Myasthenia Gravis Flashcards
What is Myasthenia Gravis
A disease of the neuromuscular junction.
It is an acquired, organ-spcific autoimmune disorder, of unknown cause, in which autoantibodies are directed agains the post-synaptic acetylcholine receptor.
Results in weakness and “fatiguability” of skeletal muscle groups.
The most commonly affected muscle are the proximal limbs, the ocular bulbar muscles.
Which organ is there a particular association of pathology in Myasthenia Gravis?
The thymus - hyperplasia in 70%, 10% have benign tumour
What are the two distinct age-groups that develop Myasthenia Gravis?
Women 20-35 - tends to be acute, severely fluctuating, more generalized and associated with HLD-B8 / DR3
Men 60-75 - more oculobulbar presentation
This is not the rule however.
What are the clinical features of Myasthenia?
All show fatiguability - features are worse after exercise ad at the end of the day.
Ocular - Ptosis, diplopia (50%)
Other cranial muscles - Weak face and jaw, dysarthria, dysphonia, dysphagia
Limb weakness - Usually proximal, shoulder and hips
Neck weakness - Neck flexion and extension, patients can present with difficulty lifting their head up
Respiratory muscle weakness - Shortness of breath
N.B Muscle wasting is rare, occurs only at end stage
How do you test for Myasthenia?
Eyes - demonstrate fatiguability by getting patient to look up for 1-2mins. OR getting the having them look down for a while then up, gets a lid twitch.
Limb reflexes are normal or increased, but fatigue on repeated testing.
Sensory examination is normal.
What investigations would you carry out in a patient with suspected Myasthenia Gravis?
1) Tensilon (edrophonium) test - fast-acting anticholinesterase (prevents breakdown of ACh). When administered bolus, symptoms of fatiguability improve within seconds, but only for 2-3 mins
2) Serum ACh receptor and MUSK (muscle specific kinase) antibodies - present in serum up to 85% of patients.
3) Electromyography - two classic findings
- Decrement in amplitude (fatiguing)
- Increased jitter using a single fibre electrode
4) Thymus imaging - if thyroid hyperplasia CT / MRI essential to asses for thyroid removal which may aid symptoms and prevent malignancy.
5) Other autoantibodies - present against striated muscle and thymus
6) Spirometry - vital capacity needs to be checked. If below 1.5 litres then transfer to ITU
How are patients with Myasthenia Gravis managed?
Course is relapsing remitting, may be brought on by illness and drugs.
1) Oral acetylcholinesterases - Pyridostigimine
- onset 60 mins, duration 3-5hrs, response determines dose
- Overdose possible and difficult to differentiate from normal disease as presents with weakness
- Only treats symptoms not underlying disease
2) Thyectomy - can improve prognosis of disease in patients with thyroid hyperplasia, esp. in those under 40.
- essential in thyoma to remove potentially malignant tumour, rarely improves symptoms
3) Immunosuppression - Corticosteroids, improves 70% of cases
- Plasmopheresis or IV immunoglobulins can be used duting acute exacerbations and when respiratory involvement.
- Azathioprine, most commonly used as steroid sparing agent, but can also use ciclosporin, methotrexate, mycophenolate.
What is Lambert-Eaton Myasthenic syndrome?
This is associated with antibodies directed against pre-synpatic voltage-gated calcium channels, resulting in a failure to release ACh into the synapse.
In many cases it is a non-metastatic manifestation of malignancy, e.g. small-cell carcinoma of the lung.
Characterised by weakness of proximal limb muscles, without ocular and cranial muscles.
Paradoxically there is a temporary improvement in power after exercise, though this is followed by a sustained period of weakness.
Reflexes are usually absent, but return after the use of muscle potentiation.
Autonomic involvement is common especially in malignancy related cases.
Electromyography shows a characteristic increase in action potential after repetitive stimulation. AChr antibodies are negative.
Guanethidine hydrochloride and 4-aminopyridine may halp.
What are the even rarer forms of Myasthenia Gravis?
- Congenital - mutation in release of ACh apparatus from pre-synaptic terminal.
- Neo-natal - transfer of antibodies across the placenta, usually resolves.
- penecillamine induced myasthenia
Also: Botulinum toxin - from clostridium botulinum, damages neuromuscular junction.
