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Poverty tied to poor cognition in patients with epilepsy
ORLANDO — , early research suggests.
Seniors with epilepsy present with multiple comorbidities, including, for example, hypertension and diabetes, and they are at increased risk of developing dementia, said study investigator Anny Reyes, PhD, a postdoctoral scholar at the University of California at San Diego.
Past research has shown neighborhood disadvantage is associated with numerous adverse health outcomes, including an increased risk for developing Alzheimer’s disease and related dementias (ADRD).
“We already know epilepsy on its own increases risks for dementia, and when you add disadvantaged to that, it’s going to increase the risk even more,” said Dr. Reyes.
Neurologists should ask their older patients with epilepsy, many of whom live alone, about food insecurity and access to resources “not just within the hospital system but also within their community,” she said.
The findings were presented at the annual meeting of the American Epilepsy Society.
Proxy Measure of Disadvantage
The incidence and prevalence of epilepsy increases with age. Older adults represent the fastest growing segment of individuals with epilepsy, said Dr. Reyes.
The new study included 40 patients with focal epilepsy, average age 67 years, from three areas: San Diego, California; Madison, Wisconsin; and Cleveland, Ohio.
Researchers collected clinical and sociodemographic information as well as vascular biomarkers. They also gathered individual-level data, including income, parental education levels, details on childhood upbringing, etc.
Using residential addresses, investigators determined the area deprivation index (ADI) value for study participants. The ADI is a proxy measure for neighborhood-level socioeconomic disadvantage that captures factors such a poverty, employment, housing, and education opportunities.
ADI values range from 1 to 10, with a higher number indicating greater neighborhood disadvantage. About 30% of the cohort had an ADI decile greater than 6.
Researchers divided subjects into Most Disadvantaged (ADI greater than 7) and Least Disadvantaged (AD 7 or less). The two groups were similar with regard to age, education level, and race/ethnicity.
But those from the most disadvantaged areas were younger, taking more antiseizure medications, had fewer years of education, lower levels of father’s education, less personal and family income, and were less likely to be diagnosed with hypertension.
Study subjects completed neuropsychological testing, including:
- Measures of learning (Rey Auditory Verbal Learning Test [RAVLT] Learning Over Trials; Wechsler Memory Scale 4th Edition [WMS-4] Logical Memory [LM] Story B immediate; and WMS-4 Visual Reproduction [VR] immediate)
- Memory (RAVLT delayed recall, WMS-4 LM delayed recall, and WMS-4 VR delayed recall)
- Language (Multilingual Naming Test, Auditory Naming Test, and animal fluency)
- Executive function/processing speed (Letter fluency and Trail-Making Test Parts A and B)
The study found a correlation between higher ADI (most disadvantaged) and poorer performance on learning (Spearman rho: -0.433; 95% CI -0.664 to -0.126; P = .006), memory (r = -0.496; 95% CI -0.707 to -0.205; P = .001), and executive function/processes speed (r = -0.315; 95% CI -0.577 to 0.006; P = .048), but no significant association with language.
Looking at individual-level data, the study found memory and processing speed “were driving the relationship, and again, patients had worse performance when they were coming from the most disadvantaged neighborhoods,” said Dr. Reyes.
The investigators also examined mood, including depression and anxiety, and subjective complaints of cognitive problems. “We found those patients residing in the most disadvantaged neighborhoods complained more about memory problems,” she said.
The results underscore the need for community-level interventions “that could provide resources in support of these older adults and their families and connect them to services we know are good for brain health,” said Dr. Reyes.
Alzheimer’s disease experts “have done a really good job of this, but this is new for epilepsy,” she added. “This gives us a great opportunity to kind of bridge the worlds of dementia and epilepsy.”
Novel Research
Commenting on the research, Rani Sarkis, MD, assistant professor of neurology, Brigham and Women’s Hospital, Boston, said the study is “very useful” as it ties social determinants of health to cognition.
“We have not been doing that” in people with epilepsy, he said.
The study, one of the first to look at the link between disadvantaged neighborhoods and cognitive impairment, “has very important” public health implications, including the need to consider access to activities that promote cognitive resilience and other brain health initiatives, said Dr. Sarkis.
Another larger study that looked at neighborhood deprivation and cognition in epilepsy was also presented at the AES meeting and published earlier this year in the journal Neurology.
That study included 800 patients with pharmaco-resistant temporal lobe epilepsy being evaluated for surgery at the Cleveland Clinic, mean age about 38 years. It examined numerous cognitive domains as well as depression and anxiety in relation to ADI generated by patient addresses and split into quintiles from least to most disadvantaged.
After controlling for covariants, the study found scores for all cognitive domains were significantly worse in the most disadvantaged quintile except for executive function, which was close to reaching significance (P = .052), said lead author Robyn M. Busch, PhD, a clinical neuropsychologist in the Epilepsy Center, Department of Neurology, Cleveland Clinic.
The study also found people in the most disadvantaged areas had more symptoms of depression and anxiety compared with people in the least disadvantaged areas, said Busch.
A Complex Issue
Although the exact mechanism tying disadvantaged areas to cognition in epilepsy isn’t fully understood, having less access to health care and educational opportunities, poor nutrition, and being under chronic stress “are all things that affect the brain,” said Dr. Busch.
“This is super complex and it’s going to be really difficult to tease apart, but we’d like to look at imaging data to see if it’s something structural, if there are functional changes in the brain or something that might help us understand this better.”
But it’s also possible that having epilepsy “might be pushing people into environments” that offer fewer employment and educational opportunities and less access to resources, she said.
The study authors and Dr. Sarkis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO — , early research suggests.
Seniors with epilepsy present with multiple comorbidities, including, for example, hypertension and diabetes, and they are at increased risk of developing dementia, said study investigator Anny Reyes, PhD, a postdoctoral scholar at the University of California at San Diego.
Past research has shown neighborhood disadvantage is associated with numerous adverse health outcomes, including an increased risk for developing Alzheimer’s disease and related dementias (ADRD).
“We already know epilepsy on its own increases risks for dementia, and when you add disadvantaged to that, it’s going to increase the risk even more,” said Dr. Reyes.
Neurologists should ask their older patients with epilepsy, many of whom live alone, about food insecurity and access to resources “not just within the hospital system but also within their community,” she said.
The findings were presented at the annual meeting of the American Epilepsy Society.
Proxy Measure of Disadvantage
The incidence and prevalence of epilepsy increases with age. Older adults represent the fastest growing segment of individuals with epilepsy, said Dr. Reyes.
The new study included 40 patients with focal epilepsy, average age 67 years, from three areas: San Diego, California; Madison, Wisconsin; and Cleveland, Ohio.
Researchers collected clinical and sociodemographic information as well as vascular biomarkers. They also gathered individual-level data, including income, parental education levels, details on childhood upbringing, etc.
Using residential addresses, investigators determined the area deprivation index (ADI) value for study participants. The ADI is a proxy measure for neighborhood-level socioeconomic disadvantage that captures factors such a poverty, employment, housing, and education opportunities.
ADI values range from 1 to 10, with a higher number indicating greater neighborhood disadvantage. About 30% of the cohort had an ADI decile greater than 6.
Researchers divided subjects into Most Disadvantaged (ADI greater than 7) and Least Disadvantaged (AD 7 or less). The two groups were similar with regard to age, education level, and race/ethnicity.
But those from the most disadvantaged areas were younger, taking more antiseizure medications, had fewer years of education, lower levels of father’s education, less personal and family income, and were less likely to be diagnosed with hypertension.
Study subjects completed neuropsychological testing, including:
- Measures of learning (Rey Auditory Verbal Learning Test [RAVLT] Learning Over Trials; Wechsler Memory Scale 4th Edition [WMS-4] Logical Memory [LM] Story B immediate; and WMS-4 Visual Reproduction [VR] immediate)
- Memory (RAVLT delayed recall, WMS-4 LM delayed recall, and WMS-4 VR delayed recall)
- Language (Multilingual Naming Test, Auditory Naming Test, and animal fluency)
- Executive function/processing speed (Letter fluency and Trail-Making Test Parts A and B)
The study found a correlation between higher ADI (most disadvantaged) and poorer performance on learning (Spearman rho: -0.433; 95% CI -0.664 to -0.126; P = .006), memory (r = -0.496; 95% CI -0.707 to -0.205; P = .001), and executive function/processes speed (r = -0.315; 95% CI -0.577 to 0.006; P = .048), but no significant association with language.
Looking at individual-level data, the study found memory and processing speed “were driving the relationship, and again, patients had worse performance when they were coming from the most disadvantaged neighborhoods,” said Dr. Reyes.
The investigators also examined mood, including depression and anxiety, and subjective complaints of cognitive problems. “We found those patients residing in the most disadvantaged neighborhoods complained more about memory problems,” she said.
The results underscore the need for community-level interventions “that could provide resources in support of these older adults and their families and connect them to services we know are good for brain health,” said Dr. Reyes.
Alzheimer’s disease experts “have done a really good job of this, but this is new for epilepsy,” she added. “This gives us a great opportunity to kind of bridge the worlds of dementia and epilepsy.”
Novel Research
Commenting on the research, Rani Sarkis, MD, assistant professor of neurology, Brigham and Women’s Hospital, Boston, said the study is “very useful” as it ties social determinants of health to cognition.
“We have not been doing that” in people with epilepsy, he said.
The study, one of the first to look at the link between disadvantaged neighborhoods and cognitive impairment, “has very important” public health implications, including the need to consider access to activities that promote cognitive resilience and other brain health initiatives, said Dr. Sarkis.
Another larger study that looked at neighborhood deprivation and cognition in epilepsy was also presented at the AES meeting and published earlier this year in the journal Neurology.
That study included 800 patients with pharmaco-resistant temporal lobe epilepsy being evaluated for surgery at the Cleveland Clinic, mean age about 38 years. It examined numerous cognitive domains as well as depression and anxiety in relation to ADI generated by patient addresses and split into quintiles from least to most disadvantaged.
After controlling for covariants, the study found scores for all cognitive domains were significantly worse in the most disadvantaged quintile except for executive function, which was close to reaching significance (P = .052), said lead author Robyn M. Busch, PhD, a clinical neuropsychologist in the Epilepsy Center, Department of Neurology, Cleveland Clinic.
The study also found people in the most disadvantaged areas had more symptoms of depression and anxiety compared with people in the least disadvantaged areas, said Busch.
A Complex Issue
Although the exact mechanism tying disadvantaged areas to cognition in epilepsy isn’t fully understood, having less access to health care and educational opportunities, poor nutrition, and being under chronic stress “are all things that affect the brain,” said Dr. Busch.
“This is super complex and it’s going to be really difficult to tease apart, but we’d like to look at imaging data to see if it’s something structural, if there are functional changes in the brain or something that might help us understand this better.”
But it’s also possible that having epilepsy “might be pushing people into environments” that offer fewer employment and educational opportunities and less access to resources, she said.
The study authors and Dr. Sarkis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO — , early research suggests.
Seniors with epilepsy present with multiple comorbidities, including, for example, hypertension and diabetes, and they are at increased risk of developing dementia, said study investigator Anny Reyes, PhD, a postdoctoral scholar at the University of California at San Diego.
Past research has shown neighborhood disadvantage is associated with numerous adverse health outcomes, including an increased risk for developing Alzheimer’s disease and related dementias (ADRD).
“We already know epilepsy on its own increases risks for dementia, and when you add disadvantaged to that, it’s going to increase the risk even more,” said Dr. Reyes.
Neurologists should ask their older patients with epilepsy, many of whom live alone, about food insecurity and access to resources “not just within the hospital system but also within their community,” she said.
The findings were presented at the annual meeting of the American Epilepsy Society.
Proxy Measure of Disadvantage
The incidence and prevalence of epilepsy increases with age. Older adults represent the fastest growing segment of individuals with epilepsy, said Dr. Reyes.
The new study included 40 patients with focal epilepsy, average age 67 years, from three areas: San Diego, California; Madison, Wisconsin; and Cleveland, Ohio.
Researchers collected clinical and sociodemographic information as well as vascular biomarkers. They also gathered individual-level data, including income, parental education levels, details on childhood upbringing, etc.
Using residential addresses, investigators determined the area deprivation index (ADI) value for study participants. The ADI is a proxy measure for neighborhood-level socioeconomic disadvantage that captures factors such a poverty, employment, housing, and education opportunities.
ADI values range from 1 to 10, with a higher number indicating greater neighborhood disadvantage. About 30% of the cohort had an ADI decile greater than 6.
Researchers divided subjects into Most Disadvantaged (ADI greater than 7) and Least Disadvantaged (AD 7 or less). The two groups were similar with regard to age, education level, and race/ethnicity.
But those from the most disadvantaged areas were younger, taking more antiseizure medications, had fewer years of education, lower levels of father’s education, less personal and family income, and were less likely to be diagnosed with hypertension.
Study subjects completed neuropsychological testing, including:
- Measures of learning (Rey Auditory Verbal Learning Test [RAVLT] Learning Over Trials; Wechsler Memory Scale 4th Edition [WMS-4] Logical Memory [LM] Story B immediate; and WMS-4 Visual Reproduction [VR] immediate)
- Memory (RAVLT delayed recall, WMS-4 LM delayed recall, and WMS-4 VR delayed recall)
- Language (Multilingual Naming Test, Auditory Naming Test, and animal fluency)
- Executive function/processing speed (Letter fluency and Trail-Making Test Parts A and B)
The study found a correlation between higher ADI (most disadvantaged) and poorer performance on learning (Spearman rho: -0.433; 95% CI -0.664 to -0.126; P = .006), memory (r = -0.496; 95% CI -0.707 to -0.205; P = .001), and executive function/processes speed (r = -0.315; 95% CI -0.577 to 0.006; P = .048), but no significant association with language.
Looking at individual-level data, the study found memory and processing speed “were driving the relationship, and again, patients had worse performance when they were coming from the most disadvantaged neighborhoods,” said Dr. Reyes.
The investigators also examined mood, including depression and anxiety, and subjective complaints of cognitive problems. “We found those patients residing in the most disadvantaged neighborhoods complained more about memory problems,” she said.
The results underscore the need for community-level interventions “that could provide resources in support of these older adults and their families and connect them to services we know are good for brain health,” said Dr. Reyes.
Alzheimer’s disease experts “have done a really good job of this, but this is new for epilepsy,” she added. “This gives us a great opportunity to kind of bridge the worlds of dementia and epilepsy.”
Novel Research
Commenting on the research, Rani Sarkis, MD, assistant professor of neurology, Brigham and Women’s Hospital, Boston, said the study is “very useful” as it ties social determinants of health to cognition.
“We have not been doing that” in people with epilepsy, he said.
The study, one of the first to look at the link between disadvantaged neighborhoods and cognitive impairment, “has very important” public health implications, including the need to consider access to activities that promote cognitive resilience and other brain health initiatives, said Dr. Sarkis.
Another larger study that looked at neighborhood deprivation and cognition in epilepsy was also presented at the AES meeting and published earlier this year in the journal Neurology.
That study included 800 patients with pharmaco-resistant temporal lobe epilepsy being evaluated for surgery at the Cleveland Clinic, mean age about 38 years. It examined numerous cognitive domains as well as depression and anxiety in relation to ADI generated by patient addresses and split into quintiles from least to most disadvantaged.
After controlling for covariants, the study found scores for all cognitive domains were significantly worse in the most disadvantaged quintile except for executive function, which was close to reaching significance (P = .052), said lead author Robyn M. Busch, PhD, a clinical neuropsychologist in the Epilepsy Center, Department of Neurology, Cleveland Clinic.
The study also found people in the most disadvantaged areas had more symptoms of depression and anxiety compared with people in the least disadvantaged areas, said Busch.
A Complex Issue
Although the exact mechanism tying disadvantaged areas to cognition in epilepsy isn’t fully understood, having less access to health care and educational opportunities, poor nutrition, and being under chronic stress “are all things that affect the brain,” said Dr. Busch.
“This is super complex and it’s going to be really difficult to tease apart, but we’d like to look at imaging data to see if it’s something structural, if there are functional changes in the brain or something that might help us understand this better.”
But it’s also possible that having epilepsy “might be pushing people into environments” that offer fewer employment and educational opportunities and less access to resources, she said.
The study authors and Dr. Sarkis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AES 2023
Genetic testing warranted in epilepsy of unknown origin
ORLANDO — , new research suggests. Investigators found that pathogenic genetic variants were identified in over 40% of patients with epilepsy of unknown cause who underwent genetic testing.
Such testing is particularly beneficial for those with early-onset epilepsy and those with comorbid developmental delay, said study investigator Yi Li, MD, PhD, clinical assistant professor, Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California.
But every patient with epilepsy of unknown etiology needs to consider genetic testing as part of their standard workup.
Dr. Li noted research showing that a diagnosis of a genetic epilepsy leads to alteration of treatment in about 20% of cases — for example, starting a specific antiseizure medication or avoiding a treatment such as a sodium channel blocker in patients diagnosed with Dravet syndrome. A genetic diagnosis also may make patients eligible for clinical trials investigating gene therapies.
Genetic testing results may end a long and exhausting “diagnostic odyssey” that families have been on, she said. Patients often wait more than a decade to get genetic testing, the study found.
The findings were presented at the annual meeting of the American Epilepsy Society.
Major Delays
About 20%-30% of epilepsy is caused by acquired conditions such as stroke, tumor, or head injury. The remaining 70%-80% is believed to be due to one or more genetic factors.
Genetic testing has become standard for children with early-onset epilepsy, but it’s not common practice among adults with the condition — at least not yet.
The retrospective study involved a chart review of patient electronic health records from 2018-2023. Researchers used the Stanford electronic health record Cohort Discovery tool (STARR) database to identify 286 patients over age 16 years with epilepsy who had records of genetic testing.
Of the 286 patients, 148 were male and 138 female, and mean age was approximately 30 years. Among those with known epilepsy types, 53.6% had focal epilepsy and 28.8% had generalized epilpesy.
The mean age of seizure onset was 11.9 years, but the mean age at genetic testing was 25.1 years. “There’s a gap of about 13 or 14 years for genetic workup after a patient has a first seizure,” said Dr. Li.
Such a “huge delay” means patients may miss out on “potential precision treatment choices,” she said.
And having a diagnosis can connect patients to others with the same condition as well as to related organizations and communities that offer support, she added.
Types of genetic testing identified in the study included panel testing, which looks at the genes associated with epilepsy; whole exome sequencing (WES), which includes all 20,000 genes in one test; and microarray testing, which assesses missing sections of chromosomes. WES had the highest diagnostic yield (48%), followed by genetic panel testing (32.7%) and microarray testing (20.9%).
These tests collectively identified pathogenic variants in 40.9% of patients. In addition, test results showed that 53.10% of patients had variants of uncertain significance.
In the full cohort, the most commonly identified variants were mutations in TSC1 (which causes tuberous sclerosis, SCN1A (which causes Dravet syndrome), and MECP2. Among patients with seizure onset after age 1 year, MECP2 and DEPDC5 were the two most commonly identified pathogenic variants.
Researchers examined factors possibly associated with a higher risk for genetic epilepsy, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. In an adjusted analysis, comorbid developmental delay (estimate 2.338; 95% confidence interval [CI], 1.402-3.900; P =.001) and seizure onset before 1 year (estimate 2.365; 95% CI, 1.282-4.366; P =.006) predicted higher yield of pathogenic variants related to epilepsy.
Dr. Li noted that study participants with a family history of epilepsy were not more likely to test positive for a genetic link, so doctors shouldn’t rule out testing in patients if there’s no family history.
Both the International League Against Epilepsy (ILAE) and the National Society of Genetic Counselors (NSGC) recommend genetic testing in adult epilepsy patients, with the AES endorsing the NSGC guideline.
Although testing is becoming increasingly accessible, insurance companies don’t always cover the cost.
Dr. Li said she hopes her research raises awareness among clinicians that there’s more they can do to improve care for epilepsy patients. “We should offer patients genetic testing if we don’t have a clear etiology.”
Valuable Evidence
Commenting on the research findings, Annapurna Poduri, MD, MPH, director, Epilepsy Genetics Program, Boston Children’s Hospital, Boston, Massachusetts, said this research “is incredibly important.”
“What’s really telling about this study and others that have come up over the last few years is they’re real-world retrospective studies, so they’re looking back at patients who have been seen over many, many years.”
The research provides clinicians, insurance companies, and others with evidence that genetic testing is “valuable and can actually improve outcomes,” said Dr. Poduri.
She noted that 20 years ago, there were only a handful of genes identified as being involved with epilepsy, most related to sodium or potassium channels. But since then, “the technology has just raced ahead” to the point where now “dozens of genes” have been identified.
Not only does knowing the genetic basis of epilepsy improve management, but it offers families some peace of mind. “They blame themselves” for their loved one’s condition, said Dr. Poduri. “They may worry it was something they did in pregnancy; for example, maybe it was because [they] didn’t take that vitamin one day.”
Diagnostic certainty also means that patients “don’t have to do more tests which might be invasive” and unnecessarily costly.
Drs. Li and Poduri report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
ORLANDO — , new research suggests. Investigators found that pathogenic genetic variants were identified in over 40% of patients with epilepsy of unknown cause who underwent genetic testing.
Such testing is particularly beneficial for those with early-onset epilepsy and those with comorbid developmental delay, said study investigator Yi Li, MD, PhD, clinical assistant professor, Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California.
But every patient with epilepsy of unknown etiology needs to consider genetic testing as part of their standard workup.
Dr. Li noted research showing that a diagnosis of a genetic epilepsy leads to alteration of treatment in about 20% of cases — for example, starting a specific antiseizure medication or avoiding a treatment such as a sodium channel blocker in patients diagnosed with Dravet syndrome. A genetic diagnosis also may make patients eligible for clinical trials investigating gene therapies.
Genetic testing results may end a long and exhausting “diagnostic odyssey” that families have been on, she said. Patients often wait more than a decade to get genetic testing, the study found.
The findings were presented at the annual meeting of the American Epilepsy Society.
Major Delays
About 20%-30% of epilepsy is caused by acquired conditions such as stroke, tumor, or head injury. The remaining 70%-80% is believed to be due to one or more genetic factors.
Genetic testing has become standard for children with early-onset epilepsy, but it’s not common practice among adults with the condition — at least not yet.
The retrospective study involved a chart review of patient electronic health records from 2018-2023. Researchers used the Stanford electronic health record Cohort Discovery tool (STARR) database to identify 286 patients over age 16 years with epilepsy who had records of genetic testing.
Of the 286 patients, 148 were male and 138 female, and mean age was approximately 30 years. Among those with known epilepsy types, 53.6% had focal epilepsy and 28.8% had generalized epilpesy.
The mean age of seizure onset was 11.9 years, but the mean age at genetic testing was 25.1 years. “There’s a gap of about 13 or 14 years for genetic workup after a patient has a first seizure,” said Dr. Li.
Such a “huge delay” means patients may miss out on “potential precision treatment choices,” she said.
And having a diagnosis can connect patients to others with the same condition as well as to related organizations and communities that offer support, she added.
Types of genetic testing identified in the study included panel testing, which looks at the genes associated with epilepsy; whole exome sequencing (WES), which includes all 20,000 genes in one test; and microarray testing, which assesses missing sections of chromosomes. WES had the highest diagnostic yield (48%), followed by genetic panel testing (32.7%) and microarray testing (20.9%).
These tests collectively identified pathogenic variants in 40.9% of patients. In addition, test results showed that 53.10% of patients had variants of uncertain significance.
In the full cohort, the most commonly identified variants were mutations in TSC1 (which causes tuberous sclerosis, SCN1A (which causes Dravet syndrome), and MECP2. Among patients with seizure onset after age 1 year, MECP2 and DEPDC5 were the two most commonly identified pathogenic variants.
Researchers examined factors possibly associated with a higher risk for genetic epilepsy, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. In an adjusted analysis, comorbid developmental delay (estimate 2.338; 95% confidence interval [CI], 1.402-3.900; P =.001) and seizure onset before 1 year (estimate 2.365; 95% CI, 1.282-4.366; P =.006) predicted higher yield of pathogenic variants related to epilepsy.
Dr. Li noted that study participants with a family history of epilepsy were not more likely to test positive for a genetic link, so doctors shouldn’t rule out testing in patients if there’s no family history.
Both the International League Against Epilepsy (ILAE) and the National Society of Genetic Counselors (NSGC) recommend genetic testing in adult epilepsy patients, with the AES endorsing the NSGC guideline.
Although testing is becoming increasingly accessible, insurance companies don’t always cover the cost.
Dr. Li said she hopes her research raises awareness among clinicians that there’s more they can do to improve care for epilepsy patients. “We should offer patients genetic testing if we don’t have a clear etiology.”
Valuable Evidence
Commenting on the research findings, Annapurna Poduri, MD, MPH, director, Epilepsy Genetics Program, Boston Children’s Hospital, Boston, Massachusetts, said this research “is incredibly important.”
“What’s really telling about this study and others that have come up over the last few years is they’re real-world retrospective studies, so they’re looking back at patients who have been seen over many, many years.”
The research provides clinicians, insurance companies, and others with evidence that genetic testing is “valuable and can actually improve outcomes,” said Dr. Poduri.
She noted that 20 years ago, there were only a handful of genes identified as being involved with epilepsy, most related to sodium or potassium channels. But since then, “the technology has just raced ahead” to the point where now “dozens of genes” have been identified.
Not only does knowing the genetic basis of epilepsy improve management, but it offers families some peace of mind. “They blame themselves” for their loved one’s condition, said Dr. Poduri. “They may worry it was something they did in pregnancy; for example, maybe it was because [they] didn’t take that vitamin one day.”
Diagnostic certainty also means that patients “don’t have to do more tests which might be invasive” and unnecessarily costly.
Drs. Li and Poduri report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
ORLANDO — , new research suggests. Investigators found that pathogenic genetic variants were identified in over 40% of patients with epilepsy of unknown cause who underwent genetic testing.
Such testing is particularly beneficial for those with early-onset epilepsy and those with comorbid developmental delay, said study investigator Yi Li, MD, PhD, clinical assistant professor, Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California.
But every patient with epilepsy of unknown etiology needs to consider genetic testing as part of their standard workup.
Dr. Li noted research showing that a diagnosis of a genetic epilepsy leads to alteration of treatment in about 20% of cases — for example, starting a specific antiseizure medication or avoiding a treatment such as a sodium channel blocker in patients diagnosed with Dravet syndrome. A genetic diagnosis also may make patients eligible for clinical trials investigating gene therapies.
Genetic testing results may end a long and exhausting “diagnostic odyssey” that families have been on, she said. Patients often wait more than a decade to get genetic testing, the study found.
The findings were presented at the annual meeting of the American Epilepsy Society.
Major Delays
About 20%-30% of epilepsy is caused by acquired conditions such as stroke, tumor, or head injury. The remaining 70%-80% is believed to be due to one or more genetic factors.
Genetic testing has become standard for children with early-onset epilepsy, but it’s not common practice among adults with the condition — at least not yet.
The retrospective study involved a chart review of patient electronic health records from 2018-2023. Researchers used the Stanford electronic health record Cohort Discovery tool (STARR) database to identify 286 patients over age 16 years with epilepsy who had records of genetic testing.
Of the 286 patients, 148 were male and 138 female, and mean age was approximately 30 years. Among those with known epilepsy types, 53.6% had focal epilepsy and 28.8% had generalized epilpesy.
The mean age of seizure onset was 11.9 years, but the mean age at genetic testing was 25.1 years. “There’s a gap of about 13 or 14 years for genetic workup after a patient has a first seizure,” said Dr. Li.
Such a “huge delay” means patients may miss out on “potential precision treatment choices,” she said.
And having a diagnosis can connect patients to others with the same condition as well as to related organizations and communities that offer support, she added.
Types of genetic testing identified in the study included panel testing, which looks at the genes associated with epilepsy; whole exome sequencing (WES), which includes all 20,000 genes in one test; and microarray testing, which assesses missing sections of chromosomes. WES had the highest diagnostic yield (48%), followed by genetic panel testing (32.7%) and microarray testing (20.9%).
These tests collectively identified pathogenic variants in 40.9% of patients. In addition, test results showed that 53.10% of patients had variants of uncertain significance.
In the full cohort, the most commonly identified variants were mutations in TSC1 (which causes tuberous sclerosis, SCN1A (which causes Dravet syndrome), and MECP2. Among patients with seizure onset after age 1 year, MECP2 and DEPDC5 were the two most commonly identified pathogenic variants.
Researchers examined factors possibly associated with a higher risk for genetic epilepsy, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. In an adjusted analysis, comorbid developmental delay (estimate 2.338; 95% confidence interval [CI], 1.402-3.900; P =.001) and seizure onset before 1 year (estimate 2.365; 95% CI, 1.282-4.366; P =.006) predicted higher yield of pathogenic variants related to epilepsy.
Dr. Li noted that study participants with a family history of epilepsy were not more likely to test positive for a genetic link, so doctors shouldn’t rule out testing in patients if there’s no family history.
Both the International League Against Epilepsy (ILAE) and the National Society of Genetic Counselors (NSGC) recommend genetic testing in adult epilepsy patients, with the AES endorsing the NSGC guideline.
Although testing is becoming increasingly accessible, insurance companies don’t always cover the cost.
Dr. Li said she hopes her research raises awareness among clinicians that there’s more they can do to improve care for epilepsy patients. “We should offer patients genetic testing if we don’t have a clear etiology.”
Valuable Evidence
Commenting on the research findings, Annapurna Poduri, MD, MPH, director, Epilepsy Genetics Program, Boston Children’s Hospital, Boston, Massachusetts, said this research “is incredibly important.”
“What’s really telling about this study and others that have come up over the last few years is they’re real-world retrospective studies, so they’re looking back at patients who have been seen over many, many years.”
The research provides clinicians, insurance companies, and others with evidence that genetic testing is “valuable and can actually improve outcomes,” said Dr. Poduri.
She noted that 20 years ago, there were only a handful of genes identified as being involved with epilepsy, most related to sodium or potassium channels. But since then, “the technology has just raced ahead” to the point where now “dozens of genes” have been identified.
Not only does knowing the genetic basis of epilepsy improve management, but it offers families some peace of mind. “They blame themselves” for their loved one’s condition, said Dr. Poduri. “They may worry it was something they did in pregnancy; for example, maybe it was because [they] didn’t take that vitamin one day.”
Diagnostic certainty also means that patients “don’t have to do more tests which might be invasive” and unnecessarily costly.
Drs. Li and Poduri report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM AES 2023
Sleep disorders linked to increased mortality risk in epilepsy
ORLANDO — , new research shows.
SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.
“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.
She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.
The findings were presented at the annual meeting of the American Epilepsy Society (AES).
The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.
The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.
They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
SUDEP Inventory
Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.
Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).
Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).
The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.
From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
Powerful Study
Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.
“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.
Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.
Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.
Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO — , new research shows.
SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.
“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.
She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.
The findings were presented at the annual meeting of the American Epilepsy Society (AES).
The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.
The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.
They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
SUDEP Inventory
Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.
Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).
Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).
The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.
From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
Powerful Study
Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.
“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.
Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.
Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.
Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO — , new research shows.
SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.
“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.
She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.
The findings were presented at the annual meeting of the American Epilepsy Society (AES).
The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.
The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.
They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
SUDEP Inventory
Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.
Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).
Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).
The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.
From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
Powerful Study
Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.
“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.
Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.
Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.
Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AES 2023
FDA warns of potentially lethal reaction to seizure meds
that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.
Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).
Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.
In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.
As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.
The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).
In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.
DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.
Label updates
As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.
“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.
They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.
DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.
DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
Adverse reactions with these medications should be reported to the FDA’s MedWatch program.
A version of this article appeared on Medscape.com.
that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.
Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).
Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.
In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.
As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.
The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).
In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.
DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.
Label updates
As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.
“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.
They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.
DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.
DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
Adverse reactions with these medications should be reported to the FDA’s MedWatch program.
A version of this article appeared on Medscape.com.
that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.
Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).
Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.
In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.
As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.
The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).
In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.
DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.
Label updates
As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.
“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.
They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.
DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.
DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
Adverse reactions with these medications should be reported to the FDA’s MedWatch program.
A version of this article appeared on Medscape.com.
New consensus guide on rare drug hypersensitivity reaction
TOPLINE:
).
METHODOLOGY:
Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.
To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.
An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.
After revisions and the second round, the group reached consensus for 93 statements overall.
TAKEAWAY:
The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.
The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.
Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.
IN PRACTICE:
“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”
SOURCE:
The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.
LIMITATIONS:
Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.
DISCLOSURES:
The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.
A version of this article appeared on Medscape.com.
TOPLINE:
).
METHODOLOGY:
Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.
To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.
An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.
After revisions and the second round, the group reached consensus for 93 statements overall.
TAKEAWAY:
The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.
The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.
Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.
IN PRACTICE:
“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”
SOURCE:
The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.
LIMITATIONS:
Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.
DISCLOSURES:
The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.
A version of this article appeared on Medscape.com.
TOPLINE:
).
METHODOLOGY:
Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.
To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.
An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.
After revisions and the second round, the group reached consensus for 93 statements overall.
TAKEAWAY:
The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.
The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.
Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.
IN PRACTICE:
“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”
SOURCE:
The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.
LIMITATIONS:
Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.
DISCLOSURES:
The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.
A version of this article appeared on Medscape.com.
Yoga linked to seizure, anxiety reduction in epilepsy
TOPLINE:
in people with epilepsy, a new study shows.
METHODOLOGY:
- Investigators included participants aged 18-60 years with epilepsy who scored ≥ 4 on the Kilifi Stigma Scale of Epilepsy. A score greater than the 66th percentile indicates the presence of strongly felt stigma.
- Patients (n = 160) had an average of one seizure per week, and most took at least two antiseizure medications.
- The intervention group (n = 80) participated in a yoga module with muscle-loosening exercises, slow and synchronized breathing, meditation, and positive affirmations. The control group (n = 80) participated in sham yoga sessions with no instructions on the breathing exercises or attention to the body movements and sensations during practice.
- Both groups participated in seven 1-hour supervised group yoga sessions over 3 months, were asked to practice the interventions at home five times per week, and received a psychoeducation module on epilepsy.
TAKEAWAY:
- Participants practicing the intervention module had significant reductions in self-perceived stigma, compared with those in the control group (P = .01).
- The proportion of participants in the intervention group who had a more than 50% seizure reduction (odds ratio, 4.11; P = .01) and complete seizure remission (OR, 7.4; P = .005) at the end of the 6-month follow-up was significantly higher than in the control group.
- Compared with those in the control group, there were also significant improvements in anxiety (P = .032) and quality of life (P < .001) in the intervention group.
- The intervention group also experienced significant improvement in mindfulness (P < .001) and cognitive impairment, compared with the control group (P < .004).
IN PRACTICE:
“This stigma can affect a person’s life in many ways, including treatment, emergency department visits, and poor mental health,” study investigator Majari Tripathi, MD, of All India Institute of Medical Sciences, New Delhi, said in a press release. “Our study showed that doing yoga can alleviate the burden of epilepsy and improve the overall quality of life by reducing this perceived stigma.”
SOURCE:
Dr. Tripathi and Kirandeep Kaur, MD, also of All India Institute of Medical Sciences, conducted the study with their colleagues. It was published online in Neurology.
LIMITATIONS:
There was no passive control or treatment as usual group, which would indicate the effect size of the intervention. In addition, there was no monitoring of seizure frequency before the study began, which may have biased the change of seizure frequency as an outcome.
DISCLOSURES:
The study investigators reported no study funding or reported disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
in people with epilepsy, a new study shows.
METHODOLOGY:
- Investigators included participants aged 18-60 years with epilepsy who scored ≥ 4 on the Kilifi Stigma Scale of Epilepsy. A score greater than the 66th percentile indicates the presence of strongly felt stigma.
- Patients (n = 160) had an average of one seizure per week, and most took at least two antiseizure medications.
- The intervention group (n = 80) participated in a yoga module with muscle-loosening exercises, slow and synchronized breathing, meditation, and positive affirmations. The control group (n = 80) participated in sham yoga sessions with no instructions on the breathing exercises or attention to the body movements and sensations during practice.
- Both groups participated in seven 1-hour supervised group yoga sessions over 3 months, were asked to practice the interventions at home five times per week, and received a psychoeducation module on epilepsy.
TAKEAWAY:
- Participants practicing the intervention module had significant reductions in self-perceived stigma, compared with those in the control group (P = .01).
- The proportion of participants in the intervention group who had a more than 50% seizure reduction (odds ratio, 4.11; P = .01) and complete seizure remission (OR, 7.4; P = .005) at the end of the 6-month follow-up was significantly higher than in the control group.
- Compared with those in the control group, there were also significant improvements in anxiety (P = .032) and quality of life (P < .001) in the intervention group.
- The intervention group also experienced significant improvement in mindfulness (P < .001) and cognitive impairment, compared with the control group (P < .004).
IN PRACTICE:
“This stigma can affect a person’s life in many ways, including treatment, emergency department visits, and poor mental health,” study investigator Majari Tripathi, MD, of All India Institute of Medical Sciences, New Delhi, said in a press release. “Our study showed that doing yoga can alleviate the burden of epilepsy and improve the overall quality of life by reducing this perceived stigma.”
SOURCE:
Dr. Tripathi and Kirandeep Kaur, MD, also of All India Institute of Medical Sciences, conducted the study with their colleagues. It was published online in Neurology.
LIMITATIONS:
There was no passive control or treatment as usual group, which would indicate the effect size of the intervention. In addition, there was no monitoring of seizure frequency before the study began, which may have biased the change of seizure frequency as an outcome.
DISCLOSURES:
The study investigators reported no study funding or reported disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
in people with epilepsy, a new study shows.
METHODOLOGY:
- Investigators included participants aged 18-60 years with epilepsy who scored ≥ 4 on the Kilifi Stigma Scale of Epilepsy. A score greater than the 66th percentile indicates the presence of strongly felt stigma.
- Patients (n = 160) had an average of one seizure per week, and most took at least two antiseizure medications.
- The intervention group (n = 80) participated in a yoga module with muscle-loosening exercises, slow and synchronized breathing, meditation, and positive affirmations. The control group (n = 80) participated in sham yoga sessions with no instructions on the breathing exercises or attention to the body movements and sensations during practice.
- Both groups participated in seven 1-hour supervised group yoga sessions over 3 months, were asked to practice the interventions at home five times per week, and received a psychoeducation module on epilepsy.
TAKEAWAY:
- Participants practicing the intervention module had significant reductions in self-perceived stigma, compared with those in the control group (P = .01).
- The proportion of participants in the intervention group who had a more than 50% seizure reduction (odds ratio, 4.11; P = .01) and complete seizure remission (OR, 7.4; P = .005) at the end of the 6-month follow-up was significantly higher than in the control group.
- Compared with those in the control group, there were also significant improvements in anxiety (P = .032) and quality of life (P < .001) in the intervention group.
- The intervention group also experienced significant improvement in mindfulness (P < .001) and cognitive impairment, compared with the control group (P < .004).
IN PRACTICE:
“This stigma can affect a person’s life in many ways, including treatment, emergency department visits, and poor mental health,” study investigator Majari Tripathi, MD, of All India Institute of Medical Sciences, New Delhi, said in a press release. “Our study showed that doing yoga can alleviate the burden of epilepsy and improve the overall quality of life by reducing this perceived stigma.”
SOURCE:
Dr. Tripathi and Kirandeep Kaur, MD, also of All India Institute of Medical Sciences, conducted the study with their colleagues. It was published online in Neurology.
LIMITATIONS:
There was no passive control or treatment as usual group, which would indicate the effect size of the intervention. In addition, there was no monitoring of seizure frequency before the study began, which may have biased the change of seizure frequency as an outcome.
DISCLOSURES:
The study investigators reported no study funding or reported disclosures.
A version of this article appeared on Medscape.com.
Artificial intelligence presents opportunities, challenges in neurologic practice
PHOENIX – and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.
Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.
He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.
Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.
It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.
Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
Trust, but verify
Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.
AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
Limitations
The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.
Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.
Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.
There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.
Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.
Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.
He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.
For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”
Dr. Morren has no relevant financial disclosures.
PHOENIX – and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.
Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.
He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.
Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.
It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.
Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
Trust, but verify
Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.
AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
Limitations
The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.
Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.
Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.
There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.
Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.
Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.
He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.
For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”
Dr. Morren has no relevant financial disclosures.
PHOENIX – and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.
Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.
He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.
Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.
It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.
Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
Trust, but verify
Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.
AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
Limitations
The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.
Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.
Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.
There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.
Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.
Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.
He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.
For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”
Dr. Morren has no relevant financial disclosures.
AT AANEM 2023
RNA therapeutics will ‘change everything’ in epilepsy
Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.
But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.
“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.
Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.
Dr. Kaye said.
Thank COVID?
Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.
Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.
Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.
RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.
Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.
“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.
“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
Hope for Dravet syndrome
Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.
Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.
The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.
“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.
Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.
“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.
“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.
“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
A promising future
Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”
And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.
Take, for example, a case reported recently in the New England Journal of Medicine.
Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.
One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.
However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”
“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.
The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.
A version of this article first appeared on Medscape.com.
Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.
But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.
“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.
Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.
Dr. Kaye said.
Thank COVID?
Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.
Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.
Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.
RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.
Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.
“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.
“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
Hope for Dravet syndrome
Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.
Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.
The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.
“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.
Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.
“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.
“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.
“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
A promising future
Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”
And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.
Take, for example, a case reported recently in the New England Journal of Medicine.
Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.
One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.
However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”
“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.
The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.
A version of this article first appeared on Medscape.com.
Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.
But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.
“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.
Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.
Dr. Kaye said.
Thank COVID?
Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.
Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.
Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.
RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.
Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.
“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.
“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
Hope for Dravet syndrome
Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.
Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.
The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.
“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.
Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.
“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.
“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.
“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
A promising future
Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”
And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.
Take, for example, a case reported recently in the New England Journal of Medicine.
Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.
One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.
However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”
“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.
The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.
A version of this article first appeared on Medscape.com.
Neurologic nuggets of wisdom for pediatric practice
WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.
Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.
“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.
Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.
Dr. Strunc offered a few more tips for diagnosing a child:
- Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
- Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
- Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
- Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.
The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
Is it epilepsy?
Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.
In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.
The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.
By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.
However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.
Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.
Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.
However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
Don’t miss those ticks
Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).
Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.
The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.
Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.
Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.
Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.
“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.
Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.
A version of this article first appeared on Medscape.com.
WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.
Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.
“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.
Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.
Dr. Strunc offered a few more tips for diagnosing a child:
- Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
- Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
- Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
- Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.
The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
Is it epilepsy?
Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.
In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.
The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.
By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.
However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.
Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.
Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.
However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
Don’t miss those ticks
Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).
Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.
The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.
Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.
Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.
Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.
“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.
Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.
A version of this article first appeared on Medscape.com.
WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.
Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.
“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.
Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.
Dr. Strunc offered a few more tips for diagnosing a child:
- Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
- Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
- Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
- Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.
The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
Is it epilepsy?
Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.
In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.
The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.
By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.
However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.
Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.
Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.
However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
Don’t miss those ticks
Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).
Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.
The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.
Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.
Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.
Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.
“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.
Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.
A version of this article first appeared on Medscape.com.
FROM AAP 2023
New European restrictions on topiramate in pregnancy
While it’s well known that topiramate can cause major congenital malformations and fetal growth restriction when used during pregnancy, recent data also suggest a possibly increased risk for neurodevelopmental disorders when topiramate is used during pregnancy, the EMA said in a statement.
The data include two observational studies that showed children born to mothers with epilepsy and who were exposed to topiramate in the womb may have a two- to threefold higher risk for neurodevelopmental disorders, in particular autism spectrum disorders (ASD), intellectual disability, or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy not taking antiepileptic medication.
For patients using topiramate for the treatment of epilepsy, the PRAC now recommends that the medicine not be used during pregnancy unless no other suitable treatment is available.
The PRAC had also recommended a pregnancy prevention program to avoid exposure of the developing fetus to topiramate. “These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate,” the EMA said.
Regardless of indication, the agency said topiramate should be used in women of childbearing age only when the following conditions of the pregnancy prevention program are met:
- A pregnancy test before starting treatment.
- Counseling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment.
- A review of ongoing treatment at least annually by completion of a risk awareness form.
The PRAC recommends that health care professionals ensure women of childbearing age are fully aware of the risks of taking topiramate during pregnancy. The committee noted that alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.
The product information for topiramate-containing medicines will be updated to further highlight the risks for neurodevelopmental disorders and the additional safety measures to be taken.
Patients and health care professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.
The new PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position.
A version of this article first appeared on Medscape.com.
While it’s well known that topiramate can cause major congenital malformations and fetal growth restriction when used during pregnancy, recent data also suggest a possibly increased risk for neurodevelopmental disorders when topiramate is used during pregnancy, the EMA said in a statement.
The data include two observational studies that showed children born to mothers with epilepsy and who were exposed to topiramate in the womb may have a two- to threefold higher risk for neurodevelopmental disorders, in particular autism spectrum disorders (ASD), intellectual disability, or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy not taking antiepileptic medication.
For patients using topiramate for the treatment of epilepsy, the PRAC now recommends that the medicine not be used during pregnancy unless no other suitable treatment is available.
The PRAC had also recommended a pregnancy prevention program to avoid exposure of the developing fetus to topiramate. “These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate,” the EMA said.
Regardless of indication, the agency said topiramate should be used in women of childbearing age only when the following conditions of the pregnancy prevention program are met:
- A pregnancy test before starting treatment.
- Counseling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment.
- A review of ongoing treatment at least annually by completion of a risk awareness form.
The PRAC recommends that health care professionals ensure women of childbearing age are fully aware of the risks of taking topiramate during pregnancy. The committee noted that alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.
The product information for topiramate-containing medicines will be updated to further highlight the risks for neurodevelopmental disorders and the additional safety measures to be taken.
Patients and health care professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.
The new PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position.
A version of this article first appeared on Medscape.com.
While it’s well known that topiramate can cause major congenital malformations and fetal growth restriction when used during pregnancy, recent data also suggest a possibly increased risk for neurodevelopmental disorders when topiramate is used during pregnancy, the EMA said in a statement.
The data include two observational studies that showed children born to mothers with epilepsy and who were exposed to topiramate in the womb may have a two- to threefold higher risk for neurodevelopmental disorders, in particular autism spectrum disorders (ASD), intellectual disability, or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy not taking antiepileptic medication.
For patients using topiramate for the treatment of epilepsy, the PRAC now recommends that the medicine not be used during pregnancy unless no other suitable treatment is available.
The PRAC had also recommended a pregnancy prevention program to avoid exposure of the developing fetus to topiramate. “These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate,” the EMA said.
Regardless of indication, the agency said topiramate should be used in women of childbearing age only when the following conditions of the pregnancy prevention program are met:
- A pregnancy test before starting treatment.
- Counseling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment.
- A review of ongoing treatment at least annually by completion of a risk awareness form.
The PRAC recommends that health care professionals ensure women of childbearing age are fully aware of the risks of taking topiramate during pregnancy. The committee noted that alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.
The product information for topiramate-containing medicines will be updated to further highlight the risks for neurodevelopmental disorders and the additional safety measures to be taken.
Patients and health care professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.
The new PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position.
A version of this article first appeared on Medscape.com.