Disorders of Neuromuscular Transmission

Question 1

Acquired Neuromuscular Disorders:

Answer 1

– Myasthenia Gravis
– Lambert-Eaton Myasthenic Syndrome
– Botulism
– Organophosphate Poisoning

Question 2

Heritable Neuromuscular Transmission:

Answer 2

– Congenital Myasthenic Syndromes

Question 3

What is needed for NMJ release?

Answer 3

Calcium

Question 4

First steps in NMT:

Answer 4

1. Action potential arrives at motor terminal
2. Voltage-gate Ca++ channels open-
   Ca++enters
3. Ach vesicles migrate and fuse
4. Ach is released into the synaptic cleft

Question 5

Last steps in NMT:

Answer 5

5. Ach binds to Ach Receptor and Na+ enters
6. End-Plate Potential is generated
7. Sarcolemma depolarizes at EPP threshold
8. Ach is degraded by Acetylcholinesterase

Question 6

Pre-synaptic disorders:

Answer 6

– Eaton-Lambert Syndrome
– Botulism
– Congenital Deficiency Ach synthesis

Question 7

Synaptic disorder:

Answer 7

Organophosphate poisoning

Question 8

Post synaptic disorders:

Answer 8

– Myasthenia Gravis
– Congenital
* Abnormal AChR

Question 9

Amount of Ach of each synaptic vesicle

Answer 9

Quantum

Question 10

Total number of quanta release/ action potential

Answer 10

Quantal content

Question 11

Autoimmune disease of the
neuromuscular junction

Answer 11

Myasthenia gravis

Question 12

Can be associated with other autoimmune disorders and neoplasms (Thymoma)

Answer 12

Myasthenia gravis

Question 13

Pathophysiology of Myasthenia gravis:

Answer 13

1. Antibodies directed against the acetylcholine receptor or other closely- associated proteins
2. Cross-linking or blocking of receptor
3. Complement-mediated destruction of end- plate

Question 14

Characterized by: droopy eyes (ptosis), double vision, nasal voice in afternoons, diffuse weakness, resiratory muscle involvement

Answer 14

Myasthenia gravis

Question 15

What is the simpson test used for?

Answer 15

Ptosis - myasthenia gravis

Question 16

Tests used for MG:

Answer 16

1.Tensilon test
2.Anti Ach R serum antibody
3.Anti Muscle Kinase
4.Anti thymoma
5.EMG

Question 17

What is Tensilon test?

Answer 17

Short-acting Acetylcholinestherase inhibitor (increases Acetylcholine)

Question 18

Which NMJ disease causes: Autoantibodies to pre-synaptic voltage gated calcium channels (motor nerve terminal)
Impairment of quantal release of Ach

Answer 18

Lambert Eaton Myasthenic Syndrome (LEMS)

Question 19

Characterized by:
- Weakness in proximal> distal muscles
- Proximal legs > arms
- Improved strength with brief-exercise
- Diminished or absent deep tendon reflexes
- Autonomic symptoms: dry mouth, blurred vision, impotence

Answer 19

LEMS

Question 20

Pre-synaptic block of acetylcholine release through cleavage of excitosis proteins (SNARE)

Answer 20

Botulism

Question 21

Three major presentations of botulism:

Answer 21

– Classic (Food-Borne)
– Infant Botulism
– Wound Botulism (IV drug injection)

Question 22

Characterized by:
18-38 hr incubation, diffuse weakness starting from eyes to limbs, reduced tendon reflex, dilated pupils, blured vision, GI problems

Answer 22

Botulism

Question 23

Dozen D’s

Answer 23

Botulism

Question 24

Accidental Poisoning with Insecticides and Nerve Gas (Sarin, Soman, Tabun)

Answer 24

Organophosphate toxicity

Question 25

Excess Acetylcholine Diseases = Constant Depolarization

Answer 25

Organophosphate toxicity Inihibition of Endogenous Acetylcholinesterase

Question 26

SLUDGE

Answer 26

salivation lacrimation urination diarrhea gi emesis

Question 27

DUMBELS

Answer 27

diarrhea urination miosis bronchospasm emesis lacrimation salivation

Question 28

Heterogeneous genetic disorders of neuromuscular transmission

Answer 28

Congenital Myasthenic Syndromes

Question 29

Most common- mutations in post-synaptic and synaptic proteins *Onset in childhood

Answer 29

Congenital Myasthenic Syndromes

Question 30

Can be associated with neoplasms:

Answer 30

Thymoma (MG) or Small Cell Lung CA (LEMS)

Question 31

Can be associated with toxins:

Answer 31

Botulism and Organophosphates