Case: 72-year-old Woman with Weakness

00:01 In this lecture, we're going to learn about infections of the neuromuscular junction.

00:06 It's a really neat topic, not commonly encountered in patients, but seen in clinical vignettes and just a really cool list of disorders.

00:15 Let's start with the case.

00:16 This is a 72-year-old woman who presented with weakness.

00:20 This 72-year-old woman had Parkinson's disease and presented for management of right foot & leg dystonia related to the Parkinson's disease.

00:30 She had been receiving botulinum toxin type A for about a year to treat this spasticity increased tone in this leg and she returned for repeat treatment.

00:40 She presented for her fifth injection of botulinum toxin with 600 total units, which is standard for a limb into the muscles of the right leg.

00:50 Three days after the treatment, she developed right leg heaviness.

00:55 One week later, she developed diplopia, dysphagia and head drop.

01:00 Her pupils were dilated and poorly reactive with intact extraocular movements.

01:06 Examination showed 4/5 weakness of the bilateral proximal arm muscles, reduced neck flexion and 1+ deep tendon reflexes, so slightly reduced deep tendon reflexes throughout the entire body.

01:20 Sensory exam was normal.

01:23 A nerve conduction study with repetitive nerve stimulation showed a 14% decrement with 3-Hz stimution that was recovered after 1 minute of maximal exercise.

01:35 With 10 seconds of voluntary muscle exercise, no incremental response was observed and acetylcholine receptor antibody testing is negative.

01:45 So a long case, some important features.

01:48 What's the diagnosis? Let's walk through some of the key findings in this case.

01:54 And let's think about the distribution, sensory findings and reflex exam, as well as any wildcard symptoms, that could point us to the localization for this peripheral nervous system complaint.

02:06 First of all, in terms of the distribution this patient presents with proximal weakness.

02:12 Importantly, there are prominent bulbar symptoms.

02:15 This patient has diplopia and ptosis and problems with bulbar function.

02:21 This entry exam is normal which points us away from a nerve problem and towards muscle or neuromuscular junction, and specifically neuromuscular junction, in this case.

02:31 The Reflex exam so slightly reduced reflexes, which we can see from a neuromuscular junction disorder, but not absent.

02:39 And there's some wildcard symptoms, she developed the diplopia, dysphagia and head drop first and this was followed by generalized weakness.

02:48 And that time course and progression of symptoms is important in evaluating this patient.

02:53 This patient had repetitive nerve stimulation and let's look specifically at that.

02:57 In this table, repetitive stimulation is where we shocked the nerve and look at muscle contraction serially over time.

03:05 This is 3-Hz stimulation, so 3 stimulations every 1 second.

03:10 With the first stimulation of the nerve, we can look at the amount of contraction, the amplitude of the muscle response and we see that the amplitude was 2.2.

03:20 A good muscle contraction as a result of that first stimulation.

03:24 And then with successive stimulations, we see that the amplitude drops.

03:29 The amount of muscle contraction goes down even though we're sending just as much signal through the nerve.

03:35 So the amplitude goes down to 1.96, .94, .84, .89, .85, .77 and we see a decremental response.

03:44 The same nerve stimulation, results in less muscle activation, less muscle contraction, less end-plate potential depolarization, to a maximum of 20%.

03:57 So what's the diagnosis? Is this seropositive myasthenia? Seronegative myasthenia? Botulinum toxin toxicity? or Organophosphate poisoning? Well, this doesn't sound like myasthenia gravis.

04:11 We see pupillary involvement, which we said we don't see with myasthenia gravis.

04:16 The symptoms started proximally in the bulbar fibers and then move distally to involve weakness, and that progression is a typical.

04:24 Typically, Myasthenia starts with weakness and then potentially the presence and likely the presence of bulbar symptoms.

04:32 The patient has no history or signs of taking prior again a phosphates or an ingestion of some kind, so organophosphate poisoning is not supported by the case presentation.

04:43 There was no testing for, excuse me, a testing for acetylcholine receptors was negative in this case.

04:48 So that's inconsistent with a diagnosis of Seropositive myasthenia gravis.

04:53 And so this is a good example of a patient who was diagnosed with iatrogenic botulism following botox toxin injection.

05:01 And the things to note about this case for the prominent pupillary involvement, involvement of autonomics, which is very specific for botulism toxicity and prominent proximal weakness spreading proximally to distally.