Myasthenia gravis Flashcards
What is the underlying cause of myasthenia gravis?
antibodies against nicotinic acetylcholine receptors on muscle fibres. this limits ability of acetylcholine to cause muscle contraction
What are 4 types of muscles which are particularly affected in myasthenia gravis?
- Proximal muscle weakness: limbs (+ face, neck)
- Extra-ocular muscles - drooping eyelids, diplopia
- Facial muscles - difficulty smiling or chewing
- Bulbar muscles - change in speech or difficulty swallowing
What is the key exacerbating feature in myasthenia gravis?
symptoms are worse after prolonged movement/ at end of day
What are 2 features of extra-ocular muscle weakness?
drooping eyelids (ptosis), diplopia
What are 2 features of facial muscle weakness?
difficulty smiling or chewing
What are 2 features of bulbar muscle weakness?
change in speech, difficulty swallowing
What are 5 features of myasthenia gravis on examination?
- Fatigable muscle weakness
- Bilateral ptosis (worse on sustained upgaze)
- Myasthenic snarl (due to facial muscle weakness)
- Head droop
- Bulbar features e.g. nasal speech, dysarthria, dysphagia
What can cause bilateral ptosis to be worse on examination in myasthenia gravis?
worse on sustained upgaze
What are 5 investigations that can be performed for the workup of myasthenia gravis?
- Blood test for serum acetylcholine receptor antibody
- Muscle-specific tyrosine kinase antibody
- CT thorax to exclude thymoma
- Repetitive nerve stimulation/ single fibre electromyography
- Tensilon test (aka edrophonium test)
What proportion of patients with generalised myasthenia gravis have a positive serum acetylcholine receptor antibody test?
80-90%
When should a test for muscle-specific tyrosine kinase antibodies be ordered?
if acetylcholine receptor antibody is negative or equivocal
What proportion of patients with myasthenia gravis has thymic involvement?
- 65% have thymic hyperplasia
- 12% have thymoma
Why is it important to perform CT thorax in suspected myasthenia gravis?
high proportion of thymic hyperplasia/thymoma, will inform decision regarding consideration for thymectomy
What will be seen following repetitive nerve stimulation in myasthenia gravis?
>10% fall in muscle action potential between the 1st and 4th action potential in a series of 10 stimulations of the alpha motor neurone
What investigation must be repeatedly carried out in myasthenic crisis and why?
serial pulmonary function tests (spirometry) - if FVC 15ml/kg or less should consider pt for mechanical ventilation
Why are serial pulmonary function tests (spirometry) needed to be performed in myasthenic crisis?
if forced vital capacity (FVC) is <15ml/kg should commence on mechanical ventilation
What does the tensilon test involve?
IV edrophonium given, which reduces muscle weakness temporarily in MG
Why is the Tensilon test no longer commonly performed?
risk of cardiac arrhythmia
What is the most sensitive electrophysiological test for myasthenia gravis?
single fibre electromyography
What does single fibre EMG involve?
special needle used to record time-locked potentials of 2 muscle fibres belonging to same motor unit
can detect impairment of neuromuscular transmission which can cause increased ‘jitter’, which is the variability in the arrive time of APs to the recording surface between consecutive discharges
What are the 3 categories of management of myasthenia gravis?
conservative, medical, surgical
What does the conservative management of myasthenia gravis involve?
regular review in neurology outpatients, involvement of MDT as required (OT, physio, SALT if dysarthria etc.)
What is the medical management of myasthenia gravis? 3 aspects
- long-term acetylcholinesterase inhibitors: pyridostigmine or neostigmine
- Immunosuppression: prednisolone acutely, cyclosporin, azathioprine, mycophenolate mofetil
- Acute crisis management: plasmapheresis, IV Ig, steroids
What is the first line acetylcholinesterase inhibitor used for myasthenia gravis?
pyridostigmine (neostigmine can also be used)
What are 4 examples of immunosuppressive drugs that can be used to treat myasthenia gravis?
- Prednisolone initially
- Azathioprine
- Cyclosporin
- Mycophenolate mofetil
What is the surgical element of myasthenia gravis management?
thymectomy
What are 2 aspects of the management of myasthenic crisis?
- Plasmapheresis
- Intravenous immunoglobulins
In which type of myasthenia gravis are antibodies less commonly seen?
disease limited to the ocular muscles
What is meant by muscle fatigability?
muscles become progressively weaker during periods of activity and slowly improve after periods of rest
What is the gender ratio of incidence of MG?
female to male 2:1
What are 4 autoimmune disorders that myasthenia gravis is associated with?
- Pernicious anaemia
- Autoimmune thyroid disorders
- Rheumatoid
- SLE
Of the remaining 10-20% who don’t test positive for anti-acetylcholine receptor antibodies, what proportion are positive for anti-muscle specific tyrosine kinase antibodies?
40%
What are 7 drugs which may exacerbate myasthenia gravis?
- Penicillamine
- Quinidine
- Procainamide
- Beta-blockers
- Lithium
- Phenytoin
- Antibiotics: gentamicin, macrolides, quinolones, tetracyclines
What is a syndrome similar to myasthenia gravis and when does it occur?
Lambert-Eaton myasthenic syndrome: in association with small cell lung cancer, and to lesser extent breast and ovarian cancer
can also occur independently as autoimmune disorder
Which cancer is Lambert-Eaton syndrome most commonly associated with?
small cell lung cancer
What causes Lambert-Eaton myasthenic syndrome?
antibody directed against presynaptic voltage-gated calcium channel in peripheral nervous system
What are 5 clinical features of Lambert-Eaton syndrome?
- Repeated muscle contractions lead to increased muscle strength - opposite of myasthenia
- Limb-girdle weakness, affecting lower limbs first
- Hyporeflexia
- Autonomic symptoms: dry mouth, impotence, difficulty micturating
- Ophthalmoplegia and ptosis NOT commonly a feature (unlike MG)
In what proportion of patients with Lambert Eaton syndrome do repeated muscle contractions lead to increased muscle strength?
only 50%; following prolonged muscle use, the strength will eventually decrease
What are 3 autonomic symptoms which may be present in Lambert-Eaton syndrome?
- Dry mouth
- Impotence
- Difficulty micturating
What is the key investigation to perform in Lambert Eaton syndrome and what will it show?
EMG: incremental response to repetitive electrical stimulation
What are 4 aspects of the management of Lambert-Eaton syndrome?
- Treatment of underlying cancer
- Immunosuppression e.g. prednisolone and/or azathioprine
- 3,4-diaminopyridine - being trialled
- IV Ig and plasmapheresis may help
How does 3, 4-diaminopyridine, which is currently being trialled, work to treat LE syndrome?
- blocks potassium channel efflux in the nerve terminal so action potential duration is increased
- calcium channels can then be open for longer and allow more acetylcholine release to stimulate muscle at end plate
