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Risk factors, prevalence and impact of comorbid autism in pediatric epilepsy: A population-based study
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 1 ( 2 0 1 7 ) e 1 8 5 ee 1 9 0
Official Journal of the European Paediatric Neurology Society
Abstracts of EPNS 2017 e 12th European Paediatric Neurology Society Congress, 20e24 June 2017, Lyon, France POSTER PRESENTATIONS Friday, June 23 EPILEPSY: EPIDEMIOLOGY AND FOLLOW-UP P3-3 Therapeutic itinerary of epileptic patients managed in loandjili general hospital Prince Eliot Galieni Sounga Bandzouzi, Christelle Oko-Lossambo, Saurel Ngassaki, Godefroy Charles Koubemba. Republic of Congo Objective: Describe the different outpatient therapeutic itinerary of the Neurology clinic Hospital of loandjili. Methods: We conducted a descriptive and analytical cross-sectional study over a period of 6 months, from 3 January 2015 to 30 June 2015, in patients with epilepsy followed in outpatient of the Neurology clinic. Results: Sixty-five patients (30.6%) were enrolled. 33 females (50.8%) and 32 males (49.2%). The average age was 24.8 years (3 years to 69 years). The majority of patients (32.3%) were aged between 10 and 19 years. The institutions where the first consultation was done were: traditional healers in 38.5%, the referral hospital in 24.6%, Prayer houses in 15.4%, and 6.2% in the Loandjili General Hospital. The time taken for suspicion of diagnosis was 3e 5 years, for the following reasons: beliefs about the disease (42.5%), ignorance of the efficacy of medical treatment (36.8%). The itinerary was tripple (60.6%), quadriple (22.2%). The statistical difference was significant compared to the time taken, p < 0.005. Conclusion: The therapeutic itinerary is multiple, it is influenced by social and cultural considerations. The traditional healers are mostly the first recipient of epileptic patients.
http://dx.doi.org/10.1016/j.ejpn.2017.04.770 P3-4 First seizure as an epilepsy manifestation in childhood: Risk factors study A. Kudlatch, L. Shalkevich. Resident of Department of Pediatric Neurology, Belarusian Medical Academy of Post-Graduate Education, Minsk, Belarus Objective: To estimate epilepsy's development (ED) in childhood probability identifying various risk factors concomitant to first seizure episode (FSE). Methods: Type of study: case series. Inclusion criteria: children 0e18 y.o. with FSE in anamnestic report. We identified age, type of the FSE and neurological status. Results: 279 1090-3798
children with FSE were examined. In 59,5% (n ¼ 166) cases the seizure episode repeated within 2 years. OR of ED in children 0e12 months was 11,9 (c2 ¼ 51,4 p < 0,01; 95% CI 5,5e26), 5e9 years was 0,46 (c2 ¼ 5,9 p < 0,05; 95% CI 0,24e0,87), 10e14 years was 0,49 (c2 ¼ 5,2 p < 0,05; 95% CI 0,26e0,91). OR of ED was 2,44 (c2 ¼ 4,6 p < 0,05; 95% CI 1,06e5,6) in focal FSE cases; 6,33 (c2 ¼ 7,6 p < 0,01; 95% CI 1,4- 28) in case of myoclonic seizures and 5,9 (c2 ¼ 6,8 p < 0,01; 95% CI 1,3e26,3) in case of absence; 0,24 (c2 ¼ 18,1 p < 0,01; 95% CI 0,2e0,5) in clonic and 0,54 (c2 ¼ 5,7 p < 0,05; 95% CI 0,33e0,9) in toniceclonic seizures cases. OR of ED was also 19,4 (c2 ¼ 78,6 p < 0,01; 95% CI 8,9e42,4)) in cases with focal neurological symptoms, 4 (c2 ¼ 20,3 p < 0,01; 95% CI 2,1e7,5) in children with psychomotor retardation and 0,043 (c2 ¼ 87,297 p < 0,01; 95% CI 0,02e0,1) in cases with soft neurological signs. Conclusion: Risk of ED is high when FSE occurs at the age of 0e12 month, has focal, myoclonic or absence type and is associated with focal neurological symptoms or psychomotor retardation.
http://dx.doi.org/10.1016/j.ejpn.2017.04.771 P3-5 Risk factors, prevalence and impact of comorbid autism in pediatric epilepsy: A population-based study E. Wirrell, L. Wong-Kisiel, E. Payne, K. Nickels. Department of Neurology, Mayo Clinic, USA Objective: To determine the prevalence and risk factors for the development of autism in a population-based, retrospective cohort of children with new-onset epilepsy. Methods: Children with epilepsy, newly-diagnosed between 1980 and 2009, while resident in Olmsted County, MN, were identified through the Rochester Epidemiology Project database. Those followed beyond two years of age were included for study. Charts were reviewed to determine if subjects had been diagnosed with autism spectrum disorder (ASD), and also to collect seizure variables. Results: 459 children were identified (53% male). Mean age at seizure onset was 6.9 years (SD 5.0) and at follow-up was 17.2 years (SD 8.7). ASD was diagnosed in 34 (7.4%) cases, and preceded seizure onset in 15 children. Of those children for whom ASD was diagnosed after seizure onset, 58% had preceding established developmental delay. The most robust factor correlating with comorbid ASD was intellectual disability at seizure onset, with ASD being diagnosed in 4/295 (1.4%) of intellectually normal children, 19/101 (18.8%) with mild delay and 9/59 (15.3%) with moderate to severe delay (p < 0.001). Other significant correlates were abnormal neurological examination (p < 0.001), male sex (p ¼ 0.013), abnormal EEG background
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(p ¼ 0.023) and lack of a genetic etiology (p ¼ 0.012). Children with earlier onset of epilepsy did not have significantly higher rates of ASD. Comorbid ASD did not impact on epilepsy outcome, with similar rates of both seizure freedom at final follow-up (65% in those with ASD versus 69% in those without ASD, p ¼ 0.61) and medical intractability or need for epilepsy surgery (29% with ASD versus 18% without ASD, p ¼ 0.12). Conclusion: Comorbid ASD affects approximately 7.4% of children with epilepsy and coexisting intellectual disability is the most significant correlate. However, ASD does not appear to adversely impact epilepsy prognosis, as the majority of children still achieve seizure freedom long-term.
http://dx.doi.org/10.1016/j.ejpn.2017.04.772 P3-6 Infantile spasms: Long-term mortality of the patients €a € , Maiju Saarinen, Dieter Schmidt. Raili Riikonen, Matti Sillanpa Department of Pediatrics, University of Eastern Finland and Kuopio University Hospital, Kuopio Finland Objective: To study the long-term survival and mortality among patients with infantile spasms. Methods: The study population included all children born in 1960e1976 and treated for infantile spasms in three tertiary care hospitals in Helsinki, Finland. The participants were prospectively followed for five decades for survival. Death data were derived from the National Causes of Death Register of the Population Register Center of Statistics Finland. Results: During follow-up, 102 (49%) of 207 patients had died at the mean age of 19 years. The mean overall annual mortality rate was 15.3 per 1,000 patient-years years. The rates ranged from 18.2 per 1,000 after 10 years to 17.2 per 1,000 after 20 years and 15.4 per 1,000 patient-years after 40 years of follow-up. One fourth (25%) had died by 17.2 (95% CI 11.8e22.7) years and 50% by 48.6 (95% CI 38.5eNA) years of follow-up. Etiology at onset was symptomatic in 87% patients and cryptogenic in 13%. The mean annual mortality rate was 3.7 per 1,000 for patients with cryptogenic etiology and 17.6 per 1,000 for those with symptomatic etiology. The hazard of death was fivefold in patients with symptomatic etiology versus cryptogenic etiology. The overall autopsy rate was 73%. Pneumonia was the most frequent cause of death (46%). All patients who died of pneumonia had symptomatic etiology. SUDEP occurred in 10 patients and was the most common epilepsy-related cause of death (10%). Conclusion: Risk of excess death of participants with infantile spams is not limited to early age but continues into adulthood, particularly in those with symptomatic etiology, and leads to death in half the cases at around 50 years of age. Measures should be directed to prevent pneumonia, the most common overall cause, and SUDEP, the most frequent seizure-related cause, of death.
http://dx.doi.org/10.1016/j.ejpn.2017.04.773 P3-7 Predictor factors of intractable childhood epilepsy: A Turkish study Senem Ayc¸a, Ramazan Deniz Oral, Halil Ural Aksoy, Muzaffer Polat. Celal Bayar Medical Faculty, Division of Pediatric Neurology, Turkey Objective: This study aimed to determine the clinical, electroencephalographic, and radiological factors associated with medically intractable seizures in children. Methods: Retrospective cohort study was conducted. A total of 241 children with diagnosed epilepsy were recruited and divided into two groups: 61
patients with drug resistant, and the other 180 patients without drug resistant. We studied the predictor factors of intractability. Results: 21 patients had epileptic encephalopathy in the drug resistant group (%45.9). Twelve patients in the drug resistant group had diagnosis of west syndrome, 4 patients had Lenaux Gastaut syndrome, 3 patients had Dravet syndrome, 5 patients had electrical status epilepticus of sleep (ESES), 2 patients had Landau Kleffner syndrome and 2 patients had Doose syndrome. Structural and metabolic disorders (% 34.6) were the most seen neuroimaging abnormallity in the drug resistant group. Focal/ multifocal pattern in EEG (%37.7) and parsiel seizure type (%42.6) were seen predominantly in the group with drug resistant. Conclusion: Onset <1 year of age, etiology of epileptic encephalopathy, abnormal neurodevelopmental status, EEG and neuroimaging abnormality, history of prematurity history of asphyxia, family history of intermarriage were predictive factors of intractability. In follow up epileptic children we should interrogate these factors and close monitoring should be done in case of predictive factors presenting; different treatment options should keep on mind.
http://dx.doi.org/10.1016/j.ejpn.2017.04.774 P3-8 The natural history and burden of illness of epilepsy in tuberous sclerosis complex (TSC): A systematic literature review A. Patel, S. Watchko, D. Nellesen, F. Herbst, M. Neary. Analysis Group, Menlo Park, CA, USA Objective: To understand the disease progression for patients with TSC and burden of TSC-associated epilepsy. Methods: A systematic literature review (SLR) was conducted of Medline, EMBASE, PsychINFO, and EBM Reviews, supplemented with abstracts from IEC, ECE, AES, and the International TSC Research Conference. Studies reporting progression of seizures and neurological manifestations in patients with TSC and the burden of TSC, including utility values associated with epilepsy were included. Results: Of 3487 studies identified, 49 were selected. TSC is a progressive autosomal-dominant genetic disorder with characteristic manifestations such as epileptic seizures, impaired cognition, and growth of subependymal giant-cell astrocytomas (SEGA) and renal angiomyolipomas (AML). In pediatric patients, SEGAs tend to grow faster (0.082 cm3/year vs. 0.026 cm3/year in adults), renal AMLs progress more slowly (0.33 cm/year vs. 1.25 cm/year), and seizures are more prevalent (71.4% vs. 32.0%). Early seizure onset (age <24 months) is associated with significantly diminished cognitive ability, impaired neurodevelopment, and autism (mean ADOS-2 total score of 11.0 vs. 5.8 in seizure-free infants). The burden of illness of TSC is remarkably high, characterized by poor quality of life (QOL), frequent physician visits, and high costs driven by neurological manifestations including epilepsy. The burden of TSC-associated epilepsy is evidenced by the decrement in health state utility values associated with refractory seizures. In general epilepsy populations, seizures of moderate severity and moderate treatment-related side effects are associated with remarkably low utility values (range: 0.48 to 0.96), and reflect the magnitude of impairment in QOL for these patients. Conclusions: This SLR provides a novel synthesis of disparate studies of the natural history and burden of illness in patients with TSC. Findings suggest the benefit of early intervention to preempt cognitive impairment and improve QOL. Limited data were identified
Official Journal of the European Paediatric Neurology Society
Abstracts of EPNS 2017 e 12th European Paediatric Neurology Society Congress, 20e24 June 2017, Lyon, France POSTER PRESENTATIONS Friday, June 23 EPILEPSY: EPIDEMIOLOGY AND FOLLOW-UP P3-3 Therapeutic itinerary of epileptic patients managed in loandjili general hospital Prince Eliot Galieni Sounga Bandzouzi, Christelle Oko-Lossambo, Saurel Ngassaki, Godefroy Charles Koubemba. Republic of Congo Objective: Describe the different outpatient therapeutic itinerary of the Neurology clinic Hospital of loandjili. Methods: We conducted a descriptive and analytical cross-sectional study over a period of 6 months, from 3 January 2015 to 30 June 2015, in patients with epilepsy followed in outpatient of the Neurology clinic. Results: Sixty-five patients (30.6%) were enrolled. 33 females (50.8%) and 32 males (49.2%). The average age was 24.8 years (3 years to 69 years). The majority of patients (32.3%) were aged between 10 and 19 years. The institutions where the first consultation was done were: traditional healers in 38.5%, the referral hospital in 24.6%, Prayer houses in 15.4%, and 6.2% in the Loandjili General Hospital. The time taken for suspicion of diagnosis was 3e 5 years, for the following reasons: beliefs about the disease (42.5%), ignorance of the efficacy of medical treatment (36.8%). The itinerary was tripple (60.6%), quadriple (22.2%). The statistical difference was significant compared to the time taken, p < 0.005. Conclusion: The therapeutic itinerary is multiple, it is influenced by social and cultural considerations. The traditional healers are mostly the first recipient of epileptic patients.
http://dx.doi.org/10.1016/j.ejpn.2017.04.770 P3-4 First seizure as an epilepsy manifestation in childhood: Risk factors study A. Kudlatch, L. Shalkevich. Resident of Department of Pediatric Neurology, Belarusian Medical Academy of Post-Graduate Education, Minsk, Belarus Objective: To estimate epilepsy's development (ED) in childhood probability identifying various risk factors concomitant to first seizure episode (FSE). Methods: Type of study: case series. Inclusion criteria: children 0e18 y.o. with FSE in anamnestic report. We identified age, type of the FSE and neurological status. Results: 279 1090-3798
children with FSE were examined. In 59,5% (n ¼ 166) cases the seizure episode repeated within 2 years. OR of ED in children 0e12 months was 11,9 (c2 ¼ 51,4 p < 0,01; 95% CI 5,5e26), 5e9 years was 0,46 (c2 ¼ 5,9 p < 0,05; 95% CI 0,24e0,87), 10e14 years was 0,49 (c2 ¼ 5,2 p < 0,05; 95% CI 0,26e0,91). OR of ED was 2,44 (c2 ¼ 4,6 p < 0,05; 95% CI 1,06e5,6) in focal FSE cases; 6,33 (c2 ¼ 7,6 p < 0,01; 95% CI 1,4- 28) in case of myoclonic seizures and 5,9 (c2 ¼ 6,8 p < 0,01; 95% CI 1,3e26,3) in case of absence; 0,24 (c2 ¼ 18,1 p < 0,01; 95% CI 0,2e0,5) in clonic and 0,54 (c2 ¼ 5,7 p < 0,05; 95% CI 0,33e0,9) in toniceclonic seizures cases. OR of ED was also 19,4 (c2 ¼ 78,6 p < 0,01; 95% CI 8,9e42,4)) in cases with focal neurological symptoms, 4 (c2 ¼ 20,3 p < 0,01; 95% CI 2,1e7,5) in children with psychomotor retardation and 0,043 (c2 ¼ 87,297 p < 0,01; 95% CI 0,02e0,1) in cases with soft neurological signs. Conclusion: Risk of ED is high when FSE occurs at the age of 0e12 month, has focal, myoclonic or absence type and is associated with focal neurological symptoms or psychomotor retardation.
http://dx.doi.org/10.1016/j.ejpn.2017.04.771 P3-5 Risk factors, prevalence and impact of comorbid autism in pediatric epilepsy: A population-based study E. Wirrell, L. Wong-Kisiel, E. Payne, K. Nickels. Department of Neurology, Mayo Clinic, USA Objective: To determine the prevalence and risk factors for the development of autism in a population-based, retrospective cohort of children with new-onset epilepsy. Methods: Children with epilepsy, newly-diagnosed between 1980 and 2009, while resident in Olmsted County, MN, were identified through the Rochester Epidemiology Project database. Those followed beyond two years of age were included for study. Charts were reviewed to determine if subjects had been diagnosed with autism spectrum disorder (ASD), and also to collect seizure variables. Results: 459 children were identified (53% male). Mean age at seizure onset was 6.9 years (SD 5.0) and at follow-up was 17.2 years (SD 8.7). ASD was diagnosed in 34 (7.4%) cases, and preceded seizure onset in 15 children. Of those children for whom ASD was diagnosed after seizure onset, 58% had preceding established developmental delay. The most robust factor correlating with comorbid ASD was intellectual disability at seizure onset, with ASD being diagnosed in 4/295 (1.4%) of intellectually normal children, 19/101 (18.8%) with mild delay and 9/59 (15.3%) with moderate to severe delay (p < 0.001). Other significant correlates were abnormal neurological examination (p < 0.001), male sex (p ¼ 0.013), abnormal EEG background
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(p ¼ 0.023) and lack of a genetic etiology (p ¼ 0.012). Children with earlier onset of epilepsy did not have significantly higher rates of ASD. Comorbid ASD did not impact on epilepsy outcome, with similar rates of both seizure freedom at final follow-up (65% in those with ASD versus 69% in those without ASD, p ¼ 0.61) and medical intractability or need for epilepsy surgery (29% with ASD versus 18% without ASD, p ¼ 0.12). Conclusion: Comorbid ASD affects approximately 7.4% of children with epilepsy and coexisting intellectual disability is the most significant correlate. However, ASD does not appear to adversely impact epilepsy prognosis, as the majority of children still achieve seizure freedom long-term.
http://dx.doi.org/10.1016/j.ejpn.2017.04.772 P3-6 Infantile spasms: Long-term mortality of the patients €a € , Maiju Saarinen, Dieter Schmidt. Raili Riikonen, Matti Sillanpa Department of Pediatrics, University of Eastern Finland and Kuopio University Hospital, Kuopio Finland Objective: To study the long-term survival and mortality among patients with infantile spasms. Methods: The study population included all children born in 1960e1976 and treated for infantile spasms in three tertiary care hospitals in Helsinki, Finland. The participants were prospectively followed for five decades for survival. Death data were derived from the National Causes of Death Register of the Population Register Center of Statistics Finland. Results: During follow-up, 102 (49%) of 207 patients had died at the mean age of 19 years. The mean overall annual mortality rate was 15.3 per 1,000 patient-years years. The rates ranged from 18.2 per 1,000 after 10 years to 17.2 per 1,000 after 20 years and 15.4 per 1,000 patient-years after 40 years of follow-up. One fourth (25%) had died by 17.2 (95% CI 11.8e22.7) years and 50% by 48.6 (95% CI 38.5eNA) years of follow-up. Etiology at onset was symptomatic in 87% patients and cryptogenic in 13%. The mean annual mortality rate was 3.7 per 1,000 for patients with cryptogenic etiology and 17.6 per 1,000 for those with symptomatic etiology. The hazard of death was fivefold in patients with symptomatic etiology versus cryptogenic etiology. The overall autopsy rate was 73%. Pneumonia was the most frequent cause of death (46%). All patients who died of pneumonia had symptomatic etiology. SUDEP occurred in 10 patients and was the most common epilepsy-related cause of death (10%). Conclusion: Risk of excess death of participants with infantile spams is not limited to early age but continues into adulthood, particularly in those with symptomatic etiology, and leads to death in half the cases at around 50 years of age. Measures should be directed to prevent pneumonia, the most common overall cause, and SUDEP, the most frequent seizure-related cause, of death.
http://dx.doi.org/10.1016/j.ejpn.2017.04.773 P3-7 Predictor factors of intractable childhood epilepsy: A Turkish study Senem Ayc¸a, Ramazan Deniz Oral, Halil Ural Aksoy, Muzaffer Polat. Celal Bayar Medical Faculty, Division of Pediatric Neurology, Turkey Objective: This study aimed to determine the clinical, electroencephalographic, and radiological factors associated with medically intractable seizures in children. Methods: Retrospective cohort study was conducted. A total of 241 children with diagnosed epilepsy were recruited and divided into two groups: 61
patients with drug resistant, and the other 180 patients without drug resistant. We studied the predictor factors of intractability. Results: 21 patients had epileptic encephalopathy in the drug resistant group (%45.9). Twelve patients in the drug resistant group had diagnosis of west syndrome, 4 patients had Lenaux Gastaut syndrome, 3 patients had Dravet syndrome, 5 patients had electrical status epilepticus of sleep (ESES), 2 patients had Landau Kleffner syndrome and 2 patients had Doose syndrome. Structural and metabolic disorders (% 34.6) were the most seen neuroimaging abnormallity in the drug resistant group. Focal/ multifocal pattern in EEG (%37.7) and parsiel seizure type (%42.6) were seen predominantly in the group with drug resistant. Conclusion: Onset <1 year of age, etiology of epileptic encephalopathy, abnormal neurodevelopmental status, EEG and neuroimaging abnormality, history of prematurity history of asphyxia, family history of intermarriage were predictive factors of intractability. In follow up epileptic children we should interrogate these factors and close monitoring should be done in case of predictive factors presenting; different treatment options should keep on mind.
http://dx.doi.org/10.1016/j.ejpn.2017.04.774 P3-8 The natural history and burden of illness of epilepsy in tuberous sclerosis complex (TSC): A systematic literature review A. Patel, S. Watchko, D. Nellesen, F. Herbst, M. Neary. Analysis Group, Menlo Park, CA, USA Objective: To understand the disease progression for patients with TSC and burden of TSC-associated epilepsy. Methods: A systematic literature review (SLR) was conducted of Medline, EMBASE, PsychINFO, and EBM Reviews, supplemented with abstracts from IEC, ECE, AES, and the International TSC Research Conference. Studies reporting progression of seizures and neurological manifestations in patients with TSC and the burden of TSC, including utility values associated with epilepsy were included. Results: Of 3487 studies identified, 49 were selected. TSC is a progressive autosomal-dominant genetic disorder with characteristic manifestations such as epileptic seizures, impaired cognition, and growth of subependymal giant-cell astrocytomas (SEGA) and renal angiomyolipomas (AML). In pediatric patients, SEGAs tend to grow faster (0.082 cm3/year vs. 0.026 cm3/year in adults), renal AMLs progress more slowly (0.33 cm/year vs. 1.25 cm/year), and seizures are more prevalent (71.4% vs. 32.0%). Early seizure onset (age <24 months) is associated with significantly diminished cognitive ability, impaired neurodevelopment, and autism (mean ADOS-2 total score of 11.0 vs. 5.8 in seizure-free infants). The burden of illness of TSC is remarkably high, characterized by poor quality of life (QOL), frequent physician visits, and high costs driven by neurological manifestations including epilepsy. The burden of TSC-associated epilepsy is evidenced by the decrement in health state utility values associated with refractory seizures. In general epilepsy populations, seizures of moderate severity and moderate treatment-related side effects are associated with remarkably low utility values (range: 0.48 to 0.96), and reflect the magnitude of impairment in QOL for these patients. Conclusions: This SLR provides a novel synthesis of disparate studies of the natural history and burden of illness in patients with TSC. Findings suggest the benefit of early intervention to preempt cognitive impairment and improve QOL. Limited data were identified