Approach
The goals of treatment are to restore neurological function lost during the acute transverse myelitis (TM) event; to initiate preventive strategies for, and symptomatic relief of, TM complications; and, when applicable, to start therapies aimed at preventing disease relapse.
Acute neurological deficits
After exclusion of compressive lesions, acute infections, and other non-TM disorders, first-line treatment of the acute neurological deficits related to TM is with intravenous methylprednisolone, typically administered daily for 3-5 consecutive days.[18] There are no controlled trials of corticosteroids for TM but the approach is extrapolated from treatment of acute multiple sclerosis (MS) attacks.
Patients with severe deficits that do not respond to corticosteroid therapy, or whose deficits worsen despite treatment, are candidates for rescue therapy with plasma exchange (plasmapheresis).[18][75][76]
Intravenous immunoglobulin (IVIG) may be considered but there are no randomised controlled trials that have assessed its efficacy.[8][18][75]
Supportive therapy and acute rehabilitation
Supportive therapy for individual symptoms such as respiratory distress, spasticity, and urinary retention may be added to the treatment regimen as required.
Respiratory failure: in a minority of patients with cervical TM, the lesion extends into the medulla and may cause neurogenic respiratory failure.[4] Close observation of respiratory parameters, including measurement of maximal respiratory pressures and forced vital capacity, and involvement of a skilled critical care team are recommended in cases of ascending cervical myelitis.
Spasticity: managed by stretching exercises, anti-spasticity drugs (e.g., baclofen, tizanidine), therapeutic botulinum toxin injections.[77]
Acute urinary retention: may be managed by bladder catheterisation. Residual neurogenic bladder symptoms may include urge incontinence, retention, or a mixed disorder, each of which requires specific treatment.[77][78]
Deep venous thrombosis (DVT) prevention: immobilised patients are at increased risk. Extrapolation of data from general medical and orthopaedic-surgery patients indicates that subcutaneous heparin or enoxaparin plus use of lower extremity compression stockings or devices reduces the risk of DVT.
Acute rehabilitation consists of passive and active therapy to maintain the range of motion of limbs, reduce spasms and the risk of contractures, and to reduce risk of decubitus ulceration.
Preventive therapy for patients with idiopathic TM or at risk of developing MS
If the final diagnosis is idiopathic TM, no preventive therapy is required.
MS disease-modifying therapy, aimed at reducing the risk of MS relapses and disability progression, may be indicated for patients with acute partial TM who are deemed to be at risk for development of MS due to the presence of typical demyelinating lesions on magnetic resonance imaging (MRI).[45][46][79][80]
There is also a high risk of relapse if patients remain seropositive for myelin oligodendrocyte glycoprotein (MOG)-IgG. The treatment approach includes an extended taper of oral prednisolone over 4-6 months with serological reassessment and initiation of immunosuppressive preventive therapy (such as azathioprine, mycophenolate, or rituximab) if MOG-IgG antibody persists or there is interim clinical relapse.[57][58]
Preventive therapy for patients at risk of recurrent TM: aquaporin-4 (AQP4) auto-antibody seropositive
Immunosuppressive therapy of indefinite duration is recommended for patients who are seropositive for AQP4 auto-antibody because of a persistent high relapse risk.[5]
Typically, immunosuppressants (e.g., rituximab, azathioprine, mycophenolate) have been used as preventive treatments for neuromyelitis optica spectrum disorder (NMOSD), and may still be used in some centres.[81][82][83][84] However, targeted therapies are now approved for the treatment of AQP4-seropositive NMOSD including eculizumab, ravulizumab, inebilizumab, and satralizumab, and are the preferred option.[85]
Eculizumab
A monoclonal antibody that binds to complement protein C5 and inhibits activation of the terminal component of complement, which is key in the pathogenesis of NMOSD.
The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved eculizumab for the treatment of NMOSD in adults who are anti-AQP4 antibody positive.
In a randomised, double-blind, phase 3 clinical trial among patients with AQP4-seropositive NMOSD, patients treated with eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression.[86]
Eculizumab increases the risk of life-threatening and potentially fatal infections caused by Neisseria meningitidis. Completed or updated vaccination for meningococcal bacteria (serogroups A, C, W, Y, and B) is recommended at least 2 weeks prior to the first dose of eculizumab, unless the risks of delaying therapy outweigh the risk of developing a serious infection in which case antibacterial prophylaxis is recommended. Monitor all patients for early signs and symptoms of meningococcal infection during treatment and evaluate immediately if infection is suspected.
Eculizumab is only available through a restricted distribution programme in some countries.
Ravulizumab
A monoclonal antibody that binds to complement protein C5 and inhibits activation of the terminal component of complement, which is key in the pathogenesis of NMOSD. It has a longer half-life compared with eculizumab, and therefore, requires less frequent dosing.
The FDA and EMA have approved ravulizumab for the treatment of NMOSD in adults who are anti-AQP4 antibody positive.
One phase 3 open-label, externally controlled interventional study, found that ravulizumab significantly decreased the risk of patients with AQP4+ NMOSD, with safety profiles similar to those of eculizumab and ravulizumab. No patients relapsed during the period of study (73.5 weeks), and the study showed a reduction in relapse risk of 98.6%.
Ravulizumab increases the risk of life-threatening and potentially fatal infections caused by Neisseria meningitidis. Completed or updated vaccination for meningococcal bacteria (serogroups A, C, W, Y, and B) is recommended at least 2 weeks prior to the first dose of eculizumab, unless the risks of delaying therapy outweigh the risk of developing a serious infection in which case antibacterial prophylaxis is recommended. Monitor all patients for early signs and symptoms of meningococcal infection during treatment and evaluate immediately if infection is suspected.
Ravulizumab is only available through a restricted distribution programme in some countries.
Inebilizumab
A monoclonal antibody that binds to the cell surface antigen CD19 on B-cell lymphocytes.
The FDA and EMA have approved inebilizumab for the treatment of NMOSD in adults who are anti-AQP4 antibody positive.
In a randomised, placebo-controlled, phase 2/3 clinical trial among patients with NMOSD, 21 (12%) of 174 participants receiving inebilizumab had an NMOSD attack, versus 22 (39%) of 56 participants receiving placebo. The rate of occurrence of adverse events was similar in the two groups.[87]
Inebilizumab has been associated with infusion reactions and premedication is required prior to infusion. Hepatitis B and tuberculosis (TB) screening, and serum immunoglobulin testing are recommended before starting treatment.
Satralizumab
A monoclonal antibody targeting the interleukin (IL)-6 receptor.
The FDA and EMA have approved satralizumab for the treatment of NMOSD in adults who are anti-AQP4 antibody positive.
In a randomised, double-blind, phase 3 trial among patients with NMOSD receiving immunosuppressant treatment, relapse occurred in 8 patients (20%) in the satralizumab arm versus 18 (43%) receiving placebo.[88] There was no significant difference in effect between the trial groups in pain and fatigue. In a subsequent phase 3, double-blind, parallel-group trial, relapse occurred in 19 (30%) patients with NMOSD receiving satralizumab monotherapy versus 16 (50%) receiving placebo.[89] In both trials, the rate of serious adverse events and infections were similar between groups.[88][89]
Hepatitis B and TB screening, and liver function testing are recommended before starting treatment.
Rituximab
A monoclonal antibody directed against the CD20 antigen on B cells.
Clinical effectiveness in NMOSD has been demonstrated in various retrospective and prospective studies with a reduction in attack rates by over 80%.[90]
One multi-centre, randomised, double-blind, placebo-controlled trial found rituximab prevented relapses for 72 weeks in patients with NMOSD who were AQP4 antibody-positive.[91]
Rituximab is more efficacious than azathioprine and mycophenolate.[90] However, studies have not compared rituximab to the newer targeted therapies as yet.
Serious and fatal infusion reactions can occur and patients should be monitored closely during the infusion. Other serious adverse effects include severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy.
Azathioprine and mycophenolate
Azathioprine and mycophenolate may still be used in some centres where targeted therapies are not an option or are contraindicated.
These drugs are associated with haematological abnormalities, an increased risk of infections, raised liver enzymes, and gastrointestinal adverse effects. Full blood count and liver function tests should be monitored during treatment.
Preventive therapy for patients at risk of recurrent TM: myelin oligodendrocyte glycoprotein (MOG)-IgG auto-antibody seropositive
In patients who are seropositive for MOG-IgG auto-antibody, preventive therapy may not be necessary after a first clinical event as some patients remain monophasic. A prolonged corticosteroid taper is often recommended to prevent early relapses.
After a clinical relapse (TM or other), treatment options may include azathioprine, mycophenolate, rituximab, IVIG, or tocilizumab.
Immunosuppressants
Several immunosuppressive treatments have been tried such as azathioprine, mycophenolate, and rituximab.[57][58][92]
IVIG
One 2022 retrospective multi-centre cohort study suggests that maintenance therapy with IVIG is associated with lower relapse risk in adults with MOG antibody-associated disease (MOGAD).[93]
Tocilizumab
Tocilizumab, an IL-6 receptor antagonist, is another treatment option.
One retrospective multi-centre study carried out in 2021 observed that patients with MOGAD or AQP4-seropositive NMOSD showed a 80% decrease in annual relapse rate during tocilizumab treatment (tocilizumab is not typically used in practice for AQP4-seropositive NMOSD).[94]
Tocilizumab is associated with an increased risk of serious infections that may lead to hospitalisation or death (e.g., active TB, invasive fungal infections, opportunistic infections). Most patients were taking other immunosuppressants. Patients should be monitored closely during treatment.
Use of this content is subject to our disclaimer