Weatherly's Woes - Myasthenia Gravis

MYASTHENIA GRAVIS

Autoimmune weakness

Myasthenia Gravis is an autoimmune disease that causes muscle weakness.

How does MG work?

It’s an autoimmune disease. Specifically, a type 2 hypersensitivity. Their immune systems don’t recognize their own Acetylcholine Receptors on their postsynaptic neuromuscular junctions (these receptors tell your muscles to move). They make antibodies that attack these helpful receptors, and over time those antibodies destroy the postsynaptic neuromuscular junction. You can probably see why MG is progressive and (eventually) irreversible. The smallest muscles lose function first, which happen to control the eyes and throat. So, that means that the first symptoms to appear are ocular (diplopia, ptosis) and pharyngeal (dysphagia).

Does it cause problems with sensation or reflexes?

Nope. Just weakness.

Why is weakness with MG fatigable?

There are only so many ACh receptors. If the patient contracts their muscles over and over and over, then eventually they will consume them all. This explains why patients with MG have fatigability; that is, their symptoms get worse the more they move. You can test this by asking them to blink rapidly.

Is MG fatal?

It can be. The clinical course can vary widely, and more often than not MG has a long drawn out course, but it should definitely be taken seriously. Many patients have sudden attacks of worsening weakness, called a myasthenic crisis, and if their breathing muscles weaken then they are vulnerable to suffocation. Also, about 15% of MG patients have a concurrent thymoma, which is absolutely fatal if it’s not excised. Every newly diagnosed case of MG should get a chest CT to rule out a thymoma.

How do you diagnose MG?

There’s a lot of tests. An ELISA test looking for antibodies to the ACh-Receptor would probably be the gold standard, but there are two other neat tricks. If you put a ziplock baggie full of ice over their eyes, their ptosis improves (not sure why it happens, but it’s cool). If you want another test, you can administer Edrophonium (Tensilon) which is a short acting ACh-Esterase Inhibitor. It should clear up their symptoms for a few moments, clinching the diagnosis.

How to treat it?

Give a long-acting AChE Inhibitor like Pyridostigmine or Neostigmine. Give them steroids, because basically every autoimmune disease is treated with steroids. And if it’s a crisis, do some plasmapheresis. And don’t forget to perform a chest CT to rule out a thymoma. If you find a thymoma, surgically remove it.

LAMBERT-EATON SYNDROME

MG lookalike

Lambert-Eaton Myasthenic Syndrome is another autoimmune condition with muscle weakness, but the immune attack is directed against presynaptic calcium receptors. is very similar to MG, so it’s easy to get the two mixed up. LEMS is a lot rarer, but I think they teach it to us because it highlights a lot of the features of MG, which is a pretty common disorder. If you ever happen to see a case of severe LEMS, their symptoms would look almost identical to a myasthenic crisis -- full body paralysis. Problem is, MG and LEMS have different treatments. But if you do the correct tests, you can parse out the truth.

Is there any difference in symptoms between LEMS and MG?

Yes. But it’s subtle. In MG the weakness was fatigable (because they burned up all of their ACh stores). But in LEMS, the weakness improves with continued use. Here’s why. Patients have a hard time getting Ca++ into their neurons. They have huge stores of ACh, but they just can’t release them without the Ca++. Therefore, if they try to contract their muscles over and over and over again, they can eventually pump enough Ca++ into the presynaptic neuron to enable neurotransmitter release. This explains why their weakness improves with use. Another difference is that LEMS causes hyporeflexia.

Is LEMS associated with thymomas too?

No. While LEMS is a paraneoplastic syndrome, it’s usually associated with small cell lung cancer instead of thymomas.

How to diagnose?

When given Edrophonium (Tensilon), their symptoms will NOT improve. Also, there are probably some specialized ELISA tests looking for Ca++ channel antibodies. An EMG (electromyograph) would confirm the results, but I don’t think that’s within the realm of this course. And don’t forget to always get a chest CT to look for small cell lung cancer!