Myasthenia Gravis: Treatment

00:01 So how do we treat patients with myasthenia gravis? Well, this is a nice graph that depicts the overview of treatment.

00:08 Patients can present in the middle of a flare or with prolonged disease and the types of treatment that we select vary based on the time of when this patient is presenting.

00:19 When a patient is suffering an acute flare of myasthenia gravis.

00:21 When the immune system is revved up.

00:24 When the neuromuscular junctions are under attack, and patients have prominent symptoms, we need to induce remission.

00:31 And to induce remission, there are two main arms of treatment.

00:35 The first is prednisone and the second is plasmapheresis, and intravenous immunoglobulin.

00:40 We're going to talk about each of these treatments in greater detail.

00:43 But plasmapheresis and intravenous immunoglobulin are key treatments that we use to induce remission of patients who are suffering a myasthenic crisis or an exacerbation of their disease.

00:55 Once remission has been achieved we want to maintain remission and we do that with a variety of agents prednisone is the most common of these.

01:03 There are other chronic immune directed therapies and sometime IVIg intravenous immunoglobulin can also be continued.

01:12 At times patients may suffer an exacerbation.

01:14 The immune system may be revved up for some reason.

01:17 They're myasthenic may flare, they may present either to the clinic or to the hospital with an exacerbation and again, we will try to induce remission either with increasing prednisone in the outpatient setting, or with plasma freezes or intravenous immunoglobulin for patients who are admitted to the hospital, and particularly those with respiratory distress.

01:37 And then finally, we want to again induce remission, and we think about prednisone and other immune directed therapies.

01:45 We also want to treat patient symptoms and symptomatic treatment includes pyridostigmine.

01:49 This is an acetylcholinesterase inhibitor.

01:52 It inhibits that enzyme that breaks down acetylcholine, and the end result is you get more acetylcholine in the synaptic cleft.

01:59 It rapidly gets into the system and is rapidly degraded and so it's taken multiple times throughout the day to improve patient symptoms.

02:08 It is not a disease modifying therapy.

02:10 It doesn't change the natural course of myasthenia gravis but can improve symptoms for patients and is taken frequently throughout the day for patients who have prominent symptoms.

02:21 Exacerbations as we saw are treated with other agents.

02:24 And the most common two agents are plasmapheresis and intravenous immunoglobulin.

02:28 And we should learn a little bit more about each of those.

02:33 Thymectomy is also an important treatment to consider.

02:36 The thymus gland is a vestigial structure that lies in the mediastinum, in the anterior part of the chest.

02:42 It's important in immune regulation.

02:45 And we've seen that patients who have a thymoma or a tumor of the thymus gland or an enlarged thymus gland are at increased risk of developing myasthenia and that their symptoms can improve when their thymus or thymoma is removed.

02:59 Importantly, with thymectomy removal of the thymoma, we don't see immediate improvement in the patient symptoms, but it can be an early treatment that can lead to long term remission.

03:11 Corticosteroids and prednisone are important treatment for long term maintenance, maintaining remission once it's been achieved.

03:18 For patients who require long term steroids and can run into complications with corticosteroids side effects, we think about steroid sparing agents like methotrexate, Imuran, and Rituxan is increasingly used in the treatment of these patients.

03:33 Let's talk a little bit more about plasmapheresis and intravenous immunoglobulin.

03:38 These are treatments used throughout neurology and specifically for treating myasthenia gravis and exacerbations or flares in this condition.

03:45 Plasmapheresis involves the removal of the acetylcholine receptor antibodies or the musc antibodies or circulating antibodies for any autoimmune condition.

03:55 In the same way, intravenous immunoglobulin also removes these from the system.

03:59 So the mechanism of action is very similar.

04:02 Plasmapheresis is apheresis treatment.

04:04 It's like dialysis.

04:05 Patients are hooked up to a machine.

04:07 their blood is circulated through the machine.

04:10 The antibodies and immune cells are filtered out of their blood and the patient's blood is put back into the patient.

04:16 So it's kind of like a dialysis treatment for immune mediated conditions.

04:21 Intravenous immunoglobulin is a treatment.

04:23 It's an infusion that's delivered to the patient.

04:27 Those intravenous immunoglobulins bind up other antibodies.

04:31 The acetylcholine receptor antibodies are the musc antibodies, and then those are then excreted through the kidneys.

04:38 Plasmapheresis is delivered in sessions and typically we think of five sessions spaced out every one to every other day.

04:44 So it's about a week to week and a half treatment.

04:47 The IVIg is delivered in successive days as well to total dose of 2 grams over the course of five days or 0.4 grams per kilogram per day.

04:58 For plasmapheresis, it's a dialysis tripe treatment.

05:01 It's a pheresis treatment, it's a filtration treatment.

05:03 So patients need central access.

05:05 That's not required for intravenous immunoglobulin, where peripheral IVs are acceptable.

05:11 There's really no superiority over the increasing number of plasmapheresis sessions or how you space out the sessions, we do five sessions, and that's a standard treatment.

05:20 For IVIg, the action is not quick.

05:23 Patients undergo the treatment over about five days.

05:26 And we typically see peak improvement at two weeks.

05:29 And we continue to see that those intravenous immunoglobulins lasts for about six weeks.

05:34 So it's a long term treatment.

05:37 Plasmapheresis has rapid onset in 3 to 10 days.

05:40 And again, we talked about IVIg, lasting as long as 30 days.

05:44 And maybe requiring as long as 30 days to see peak improvement.

05:48 And we should be cautious with each of these treatments.

05:50 For plasmapheresis, we need to be cautious for patients who have sepsis or hypotension, or could be at risk for bleeding.

05:56 And there are some important side effects with intravenous immunoglobulin.

05:59 Patients who have an IGA deficiency can develop anaphylaxis.

06:02 So all patients who receive IVIg should undergo IGA testing prior to that treatment.

06:07 And we can see things like renal failure, pulmonary edema, thrombotic complications like stroke or heart attack, and aseptic meningitis.

06:17 What are some precipitants of myasthenia gravis? What causes the exacerbations the flares of this disorder that we may want to counsel patients to avoid? Well, some of the things that we think about in history, we think about medical treatments and the lack of medical treatments or tapering of medical treatments like steroids can induce an exacerbation.

06:39 Use of certain medications can drive a myasthenia exacerbation magnesium and some beta blockers as well as antibiotics are important causes of an exacerbation.

06:49 Infections can contribute to worsening of myasthenia and can contribute to myasthenic crisis, aspiration events, surgeries or other stressors, emotional stress.

06:59 Hot environments can cause temporary or transient worsening of symptoms and hyperthyroidism.

07:05 There are a number of potential exacerbates that should be avoided in patients and are important in counseling.