Multiple sclerosis (including transverse myelitis)

Author(s): Linda E. Krach, MD, Stacy Stibb, DO

Originally published:09/20/2013

Last updated:09/20/2013

1. DISEASE/DISORDER:

Definition

Pediatric multiple sclerosis(MS) and transverse myelitis(TM) are immune-mediated diseases resulting in inflammation and demyelination of the central nervous system, and include a component of axonal loss and neurodegeneration in MS.

Etiology

The exact etiology is unknown. In MS, genetic and environmental factors are thought to contribute to the disease. TM can be idiopathic or disease-associated. In children, idiopathic TM accounts for 89% of the cases, with the child having a mild illness, a recent vaccine, allergy injection, or sustaining mild trauma prior to onset of symptoms. Disease-associated TM is secondary to an underlying autoimmune disorder such as MS, acute disseminated encephalomyelitis, or systemic lupus erythematosus.1

Epidemiology including risk factors and primary prevention

According to current studies, the incidence of pediatric MS ranges between 0.18 and 0.51 per 100,000.2 It has been shown that 3-5% of all individuals with MS experience their first attack during childhood. Risk factors include female gender if diagnosed post-pubertal, low vitamin D concentration, cigarette smoke exposure, remote Epstein Barr virus infection, the HLA-DRB1 gene, and a family history of MS.3 Acute TM is reported in 1 to 8 cases per million people in the U.S. with 20% of these cases occurring in children.1 No risk factors have been identified for TM.

Patho-anatomy/physiology

Active demyelinating lesions demonstrate a component of perivascular inflammation combined with lipid laden macrophages and large reactive astrocytes. In MS, there is heterogeneity regarding the pattern of inflammation, with two patterns involving T cell and macrophage inflammation and another two demonstrating oligodendrocyte apopotosis or death. In TM, the inflammation is associated with T cell and monocyte infiltration. Molecular mimicry, superantigen effect, humoral-based dysregulation, interleukin-mediated toxicity, and elevated immunoglobuin levels are mechanisms thought to lead to inflammatory infiltration of the spinal cord.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Multiple Sclerosis:

  1. New onset: Typically presents with optic neuritis, monofocal brainstem, or polyfocal neurologic deficits.
  2. Subacute: Pediatric MS follows a relapsing-remitting course; greater than 75% of children with MS will experience a second attack within the first year. Children also have a higher relapse rate in their early years and are on average 10 years younger at the time of evolution to secondary progressive MS, compared to adults.3
  3. Chronic/stable: Between attacks of relapsing-remitting MS, children return to their baseline function but once they evolve into secondary progressive MS they will experience a slow continual deterioration of function.

Transverse Myelitis:

  1. New onset: Presents with complaints of pain, sensory loss in a band-like distribution, and bowel/bladder dysfunction.
  2. Subacute: Recovery typically starts 7 days after onset but symptoms can persist for months.
  3. Chronic/Stable: Some individuals have persistent motor and/or bladder deficits. Rarely do children experience a repeat episode of TM.

Specific secondary or associated conditions and complications

Children with MS can experience spasticity, bowel/bladder/sexual dysfunction, pain, cognitive and functional impairments. There is a risk for developing depression and significant fatigue. Children with TM can demonstrate a range of outcomes, from no residual neurological deficit to complete paralysis with neurogenic bowel and bladder, as well as ongoing pain.

2. ESSENTIALS OF ASSESSMENT

History

The location of the demyelinating lesion will determine what type of symptoms the individual is experiencing. Specific information to collect includes any motor or sensory abnormalities, bowel or bladder dysfunction, vision abnormalities, previous attacks, rapidity of progression of symptoms, recent illness/immunizations, associated signs/symptoms, family history of neurologic disorders, and current functional history.

Physical examination

A full neurologic and functional assessment should be performed. Examination should include evaluation of tone, cognition, cranial nerves, reflexes (including abdominal and bulbocavernous reflexes), and gait. A thorough assessment to determine a spinal motor or sensory level, including a rectal exam, as well as determination regarding a partial or complete level is appropriate. Ophthalmological examination is warranted to determine if subclinical optic neuritis exists. Serial examinations will help to assess for changes or progression of disease. Depression screening is appropriate.

Functional assessment

The Functional Independence Measure for Children (WeeFIM) can be used to assess functional independence in children ages 6 months to 7 years. It rates 18 items within the 3 categories of self-care, mobility, and cognition.4 The Kurtzke Expanded Disability Scale can be used in MS to assess and follow function. It contains 8 functional systems: visual, pyramidal, brainstem, cerebellar, sensory, bowel and bladder, cerebral, and other, which are each rated from 0-5, representing limited to severe impairment.5 Although the Kurtzke Expanded Disability Scale has been used for over 30 years, there is no literature describing specific psychometric properties. It has been used in children as well as adults, since the clinical manifestations of MS are similar in the two populations.

Laboratory studies

Cerebrospinal fluid should be sent for viral and bacterial culture as well as evaluation for cellular profiles, oligoclonal bands, and IgG. Vitamin D level, evaluation for previous Epstein Barr virus, and HLA-DRB1 can be assessed, as they are associated with increased risk of MS. Since TM can be idiopathic or secondary to an underlying autoimmune disease, serum evaluation should be directed to assess for underlying pathology.

Imaging

In both diseases, MRI of the brain and spinal cord should be obtained, including the use of gadolinium in order to more accurately assess for active MS lesions, inflammation, infection, and possible tumor presence. Current diagnostic criteria for MS allows for specific findings on brain MRI to substitute for clinical relapses and therefore allow a diagnosis of MS with a first clinical attack. In TM it is imperative to rule out any compressive etiology within the spine that could present with similar symptoms and warrant emergent neurosurgical intervention. Spine lesions in MS typically are small areas of patchy hyperintense T2 signals spanning fewer than 3 spinal segments and involving only a portion of the transverse diameter of the cord, as opposed to TM where the pattern is symmetric, uniform, spanning 3 or more consecutive vertebral levels, and can involve the entire diameter of the cord.1

Supplemental assessment tools

Urodynamic studies can be performed to further assess bladder function. Ophthalmologic examination, including visual evoked potentials and ocular coherence tomography, can be used to assess for optic neuritis in young children who cannot describe visual changes, and also to assess for subclinical optic neuritis. Neuropsychological testing can assess for cognitive abnormalities in memory, problem solving, attention, and executive function, all of which can often be found in MS patients.

Early predictions of outcomes

Poorer prognosis in MS is associated with increased relapse rate in the first 2 years of disease, onset in the very young, and severity of initial events. Severity of initial demyelination events was found to be worse in non-whites, as well as initial localization within the optic nerve or cerebral hemispheres. Poorer prognosis in TM has been associated with idiopathic TM, severe motor weakness at nadir, high anatomic rostral border of sensory level, longitudinal extension of cord lesion, need for ventilatory support, and younger age at onset.1

Environmental

Obtaining information and assessment of the individual’s home and school environment are necessary to make any proper modifications or accomodations to allow the child to be as independent as possible.

Social role and social support system

It is important to inquire about and address any concerns regarding the disease’s impact on quality of life, school and eventual ability to work, impact on recreational and functional activities for the child, as well as how the disease can impact the entire family. Inquiring about the child’s support system should address whether there are family members, friends, community groups, etc. available that can lend physical and emotional support.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

After a diagnosis of MS, children are started on disease-modifying agents. The first line agents include beta interferons and glatiramer acetate. Acute relapses are treated with IV methylprednisolone of 20-30 mg/kg/day over 3-5 days. If symptoms recur or there is a worsening of symptoms after discontinuation of IV steroids, an oral taper can be added. If the relapse is severe or there is incomplete recovery after high dose steroids, a second pulse of IV steroids can be given, intravenous immunoglobulin(IVIG) 2g/kg over 2-5 days can be trialed, and/or plasma exchange can be used.

First line treatment for noninfectious immune-mediated TM includes IV methylprednisolone at 30mg/kg/day for 5-7 days with a maximum dose of 1g/day followed by an oral corticosteroid taper of 1mg/kg/day for 3-4 weeks. If there is no clinical improvement within 24-48 hours IVIG can be given at 2g/kg divided over 2-5 days. Children with TM usually do not need additional treatment aimed at their disease after the acute phase. 1,6,7,8

At different disease stages

Stage MS TM
New onset/acute -Proper medical management
-Evaluate for bowel/bladder dysfunction. Start appropriate programs with intermittent catherization or bowel program.
-Initiate PT, OT, SLP to maintain range of motion, prevent contractures, orthotic evaluation, assess cognition and swallow.
Same as MS
Subacute -Course is relapsing-remitting, so child should return to baseline between episodes.
-Encourage continued physical activity, especially aerobic exercise to fend against fatigue and depression.
-Continued cognitive exercises focusing on memory and processing speed.
Ongoing deficits may exist most frequently with bladder dysfunction and pain. Address these deficits with proper medications and bladder programs as well as early involvement in a pain program if necessary.
Chronic/stable As the child evolves into a secondary progressive disease, care should focus on symptom management for spasticity, pain, bowel/bladder/sexual dysfunction, fatigue, sleep hygiene, and depression. Continue to evaluate child on a regular basis as their disease progresses for changes in cognitive and functional status and obtain new equipment or initiate therapy as appropriate. Not a chronic disease
Pre-terminal or end of life care Assure patient is comfortable and that patient has the emotional and physical support necessary.

Coordination of care

It is imperative to have open communication between the medical personnel involved (physiatry, neurology, psychology, psychiatry, urology, ophthalmology), therapists (PT, OT, SLP), social work, as well as the child’s school and family members throughout their disease course. Children affected by TM may require inpatient rehabilitation to address deficits in mobility and ADLs, as well as equipment assessment, depending on their residual deficits. Children with MS may initally need only outpatient basis due to the fact that between flares they should return to their baseline function; as their disease progresses more intensive therapy may be warranted. Specific deficits will determine the medical specialties involved.

Patient & family education

Emerging/unique Interventions

The WeeFIM can be used to assess function over time. The Kurtzke Expanded Disability Status Scale can be used in individuals with MS to assess function. The Modified Ashworth Scale can be used to assess spasticity pre- and post-treatment. There are various fatigue, depression, and quality of life scales that can be used in children and adolescents to follow their symptoms over time.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Periodic follow-up is advised to assess the child’s function and help address any deficits early.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

New oral medications target the immune system and the immunopathologic process of MS: those tested in adults include Cladribine, Fingolimod, Teriflunomide, Fumarate, and Laquinimod. They have been shown to decrease MRI activity and/or decrease relapse rates. Monoclonal antibodies targeting the immunopathologic process include Rituximab, Daclizumab, and Alentuzumab,which have shown promise in decreasing MRI and disease activity as well.7

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

Controlled treatment trials have occurred in adults to assess disease-modifying medication efficacy, but no trials have occurred in children.

REFERENCES

1. Wolf VL, Lupo PJ, Lotze TE. Pediatric acute transverse myelitis overview and differential diagnosis. Journal of Child Neurology. 2012;27(11):1426–1436.

2. Vargas-Lowy D, Chitnis T. Pathogenesis of pediatric multiple sclerosis. Journal of Child Neurology. 2012;27(11):1394–1407.

3. Bigi S, Banwell B. Pediatric multiple sclerosis. Journal of Child Neurology. 2012;27(11):1378–1383.

4. http://www.udsmr.org/Documents/WeeFIM/WeeFIM_II_System.pdf

5.Thomas T, Branson HM, Verhey LH, et al. The demographic, clinical, and magnetic resonance imaging (MRI) features of transverse myelitis in children. Journal of Child Neurology. 2012;27(1):11–21.

6. Chitnis T, Tenembaum S, Banwell B, et al. Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Multiple Sclerosis. (Houndmills, Basingstoke, England). 2012;18(1):116–127.

7. Ghezzi A. Therapeutic strategies in childhood multiple sclerosis. Therapeutic Advances in Neurological Disorders. 2010;3(4):217–228.

8. Yeh EA. Management of children with multiple sclerosis. Paediatric Drugs. 2012;14(3):165–177.

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Author Disclosure

Linda E. Krach, MD
Medtronic Inc: research grant as principle investigator

Stacy Stibb, DO
Nothing to Disclose

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