Myasthenia Gravis and the Eye (Video)

In this video, Dr. Mizen speaks about some of the ocular manifestations of Myasthenia Gravis and the eye complaints that patients may present to you complaining about. Dr. Mizen speaks about the ocular manifestations of myasthenia Gravis. Another video on myasthenia. This one seems to be at the same event as this other video. The end credits mention visiting myastheniagravis.org for more videos. I can’t find any more videos on that site, but I belive this full lecture is available for ordering.

Myasthenia Gravis (editor’s comments)

Myasthenia gravis is a rare autoimmune disease in which the body develops autoimmune antibodies to the nicotinic acetylcholine receptors located at the neuromuscular junction of striated muscle. This leads to fatigable muscles and often involves the eye, causing diplopia and ptosis.

Mechanism:
MG patients develop autoantibodies that actually bind to the receptor and block the receptor binding sites, and eventually destroy the receptor entirely, leaving patients with decreased numbers of Ach receptors … once the number drops below 30% normal, then the patient becomes symptomatic, with easily fatigability. Interestingly, only striated muscle is affected, as both smooth and cardiac muscle appear to have different antigenicity, and are unaffected with this disease. The bulbar muscles, however, are quite susceptable, and the majority of patients with MG have ocular complaints … the ophthalmologist is often the first doctor to diagnose the disorder.

Clinical Signs:
These patients often present with ocular “fatigability” …as the day progresses, the symptoms often worsen.
Ptosis: This is one of the most common ocular findings. The eyelids become droppy from fatigue of the levator palpebrae muscles. To test this, you can work this muscle with the arm test … hold your finger up in the air and have your patient look at it … see who gets tired first, the patient’s eyelid or your arm.
Double vision: The double vision in these patients can look like an isolated nerve palsy, a mixture of nerves, or may not fall into any specific nerve combination. A changing palsy is more indiciative of a process like MG. It can give a pseudo-INO The pupil is never involved. The vertical muscles are often involved (often the inferior rectus). If a horizontal muscle is involved, it’s often the lateral rectus.
Cogan’s Eyelid twitch: Have the patient look down, then look in the primary position. A temporary overelevation of the upper-eyelid is seen before the eyelid returns to its previous ptotic position.

Systemic findings: Problems with mastication, talking, drinking and difficulty swallowing and neck weakness are all classic non-ocular symptoms. Aspiration pneumonia and respiratory failure from a reduced gag reflex and inability to clear secretions is the big killer with this disease.

Stressors: The disease can be exacerbated or unmasked by various stressors to the acetylcholine system … these include several antibiotics and antiarrhythmics. There are many stressors, so I won’t list them.

Who gets it?
MG typically occurs in men over 60, and woman under 40. It can also occur in children as a congenital condition or as a transitory “neonatal MG” that occurs for a few weeks from the mother’s antibodies circulating through the infant … so if you see a newborn with droopy eyelids, think about this as a possibility.

Testing:
Tensilon (edrophonium) test: This is the classic test for MG, though we don’t use it often in the eye clinic (the neuro people seem to use it more often, though). Edrophonium is a rapid, short-acting antichoinesterase that blocks ACh breakdown … leading to high levels. You give a test dose of 1mg, then optionally another 4mg, then another 4mg separated by a minute. Patients typically get better in about a minute. This test is potentially dangerous however, with the patient developing profuse lacrimation, sweating, nausea, vomiting … and they can even developa dangerous bronchosasm, bradycardia, and heart block. Atropine is often given concurrently as an antidote. Of interest, this test also works for botulism poisoning.

Sleep Test: A rest test, where you have the patient sit in a dark room with their eyes closed for 30 minutes. Then check their ptosis and EOMs right when they “wake up”

IcePack Test: The theory behind this is that neurotransmission improves with cold temperature … in fact, higher core temperature is one of the exasperating symptoms for MG crises. . However, it may just be the ice-pack allowing the eye to rest that is actually doing all the work. You apply the icepack for two-minutes.
EMG: Shows fatiguability (decreased response) as expected

The Walker??? Test
This is an interesting test. Basically, you place a blood-pressure cuff on the arm to restrict venous flow to the rest of the body. Then you have the patient workout the arm. This builds up antibodies in that part of the body, when you take the cuff off, the patient’s ocular symptoms suddenly gets worse. This is a useful test for kids who will resist the sleep and ice-pack tests.

Labwork: Can get anti-acetylcholine receptor antibodies. There are three types available:
a. Binding antibodies: most common
b. Blocking antibodies: less common
c. Modulating antibodies: less common
Generally, you only check the binding antibodies, and get the others if these come back negative. According to Odel, he orders the entire panel, and an overall AchRab level. You can also get MUSK antibodies if none of the above come back positive. In non-sytemic MG, sometimes the yield on ACHR antibodies is only 60%.

Associated Findings:
Thymus: These patients have associated thymus problems, and the thymus is thought to be the location of autoantibody formation. Up to 15% will show a thymoma on initial CT, so this test is always ordered on new MG patients as its highly accurate. A much larger percentage (like 85%) have thymus hyperplasia.
Thyroid Disorders: Seen in approximately 10% of patients, so we check for other autoimmune processes like lupus.
Other autoimmune disorders like lupus, and rheymatoid arthritis

Treatment:
You can treat with longer-acting Ach-esterase inhibitors, steroids, and immunosupression. In the ICU setting, can also give IVIG and plasmapheresis.