Neuromuscular Disorders

Question 1

how do motor neurones supply muscles?

Answer 1

via the NMJ

Question 2

presynaptic NMJ disorders

Answer 2

1. curare
2. botulism botox
3. Lambert Eaton Myasthenic Syndrome (LEMS)

Question 3

postsynaptic NMJ disorders

Answer 3

myasthenia gravis

Question 4

what is curare?

Answer 4

dangerous toxin used in hunting that occupies AChR and does not open ion channel so no muscle contraction (no respiration)

Question 5

where is botulism toxin found?

Answer 5

soil
food
wounds (infected)
IV drug users- black tar heroin

Question 6

what does the botulism toxin do to the body?

Answer 6

cleaves presynaptic proteins involved in vesicle formation and blocks vesicle docking with presynaptic membrane so there is no release of ACh

rapid onset weakness without sensory loss

Question 7

what is LEMS?

Answer 7

antibodies to presynaptic Ca2+ channels

Question 8

what condition is LEMS associated with?

Answer 8

small cell carcinoma

Question 9

management of LEMS

Answer 9

3-4 diaminopyridine (blocks K+ channels)

Question 10

what is myasthenia gravis?

Answer 10

AI antibodies to AChR leading to reduced functioning receptors causing muscle weakness and fatiguability

most patients have thymus involvement

Question 11

two peaks of incidence in myasthenia gravis?

Answer 11

women in 30s

men 60-70s

Question 12

presentation of myasthenia gravis

Answer 12

weakness worse throughout the day commonly in extraocular, facial and bulbar muscles (drooping eyelids, diplopia, struggle chew/ speak at the end of the day)
proximal limb weakness
SOB

Question 13

diagnosis of myasthenia gravis

Answer 13

antibodies to ACh-R and MuSK

edrophonium test= neostigmine given which blocks breakdown and reverses weakness (trial of therapy)

Question 14

management of myasthenia gravis

Answer 14

acetylcholinesterase inhibitors e.g. pyridostigmine
IV immunoglobulin or plasma exchange in emergency (CRISIS)
thymectomy
steroids and steroid-sparing agents

Question 15

immune-mediated muscle diseases

Answer 15

1. polymyositis

2. dermatomyositis

Question 16

presentation of polymyositis

Answer 16

over 40 presenting with symmetrical, progressive proximal weakness developing over weeks- months

Question 17

diagnosis of polymyositis

Answer 17

high CK

Question 18

management of polymyositis

Answer 18

responds to steroids

Question 19

presentation of dermatomyositis

Answer 19

symmetrical proximal muscle weakness with skin lesions (heliotrope on face)

50% have underlying malignancy

Question 20

example of degenerative muscle disease

Answer 20

inclusion body myositis

Question 21

presentation of inclusion body myositis

Answer 21

slow progressive weakness in 60s with characteristic thumb sparing

Question 22

management of inclusion body myositis

Answer 22

poor response to steroids

Question 23

examples of muscular dystrophies

Answer 23

myotonic dystrophy
Duchenne’s
Becker’s

Question 24

what is myotonic dystrophy?

Answer 24

AD multisystem disorder with trinucleotide repeat

Question 25

presentation of myotonic dystrophy

Answer 25

weakness
frontal balding
cataracts
ptosis
onset in 30s
positive FH

Question 26

presentation of Duchenne’s

Answer 26

woody texture muscle swelling (calves)
toe walker
positive Gower’s sign

Question 27

presentation of Becker’s

Answer 27

woody texture calves

proximal limb wasting

Question 28

risk in use of steroids to do with muscles

Answer 28

necrotising myopathy with risk of rhabdomyolysis

Question 29

what is rhabdomyolysis?

Answer 29

dissolution of the muscle with leakage of toxic intracellular contents into plasma

Question 30

causes of rhabdomyolysis

Answer 30

crush injuries
toxins
post-convulsions extreme exercise e.g. post-marathon

Question 31

presentation of rhabdomyolysis

Answer 31

triad of myalgia, muscle weakness and myoglobinuria leading to DIC and renal failure