Diagnosis and Reasoning
This 4 year old boy has developed acute generalized weakness - a distressing presentation with a wide differential diagnosis.
However, examination reveals a sensory level at C5-6, along with motor deficits below this point. This is strongly suggestive of an acute myelopathy.
The first consideration should be compressive lesions (such as neoplasms, hematomas, epidural or paraspinal abscesses, or vascular malformations), as these require urgent neurosurgical intervention.
Other causes of acute myelopathy include inflammatory etiologies such as transverse myelitis, multiple sclerosis and neuromyelitis optica; note that the acuteness of onset and rapidity of progression of symptoms make the latter two clinically less likely.
Though considered rare in the pediatric age group, anterior spinal artery syndrome is another differential diagnosis of acute myelopathy.
An urgent spinal MRI is an obvious initial investigation; this will detect any compressive lesions amenable to neurosurgical intervention, and may provide useful information if an inflammatory etiology is present.
The MRI excludes compressive lesions and reveals inflammation involving the C5-C6 spinal segments, confirmed by gadolinium enhancement; along with the clinical picture, this is sufficient to diagnose transverse myelitis.
The next step should be determination of the likely causative etiology.
Transverse myelitis is often a post-infective manifestation; thus, this could very likely be attributed to the respiratory tract infection he suffered from 10 days ago. Other possibilities to keep in mind include tuberculous myelitis and HIV induced direct transverse myelitis.
Thus, a lumbar puncture should be carried out, and serological studies performed; once results become available, these may identify the likely causative organism.
The pleocytosis and high protein level seen in this patient's cerebrospinal fluid (CSF) report provide further evidence in support of an inflammatory lesion. Note that the negative Ziehl-Neelsen stain does not necessarily exclude tuberculous myelitis.
Nerve Conduction Studies (NCS) and creatine phosphokinase (CPK) levels do not carry diagnostic value in this case.
As he is in the rapidly progressive acute phase of myelitis, IV corticosteroids are essential; this will help resolve the inflammatory process. Physiotherapy is important for his rehabilitation.
Antibiotics are not indicated as the respiratory tract infection has already resolved.
Acute transverse myelitis is a spinal cord syndrome where there is a relatively abrupt onset of motor, sensory and autonomic symptomatology due to demyelination.
Across all age populations in the United States, the incidence is reported to be 1 to 8 per million population, with approximately 20% of cases occurring in children. Two peaks of incidence are encountered in the pediatric age group: between 0 to 2 years, and between 5 to 17 years.
The pathological hallmark of transverse myelitis is the presence of focal collections of lymphocytes and monocytes, with varying degrees of demyelination and axonal degeneration in the spinal cord.
This demyelination occurs in association with acute demyelinating diseases of the central nervous system such as multiple sclerosis or neuromyelitis optica; in association with systemic autoimmune or inflammatory diseases; and idiopathically following infections or immunization; the last is postulated to be due to immune mediated inflammation resulting from exposure to viral antigens.
Infectious agents known to give rise to transverse myelitis include M. pneumoniae, viruses of the Herpesviridae family such as Cytomegalovirus, Epstein-Barr virus, and Varicella Zoster virus, and parasites such as Schistosoma spp.
M. tuberculosis and Human Immunodeficiency Virus (HIV) may also give rise to the condition.
Vaccines known to cause the disease include the oral polio vaccination, tetanus toxoid, cholera, typhoid fever, and plasma derived hepatitis B vaccine.
Note that the postinfectious, post-vaccination and idiopathic forms of transverse myelitis give rise to a monophasic syndrome, whereas demyelinating diseases and autoimmune diseases are associated with a high risk of future attacks.
The symptoms and signs depend on the level of the spinal cord affected and the extent of involvement of the long tracts.
Considering the motor system, involvement of the upper cervical segments results in respiratory paralysis due to involvement of the diaphragm (C2-C5); lesions at the thoracic level result in spastic diplegia, while involvement of the lower spine (L1-S5) gives rise to a combination of upper and lower motor neuron signs.
Note that in the acute stage, hypotonia and diminished reflexes occur due to spinal shock; this gradually changes into spasticity and exaggerated reflexes over the next couple of weeks.
The degree of sensory impairment varies depending on the extent of cord involvement; a sensory level is usually present. Neuropathic pain in the affected region is reported with lateral extension; this usually involves the sensory distribution of the diseased spinal segments.
Urinary retention is also a common early manifestation, due to autonomic involvement.
Transverse myelitis is a diagnosis of exclusion; thus conditions such as extrinsic spinal cord compression, ischemia, tumours and arteriovenous malformations should be initially excluded via neuroimaging studies.
Previous spinal irradiation and vitamin B12 deficiency can also mimic this picture, and should be excluded in the history.
The American Academy of Neurology (AAN) has defined diagnostic criteria for transverse myelitis. These include:
- Bilateral (but not necessarily symmetrical) sensorimotor and autonomic spinal cord dysfunction
- A clearly defined sensory level
- Progression to the nadir of clinical deficits between 4 hours to 21 days after the onset of symptoms
- Demonstration of spinal cord inflammation via detection of cerebrospinal pleomorphism, an elevated IgG index, or an MRI revealing a gadolinium-enhancing cord lesion
- Exclusion of compressive, postradiation, neoplastic and vascular causes.
Following establishment of the diagnosis of transverse myelitis, a search for the causative etiology should be considered; this will facilitate prediction of the course of the disease and also provide information regarding the need of prophylaxis against future neurological events.
Important infectious agents to consider include M. pneumoniae, Epstein Barr Virus (EBV), and Cytomegalovirus (CMV); these can be detected via enzyme linked immunosorbent assay (ELISA) of the cerebrospinal fluid (CSF).
Autoimmune diseases should also be excluded via assays for antinuclear antibodies (ANA), anti dsDNA antibodies, extracellular nuclear antibodies (ENA), rheumatoid factor (RFs) and antiphospholipid antibodies.
Despite conflicting reports, steroids remain the standard first line intervention for transverse myelitis.
High dose IV methylprednisolone is used (30 mg/kg/day) for 3 to 5 days in severe cases; oral regimens can be used in relatively mild episodes which do not require hospitalisation.
Potential adverse effects of pulsed corticosteroid therapy include, gastrointestinal disturbances, insomnia, headache, hyperglycemia, hypertension and glycemic imbalances.
Rescue therapy with plasma exchange may result in improvement in patients with partial sensory motor deficits who fail to respond to corticosteroid therapy.
IV immunoglobulins (which are typically dosed at 2g/kg) are considered to be another option in patients with a poor response to corticosteroids; however, at the time of writing, there is little evidence to support their use.
In patients with associated demyelinating disease, long term immunomodulatory or immunosuppressive therapy may reduce the risk of recurrence.
Rehabilitation should begin as soon as possible, with the goals being maintenance of the range of movement, stretching, and preservation of bladder and bowel continence.
The prognosis of transverse myelitis ranges from complete recovery with no residual deficits, to complete paralysis, and even death; the length of the lesion is the most important prognostic factor;
Multiple case series have shown the occurrence of complete recovery in 33% to 50% of children, with poor outcomes in 10% to 20%.
The rate of recovery varies between individuals, and also depends on the underlying cause; some persons continue to improve over as long as 2 years afterwards.
Take home messages
1. In the pediatric age group, acute myelopathy is usually due to compressive or inflammatory causes.
2. The diagnosis of transverse myelitis requires a supportive clinical picture, as well as imaging or serological evidence of spinal inflammation.
3. High dose intravenous (IV) corticosteroids are the first line of treatment.
4. Most individuals recover completely, although this may take months to years.
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