PEDIATRIC MULTIPLE SCLEROSIS

Lauren B. Krupp, MD

Professor of Neurology

Director of the National Pediatric MS Center

Stony Brook University Medical Center

 Multiple sclerosis (MS) is an immune mediated inflammatory demyelinating disorder of   the central nervous system (CNS). Children and adolescents can develop MS although less commonly than adults.  An estimated 2-3 % of patients with MS are under age 18.  [1, 2] .

DEFINITION

To facilitate clinical research and establish uniform criteria for the diagnosis, an operational and consensus based definition for pediatric MS was developed. [3]. The criteria for the diagnosis require:

1) Multiple episodes of CNS demyelination disseminated in time and space with no lower age limit

2) MRI findings can be applied to meet dissemination in space criteria if they show three of the following four features – 1) nine or more white matter lesions or one gadolinium enhancing lesion, 2) three or more periventricular lesions 3) one juxtacortical lesion, 4) an infratentorial or spinal cord lesion

3) The combination of an abnormal cerebral spinal fluid (CSF) and two lesions on the MRI, of which one must be in the brain, can also be used to meet dissemination in space criteria; the CSF must show either oligoclonal bands (OCB) or an elevated IgG index

4) MRI can be used to satisfy criteria for dissemination in time following the initial clinical event, even in the absence of a new clinical demyelinating event. A new gadolinium enhancing lesion or new T2 lesion 3 months after the clinical event can be a surrogate for another clinical event.

This definition is distinguished from self-limited demyelinating disorders such as acute disseminated encephalomyelitis (ADEM) which in contrast to pediatric MS is associated with encephalopathy and typically shows large ( 1 – 2 cm or more) lesions of the white matter as well as the deep grey matter within the brain.

DEMOGRAPHIC FEATURES OF PEDIATRIC MS

The disease usually begins with a mean age of onset between 8- 14 years of age, depending on whether the cohort has a cut off below 16 or 18.  [1, 2, 4]

The distribution of boys and girls varies according to age. For children equal to or above age 10, girls outnumber boys by approximately 2.5:1.  [1, 2, 5, 6]  For children below age 10 the ratio of girls and boys is approximately 0.5:1. [7, 8]  . These demographic features suggest sex hormones play a role in MS pathogenesis which is also suggested from data in adult MS. [9]

CLINICAL FINDINGS

Symptoms and Signs

Presenting symptoms of MS often depend on the location of the white matter lesions. Initial symptoms can include optic neuritis (unilateral or bilateral), motor weakness, balance problems, sensory disturbance, loss of coordination, bladder dysfunction, or problems related to brainstem involvement (facial numbness, diplopia). [10] A polysymptomatic onset occurs in 8-67% of the patients. [1, 2, 5, 10]

At presentation, children tend to have more brainstem and cerebellar symptoms, encephalopathy, or optic neuritis than do adults. [11, 12] Among those under six, seizures, marked alteration in consciousness, a polysymptomatic onset, and atypical MRIs  are more frequent.  [7, 11]

MRI findings

Lesions predominantly involve the white matter. In contrast, cortical or central gray involvement is uncommon. [4] In figure 1, an MRI from a typical patient with MS is shown. The lesions tend to be discrete, often associated with gadolinium enhancement, and are usually periventricular in location. [5] However, some children lack typical MRI findings of MS and have either large tumefactive lesions associated with edema or deep grey matter involvement. [13]

Figure 1: 15 year old with MS and typical white matter lesions

Disease course

In over 93% - 98% of cases [10] the disease course at onset is characterized by relapses and remissions. A progressive course without relapses in pediatric MS usually suggests an alternative diagnosis. 

Adults usually transition to secondary progressive MS, 7-10 years after diagnosis, In contrast children transition more slowly, approximately 20 years following the diagnosis. [6, 11, 12]

PROGNOSTIC FACTORS

Features at the time of a child’s first demyelinating event, increase the likelihood of a subsequent event include the presentation of  optic neuritis or if the child is older than 10 years. [14]  A decreased risk for a second event is noted in children presenting with spinal cord symptoms or alteration in mental status. [14]

Negative prognostic factors regarding disease course