2. INTRODUCTION
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central
nervous system, including the brain, spinal cord and optic nerves.
The term “ pediatric MS ” is applied to children with MS (< 10 years of age) and
adolescents ( < 18 years of age).
Pediatric multiple sclerosis (MS) is similar to adult MS in the kinds of symptoms that
occur.
MS is a challenging diagnosis in children, especially in prepubescent children
because of the atypical clinical, biological, and MRI presentations and the broader
spectrum of potential differential diagnoses specific to that age range.
3. EPIDEMIOLOGY
2.2% to 5% of all MS cases.
Within the pediatric age group, the incidence is highest in those between 13 and
16 years of age.
A small, but important, subgroup is younger than 10 years of age.
For subjects < 6 years of age, female to male ratio is 0.8:1
Children aged between 6 to 10 years have a ratio of 1.6:1
In patients >10 years of age, female to male ratio is 2.1:1
In adolescents: Females predominate 3:1
MS is more common in Caucasians, but can occur in other populations.
4. RISK FACTORS
There may be a link with reduced vitamin D levels and decreased sun exposure.
Children exposed to passive smoking.
Exposure to Epstein-Barr virus
Having a mother or father with MS increases the risk of having MS to about 3% to 5 % and having an
identical twin with MS increases the risk to about 30%.
emotional stress may increase the symptoms of MS
attacks of MS are more likely after infections.
HLA-DRB1 gene plays a role in MS
5. CLASSIFICATION OF MS
Relapsing-remitting: Patients have attacks of symptoms/signs, with or without recovery, but between attacks
have no interval worsening.
Secondary progressive: This is often after a few years of relapsing-remitting MS. The pattern changes from a
relapsing pattern to progressive in between attacks, usually with fewer attacks
Primary progressive: Gradual onset from the beginning, no attacks. This seems to occur in the older adult age
group.
Progressive relapsing: This is a rare form, and begins with a progressive course, while later developing attacks.
Fulminant: Very severe, rapidly progressive MS. This is a rare form of MS.
6. SIGNS AND SYMPTOMS
Children are polysymptomatic (50%-70%) as well as monosymptomatic
(30%-70%).
They present with a wide variety of symptoms including sensory deficits,
ON, brainstem-related deficits, motor deficits, and gait disorders.
Seizures are estimated to occur in 5%.
ON may be underreported in pediatric MS, especially in younger children
who may have difficulties in verbalizing this symptom or who have not yet
started to read.
7. SIGNS AND SYMPTOMS
Fatigue that limits recreational and scholastic activities is a common symptom of
pediatric MS.
Children also appear to be exceptionally vulnerable to cognitive disability.
The most common impairments are complex attention, visuomotor integration,
confrontation naming, receptive language, and executive function while verbal
fluency tends to be relatively intact.
Patients may also have a symptom called Lhermitte's phenomenon, in which they
feel electrical tingling or shocks down their back, arms or legs when they bend their
neck forwards.
9. CLINICALLY ISOLATED SYNDROME
(CIS)
Clinically isolated syndrome (CIS) is one of the MS disease courses.
CIS refers to a first episode of neurologic symptoms that lasts at least 24 hours and is
caused by inflammation or demyelination.
CIS can be either monofocal or multifocal.
The significance of CIS is to determine the risk and progression of MS. If CIS is
accompanied with MRI findings of lesion then the risk is of 80%.
With CIS, an MRI may demonstrate damage only in the area responsible for the
current symptoms; with MS, there may be multiple lesions on MRI in different areas of
the brain.
10. DIFFERENTIAL DIAGNOSIS
1. Acute Disseminated Encephalomyelitis (ADEM) is a brief but intense attack of
inflammation in the brain and spinal cord and occasionally the optic nerves that damages
the brain’s myelin.
The cause of ADEM is not clear but in more than half of the cases, symptoms appear following a viral
or bacterial infection.
Typical symptoms of ADEM such as fever, headache and confusion, vomiting, and seizures can be
seen in pediatric MS onset especially in patients younger than 11 years.
ADEM occurs more frequently in winter and spring; MS has no seasonal variation.
ADEM occurs more frequently in males; MS more frequently in females.
11. DIFFERENTIAL DIAGNOSIS
2. Neuromyelitis optica (NMO), the criteria for its diagnosis require optic neuritis and transverse
myelitis.
3. Encephalitic or meningo-encephalitic infectious, CNS Lyme disease may manifest with multifocal
white matter lesions and a relapsing/remitting clinical course.
4. Vascular and autoimmune disorders - CNS angiitis, SLE, Behçet disease, neurosarcoidosis, and
Sjogren's disease.
5. Cranial neoplasms, particularly CNS lymphoma, may mimic a tumefactive presentation of MS on
neuroimaging and complicate the diagnosis.
6. Leukodystrophies - key features are bilateral and symmetric involvement on MRI that appears fairly
homogenous.
12. 2017 McDonald Criteria
Clinical Presentation Additional data for MS Diagnosis
≥2 clinical attacks and objective clinical
evidence of ≥2 lesions
None
≥2 clinical attacks and objective clinical
evidence of 1 lesion
DIS: an additional clinical attack
implicating a different CNS site or by MRI
1 clinical attack and objective clinical
evidence of ≥ 2 lesions
DIT: an additional clinical attack or by MRI
Or CSF-specific oligoclonal bands
1 clinical attacks and objective clinical
evidence of 1 lesion
DIS: an additional clinical attack
implicating a different CNS site or by MRI
DIT: an additional clinical attack or by MRI
Or CSF-specific oligoclonal bands
13. DIAGNOSIS
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.
Oligoclonal bands (OCB) in the CSF are an indication of MS in children.
Positive OCB may be found in 29% of patients with ADEM.
The IgG index has been found to be elevated in adolescents.
Serum: Complete blood cell count, erythrocyte sedimentation rate (ESR), C-
reactive protein, NMO antibodies, antinuclear panel, thyroid-stimulating
hormone, vitamin B12
14. MRI
T2-weighted and Gadolinium enhanced T1-weighted brain MRI correlate with
active inflammation and demyelination.
The presence of at least two of the following:
five or more lesions
two or more periventricular lesions.
one brainstem lesion
This criteria can distinguish MS from other nondemyelinating disease with
85% sensitivity and 98% specificity.
Brain lesions in younger children (< 11 years) tend to be large with poorly
defined borders and frequently confluent at disease onset.
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19. DIAGNOSIS
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.
Retinal optical coherence tomography (OCT) allows high-resolution
viewing of unmyelinated axons and other retinal structures. It is used as a
method to quantifying neuroaxonal loss in MS.
20. 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.
21. TREATMENT
In general, one of four treatments is used as a first-choice medication for
MS:
1. IFN-beta 1a intramuscular (IM) injection at a dose of 30 micrograms (μg) once
weekly is usually well tolerated in children with MS.
2. Interferon beta 1a subcutaneous (SC) injection of 44 μg three times a week
with a minimum of 48 hours between each dose at a lower dose of 22 μg three
times a week.
3. Glatiramer acetate (GA) at a standard doses of 20 mg daily.
4. Interferon-beta-1b every other day subcutaneous dosing.
22. TREATMENT
Mitoxantrone and natalizumab are powerful medications which are usually
reserved for patients with more severe MS or MS that does not respond to
standard front line agents.
Plasmapheresis is helpful for patients with a severe attack of MS not
responding to standard steroid therapy.
MANAGEMENT OF RELAPSE
The usual treatment for an acute relapse is corticosteroids with doses of
parenteral methylprednisolone ranging from 10 to 30 mg/kg. In most instances,
the maximum dose is 1000 mg administered intravenously (IV) once daily in the
morning for 3–5 days.
23. REFERENCE
Duquette P, Murray TJ, Pleines J, Ebers GC, Sadovnick D, Weldon P, et al. Multiple sclerosis in
childhood: Clinical profile in 125 patients. J Pediatr. 1987;111:359–63. [PubMed]
Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D. Early onset multiple sclerosis: A
longitudinal study. Neurology. 2002;59:1006–10. [PubMed]
Ghezzi A, Deplano V, Faroni J, Grasso MG, Liguori M, Marrosu G, et al. Multiple sclerosis in
childhood: Clinical features of 149 cases. Mult Scler. 1997;3:43–6.
Sindern E, Haas J, Stark E, Wurster U. Early onset MS under the age of 16: Clinical and paraclinical
features. Acta Neurol Scand. 1992;86:280–4.
Ruggieri M, Polizzi A, Pavone L, Grimaldi LM. Multiple sclerosis in children under 6 years of
age. Neurology. 1999;53:478–84.
