Neuromuscular Disease

Question 1

How does curare affect cholinergic transmission and muscle contraction?

Answer 1

Competes for and blocks ACh receptor so no muscle stimulation occurs

Question 2

Curare is only toxic when administered how?

Answer 2

Intravenous

Intramuscular

Question 3

How does Botox affect cholinergic transmission and muscle contraction?

Answer 3

Cleaves proteins involved in ACh vesicle formation and blocks vesicle docking to prevent exocytosis

Question 4

What happens molecularly in Lambert Eaton myasthenic syndrome?

Answer 4

Antibodies attack presynaptic Ca channels resulting in less NT release

Question 5

Which cancer is associated with Lambert Eaton syndrome?

Answer 5

Small cell carcinoma (typically of the lung)

Question 6

Which disease is the most common neuromuscular junction disorder?

Answer 6

Myasthenia gravis

Question 7

Autoantibodies attack what in myasthenia gravis? What does this cause?

Answer 7

ACh receptors (MUSK receptors)
Triggers inflammatory cascades that damage the folds of the postsynaptic membrane

Question 8

When do symptoms start in myasthenia gravis?

Answer 8

When ACh receptors reduced to 30% of normal

Question 9

A patient must have Autoantibodies to suggest myasthenia gravis. True/False?

Answer 9

False

Patient with fatigue and weakness without antibodies may still have it

Question 10

Which organ must be screened/assessed in people with myasthenia gravis? What other investigations can be performed?

Answer 10

Thymus (arrange CT chest to check for thymoma or hyperplasia)
Ice test to reduce ptosis
Autoantibody screen
Electromyography
Muscle biopsy

Question 11

Females are more affected than males by myasthenia gravis. True/False? What age group is most commonly affected?

Answer 11

True

20-30s

Question 12

List clinical features of myasthenia gravis

Answer 12

Fluctuating weakness (typically proximal limbs)
Tiredness at end of the day
Extraocular weakness (ptosis, diplopia, ophthalmaplegia) - DIFFICULTY READING
Facial and bulbar weakness - DIFFICULTY CHEWING

Question 13

What is the acute treatment for myasthenia gravis?

Answer 13

Acetylcholinesterase inhibitor (pyridosigmine)
IV immunoglobulin/ plasma exchange
Thymectomy

Question 14

What are muscle fasciculations?

Answer 14

Visible fine fast spontaneous twitches that occur in denervated muscle that become excited
Indicates problem in motor neurone

Question 15

What is myotonia? It occurs due to a problem in what ion channel?

Answer 15

Failure of muscle relaxation after use

Chlorine channel

Question 16

What is the commonest muscular dystrophy?

Answer 16

Myotonic dystrophy

Question 17

List clinical features of myotonic dystrophy

Answer 17

Myotonia
Weakness
Cataracts ('christmas tree')
Ptosis
Frontal balding
Cardiac defects

Question 18

What is the synapse between a motor neurone and muscle called?

Answer 18

Motor end plate

Question 19

What ion channel is responsible for the release of acetylcholine into the synaptic cleft?

Answer 19

Ca voltage-gated channel

Question 20

What is the outcome of acetylcholine binding to the post-synaptic receptor?

Answer 20

Renders the membrane potential permeable to sodium and potassium ions and depolarisation starts an action potential at motor end plate

Question 21

What drug is used to manage Lambert Eaton myasthenic syndrome?

Answer 21

3-4 diaminopyridine

Question 22

Name two pre-synaptic disorders affecting the NMJ

Answer 22

Botulinism

Lambert Eaton myasthenic syndrome

Question 23

Which part of the NMJ does myasthenia gravis affect?

Answer 23

Post-synaptic membrane

Question 24

What is the long term management for myasthenia gravis?

Answer 24

Immunomodulators
Steroids
Steroid sparing agents (azathioprine, mycophenolate)

Question 25

Which drug should be avoided in myasthenia gravis?

Answer 25

Gentamicin

Question 26

What are the three main types of muscle found within the body?

Answer 26

Skeletal Smooth Cardiac

Question 27

What are the three main types of muscle FIBRES found within the body?

Answer 27

1. Slow oxidative 2a. Fast oxidative 2b. Fast glycotic

Question 28

Outline the process of muscle contraction

Answer 28

1. ATP is hydrolysed into ADP and Pi which binds to the mysosin head forming a crossbridge 2. Crossbridge attaches to actin 3. Myosin head pivots and bends as it pulls on actin, sliding towards the M line (ADP + Pi are released) 4. New ATP attaches to myosin head and crossbridge detaches 5. ATP splits into ADP + Pi and myosin head cocks

Question 29

What are the four main clinical signs of muscle disease?

Answer 29

Myalgia Muscle weakness Wasting Hyporeflexia

Question 30

Name the two main causes of immune-mediated muscle disorder

Answer 30

Polymyositis | Dermatomyositis

Question 31

List the main causes of muscle disorders

Answer 31

``` Immune Inherited Congenital Infective Toxic (drugs, venoms) ```

Question 32

What is the characteristic clinical picture suggesting inclusion body myositis?

Answer 32

Slowly progressive weakness occuring in 60s with thumb sparing Little response to steroid

Question 33

What is the mechanism behind muscular dystrophy?

Answer 33

Abnormality in protein causing movement of muscle

Question 34

Which micro-organisms most commonly cause muscle disorders?

Answer 34

Viral (coxsachie, trypanosomiasis) Cistercosis (uncooked pork) Borellia

Question 35

What class of drug, in particular, can cause myopathy as a common side effect?

Answer 35

Statins

Question 36

What is rhabdomyolysis?

Answer 36

Damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma

Question 37

What is the potential aetiology of rhabdomyolysis?

Answer 37

Crush injury Toxin Post convulsion Extreme exercise

Question 38

List the clinical features of rhabdomyolysis

Answer 38

Triad of myalgia, weakness, myoglobinuria

Question 39

List potential complications of rhabdomyolysis

Answer 39

Acute renal failure | Disseminated intravascular coagulation

Question 40

What is the genetic mechanism behind myotonic dystrophy?

Answer 40

Chromosome 19 trinucleotide expansion

Question 41

What is the broad presenting picture in NMJ disease?

Answer 41

Fatiguable motor symptoms with no sensory symptoms

Question 42

What is the first and second line investigation in myasthenia gravis?

Answer 42

1. AChR antibodies | 2. MUSK antibodies