There has been an increasing awareness of the occurrence of multiple sclerosis (MS) in children and adolescents since approximately 2004. Whether this is due to a true increase in incidence or improved diagnostic criteria and dedicated pediatric MS centers is still unclear. However, it is clear that children can get MS and that this form of disease requires specialized treatment and management.
Pediatric MS is defined as MS with an onset younger than age 18 years. There are some variances in the literature, using a cutoff of age 16 years; however, for practical purposes, most studies including treatment trials use age 18 years as the cutoff.1
There have been reports of children as young as 2.5 to 3 years old at the time of the first attack of MS; however, the vast majority of patients are 11 years or older, with a mean age at onset of 15 years in the US Network of Pediatric MS Centers at the first symptom. Puberty seems to be an important transition time for the onset of pediatric MS,2 with 80% to 85% of children being peripubertal or postpubertal at the time of the first symptoms in a large US cohort.3 Approximately 3% to 5% of all MS patients are pediatric at the time of first symptoms.4
Reports from many centers around the world indicate that the pediatric MS occurs in many regions. Higher prevalence rates are generally reported from regions more distal to the equator. The estimated incidence is approximately 0.51 per 100,000 insured persons less than age 18 years5 in a California study, and 2009 to 2011 incidence was estimated at 0.64 per 100,000 in an incidence study from Germany.3,6 A recent report from Canada found the age-standardized annual incidence of MS in the pediatric population ranged from 0.99 to 1.24 per 100,000 population, and the age-standardized prevalence ranged from 4.03 to 6.8 per 100,000 population.7
The diagnosis of pediatric MS rests on clinical and magnetic resonance imaging (MRI) features, and the updated diagnostic criteria published in 2013 from the International Pediatric MS Study Group8 have been the general standard for diagnosis. However, these criteria are updated every 4 to 5 years as more information regarding MRI features and differential diagnosis becomes available. The diagnostic criteria for pediatric MS are listed in Table 20.1.
Typical MRIs from a pediatric patient with MS are shown in Figure 20.1.
Differential Diagnosis
The differential diagnosis of pediatric MS is similar to that of adult MS, with the following caveats. Acute disseminated encephalomyelitis (ADEM) occurs mainly in children9 and is an important differential diagnosis of pediatric MS. Rarely, ADEM events are the first event of pediatric MS, and for this reason, children with ADEM should be followed longitudinally by a neurologist. Some differentiating features of ADEM and pediatric MS are listed in Table 20.2.
Other similarly appearing white matter disorders include neuromyelitis optica-spectrum disorder6,10 and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disorders.11,12,13 Testing for Aquaporin-4 antibody and MOG antibodies should be sent in any child with an acute demyelinating syndrome (ADS), and if negative, consider repeating within a year or again for highly suspicious cases.
The differential diagnosis of pediatric MS is broad and includes infectious, metabolic, and other autoimmune disorders (Table 20.3). Red flags for a diagnosis other than pediatric MS include a progressive disease course from onset, prominent seizures, rapid cognitive decline and headaches, multisystemic involvement, onset before age 2 years, and family history of severe neurological deficits.
TABLE 20.1 SUMMARY OF PROPOSED DEFINITIONS OF PEDIATRIC ACQUIRED DEMYELINATING SYNDROMES (IPMSSG CRITERIA): DIAGNOSIS OF PEDIATRIC MS MUST MEET CRITERIA FOR BOTH DISSEMINATION IN TIME AND DISSEMINATION IN SPACE
Dissemination in Time (DIT)
Dissemination in Space (DIS)
One of the following DIT criteria must be met:
Two or more nonencephalopathic (e.g., non-acute disseminated encephalomyelitis [ADEM]) clinical CNS events with presumed inflammatory cause separated by more than 30 d involving more than one area of the CNS
One nonencephalopathic episode typical of MS that is associated with MRI findings consistent with 2010 Revised McDonald criteria for DIS and in which a follow-up MRI shows at least one new enhancing or nonenhancing lesion consistent with DIT MS criteria (irrespective of its timing with reference to a baseline scan)
One ADEM attack followed by a nonencephalopathic clinical event, 3 or more months after symptom onset, that is associated with new MRI lesions that fulfill 2010 Revised McDonald DIS criteria (at least one T2 lesion in two of the following areas: periventricular. juxtacortical, infratentorial, and spinal cord)
A first, single acute event that does not meet ADEM criteria and whose MRI findings are consistent with the 2010 Revised McDonald criteria for DIS and DIT (simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any time). These criteria apply only to children <12 y old
2010 Revised McDonald criteria for DIS; at least one T2 lesion in two of the following areas:
Monofocal or polyfocal neurological symptoms (such as optic neuritis, transverse myelitis, brainstem syndromes) without encephalopathy
Disease course
Symptoms can fluctuate/appear within a 3-mo period. Then generally remits and remains monophasic
Polyphasic—new attacks or new MRI lesions occurring with separation in time by at least 1 mo
CSF features
WBC 50-70 (60%-70% lymphocytes); no oligoclonal bands
WBC 15-30 (90%-95% lymphocytes); positive oligoclonal bands in 70%-85%
MRI features
Fluffy, diffuse lesions in the subcortical white matter or thalamus/basal ganglia. Lesions can occur in other areas including optic nerve, brainstem, spinal cord
Periventricular lesions ovoid discrete lesions. Involvement of the corpus callosum. Lesions can occur in other areas including optic nerve, brainstem, spinal cord
ADEM, acute disseminated encephalomyelitis; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; MS, multiple sclerosis; WBC, white blood cell.
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