Neuromuscular junction disorders Flashcards
What is the pathogenesis of myasthenia gravis?
antibody mediated attack causes accelerated turnover of receptors, rapid endocytosis of receptors, complement medicated damage to muscle end plate and blaockage of the active site of the AChR
What leads to fatiguibility in MG?
Pre-synaptic rundown and decreased number of receptors
How many patients with MG have thymic pathology?
75%
- 65% have hyperplastic thymus
- 10% have thymic tumors
Who does MG mostly occur in?
more common in women
peak incidence 20-30 years in females, >50 in males
What are the clinical features of MG?
crainial muscle weakness
- diplopia + ptosis
- facial weakness, chewing weakness, nasal speech, difficulty swallowing
- typically worse later in day and better on rest
- upper limb weakness with preserved reflexes
- severe weakness of respiratory muscles = myasthenic crisis
- no sensory impairment
Examination findings in MG?
ptosis, diplopia motor power survey - forward abduction time of arms time to develop ptosis on upward gaze FVC Absence of other neurology
What are some tests that can be done to assess for MG
Icepack test
- application of ice over eyelid should cause improvement as acetylcholinesterase enzyme is inhibited at temps less than 28 degrees
Tensilon test
- administer edrophonium (short acting acetylcholinesterase inhibitor) should lead to improvement in muscle strength
Serology in MG?
anti-AChR antibodies positive in 85% of generalised MG
Ocular MG is often seronegative
40% of anti-AChR negative patients are positive for antibodies to muscle specific receptor tyrosine kinase
What conditions are associated with MG?
Thymic hyperplasia Thymoma Hyperthyroidism Hashimotos thyroiditis RA, SLE
What screening tests should be performed in patients with MG?
CT of mediastinum/CXR ANA, RF, Antithyroid antibodies TFT's Blood glucose, mantoux, quanterferon (implications for treatment) Lung function tests
What are treatment options for MG?
Acteylcholinesterase inhibitors (pyridostigmine) Thymectomy in selected patients results in outcomes over years Immunosuppression (steroids, mycophenolate/azathioprine, calcineurin inhibitors) Plasmaphoresis and IVIg for stablisisation pre thymectomy r critically unwell patients
What is a myasthenic crisis?
exacerbation of weakness severe enough to cause respiratory failure
Usual precipitant is infection
Treat with antibiotics, respiratory support, physio, plasmaphoresis and IvIg
What is a cholinergic crisis in MG?
too much acetylcholinesterase inhibitor leading to bombardment of AchR by acetylcholine leading to flaccid paralysis
Sometimes confused between myasthenic crisis
What are some drugs that can exacerbate MG?
aminoglycasides, quinolones, macrolides non-depolarising muscle relaxants B-blockers Local anesthetics Botox Quinine Magnesium Penicilliamine can cause MG
What is lambert-eaton myasthenic syndrome?
paraneoplastic syndrome, usually caused by small cell lung cancer
autoantibodies against P/Q type calcium channels which leads to decreased release of calcium from the pre-synaptic terminal
What are the differences between LEMS and MG?
LEMS
- affects proximal muscles of lower limbs
- strength and reflexes increase with repition
- autonomic symptoms are common
Where does botox affect the NMJ?
bacterial toxins produced by clostridum botulisim cleave proteins that are essential for the release of acetylcholine vesicles from the pre-synaptic membrane
How do non depolarising muscle relaxants work?
competitively block binding of Ach to AchR blocking the generation of an action potential
Examples: Curare, vecuronium, rocuronium, pancruonium
Can be reversed by actelycholineesterase inhibitors
How do depolarising muscle relaxants work?
binds to AchR and activates it causing activation of channels and generation of an action potential which leads to muscle contraction then the muscle becomes refractory and flaccid paralysis occurs
Example: succinyl choline (suxamethonium)
Cant be reversed by actetylcholine-esterase inhibitors
How do reversible acetylcholinesterase inhibitors?
prevent breakdown of aceytlcholine by acetylcholinesterase leading to increased binding and depolarisation of muscle end plate
What are some examples of irreversible acetycholinesterase inhibitors?
Organophosphates
- insectisides (malathion)
- nerve gas
How does atropine work?
competitive reversible agonist of muscarinic acetylcholine receptors
