Myasthenia Gravis

    • Autoimmune attack on muscle acetylcholine receptors that impairs neuromuscular transmission
    • Affects all somatic muscles in the body, but particularly the levator palpebrae superioris, extraocular muscles, and orbicularis oculi
    • Favors young women and old men
    • First clinical manifestations are often ptosis and diplopia (50%)
    • Ptosis worsens with sustained upgaze, improves with restful eye closure and an icepack on the eyelids
    • Ocular ductions, even if reduced, are usually of normal speed
    • Orbicularis oculi is often weak, interfering with forceful eyelid contraction
    • No pupillary or accommodation abnormalities
    • Weakness of proximal limb muscles, chewing, swallowing, or breathing in generalized myasthenia gravis
    • Thymus tumor present in 10% or fewer patients
    • Internuclear ophthalmoplegia
      • Tip: myasthenia gravis often causes prominent weakness of medial rectus contraction, producing an adduction deficit that resembles INO (“pseudo INO”); in myasthenia, adduction starts at normal velocity but slows down, whereas in third nerve palsy, adduction starts slowly and remains slow; this distinction is not easily apparent clinically, but will be evident on formal eye movement recordings
    • Third nerve palsy
      • Tip: if myasthenic deficits appear limited to one eye, pupil-sparing third nerve palsy may be misdiagnosed, but as third nerve palsy is the more urgent diagnosis, it is not a mistake to order prompt vascular imaging to rule out aneurysmal compression of the third nerve in such cases
    • Genetic extraocular myopathy (chronic progressive external ophthalmoplegia)
    • Graves disease
    • Congenital myasthenia
    • Orbital myositis
    • Drug-induced neuromuscular transmission disorder
    • Venom-induced neuromuscular transmission disorder
    • Botulism
    • Ptosis of previous trauma, surgery, or inflammation
    • Ocular motor cranial nerve palsy
    • Fisher variant of Guillain–Barré syndrome
    • Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
    • Decompensated phoria
    • Skew deviation
    • Acquired ocular motor apraxia
    • Progressive supranuclear palsy
    • Exclude reduced pupil constriction to light, which would eliminate myasthenia gravis as a diagnosis (unless the patient had previous intraocular surgery or other trauma as the cause of this feature!)
    • Exclude marked improvement in ocular ductions with doll’s eye maneuver, which would suggest progressive supranuclear palsy
    • Exclude absent deep tendon reflexes, which would suggest Fisher variant or CIDP
    • Exclude family history of a similar disorder, slowly progressive features, and other myopathic features, which would suggest genetic extraocular myopathy
    • Look for improvement in ptosis after the patient has taken a 30-minute nap (“sleep test”) or has had ice placed on the ptotic eyelid for 5 minutes (“ice test”)
    • Tip: sleep and ice tests are not diagnostically useful in patients who have ocular misalignment without ptosis
    • Follow this diagnostic sequence
      • Order the acetylcholine receptor binding antibody test, which will be positive in 50%-70% of ocular myasthenia and never in non-myasthenic conditions (100% specific)
      • If the antibody test is positive, order chest CT to rule out a thymic mass
      • If chest CT shows a thymic mass, perform chest MRI to differentiate thymoma from thymic hyperplasia
      • Refer for surgery if imaging suggests a thymoma
      • If the antibody test is negative, consider ordering single-fiber electromyography, which should show excessive jitter in 80% of ocular myasthenia cases, but false positives occur even with expertise
    • 50% of patients with ophthalmic manifestations eventually develop systemic weakness (involving muscles of limb girdle, face, neck, mastication, swallowing, phonation, and breathing), usually within 2 years of onset of ophthalmic manifestations
    • Diagnosis of myasthenia gravis can be confirmed in 90% of patients by a combination of a positive serum acetylcholine receptor binding antibody (ARAB) and the finding of jitter on single-fiber electromyography (SFEMG)
    • Tip: repetitive stimulation electromyography is usually normal in patients with purely ocular manifestations
    • Pyridostigmine 60–240mg every 3–6 hours may alleviate ophthalmic manifestations, but is less effective than prednisone 10-20mg/day and other immunomodulatory agents (azathioprine, cyclosporine, mycophenolate mofetil)
    • Intravenous immunoglobulin and plasmapheresis are reserved for debilitating ophthalmic and neurologic manifestations
    • Prism spectacles are useful for lingering diplopia
    • Patching one eye or inserting an opaque contact lens relieves diplopia when prisms are not fully effective
    • Eye muscle surgery often relieves diplopia, but…
    • Trap: do not perform eye muscle surgery unless myasthenic diplopia is present in primary gaze position and has been stable for at least one year despite appropriate treatment, including prisms
    • Eyelid surgery is useful for chronic stable ptosis
    • Spontaneous remissions occur in 20% of patients at any time after diagnosis

    Extraocular Muscle Disorders

    Genetic Extraocular Myopathies Orbital Myositis Graves Disease Myasthenia Gravis