Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute neurological deficits

1st line – corticosteroid

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ACUTE
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acute neurological deficits
1st line – 

corticosteroid

First-line treatment of the acute neurological deficits related to transverse myelitis (TM) is with intravenous methylprednisolone, typically administered daily for 3-5 consecutive days.[18] Some clinicians follow the intravenous therapy with an oral corticosteroid taper for 5-14 days.

There are no controlled trials of corticosteroids for TM, but the approach is extrapolated from treatment of acute multiple sclerosis (MS) attacks. Treatment with intravenous methylprednisolone is associated with more rapid recovery of neurological deficits in MS, and clinical experience suggests similar results in TM.[77]

Adverse effects of corticosteroids include hyperglycaemia, hypertension, paraesthesias, tremor, anxiety, insomnia, and increased risk of infection, but resolve quickly after therapy is discontinued.

Primary options

methylprednisolone: 1000 mg intravenously once daily for 3-5 days

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Consider – supportive care + acute rehabilitation

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ACUTE
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acute neurological deficits
Consider – 

supportive care + acute rehabilitation

Additional treatment recommended for SOME patients in selected patient group

In a minority of patients with cervical transverse myelitis, 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 is managed by stretching exercises, anti-spasticity drugs (e.g., baclofen, tizanidine), and therapeutic botulinum toxin injections.[77]

Acute urinary retention may be managed by bladder catheterisation.

Deep vein thrombosis prophylaxis (heparin or enoxaparin with compression) should always be considered in immobilised patients.

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.

2nd line – plasma exchange (plasmapheresis) or intravenous immunoglobulin (IVIG)

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ACUTE
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acute neurological deficits
2nd line – 

plasma exchange (plasmapheresis) or intravenous immunoglobulin (IVIG)

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.[18][75][76]

A randomised controlled crossover trial for patients with severe, corticosteroid-refractory central nervous system demyelinating events showed that clinically meaningful improvement occurred more frequently during plasma exchange (42%) compared with sham exchange (6%).[75] This study included some patients with transverse myelitis. The protocol utilised a total of 7 exchanges administered every other day. Risks of plasma exchange include line infection, sepsis, thrombosis, and bleeding.

IVIG may be considered but there are no randomised controlled trials that have assessed its efficacy.[8][18][75]

Primary options

normal immunoglobulin human: consult specialist for guidance on dose

Consider – supportive care + acute rehabilitation

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ACUTE
|
acute neurological deficits
Consider – 

supportive care + acute rehabilitation

Additional treatment recommended for SOME patients in selected patient group

In a minority of patients with cervical transverse myelitis, 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 is 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.

Deep vein thrombosis prophylaxis should always be considered in immobilised patients.

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.

ONGOING

idiopathic transverse myelitis (TM)

1st line – observation

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ONGOING
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idiopathic transverse myelitis (TM)
1st line – 

observation

If the final diagnosis is idiopathic transverse myelitis (TM), no preventive therapy is required.

Therapy aimed at preventing future attacks is not required for single-event TM, where diagnostic evaluation does not reveal risk for recurrent events or a specific underlying diagnosis.

at risk for multiple sclerosis (MS) (typical demyelinating lesions on MRI)

1st line – multiple sclerosis (MS) disease-modifying therapies

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ONGOING
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at risk for multiple sclerosis (MS) (typical demyelinating lesions on MRI)
1st line – 

multiple sclerosis (MS) disease-modifying therapies

Acute partial transverse myelitis is associated with high risk for multiple sclerosis (MS) when the brain MRI shows typical demyelinating lesions.

Disease-modifying therapies aim to reduce the risk of MS relapses and disability progression. Selection of initial therapy is guided by characteristics of the disease course, imaging findings, and patient characteristics and preferences. The 2018 American Academy of Neurology practice guidelines on disease-modifying therapies for people with MS address questions such as how to select the initial therapy and subsequent therapies, how best to monitor treatment response, and when to switch or discontinue treatment.[80] For detailed information on the management of MS, please see our Multiple sclerosis topic.

aquaporin-4 (AQP4) auto-antibody seropositive

1st line – immunosuppressive treatment

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ONGOING
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aquaporin-4 (AQP4) auto-antibody seropositive
1st line – 

immunosuppressive treatment

Longitudinally extensive transverse myelitis (TM) should prompt testing for aquaporin-4 (AQP4)-IgG antibodies.[9][21]​​ AQP4-IgG seropositive patients have a very high risk for recurrent TM or optic neuritis (more than 50% risk of recurrence at 1 year).[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, is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) 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, is approved by the FDA and EMA for the treatment of NMOSD in adults who are anti-AQP4 antibody positive. It has a longer half-life compared with eculizumab, and therefore, requires less frequent dosing. 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%.[95] 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, is approved by the FDA and EMA 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 screening, and serum immunoglobulin testing are recommended before starting treatment.

Satralizumab, a monoclonal antibody targeting the interleukin (IL)-6 receptor, is approved by the FDA and EMA 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 tuberculosis screening, and liver function testing are recommended before starting treatment.

Rituximab, a monoclonal antibody directed against the CD20 antigen on B cells, may also be used in patients who are AQP4 antibody-positive. Its clinical effectiveness in NMOSD has been demonstrated in various retrospective and prospective studies with a reduction in attack rates by over 80%.[90] One mult-icentre, 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 may still be used in some centres where targeted therapies are not an option or are contraindicated. These drugs are associated with hematologic abnormalities, an increased risk of infections, elevated liver enzymes, and gastrointestinal adverse effects. Full blood count and liver function tests should be monitored during treatment.

Primary options

eculizumab: 900 mg intravenously once weekly for 4 weeks, followed by 1200 mg once weekly for 1 week, then 1200 mg every 2 weeks

OR

ravulizumab: 40-59 kg body weight: 2400 mg intravenously as single dose, followed by 3000 mg every 8 weeks (starting 2 weeks after the first dose); 60-99 kg body weight: 2700 mg intravenously as single dose, followed by 3300 mg every 8 weeks (starting 2 weeks after the first dose); ≥100 kg body weight: 3000 mg intravenously as single dose, followed by 3600 mg every 8 weeks (starting 2 weeks after the first dose)

OR

inebilizumab: 300 mg intravenously on day 1, followed by 300 mg after 2 weeks, then 300 mg every 6 months (starting 6 months after the first dose)

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OR

satralizumab: 120 mg subcutaneously every 2 weeks for 3 doses (weeks 0, 2, and 4), followed by 120 mg every 4 weeks

Secondary options

rituximab: 1000 mg intravenously every 2 weeks for 2 doses (or 375 mg/square metre of body surface area once weekly for 4 doses), followed by 500-1000 mg every 6 months

Tertiary options

azathioprine: 2.5 to 3 mg/kg orally once daily

OR

mycophenolate mofetil: 1-2 g/day orally given in 2 divided doses

myelin oligodendrocyte glycoprotein-IgG auto-antibody seropositive

1st line – consider immunosuppressive treatment

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ONGOING
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myelin oligodendrocyte glycoprotein-IgG auto-antibody seropositive
1st line – 

consider immunosuppressive treatment

Longitudinally extensive transverse myelitis (TM) should prompt testing for myelin oligodendrocyte glycoprotein (MOG)-IgG antibodies.[9][21]

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), several immunosuppressive treatments have been tried such as azathioprine, mycophenolate, and rituximab.[57][58][92]

One 2022 retrospective multi-centre cohort study suggests that maintenance therapy with intravenous immunoglobulin is associated with lower relapse risk in adult patients with MOG antibody-associated disease (MOGAD).[93]

Tocilizumab, an interleukin (IL)-6 receptor antagonist, is also an option. One retrospective multi-centre study carried out in 2021 observed that patients with MOGAD showed a 80% decrease in annual relapse rate during tocilizumab treatment.[94] Tocilizumab is associated with an increased risk of serious infections that may lead to hospitalisation or death (e.g., active tuberculosis, invasive fungal infections, opportunistic infections). Most patients were taking other immunosuppressants. Patients should be monitored closely during treatment.

Primary options

azathioprine: consult specialist for guidance on dose

OR

mycophenolate mofetil: consult specialist for guidance on dose

OR

rituximab: consult specialist for guidance on dose

OR

normal immunoglobulin human: consult specialist for guidance on dose

OR

tocilizumab: consult specialist for guidance on dose

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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