Version May 2024
INTRODUCTION — Acute transverse myelitis (TM) is a rare, acquired neuroimmune spinal cord disorder that can present with the rapid onset of weakness, sensory alterations, and bowel or bladder dysfunction. TM can occur as an independent entity, usually as a postinfectious complication, but TM also exists on a continuum of neuroinflammatory disorders that includes acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), and acute flaccid myelitis (AFM). The clinical features, diagnostic workup, and acute and chronic therapies differ among these forms of TM.
This topic will review the treatment and prognosis of acute TM. Other aspects of TM are discussed separately. (See "Transverse myelitis: Etiology, clinical features, and diagnosis".)
IDIOPATHIC TRANSVERSE MYELITIS — TM is considered idiopathic when the cause is not identified despite a comprehensive evaluation. (See "Transverse myelitis: Etiology, clinical features, and diagnosis", section on 'Idiopathic'.)
Initial therapy of idiopathic TM — Acute attacks of idiopathic TM are typically treated with a short course of high-dose intravenous glucocorticoids, with or without plasma exchange (PLEX).
TM without motor impairment — We suggest high-dose intravenous glucocorticoid treatment for patients with acute idiopathic TM. Glucocorticoid treatment should be started as soon as possible; there are few contraindications. Thus, a clinician does not need to wait for the workup to be complete before starting therapy.
●Glucocorticoid regimens – Our preferred regimens are methylprednisolone (30 mg/kg up to 1000 mg daily) or dexamethasone (120 to 200 mg daily for adults) for three to five days. A longer glucocorticoid treatment course or more aggressive regimens may be warranted based upon the clinical course and radiologic parameters; examples include patients with severe sensory deficits that affect activities of daily living, lesions near the brainstem, or poor response to initial therapy with minimal improvement of lesion enhancement on magnetic resonance imaging (MRI).
●Adverse effects – Short-term high-dose glucocorticoid therapy is associated with relatively few side effects in most patients, although mental status changes, increased susceptibility to infection, and gastric disturbance are potential complications. Psychiatric adverse effects can include increased depressive, manic, and hypomanic symptoms [1,2]. To mitigate these adverse effects, strategies include the prophylactic use of a proton pump inhibitor in the morning and/or low-dose clonazepam as needed at night while on glucocorticoid treatment. Patients with diabetes mellitus may need to be hospitalized to monitor glucose levels.
Intravenous glucocorticoids have long been considered the standard of care and first-line therapy in acute idiopathic TM. Even without placebo-controlled trials evaluating glucocorticoids specifically in TM [3], there is evidence that intravenous glucocorticoids are effective in the short term in acute inflammatory central nervous system (CNS) diseases like TM, such as multiple sclerosis. (See "Treatment of acute exacerbations of multiple sclerosis in adults", section on 'Initial therapy with glucocorticoids'.)
TM with motor impairment — In addition to high-dose glucocorticoid therapy (see 'TM without motor impairment' above), we suggest treatment with PLEX for patients who have acute TM with motor impairment [4]. While there is a lack of prospective studies determining the best timing and sequencing of PLEX relative to glucocorticoids, there are studies that have supported a unique response to PLEX for patients with anti-aquaporin 4 (AQP4)-mediated myelitis [5,6]. Better outcomes have been observed in patients with earlier PLEX. Given that patients with a first event of TM require intervention before all test results are back, it is our practice to start PLEX early after admission for patients with significant deficits; waiting until glucocorticoid treatments are completed is not necessary.
●PLEX regimens – Our preferred regimen is five to seven treatments, each with exchanges of 1.1 to 1.5 plasma volumes, every other day for 8 to 14 days; alternatively, the first two PLEX treatments can be given on successive days, with the remaining three treatments given every other day [7]. Most patients can receive albumin instead of plasma as the replacement fluid, but fibrinogen levels should be monitored.
●Adverse effects of PLEX – Complications of PLEX are presented separately. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology" and "Therapeutic apheresis (plasma exchange or cytapheresis): Complications".)
Retrospective observational studies suggest that PLEX may be effective for some patients with acute CNS demyelinating diseases, including patients with severe idiopathic TM, who fail to respond to high-dose glucocorticoid treatment [8-12].
Subsequent therapy for patients who progress — For patients who continue to progress despite intravenous glucocorticoid and PLEX treatment, we confirm the diagnosis of idiopathic TM with special attention to ruling out vascular myelopathies. We then consider the use of intravenous cyclophosphamide (800 to 1200 mg/m2 administered as a single pulse dose) [13], using shared decision-making discussions with the patient that emphasize uncertain benefits and potential harms of treatment, including hemorrhagic cystitis and cytopenia.
Recurrent idiopathic TM — For patients with recurrent idiopathic TM, chronic immunomodulatory therapy is a reasonable treatment option. Each acute event is treated with steroids with or without PLEX as noted above (see 'Initial therapy of idiopathic TM' above), and we repeat the work-up to look for an underlying cause. When a systemic cause cannot be found, we offer patients treatment with mycophenolate (2 to 3 g daily) or intravenous rituximab (1000 mg every six months) in a shared decision-making process, but other immunosuppressive regimens may be used in patients with systemic inflammatory disease [14].
Symptomatic care
Rehabilitation — Rehabilitation after TM is poorly studied, but the problems are similar to those encountered with recovery from spinal cord injury in general, where more published evidence is available [13]. (See "Chronic complications of spinal cord injury and disease".)
Most patients with acute TM will need acute rehabilitation, while approximately two-thirds will need long-term rehabilitation [15].
Physical and occupational therapy for acute TM should be started early (as soon as the patient is medically stable) to begin strengthening, range-of-motion, and compensatory strategies along with assessment and fitting for assistive devices [13]. These measures help to improve function and avoid problems like skin breakdown and joint contractures.
Complications of TM — Sequelae of TM may include a number of complications and residual effects including bladder and bowel dysfunction, sexual dysfunction, skin breakdown, spasticity, pain, immobility, loss of self-care (eg, bathing, dressing, eating), and psychosocial problems including depression and suicidality [13].
Management of specific complications is reviewed separately:
●Bowel dysfunction (see "Chronic complications of spinal cord injury and disease", section on 'Gastrointestinal complications')
●Bladder dysfunction (see "Chronic complications of spinal cord injury and disease", section on 'Bladder dysfunction')
●Sexual dysfunction (see "Chronic complications of spinal cord injury and disease", section on 'Sexual dysfunction')
●Skin breakdown (see "Chronic complications of spinal cord injury and disease", section on 'Pressure ulcers')
●Spasticity (see "Chronic complications of spinal cord injury and disease", section on 'Spasticity')
●Pain (see "Chronic complications of spinal cord injury and disease", section on 'Pain syndromes')
●Immobility (see "Chronic complications of spinal cord injury and disease", section on 'Musculoskeletal complications' and "Chronic complications of spinal cord injury and disease", section on 'Functional deficits')
●Psychosocial problems (see "Chronic complications of spinal cord injury and disease", section on 'Psychiatric complications')
Prognosis
Recovery — Most patients with idiopathic TM have at least a partial recovery, which usually begins within one to three months and continues with exercise and rehabilitation therapy [16]. Recovery can proceed over years. Older studies reported that some degree of disability persisted in approximately 40 percent of patients [16,17]. These outcomes, however, were recorded before neuromyelitis optica spectrum disorder (NMOSD) was clearly defined as a disease and during a period when patients were not routinely treated with PLEX acutely. We suspect that the outcomes have improved over time.
A very rapid onset with paraplegia and spinal shock has been associated with poorer outcomes [16,18-20]. Age younger than three years at onset of TM has also been associated with a poorer outcome in one case series [17].
Research is needed to define biomarkers of disease that predict outcome and risk of recurrence. Ongoing aggressive rehabilitation with activity-based therapy is recommended in these patients. (See 'Rehabilitation' above.)
Recurrence — The majority of patients with idiopathic TM experience a monophasic disease. Recurrence has been reported in 25 to 33 percent of patients with idiopathic TM [21-23], but these studies include cohorts that predated the widespread use of testing for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) immune globulin G (IgG) autoantibodies. In addition, TM can recur in a subset of patients with a history of systemic autoimmune disease. With disease-associated TM, the recurrence rate may be as high as 70 percent [24-26].
Features present at the time of the initial acute onset of TM that may predict recurrence (table 1) include the following [23,27]:
●Multifocal or longitudinally extensive lesions in the spinal cord on MRI
●Brain lesions on MRI
●Presence of one or more autoantibodies (antinuclear antibody [ANA], double-stranded deoxyribonucleic acid [dsDNA], phospholipid, cytoplasmic antineutrophil cytoplasmic antibodies [c-ANCA])
●Underlying mixed connective tissue disease
●Presence of oligoclonal bands in the cerebrospinal fluid
●Seropositivity for AQP4 IgG autoantibody (see "Neuromyelitis optica spectrum disorder (NMOSD): Clinical features and diagnosis", section on 'AQP4 autoantibody')
●Persistent seropositivity for the MOG IgG autoantibody (see "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Clinical features and diagnosis", section on 'MOG autoantibody')
In patients with acute complete idiopathic TM (ie, with complete or near complete neurologic deficits including paresis, sensory loss, and autonomic dysfunction below the level of the lesion), MRI of the brain is almost always normal. These patients are less likely to present with oligoclonal bands, less likely to relapse with a second bout of myelitis, and less likely to transition to clinically definite multiple sclerosis. (See 'Progression to multiple sclerosis' below.)
Progression to multiple sclerosis — The risk of progression to multiple sclerosis for patients presenting with acute TM is reviewed in detail separately. (See "Management of clinically and radiologically isolated syndromes suggestive of multiple sclerosis", section on 'Risk of progression to multiple sclerosis'.)
SECONDARY (DISEASE-RELATED) TRANSVERSE MYELITIS
CNS demyelinating disorders — TM is a common manifestation of multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and acute disseminated encephalomyelitis (ADEM).
●Acute treatment – Acute attacks of TM in patients with most types of central nervous system (CNS) demyelinating disorders are typically treated with a short course of high-dose intravenous glucocorticoids and, in cases of NMOSD or patients with significant motor deficits, with adjunctive plasma exchange (PLEX). The treatment of these conditions is reviewed in detail elsewhere:
•Multiple sclerosis (see "Treatment of acute exacerbations of multiple sclerosis in adults", section on 'Initial therapy with glucocorticoids')
•NMOSD (see "Neuromyelitis optica spectrum disorder (NMOSD): Treatment and prognosis", section on 'Acute treatment')
•ADEM (see "Acute disseminated encephalomyelitis (ADEM) in adults", section on 'Initial therapy' and "Acute disseminated encephalomyelitis (ADEM) in children: Treatment and prognosis", section on 'Initial immunotherapy')
●Attack prevention – Prevention of recurrent attacks for secondary (disease-related) TM due to CNS demyelinating disorders primarily involves immune-modulating disease-modifying therapy, as reviewed separately:
•Multiple sclerosis (see "Management of clinically and radiologically isolated syndromes suggestive of multiple sclerosis" and "Initial disease-modifying therapy for relapsing-remitting multiple sclerosis in adults" and "Treatment and prognosis of pediatric multiple sclerosis" and "Treatment of secondary progressive multiple sclerosis in adults" and "Treatment of primary progressive multiple sclerosis in adults")
•NMOSD (see "Neuromyelitis optica spectrum disorder (NMOSD): Treatment and prognosis", section on 'Attack prevention')
Systemic autoimmune disorders — Acute attacks of TM in patients with most types of systemic autoimmune disorders are typically treated with a short course of high-dose intravenous glucocorticoids, with or without PLEX, similar to acute idiopathic TM (see 'Initial therapy of idiopathic TM' above). However, in severe cases of myelitis secondary to systemic lupus erythematosus, cyclophosphamide may be beneficial. In the clinical experience of the authors, intravenous cyclophosphamide for patients with aggressive TM has been associated with good outcomes, but this was most notable in patients with systemic lupus erythematosus. One small, uncontrolled observational study provides additional limited support for the use of cyclophosphamide in this subset of patients [11]. Given the methodologic limitations of this study, this finding requires confirmation in randomized controlled trials.
The approach to the treatment of acute TM, attack prevention, and maintenance therapy for several systemic inflammatory disorders is discussed elsewhere:
●Behçet syndrome (see "Treatment of Behçet syndrome", section on 'Neurologic disease')
●Sarcoidosis (see "Neurologic sarcoidosis", section on 'Treatment')
●Sjögren’s disease (see "Neurologic manifestations of Sjögren's disease", section on 'Focal or multifocal demyelination/inflammation')
●Systemic lupus erythematosus (see "Neurologic and neuropsychiatric manifestations of systemic lupus erythematosus", section on 'Myelitis')
Paraneoplastic disorders — Treatment for TM due to a paraneoplastic etiology includes glucocorticoids and PLEX as described above for acute idiopathic TM (see 'Initial therapy of idiopathic TM' above), but long-term remission is based on therapy directed at the underlying malignancy, along with immunotherapy in most cases [28,29]. (See "Overview of paraneoplastic syndromes of the nervous system", section on 'Treatment and prognosis'.)
Infectious causes — Treatment of acute attacks of TM in rare patients with an infectious cause varies according to the specific infectious agent (table 2). Glucocorticoids and antiviral agents are often used for acute TM associated with viral infections, but there is no high-quality evidence or consensus about management, and the use of anti-inflammatory therapies is controversial.
Refer to individual UpToDate topic reviews for specific antiviral and antimicrobial treatment recommendations.
●(See "Acute flaccid myelitis", section on 'Treatment'.)
●(See "Treatment and prevention of West Nile virus infection".)
●(See "Treatment of herpes zoster", section on 'Neurologic complications'.)
●(See "Central nervous system tuberculosis: Treatment and prognosis", section on 'Transverse myelitis'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Multiple sclerosis and related disorders".)
SUMMARY AND RECOMMENDATIONS
●Acute treatment for idiopathic transverse myelitis (TM)
•TM without motor impairment – For patients with acute idiopathic TM, we suggest high-dose intravenous glucocorticoid treatment (Grade 2C). Our preferred regimens are methylprednisolone (30 mg/kg up to 1000 mg daily) or dexamethasone (up to 200 mg daily for adults) for three to five days. (See 'TM without motor impairment' above.)
•TM with motor impairment – For patients with acute TM complicated by motor impairment, we suggest plasma exchange (PLEX) in addition to glucocorticoid treatment (Grade 2C). Our preferred regimen is five treatments, each with exchanges of 1.1 to 1.5 plasma volumes, every other day for 10 days; alternatively, the first two PLEX treatments can be given on successive days, with the remaining three treatments given every other day. (See 'TM with motor impairment' above.)
●Progression despite initial therapy – For patients with TM who continue to progress despite intravenous glucocorticoid and PLEX treatment, we confirm the diagnosis of idiopathic TM with special attention to ruling out vascular myelopathies. We then consider the use of intravenous cyclophosphamide, using shared decision-making discussions with the patient. (See 'Subsequent therapy for patients who progress' above.)
●Attack prevention – For patients with recurrent idiopathic TM, chronic immunomodulatory therapy is a reasonable treatment option, but supportive evidence is sparse. Using a shared decision-making process, we offer patients treatment with mycophenolate (2 to 3 g daily) or intravenous rituximab (1000 mg every six months), but other immunosuppressive regimens may be used in patients with systemic inflammatory disease [14]. (See 'Recurrent idiopathic TM' above.)
●Complications of TM – Sequelae of TM may include several complications and residual effects including bladder and bowel dysfunction, sexual dysfunction, skin breakdown, spasticity, pain, immobility, loss of self-care (eg, bathing, dressing, eating), and psychosocial problems including depression and suicidality. Physical and occupational therapy for acute TM should be started early (as soon as the patient is medically stable). The management of specific complications is reviewed separately, with links to appropriate UpToDate topics listed above. (See 'Rehabilitation' above.)
●Prognosis of idiopathic TM
•Degree of recovery – Most patients with idiopathic TM have at least a partial recovery, which usually begins within one to three months and continues with exercise and rehabilitation therapy. Some degree of persistent disability is common. A very rapid onset with complete paraplegia and spinal shock has been associated with poorer outcomes. Recovery can continue over years. (See 'Recovery' above.)
•Risk of recurrence – Most patients with TM experience monophasic disease. Recurrence has been reported in 25 to 33 percent of patients with idiopathic TM, although this usually signals a systemic condition. With disease-associated (secondary) TM, the recurrence rate may be as high as 70 percent. (See 'Recurrence' above.)
•Risk of multiple sclerosis – The risk of progression to multiple sclerosis for patients presenting with acute TM is reviewed in detail separately. (See "Management of clinically and radiologically isolated syndromes suggestive of multiple sclerosis", section on 'Risk of progression to multiple sclerosis'.)
●Secondary (disease-related) TM – The treatment of TM due to central nervous system (CNS) demyelinating disorders, systemic autoimmune disorders, paraneoplastic disorders, and infectious causes is reviewed separately, with links to appropriate UpToDate topics listed above. (See 'Secondary (disease-related) transverse myelitis' above.)
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