6: Neuromuscular disorders

Question 1

What is the neuromuscular junction?

Answer 1

Synapse between LMNs and muscle fibres

Question 2

Which horn of the spinal cord contains motor neurons?

Answer 2

Anterior (ventral horn)

Question 3

What is a motor end plate?

Answer 3

The muscle-end of the neuromuscular junction

Question 4

Each motor neuron may supply (one / many) muscle(s).

Each muscle is supplied by (only one / many) motor neuron(s).

Answer 4

many

only one

Question 5

Which neurotransmitter passes into the synaptic cleft of the NMJ in response to an action potential?

Answer 5

ACh

Question 6

Which ions are involved in the wave of depolarisations along a nerve axon?

Answer 6

Na+ IN

K+ OUT

Question 7

Which ion triggers the release of neurotransmitter into the synaptic cleft of the NMJ?

Answer 7

Ca2+

Question 8

Which enzyme clears up remaining ACh from the synaptic cleft?

Answer 8

Acetylcholinesterase

Question 9

Which toxin occupies ACh receptors in the synaptic cleft, preventing muscle contraction?

Answer 9

Tubocurarine

‘flying death’, poison arrows etc.

Question 10

Which receptor is blocked by tubocurarine?

What happens as a result?

Answer 10

ACh receptor

Muscle paralysis (inc. respiratory)

Question 11

Which poison inhibits acetylcholinesterase, causing muscle paralysis and death?

Answer 11

Novichok

Question 12

What cannot be released if there is a problem with the Ca2+ channels of the pre-synaptic neurons involved in NMJs?

Answer 12

ACh

Question 13

What is botulism?

Answer 13

Infection by Clostridium botulinum

Which produces Botulinum toxin

Question 14

What is the effect of botulinum toxin?

Why?

Answer 14

Muscle weakness

Blocks ACh release at pre-synaptic terminal

Question 15

How do the following nerve agents affect the neuromuscular junction?

a) tubocurarine
b) NOVICHOK
c) Botulinum toxin?

Answer 15

a) ACh receptor antagonists

b) Acetylcholinesterase inhibitor

c) Blocks secretion of ACh at pre-synaptic terminal

Question 16

Name an autoimmune disease which affects the neuromuscular junction at the

a) post-synaptic
b) pre-synaptic end?

Answer 16

a) Myaesthenia gravis

b) Lambert-Eaton syndrome

Question 17

What is the main symptom of Lambert-Eaton syndrome?

Answer 17

Muscle weakness

Question 18

What condition is Lambert-Eaton syndrome associated with?

Answer 18

Small cell lung cancer

Question 19

What antibodies are produced in Lambert-Eaton syndrome?

Answer 19

Ca2+ channel antibodies

So not as much ACh is released into NMJ, causing muscle weakness

Question 20

The drug 3-4-diaminopyridine is used to treat symptoms of Lambert-Eaton syndrome.

How does it work?

Answer 20

Blocks K+ channels

So action potential lasts for longer, more Ca2+ has the chance to enter the pre-synaptic terminal and more ACh can be secreted into the NMJ

Question 21

What is a rare post-synaptic disorder causing muscle weakness and fatigue?

Answer 21

Myaesthenia gravis

Question 22

Myaesthenia gravis is an ___ disease.

Answer 22

autoimmune

Question 23

When does the incidence of myaesthenia gravis peak?

Answer 23

Early 20s

Elderly

Question 24

What is the pathophysiology of myaesthenia gravis?

Answer 24

Autoimmune disease

Autoantibodies BIND TO ACh receptors of neuromuscular junction

Resulting in muscle weakness and fatigability

Question 25

Which antibodies are seen in 90% of patients with **myaesthenia gravis**?

Answer 25

**ACh receptor antibodies**

Question 26

Which **immune organ** undergoes hyperplasia in myaesthenia gravis?

Answer 26

**Thymus** Particularly in young people

Question 27

**(Men / women)** tend to develop myaesthenia gravis.

Answer 27

**Women** autoimmune disease

Question 28

What is the course of **weakness** seen in myaesthenia gravis?

Answer 28

**Fluctuating**

Question 29

Which muscles tend to be affected in **myaesthenia gravis**?

Answer 29

**Extraocular muscles** **Facial muscles** **Bulbar muscles** (chewing, speaking, swallowing)

Question 30

What tends to cause death in late **myaesthenia gravis**?

Answer 30

**Respiratory muscle weakness**

Question 31

Which movements can you ask a patient to do to investigate suspected **myaesthenia gravis**?

Answer 31

**Blinking** **Neck flexion**

Question 32

What is the **acute management** of **myaesthenia gravis**?

Answer 32

**Acetylcholinesterase inhibitor** e.g pyridostigmine **IV Ig** - for autoimmune problem **Thymectomy** - surgical removal of thymus

Question 33

What does testing **blinking** and **neck flexion** in a myaesthenia gravis patient demonstrate?

Answer 33

**Muscle fatigability**

Question 34

What is the **long-term pharmacological management** for myaesthenia gravis?

Answer 34

**Immunosuppression:** Steroids Steroid-sparing DMARDs - azathioprine, mycophenolate mofetil

Question 35

Which **antibiotic** should you avoid in patients with **myaesthenia gravis**? Why?

Answer 35

**Gentamicin** Aminoglycoside antibiotics cause **Myaesthenic crisis** - respiratory failure, aspiration pneumonia

Question 36

What is a **myaesthenic crisis**?

Answer 36

**Emergency presentation of myaesthenia gravis** Respiratory depression due to weakness of intercostal muscles, inability to breathe +/- aspiration pneumonia, brought on by drugs including **gentamicin**

Question 37

How is a **myaesthenic crisis** treated?

Answer 37

**Intubation** **High dose corticosteroids** **Plasma exchange / immunoglobulin**

Question 38

Describe how **smooth muscle** looks under the microscope.

Answer 38

**Non-striated** **Single, central nucleus**

Question 39

Describe how **cardiac muscle** looks under the microscope.

Answer 39

**Striated** **Single, central nucleus**

Question 40

Describe how **skeletal muscle** looks under the microscope.

Answer 40

**Striated** **Multiple nuclei found at the cell membrane**

Question 41

What colour are muscle fibres which rely on a) **aerobic respiration** b) **anaerobic respiration**?

Answer 41

**a) Red** **b) White**

Question 42

What are **type I** muscle fibres also known as? What type of activity are they best for?

Answer 42

**Slow oxidative** Long duration exercise e.g distance running as they fatigue slowest

Question 43

What are **type IIa** muscle fibres also known as? What activities are they best suited for?

Answer 43

**Fast oxidative** Medium intensity, longer duration exercise e.g a 1000m race, fatigue faster than type I fibres

Question 44

What are **type IIb** muscle fibres also known as? What activities are they best suited for?

Answer 44

**Fast glycolytic** Rely on glycolysis only, so fatigue quickly; best for sprinting, weightlifting over a very short duration

Question 45

What are the **functional units** of muscle called?

Answer 45

**Sarcomeres**

Question 46

What is a **fasciculation**?

Answer 46

**Visible muscle twitch**

Question 47

**Abnormal fasciculations** indicate a problem with the **(motor neuron / muscle).**

Answer 47

**motor neuron** specifically the LMN

Question 48

What is **myotonia**?

Answer 48

**Failure of muscle after being used** (e.g patient can't release from a handshake)

Question 49

What ion is involved in **myotonia**?

Answer 49

**Cl-**

Question 50

What are some **inflammatory myopathies** which cause muscle **weakness**?

Answer 50

**Polymyositis** **Dermatomyositis** **Inclusion body myositis**

Question 51

Which type of **myositis** is atypical, develops in your 60s and spares the thumb?

Answer 51

**Inclusion body myositis**

Question 52

What does **dystrophy** mean?

Answer 52

**Abnormal atrophy of a structure** (usually muscle)

Question 53

What is a **genetic disease** causing **myotonia** **muscle weakness** **cardiac problems** **ptosis, frontal balding** and **cataracts?**

Answer 53

**Myotonic dystrophy**

Question 54

What is the **mode of inheritance** of **myotonic dystrophy**?

Answer 54

**Autosomal dominant**

Question 55

Apart from **myotonic dystrophy**, what are two other common **dystrophic diseases** you need to know?

Answer 55

**Muscular dystrophy** Duchenne and Becker

Question 56

**Myotonic dystrophy** is caused by abnormal **trinucleotide repeats** and shows **anticipation**, meaning that the further down a family tree you go, the more likely you are to inherit it. Which other neurological disease behaves like this?

Answer 56

**Huntington's disease** **CAG repeats with anticipation**

Question 57

Is muscular dystrophy an inflammatory problem?

Answer 57

**No**

Question 58

**Duchenne** and **Becker muscular dystrophies** affect only \_\_\_.

Answer 58

**boys** **X-linked recessive inheritance**

Question 59

What are the symptoms of **muscular dystrophy**?

Answer 59

**Progressive muscle weakness and wasting**

Question 60

What are **important drugs** which cause **myopathy** as a side effect?

Answer 60

**Statins** **Steroids** (if used for long enough, also atrophy)

Question 61

What is **rhabdomyolysis**?

Answer 61

**Skeletal muscle damage** releases **toxins** into bloodstream

Question 62

What are some common causes of **rhabdomyolysis**?

Answer 62

**Extreme exercise** **Crush injury** **Status epilepticus**

Question 63

Which organs are damaged by **rhabdomyolysis**?

Answer 63

**Kidneys**