Myasthenia Gravis Flashcards
Define myasthenia gravis.
A chronic autoimmune disorder of the post-synaptic membrane at the NMJ in skeletal muscle. Characterised by muscle weakness that increases with exercise and improves with rest.
What is the aetiology of MG?
Antibodies are present at the NMJ against:
- nicotonic AChR (80-90%)
- muscle-specific tyrosine kinase MuSK (3-7%)
- others have no detectable AChR antibodies
Removal of antibodies (by plasma exchange or reduction by immunosuppression) ameliorates symptoms.
Thymic follicular hyperplasia occurs in 70% and thymoma in 10% patients and may be associated with the aetiology.
What is the pathophysiology of MG?
- Antibodies attack AChRs which causes destruction of post-synaptic membrane
- Reduced AChRs means less binding sites for ACh to bind reducing consistent generation of muscle fibre action potentials causing skeletal muscle weakness
What is the MG classification system?
What are the risk factors for myasthenia gravis?
- FHx of AI disease
- genetic markers - specific HLA genes and nucleotide polymorphisms
- cancer-targeted therapy - checkpoint inhibitors can induce MG
Typical case history?
A 25-year-old woman presents with recurrent slurring of speech that worsens when she continues to talk. She has trouble swallowing, which deteriorates when she continues to eat, and has double vision that gets worse when sewing, reading, or watching TV. She reports that her head is heavy and hard to hold up. Her symptoms have progressively deteriorated over the past 6 months. She has intermittent weakness in her legs and arms. She is fearful of falling due to her legs giving way and she has trouble combing her hair or putting on deodorant. She reports a feeling of generalised fatigue and is occasionally short of breath.
A 76-year-old man reports double vision for the past 2 months. Within the past 2 weeks he has developed bilateral ptosis (drooping eyelids). His ptosis is so severe at times that he holds his eyes open to read. He is unable to drive due to the ptosis and the diplopia (double vision). His symptoms are generally better in the morning and progress throughout the day.
What are the signs and symptoms of MG?
Signs:
- presents as 1 of 3 forms: ocular, oropharyngeal or generalised
- proximal limb weakness
- abduction time <3min (arms outstretched)
- may be better in morning
- ptosis time (normal = >3min) - ask patient to look up and record when ptosis develops
- pulling opposite eyelid causes ptosis in the contralateral eye
- cooling eyelid with icepack for 2mins improves ptosis
- normal reflexes, sensation, autonomic function
- muscle wasting only in MuSK subtype of MG
Symptoms
- diplopia
- dysarthria
- dysphagia
- facial paresis
- SOB
- nasal speech - weakness of oropharyngeal muscles
What investigations would you do for MG?
- Serum AChR antibody analysis - good specificity but poor sensitivity for ocular MG
- MuSK antibodies- positive in 70% of AChR negative MG
- serial pulmonary function tests - if suspecting myasthenic crisis or pre-crisis
Other:
- CT chest- for thymoma found in 15%
- Nerve conduction studies e.g. repetitive nerve stimulation - >10% decrease in muscle action potential amplitude between 1st and 4th test in a sequence of 10
No longer done = Tensilon test - Tensilon prevents the breakdown of the chemical acetylcholine, it is injected into muscle to help distinguish MG from other causes of weakness.
How is MG managed?
- AChE inhibitors - pyridostigmine, dose depends on severity of symptoms
- Immunosuppression -
- Corticosteroid (prednisolone), given if pyridostigmine is not effective
- Azathioprine
- Rituximab
- Plasmapharesis and IVIG
- Surgery - thymectomy is effective even in those without a thymoma
Other:
- Cyclophosphamide, Eculizumab/Ravilizumab (C5 complement inhibitor mAb), Efgartigimod alfa (IgG1)
How common is MG?
Uncommon 100-200/million of population
All ethnic groups
Women more affected than men
Men have later age of onset (women 30-60yrs; men 70yrs)
Name 3 causes of ptosis.
Causes of ptosis:
- third nerve palsy,
- Horners syndrome,
- age
- myasthenia gravis.
Full list of causes:
- Involutional (i.e. ageing)
- Congenital (if severe, this may obscure the visual axis, preventing a clear retinal image being formed and thus causing amblyopia)
- Mechanical, e.g. eyelid tumour, inflammation with eyelid swelling (e.g. in preseptal or orbital cellulitis) or uncommonly, enophthalmos (e.g. due to orbital fracture)
- Neuromuscular junction (NMJ) disease, e.g. myasthenia gravis. This would typically be variable and fatiguable.
- Myopathy, e.g. chronic progressive external ophthalmoplegia
- Neurological, e.g. third nerve palsy (classically associated with all eye movements reduced except abduction, and an abnormally large pupil), Horner’s syndrome
Why is there diplopia in MG?
MG = DIPLOPIA secondary to abnormal eye movement- occurs as eyes are essentially pointed at different things. This does not occur in CPOE as the movement is symmetrical.
How common is a myasthenic crisis in MG?
~20% will experience this within 2yrs of diagnosis
MC = crisis requiring mechanical ventilation
May be precipitated by infection, aspiration, corticosteroids, surgery and medications.
What is the management where myasthenic crisis is suspected?
- Serial FVC measurements - ventilate if FVC <15ml/kg (normal is ~60)
- Mechanical ventilation
- Immediate IVIG or plasma exchange
- Immunosuppression
- Monoclonal antibody treatment
What are the complications of MG?
- Pyridostigmine SE
- Respiratory failure
- Impaired swallowing
- Acute aspiration
- Secondary pneumonia
- Cardiac complications - myocarditis, takotsubo cardiomyopathy
- Plasma exchange SE - coagulopathy, thrombocytopenia, electrolyte disturbance
- IVIG SE - fever, chills, headache, aseptic meningitis
- Thyroid disorders - linked to Graves’, hyperthyroidism, Hashimoto’s
Compare and contrast MG and LEMS.
