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

severe respiratory or bulbar weakness

1st line – intubation and mechanical ventilation

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ACUTE
|
severe respiratory or bulbar weakness
1st line – 

intubation and mechanical ventilation

Severe respiratory or bulbar weakness is a neurological emergency. Severe weakness may be provoked by infections, medications, surgery, or trauma, although this is uncommon in Lambert-Eaton myasthenic syndrome (LEMS) and should prompt evaluation for an alternative aetiology such as a myasthaenia gravis/LEMS overlap syndrome.

Serial measurements of FVC and negative inspiratory force should be taken using an appropriate interface for patients with severe bulbar weakness. Indication for mechanical ventilation includes FVC of ≤15 mL/kg and negative inspiratory force of ≤20 cm H₂O. Neither abnormal ABGs nor pulse oxygenation reflects the degree of respiratory weakness because abnormalities in either occur late in the course after clinical decompensation.

Plus – plasma exchange or intravenous immunoglobulin (IVIG)

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ACUTE
|
severe respiratory or bulbar weakness
Plus – 

plasma exchange or intravenous immunoglobulin (IVIG)

Treatment recommended for ALL patients in selected patient group

Plasma exchange or high-dose IVIG may be used to induce relatively rapid but transient improvement in symptoms.[47][48]​​

An observational study showed that treatment with plasma exchange may result in short-term improvement, although repeated courses may be necessary to sustain improvement.[48]

One small randomised controlled trial demonstrated short-term improvement for IVIG (up to 8 weeks), although it is unclear whether scheduled infusions produce sustained improvement.[17]​​[39]​​ Maximum improvement is noted at 2-4 weeks following infusion, with associated decline in serum voltage-gated calcium-channel antibody titres.[17]

IVIG should be used with caution in patients with suspected malignancy due to the increased risk of thrombosis.

Pre-treatment with paracetamol and diphenhydramine should be considered with IVIG.

Primary options

plasma exchange: 2-3 L plasma volume during each of 5 treatments on alternate days over 2-week period

OR

paracetamol: 1 g orally administered 30 minutes prior to commencing high-dose IVIG, maximum 4 g/day

and

diphenhydramine: 25-50 mg orally administered 30 minutes prior to commencing high-dose IVIG, maximum 200 mg/day

and

normal immunoglobulin human: 2 g/kg total dose intravenously given over 2-5 days

Plus – supportive care

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ACUTE
|
severe respiratory or bulbar weakness
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care includes deep vein thrombosis prophylaxis, peptic ulcer prophylaxis, adequate nutrition and hydration, and avoiding infections and drugs that may worsen neuromuscular symptoms. The most common medications on this list include antibiotics (macrolides, aminoglycosides, fluoroquinolones) and beta-blockers. Other medications that impair neuromuscular transmission include magnesium, lithium, quinidine, calcium-channel blockers, procainamide, and immune checkpoint inhibitors.[42]​ Intravascular contrast agents containing ionic or chelating agents should be avoided because use has resulted in exacerbation of weakness.[43] Neuromuscular blocking agents, such as vecuronium and curare, should be used cautiously, as use may result in prolonged neuromuscular blockade. A complete reference of drugs impairing neuromuscular transmission is available. MGFA: medications and myasthenia gravis Opens in new window

ONGOING

without severe respiratory or bulbar weakness

1st line – treatment of underlying cause

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ONGOING
|
without severe respiratory or bulbar weakness
1st line – 

treatment of underlying cause

A priority in treating patients with Lambert-Eaton myasthenic syndrome (LEMS) is to thoroughly evaluate for underlying cancer and to treat the cancer appropriately.

Around 50% of patients with LEMS have underlying cancer, usually small cell lung cancer.[2][8][9]​ Treatment of the underlying cancer can often result in substantial clinical improvement in LEMS. See Small Cell Lung Cancer (Management approach).

Plus – amifampridine ± pyridostigmine

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ONGOING
|
without severe respiratory or bulbar weakness
Plus – 

amifampridine ± pyridostigmine

Treatment recommended for ALL patients in selected patient group

First-line treatments focus on symptomatic improvement by augmenting neuromuscular transmission.

Amifampridine (also known as 3,4-diaminopyridine [3,4-DAP]) is approved by the US Food and Drug Administration for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults. In clinical trials, patients randomised to amifampridine experienced significantly greater improvement (per the Quantitative Myasthenia Gravis score, a 13-item physician-rated categorical scale assessing muscle weakness) than those receiving placebo.[40]​ Amifampridine can rarely cause seizures and the risk increases with use of higher doses. Therefore it is contraindicated in patients with a history of seizure disorders. Paraesthesia, headache, and nausea are among the most commonly reported adverse effects.

Although pyridostigmine does not usually produce significant improvement in LEMS-related neuromuscular weakness, as monotherapy or additive improvement in combination with amifampridine it may improve dry mouth and taste dysfunction, and so may be used in conjunction with amifampridine therapy.[41]

Primary options

amifampridine: 15-30 mg/day orally given in 3-4 divided doses initially, increase by 5 mg/day increments every 3-4 days according to response, maximum 80 mg/day (or 20 mg/dose)

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OR

amifampridine: 15-30 mg/day orally given in 3-4 divided doses initially, increase by 5 mg/day increments every 3-4 days according to response, maximum 80 mg/day (or 20 mg/dose)

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and

pyridostigmine: 30-60 mg orally twice daily initially, increase by 30-60 mg/day increments to usual dose of 60-120 mg every 3-4 hours while awake, maximum 540 mg/day

Plus – supportive care

Back
ONGOING
|
without severe respiratory or bulbar weakness
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care includes deep vein thrombosis prophylaxis, peptic ulcer prophylaxis, adequate nutrition and hydration, and avoiding infections and drugs that may worsen neuromuscular symptoms. The most common medications on this list include antibiotics (macrolides, aminoglycosides, fluoroquinolones) and beta-blockers. Other medications that impair neuromuscular transmission include magnesium, lithium, quinidine, calcium-channel blockers, procainamide, and immune checkpoint inhibitors.[42]​ Intravascular contrast agents containing ionic or chelating agents should be avoided because use has resulted in exacerbation of weakness.[43] Neuromuscular blocking agents, such as vecuronium and curare, should be used cautiously because use may result in prolonged neuromuscular blockade. A complete reference of drugs impairing neuromuscular transmission is available. MGFA: medications and myasthenia gravis Opens in new window

Consider – immunomodulators

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ONGOING
|
without severe respiratory or bulbar weakness
|
refractory to treatment
Consider – 

immunomodulators

Additional treatment recommended for SOME patients in selected patient group

Prednisone (prednisolone), alone or in conjunction with azathioprine, is the most frequently used regimen.[9]​​[22][44]​​

Azathioprine often enables lower doses of corticosteroids to be used.​​[18]​​[44]​ However, a serious idiosyncratic allergic reaction (rash, fever, nausea, vomiting, and abdominal pain) occurs in 10% to 15% of patients in early treatment; this resolves within 24 hours of stopping azathioprine and recurs with rechallenge.[45][46]

Mycophenolate and ciclosporin may be also used, although evidence of benefit is limited.​[18] Mycophenolate is preferred over ciclosporin.

Substantial and continuing doses of immunosuppressive medications may be required. However, in patients with an underlying cancer (CA-LEMS), prolonged immunosuppression should be avoided.

Primary options

prednisolone: 40-60 mg orally once daily initially, increase by 5 mg/day increments every 3 days to a dose of 80 mg once daily, continue until clinical improvement or for 2-3 months, whichever is earlier, then taper gradually

OR

prednisolone: 40-60 mg orally once daily initially, increase by 5 mg/day increments every 3 days to a dose of 80 mg once daily, continue until clinical improvement or for 2-3 months, whichever is earlier, then taper gradually

and

azathioprine: 50 mg orally once daily initially, increase by 50 mg/day increments once weekly according to response, maximum 2-3 mg/kg/day

Secondary options

mycophenolate mofetil: 1000 mg orally twice daily initially, increase by 500 mg/day increments according to response, maximum 3000 mg/day

Tertiary options

ciclosporin: 2.5 to 4 mg/kg/day orally given in divided doses

More

Consider – plasma exchange or intravenous immunoglobulin (IVIG)

Back
ONGOING
|
without severe respiratory or bulbar weakness
|
refractory to treatment
Consider – 

plasma exchange or intravenous immunoglobulin (IVIG)

Additional treatment recommended for SOME patients in selected patient group

Plasma exchange or high-dose IVIG may be used to induce relatively rapid but transient improvement in symptoms.[47][48]

An observational study showed that treatment with plasma exchange may result in short-term improvement, although repeated courses may be necessary to sustain improvement.[48]​​

One small randomised controlled trial demonstrated short-term improvement for IVIG (up to 8 weeks), although it is unclear whether scheduled infusions produce sustained improvement.[17]​​[39]​​ Maximum improvement is noted at 2-4 weeks following infusion, with associated decline in serum voltage-gated calcium-channel antibody titres.[17]

IVIG should be used with caution in patients with suspected malignancy due to the increased risk of thrombosis.

Pre-treatment with paracetamol and diphenhydramine should be considered with IVIG.

Primary options

plasma exchange: 2-3 L plasma volume during each of 5 treatments on alternate days over 2-week period

OR

paracetamol: 1 g orally administered 30 minutes prior to commencing high-dose IVIG, maximum 4 g/day

and

diphenhydramine: 25-50 mg orally administered 30 minutes prior to commencing high-dose IVIG, maximum 200 mg/day

and

normal immunoglobulin human: 2 g/kg total dose intravenously given over 2-5 days

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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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