Clinical - Muscular

Question 1

What causes Neuromotonia (NMT/Isaac’s Syndrome)?

Answer 1

Auto-antibodies against voltage-activated K+ channels in the motor neurone disrupt function resulting in hyperexcitability (repetitive firing)

Question 2

What is the treatment for Neuromotonia (NMT/Isaac’s Syndrome)?

Answer 2

Anti-convulsants (e.g. carbamazepine, phenytoin) which block voltage-activated Na+ channels

Question 3

What is the clinical description of Lambert-Eaton Myasthenia Syndrome, and what is it associated with?

Answer 3

Muscle weakness in the limbs, very rare and associated with small cell carcinoma of the lung

Question 4

What causes Lambert-Eaton Myasthenia Syndrome?

Answer 4

Auto-Antibodies against voltage-activated Ca2+ channels in the motor neurone terminal result in reduced Ca2+ entry in response to depolarization and hence reduced vesicular release of ACh

Question 5

What is the treatment for Lambert-Eaton Myasthenia Syndrome?

Answer 5

anticholinesterases (e.g. pyridostigmine) and potassium channel blockers (e.g. 3,4-diaminopyridine) which increase the concentration of ACh in the synaptic cleft

Question 6

What is the presentation of Myasthenia Gravis (MG)?

Answer 6

Characterised by progressively increasing muscle weakness during periods of activity (fatiguability, contrast with LEMS that may transiently improve upon exertion). Often weakness of the eye and eyelid muscles is a presenting feature

Question 7

What causes Myasthenia Gravis (MG)?

Answer 7

Auto-antibodies against nicotinic ACh receptors in the endplate result in reduction in the number of functional channels and hence the amplitude of the e.p.p.

Question 8

What is the treatment for Myasthenia Gravis (MG)?

Answer 8

Anticholinesterases (e.g. edrophonium for diagnosis, pyridostigmine for long term treatment) and a variety of immunosuppressant agents (e.g. azathioprine). Anticholinesterase increase the concentration of ACh in the synaptic cleft

Question 9

What is Botulinum toxin?

Answer 9

Extremely potent exotoxin toxin (related to tetanus and diptheria toxins) that acts at motor neurone terminals to irreversibly inhibit ACh release

Question 10

What are the clinical uses of Botulinum toxin?

Answer 10

• Low dose botulinum haemaglutin complex can be administered by intramuscular injection to treat overactive muscles (dystonias) eg. squints
• Botox injections

Question 11

What effects do curare-like compounds have?

Answer 11

• Interfere with the postsynaptic action of acetylcholine by acting as competitive antagonists of the nicotinic ACh receptor
• Reduce the amplitude of the endplate potential (e.p.p.) to below the threshold for muscle fibre action potential generation