1. Muscle weakness Index case Year 1 Michaelmas Term

2. The case: 27 year old woman 4 month history of increasing weakness in arms Gets worse with repetitive tasks such as chopping food Noticed her speech becoming strange Difficulty swallowing and chewing food Double vision- can no longer read a newspaper Boyfriend says her eyes look droopy

4. Some medical words: Difficulty speaking? Difficulty swallowing? Droopy eyelids? Double vision?

5. Some medical words: Difficulty speaking? dysarthria Difficulty swallowing? dysphagia Droopy eyelids? ptosis Double vision? diplopia

6. A differential diagnosis?

7. nerves? (e.g multiple sclerosis) muscles? (e.g polymyositis) neuromuscular junction? -autoimmune: myasthenia gravis -infectious: e.g botulism - neoplastic: e.g Lambert Eaton syndrome -toxic: e.g organophosphate poisoning; snake bite

8. What is myasthenia gravis?

9. myasthenia gravis Autoimmune condition. IgG antibodies deposited at post synaptic membrane receptors causes interference and later destruction of acetylcholine receptors Incidence: 5:100,000 women >men 10% cases in children Thymoma in 10% cases

11. How is Ach released at the NMJ?

12. The neuromuscular junction: Depolarisation of nerve ending Influx of ca++ ions Vesicles of Ach released into neuro- synaptic junction Diffusion to receptors on motor endplate

13. The neuromuscular junction: Ach on receptor causes influx of sodium ions Initiates action potential in muscle cell Ach destroyed by acetylcholineesterase into acetic acid and choline Choline taken up by nerve ending

14. Why do the patient’s symptoms get worse with repetitive movement?

15. Increased use of Ach receptors exhausts the system with reduced numbers of active receptors. Small muscles (in eyes, face, throat) and proximal limb muscles affected first

16. How might you confirm the diagnosis? Clinical picture IgG antibodies 90% Tensilon (edrophonium test): an anticholinesterase is injected IV with a rapid improvement for 2-3 minutes CT or MRI scan for thymoma

17. How might you treat myasthenia? Oral anticholinesterases neostigmine and pyridostigmine Autoimmune suppression with steroids or azathioprine Thymectomy, especially in young patients with high levels of antibodies

18. Other causes of N-M-J dysfunction?

19. “Botox” and botulism: toxin from clostridium botulinum prevents release of Ach at presynaptic junction- causes paralysis

21. Lambert-Eaton syndrome Presynaptic impaired release of Ach 60% cases associated with small cell carcinoma of lung Presents like myasthenia gravis

22. snakebite

23. Snake venom: neurotoxin Beta- neurotoxin blocks presynaptic membrane (Ach release) Alpha neurotoxin blocks post-synaptic membrane Both cause paralysis

24. Any other situations a doctor might need to know about N-M-Js?

25. Neuromuscular blockers in anaesthesia Either competitive drugs e.g. pancuronium which block receptor Or depolarising blockers, which act on the Ach receptor to trigger ion channels but are not reversed by Achesterase e.g. suxamethonium