Myasthenia Gravis, Emergency Medicine

Basics

Description

- Acute or subacute, with relapses and remissions - Associated with thymoma in 15% and thymic hyperplasia in 65% - Myasthenic crisis: - Respiratory failure or inability to protect airway due to weakness - Triggers: - Infection - Surgery - Trauma - Pregnancy - Medication changes (e.g., rapid tapering of steroids)

- Antibody-mediated attack on nicotinic acetylcholine receptors - Up to 20% of patients may be acetylcholine receptor antibody (AChR Ab) negative - Penicillamine can cause MG as well as other autoimmune conditions - Many medications may worsen myasthenic weakness: - Aminoglycosides, macrolides, quinolones, antimalarials - Local anesthetics - Antidysrhythmics (propafenone, quinidine, procainamide) - Ž ²-Blockers, calcium-channel blockers - Anticonvulsants (phenytoin, carbamazepine) - Antipsychotics (phenothiazine, atypicals) - Neuromuscular blocking agents - Iodine-containing radiocontrast

- Bulbar and facial muscle weakness: - Trouble chewing, speaking, swallowing - Inability to keep jaw closed after chewing - Slurred, nasal speech

- Ocular findings: - Ptosis, diplopia - Inability to keep eyelid shut against resistance - No pupillary changes

- Other tests for initial diagnosis: - Antistriated muscle antibody - Antinuclear antibody - Rheumatoid factor - ESR

- Edrophonium (Tensilon) test: - Short-acting AChE inhibitor - A positive test produces rapid, short-lived (2 " “5 min) improvement in strength - Sensitivity 95% in generalized MG and 86% in ocular MG - False positives possible with Lambert " “Eaton, Guillain " “Barre, MS, botulism, and others - Keep patient on cardiac monitor during test. - Atropine at bedside for possible bradycardia - Suction at bedside for possible increased secretions

Antibody-mediated condition that results in painless, fatigable muscle weakness
Ocular or generalized:Ocular (eyelids and extraocular) muscle weakness:Most common initial symptom (60%) ¢ ˆ ¼80% of myasthenia gravis (MG) patients who present with ocular weakness initially will progress to general weakness within 2 yr.Generalized:Usually affects proximal limbs, axial muscle groups such as neck, face, bulbar muscles
Acute or subacute, with relapses and remissions
Associated with thymoma in 15% and thymic hyperplasia in 65%
Myasthenic crisis:Respiratory failure or inability to protect airway due to weaknessTriggers:InfectionSurgeryTraumaPregnancyMedication changes (e.g., rapid tapering of steroids)Difficult to distinguish from cholinergic crisis resulting from excessive doses of acetylcholinesterase (AChE) inhibitors:Cholinergic crisis may also include muscarinic effects such as sweating, lacrimation, salivation, and GI hyperactivity in addition to weakness.

Epidemiology

Pediatric MG is rare and distinct:Congenital MG: Genetic defectJuvenile MG: Autoimmune disorderTransient neonatal MG: Postdelivery complication from placental transfer of maternal antibodies
Adult MG has bimodal distribution:1st peak in 2nd and 3rd decades affecting mostly women2nd peak in 6th and 7th decades affecting men

Etiology

Antibody-mediated attack on nicotinic acetylcholine receptors
Up to 20% of patients may be acetylcholine receptor antibody (AChR Ab) negative
Penicillamine can cause MG as well as other autoimmune conditions
Many medications may worsen myasthenic weakness:Aminoglycosides, macrolides, quinolones, antimalarialsLocal anestheticsAntidysrhythmics (propafenone, quinidine, procainamide) Ž ²-Blockers, calcium-channel blockersAnticonvulsants (phenytoin, carbamazepine)Antipsychotics (phenothiazine, atypicals)Neuromuscular blocking agentsIodine-containing radiocontrast

Diagnosis

Signs and Symptoms

Fluctuating focal weakness ‚

History

Symptoms worsen with repeated activity:
Ocular weakness:DiplopiaPtosis while driving or reading
Bulbar and facial muscle weakness:Trouble chewing, speaking, swallowingInability to keep jaw closed after chewingSlurred, nasal speech
Limb weakness:Difficulty climbing stairs, rising from chair, reaching up with arms

Physical Exam

Ocular findings:Ptosis, diplopiaInability to keep eyelid shut against resistanceNo pupillary changes
Bulbar and facial findings:Ask patient to count to 100; look for changes in speech.Decreased facial expressionHead droop
Limb findings:Repetitive testing of proximal muscles or small muscles of hand results in weakness.Reflex and sensory exam are normal.

Essential Workup

Assess for respiratory compromise
Search for secondary triggers (e.g., infectious source)

Diagnosis Tests & Interpretation

Lab

CBC
Electrolytes
LFTs
Thyroid function tests
Anti-AChR Ab:Positive in 90% with generalized diseasePositive in 50% with ocular disease
Other tests for initial diagnosis:Antistriated muscle antibodyAntinuclear antibodyRheumatoid factorESR

Imaging

Head CT or MRI to rule out compressive lesions causing cranial nerve findings
Chest CT with contrast to look for associated thymoma
CXR as needed to evaluate for infectious source

Diagnostic Procedures/Surgery

Edrophonium (Tensilon) test:Short-acting AChE inhibitorA positive test produces rapid, short-lived (2 " “5 min) improvement in strengthSensitivity 95% in generalized MG and 86% in ocular MGFalse positives possible with Lambert " “Eaton, Guillain " “Barre, MS, botulism, and othersKeep patient on cardiac monitor during test.Atropine at bedside for possible bradycardiaSuction at bedside for possible increased secretions
Ice test:Place ice on eyelid for 2 min.Improvement in ptosis suggests MG.

Differential Diagnosis

Amyotrophic lateral sclerosis
Botulism
Electrolyte abnormalities
Graves disease
Guillain " “Barre syndrome
Hyperthyroidism
Inflammatory muscle disorders
Intracranial mass lesions
Lambert " “Eaton syndrome
Multiple sclerosis
Periodic paralysis
Tick paralysis

Treatment

Pre-Hospital

Attention to airway management ‚

Initial Stabilization/Therapy

Myasthenic crisis: ‚

Most important is early intubation and mechanical ventilation.
Signs of impending failure:Vital capacity <20 mL/kgNegative inspiratory pressure > " “30 cm H2ONegative expiratory pressure <40 cm H2O
Considerations regarding paralytics:Decreased sensitivity to depolarizing agents may necessitate higher dose; consider doubling the usual dose of succinylcholine.Nondepolarizing agents can cause extended paralysis; consider halving the usual dose.Others recommend midazolam, etomidate, or thiopental instead.

Ed Treatment/Procedures

Treat infections aggressively.
Search for and remove triggers.Careful medication history.
Myasthenic crisis may require plasmapheresis or IV gamma globulin (IVIG).Plasmapheresis: Remove 1 " “1.5 plasma volume each session ƒ — 5 sessionsIVIG: 0.4 mg/kg/d ƒ — 5 days
Initiate high-dose corticosteroids.
Discontinue AChE inhibitors while intubated.
Atropine for AChE inhibitor effects (bradycardia, GI symptoms, increased bronchial or oral secretions)

Medication

First Line

Edrophonium (Tensilon): 2 mg IV over 15 " “30 sec; if no effect after 45 sec, can give 2nd dose of 3 mg IV. If still no response, final dose of 5 mg IV can be given (total 10 mg).
Prednisolone 1 mg/kg/d for crisis
Atropine for cholinergic crisis 0.5 mg IV or IM

Second Line

Other medications that may be initiated by neurologist: ‚

Prednisone, AChE inhibitors, azathioprine, mycophenolate, mofetil, cyclosporine, tacrolimus, rituximab

Follow-Up

Disposition

Admission Criteria

New-onset myasthenic symptoms
Diagnosis unclear, but myasthenia a possibility
Myasthenic patients with worsening symptoms
Myasthenic crisis or questionable respiratory status mandates admission to ICU.

Discharge Criteria

Myasthenic patients who are improving can be considered for discharge in consultation with neurology. ‚

Followup Recommendations

Any discharged patient should have neurology follow-up arranged. ‚

Pearls and Pitfalls

Search for signs of myasthenic crisis in any MG patient who presents to the ED.
Search carefully for secondary conditions in patients with worsening MG.
Place patient on cardiac monitor and keep atropine and suction at bedside when performing edrophonium test.

Additional Reading

Bershad ‚ EM, Feen ‚ ES, Suarez ‚ JI. Myasthenia gravis crisis. South Med J. 2008;101:63 " “69.
Conti-Fine ‚ BM, Milani ‚ M, Kaminski ‚ HJ. Myasthenia gravis: Past, present and future. J Clin Invest. 2006;116:2843 " “2854.
Gajdos ‚ P, Chevret ‚ S, Toyka ‚ KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev. 2012;12:CD002277.
Scherer ‚ K, Bedlack ‚ RS, Simel ‚ DL. Does this patient have myasthenia gravis? JAMA. 2005;293:1906 " “1914.
Thieben ‚ MJ, Blacker ‚ DJ, Liu ‚ PY, et al. Pulmonary function tests and blood gases in worsening myasthenia gravis. Muscle Nerve. 2005;32:664 " “667.

Codes

ICD9

358.00 Myasthenia gravis without (acute) exacerbation
358.01 Myasthenia gravis with (acute) exacerbation
775.2 Neonatal myasthenia gravis
358.0 Myasthenia gravis

ICD10

G70.00 Myasthenia gravis without (acute) exacerbation
G70.01 Myasthenia gravis with (acute) exacerbation
P94.0 Transient neonatal myasthenia gravis
G70.0 Myasthenia gravis

SNOMED

91637004 myasthenia gravis (disorder)
77461000119109 Myasthenia gravis with exacerbation (disorder)
82178003 Neonatal myasthenia gravis
230686005 Generalized myasthenia (disorder)
31839002 Myasthenia gravis, adult form (disorder)
55051001 Myasthenia gravis, juvenile form (disorder)