OVERVIEW: What every practitioner needs to know
Are you sure your patient has transverse myelitis? What are the typical findings for this disease?
Rapidly progressive paraparesis that usually affects the legs but may include the arms as well. Often the initial complaint is loss of ability to walk.
Accompanying distinct level of sensory loss. Commonly, it occurs from the mid or lower back down to the legs.
Pain is often present. It can be described as burning or tingling.
Numbness is also a common finding.
Incontinence involving bladder and/or bowel.
Secondary signs and symptoms
Replacement of flaccidity by upper motor neuron lesion signs, such as spasticity; generally occurs by the second week of illness.
Urinary symptoms may include urgency, inability to void, incontinence.
Thoracic sensory and motor levels are most commonly reported.
Cervical level involvement in children is not infrequent.
More than 80% of patients progress to maximal involvement by 10 days after onset, with a range from 4 to 21 days.
Recovery phase from onset of motor recovery to ultimate neurologic level of function may occur over months to years.
What other disease/condition shares some of these symptoms?
Multiple sclerosis – first presentation
Acute disseminated encephalomyelitis (ADEM)
Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome)
Connective tissue disorders
systemic lupus erythematosus
Central nervous system infections
leukemia/lymphoma virus -1
What are the priorities in the diagnostic evaluation?
The FIRST priority is to rule out a compressive spinal cord lesion. In the presence of a suggestive history and physical exam, order a gadolinium-enhanced MRI of the entire spine before doing a lumbar puncture to obtain CSF. (Spinal cord immobilization should be considered when a spinal cord injury is suspected or cannot be ruled out.)
The SECOND priority is to determine whether spinal cord inflammation is present by obtaining and examining CSF and reviewing the spinal cord MRI with a neuroradiologist.
The THIRD priority is to define the extent of CNS involvement. Multiple sclerosis and acute disseminated encephalomyelopathy (ADEM) may be present in this setting. A gadolinium-enhanced brain MRI and visual evoked potentials should be obtained to look for these entities.
Disc herniations, epidural hematomas, vertebral body compression fractures, and spondylosis are common causes of compressive myelopathy, and may present without an obvious history of trauma.
Timely and accurate identification of these conditions is critical because immobilization of neck and spine to prevent further injury, neurosurgical consultation, and treatment with high-dose methylprednisolone may be required for some patients.
If transverse myelitis is suspected despite a normal spine MRI, re-examine the history, perform another physical examination, and evaluate the MRI with an experienced neuroradiologist and consult with a child neurologist.
How to do I distinguish between transverse myelitis and Guillain-Barré syndrome (acute inflammatory demyelinating polyradiculoneuropthy)?
These two conditions are often confused because both may present with rapidly progressing sensory and motor loss involving the lower extremities. Table I lists findings that favor one condition over the other.
|Transverse myelitis||Guillain-Barré Syndrome|
|Presentation||“pure” paraparesis with corresponding sensory level||progressive motor loss and weakness involving the lower extremities more than the upper; typically an “ascending” pattern|
|Deep tendon reflexes (DTRs)||usually increased, but may be absent in “fulminant” cases||usually are areflexic, but may have retained reflexes early in the course|
|Urinary urgency or retention||common early finding||not typical|
|Dysesthetic pain||may be present||may be present|
|MRI spinal cord||typically shows an area of inflammation||no spinal cord inflammation|
|CSF findings||elevation in both protein and cell count (but this is inconsistent)||albuminocytologic dissociation (elevation in protein beyond first week and cell count < 10)|
What caused this disease to develop at this time?
A preceding illness, including nonspecific symptoms such as fever, nausea, and muscle pain, has been reported in about 40% of children within 3 weeks of the onset of transverse myelitis.
The relationship between preceding immunization or infection and transverse myelitis is unclear.
Transverse myelitis may be the first manifestation of multiple sclerosis, but the reported association has a very broad range (6%-43% of cases).
Table II lists the estimated incidence of predisposing conditions for transverse myelitis.
|Associated mixed systemic connective tissue disorder||8% to 16.5%|
|Direct infection of spinal cord||up to 5%|
|Vascular cause||up to 14%|
|Idiopathic||10% to 45%|
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Obtain cerebrospinal fluid after ruling out a compressive myelopathy.
The absence of pleocytosis would suggest a non-inflammatory cause for the symptoms, such as arteriovenous malformations, epidural lipomatosis, fibrocartilaginous embolism, or possible early inflammatory myelopathy (i.e., a false negative CSF).
The presence of increased protein and increased cells in CSF would support a diagnosis of transverse myelitis.
Although cerebrospinal fluid findings in transverse myelitis are not consistent, and an elevated cell count may be absent, there is usually a moderate lymphocytic pleocytosis and elevated protein level.
Blood tests looking for evidence of a connective tissue or infectious disorder would aid in determining a cause and potential treatment options.
Would imaging studies be helpful? If so, which ones?
Rule out compressive spinal cord myelopathy by ordering a gadolinium-enhanced MRI of the entire spine.
Assess for the possibility of multifocal CNS lesions by ordering a gadolinium-enhanced brain MRI and visual evoked potentials.
This sagittal T2-weighted MRI image shows a hyperintense white area of inflammation in the cervical spinal cord (Figure 1).
Image courtesy of Thierry Huisman, MD
X-rays of the entire spine may be required to assess for vertebral fractures and potential spinal cord injury.
If you are able to confirm that the patient has transverse myelitis, what treatment should be initiated?
FIRST-line treatment after diagnosis is made: Begin high-dose intravenous steroids for 3 to 5 days, followed by oral taper over 1 to 3 weeks.
SECOND-line treatment if no or poor response to IV steroids after 3 to 5 days: Consider initiation of rescue therapy with plasma exchange transfusion.
THIRD-line treatment if continued poor response or if there is a recurrence: Consider other immunomodulatory approaches; however, very little evidence is available demonstrating effectiveness in children, and there is risk for severe associated adverse effects.
Other aspects affecting treatment decisions
The goal of therapy is to halt progression of spinal cord inflammation and minimize its destructive effects on the spinal cord.
The consensus is that high-dose anti-inflammatory treatment provides the best chance to achieve these goals.
The available evidence, which is based on only a few studies, suggests that high-dose intravenous steroids may be effective in improving outcome in children. These studies are limited by small numbers of study subjects and non-rigorous definitions of transverse myelitis.
Low dose oral or intravenous glucocorticosteroid treatment may not be as effective in improving the outcome.
The decision to continue steroids or to add a new treatment is often based on the clinical course and MRI appearance at the end of 5 days of IV high-dose steroid treatment.
What are the adverse effects associated with each treatment option?
High-dose steroids: gastrointestinal symptoms, insomnia, headaches, anxiety, mania, hypertension, hyperglycemia, electrolyte disturbances
Plasma exchange: hypotension, electrolyte imbalance, coagulopathy, thromobocytopenia, catheter-related thrombosis, infection
What about long-term management?
Ongoing management at a center specializing in rehabilitation of children with spinal cord injury is recommended.
If behavioral problems (e.g., anger, apathy, sadness) occur, consider depression, and refer for mental health services.
Table III summarizes approaches to long-term needs.
Clean intermittent catheterization
Renal function studies:
-anticholinergic for hyperactive detrusor muscle
-adrenergic blocker for sphincter dysfunction
Monitor for urinary tract infection
Cranberry juice for urine acidification
High fiber diet
Timed evacuation post meals
Analgesics drugs; avoid overuse
Transcutaneous electrical nerve stimulation (TENS) unit
Family and/or individual mental health therapy
– excercise bikes
– electrical stimulation
Energy conservation strategies
Is there a role for nerve transfers?
Microsurgical nerve transfer techniques have been used to restore upper extremity function in TM. Intact distal nerve fascicles from a “donor” nerve are connected to distal branches of injured “targeted” nerves. Best outcomes are noted if this surgery occurs within a year after the onset of TM.
What can you tell the family about potential outcomes about prognosis?
Clinical outcome for children with acute TM is not well understood due to the rarity of the condition, variability in presentation, and the paucity of reliable information.
Most patients experience some spontaneous recovery within 6 months, with additional improvement for up to 2 years.
Approximately 1/3 of patients have little or no neurologic sequelae.
Age at onset under 3 years is associated with a worse outcome.
Factors predicting a better outcome: shorter interval to diagnosis, absence of complete paraplegia, and lower sensory levels by neurologic examination.
A small subset of children with transverse myelitis eventually develop multiple sclerosis.
What causes this disease and how frequent is it?
No preceding factor is identified in 10%-45% of cases.
1400 new cases are diagnosed in the United States per year.
20% of cases occur in persons under the age of 18 years.
The condition affects all ages from infancy through adolescence, with bimodal peaks of 0 to 3 years and 10 to 18 years.
There is no known genetic predisposition.
A preceding infectious process is reported in 47% of cases.
A preceding immunization or allergy shot within 30 days of onset is reported in 28% of cases.
Can TM occur more than once?
Acute transverse myelitis (ATM) may be best described as a demyelinating process of sudden onset limited to the spinal cord that occurs one time and is limited to one site.
About 75%-90% of TM cases fit this profile.
In a minority of cases, a repeat attack on the central nervous system occurs.
The possibility of a recurrent demyelinating myelopathy, such as relapsing transverse myelitis, multiple sclerosis, or neuromyelitis optica, should be considered.
What complications might you expect from the disease or treatment of the disease?
Ambulation or mobility deficit
Incontinence from neurogenic bladder and/or bowel
Sensory deficits consisting of pain and/or numbness
Are additional laboratory studies available; even some that are not widely available?
The differential diagnoses for a child with transverse myelitis are listed above. The number of tests that could be ordered to identify a specific infectious or rheumatologic etiology can be quite large. The clinical context should guide the selection of additional laboratory studies.
How can transverse myelitis be prevented?
Idiopathic acute transverse myelitis cannot be prevented.
Are there variant forms of transverse myelitis?
Acute flaccid myelitis (AFM) may be a variant form of transverse myelitis. Inflammation of the spinal cord, mostly affecting the grey matter, is present. Clinically, AFM has features suggesting a lower motor neuron injury. This accounts for the weakness and lack of muscle tone seen in these cases. This is in contrast to typical transverse myelitis that results in spasticity and signs consistent with an upper motor neuron lesion. There is disagreement as to whether AFM should be considered a separate entity or be considered a subtype of TM.
AFM is diagnosed in the same manner as classic TM. Clinical exam, spine MRI, and lumbar puncture are required. In some cases, the diagnostic picture can be further clarified by a nerve conduction/EMG study to document a lower motor neuron type of injury.
AFM has been associated with enterovirus infections, specifically the D68 strain. This virus was first identified in 1962 and usually causes respiratory illness. In 2014, a widespread outbreak occurred that included 25 patients with AFM. Although enterovirus has been isolated from respiratory tract secretions, it has not been isolated from spinal fluid. Not all cases of AFM are associated with enterovirus infections.
The treatment for AFM is the same as for TM. Data on prognosis is limited. Recovery is most likely related to the severity of the paralysis at onset of the disease with those who are affected more completely at onset having a worse outcome.
Every child is unique and management decisions should be made in collaboration with a child neurologist with experience in these cases.
What is the evidence?
Defresne, P, Meyer, L, Tardieu, M. “Efficacy of high dose steroid therapy in children with severe acute transverse myelitis”. J Neurol Neurosurg Psychiatry. vol. 71. 2001. pp. 272-4. (Multicenter controlled study of 12 children receiving intravenous methylprednisolone compared to historic control group of 17 patients. Significant beneficial effects of treatment were reported.)
Dorsi, MJ, Belzberg, A. “Nerve transfers for restoration of upper extremity motor function in a child with upper extremity motor deficits due to transverse myelitis: Case report”. Microsurgery. vol. 32. 2012. pp. 64-67. (First case report describing this technique).
Greninger, AL, Naccache, SN, Messacar, K. “A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-2014): a retrospective study”. Lancet. vol. 15. 2015. pp. 671-682. (Describes the rare but severe complication of enterovirus D68 strain resulting in acute flaccid myelitis.)
Kerr, DA, Krishnan, C, Pidcock, FS, Singer, HS, Kossoff, EH, Hartman, AL, Crawford, TO. “Acute transverse myelitis”. 2005. pp. 445-51. (This chapter reviews treatment options and provides information regarding second and third tier treatments. It includes an instructive flow diagram.)
Pidcock, FS, Krishnan, C, Crawford, TO. “Acute transverse myelitis in childhood: center-based analysis of 47 cases”. Neurology. vol. 68. 2007. pp. 1474-80.
Ongoing controversies regarding etiology, diagnosis, treatment
The primary controversy associated with acute transverse myelitis in childhood is whether it occurs as the result of a neuroimmune response triggered by a preceding immunization. Immunization of a child who has had transverse myelitis is also controversial. In general, the need to prevent serious childhood infectious diseases outweighs the unlikely recurrence of myelitis. This is a situation where individualized clinical judgment should be applied.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has transverse myelitis? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- If you are able to confirm that the patient has transverse myelitis, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What causes this disease and how frequent is it?
- What complications might you expect from the disease or treatment of the disease?
- Are additional laboratory studies available; even some that are not widely available?
- How can transverse myelitis be prevented?
- Are there variant forms of transverse myelitis?
- What is the evidence?
- Ongoing controversies regarding etiology, diagnosis, treatment