Childhood-onset epilepsy with and without preceding febrile seizures.

OBJECTIVE: To identify characteristics in children with epilepsy that differ between those who did versus did not have a history of preceding febrile seizures. BACKGROUND: Febrile seizures precede epilepsy in 10 to 15% of children. Little is known about the specific types of epilepsy associated with febrile seizures. METHODS: In a community-based, prospectively identified cohort of children, the association between prior febrile seizures and characteristics of the children's epilepsy (seizure type, epilepsy syndrome, age at onset, underlying etiology, family history) were examined for 524 of the children who were aged > or =1 year at onset of epilepsy. RESULTS: Seventy-three (13.9%) had febrile seizures. Children with febrile seizures were more likely to have a first-degree or a second-higher-degree relative with febrile seizures and less likely to have childhood absence epilepsy and absence seizures compared with children without febrile seizures. This was especially true for simple febrile seizures. There was no specific association with localization-related forms of epilepsy. Complex, but not simple, febrile seizures were associated with younger age at onset of epilepsy. There was no evidence that focal or prolonged febrile seizures were associated with localization-related epilepsy or temporal lobe epilepsy per se. Of the three children whose initial MRIs demonstrated hippocampal atrophy, none had a history of febrile seizures. CONCLUSIONS: At the time of diagnosis, febrile seizures are not specifically related to temporal lobe epilepsy or localization-related epilepsy in general. A genetic component for febrile seizures is suggested by its positive associations with family history, especially for simple febrile seizures. Complex febrile seizures represent an underlying age-dependent susceptibility.

Early development of intractable epilepsy in children: a prospective study.

BACKGROUND: Little is known about early prediction of intractable epilepsy (IE) in children. Such information could help guide the early use of new therapies in selected patients. METHODS: Children with newly diagnosed epilepsy (n = 613) were prospectively identified from child neurology practices in Connecticut (1993--1997) and followed-up for the occurrence of IE (failure of > or = 2 drugs, > or = 1 seizure/month, over 18 months) [corrected]. Etiology and epilepsy syndromes were classified per International League Against Epilepsy guidelines. RESULTS: The median follow-up is 4.8 years, and 599 (97.7%) have been followed for more than 18 months. Sixty children (10.0%) have met the criteria for IE, including 34.6% with cryptogenic/symptomatic generalized, 2.7% with idiopathic, 10.7% with other localization-related, and 8.2% with unclassified epilepsy (p < 0.0001). After multivariable adjustment for epilepsy syndrome, initial seizure frequency (p < 0.0001), focal EEG slowing (p = 0.02), and acute symptomatic or neonatal status epilepticus (p = 0.001) were associated with an increased risk of IE, and age at onset between 5 and 9 years was associated with a lowered risk (p = 0.03). The absolute number of seizures and unprovoked or febrile status epilepticus were not associated substantially with IE. CONCLUSIONS: Approximately 10% of children meet criteria for IE early in the course of their epilepsy. Cryptogenic/symptomatic generalized syndromes carry the highest risk and idiopathic syndromes the lowest. Half of IE occurs in children with nonidiopathic localization-related syndromes. Initial seizure frequency is highly predictive of IE. By contrast, absolute number of seizures and unprovoked or febrile status epilepticus are not.

Treatment of newly diagnosed pediatric epilepsy: a community-based study.

OBJECTIVE: To determine the patterns and frequency of treatment and use of specific drugs for newly diagnosed pediatric epilepsy. DESIGN AND SETTING: Prospective, community-based study. Children were recruited from physicians in Connecticut from 1993 to 1997. PATIENTS: Children aged 1 month through 15 years at the time of their first seizure, who had 2 or more unprovoked seizures, and who were newly diangosed during the recruitment period were eligible. MAIN OUTCOME MEASURE: Initiation of treatment at diagnosis and within 1 year after diagnosis of epilepsy. RESULTS: Of 613 children, 482 (78.6%) were treated at the time of initial diagnosis. By 6 months another 10.3% were treated, and by 12 months 90% of the cohort had been treated. The most commonly prescribed antiepileptic drug (AED) was carbamazepine (38.8%) followed by sodium valproate (18.4%). Only 1 child received an investigational drug and none received any of the most recently approved drugs as a first AED. Children with idiopathic and secondarily generalized forms of epilepsy were most likely to be treated (90%-100%), whereas children with idiopathic localization-related epilepsy were least likely to be treated (50.8%). Approximately 80% of those with other forms of epilepsy were treated at the time of diagnosis. Use of specific medications reflected current guidelines and recommendations for treatment of specific seizure types and syndromes. CONCLUSIONS: In Connecticut, approximately 20% of children with epilepsy are not treated at the time of initial diagnosis, and around 10% continue to be untreated after 1 year. This most likely reflects the increased understanding of the nature of pediatric epilepsy and concerns regarding the adverse effects of AEDs. The most commonly used first drugs are carbamazepine and valproate. Follow-up of this cohort may help provide information to guide the use of recently approved AEDs.

Simultaneous quantitation of norepinephrine, dopamine and serotonin in brain during and following chronic naltrexone administration.

The effects of chronic administration of the narcotic antagonist naltrexone on regional brain levels of norepinephrine, dopamine and serotonin were studied in order to determine whether central monoaminergic neurons are tonically modulated by central opioid systems. Chronic exposure to naltrexone (8 days) is associated with a significant increase in the content of norepinephrine in the mesolimbic forebrain and the content of dopamine in the frontal cortex and striatum. Ten days following naltrexone pellet removal the above levels returned to control values but thalamic dopamine content was reduced 10-fold. These data suggest that the affected brain regions receive an opioidergic input that is tonically active.

Defining early seizure outcomes in pediatric epilepsy: the good, the bad and the in-between.

PURPOSE: To examine different approaches to classifying seizure outcomes. METHODS: In a prospective cohort study of children (N=613) with newly diagnosed epilepsy, seizure outcomes at 2 years were classified as 'good' (> or =1 year remission), 'bad' or 'intractable' (> or = AED failures, > or =1 seizure/month over > or =18 months), and 'indeterminate' (neither 'good' nor 'bad'). Outcomes at 2 years were compared to outcomes in those followed 4 or more years. The associations of three commonly studied prognostic factors, etiology, age at onset, and syndromic grouping with the three-level outcome were assessed. RESULTS: 595 (97.1%) children were followed > or =2 years. A 'good', indeterminate, and 'bad' outcome was present in 314 (52.8%), 235 (38.3%), and 46 (7.7%) children. Problems with treatment were recorded in 64.7% of the indeterminate group. In 390 children followed > or =4 years, early 'good' and 'bad' outcomes persisted in approximately 80%. About half of those with indeterminate 2-year outcomes later achieved remission, 8% met criteria for intractability, and 37% remained indeterminate. Most of the associations with etiology, age, and syndrome were due to variation in the proportion that met criteria for intractability and not remission. CONCLUSIONS: Many children have indeterminate outcomes, often in association with treatment issues. Clearly 'good' and 'bad' early outcomes can be identified and persist > or =2 years later. In the absence of pharmaco-resistance, lack of early remission (indeterminate outcome) is usually not associated with a bad outcome, at least over the next few years.

The epidemiology of epilepsy. Past, present, and future.

Much has been learned from epidemiologic studies about the frequency, causes, natural history, and prognosis of epilepsy and other seizure disorders. This knowledge has resulted in significant changes in the clinical management of individuals who have seizures and epilepsy. Recent changes in the known causal factors and diagnostic technologic advances, among other factors, will affect the epidemiology and prognosis of epilepsy. Continued epidemiologic monitoring of this common neurologic condition is necessary to ensure an accurate understanding of the current forms of the disorder.

Neuroimaging in children with newly diagnosed epilepsy: A community-based study.

BACKGROUND: Neuroimaging is generally considered a part of the evaluation of seizures and epilepsy. There is limited information about its current use in the initial evaluation of pediatric epilepsy and about its yield during the initial diagnosis of epilepsy. We describe the patterns in the use and yield of diagnostic imaging in children with newly diagnosed epilepsy in a community-based study. METHODS: Children were recruited when first diagnosed with epilepsy by participating physicians in Connecticut (1993-1997). Definitions for etiology and underlying epilepsy syndromes are as published by the International League Against Epilepsy. RESULTS: Of 613 children, 488 (79.6%) had imaging: 388 (63. 3%) magnetic resonance imaging, 197 (32.1%) computed tomography scans, and 97 (15.8%) both. Half of children with idiopathic generalized epilepsy had imaging studies compared with 70% to 100% of children with other forms of epilepsy, depending on the specific type. Etiologically relevant abnormalities were found in 62 (12.7% of those imaged). Fourteen of these children had otherwise completely normal presentations and histories. Their abnormalities included tuberous sclerosis (N = 4), tumors (N = 2), an arteriovenous malformation later diagnosed as a tumor, a cavernous angioma, cerebral malformations (N = 3), and other abnormalities (N = 3). Thirteen of the 14 had partial seizures and 12 had focal electroencephalographic (EEG) findings. Only 1 had neither. CONCLUSIONS: In children with newly diagnosed epilepsy, neuroimaging reveals a small but significant number of serious abnormalities not previously suspected. Most of these children have partial seizures or focal EEG abnormalities. Neuroimaging should be considered during the evaluation of children with newly diagnosed epilepsy, especially for those with neurologic deficits or partial seizures or focal EEG abnormalities that are not part of an idiopathic localization-related epilepsy syndrome.

Classification of childhood epilepsy syndromes in newly diagnosed epilepsy: interrater agreement and reasons for disagreement.

PURPOSE: The International League Against Epilepsy (ILAE) classification of the epilepsies is in increasingly widespread use. The following analysis was done to assess the interrater agreement in classifying epilepsy syndromes in children with newly diagnosed epilepsy. METHODS: In a prospective, community-based study, 613 children with newly diagnosed epilepsy were recruited. Based on information available at diagnosis or generated as part of the initial diagnostic assessment, three pediatric neurologists independently classified epilepsy syndromes. Interrater agreement was assessed with kappa. RESULTS: Interrater agreement was extremely good, with kappa scores > or = 0.80 for almost all comparisons. Relatively limited quality of the EEG and seizure information in some cases, as well as discrepancies between the two, were associated with a tendency for more disagreement. CONCLUSIONS: A high degree of interrater agreement was obtained in this study, indicating that the system for classifying syndromes can be meaningfully used in a community-based sample. Quality of the information, which is often, by necessity, less than optimal in newly diagnosed epilepsy, is a potential barrier to identification of syndromes. A substantial proportion of children were classified into relatively nonspecific syndromes. Over time, additional information may come to light to allow more precise identification of their forms of epilepsy. In an epidemiologic setting, the ILAE classification of the epilepsies can be successfully used with a high degree of reliability to classify newly diagnosed epilepsy in children.

Newly diagnosed epilepsy in children: presentation at diagnosis.

PURPOSE: The current understanding of epilepsy has changed significantly in the past 2 decades. This report presents a description of newly diagnosed childhood-onset epilepsy, with a special emphasis on epilepsy syndromes, in a large, prospectively ascertained community-based cohort evaluated and diagnosed in the mid-1990s. METHODS: Children, aged 0 through 15 years at the time of the first seizure, were prospectively identified at the time of diagnosis of epilepsy through the practices of 16 of the 17 child neurologists in Connecticut as well as five adult neurologists and seven pediatricians from January 1993 through December 1997. Parents were interviewed, and all relevant medical records were reviewed. Classification of seizures and of epilepsy syndromes was done for each child by each of three pediatric neurologists. Discrepancies were resolved in conference. RESULTS: A total of 613 children was recruited into the study. The median age at time of the first seizure was 5.3 years. Half the cohort was boys. Eighteen percent had a remote symptomatic etiology. Epilepsy syndromes were classifiable in all but four children, although some syndromes are, by definition, relatively nonspecific. In this childhood-onset cohort, 58.6% of the syndromes were localization related, 29.0% generalized, and 12.4% undetermined as to whether focal or generalized. Benign rolandic epilepsy occurred in 10% of the cohort. Primarily generalized syndromes accounted for 20.6%, with childhood absence being the single most common syndrome in this subgroup (12.1% of the cohort). Secondarily generalized syndromes accounted for 8.5% of the total, with infantile spasms being the most common in this grouping (3.9% of the cohort). CONCLUSIONS: This study presents a description of childhood- and adolescent-onset epilepsy as it is diagnosed and evaluated in the 1990s in one state in the United State and based on current classification guidelines. The results should be generalizable to the rest of the country. The prognostic value of early identification of epilepsy syndromes will be determined through subsequent follow-up of this cohort.

Status epilepticus in children with newly diagnosed epilepsy.

Status epilepticus (SE) constitutes a neurological emergency and may be of prognostic value in individuals with epilepsy. Little is known about the associations between other prognostic factors in epilepsy and the occurrence of SE. The following study examines associations between clinical characteristics of children with newly diagnosed epilepsy and the occurrence of SE when epilepsy is first diagnosed. Children were recruited prospectively from the practices of physicians throughout Connecticut. Information was collected via standardized interviews with parents and review of pertinent records. Analyses were performed for any SE, unprovoked SE only, and previous provoked SE. Of 613 children, 56 (9.1%) had one or more episodes of SE by the time the diagnosis of epilepsy was established. Factors correlated with SE during an unprovoked seizure were partial seizures and previous craniotomy. For SE during a provoked seizure, correlates were primarily young age at onset of epilepsy and nonidiopathic epilepsy syndrome. To date, subsequent SE has occurred in 4.3% of children without and in 19.6% of those with SE at diagnosis. By the time epilepsy is first diagnosed in children, SE has already occurred in a substantial minority. It is correlated with specific clinical characteristics in the children, which differ depending on whether the SE was provoked or unprovoked. SE has a high risk of recurring.

How well can epilepsy syndromes be identified at diagnosis? A reassessment 2 years after initial diagnosis.

PURPOSE: Epilepsy syndromes can be identified very early in the course of a seizure disorder. It is unclear how accurate and resilient such early classifications are. We compared the classification of epilepsy syndromes made previously on the basis of information available at diagnosis with those made 2 years later in a cohort of children with newly diagnosed epilepsy. METHODS: Children (n = 613) were prospectively identified at the time of initial diagnosis by participating physicians in Connecticut between 1993 and 1997. Classification of epilepsy syndrome according to International League Against Epilepsy guidelines was made previously based on all relevant information available at diagnosis. All cases were reclassified again after 2 years of additional evidence had accumulated. The distributions of syndromes at diagnosis and at 2 years are compared and reasons for changes examined. RESULTS: After 2 years, syndromes remained the same in 86.3% of the cohort and changes occurred in 13.7% (n = 84). Evolution of the syndrome occurred in 24 children (3.9%), and rectification to the initial diagnosis occurred in 60 children (9.8%). The most common scenario for evolution of a syndrome was from West syndrome (n = 5), undetermined (n = 4), or symptomatic localization-related epilepsy (n = 3) to the Lennox-Gastaut syndrome. The most common rectification of initial classifications involved incompletely classified syndromes (cryptogenic localization-related and undetermined syndromes; n = 36). In a few instances, a fully specified syndrome was reclassified to another apparently unrelated syndrome. In these cases, initial information at diagnosis had been difficult to interpret. CONCLUSIONS: Epilepsy syndromes can, for the most part, be identified at the time of initial diagnosis. Two years later, rectifications were made in only 9.8% of cases, and most of these involved syndromes that represented incomplete classifications in the first place. Significant changes were rare. The International League Against Epilepsy classification of the epilepsies can be meaningfully applied in epidemiological studies of newly diagnosed pediatric epilepsy.

Status epilepticus after the initial diagnosis of epilepsy in children.

OBJECTIVES: To determine the risk and predictors of status epilepticus in children after they have been diagnosed with epilepsy. METHODS: In a prospective community-based cohort study of 613 children, the occurrence of status epilepticus after the initial diagnosis of epilepsy was ascertained. Parents were called every 3 months, and interval medical records were reviewed every 6 months. Predictors of primary interest included a history of status before the diagnosis of epilepsy, age at onset, underlying etiology, and epilepsy syndrome. Data were analyzed with chi2 tests, Kaplan-Meier analyses, and Cox proportional hazards models. RESULTS: Of 613 children followed a median of 8.0 years, 58 (9.5%) had > or =1 episode of status epilepticus during follow-up evaluation. The first episode occurred a median of 2.5 years after initial diagnosis (range, <1 month to 8.8 years). A history of previous status epilepticus was strongly associated with subsequent status epilepticus (18/56 [32.1%] vs 40/557 [7.2%]; p < 0.0001). Younger age at onset and symptomatic etiology contributed independently to the risk of status epilepticus. Mortality was higher in children with status epilepticus before diagnosis, largely secondary to underlying cause. CONCLUSIONS: Status epilepticus occurs in approximately 10% of children after initial diagnosis of epilepsy. Status epilepticus before initial diagnosis, young age at onset, and symptomatic etiology independently influence the risk of status epilepticus. In those without status epilepticus before diagnosis, the risk is modest and is realized over a prolonged period. For children at highest risk, maintaining abortive therapy in the home may be a reasonable precaution.

Two-year remission and subsequent relapse in children with newly diagnosed epilepsy.

PURPOSE: Although remission is the ultimate measure of seizure control in epilepsy, and epilepsy syndrome should largely determine this outcome, little is known about the relative importance of syndrome versus other factors traditionally examined as predictors of remission or of relapse after remission. The purpose of this study was to examine remission and relapse with respect to the epilepsy syndrome and other factors traditionally considered with respect to seizure outcome. METHODS: A prospectively identified cohort of 613 children with newly diagnosed epilepsy was assembled and is actively being followed to determine seizure outcomes. Epilepsy syndrome and etiology were classified at diagnosis and again 2 years later. Remission was defined as 2 years completely seizure-free, and relapse as the recurrence of seizures after remission. Multivariable analysis was performed with the Cox proportional hazards model. RESULTS: Five hundred ninety-four of the original 613 children were followed > or = 2 years (median follow-up, 5 years). Remission occurred in 442 (74%), of whom 107 (24%) relapsed. On multivariable analysis, idiopathic generalized syndromes and age at onset between 5 and 9 years were associated with a substantially increased remission rate, whereas remote symptomatic etiology, family history of epilepsy, seizure frequency, and slowing on the initial EEG were associated with a decreased likelihood of attaining remission. Young onset age (<1 year) and seizure type were not important after adjustment for these predictors. Relapses occurred more often in association with focal slowing on the initial EEG and with juvenile myoclonic epilepsy. Benign rolandic epilepsy and age at onset <1 year were associated with markedly lower risks of relapse. About one fourth of relapses were apparently spontaneous while the child was taking medication with good compliance, and more than half occurred in children who were tapering or had fully stopped medication. CONCLUSIONS: A large proportion of children with epilepsy remit. Symptomatic etiology, family history, EEG slowing, and initial seizure frequency negatively influence, and age 5-9 years and idiopathic generalized epilepsy positively influence the probability of entering remission. Factors that most influence relapse tend to be different from those that influence remission.