Myasthenia Gravis (MG) Flashcards
Definition
Chronic autoimmune neuromuscular disease of the neuromuscular junction that causes weakness of skeletal muscles.
Symptoms
- Drooping of one of both eyelids (ptosis)
- Blurred vision or double vision (diplopia) due to weakness of muscles that control eye movements
- A change in facial expression
- Shortness of breath (late sign)
- Difficulty swallowing/choking
- Impaired speech (dysarthia)
- Weakness in arms, hands, fingers, legs and neck (generally worse throughout the day)
- Poor sleep quality
- Cogan’s lid twitch (twitch in eyelid when opening and closing eyes)
- Bulbar weakness (sign as nasal sound)
- Curtis sign (lift one eye lid up and other comes down)
- Temperature dependent phenomenon (ice on eyes test - transient opening of eyes, improves conduction transiently)
Characterisation
- Anti-body mediated disease
- Pathology at NMJ
- Anti-acetylcholine receptor antibody identified and shown to be pathogenic
How do we know that it is an anti-body mediated disease?
- Antibodies present at NMJ
- Antibodies from MG patients cause MG symptoms when injected into rodents
- Immunisation of animals reproduces the disease
- Therapies that remove antibodies ameliorate the disease
Clinical presentation types
Pure ocular MG - eyes
Generalised MG - ocular plus another muscle group
Myasthenia crisis - become unwell rapidly due to bulbar dysfunction or respiratory failure
rare congenital forms
genetic abnormalities
Generalised MG
- Usually ocular plus weakness of another muscle group
- Bulbar dysfunction can happen early on
- Proximal weakness
- Respiratory muscle weakness
- Strength of lips and eyes impaired
- Neck weakness
Investigations
Antibody tests
- AChR, MUSK, Thyroid
- AChR positive in 80% but only 50% in ocular MG
- If AChR negative send for MUSK antibodies
- Some patients won’t have any antibodies detected probably because they haven’t been discovered yet
- A positive clinical picture and a positive antibody test = accurate diagnosis
EMG
- If antibodies negative
- Single-fibre EMG
- Jitter phenomenon
- Typical features = decremental loss of compound muscle action potentials or CMAP and on SFEMG the jitter phenomenon and block
- SF EMG more sensitive (choose muscle, put in needle electrode into adjacent muscle fibres)
- In a health person - when fired, both fibres should be activated concurrently
- In MG = don’t activate concurrently, showing problem with NMJ
- Loss of postsynaptic receptors is random
- Jitter = a delay between concurrent activation of motor fibres in the same motor unit, demonstrates fatigability within a single motor unit itself
- Jitter - non-specific sign of abnormal neuromuscular transmission and can be seen in other motor unit diseases but SF EMG 95% sensitive for MG
CT Thorax
- Thymoma (tumour of thymus gland)
- Usually benign but malignant potential
- Association between thymoma and MG
- Thymic hyperplasia (enlarged thymus gland but no tumour - take tumour out but surgery risk high)
Tensilon test
- Pharmacological test used for diagnosis of a certain neural disease (MG)
- 10mg edrophonium (AchE inhibitor)
- Injected intravenously
- Patient with MG - improvement in muscle strength and endurance with repetitive movements
- Allows accumulation of Ach in the NMJ, makes more Ach available to muscle receptors, increasing muscle strength in MG
- Has to be discontinued because of the risk of causing aystoyle
respiratory function
- Forced capacity test
- Patients often show lower lung capacity
- less than 1 in MG
Treatment Principles
- Increase synaptic cleft Ach concentration (symptomatic)- Pyriostigimine (Ach inhibitor) can control ocular MG
- Control aberrant immune response with steroids to control disease
- Remove effect of circulating antibodies (treat crisis) - IVIG or PE
Treatment
Pyridostigmine - 30mg qid increasing to 60mg after 3-5 days
Steroids (1st line) - up to 50mg alt days in ocular MG, 100mg alt days in generalised MG, a lot of people can manage with a small dose of steroids
Steroid-sparing agents (2nd line) - When patient has relapsed on steroids, azathiprine/mycophenolate/methatrexate
Thymectomy - for thymoma removal, if the patient is young with positive antibodies consider this
Treating MG crisis
IVIG - consists of immune globulins collected from donors and acts to destroy and neutralize the autoantibodies and block the production of new autoantibodies. Works quickly to suppress the immune system but wares off after a few weeks
Maximise everything else - build up steroids (can get steroid dip when high dose steroids temporarily exacerbate symptoms)
ventilation and feeding - prevent complications
PE - wash blood through a filter to remove bad antibodies
Prognosis
90% chance of remission
good but takes months to improve
risk of iatrogenic side effects
10% have brittle disease - difficult to manage
Pathology
Autoimmune reaction
Malfunction of immune system
Body produces autoantibodies that attack a specific receptor located on the surface of muscle cells, receptors found at NMJ, where nerve cells interact with muscle cells.
Normally, nerve cell stimulated by nerve impulse releases Ach across NMJ and binds to receptors on muscle cell, triggering muscle contraction
In MG, autoantibodies bind to receptors, prevent Ach from binding to them and preventing the muscle from responding to the nerve signal
