BLOG: How can I tell if my patient has myasthenia gravis?

Last month a patient of mine came back to the clinic telling me of his difficulty with his glasses. His complaints have always been variable, but mostly stating that he has difficulty reading letters, whether they are far or near.

In the past, we have attributed these complaints to uncorrected astigmatism, progressive-addition lens-misalignment or decompensating exophoria, depending on the day. Frustratingly, these complaints mostly happened at his house, and we weren’t able to manifest the symptoms in the hospital. But the last visit was a little different – that time he used the words “double vision.”

I reassessed his complaints and realized that his “blurring” could be rephrased as “ghosting,” and the fact that we don’t see signs during the (usually morning) eye exam could be rephrased as it happening more at night. Then I looked at his eyelids and thought I saw the left upper lid as slightly ptotic compared to the right.

For this patient, most doctors would suspect myasthenia gravis (MG), with the classic symptoms of extraocular muscle (EOM) and superior levator weakness, especially at the end of the day. Before we go any further about how to diagnose MG, let’s explore the pathophysiology.

In normal neuromuscular transmission, acetylcholine (ACh) is stored in the presynaptic motor nerve terminus and released into the synapse when an action potential travels down that nerve. Free-floating ACh is then bound by acetylcholine receptors (AChRs) in the post-synaptic muscle. A cation channel in each AChR opens, producing depolarization in the muscle and – if the depolarization is large enough – generating an action potential down the muscle fiber, resulting in muscle contraction. At some point, the process ends by acetylcholinesterase (AChE) diffusing enough ACh away from the AChRs.

Patients with MG have circulating anti-AChR antibodies that function to block, damage and destroy AChRs, making it much harder for a muscle to generate a strong enough depolarization to stimulate an action potential for muscle contraction. The hallmark features of MG are the weakness and fatigability of the affected skeletal muscles, thus the reason why a patient’s symptoms are usually better in the morning (or after a nap) and worse in the evening.

Because the lids and EOMs are usually the first muscles affected, eye doctors will often be the first specialists to confront and diagnose this condition. In fact, in 70% of cases, the levator palpebrae superioris and EOMs are the first muscles affected and are eventually affected in 90% of MG cases (Newman et al.). The disease may then progress to affect limb, bulbar and respiratory muscles.

Without medical treatment, the death rate is 25% to 31% and is typically due to respiratory failure; with medical treatment, the death rate is only 3% to 4% (Gajdos et al.). Bulbar muscles, incidentally, are those of the mouth and throat associated with speaking and swallowing. They are innervated by the lower cranial nerves (7 to 12), which originate from the medulla, which is bulb-shaped – hence the name.

But what’s the next step to confirm the diagnosis? Once suspected, most of us perform: extended upgaze test (which worsens a ptosis/diplopia by fatiguing it), icepack test (which improves a ptosis/diplopia by slowing down AChE) or sleep test (which improves a ptosis/diplopia by allowing time for ACh to replenish). But sometimes these results can be equivocal, and it’s hard to be confident with a MG diagnosis.

The good news is there is a blood test for MG called anti-acetylcholine receptor antibodies. It has a very high specificity, so if positive there is a 99% likelihood the patient has MG (Benatar). The sensitivity is also relatively high at 84%, so if the test is negative, then the diagnosis is likely excluded. The bad news is that if the MG is early enough – like when only ocular signs are manifest – the sensitivity drops to 29% to 61%, and a negative test does not help exclude the diagnosis.

So, by all means order the blood test and, if positive, hang your hat on that diagnosis. But if negative, then consider additional testing such as edrophonium (Tensilon) testing, repetitive nerve stimulation and/or single-fiber electromyography, all of which would be done in a neurologist’s office outside of typical eye care settings.

We all see ptosis in our clinics, and sometimes they can be pretty subtle. But when you see one, keep your diagnostic senses on-guard for MG – ask the patient about vision changes, not just diplopia. Most MG patients don’t walk in with a dramatic ptosis and complaints of double vision at the end of the day. A probing case history can help increase your suspicion and not be fooled like I was with this patient, and have a low threshold to order the anti-AChR test, which is unequivocal if positive.

Once diagnosed, these patients should be treated by a specialist in neuromuscular disease, but with appropriate input from you, their eye doctor. An early diagnosis and proper treatment of this difficult disease can allow almost all MG patients to live full and productive lives.

References :

Benatar M. Neuromuscular Disorders. 2007;17(3):267-268. doi: 10.1016/j.nmd.2006.12.007.

Gajdos P, et al. Cochrane Database Syst Rev. 2008;23(1):CD002277. doi: 10.1002/14651858.CD002277.

Kasper et al. Harrison’s Principles of Internal Medicine, 16^th edition. 2005. New York: McGraw-Hill; 2518-2523.

Miller NR, et al. Walsh and Hoyt's Clinical Neuro-Ophthalmology: The Essentials, second edition. 2008. Philadelphia: Lippincott Williams & Wilkins; 407-417.