User login
BANGKOK – Katherine B. Howell, MD, reported at the International Epilepsy Congress.
“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.
She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.
“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.
She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.
“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.
The full spectrum of SEI
With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.
The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.
“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.
About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.
SEI etiologies
A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.
The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.
In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.
Outcomes
“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.
However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.
Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.
bjancin@mdedge.com
SOURCE: Howell KB et al. IEC 2019, Abstract P053.
BANGKOK – Katherine B. Howell, MD, reported at the International Epilepsy Congress.
“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.
She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.
“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.
She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.
“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.
The full spectrum of SEI
With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.
The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.
“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.
About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.
SEI etiologies
A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.
The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.
In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.
Outcomes
“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.
However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.
Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.
bjancin@mdedge.com
SOURCE: Howell KB et al. IEC 2019, Abstract P053.
BANGKOK – Katherine B. Howell, MD, reported at the International Epilepsy Congress.
“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.
She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.
“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.
She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.
“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.
The full spectrum of SEI
With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.
The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.
“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.
About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.
SEI etiologies
A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.
The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.
In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.
Outcomes
“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.
However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.
Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.
bjancin@mdedge.com
SOURCE: Howell KB et al. IEC 2019, Abstract P053.
REPORTING FROM IEC 2019
