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 (Modified from Wingerchuk et al, 2015; Krupp et al, 2013; Sadaka et al, 2012; Banwell et al, 2011) 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 (Alper G et al, 2009; Neuteboom RF et al, 2008; Banwell et al., 2007; Dale RC et al, 2007).
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
- 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.
- Similar to adults, roughly 30% of pediatric MS patients will have an inadequate response to their injectable DMT, and thus need to be switched to another treatment.
- Of patients who switch between standard injectable therapies due to inadequate response, over 40% will continue to have breakthrough disease and require treatment escalation to a second-line agent (Yeh et al., 2011).
- 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 (Waldman et al., 2011).
- 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.