Four-year outcome after early withdrawal of antiepileptic drugs in childhood epilepsy.

Four-year follow-up of children with epilepsy included in a randomized trial of early withdrawal of antiepileptic drugs showed that 51% achieved a terminal remission of at least 2 years without medication and 21% with medication; 15% had seizures during the fourth year. Early medication withdrawal is not recommended as standard practice in children with a rapid response to medication. The authors developed a model to predict outcome if withdrawal is considered.

Three to four years after diagnosis: cognition and behaviour in children with 'epilepsy only'. A prospective, controlled study.

A 3.5-year follow-up study of cognition and behaviour in 42 children with newly diagnosed idiopathic or cryptogenic epilepsy ('epilepsy only') attending mainstream education and 30 healthy gender-matched classmate controls was carried out to identify differences between groups, to detect factors that contribute to the difference and its change over time, and to establish the proportion of poorly performing children. The neuropsychological battery covered the major domains of cognition, mental and motor speed and academic language skills. Children were tested at the time of diagnosis (before any anti-epileptic drug treatment started) and 3, 12 and approximately 42 months later. Parents and teachers completed behaviour checklists, for which the scoring was adapted to prevent any influence of epilepsy-related ambiguity. Based on parental interviews at the time of diagnosis, children with epilepsy were categorized as having longstanding behavioural and/or learning problems, as belonging to a troubled family, as being exposed to 'off-balance' parenting starting at the time of epilepsy onset and/or as reacting maladaptively to the changes in relation to the onset of epilepsy. Throughout follow-up, the group of children with epilepsy only performed less well than healthy classmates on measures of learning, memory span for words, attention and behaviour. After controlling for school delay, proactive interference (number of responses to the same images as in the learning trials, but now presented in reordered locations) was the only remaining variable that distinguished the group of children with epilepsy only. Group-wise, no changes in cognitive and behavioural differences over time were found, but instability in individual performances appeared to characterize children with epilepsy only. Rather than intrinsically epilepsy-related variables, such as idiopathic versus cryptogenic aetiology, seizure control or anti-epileptic drug treatment, the child's prediagnostic learning and behavioural histories and the parents' ability to continue their habitual parenting in the face of the diagnosis of epilepsy only were shown by both group-wise and case-by-case analyses to be important for understanding the cognitive and behavioural functioning of the children with epilepsy only.

Interrater agreement of the diagnosis and classification of a first seizure in childhood. The Dutch Study of Epilepsy in Childhood.

OBJECTIVE: To assess the interrater agreement of the diagnosis and the classification of a first paroxysmal event in childhood. METHODS: The descriptions of 100 first paroxysmal events were submitted to two panels each consisting of three experienced paediatric neurologists. Each observer independently made a diagnosis based on clinical judgment and thereafter a diagnosis based on predefined descriptive criteria. Then, the observers discussed all patients within their panel. The agreement between the six individual observers was assessed before discussion within each panel and after that, between the two panels. RESULTS: Using their clinical judgement, the individual observers reached only fair to moderate agreement on the diagnosis of a first seizure (mean (SE) kappa 0.41 (0.03)). With use of defined descriptive criteria the mean (SE) kappa was 0.45 (0.03). The kappa for agreement between both panels after intra-panel discussion increased to 0.60 (0.06). The mean (SE) kappa for the seizure classification by individual observers was 0.46 (0.02) for clinical judgment and 0.57 (0.03) with use of criteria. After discussion within each panel the kappa between the panels was 0.69 (0.06). In 24 out of 51 children considered to have had a seizure, agreement was reached between the panels on a syndrome diagnosis. However, the epileptic syndromes were in most cases only broadly defined. CONCLUSIONS: The interrater agreement on the diagnosis of a first seizure in childhood is just moderate. This phenomenon hampers the interpretation of studies on first seizures in which the diagnosis is only made by one observer. The use of a panel increased the interrater agreement considerably. This approach is recommended at least for research purposes. Classification into clinically relevant syndromes is possible only in a very small minority of children with a single seizure.

Immunoglobulins in children with epilepsy: the Dutch Study of Epilepsy in Childhood.

In an unselected cohort of 282 children, serum immunoglobulin (Ig) concentrations were determined shortly after the first presentation with one or more unprovoked epileptic seizures and before the start of treatment with anti-epileptic drugs (AEDs), and after 9-18 months of AEDs use. At intake, IgA, IgG1, IgG2 and IgG4 concentrations were significantly higher than published reference values in healthy age-matched controls. In a subset of 127 children, Ig levels at intake were compared with those after AEDs use for 9-18 months. IgA and IgG4 levels had decreased significantly to normal concentrations, but IgG1 and IgG3 levels increased significantly. To determine the influence of AEDs, Ig levels in children who used carbamazepine or valproic acid monotherapy were analysed separately. The use of carbamazepine was associated with a significant decrease of IgA and IgG4 levels, and the use of valproic acid with a significant decrease of IgA and increase of IgG1 levels. In conclusion, humoral immunity is already altered in children shortly after the first presentation with epileptic seizures. Whether this is the consequence of an exogenous event, and to what extent this is related to an interaction of the central nervous system and the immune system, remains to be evaluated. Treatment with AEDs, such as carbamazepine and valproic acid, is associated with significant changes of Ig (sub)class concentrations.

The accuracy of the diagnosis of paroxysmal events in children.

OBJECTIVE: To assess the accuracy of the diagnosis of epileptic seizures in children. METHODS: The Dutch Study of Epilepsy in Childhood is a prospective hospital-based study of 881 children referred because of possible seizures. The diagnosis was based on predefined descriptive criteria, as applied by a panel of three pediatric neurologists. Children with a definite other diagnosis were excluded. All children with unclear events were followed up for 1 year and children with seizures were followed up for 2 years to assess the accuracy of the diagnosis. RESULTS: In 170 of 224 children seen after a single event, the incident was classified initially as epileptic, in 54 as unclear. In none of the 170 children did the diagnosis prove to be wrong. In four of the 54 children, recurrent episodes enabled a definite diagnosis of epilepsy. In 412 of the 536 children seen with multiple events, an initial diagnosis of epilepsy was made. After follow-up, this initial diagnosis was probably incorrect in 19. In contrast, seven of 124 children with multiple unclear episodes at intake later received the diagnosis epilepsy. CONCLUSIONS: A false-positive diagnosis of epilepsy was made in 4.6%, whereas a definite diagnosis of epilepsy or seizure was delayed in 5.6% of children with multiple unclear events and in 7.4% of children with one unclear event.

Behavioral problems in children with newly diagnosed idiopathic or cryptogenic epilepsy attending normal schools are in majority not persistent.

PURPOSE: To investigate relevant adults' perceptions of behavioral problems in 66 children with newly diagnosed "epilepsy only" and in 63 healthy gender-matched classmates. METHODS: Parents' and teachers' perceptions of the children's behavioral problems were quantified by using the Total Problem score of the Child Behavior Checklist (CBCL) and the Teacher's Report Form (TRF), after correction for epilepsy-related item ambiguity. Questionnaires were filled out immediately after diagnosis and 3 and 12 months later. Relations with demographic and educational variables, school attitudes, and interview-derived prior adversities were analyzed. RESULTS: As a group, children with cryptogenic rather than those with idiopathic epilepsy have more behavioral problems than do healthy classmates. Family troubles and long-standing behavioral and learning problems are associated with more behavioral problems. The child's adaptation to the adversity of epilepsy onset is important. No adverse effect of antiepileptic drug (AED) treatment was found. Although the percentages of patients with clinically relevant (mean of controls + 2 SD) behavioral problems are consistently 25% (parents) and 22% (teachers), at each assessment, different children contribute to these percentages. In not a single child did parents and teachers agree on the presence of clinically relevant behavioral problems. CONCLUSIONS: (a) Behavioral problems are common in "epilepsy only," but are not persistent. (b) Agreement between parent's and teacher's perceptions of behavior is low. (c) Behavioral problems are perceived to occur already in the earliest stage of the disease.

Learning and memory of school children with epilepsy: a prospective controlled longitudinal study.

The aim of the study was to determine whether learning and memory are compromised in school children with recently diagnosed idiopathic and/or cryptogenic epilepsy and to study relationships between learning and memory and psychosocial and epilepsy variables. Word span and learning of locations were assessed within 48 hours after diagnosis of epilepsy and three and 12 months later, in 69 school children with epilepsy (aged 9.1 years, SD 2.7; 33 males, 36 females) and 66 classmates. Results showed that patients and controls performed similarly in registration, recall, and retention. Patients recalled slightly less than controls when probed under conditions of increased demand on working memory. Maladaptive reactions of parents and children to the onset of epilepsy and not reaching 6-months of seizure remission contributed to poor performance. Individually, those patients who required special assistance at school, under-performed occasionally in one or the other component of memory. Although the proportion of under-performers was stable over time, the children composing the group did change. It was concluded that school children with new onset idiopathic or cryptogenic epilepsy are inordinately vulnerable when processing memory tasks. The vulnerability is neither persistent nor memory-specific.

Nonsymptomatic generalized epilepsy in children younger than six years: excellent prognosis, but classification should be reconsidered after follow-up: the Dutch Study of Epilepsy in Childhood.

PURPOSE: To assess the prognosis and the accuracy of the epilepsy classification in young children with nonsymptomatic generalized epilepsy. METHODS: Of the cohort of the Dutch Study of Epilepsy in Childhood (n = 466), all children younger than 6 years with a diagnosis of idiopathic (IGE) or cryptogenic (CGE) generalized epilepsy either at intake (n = 108) and/or after 2 years of follow-up (n = 102) were included. The number of reclassifications after 2 years was determined, and the reasons for reclassification were analyzed. All children receiving a diagnosis of IGE or CGE at 2 years were followed up for 5 years to study their outcome in terms of terminal remission (TR). Data on their level of intellectual functioning were collected at the start of this analysis. RESULTS: The epilepsy syndrome was reclassified in 17 children. In 14 of them, the seizure type also was reclassified, and in three, the course of the epilepsy determined the new epilepsy type. Two other children had a reclassification of their seizure types without a change of the epilepsy type. Many children were categorized as having IGE not otherwise specified. In all probability, this is a heterogeneous group, containing patients with various epilepsy syndromes, with generalized tonic-clonic seizures as a common hallmark. Of the 102 children with IGE or CGE at 2 years of follow-up, 75% had a TR of >6 months after 2 years, and 85% a TR of >or=1 year after 5 years. CONCLUSIONS: In a fair proportion of children with nonsymptomatic generalized epilepsy in this age group, it is not possible to classify firmly the epilepsy and/or the seizures immediately after the intake. Instead, they are reclassified during the course of the disease. This and the apparent heterogeneity of the category IGE not otherwise specified point to inherent drawbacks of the current International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The prognosis of IGE at this young age is generally excellent.

Long term course of childhood epilepsy following relapse after antiepileptic drug withdrawal.

OBJECTIVE: To explore the course of epilepsy following relapse after antiepileptic drug (AED) withdrawal. METHODS: Forty two patients were identified with onset of epilepsy in childhood in whom AEDs had been withdrawn after at least 2 years of seizure freedom, and in whom a relapse had occurred. Two patients were lost to follow up. RESULTS: Median follow up after AED withdrawal was 5.9 years (range 1.6-13.2 years). Relapse occurred in more than half of the patients within 6 months of AED withdrawal. At the end of follow up, 12 patients (30%) were seizure free for at least 1 year (mean 10.4 years) without medication; 16 (40%) were seizure free for at least 1 year (mean 5.3 years) with ongoing medication; and 12 patients (30%) were seizure free for less than 1 year with medication. No status epilepticus occurred in any patient after withdrawal. Age at onset, if over the age of 5, combined with normal intelligence were predictive of an excellent outcome; presence of a neurological disorder, and hence symptomatic aetiology, was predictive of poor outcome after a relapse. CONCLUSIONS: Fears that premature withdrawal of AEDs might result in uncontrollable seizures were unsubstantiated in this study. The current practice of withdrawing AEDs in children who have been seizure free for 2 years can be beneficial to most of these patients.

Attention deficits are not characteristic of schoolchildren with newly diagnosed idiopathic or cryptogenic epilepsy.

PURPOSE: To compare problems of attention in schoolchildren with newly diagnosed idiopathic or cryptogenic epilepsy with those in healthy classmates. METHODS: A computerized battery of tasks comprised Reaction Time (RT) measurement, Trail making (Color Trails 1 and 2), Manual Tapping and Steadiness, and a newly developed task of sustained attention (Balloon Piercing). SUBJECTS: Fifty-one children with epilepsy (age 7-16 years) and 48 gender- and age-matched classmates were assessed thrice: within 48 h after diagnosis [before start of antiepileptic drugs (AEDs)], and 3 and 12 months later. Significantly more children with epilepsy (51%) than control children (27%) had required special educational assistance at school. RESULTS: Children with epilepsy could not be distinguished from controls in execution times or motor speed. However, errors were more frequent among patients in a "go-no-go" RT task, and errors of omission in a task requiring sustained attention. Within the group of children with epilepsy, those with prior school or behavior difficulties and those whose parents reacted maladaptively to the onset and diagnosis of epilepsy performed worse than those without these adversities, in the sense that their RT increased inordinately with increasing task difficulty. Epilepsy-related variables did not explain any variance. Transient inordinately poor performances were found in 69% of patients and 40% of controls. CONCLUSIONS: Children with newly diagnosed "epilepsy only" do not have persistent attention deficits. AED treatment has no detrimental effect on attention. Prior school and behavior difficulties and a maladaptive reaction to the onset of epilepsy rather than epilepsy variables are related to decreased attentional efficiency.