ADD-ONS / SPECIAL NEUROLOGY
Acute transverse myelitis (ATM)
David Goldemund M.D.
Updated on 24/05/2024, published on 23/05/2024
Updated on 24/05/2024, published on 23/05/2024
Introduction
- acute transverse myelitis (ATM) is a relatively rare inflammatory disease of the spinal cord (incidence approximately 1–4 cases/million/year [Transverse Myelitis Consortium Working Group, 2002]
- peaks at ages 10-19 and then 30-39 years
- a pathobiologically heterogeneous syndrome characterized by acute or subacute spinal cord dysfunction with a severe prognosis – many patients end up with severe residual deficits
- onset acute (hours) or subacute (up to 3 weeks)
- most common causes:
- infectious, para/post-infectious
- demyelinating diseases (MS/CIS, NMOSD)
- idiopathic – without any clear etiology despite a thorough investigation
- diagnosis is often challenging in the initial phase and includes 2 steps:
- confirmation of myelitis (differentiation from tumor, external compression, spinal ischemia/hematoma)
- determination of the cause of myelitis
Etiology
- myelitis is associated with multiple conditions
- spinal involvement is a common manifestation of MS, not rarely presenting as the first symptom
- lesions typically span 1–2 segments, are asymmetrical, and often located in the dorsolateral region, particularly in the cervical and thoracic cord
- in the acute phase, they show postcontrast enhancement
- clinically, they usually present as incomplete spinal lesions
- diagnosis is often supported by a positive brain MRI finding and evidence of intrathecal IgG synthesis with oligoclonal bands on isoelectric focusing
- an autoimmune disease affecting the cells of salivary, lacrimal, and other glands (pancreas, vaginal glands, parotid gland)
- clinically presents as dry mouth (xerostomia), swallowing disorders, bad breath, increased tooth decay, dry eyes (xerophthalmia) with burning sensations, and intolerance to sunlight
- typically manifests in the 5-6th decade of life
- CNS involvement occurs in 25-30% of patients; myelitis is rare (only about 1% of affected individuals) and is usually described as long, expansively behaving central T2 hyperintense lesions
- Sjögren’s syndrome is often associated with other autoimmune diseases, such as RA, SLE, or NMO
- CNS involvement in SLE is relatively common (up to 50%)
- typically, it presents as aseptic meningitis or vascular involvement (vasculitis, ischemic cerebrovascular stroke)
- myelitis is rare (2-3%)
- many cases described as myelitis due to SLE were, in fact, SLE-associated NMO
- NMO usually presents as LETM, often with subsequent development of optic neuritis
- AQP4-IgG antibodies are found in the serum – test all patients with SLE who develop optic neuritis (ON) or myelitis
- direct infectious involvement
- history of infectious disease in the last 4 weeks combined with laboratory evidence of the infectious agent (cultural, serological, or PCR)
- post-infectious / post-vaccination complications
- MRI findings are non-specific, mostly long T2 hyperintense lesions with saturation after contrast agent administration
Clinical presentation
- back pain
- fast, usually gradual, development of motor, sensory, and autonomic dysfunction (typically within > 4 hours and < 3-4 weeks)
- an apoplectic onset with deficits reaching the nadir in < 4 hours indicates a vascular event
- motor and sensory deficits correspond to the level of the lesion and are usually bilateral, characterized by para- or quadriparesis/plegia
- autonomic dysfunction is almost always present in the form of impairment of bladder, sexual, gastrointestinal, cardiovascular, and thermoregulatory functions
- the brain is not affected in cases of idiopathic ATM
- fever (infectious etiology)
Diagnostic evaluation
Diagnostic criteria for myelitis
(Transverse Myelitis Consortium Working Group, 2002)
The diagnostic evaluation of ATM involves a combination of clinical assessment, imaging studies, and laboratory tests, including CSF analysis. The goal is to confirm the diagnosis, identify the underlying cause, and rule out other conditions
- typical clinical presentation – progressive bilateral (may be asymmetric) motor deficit with sensory level and development within 4 hours to 21 days
- the 4-hour interval is proposed to distinguish acute spinal infarction with sudden onset. However, it is not a reliable diagnostic feature as inflammatory myelitis can present with very rapid onset < 4 hours, whereas ischemia in AVM can be gradual (> 4 hours) [Nohejlová, 2018]
- the motor and sensory deficit is accompanied by autonomic dysfunction
- lesion on MRI
- Longitudinally Extensive Transverse Myelitis (LETM) – lesion ≥ 3 segments, usually affecting the entire cross-section of the spinal cord (> 2/3) [DeSanto, 2011]
- Acute Partial Transverse Myelitis (APTM) with lesions < 2 segments and usually eccentric asymmetric involvement
- the lesion is not bright on DWI
- initially, MRI findings may be negative
- evidence of inflammation
- CSF: pleocytosis, increased IgG index
- presence of enhancement on MRI after gadolinium administration (baseline imaging may show no enhancement)
- both infectious and autoimmune spinal cord inflammation have similar clinical and laboratory manifestations
- infectious etiology is indicated by the presence of the pathogen in CSF or a positive antibody index in serum and CSF, systemic signs of infection, and epidemiological history
- exclusion of non-inflammatory etiology of spinal lesion (MRI, CT myelography if MRI is contraindicated)
- extramedullary compression
- intramedullary tumor
- spinal ischemia (occlusion of the anterior spinal artery with typical lesion localization, spinal AV malformation, aortic dissection, etc.) – onset usually < 4 hours
- determine the etiological diagnosis of myelitis (see table above)
- idiopathic – extensive diagnostics do not reveal any other disease
- secondary (infection, demyelination disease, systemic disease-related ATM, etc.)
- T2 – hyperintense
- T1 – isointense or hypointense
- T1C+ – usually postcontrast enhancement is present (diffuse, focal, peripheral) but may be absent initially
- DWI – negative
- the spinal cord is enlarged, lesion occupies > 2/3 of the cross-sectional area of the cord
- assessment of the longitudinal extent of the lesion on MRI
- longitudinally extensive transverse myelitis (LETM) – isolated lesion that extends across ≥ 3 vertebral segments, usually affecting the entire cross-section of the spinal cord
- partial transverse myelitis (APTM) with lesions that extend across ≤ 2 segments and often with eccentric partial involvement on axial scans
- a brain MRI should be obtained in all patients
- look for evidence of concomitant or prior lesions that may provide clues about the etiology
- up to 40% of patients have asymptomatic brain lesions at the time of the first ATM attack (⇒ CIS/MS)
- the presence of MS-like brain lesions in patients with partial TM portends a high risk of transition to clinically definite MS in 3-5 years
- idiopathic ATM may have normal baseline MRI findings in up to 40% of cases, or the lesion may not enhance after contrast administration ⇒ DDx of ischemia is challenging in the acute stage [Scotti, 2001]
- follow-up MRI is recommended after 2-7 days
- spinal cord enlargement
- various degrees of post-contrast enhancement, including its absence
- if MRI is contraindicated, perform myelo-CT to exclude spinal cord compression
- look for signs of infection, inflammation, or malignancy
- typical findings in ATM include pleocytosis, increased protein concentration, and the presence of oligoclonal bands
- CSF culture may be performed if an infectious cause is suspected
- initially, normal CSF findings are described in up to 50% of cases; in such cases, a follow-up examination after 2-7 days is recommended
- complete blood count, inflammatory markers (e.g., ESR, CRP)
- serologic screening
- serologic tests for borrelia, Mycoplasma pneumoniae, and neurotropic viruses in the serum and CSF
- direct detection of borrelia, herpes viruses, and enteroviruses in serum and CSF using PCR
- autoimmune panels (IgM, IgA, and IgG, C3 and C4 components of complement and circulating immune complexes, antinuclear antibodies, etc.)
- antibodies against aquaporin 4 (AQP4-IgG) in the serum
- highly specific biomarker for neuromyelitis optica (NMO), especially in patients with longitudinally extensive transverse myelitis
- testing for vitamin deficiencies (e.g., vitamin B12) and toxicology screens
- screening for paraneoplastic syndromes if a malignancy is suspected
- somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) to assess the functional integrity of sensory and motor pathways
Differential diagnosis of myelitis
- spinal cord infarction (ischemia in the anterior spinal artery territory, AVM, aortic dissection)
- older patients (> 50 years) are more likely to suffer spinal cord infarction
- usually sudden onset (may not apply to AVM)
- in the early phase, cerebrospinal fluid findings are negative; post-contrast enhancement of the lesion is usually absent (appears more in the subacute phase)
- the spinal cord is enlarged, the lesion is hyperintense on T2 and DWI (restricted diffusion)
- multiple segments are affected, with the maximum occurrence in the upper thoracic and thoracolumbar segments
- on T2, hyperintensity may also be visible in the vertebral body (infarction)
- hematomyelia
- spinal tumor
- MRI shows mass lesion with or without enhancement
- slowly progressive clinical course
- external compression (hematoma, meningioma, neurinoma, etc.)
- vitamin B12 deficiency
- subacute combined degeneration of the spinal cord
- macrocytic anemia, elevated methylmalonic acid, and homocysteine levels
- MRI may show hyperintensity in the posterior columns
- toxic myelopathy
- exposure to toxic substances (e.g., radiation, chemotherapy agents, illicit drugs)
- history of toxin exposure
- MRI may show diffuse spinal cord changes
- degenerative spinal conditions
- spinal stenosis or herniated disc with cord compression
- gradual progression or fluctuation of symptoms
- MRI showing structural abnormalities
Management
Immunomodulatory therapy
- high-dose IV corticosteroids
- e.g., 1 g/day for 3-5 days followed by oral tapering
- it has not been demonstrated that the administration of corticosteroids worsens the clinical outcomes in patients with spinal cord ischemia or infection
- if corticosteroids fail, escalation of therapy proceeds with
- plasmapheresis:
- considered for patients not responding to corticosteroids
- typically 5-7 exchanges
- Intravenous Immunoglobulin (IVIG):
- dose: 0.4 g/kg/day for 5 days (total dose 2g/kg)
- used in refractory cases or when plasmapheresis is not available
- disease-specific Treatments:
- MS/CIS-related myelitis: Disease-modifying therapies (e.g., interferons, glatiramer acetate, natalizumab)
- NMOSD: Immunosuppressive agents (e.g., azathioprine, rituximab, mycophenolate mofetil)
- autoimmune myelitis: depending on the underlying condition, agents such as cyclophosphamide, methotrexate, or monoclonal antibodies
- CPA dose: usually 500 – 1000 mg/ m2 IV
Specific, causal therapy
For example:
- neuroborreliosis – ceftriaxone (LENDACIN) 2 g/day intravenously for 14–21 days
- herpetic infection – acyclovir (HERPESIN)
General therapy
- rehabilitation
- prevention of complications (decubitus, contractures, secondary infections)
- management of spasticity
- urinary tract care
Prognosis
- in more than 60% of cases, significant residual spinal symptoms persist, or no improvement occurs
- better prognosis can be expected:
- in younger individuals with a subacute onset and early clinical improvement
- in myelitis due to MS/CIS, NMOSD, or neuroborreliosis that responds well to therapy
- worse prognosis is associated with acute onset of myelitis (hours/days) with severe initial neurological impairment, incontinence, lesion detected in the cervical cord, and idiopathic etiology
