Neuromuscular Junction Disorders: Clinical Features and Pathophysiology

00:00 And again, when we evaluate patients, we're thinking of the distribution.

00:05 Where are the problems? Where does this weakness occur? We should see presence of bulbar findings.

00:11 And the presence of ptosis, diplopia, dysarthria, and dysphasia point towards a neuromuscular junction etiology.

00:19 Sensory findings are normal.

00:21 Reflex examination often shows normal reflexes.

00:24 And we're looking for that wildcard symptom the presence of fatigability.

00:28 Symptoms that worsen when muscles are contracted.

00:32 After our first step is, to localize to the neuromuscular junction, we move to step two.

00:37 What is this junctional disorder? And we can walk through the types of problems that pathophysiologic processes that occur in the body.

00:45 We can look for immune disorders.

00:47 And the immune disorder at the neuromuscular junction is called Myasthenia gravis.

00:51 We can look for infections.

00:53 And the primary infection to effect the neuromuscular junction is botulism.

00:57 It has a tropism and affinity for the neuromuscular junction.

01:02 The neoplastic or paraneoplastic disorder that affects the neuromuscular junction is called Lambert-Eaton myasthenic syndrome.

01:09 Toxins and metabolic problems can also affect the neuromuscular junction.

01:14 And there are specific drugs that we need to think about that can cause problems in the neuromuscular junction.

01:20 And then there are some inherited and congenital problems.

01:23 Congenital Myasthenia, and Neonatal myasthenia that can also affect the neuromuscular junction.

01:29 We're going to walk through each of these disorders in subsequent lectures.

01:33 But right now, I want you to know that those are the conditions that we should focus on when we're dealing with a problem or a patient who presents with neuromuscular junction signs and symptoms.

01:43 So let's look at where those occur.

01:45 We said junctional disorders should be broken down into presynaptic and postsynaptic disorders, where to each one of those fall.

01:52 Well, Myasthenia gravis the most common junctional disorder and one that we really need to know is a postsynaptic problem.

01:58 This disorder results from problems abnormality with the postsynaptic acetylcholine receptor.

02:06 Anesthetics affect the postsynaptic action of acetylcholine binding to that postsynaptic acetylcholine receptor and muscle depolarization.

02:15 Lambert-Eaton Myas Syndrome.

02:17 Myasthenic syndrome is an important cause of a presynaptic junctional disorder.

02:21 Antibodies to the presynaptic voltage-gated calcium channels prevent that influx of calcium and the communication can't proceed down the presynaptic terminus into the junction.

02:34 Botulism is a disorder and infection that affects the binding of the vesicles to the presynaptic membrane.

02:40 And so this is also another important presynaptic junctional disorder.

02:44 And then lastly, cholinestarase inhibitors affect that cholinestarase enzyme in the synaptic cleft.

02:51 So again, I want you to know about the important presynaptic and postsynaptic disorders that affect the neuromuscular junction.