Muscle weakness

Index case Year 1

Michaelmas Term

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

Some medical words:

• Difficulty speaking?

• Difficulty swallowing?

• Droopy eyelids?

• Double vision?

Some medical words:

• Difficulty speaking? dysarthria

• Difficulty swallowing? dysphagia

• Droopy eyelids? ptosis

• Double vision? diplopia

A differential diagnosis?

A differential diagnosis?

• 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

What is myasthenia gravis?

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

How is Ach released at the NMJ?

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

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

Why do the patient’s symptoms get worse with repetitive

movement?

Why do the patient’s symptoms get worse with repetitive

movement?

• 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

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

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

Other causes of N-M-J dysfunction?

Other causes of N-M-J dysfunction?

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

Lambert-Eaton syndrome

• Presynaptic impaired release of Ach

• 60% cases associated with small cell carcinoma of lung

• Presents like myasthenia gravis

snakebite

Snake venom: neurotoxin

• Beta- neurotoxin blocks presynaptic membrane (Ach release)

• Alpha neurotoxin blocks post-synaptic membrane

• Both cause paralysis

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

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

• 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