Neuromuscular Junction Disorders

Question 1

What limits the ability of ACh to generate an EPP normally?

Answer 1

Acetylcholinesterase

Question 2

During repeated contractions in exercise, less ACh is released, but why do muscles not fail normally?

Answer 2

Although the EPP amplitudes are thereby decreased, they still remain above the threshold for generating muscle fiber action potentials, and adequate muscle contraction is still achieved.

Question 3

What happens to ACh receptors in myasthenia gravis and how does this lead to the effects of the disease?

Answer 3

Many AChR are degraded or blocked, less ACh is able to bind, producing EPPs which are either initially below the threshold for generating muscle fiber action potentials or which become too low during repeated muscle contractions.

Question 4

Myasthenia Gravis

Answer 4

Myasthenia gravis (MG) is an autoimmune disorder of the postsynaptic NMJ.

Question 5

Lambert-Eaton Myasthenic Syndrome

Answer 5

Autoimmune disease with the target being the voltage-gated calcium channel at the presynaptic membrane

Question 6

What is seen on microscopy of the NMJ in myasthenia gravis?

Answer 6

The normal architecture and folding of the postsynaptic NMJ is lost when viewed under electron microscopy.

Question 7

What is a common abnormality associated with myasthenia gravis?

Answer 7

In most myasthenic patients, abnormalities of the thymus occur, consisting more commonly of glandular enlargement or hyperplasia, and less commonly of a thymic tumor or thymoma.

Question 8

What are some common symptoms of myasthenia gravis?

Answer 8

• ptosis (eyelid drooping)
• diplopia (double vision from asymmetrically weak extraocular muscles)
• dysarthria (slurred speech)
• dysphagia (weakness of swallowing)

Question 9

Ocular Myasthenia

Answer 9

A small group of MG patients who only have visual symptoms of MG

Question 10

Neonatal Myasthenia

Answer 10

Healthy newborns of myasthenic mothers may have MG symptoms for a few days, until maternal antibodies “wash out” of their system.

Question 11

Myasthenic Crisis

Answer 11

Profound weakness may cause quadriplegia, with the patient unable to speak, swallow or breathe. Myasthenic crisis may be suddenly triggered by a serious infection or other systemic illness in a myasthenic patient.

Question 12

How is MG diagnosed?

Answer 12

Injection with edrophonium. If there is marked improvement, the diagnosis is highly supported.

Question 13

What is the most specific test for myasthenia gravis?

Answer 13

Serum AChR Ab

Question 14

What is the main drug used to treat MG?

Answer 14

Anticholinesterase Drugs

Question 15

What is a surgical procedure that can possibly help MG patients?

Answer 15

Thymectomy

Question 16

What are some immune system treatment options for MG?

Answer 16

• Corticosteroids
• Plasmapheresis
• IVIG

Question 17

What are the symptoms of Lambert-Eaton Myasthenia Syndrome?

Answer 17

As another NMJ disorder, muscle fatigue and weakness occur in LEMS, but tend to affect the proximal muscles of the shoulders and hips as well as the trunk, mimicking the weakness also seen in a myopathy. Symptoms do not usually involve the eyes, swallowing, or speech.

Question 18

What are some symptoms of LEMS that differs from MG?

Answer 18

• dry mouth
• orthostatic hypotension
• erectile dysfunction

Question 19

What can the autoimmune dysfunction of LEMS be associated with?

Answer 19

Small Cell Carcinoma of the Lung

Question 20

How is LEMS diagnosed?

Answer 20

Repetitive nerve stimulation and other tests in the electromyography laboratory usually show presynaptic NMJ abnormalities typical of LEMS.