Myasthenia Gravis: Clinical and Serological Tests – Diagnosis

00:01 How do we evaluate patients? What do we do on exam? How do we use provocative testing? And what laboratory studies should we consider to work up a patient who were concerned may have myasthenia? Well, the first is we perform a comprehensive neurologic exam.

00:16 Looking for signs of weakness and fatigability.

00:19 If we see the presence of ptosis, there's two really neat examination techniques that can evaluate that ptosis and point to that problem being from the neuromuscular junction.

00:30 And so these tests are performed when there is prominent bulbar weakness or prominent ptosis.

00:35 The first is the ice-pack test.

00:37 This is a really neat test.

00:39 And we're looking for resolution of ptosis.

00:42 So we saw those images of patients whose eyes were closed, and we place an ice-pack, and we see that the eye opens.

00:49 Why does this happen? Well, it turns out when you cool down the neuromuscular junction, this improves neurotransmission.

00:56 And so we see better acetylcholine quanta released into the neuromuscular junction, and better depolarization of muscles.

01:04 To perform this test, a patient is put at the bedside, we get a cold ice-pack and place it over the eye.

01:12 After about a minute, we look for rapid resolution of ptosis.

01:16 And this occurs quickly and needs to be evaluated quickly after performing this test.

01:21 The second neat bedside test that can evaluate for the presence of a junctional disorder is the edrophonium test.

01:27 This is also called the Tensilon test.

01:29 And again, we're looking for resolution of ptosis.

01:33 This is a medication that can improve transmission at the neuromuscular junction.

01:37 And so we're also looking for the presence of ptosis prior to the test that resolves immediately after.

01:44 What about serologic testing? What studies can we do to evaluate for myasthenia gravis? Well remember, myasthenia is an inflammatory disorder.

01:53 It's an autoimmune condition.

01:55 And it's characterized by the presence of autoreactive antibodies.

01:59 So we're going to look at those in the circulating system.

02:03 The serologic studies that are performed include looking for acetylcholine receptor antibodies, anti-MuSK, the muscle specific kinase antibodies.

02:12 And there are some other increasingly described antibodies that we'll talk about.

02:16 And we can categorize the myasthenia as seropositive in patients who have the presence of one of those antibodies, and seronegative in those that have a clinical presentation consistent with myasthenia but the absence of antibodies.

02:31 So let's look a little bit closer at the postsynaptic acetylcholine receptor.

02:36 Myasthenia is characterized by antibodies that bind to recognize an auto react to this receptor.

02:43 And we can see antibodies that bind to many of these areas.

02:47 Here you can see the extracellular space, the sarcolemma, which is the cell membrane of the muscle and the muscle tissue itself.

02:55 The acetylcholine receptor lies on this membrane recognizes acetylcholine quanta in the synaptic cleft, and results in activation of the muscle as a result of bringing sodium in to the muscle cell.

03:08 Acetylcholine receptor antibodies bind to this receptor and result in the loss of function inability to bring sodium into the muscle and activate the muscle for contraction.

03:18 The second antibody that we see is the antibody to MuSK.

03:21 And you can see the MuSK component of this acetylcholine receptor here.

03:25 A docking enzyme that's critical for its action.

03:29 So let's look a little bit closer at the types of myasthenia based on serologic testing.

03:33 And understand the features of those antibody tests.

03:37 Well, acetylcholine receptor antibodies are present in the vast majority of myasthenics.

03:42 80% of myasthenics will find the presence of acetylcholine receptors.

03:47 And there's a 20% remission rate, which is great.

03:50 We also see acetylcholine receptor antibodies in patients with ocular myasthenia.

03:55 That myasthenia that has a predilection for the bulbar fibres and really ptosis with an absence of generalized weakness.

04:03 Anti-MuSK antibodies are the second antibody that we test for.

04:06 And these we find in approximately 30% to 40% of patients who don't have acetylcholine receptors.

04:13 So our test initially is to look for acetylcholine receptor antibodies.

04:16 And if positive a diagnosis of myasthenia is made.

04:19 If negative of the physician or clinician should consider testing for MuSK antibody positive myasthenia.

04:26 There's a smaller chance of remission rate with MuSK antibody myasthenia.

04:30 And patients often have more prominent ocular symptoms with a paucity of systemic complaints in some of these patients.

04:37 The last antibody that we can look for is the anti-striational protein.

04:41 And this is present in 80% of thymomatous myasthenia gravis or myasthenia gravis that occurs in a patient with a thymoma, and 30% of nonthymomatous myasthenic patients.

04:52 And these antibodies are slightly less specific than acetylcholine receptor and MuSK antibody myasthenia.

04:58 About 15% of patient will not have the presence of circulating antibodies and will be defined as seronegative myasthenia gravis.

05:07 So we have to trust our examination Patients who present with typical findings of a junctional disorder and have other testing that's consistent with a junctional problem can be diagnosed with myasthenia even in the absence of circulating antibodies.

05:21 What other diagnostic tests can be performed? Well, one that we rely on heavily in neurology is the EMG nerve conduction study.

05:30 And this stands for electromyography, which is looking at the muscle specifically with a needle and nerve conduction velocity testing, which is shocking nerves to see how they communicate.

05:41 You can see both of these tests here.

05:42 The picture on the bottom is demonstrating a nerve conduction velocity examination.

05:47 We take a probe and put it where a nerve is at the surface of the skin.

05:52 And we shocked both a sensory nerve or a motor nerve and see what happens.

05:56 For the sensory nerve, we're looking at conduction up that sensory nerve, and seeing how fast the conduction is.

06:02 And looking at the myelination of the sensory nerve and the number of axons in the sensory nerve to look for problems in nerve transmission.

06:10 We can also look at motor nerves, and we shock a motor nerve, and look at contraction of the muscle.

06:16 And that helps us to look at both the motor nerve, the neuromuscular junction, and the integrity of the muscle as well.

06:23 In the top picture, we're looking at an EMG or electromyography.

06:27 And this is where we take a small needle and put it into a muscle and record the signal around that muscle.

06:32 We can look for problems where nerves are not innervating muscles, or where muscles could be damaged.

06:39 When we're evaluating a neuromuscular junction disorder, when critical EMG nerve conduction test is repetitive stimulation.

06:46 And this is a special technique a way to do nerve conduction to look at repetitive activation of a muscle, to see the problem in the neuromuscular junction.

06:56 We see problems with repetitive stimulation about 90% of patients who have a neuromuscular junction disorder and specifically myasthenia gravis.

07:05 And the last test that we can look at is called Single-fiber EMG.

07:09 And this was looking very specifically not at the entire muscle itself, but individual neuromuscular junctions looking for problems with transmission across the junction, and that's called jitter.

07:20 And the presence of jitter on a single fiber EMG is highly specific for a diagnosis of a junctional disorder and is seen in patients with myasthenia gravis in up to 96% to 99% of those patients.

07:33 So these are the tools in our armamentarium to evaluate patients who have weakness that appears to be from a neuromuscular junction condition.