Transverse Myelitis

Basics

Description

An acute or subacute inflammatory lesion of the spinal cord manifesting with the appearance of new autonomic, motor, and sensory symptoms. The “transverse” descriptor is a reference to the classic symptom presentation with an identifiable sensory level traversing the midline. Transverse myelitis (TM) is associated with cerebrospinal fluid (CSF) or radiographic abnormalities consistent with an inflammatory spinal cord lesion. TM is usually monophasic but can be a manifestation of a chronic disease.

Epidemiology

  • Incidence: Estimated 1–8/million cases per year in the United States (20% children) or approximately 300 affected children annually. There are two incidence distributions in children—a peak between 0 and 2 years of age and another broader distribution from 5 to 17 years of age.
  • Prevalence: estimated 34,000 in the United States with disabilities due to TM
  • The female-to-male ratio is approximately 1:1 for <10 years, with a female predominance observed after age 10 years (2.6:1) in a North American cohort.

Risk Factors

  • Fever, findings consistent with infection, or vaccinations in the preceding weeks are reported in the majority (>50%) of children with TM, but specific infections are rarely diagnosed.
  • Mild trauma and obesity are associated with an increased risk of TM.

Etiology

Unknown. Several infectious and autoimmune conditions have been associated with TM without a clear unifying immunopathogenesis.

Commonly Associated Conditions

  • TM in children is predominantly idiopathic.
  • TM can be a manifestation of the acquired demyelinating syndromes, for example, acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), or neuromyelitis optica (NMO).
  • The enteroviruses (coxsackie A7, 9, 23, and B strains) and other viruses (dengue fever, hepatitis, human herpes, influenza, polio, and West Nile virus) have been reported in association with acute TM.
  • TM can occur during acute mycoplasma, spirochete, or parasitic infections.
  • TM has been reported in combination with Guillain-Barré syndrome (GBS).
  • TM can occur as part of a systemic autoimmune inflammatory disease (mixed connective tissue disease, systemic sclerosis, systemic lupus erythematosus, sarcoidosis, Sjögren syndrome, Behçet disease, juvenile rheumatoid arthritis, autoimmune thyroid disease, or antiphospholipid syndrome).
  • Metabolic deficiencies and mitochondrial disease can cause TM-like presentations.

Diagnosis

History

  • Children with TM most commonly (∼60%) report pain (in neck, back, and lower extremities) as their initial symptom, followed by motor deficits (∼30%) and sensory loss (∼10%). Loss of bladder/bowel control, gait disturbances, and visual loss are also noted.
  • Pediatric TM is often postinfectious and can be found after vaccinations. A history within the past 30 days of vaccination, fever, upper respiratory symptoms, leukocytosis, or other indications of a recent infection is noted in the majority of cases.
  • A sudden precipitous onset or acute total sensory/motor/reflex loss below a spinal level should provoke an emergent exploration of potential obstructive, vascular, or traumatic etiologies, as TM symptoms evolve over hours to days, not minutes.
  • A prior history of paroxysmal neurologic symptoms such as transient sensory deficits, weakness, trigeminal neuralgia, or visual loss may suggest this TM presentation is a relapse of a neuroimmune disease.
  • A prior history of known/suspected systemic autoimmune disease or coagulopathy should be used to guide subsequent evaluation.
  • Radiation exposure can cause a TM-like presentation with a latency of up to 10 years.

Physical Exam

  • A complete neurologic examination is imperative. Typical examination findings include a bandlike sensory level with distal sensory loss, weakness of the lower extremities, ataxia, and urinary retention. Reflexes may be increased or diminished, and abnormal extensor response of the great toe (Babinski sign) is often present.
  • Findings are usually bilateral and symmetric and referable to a spinal level (usually thoracic) but can be relatively asymmetric or in rare instances exclusively unilateral.
  • Closely monitor heart rate and blood pressure. TM lesions anywhere from the brainstem to the upper thoracic cord could disrupt sympathetic–parasympathetic balance, resulting in bradycardia and hypotension. In lesions of the thoracic cord, autonomic dysreflexia can occur as a late complication.
  • Follow patient respiratory status because lesions of the cervical cord at or above level C5 could impair diaphragm function. Brainstem lesions can involve the nucleus of spinal accessory nerve, causing pharyngeal muscle weakness and loss of airway patency. Respiratory decompensation is less common in TM than in GBS.
  • Also observe for deficits of proprioception and vibration sense indicating involvement of the posterior columns (suggesting syphilis, B12 deficiency.)
  • Concurrent diminished visual acuity, blindness, loss of color vision, or optic nerve pallor indicates optic neuritis. Rapid vision loss with TM is likely NMO and mandates aggressive treatment.
  • Spinal shock, characterized by suspension of spinal cord function and areflexia below a spinal level, may occur early in TM. Loss of reflexes also raises concern for GBS.
  • Fever and neck pain are common findings in TM but when present with other indications of meningeal irritation increases importance of evaluation for meningitis.
  • Excessive irritability, stupor, altered awareness, or neurocognitive problems suggest encephalopathy due to ADEM.
  • The examination of the infant with TM is challenging. Lack of spontaneous movement or resistance to examination, asymmetric movements, absent response to painful stimuli, bladder distension or abdominal fullness, or priapism can be presenting signs in infants. Muscle, bone, or joint pain may cause refusal to ambulate/bear weight without spinal cord pathology.

Diagnostic Tests and Interpretation

Lab

  • Complete blood cell count and differential to assess for acute infection
  • Serum aquaporin-4 IgG. Consider repeating if prior negative result for recurrence of TM (∼80% of children seropositive in relapsing NMO vs. 13% in initial TM), if optic neuritis also present, or MRI findings suggestive of NMO. CSF aquaporin-4 IgG may be more sensitive than serum assay.
  • Lumbar puncture (if no risk of herniation) and CSF analysis
    • Cell count (mean ∼200 WBCs/μL in TM; cell counts >30–50 more likely to have NMO than MS)
    • Protein (elevated in 20–50% of TM cases; elevated protein and low CSF cell count is more typical of GBS)
    • Glucose (if low consider infectious etiology)
    • CSF Gram stain and culture
    • IgG index (elevated in MS)
    • Oligoclonal bands (present in 90% of MS and 30% of NMO cases)

If history, examination findings, or endemic likelihood, consider these additional studies:

  • CSF: Enterovirus, human herpesvirus (HHV) 1/2/6, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), dengue, or West Nile viral DNA polymerase chain reaction (PCR); paraneoplastic panel, lactate, pyruvate
  • Mycoplasma pneumoniae IgM/IgG with throat swab PCR, Bartonella henselae IgM/IgG titer, Borrelia burgdorferi IgM/IgG, rapid plasma reagin (RPR), hepatitis A/B/C, or influenza testing
  • If chronic myelopathy is present, evaluate for mumps, measles, HIV, human T-lymphotropic virus (HTLV) I/II
  • Purified protein derivative (PPD) with anergy panel, tuberculosis culture
  • Schistosomiasis stool or urine examination
  • Autoimmune disease: antinuclear antibody (ANA), rheumatoid factor (RF), anti-dsDNA antibody, antiphospholipid antibodies, angiotensin-converting enzyme (with chest radiography) antithyroid antibodies, rheumatologic or paraneoplastic panel
  • Prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), and coagulopathy panel
  • Copper or B12 serum levels
  • Mitochondrial function serum testing

Imaging

  • Inflammation of the spinal cord identified by imaging or CSF findings is required for a diagnosis of TM. Acute neurologic deficits referring to the spinal cord mandate emergent spinal imaging. An MRI scan with gadolinium enhancement of the whole spine is preferred; short inversion time inversion recovery (STIR) sequences are sensitive for identifying abnormalities. If patient cannot tolerate lengthy scan, or there is a time-critical concern, scanning segments where symptoms localize can suffice. Full spine and brain should be imaged later to establish presence of clinically silent lesions or baseline imaging.
  • Longitudinally extensive TM (T2 hyperintense lesion spanning ≥3 segments) is typical of idiopathic TM or NMO, not MS.
  • Selective enhancement of the nerve roots without cord involvement suggests GBS.
  • All patients presenting with acute TM should have an ophthalmologic examination with ocular coherence tomography and visual-evoked potentials. Subclinical optic neuritis suggests a diagnosis of MS or NMO.
  • MRI of the brain with contrast or dedicated optic nerve imaging is needed with encephalopathy/brain lesions or optic nerve involvement. Lesions in subcortical white matter suggest ADEM or MS.

Diagnostic Procedures/Other

An electromyogram and nerve conduction studies can be used in clinically ambiguous cases to differentiate GBS from TM.

Differential Diagnosis

  • Infectious myelitis
  • Postradiation myelopathy
  • Compressive myelopathy
    • Trauma
    • Extramedullary: arteriovenous malformation, discitis, epidural abscess, vertebral osteomyelitis, tumor
    • Intramedullary: arteriovenous malformation, tumor
  • Ischemic myelopathy
    • Spinal cord infarct, angiitis/vasculitis, fibrocartilaginous embolism
  • Autoimmune
    • Acquired demyelination syndromes
    • Systemic autoimmune disease
    • Paraneoplastic syndrome

Treatment

Medication (Drugs)

First Line

  • Methylprednisolone IV (dose: 30 mg/kg/day or a maximum dose of 1 g/day) or an oral equivalent is recommended initial treatment for noninfectious TM. Strong evidence exists in adults (not children) for efficacy in TM. Typical treatment length is 5–7 days followed by oral corticosteroid taper starting at dose of 1 mg/kg/day (maximum 60 mg/day prednisone equivalent) over 3–4 weeks.

Second Line

  • If steroids are not effective or contraindicated, plasmapheresis is an alternative. Evidence exists for efficacy of plasmapheresis treatment in children. Typically, 5–7 exchanges are performed. Consider for NMO with progressive visual loss.
  • Intravenous immunoglobulin G (IVIG; dose: 2 g/kg divided over 2–5 days) is an alternative or add-on treatment.
  • Cyclophosphamide (dose: 500–750 mg/m2) administered once is reportedly effective in refractory TM cases.
  • Immunomodulatory therapies for MS can begin after acute treatment. Rituximab is an option for TM due to NMO.

General Measures

  • Most patients will have urinary retention and constipation, so appropriate bowel/bladder regimen should be implemented proactively.
  • Short-term and long-term pain management plans are needed in almost all TM patients.

Additional Treatment

  • Physical, occupational, or speech/language therapists should be engaged as soon as possible to maintain function during hospitalization and assess needs for possible longer duration placement.
  • Long-term neurologic follow-up (1–3 years) is necessary to assess for new symptoms, recurrence, and zenith of recovery.

Ongoing Care

Prognosis

  • Complete recovery in 33–50% of pediatric cases. Up to 20% can have significant residual disabilities (not ambulatory, severe sensory loss, lack of sphincter control).
  • Mortality due to acute TM is <5%.
  • Infants may have extensive lesions and worse outcomes. Other factors associated with a poorer prognosis: rapid onset of symptoms (<24 hours to nadir), more sensory loss/weakness or length of time spent at symptom nadir, need for ventilation, longitudinal extent of lesion, higher sensory level, or diminished/absent reflexes at onset

Additional Reading

  1. Banwell B, Kennedy J, Sadovnick D, et al. Incidence of acquired demyelination of the CNS in Canadian children. Neurology. 2009;72(3):232–239.  [PMID:19153370]
  2. Defresne P, Hollenberg H, Husson B, et al. Acute transverse myelitis in children: clinical course and prognostic factors. J Child Neurol. 2003;18(6):401–406.  [PMID:12886975]
  3. Pidcock FS, Krishnan C, Crawford TO, et al. Acute transverse myelitis in childhood: center-based analysis of 47 cases. Neurology. 2007;68(18):1474–1480.  [PMID:17470749]
  4. Scott TF, Frohman EM, De Seze J, et al. Evidence-based guideline: clinical evaluation and treatment of transverse myelitis. Neurology. 2011;77(24):2128–2134.  [PMID:22156988]
  5. Thomas T, Branson HM, Verhey LH, et al. The demographic, clinical, and magnetic resonance imaging (MRI) features of transverse myelitis in children. J Child Neurol. 2012;27(1):11–21.  [PMID:21968984]

Codes

ICD-9

  • 341.20 Acute (transverse) myelitis NOS
  • 341.22 Idiopathic transverse myelitis
  • 341.21 Acute (transverse) myelitis in conditions classified elsewhere
  • 049.9 Unspecified non-arthropod-borne viral diseases of central nervous system

ICD-10

  • G37.3 Acute transverse myelitis in demyelinating disease of central nervous system
  • A89 Unspecified viral infection of central nervous system

SNOMED

  • 47000000 Acute transverse myelitis
  • 425756000 Idiopathic transverse myelitis
  • 230197009 Acute viral transverse myelitis (disorder)

FAQ

  • Q: What is the typical clinical timeline of TM?
  • A: TM symptoms typically begin over 2–3 days. Functional nadir can occur within hours to 1 month of onset. This nadir averages 7 days before recovery. Patient recovery can be rapid (within weeks) or span years.
  • Q: What is the likelihood of recurrence?
  • A: 60–80% of pediatric TM is monophasic. Approximately 15% of patients with TM will be diagnosed with MS or NMO and therefore would be at risk for a relapse.

Authors

Paul R. Lee

Avindra Nath


© Wolters Kluwer Health Lippincott Williams & Wilkins

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