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The reliability of visual interpretation of electroencephalograms (EEG) is of great importance in assessing the value of this diagnostic tool. We prospectively obtained 50 standard EEGs and 61 EEGs after partial sleep deprivation from 93 children (56 males, 37 females) with a mean age of 6 years 10 months (SE 5mo; range 4mo-15y 7mo) with one or more newly diagnosed, unprovoked seizures. Two clinical neurophysiologists independently classified the background pattern and the presence of epileptiform discharges or focal non-epileptiform abnormalities of each EEG. The agreement was substantial for the interpretation of the EEG as normal or abnormal (kappa 0.66), almost perfect for the presence of epileptiform discharges (kappa 0.83), substantial for the occurrence of an abnormal background pattern (kappa 0.73), and moderate for the presence of focal non-epileptiform discharges (kappa 0.54). In conclusion, the reliability of the visual interpretation of EEGs in children is almost perfect as regards the presence of epileptiform abnormalities, and moderate to substantial for the presence of other abnormalities. [ABSTRACT FROM AUTHOR]

Objective: This nationwide cohort study evaluates seizure responses to immunotherapy and antiepileptic drugs (AEDs) in patients with anti-leucine-rich glioma-inactivated 1 (LGI1), anti-NMDA receptor (NMDAR), and anti-gamma-aminobutyric-acid B receptor (GABA B R) encephalitis., Methods: Anti-LGI1, anti-NMDAR, and anti-GABA B R encephalitis patients with new-onset seizures were included. Medical information about disease course, AEDs and immunotherapies used, effects, and side effects were collected. Outcome measures were (1) seizure freedom while using AEDs or immunotherapy, (2) days to seizure freedom from start of AEDs or immunotherapy, and (3) side effects., Results: Of 153 patients with autoimmune encephalitis (AIE) (53 LGI1, 75 NMDAR, 25 GABA B R), 72% (n = 110) had epileptic seizures, and 89% reached seizure freedom. At least 53% achieved seizure freedom shortly after immunotherapy, and 14% achieved seizure freedom while using only AEDs ( p < 0.0001). This effect was similar in all types ( p = 0.0001; p = 0.0005; p = 0.013, respectively). Median time to seizure freedom from AEDs start was 59 days (interquartile range [IQR] 27-160), and 28 days from start of immunotherapy (IQR 9-71, p < 0.0001). Side effects were psychotic behavior and suicidal thoughts by the use of levetiracetam, and rash by the use of carbamazepine. Carbamazepine was more effective than levetiracetam in reducing seizures in anti-LGI1 encephalitis ( p = 0.031). Only 1 patient, of 86 surviving patients, developed epilepsy after resolved encephalitis., Conclusion: Epilepsy after resolved encephalitis was rare in our cohort of patients with AIE treated with immunotherapy. In addition, seizure freedom is achieved faster and more frequently after immunotherapy. Therefore, AEDs should be considered as add-on treatment, and similar to treatment of other encephalitis symptoms, immunotherapy is crucial., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

It is unknown whether treatment with antiepileptic drugs in children with epilepsy with a presumed good prognosis is always necessary. We aimed to study the course of newly diagnosed epilepsy in children with a presumed good prognosis who are managed without AED treatment. A total of 151 children (one month to 12 years of age) with two to five lifetime unprovoked seizures (excluding febrile convulsions), were followed for three years. Treatment was initially withheld. Children with symptomatic epilepsy, or absence or myoclonic epilepsy, were excluded. AED treatment was started after >10 lifetime seizures or an episode of status epilepticus during follow-up, or if the parents or treating physician deemed it otherwise necessary. During follow-up, 113 children continued to meet our criteria for refraining from treatment with antiepileptic drugs, yet 30 started treatment at the request of the parents. Thirty-eight children at some time met the criteria to start treatment, but the parents of 16 declined treatment. In all, 99 (66%) children maintained the no-treatment regime. Ninety-eight children (65% of 151) reached terminal remission for at least one year, including 83 who did not receive antiepileptic drug treatment (84% of the untreated 99). Mean terminal remission was significantly longer in the group with a total of <10 seizures compared to those with >10 seizures. Treatment did not increase the length of terminal remission. Adverse events, including traumatic injury, occurred equally in the treated and untreated children. Measures of quality of life suggested a better outcome in those without treatment. Children with newly diagnosed epilepsy with a presumed good prognosis may not need immediate AED treatment. Postponing treatment does not alter the chance of remission or the risk of accidents and adverse events and appears to be associated with a good quality of life.

Purpose: To quantify underreferral for epilepsy surgery in The Netherlands, and reveal its causes., Methods: Cross-sectional sample of medical files of epilepsy patients from eight general hospitals and two tertiary care epilepsy centers. We selected patients, not seizure free despite 3 or more anti-epileptic drugs. Medical records were judged by an expert panel whether referral should have been done according to published Dutch guidelines. The treating neurologists were confronted with the panel's judgement., Key Findings: In a sample of 1424 patients, 69 had been referred; another 265 were intractable and not referred; 139 of these 265 patients should have been according to the panel. In 89 of 139 patients, the neurologist gave additional arguments for not referring, mainly the physician's estimate of (low) seizure burden or the patient's psychological condition. In 66 of 89 cases, this could not convince the panel. Attitudes were similar in secondary and tertiary treatment centers. Multivariable data analysis showed independent predictors of incorrectly, versus correctly, not referred patients., Significance: Substantial underreferral exists in The Netherlands, withholding refractory patients seizure freedom. Adherence to existing guidelines, better prioritizing of surgical work-up, and unprejudiced discussion of surgical treatment with the patient, could lead to 2-2.5 times more referrals., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: To determine long-term outcome in a cohort of children with newly diagnosed benign childhood epilepsy with centrotemporal spikes (BECTS)., Methods: 29 children with BECTS were included in the Dutch Study of Epilepsy in Childhood. Each child was followed for 5 years, and subsequently contacted 12-17 years after enrolment to complete a structured questionnaire. Twenty children had typical BECTS, nine had atypical BECTS (age at onset <4 years, developmental delay or learning difficulties at inclusion, other seizure types, atypical EEG abnormalities)., Results: Mean age at onset of epilepsy was 8.0 years with slight male preponderance. Most common seizure-types before enrolment were generalized tonic-clonic seizures (GTCS) and simple partial seizures; in 86% of the children seizures occurred during sleep. After 12-17 years, 96% had a terminal remission (TR(F)) of more than 5 years and 89% of more than 10 years. Mean duration of epilepsy was 2.7 years; mean age at reaching TR(F) was 10.6 years. Many children (63%) had experienced one or more (secondary) GTCS. Antiepileptic drugs were used by 79% of the children with a mean duration of 3.0 years. None of the children seemed to have developed learning problems or an arrest of cognitive development during follow-up. No significant differences were observed in patient characteristics or outcome between children with typical BECTS and children with atypical BECTS., Conclusions: All children in our cohort, both those with typical and atypical BECTS, had a very good prognosis with high remission rates after 12-17 years. None of the predictive factors for disease course and outcome observed in earlier studies (other seizure types, age at onset, multiple seizures at onset) were prognostic in our cohort., (Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Complaints about side-effects of antiepileptic drugs (AEDs) may be overlooked in clinical practice. We assessed the value and risks of an active intervention policy for reported complaints in a randomized controlled pragmatic trial., Methods: This randomized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals. They were considered well-managed by their treating physician, but reported moderate to severe complaints on a questionnaire (SIDAED, assessing SIDe effects in AED treatment). The intervention was adjustment of AED treatment (53 patients), either reduction of dose or switch of AED, versus continuation of treatment unchanged (58 control patients) during 7 months. Primary outcomes were quality of life (Qolie-10) and complaints score. Secondary outcome measures were the occurrence of seizures or adverse events., Results: After 7 months, the relative risk (RR) for improvement in quality of life was 1.80 (1.04-3.12) for the intervention group compared to control and the RR of decrease in complaints was 1.34 (0.88-2.05). In 58% of patients randomized to adjustment, the medication had indeed been changed., Discussion: In conclusion, despite a possible risk of seizure recurrence, adjustment of drug treatment in well-managed patients with epilepsy, who report considerable complaints, improves the quality of life.

Summary: We determined long-term outcome and the predictive value of baseline and EEG characteristics on seizure activity evolution in 47 children with newly diagnosed childhood absence epilepsy (CAE) included in the Dutch Study of Epilepsy in Childhood. All children were followed for 12-17 years. The children were subdivided in three groups for the analyses: those becoming seizure-free (I) within 1 month after enrolment; (II) 1-6 months after enrolment; and (III) more than 6 months after enrolment or having seizures continuing during follow-up. No significant differences were observed between groups in sex, age at onset, occurrence of febrile seizures, and positive first-degree family history for epilepsy. All groups had high remission rates after 12-17 years. Significantly more relapses occurred in group III than in group I. Total duration of epilepsy and mean age at final remission were 3.9 and 9.5 years, respectively, being significantly longer and higher in group III than in groups I and II. In all groups only a small number of children (total 13%) developed generalized tonic-clonic seizures. In conclusion, our children with CAE had an overall good prognosis with few children (7%) still having seizures after 12-17 years. Remission rate in children with CAE cannot be predicted on the basis of baseline and EEG characteristics. The early clinical course (i.e. the first 6 months) has some predictive value with respect to the total duration of absence epilepsy.

Epilepsy is very common. The prevalence in the Netherlands is 5:1000 inhabitants. The diagnosis is mostly made on clinical grounds and often incorrectly. If there are doubts about the diagnosis, the patient can be referred to a specialised centre for a seizure registration with an EEG and video recording. The disorder generally responds well to treatment with anti-epileptics. Some 60-70% of patients treated with these remain free of seizures. If medicinal treatment fails then a surgical intervention can be considered. For patients with temporal epilepsy in particular, there is quite a high chance that a surgical intervention will resolve the symptoms. Where it proves difficult to satisfactorily adjust the medication of a patient, stimulation of the left vagus nerve can be considered. Paying more attention to the side effects of the medication and the limitations imposed on the patients can reduce the negative influence of epilepsy on the quality of life.

Purpose: To study course and outcome of epilepsy in children having had a status epilepticus (SE) as the presenting sign or after the diagnosis., Methods: A total of 494 children with newly diagnosed epilepsy, aged 1 month through 15 years, were followed prospectively for 5 years., Results: A total of 47 Children had SE. Forty-one of them had SE when epilepsy was diagnosed. For 32 (78%), SE was the first seizure. SE recurred in 13 out of 41 (32%). Terminal remission at 5 years (TR5) was not significantly worse for these 41 children: 31.7% had a TR5 <1 year versus 21.2% of 447 children without SE. They were not more often intractable. Five out of six children with first SE after diagnosis had a TR5 <1 year. Mortality was not significantly increased for children with SE. Independent factors associated with SE at presentation were remote symptomatic and cryptogenic etiology, and a history of febrile convulsions. Children with first SE after inclusion more often had symptomatic etiology., Conclusions: Although we find a trend for shorter TR5 in children with SE at presentation, outcome and mortality are not significantly worse. Etiology is an important factor for prognosis. Children with SE during the course of their epilepsy have a worse prognosis and a high recurrence rate of SE. This outcome is not due to the SE itself, but related to the etiology and type of epilepsy. The occurrence of SE is just an indicator of the severity of the disease.

Purpose: To validate two prognostic models for childhood-onset epilepsy designed to predict a terminal remission of <6 months at 2 years after diagnosis in children referred to the hospital., Methods: A hospital-based cohort of children with newly diagnosed epilepsy was recruited and followed up for 2 years to validate previously developed models. One model was based on variables collected at intake, and the other was based on intake variables plus variables collected during the first 6 months of follow-up. The accuracy of both models was estimated by measuring the area under the receiver-operant-characteristic curves (ROC area)., Results: The ROC area of the model developed with intake variables was 0.69 [95% confidence interval (CI), 0.64-0.74] for the original cohort and 0.62 (95% CI, 0.55-0.69) for the validation cohort. The best combination of sensitivity and specificity for the original cohort was 61.6% and 69.1%, whereas it was 60.0% and 61.4% for the validation cohort. For the model with intake and 6-month variables combined, the ROC area was 0.78 (95% CI, 0.73-0.82) for the original cohort and 0.71 (95% CI, 0.64-0.78) for the validation cohort. The sensitivity and specificity were 72.6% and 73.1%, respectively, for the original cohort and 67.4% and 60.2%, respectively, for the validation cohort., Conclusions: Although both models predict outcome better than chance, they are insufficiently accurate to be of practical value. Both models performed marginally less well with the validation cohort than with the original cohort, but in both instances, the model based on intake and 6-month variables was more accurate.

Objectives: Side-effects of anti-epileptic drugs (AEDs) may be overlooked in patients with epilepsy in everyday clinical practice. The aim of this study was to assess the prevalence and severity of subjective complaints in patients who were considered to be well-controlled and to assess whether these complaints are related to medication, personality traits, or other determinants., Methods: We included patients with epilepsy who were considered to be well-controlled in a cross-sectional study in seven hospitals in the Netherlands. Their medication had not been changed for six months and an apparent reason to change the medication was lacking at the time of enrolment. Subjective complaints were assessed with a 46-item questionnaire. Using multivariable linear regression modeling, we assessed whether patient characteristics, epilepsy characteristics, medication, quality of life (Qolie-10), and personality traits (SCL-90) explained the presence and severity of complaints., Results: Of 173 included patients, 67% reported moderate to severe subjective complaints on the questionnaire. Cognitive complaints were reported most frequently. Multivariate modeling showed that 61% of the variance in reported complaints could be explained by included determinants. The prevalence and severity of complaints was associated with AED polytherapy and higher scores on psycho neuroticism., Conclusions: Patients who were considered to be well-controlled proved to report an unexpectedly high number of subjective complaints. Both medication and aspects of personality contributed to the level of complaints. Our study illustrates that subjective side-effects are easily overlooked in everyday clinical practice, possibly because in practice a generally phrased question is used to detect side-effects.

The hypothesis that brain damage during infancy causes pathological left-handedness was tested by assessing handedness in 182 survivors of childhood non-Hemophilus influenza type b bacterial meningitis in the Netherlands (mean age of 9.7 years). These children were selected randomly after clustering them into those with or without parental report on academic and behavioural problems. Medical records were obtained from the hospitals, while handedness and neurodevelopmental outcome were assessed at school age. Logistic regression analysis was used to study the relationship between a severity score of bacterial meningitis and handedness. Fifteen percent were left-handed. Severity of childhood bacterial meningitis was related to left-handedness (Odds ratio (OR) 6.2, 95% confidence interval (CI) 2.0-18.6 for those with a total severity score above the median as compared to those below). Compared to non-left-handed children, left-handed children had lower IQ (mean difference -6.6, 95% CI -12 to -1.2), tended to have lower vocabulary scores on WISC-r (-1.0, -2.1 to 0), and lower Beery scores on visual-motor integration (-4.9, -10.1 to 0.4). Left-handed children also tended to have more combined academic and behavioural limitations (OR 2.7, 95% CI 0.9-8.6), lower manual speed of the dominant hand (mean difference -9 taps, p < 0.05) and better manual steadiness in the non-dominant hand (mean difference of contact's time -2.7 s, p < 0.05). Left-handed post-meningitic children generally have worse neurodevelopmental outcome than non-left-handed survivors. Our results support the role of early life brain damage in left-handedness.

The diagnosis of a first seizure or epilepsy may be subject to interobserver variation and inaccuracy with possibly far-reaching consequences for the patients involved. We reviewed the current literature. Studies on the interobserver variation of the diagnosis of a first seizure show that such a diagnosis is subject to considerable interobserver disagreement. Interpretation of the electroencephalogram (EEG) findings is also subject to interobserver disagreement and is influenced by the threshold of the reader to classify EEG findings as epileptiform. The accuracy of the diagnosis of epilepsy varies from a misdiagnosis rate of 5% in a prospective childhood epilepsy study in which the diagnosis was made by a panel of three experienced pediatric neurologists to at least 23% in a British population-based study, and may be even higher in everyday practice. The level of experience of the treating physician plays an important role. The EEG may be helpful but one should be reluctant to make a diagnosis of epilepsy mainly on the EEG findings without a reasonable clinical suspicion based on the history. Being aware of the possible interobserver variation and inaccuracy, adopting a systematic approach to the diagnostic process, and timely referral to specialized care may be helpful to prevent the misdiagnosis of 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.

Background: Few data exist with respect to the occurrence of chronic side effects due to antiepileptic drugs (AED) in routine clinical practice., Objective: To evaluate the prevalence of subjective complaints which patients with epilepsy regard as side effects of their AED treatment in a community-based population., Methods: Cross-sectional study. Subjects were identified through the database of AED-use in the pharmacies in a suburban area in The Netherlands. Respondents completed a brief questionnaire about their epilepsy, including a checklist with 30 complaints, which are common in AED users., Results: We present data of 346 responding adults with treated epilepsy from a population of 107,000 adult inhabitants. Eighty percent was using monotherapy, with few patients taking new AEDs. Almost 60% of the patients reported complaints probably due to side effects in at least three domains. General CNS-related side effects were reported most often; memory problems (21.4% of the patients) and fatigue (20.3%) were dominant. Polytherapy was associated with more side effects than monotherapy. We identified differences in profiles of complaints between valproate, carbamazepine and phenytoin monotherapy. Complaints were not substantially associated with ongoing seizures or other treatment factors., Conclusions: The majority of patients taking AEDs for epilepsy think they have side effects form their drugs, even when seizures were in remission and when monotherapy was used. Our findings suggest a need to improve monitoring of complaints of side effects of AEDs and to explore the feasibility of interventions aimed at reduction of such complaints in everyday clinical practice.

Knowing the prognosis of epilepsy will undoubtedly influence the treatment strategy. This study aimed to define the prospects of newly diagnosed childhood epilepsy, assess the dynamics of its course, identify relevant variables and develop models to assess the individual prognosis. Four hundred and fifty-three children with newly diagnosed epilepsy were followed for 5 years. Terminal remission at 5 years (TR5) was compared with terminal remission at 2 years (TR2) and with the longest remission during follow-up. Variables defined at intake and at 6 months of follow-up were analysed for their prognostic relevance. In multivariate analyses, combinations of variables were tested to develop reliable models for the calculation of the individual prognosis. Data on treatment, course during follow-up and epilepsy syndromes were also studied. Three hundred and forty-five children (76%) had a TR5 >1 year, 290 (64%) >2 years and 65 (14%) had not had any seizure during the entire follow-up. Out of 108 children (24%) with TR5 <1 year, 27 were actually intractable at 5 years. Medication was started in 388 children (86%). In 227 of these (59%), anti-epileptic drugs (AEDs) could be withdrawn. A TR5 >1 year was attained by 46% on one AED, on the second AED by 19%, and by 9% on all additional AED regimes. Almost 60% of the children treated with a second or additional AED regime had a TR5 >1 year. Variables predicting the outcome at intake were aetiology, history of febrile seizures and age. For intake and 6-month variables combined, sex, aetiology, postictal signs, history of febrile seizures and TR at 6 months were significant. The model derived from intake variables only predicted TR5 <1 year correctly in 36% and TR5 >1 year in 85% (sensitivity 0.65, specificity 0.64). The corresponding values for the model derived from intake and 6-month variables were 43 and 88% (sensitivity 0.69, specificity 0.71). The course of the epilepsy was constantly favourable in 51%, steadily poor in 17%, improving in 25% and deteriorating in 6%. Intractability was in part only a temporary phenomenon. The outcome at 5 years in this cohort of children with newly diagnosed epilepsy was favourable in 76%; 64% were off medication at that time. Almost a third of the children had a fluctuating course; improvement was clearly more common than deterioration. After failure of the first AED, treatment can still be successful. Models predicting the outcome have fewer misclassifications when predicting a long terminal remission than when predicting continuing seizures.

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.

The antiepileptic drug primidone is to be withdrawn from sale by January 2004. After this date, the drug will still be available for a time, but only on a limited basis. Most primidone users are elderly patients who have been prescribed this drug for many years. Changing to a new drug constitutes a health risk for them. If primidone treatment is discontinued too quickly, withdrawal seizures may appear, some of which may be severe. In patients who have not suffered an epileptic seizure for many years, discontinuing medication may be considered. Whenever continuation of anticonvulsive treatment is desirable, it may probably be a good idea to switch over to some newer antiepileptic drug. If a simple and quick substitution is essential, primidone may be replaced by its main metabolite: phenobarbital. General practitioners and neurologists are strongly advised to alter patients' medication in good time.

Introduction: Several guidelines recommend the use of propofol for the treatment of refractory status epilepticus. An increased mortality rate in high dose, long-term treatment with propofol in adult patients was published recently. This prompted us to assess the literature on the scientific evidence for the efficacy and safety of propofol in the treatment of refractory status epilepticus., Methods: Medline was searched and the three authors independently reviewed all Medline abstracts for selection of papers., Results: We included 22 articles with original data on the use of propofol in refractory status epilepticus. Randomised clinical trials were lacking. Two non-randomised studies compared propofol with barbiturates and midazolam respectively. Both studies reported a higher risk of mortality for propofol. In addition, case reports and case series on the use of propofol as anaesthetic or sedative in children and adults reported several lethal cases., Conclusions: Serious doubts may be raised on the safety of propofol in the treatment of refractory status epilepticus. The two non-randomised studies and several case reports show an increased risk of mortality. Guidelines should not recommend the use of propofol as a routine treatment in refractory status epilepticus before a proper randomised trial has been performed.

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.

Objective: This study aimed at exploring the psychosocial reactions to epilepsy in a group of patients with uncomplicated well-controlled epilepsy., Method: One hundred and ninety-eight patients, referred by neurologists in a general hospital completed a questionnaire, consisting of simple open questions about the epilepsy and the drug treatment. Additionally, the patients were asked to complete the QOLIE-10-scale as well as a short questionnaire with questions about attitudes towards epilepsy and the treatment., Results: The overall psychosocial outcome was favourable in our study sample. About 50% of the patients have a paid job, have an average educational level and the majority (almost 70%) of the patients have a partner. This is not different from findings in the general population. In line with these social findings, the patients report in majority that the epilepsy is well integrated: as a rule the family and friend are informed and they feel that the epilepsy is accepted in society. Restrictions are limited to activities such as swimming. Consequently, quality of life (QOL) is high for the majority of the patients, with only 6% of the patients reporting a low QOL., Discussion: It is often claimed that people with epilepsy, as a group, have more psychosocial problems than control populations of healthy subjects. As this may be true for the average comparisons between patients with epilepsy and controls, we must take into account during clinical practice that these problems occur predominantly in the minority of patients with refractory epilepsy. Patients with well-controlled epilepsy do not show worrying reactions to the epilepsy.

We used a parent-completed 20-item "side effect scale" quantifying complaints that parents perceive to be caused by antiepileptic drugs (AEDs) in 108 children with active epilepsy. We studied the associations between parent-reported complaints, severity of seizures, and restrictions due to epilepsy, and clinical data including number and AED load. In 85% of the children at least one complaint was reported, in less than 20% complaints were perceived as a substantial problem. In a multivariate analysis, there was no significant relationship between the "side effect scale" score and AED load, or the number of AEDs. However, complaints were associated with parent-reported frequency and severity of seizures. We conclude that the adverse effects of seizures or parental concern about the severity and intractability of seizures in their children may have influenced the reported complaints.

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.

Objective: Long-term follow-up studies of patients with epilepsy have revealed an increased mortality risk compared with the general population. Mortality of children who have epilepsy in modern times is as yet unknown. Therefore, the objective of this study was to determine mortality of children who have epilepsy in comparison with the general population., Methods: Between August 1988 and August 1992, 472 children, aged 1 month to 16 years, who presented in 1 of the participating hospitals with 2 or more newly diagnosed unprovoked seizures or at least 1 status epilepticus were enrolled in the study. All children were followed for 5 years or until death. The number of deaths observed during follow-up was compared with the expected number of deaths in the same age group in the general population in the Netherlands., Results: Nine children died during follow-up, amounting to a mortality rate of 3.8/1000 person-years, which is sevenfold higher than expected (95% confidence interval = 2.4-11.5). No deaths were observed among the 328 children who had epilepsy of nonsymptomatic cause. All deceased children had epilepsy that was caused by a static or progressive neurologic disorder (mortality risk = 22.9; 95% confidence interval = 7.9-37.9). None of them died from sudden unexpected and unexplained death of epilepsy., Conclusions: In our cohort, we found no indication that children who have nonsymptomatic epilepsy have an increased mortality risk compared with the general population, whereas children who have symptomatic epilepsy have a 20-fold increased mortality risk. These data provide guidance for counseling parents of children who have epilepsy.

Purpose: To examine which variables available early in the course of childhood epilepsy are associated with a poor short-term outcome and to develop models to predict such an outcome., Methods: We prospectively followed up 466 children with newly diagnosed epilepsy for 2 years. Variables were collected at intake and after 6 months. Outcome was defined as the duration of the terminal remission (TR): poor (<6 months) and not poor (> or =6 months)., Results: Of the subjects, 31% had a poor outcome. Multivariate analysis based on the intake variables identified number of seizures, seizure type, and etiology as risk factors for a poor outcome. With the intake and 6-month variables combined, seizure type, etiology, the number of seizures, and not attaining a 3-month remission during these 6 months, and the EEG at 6 months were predictive variables. A predictive model based on the multivariate logistic-regression analysis with the intake variables was correct in 56% of the children in whom it predicted a poor outcome and in 73% of the children in whom it predicted a not-poor outcome. With the intake and 6-month variables together, these percentages were 66 and 79%, respectively. The sensitivity of these models was low (29 and 47%, respectively); the specificity was good (90 and 89%)., Conclusions: The 2-year outcome of childhood epilepsy is closely related to its early course. The prognosis is poor in approximately 30% of patients. By using our data, the prediction of a poor outcome is correct in almost two thirds of the patients; however, the models produce many false-negative predictions.

Background: It is not known how many children with epilepsy may not need treatment with antiepileptic drugs (AEDs), how many respond unsatisfactorily to subsequent treatment regimens, and how many achieve "acceptable control" despite lack of remission., Methods: In a prospective multicenter hospital-based study, 494 children with a broad range of seizure types and types of epilepsy were followed up for at least 2 years. There was no standard treatment protocol. We describe the treatment strategies applied to these children by the neurologists in charge and outcome with respect to remission from seizures., Results: Treatment was initially withheld in 29% of the children, and after 2 years 17% still had not received any AEDs. There were no serious complications caused by withholding treatment. Of the children treated with AEDs, 60% were still using the first AED after 2 years; 80% received monotherapy and 20%, polytherapy. Children with severe symptomatic epilepsies, such as the West or Lennox-Gastaut syndrome, received polytherapy early on in the course of treatment. When 3 regimens had failed, the chance of achieving a remission of more than 1 year with subsequent regimens was 10%. Nevertheless, 15 of 50 children receiving AEDs in whom the "longest remission ever" was less than 6 months did achieve acceptable seizure control according to the neurologist in charge of treatment. Hence, of 494 children, only 35 (7%) developed an intractable form of epilepsy, defined as failure to bring seizures under acceptable control., Conclusions: A substantial percentage of children with new-onset epilepsy did not need treatment with AEDs. Chances of achieving a good outcome declined with subsequent treatment regimens. Not all children with recurrent seizures were suffering from intractable epilepsy; some had achieved acceptable control of seizures.

Objective: To assess the accuracy of the diagnosis of a first unprovoked seizure in childhood, the recurrence rate within two years, the risk factors for recurrence, and the long term outcome two years after recurrence., Methods: One hundred and fifty six children aged 1 month to 16 years after a first seizure, and 51 children with a single disputable event were followed up. The diagnosis of a seizure was confirmed by a panel of three child neurologists on the basis of predescribed diagnostic criteria. None of the children was treated after the first episode., Results: Five children with a disputable event developed epileptic seizures during follow up. The diagnosis did not have to be revised in any of the 156 children with a first seizure. The overall recurrence rate after two years was 54%. Significant risk factors were an epileptiform EEG (recurrence rate 71%) and remote symptomatic aetiology and/or mental retardation (recurrence rate 74%). For the 85 children with one or more recurrences, terminal remission irrespective of treatment two years after the first recurrence was >12 months in 50 (59%),

We studied recurrence rate, risk factors for recurrence, and outcome after recurrence in children after early withdrawal of antiepileptic drugs (AEDs). One hundred sixty-one children with newly diagnosed epilepsy who had become seizure free within 2 months after starting treatment and remained so for 6 months were randomly assigned to immediate withdrawal of AEDs (n = 78) or continuation of treatment for another 6 months followed by withdrawal (n = 83). The probability of remaining seizure free at 24 months after randomization was 51% (95% CI, 40 to 62) in Group A and 52% (41 to 63) in Group B. Significant predictive factors for relapse were partial epilepsy, seizure onset at 12 years or older, defined etiology, and epileptiform EEG before randomization. At the end of follow-up (median, 41.9 months), 129 children (80.6%) had a terminal remission of at least 1 year, 88 without AEDs and 41 with AEDs. No significant difference in outcome was found between Groups A and B. In children with epilepsy and an early response to therapy, AED withdrawal after 6 or 12 months of treatment leads to seizure recurrence in approximately half of all patients regardless of the duration of therapy. More than 60% of those with one or more recurrences reach a terminal remission of at least 1 year after long-term follow-up with or without AEDs.

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 seizure type as the proband. These findings confirm the role of genetic factors in the pathogenesis of epilepsy.

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.

Purpose: We wished to compare a parent-completed scale quantifying seizure severity (SS) in children with various seizure types with the clinicians' impression of SS and other clinical data., Methods: The parents of 117 children with recurrent seizures completed a 13-item, subjective scale (The Hague Seizure Severity Scale, HASS). Eight treating neurologists quantified SS on a 10-point Visual Analog Scale (VAS) and supplied other clinical data., Results: Both the HASS and the VAS assessments of SS showed considerable variation within one seizure type. Significant differences were noted between groups with (a) absences and simple partial seizures (SPS), (b) complex partial seizures (CPS), and (c) generalized tonic-clonic seizures (GTCS). The correlation coefficient between the neurologists' and the parents' scores was 0.45 but did not exceed 0.26 after stratification for seizure type. The parents' score was not substantially influenced by various other clinical variables. The neurologists' score was correlated with resistance to treatment and presence of mental retardation., Conclusions: The SS ratings of the parents and the neurologists were not substantially correlated. The consideration that parents, as eyewitnesses to the seizures, are probably better judges of SS than clinicians may favor the use of a parent-completed scale to quantify SS. The HASS is a valid and reliable measure of parent-perceived SS that can be useful as an outcome measure in childhood epilepsy.

Objective: To assess decleration and acceleration in the disease process in the initial phase of epilepsy in children with new onset tonic-clonic seizures., Study Design: Hospital based follow up study., Setting: Two university hospitals, a general hospital, and a children's hospital in the Netherlands., Patients: 204 children aged 1 month to 16 years with idiopathic or remote symptomatic, newly diagnosed, tonic-clonic seizures, of whom 123 were enrolled at time of their first ever seizure; all children were followed until the start of drug treatment (78 children), the occurrence of the fourth untreated seizure (41 children), or the end of the follow up period of two years (85 untreated children)., Main Outcome Measures: Analysis of disease pattern from first ever seizure. The pattern was categorised as decelerating if the child became free of seizures despite treatment being withheld. In cases with four seizures, the pattern was categorised as decelerating if successive intervals increased or as accelerating if intervals decreased. Patterns in the remaining children were classified as uncertain., Results: A decelerating pattern was found in 83 of 85 children who became free of seizures without treatment. Three of the 41 children with four or more untreated seizures showed a decelerating pattern and eight an accelerating pattern. In 110 children the disease process could not be classified, mostly because drug treatment was started after the first, second, or third seizure. The proportion of children with a decelerating pattern (42%, 95% confidence interval 35% to 49%) may be a minimum estimate because of the large number of patients with an uncertain disease pattern., Conclusions: Though untreated epilepsy is commonly considered to be a progressive disorder with decreasing intervals between seizures, a large proportion of children with newly diagnosed, unprovoked tonic-clonic seizures have a decelerating disease process. The fear that tonic-clonic seizures commonly evolve into a progressive disease should not be used as an argument in favour of early drug treatment in children with epilepsy.

We have developed two outcome measures for childhood epilepsy: a seizure severity (SS) scale and a side-effects (SE) scale. Both scales have been designed for completion by parents. The scales were tested in two pilot phases and the results of this stepwise analysis are described here. The final scales' psychometric properties were assessed in a group of 80 children with active epilepsy, representative of the population at whom the scales were aimed: children with chronic epilepsy, aged 4-16 years, including all seizure types and epilepsies, as well as children with neurological comorbidity. The SS scale and SE scale showed good internal consistency and test-retest stability. Although there was a significant positive correlation between the SS scale and the SE scale, this was low, indicating that the scales measure a different clinical trait. The SE scale consisted of two subscales: a Toxic subscale, measuring the severity of dose-related side-effects, and a Chronic subscale, measuring the severity of long-term behavioural and cognitive side-effects. These subscales for side-effects showed a high correlation and can be used as a joint scale. These scales have the potential to improve outcome assessment in childhood epilepsy and they can be used to assess important aspects of quality of life in this population.

We prospectively studied the reliability and accuracy of the electroencephalogram as a predictor of the risk of recurrence within 2 years in 157 patients with untreated idiopathic first seizures. In all patients, a standard electroencephalogram and, if necessary, an electroencephalogram after partial sleep deprivation were obtained. All electroencephalograms were scored by one observer according to a fixed protocol. The finding of epileptic discharges was associated with a risk of recurrence of 83% (95% confidence interval, 69% to 97%) vs 41% (95% confidence interval, 29% to 53%) in patients with nonepileptic abnormalities and 12% (95% confidence interval, 3% to 21%) in patients in whom both electroencephalograms were normal. The sensitivity proved to be 48%. Interobserver agreement among four neurologists, who independently read 50 electroencephalograms, was found to be moderate. Predictive value for each observer, however, was good. We conclude that electroencephalogram findings may play a role in the decision to initiate or delay treatment after an idiopathic first seizure.

Objective: To assess the accuracy of the diagnosis, recurrence rate, and fate after the first recurrence in adult patients with an untreated idiopathic first seizure., Design: Hospital based follow up study., Setting: One university hospital and three general hospitals in The Netherlands., Patients: 165 patients aged 15 years or more with a clinically presumed idiopathic seizure; diagnosis was based on a description of the episode according to prespecified diagnostic criteria., Main Outcome Measures: Results of additional investigations and follow up regarding the accuracy of the diagnosis; first recurrence; and response to treatment after the first recurrence., Results: Computed tomography showed major abnormalities in 5.5% of the patients and follow up led to doubts about the initial clinical diagnosis in another 6%. Cumulative risk of recurrence was 40% at two years. The cumulative risk of recurrence at two years was 81% (95% confidence interval 66% to 97%) in patients with epileptic discharges on a standard or partial sleep deprivation electroencephalogram, 39% (27% to 51%) in patients with other electroencephalographic abnormalities, and 12% (3% to 21%) in patients with normal electroencephalograms. Treatment was initiated in most patients who had one or more recurrences; 40 (70%) patients were completely controlled, eight (14%) had sporadic seizures, and nine (16%) did not become free of seizures within one year despite treatment., Conclusions: The decision to initiate or delay treatment should be based on electroencephalographic findings.