What is myasthenia gravis?
This is an acquired condition characterised by autoimmune destruction of nicotinic acetylcholine receptors on the post-synaptic side of the NMJ. B and T cell mediated IgG autoantibodies are created which attack the postsynaptic acetylcholine receptors at the neuromuscular junction. This causes the physical symptoms of weakness and fatigability.
What is the pathophysiology of myasthenia gravis?
Antibodies to acetylcholine receptor protein (anti-AChR antibodies) are commonly found. Immune complexes of anti-AChR IgG and complement are deposited at the postsynaptic membranes, causing interference with and later destruction of AChRs.
A second group of antibodies against muscle-specific receptor tyrosine kinase (anti-MuSK antibodies) have been identified in anti-AChR antibody negative cases. Ocular muscle MG is another subgroup.
What proportion of those with myasthenia gravis have thymic hyperplasia?
70% - below the age of 40
What proportion of those with myasthenia gravis have a thymic tumour?
10% - incidence increases with age
What disease processes are associated with the development of myasthenia gravis?
- Thyroid disease
- Rheumatoid disease
- Pernicious anaemia
- Thymic hyperplasia/thymoma
What age is myasthenia gravis more common in women?
What age range is myasthenia gravis more commonly associated with being male?
What are symptoms of myasthenia gravis?
Slowly increasing/relapsing muscular fatigue. Muscle groups affected include:
- Limb girdle
What signs might you see in someone with myasthenia gravis?
- Ocular - Ptosis, Diplopia
- Bulbar - dysphagia, dysphonia, dysarthria, dropping face
- Peek sign
- Voice fading - counting to 50
What might patients with myasthenia gravis report with regards to their experience of their symptoms?
Best time is in the morning, and get worse as the day goes on
What can exacerbate symptoms experienced in myasthenia gravis?
- Change of climate
What drugs can exacerbate myasthnic symptoms?
If someone presented with features of myasthenia gravis, what would be your differential diagnosis?
- Polymyositis/other myopathies
- Takayasu's Arteritis
What is the general couse of myasthnia gravis?
Has a fluctuating/relapsing/remitting course, but over time this progresses to severe disease, where respiratory difficulties become prominent
What effect does myasthenia gravis have on reflexes?
Normally preserved, but can demonstrate fatiguability
What investigations might you do in someone with suspected myasthenia gravis?
- Serum antibody - Anti-AChR antibodies, MUSK antibodies
- Imaging - CT
- Ice applicaiton test
- Tensilon test
What percentage of cases are anti-AChR antiobodies found in myaesthenia gravis?
What are the characteristic features of those with myaesthenia gravis with Anti-MUSK antibodies?
Weakness predominantly in bulbar, facial and neck muscles
What might EMG show in someone with myaesthenia gravis?
A characteristic decrement with repetetive stimulation
Why would you do a CT in someone with suspected myaethenia gravis?
To exclude Thymoma
What is the tensilon test?
Not commonly used test
IV edrophonium - weakness improves within seconds, and can last up to 5 minutes
How would you manage someone with myaethenia gravis?
- Anticholinesterase - pyridostigmine
- Immunosuppression - Treat relapse with prednisolone for extended period (depending on response)
- Thymectomy - beneficial even in those without thymoma
- Consider plasmapheresis/IVIG - exacerbation
What are side effects to anticholinesterase medication?
- Increased salivation, lacrimtion
What would you give in combination with steroid therapy for relapses of myaesthenia gravis?
Osteoporotic prophylactic treatment
What is a myaesthenic crisis?
Life-threatening weakness of the resp. muscles during a relapse
What else could be a cause of features of a myaesthenic crisis?
Cholinergic crisis - overtreatment with anticholinesterase drugs
How would you manage someone with a myaesthnic crisis?
- Monitor forced vital capacity
- Ventilatory support
- Identify cause (infection/meds)
- Treat with plasmapheresis/IVIG
What is Lambert-Eaton myasthenic-syndrome?
Often a paraneoplastic manifestation of SCLC due to defective acetylcholine release at the NMJ. Can be caused by other disease processes including thyroid disease and T1DM
What are antibodies in Lambert-Eaton-myasthenic syndrome against?
Voltage-gated Ca2+ channels on the pre-synaptic membrane
What are features Lambert-Eaton Myasthenic Syndrome?
- Gait difficulty preceding eye/Bulbar signs
- Autonomic involvement
- Proximal limb weakness
What autonomic features can present in Lambert-Eaton myasthenic syndrome?
- Dry mouth
What are features of proximal muscle weakness seen in Lambert-Eaton Myasthenic syndrome, and why does this differ from myasthenia gravis?
Tends to improve after a few minutes of muscle contraction
How would you investigate someone for suspected Lambert-Eaton myasthenic syndrome?
- EMG + repetetive stimulation
- Serum antibodies - P/Q-type VGCC antibodies
What proportion of those with Lambert-Eaton myasthenic syndrome are anti-P/Q type VGCC antibody positive?
How would you manage someone with Lambert-Eaton myasthenic syndrome?
What would you consider doing in someone with diagnosed Lambert-Eaton myasthenic syndrome who had not been found to have SCLC?
Do regular high res CXR/CT - syndrome can precede cancer by > 4yrs
How do anticholinesterase medications work?
Reduce the rate of degradation of ACh, thus increasing its chance of triggering an end-plate potential