Neuromuscular Junction Disorders

Question 1

How does the NMJ normally work

Answer 1

• –AP depolarizes motor nerve terminal, Ca influx facilitates release of ACh, ACh binds at specific sarcolemmal nicotinic AChR
• –If enough AChR is bound, end plate depolarizes (EPP), and EPP exceeds threshold for single muscle fiber to contract
• –Co-activation of many muscle fibers causes muscle to contract

Question 2

what limits the action of ACh

Answer 2

AChE

Question 3

what is the safety factor

Answer 3

—Slight decrease in ACh release with exercise is insignificant, since more than enough ACh is normally released (“safety factor”)

Question 4

what is an example of a postsynaptic NMJ disorder

Answer 4

Myasthenia gravis

Question 5

what are 3 presynaptic NMJ disorders

Answer 5

Lambert-Eaton myasthenic syndrome
Botulism
Congenital myasthenia (rare disorders of the NMJ)

Question 6

what is the immune target in Myasthenia gravis

Answer 6

nAChR

Question 7

what is the immune target in Lambert-Eaton

Answer 7

voltage-gated Ca channel (leads to decreased release of ACh)

Question 8

what type of drugs can be used to improve myasthenia gravis?

Answer 8

AChE inhibitors - to increase the amplitude and duration of the EPP

Question 9

How does botulism cause a NMJ disorder

Answer 9

exotoxin inhibits ACh release

Question 10

What changes to the NMJ can be seen in Myasthenia gravis with an electron microscope

Answer 10

loss of normal architecture, AChRs and folding of the postsynaptic NMJ

Question 11

what are symptoms of generalized MG

Answer 11

ptosis, diplopia, dysarthria, dysphagia; respiratory, facial, neck and limb weakness.

severity ranges from person to person, fatigue may occur with some activities.

preserved sensation and reflexes

Question 12

what are symptoms of ocular MG

Answer 12

ptosis, diplopia only symptoms after 2-3 years

doesn’t progress

Question 13

what changes occur to sensation and reflexes in MG

Answer 13

none -the function is preserved

Question 14

which muscles are most commonly affected by MG

Answer 14

eye and mouth muscles

Question 15

describe the process of developing MG

Answer 15

APCs take up AChR and present it to T-cells which recognoize the AChR and interact with B cells stimulating them to produce antibodies to AChR

Question 16

Normally how does exercise affect the amount of ACh released

Answer 16

it decreases slightly but is still well above threshold (safety factor)

Question 17

In MG how does exercise affected the amount of ACh released

Answer 17

EPP is reduced narrowing the safety factor. The amount of ACh released decreases until it is below threshold.

Question 18

how is MG diagnosed

Answer 18

typical clinical features + Positive Tensilon (edrophonium) test

or EMG showing abnormal NMJ transmission
or elevated serum Ab titre to AChR (most specific)

Question 19

what is the most specific way to diagnose MG

Answer 19

Elevated serum Ab titre to AChR (80-90% in generalized and 50% in ocular)

Question 20

what is the Tensilon test

Answer 20

IV injection of short-acting AChE inhibitor show an objective decrease in weakness. i.e. speech or ptosis may improve

Question 21

3 treatment options for MG

Answer 21

1. Anticholinesterase drugs
2. Thymectomy
3. immunosuppressant drugs

Question 22

how do anticholinesterase drugs work in MG

Answer 22

inhibit AChE and enhance the effect of released ACh, imporves symptoms

Question 23

how does a thymectomy help in MG

Answer 23

• contains AChR-like material, where autoimmune response initiated?
• hyperplastic thymus or thymoma (rarer) occur in MG

Question 24

what tumor is associated with MG

Answer 24

thymoma

Question 25

what “quick fixes” can be used in acute exasterbations of MG

Answer 25

plasmapheresis or IVIG

Question 26

how does immunosuppressive therapy affect the NMJ

Answer 26

immunosuppressive therapy may shift the balance closer to the normal state by allowing more time for ACh receptors to undergo resynthesis and repair

Question 27

what are the clinical symptoms of Lamber-eaton myasthenic syndrome (LEMS)

Answer 27

• fatigable weakness of proximal limbs, trunk—mimics a myopathy (often begins with shoulder and hips)
• exertion briefly improves power and hyporeflexia
• autonomic symptoms (dry mouth, orthostasis, ED)

Question 28

what cancer is often linked to lambert-eaton

Answer 28

small cell carcinoma

Question 29

how is lambert-eaton diagnosed

Answer 29

nerve stimulation tests, EMG, occasional detection of specific antibodies

Question 30

what happens when a pt with lambert-eatons begins to exercise

Answer 30

they temporarily gain strength

Question 31

treatment for lambert-eaton syndrome

Answer 31

• look for and treat underlying cancer (will improve neurological symptoms)
• drugs to enhance ACh release (guanidine, 3,4-diaminopyridine)
• immunosuppressive therapy (suboptimal success)

Question 32

hows does MG affect the thymus

Answer 32

usually glandular enlargement or hyperplasia, less commonly a thymic tumor or thymoma

Question 33

at what age does MG present

Answer 33

any age

Question 34

does MS cause pain, sensory, or cognitive impairment?

Answer 34

no

Question 35

what is a myasthenic crisis

Answer 35

profound weakness may cause quadriplegia with the patient unable to speak, swallow or breath

neurologic emergency

sensation and reflexes remain normal - may help differentiate from other causes

Question 36

what can trigger a myasthenic crisis

Answer 36

serious infection or systemic illness in a myasthenic patient or may unpredictable develop over days in someone with severe MG