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A boy who lives with MS sits on the stoop of his house between his two brothers.
Joshua (center)
Diagnosed in 2015

Pediatric MS

Overview

Belman et al., 2016; Chitnis et al., 2009; Boiko et al., 2002; Duquette et al., 1987). POMS is almost exclusively diagnosed as a relapsing-remitting course, with frequency of primary progressive MS estimated at up to 7% (Abdel-Mannan, 2020). This is in stark contrast to adult-onset MS. In the adult population, primary progressive MS is much more frequent." c-nmssatomrichtext_nmssatomrichtext-host="">
Pediatric-onset multiple sclerosis (POMS) occurs when MS is diagnosed before 18 years of age. Approximately 3%-5% of all individuals with MS experience disease onset before age 16 (Belman et al., 2016; Chitnis et al., 2009; Boiko et al., 2002; Duquette et al., 1987). POMS is almost exclusively diagnosed as a relapsing-remitting course, with frequency of primary progressive MS estimated at up to 7% (Abdel-Mannan, 2020). This is in stark contrast to adult-onset MS. In the adult population, primary progressive MS is much more frequent.
  • factors are associated with the development of MS. This review discusses genetic and environmental risk factors in POMS.
  • Maternal illness during pregnancy, pesticide exposure due to paternal occupation and use of pesticides in the household during pregnancy may increase the chance an unborn child will develop MS. Delivery by Cesarean section may decrease the risk of developing MS in childhood (Graves et al., 2016).
  • The onset of puberty seems to increase the likelihood of developing MS in those assigned female at birth, as they are 2-3 times more likely than those assigned male at birth to develop MS once puberty begins. Interestingly, there is no sex difference prior to pubertal onset, suggesting the potential role hormonal differences may play in MS pathophysiology (Ahn et al., 2015; Belman et al., 2016; ).
  • Later age at menarche may decrease the risk of developing MS (Ahn et al., 2015).
  • The gut microbiome has been implicated in small studies, but still needs validation in larger cohorts (Tremlett et al., 2016). A large study looking at how diet might affect relapse rate in POMS was recently completed, with results forthcoming.
  • Ancestry appears to play a role in adult MS. However, place of birth, regardless of ancestry, appears to factor more into POMS compared to adult-onset MS (Kennedy et al., 2006).
  • Children with a first-degree relative with MS (i.e., parent or sibling) have been shown to have a 2%-4% increased risk of developing MS (Esposito et al., 2015; Nielsen et al., 2005).
Social Determinants of Health
In addition to the factors highlighted above, according to the World Health Organization, numerous studies suggest that social determinants of health (SDoH) account for 30%-55% of health outcomes overall. Addressing SDoH is, therefore, crucial to improving the health and lives of people living with chronic diseases like MS. Some social determinants of health that can influence the trajectory of one’s healthcare journey include:
  • Access to affordable and adequate healthcare services
  • Early childhood development
  • Education
  • Employment status and job security
  • Food security
  • Housing, basic amenities and the environment
  • Income and social protection
  • Social inclusion and non-discrimination
  • Structural conflict
  • Work-life conditions
The ability to access care, which is affected by these SDoH, can impact the course of the disease. Addressing SDoH issues can, therefore, help improve disease-specific outcomes and quality of life for your patients. The pediatric-onset MS patients and families who utilize their healthcare team are more likely to recognize and address these factors." c-nmssatomrichtext_nmssatomrichtext-host="">
  • Environmental, genetic and familial factors are associated with the development of MS. This review discusses genetic and environmental risk factors in POMS.
  • Maternal illness during pregnancy, pesticide exposure due to paternal occupation and use of pesticides in the household during pregnancy may increase the chance an unborn child will develop MS. Delivery by Cesarean section may decrease the risk of developing MS in childhood (Graves et al., 2016).
  • The onset of puberty seems to increase the likelihood of developing MS in those assigned female at birth, as they are 2-3 times more likely than those assigned male at birth to develop MS once puberty begins. Interestingly, there is no sex difference prior to pubertal onset, suggesting the potential role hormonal differences may play in MS pathophysiology (Ahn et al., 2015; Belman et al., 2016; ).
  • Later age at menarche may decrease the risk of developing MS (Ahn et al., 2015).
  • The gut microbiome has been implicated in small studies, but still needs validation in larger cohorts (Tremlett et al., 2016). A large study looking at how diet might affect relapse rate in POMS was recently completed, with results forthcoming.
  • Ancestry appears to play a role in adult MS. However, place of birth, regardless of ancestry, appears to factor more into POMS compared to adult-onset MS (Kennedy et al., 2006).
  • Children with a first-degree relative with MS (i.e., parent or sibling) have been shown to have a 2%-4% increased risk of developing MS (Esposito et al., 2015; Nielsen et al., 2005).
Social Determinants of Health
In addition to the factors highlighted above, according to the World Health Organization, numerous studies suggest that social determinants of health (SDoH) account for 30%-55% of health outcomes overall. Addressing SDoH is, therefore, crucial to improving the health and lives of people living with chronic diseases like MS. Some social determinants of health that can influence the trajectory of one’s healthcare journey include:
  • Access to affordable and adequate healthcare services
  • Early childhood development
  • Education
  • Employment status and job security
  • Food security
  • Housing, basic amenities and the environment
  • Income and social protection
  • Social inclusion and non-discrimination
  • Structural conflict
  • Work-life conditions
The ability to access care, which is affected by these SDoH, can impact the course of the disease. Addressing SDoH issues can, therefore, help improve disease-specific outcomes and quality of life for your patients. The pediatric-onset MS patients and families who utilize their healthcare team are more likely to recognize and address these factors.

  • Gorman et al., 2009; Benson et al., 2014).
    • Disability accrual is slower in children compared to adults.
    • On average, POMS patients show significant disability at an age 10 years younger than their early adult-onset MS counterparts (Harding et al., 2012; Renoux et al., 2007).
  • POMS patients tend to be polysymptomatic at presentation but recover from relapses more quickly than adults; on average over 4 weeks compared to 6-8 weeks in adults (). POMS patients have a higher MRI T2 lesion burden than adults (Waubant et al., 2009). Post-mortem comparison found more extensive axonal injury in the demyelinating lesions of pediatric brains than in adults. Therefore, childhood MS appears to be more inflammatory, at least early on (Pfeifenbring et al., 2015).
  • Approximately one-third of POMS patients show evidence of significant cognitive impairment early on (Amato et al., 2008), with significant progression within 2 years (Amato et al., 2010).
    • Over half demonstrate a decline in cognitive indices over 5 years. However, there was the potential for compensation and improvement in some subjects, which showcases the importance of systemic cognitive screening and the development of effective treatment strategies (Amato et al., 2014). Further study is needed to better understand the variables that positively influenced the improvement seen in some subjects.
    • " c-nmssatomrichtext_nmssatomrichtext-host="">
    • POMS patients experience 2-3 times more frequent relapses in the first 6 years post-diagnosis than adults with early-onset MS (Gorman et al., 2009; Benson et al., 2014).
      • Disability accrual is slower in children compared to adults.
      • On average, POMS patients show significant disability at an age 10 years younger than their early adult-onset MS counterparts (Harding et al., 2012; Renoux et al., 2007).
    • POMS patients tend to be polysymptomatic at presentation but recover from relapses more quickly than adults; on average over 4 weeks compared to 6-8 weeks in adults (). POMS patients have a higher MRI T2 lesion burden than adults (Waubant et al., 2009). Post-mortem comparison found more extensive axonal injury in the demyelinating lesions of pediatric brains than in adults. Therefore, childhood MS appears to be more inflammatory, at least early on (Pfeifenbring et al., 2015).
    • Approximately one-third of POMS patients show evidence of significant cognitive impairment early on (Amato et al., 2008), with significant progression within 2 years (Amato et al., 2010).
      • Over half demonstrate a decline in cognitive indices over 5 years. However, there was the potential for compensation and improvement in some subjects, which showcases the importance of systemic cognitive screening and the development of effective treatment strategies (Amato et al., 2014). Further study is needed to better understand the variables that positively influenced the improvement seen in some subjects.

  • Find Doctors & Resources Tool.
    Information for Diagnosing Pediatric MS
    Two consensus reports — one by neurologists in the United States and one by the International Pediatric MS Study Group (IPMSSG) — provide helpful insights into the diagnosis and management of MS in the pediatric population.The free-access Neurology supplement on Pediatric Demyelinating Disorders, from the 2016 IPMSSG, provides a comprehensive review of pediatric demyelinating disorders, including MS.See tools for making a diagnosis.
    Differential Diagnosis
    The challenge in differential diagnosis lies in distinguishing MS from the numerous other disorders in children that can also present with demyelinating events. To distinguish other demyelinating events from POMS, the International Pediatric MS Study Group (IPMSSG) (Krupp et al., 2007) proposed consensus definitions for:
    • Monophasic acute disseminated encephalomyelitis (ADEM — an essential feature of which is the presence of encephalopathy)
    • Neuromyelitis optica spectrum disorder (NMOSD)
    • Clinically isolated syndrome (CIS).
    The IPMSSG also proposed a minimum diagnostic battery for pediatric patients with an initial inflammatory demyelinating event.This chart (modified from Wingerchuk et al., 2015; Krupp et al., 2013; Sadaka et al., 2012; Banwell et al., 2011) demonstrates a diagnostic pathway for a child experiencing an acute CNS demyelinating event, followed by a second episode of neurologic dysfunction. Historically, <10% of children presenting with ADEM were eventually diagnosed with MS. However, the relatively recent discovery of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), a common presentation of which is ADEM, will likely alter the landscape as more research is conducted on MOGAD.Clinically isolated syndrome (CIS) occurs when there is a clinical demyelinating event without sufficient radiologic findings to satisfy an MS diagnosis. In several studies utilizing the IPMSSG criteria, the risk of MS after an episode of pediatric-onset CIS was shown to range from 26%-62% (Alper G et al., 2009; Neuteboom RF et al., 2008; Banwell et al., 2007; Dale RC et al., 2007). Classification of first and subsequent episodes of acquired CNS demyelination, along with its differential diagnoses, clinical features and outcomes, were reviewed by Banwell et al. in 2007.Radiologically isolated syndrome (RIS) occurs when a patient’s MRI is consistent with MS, but the patient has not experienced a clinical demyelinating event. Consider long-term treatment of CIS or RIS patients on a case-by-case basis." c-nmssatomrichtext_nmssatomrichtext-host="">
    Diagnosing and treating POMS early helps prevent disease progression. As with adults, evaluate any child or adolescent who experiences a demyelinating event for MS. Diagnostic confirmation depends on:
    • Medical history
    • Examination
    • Interpretation of paraclinical testing
    • Exclusion of mimics and alternative etiologies
    A pediatric MS specialist best achieves this. Your patients can search for local pediatric MS specialists with the Find Doctors & Resources Tool.
    Information for Diagnosing Pediatric MS
    Two consensus reports — one by neurologists in the United States and one by the International Pediatric MS Study Group (IPMSSG) — provide helpful insights into the diagnosis and management of MS in the pediatric population.The free-access Neurology supplement on Pediatric Demyelinating Disorders, from the 2016 IPMSSG, provides a comprehensive review of pediatric demyelinating disorders, including MS.See tools for making a diagnosis.
    Differential Diagnosis
    The challenge in differential diagnosis lies in distinguishing MS from the numerous other disorders in children that can also present with demyelinating events. To distinguish other demyelinating events from POMS, the International Pediatric MS Study Group (IPMSSG) (Krupp et al., 2007) proposed consensus definitions for:
    • Monophasic acute disseminated encephalomyelitis (ADEM — an essential feature of which is the presence of encephalopathy)
    • Neuromyelitis optica spectrum disorder (NMOSD)
    • Clinically isolated syndrome (CIS).
    The IPMSSG also proposed a minimum diagnostic battery for pediatric patients with an initial inflammatory demyelinating event.This chart (modified from Wingerchuk et al., 2015; Krupp et al., 2013; Sadaka et al., 2012; Banwell et al., 2011) demonstrates a diagnostic pathway for a child experiencing an acute CNS demyelinating event, followed by a second episode of neurologic dysfunction. Historically, <10% of children presenting with ADEM were eventually diagnosed with MS. However, the relatively recent discovery of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), a common presentation of which is ADEM, will likely alter the landscape as more research is conducted on MOGAD.Clinically isolated syndrome (CIS) occurs when there is a clinical demyelinating event without sufficient radiologic findings to satisfy an MS diagnosis. In several studies utilizing the IPMSSG criteria, the risk of MS after an episode of pediatric-onset CIS was shown to range from 26%-62% (Alper G et al., 2009; Neuteboom RF et al., 2008; Banwell et al., 2007; Dale RC et al., 2007). Classification of first and subsequent episodes of acquired CNS demyelination, along with its differential diagnoses, clinical features and outcomes, were reviewed by Banwell et al. in 2007.Radiologically isolated syndrome (RIS) occurs when a patient’s MRI is consistent with MS, but the patient has not experienced a clinical demyelinating event. Consider long-term treatment of CIS or RIS patients on a case-by-case basis.

  • study looking at the use of teriflunomide (Aubagio ®) in treating POMS did not meet its primary endpoint of decreasing time to first confirmed clinical relapse; however, it did meet its secondary endpoint of significantly reducing disease activity on MRI scans compared to placebo.
  • Other oral therapies for MS, including dimethyl fumarate (Tecfidera®), continue to be studied in clinical trials for treating POMS.
    • Prior to oral and high-efficacy therapies becoming available, many of the older disease-modifying therapies prescribed for adults with MS were also prescribed for children. These included interferon beta-1a (Avonex®, Betaseron®) and glatiramer acetate (Copaxone®).
    • Small retrospective studies, case studies and unblinded controlled trials have demonstrated the safety and efficacy of these self-injectable drugs (Banwell et al., 2006, Tenenbaum et al., 2013, Kornek et al., 2003).
    • Initial treatment of POMS with newer DMTs (oral and infusible medications) has shown better disease activity control compared to 1st generation injectables in clinical trials, showcasing the effectiveness of newer therapies.
    Regarding infusion therapies, an observational study of natalizumab (Tysabri®) showed that its safety and efficacy in children were similar to those seen in the adult MS population (Ghezzi et al., 2015). Additional infusion trials are currently underway.In addition to the adult FDA-approved therapies used in POMS, another treatment not FDA-approved for MS, rituximab (Rituxan®), has been studied in small trials of pediatric patients, demonstrating both safety and efficacy. Rituximab is widely used in other pediatric autoimmune disorders and has a safety profile similar to other B-cell depleting agents widely used in adults (e.g., ocrelizumab) (Dale et al., 2014).
    Treatment Strategies
    POMS is usually highly active, characterized by more frequent relapses, rapid lesion accrual early in the disease course and more cognitive and physical disability at an earlier age than in adult-onset MS (Hacohen et al., 2020). In a cohort study comparing initial treatment with newer DMTs versus older 1st-generation injectables in POMS patients or those with CIS, newer DMTs provided better disease control and safety profiles similar to those observed in adults. However, long-term safety data are still needed in children (Krysko et al., 2020). Due to the highly active nature of POMS and earlier age of conversion to secondary progressive MS, initial treatment with newer, higher-efficacy DMTs is being increasingly recommended (Hacohen et al., 2020).
    Starting or Switching Disease-Modifying Therapies
    Ultimately, starting or switching to a disease-modifying therapy in children and adolescents requires an in-depth discussion between the provider, patient and family. It should include:
    • Understanding the goals and expectations of the child and family
    • Sharing the safety, efficacy and monitoring profile of the various treatment options
    • Proactively discussing factors that could affect adherence (cost, route of administration, dosage, transportation)
    By understanding what is important to the child and family and addressing concerns, fears and potential challenges, providers, patients and families can participate in a shared decision-making process to determine the therapy that best meets each patient’s individual needs.The International Pediatric MS Study Group (IPMSSG) has written a series of articles highlighting the advances, unanswered questions and challenges in diagnosing and treating MS in children.A publication from the MS International Federation (MSIF) summarizes." c-nmssatomrichtext_nmssatomrichtext-host="">
    Fingolimod (Gilenya®, Tascenso ODT®) is indicated for treating children and adolescents 10 years of age or older with relapsing-remitting MS. Other DMTs are frequently used off-label in this population.
    • A study looking at the use of teriflunomide (Aubagio ®) in treating POMS did not meet its primary endpoint of decreasing time to first confirmed clinical relapse; however, it did meet its secondary endpoint of significantly reducing disease activity on MRI scans compared to placebo.
    • Other oral therapies for MS, including dimethyl fumarate (Tecfidera®), continue to be studied in clinical trials for treating POMS.
    Prior to oral and high-efficacy therapies becoming available, many of the older disease-modifying therapies prescribed for adults with MS were also prescribed for children. These included interferon beta-1a (Avonex®, Betaseron®) and glatiramer acetate (Copaxone®).
    • Small retrospective studies, case studies and unblinded controlled trials have demonstrated the safety and efficacy of these self-injectable drugs (Banwell et al., 2006, Tenenbaum et al., 2013, Kornek et al., 2003).
    • Initial treatment of POMS with newer DMTs (oral and infusible medications) has shown better disease activity control compared to 1st generation injectables in clinical trials, showcasing the effectiveness of newer therapies.
    Regarding infusion therapies, an observational study of natalizumab (Tysabri®) showed that its safety and efficacy in children were similar to those seen in the adult MS population (Ghezzi et al., 2015). Additional infusion trials are currently underway.In addition to the adult FDA-approved therapies used in POMS, another treatment not FDA-approved for MS, rituximab (Rituxan®), has been studied in small trials of pediatric patients, demonstrating both safety and efficacy. Rituximab is widely used in other pediatric autoimmune disorders and has a safety profile similar to other B-cell depleting agents widely used in adults (e.g., ocrelizumab) (Dale et al., 2014).
    Treatment Strategies
    POMS is usually highly active, characterized by more frequent relapses, rapid lesion accrual early in the disease course and more cognitive and physical disability at an earlier age than in adult-onset MS (Hacohen et al., 2020). In a cohort study comparing initial treatment with newer DMTs versus older 1st-generation injectables in POMS patients or those with CIS, newer DMTs provided better disease control and safety profiles similar to those observed in adults. However, long-term safety data are still needed in children (Krysko et al., 2020). Due to the highly active nature of POMS and earlier age of conversion to secondary progressive MS, initial treatment with newer, higher-efficacy DMTs is being increasingly recommended (Hacohen et al., 2020).
    Starting or Switching Disease-Modifying Therapies
    Ultimately, starting or switching to a disease-modifying therapy in children and adolescents requires an in-depth discussion between the provider, patient and family. It should include:
    • Understanding the goals and expectations of the child and family
    • Sharing the safety, efficacy and monitoring profile of the various treatment options
    • Proactively discussing factors that could affect adherence (cost, route of administration, dosage, transportation)
    By understanding what is important to the child and family and addressing concerns, fears and potential challenges, providers, patients and families can participate in a shared decision-making process to determine the therapy that best meets each patient’s individual needs.The International Pediatric MS Study Group (IPMSSG) has written a series of articles highlighting the advances, unanswered questions and challenges in diagnosing and treating MS in children.A publication from the MS International Federation (MSIF) summarizes.

  • psychiatric comorbidities (especially anxiety and depression) are all important considerations. While a detailed neuropsychological evaluation by a trained professional can be helpful, POMS support groups can also provide additional crucial information, resources and networks for both patients and their families facing this complex and life-long disease. Other resources to consider as part of the care team include:
    • Pediatric or adolescent psychologists and psychiatrists
    • School guidance counselors, psychologists, teachers, mentors and administrators
    • Support groups with other patients and families facing this disease
    • Neuropsychologist to objectively characterize any neurocognitive deficits and track them over time
    " c-nmssatomrichtext_nmssatomrichtext-host="">
    In any patient diagnosed with POMS, poor academic performance, difficulty with peer relations, low self-esteem, difficulty with accepting the diagnosis, fatigue and psychiatric comorbidities (especially anxiety and depression) are all important considerations. While a detailed neuropsychological evaluation by a trained professional can be helpful, POMS support groups can also provide additional crucial information, resources and networks for both patients and their families facing this complex and life-long disease. Other resources to consider as part of the care team include:
    • Pediatric or adolescent psychologists and psychiatrists
    • School guidance counselors, psychologists, teachers, mentors and administrators
    • Support groups with other patients and families facing this disease
    • Neuropsychologist to objectively characterize any neurocognitive deficits and track them over time

    • Good sleep hygiene (≥ 8 hours of restorative sleep each night)
    • A healthy diet high in fruits, vegetables, whole grains, lean protein, polyunsaturated fats while minimizing processed foods, refined sugars and saturated fats from meat or dairy
    • Staying well hydrated (depends on body weight and daily activity level)
    • Daily aerobic exercise (≥ 30 minutes or more as tolerated)
    • Rehab services such as physical and occupational therapy
    • Stress reduction techniques and emotional wellness activities (e.g., yoga, meditation, mindfulness)
    • Avoiding tobacco exposure (active and passive), alcohol and drugs
    • Addressing and treating comorbid medical problems such as obesity, ADHD, headaches and psychiatric conditions by meeting regularly with a psychologist and/or psychiatrist
    • Routine health maintenance screening and vaccination (non-live vaccines if on certain DMTs) through a primary care provider
    • Vitamin D supplementation with a goal total vitamin D level of 40-60 ng/mL
    • Other vitamin supplementation as appropriate (e.g., iron or B12) (Petrin et al., 2018)

    • Considerations for Transitioning From a Pediatric to Adult Care Team

    Network of Pediatric MS Centers

    Resources for Patients, Families and Caregivers

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