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BALTIMORE—Lack of evidence for disease-modifying therapies (DMTs) in children presents a significant challenge in pediatric multiple sclerosis (MS). Forty percent of children with pediatric MS discontinue DMTs for inefficacy or side effects, according to an overview presented at the 141st Annual Meeting of the American Neurological Association.
“We need to keep working on clinical trials in kids and not shy away from investigating the stronger agents,” said Jennifer Graves, MD, PhD, Assistant Professor of Neurology at the University of California, San Francisco School of Medicine. Future studies should incorporate comprehensive outcomes that include measures of cognition, brain volume, and retinal integrity, she added. National and international collaborations currently under way may help achieve sample sizes that could provide conclusive evidence. 
Pediatric MS Has Distinctive Features
Nearly 5% of patients with MS have pediatric onset of symptoms; 20%–30% of these patients have onset before age 11. The mean age of onset for pediatric MS is 13. In several ways, the course of MS is different in children than in adults. Children typically have higher relapse rates than adults and are less likely to develop primary or secondary progressive MS in their childhood. Neurologists are concerned, however, about the possibility that these children will develop secondary progression in their 20s or 30s.
“A lot of these kids drop off the map between seeing us in pediatric centers and moving to adult MS centers. Often, these are the people that show up at [age] 30 with significant disability and high lesion burdens because they dropped out of care when they left their parents’ homes,” said Dr. Graves.
Unlike in adult MS, the gender ratio is approximately equal in prepubertal pediatric MS. There is a near 1:1 ratio of females to males in children who present before age 11, but the ratio increases over time to 2:1 or 3:1 in adolescents and adults. Postpubertal and adult patients with MS have similar features, but prepubertal patients have features distinct from those of adult MS. For example, prepubertal patients have a lower prevalence of oligoclonal bands. Their MRI lesions tend to be larger and less distinct and sometimes resolve completely. In addition, children tend to have better motor, visual, and cerebellar recovery from relapses than adults.
A study published in the July issue of Pediatrics described the demographic and clinical characteristics of patients with pediatric MS in the United States. Of the 490 children and adolescents enrolled, 28% developed symptoms before age 12. Sixty-seven percent of participants identified as white, 21% as African-American, and 70% as non-Hispanic. Thirty-nine percent of patients had one or two foreign-born parents. Approximately 31% of patients had a prodrome (often infectious), which occurred mostly in children under age 12. Researchers observed a difference in the type of relapses in children under 12, compared with adolescents and adults. Young children tended to have more cerebellar symptoms, encephalopathy, and greater lesion burden in the posterior fossa.
Perinatal Risk Factors in Pediatric MS
In work from the US Network of Pediatric MS Centers presented at the 68th Annual Meeting of the American Academy of Neurology, Cesarean section (C-section) was associated with a 60% reduced odds of having pediatric-onset MS. The association remained statistically significant after the researchers adjusted for socioeconomic status and other maternal variables such as BMI, age, gestational diabetes, pre-eclampsia, and birth complications. While the mechanism of the association remains unknown, it is of interest in light of the new insights regarding the microbiome and MS. Children born by C-section typically have different gut flora for at least the first year of life, said Dr. Graves. When the data were adjusted for C-section result, maternal illness was independently associated with a twofold increase in the risk of pediatric MS.
The mechanism of maternal illness effects on MS risk have yet to be elucidated, but in animal models of MS, exposure during pregnancy to certain bacterial antigens can result in a proinflammatory Th17 phenotype and may cause long-term effects in offspring. An exploratory analysis in this perinatal risk factor study revealed that variables associated with agricultural work by the parent and home use of pesticides and insecticides were associated with a twofold increased risk of pediatric MS.
Diet, BMI, and Exercise
Diets high in salt have been associated with high relapse rate in adults. This association has not been found in pediatric MS, however. High fat intake is associated with high relapse rate in children with MS, according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS. Diets rich in fruits and vegetables are linked to a lower relapse rate, even after adjusting for fat intake.
In addition, data indicate that BMI is directly proportional to the risk for pediatric MS. Vigorous activity, however, is associated with decreased risk of pediatric MS, a decreased number of T2 lesions, and a decreased relapse rate, according to a Canadian study.
Role of Risk Genes and Genetic Ancestry in Pediatric MS
Genetics may play a key role in the development of early-onset pediatric MS. Researchers are analyzing data in the United States for people of multiple genetic ancestries. Of 110 nonhuman leukocyte antigen (HLA) risk variants for adult MS, 36 may increase the risk of pediatric MS, either at the level of single-nucleotide polymorphisms (SNPs) or as an aggregate genetic risk factor. The effect size of each SNP is greater in children than in adults; each SNP may increase the risk of MS by twofold or more.
Imaging Efforts
Imaging could improve understanding of pediatric MS. National and international efforts to standardize protocols for 3-T imaging, volumetric scans, and diffusion tensor imaging (DTI) are under way. DTI already has revealed abnormal fractional anisotropy in pediatric MS, and this abnormality is associated with cognitive difficulty. MRI and optical coherence tomography (OCT) help to distinguish between MS, neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM).
OCT imaging in children indicates similar levels of neuronal and axonal injury as in adults, despite better visual recovery in children. In a study published in the Multiple Sclerosis Journal, boys with pediatric MS were found to have greater axonal loss than girls with pediatric MS.
Testing DMTs’ Efficacy
Several studies of DMTs in pediatric MS are under way. PARADIGMS is an ongoing, 24-month, double-blind, double-randomized trial investigating the effect of fingolimod on relapse rate in pediatric MS. The control group is receiving
Observational registries are studying the safety and clinical experience with disease modifying agents in children. Investigators recently published data for 100 children in an Italian registry of patients with MS treated with natalizumab. The treatment decreased relapse rate to 0.1. Approximately 28% of the population had no evidence of disease activity. The drug appeared to be well tolerated in children and to be efficacious.
—Erica Tricarico
Suggested Reading
Belman AL, Krupp LB, Olsen CS, et al. Characteristics of children and adolescents with multiple sclerosis. Pediatrics. 2016;138(1).
BALTIMORE—Lack of evidence for disease-modifying therapies (DMTs) in children presents a significant challenge in pediatric multiple sclerosis (MS). Forty percent of children with pediatric MS discontinue DMTs for inefficacy or side effects, according to an overview presented at the 141st Annual Meeting of the American Neurological Association.
“We need to keep working on clinical trials in kids and not shy away from investigating the stronger agents,” said Jennifer Graves, MD, PhD, Assistant Professor of Neurology at the University of California, San Francisco School of Medicine. Future studies should incorporate comprehensive outcomes that include measures of cognition, brain volume, and retinal integrity, she added. National and international collaborations currently under way may help achieve sample sizes that could provide conclusive evidence.
Pediatric MS Has Distinctive Features
Nearly 5% of patients with MS have pediatric onset of symptoms; 20%–30% of these patients have onset before age 11. The mean age of onset for pediatric MS is 13. In several ways, the course of MS is different in children than in adults. Children typically have higher relapse rates than adults and are less likely to develop primary or secondary progressive MS in their childhood. Neurologists are concerned, however, about the possibility that these children will develop secondary progression in their 20s or 30s.
“A lot of these kids drop off the map between seeing us in pediatric centers and moving to adult MS centers. Often, these are the people that show up at [age] 30 with significant disability and high lesion burdens because they dropped out of care when they left their parents’ homes,” said Dr. Graves.
Unlike in adult MS, the gender ratio is approximately equal in prepubertal pediatric MS. There is a near 1:1 ratio of females to males in children who present before age 11, but the ratio increases over time to 2:1 or 3:1 in adolescents and adults. Postpubertal and adult patients with MS have similar features, but prepubertal patients have features distinct from those of adult MS. For example, prepubertal patients have a lower prevalence of oligoclonal bands. Their MRI lesions tend to be larger and less distinct and sometimes resolve completely. In addition, children tend to have better motor, visual, and cerebellar recovery from relapses than adults.
A study published in the July issue of Pediatrics described the demographic and clinical characteristics of patients with pediatric MS in the United States. Of the 490 children and adolescents enrolled, 28% developed symptoms before age 12. Sixty-seven percent of participants identified as white, 21% as African-American, and 70% as non-Hispanic. Thirty-nine percent of patients had one or two foreign-born parents. Approximately 31% of patients had a prodrome (often infectious), which occurred mostly in children under age 12. Researchers observed a difference in the type of relapses in children under 12, compared with adolescents and adults. Young children tended to have more cerebellar symptoms, encephalopathy, and greater lesion burden in the posterior fossa.
Perinatal Risk Factors in Pediatric MS
In work from the US Network of Pediatric MS Centers presented at the 68th Annual Meeting of the American Academy of Neurology, Cesarean section (C-section) was associated with a 60% reduced odds of having pediatric-onset MS. The association remained statistically significant after the researchers adjusted for socioeconomic status and other maternal variables such as BMI, age, gestational diabetes, pre-eclampsia, and birth complications. While the mechanism of the association remains unknown, it is of interest in light of the new insights regarding the microbiome and MS. Children born by C-section typically have different gut flora for at least the first year of life, said Dr. Graves. When the data were adjusted for C-section result, maternal illness was independently associated with a twofold increase in the risk of pediatric MS.
The mechanism of maternal illness effects on MS risk have yet to be elucidated, but in animal models of MS, exposure during pregnancy to certain bacterial antigens can result in a proinflammatory Th17 phenotype and may cause long-term effects in offspring. An exploratory analysis in this perinatal risk factor study revealed that variables associated with agricultural work by the parent and home use of pesticides and insecticides were associated with a twofold increased risk of pediatric MS.
Diet, BMI, and Exercise
Diets high in salt have been associated with high relapse rate in adults. This association has not been found in pediatric MS, however. High fat intake is associated with high relapse rate in children with MS, according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS. Diets rich in fruits and vegetables are linked to a lower relapse rate, even after adjusting for fat intake.
In addition, data indicate that BMI is directly proportional to the risk for pediatric MS. Vigorous activity, however, is associated with decreased risk of pediatric MS, a decreased number of T2 lesions, and a decreased relapse rate, according to a Canadian study.
Role of Risk Genes and Genetic Ancestry in Pediatric MS
Genetics may play a key role in the development of early-onset pediatric MS. Researchers are analyzing data in the United States for people of multiple genetic ancestries. Of 110 nonhuman leukocyte antigen (HLA) risk variants for adult MS, 36 may increase the risk of pediatric MS, either at the level of single-nucleotide polymorphisms (SNPs) or as an aggregate genetic risk factor. The effect size of each SNP is greater in children than in adults; each SNP may increase the risk of MS by twofold or more.
Imaging Efforts
Imaging could improve understanding of pediatric MS. National and international efforts to standardize protocols for 3-T imaging, volumetric scans, and diffusion tensor imaging (DTI) are under way. DTI already has revealed abnormal fractional anisotropy in pediatric MS, and this abnormality is associated with cognitive difficulty. MRI and optical coherence tomography (OCT) help to distinguish between MS, neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM).
OCT imaging in children indicates similar levels of neuronal and axonal injury as in adults, despite better visual recovery in children. In a study published in the Multiple Sclerosis Journal, boys with pediatric MS were found to have greater axonal loss than girls with pediatric MS.
Testing DMTs’ Efficacy
Several studies of DMTs in pediatric MS are under way. PARADIGMS is an ongoing, 24-month, double-blind, double-randomized trial investigating the effect of fingolimod on relapse rate in pediatric MS. The control group is receiving
Observational registries are studying the safety and clinical experience with disease modifying agents in children. Investigators recently published data for 100 children in an Italian registry of patients with MS treated with natalizumab. The treatment decreased relapse rate to 0.1. Approximately 28% of the population had no evidence of disease activity. The drug appeared to be well tolerated in children and to be efficacious.
—Erica Tricarico
Suggested Reading
Belman AL, Krupp LB, Olsen CS, et al. Characteristics of children and adolescents with multiple sclerosis. Pediatrics. 2016;138(1).
BALTIMORE—Lack of evidence for disease-modifying therapies (DMTs) in children presents a significant challenge in pediatric multiple sclerosis (MS). Forty percent of children with pediatric MS discontinue DMTs for inefficacy or side effects, according to an overview presented at the 141st Annual Meeting of the American Neurological Association.
“We need to keep working on clinical trials in kids and not shy away from investigating the stronger agents,” said Jennifer Graves, MD, PhD, Assistant Professor of Neurology at the University of California, San Francisco School of Medicine. Future studies should incorporate comprehensive outcomes that include measures of cognition, brain volume, and retinal integrity, she added. National and international collaborations currently under way may help achieve sample sizes that could provide conclusive evidence.
Pediatric MS Has Distinctive Features
Nearly 5% of patients with MS have pediatric onset of symptoms; 20%–30% of these patients have onset before age 11. The mean age of onset for pediatric MS is 13. In several ways, the course of MS is different in children than in adults. Children typically have higher relapse rates than adults and are less likely to develop primary or secondary progressive MS in their childhood. Neurologists are concerned, however, about the possibility that these children will develop secondary progression in their 20s or 30s.
“A lot of these kids drop off the map between seeing us in pediatric centers and moving to adult MS centers. Often, these are the people that show up at [age] 30 with significant disability and high lesion burdens because they dropped out of care when they left their parents’ homes,” said Dr. Graves.
Unlike in adult MS, the gender ratio is approximately equal in prepubertal pediatric MS. There is a near 1:1 ratio of females to males in children who present before age 11, but the ratio increases over time to 2:1 or 3:1 in adolescents and adults. Postpubertal and adult patients with MS have similar features, but prepubertal patients have features distinct from those of adult MS. For example, prepubertal patients have a lower prevalence of oligoclonal bands. Their MRI lesions tend to be larger and less distinct and sometimes resolve completely. In addition, children tend to have better motor, visual, and cerebellar recovery from relapses than adults.
A study published in the July issue of Pediatrics described the demographic and clinical characteristics of patients with pediatric MS in the United States. Of the 490 children and adolescents enrolled, 28% developed symptoms before age 12. Sixty-seven percent of participants identified as white, 21% as African-American, and 70% as non-Hispanic. Thirty-nine percent of patients had one or two foreign-born parents. Approximately 31% of patients had a prodrome (often infectious), which occurred mostly in children under age 12. Researchers observed a difference in the type of relapses in children under 12, compared with adolescents and adults. Young children tended to have more cerebellar symptoms, encephalopathy, and greater lesion burden in the posterior fossa.
Perinatal Risk Factors in Pediatric MS
In work from the US Network of Pediatric MS Centers presented at the 68th Annual Meeting of the American Academy of Neurology, Cesarean section (C-section) was associated with a 60% reduced odds of having pediatric-onset MS. The association remained statistically significant after the researchers adjusted for socioeconomic status and other maternal variables such as BMI, age, gestational diabetes, pre-eclampsia, and birth complications. While the mechanism of the association remains unknown, it is of interest in light of the new insights regarding the microbiome and MS. Children born by C-section typically have different gut flora for at least the first year of life, said Dr. Graves. When the data were adjusted for C-section result, maternal illness was independently associated with a twofold increase in the risk of pediatric MS.
The mechanism of maternal illness effects on MS risk have yet to be elucidated, but in animal models of MS, exposure during pregnancy to certain bacterial antigens can result in a proinflammatory Th17 phenotype and may cause long-term effects in offspring. An exploratory analysis in this perinatal risk factor study revealed that variables associated with agricultural work by the parent and home use of pesticides and insecticides were associated with a twofold increased risk of pediatric MS.
Diet, BMI, and Exercise
Diets high in salt have been associated with high relapse rate in adults. This association has not been found in pediatric MS, however. High fat intake is associated with high relapse rate in children with MS, according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS. Diets rich in fruits and vegetables are linked to a lower relapse rate, even after adjusting for fat intake.
In addition, data indicate that BMI is directly proportional to the risk for pediatric MS. Vigorous activity, however, is associated with decreased risk of pediatric MS, a decreased number of T2 lesions, and a decreased relapse rate, according to a Canadian study.
Role of Risk Genes and Genetic Ancestry in Pediatric MS
Genetics may play a key role in the development of early-onset pediatric MS. Researchers are analyzing data in the United States for people of multiple genetic ancestries. Of 110 nonhuman leukocyte antigen (HLA) risk variants for adult MS, 36 may increase the risk of pediatric MS, either at the level of single-nucleotide polymorphisms (SNPs) or as an aggregate genetic risk factor. The effect size of each SNP is greater in children than in adults; each SNP may increase the risk of MS by twofold or more.
Imaging Efforts
Imaging could improve understanding of pediatric MS. National and international efforts to standardize protocols for 3-T imaging, volumetric scans, and diffusion tensor imaging (DTI) are under way. DTI already has revealed abnormal fractional anisotropy in pediatric MS, and this abnormality is associated with cognitive difficulty. MRI and optical coherence tomography (OCT) help to distinguish between MS, neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM).
OCT imaging in children indicates similar levels of neuronal and axonal injury as in adults, despite better visual recovery in children. In a study published in the Multiple Sclerosis Journal, boys with pediatric MS were found to have greater axonal loss than girls with pediatric MS.
Testing DMTs’ Efficacy
Several studies of DMTs in pediatric MS are under way. PARADIGMS is an ongoing, 24-month, double-blind, double-randomized trial investigating the effect of fingolimod on relapse rate in pediatric MS. The control group is receiving
Observational registries are studying the safety and clinical experience with disease modifying agents in children. Investigators recently published data for 100 children in an Italian registry of patients with MS treated with natalizumab. The treatment decreased relapse rate to 0.1. Approximately 28% of the population had no evidence of disease activity. The drug appeared to be well tolerated in children and to be efficacious.
—Erica Tricarico
Suggested Reading
Belman AL, Krupp LB, Olsen CS, et al. Characteristics of children and adolescents with multiple sclerosis. Pediatrics. 2016;138(1).
