Transverse myelitis

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By Anthony T Reder MD

Transverse myelitis is a diagnosis of exclusion. Potentially treatable diseases such as cord compression, local tumor, paraneoplastic disease, infection, vascular causes, and connective tissue diseases must be ruled out.

Symptom management. Most patients with transverse myelitis will have paraplegia of the lower limbs for weeks or months, and in some the paresis is permanent. Prevention of deep vein thrombosis and decubitus ulcers is essential. Spastic legs can be relaxed with physical therapy with active and passive range of motion exercises and stretching plus baclofen, tizanidine, benzodiazepines, or dantrolene (removed from some markets including the United States). Intrathecal baclofen is useful for severe spasticity unrelieved by oral drugs. Weakness may be improved with amantadine, methylphenidate, and 4-aminopyridine and 3,4-diaminopyridine (fampridine).

Autonomic instability from disruption of sympathetic feedback may increase sensitivity to pain. Central neuropathic pain in multiple sclerosis, and presumably in some cases of transverse myelitis, is strongly linked to T1-T6 cord lesions. These lesions disrupt the longitudinally-extensive intermediomedial nucleus that surrounds the midthoracic central canal (Okuda et al 2014). Pain is usually not a problem after the initial symptoms resolve, but pain may be relieved with muscle stretching or by therapy with gabapentin, carbamazepine, phenytoin, amitriptyline, or oral or intrathecal baclofen (Herman et al 1992). Orthostatic hypotension can be treated with compression stockings, hydration, salt, and fludrocortisone or midodrine.

Anticholinergics can reduce urinary frequency caused by a spastic bladder. Self-catheterization is far superior to indwelling catheters for treatment of incontinence. Recurrent urinary tract infections after apparent recovery should be investigated; they suggest a second insult from multiple sclerosis. Acute and chronic rehabilitation is helpful for recovery from transverse myelitis (Krishnan et al 2004). Maximization of load bearing in affected limbs, optimization of sensory cues, and patterned nonspecific training, as well as functional electrical stimulation and neurotrophin induction have been detailed (Sadowsky et al 2011).

Treating the underlying disease process. Transverse myelitis has traditionally been treated with oral or intravenous glucocorticoids or intravenous adrenocorticotropic hormone. High-dose intravenous steroid therapy is associated with prompt clinical improvement (Dowling et al 1980; Kennedy and Weir 1988). Oral and intravenous steroids and IVIG had no effect on eventual outcome in a retrospective study of 50 Japanese children (Miyazawa et al 2003). Lessons from the treatment of other demyelinating diseases may also be relevant because they share many of the clinical and pathological facets of transverse myelitis. In multiple sclerosis, glucocorticoid or adrenocorticotropic hormone therapy shortens the duration of symptoms but glucocorticoids do not change the long-term outlook. In optic neuritis, high-dose intravenous methylprednisolone improves vision and appears to prevent recurrences compared to oral prednisone alone or placebo (Beck et al 1992). A more prolonged steroid taper than that described by Beck and colleagues may be advisable based on a rat model of postvaccinal encephalomyelitis (Reder et al 1994), hard data in humans are lacking. Similarly, acute disseminated encephalomyelitis responds dramatically to glucocorticoids, but symptoms flare up on sudden withdrawal (Ziegler 1966), so a taper is advised. Idiopathic transverse myelitis, however, may have a different pathogenesis than these diseases.

Therapy to prevent future attacks must weigh the odds of subsequent multiple sclerosis versus the cost and side effects of partially effective drugs. Multiple sclerosis is often associated with transverse myelitis.

Interferon-beta and glatiramer acetate reduce the number and severity of multiple sclerosis relapses and decrease the lesion load on MRI scans (Interferon-Beta Multiple Sclerosis Study Group 1993; Johnson et al 1998; Jacobs et al 2000). These drugs also have clear benefit in controlled trials of clinically isolated syndromes, including transverse myelitis, but these study patients had associated brain MRI lesions. Because transverse myelitis may be a forme fruste of multiple sclerosis, interferon or glatiramer acetate therapy should be considered if multiple sclerosis is of high probability—when there is a family history of multiple sclerosis, brain MRI lesions, positive CSF oligoclonal bands, and positive evoked potentials.

A number of studies from the Mayo Clinic and other case reports suggest that plasma exchange can benefit severe attacks of CNS demyelination (Keegan et al 2002; Greenberg et al 2007). Anecdotal evidence suggests azathioprine or cyclophosphamide therapy is helpful (Greenberg et al 2007), but this sample included many cases of other autoimmune diseases causing transverse myelitis (Kumar et al 2008) and these drugs are not FDA-approved for therapy of multiple sclerosis and transverse myelitis.

Recurrent transverse myelitis would appear to be a form of multiple sclerosis, although according to Scott it infrequently develops into multiple sclerosis when the brain MRI is negative (Scott 2007). Approved disease-modifying drugs are likely to be most effective in preventing further attacks.

If serum NMO-IgG antibodies are positive, the disease is quite different from multiple sclerosis or idiopathic transverse myelitis. In this case, intravenous immunoglobulin, plasmapheresis, and natalizumab can be considered, but rituximab is likely to be the best therapy (Cree et al 2005). Interferon beta may be unhelpful or dangerous in patients with positive NMO-IgG or CNS Sjögren disease (Javed et al 2008).

One patient may have improved with intrathecal acidic fibroblast growth factor.

Tumor necrosis factor blockers, effective in rheumatoid arthritis, have precipitated transverse myelitis and other demyelinating syndromes.

In This Article

Historical note and nomenclature
Clinical manifestations
Clinical vignette
Pathogenesis and pathophysiology
Differential diagnosis
Diagnostic workup
Prognosis and complications
References cited