Myasthenia Gravis

What is myasthenia gravis (MG)?

An autoimmune neuromuscular junction disorder caused by antibodies against acetylcholine receptors or MuSK, leading to fluctuating skeletal muscle weakness.

What causes MG?

Autoantibodies attack ACh receptors at the neuromuscular junction, reducing receptor availability and impairing neuromuscular transmission.

What epidemiologic features are associated with MG?

• Young women

• Older men

• Association with thymic abnormalities (hyperplasia or thymoma)

What are major risk factors for MG?

• Thymoma

• Autoimmune diseases

• Female sex (younger onset)

What is the underlying pathophysiology of MG?

Antibodies target ACh receptors or MuSK proteins, causing decreased neuromuscular transmission and fatigable muscle weakness.

What symptoms commonly occur in MG?

• Fatigable weakness

• Ptosis/diplopia

• Worsens with activity

• Dysphagia

• Dysarthria

• Proximal weakness

• Normal sensation

• Normal reflexes

What is the hallmark feature of MG?

Weakness that worsens with use and improves with rest.

What ocular symptoms are common in MG?

Ptosis and diplopia due to extraocular muscle involvement.

What bulbar symptoms may occur in MG?

Dysphagia, dysarthria, and difficulty chewing.

What physical exam findings are typical in MG?

• Ptosis

• Proximal UE weakness

• Normal LE strength

• Normal sensation

• Normal reflexes

• Normal gait

What is Cogan’s lid twitch?

A brief upward overshoot of the eyelid when returning from downward gaze, suggestive of MG.

What bedside tests help diagnose MG?

• Ice pack test (ptosis improves)

• Sustained upward gaze test

• Romberg test (normal)

How does the ice pack test work?

Cooling improves neuromuscular transmission, temporarily improving ptosis.

What laboratory tests are used in evaluating MG?

• AChR antibodies

• MuSK antibodies

• CBC

• CMP

• TSH w/ reflex

• ESR/CRP

• ANA

• B12

What antibody is most specific for MG?

AChR‑binding antibodies.

What electrodiagnostic studies help diagnose MG?

Repetitive nerve stimulation (RNS) and electromyography (EMG).

What EMG finding is characteristic of MG?

Decremental response with repetitive nerve stimulation.

What is the most sensitive diagnostic test for MG?

Single‑fiber EMG.

What imaging study should be performed in MG?

Chest CT to evaluate for thymoma.

Why is chest CT important in MG?

Thymoma is strongly associated with MG and may require surgical removal.

What diagnostic criteria support MG?

• Positive AChR antibodies

• Fatigable weakness

• EMG decrement

• Ice pack improvement

What are the primary treatment goals in MG?

• Improve neuromuscular transmission

• Reduce autoimmune activity

• Manage symptoms

• Prevent myasthenic crisis

What is the first‑line symptomatic treatment for MG?

Pyridostigmine

What are common side effects of pyridostigmine?

Cholinergic symptoms such as diarrhea, abdominal cramping, and increased salivation.

What chronic immunotherapy is used in MG?

Glucocorticoids

What rapid immunomodulating treatments provide short‑term relief in MG?

Plasmapheresis and IVIG

What steroid‑sparing agents may be used in MG?

Azathioprine or mycophenolate.

What surgical treatment is used in MG?

Thymectomy, even in some patients without thymoma.

What medications can worsen MG?

Aminoglycosides, fluoroquinolones, beta‑blockers, magnesium.

What complications can occur in MG?

• Myasthenic crisis

• Cholinergic crisis

• Aspiration risk

What is myasthenic crisis?

Life‑threatening respiratory muscle weakness requiring ventilatory support.

How is myasthenic crisis treated?

Plasmapheresis or IVIG plus respiratory support.

What is cholinergic crisis?

Excessive AChE inhibitor use causing weakness, salivation, diarrhea, and miosis.

How is cholinergic crisis treated?

Stop AChE inhibitors and provide supportive care.

How is MG monitored over time?

• Respiratory function (FVC)

• Symptom progression

• Antibody levels

• Thymoma recurrence if removed

What lifestyle modifications help manage MG?

Avoid triggers such as infection, stress, heat, and medications that worsen MG.

What is Lambert‑Eaton myasthenic syndrome (LEMS)?

A presynaptic disorder causing proximal weakness that improves with activity, associated with small cell lung cancer.

How does LEMS differ from MG?

• LEMS improves with activity

• Hyporeflexia

• Autonomic symptoms

• Often paraneoplastic

What is the treatment for LEMS?

Treat underlying cancer and 3,4‑diaminopyridine.

What is botulism?

A toxin‑mediated disorder causing descending paralysis and pupillary involvement.

What is the treatment for botulism?

Botulinum antitoxin

What is Guillain‑Barré syndrome (GBS)?

An autoimmune demyelinating disorder causing ascending paralysis and areflexia.

What is the treatment for GBS?

IVIG or plasmapheresis

How does ALS differ from MG?

ALS has mixed UMN/LMN signs, no fatigability, and no ocular involvement.

How do cranial nerve lesions or brainstem tumors differ from MG?

They cause focal deficits that are not fatigable and show abnormalities on imaging.

How does Lyme disease mimic MG?

Facial nerve palsy and weakness

What is the treatment for neurologic Lyme disease?

IV ceftriaxone

What are the highest‑yield clinical pearls for MG?

• MG worsens with activity and improves with rest

• AChR antibodies are diagnostic

• Ice pack test improves ptosis

• Thymoma strongly associated with MG

• LEMS improves with activity

• Avoid aminoglycosides and fluoroquinolones