12. Myasthenia Gravis Flashcards
Define myasthenia gravis.
A chronic autoimmune disorder due to autoantibodies against nicotinic Acetylcholine receptors (AChR) in the NMJ that causes muscle weakness that gets progressively worse with activity and improves with rest.
-> Specifically the postsynaptic membrane of neuromuscular junction of skeletal muscle
Describe the epidemiology of myasthenia gravis.
- More common in FEMALES than males
- Peak age of incidence at 30 yrs in women
- Peak age of incidence at 60 yrs in males
Give some risk factors for myasthenia gravis.
- Female
- Family history
- Autoimmune disease: RA and SLE
- Thymoma (tumour of the thymus gland) and Thymic hyperplasia
- 10-20% of patients with myasthenia gravis have a thymoma
- 20-40% of patients with a thymoma develop myasthenia gravis
What condition is myasthenia gravis associated with?
Thymoma and thymic hyperplasia
Normal physiology:
What normally happens at the neuromuscular junction to trigger muscle contraction?
- Depolarisation of lower motor neurone = calcium channels open
- Calcium influx into LMN
- Calcium = exocytosis of ACh from vesicles
- ACh crosses synapse and binds to postsynaptic receptors
- ACh binding opens the intrinsic channel, potassium out sodium in
- Voltage gated sodium channels open = depolarisation along T-tubule
- Depolarisation = opening of calcium stores in sarcoplasmic reticulum
- Calcium = contraction
Describe the pathophysiology behind myasthenia gravis.
Autoimmune disease mediated by antibodies to nicotinic acetylcholine receptor (nAChR).
- Plasma B cells produce anti-acetylcholine receptor antibodies (IgG)
- Bind to the postsynaptic NMJ receptors - nAChR
- Blocks the receptor and prevents ACh binding - blocks the excitatory effect of ACh.
- Fewer APs fire -> muscles don’t respond to CNS signal
- Muscle weakness + fatigue.
- Anti-acetylcholine receptor antibodies also activate the classical complement pathway.
- Causes inflammation + destruction of the muscle cell and decreases the no. of AChRs on the surface.
- Worse symptoms.
OVERALL: Immune complexes of anti-ACh receptor IgG and complement are deposited at the post-synaptic membranes.
What is the characteristic feature of myasthenia gravis?
Weakness that gets worse with muscle use and improves with rest.
Give some general features of myasthenia gravis.
- Fatigue
- Muscle weakness
- Fatigue when chewing
- Dysarthia - weakness in facial movement
- Dysphagia - weakness with swallowing
- Slurred speech + SOB
Which muscle groups are affected by myasthenia gravis, in order of most affected?
Muscle groups affected in order:
* Extra-ocular
* Bulbar - swallowing & chewing
* Face
* Neck
* Trunk
What might patients complain of in myasthenia gravis?
“Stairs, chairs and hair”
- Can’t get up out of chairs, can’t walk up the full flight of stairs, can’t brush their hair.
Give some ocular manifestations of myasthenia gravis.
- Extraocular muscle weakness causing double vision (diplopia)
- Eyelid weakness causing drooping of the eyelids (ptosis)
- Upward gaze
- Complex opthalmoplegia
List 3 things that can worsen the weakness of myasthenia gravis.
- Pregnancy
- Hypokalaemia
- Infection
- Emotion
- Exercise
- Change of climate
- Drugs - opiates, beta-blockers, gentamicin and tetracycline
What auto antibodies might be present in someone with myasthenia gravis?
- Anti-AChR antibodies.
- Antibodies against muscle tyrosine kinase - anti-MuSK antibodies.
Are antibodies always present in myasthenia gravis?
No
- In fact, anti-AchR antibodies only present in 80% patients and only 50% of ocular
What investigations might you do it see if someone has myasthenia gravis?
- Serum anti-Ach receptor antibodies.
- Ask the patient to count to 50.
Investigations for myasthenia gravis.
- Physical examination - 2 main ways:
1) Ask patient to count to 50
-> As they reach the higher numbers, their voice becomes less audible.
2) Hold your finger up high and ask the patient to keep looking at it, without lifting head up.
-> After a few seconds, they will be unable to keep their eyes raised. - Looking for autoantibodies:
-> 1st: Acetylcholine receptor (ACh-R) antibodies (85% of patients)
If tests negative, then test:
-> Muscle-specific kinase (MuSK) antibodies (10% of patients)
-> LRP4 (low-density lipoprotein receptor-related protein 4) antibodies (less than 5%) - Crushed ice test
- Ice is applied to ptosis for 3 minutes
- If symptoms improve: it’s ikely MG - Thyroid function tests for all patients
- Neurophysiology tests:
1) Nerve conduction study (NCS)
2) Single fibre electromyography (EMG)
-> Decremental potentiation - response decreases as stimulus is repeated = this will tell you if there is fatiguability. - MR scan of the brain
- CT/MRI of the thymus
- Edrophonium/Tensilon test (rarely used now):
-> Tensilon = short-acting acetylcholinesterase inhibitor
-> Watch for a transient improvement in muscle strength
