Pediatric Multiple Sclerosis Workup

Updated: Jan 03, 2022
  • Author: Alice K Rutatangwa, DO, MSc; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA  more...
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Laboratory Studies

The CSF profile in childhood-onset multiple sclerosis (MS) may vary by age. Typically, WBC counts range from 0-50 cells/mm3, with a lymphocytic predominance. [38] However, it has been shown that children younger than 11 years have more neutrophils in the CSF than older children. [39]

While one study reports OCB in the CSF of up to 92% of children with MS, [40] another study found OCB to be less common in younger children (43% vs 63% in adolescents). [39] By contrast, in ADEM, 0%–29% of cases are found to have OCB. [38, 30, 41, 31] Within the French KIDMUS cohort, 94% (69 of 72) of children with positive OCB results went on to develop MS. [42]

The IgG index has been found to be elevated in 68% of adolescents (>11 years) with MS but in 35% of younger children (< 11 years). [39] These features tend to depend on age rather than disease duration. This distinct CSF IgG and cellular profile in younger children tends to vanish on repeat CSF analysis (mean 19 months after initial analysis), suggesting a transient immunological phenomenon associated with disease onset.


Imaging Studies

In a small study, patients with pediatric MS were reported to have fewer brain MRI T2-bright foci and more frequent large MS lesions than reported in adults with MS. [33] However, more recent data collected at disease onset have shown that children with MS may have a higher lesion burden on their initial brain MRI scan than adults, especially in the brainstem and cerebellum. [4]

Brain lesions in younger children (< 11 years) tend to be large with poorly defined borders and frequently confluent at disease onset. New diagnostic criteria for pediatric MS (a revised version of the adult McDonald criteria) have been proposed; they are very preliminary, based on a very small retrospective cohort not including patients with ADEM or NMO. [43] The authors compared 38 children with MS with 45 children with migraine or lupus who had brain MRI abnormalities. The presence of at least 2 of the following 3 criteria distinguished MS from migraine and lupus with better sensitivity (85%) and specificity (98%): (1) 5 or more T2-bright foci, (2) 2 or more periventricular T2-bright foci, and (3) one or more T2-bright areas in the brainstem.

A companion paper included a retrospective analysis of brain MRI scans performed within 1 month of symptom onset in 48 children with an initial demyelinating event (28 with a final diagnosis of MS and 20 with ADEM). [44] They reported that the children could be categorized as having MS versus ADEM with 81% sensitivity and 95% specificity based on 2 of the following 3 brain MRI criteria: (1) absence of a diffuse bilateral T2-bright lesion pattern, (2) the presence of T1 “black holes,” and (3) the presence of 2 or more T2-bright periventricular foci.

Periventricular white matter lesions are not specific to MS, as they are also seen in other pediatric CNS demyelinating diseases, such as NMO.

Periventricular increased T2 signal, as shown in t Periventricular increased T2 signal, as shown in this FLAIR image, can be seen in neuromyelitis optica given the dense concentration of aquaporin 4 water channels in this area.
Increased T2 signal at the cervicomedullary juncti Increased T2 signal at the cervicomedullary junction, as seen in a pediatric patient with MS.
An enhancing lesion in the right superior frontopa An enhancing lesion in the right superior frontoparietal region. Image 4 shows the same lesion on FLAIR imaging.
FLAIR image of lesion in the right superior fronto FLAIR image of lesion in the right superior frontoparietal region.
This sagittal T2 image of the cervical spine shows This sagittal T2 image of the cervical spine shows small hyperintense lesions typical of MS at C2 C3.
This axial FLAIR image shows bilateral, left predo This axial FLAIR image shows bilateral, left predominant confluent signal change. There is also an area of gray matter involvement in the right frontal region. This image would not be sufficient to distinguish an episode of ADEM from pediatric MS in a pre-pubertal child.

Proposed Approach to Evaluation of White Matter Changes in a Child

Tier 1 consists of the following:

  • CSF: OCB, IgG index, cell count, protein, glucose, HSV, lyme

  • Serum: Complete blood cell (CBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein, NMO antibodies (in cases of optic neuritis and/or longitudinally extensive transverse myelitis), antinuclear panel (including SSA, SSB), thyroid-stimulating hormone, vitamin B12

  • Imaging: Brain and cervical spine MRI with/without gadolinium

  • Other: Ophthalmology (if optic neuritis)

Tier 2 consists of the following:

  • CSF: EBV, cytology, bacterial, fungal, viral cultures

  • Serum: Angiotensin-converting enzyme, HIV, rapid plasma reagin/fluorescent treponemal antibody absorption

  • Imaging: Repeat brain MRI, entire spinal cord with/without gadolinium; chest radiography (sarcoid)

Tier 3 consists of the following:

  • CSF: Human T-lymphotropic virus 1, measles antibodies (subacute sclerosing panencephalitis), lactate, pyruvate

  • Serum: Serum amino acids, mitochondrial panel, WBC enzymes, very long chain fatty acids, acylcarnitine profile, lysosomal enzymes

  • Imaging: Magnetic resonance spectroscopy, magnetic resonance angiography


Low-Contrast Letter Acuity Charts

Low-contrast letter acuity charts (LCLA, Sloan charts) have been shown to provide a sensitive and reliable assessment of visual acuity in the patients with pediatric MS. [45]


Visual Evoked Potentials

Prolonged visual evoked potentials may indicate prior asymptomatic demyelination of optic nerves. Caution must be exercised in young children, as the results are highly dependent on attention.


Optical Coherence Tomography

Optical coherence tomography (OCT) uses near-infrared light to quantify the thickness of the retinal nerve fiber layer (RNFL) (which contains only nonmyelinated axons). It has been shown to provide a sensitive evaluation of the RNFL thickness in this population, a correlate of optic atrophy. [45]