Pediatrics

Bacteria on children’s skin was similar to their mothers’ and affected by factors that included method of delivery and breastfeeding in a study of 154 children aged 10 years and younger.

Understanding the skin microbiome is important to determine whether certain bacteria may be helpful or harmful, but skin microbiome studies in children are limited, wrote Ting Zhu of Fudan University, Shanghai, China, and colleagues.

In a study published in the Journal of Investigative Dermatology, the researchers compared the skin microbiota of the 158 children aged 1-10 years and 50 mothers using 16S rRNA gene amplicon sequencing after collecting study samples from three skin areas: face, calf, and ventral forearm. The samples were pooled into 36 groups based on age, gender, and skin site.

“We observed significant differences in alpha diversity and the most prevalent taxa and identified factors that contributed to variation at each site,” the authors reported.

Overall, the “alpha diversity” – a measure of microbial diversity used in microbiome studies – of the skin microbiome increased with age, with the highest alpha diversity seen in the 10-year-olds (n = 28), notably on the face, but differences in alpha diversity between skin sites were seen only in the 1-year-olds (n = 26). Overall, the most commonly identified bacterial phyla at all skin sites in children were Proteobacteria (42%), Firmicutes (25%), Actinobacteria (13%), and Bacteroidetes (11%). In the three sites, the genera with high relative abundance (over 3%) included Streptococcus (13%), Enhydrobacter (6%), and Propionibacterium (5%). Of these, Streptococcus and Granulicatella showed negative linear correlations with age.

The researchers found significant differences between the bacterial communities of 10-year-olds delivered by Cesarean section and those delivered vaginally, particularly in the facial samples; however the difference wasn’t observed among face samples taken from 1-year-olds, according to the authors. They found significant variation in bacteria in calf samples based on whether the children were fed breast milk, formula, or a combination.

When the researchers examined the correlations between mother/child pairs, they found that the relative abundance of most bacteria in the children were more similar to their mothers than to unrelated adults, and they found the strongest correlations for the genera Deinococcus, Microbacterium, Chryseobacterium, Klebsiella, and Enhydrobacter. The relationships between the bacterial communities of mothers and children may be influenced by the shared living environment, topical products, and daily diet, they noted.

The study findings were limited by not controlling for certain variables, including daily diet, choice of topical products, bathing habits, and daily variation in environmental factors, the researchers wrote. However, the results show “that the skin microbiome is strongly affected by the surrounding microenvironment and that the alpha diversity of the skin microbiome increases during childhood,” they concluded.

The study was fully funded by Johnson & Johnson International, and several coauthors are employees of that company. Lead author Ms. Zhu had no financial conflicts to disclose.

SOURCE: Zhu T et al. J Invest Dermatol. 2019 August 13. doi: 10.1016/j.jid.2019.05.018.

Bacteria on children’s skin was similar to their mothers’ and affected by factors that included method of delivery and breastfeeding in a study of 154 children aged 10 years and younger.

Understanding the skin microbiome is important to determine whether certain bacteria may be helpful or harmful, but skin microbiome studies in children are limited, wrote Ting Zhu of Fudan University, Shanghai, China, and colleagues.

In a study published in the Journal of Investigative Dermatology, the researchers compared the skin microbiota of the 158 children aged 1-10 years and 50 mothers using 16S rRNA gene amplicon sequencing after collecting study samples from three skin areas: face, calf, and ventral forearm. The samples were pooled into 36 groups based on age, gender, and skin site.

“We observed significant differences in alpha diversity and the most prevalent taxa and identified factors that contributed to variation at each site,” the authors reported.

Overall, the “alpha diversity” – a measure of microbial diversity used in microbiome studies – of the skin microbiome increased with age, with the highest alpha diversity seen in the 10-year-olds (n = 28), notably on the face, but differences in alpha diversity between skin sites were seen only in the 1-year-olds (n = 26). Overall, the most commonly identified bacterial phyla at all skin sites in children were Proteobacteria (42%), Firmicutes (25%), Actinobacteria (13%), and Bacteroidetes (11%). In the three sites, the genera with high relative abundance (over 3%) included Streptococcus (13%), Enhydrobacter (6%), and Propionibacterium (5%). Of these, Streptococcus and Granulicatella showed negative linear correlations with age.

The researchers found significant differences between the bacterial communities of 10-year-olds delivered by Cesarean section and those delivered vaginally, particularly in the facial samples; however the difference wasn’t observed among face samples taken from 1-year-olds, according to the authors. They found significant variation in bacteria in calf samples based on whether the children were fed breast milk, formula, or a combination.

When the researchers examined the correlations between mother/child pairs, they found that the relative abundance of most bacteria in the children were more similar to their mothers than to unrelated adults, and they found the strongest correlations for the genera Deinococcus, Microbacterium, Chryseobacterium, Klebsiella, and Enhydrobacter. The relationships between the bacterial communities of mothers and children may be influenced by the shared living environment, topical products, and daily diet, they noted.

The study findings were limited by not controlling for certain variables, including daily diet, choice of topical products, bathing habits, and daily variation in environmental factors, the researchers wrote. However, the results show “that the skin microbiome is strongly affected by the surrounding microenvironment and that the alpha diversity of the skin microbiome increases during childhood,” they concluded.

The study was fully funded by Johnson & Johnson International, and several coauthors are employees of that company. Lead author Ms. Zhu had no financial conflicts to disclose.

SOURCE: Zhu T et al. J Invest Dermatol. 2019 August 13. doi: 10.1016/j.jid.2019.05.018.

Bacteria on children’s skin was similar to their mothers’ and affected by factors that included method of delivery and breastfeeding in a study of 154 children aged 10 years and younger.

Understanding the skin microbiome is important to determine whether certain bacteria may be helpful or harmful, but skin microbiome studies in children are limited, wrote Ting Zhu of Fudan University, Shanghai, China, and colleagues.

In a study published in the Journal of Investigative Dermatology, the researchers compared the skin microbiota of the 158 children aged 1-10 years and 50 mothers using 16S rRNA gene amplicon sequencing after collecting study samples from three skin areas: face, calf, and ventral forearm. The samples were pooled into 36 groups based on age, gender, and skin site.

“We observed significant differences in alpha diversity and the most prevalent taxa and identified factors that contributed to variation at each site,” the authors reported.

Overall, the “alpha diversity” – a measure of microbial diversity used in microbiome studies – of the skin microbiome increased with age, with the highest alpha diversity seen in the 10-year-olds (n = 28), notably on the face, but differences in alpha diversity between skin sites were seen only in the 1-year-olds (n = 26). Overall, the most commonly identified bacterial phyla at all skin sites in children were Proteobacteria (42%), Firmicutes (25%), Actinobacteria (13%), and Bacteroidetes (11%). In the three sites, the genera with high relative abundance (over 3%) included Streptococcus (13%), Enhydrobacter (6%), and Propionibacterium (5%). Of these, Streptococcus and Granulicatella showed negative linear correlations with age.

The researchers found significant differences between the bacterial communities of 10-year-olds delivered by Cesarean section and those delivered vaginally, particularly in the facial samples; however the difference wasn’t observed among face samples taken from 1-year-olds, according to the authors. They found significant variation in bacteria in calf samples based on whether the children were fed breast milk, formula, or a combination.

When the researchers examined the correlations between mother/child pairs, they found that the relative abundance of most bacteria in the children were more similar to their mothers than to unrelated adults, and they found the strongest correlations for the genera Deinococcus, Microbacterium, Chryseobacterium, Klebsiella, and Enhydrobacter. The relationships between the bacterial communities of mothers and children may be influenced by the shared living environment, topical products, and daily diet, they noted.

The study findings were limited by not controlling for certain variables, including daily diet, choice of topical products, bathing habits, and daily variation in environmental factors, the researchers wrote. However, the results show “that the skin microbiome is strongly affected by the surrounding microenvironment and that the alpha diversity of the skin microbiome increases during childhood,” they concluded.

The study was fully funded by Johnson & Johnson International, and several coauthors are employees of that company. Lead author Ms. Zhu had no financial conflicts to disclose.

SOURCE: Zhu T et al. J Invest Dermatol. 2019 August 13. doi: 10.1016/j.jid.2019.05.018.

High levels of enterovirus (EV) peptides were found in the cerebrospinal fluid (CSF) and serum samples of individuals with acute flaccid myelitis (AFM) that were not present in a variety of control individuals, according to the results of a small study of patients with and without AFM published online in mBio.

CDC

In 2018, CSF samples from AFM patients were investigated by viral-capture high-throughput sequencing. These CSF and serum samples, as well as those from multiple controls, were tested for antibodies to human EVs using peptide microarrays, according to Nischay Mishra, PhD, of Columbia University, New York, and colleagues.

Although EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case, antibodies to EV peptides were present in 11 of 14 AFM patients (79%), which was a significantly higher rate than in control groups, including non-AFM patients (1 of 5, or 20%), children with Kawasaki disease (0 of 10), and adults with non-AFM CNS diseases (2 of 11, 18%), according to the authors.

In addition, 6 of 14 (43%) CSF samples and 8 of 11 (73%) serum samples from AFM patients were immunoreactive to an EV-D68–specific peptide, whereas samples from the three control groups were not immunoreactive in either CSF or sera. Previous studies have suggested that infection with EV-D68 and EV-A71 may contribute to AFM.

“There have been 570 confirmed cases since CDC began tracking AFM in August 2014. AFM outbreaks were reported to the CDC in 2014, 2016, and 2018. AFM affects the spinal cord and is characterized by the sudden onset of muscle weakness in one or more limbs. Spikes in AFM cases, primarily in children, have coincided in time and location with outbreaks of EV-D68 and a related enterovirus, EV-A71,” according to an NIH media advisory discussing the article.

In particular, as the study authors point out, a potential link to EV-D68 has also been based on the presence of viral RNA in some respiratory and stool specimens and the observation that EV-D68 infection can result in spinal cord infection.

“While other etiologies of AFM continue to be investigated, our study provides further evidence that EV infection may be a factor in AFM. In the absence of direct detection of a pathogen, antibody evidence of pathogen exposure within the CNS can be an important indicator of the underlying cause of disease,” Dr. Mishra and his colleagues added.

“These initial results may provide avenues to further explore how exposure to EV may contribute to AFM as well as the development of diagnostic tools and treatments,” the researchers concluded.

The study was funded by the National Institutes of Health. The authors reported that they had no competing financial interests.

[email protected]

SOURCE: Mishra N et al. mBio. 2019 Aug;10(4):e01903-19.

High levels of enterovirus (EV) peptides were found in the cerebrospinal fluid (CSF) and serum samples of individuals with acute flaccid myelitis (AFM) that were not present in a variety of control individuals, according to the results of a small study of patients with and without AFM published online in mBio.

CDC

In 2018, CSF samples from AFM patients were investigated by viral-capture high-throughput sequencing. These CSF and serum samples, as well as those from multiple controls, were tested for antibodies to human EVs using peptide microarrays, according to Nischay Mishra, PhD, of Columbia University, New York, and colleagues.

Although EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case, antibodies to EV peptides were present in 11 of 14 AFM patients (79%), which was a significantly higher rate than in control groups, including non-AFM patients (1 of 5, or 20%), children with Kawasaki disease (0 of 10), and adults with non-AFM CNS diseases (2 of 11, 18%), according to the authors.

In addition, 6 of 14 (43%) CSF samples and 8 of 11 (73%) serum samples from AFM patients were immunoreactive to an EV-D68–specific peptide, whereas samples from the three control groups were not immunoreactive in either CSF or sera. Previous studies have suggested that infection with EV-D68 and EV-A71 may contribute to AFM.

“There have been 570 confirmed cases since CDC began tracking AFM in August 2014. AFM outbreaks were reported to the CDC in 2014, 2016, and 2018. AFM affects the spinal cord and is characterized by the sudden onset of muscle weakness in one or more limbs. Spikes in AFM cases, primarily in children, have coincided in time and location with outbreaks of EV-D68 and a related enterovirus, EV-A71,” according to an NIH media advisory discussing the article.

In particular, as the study authors point out, a potential link to EV-D68 has also been based on the presence of viral RNA in some respiratory and stool specimens and the observation that EV-D68 infection can result in spinal cord infection.

“While other etiologies of AFM continue to be investigated, our study provides further evidence that EV infection may be a factor in AFM. In the absence of direct detection of a pathogen, antibody evidence of pathogen exposure within the CNS can be an important indicator of the underlying cause of disease,” Dr. Mishra and his colleagues added.

“These initial results may provide avenues to further explore how exposure to EV may contribute to AFM as well as the development of diagnostic tools and treatments,” the researchers concluded.

The study was funded by the National Institutes of Health. The authors reported that they had no competing financial interests.

[email protected]

SOURCE: Mishra N et al. mBio. 2019 Aug;10(4):e01903-19.

High levels of enterovirus (EV) peptides were found in the cerebrospinal fluid (CSF) and serum samples of individuals with acute flaccid myelitis (AFM) that were not present in a variety of control individuals, according to the results of a small study of patients with and without AFM published online in mBio.

CDC

In 2018, CSF samples from AFM patients were investigated by viral-capture high-throughput sequencing. These CSF and serum samples, as well as those from multiple controls, were tested for antibodies to human EVs using peptide microarrays, according to Nischay Mishra, PhD, of Columbia University, New York, and colleagues.

Although EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case, antibodies to EV peptides were present in 11 of 14 AFM patients (79%), which was a significantly higher rate than in control groups, including non-AFM patients (1 of 5, or 20%), children with Kawasaki disease (0 of 10), and adults with non-AFM CNS diseases (2 of 11, 18%), according to the authors.

In addition, 6 of 14 (43%) CSF samples and 8 of 11 (73%) serum samples from AFM patients were immunoreactive to an EV-D68–specific peptide, whereas samples from the three control groups were not immunoreactive in either CSF or sera. Previous studies have suggested that infection with EV-D68 and EV-A71 may contribute to AFM.

“There have been 570 confirmed cases since CDC began tracking AFM in August 2014. AFM outbreaks were reported to the CDC in 2014, 2016, and 2018. AFM affects the spinal cord and is characterized by the sudden onset of muscle weakness in one or more limbs. Spikes in AFM cases, primarily in children, have coincided in time and location with outbreaks of EV-D68 and a related enterovirus, EV-A71,” according to an NIH media advisory discussing the article.

In particular, as the study authors point out, a potential link to EV-D68 has also been based on the presence of viral RNA in some respiratory and stool specimens and the observation that EV-D68 infection can result in spinal cord infection.

“While other etiologies of AFM continue to be investigated, our study provides further evidence that EV infection may be a factor in AFM. In the absence of direct detection of a pathogen, antibody evidence of pathogen exposure within the CNS can be an important indicator of the underlying cause of disease,” Dr. Mishra and his colleagues added.

“These initial results may provide avenues to further explore how exposure to EV may contribute to AFM as well as the development of diagnostic tools and treatments,” the researchers concluded.

The study was funded by the National Institutes of Health. The authors reported that they had no competing financial interests.

[email protected]

SOURCE: Mishra N et al. mBio. 2019 Aug;10(4):e01903-19.

Prophylactic treatment with bisphosphonates could significantly improve bone mineral density (BMD) in children and adolescents receiving steroids for chronic rheumatic disease, a study has found.

A paper published in EClinicalMedicine reported the outcomes of a multicenter, double-dummy, double-blind, placebo-controlled trial involving 217 patients who were receiving steroid therapy for juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis, or juvenile vasculitis. The patients were randomized to risedronate, alfacalcidol, or placebo, and all of the participants received 500 mg calcium and 400 IU vitamin D daily.

Lumbar spine and total body (less head) BMD increased in all groups, but the greatest increase was seen in patients treated with risedronate.

After 1 year, lumbar spine and total body (less head) BMD had increased in all groups, compared with baseline, but the greatest increase was seen in patients who had been treated with risedronate.

The lumbar spine areal BMD z score remained the same in the placebo group (−1.15 to −1.13), decreased from −0.96 to −1.00 in the alfacalcidol group, and increased from −0.99 to −0.75 in the risedronate group.

The change in z scores was significantly different between placebo and risedronate groups, and between risedronate and alfacalcidol groups, but not between placebo and alfacalcidol.

“The acquisition of adequate peak bone mass is not only important for the young person in reducing fracture risk but also has significant implications for the development of osteoporosis in later life, if peak bone mass is suboptimal,” wrote Madeleine Rooney, MBBCH, from the Queens University of Belfast, Northern Ireland, and associates.

There were no significant differences between the three groups in fracture rates. However, researchers were also able to compare Genant scores for vertebral fractures in 187 patients with pre- and posttreatment lateral spinal x-rays. That showed that the 54 patients in the placebo arm and 52 patients in the alfacalcidol arm had no change in their baseline Genant score of 0 (normal). However, although all 53 patients in the risedronate group had a Genant score of 0 at baseline, at 1-year follow-up, 2 patients had a Genant score of 1 (mild fracture), and 1 patient had a score of 3 (severe fracture).

In biochemical parameters, researchers saw a drop in parathyroid hormone in the placebo and alfacalcidol groups, but a rise in the risedronate group. However, the authors were not able to see any changes in bone markers that might have indicated which patients responded better to treatment.

Around 90% of participants in each group were also being treated with disease-modifying antirheumatic drugs. The rates of biologic use were 10.5% in the placebo group, 23.9% in the alfacalcidol group, and 10.1% in the risedronate group.

The researchers also noted a 7% higher rate of serious adverse events in the risedronate group, but emphasized that there were no differences in events related to the treatment.

In an accompanying editorial, Ian R. Reid, MBBCH, of the department of medicine, University of Auckland (New Zealand) noted that the study was an important step toward finding interventions for the prevention of steroid-induced bone loss in children. “The present study indicates that risedronate, and probably other potent bisphosphonates, can provide bone preservation in children and young people receiving therapeutic doses of glucocorticoid drugs, whereas alfacalcidol is without benefit. The targeted use of bisphosphonates in children and young people judged to be at significant fracture risk is appropriate. However, whether preventing loss of bone density will reduce fracture incidence remains to be established.”

The study was funded by Arthritis Research UK. No conflicts of interest were declared.
 

SOURCE: Rooney M et al. EClinicalMedicine. 2019 Jul 3. doi: 10.1016/j.eclinm.2019.06.004.

Prophylactic treatment with bisphosphonates could significantly improve bone mineral density (BMD) in children and adolescents receiving steroids for chronic rheumatic disease, a study has found.

A paper published in EClinicalMedicine reported the outcomes of a multicenter, double-dummy, double-blind, placebo-controlled trial involving 217 patients who were receiving steroid therapy for juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis, or juvenile vasculitis. The patients were randomized to risedronate, alfacalcidol, or placebo, and all of the participants received 500 mg calcium and 400 IU vitamin D daily.

Lumbar spine and total body (less head) BMD increased in all groups, but the greatest increase was seen in patients treated with risedronate.

After 1 year, lumbar spine and total body (less head) BMD had increased in all groups, compared with baseline, but the greatest increase was seen in patients who had been treated with risedronate.

The lumbar spine areal BMD z score remained the same in the placebo group (−1.15 to −1.13), decreased from −0.96 to −1.00 in the alfacalcidol group, and increased from −0.99 to −0.75 in the risedronate group.

The change in z scores was significantly different between placebo and risedronate groups, and between risedronate and alfacalcidol groups, but not between placebo and alfacalcidol.

“The acquisition of adequate peak bone mass is not only important for the young person in reducing fracture risk but also has significant implications for the development of osteoporosis in later life, if peak bone mass is suboptimal,” wrote Madeleine Rooney, MBBCH, from the Queens University of Belfast, Northern Ireland, and associates.

There were no significant differences between the three groups in fracture rates. However, researchers were also able to compare Genant scores for vertebral fractures in 187 patients with pre- and posttreatment lateral spinal x-rays. That showed that the 54 patients in the placebo arm and 52 patients in the alfacalcidol arm had no change in their baseline Genant score of 0 (normal). However, although all 53 patients in the risedronate group had a Genant score of 0 at baseline, at 1-year follow-up, 2 patients had a Genant score of 1 (mild fracture), and 1 patient had a score of 3 (severe fracture).

In biochemical parameters, researchers saw a drop in parathyroid hormone in the placebo and alfacalcidol groups, but a rise in the risedronate group. However, the authors were not able to see any changes in bone markers that might have indicated which patients responded better to treatment.

Around 90% of participants in each group were also being treated with disease-modifying antirheumatic drugs. The rates of biologic use were 10.5% in the placebo group, 23.9% in the alfacalcidol group, and 10.1% in the risedronate group.

The researchers also noted a 7% higher rate of serious adverse events in the risedronate group, but emphasized that there were no differences in events related to the treatment.

In an accompanying editorial, Ian R. Reid, MBBCH, of the department of medicine, University of Auckland (New Zealand) noted that the study was an important step toward finding interventions for the prevention of steroid-induced bone loss in children. “The present study indicates that risedronate, and probably other potent bisphosphonates, can provide bone preservation in children and young people receiving therapeutic doses of glucocorticoid drugs, whereas alfacalcidol is without benefit. The targeted use of bisphosphonates in children and young people judged to be at significant fracture risk is appropriate. However, whether preventing loss of bone density will reduce fracture incidence remains to be established.”

The study was funded by Arthritis Research UK. No conflicts of interest were declared.
 

SOURCE: Rooney M et al. EClinicalMedicine. 2019 Jul 3. doi: 10.1016/j.eclinm.2019.06.004.

Prophylactic treatment with bisphosphonates could significantly improve bone mineral density (BMD) in children and adolescents receiving steroids for chronic rheumatic disease, a study has found.

A paper published in EClinicalMedicine reported the outcomes of a multicenter, double-dummy, double-blind, placebo-controlled trial involving 217 patients who were receiving steroid therapy for juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis, or juvenile vasculitis. The patients were randomized to risedronate, alfacalcidol, or placebo, and all of the participants received 500 mg calcium and 400 IU vitamin D daily.

Lumbar spine and total body (less head) BMD increased in all groups, but the greatest increase was seen in patients treated with risedronate.

After 1 year, lumbar spine and total body (less head) BMD had increased in all groups, compared with baseline, but the greatest increase was seen in patients who had been treated with risedronate.

The lumbar spine areal BMD z score remained the same in the placebo group (−1.15 to −1.13), decreased from −0.96 to −1.00 in the alfacalcidol group, and increased from −0.99 to −0.75 in the risedronate group.

The change in z scores was significantly different between placebo and risedronate groups, and between risedronate and alfacalcidol groups, but not between placebo and alfacalcidol.

“The acquisition of adequate peak bone mass is not only important for the young person in reducing fracture risk but also has significant implications for the development of osteoporosis in later life, if peak bone mass is suboptimal,” wrote Madeleine Rooney, MBBCH, from the Queens University of Belfast, Northern Ireland, and associates.

There were no significant differences between the three groups in fracture rates. However, researchers were also able to compare Genant scores for vertebral fractures in 187 patients with pre- and posttreatment lateral spinal x-rays. That showed that the 54 patients in the placebo arm and 52 patients in the alfacalcidol arm had no change in their baseline Genant score of 0 (normal). However, although all 53 patients in the risedronate group had a Genant score of 0 at baseline, at 1-year follow-up, 2 patients had a Genant score of 1 (mild fracture), and 1 patient had a score of 3 (severe fracture).

In biochemical parameters, researchers saw a drop in parathyroid hormone in the placebo and alfacalcidol groups, but a rise in the risedronate group. However, the authors were not able to see any changes in bone markers that might have indicated which patients responded better to treatment.

Around 90% of participants in each group were also being treated with disease-modifying antirheumatic drugs. The rates of biologic use were 10.5% in the placebo group, 23.9% in the alfacalcidol group, and 10.1% in the risedronate group.

The researchers also noted a 7% higher rate of serious adverse events in the risedronate group, but emphasized that there were no differences in events related to the treatment.

In an accompanying editorial, Ian R. Reid, MBBCH, of the department of medicine, University of Auckland (New Zealand) noted that the study was an important step toward finding interventions for the prevention of steroid-induced bone loss in children. “The present study indicates that risedronate, and probably other potent bisphosphonates, can provide bone preservation in children and young people receiving therapeutic doses of glucocorticoid drugs, whereas alfacalcidol is without benefit. The targeted use of bisphosphonates in children and young people judged to be at significant fracture risk is appropriate. However, whether preventing loss of bone density will reduce fracture incidence remains to be established.”

The study was funded by Arthritis Research UK. No conflicts of interest were declared.
 

SOURCE: Rooney M et al. EClinicalMedicine. 2019 Jul 3. doi: 10.1016/j.eclinm.2019.06.004.

BANGKOK – For a form of epilepsy treatment that’s been around since the 1920s, ketogenic diet therapy has lately been the focus of a surprising wealth of clinical research and development, Suvasini Sharma, MD, observed at the International Epilepsy Congress.

Bruce Jancin/MDedge News

This high-fat, low-carbohydrate diet is now well established as a valid and effective treatment option for children and adults with drug-refractory epilepsy who aren’t candidates for surgery. That’s about a third of all epilepsy patients. And as the recently overhauled pediatric ketogenic diet therapy (KDT) best practice consensus guidelines emphasize, KDT should be strongly considered after two antiepileptic drugs have failed, and even earlier for several epilepsy syndromes, noted Dr. Sharma, a pediatric neurologist at Lady Hardinge Medical College and Kalawati Saran Children’s Hospital in New Delhi, and a coauthor of the updated guidelines.

“The consensus guidelines recommend that you start thinking about the diet early, without waiting for every drug to fail,” she said at the congress, sponsored by the International League Against Epilepsy.

Among the KDT-related topics she highlighted were the recently revised best practice consensus guidelines; an expanding role for KDT in infants, critical care settings, and in epileptic encephalopathies; mounting evidence that KDT provides additional benefits beyond seizure control; and promising new alternative diet therapies. She also described the challenges of using KDT in a low-resource nation such as India, where most of the 1.3 billion people shop in markets where food isn’t packaged with the nutritional content labels essential to traditional KDTs, and low literacy is common.


 

KDT best practice guidelines

The latest guidelines, which include the details of standardized KDT protocols as well as a summary of recent translational research into mechanisms of action, replace the previous 10-year-old version. Flexibility is now the watchword. While the classic KDT was started as an inpatient intervention involving several days of fasting followed by multiday gradual reintroduction of calories, that approach is now deemed optional (Epilepsia Open. 2018 May 21;3[2]:175-92).

“By and large, the trend now is going to nonfasting initiation on an outpatient basis, but with more stringent monitoring,” according to Dr. Sharma.

The guidelines note that while the research literature shows that, on average, KDT results in about a 50% chance of at least a 50% reduction in seizure frequency in patients with drug-refractory epilepsy, there are a dozen specific conditions with 70% or greater responder rates: infantile spasms, tuberous sclerosis, epilepsy with myoclonic-atonic seizures, Dravet syndrome, glucose transporter 1 deficiency syndrome (Glut 1DS), pyruvate dehydrogenase deficiency (PDHD), febrile infection-related epilepsy syndrome (FIRES), super-refractory status epilepticus (SRSE), Ohtahara syndrome, complex I mitochondrial disorders, Angelman syndrome, and children with gastrostomy tubes. For Glut1DS and PDHD, KDTs should be considered the treatment of first choice.

Traditionally, KDTs weren’t recommended for children younger than age 2 years. There were concerns that maintaining ketosis and meeting growth requirements were contradictory goals. That’s no longer believed to be so. Indeed, current evidence shows that KDT is highly effective and well tolerated in infants with refractory epilepsy. European guidelines address patient selection, pre-KDT counseling, preferred methods of initiation and KDT discontinuation, and other key issues (Eur J Paediatr Neurol. 2016 Nov;20[6]:798-809).

The guidelines recognize four major, well-studied types of KDT: the classic long-chain triglyceride-centric diet; the medium-chain triglyceride diet; the more user-friendly modified Atkins diet; and low glycemic index therapy. Except in children younger than 2 years old, who should be started on the classic KDT, the consensus panel recommended that the specific KDT selected should be based on the family and child situation and the expertise at the local KDT center. Perceived differences in efficacy between the diets aren’t supported by persuasive evidence.
 

KDT benefits beyond seizure control

“Most of us who work in the diet scene are aware that patients often report increased alertness, and sometimes improved cognition,” said Dr. Sharma.

That subjective experience is now supported by evidence from a randomized, controlled trial. Dutch investigators who randomized 50 drug-refractory pediatric epilepsy patients to KDT or usual care documented a positive impact of the diet therapy on cognitive activation, mood, and anxious behavior (Epilepsy Behav. 2016 Jul;60:153-7).

More recently, a systematic review showed that while subjective assessments support claims of improved alertness, attention, and global cognition in patients on KDT for refractory epilepsy, structured neuropsychologic testing confirms the enhanced alertness but without significantly improved global cognition. The investigators reported that the improvements were unrelated to decreases in medication, the type of KDT or age at its introduction, or sleep improvement. Rather, the benefits appeared to be due to a combination of seizure reduction and direct effects of KDT on cognition (Epilepsy Behav. 2018 Oct;87:69-77).

There is also encouraging preliminary evidence of a possible protective effect of KDT against sudden unexpected death in epilepsy (SUDEP) in a mouse model (Epilepsia. 2016 Aug;57[8]:e178-82. doi: 10.1111/epi.13444).
 

The use of KDT in critical care settings

Investigators from the pediatric Status Epilepticus Research Group (pSERG) reported that 10 of 14 patients with convulsive refractory status epilepticus achieved EEG seizure resolution within 7 days after starting KDT. Moreover, 11 patients were able to be weaned off their continuous infusions within 14 days of starting KDT. Treatment-emergent gastroparesis and hypertriglyceridemia occurred in three patients (Epilepsy Res. 2018 Aug;144:1-6).

“It was reasonably well tolerated, but they started it quite late – a median of 13 days after onset of refractory status epilepticus. It should come much earlier on our list of therapies. We shouldn’t be waiting 2 weeks before going to the ketogenic diet, because we can diagnose refractory status epilepticus within 48 hours after arrival in the ICU most of the time,” Dr. Sharma said.

Austrian investigators have pioneered the use of intravenous KDT as a bridge when oral therapy is temporarily impossible because of status epilepticus, surgery, or other reasons. They reported that parental KDT with fat intake of 3.5-4 g/kg per day was safe and effective in their series of 17 young children with epilepsy (Epilepsia Open. 2017 Nov 16;3[1]:30-9).
 

The future: nonketogenic diet therapies

KDT in its various forms is just too demanding and restrictive for some patients. Nonketotic alternatives are being explored.

Triheptanoin is a synthetic medium-chain triglyceride in the form of an edible, odorless, tasteless oil. Its mechanism of action is by anaplerosis: that is, energy generation via replenishment of the tricarboxylic acid cycle. After demonstration of neuroprotective and anticonvulsant effects in several mouse models, Australian investigators conducted a pilot study of 30- to 100-mL/day of oral triheptanoin as add-on therapy in 12 children with drug-refractory epilepsy. Eight of the 12 took triheptanoin for longer than 12 weeks, and 5 of those 8 experienced a sustained greater than 50% reduction in seizure frequency, including 1 who remained seizure free for 30 weeks. Seven children had diarrhea or other GI side effects (Eur J Paediatr Neurol. 2018 Nov;22[6]:1074-80).

Parisian investigators have developed a nonketotic, palatable combination of amino acids, carbohydrates, and fatty acids with a low ratio of fat to protein-plus-carbohydrates that provided potent protection against seizures in a mouse model. This suggests that the traditional 4:1 ratio sought in KDT isn’t necessary for robust seizure reduction (Sci Rep. 2017 Jul 14;7[1]:5496).

“This is probably going to be the future of nutritional therapy in epilepsy,” Dr. Sharma predicted.

She reported having no financial conflicts regarding her presentation.

[email protected]

BANGKOK – For a form of epilepsy treatment that’s been around since the 1920s, ketogenic diet therapy has lately been the focus of a surprising wealth of clinical research and development, Suvasini Sharma, MD, observed at the International Epilepsy Congress.

Bruce Jancin/MDedge News

This high-fat, low-carbohydrate diet is now well established as a valid and effective treatment option for children and adults with drug-refractory epilepsy who aren’t candidates for surgery. That’s about a third of all epilepsy patients. And as the recently overhauled pediatric ketogenic diet therapy (KDT) best practice consensus guidelines emphasize, KDT should be strongly considered after two antiepileptic drugs have failed, and even earlier for several epilepsy syndromes, noted Dr. Sharma, a pediatric neurologist at Lady Hardinge Medical College and Kalawati Saran Children’s Hospital in New Delhi, and a coauthor of the updated guidelines.

“The consensus guidelines recommend that you start thinking about the diet early, without waiting for every drug to fail,” she said at the congress, sponsored by the International League Against Epilepsy.

Among the KDT-related topics she highlighted were the recently revised best practice consensus guidelines; an expanding role for KDT in infants, critical care settings, and in epileptic encephalopathies; mounting evidence that KDT provides additional benefits beyond seizure control; and promising new alternative diet therapies. She also described the challenges of using KDT in a low-resource nation such as India, where most of the 1.3 billion people shop in markets where food isn’t packaged with the nutritional content labels essential to traditional KDTs, and low literacy is common.


 

KDT best practice guidelines

The latest guidelines, which include the details of standardized KDT protocols as well as a summary of recent translational research into mechanisms of action, replace the previous 10-year-old version. Flexibility is now the watchword. While the classic KDT was started as an inpatient intervention involving several days of fasting followed by multiday gradual reintroduction of calories, that approach is now deemed optional (Epilepsia Open. 2018 May 21;3[2]:175-92).

“By and large, the trend now is going to nonfasting initiation on an outpatient basis, but with more stringent monitoring,” according to Dr. Sharma.

The guidelines note that while the research literature shows that, on average, KDT results in about a 50% chance of at least a 50% reduction in seizure frequency in patients with drug-refractory epilepsy, there are a dozen specific conditions with 70% or greater responder rates: infantile spasms, tuberous sclerosis, epilepsy with myoclonic-atonic seizures, Dravet syndrome, glucose transporter 1 deficiency syndrome (Glut 1DS), pyruvate dehydrogenase deficiency (PDHD), febrile infection-related epilepsy syndrome (FIRES), super-refractory status epilepticus (SRSE), Ohtahara syndrome, complex I mitochondrial disorders, Angelman syndrome, and children with gastrostomy tubes. For Glut1DS and PDHD, KDTs should be considered the treatment of first choice.

Traditionally, KDTs weren’t recommended for children younger than age 2 years. There were concerns that maintaining ketosis and meeting growth requirements were contradictory goals. That’s no longer believed to be so. Indeed, current evidence shows that KDT is highly effective and well tolerated in infants with refractory epilepsy. European guidelines address patient selection, pre-KDT counseling, preferred methods of initiation and KDT discontinuation, and other key issues (Eur J Paediatr Neurol. 2016 Nov;20[6]:798-809).

The guidelines recognize four major, well-studied types of KDT: the classic long-chain triglyceride-centric diet; the medium-chain triglyceride diet; the more user-friendly modified Atkins diet; and low glycemic index therapy. Except in children younger than 2 years old, who should be started on the classic KDT, the consensus panel recommended that the specific KDT selected should be based on the family and child situation and the expertise at the local KDT center. Perceived differences in efficacy between the diets aren’t supported by persuasive evidence.
 

KDT benefits beyond seizure control

“Most of us who work in the diet scene are aware that patients often report increased alertness, and sometimes improved cognition,” said Dr. Sharma.

That subjective experience is now supported by evidence from a randomized, controlled trial. Dutch investigators who randomized 50 drug-refractory pediatric epilepsy patients to KDT or usual care documented a positive impact of the diet therapy on cognitive activation, mood, and anxious behavior (Epilepsy Behav. 2016 Jul;60:153-7).

More recently, a systematic review showed that while subjective assessments support claims of improved alertness, attention, and global cognition in patients on KDT for refractory epilepsy, structured neuropsychologic testing confirms the enhanced alertness but without significantly improved global cognition. The investigators reported that the improvements were unrelated to decreases in medication, the type of KDT or age at its introduction, or sleep improvement. Rather, the benefits appeared to be due to a combination of seizure reduction and direct effects of KDT on cognition (Epilepsy Behav. 2018 Oct;87:69-77).

There is also encouraging preliminary evidence of a possible protective effect of KDT against sudden unexpected death in epilepsy (SUDEP) in a mouse model (Epilepsia. 2016 Aug;57[8]:e178-82. doi: 10.1111/epi.13444).
 

The use of KDT in critical care settings

Investigators from the pediatric Status Epilepticus Research Group (pSERG) reported that 10 of 14 patients with convulsive refractory status epilepticus achieved EEG seizure resolution within 7 days after starting KDT. Moreover, 11 patients were able to be weaned off their continuous infusions within 14 days of starting KDT. Treatment-emergent gastroparesis and hypertriglyceridemia occurred in three patients (Epilepsy Res. 2018 Aug;144:1-6).

“It was reasonably well tolerated, but they started it quite late – a median of 13 days after onset of refractory status epilepticus. It should come much earlier on our list of therapies. We shouldn’t be waiting 2 weeks before going to the ketogenic diet, because we can diagnose refractory status epilepticus within 48 hours after arrival in the ICU most of the time,” Dr. Sharma said.

Austrian investigators have pioneered the use of intravenous KDT as a bridge when oral therapy is temporarily impossible because of status epilepticus, surgery, or other reasons. They reported that parental KDT with fat intake of 3.5-4 g/kg per day was safe and effective in their series of 17 young children with epilepsy (Epilepsia Open. 2017 Nov 16;3[1]:30-9).
 

The future: nonketogenic diet therapies

KDT in its various forms is just too demanding and restrictive for some patients. Nonketotic alternatives are being explored.

Triheptanoin is a synthetic medium-chain triglyceride in the form of an edible, odorless, tasteless oil. Its mechanism of action is by anaplerosis: that is, energy generation via replenishment of the tricarboxylic acid cycle. After demonstration of neuroprotective and anticonvulsant effects in several mouse models, Australian investigators conducted a pilot study of 30- to 100-mL/day of oral triheptanoin as add-on therapy in 12 children with drug-refractory epilepsy. Eight of the 12 took triheptanoin for longer than 12 weeks, and 5 of those 8 experienced a sustained greater than 50% reduction in seizure frequency, including 1 who remained seizure free for 30 weeks. Seven children had diarrhea or other GI side effects (Eur J Paediatr Neurol. 2018 Nov;22[6]:1074-80).

Parisian investigators have developed a nonketotic, palatable combination of amino acids, carbohydrates, and fatty acids with a low ratio of fat to protein-plus-carbohydrates that provided potent protection against seizures in a mouse model. This suggests that the traditional 4:1 ratio sought in KDT isn’t necessary for robust seizure reduction (Sci Rep. 2017 Jul 14;7[1]:5496).

“This is probably going to be the future of nutritional therapy in epilepsy,” Dr. Sharma predicted.

She reported having no financial conflicts regarding her presentation.

[email protected]

BANGKOK – For a form of epilepsy treatment that’s been around since the 1920s, ketogenic diet therapy has lately been the focus of a surprising wealth of clinical research and development, Suvasini Sharma, MD, observed at the International Epilepsy Congress.

Bruce Jancin/MDedge News

This high-fat, low-carbohydrate diet is now well established as a valid and effective treatment option for children and adults with drug-refractory epilepsy who aren’t candidates for surgery. That’s about a third of all epilepsy patients. And as the recently overhauled pediatric ketogenic diet therapy (KDT) best practice consensus guidelines emphasize, KDT should be strongly considered after two antiepileptic drugs have failed, and even earlier for several epilepsy syndromes, noted Dr. Sharma, a pediatric neurologist at Lady Hardinge Medical College and Kalawati Saran Children’s Hospital in New Delhi, and a coauthor of the updated guidelines.

“The consensus guidelines recommend that you start thinking about the diet early, without waiting for every drug to fail,” she said at the congress, sponsored by the International League Against Epilepsy.

Among the KDT-related topics she highlighted were the recently revised best practice consensus guidelines; an expanding role for KDT in infants, critical care settings, and in epileptic encephalopathies; mounting evidence that KDT provides additional benefits beyond seizure control; and promising new alternative diet therapies. She also described the challenges of using KDT in a low-resource nation such as India, where most of the 1.3 billion people shop in markets where food isn’t packaged with the nutritional content labels essential to traditional KDTs, and low literacy is common.


 

KDT best practice guidelines

The latest guidelines, which include the details of standardized KDT protocols as well as a summary of recent translational research into mechanisms of action, replace the previous 10-year-old version. Flexibility is now the watchword. While the classic KDT was started as an inpatient intervention involving several days of fasting followed by multiday gradual reintroduction of calories, that approach is now deemed optional (Epilepsia Open. 2018 May 21;3[2]:175-92).

“By and large, the trend now is going to nonfasting initiation on an outpatient basis, but with more stringent monitoring,” according to Dr. Sharma.

The guidelines note that while the research literature shows that, on average, KDT results in about a 50% chance of at least a 50% reduction in seizure frequency in patients with drug-refractory epilepsy, there are a dozen specific conditions with 70% or greater responder rates: infantile spasms, tuberous sclerosis, epilepsy with myoclonic-atonic seizures, Dravet syndrome, glucose transporter 1 deficiency syndrome (Glut 1DS), pyruvate dehydrogenase deficiency (PDHD), febrile infection-related epilepsy syndrome (FIRES), super-refractory status epilepticus (SRSE), Ohtahara syndrome, complex I mitochondrial disorders, Angelman syndrome, and children with gastrostomy tubes. For Glut1DS and PDHD, KDTs should be considered the treatment of first choice.

Traditionally, KDTs weren’t recommended for children younger than age 2 years. There were concerns that maintaining ketosis and meeting growth requirements were contradictory goals. That’s no longer believed to be so. Indeed, current evidence shows that KDT is highly effective and well tolerated in infants with refractory epilepsy. European guidelines address patient selection, pre-KDT counseling, preferred methods of initiation and KDT discontinuation, and other key issues (Eur J Paediatr Neurol. 2016 Nov;20[6]:798-809).

The guidelines recognize four major, well-studied types of KDT: the classic long-chain triglyceride-centric diet; the medium-chain triglyceride diet; the more user-friendly modified Atkins diet; and low glycemic index therapy. Except in children younger than 2 years old, who should be started on the classic KDT, the consensus panel recommended that the specific KDT selected should be based on the family and child situation and the expertise at the local KDT center. Perceived differences in efficacy between the diets aren’t supported by persuasive evidence.
 

KDT benefits beyond seizure control

“Most of us who work in the diet scene are aware that patients often report increased alertness, and sometimes improved cognition,” said Dr. Sharma.

That subjective experience is now supported by evidence from a randomized, controlled trial. Dutch investigators who randomized 50 drug-refractory pediatric epilepsy patients to KDT or usual care documented a positive impact of the diet therapy on cognitive activation, mood, and anxious behavior (Epilepsy Behav. 2016 Jul;60:153-7).

More recently, a systematic review showed that while subjective assessments support claims of improved alertness, attention, and global cognition in patients on KDT for refractory epilepsy, structured neuropsychologic testing confirms the enhanced alertness but without significantly improved global cognition. The investigators reported that the improvements were unrelated to decreases in medication, the type of KDT or age at its introduction, or sleep improvement. Rather, the benefits appeared to be due to a combination of seizure reduction and direct effects of KDT on cognition (Epilepsy Behav. 2018 Oct;87:69-77).

There is also encouraging preliminary evidence of a possible protective effect of KDT against sudden unexpected death in epilepsy (SUDEP) in a mouse model (Epilepsia. 2016 Aug;57[8]:e178-82. doi: 10.1111/epi.13444).
 

The use of KDT in critical care settings

Investigators from the pediatric Status Epilepticus Research Group (pSERG) reported that 10 of 14 patients with convulsive refractory status epilepticus achieved EEG seizure resolution within 7 days after starting KDT. Moreover, 11 patients were able to be weaned off their continuous infusions within 14 days of starting KDT. Treatment-emergent gastroparesis and hypertriglyceridemia occurred in three patients (Epilepsy Res. 2018 Aug;144:1-6).

“It was reasonably well tolerated, but they started it quite late – a median of 13 days after onset of refractory status epilepticus. It should come much earlier on our list of therapies. We shouldn’t be waiting 2 weeks before going to the ketogenic diet, because we can diagnose refractory status epilepticus within 48 hours after arrival in the ICU most of the time,” Dr. Sharma said.

Austrian investigators have pioneered the use of intravenous KDT as a bridge when oral therapy is temporarily impossible because of status epilepticus, surgery, or other reasons. They reported that parental KDT with fat intake of 3.5-4 g/kg per day was safe and effective in their series of 17 young children with epilepsy (Epilepsia Open. 2017 Nov 16;3[1]:30-9).
 

The future: nonketogenic diet therapies

KDT in its various forms is just too demanding and restrictive for some patients. Nonketotic alternatives are being explored.

Triheptanoin is a synthetic medium-chain triglyceride in the form of an edible, odorless, tasteless oil. Its mechanism of action is by anaplerosis: that is, energy generation via replenishment of the tricarboxylic acid cycle. After demonstration of neuroprotective and anticonvulsant effects in several mouse models, Australian investigators conducted a pilot study of 30- to 100-mL/day of oral triheptanoin as add-on therapy in 12 children with drug-refractory epilepsy. Eight of the 12 took triheptanoin for longer than 12 weeks, and 5 of those 8 experienced a sustained greater than 50% reduction in seizure frequency, including 1 who remained seizure free for 30 weeks. Seven children had diarrhea or other GI side effects (Eur J Paediatr Neurol. 2018 Nov;22[6]:1074-80).

Parisian investigators have developed a nonketotic, palatable combination of amino acids, carbohydrates, and fatty acids with a low ratio of fat to protein-plus-carbohydrates that provided potent protection against seizures in a mouse model. This suggests that the traditional 4:1 ratio sought in KDT isn’t necessary for robust seizure reduction (Sci Rep. 2017 Jul 14;7[1]:5496).

“This is probably going to be the future of nutritional therapy in epilepsy,” Dr. Sharma predicted.

She reported having no financial conflicts regarding her presentation.

[email protected]

PHILADELPHIA – U.S. children and teens who were hospitalized because of asthma had twice the rate of migraine headache when compared with a similar pediatric population without asthma. The finding is based on an analysis of more than 11 million U.S. pediatric hospitalizations over the course of a decade.

Among children and adolescents aged 3-21 years who were hospitalized for asthma, migraine rates were significantly higher among girls, adolescents, and whites, compared with boys, children aged 12 years or younger, and nonwhites, respectively, in a trio of adjusted analyses, Riddhiben S. Patel, MD, and associates reported in a poster at the annual meeting of the American Headache Society.

“Our hope is that, by establishing an association between childhood asthma and migraine, [these children] may be more easily screened for, diagnosed, and treated early by providers,” wrote Dr. Patel, a pediatric neurologist and headache specialist at the University of Mississippi, Jackson, and associates.

Their analysis used administrative billing data collected by the Kids’ Inpatient Database, maintained by the U.S. Healthcare Cost and Utilization Project. The project includes a representative national sample of about 3 million pediatric hospital discharges every 3 years. The study used data from 11,483,103 hospitalizations of children and adolescents aged 3-21 years during 2003, 2006, 2009, and 2012, and found an overall hospitalization rate of 0.8% billed for migraine. For patients also hospitalized with a billing code for asthma, the rate jumped to 1.36%, a 120% statistically significant relative increase in migraine hospitalizations after adjustment for baseline demographic differences, the researchers said.

Among the children and adolescents hospitalized with an asthma billing code, the relative rate of also having a billing code for migraine after adjustment was a statistically significant 80% higher in girls, compared with boys, a statistically significant 7% higher in adolescents, compared with children 12 years or younger, and was significantly reduced by a relative 45% rate in nonwhites, compared with whites.

The mechanisms behind these associations are not known, but could involve mast-cell degranulation, autonomic dysfunction, or shared genetic or environmental etiologic factors, the authors said.

Dr. Patel reported no relevant disclosures.

[email protected]

SOURCE: Patel RS et al. Headache. 2019 June;59[S1]:1-208, Abstract P78.

PHILADELPHIA – U.S. children and teens who were hospitalized because of asthma had twice the rate of migraine headache when compared with a similar pediatric population without asthma. The finding is based on an analysis of more than 11 million U.S. pediatric hospitalizations over the course of a decade.

Among children and adolescents aged 3-21 years who were hospitalized for asthma, migraine rates were significantly higher among girls, adolescents, and whites, compared with boys, children aged 12 years or younger, and nonwhites, respectively, in a trio of adjusted analyses, Riddhiben S. Patel, MD, and associates reported in a poster at the annual meeting of the American Headache Society.

“Our hope is that, by establishing an association between childhood asthma and migraine, [these children] may be more easily screened for, diagnosed, and treated early by providers,” wrote Dr. Patel, a pediatric neurologist and headache specialist at the University of Mississippi, Jackson, and associates.

Their analysis used administrative billing data collected by the Kids’ Inpatient Database, maintained by the U.S. Healthcare Cost and Utilization Project. The project includes a representative national sample of about 3 million pediatric hospital discharges every 3 years. The study used data from 11,483,103 hospitalizations of children and adolescents aged 3-21 years during 2003, 2006, 2009, and 2012, and found an overall hospitalization rate of 0.8% billed for migraine. For patients also hospitalized with a billing code for asthma, the rate jumped to 1.36%, a 120% statistically significant relative increase in migraine hospitalizations after adjustment for baseline demographic differences, the researchers said.

Among the children and adolescents hospitalized with an asthma billing code, the relative rate of also having a billing code for migraine after adjustment was a statistically significant 80% higher in girls, compared with boys, a statistically significant 7% higher in adolescents, compared with children 12 years or younger, and was significantly reduced by a relative 45% rate in nonwhites, compared with whites.

The mechanisms behind these associations are not known, but could involve mast-cell degranulation, autonomic dysfunction, or shared genetic or environmental etiologic factors, the authors said.

Dr. Patel reported no relevant disclosures.

[email protected]

SOURCE: Patel RS et al. Headache. 2019 June;59[S1]:1-208, Abstract P78.

PHILADELPHIA – U.S. children and teens who were hospitalized because of asthma had twice the rate of migraine headache when compared with a similar pediatric population without asthma. The finding is based on an analysis of more than 11 million U.S. pediatric hospitalizations over the course of a decade.

Among children and adolescents aged 3-21 years who were hospitalized for asthma, migraine rates were significantly higher among girls, adolescents, and whites, compared with boys, children aged 12 years or younger, and nonwhites, respectively, in a trio of adjusted analyses, Riddhiben S. Patel, MD, and associates reported in a poster at the annual meeting of the American Headache Society.

“Our hope is that, by establishing an association between childhood asthma and migraine, [these children] may be more easily screened for, diagnosed, and treated early by providers,” wrote Dr. Patel, a pediatric neurologist and headache specialist at the University of Mississippi, Jackson, and associates.

Their analysis used administrative billing data collected by the Kids’ Inpatient Database, maintained by the U.S. Healthcare Cost and Utilization Project. The project includes a representative national sample of about 3 million pediatric hospital discharges every 3 years. The study used data from 11,483,103 hospitalizations of children and adolescents aged 3-21 years during 2003, 2006, 2009, and 2012, and found an overall hospitalization rate of 0.8% billed for migraine. For patients also hospitalized with a billing code for asthma, the rate jumped to 1.36%, a 120% statistically significant relative increase in migraine hospitalizations after adjustment for baseline demographic differences, the researchers said.

Among the children and adolescents hospitalized with an asthma billing code, the relative rate of also having a billing code for migraine after adjustment was a statistically significant 80% higher in girls, compared with boys, a statistically significant 7% higher in adolescents, compared with children 12 years or younger, and was significantly reduced by a relative 45% rate in nonwhites, compared with whites.

The mechanisms behind these associations are not known, but could involve mast-cell degranulation, autonomic dysfunction, or shared genetic or environmental etiologic factors, the authors said.

Dr. Patel reported no relevant disclosures.

[email protected]

SOURCE: Patel RS et al. Headache. 2019 June;59[S1]:1-208, Abstract P78.

LJUBLJANA, SLOVENIA – A new age-adjusted quick Sequential Organ Failure Assessment (qSOFA) score designed for use in children presenting to the ED with fever showed good predictive value for admission to critical care within the next 48 hours, Aakash Khanijau, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“In the needle-in-a-haystack scenario that’s seen in pediatric emergency departments, our novel, age-adjusted qSOFA score could potentially improve the rapid identification and treatment of children with suspected sepsis presenting to the ED,” said Dr. Khanijau of the University of Liverpool (England).

He presented an exceptionally large retrospective validation study of the score’s performance in 12,393 children (median age, 2.5 years) who presented to EDs with fever, of whom 1,521 were admitted for suspected sepsis. Of the hospitalized children, 145 were admitted to critical care within the first 48 hours.

The pediatric qSOFA score had 72% sensitivity and 85% specificity for critical care admission within 48 hours, with a positive predictive value of 5.4% and, more importantly, a whopping negative predictive value of 99.6%.

“That very high negative predictive value underlines the powerful discriminatory nature of our tool in the emergency department setting,” Dr. Khanijau observed, adding that the score’s area under the receiver operating characteristic curve was 0.81, which is considered a good predictive value.

The impetus for developing an age-adjusted pediatric qSOFA score stems from the fact that the original qSOFA score was designed for rapid assessment of adults with suspected sepsis and isn’t applicable in children. Other existing scores, including SIRS (the Systemic Inflammatory Response Syndrome criteria), the full SOFA, and PELOD-2 (the Pediatric Logistic Organ Dysfunction score), take longer to determine than the adapted qSOFA in a setting where speed is of the essence, he explained.

The original qSOFA components are altered mentation, systolic blood pressure, and respiratory rate. The novel score developed by Dr. Khanijau and coworkers swaps out systolic BP in favor of capillary refill time and age-adjusted heart rate using the thresholds previously established in a landmark study from the Children’s Hospital of Philadelphia (Pediatrics. 2013 Apr;131[4]:e1150-7.)

“Our reasoning here is that arterial hypertension is known to be a much later sign of circulatory compromise in children and may provide less discriminatory value than signs such as delayed capillary refill time and tachycardia early in presentation in the emergency department,” according to Dr. Khanijau.


The novel scoring system features four criteria. One point each is given for a capillary refill time of 3 seconds or longer; anything less than “Alert” on the Alert, Responds to Voice, Respond to Pain, and Unresponsive scale; a heart rate above the 99th percentile on the age-adjusted curves; and a respiratory rate above the age-adjusted 99th percentile. Thus, scores can range from 0 to 4. In the validation study, a score of 2 or more spelled a 890% increased likelihood of being admitted to a critical care setting within 48 hours. It was also associated with a 100-fold increased likelihood of death during the hospitalization, which occurred in 10 children.

Asked how the new predictive score could change clinical management, Dr. Khanijau replied, “I think the key thing it does here is it identifies the children at risk of requiring critical care and should therefore motivate us in the children achieving that threshold to promptly investigate thoroughly for suspected sepsis using the more comprehensive tools, like the full SOFA.”

He reported having no financial conflicts of interest regarding his study.

[email protected]

SOURCE: Khanijau A et al. ESPID 2019, Abstract.

LJUBLJANA, SLOVENIA – A new age-adjusted quick Sequential Organ Failure Assessment (qSOFA) score designed for use in children presenting to the ED with fever showed good predictive value for admission to critical care within the next 48 hours, Aakash Khanijau, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“In the needle-in-a-haystack scenario that’s seen in pediatric emergency departments, our novel, age-adjusted qSOFA score could potentially improve the rapid identification and treatment of children with suspected sepsis presenting to the ED,” said Dr. Khanijau of the University of Liverpool (England).

He presented an exceptionally large retrospective validation study of the score’s performance in 12,393 children (median age, 2.5 years) who presented to EDs with fever, of whom 1,521 were admitted for suspected sepsis. Of the hospitalized children, 145 were admitted to critical care within the first 48 hours.

The pediatric qSOFA score had 72% sensitivity and 85% specificity for critical care admission within 48 hours, with a positive predictive value of 5.4% and, more importantly, a whopping negative predictive value of 99.6%.

“That very high negative predictive value underlines the powerful discriminatory nature of our tool in the emergency department setting,” Dr. Khanijau observed, adding that the score’s area under the receiver operating characteristic curve was 0.81, which is considered a good predictive value.

The impetus for developing an age-adjusted pediatric qSOFA score stems from the fact that the original qSOFA score was designed for rapid assessment of adults with suspected sepsis and isn’t applicable in children. Other existing scores, including SIRS (the Systemic Inflammatory Response Syndrome criteria), the full SOFA, and PELOD-2 (the Pediatric Logistic Organ Dysfunction score), take longer to determine than the adapted qSOFA in a setting where speed is of the essence, he explained.

The original qSOFA components are altered mentation, systolic blood pressure, and respiratory rate. The novel score developed by Dr. Khanijau and coworkers swaps out systolic BP in favor of capillary refill time and age-adjusted heart rate using the thresholds previously established in a landmark study from the Children’s Hospital of Philadelphia (Pediatrics. 2013 Apr;131[4]:e1150-7.)

“Our reasoning here is that arterial hypertension is known to be a much later sign of circulatory compromise in children and may provide less discriminatory value than signs such as delayed capillary refill time and tachycardia early in presentation in the emergency department,” according to Dr. Khanijau.


The novel scoring system features four criteria. One point each is given for a capillary refill time of 3 seconds or longer; anything less than “Alert” on the Alert, Responds to Voice, Respond to Pain, and Unresponsive scale; a heart rate above the 99th percentile on the age-adjusted curves; and a respiratory rate above the age-adjusted 99th percentile. Thus, scores can range from 0 to 4. In the validation study, a score of 2 or more spelled a 890% increased likelihood of being admitted to a critical care setting within 48 hours. It was also associated with a 100-fold increased likelihood of death during the hospitalization, which occurred in 10 children.

Asked how the new predictive score could change clinical management, Dr. Khanijau replied, “I think the key thing it does here is it identifies the children at risk of requiring critical care and should therefore motivate us in the children achieving that threshold to promptly investigate thoroughly for suspected sepsis using the more comprehensive tools, like the full SOFA.”

He reported having no financial conflicts of interest regarding his study.

[email protected]

SOURCE: Khanijau A et al. ESPID 2019, Abstract.

LJUBLJANA, SLOVENIA – A new age-adjusted quick Sequential Organ Failure Assessment (qSOFA) score designed for use in children presenting to the ED with fever showed good predictive value for admission to critical care within the next 48 hours, Aakash Khanijau, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“In the needle-in-a-haystack scenario that’s seen in pediatric emergency departments, our novel, age-adjusted qSOFA score could potentially improve the rapid identification and treatment of children with suspected sepsis presenting to the ED,” said Dr. Khanijau of the University of Liverpool (England).

He presented an exceptionally large retrospective validation study of the score’s performance in 12,393 children (median age, 2.5 years) who presented to EDs with fever, of whom 1,521 were admitted for suspected sepsis. Of the hospitalized children, 145 were admitted to critical care within the first 48 hours.

The pediatric qSOFA score had 72% sensitivity and 85% specificity for critical care admission within 48 hours, with a positive predictive value of 5.4% and, more importantly, a whopping negative predictive value of 99.6%.

“That very high negative predictive value underlines the powerful discriminatory nature of our tool in the emergency department setting,” Dr. Khanijau observed, adding that the score’s area under the receiver operating characteristic curve was 0.81, which is considered a good predictive value.

The impetus for developing an age-adjusted pediatric qSOFA score stems from the fact that the original qSOFA score was designed for rapid assessment of adults with suspected sepsis and isn’t applicable in children. Other existing scores, including SIRS (the Systemic Inflammatory Response Syndrome criteria), the full SOFA, and PELOD-2 (the Pediatric Logistic Organ Dysfunction score), take longer to determine than the adapted qSOFA in a setting where speed is of the essence, he explained.

The original qSOFA components are altered mentation, systolic blood pressure, and respiratory rate. The novel score developed by Dr. Khanijau and coworkers swaps out systolic BP in favor of capillary refill time and age-adjusted heart rate using the thresholds previously established in a landmark study from the Children’s Hospital of Philadelphia (Pediatrics. 2013 Apr;131[4]:e1150-7.)

“Our reasoning here is that arterial hypertension is known to be a much later sign of circulatory compromise in children and may provide less discriminatory value than signs such as delayed capillary refill time and tachycardia early in presentation in the emergency department,” according to Dr. Khanijau.


The novel scoring system features four criteria. One point each is given for a capillary refill time of 3 seconds or longer; anything less than “Alert” on the Alert, Responds to Voice, Respond to Pain, and Unresponsive scale; a heart rate above the 99th percentile on the age-adjusted curves; and a respiratory rate above the age-adjusted 99th percentile. Thus, scores can range from 0 to 4. In the validation study, a score of 2 or more spelled a 890% increased likelihood of being admitted to a critical care setting within 48 hours. It was also associated with a 100-fold increased likelihood of death during the hospitalization, which occurred in 10 children.

Asked how the new predictive score could change clinical management, Dr. Khanijau replied, “I think the key thing it does here is it identifies the children at risk of requiring critical care and should therefore motivate us in the children achieving that threshold to promptly investigate thoroughly for suspected sepsis using the more comprehensive tools, like the full SOFA.”

He reported having no financial conflicts of interest regarding his study.

[email protected]

SOURCE: Khanijau A et al. ESPID 2019, Abstract.

SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.

Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.

Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).

Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.

Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).

“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.

Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).

As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.

Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).

The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.

Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.

Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).

Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.

Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).

“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.

Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).

As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.

Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).

The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

SEATTLE – Procalcitonin, a marker of bacterial infection, rises and peaks sooner than C-reactive protein (CRP), and is especially useful to help rule out invasive bacterial infections in young infants and pediatric community acquired pneumonia due to typical bacteria, according to a presentation at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

It’s “excellent for identifying low risk patients” and has the potential to decrease lumbar punctures and antibiotic exposure, but “the specificity isn’t great,” so there’s the potential for false positives, said Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

There was great interest in procalcitonin at the meeting; the presentation room was packed, with a line out the door. It’s used mostly in Europe at this point. Testing is available in many U.S. hospitals, but a large majority of audience members, when polled, said they don’t currently use it in clinical practice, and that it’s not a part of diagnostic algorithms at their institutions.

Levels of procalcitonin, a calcitonin precursor normally produced by the thyroid, are low or undetectable in healthy people, but inflammation, be it from infectious or noninfectious causes, triggers production by parenchymal cells throughout the body.

Levels began to rise as early as 2.5 hours after healthy subjects in one study were injected with bacterial endotoxins, and peaked as early as 6 hours; CRP, in contrast, started to rise after 12 hours, and peaked at 30 hours. Procalcitonin levels also seem to correlate with bacterial load and severity of infection, said Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University (J Pediatr Intensive Care. 2016 Dec;5[4]:162-71).

Due to time, the presenters focused their talk on community acquired pneumonia (CAP) and invasive bacterial infections (IBI) in young infants, meaning essentially bacteremia and meningitis.

Different studies use different cutoffs, but a procalcitonin below, for instance, 0.5 ng/mL is “certainly more sensitive [for IBI] than any single biomarker we currently use,” including CRP, white blood cells, and absolute neutrophil count (ANC). “If it’s negative, you’re really confident it’s negative,” but “a positive test does not necessarily indicate the presence of IBI,” Dr. McCulloh said (Pediatrics. 2012 Nov;130[5]:815-22).

“Procalcitonin works really well as part of a validated step-wise rule” that includes, for instance, CRP and ANC; “I think that’s where its utility is. On its own, it is not a substitute for you examining the patient and doing your basic risk stratification, but it may enhance your decision making incrementally above what we currently have,” he said.

Meanwhile, in a study of 532 children a median age of 2.4 years with radiographically confirmed CAP, procalcitonin levels were a median of 6.1 ng/mL in children whose pneumonia was caused by Streptococcus pneumoniae or other typical bacteria, and no child infected with typical bacteria had a level under 0.1 ng/mL. Below that level, “you can be very sure you do not have typical bacteria pneumonia,” said Marie Wang, MD, also a pediatric infectious disease specialist at Stanford (J Pediatric Infect Dis Soc. 2018 Feb 19;7[1]:46-53).

As procalcitonin levels went up, the likelihood of having bacterial pneumonia increased; at 2 ng/mL, 26% of subjects were infected with typical bacteria, “but even in that group, 58% still had viral infection, so you are still detecting a lot of viral” disease, she said.

Prolcalcitonin-guided therapy – antibiotics until patients fall below a level of 0.25 ng/ml, for instance – has also been associated with decreased antibiotic exposure (Respir Med. 2011 Dec;105[12]:1939-45).

The speakers had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

BANGKOK – The mortality rate is high in children with superrefractory status epilepticus, with fulminant cerebral edema emerging as the leading cause of death in a retrospective, single-center study presented by Maggie Lo Yee Yau, MD, at the International Epilepsy Congress.

“Death in these children usually occurred within the first few days after admission to the pediatric ICU,” she said at the congress sponsored by the International League Against Epilepsy.

Bruce Jancin/MDedge News

[email protected]

BANGKOK – The mortality rate is high in children with superrefractory status epilepticus, with fulminant cerebral edema emerging as the leading cause of death in a retrospective, single-center study presented by Maggie Lo Yee Yau, MD, at the International Epilepsy Congress.

“Death in these children usually occurred within the first few days after admission to the pediatric ICU,” she said at the congress sponsored by the International League Against Epilepsy.

Bruce Jancin/MDedge News

[email protected]

BANGKOK – The mortality rate is high in children with superrefractory status epilepticus, with fulminant cerebral edema emerging as the leading cause of death in a retrospective, single-center study presented by Maggie Lo Yee Yau, MD, at the International Epilepsy Congress.

“Death in these children usually occurred within the first few days after admission to the pediatric ICU,” she said at the congress sponsored by the International League Against Epilepsy.

Bruce Jancin/MDedge News

[email protected]

AUSTIN, TEX. – Adolescents with moderate to severe atopic dermatitis who used dupilumab experienced significant improvements in signs and symptoms of the condition, with minimal safety concerns, according to results of a phase 3 study.

Doug Brunk/MDedge News

“Dupilumab works as effectively in adolescents as in adults,” Randy Prescilla, MD, one of the study authors, said in an interview at the annual meeting of the Society for Pediatric Dermatology. “It gives us promise that we could go into other age groups with the same optimism. We are enrolling patients in even younger age groups.”

The double-blind, placebo-controlled study analyzed the efficacy and safety of dupilumab monotherapy in patients between the ages of 12 and 17 years with moderate to severe atopic dermatitis (AD) inadequately controlled with topical therapies. In the United States, dupilumab is approved for those aged 12 years and older with moderate to severe disease inadequately controlled by topical prescription treatments or when those therapies are not advisable.

For the 16-week study, Dr. Prescilla, global medical affairs director of pediatric dermatology for Sanofi Genzyme, and colleagues randomized 251 patients to one of three groups: dupilumab every 2 weeks (200 mg if baseline weight was less than 60 kg; 300 mg if that weight was 60 kg or more); 300 mg dupilumab every 4 weeks; or placebo every 2 weeks.

At week 16, a significantly higher proportion of patients in the two drug treatment groups had Investigator’s Global Assessment scores of 0/1, compared with those in the placebo group (24.4%, 17.9%, and 2.4%) as well as a significantly higher percentage of patients who achieved at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) score (41.5%, 38.1%, and 8.2%).

In addition, patients in the two drug treatment groups experienced improved percent change in least square-means on the EASI from baseline to week 16, compared with those in the placebo group (–65.9%, –64.8%, and –23.6%), the Peak Pruritus Numerical Rating Scale (–47.9%, –45.5%, and –19.0%), body surface area affected by AD (–30.1%, –33.4%, and –11.7%), and in the SCORing AD clinical tool (P less than .001 for all comparisons).


Between baseline and week 16, scores on the Children’s Dermatology Life Quality Index and Patient-Oriented Eczema Measure improved significantly in the two dupilumab groups, compared with the placebo group. The rate of skin infection was higher in the placebo group (20%), compared with 11% in the group that received dupilumab every 2 weeks and 13.3% in the group receiving the drug every 4 weeks.

Conjunctivitis occurred more frequently with dupilumab treatment (9.8% in the every-2-weeks dupilumab group, 10.8% in the every-4-weeks dupilumab group, and 4.7% in the placebo group) as did injection site reactions (8.5%, 6.0%, and 3.5%). Two adverse events, one of which was serious, occurred in the placebo group.

Dr. Prescilla acknowledged certain limitations of the study, including its small sample size and the fact that it was limited to 16 weeks. “However, smaller sample size and duration are typical for this type of study and in line with the study design of the SOLO 1 and SOLO 2 studies in adults,” he said.

On Aug. 6, the European Commission extended the marketing authorization for dupilumab in the European Union to include adolescents 12-17 years of age with moderate to severe atopic dermatitis who are candidates for systemic therapy. On the same day, Sanofi Genzyme and Regeneron announced positive topline results in a phase 3 trial in children aged 6-11 years with severe AD.

The study’s principal investigator was Amy S. Paller, MD. The study was funded by Sanofi Genzyme and Regeneron. Dr. Prescilla is an employee of Sanofi Genzyme.

[email protected]

AUSTIN, TEX. – Adolescents with moderate to severe atopic dermatitis who used dupilumab experienced significant improvements in signs and symptoms of the condition, with minimal safety concerns, according to results of a phase 3 study.

Doug Brunk/MDedge News

“Dupilumab works as effectively in adolescents as in adults,” Randy Prescilla, MD, one of the study authors, said in an interview at the annual meeting of the Society for Pediatric Dermatology. “It gives us promise that we could go into other age groups with the same optimism. We are enrolling patients in even younger age groups.”

The double-blind, placebo-controlled study analyzed the efficacy and safety of dupilumab monotherapy in patients between the ages of 12 and 17 years with moderate to severe atopic dermatitis (AD) inadequately controlled with topical therapies. In the United States, dupilumab is approved for those aged 12 years and older with moderate to severe disease inadequately controlled by topical prescription treatments or when those therapies are not advisable.

For the 16-week study, Dr. Prescilla, global medical affairs director of pediatric dermatology for Sanofi Genzyme, and colleagues randomized 251 patients to one of three groups: dupilumab every 2 weeks (200 mg if baseline weight was less than 60 kg; 300 mg if that weight was 60 kg or more); 300 mg dupilumab every 4 weeks; or placebo every 2 weeks.

At week 16, a significantly higher proportion of patients in the two drug treatment groups had Investigator’s Global Assessment scores of 0/1, compared with those in the placebo group (24.4%, 17.9%, and 2.4%) as well as a significantly higher percentage of patients who achieved at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) score (41.5%, 38.1%, and 8.2%).

In addition, patients in the two drug treatment groups experienced improved percent change in least square-means on the EASI from baseline to week 16, compared with those in the placebo group (–65.9%, –64.8%, and –23.6%), the Peak Pruritus Numerical Rating Scale (–47.9%, –45.5%, and –19.0%), body surface area affected by AD (–30.1%, –33.4%, and –11.7%), and in the SCORing AD clinical tool (P less than .001 for all comparisons).


Between baseline and week 16, scores on the Children’s Dermatology Life Quality Index and Patient-Oriented Eczema Measure improved significantly in the two dupilumab groups, compared with the placebo group. The rate of skin infection was higher in the placebo group (20%), compared with 11% in the group that received dupilumab every 2 weeks and 13.3% in the group receiving the drug every 4 weeks.

Conjunctivitis occurred more frequently with dupilumab treatment (9.8% in the every-2-weeks dupilumab group, 10.8% in the every-4-weeks dupilumab group, and 4.7% in the placebo group) as did injection site reactions (8.5%, 6.0%, and 3.5%). Two adverse events, one of which was serious, occurred in the placebo group.

Dr. Prescilla acknowledged certain limitations of the study, including its small sample size and the fact that it was limited to 16 weeks. “However, smaller sample size and duration are typical for this type of study and in line with the study design of the SOLO 1 and SOLO 2 studies in adults,” he said.

On Aug. 6, the European Commission extended the marketing authorization for dupilumab in the European Union to include adolescents 12-17 years of age with moderate to severe atopic dermatitis who are candidates for systemic therapy. On the same day, Sanofi Genzyme and Regeneron announced positive topline results in a phase 3 trial in children aged 6-11 years with severe AD.

The study’s principal investigator was Amy S. Paller, MD. The study was funded by Sanofi Genzyme and Regeneron. Dr. Prescilla is an employee of Sanofi Genzyme.

[email protected]

AUSTIN, TEX. – Adolescents with moderate to severe atopic dermatitis who used dupilumab experienced significant improvements in signs and symptoms of the condition, with minimal safety concerns, according to results of a phase 3 study.

Doug Brunk/MDedge News

“Dupilumab works as effectively in adolescents as in adults,” Randy Prescilla, MD, one of the study authors, said in an interview at the annual meeting of the Society for Pediatric Dermatology. “It gives us promise that we could go into other age groups with the same optimism. We are enrolling patients in even younger age groups.”

The double-blind, placebo-controlled study analyzed the efficacy and safety of dupilumab monotherapy in patients between the ages of 12 and 17 years with moderate to severe atopic dermatitis (AD) inadequately controlled with topical therapies. In the United States, dupilumab is approved for those aged 12 years and older with moderate to severe disease inadequately controlled by topical prescription treatments or when those therapies are not advisable.

For the 16-week study, Dr. Prescilla, global medical affairs director of pediatric dermatology for Sanofi Genzyme, and colleagues randomized 251 patients to one of three groups: dupilumab every 2 weeks (200 mg if baseline weight was less than 60 kg; 300 mg if that weight was 60 kg or more); 300 mg dupilumab every 4 weeks; or placebo every 2 weeks.

At week 16, a significantly higher proportion of patients in the two drug treatment groups had Investigator’s Global Assessment scores of 0/1, compared with those in the placebo group (24.4%, 17.9%, and 2.4%) as well as a significantly higher percentage of patients who achieved at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) score (41.5%, 38.1%, and 8.2%).

In addition, patients in the two drug treatment groups experienced improved percent change in least square-means on the EASI from baseline to week 16, compared with those in the placebo group (–65.9%, –64.8%, and –23.6%), the Peak Pruritus Numerical Rating Scale (–47.9%, –45.5%, and –19.0%), body surface area affected by AD (–30.1%, –33.4%, and –11.7%), and in the SCORing AD clinical tool (P less than .001 for all comparisons).


Between baseline and week 16, scores on the Children’s Dermatology Life Quality Index and Patient-Oriented Eczema Measure improved significantly in the two dupilumab groups, compared with the placebo group. The rate of skin infection was higher in the placebo group (20%), compared with 11% in the group that received dupilumab every 2 weeks and 13.3% in the group receiving the drug every 4 weeks.

Conjunctivitis occurred more frequently with dupilumab treatment (9.8% in the every-2-weeks dupilumab group, 10.8% in the every-4-weeks dupilumab group, and 4.7% in the placebo group) as did injection site reactions (8.5%, 6.0%, and 3.5%). Two adverse events, one of which was serious, occurred in the placebo group.

Dr. Prescilla acknowledged certain limitations of the study, including its small sample size and the fact that it was limited to 16 weeks. “However, smaller sample size and duration are typical for this type of study and in line with the study design of the SOLO 1 and SOLO 2 studies in adults,” he said.

On Aug. 6, the European Commission extended the marketing authorization for dupilumab in the European Union to include adolescents 12-17 years of age with moderate to severe atopic dermatitis who are candidates for systemic therapy. On the same day, Sanofi Genzyme and Regeneron announced positive topline results in a phase 3 trial in children aged 6-11 years with severe AD.

The study’s principal investigator was Amy S. Paller, MD. The study was funded by Sanofi Genzyme and Regeneron. Dr. Prescilla is an employee of Sanofi Genzyme.

[email protected]

BANGKOK – Neonatal and early infantile epileptic syndromes are more common than previously thought, accounting for nearly one in six cases of severe epilepsies of infancy in a comprehensive Australian population-based study, Katherine B. Howell, MD, reported at the International Epilepsy Congress.

“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.

She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.

“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.

She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.

“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.

The full spectrum of SEI

With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.

The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.


“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.

About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.

SEI etiologies

A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.

The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.

In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.

Outcomes

“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.

However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.

Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.

[email protected]

SOURCE: Howell KB et al. IEC 2019, Abstract P053.

BANGKOK – Neonatal and early infantile epileptic syndromes are more common than previously thought, accounting for nearly one in six cases of severe epilepsies of infancy in a comprehensive Australian population-based study, Katherine B. Howell, MD, reported at the International Epilepsy Congress.

“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.

She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.

“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.

She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.

“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.

The full spectrum of SEI

With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.

The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.


“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.

About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.

SEI etiologies

A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.

The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.

In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.

Outcomes

“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.

However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.

Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.

[email protected]

SOURCE: Howell KB et al. IEC 2019, Abstract P053.

BANGKOK – Neonatal and early infantile epileptic syndromes are more common than previously thought, accounting for nearly one in six cases of severe epilepsies of infancy in a comprehensive Australian population-based study, Katherine B. Howell, MD, reported at the International Epilepsy Congress.

“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.

She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.

“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.

She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.

“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.

The full spectrum of SEI

With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.

The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.


“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.

About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.

SEI etiologies

A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.

The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.

In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.

Outcomes

“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.

However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.

Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.

[email protected]

SOURCE: Howell KB et al. IEC 2019, Abstract P053.