CONTENTS

• Rapid Reference 🚀
• Myasthenia Gravis: Background information
  • Pathophysiology
  • Presentation
  • Diagnosis
  • Serologic testing & types
  • Drugs to avoid in myasthenia gravis
• Myasthenic crisis: diagnosis
  • Diagnosis of myasthenic crisis: basics
  • Differentiation from cholinergic crisis
  • Triggers of myasthenic crisis
• Myasthenic crisis: treatment
  • Blood gas monitoring
  • Bedside pulmonary function tests
  • Respiratory support
  • Nutrition & GI access
  • Pyridostigmine
  • Steroid
  • PLEX vs. IVIG
• Special situations:
  • Checkpoint inhibitor induced myasthenia gravis
  • Myasthenia gravis in pregnancy ➡️
• Podcast
• Questions & discussion
• Pitfalls

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rapid reference: myasthenic crisis

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evaluation 📖

• Chest X-ray and lung ultrasound (exclude other lung disease).
• Electrolytes (including Ca/Mg/Phos), CBC with differential.
• Beta-HCG if pregnancy possible.
• Infectious workup or TSH level (if symptoms of infection or thyroid disease).
• Forced vital capacity (FVC).

respiratory support 📖

• Consider early HFNC or BiPAP if mild-moderate respiratory distress or tachypnea.
• Intubation only if clinically indicated.

pyridostigmine 📖

• New diagnosis of MG: May initiate at 60 mg PO q6hr.
• Chronic MG and not intubated: Continue prior dose, unless it's extremely high.
• May add glycopyrrolate to reduce oral secretions (e.g., 1 mg with each dose).

plasma exchange / IVIG 📖

• Plasma exchange is preferred (it is the fastest approach to stabilize disease).
• If plasma exchange is contraindicated/unavailable, may use IVIG.

monitoring 📖

• Most useful: Usual monitoring (vital signs, clinical appearance, subjective dyspnea, etc.)
• Forced vital capacity 2-3 times daily (DO NOT wake up patient for this).
• (Do not measure negative inspiratory force).

medications to avoid 📖

• Antibiotics: Aminoglycosides, Fluoroquinolones, Macrolides (e.g., azithromycin), Telithromycin.
• Cardiovascular:
  • Beta-blockers.
  • Class-Ia antiarrhythmics (especially procainamide).
  • Statins.
• Other drugs commonly used in ICU:
  • IV magnesium.
  • Corticosteroids.
  • Contrast dye (although modern contrast dyes are probably fine).
• Miscellaneous:
  • Checkpoint inhibitors.
  • Chloroquine/hydroxychloroquine.
  • Desferrioxamine.
  • D-penicillamine.
  • Quinine.

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pathophysiology of MG

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pathophysiology

• Acetylcholine is released in discrete quantities into our neuromuscular junctions in order to elicit muscle contraction. With repeated contractions, the amount of acetylcholine released diminishes. However, because of the evolutionary importance of the task (think being chased by a sabre-tooth tiger), the quantity of acetylcholine released is more than is necessary to trigger this response, even with repeated muscle contractions.
• Myasthenia gravis results from the formation of autoantibodies that bind to acetylcholine receptors on skeletal muscle.
• Anti-acetylcholine receptor antibodies impair transmission at the neuromuscular junction in a few ways:
  • Direct reversible inhibition of acetylcholine binding to its receptor.
  • Antibodies can lead to destruction of acetylcholine receptors via complement fixation, decreasing the number of receptors.
  • Antibodies lead to internalization of the receptor into the muscle cell.
• When acetylcholine receptors are diminished in number, the lower amount of acetylcholine released into the NMJ during repeated contractures will eventually lead to transmission failure.
• Clinically this is what causes fatigable skeletal muscle weakness.

treatments

• Acetylcholinesterase inhibitors (e.g. physostigmine) – these decrease the breakdown of acetylcholine within the neuromuscular junction.  This may boost signaling of the muscle cell.
• Immunosuppressive therapies are aimed at reduction in the synthesis of auto-antibodies.
• Plasmapheresis may directly remove auto-antibodies.

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presentation of MG

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distribution

• Eyes and bulbar muscles tend to be involved early (ptosis and diplopia are common).
  • Only skeletal muscles are involved (not the pupils).
  • Isolated weakness in certain ocular muscles can occur, mimicking internuclear ophthalmoplegia or various cranial nerve palsies. (Louis 2021)
• Generalized weakness can also occur (e.g. involving diaphragm and limbs).
  • Limb weakness is usually proximal > distal.

features of weakness

• Fatigability: ongoing effort rapidly provokes worsening weakness. Strength improves with rest.
  • As such, symptoms tend to be worse at the end of the day and best right after waking up
• Asymmetric and fluctuating in severity over time.
• Normal sensation and normal pupillary reflexes.
• Deep tendon reflexes are normal (until severe weakness occurs).

epidemiology

• Incidence in women peaks in their 20s's-30's, whereas incidence in men peaks in their 60's-80's.(33896522)
• Can be associated with:
  • Thymoma or thymic hyperplasia.
  • Other autoimmune diseases (e.g., hyperthyroidism, lupus, rheumatoid arthritis, polymyositis).
  • Lymphoma.
  • Checkpoint inhibitor use.📖

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diagnosis of MG

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ice pack test

• Measure eye opening or assess extra-ocular movements of most affected eye.
• Place ice pack over patient's eye that is affected with ptosis or ophthalmoparesis for 2-5 minutes.(31794470)
• Improvement following ice (improved movement or improved eye opening aperture) supports a diagnosis of myasthenia gravis. This improvement occurs due to reduced activity of acetylcholinesterases at lower temperatures.(34618763)
• Test is cheap, safe, noninvasive – and surprisingly sensitive (~90%) and specific (~80%).(28916122)

electrodiagnostic testing (EMG)

• (1) Repeated stimulation causes rapid deterioration in muscle responses (fatigability).
  • Sensitivity isn't fantastic (usually ~50%, but closer to ~80% in myasthenic crisis).(33223079, 30743297)
  • A decrease of >10% in the compound motor action potential (CMAP) with repeated stimulation indicates a defect in neuromuscular transmission.(31794470)
• (2) Single-fiber EMG
  • In the ICU setting it is generally impossible due to electrical interferences.(30743297)
  • Single-fiber EMG compares contraction in closely adjacent muscle fibers in the same motor unit. Desynchronized activity of adjacent fibers (“jitter”) supports a diagnosis of myasthenia gravis. This has higher sensitivity than repeated stimulation (~90%, up to 99% if examining a weak muscle), but it's not entirely specific for myasthenia gravis.

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serology & serologic testing

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Serologies are not helpful for the initial diagnosis of MG among critically ill patients, because sluggish turn-around time limits the ability of this test to guide immediate treatment decisions. However, serologic typing may help predict how patients may manifest and respond to various therapies.

anti-AcH-R

• 80% of patients have antibodies against the acetylcholine receptor (AcH-R). The specificity of a positive anti-AcH antibody result is high (>99%).(33223079)
• These patients have typical presentation and response to treatment.
• May correlate with thymic hyperplasia and thymoma.

MuSK

• Patients have antibodies against muscle-specific receptor tyrosine kinase (MuSK), another protein involved in acetylcholine signaling. (33223079)
• Epidemiology:
  • This constitutes ~4% of all patients with myasthenia gravis, and ~40% of patients who lack antibodies against the acetylcholine receptor.
  • Patients are typically young women.
• Clinical presentation:
  • Bulbar and respiratory muscles are preferentially affected.(37114503)
  • Patients tend to have high disease severity with a high frequency of respiratory crises (with prominent involvement of the diaphragm).
  • There is often prominent involvement of bulbar muscles with facial weakness/atrophy and pharyngeal involvement.
• Management:
  • Patients tend to respond well to plasma exchange and prednisone, but less well to IVIG or pyridostigmine (which may cause profuse fasciculations).(27358333; 36333027)

lipoprotein receptor-related protein 4 (LPR4-Ab)

• Epidemiology:
  • May account for ~2% of patients with myasthenia gravis.(33896522)
  • Peak onset 30-50 years old, female predominance.
• Clinical significance:(36333027)
  • Response to therapy is similar to patients with anti-AcH-receptor antibodies.
  • Disease tends to be early-onset, with milder symptoms at onset.
  • LPR4-antibodies are not specific to myasthenia gravis (may also be present in amyotrophic lateral sclerosis).

anti-striational muscle antibodies (StrAbs) including titin, ryanodine receptor, or potassium channel antibodies

• Anti-ryanodine receptor antibodies: (36333027)
  • Tend to have more severe, generalized, or predominantly bulbar weakness.
  • May have frequent myasthenic crises.
• Anti-potassium channel (Anti-Kv1.4): (36333027)
  • Bulbar involvement may be prominent, with frequent crises.
  • QT prolongation with myocarditis may occur.

seronegative

• ~5% of patients may lack any identifiable antibody.
• Management is similar to patients with anti-AChR-antibody.

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drugs to avoid in MG

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Many drugs have been implicated in exacerbation of myasthenia, but the evidentiary strength is generally very low. This creates a challenging task of avoiding genuinely dangerous medications, yet not withholding useful medications due to unnecessary fear. The list below is based on the 2020 international consensus guidelines for management of myasthenia gravis.(33144515) This is also consistent with a recent literature review by Sheikh et al.(33917535)

antibiotics

• Aminoglycosides – May worsen MG, use cautiously if no alternative.
• Fluoroquinolones – Associated with worsening MG; use cautiously, if at all.
• Macrolides (e.g., erythromycin, clarithromycin, azithromycin) – May worsen MG; use cautiously, if at all.
• Telithromycin – Causes severe, often fatal exacerbation of MG. Do not use.

cardiovascular

• Beta-blockers – Potentially dangerous, may worsen MG. Use cautiously. Even ophthalmic formulations can be problematic.
• Procainamide (and probably other Class-Ia antiarrhythmics) – May worsen MG; use with caution.
• Statins – May worsen or precipitate MG. Evaluate closely for worsening MG when statin therapy initiated.

miscellaneous

• Intravenous magnesium – Use only if absolutely necessary and observe for worsening. Safety might be improved by infusing magnesium very slowly, to avoid transient elevations in serum magnesium levels.
• Corticosteroids – Standard treatment for myasthenia, but may cause transient worsening during the first two weeks (discussed further below).
• Iodinated radiocontrast dye – Modern agents appear safer than prior agents. Use cautiously and observe for worsening.
• Checkpoint inhibitors – Can precipitate or worsen MG. 📖
• Chloroquine and hydroxychloroquine – may precipitate or worsen myasthenia, use only if necessary and observe for worsening.
• Botulinum toxin – Avoid use.
• Desferrioxamine – May worsen myasthenia.
• D-penicillamine – Strongly associated with causing myasthenia, avoid use.
• Quinine – Prohibited, except in some cases of malaria.
• Succinylcholine – May be ineffective in causing paralysis; more on this below.

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diagnosis of myasthenic crisis

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definition?

• The term “myasthenic crisis” is used by different authors in various ways, which may lead to confusion:
  • (#1) Some authors use “myasthenic crisis” to refer solely to patients with myasthenia gravis exacerbation requiring intubation or noninvasive ventilation.(27907966)
  • (#2) Some authors use “myasthenic crisis” to refer to any exacerbation of myasthenia gravis which causes or threatens to cause frank respiratory failure.(28916122)
• Myasthenia crisis is used in this chapter to refer to any patient with respiratory dysfunction due to myasthenia gravis who requires ICU admission.
• Myasthenic crisis may be the initial manifestation of myasthenia gravis in ~20% of patients.(30743297)

Don't assume that every patient with myasthenia gravis who presents with dyspnea has a myasthenic crisis! Patients with myasthenia gravis can have cardiopulmonary disease like anyone else (e.g., pneumonia, heart failure, pulmonary embolism).

diagnosis of a myasthenic crisis requires two components:

• (1) Careful cardiopulmonary evaluation with exclusion of other active processes:
  • At a minimum this should involve a thoughtful history, chest X-ray, EKG, and lung ultrasonography.
  • Other tests added as necessary (e.g., CT angiography to exclude PE).
• (2) Evidence of worsening muscular weakness:
  • History and physical may be helpful (e.g., patient reports increasing limb weakness and this is confirmed on exam).
  • Forced Vital Capacity (FVC) should be measured if the patient isn't extremely dyspneic. Forced vital capacity should be reduced in order to make a diagnosis of myasthenic crisis.

differential diagnosis of a myasthenic crisis: related entities to consider

• (1) Cholinergic crisis – more on this below.
• (2) Adrenal crisis 📖: Many patients with myasthenia are maintained on chronic prednisone for months or years. Adrenal crisis may occur in the following situations:
  • (1) Prednisone is abruptly stopped (e.g., due to weakness or inability to swallow medications).
  • (2) Patient on chronic low-dose prednisone (e.g., 5 mg) is exposed to a new source of physiologic stress.
• (3) Thyroid storm or myxedema coma – Autoimmune thyroid disease is associated with myasthenia gravis.

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myasthenic vs cholinergic crisis

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what is a cholinergic crisis?

• Excessive doses of acetylcholinesterase inhibitor (e.g. pyridostigmine) lead to excessive levels of acetylcholine, which acts as a depolarizing paralytic! (similar to succinylcholine).
• Cholinergic crisis is widely feared, but in modern practice this is almost nonexistent.
  • Historically, higher doses of pyridostigmine were used, so cholinergic crisis was a more relevant problem.
  • Cholinergic crisis doesn't occur in patients taking standard pharmacologic doses of pyridostigmine (<120 mg every 3 hours).(30743297)
  • Cholinergic crisis can occur if patients are self-medicating with excessive doses of pyridostigmine.(Torbey, 2019)

clinical features of a cholinergic crisis

• (1) Patient has a history of using escalating doses of acetylcholinesterase inhibitor medication.
  • Cholinergic crisis is unlikely if pyridostigmine dose is below 120 mg q3hr.
• (2) Fasciculation of skeletal muscles.
• (3) Features of acetylcholine excess affecting the autonomic nervous system:
  • Nausea/vomiting, diarrhea, salivation, lacrimation, diaphoresis.
  • Miosis.
  • Bradycardia.

management of cholinergic crisis

• Withhold any further administration of acetylcholinesterase inhibitor.
• Supportive therapy (e.g., intubation if clinically warranted).
• Once the patient has recovered, lower doses of acetylcholinesterase may be re-introduced.

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triggers of myasthenic crisis

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In addition to treatment of the myasthenia gravis, it may be important to treat the trigger of the crisis. In ~20% of patients, myasthenic crisis may be the initial presentation of myasthenia.(32733360) In many other patients, myasthenic crisis may be precipitated by another problem, including:

• Infection (cause ~40% of crises; especially pneumonia).(37114503)
• Medications:
  • Medications that exacerbate myasthenia (list above).
  • Not taking myasthenia gravis medications as prescribed (e.g., pyridostigmine)
  • Tapering of immunosuppressive medications.
  • Initiation or discontinuation of steroid.(discussed further below)(Nelson 2020)
• Electrolyte abnormality (essentially any abnormality, including Ca/Phos/Mg).
• Thyroid disease (either hypothyroid or hyperthyroid; note that myasthenia gravis is associated with autoimmune thyroid disease).
• Surgery/trauma.
• Pregnancy, delivery.
• Aspiration pneumonitis.
• No cause is found in about a third of patients.(Jallo 2021)

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respiratory support

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noninvasive respiratory support (HFNC or BiPAP)

• In order to work, high-flow nasal cannula (HFNC) or BiPAP must be started early, when the patient is in only mild respiratory distress. The goal is to reduce the work of breathing and thereby prevent respiratory exhaustion.
  • These modalities will fail if initiated when the patient is already in extremis.
• When in doubt regarding whether the patient needs any support at all, consider high-flow nasal cannula (HFNC). This is extremely safe and may reduce work of breathing (due to reduced anatomic dead space, with improved ventilatory efficiency).
• Evidentiary support is strongest for BiPAP, so this might be the first-line therapy for mild-moderate dyspnea.(18195139, 12451217) If BiPAP cannot be tolerated or is contraindicated (e.g. due to intolerance or significant respiratory secretions), then HFNC may be tried.
  • Some patients develop upper airway collapse, due to oropharyngeal bulbar weakness.(37114503)  BiPAP may help this, by providing a pneumatic stent to maintain airway patency.
• Close supervision in an ICU is required to ensure that these modalities are working (e.g., on BiPAP, the minute ventilation and tidal volume should be monitored).

decision to intubate: bedside respiratory assessment

• Some general principles:
  • The decision to intubate should NOT be made solely on the basis of pulmonary function tests.
  • There is usually no indication to trend ABG/VBG in order to make this decision either.
  • Intubation is always a clinical decision.
  • Trajectory over time is extremely important.
  • When in doubt, prepare for intubation and continue to monitor the patient carefully.
• Components to consider may include the following:
• Patient appearance:
  • Respiratory rate.
  • Work of breathing; any signs of distress.
• Cough strength & bulbar symptoms: Cough efficacy, ability to clear secretions, and ability to protect airway.
• Strength: Trends in weakness (e.g. especially neck flexion weakness, which may tend to track with respiratory muscle weakness better than limb weakness).(37114503)
• FVC: Value and trends in forced vital capacity.
• Oxygenation:
  • Generally, myasthenia shouldn't cause significant hypoxemia.
  • Progressively worsening hypoxemia is a worrisome sign that may suggest progressive atelectasis, aspiration, or an alternative overlooked diagnosis.
• Chest radiograph: Signs of worsening lobar collapse or aspiration would support the need for intubation.

intubation procedure

• A non-depolarizing paralytic should be used (e.g. rocuronium). The dose should be reduced by ~50% compared to the usual dose (e.g. a dose of ~0.6 mg/kg rocuronium may be reasonable).
  • Succinylcholine may fail to work due to reduced acetylcholine receptor density on muscle.
• Patients with dysautonomia due to GBS may be at risk of hypotension and/or bradycardia following intubation. Consider having epinephrine ready to manage this complication.

extubation & tracheostomy

• Patients can generally be extubated within 1-2 weeks, with only ~20% of intubated patients requiring tracheostomy.(Nelson, 2020; 34618763) Consequently, efforts generally focus on weaning mechanical ventilation, rather than early tracheostomy. Aggressive management of myasthenia gravis (e.g., plasma exchange) may enhance muscle strength and facilitate early extubation.
• Extubation may generally be pursued in the standard fashion. 📖  Planned extubation to BiPAP support may help reduce the risk of reintubation.  This may be followed by a short duration of nocturnal BiPAP, to provide additional support until full recovery has occurred.(37114503)
• Risk factors for inability to extubate include:(34618763, 37114503)
  • Age >50 years old.
  • Pre-intubation serum bicarbonate >30 mM.
  • Vital capacity remains <25 ml/kg during the first week of intubation.
  • Comorbidities, such as pneumonia.
  • MuSK antibody positivity.

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nutrition & GI access

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Some patients may have bulbar weakness causing dysphagia and risk of aspiration.

• If the patient is unable to protect their airway (e.g. inability to handle secretions, gurgling), then intubation is required.
• If the patient is able to protect their airway but is at increased risk for aspiration, there should be a low threshold to place a small-bore nasoenteric feeding tube.

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pyridostigmine

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basics

• Pyridostigmine is an acetylcholinesterase inhibitor. It increases levels of acetylcholine in the synapse, improving nerve transmission.
• Excessive doses of pyridostigmine can be problematic for a few reasons:
  • (1) Increased secretions can be problematic, especially in patients with bulbar weakness or weak cough.
  • (2) Profoundly excessive doses can cause a cholinergic crisis (with currently used dosing, this is rare; more on this above).
• Glycopyrrolate or hyoscyamine may be used to reduce secretions caused by pyridostigmine (e.g., 1 mg PO glycopyrrolate 💊 or 0.125 mg PO hyoscyamine 💊 with each dose of physostigmine).(27907966, 29655452)

general dosing information for pyridostigmine

• The starting dose is often 60 mg PO q6hr.
• The dose may be up-titrated to a maximum dose of 120 mg PO q4hr.
• Pyridostigmine can be given intravenously, but at 1/30th the dose of oral medication. However, be aware that the half-life of pyridostigmine when administered IV will be extremely short.
• Always be cautious for emergence of anticholinergic side-effects (e.g., increased secretions, bradycardia).

approach to pyridostigmine in a myasthenic crisis

• There isn't much evidence on this (with available literature nicely reviewed by Prado et al.).(34292475) Reasonable practice might be as follows:
• Intubated patients, previously on chronic pyridostigmine:
  • Pyridostigmine is generally held initially to reduce airway secretions and increase sensitivity to pyridostigmine (a brief drug holiday may increase responsiveness when treatment is resumed).
  • Pyridostigmine should be restarted as the patient is approaching extubation.(27907966)
• Non-intubated patients, previously on chronic pyridostigmine:
  • Continue the patient's home dosing regimen.
  • Pyridostigmine should never be stopped in patients who are not intubated.(33896522) One cause of myasthenic crisis is not taking pyridostigmine as prescribed, so it doesn't make sense to hold the patient's pyridostigmine – this could make matters even worse.
• New diagnosis of myasthenia (pyridostigmine naive patient):
  • It may be reasonable to start at a low dose (e.g., 60 mg PO q6hr).
  • (If the patient has already been intubated, pyridostigmine might be initiated as the patient is approaching extubation.)

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steroid & immunomodulatory treatment

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background information on steroid in myasthenia gravis

• Steroid is often used for patients with myasthenia gravis to reduce the production of anti-acetylcholine antibody (e.g., 0.5-1 mg/kg prednisone or ~60 mg/day prednisone).
• Steroid usually takes 2-3 weeks to cause clinical improvement.
• ⚠️ Initiation of steroid may cause clinical deterioration (indeed, steroid initiation can cause myasthenic crisis). Deterioration may occur in about half of patients. This usually occurs 5-10 days after steroid initiation, and may last for several days.(LaHue 2021)

management of steroid for patients with myasthenic crisis

• For patients previously on steroid: continue the same dosage initially. After patients have received plasmapheresis/IVIG and improved substantially, dose escalation may be considered (if the initial dose was low).(37114503)  
• For patients not previously on steroid, two possible approaches may be reasonable:
  • (1) It's usually best to delay steroid initiation for several days after initial admission (e.g., until after the patient has received plasmapheresis/IVIG and improved substantially). (27358333)
  • (2) An alternative approach is to start steroid at a low dose (e.g., 20 mg prednisone) and then very gradually up-titrate the dose.  This dose may be low enough that it doesn't provoke deterioration of the myasthenia gravis.

alternative immunosuppression

• If steroid is contraindicated or previously ineffective, other treatments may be used (e.g., azathioprine, cyclosporine, rituximab, methotrexate).
• These agents will take forever to start working – so again, there's no rush here.

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PLEX versus IVIG

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There is no high-quality evidence regarding the selection of PLEX vs. IVIG. However, most experts and guidelines believe that plasma exchange works more quickly.(27358333, 37114503)

plasma exchange (PLEX) is first-line for severe exacerbation

• Plasma exchange usually causes improvement in a few days. It directly removes anti-acetylcholine receptor antibody from the body.
• The main advantage of plasma exchange is more rapid response compared to IVIG (which may take some weeks to see improvement).(32733360) Improvement usually seen by the second or third plasmapheresis session.(37114503) Rapid efficacy is especially important for patients who are at risk of requiring intubation, or patients who have been intubated (because the risk of ventilator-associated complications rises with each additional day of invasive ventilation).
• Plasma exchange may be more effective in MuSK+ patients.

IVIG may be useful for less severe exacerbations

• IVIG takes longer to work (e.g., 2-3 weeks), but the efficacy may be more sustained.
• IVIG can be used in situations where plasma exchange is unavailable or contraindicated.
• The dose of IVIG is 2 grams/kg, usually divided over 2 or 5 days.

further discussion:

• Plasma exchange: 📖
• IVIG: 📖
• Choice of plasma exchange vs. IVIG: 📖

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checkpoint inhibitor induced myasthenia gravis

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basics

• Checkpoint inhibitors may exacerbate myasthenia gravis, or cause de novo illness (more frequently the latter).
• Myasthenia usually occurs about a month after initiation of checkpoint inhibitor therapy (with a range of 6 days to 16 weeks).(33144515)
• Usually associated with anti-PD1 monotherapy (nivolumab, pembrolizumab, cemiplimab) or combination therapy.(32487905)

clinical features

• The usual presentation is with typical findings of myasthenia gravis (e.g., ptosis, diplopia, dysphagia, weakness, and dyspnea).(32487905)
• May have disproportionately severe respiratory and bulbar weakness, with a greater tendency to present with myasthenic crisis.(31794471)

differential diagnosis includes:

• Myositis or Miller-Fisher variant of Guillain-Barre syndrome may present with prominent ocular/bulbar symptoms.
  • Checkpoint-induced oculobulbar myositis may mimic myasthenia gravis closely.
• Patients may often have a combination of myasthenia with simultaneous myositis, myocarditis, and/or thyroiditis (33144515)
  • ⚠️ The combination of myasthenia gravis, myositis, and myocarditis is common. The presence of any one of these three should prompt evaluation for all three disorders. Among patients with myasthenia gravis, ~16% may have myositis and ~9% may have myocarditis.(34172516)
• Dyspnea may be due to checkpoint pneumonitis.
• Patients may be suffering from various other neurologic complications from cancer (more on these here). 📖

evaluation

• Bedside pulmonary function tests (forced vital capacity and negative inspiratory force). 📖
• Labs
  • Creatinine kinase and aldolase (to evaluate for myositis).
  • Troponin (to evaluate for checkpoint myocarditis).
  • TSH and free T4 (noting that checkpoint inhibitors may cause pituitary or thyroid gland dysfunction).
  • Acetylcholine receptor and anti-striated muscle antibodies (although these tests may have reduced sensitivity for checkpoint-induced myasthenia gravis and slow turnaround time).
• MRI of brain and/or spine may be useful, depending on anatomic distribution of weakness
• Electrodiagnostic studies (these may not have excellent performance, but they offer the ability to evaluate broadly for myositis, polyneuropathy, and/or myasthenia gravis).

treatment

• Pyridostigmine starting 30 mg TID and up-titrating to a maximum of 120 mg QID as tolerated.
• Prednisone 1-1.5 mg/kg/day. Early aggressive treatment with high-dose steroids may be helpful.(33144515)
• Intravenous immunoglobulin (IVIG; 0.4 grams/kg/day for five days) or plasmapheresis for severe symptoms (including any dyspnea, facial weakness, or dysphagia)
  • Make sure to draw serologies before these therapies.
• Avoid medications that can worsen myasthenia (beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, macrolides) – see a full list above.

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• Don't assume that a dyspneic patient with myasthenia gravis is necessarily having a myasthenic crisis: these patients may also have any other cause of respiratory failure (e.g. pneumonia, heart failure).
• Don't harass patients with scheduled and extremely frequent measurements of pulmonary mechanics.
• Don't intubate patients based on arbitrary cutoff values in pulmonary mechanics (there's zero data to support this practice).
• Be extremely careful about starting new medications in patients with myasthenia gravis – consider the list of contraindicated medications above.

Acknowledgement: Thanks to Dr. Richard Choi (@rkchoi) for thoughtful comments on this chapter.

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