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Myasthenia Gravis (MG)

URGENT — Neuro

Symptoms

painless, variable, and often asymmetric droopy eyelid (ptosis)

double vision (diplopia) that fluctuates or worsens with fatigue

symptoms typically worse later in the day or after sustained activity

facial weakness (flat smile), weak chewing, or difficulty swallowing (dysphagia)

proximal limb weakness (difficulty with stairs or overhead reaching)

shortness of breath (medical emergency: myasthenic crisis)

Clinical Findings

Hallmark features

  • fatigability: muscle strength declines with repeated use or over time
  • variable motility: can mimic any pupil-sparing cranial nerve palsy or gaze palsy
  • normal pupils: pupils are never involved; their involvement excludes MG

Bedside diagnostics

  • cogan lid twitch: brief upward overshoot of the lid after looking from down to primary gaze
  • curtain sign (enhanced ptosis): lifting the more-ptotic lid causes the other lid to drop
  • ice pack test: 2 minutes of cooling improves ptosis by ≥2 mm (increases ACh half-life)
  • orbicularis weakness: eyelids are easily pried open against the patient's resistance

Systemic signs

  • "MG sneer": mid-facial weakness on attempted smiling
  • bulbar signs: dysarthria (slurred speech) and weak cough

Etiology

Autoimmune mechanism

  • post-synaptic acetylcholine receptor (AChR) antibodies block neuromuscular transmission
  • subset cases involve anti-MuSK or anti-LRP4 antibodies

Thymic involvement

  • 10–15% of patients have a thymoma; thymic hyperplasia is common in younger patients

Overlap

  • associated with other autoimmune conditions like Graves disease (5%), SLE, and RA

Red Flags

bulbar symptoms (slurred speech, difficulty swallowing) → impending crisis

shortness of breath or weak respiratory effort → admit for FVC/NIF monitoring

thymoma on chest CT → requires surgical thymectomy

use of contra-indicated meds (e.g., fluoroquinolones, beta-blockers, magnesium)

Investigations

Clinical tests

  • ice pack test or rest test (30 minutes of dark rest) to observe improvement
  • sustained upgaze for 60 seconds to document progressive ptosis

Laboratory & imaging

  • serology: acetylcholine receptor (AChR) binding, blocking, and modulating antibodies
  • chest CT (mandatory): to rule out thymoma in all confirmed cases
  • thyroid function tests (TSH, fT4): screen for concurrent Graves disease

Electrophysiology

  • single-fiber EMG (SFEMG): most sensitive test for ocular MG (increased jitter)
  • repetitive nerve stimulation: look for decremental response

Treatment

Pharmacologic

  • pyridostigmine (Mestinon): first-line symptomatic relief (anticholinesterase)
  • systemic steroids: used for persistent ocular symptoms; hospitalize for initiation if risk of crisis
  • steroid-sparing agents: mycophenolate, azathioprine, or rituximab (especially for anti-MuSK)

Acute intervention

  • plasmapheresis or IVIG: for myasthenic crisis or pre-surgical optimization

Surgical

  • thymectomy: indicated for thymoma and often beneficial for generalized AChR+ disease

Clinical Pearl

MG is the great imitator of other ocular motility disorders. Anti-AChR antibodies positive in 85% generalized, 50% ocular MG. Anti-MuSK positive in seronegative generalized MG. Tensilon (edrophonium) test largely replaced by ice pack test (safer, no cardiac risk). CT chest mandatory — 10-15% have thymoma. Ocular MG: 50% generalize within 2 years.

Differential Diagnosis

  • thyroid eye disease (TED)
  • chronic progressive external ophthalmoplegia (CPEO)
  • third nerve palsy (check pupils!)
  • eaton-lambert syndrome (strength increases with exercise)
  • myotonic dystrophy

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