Validation of two prognostic models predicting outcome at two years after diagnosis in a new cohort of children with epilepsy:The Dutch study of epilepsy in childhood

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

Mortality risk in children with epilepsy:The Dutch Study of Epilepsy in Childhood

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

Mortality risk in children with epilepsy:The Dutch Study of Epilepsy in Childhood

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

Long-term outcome of childhood absence epilepsy: Dutch Study of Epilepsy in Childhood

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 (1) within 1 month after enrolment; (11) 1-6 months after enrolment; and (111) 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. (C) 2008 Elsevier B.V. All rights reserved

Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease

Cowden disease, also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome with a high risk of breast and thyroid cancer, The gene involved has been localized to chromosome 10q22-23. Recently, the tumour suppressor gene PTEN/MMAC1, encoding a putative protein tyrosine or dual-specificity phosphatase, was cloned from that region and three mutations were detected in patients with Cowden disease, We confirmed that the PTEN/MMAC1 gene is indeed the gene for Cowden disease by a refined localization of the gene to the interval between D10S1761 and D10S541, which contains the PTEN/MMAC1 gene and by mutation analysis in eight unrelated familial and 11 sporadic patients with Cowden disease. Eight different mutations were detected in various regions of the PTEN/MMAC1 gene, One mutation was detected twice, All detected changes in the gene can be predicted to have a very deleterious effect on the putative protein, Five of the nine patients have a mutation in exon 5 coding for the putative active site and flanking amino acids. Evaluation of the clinical data of the patients in which a mutation could be detected gives no clear indications for a correlation between the genotype and phenotype, In 10 patients no mutation could be detected so far, In support of the linkage data, no evidence has emerged from the phenotype of these patients suggestive for genetic heterogeneity