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Pediatric MS

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Overview

Approximately 3-5% of all individuals with MS experience disease onset before age 16 (Chitnis et al., 2009; Boiko et al., 2002; Duquette et al., 1987). Two recent consensus reports – one by neurologists in the United States and one by the International Pediatric MS Study Group (IPMSSG) – provide helpful insights into the management of MS in the pediatric population.

Disease course in pediatric multiple sclerosis

  • Pediatric-onset MS is similar to adult-onset relapsing-remitting MS.
  • Children experience 2-3 times more frequent relapses than adults with early MS (Gorman et al., 2009).
  • Approximately one-third of children show evidence of significant cognitive impairment early on (Amato et al., 2008), with significant progression within two years (Amato et al., 2010).
  • Progression of motor disability (as measured by EDSS in children takes longer than in adults (Harding et al, 2012; Simone et al., 2002).
  • Pediatric-onset MS patients reach disability milestones at a younger age than their adult-onset counterparts (Harding et al, 2012).
  • Pediatric MS patients have a higher T2 lesion burden than adult MS patients, supporting the conclusion that MS in children is more inflammatory (Waubant et al., 2009).

Diagnosis of pediatric MS

As is true in adults, children with two discrete demyelinating events separated in time and space meet criteria for a diagnosis of MS. The challenge lies in ruling out other disorders that could be mistaken for MS, and distinguishing between MS and various transient demyelinating syndromes that can occur in children. The Pediatric International Study Group (Krupp et al., 2007) proposed consensus definitions for monophasic acute disseminated encephalomyelitis (ADEM – an essential feature of which is the presence of encephalopathy), variants of ADEM associated with a repeat episode, neuromyelitis optica (NMO), clinically isolated syndrome (CIS), and pediatric MS, and updated those definitions in 2013. The International Study Group has also proposed a minimum diagnostic battery for use in pediatric patients with an initial inflammatory demyelinating event.

This chart (Banwell et al., 2007) demonstrates the decision path for diagnosing a child who has experienced an acute CNS demyelinating event and then experiences a second episode of neurologic dysfunction. Note that a subset of patients with ADEM (which typically follows a self-limited disease course) experience relapses of disease activity. Some of these patients are reclassified as MS based on the nature of the clinical events, laboratory findings, and subsequent MRI changes. While the risk of developing MS following an episode of ADEM in childhood is <10%, the risk following an episode of CIS has been shown to be 26% to 62% in several recent studies using the International Study Group criteria (Dale RC et al, 2007; Neuteboom RF et al, 2008; Alper G et al, 2009; Banwell et al., 2007). 

Diagnosing acquired inflammatory CNS demyelination in children

Classification of acquired inflammatory CNS demyelination in children (.pdf), including the first attack of demyelination and further demyelinating attacks

Prognostic factors after a first attack of inflammatory CNS demyelination in children by Branwell et al (2007)

Treatment recommendations for pediatric MS

The following conclusions emerge from the American and International consensus efforts:
  • The beta interferons and glatiramer acetate are accepted as standard of care in pediatric MS patients.
  • Clinical experience suggests that the short-term safety profile of these first-line medications in children is similar to that seen in adults (Chitnis et al., 2012).
  • The International study group proposed the following working definition for an inadequate treatment response to first-line therapies:
    • Minimum time on full-dose therapy of 6 months + fully compliant on treatment + one of the following:
      • Increase or no reduction in relapse rate, or new T2 or contrast enhancing lesions on MRI from pre-treatment period
      • > 2 relapses (clinical or MRI relapses) within a 12-month period
    • Defining an inadequate treatment response should be individualized for each patient, taking into account a variety of factors, including symptoms, relapse recovery, disease progression, and rapid cognitive decline.
  • Despite significant variation in the definition of treatment failure within the group, the American consensus group indicated that they would stop or change a disease-modifying therapy if there was an increase in relapse rate or side effects that interfered with functioning.
  • Additional therapy options for sub-optimal responders may include:
  • Emerging therapies need to be studied in the pediatric MS population.
  • In addition to managing the disease course, careful attention must be paid to the psychosocial consequences of pediatric MS, including those affecting the child’s self-esteem, ability to function at home, at school, and with peers, and the impact on the family.

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