, 3- and 5-year remission rates were 68, 64, and 58%. There was no statistically significant difference regarding time points of achieving a 1-year remission after epilepsy diagnosis and the subsequent probability during follow-up of attaining a 5-year remission. Having seizures within 1 year after beginning with an AED was a statistically significant predictor of never achieving 1-year remission of seizures during follow-up (refractory seizures). Other stratified variables were not statistically significant predictors. CONCLUSIONS: Seizure prognosis for the majority of patients with newly diagnosed epilepsy is good. The time required after epilepsy diagnosis to achieve a 1-year remission of seizures does not affect the probability of additionally achieving a 5-year remission. Patients with refractory seizures can be identified within a few years from diagnosis of epilepsy. These patients must be targeted early for optimization of pharmacologic treatment, possible surgery, and psychosocial intervention.     

Early Discontinuation of Treatment in Children with Uncomplicated Epilepsy: A Prospective Study with a Model for Prediction of Outcome

Summary: Purpose: The main purpose of the present study was to identify predictor variables with significant influence on seizure outcome after discontinuation of treatment in children with uncomplicated epilepsy and to analyze whether these variables, included in a prognostic model could identify children in whom 1-year treatment would be sufficient.
Methods: Before initiation of treatment in children aged 2–16 years with uncomplicated epilepsy, the duration of treatment was randomized to 1 year (group I) or 3 years (group II). At the end of the allotted period, treatment was discontinued in 161 children who had been seizure free during the previous 6 months. The mean follow-up period after treatment was 5.8 years. Twenty-three predictor variables were analyzed by survival methods regarding their influences on the outcome.
Results: At the latest follow-up check, 60 children (37%) had relapsed. The following predictor variables were selected by multiple regression analysis and constituted a model with a simple scoring system: age at seizure onset; seizure type; generalized, irregular spike-wave activity on EEG after 1 year of treatment; and persistent 3-Hz spike-wave activity after 6 months of treatment in children with absence epilepsy. In group I, the remission rate was 73% in children with high prognostic scores, 10% in children with low scores, and 40% in those with intermediate scores (log-rank test, p = 0.0001).
Conclusions: After 1 year of treatment, our prognostic model identified children in whom treatment could be withdrawn at that time. Our model should be easily applicable in clinical practices and may be of clinical importance in determining the duration of treatment in children with uncomplicated epilepsy.     

Cognitive and Behavioral Outcomes of Epileptic Syndromes: Implications for Education and Clinical Practice

Summary:  The educational and social progress of a child with epilepsy depends not only on seizure control but also on cognitive and behavioral factors. The various epilepsy syndromes of childhood and adolescence differ greatly in terms of cognitive and behavioral outcome. A high proportion of babies who have West syndrome and children who have Dravet syndrome (severe myoclonic epilepsy in infancy) will have long-term cognitive and behavioral problems. The Lennox-Gastaut syndrome also often has a poor prognosis in this regard. Children with the Landau-Kleffner syndrome have a variable prognosis, some regain speech and others have permanent speech impairment. Benign childhood epilepsy with centrotemporal spikes is now recognised as lying on a spectrum with the Landau-Kleffner syndrome: mild cases have few if any cognitive or behavioral problems but others may have quite severe difficulties. People with juvenile myoclonic epilepsy may have characteristics suggesting frontal lobe impairment. The educational and social impairments associated with the epilepsy syndromes of childhood and adolescence are of major importance but they have been the subject of remarkably few well-performed studies. The impairments are not always necessarily permanent and it seems highly likely that the cognitive and behavioural outcome of at least some of these syndromes can be influenced greatly by early effective treatment with either antiepileptic medication or surgery.     

Differences Between Patients with Temporal Lobe Seizures and Those with Other Forms of Epileptic Attacks

Seventy-eight patients with temporal lobe type seizures were precisely matched for age, sex, and Wechsler I.Q. levels with patients suffering from other seizure types. Statistically significant differences were established between the groups in regard to treatment response, etiologies, and behavioral variables. Further analysis of the data showed that the behavioral problems of the temporal lobe patients were present only in that group that suffered from more than one seizure type. The temporal lobe epilepsy group having only one seizure type differed from the controls with one seizure type in regard to etiological factors; they actually showed better performance on certain subscales of the WAIS, as well as better employment records. The clinical impression of the temporal lobe epilepsy patient usually presenting more difficulties than other patients with epilepsy results from the fact that the temporal lobe patients have, in the overwhelming majority of instances, more than one seizure type.     

Effects of Sleep and Sleep Stage on Epileptic and Nonepileptic Seizures

Summary: Purpose: Previous studies of patients with epilepsy and animal models of epilepsy suggest that sleep increases the frequency, duration, and secondary generalization of seizures. This information is, however, incomplete.
Methods: We retrospectively examined video-EEG monitoring reports from our comprehensive epilepsy center. We recorded seizure type, site of onset (for partial seizures), sleep state at onset, and whether partial seizures secondarily generalized. Seizures arising from sleep were then reviewed to determine sleep state.
Results: We analyzed 1,116 seizures in 188 patients. Thirty-five percent of complex partial seizures (CPSs) starting during sleep underwent secondary generalization compared with 18% in wakefulness (p < 0.0001). Frontal lobe CPSs secondarily generalized at equal rates during sleep (22%) and wakefulness (20%), but temporal lobe CPSs generalized much more frequently during sleep (45%) than in wakefulness (19%; p < 0,0001). Frontal lobe seizures were more likely to occur during sleep (37%) than were temporal lobe seizures (26%; p = 0.0068). CPSs were more frequent in stages 1 and 2 and occurred rarely during REM. Seizures starting during slow-wave sleep were significantly longer than seizures starting during wakefulness or stage 2 sleep. Psychogenic nonepileptic seizures (PNESs) were rare between midnight and 6 a.m. and never occurred during sleep.
Conclusions: Sleep has a pronounced effect on secondary generalization of partial seizures, especially those of temporal lobe origin. Frontal lobe seizures occur more often during sleep than do temporal lobe seizures, and occurrence during sleep helps to distinguish PNESs from CPSs.     

Experience with the International League Against Epilepsy Classifications of Epileptic Seizures (1981) and Epilepsies and Epileptic Syndrome (1989) in Epileptic Children in a Developing Country

Four hundred eighty-three epileptic children attending the Pediatric Epilepsy Clinic at Bai Jerbai Wadia Hospital for Children, Bombay, India were classified according to the International League Against Epilepsy (ILAE) classification of epileptic seizures (1981) and epilepsies and epileptic syndromes (1989). The predominant seizures were partial (53.6), generalized (40.3%), and unclassifiable (6%). In epilepsies and epileptic syndromes, 55.3% were partial, 27% were generalized, 13.5% were undetermined, and 4.1% were special syndromes. Although our results were similar in many respects to those of other reported series, some differences were observed in the incidence of partial and generalized seizures, and partial and generalized epileptic syndromes and their subgroups, such as idiopathic, symptomatic, and cryptogenic partial syndromes, idiopathic generalized syndromes, and symptomatic specific syndromes. These differences are probably due to different age limits, methods of case ascertainment and inclusion criteria, different genetic and environmental factors, variable interpretation of clinical and EEG features, and lack of facilities for investigation in developing countries. Despite various limitations, we were able to classify most cases; the ILAE classification can be used in developing countries so that comparison can be made with other studies.     

Familial Occurrence of Epilepsy in Children with Newly Diagnosed Multiple Seizures: Dutch Study of Epilepsy in Childhood

Summary: Purpose: To study the familial occurrence of epilepsy in children with newly diagnosed multiple unprovoked seizures. Methods: Between August 1988 and September 1992, 462 children with two or more unprovoked seizures were included in the prospective Dutch Study of Epilepsy in Childhood. Seizures and epilepsy syndromes of probands were classified according to the International Classifications. Probands with at least 1 first-degree relative with epilepsy were selected. Seizures and syndromes of their relatives were classified using medical files and telephone interviews. Results: In 42% of the probands, the epilepsy was classified as localization-related, in 57% as generalized, and in 1% as undetermined whether focal or generalized. The 47 (10.2%) children with at least 1 first-degree relative with epilepsy less frequently had localization-related epilepsy (23%) and more often had generalized epilepsy (77%) as compared with the total group of probands. Fifty-eight first-degree and 21 other relatives had epilepsy. Thirty-three of the 40 (83%) first-degree relatives with idiopathic or cryptogenic epilepsy had the same seizure type as the proband, but detailed information about their seizures was sometimes difficult to obtain. Of the 12 first-degree relatives with epilepsy syndromes classifiable according to the International League Against Epilepsy (ILAE) 7 (58%) had the same syndrome as the proband. Conclusions: In 10% of children with newly diagnosed epilepsy, the condition is familial. Relatively more often, these children have generalized epilepsy syndromes as compared with children with a negative family history. Most of the relatives with idiopathic or cryptogenic epilepsy had the same sei- zure type as the proband. These findings confirm the role of genetic factors in the pathogenesis of epilepsy.     

Characteristics of Seizures in a Population-Based Series of Mentally Retarded Children with Active Epilepsy

Summary: Purpose: The characteristics of seizures were analysed in a population-based study of active epilepsy in 6-to 13-year-old mentally retarded children. Methods: The search procedure included diagnostic registers, EEG registers, and registers of the Education of the Subnormal. Medical files were scrutinized, and clinical examinations and interviews with parents or caretakers or both were performed. Results: The median age of seizure onset was 1·3 years, 3·1 for children with mild retardation and 0·8 for children with severe retardation. Among the 98 children identified, current seizure groups were partial in 20, generalized in 59, and mixed in 19. The prevailing seizure types were tonic-clonic, myoclonic, atypical absences, and partial complex seizures, present in 42, 33, 23, and 23 children, respectively. A total of 46 children had more than one seizure type. Seizures every day/week occurred in 44 children. There was a constancy between seizure type at onset and later seizure type. Neonatal seizures (n = 25), infantile spasms (n = 12), and status epilepticus (n = 37) occurred independent of one another. Prognostic factors for poor neurologic outcome were early onset of epilepsy, infantile spasms as onset type, and prior neonatal seizures. Children with only partial seizures less frequently had severe mental retardation, cerebral palsy, and visual impairment than those with only generalized seizures. Conclusions: Epilepsies in children with mental retardation are characterized by severe seizure manifestations. The brain damage giving rise to mental retardation and epilepsy is probably the main factor in terms of seizure outcome.     

Behavioral side-effects of levetiracetam in children with epilepsy: A systematic review

PurposeChildren with epilepsy are more likely to have behavioral problems compared to children without epilepsy. Literature suggests that levetiracetam leads to behavioral side-effects in children with epilepsy. The objective of this study is to provide a better overview of the frequency and variety of behavioral side-effects, which can be initiated by levetiracetam therapy in children with epilepsy.MethodElectronic databases used in the search were PubMed, Medline, Cochrane and Embase. Studies were eligible for inclusion when they included children from one month to 18 years of age with a diagnosis of epilepsy, used levetiracetam, had other AEDs on a stable regimen for at least two months, reported about behavioral side-effects and had a follow-up of at least two weeks. Quality assessments and data collection were carried out for all eligible studies.ResultsThirteen studies, including 727 patients using levetiracetam, were included in this systematic review. Three randomized controlled trials showed a total of 62 behavioral side-effects in 203 patients, effects which led to discontinuation of levetiracetam in only two of 102 patients (2.0%). Hostility, nervousness and aggression were reported mostly. Meta-analysis showed a statistically significant relative risk of 2.18 for the total number of behavioral side-effects for levetiracetam versus placebo. Observational studies showed mixed results with both behavioral deteriorations and improvements following levetiracetam.ConclusionBased on the findings in this systematic review, children using levetiracetam have a risk of developing several behavioral side-effects such as aggression, hostility and nervousness compared to children who do not use levetiracetam.     

Components of Attention in Children with Complex Partial Seizures With and Without ADHD

Summary: Purpose: To evaluate attentional difficulties in children with complex partial seizures, we reviewed the records of 12 children with complex partial seizures with attention deficient hyperactivity disorder (CPS/ADHD); 21 children with CPS without ADHD (CPS); 22 children with ADHD; and 15 control children.
Methods: Each child completed a computerized performance test (CPT), which evaluated sustained attention, inhibition of response, response time, and consistency of response. The ADHD groups also completed the CPT after a dose of methylphenidate.
Results: The results found poorest performance on the CPT by the CPS/ADHD group. Particular difficulty in attention was found for children with epilepsy regardless of the ADHD diagnosis. When methylphenidate was administered to the ADHD groups, both groups improved in performance on the CPT.
Conclusions: Epilepsy may predispose children to attention problems that can significantly interfere with learning. Similar improvement for children with CPS/ADHD was found with methylphenidate compared with baseline as for children with ADHD but without CPS.     

Outcome After Discontinuation of Antiepileptic Drug Therapy in Children with Epilepsy

We studied recurrence risks and predictive factors of relapse after antiepileptic drug (AED) discontinuation in a prospective analysis of 425 children with epilepsy who had not had a seizure for at least 2 years (follow-up after withdrawal 1.6-12 years, mean 8 years). Factors closely related by multivariate analysis to relapse were neurologic abnormalities, mental retardation, seizure type (infantile spasms, absence seizures), and appearance or persistence of EEG abnormalities during the course of the illness and before discontinuation. When multivariate analysis was performed to evaluate outcome of patients with a first relapse (isolated vs. multiple relapses), the variables closely related to a poor prognosis were etiologic factors, first relapse characterized by more than one seizure in a 24-h period, seizure-free period less than 4 years, unchanged seizure type at first relapse, more than one AED for seizure control, and abnormal EEG before the first relapse. In itself, resumption of therapy did not influence outcome. At the study cutoff point, 88% of patients with relapse were again seizure-free. We conclude that AEDs can safely be discontinued if predictive factors are considered to individualize the risk of relapse for each patient.     

Discontinuing Medication in Epileptic Children: A Study of Risk Factors Related to Recurrence

We studied 70 children who had experienced at least two seizures before age 12 years, excluding febrile seizures, neonatal seizures, or seizures occurring during a metabolic, or infectious insult to the central nervous system (CNS) and who had been seizure free for at least 2 years. Twenty children (28.5%) experienced a recurrence, 75% during antiepileptic (AED) drug discontinuation or less than 6 months after discontinuation. Risk factors statistically related to seizure recurrence were greater than 10 seizures before seizure control, an abnormal EEG in the year before AED discontinuation, presence of focal neurologic signs and/or mental retardation, and presence of a mixed seizure pattern. Fourteen children (70%) with recurrence had two or more risk factors, whereas 36 (72%) without recurrence had no risk factor or only one. We conclude that a selected group of epileptic children who remain seizure-free for a period of at least 2 years can have AEDs discontinued based on presence or absence of risk factors.     

Discontinuation of Antiepileptic Drugs in Children Who Have Outgrown Epilepsy: Effects on Cognitive Function

Summary: Cognitive function is frequently impaired in children with epilepsy, compared with age-matched controls. It can be hard to evaluate the significance of various contributory factors. The effects of antiepileptic drugs may be studied in children who have outgrown their epilepsy but are still being treated. A multicenter study to assess various aspects of cognitive function in children with different forms of epilepsy, both during and after treatment with antiepileptic drugs, is currently under way. Definitive results are not yet available; interim analysis of the findings suggests that short-term memory is decreased in all subgroups of children being treated for epilepsy, compared to controls.     

The Diagnostic Yield of a Second EEG After Partial Sleep Deprivation: A Prospective Study in Children with Newly Diagnosed Seizures

Summary: Purpose: To assess the diagnostic yield of a repeated EEG (REPEEG) after partial sleep deprivation (SD) in children and adolescents with one or more seizures who previously had had a standard EEG (STDEEG) without epileptiform abnormalities (EAs). In the literature, 32–75% of such REPEEGs after SD were reported to show EA. Methods: In a prospective, multicentred study, we selected children aged 1 month to 16 years with one or more idiopathic or remote symptomatic newly diagnosed seizures. A REPEEG was recorded in children without EAs in their STDEEG. Results: Of 552 children and adolescents who entered the study, 243 (44%) had a STDEEG without EAs. In 177 (73% of eligible children), REPEEGs were recorded after SD. We found EAs in 61 (34.5%) REPEEGs and new nonepileptiform abnormalities in five (1%). In 552 children in the total cohort, the REPEEG thus added 11% with EAs to the 56% with EAs in the STDEEG. Of REPEEGs, 81% included sleep compared with 20% of STDEEGs. In about half the REPEEGs, EAs occurred during sleep only. One child had tonic-clonic seizures probably related to the SD. Conclusions: One third of REPEEGs yielded new diagnostic information. Partial, age-dependent SD was highly effective in inducing sleep, which is important because in many cases EAs were found only during EEG recording in sleep. The procedure was safe and convenient.