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Erik Greb joined the staff of Neurology Reviews in January 2012. Since then, he has attended scientific conferences, conducted video interviews, and written about clinical research in multiple sclerosis, epilepsy, Parkinson's disease, Alzheimer's disease, stroke, and other neurologic disorders. In addition to news articles, Erik has written investigative stories about multiple sclerosis, headache, and epilepsy. He previously wrote about pharmaceutical manufacturing, drug formulation and delivery, quality assurance, and regulation for Pharmaceutical Technology.
Functional outcomes of SLAH may be superior to those of open resection
BALTIMORE – , according to data presented at the annual meeting of the American Epilepsy Society. In addition, improvements in functional status are strongly associated with improvements in global cognitive performance.
Previous data have indicated that SLAH results in superior cognitive outcomes, compared with selective and standard open resection, in the treatment of medial temporal lobe epilepsy. The rates of seizure freedom following these procedures are equivalent. Daniel Drane, PhD, associate professor of neurology at Emory University in Atlanta, and colleagues hypothesized that the preservation of cognitive skills following SLAH would be apparent in real-world settings. To test this hypothesis, they investigated changes in functional status following SLAH.
Functional status correlated with neurocognitive change
Dr. Drane and colleagues compared functional outcomes in 53 patients who underwent SLAH at the Emory University Epilepsy Center and 20 patients who underwent open resection at the same center. The investigators created a hierarchical classification of functional status using the following criteria (from best to worst): employed and independent with all activities of daily living (ADLs), unemployed and independent with all ADLs, unemployed and independent with lower ADLs only (i.e., independent with self-care, but not with management of finances, medications, etc.), and unemployed and unable to manage any ADLs without assistance. Dr. Drane and colleagues rated all patients on these criteria at baseline and at 1 year after surgery. They classified patients as improving, declining, or remaining stable in functional status. Finally, the investigators used Fisher’s exact test to compare the proportional ratings of change between surgical procedures.
At baseline, the proportions of patients in each functional group were similar between patients who later underwent SLAH and those who later underwent open resection. Significantly more patients who underwent SLAH, however, had functional improvement, compared with patients who underwent open resection (13.2% vs. 0%). Furthermore, fewer patients who underwent SLAH had functional decline, compared with those who underwent open resection (3.7% vs. 35%).
Dr. Drane and colleagues found a strong correlation between functional status and global ratings of neurocognitive change, but no correlation between functional status and seizure-freedom status. Patients who underwent SLAH were less likely to have a decline in employment status than were patients who underwent open resection were (4.2% vs. 45.4%).
Weighing surgical options for a given patient
“This study provides a real-world metric of meaningful change following surgery, which is, critically, independent of seizure freedom outcome,” said Dr. Drane. “If a patient becomes seizure free but declines in functional status, presumably due to compromised cognitive function, this outcome is likely not going to lead to a better quality of life. Overall, our data suggest that functional status is driven more by cognitive outcome than by seizure freedom, and that it is an equally important metric for determining whether or not surgery has been successful. We would hope that the epilepsy surgical team would try to balance the desire to achieve seizure freedom against the potential risks and benefits of surgery on cognitive performance and functional status.”
Neurologists must consider various factors when deciding whether open resection or SLAH is the better option for a given patient. “Our prior work has shown that SLAH will not cause naming or object recognition deficits, while such deficits will result in a substantial proportion of patients undergoing open resection procedures,” said Dr. Drane. “Declarative memory can seemingly be hurt by either procedure, although it would appear that rates of decline are substantially less following SLAH. As functional status appears to be related to cognitive outcome, SLAH would always be the better choice from the standpoint of risk analysis, particularly since one can almost always go back an complete an open resection at a later date.
“Seizure freedom rates appear to be slightly higher with open resection than with SLAH,” Dr. Drane continued. “This [result] would be the one factor that would represent the one reason to opt for an open resection rather than SLAH. Factors that might push one in this direction could be risk for SUDEP (i.e., someone at very high risk may want to just be done with the seizures) and impaired baseline cognitive functioning (i.e., someone with severely impaired cognitive functioning might be viewed as having less to lose). In the latter case, however, we would caution that low-functioning individuals can sometimes lose their remaining functional abilities even if we cannot do a very good job of measuring cognitive change in such cases due to their poor baseline performance.”
The hemisphere to undergo operation also may influence the choice of procedure. “Some epileptologists will suggest that the choice of using SLAH is more important for patients having surgery involving their language-dominant cerebral hemisphere,” said Dr. Drane. “While postsurgical deficits in these patients are clearly more easy to identify, I would argue that a case can be made for starting with SLAH in the nondominant temporal lobe cases as well. Many of the functions that can be potentially harmed by surgical procedures involving the nondominant (typically right) hemisphere have more subtle effects, but their cumulative impact can yet be harmful.”
The study was partially supported by funding from the National Institutes of Health and Medtronic. The investigators did not report any conflicts of interest.
SOURCE: Drane DL et al. AES 2019. Abstract 1.34.
BALTIMORE – , according to data presented at the annual meeting of the American Epilepsy Society. In addition, improvements in functional status are strongly associated with improvements in global cognitive performance.
Previous data have indicated that SLAH results in superior cognitive outcomes, compared with selective and standard open resection, in the treatment of medial temporal lobe epilepsy. The rates of seizure freedom following these procedures are equivalent. Daniel Drane, PhD, associate professor of neurology at Emory University in Atlanta, and colleagues hypothesized that the preservation of cognitive skills following SLAH would be apparent in real-world settings. To test this hypothesis, they investigated changes in functional status following SLAH.
Functional status correlated with neurocognitive change
Dr. Drane and colleagues compared functional outcomes in 53 patients who underwent SLAH at the Emory University Epilepsy Center and 20 patients who underwent open resection at the same center. The investigators created a hierarchical classification of functional status using the following criteria (from best to worst): employed and independent with all activities of daily living (ADLs), unemployed and independent with all ADLs, unemployed and independent with lower ADLs only (i.e., independent with self-care, but not with management of finances, medications, etc.), and unemployed and unable to manage any ADLs without assistance. Dr. Drane and colleagues rated all patients on these criteria at baseline and at 1 year after surgery. They classified patients as improving, declining, or remaining stable in functional status. Finally, the investigators used Fisher’s exact test to compare the proportional ratings of change between surgical procedures.
At baseline, the proportions of patients in each functional group were similar between patients who later underwent SLAH and those who later underwent open resection. Significantly more patients who underwent SLAH, however, had functional improvement, compared with patients who underwent open resection (13.2% vs. 0%). Furthermore, fewer patients who underwent SLAH had functional decline, compared with those who underwent open resection (3.7% vs. 35%).
Dr. Drane and colleagues found a strong correlation between functional status and global ratings of neurocognitive change, but no correlation between functional status and seizure-freedom status. Patients who underwent SLAH were less likely to have a decline in employment status than were patients who underwent open resection were (4.2% vs. 45.4%).
Weighing surgical options for a given patient
“This study provides a real-world metric of meaningful change following surgery, which is, critically, independent of seizure freedom outcome,” said Dr. Drane. “If a patient becomes seizure free but declines in functional status, presumably due to compromised cognitive function, this outcome is likely not going to lead to a better quality of life. Overall, our data suggest that functional status is driven more by cognitive outcome than by seizure freedom, and that it is an equally important metric for determining whether or not surgery has been successful. We would hope that the epilepsy surgical team would try to balance the desire to achieve seizure freedom against the potential risks and benefits of surgery on cognitive performance and functional status.”
Neurologists must consider various factors when deciding whether open resection or SLAH is the better option for a given patient. “Our prior work has shown that SLAH will not cause naming or object recognition deficits, while such deficits will result in a substantial proportion of patients undergoing open resection procedures,” said Dr. Drane. “Declarative memory can seemingly be hurt by either procedure, although it would appear that rates of decline are substantially less following SLAH. As functional status appears to be related to cognitive outcome, SLAH would always be the better choice from the standpoint of risk analysis, particularly since one can almost always go back an complete an open resection at a later date.
“Seizure freedom rates appear to be slightly higher with open resection than with SLAH,” Dr. Drane continued. “This [result] would be the one factor that would represent the one reason to opt for an open resection rather than SLAH. Factors that might push one in this direction could be risk for SUDEP (i.e., someone at very high risk may want to just be done with the seizures) and impaired baseline cognitive functioning (i.e., someone with severely impaired cognitive functioning might be viewed as having less to lose). In the latter case, however, we would caution that low-functioning individuals can sometimes lose their remaining functional abilities even if we cannot do a very good job of measuring cognitive change in such cases due to their poor baseline performance.”
The hemisphere to undergo operation also may influence the choice of procedure. “Some epileptologists will suggest that the choice of using SLAH is more important for patients having surgery involving their language-dominant cerebral hemisphere,” said Dr. Drane. “While postsurgical deficits in these patients are clearly more easy to identify, I would argue that a case can be made for starting with SLAH in the nondominant temporal lobe cases as well. Many of the functions that can be potentially harmed by surgical procedures involving the nondominant (typically right) hemisphere have more subtle effects, but their cumulative impact can yet be harmful.”
The study was partially supported by funding from the National Institutes of Health and Medtronic. The investigators did not report any conflicts of interest.
SOURCE: Drane DL et al. AES 2019. Abstract 1.34.
BALTIMORE – , according to data presented at the annual meeting of the American Epilepsy Society. In addition, improvements in functional status are strongly associated with improvements in global cognitive performance.
Previous data have indicated that SLAH results in superior cognitive outcomes, compared with selective and standard open resection, in the treatment of medial temporal lobe epilepsy. The rates of seizure freedom following these procedures are equivalent. Daniel Drane, PhD, associate professor of neurology at Emory University in Atlanta, and colleagues hypothesized that the preservation of cognitive skills following SLAH would be apparent in real-world settings. To test this hypothesis, they investigated changes in functional status following SLAH.
Functional status correlated with neurocognitive change
Dr. Drane and colleagues compared functional outcomes in 53 patients who underwent SLAH at the Emory University Epilepsy Center and 20 patients who underwent open resection at the same center. The investigators created a hierarchical classification of functional status using the following criteria (from best to worst): employed and independent with all activities of daily living (ADLs), unemployed and independent with all ADLs, unemployed and independent with lower ADLs only (i.e., independent with self-care, but not with management of finances, medications, etc.), and unemployed and unable to manage any ADLs without assistance. Dr. Drane and colleagues rated all patients on these criteria at baseline and at 1 year after surgery. They classified patients as improving, declining, or remaining stable in functional status. Finally, the investigators used Fisher’s exact test to compare the proportional ratings of change between surgical procedures.
At baseline, the proportions of patients in each functional group were similar between patients who later underwent SLAH and those who later underwent open resection. Significantly more patients who underwent SLAH, however, had functional improvement, compared with patients who underwent open resection (13.2% vs. 0%). Furthermore, fewer patients who underwent SLAH had functional decline, compared with those who underwent open resection (3.7% vs. 35%).
Dr. Drane and colleagues found a strong correlation between functional status and global ratings of neurocognitive change, but no correlation between functional status and seizure-freedom status. Patients who underwent SLAH were less likely to have a decline in employment status than were patients who underwent open resection were (4.2% vs. 45.4%).
Weighing surgical options for a given patient
“This study provides a real-world metric of meaningful change following surgery, which is, critically, independent of seizure freedom outcome,” said Dr. Drane. “If a patient becomes seizure free but declines in functional status, presumably due to compromised cognitive function, this outcome is likely not going to lead to a better quality of life. Overall, our data suggest that functional status is driven more by cognitive outcome than by seizure freedom, and that it is an equally important metric for determining whether or not surgery has been successful. We would hope that the epilepsy surgical team would try to balance the desire to achieve seizure freedom against the potential risks and benefits of surgery on cognitive performance and functional status.”
Neurologists must consider various factors when deciding whether open resection or SLAH is the better option for a given patient. “Our prior work has shown that SLAH will not cause naming or object recognition deficits, while such deficits will result in a substantial proportion of patients undergoing open resection procedures,” said Dr. Drane. “Declarative memory can seemingly be hurt by either procedure, although it would appear that rates of decline are substantially less following SLAH. As functional status appears to be related to cognitive outcome, SLAH would always be the better choice from the standpoint of risk analysis, particularly since one can almost always go back an complete an open resection at a later date.
“Seizure freedom rates appear to be slightly higher with open resection than with SLAH,” Dr. Drane continued. “This [result] would be the one factor that would represent the one reason to opt for an open resection rather than SLAH. Factors that might push one in this direction could be risk for SUDEP (i.e., someone at very high risk may want to just be done with the seizures) and impaired baseline cognitive functioning (i.e., someone with severely impaired cognitive functioning might be viewed as having less to lose). In the latter case, however, we would caution that low-functioning individuals can sometimes lose their remaining functional abilities even if we cannot do a very good job of measuring cognitive change in such cases due to their poor baseline performance.”
The hemisphere to undergo operation also may influence the choice of procedure. “Some epileptologists will suggest that the choice of using SLAH is more important for patients having surgery involving their language-dominant cerebral hemisphere,” said Dr. Drane. “While postsurgical deficits in these patients are clearly more easy to identify, I would argue that a case can be made for starting with SLAH in the nondominant temporal lobe cases as well. Many of the functions that can be potentially harmed by surgical procedures involving the nondominant (typically right) hemisphere have more subtle effects, but their cumulative impact can yet be harmful.”
The study was partially supported by funding from the National Institutes of Health and Medtronic. The investigators did not report any conflicts of interest.
SOURCE: Drane DL et al. AES 2019. Abstract 1.34.
REPORTING FROM AES 2019
EEG abnormalities may indicate increased risk for epilepsy in patients with autism
BALTIMORE – , according to research presented at the annual meeting of the American Epilepsy Society. In addition, a positive family history of febrile seizures also is associated with an increased risk of epilepsy in this population.
The literature suggests that the prevalence of epilepsy in patients with ASD ranges from 5% to 40%. This broad range may result from the heterogeneity of epilepsy risk factors among patients with ASD. These risk factors include intellectual disability, age, and syndromic forms of ASD such as tuberous sclerosis complex. Regardless of whether they have epilepsy, approximately 60% of patients with ASD have EEG abnormalities. The prognostic implications of these abnormalities are uncertain.
Investigators reviewed patients’ charts retrospectively
Divya Nadkarni, MD, a neurologist at Ronald Reagan UCLA Medical Center in Los Angeles, and colleagues sought to clarify the relationship between risk factors such as EEG abnormalities and subsequent epilepsy in patients with ASD. They retrospectively identified patients who were followed jointly at UCLA and at Pediatric Minds, a neurodevelopmental clinic in Torrance, Calif. Eligible patients had a diagnosis of ASD, based on criteria from DSM-IV, DSM-5, or the Autism Diagnostic Observation Schedule. In addition, patients had overnight, continuous video EEG evaluation and a minimum follow-up of 1 week after EEG. Patients with a history of epilepsy before the initial EEG evaluation were excluded. Dr. Nadkarni and colleagues collected clinical and electrographic data by chart review.
The study’s primary outcome was time to onset of epilepsy. Among the variables that the investigators analyzed were EEG abnormalities, which they defined as focal slowing or generalized or focal epileptiform discharges. The other variables were history of febrile seizures, family history of epilepsy, family history of febrile seizures, and family history of ASD. Dr. Nadkarni and colleagues analyzed the data using the Kaplan–Meier method and Cox proportional hazards models.
In all, 164 patients met the study’s inclusion criteria. The population’s median age at the initial EEG evaluation was 4.5 years. The median follow-up after this evaluation was 2.4 years. The investigators found 63 patients (38.4%) with abnormal EEGs, and 18 patients (11%) subsequently developed epilepsy after a median of 1.9 years.
Family history of febrile seizures was associated with time to epilepsy onset
The time to epilepsy onset was associated with abnormalities on the initial overnight continuous EEG. The hazard ratio of epilepsy among patients with EEG abnormalities was 8.0. Approximately one-third of patients with EEG abnormalities developed subsequent epilepsy, compared with approximately 5% of patients without EEG abnormalities, said Dr. Nadkarni.
In addition, time to epilepsy onset was independently associated with a positive family history of febrile seizures. This finding was unexpected, said Dr. Nadkarni. The hazard ratio of epilepsy among patients with a positive family history of febrile seizures was 12.6.
The patient’s own history of febrile seizures was not associated with time to epilepsy onset. One potential explanation for this result is that it is difficult to distinguish between febrile seizure and seizure with fever in the general pediatric population. Making this distinction in children with ASD, who may have atypical febrile seizures, might be still more difficult, said Dr. Nadkarni.
Time for guideline updates?
“Statements from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the American Academy of Neurology, and the Child Neurology Society do not currently recommend routine EEG screening for all children with ASD,” said Dr. Nadkarni. Investigators are suggesting that the guidelines should be reevaluated, however. “Research shows that EEG abnormalities, particularly epileptiform abnormalities, are associated with worse outcome, in terms of developmental and adaptive functioning. EEG endophenotypes in ASD are starting to be elucidated ... That’s one reason to consider EEG screening.” Furthermore, preliminary connectivity research suggests that EEG screening of high-risk siblings of children with ASD may predict the development of ASD.
The small cohort and retrospective design were among the study’s limitations, said Dr. Nadkarni. Some patients were lost to follow-up, and some data were missing from patients’ charts.
“In our opinion, further study – ideally, a prospective, observational cohort study – might be warranted to determine whether overnight continuous EEG monitoring might be useful as a screening tool for epilepsy in patients with ASD,” Dr. Nadkarni concluded.
The study was conducted without external funding, and the investigators had no disclosures.
SOURCE: Nadkarni D et al. AES 2019. Abstract 1.29.
BALTIMORE – , according to research presented at the annual meeting of the American Epilepsy Society. In addition, a positive family history of febrile seizures also is associated with an increased risk of epilepsy in this population.
The literature suggests that the prevalence of epilepsy in patients with ASD ranges from 5% to 40%. This broad range may result from the heterogeneity of epilepsy risk factors among patients with ASD. These risk factors include intellectual disability, age, and syndromic forms of ASD such as tuberous sclerosis complex. Regardless of whether they have epilepsy, approximately 60% of patients with ASD have EEG abnormalities. The prognostic implications of these abnormalities are uncertain.
Investigators reviewed patients’ charts retrospectively
Divya Nadkarni, MD, a neurologist at Ronald Reagan UCLA Medical Center in Los Angeles, and colleagues sought to clarify the relationship between risk factors such as EEG abnormalities and subsequent epilepsy in patients with ASD. They retrospectively identified patients who were followed jointly at UCLA and at Pediatric Minds, a neurodevelopmental clinic in Torrance, Calif. Eligible patients had a diagnosis of ASD, based on criteria from DSM-IV, DSM-5, or the Autism Diagnostic Observation Schedule. In addition, patients had overnight, continuous video EEG evaluation and a minimum follow-up of 1 week after EEG. Patients with a history of epilepsy before the initial EEG evaluation were excluded. Dr. Nadkarni and colleagues collected clinical and electrographic data by chart review.
The study’s primary outcome was time to onset of epilepsy. Among the variables that the investigators analyzed were EEG abnormalities, which they defined as focal slowing or generalized or focal epileptiform discharges. The other variables were history of febrile seizures, family history of epilepsy, family history of febrile seizures, and family history of ASD. Dr. Nadkarni and colleagues analyzed the data using the Kaplan–Meier method and Cox proportional hazards models.
In all, 164 patients met the study’s inclusion criteria. The population’s median age at the initial EEG evaluation was 4.5 years. The median follow-up after this evaluation was 2.4 years. The investigators found 63 patients (38.4%) with abnormal EEGs, and 18 patients (11%) subsequently developed epilepsy after a median of 1.9 years.
Family history of febrile seizures was associated with time to epilepsy onset
The time to epilepsy onset was associated with abnormalities on the initial overnight continuous EEG. The hazard ratio of epilepsy among patients with EEG abnormalities was 8.0. Approximately one-third of patients with EEG abnormalities developed subsequent epilepsy, compared with approximately 5% of patients without EEG abnormalities, said Dr. Nadkarni.
In addition, time to epilepsy onset was independently associated with a positive family history of febrile seizures. This finding was unexpected, said Dr. Nadkarni. The hazard ratio of epilepsy among patients with a positive family history of febrile seizures was 12.6.
The patient’s own history of febrile seizures was not associated with time to epilepsy onset. One potential explanation for this result is that it is difficult to distinguish between febrile seizure and seizure with fever in the general pediatric population. Making this distinction in children with ASD, who may have atypical febrile seizures, might be still more difficult, said Dr. Nadkarni.
Time for guideline updates?
“Statements from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the American Academy of Neurology, and the Child Neurology Society do not currently recommend routine EEG screening for all children with ASD,” said Dr. Nadkarni. Investigators are suggesting that the guidelines should be reevaluated, however. “Research shows that EEG abnormalities, particularly epileptiform abnormalities, are associated with worse outcome, in terms of developmental and adaptive functioning. EEG endophenotypes in ASD are starting to be elucidated ... That’s one reason to consider EEG screening.” Furthermore, preliminary connectivity research suggests that EEG screening of high-risk siblings of children with ASD may predict the development of ASD.
The small cohort and retrospective design were among the study’s limitations, said Dr. Nadkarni. Some patients were lost to follow-up, and some data were missing from patients’ charts.
“In our opinion, further study – ideally, a prospective, observational cohort study – might be warranted to determine whether overnight continuous EEG monitoring might be useful as a screening tool for epilepsy in patients with ASD,” Dr. Nadkarni concluded.
The study was conducted without external funding, and the investigators had no disclosures.
SOURCE: Nadkarni D et al. AES 2019. Abstract 1.29.
BALTIMORE – , according to research presented at the annual meeting of the American Epilepsy Society. In addition, a positive family history of febrile seizures also is associated with an increased risk of epilepsy in this population.
The literature suggests that the prevalence of epilepsy in patients with ASD ranges from 5% to 40%. This broad range may result from the heterogeneity of epilepsy risk factors among patients with ASD. These risk factors include intellectual disability, age, and syndromic forms of ASD such as tuberous sclerosis complex. Regardless of whether they have epilepsy, approximately 60% of patients with ASD have EEG abnormalities. The prognostic implications of these abnormalities are uncertain.
Investigators reviewed patients’ charts retrospectively
Divya Nadkarni, MD, a neurologist at Ronald Reagan UCLA Medical Center in Los Angeles, and colleagues sought to clarify the relationship between risk factors such as EEG abnormalities and subsequent epilepsy in patients with ASD. They retrospectively identified patients who were followed jointly at UCLA and at Pediatric Minds, a neurodevelopmental clinic in Torrance, Calif. Eligible patients had a diagnosis of ASD, based on criteria from DSM-IV, DSM-5, or the Autism Diagnostic Observation Schedule. In addition, patients had overnight, continuous video EEG evaluation and a minimum follow-up of 1 week after EEG. Patients with a history of epilepsy before the initial EEG evaluation were excluded. Dr. Nadkarni and colleagues collected clinical and electrographic data by chart review.
The study’s primary outcome was time to onset of epilepsy. Among the variables that the investigators analyzed were EEG abnormalities, which they defined as focal slowing or generalized or focal epileptiform discharges. The other variables were history of febrile seizures, family history of epilepsy, family history of febrile seizures, and family history of ASD. Dr. Nadkarni and colleagues analyzed the data using the Kaplan–Meier method and Cox proportional hazards models.
In all, 164 patients met the study’s inclusion criteria. The population’s median age at the initial EEG evaluation was 4.5 years. The median follow-up after this evaluation was 2.4 years. The investigators found 63 patients (38.4%) with abnormal EEGs, and 18 patients (11%) subsequently developed epilepsy after a median of 1.9 years.
Family history of febrile seizures was associated with time to epilepsy onset
The time to epilepsy onset was associated with abnormalities on the initial overnight continuous EEG. The hazard ratio of epilepsy among patients with EEG abnormalities was 8.0. Approximately one-third of patients with EEG abnormalities developed subsequent epilepsy, compared with approximately 5% of patients without EEG abnormalities, said Dr. Nadkarni.
In addition, time to epilepsy onset was independently associated with a positive family history of febrile seizures. This finding was unexpected, said Dr. Nadkarni. The hazard ratio of epilepsy among patients with a positive family history of febrile seizures was 12.6.
The patient’s own history of febrile seizures was not associated with time to epilepsy onset. One potential explanation for this result is that it is difficult to distinguish between febrile seizure and seizure with fever in the general pediatric population. Making this distinction in children with ASD, who may have atypical febrile seizures, might be still more difficult, said Dr. Nadkarni.
Time for guideline updates?
“Statements from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the American Academy of Neurology, and the Child Neurology Society do not currently recommend routine EEG screening for all children with ASD,” said Dr. Nadkarni. Investigators are suggesting that the guidelines should be reevaluated, however. “Research shows that EEG abnormalities, particularly epileptiform abnormalities, are associated with worse outcome, in terms of developmental and adaptive functioning. EEG endophenotypes in ASD are starting to be elucidated ... That’s one reason to consider EEG screening.” Furthermore, preliminary connectivity research suggests that EEG screening of high-risk siblings of children with ASD may predict the development of ASD.
The small cohort and retrospective design were among the study’s limitations, said Dr. Nadkarni. Some patients were lost to follow-up, and some data were missing from patients’ charts.
“In our opinion, further study – ideally, a prospective, observational cohort study – might be warranted to determine whether overnight continuous EEG monitoring might be useful as a screening tool for epilepsy in patients with ASD,” Dr. Nadkarni concluded.
The study was conducted without external funding, and the investigators had no disclosures.
SOURCE: Nadkarni D et al. AES 2019. Abstract 1.29.
REPORTING FROM AES 2019
Biopsy not required to diagnose most cases of pediatric celiac disease
(ESPGHAN). The authors recommend that the diagnosis be established with a two-stage blood test instead of an endoscopy, which children often find distressing.
The guidance was published in the Journal of Pediatric Gastroenterology and Nutrition. The document is an update of ESPGHAN’s 2012 guidance.
About half of children with suspected celiac disease undergo a biopsy to confirm the diagnosis. By reducing the number of biopsies, and the anesthesia required to perform them, the new guidelines could reduce European health care costs.
Steffen Husby, MD, of Odense (Denmark) University Hospital, and colleagues recommend testing for total IgA and anti-intestinal transglutaminase 2 (TGA-IgA) antibodies as initial screening in children with suspected celiac disease. An IgG-based test is indicated only when total IgA is low or undetectable, according to the authors. Physicians should refer children with positive results to a pediatric gastroenterologist. If the level of TGA-IgA is 10 or more times the upper limit of normal, and the family agrees, the physician may diagnose celiac disease without a biopsy, provided that endomysial antibodies test positive in a second blood sample, according to the guidance. For children with a positive TGA-IgA level of less than 10 times the upper limit of normal, however, at least four biopsies from the distal duodenum and at least one from the bulb are required to establish the diagnosis.
Physicians can diagnose celiac disease in children with no symptoms without the need for a biopsy using the same criteria as they use for symptomatic children, wrote Dr. Husby and colleagues. Clinicians, parents, and, when appropriate, children should participate in the decision about whether to perform a biopsy.
Celiac disease is the most prevalent food-related chronic disease in European children, but as much as 80% of children with celiac disease are undiagnosed. The prevalence of celiac disease is increasing, and undiagnosed children with this disease are at risk of nutritional and developmental problems, as well as long-term health complications. Although celiac disease is easy to detect and treat, 10-13 years may elapse between symptom onset and the time of diagnosis. The new guidelines are intended to facilitate diagnosis and increase its accuracy, thus enabling earlier diagnosis and improved detection, according to ESPGHAN.
“These new guidelines mean that more than half of all children being investigated for celiac disease will no longer need to have an invasive biopsy,” said Luisa Mearin Manrique, MD, PhD, professor of pediatrics at Leiden (the Netherlands) University and senior author of the guidelines, in a press release. “This is a big step forward in our mission to ensure that children can be diagnosed and effectively treated for celiac disease. It is scandalous that so many children go so long, often up to 10 years, without diagnosis. Removing the need for biopsy in order to achieve diagnosis will reduce the stresses associated with such an invasive procedure and mean that diagnoses are quicker and cheaper for health care systems.”
No conflicts of interest were reported.
SOURCE: Husby S et al. J Pediatr Gastroenterol Nutr. 2020;70(1):141-56.
(ESPGHAN). The authors recommend that the diagnosis be established with a two-stage blood test instead of an endoscopy, which children often find distressing.
The guidance was published in the Journal of Pediatric Gastroenterology and Nutrition. The document is an update of ESPGHAN’s 2012 guidance.
About half of children with suspected celiac disease undergo a biopsy to confirm the diagnosis. By reducing the number of biopsies, and the anesthesia required to perform them, the new guidelines could reduce European health care costs.
Steffen Husby, MD, of Odense (Denmark) University Hospital, and colleagues recommend testing for total IgA and anti-intestinal transglutaminase 2 (TGA-IgA) antibodies as initial screening in children with suspected celiac disease. An IgG-based test is indicated only when total IgA is low or undetectable, according to the authors. Physicians should refer children with positive results to a pediatric gastroenterologist. If the level of TGA-IgA is 10 or more times the upper limit of normal, and the family agrees, the physician may diagnose celiac disease without a biopsy, provided that endomysial antibodies test positive in a second blood sample, according to the guidance. For children with a positive TGA-IgA level of less than 10 times the upper limit of normal, however, at least four biopsies from the distal duodenum and at least one from the bulb are required to establish the diagnosis.
Physicians can diagnose celiac disease in children with no symptoms without the need for a biopsy using the same criteria as they use for symptomatic children, wrote Dr. Husby and colleagues. Clinicians, parents, and, when appropriate, children should participate in the decision about whether to perform a biopsy.
Celiac disease is the most prevalent food-related chronic disease in European children, but as much as 80% of children with celiac disease are undiagnosed. The prevalence of celiac disease is increasing, and undiagnosed children with this disease are at risk of nutritional and developmental problems, as well as long-term health complications. Although celiac disease is easy to detect and treat, 10-13 years may elapse between symptom onset and the time of diagnosis. The new guidelines are intended to facilitate diagnosis and increase its accuracy, thus enabling earlier diagnosis and improved detection, according to ESPGHAN.
“These new guidelines mean that more than half of all children being investigated for celiac disease will no longer need to have an invasive biopsy,” said Luisa Mearin Manrique, MD, PhD, professor of pediatrics at Leiden (the Netherlands) University and senior author of the guidelines, in a press release. “This is a big step forward in our mission to ensure that children can be diagnosed and effectively treated for celiac disease. It is scandalous that so many children go so long, often up to 10 years, without diagnosis. Removing the need for biopsy in order to achieve diagnosis will reduce the stresses associated with such an invasive procedure and mean that diagnoses are quicker and cheaper for health care systems.”
No conflicts of interest were reported.
SOURCE: Husby S et al. J Pediatr Gastroenterol Nutr. 2020;70(1):141-56.
(ESPGHAN). The authors recommend that the diagnosis be established with a two-stage blood test instead of an endoscopy, which children often find distressing.
The guidance was published in the Journal of Pediatric Gastroenterology and Nutrition. The document is an update of ESPGHAN’s 2012 guidance.
About half of children with suspected celiac disease undergo a biopsy to confirm the diagnosis. By reducing the number of biopsies, and the anesthesia required to perform them, the new guidelines could reduce European health care costs.
Steffen Husby, MD, of Odense (Denmark) University Hospital, and colleagues recommend testing for total IgA and anti-intestinal transglutaminase 2 (TGA-IgA) antibodies as initial screening in children with suspected celiac disease. An IgG-based test is indicated only when total IgA is low or undetectable, according to the authors. Physicians should refer children with positive results to a pediatric gastroenterologist. If the level of TGA-IgA is 10 or more times the upper limit of normal, and the family agrees, the physician may diagnose celiac disease without a biopsy, provided that endomysial antibodies test positive in a second blood sample, according to the guidance. For children with a positive TGA-IgA level of less than 10 times the upper limit of normal, however, at least four biopsies from the distal duodenum and at least one from the bulb are required to establish the diagnosis.
Physicians can diagnose celiac disease in children with no symptoms without the need for a biopsy using the same criteria as they use for symptomatic children, wrote Dr. Husby and colleagues. Clinicians, parents, and, when appropriate, children should participate in the decision about whether to perform a biopsy.
Celiac disease is the most prevalent food-related chronic disease in European children, but as much as 80% of children with celiac disease are undiagnosed. The prevalence of celiac disease is increasing, and undiagnosed children with this disease are at risk of nutritional and developmental problems, as well as long-term health complications. Although celiac disease is easy to detect and treat, 10-13 years may elapse between symptom onset and the time of diagnosis. The new guidelines are intended to facilitate diagnosis and increase its accuracy, thus enabling earlier diagnosis and improved detection, according to ESPGHAN.
“These new guidelines mean that more than half of all children being investigated for celiac disease will no longer need to have an invasive biopsy,” said Luisa Mearin Manrique, MD, PhD, professor of pediatrics at Leiden (the Netherlands) University and senior author of the guidelines, in a press release. “This is a big step forward in our mission to ensure that children can be diagnosed and effectively treated for celiac disease. It is scandalous that so many children go so long, often up to 10 years, without diagnosis. Removing the need for biopsy in order to achieve diagnosis will reduce the stresses associated with such an invasive procedure and mean that diagnoses are quicker and cheaper for health care systems.”
No conflicts of interest were reported.
SOURCE: Husby S et al. J Pediatr Gastroenterol Nutr. 2020;70(1):141-56.
FROM THE JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
Serum levels of neurofilament light are increased before clinical onset of MS
(MS), according to research published in the January issue of JAMA Neurology. These results lend weight to the idea that MS has a prodromal phase, and this phase appears to be associated with neurodegeneration, according to the authors.
Patients often have CNS lesions of various stages of development at the time of their first demyelinating event, and this finding was one basis for neurologists’ hypothesis of a prodromal phase of MS. The finding that one-third of patients with radiologically isolated syndrome develop MS within 5 years also lends credence to this idea. Diagnosing MS early would enable early treatment that could prevent demyelination and the progression of neurodegeneration.
Researchers compared presymptomatic and symptomatic samples
With this idea in mind, Kjetil Bjornevik, MD, PhD, a member of the neuroepidemiology research group at Harvard TH Chan School of Public Health in Boston, and colleagues evaluated whether serum levels of NfL, a marker of ongoing neuroaxonal degeneration, were increased in the years before and around the time of clinical onset of MS. For their study population, the investigators chose active-duty U.S. military personnel who have at least one serum sample stored in the U.S. Department of Defense Serum Repository. Samples are collected after routine HIV type 1 antibody testing.
Within this population, Dr. Bjornevik and colleagues identified patients with MS who had at least one presymptomatic serum sample. The date of clinical MS onset was defined as the date of the first neurologic symptoms attributable to MS documented in the medical record. The investigators randomly selected two control individuals from the population and matched them to each case by age, sex, race or ethnicity, and dates of sample collection. Eligible controls were on active duty on the date of onset of the matched case.
Dr. Bjornevik and colleagues identified 245 patients with MS. Among this sample, the researchers selected two groups that each included 30 cases and 30 controls. The first group included patients who had provided at least one serum sample before MS onset and one sample within 2 years after MS onset. The second group included cases with at least two presymptomatic serum samples, one of which was collected more than 5 years before MS diagnosis, and the other of which was collected between 2 and 5 years before diagnosis. The investigators handled pairs of serum samples in the same way and assayed them in the same batch. The order of the samples in each pair was arranged at random.
Levels were higher in cases than in controls
About 77% of the population was male. Sixty percent of participants were white, 28% were black, and 6.7% were Hispanic. The population’s mean age at first sample collection was approximately 27 years. Mean age at MS onset was approximately 31 years.
For patients who provided samples before and after the clinical onset of MS, serum NfL levels were higher than in matched controls at both points. Most patients who passed from the presymptomatic stage to the symptomatic stage had a significant increase in serum NfL level (i.e., from a median of 25.0 pg/mL to a median of 45.1 pg/mL). Serum NfL levels at the two time points in controls did not differ significantly. For any given patient, an increase in serum NfL level from the presymptomatic measurement to the symptomatic measurement was associated with an increased risk of MS.
In patients with two presymptomatic samples, serum NfL levels were significantly higher in both samples than in the corresponding samples from matched controls. In cases, the earlier sample was collected at a median of 6 years before clinical onset of MS, and the later sample was collected at a median of 1 year before clinical onset. The serum NfL levels increased significantly between the two points for cases (i.e., a median increase of 1.3 pg/mL per year), but there was no significant difference in serum NfL level between the two samples in controls. A within-patient increase in presymptomatic serum NfL level was associated with an increased risk of MS.
Population included few women
“Our study differs from previous studies on the prodromal phase of MS because these have used indirect markers of this phase, which included unspecific symptoms or disturbances occurring before the clinical onset, compared with a marker of neurodegeneration,” wrote Dr. Bjornevik and colleagues. Initiation of treatment with disease-modifying therapy is associated with reductions in serum NfL levels, and this association could explain why some patients in the current study had higher NfL levels before MS onset than afterward. Furthermore, serum NfL levels are highly associated with levels of NfL in cerebrospinal fluid. “Thus, our findings of a presymptomatic increase in serum NfL not only suggest the presence of a prodromal phase in MS, but also that this phase is associated with neurodegeneration,” wrote the investigators.
The study’s well-defined population helped to minimize selection bias, and the blinded, randomized method of analyzing the serum samples eliminated artifactual differences in serum NfL concentrations. But the small sample size precluded analyses that could have influenced clinical practice, wrote Dr. Bjornevik and colleagues. For example, the researchers could not evaluate distinct cutoffs in serum NfL level that could mark the beginning of the prodromal phase of MS. Nor could they determine whether presymptomatic serum NfL levels varied with age at clinical onset, sex, or race. The small number of women in the sample was another limitation of the study.
The Swiss National Research Foundation and the National Institute of Neurologic Disorders and Stroke funded the study. Several of the investigators received fees from various drug companies that were unrelated to the study, and one researcher received grants from the National Institutes of Health during the study.
SOURCE: Bjornevik K et al. JAMA Neurol. 2020;77(1):58-64.
(MS), according to research published in the January issue of JAMA Neurology. These results lend weight to the idea that MS has a prodromal phase, and this phase appears to be associated with neurodegeneration, according to the authors.
Patients often have CNS lesions of various stages of development at the time of their first demyelinating event, and this finding was one basis for neurologists’ hypothesis of a prodromal phase of MS. The finding that one-third of patients with radiologically isolated syndrome develop MS within 5 years also lends credence to this idea. Diagnosing MS early would enable early treatment that could prevent demyelination and the progression of neurodegeneration.
Researchers compared presymptomatic and symptomatic samples
With this idea in mind, Kjetil Bjornevik, MD, PhD, a member of the neuroepidemiology research group at Harvard TH Chan School of Public Health in Boston, and colleagues evaluated whether serum levels of NfL, a marker of ongoing neuroaxonal degeneration, were increased in the years before and around the time of clinical onset of MS. For their study population, the investigators chose active-duty U.S. military personnel who have at least one serum sample stored in the U.S. Department of Defense Serum Repository. Samples are collected after routine HIV type 1 antibody testing.
Within this population, Dr. Bjornevik and colleagues identified patients with MS who had at least one presymptomatic serum sample. The date of clinical MS onset was defined as the date of the first neurologic symptoms attributable to MS documented in the medical record. The investigators randomly selected two control individuals from the population and matched them to each case by age, sex, race or ethnicity, and dates of sample collection. Eligible controls were on active duty on the date of onset of the matched case.
Dr. Bjornevik and colleagues identified 245 patients with MS. Among this sample, the researchers selected two groups that each included 30 cases and 30 controls. The first group included patients who had provided at least one serum sample before MS onset and one sample within 2 years after MS onset. The second group included cases with at least two presymptomatic serum samples, one of which was collected more than 5 years before MS diagnosis, and the other of which was collected between 2 and 5 years before diagnosis. The investigators handled pairs of serum samples in the same way and assayed them in the same batch. The order of the samples in each pair was arranged at random.
Levels were higher in cases than in controls
About 77% of the population was male. Sixty percent of participants were white, 28% were black, and 6.7% were Hispanic. The population’s mean age at first sample collection was approximately 27 years. Mean age at MS onset was approximately 31 years.
For patients who provided samples before and after the clinical onset of MS, serum NfL levels were higher than in matched controls at both points. Most patients who passed from the presymptomatic stage to the symptomatic stage had a significant increase in serum NfL level (i.e., from a median of 25.0 pg/mL to a median of 45.1 pg/mL). Serum NfL levels at the two time points in controls did not differ significantly. For any given patient, an increase in serum NfL level from the presymptomatic measurement to the symptomatic measurement was associated with an increased risk of MS.
In patients with two presymptomatic samples, serum NfL levels were significantly higher in both samples than in the corresponding samples from matched controls. In cases, the earlier sample was collected at a median of 6 years before clinical onset of MS, and the later sample was collected at a median of 1 year before clinical onset. The serum NfL levels increased significantly between the two points for cases (i.e., a median increase of 1.3 pg/mL per year), but there was no significant difference in serum NfL level between the two samples in controls. A within-patient increase in presymptomatic serum NfL level was associated with an increased risk of MS.
Population included few women
“Our study differs from previous studies on the prodromal phase of MS because these have used indirect markers of this phase, which included unspecific symptoms or disturbances occurring before the clinical onset, compared with a marker of neurodegeneration,” wrote Dr. Bjornevik and colleagues. Initiation of treatment with disease-modifying therapy is associated with reductions in serum NfL levels, and this association could explain why some patients in the current study had higher NfL levels before MS onset than afterward. Furthermore, serum NfL levels are highly associated with levels of NfL in cerebrospinal fluid. “Thus, our findings of a presymptomatic increase in serum NfL not only suggest the presence of a prodromal phase in MS, but also that this phase is associated with neurodegeneration,” wrote the investigators.
The study’s well-defined population helped to minimize selection bias, and the blinded, randomized method of analyzing the serum samples eliminated artifactual differences in serum NfL concentrations. But the small sample size precluded analyses that could have influenced clinical practice, wrote Dr. Bjornevik and colleagues. For example, the researchers could not evaluate distinct cutoffs in serum NfL level that could mark the beginning of the prodromal phase of MS. Nor could they determine whether presymptomatic serum NfL levels varied with age at clinical onset, sex, or race. The small number of women in the sample was another limitation of the study.
The Swiss National Research Foundation and the National Institute of Neurologic Disorders and Stroke funded the study. Several of the investigators received fees from various drug companies that were unrelated to the study, and one researcher received grants from the National Institutes of Health during the study.
SOURCE: Bjornevik K et al. JAMA Neurol. 2020;77(1):58-64.
(MS), according to research published in the January issue of JAMA Neurology. These results lend weight to the idea that MS has a prodromal phase, and this phase appears to be associated with neurodegeneration, according to the authors.
Patients often have CNS lesions of various stages of development at the time of their first demyelinating event, and this finding was one basis for neurologists’ hypothesis of a prodromal phase of MS. The finding that one-third of patients with radiologically isolated syndrome develop MS within 5 years also lends credence to this idea. Diagnosing MS early would enable early treatment that could prevent demyelination and the progression of neurodegeneration.
Researchers compared presymptomatic and symptomatic samples
With this idea in mind, Kjetil Bjornevik, MD, PhD, a member of the neuroepidemiology research group at Harvard TH Chan School of Public Health in Boston, and colleagues evaluated whether serum levels of NfL, a marker of ongoing neuroaxonal degeneration, were increased in the years before and around the time of clinical onset of MS. For their study population, the investigators chose active-duty U.S. military personnel who have at least one serum sample stored in the U.S. Department of Defense Serum Repository. Samples are collected after routine HIV type 1 antibody testing.
Within this population, Dr. Bjornevik and colleagues identified patients with MS who had at least one presymptomatic serum sample. The date of clinical MS onset was defined as the date of the first neurologic symptoms attributable to MS documented in the medical record. The investigators randomly selected two control individuals from the population and matched them to each case by age, sex, race or ethnicity, and dates of sample collection. Eligible controls were on active duty on the date of onset of the matched case.
Dr. Bjornevik and colleagues identified 245 patients with MS. Among this sample, the researchers selected two groups that each included 30 cases and 30 controls. The first group included patients who had provided at least one serum sample before MS onset and one sample within 2 years after MS onset. The second group included cases with at least two presymptomatic serum samples, one of which was collected more than 5 years before MS diagnosis, and the other of which was collected between 2 and 5 years before diagnosis. The investigators handled pairs of serum samples in the same way and assayed them in the same batch. The order of the samples in each pair was arranged at random.
Levels were higher in cases than in controls
About 77% of the population was male. Sixty percent of participants were white, 28% were black, and 6.7% were Hispanic. The population’s mean age at first sample collection was approximately 27 years. Mean age at MS onset was approximately 31 years.
For patients who provided samples before and after the clinical onset of MS, serum NfL levels were higher than in matched controls at both points. Most patients who passed from the presymptomatic stage to the symptomatic stage had a significant increase in serum NfL level (i.e., from a median of 25.0 pg/mL to a median of 45.1 pg/mL). Serum NfL levels at the two time points in controls did not differ significantly. For any given patient, an increase in serum NfL level from the presymptomatic measurement to the symptomatic measurement was associated with an increased risk of MS.
In patients with two presymptomatic samples, serum NfL levels were significantly higher in both samples than in the corresponding samples from matched controls. In cases, the earlier sample was collected at a median of 6 years before clinical onset of MS, and the later sample was collected at a median of 1 year before clinical onset. The serum NfL levels increased significantly between the two points for cases (i.e., a median increase of 1.3 pg/mL per year), but there was no significant difference in serum NfL level between the two samples in controls. A within-patient increase in presymptomatic serum NfL level was associated with an increased risk of MS.
Population included few women
“Our study differs from previous studies on the prodromal phase of MS because these have used indirect markers of this phase, which included unspecific symptoms or disturbances occurring before the clinical onset, compared with a marker of neurodegeneration,” wrote Dr. Bjornevik and colleagues. Initiation of treatment with disease-modifying therapy is associated with reductions in serum NfL levels, and this association could explain why some patients in the current study had higher NfL levels before MS onset than afterward. Furthermore, serum NfL levels are highly associated with levels of NfL in cerebrospinal fluid. “Thus, our findings of a presymptomatic increase in serum NfL not only suggest the presence of a prodromal phase in MS, but also that this phase is associated with neurodegeneration,” wrote the investigators.
The study’s well-defined population helped to minimize selection bias, and the blinded, randomized method of analyzing the serum samples eliminated artifactual differences in serum NfL concentrations. But the small sample size precluded analyses that could have influenced clinical practice, wrote Dr. Bjornevik and colleagues. For example, the researchers could not evaluate distinct cutoffs in serum NfL level that could mark the beginning of the prodromal phase of MS. Nor could they determine whether presymptomatic serum NfL levels varied with age at clinical onset, sex, or race. The small number of women in the sample was another limitation of the study.
The Swiss National Research Foundation and the National Institute of Neurologic Disorders and Stroke funded the study. Several of the investigators received fees from various drug companies that were unrelated to the study, and one researcher received grants from the National Institutes of Health during the study.
SOURCE: Bjornevik K et al. JAMA Neurol. 2020;77(1):58-64.
FROM JAMA NEUROLOGY
Chronic cough in COPD linked to more severe disease
, according to research published in CHEST.
The results indicate “that chronic cough in individuals with COPD is associated with a more severe disease phenotype, which could be helpful for stratifying management of COPD in the future,” wrote Eskild Landt, PhD, a research assistant at Zealand University Hospital in Køge, Denmark, and colleagues.
A study by published in the Journal of Allergy and Clinical Immunology: In Practice (2019;7[6]:1783-92.e8) indicated that in patients with asthma, chronic cough was associated with worse respiratory symptoms, more health care utilization, decreased lung function, and increased inflammatory markers in blood. Dr. Landt and colleagues hypothesized that patients with COPD and chronic cough had a similar pattern of disease severity.
To test their hypothesis, they identified individuals with COPD and chronic cough among 43,271 participants in the Copenhagen General Population Study, a population-based cohort study. The researchers defined COPD as a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 in individuals without asthma. Consecutive individuals answered questions about chronic cough, which was defined as a cough lasting more than 8 weeks, and responded to the Leicester Cough Questionnaire. They also underwent a physical health examination, including prebronchodilatory spirometry, and gave blood for biochemical analyses. The blood was analyzed for high-sensitive C-reactive protein, fibrinogen, leukocytes, eosinophils, neutrophils, and immunoglobulin E (i.e., inflammatory biomarkers).
Dr. Landt and colleagues identified 8,181 patients (19% of the population) with COPD, 796 (10%) of whom had chronic cough. Of the 33,364 participants without COPD, 1,585 (5%) had chronic cough. For patients with COPD and chronic cough, median total Leicester Cough Questionnaire score was 17.7, corresponding to 5.9 for the physical domain, 5.6 for the psychological domain, and 6.3 for the social domain.
Among participants with COPD, those with chronic cough had higher rates of sputum production (60% versus 8%), wheezing (46% versus 14%), dyspnea (66% versus 38%), chest pain or tightness (9% versus 4%), nighttime dyspnea (8% versus 3%), episodes of acute bronchitis or pneumonias in the past 10 years (45% versus 25%), and general practitioner visits in the past 12 months (53% versus 37%). In addition, these participants had lower FEV1% of predicted (81% versus 89%), lower ratio of FEV1 to FVC (0.64 versus 0.66), and higher levels of high-sensitive C-reactive protein, fibrinogen, leukocytes, neutrophils, eosinophils, and immunoglobulin E in blood.
“To our knowledge, this is the first study reporting Leicester Cough Questionnaire score for randomly selected individuals with COPD from a general population setting,” wrote Dr. Landt and colleagues. The study’s strengths include its randomly chosen population-based sample and investigator blinding to disease status and clinical outcome, they added. Some patients with the most severe types of COPD and chronic cough may not have attended the physical examination and participated in the study, however, and this factor could have biased the results. Furthermore, nearly the entire sample was white, so the results may not be generalizable to other ethnicities. “That said, we are not aware of results to suggest that our findings should not be relevant to individuals of all races,” wrote the investigators.
The study was funded by the private Lundbeck Foundation, as well as by the Danish Lung Association and the Danish Cancer Society. Several authors reported receiving grants and fees from AstraZeneca, GlaxoSmithKline, and Novartis that were unrelated to the study.
SOURCE: Landt E et al. CHEST. 2020 Jan 24. doi: 10.1016/j.chest.2019.12.038.
, according to research published in CHEST.
The results indicate “that chronic cough in individuals with COPD is associated with a more severe disease phenotype, which could be helpful for stratifying management of COPD in the future,” wrote Eskild Landt, PhD, a research assistant at Zealand University Hospital in Køge, Denmark, and colleagues.
A study by published in the Journal of Allergy and Clinical Immunology: In Practice (2019;7[6]:1783-92.e8) indicated that in patients with asthma, chronic cough was associated with worse respiratory symptoms, more health care utilization, decreased lung function, and increased inflammatory markers in blood. Dr. Landt and colleagues hypothesized that patients with COPD and chronic cough had a similar pattern of disease severity.
To test their hypothesis, they identified individuals with COPD and chronic cough among 43,271 participants in the Copenhagen General Population Study, a population-based cohort study. The researchers defined COPD as a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 in individuals without asthma. Consecutive individuals answered questions about chronic cough, which was defined as a cough lasting more than 8 weeks, and responded to the Leicester Cough Questionnaire. They also underwent a physical health examination, including prebronchodilatory spirometry, and gave blood for biochemical analyses. The blood was analyzed for high-sensitive C-reactive protein, fibrinogen, leukocytes, eosinophils, neutrophils, and immunoglobulin E (i.e., inflammatory biomarkers).
Dr. Landt and colleagues identified 8,181 patients (19% of the population) with COPD, 796 (10%) of whom had chronic cough. Of the 33,364 participants without COPD, 1,585 (5%) had chronic cough. For patients with COPD and chronic cough, median total Leicester Cough Questionnaire score was 17.7, corresponding to 5.9 for the physical domain, 5.6 for the psychological domain, and 6.3 for the social domain.
Among participants with COPD, those with chronic cough had higher rates of sputum production (60% versus 8%), wheezing (46% versus 14%), dyspnea (66% versus 38%), chest pain or tightness (9% versus 4%), nighttime dyspnea (8% versus 3%), episodes of acute bronchitis or pneumonias in the past 10 years (45% versus 25%), and general practitioner visits in the past 12 months (53% versus 37%). In addition, these participants had lower FEV1% of predicted (81% versus 89%), lower ratio of FEV1 to FVC (0.64 versus 0.66), and higher levels of high-sensitive C-reactive protein, fibrinogen, leukocytes, neutrophils, eosinophils, and immunoglobulin E in blood.
“To our knowledge, this is the first study reporting Leicester Cough Questionnaire score for randomly selected individuals with COPD from a general population setting,” wrote Dr. Landt and colleagues. The study’s strengths include its randomly chosen population-based sample and investigator blinding to disease status and clinical outcome, they added. Some patients with the most severe types of COPD and chronic cough may not have attended the physical examination and participated in the study, however, and this factor could have biased the results. Furthermore, nearly the entire sample was white, so the results may not be generalizable to other ethnicities. “That said, we are not aware of results to suggest that our findings should not be relevant to individuals of all races,” wrote the investigators.
The study was funded by the private Lundbeck Foundation, as well as by the Danish Lung Association and the Danish Cancer Society. Several authors reported receiving grants and fees from AstraZeneca, GlaxoSmithKline, and Novartis that were unrelated to the study.
SOURCE: Landt E et al. CHEST. 2020 Jan 24. doi: 10.1016/j.chest.2019.12.038.
, according to research published in CHEST.
The results indicate “that chronic cough in individuals with COPD is associated with a more severe disease phenotype, which could be helpful for stratifying management of COPD in the future,” wrote Eskild Landt, PhD, a research assistant at Zealand University Hospital in Køge, Denmark, and colleagues.
A study by published in the Journal of Allergy and Clinical Immunology: In Practice (2019;7[6]:1783-92.e8) indicated that in patients with asthma, chronic cough was associated with worse respiratory symptoms, more health care utilization, decreased lung function, and increased inflammatory markers in blood. Dr. Landt and colleagues hypothesized that patients with COPD and chronic cough had a similar pattern of disease severity.
To test their hypothesis, they identified individuals with COPD and chronic cough among 43,271 participants in the Copenhagen General Population Study, a population-based cohort study. The researchers defined COPD as a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 in individuals without asthma. Consecutive individuals answered questions about chronic cough, which was defined as a cough lasting more than 8 weeks, and responded to the Leicester Cough Questionnaire. They also underwent a physical health examination, including prebronchodilatory spirometry, and gave blood for biochemical analyses. The blood was analyzed for high-sensitive C-reactive protein, fibrinogen, leukocytes, eosinophils, neutrophils, and immunoglobulin E (i.e., inflammatory biomarkers).
Dr. Landt and colleagues identified 8,181 patients (19% of the population) with COPD, 796 (10%) of whom had chronic cough. Of the 33,364 participants without COPD, 1,585 (5%) had chronic cough. For patients with COPD and chronic cough, median total Leicester Cough Questionnaire score was 17.7, corresponding to 5.9 for the physical domain, 5.6 for the psychological domain, and 6.3 for the social domain.
Among participants with COPD, those with chronic cough had higher rates of sputum production (60% versus 8%), wheezing (46% versus 14%), dyspnea (66% versus 38%), chest pain or tightness (9% versus 4%), nighttime dyspnea (8% versus 3%), episodes of acute bronchitis or pneumonias in the past 10 years (45% versus 25%), and general practitioner visits in the past 12 months (53% versus 37%). In addition, these participants had lower FEV1% of predicted (81% versus 89%), lower ratio of FEV1 to FVC (0.64 versus 0.66), and higher levels of high-sensitive C-reactive protein, fibrinogen, leukocytes, neutrophils, eosinophils, and immunoglobulin E in blood.
“To our knowledge, this is the first study reporting Leicester Cough Questionnaire score for randomly selected individuals with COPD from a general population setting,” wrote Dr. Landt and colleagues. The study’s strengths include its randomly chosen population-based sample and investigator blinding to disease status and clinical outcome, they added. Some patients with the most severe types of COPD and chronic cough may not have attended the physical examination and participated in the study, however, and this factor could have biased the results. Furthermore, nearly the entire sample was white, so the results may not be generalizable to other ethnicities. “That said, we are not aware of results to suggest that our findings should not be relevant to individuals of all races,” wrote the investigators.
The study was funded by the private Lundbeck Foundation, as well as by the Danish Lung Association and the Danish Cancer Society. Several authors reported receiving grants and fees from AstraZeneca, GlaxoSmithKline, and Novartis that were unrelated to the study.
SOURCE: Landt E et al. CHEST. 2020 Jan 24. doi: 10.1016/j.chest.2019.12.038.
FROM CHEST
Dependent trait in chronic migraine may predict nonresponse to onabotulinumtoxin A
according to research published in the January issue of Headache. The research may be the first to show that personality traits predict response to onabotulinumtoxin A in this population.
“These findings point out that conducting an evaluation of personality traits in patients with chronic migraine might be helpful in the prediction of the course and election of the treatment, as well as identifying patients who might benefit from a multidisciplinary approach,” wrote Alicia Gonzalez-Martinez, MD, of the Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria de La Princesa in Madrid and colleagues. “Categorical questionnaires such as the Salamanca screening test seem to be useful for this purpose.”
Researchers used ICD-10 personality criteria
Personality patterns in patients with migraine and other primary headaches have been the subject of decades of research. Munoz et al. found that certain personality traits are associated with migraine and chronic migraine, and this association may influence clinical management and treatment. The effect of personality traits on response to treatment, however, had not been studied previously.
Dr. Gonzalez-Martinez and colleagues hypothesized that cluster C traits (e.g., obsessive-compulsive, dependent, and anxious), as defined by ICD-10, are associated with nonresponse to onabotulinumtoxin A. To test this hypothesis, they conducted a case-control observational study in a cohort of patients with chronic migraine. Eligible patients presented to one of two headache units of a tertiary hospital between January and May 2018. The investigators obtained a complete headache history and demographic information from each patient. Patients had at least two treatment cycles of onabotulinumtoxin A. Dr. Gonzalez-Martinez and colleagues defined treatment response as a reduction in the number of monthly migraine days of at least 50% after at least two treatment cycles.
The investigators assessed participants’ personality traits by administering the Salamanca test, a brief categorical inventory that examines 11 personality traits using 22 questions. Patients completed the test at the beginning of the study period and before they were classified as responders or nonresponders.
Medication overuse was a potential confounder
The study population included 112 patients with chronic migraine. One hundred patients (89%) were women. Participants’ mean age at initiation of onabotulinumtoxin A treatment was 43 years. The population’s mean duration of chronic migraine was 29 months. Eighty-three patients (74.1%) had medication overuse, and 96 (85.7%) responded to onabotulinumtoxin A.
Cluster A traits in the population included paranoid (prevalence, 10.7%), schizoid (38.4%), and schizotypal (7.1%). Cluster B traits included histrionic (50%), antisocial (1.8%), narcissistic (9.8%), emotional instability subtype impulsive (27.7%), and emotional instability subtype limit (EISL, 24.1%). Cluster C traits were anxious (58.9%) anancastic (i.e., obsessive-compulsive, 54.5%), and dependent (32.1%).
The investigators found no differences in demographics between responders and nonresponders. In a univariate analysis, dependent traits (e.g., passivity and emotional overdependence on others) and EISL traits (e.g., impulsivity and disturbed self-image) were significantly more common among nonresponders. In a multivariate analysis, dependent traits remained significantly associated with nonresponse to onabotulinumtoxin A.
Medication overuse was a potential confounder in the study, according to Dr. Gonzalez-Martinez and colleagues. One of the study’s limitations was its absence of a healthy control group. Another was the fact that the psychometrics of the Salamanca screening test have not been published in a peer-reviewed journal and may need further examination.
Dependent personality “may also be part of the proposed chronic pain sufferer personality,” wrote the investigators. “Early detection of personality traits could improve management and outcome of chronic migraine patients. Additionally, the possibility to predict the effectiveness of onabotulinumtoxin A therapy may reduce costs and latency time of effect in patients with improbable effectiveness.”
The study had no outside funding, and the authors reported no conflicts of interest.
SOURCE: Gonzalez-Martinez A et al. Headache. 2020;60(1):153-61.
according to research published in the January issue of Headache. The research may be the first to show that personality traits predict response to onabotulinumtoxin A in this population.
“These findings point out that conducting an evaluation of personality traits in patients with chronic migraine might be helpful in the prediction of the course and election of the treatment, as well as identifying patients who might benefit from a multidisciplinary approach,” wrote Alicia Gonzalez-Martinez, MD, of the Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria de La Princesa in Madrid and colleagues. “Categorical questionnaires such as the Salamanca screening test seem to be useful for this purpose.”
Researchers used ICD-10 personality criteria
Personality patterns in patients with migraine and other primary headaches have been the subject of decades of research. Munoz et al. found that certain personality traits are associated with migraine and chronic migraine, and this association may influence clinical management and treatment. The effect of personality traits on response to treatment, however, had not been studied previously.
Dr. Gonzalez-Martinez and colleagues hypothesized that cluster C traits (e.g., obsessive-compulsive, dependent, and anxious), as defined by ICD-10, are associated with nonresponse to onabotulinumtoxin A. To test this hypothesis, they conducted a case-control observational study in a cohort of patients with chronic migraine. Eligible patients presented to one of two headache units of a tertiary hospital between January and May 2018. The investigators obtained a complete headache history and demographic information from each patient. Patients had at least two treatment cycles of onabotulinumtoxin A. Dr. Gonzalez-Martinez and colleagues defined treatment response as a reduction in the number of monthly migraine days of at least 50% after at least two treatment cycles.
The investigators assessed participants’ personality traits by administering the Salamanca test, a brief categorical inventory that examines 11 personality traits using 22 questions. Patients completed the test at the beginning of the study period and before they were classified as responders or nonresponders.
Medication overuse was a potential confounder
The study population included 112 patients with chronic migraine. One hundred patients (89%) were women. Participants’ mean age at initiation of onabotulinumtoxin A treatment was 43 years. The population’s mean duration of chronic migraine was 29 months. Eighty-three patients (74.1%) had medication overuse, and 96 (85.7%) responded to onabotulinumtoxin A.
Cluster A traits in the population included paranoid (prevalence, 10.7%), schizoid (38.4%), and schizotypal (7.1%). Cluster B traits included histrionic (50%), antisocial (1.8%), narcissistic (9.8%), emotional instability subtype impulsive (27.7%), and emotional instability subtype limit (EISL, 24.1%). Cluster C traits were anxious (58.9%) anancastic (i.e., obsessive-compulsive, 54.5%), and dependent (32.1%).
The investigators found no differences in demographics between responders and nonresponders. In a univariate analysis, dependent traits (e.g., passivity and emotional overdependence on others) and EISL traits (e.g., impulsivity and disturbed self-image) were significantly more common among nonresponders. In a multivariate analysis, dependent traits remained significantly associated with nonresponse to onabotulinumtoxin A.
Medication overuse was a potential confounder in the study, according to Dr. Gonzalez-Martinez and colleagues. One of the study’s limitations was its absence of a healthy control group. Another was the fact that the psychometrics of the Salamanca screening test have not been published in a peer-reviewed journal and may need further examination.
Dependent personality “may also be part of the proposed chronic pain sufferer personality,” wrote the investigators. “Early detection of personality traits could improve management and outcome of chronic migraine patients. Additionally, the possibility to predict the effectiveness of onabotulinumtoxin A therapy may reduce costs and latency time of effect in patients with improbable effectiveness.”
The study had no outside funding, and the authors reported no conflicts of interest.
SOURCE: Gonzalez-Martinez A et al. Headache. 2020;60(1):153-61.
according to research published in the January issue of Headache. The research may be the first to show that personality traits predict response to onabotulinumtoxin A in this population.
“These findings point out that conducting an evaluation of personality traits in patients with chronic migraine might be helpful in the prediction of the course and election of the treatment, as well as identifying patients who might benefit from a multidisciplinary approach,” wrote Alicia Gonzalez-Martinez, MD, of the Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria de La Princesa in Madrid and colleagues. “Categorical questionnaires such as the Salamanca screening test seem to be useful for this purpose.”
Researchers used ICD-10 personality criteria
Personality patterns in patients with migraine and other primary headaches have been the subject of decades of research. Munoz et al. found that certain personality traits are associated with migraine and chronic migraine, and this association may influence clinical management and treatment. The effect of personality traits on response to treatment, however, had not been studied previously.
Dr. Gonzalez-Martinez and colleagues hypothesized that cluster C traits (e.g., obsessive-compulsive, dependent, and anxious), as defined by ICD-10, are associated with nonresponse to onabotulinumtoxin A. To test this hypothesis, they conducted a case-control observational study in a cohort of patients with chronic migraine. Eligible patients presented to one of two headache units of a tertiary hospital between January and May 2018. The investigators obtained a complete headache history and demographic information from each patient. Patients had at least two treatment cycles of onabotulinumtoxin A. Dr. Gonzalez-Martinez and colleagues defined treatment response as a reduction in the number of monthly migraine days of at least 50% after at least two treatment cycles.
The investigators assessed participants’ personality traits by administering the Salamanca test, a brief categorical inventory that examines 11 personality traits using 22 questions. Patients completed the test at the beginning of the study period and before they were classified as responders or nonresponders.
Medication overuse was a potential confounder
The study population included 112 patients with chronic migraine. One hundred patients (89%) were women. Participants’ mean age at initiation of onabotulinumtoxin A treatment was 43 years. The population’s mean duration of chronic migraine was 29 months. Eighty-three patients (74.1%) had medication overuse, and 96 (85.7%) responded to onabotulinumtoxin A.
Cluster A traits in the population included paranoid (prevalence, 10.7%), schizoid (38.4%), and schizotypal (7.1%). Cluster B traits included histrionic (50%), antisocial (1.8%), narcissistic (9.8%), emotional instability subtype impulsive (27.7%), and emotional instability subtype limit (EISL, 24.1%). Cluster C traits were anxious (58.9%) anancastic (i.e., obsessive-compulsive, 54.5%), and dependent (32.1%).
The investigators found no differences in demographics between responders and nonresponders. In a univariate analysis, dependent traits (e.g., passivity and emotional overdependence on others) and EISL traits (e.g., impulsivity and disturbed self-image) were significantly more common among nonresponders. In a multivariate analysis, dependent traits remained significantly associated with nonresponse to onabotulinumtoxin A.
Medication overuse was a potential confounder in the study, according to Dr. Gonzalez-Martinez and colleagues. One of the study’s limitations was its absence of a healthy control group. Another was the fact that the psychometrics of the Salamanca screening test have not been published in a peer-reviewed journal and may need further examination.
Dependent personality “may also be part of the proposed chronic pain sufferer personality,” wrote the investigators. “Early detection of personality traits could improve management and outcome of chronic migraine patients. Additionally, the possibility to predict the effectiveness of onabotulinumtoxin A therapy may reduce costs and latency time of effect in patients with improbable effectiveness.”
The study had no outside funding, and the authors reported no conflicts of interest.
SOURCE: Gonzalez-Martinez A et al. Headache. 2020;60(1):153-61.
FROM HEADACHE
Should a normal-appearing hippocampus be resected in a patient with temporal lobe epilepsy?
BALTIMORE – according to an analysis presented at the annual meeting of the American Epilepsy Society. Long-term seizure outcomes, however, are similar between resected and nonresected patients. In addition, sparing a normal-appearing hippocampus is correlated with a lower risk of verbal deficits, but long-term outcomes are unclear.
Neurologists have not arrived at a consensus about the best surgical management of patients with temporal lobe epilepsy and a hippocampus that appears normal on MRI. Few studies have examined seizure and neuropsychologic outcomes in this population, and this scarcity of data makes counseling patients difficult.
A review of data for surgical patients
To investigate this question, Marcia E. Morita-Sherman, MD, from the Cleveland Clinic, and colleagues retrospectively reviewed data for 152 patients who underwent surgery for temporal lobe epilepsy at the Cleveland Clinic during 2010-2018. Eligible participants were older than 16 years, and the researchers excluded patients with MRI or pathologic signs of hippocampal sclerosis and those with prior surgeries from the analysis.
To examine neuropsychological outcomes, Dr. Morita-Sherman and colleagues compared measures of verbal memory, visual memory, and confrontation naming that had been obtained before surgery and at 6 months after surgery. They measured hippocampal volume using Neuroquant. They categorized resections as dominant or nondominant according to patients’ handedness or language lateralization. The investigators classified 74 patients as having a spared hippocampus and 78 patients as having a resected hippocampus. They classified neuropsychological outcomes as showing decline or no decline using epilepsy-specific reliable change indexes.
Type of surgery affected memory and naming
Approximately 40% of patients had seizure recurrence within 1 year after surgery, and 63% had seizure recurrence within 6 years after surgery. The rate of invasive EEG was similar between patients with a spared hippocampus (50%) and those with a resected hippocampus (47%). In a univariate analysis, male sex, longer epilepsy duration, normal MRI, history of invasive evaluation, and acute postoperative seizures were associated with a higher risk of seizure recurrence. Patients with a spared hippocampus had a higher risk of early seizure recurrence, compared with patients with a resected hippocampus, but the difference was not statistically significant. Long-term seizure outcomes were similar between the two groups.
Neuropsychological outcomes were available for 86 patients. Among 56 patients who underwent surgery on the dominant side, those with spared-hippocampal surgery, compared with those with resected-hippocampal surgery, had lower rates of clinically meaningful declines in verbal memory (39.7% vs. 70.4%) and naming (40.7% vs. 79.2%). The investigators found no significant difference in the 30 patients with nondominant surgeries.
“Sparing the hippocampus in a tailored temporal lobe resection doesn’t necessarily prevent any memory decline. Close to 40% of our patients where the hippocampus was spared had a clinically significant memory loss,” said Lara E. Jehi, MD, an epileptologist at the Cleveland Clinic and one of the investigators. “Including the hippocampus in the resection seems to correlate with better odds of seizure freedom, at least in the short term. We need more research to study the long-term memory and naming implications of hippocampal sparing versus resection.”
The study was funded by a grant from the National Institutes of Health. The investigators reported no conflicts of interest. [email protected]
SOURCE: Morita-Sherman ME et al. AES 2019, Abstract 1.336.
BALTIMORE – according to an analysis presented at the annual meeting of the American Epilepsy Society. Long-term seizure outcomes, however, are similar between resected and nonresected patients. In addition, sparing a normal-appearing hippocampus is correlated with a lower risk of verbal deficits, but long-term outcomes are unclear.
Neurologists have not arrived at a consensus about the best surgical management of patients with temporal lobe epilepsy and a hippocampus that appears normal on MRI. Few studies have examined seizure and neuropsychologic outcomes in this population, and this scarcity of data makes counseling patients difficult.
A review of data for surgical patients
To investigate this question, Marcia E. Morita-Sherman, MD, from the Cleveland Clinic, and colleagues retrospectively reviewed data for 152 patients who underwent surgery for temporal lobe epilepsy at the Cleveland Clinic during 2010-2018. Eligible participants were older than 16 years, and the researchers excluded patients with MRI or pathologic signs of hippocampal sclerosis and those with prior surgeries from the analysis.
To examine neuropsychological outcomes, Dr. Morita-Sherman and colleagues compared measures of verbal memory, visual memory, and confrontation naming that had been obtained before surgery and at 6 months after surgery. They measured hippocampal volume using Neuroquant. They categorized resections as dominant or nondominant according to patients’ handedness or language lateralization. The investigators classified 74 patients as having a spared hippocampus and 78 patients as having a resected hippocampus. They classified neuropsychological outcomes as showing decline or no decline using epilepsy-specific reliable change indexes.
Type of surgery affected memory and naming
Approximately 40% of patients had seizure recurrence within 1 year after surgery, and 63% had seizure recurrence within 6 years after surgery. The rate of invasive EEG was similar between patients with a spared hippocampus (50%) and those with a resected hippocampus (47%). In a univariate analysis, male sex, longer epilepsy duration, normal MRI, history of invasive evaluation, and acute postoperative seizures were associated with a higher risk of seizure recurrence. Patients with a spared hippocampus had a higher risk of early seizure recurrence, compared with patients with a resected hippocampus, but the difference was not statistically significant. Long-term seizure outcomes were similar between the two groups.
Neuropsychological outcomes were available for 86 patients. Among 56 patients who underwent surgery on the dominant side, those with spared-hippocampal surgery, compared with those with resected-hippocampal surgery, had lower rates of clinically meaningful declines in verbal memory (39.7% vs. 70.4%) and naming (40.7% vs. 79.2%). The investigators found no significant difference in the 30 patients with nondominant surgeries.
“Sparing the hippocampus in a tailored temporal lobe resection doesn’t necessarily prevent any memory decline. Close to 40% of our patients where the hippocampus was spared had a clinically significant memory loss,” said Lara E. Jehi, MD, an epileptologist at the Cleveland Clinic and one of the investigators. “Including the hippocampus in the resection seems to correlate with better odds of seizure freedom, at least in the short term. We need more research to study the long-term memory and naming implications of hippocampal sparing versus resection.”
The study was funded by a grant from the National Institutes of Health. The investigators reported no conflicts of interest. [email protected]
SOURCE: Morita-Sherman ME et al. AES 2019, Abstract 1.336.
BALTIMORE – according to an analysis presented at the annual meeting of the American Epilepsy Society. Long-term seizure outcomes, however, are similar between resected and nonresected patients. In addition, sparing a normal-appearing hippocampus is correlated with a lower risk of verbal deficits, but long-term outcomes are unclear.
Neurologists have not arrived at a consensus about the best surgical management of patients with temporal lobe epilepsy and a hippocampus that appears normal on MRI. Few studies have examined seizure and neuropsychologic outcomes in this population, and this scarcity of data makes counseling patients difficult.
A review of data for surgical patients
To investigate this question, Marcia E. Morita-Sherman, MD, from the Cleveland Clinic, and colleagues retrospectively reviewed data for 152 patients who underwent surgery for temporal lobe epilepsy at the Cleveland Clinic during 2010-2018. Eligible participants were older than 16 years, and the researchers excluded patients with MRI or pathologic signs of hippocampal sclerosis and those with prior surgeries from the analysis.
To examine neuropsychological outcomes, Dr. Morita-Sherman and colleagues compared measures of verbal memory, visual memory, and confrontation naming that had been obtained before surgery and at 6 months after surgery. They measured hippocampal volume using Neuroquant. They categorized resections as dominant or nondominant according to patients’ handedness or language lateralization. The investigators classified 74 patients as having a spared hippocampus and 78 patients as having a resected hippocampus. They classified neuropsychological outcomes as showing decline or no decline using epilepsy-specific reliable change indexes.
Type of surgery affected memory and naming
Approximately 40% of patients had seizure recurrence within 1 year after surgery, and 63% had seizure recurrence within 6 years after surgery. The rate of invasive EEG was similar between patients with a spared hippocampus (50%) and those with a resected hippocampus (47%). In a univariate analysis, male sex, longer epilepsy duration, normal MRI, history of invasive evaluation, and acute postoperative seizures were associated with a higher risk of seizure recurrence. Patients with a spared hippocampus had a higher risk of early seizure recurrence, compared with patients with a resected hippocampus, but the difference was not statistically significant. Long-term seizure outcomes were similar between the two groups.
Neuropsychological outcomes were available for 86 patients. Among 56 patients who underwent surgery on the dominant side, those with spared-hippocampal surgery, compared with those with resected-hippocampal surgery, had lower rates of clinically meaningful declines in verbal memory (39.7% vs. 70.4%) and naming (40.7% vs. 79.2%). The investigators found no significant difference in the 30 patients with nondominant surgeries.
“Sparing the hippocampus in a tailored temporal lobe resection doesn’t necessarily prevent any memory decline. Close to 40% of our patients where the hippocampus was spared had a clinically significant memory loss,” said Lara E. Jehi, MD, an epileptologist at the Cleveland Clinic and one of the investigators. “Including the hippocampus in the resection seems to correlate with better odds of seizure freedom, at least in the short term. We need more research to study the long-term memory and naming implications of hippocampal sparing versus resection.”
The study was funded by a grant from the National Institutes of Health. The investigators reported no conflicts of interest. [email protected]
SOURCE: Morita-Sherman ME et al. AES 2019, Abstract 1.336.
REPORTING FROM AES 2019
Synaptic pruning deficits may cause tremor in essential tremor
according to an investigation published January 15 in Science Translational Medicine. These synaptic pruning deficits result from insufficiency of glutamate receptor delta 2 (GluR[delta]2) protein. The findings indicate molecular, structural, physiological, and behavioral factors that contribute to tremor and might influence future treatment of essential tremor, the authors wrote.
Essential tremor has a complex etiology that includes genetic and environmental factors. Its pathophysiology is poorly understood. First author Ming-Kai Pan, MD, assistant professor of medical research and neurology at National Taiwan University Hospital in Taipei, and colleagues previously observed pruning deficits of CF-PC synapses in the cerebellum of deceased patients with essential tremor. An excess of CF-PC synapses are a prominent feature of essential tremor, but not of other cerebellar degenerative disorders. Researchers have observed this pathology consistently in patients with essential tremor who have diverse clinical features. Dr. Pan and colleagues therefore chose to examine these synaptic changes to clarify the pathophysiology of essential tremor.
Patients had more CF synapses than did controls
The investigators performed a pathological examination of postmortem cerebellar tissue from patients with essential tremor and controls to identify microstructural changes in essential tremor. Next, they applied these changes to mouse models of essential tremor and examined the corresponding structural, electrophysiologic, and behavioral changes. Finally, Dr. Pan and colleagues used cerebellar EEG to validate their findings in patients with essential tremor.
Compared with age-matched controls, patients with essential tremor had more CF synapses in the parallel-fiber synaptic territory on PC dendrites. Patients also had an approximately 75% reduction in mean GluR(delta)2 expression, compared with controls. The amount of GluR(delta)2 was inversely correlated with the percentage of CFs extending to parallel-fiber synaptic territory. The findings suggest that PC synaptic pathology in essential tremor might be related to reduced GluR(delta)2 expression, Dr. Pan and colleagues wrote.
The investigators examined a mouse model that produces 10% of full-length GluR(delta)2 protein. These mice had significant reduction of GluR(delta)2 in the cerebellar cortex and the PC dendrites. In addition, the mice consistently developed CF synapses innervating distal, thin PC dendrites. The investigators observed a 20-Hz tremor in the mice that occurred mainly during action and rarely during rest.
Dr. Pan and colleagues injected a virus containing GluR(delta)2 protein into the mice’s brains to test the protein’s relationship to tremor. Five days after the injection, the mice’s brains were expressing GluR(delta)2 protein reliably. By 4-6 days after injection, the mice’s tremor had been reduced. It returned to baseline levels at 12-14 days after injection. Injecting a control virus did not affect tremor.
Cerebellar oscillatory indexes were correlated with tremor scores
When the researchers examined local field potentials in mouse cerebellum, they found cerebellar oscillations at 20 Hz that were consistent with the observed tremor. “Putting the evidence together, GluR(delta)2 insufficiency causes CF synaptic pruning deficits, and the surplus CF-PC synaptic activity generates excessive cerebellar oscillations, which drive tremor,” Dr. Pan and colleagues reported.
Next, the researchers performed cerebellar EEG in 10 patients with essential tremor and 10 age-matched controls. Patients had cerebellar oscillations at 4-12 Hz, which are the human tremor frequencies. In an expanded cohort of 20 patients with essential tremor and 20 controls, the cerebellar oscillatory indexes were correlated with tremor scores in patients, which showed that the former could be an index of tremor severity. “Currently, diagnosis of essential tremor is based on pure clinical tremor phenomenology and direct tremor measurement, without a physiological marker indicating the underlying brain circuitry abnormalities,” they wrote. “Cerebellar oscillations can be a physiological signature and a therapeutic target for essential tremor.”
The research was funded by grants from the National Institutes of Health, the Parkinson’s Foundation, the International Essential Tremor Foundation, the Ministry of Science and Technology in Taiwan, and the National Taiwan University Hospital. The authors declared that they had no competing interests.
SOURCE: Pan M-K et al. Sci Transl Med. 2020;12:eaay1769. doi: 10.1126/scitranslmed.aay1769.
according to an investigation published January 15 in Science Translational Medicine. These synaptic pruning deficits result from insufficiency of glutamate receptor delta 2 (GluR[delta]2) protein. The findings indicate molecular, structural, physiological, and behavioral factors that contribute to tremor and might influence future treatment of essential tremor, the authors wrote.
Essential tremor has a complex etiology that includes genetic and environmental factors. Its pathophysiology is poorly understood. First author Ming-Kai Pan, MD, assistant professor of medical research and neurology at National Taiwan University Hospital in Taipei, and colleagues previously observed pruning deficits of CF-PC synapses in the cerebellum of deceased patients with essential tremor. An excess of CF-PC synapses are a prominent feature of essential tremor, but not of other cerebellar degenerative disorders. Researchers have observed this pathology consistently in patients with essential tremor who have diverse clinical features. Dr. Pan and colleagues therefore chose to examine these synaptic changes to clarify the pathophysiology of essential tremor.
Patients had more CF synapses than did controls
The investigators performed a pathological examination of postmortem cerebellar tissue from patients with essential tremor and controls to identify microstructural changes in essential tremor. Next, they applied these changes to mouse models of essential tremor and examined the corresponding structural, electrophysiologic, and behavioral changes. Finally, Dr. Pan and colleagues used cerebellar EEG to validate their findings in patients with essential tremor.
Compared with age-matched controls, patients with essential tremor had more CF synapses in the parallel-fiber synaptic territory on PC dendrites. Patients also had an approximately 75% reduction in mean GluR(delta)2 expression, compared with controls. The amount of GluR(delta)2 was inversely correlated with the percentage of CFs extending to parallel-fiber synaptic territory. The findings suggest that PC synaptic pathology in essential tremor might be related to reduced GluR(delta)2 expression, Dr. Pan and colleagues wrote.
The investigators examined a mouse model that produces 10% of full-length GluR(delta)2 protein. These mice had significant reduction of GluR(delta)2 in the cerebellar cortex and the PC dendrites. In addition, the mice consistently developed CF synapses innervating distal, thin PC dendrites. The investigators observed a 20-Hz tremor in the mice that occurred mainly during action and rarely during rest.
Dr. Pan and colleagues injected a virus containing GluR(delta)2 protein into the mice’s brains to test the protein’s relationship to tremor. Five days after the injection, the mice’s brains were expressing GluR(delta)2 protein reliably. By 4-6 days after injection, the mice’s tremor had been reduced. It returned to baseline levels at 12-14 days after injection. Injecting a control virus did not affect tremor.
Cerebellar oscillatory indexes were correlated with tremor scores
When the researchers examined local field potentials in mouse cerebellum, they found cerebellar oscillations at 20 Hz that were consistent with the observed tremor. “Putting the evidence together, GluR(delta)2 insufficiency causes CF synaptic pruning deficits, and the surplus CF-PC synaptic activity generates excessive cerebellar oscillations, which drive tremor,” Dr. Pan and colleagues reported.
Next, the researchers performed cerebellar EEG in 10 patients with essential tremor and 10 age-matched controls. Patients had cerebellar oscillations at 4-12 Hz, which are the human tremor frequencies. In an expanded cohort of 20 patients with essential tremor and 20 controls, the cerebellar oscillatory indexes were correlated with tremor scores in patients, which showed that the former could be an index of tremor severity. “Currently, diagnosis of essential tremor is based on pure clinical tremor phenomenology and direct tremor measurement, without a physiological marker indicating the underlying brain circuitry abnormalities,” they wrote. “Cerebellar oscillations can be a physiological signature and a therapeutic target for essential tremor.”
The research was funded by grants from the National Institutes of Health, the Parkinson’s Foundation, the International Essential Tremor Foundation, the Ministry of Science and Technology in Taiwan, and the National Taiwan University Hospital. The authors declared that they had no competing interests.
SOURCE: Pan M-K et al. Sci Transl Med. 2020;12:eaay1769. doi: 10.1126/scitranslmed.aay1769.
according to an investigation published January 15 in Science Translational Medicine. These synaptic pruning deficits result from insufficiency of glutamate receptor delta 2 (GluR[delta]2) protein. The findings indicate molecular, structural, physiological, and behavioral factors that contribute to tremor and might influence future treatment of essential tremor, the authors wrote.
Essential tremor has a complex etiology that includes genetic and environmental factors. Its pathophysiology is poorly understood. First author Ming-Kai Pan, MD, assistant professor of medical research and neurology at National Taiwan University Hospital in Taipei, and colleagues previously observed pruning deficits of CF-PC synapses in the cerebellum of deceased patients with essential tremor. An excess of CF-PC synapses are a prominent feature of essential tremor, but not of other cerebellar degenerative disorders. Researchers have observed this pathology consistently in patients with essential tremor who have diverse clinical features. Dr. Pan and colleagues therefore chose to examine these synaptic changes to clarify the pathophysiology of essential tremor.
Patients had more CF synapses than did controls
The investigators performed a pathological examination of postmortem cerebellar tissue from patients with essential tremor and controls to identify microstructural changes in essential tremor. Next, they applied these changes to mouse models of essential tremor and examined the corresponding structural, electrophysiologic, and behavioral changes. Finally, Dr. Pan and colleagues used cerebellar EEG to validate their findings in patients with essential tremor.
Compared with age-matched controls, patients with essential tremor had more CF synapses in the parallel-fiber synaptic territory on PC dendrites. Patients also had an approximately 75% reduction in mean GluR(delta)2 expression, compared with controls. The amount of GluR(delta)2 was inversely correlated with the percentage of CFs extending to parallel-fiber synaptic territory. The findings suggest that PC synaptic pathology in essential tremor might be related to reduced GluR(delta)2 expression, Dr. Pan and colleagues wrote.
The investigators examined a mouse model that produces 10% of full-length GluR(delta)2 protein. These mice had significant reduction of GluR(delta)2 in the cerebellar cortex and the PC dendrites. In addition, the mice consistently developed CF synapses innervating distal, thin PC dendrites. The investigators observed a 20-Hz tremor in the mice that occurred mainly during action and rarely during rest.
Dr. Pan and colleagues injected a virus containing GluR(delta)2 protein into the mice’s brains to test the protein’s relationship to tremor. Five days after the injection, the mice’s brains were expressing GluR(delta)2 protein reliably. By 4-6 days after injection, the mice’s tremor had been reduced. It returned to baseline levels at 12-14 days after injection. Injecting a control virus did not affect tremor.
Cerebellar oscillatory indexes were correlated with tremor scores
When the researchers examined local field potentials in mouse cerebellum, they found cerebellar oscillations at 20 Hz that were consistent with the observed tremor. “Putting the evidence together, GluR(delta)2 insufficiency causes CF synaptic pruning deficits, and the surplus CF-PC synaptic activity generates excessive cerebellar oscillations, which drive tremor,” Dr. Pan and colleagues reported.
Next, the researchers performed cerebellar EEG in 10 patients with essential tremor and 10 age-matched controls. Patients had cerebellar oscillations at 4-12 Hz, which are the human tremor frequencies. In an expanded cohort of 20 patients with essential tremor and 20 controls, the cerebellar oscillatory indexes were correlated with tremor scores in patients, which showed that the former could be an index of tremor severity. “Currently, diagnosis of essential tremor is based on pure clinical tremor phenomenology and direct tremor measurement, without a physiological marker indicating the underlying brain circuitry abnormalities,” they wrote. “Cerebellar oscillations can be a physiological signature and a therapeutic target for essential tremor.”
The research was funded by grants from the National Institutes of Health, the Parkinson’s Foundation, the International Essential Tremor Foundation, the Ministry of Science and Technology in Taiwan, and the National Taiwan University Hospital. The authors declared that they had no competing interests.
SOURCE: Pan M-K et al. Sci Transl Med. 2020;12:eaay1769. doi: 10.1126/scitranslmed.aay1769.
FROM SCIENCE TRANSLATIONAL MEDICINE
Comorbidity rates remain stable over 10 years in childhood-onset epilepsy
BALTIMORE – , according to research presented at the annual meeting of the American Epilepsy Society. Compared with controls, however, young adults with childhood-onset epilepsy have higher rates of psychiatric comorbidity.
The findings suggest that “diagnoses that are identified at baseline continue to be a problem over time,” said Jana E. Jones, PhD, associate professor of neuropsychology at the University of Wisconsin in Madison. Although neurologists understand that comorbidities are common among patients with childhood-onset epilepsy, “it would be good for us to continue to learn what factors are influencing this,” she added.
Investigators sought predictors of outcomes at 10 years
Since 2004, Dr. Jones and her colleagues at the University of Wisconsin have been conducting a study of patients with childhood-onset epilepsy. After the population had completed 10 years of follow-up, the researchers analyzed the data to identify potential patterns of medical and psychiatric comorbidities. One question that they sought to answer was whether any baseline factors could predict outcomes at 10 years.
The researchers analyzed data for 53 patients with childhood-onset epilepsy and 55 controls without epilepsy. At baseline, participants were between ages 8 years and 18 years and had no intellectual disability or neurologic impairment. Within 1 year of epilepsy diagnosis, each participant underwent a psychiatric interview based on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Ten years later, participants underwent the Composite International Diagnostic Interview (CIDI), a psychiatric interview for adults. Information about medical comorbidities was collected through interviews and record review at baseline and through an online survey at the 10-year follow-up.
Participants’ mean age at baseline was 12 years. Mean IQ was 105 for the epilepsy group and 109 for the control group. At 10 years, participants’ mean age was about 23 years. Among patients with epilepsy, 55% had focal epilepsy, and 42% had generalized epilepsy. About 40% of participants with epilepsy were in remission at 10 years, which Dr. Jones and colleagues defined as having achieved 5 years without taking medications and without having seizures. At 10 years after diagnosis, 51% of patients with epilepsy were not taking any seizure medication, including approximately 11% of patients with epilepsy who were not categorized as in remission. Most patients taking medication were on monotherapy.
Trends in psychiatric and medical comorbidities
At baseline, approximately 75% of children with epilepsy had a psychiatric or medical diagnosis, compared with 40% of controls. At the 10-year follow-up, 62% of children with epilepsy had a psychiatric diagnosis, compared with 35% of controls. Among controls, 4% had a medical comorbidity (i.e., asthma) alone at baseline. Asthma was the most common medical comorbidity at baseline among patients with epilepsy, and other comorbidities included sleep disorder, head injury, and scoliosis. Six percent of patients had a medical comorbidity alone at baseline. The proportion of patients with both psychiatric and medical comorbidity was 8% at baseline. Patients with epilepsy at baseline had an increased risk of psychiatric comorbidity.
At 10 years, the most common medical comorbidity among patients with epilepsy was head injury (18.9%), followed by allergies and asthma. The rate of migraine was about 13% among controls and slightly less in the epilepsy group. Dr. Jones and colleagues found no significant differences in medical comorbidities between groups at 10 years. At that point, the rate of medical comorbidity was 4% among patients and 11% among controls.
The rate of psychiatric comorbidity remained relatively stable over 10 years, said Dr. Jones. Approximately 47% of patients with epilepsy had a psychiatric diagnosis at 10 years, compared with 29% of controls. In addition, 38% of patients with epilepsy had both psychiatric and medical diagnoses, compared with 29% of controls. Epilepsy increased the risk of psychiatric comorbidity at the 10-year follow-up. Neither medications, remission status, nor seizure type predicted any comorbidity at 10 years.
Dr. Jones and colleagues compared comorbidity rates between the study sample and the National Comorbidity Survey Replication (NCS-R), which reported population-based data that included an epilepsy sample. About 47% of the epilepsy group had an anxiety disorder, compared with 40.7% in the NCS-R. The rate of anxiety disorders was higher in the control group (45.5%) than in the control group (30.8%) in the NCS-R. Approximately 26.4% of the population in Dr. Jones’s study had a mood disorder, compared with 25.9% in the National Comorbidity Survey.
Dr. Jones and colleagues are conducting 15-year follow-up of their original population. One question they will examine is whether medical comorbidities will increase in patients with childhood-onset epilepsy as they approach age 30 years.
Two of the investigators received funding in the form of a grant from the National Institutes of Health.
SOURCE: Kesselmayer RF et al. AES 2019. Abstract 1.288.
BALTIMORE – , according to research presented at the annual meeting of the American Epilepsy Society. Compared with controls, however, young adults with childhood-onset epilepsy have higher rates of psychiatric comorbidity.
The findings suggest that “diagnoses that are identified at baseline continue to be a problem over time,” said Jana E. Jones, PhD, associate professor of neuropsychology at the University of Wisconsin in Madison. Although neurologists understand that comorbidities are common among patients with childhood-onset epilepsy, “it would be good for us to continue to learn what factors are influencing this,” she added.
Investigators sought predictors of outcomes at 10 years
Since 2004, Dr. Jones and her colleagues at the University of Wisconsin have been conducting a study of patients with childhood-onset epilepsy. After the population had completed 10 years of follow-up, the researchers analyzed the data to identify potential patterns of medical and psychiatric comorbidities. One question that they sought to answer was whether any baseline factors could predict outcomes at 10 years.
The researchers analyzed data for 53 patients with childhood-onset epilepsy and 55 controls without epilepsy. At baseline, participants were between ages 8 years and 18 years and had no intellectual disability or neurologic impairment. Within 1 year of epilepsy diagnosis, each participant underwent a psychiatric interview based on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Ten years later, participants underwent the Composite International Diagnostic Interview (CIDI), a psychiatric interview for adults. Information about medical comorbidities was collected through interviews and record review at baseline and through an online survey at the 10-year follow-up.
Participants’ mean age at baseline was 12 years. Mean IQ was 105 for the epilepsy group and 109 for the control group. At 10 years, participants’ mean age was about 23 years. Among patients with epilepsy, 55% had focal epilepsy, and 42% had generalized epilepsy. About 40% of participants with epilepsy were in remission at 10 years, which Dr. Jones and colleagues defined as having achieved 5 years without taking medications and without having seizures. At 10 years after diagnosis, 51% of patients with epilepsy were not taking any seizure medication, including approximately 11% of patients with epilepsy who were not categorized as in remission. Most patients taking medication were on monotherapy.
Trends in psychiatric and medical comorbidities
At baseline, approximately 75% of children with epilepsy had a psychiatric or medical diagnosis, compared with 40% of controls. At the 10-year follow-up, 62% of children with epilepsy had a psychiatric diagnosis, compared with 35% of controls. Among controls, 4% had a medical comorbidity (i.e., asthma) alone at baseline. Asthma was the most common medical comorbidity at baseline among patients with epilepsy, and other comorbidities included sleep disorder, head injury, and scoliosis. Six percent of patients had a medical comorbidity alone at baseline. The proportion of patients with both psychiatric and medical comorbidity was 8% at baseline. Patients with epilepsy at baseline had an increased risk of psychiatric comorbidity.
At 10 years, the most common medical comorbidity among patients with epilepsy was head injury (18.9%), followed by allergies and asthma. The rate of migraine was about 13% among controls and slightly less in the epilepsy group. Dr. Jones and colleagues found no significant differences in medical comorbidities between groups at 10 years. At that point, the rate of medical comorbidity was 4% among patients and 11% among controls.
The rate of psychiatric comorbidity remained relatively stable over 10 years, said Dr. Jones. Approximately 47% of patients with epilepsy had a psychiatric diagnosis at 10 years, compared with 29% of controls. In addition, 38% of patients with epilepsy had both psychiatric and medical diagnoses, compared with 29% of controls. Epilepsy increased the risk of psychiatric comorbidity at the 10-year follow-up. Neither medications, remission status, nor seizure type predicted any comorbidity at 10 years.
Dr. Jones and colleagues compared comorbidity rates between the study sample and the National Comorbidity Survey Replication (NCS-R), which reported population-based data that included an epilepsy sample. About 47% of the epilepsy group had an anxiety disorder, compared with 40.7% in the NCS-R. The rate of anxiety disorders was higher in the control group (45.5%) than in the control group (30.8%) in the NCS-R. Approximately 26.4% of the population in Dr. Jones’s study had a mood disorder, compared with 25.9% in the National Comorbidity Survey.
Dr. Jones and colleagues are conducting 15-year follow-up of their original population. One question they will examine is whether medical comorbidities will increase in patients with childhood-onset epilepsy as they approach age 30 years.
Two of the investigators received funding in the form of a grant from the National Institutes of Health.
SOURCE: Kesselmayer RF et al. AES 2019. Abstract 1.288.
BALTIMORE – , according to research presented at the annual meeting of the American Epilepsy Society. Compared with controls, however, young adults with childhood-onset epilepsy have higher rates of psychiatric comorbidity.
The findings suggest that “diagnoses that are identified at baseline continue to be a problem over time,” said Jana E. Jones, PhD, associate professor of neuropsychology at the University of Wisconsin in Madison. Although neurologists understand that comorbidities are common among patients with childhood-onset epilepsy, “it would be good for us to continue to learn what factors are influencing this,” she added.
Investigators sought predictors of outcomes at 10 years
Since 2004, Dr. Jones and her colleagues at the University of Wisconsin have been conducting a study of patients with childhood-onset epilepsy. After the population had completed 10 years of follow-up, the researchers analyzed the data to identify potential patterns of medical and psychiatric comorbidities. One question that they sought to answer was whether any baseline factors could predict outcomes at 10 years.
The researchers analyzed data for 53 patients with childhood-onset epilepsy and 55 controls without epilepsy. At baseline, participants were between ages 8 years and 18 years and had no intellectual disability or neurologic impairment. Within 1 year of epilepsy diagnosis, each participant underwent a psychiatric interview based on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Ten years later, participants underwent the Composite International Diagnostic Interview (CIDI), a psychiatric interview for adults. Information about medical comorbidities was collected through interviews and record review at baseline and through an online survey at the 10-year follow-up.
Participants’ mean age at baseline was 12 years. Mean IQ was 105 for the epilepsy group and 109 for the control group. At 10 years, participants’ mean age was about 23 years. Among patients with epilepsy, 55% had focal epilepsy, and 42% had generalized epilepsy. About 40% of participants with epilepsy were in remission at 10 years, which Dr. Jones and colleagues defined as having achieved 5 years without taking medications and without having seizures. At 10 years after diagnosis, 51% of patients with epilepsy were not taking any seizure medication, including approximately 11% of patients with epilepsy who were not categorized as in remission. Most patients taking medication were on monotherapy.
Trends in psychiatric and medical comorbidities
At baseline, approximately 75% of children with epilepsy had a psychiatric or medical diagnosis, compared with 40% of controls. At the 10-year follow-up, 62% of children with epilepsy had a psychiatric diagnosis, compared with 35% of controls. Among controls, 4% had a medical comorbidity (i.e., asthma) alone at baseline. Asthma was the most common medical comorbidity at baseline among patients with epilepsy, and other comorbidities included sleep disorder, head injury, and scoliosis. Six percent of patients had a medical comorbidity alone at baseline. The proportion of patients with both psychiatric and medical comorbidity was 8% at baseline. Patients with epilepsy at baseline had an increased risk of psychiatric comorbidity.
At 10 years, the most common medical comorbidity among patients with epilepsy was head injury (18.9%), followed by allergies and asthma. The rate of migraine was about 13% among controls and slightly less in the epilepsy group. Dr. Jones and colleagues found no significant differences in medical comorbidities between groups at 10 years. At that point, the rate of medical comorbidity was 4% among patients and 11% among controls.
The rate of psychiatric comorbidity remained relatively stable over 10 years, said Dr. Jones. Approximately 47% of patients with epilepsy had a psychiatric diagnosis at 10 years, compared with 29% of controls. In addition, 38% of patients with epilepsy had both psychiatric and medical diagnoses, compared with 29% of controls. Epilepsy increased the risk of psychiatric comorbidity at the 10-year follow-up. Neither medications, remission status, nor seizure type predicted any comorbidity at 10 years.
Dr. Jones and colleagues compared comorbidity rates between the study sample and the National Comorbidity Survey Replication (NCS-R), which reported population-based data that included an epilepsy sample. About 47% of the epilepsy group had an anxiety disorder, compared with 40.7% in the NCS-R. The rate of anxiety disorders was higher in the control group (45.5%) than in the control group (30.8%) in the NCS-R. Approximately 26.4% of the population in Dr. Jones’s study had a mood disorder, compared with 25.9% in the National Comorbidity Survey.
Dr. Jones and colleagues are conducting 15-year follow-up of their original population. One question they will examine is whether medical comorbidities will increase in patients with childhood-onset epilepsy as they approach age 30 years.
Two of the investigators received funding in the form of a grant from the National Institutes of Health.
SOURCE: Kesselmayer RF et al. AES 2019. Abstract 1.288.
REPORTING FROM AES 2019
AED exposure from breastfeeding appears to be low
, according to a study published online ahead of print Dec. 30, 2019, in JAMA Neurology. The results may explain why previous research failed to find adverse neurodevelopmental effects of breastfeeding in infants whose mothers are undergoing AED treatment, said the authors.
“The results of this study add support to the general safety of breastfeeding by mothers with epilepsy who take AEDs,” wrote Angela K. Birnbaum, PhD, professor of experimental and clinical pharmacology at the University of Minnesota in Minneapolis, and colleagues.
Investigators measured infants’ blood AED concentrations
To date, medical consensus about the safety of breastfeeding while the mother is taking AEDs has been elusive. Researchers have investigated breast milk concentrations of AEDs as surrogate markers of AED concentrations in children. Breast milk concentrations, however, do not account for differences in infant pharmacokinetic processes and thus could misrepresent AED exposure in children through breastfeeding.
Dr. Birnbaum and colleagues sought to measure blood concentrations of AEDs in mothers with epilepsy and the infants that they breastfed to achieve an objective measure of AED exposure through breastfeeding. They examined data collected from December 2012 to October 2016 in the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study. Eligible participants were pregnant women with epilepsy between the ages of 14 and 45 years whose pregnancies had progressed to fewer than 20 weeks’ gestational age and who had IQ scores greater than 70 points. Participants were followed up throughout pregnancy and for 9 months post partum. Children were enrolled at birth.
The investigators collected blood samples from mothers and infants who were breastfed at the same visit, which occurred at between 5 and 20 weeks after birth. The volume of ingested breast milk delivered through graduated feeding bottles each day and the total duration of all daily breastfeeding sessions were recorded. For infants, blood samples were collected from the plantar surface of the heel and stored as dried blood spots on filter paper. The study’s primary endpoint was the percentage of infant-to-mother concentration of AEDs. Concentrations of AEDs in infants at less than the lower limit of quantification were assessed as half of the lower limit.
Exposure in utero may be greater than exposure through breast milk
In all, the researchers enrolled 351 pregnant women with epilepsy into the study and collected data on 345 infants. Two hundred twenty-two (64.3%) of the infants were breastfed, and 146 (42.3%) had AED concentrations available. After excluding outliers and mothers with missing concentration data, Dr. Birnbaum and colleagues included 164 matching infant-mother concentration pairs in their analysis (i.e., of 135 mothers and 138 infants). Approximately 52% of the infants were female, and their median age at blood collection was 13 weeks. The mothers’ median age was 32 years. About 82% of mothers were receiving monotherapy. The investigators found no demographic differences between groups of mothers taking various AEDs.
Sixty-eight infants (49.3%) had AED concentrations that were less than the lower limit of quantification. AED concentration was not greater than the lower limit of quantification for any infants breastfed by mothers taking carbamazepine, oxcarbazepine, valproic acid, or topiramate. Most levetiracetam (71.4%) and zonisamide (60.0%) concentrations in infants were less than the lower limit of quantification. Most lamotrigine concentrations in infants (88.6%) were greater than the lower limit of quantification.
The median percentage of infant-to-mother concentration was 28.9% for lamotrigine, 5.3% for levetiracetam, 44.2% for zonisamide, 5.7% for carbamazepine, 5.4% for carbamazepine epoxide, 0.3% for oxcarbazepine, 17.2% for topiramate, and 21.4% for valproic acid. Multiple linear regression models indicated that maternal concentration was significantly associated with lamotrigine concentration in infants, but not levetiracetam concentration in infants.
“Prior studies at delivery demonstrated that umbilical-cord concentrations were nearly equal to maternal concentrations, suggesting extensive placental passage to the fetus,” wrote Dr. Birnbaum and colleagues. “Therefore, the amount of AED exposure via breast milk is likely substantially lower than fetal exposure during pregnancy and appears unlikely to confer any additional risks beyond those that might be associated with exposure in pregnancy, especially given prior studies showing no adverse neurodevelopmental effects of breastfeeding while taking AEDs.”
The investigators acknowledged several limitations of their research, including the observational design of the MONEAD study. The amount of AED in participants’ breast milk is unknown, and the investigators could not calculate relative infant dosages. Only one blood sample was taken per infant, thus the results may not reflect infants’ total exposure over time.
The National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Development funded the research. The authors reported receiving research support from various pharmaceutical companies.
SOURCE: Birnbaum AK et al. JAMA Neurol. 2019 Dec 30. doi: 10.1001/jamaneurol.2019.4443.
, according to a study published online ahead of print Dec. 30, 2019, in JAMA Neurology. The results may explain why previous research failed to find adverse neurodevelopmental effects of breastfeeding in infants whose mothers are undergoing AED treatment, said the authors.
“The results of this study add support to the general safety of breastfeeding by mothers with epilepsy who take AEDs,” wrote Angela K. Birnbaum, PhD, professor of experimental and clinical pharmacology at the University of Minnesota in Minneapolis, and colleagues.
Investigators measured infants’ blood AED concentrations
To date, medical consensus about the safety of breastfeeding while the mother is taking AEDs has been elusive. Researchers have investigated breast milk concentrations of AEDs as surrogate markers of AED concentrations in children. Breast milk concentrations, however, do not account for differences in infant pharmacokinetic processes and thus could misrepresent AED exposure in children through breastfeeding.
Dr. Birnbaum and colleagues sought to measure blood concentrations of AEDs in mothers with epilepsy and the infants that they breastfed to achieve an objective measure of AED exposure through breastfeeding. They examined data collected from December 2012 to October 2016 in the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study. Eligible participants were pregnant women with epilepsy between the ages of 14 and 45 years whose pregnancies had progressed to fewer than 20 weeks’ gestational age and who had IQ scores greater than 70 points. Participants were followed up throughout pregnancy and for 9 months post partum. Children were enrolled at birth.
The investigators collected blood samples from mothers and infants who were breastfed at the same visit, which occurred at between 5 and 20 weeks after birth. The volume of ingested breast milk delivered through graduated feeding bottles each day and the total duration of all daily breastfeeding sessions were recorded. For infants, blood samples were collected from the plantar surface of the heel and stored as dried blood spots on filter paper. The study’s primary endpoint was the percentage of infant-to-mother concentration of AEDs. Concentrations of AEDs in infants at less than the lower limit of quantification were assessed as half of the lower limit.
Exposure in utero may be greater than exposure through breast milk
In all, the researchers enrolled 351 pregnant women with epilepsy into the study and collected data on 345 infants. Two hundred twenty-two (64.3%) of the infants were breastfed, and 146 (42.3%) had AED concentrations available. After excluding outliers and mothers with missing concentration data, Dr. Birnbaum and colleagues included 164 matching infant-mother concentration pairs in their analysis (i.e., of 135 mothers and 138 infants). Approximately 52% of the infants were female, and their median age at blood collection was 13 weeks. The mothers’ median age was 32 years. About 82% of mothers were receiving monotherapy. The investigators found no demographic differences between groups of mothers taking various AEDs.
Sixty-eight infants (49.3%) had AED concentrations that were less than the lower limit of quantification. AED concentration was not greater than the lower limit of quantification for any infants breastfed by mothers taking carbamazepine, oxcarbazepine, valproic acid, or topiramate. Most levetiracetam (71.4%) and zonisamide (60.0%) concentrations in infants were less than the lower limit of quantification. Most lamotrigine concentrations in infants (88.6%) were greater than the lower limit of quantification.
The median percentage of infant-to-mother concentration was 28.9% for lamotrigine, 5.3% for levetiracetam, 44.2% for zonisamide, 5.7% for carbamazepine, 5.4% for carbamazepine epoxide, 0.3% for oxcarbazepine, 17.2% for topiramate, and 21.4% for valproic acid. Multiple linear regression models indicated that maternal concentration was significantly associated with lamotrigine concentration in infants, but not levetiracetam concentration in infants.
“Prior studies at delivery demonstrated that umbilical-cord concentrations were nearly equal to maternal concentrations, suggesting extensive placental passage to the fetus,” wrote Dr. Birnbaum and colleagues. “Therefore, the amount of AED exposure via breast milk is likely substantially lower than fetal exposure during pregnancy and appears unlikely to confer any additional risks beyond those that might be associated with exposure in pregnancy, especially given prior studies showing no adverse neurodevelopmental effects of breastfeeding while taking AEDs.”
The investigators acknowledged several limitations of their research, including the observational design of the MONEAD study. The amount of AED in participants’ breast milk is unknown, and the investigators could not calculate relative infant dosages. Only one blood sample was taken per infant, thus the results may not reflect infants’ total exposure over time.
The National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Development funded the research. The authors reported receiving research support from various pharmaceutical companies.
SOURCE: Birnbaum AK et al. JAMA Neurol. 2019 Dec 30. doi: 10.1001/jamaneurol.2019.4443.
, according to a study published online ahead of print Dec. 30, 2019, in JAMA Neurology. The results may explain why previous research failed to find adverse neurodevelopmental effects of breastfeeding in infants whose mothers are undergoing AED treatment, said the authors.
“The results of this study add support to the general safety of breastfeeding by mothers with epilepsy who take AEDs,” wrote Angela K. Birnbaum, PhD, professor of experimental and clinical pharmacology at the University of Minnesota in Minneapolis, and colleagues.
Investigators measured infants’ blood AED concentrations
To date, medical consensus about the safety of breastfeeding while the mother is taking AEDs has been elusive. Researchers have investigated breast milk concentrations of AEDs as surrogate markers of AED concentrations in children. Breast milk concentrations, however, do not account for differences in infant pharmacokinetic processes and thus could misrepresent AED exposure in children through breastfeeding.
Dr. Birnbaum and colleagues sought to measure blood concentrations of AEDs in mothers with epilepsy and the infants that they breastfed to achieve an objective measure of AED exposure through breastfeeding. They examined data collected from December 2012 to October 2016 in the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study. Eligible participants were pregnant women with epilepsy between the ages of 14 and 45 years whose pregnancies had progressed to fewer than 20 weeks’ gestational age and who had IQ scores greater than 70 points. Participants were followed up throughout pregnancy and for 9 months post partum. Children were enrolled at birth.
The investigators collected blood samples from mothers and infants who were breastfed at the same visit, which occurred at between 5 and 20 weeks after birth. The volume of ingested breast milk delivered through graduated feeding bottles each day and the total duration of all daily breastfeeding sessions were recorded. For infants, blood samples were collected from the plantar surface of the heel and stored as dried blood spots on filter paper. The study’s primary endpoint was the percentage of infant-to-mother concentration of AEDs. Concentrations of AEDs in infants at less than the lower limit of quantification were assessed as half of the lower limit.
Exposure in utero may be greater than exposure through breast milk
In all, the researchers enrolled 351 pregnant women with epilepsy into the study and collected data on 345 infants. Two hundred twenty-two (64.3%) of the infants were breastfed, and 146 (42.3%) had AED concentrations available. After excluding outliers and mothers with missing concentration data, Dr. Birnbaum and colleagues included 164 matching infant-mother concentration pairs in their analysis (i.e., of 135 mothers and 138 infants). Approximately 52% of the infants were female, and their median age at blood collection was 13 weeks. The mothers’ median age was 32 years. About 82% of mothers were receiving monotherapy. The investigators found no demographic differences between groups of mothers taking various AEDs.
Sixty-eight infants (49.3%) had AED concentrations that were less than the lower limit of quantification. AED concentration was not greater than the lower limit of quantification for any infants breastfed by mothers taking carbamazepine, oxcarbazepine, valproic acid, or topiramate. Most levetiracetam (71.4%) and zonisamide (60.0%) concentrations in infants were less than the lower limit of quantification. Most lamotrigine concentrations in infants (88.6%) were greater than the lower limit of quantification.
The median percentage of infant-to-mother concentration was 28.9% for lamotrigine, 5.3% for levetiracetam, 44.2% for zonisamide, 5.7% for carbamazepine, 5.4% for carbamazepine epoxide, 0.3% for oxcarbazepine, 17.2% for topiramate, and 21.4% for valproic acid. Multiple linear regression models indicated that maternal concentration was significantly associated with lamotrigine concentration in infants, but not levetiracetam concentration in infants.
“Prior studies at delivery demonstrated that umbilical-cord concentrations were nearly equal to maternal concentrations, suggesting extensive placental passage to the fetus,” wrote Dr. Birnbaum and colleagues. “Therefore, the amount of AED exposure via breast milk is likely substantially lower than fetal exposure during pregnancy and appears unlikely to confer any additional risks beyond those that might be associated with exposure in pregnancy, especially given prior studies showing no adverse neurodevelopmental effects of breastfeeding while taking AEDs.”
The investigators acknowledged several limitations of their research, including the observational design of the MONEAD study. The amount of AED in participants’ breast milk is unknown, and the investigators could not calculate relative infant dosages. Only one blood sample was taken per infant, thus the results may not reflect infants’ total exposure over time.
The National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Development funded the research. The authors reported receiving research support from various pharmaceutical companies.
SOURCE: Birnbaum AK et al. JAMA Neurol. 2019 Dec 30. doi: 10.1001/jamaneurol.2019.4443.
FROM JAMA NEUROLOGY