Presenting symptoms of MS often depend on the location of the white-matter lesions. Initial symptoms typically 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). In different clinical series, motor, visual, or sensory disturbances are the most common presentation (5). A polysymptomatic onset has been described in 8% to 67% of the patients (1,2,5,7).

At presentation, children compared with adults tend to have more brainstem and cerebellar symptoms, encephalopathy, or optic neuritis (12,13). Among those younger than 6 years, seizures, marked alteration in consciousness, a polysymptomatic onset, and atypical MRIs are more frequent (9,12).

The MRI is extremely valuable in the diagnosis of MS. In contrast to other demyelinating disorders of childhood, MS lesions predominantly involve the white matter (Fig. 15.1). Cortical or central gray matter involvement is uncommon (6). The lesions tend to be discrete, often associated with gadolinium enhancement, and are usually periventricular (7). Although it is less true of the youngest pediatric MS group, many older children have MRI
findings that are similar to those of adults. In adults, criteria for a “positive MRI” include three of the four requirements: (a) one gadolinium-enhancing lesion or nine lesions involving the white matter, (b) three or more periventricular lesions, (c) an infratentorial, and (d) a juxtacortical lesion. A lesion involving the spinal cord can be used as either one of the nine lesions or instead be of an infratentorial location. If a child or teenager with possible MS meets the MRI criteria established for adults with MS, then the MRI findings are highly supportive of the MS diagnosis. Moreover, these children tend to have a worse prognosis than do those whose MRIs are less specific.

Some children with MS who lack typical MRI findings can have large tumefactive lesions associated with edema, rarely a mass effect, or deep grey-matter involvement (14). In these cases, the diagnosis can be more challenging.

The course in more than 93% to 98% of pediatric MS cases (5) is characterized by relapses and remissions. Relapses are defined as the development of new neurological symptoms and signs lasting at least 24 hours that subsequently improve or stabilize. A progressive course without relapses is rare and usually suggests an alternative diagnosis. Over time (sometimes decades), most children with MS accumulate neurological impairments. However, this progression occurs more gradually in children than in adults with the disease (12,13). Less commonly, pediatric MS can have an aggressive course, and severe deficits during childhood can develop (15).

The classification of MS subtypes refers to the different patterns of the disease course. Although this classification was developed for adult MS cases, it also applies to pediatric ones. The relapsing-remitting MS (RRMS) subtype is the most common type. Residual deficits may or may not develop from the relapse. Over time, most adults and children with MS will have a transition from a relapsing-remitting course to progression, defined as secondary progressive MS. During the progressive phase of the disease, patients simply insidiously and gradually accumulate increasing deficits. A much less common MS subtype—estimated in most series of children to occur in fewer than 3%—is primary progressive MS. In this subtype, no relapses occur at the onset, but instead, patients follow
a steadily progressive course from the beginning. In primary progressive MS, symptoms and signs accumulate over time, and relapses never occur. Another even more rare MS subtype is progressive relapsing MS. In these patients, the initial course is one of gradual progression; however, these individuals subsequently have occasional relapses, and such individuals are classified as having progressive relapsing MS.

Patients with relapsing-remitting disease will make a transition to a secondary progressive course at different rates. Among adults, the transition typically occurs 7 to 10 years after diagnosis. In contrast, children progress more gradually, and a secondary progressive form of the disease develops approximately 20 years after the diagnosis. During the same time period, in more than half of children with MS, permanent deficits will develop (8,12,13). Hence, the majority of children and adolescents will grapple with the more disabling aspects of their disease during young adulthood. However, compared with an adult onset, those with a pediatric onset will have permanent deficits, including inability to ambulate independently, at a significantly younger age (2,8,12,13).

Many aspects of pediatric MS pose challenges to families beyond those associated with chronic illness. The condition is rare, its course is uncertain, its manifestations are unpredictable and varied, and therapies are incomplete. Behavioral problems include denial,
difficulty with family and peers, and noncompliance with therapy (20). A further concern is that perceived stress can increase the probability of another MS relapse (21).

Young people with MS or other chronic diseases may be at a particularly high risk for additional psychological problems (22) because of the effects of the disease on the brain, as well as the psychological reaction to the chronic illness. In adults with MS, depression is associated with an increased lesion burden in the inferior-medial frontal-temporal areas (23). Similar findings might be expected to apply to children with MS.

In our experience of 13 children with MS, unselected for psychiatric illness and who underwent psychiatric interviews, six (46%) had affective disorders including major depression, anxiety disorder, and panic attacks. Much more information on psychiatric complications of MS comes from studies of adults. All show that affective disorders are frequent (24) and are more common compared with other neurological diseases with similar levels of disability.

More than 25% of adults with MS from community samples have depression (25). The lifetime prevalence of major depression in clinical samples is even higher—approximately 40% to 50% (26,27). Although more studies have addressed the depression associated with MS, anxiety disorders are another frequent and disabling problem. In various samples, 34% have anxiety, and 25% need treatment for it (24).