Multiple Sclerosis in Children

Multiple Sclerosis in ChildrenEvaluating children in the ED is challenging. They often have a difficult time describing specific symptoms. Moreover, the symptom description is commonly “interpreted” by a third party (that wild and crazy party otherwise known as their parents/guardians). This can make determining reasonable evaluations difficult. Is that episode of Syncope more concerning or was it a Breath Holding Spell?  Should we be worried about Myocarditis for this complaint of Chest Pain? Some of these issues become easier for us to evaluate, as we encounter them commonly; however, the complaint of Vertigo, Ataxia, weakness, numbness, or visual changes can easily leave us scratching out heads. One item can come to mind when dealing with adults who present with “odd” neurologic complaints is multiple sclerosis. Does this occur in children? You bet it does. Let us take a minute to review – Multiple Sclerosis in Children:

 

Multiple Sclerosis in Children: Basics

  • Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease
    • It affects the Central Nervous System
    • Symptoms may progress, relapse, and remit.
  • Risk Factors:
    • Sex hormones:
      • Prior to puberty, the female:male ratio is about equal.
      • After puberty, MS is more common in females [Alroughani, 2018; Yeshokumar, 2017; Waldman, 2016]
    • Viral infections: [Yeshokumar, 2017]
      • Epstein-Barr virus
      • Cytomegalovirus
    • Smoke: [Yeshokumar, 2017]
      • Smokers have increased risk for developing MS.
      • Passive smoke exposure also appears to be associated with risk.
    • Genetics:
      • HLA-DRB1*15 allele confers increased risk
  • The prevalence and incidence of Pediatric Multiple Sclerosis is not fully known. [Alroughani, 2018; Waldman, 2016]
    • Thought to be underestimated overall.
    • Many different diagnostic criteria have been proposed. [Alroughani, 2018]
      • Requires at least 2 episodes attributed to inflammatory process that occur >30 days apart and involving >1 CNS area.
      • MRI findings are important to help make the diagnosis (there can be occult lesions)
      • McDonald Criteria can help make diagnosis using MRI findings upon 1st presentation. [Sadaka, 2012]
  • Children can present with a wide variety of symptoms / conditions [Alroughani, 2018; Waldman, 2016]:
    • Sensory Symptoms
      • ex, paresthesias
    • Brainsteam – Cerebellar Symptoms
      • ex, ataxia, transverse myelitis
    • Motor Symptoms
      • ex, weakness, diplopia, urinary symptoms
      • A common complaint is “Fatigue.”
    • Optic Neuritis
      • Inflammation in the optic nerve.
      • Common presenting condition of MS, but can be associated with other conditions or be isolated. [Lehman, 2018]
      • Leads to:
        • Decreased Visual Acuity
        • Visual Field Cuts
        • Decreased Color Vision
        • Afferent Pupillary Defect (if unilateral involvement)
      • It is difficult to diagnosis in children, so objective testing is performed. [Lehman, 2018]
        • Ocular Coherence Tomography (OCT) is useful for ophthalmologist to use to make diagnosis.
        • Noninvasive way to image and measure the retinal layers.
        • Optic Neuritis has characteristic patterns seen on OCT.

 

Multiple Sclerosis in Children: Not Adults

  • Pediatric MS is typically defined as occurring before age 16 yrs
    • This varies slightly between authors and may be inclusive of 18 yrs. [Alroughani, 2018]
    • 3 – 10% of patients with MS will present under age 16 years. [Alroughani, 2018]
  • Compared to adults, MS in Children is: [Alroughani, 2018; Waldman, 2016]
    • More likely to have a more aggressive disease onset with disability.
    • More likely to have a polyfocal onset.
    • More likely to have resolution of symptoms after initial presentation.
    • More likely to have a relapsing-remitting course.
    • More likely to be associated with more frequent relapses.
    • More likely to have more pronounced acute axonal damage.
    • More likely to have slower disease progression over time.
  • Children < 12 years of age differ clinically from older adolescents with MS. [Alroughani, 2018; Waldman, 2016]
    • More likely to present with atypical symptoms
    • More likely to have ADEM-like first attack
    • Have large, ill-defined lesions early in the disease course
    • Less likely to have CSF oligoclonal IgG bands.
  • Overtime, MS has been shown to be associated with significant cognitive impairment in children also. [Alroughani, 2018]

 

Multiple Sclerosis in Children: Ddx

  • MS may not be clearly diagnosed until after several episodes have occurred.
  • Numerous other conditions can share similar constellation of symptoms and initial presentation. [Alroughani, 2018; Yeshokumar, 2017]
    • Systemic Lupus Erythematosus
    • Sjorgen Syndrome
    • Leukodystrophies
    • Neurosarcoidosis
    • ADEM (Acute Disseminated Encephalomyelitis)
      • MS can present similarly to ADEM on initial presentation.
      • Can have seizures and altered mental status and headache.
    • Encephalitis:
      • MS can present with fever in pediatric patients.
      • Consider including oligoclonal IgG bands in CSF of patients with encephalitis

 

Multiple Sclerosis in Children: Tx

  • The FDA has not listed any pediatric specific therapies, but several adult strategies have been used safely and with good success. [Alroughani, 2018]
  • Generally, it is considered best to start therapy early, so early diagnosis is helpful.
  • First Line Therapies: [Alroughani, 2018; Yeshokumar, 2017]
    • Interferon Beta
    • Glatiramer Acetate
  • Second Line Therapies: [Alroughani, 2018; Yeshokumar, 2017]
    • Natalizumab
    • Rituximab
    • Other novel immuno-modulators
  • Ancillary Therapies: [Yeshokumar, 2017]
    • IV corticosteroids may be given to help speed symptom recovery.
    • IV immunoglobulin and plasma exchange has also been used.

 

Moral of the Morsel

  • Don’t forget the kids! Multiple Sclerosis does affect children!
  • Don’t forget the eyes! Optic neuritis may be the first sign of MS. Discuss with Ophthalmology to ensure appropriate follow-up and imaging.
  • If it doesn’t make “sense,” consider MS! While you may not make the diagnosis of MS often, early diagnosis is helpful to the patient and we should, therefore, remain vigilant for it.

 

References

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Lehman SS1, Lavrich JB2. Pediatric optic neuritis. Curr Opin Ophthalmol. 2018 Sep;29(5):419-422. PMID: 30096089. [PubMed] [Read by QxMD]

Öztürk Z1, Yılmaz Ü2, Konuşkan B3, Gücüyener K1, Demir E1, Anlar B3; Turkish Pediatric Multiple Sclerosis Study Group. Multiple Sclerosis with Onset Younger Than 10 Years in Turkey. Neuropediatrics. 2018 Feb;49(1):51-58. PMID: 29183093. [PubMed] [Read by QxMD]

Yeshokumar AK1, Narula S, Banwell B. Pediatric multiple sclerosis. Curr Opin Neurol. 2017 Jun;30(3):216-221. PMID: 28323645. [PubMed] [Read by QxMD]

Gianfrancesco MA1, Stridh P2, Shao X1, Rhead B3, Graves JS4, Chitnis T5, Waldman A6, Lotze T7, Schreiner T8, Belman A9, Greenberg B10, Weinstock-Guttman B11, Aaen G12, Tillema JM13, Hart J14, Caillier S14, Ness J15, Harris Y15, Rubin J16, Candee M17, Krupp L9, Gorman M18, Benson L18, Rodriguez M13, Mar S19, Kahn I20, Rose J21, Roalstad S22, Casper TC22, Shen L23, Quach H1, Quach D1, Hillert J24, Hedstrom A24, Olsson T2, Kockum I2, Alfredsson L25, Schaefer C26, Barcellos LF27, Waubant E4; Network of Pediatric Multiple Sclerosis Centers. Genetic risk factors for pediatric-onset multiple sclerosis. Mult Scler. 2017 Oct 1:1352458517733551. PMID: 28980494. [PubMed] [Read by QxMD]

Yılmaz Ü1, Anlar B2, Gücüyener K3; Turkish Pediatric Multiple Sclerosis Study Group. Characteristics of pediatric multiple sclerosis: The Turkish pediatric multiple sclerosis database. Eur J Paediatr Neurol. 2017 Nov;21(6):864-872. PMID: 28694135. [PubMed] [Read by QxMD]

Waldman A1, Ness J2, Pohl D2, Simone IL2, Anlar B2, Amato MP2, Ghezzi A2. Pediatric multiple sclerosis: Clinical features and outcome. Neurology. 2016 Aug 30;87(9 Suppl 2):S74-81. PMID: 27572865. [PubMed] [Read by QxMD]

Ghezzi A1, Amato MP2, Makhani N2, Shreiner T2, Gärtner J2, Tenembaum S2. Pediatric multiple sclerosis: Conventional first-line treatment and general management. Neurology. 2016 Aug 30;87(9 Suppl 2):S97-S102. PMID: 27572869. [PubMed] [Read by QxMD]

Charvet LE1, O’Donnell EH2, Belman AL1, Chitnis T2, Ness JM3, Parrish J4, Patterson M5, Rodriguez M5, Waubant E6, Weinstock-Guttman B4, Krupp LB7; US Network of Pediatric MS Centers. Longitudinal evaluation of cognitive functioning in pediatric multiple sclerosis: report from the US Pediatric Multiple Sclerosis Network. Mult Scler. 2014 Oct;20(11):1502-10. PMID: 24687807. [PubMed] [Read by QxMD]

Krupp LB1, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, Ghezzi A, Hintzen R, Kornberg A, Pohl D, Rostasy K, Tenembaum S, Wassmer E; International Pediatric Multiple Sclerosis Study Group. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler. 2013 Sep;19(10):1261-7. PMID: 23572237. [PubMed] [Read by QxMD]

Chitnis T1, Tenembaum S, Banwell B, Krupp L, Pohl D, Rostasy K, Yeh EA, Bykova O, Wassmer E, Tardieu M, Kornberg A, Ghezzi A; International Pediatric Multiple Sclerosis Study Group. Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult Scler. 2012 Jan;18(1):116-27. PMID: 22146610. [PubMed] [Read by QxMD]

Sadaka Y1, Verhey LH, Shroff MM, Branson HM, Arnold DL, Narayanan S, Sled JG, Bar-Or A, Sadovnick AD, McGowan M, Marrie RA, Banwell B; Canadian Pediatric Demyelinating Disease Network. 2010 McDonald criteria for diagnosing pediatric multiple sclerosis. Ann Neurol. 2012 Aug;72(2):211-23. PMID: 22926854. [PubMed] [Read by QxMD]

Kuntz NL1, Chabas D, Weinstock-Guttman B, Chitnis T, Yeh EA, Krupp L, Ness J, Rodriguez M, Waubant E; Network of US Pediatric Multiple Sclerosis Centers. Treatment of multiple sclerosis in children and adolescents. Expert Opin Pharmacother. 2010 Mar;11(4):505-20. PMID: 20163265. [PubMed] [Read by QxMD]

Yeh EA1, Chitnis T, Krupp L, Ness J, Chabas D, Kuntz N, Waubant E; US Network of Pediatric Multiple Sclerosis Centers of Excellence. Pediatric multiple sclerosis. Nat Rev Neurol. 2009 Nov;5(11):621-31. PMID: 19826402. [PubMed] [Read by QxMD]

Sean M. Fox

I enjoy taking care of patients and I finding it endlessly rewarding to help train others to do the same. I trained at the Combined Emergency Medicine and Pediatrics residency program at University of Maryland, where I had the tremendous fortune of learning from world renown educators and clinicians. Now I have the unbelievable honor of working with an unbelievably gifted group of practitioners at Carolinas Medical Center. I strive every day to inspire my residents as much as they inspire me.

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