Myasthenia Gravis

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Introduction

Myasthenia gravis (MG) is an acquired autoimune disorder affecting the neuromuscular junction.

The Case of...

a simple case introducing clincial presentation and calling for a differential diagnosis. To get students thinking.

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Causes and Risk Factors

MG is caused by autoantibodies directed at the acetylcholine receptor (AChR), leading to receptor deficiency. Circulating antibodies are present in 70-80% of patients. Other antibodies may be present against muscle-specific tyrosine kinase or striate muscle itself.

Incidence is 2-5 per million, and prevalence is 13-64 per million. Female to male ratio is 6:4. MG can occur at any age, but peaks in the 3rd decade for women and in the 6th-7th decade for men.

Two-thirds of patients have thymic hyperplasia, and 10-15% have thymoma. In approximately 10% of patients, MG is associated with another autoimmune disease.

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Pathophysiology

The deposition of IgG and complement at the postsynaptic membrane leads to blockage of ACh binding and AChR destruction.

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Signs and Symptoms

MG can selectively affect the external ocular muscles (ocular MG) or the entire muscle system (generalized MG).

history
physical exam

History

Symptoms tend to fluctuate, being worse in the day. They can be provoked or worsened by exertion, infections, menses, and stress.

Ocular involvement is typically bilateral, assymetric, and associated with ptosis and diplopia. Weakness in facial muscles results in a loss of facial expression, a smile resembling a snarl, nasal regurgitation of liquids, choking, and slurred, nasal speech. Fatigability of limb muscles can lead to difficulties combing hair, lifting objects repeatedly, climbing stairs, walking, and running.

Physical Exam

Fatigue is most reliably demonstrated in the eyes. The curtain sign describes worsening ptosis with upgaze, or asymmetric nystagmus on extreme lateral or medial gaze.

Proximal limb muscles tend to be more affected than distal muscles.

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Investigations

lab investigations
diagnostic imaging

Lab Investigations

Serology

AChR antibody testing is positive in almost everyone with severe MG, 80% of people with mild generalized MG, and 50% of people with ocular MG. Other antibodies may be present against muscle-specific tyrosine kinase (MuSK), or against striated muscle.

Anticholinesterase testing

Edophonium can be given 2mg IV over 15 seconds, with another 8mg injected if no response is seen over 30-45 seconds. Evaluation of muscle response should be done in areas not influenced by motivation, such as degree of ptosis or occular eye movements. Caution must be used in patients with cardiac disease to avoid bradycardia, AV block, or cardiac arrest. It should not be used in patients with respiratory distress.

Diagnostic Imaging

EMG

EMG testing of a motor nerve at 2-3 Hz results in >10% decrease in signal amplitude after 5 tests. At least two proximal and at least two distal muscles should be tested.