Myasthenia Gravis Flashcards
Define Myasthenia Gravis
Autoimmune disease affecting the nicotinic acetylcholine receptors at neuromuscular junction, causing weakness of skeletal muscles
Aetiology of myasthenia gravis
Impairment of neuromuscular junction transmission.
Most commonly due to auto-antibodies against the nicotinic acetylcholine receptor (90%)
Paraneoplastic (Lambert-Eaton) - auto-antibodies against pre-synaptic calcium ion channels, impairing acetylcholine release
3-7% have auto-antibodies against muscle-specific tyrosine kinase
Risk factors for myasthenia gravis
Other autoimmune conditions e.g. pernicious anaemia, AI thyroid, RhA, SLE
Thymoma development (breakdown in immune tolerance in thymus)
Thymic hyperplasia (50-70%)
Epidemiology of myasthenia gravis
Uncommon
More common in females at younger ages
Equal gender distribution at middle age
In patients >50 years there is a male preponderance
Symptoms of myasthenia gravis
Muscle fatigability
- Muscle weakness that worsens with repetitive use or towards end of day
- Improves with rest
Diplopia
Dysphagia
Dysarthria
Proximal limb weakness
Facial paresis (myasthenic snarl)
Difficulty smiling, chewing or swallowing (nasal regurgitation of fluid)
SOB
Exacerbated by: penicillamine, antibiotics e.g. gentamicin, beta blockers, phenytoin, quinidine, procainamide, lithium
Signs of myasthenia gravis on examination
May have a normal neurological exam initially - changes on repeated exams
May be generalised (affecting many muscle groups), bulbar (affecting bulbar muscles), or ocular (affecting only the eyes)
Eyes:
- Bilateral ptosis, may be asymmetrical
- Complex ophthalmoplegia
- Test for ocular fatiguability by asking patient to sustain upward gaze for 1 min and watch for progressive ptosis
- “Ice on eyes” - placing ice-packs on eyelids for 2 mins can improve neuromuscular transmission, reducing ptosis (improves >2mm from baseline)
Bulbar:
- Reading aloud may provoke a dysarthria or nasal speech after 3 minutes
Limbs:
- Test the power of a muscle before and after repeated use e.g. 20 repetitions
Investigations for myasthenia gravis
AChR antibodies: positive (80-90%)
Muscle specific receptor TK AB (MuSK): positive
CK: normal (exclude myopathy)
TFTs: normal (exclude hyperT)
Nerve conduction studies: decrements of muscle AP (differentiate from Lambert-Eaton
EMG: “jitter” (variability in latency from sitmulus to muscle)
CT thorax/CXR: ?thymoma or hyperplasia, SCLC
Tensilon: power returns in 1 minute (given acetylcholinesterase blockers)
Pulmonary function testing
Management for myasthenia gravis
1st line (symptomatic) = long-acting AChE inhibitors (pyridostigmine, neostigmine)
1st line (long-term control) = immunosuppression:
- 1st → prednisolone
- 2nd → azathioprine, cyclosporine, mycophenolate mofetil
Surgical: Thymectomy
Complications of myasthenia gravis
Myasthenic crisis
Respiratory failure
Impaired swallow -> Acute aspiration -> secondary pneumonia
Cardiac impairment e.g. myocarditis, giant cell myocarditis, takotsubo cardiomyopathy
Thyroid disorders
What is a myasthenic crisis and how does it present
Characterised by FVC ≤1L, negative inspiratory force ≤20cmH2O, and need for ventilation
Reduced RR, background of MG
Accessory muscle usage (weak inspiratory muscles)
Weak cough (weak expiratory muscles)
What investigations should be done for suspected myasthenic crisis and how is it managed
Ix: ABG (hypercapnia before hypoxia), FVC
Mx: plasmapheresis, IVIG, intubation
What are thymomas associated with
Most common tumour of ant. mediastinum (50-70yo)
Associations: MG (30-40%), red cell aplasia, dermatomyositis, SLE, SIADH
Death by compression of airway or cardiac tamponade
Prognosis for myasthenia gravis
Most, but not all, patients enjoy good quality of life and normal lifespan due to advances in diagnosis and immunosuppressive treatment
However, the onset of improvement varies greatly from days to months, and some patients have a significant burden of disease.
A prompt response to corticosteroid monotherapy is typical for older men with ocular MG whereas generalised symptoms are slower to improve and require more aggressive therapy.
How does Lambert Eaton present differently to myasthenia gravis
Muscle weakness improves with repeated use
Associated with SCLC
Antibody to the presynaptic voltage-gated calcium channel (VGCC)
