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O2-6 Medical and socioeconomic outcome in adulthood of childhood onset epilepsy: Findings from the National Child Development Study
S4
Oral presentations
O2-5 The clinical spectrum of STXBP1 mutations in early onset epileptic encephalpathy: between Ohtahara-syndrome and West syndrome?
O2-6 Medical and socioeconomic outcome in adulthood of childhood onset epilepsy: Findings from the National Child Development Study
B. Ceulemans1,2,3 *, S. Weckhuysen4,5,6 , K. Verhaert1 , L. Deprez7,8,9 , A. Holmgren7,8,9 , A. Janssen10 , W. Van Paesschen11 , A. Jordanova4,5,12 , L. Lagae3,13 , P. De Jonghe4,5,14 . 1 Child Neurology, University Hospital of Antwerp, Antwerp, Belgium; 2 Child Neurology, University of Antwerp, Antwerp, Belgium; 3 Child Neurology, Epilepsy Centre Pulderbos, Pulderbos, Belgium; 4 Neurology, University of Antwerp, Antwerp, Belgium; 5 Neurology, Department of Molecular Genetics, VIB, Antwerp, Belgium; 6 Neurology, Epilepsy Centre Kempenhaeghe, Oosterhout, The Netherlands; 7 Biochemistry, University of Antwerp, Antwerp, Belgium; 8 Biochemistry, Department of Molecular Genetics, VIB, Antwerp, Belgium; 9 Biochemistry, Institute Born-Bunge, Antwerp, Belgium; 10 Child Neurology, University Hospital of Brussels, Brussels, Belgium; 11 Neurology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium; 12 Neurology, Institute Born-Bunge, Antwerp, Belgium; 13 Child Neurology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium; 14 Neurology, University Hospital of Antwerp, Antwerp, Belgium
R.F. Chin1,2,4 *, S. Pujar1,4 , P. Cumberland2 , C. Peckham2 , E. Ross2 , R.C. Scott1,2,3 . 1 Neurosciences, UCL − Institute of Child Health, London, United Kingdom; 2 MRC Centre of Epidemiology for Child Health, UCL − Institute of Child Health, London, United Kingdom; 3 Radiology and Physics, UCL − Institute of Child Health, London, United Kingdom; 4 The National Centre for Young People with Epilepsy, Lingfield, United Kingdom
Purpose: Within the group of early onset epileptic encephalopathies, Ohtahara and West syndrome are clearly defined syndromes. However some children present with a more atypical epileptic clinical presentation are difficult to classify in one of these syndromes. Recently de novo STXBP1 mutations have been identified in Ohtahara-syndrome. We tried to describe the clinical spectrum of children with STXBP1 mutations. Methods: A clinical well described group of 40 children with early onset epileptic encephalopathies with clear clinical description were screened for mutations in STXBP1 by performing sequence analysis of exons and intron-exon boundaries. These patients were also analyzed for the presence of microdeletions in STXBP1 using a quantitative PCR method named multiplex amplification quantification (MAQ). Correlation is made with the clinical syndrome. Results: Five novel mutations were found, including one splice-site, one frame shift and one nonsense mutation and two deletions affecting one or more entire exons. The mutations were proven ‘de novo’ mutations except for 2 where parental or maternal DNA was not available for examination. All 5 mutations were predicted to cause a loss of function, supporting their pathogenic nature. A clinical characteristics of the patients is very variable. The age of onset of the epilepsy ranges 3 days to 4, 5 months. Seizures can be atypical lateralized tonic seizures to typical epileptic spasms. The EEG pattern also varies from focal epileptic activity to typical patterns of hypsarrhythmia. Importantly, none of the children showed a suppression burst pattern on EEG. Four of the five patients became seizure free, two of which reacted immediately to vigabatrin. One child still has refractory seizures and is on polytherapy. All developed a severe mental retardation and three showed ataxia on clinical examination. Conclusion: In our patients, the clinical pattern of children with STXBP1 mutations seems to start with an early epileptic encephalopathy, situated between Othahara and West syndrome, with a remarkably good chance of seizure control but always with a severe effect on cognitive development.
Epilepsy is an important cause of illness during childhood. To increase understanding of the long-term outcomes of childhood epilepsy we investigated health and social outcomes in adulthood using data from a national cohort study, the 1958 British National Child Development Study (NCDS). Members have been followed since birth by interview/clinical examination at 7, 11, 16, 23, 33, 41 years with extensive data about biological, social, and lifestyle factors. Methods: 14761 (85% and representative) of the original 17414 NCDS members still participating at age 16 years were included. 99 (0.7%) (51 male) had epilepsy onset 16 yrs. Childhood epilepsy cases have been validated and classified. We examined social interaction, mental and general health, employment, education, and personal relationships. Regression techniques, adjusting for confounders, were used to investigate epilepsy as a risk factor for adverse outcomes. Results: Special needs schooling and history of status epilepticus were predictors for continued seizures at age 21 yrs. Compared to people without epilepsy, at 23 yrs people with childhood onset epilepsy were less likely to participate in sports (Odds Ratio [OR] 0.29; 95% CI 0.14 0.59, p = 0.001). At 33 yrs they were more likely to be depressed (OR 1.9; 95% CI 1.0−3.7, p = 0.05), less likely to be employed (OR 0.28; 95% CI 0.13 0.61, p = 0.001), less likely to have been married (OR 0.57; 95% CI 0.34 0.95, p = 0.03) and less likely to be a parent (OR 0.44; 95% CI 0.27 0.71, p = 0.001). They were sixfold (95% CI 1.4 26.1, p = 0.02) more likely to die by 41 yrs. Conclusion: In adulthood people with childhood onset epilepsy have markedly increased medical and socioeconomic difficulties compared to the general population. Session 3: Parallel free papers session Royal Hall 30 September 2009, 16.30 18.00 O3-1 Nocturnal oxyhemoglobin desaturation, reticulocytosis and intracranial arteriopathy in children with sickle cell disease N. Dlamini1,2 *, R.S. Bucks3 , S. Trompeter4 , M. Bynevelt5 , D.G. Gadian6 , D.E. Saunders5 , R. Lane7 , J.P. Evans4 , T.C. Cox5 , F.J. Kirkham2 . 1 Neurosciences, Evelina Children’s Hospital, London, United Kingdom; 2 Neurosciences, Institute of Child Health, London, United Kingdom; 3 School of Psychology, University of Western Australia, Perth, Australia; 4 Haematology, Great Ormond Street Hospital, London, United Kingdom; 5 Radiology, Great Ormond Street Hospital, London, United Kingdom; 6 Radiology and Physics, Institute of Child Health, London, United Kingdom; 7 Respiratory Medicine, Great Ormond Street Hospital, London, United Kingdom Objective: To determine 1. whether the severity of nocturnal oxyhemoglobin desaturation (NOD) is associated with the degree of arteriopathy, measured as signal loss in the terminal internal carotid, middle and anterior cerebral arteries on MRA 2. whether clinically active cerebrovascular disease is associated with hemolysis. Methods: Of 95 East London children with SCD without prior stroke who had overnight pulse oximetry, 47 (26 boys, 39 hemoglobin SS; mean age 9.1±3.1 years) also had MRA, steady state hemoglobin and reticulocyte count within 34 months.
Oral presentations
O2-5 The clinical spectrum of STXBP1 mutations in early onset epileptic encephalpathy: between Ohtahara-syndrome and West syndrome?
O2-6 Medical and socioeconomic outcome in adulthood of childhood onset epilepsy: Findings from the National Child Development Study
B. Ceulemans1,2,3 *, S. Weckhuysen4,5,6 , K. Verhaert1 , L. Deprez7,8,9 , A. Holmgren7,8,9 , A. Janssen10 , W. Van Paesschen11 , A. Jordanova4,5,12 , L. Lagae3,13 , P. De Jonghe4,5,14 . 1 Child Neurology, University Hospital of Antwerp, Antwerp, Belgium; 2 Child Neurology, University of Antwerp, Antwerp, Belgium; 3 Child Neurology, Epilepsy Centre Pulderbos, Pulderbos, Belgium; 4 Neurology, University of Antwerp, Antwerp, Belgium; 5 Neurology, Department of Molecular Genetics, VIB, Antwerp, Belgium; 6 Neurology, Epilepsy Centre Kempenhaeghe, Oosterhout, The Netherlands; 7 Biochemistry, University of Antwerp, Antwerp, Belgium; 8 Biochemistry, Department of Molecular Genetics, VIB, Antwerp, Belgium; 9 Biochemistry, Institute Born-Bunge, Antwerp, Belgium; 10 Child Neurology, University Hospital of Brussels, Brussels, Belgium; 11 Neurology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium; 12 Neurology, Institute Born-Bunge, Antwerp, Belgium; 13 Child Neurology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium; 14 Neurology, University Hospital of Antwerp, Antwerp, Belgium
R.F. Chin1,2,4 *, S. Pujar1,4 , P. Cumberland2 , C. Peckham2 , E. Ross2 , R.C. Scott1,2,3 . 1 Neurosciences, UCL − Institute of Child Health, London, United Kingdom; 2 MRC Centre of Epidemiology for Child Health, UCL − Institute of Child Health, London, United Kingdom; 3 Radiology and Physics, UCL − Institute of Child Health, London, United Kingdom; 4 The National Centre for Young People with Epilepsy, Lingfield, United Kingdom
Purpose: Within the group of early onset epileptic encephalopathies, Ohtahara and West syndrome are clearly defined syndromes. However some children present with a more atypical epileptic clinical presentation are difficult to classify in one of these syndromes. Recently de novo STXBP1 mutations have been identified in Ohtahara-syndrome. We tried to describe the clinical spectrum of children with STXBP1 mutations. Methods: A clinical well described group of 40 children with early onset epileptic encephalopathies with clear clinical description were screened for mutations in STXBP1 by performing sequence analysis of exons and intron-exon boundaries. These patients were also analyzed for the presence of microdeletions in STXBP1 using a quantitative PCR method named multiplex amplification quantification (MAQ). Correlation is made with the clinical syndrome. Results: Five novel mutations were found, including one splice-site, one frame shift and one nonsense mutation and two deletions affecting one or more entire exons. The mutations were proven ‘de novo’ mutations except for 2 where parental or maternal DNA was not available for examination. All 5 mutations were predicted to cause a loss of function, supporting their pathogenic nature. A clinical characteristics of the patients is very variable. The age of onset of the epilepsy ranges 3 days to 4, 5 months. Seizures can be atypical lateralized tonic seizures to typical epileptic spasms. The EEG pattern also varies from focal epileptic activity to typical patterns of hypsarrhythmia. Importantly, none of the children showed a suppression burst pattern on EEG. Four of the five patients became seizure free, two of which reacted immediately to vigabatrin. One child still has refractory seizures and is on polytherapy. All developed a severe mental retardation and three showed ataxia on clinical examination. Conclusion: In our patients, the clinical pattern of children with STXBP1 mutations seems to start with an early epileptic encephalopathy, situated between Othahara and West syndrome, with a remarkably good chance of seizure control but always with a severe effect on cognitive development.
Epilepsy is an important cause of illness during childhood. To increase understanding of the long-term outcomes of childhood epilepsy we investigated health and social outcomes in adulthood using data from a national cohort study, the 1958 British National Child Development Study (NCDS). Members have been followed since birth by interview/clinical examination at 7, 11, 16, 23, 33, 41 years with extensive data about biological, social, and lifestyle factors. Methods: 14761 (85% and representative) of the original 17414 NCDS members still participating at age 16 years were included. 99 (0.7%) (51 male) had epilepsy onset 16 yrs. Childhood epilepsy cases have been validated and classified. We examined social interaction, mental and general health, employment, education, and personal relationships. Regression techniques, adjusting for confounders, were used to investigate epilepsy as a risk factor for adverse outcomes. Results: Special needs schooling and history of status epilepticus were predictors for continued seizures at age 21 yrs. Compared to people without epilepsy, at 23 yrs people with childhood onset epilepsy were less likely to participate in sports (Odds Ratio [OR] 0.29; 95% CI 0.14 0.59, p = 0.001). At 33 yrs they were more likely to be depressed (OR 1.9; 95% CI 1.0−3.7, p = 0.05), less likely to be employed (OR 0.28; 95% CI 0.13 0.61, p = 0.001), less likely to have been married (OR 0.57; 95% CI 0.34 0.95, p = 0.03) and less likely to be a parent (OR 0.44; 95% CI 0.27 0.71, p = 0.001). They were sixfold (95% CI 1.4 26.1, p = 0.02) more likely to die by 41 yrs. Conclusion: In adulthood people with childhood onset epilepsy have markedly increased medical and socioeconomic difficulties compared to the general population. Session 3: Parallel free papers session Royal Hall 30 September 2009, 16.30 18.00 O3-1 Nocturnal oxyhemoglobin desaturation, reticulocytosis and intracranial arteriopathy in children with sickle cell disease N. Dlamini1,2 *, R.S. Bucks3 , S. Trompeter4 , M. Bynevelt5 , D.G. Gadian6 , D.E. Saunders5 , R. Lane7 , J.P. Evans4 , T.C. Cox5 , F.J. Kirkham2 . 1 Neurosciences, Evelina Children’s Hospital, London, United Kingdom; 2 Neurosciences, Institute of Child Health, London, United Kingdom; 3 School of Psychology, University of Western Australia, Perth, Australia; 4 Haematology, Great Ormond Street Hospital, London, United Kingdom; 5 Radiology, Great Ormond Street Hospital, London, United Kingdom; 6 Radiology and Physics, Institute of Child Health, London, United Kingdom; 7 Respiratory Medicine, Great Ormond Street Hospital, London, United Kingdom Objective: To determine 1. whether the severity of nocturnal oxyhemoglobin desaturation (NOD) is associated with the degree of arteriopathy, measured as signal loss in the terminal internal carotid, middle and anterior cerebral arteries on MRA 2. whether clinically active cerebrovascular disease is associated with hemolysis. Methods: Of 95 East London children with SCD without prior stroke who had overnight pulse oximetry, 47 (26 boys, 39 hemoglobin SS; mean age 9.1±3.1 years) also had MRA, steady state hemoglobin and reticulocyte count within 34 months.