Surgery to cure Myasthenia Gravis

In episode 18, we talked about the antibodies seen in myasthenia gravis. But we didn’t really get to go into the details of how a patient with myasthenia should be managed. In this episode, we take the time to do just that:

So you’ve made the diagnosis.  High five! 😎 What next? In managing myasthenia, I like to think about FOUR major approaches to treatment.

  1. Pyridostigmine — for symptomatic relief
  2. Corticosteroids — to suppress B and T-cell activity
  3. Steroid-sparing agents like azathioprine — to reduce the need for corticosteroids
  4. Surgery

Our “go-to” drug, one most patients tolerate, is the cholinesterase inhibitor, pyridostigmine.

Mestinon (generic: pyridostigmine).

Because of the major cholinergic side effects (nausea, diarrhea, bradycardia, etc), most providers start at a low dose (30mg TID or so) and increase as tolerated to 60 or 90mg 4-6 times daily. Pyridostigmine has the effect on myasthenia equivalent to damage done by a BB gun. It’s not exactly a toy, but it takes a lot of it to make a little bit of damage.

If you want something stronger than a BB gun, you tank up your patient with steroids. This would be like using a shotgun. And like a shotgun, which sprays a bunch of tiny metal pellets in all directions, steroids impact the human body in all kinds of ways—good and bad. Specifically in myasthenia, it acts to suppress T and B-cell function, which are implicated in antibody formation and acetylcholine receptor degradation. But it also causes osteoporosis, cataracts, insulin resistance and hyperglycemia, it negatively impacts sleep, and so on. Unlike pyridostigmine which can work within half an hour, steroids begin to take effect after 2-3 weeks and are maximally effective after 5 or 6 months. 

But you can’t go on using a shotgun forever. You need something more targeted. Like a rifle. Only this rifle is called azathioprine. Or cyclosporine or mycophenolate mofetil. Azathioprine works by inhibiting purine synthesis in rapidly dividing cells—like B and T cells. Cyclosporine inhibits release of Il-2 and T-cell activation. And mycophenolate works by inhibiting nucleotide synthesis, which also slows T and B-cell replication. Now, when choosing which of these steroid-sparing drugs to use in a patient with myasthenia, I usually consider what are the contraindications to therapy. For instance, a patient with chronic liver disease should not get azathioprine. It can cause hepatotoxicity, and this only makes pre-existing liver disease worse. Leukopenia is also not a good foundation on which to start azathioprine and it’s also bad for starting mycophenolate, so you might go with cyclosporine here. Renal disease, on the other hand, is a contraindication for cyclosporine, so that takes you back to mycophenolate or azathioprine again. And compared to steroids which take effect after a few weeks, these immunomodulators may take months to a year before patients really improve.

Treatment options for myasthenia, courtesy of UpToDate.com.

So what can you do in the interim to speed up the process? Well, as you probably know, there are acute and rapidly effective immunomodulating therapies you can use—which we often use for acute flares of myasthenia or crises. These include plasmapheresis or intravenous immune globulin. As far as which one to choose, IV Ig and plasmapheresis are considered equivalent interventions, just like their efficacy in treating Guillain Barre Syndrome.

What if you don’t like guns? You’re a pacifist, and you hate this whole NRA analogy I’ve been conceiving. Well it turns out, thymectomy works extremely well in patients with thymoma…For a lot of reasons!! And that’s really the point of this episode, discussing why and how thymectomy works, and who should be considered for this surgical procedure. To learn more, I suggest you myasthenia gravis-tate toward the audio content the history and current state of thymectomy are reviewed.

 

[Jim Siegler]


REFERENCES

  1. Schneider-Gold C, Gajdos P, Toyka KV and Hohlfeld RR. Corticosteroids for myasthenia gravis. The Cochrane database of systematic reviews. 2005:CD002828.
  2. Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A, Strobel P, Mazia C, Oger J, Cea JG, Heckmann JM, Evoli A, Nix W, Ciafaloni E, Antonini G, Witoonpanich R, King JO, Beydoun SR, Chalk CH, Barboi AC, Amato AA, Shaibani AI, Katirji B, Lecky BR, Buckley C, Vincent A, Dias-Tosta E, Yoshikawa H, Waddington-Cruz M, Pulley MT, Rivner MH, Kostera-Pruszczyk A, Pascuzzi RM, Jackson CE, Garcia Ramos GS, Verschuuren JJ, Massey JM, Kissel JT, Werneck LC, Benatar M, Barohn RJ, Tandan R, Mozaffar T, Conwit R, Odenkirchen J, Sonett JR, Jaretzki A, 3rd, Newsom-Davis J, Cutter GR and Group MS. Randomized Trial of Thymectomy in Myasthenia Gravis. The New England journal of medicine. 2016;375:511-22.

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