Myasthenia gravis Flashcards
What is myasthenia gravis?
A weakness of the skeletal muscle that usually worsens as the day progresses
- It is caused by the production of autoantibodies to the nicotinic acetylcholine receptors, leading to the blockage of receptors and inability to pass on the contracting signal from CNS.
What type of reaction causes MG?
A type 2 hypersensitivity reaction- an antibody-mediated immune reaction in which IgG or IgM antibodies are directed against cellular antigens and cause destruction of cells and tissue damage.
What is the peak age for a diagnoses in males and the peak age for diagnoses in females?
- Males- peaks at 60-80 years old
- Females- peaks at 20-30 years old
The cause of this largely bimodal distribution is unknown
What are the symptoms of myasthenia graves?
- Weakness that increases with increased muscle use and decreases with rest
- Often occular symptoms (eyes)
e.g.
Ptosis- drooping of the eyelids
Diplopia- Double vision
Restricted eye and facial movements- worsen when tired and at night - lack of facial expression
- slurred speech
- difficulties in chewing or swallowing
-arms, leg, neck weakness - shortness of breath- if it become so severe, it is known as myasthenic crisis
What is myasthenic crisis and how is it treated?
Myasthenia is acute worsening of symptoms that causes a decrease in the function of the muscles required for breathing.
- It can be life threatening
- Is often triggered by another illness e.g. a respiratory tract infection
Treatment- immunomodulatory therapies- tries to remove these harmful antibodies:
- IV immunoglobulin
- Plasma exchange
What are the tests used for diagnosing myasthenia gravis?
ICE TEST:
Ice is put on the muscle
Asses whether cooling the muscle, improves the symptoms
BLOOD TEST:
Looks for levels of autoantibodies
85% of MG cases show acetylcholine receptor antibodies
10% show MUSK antibodies (muscle specific receptor tyrosine kinase antibodies)
5%- LRP4 antibodies- low-density lipoprotein receptor protein 4 antibodies
ELECTROMYOGRAM- measures compound action potential in response to treated stimulation- would see a decrease in size of muscle response
EDROPHONIUM TEST-
Give a short-acting acetylcholinesterase inhibitor- IV Edrophonium chloride
prevents acetylcholine breakdown= should temporarily decrease muscle weakness and increase strength
CAT SCAN
Excludes a thymoma- a tumour on the thymus gland (malignant cancer cells found on the thymus). it is linked to MG- makes MG a paraneoplastic disease caused by the presence of the thymoma
What are the treatment options for myasthenia gravis?
ACETYLCHOLINESTERASE INHIBITORS:
e.g. Pyridostigmine, Neostigmine
Acetylcholinesterase is an enzyme that degrades acetylcholine on the post-synaptic membrane to terminate muscle contraction(= muscle relaxes). In MG, we want to boos transmission so inhibit acetylcholinesterase breaking down acetylcholine. increases contraction and activity of muscle.
Provides symptomatic relief
IMMUNOSUPPRESSIVE THERAPY: decreases antibody production
E.g. Oral steroids e.g. prednisone
Azathoprine (DMARD)
Ciclosporin
THYMECTOMY- Surgical removal of the thymus gland
MONOCLONAL ANTIBODIES- e.g.g Rituximab- targets and destroys b-cells
What muscles are affected the most in myasthenia graves?
MG is ‘use-dependent’ and therefore the muscles that are used the most are the most impacted. For examples, muscles in the face and eyes are used constantly= moist affected
What is the pathophysiology of myasthenia gravis?
NORMALLY at a neuromuscular junction:
- An action potential opens voltage-gated calcium channels
- Calcium then enters the synaptic terminal and causes exocytosis of acetylcholine
- Acetylcholine is a neurotransmitter and diffuses across the synaptic cleft and to its nicotinic acetylcholine receptors on the post-synaptic neurone
- this causes the opening of ligand-gated ion channels= Na+ enters the cell and causes it to reach end-plate potential= firing of action potential therefore leading to muscle contraction.
HOWEVER, in myasthenia gravis, B-cells make autoantibodies to acetylcholine that bind to the nicotinic receptors in the muscle cells. This decreases the number of nicotinic acetylcholine receptors available for acetylcholine to bind (neurotransmitter)= causes a loss of transmission across the synapse. Muscles can’t contract as they arent recieivng the message from the CNS.
Additionally, Anti-acetylcholine receptor antibodies can also activate the classical pathway of the complement system. This leads to an enzymatic cascade which causes inflammation and destruction of muscle cells and decreases the expression of Ach receptors on their surface.
- Can also be a result of muscle-specific receptor tyrosine kinase antibodies which attack proteins inside the muscle cells, causing the cells to be destroyed.
- lastly, can be a consequence of underlyig cancer e.g.g bronchogenic carcinoma or a result of a thymoma on the thymus gland
What are the triggers that Myasthenia graves patients are told to avoid (worsen the -condition by exacerbating muscle weakness)?
- Infection- give annual flu and also pneumococcal vaccine
- Stress/trauma
- Thyroid dysfunction
- Withdrawal of acetylcholinesterase inhibitors
- Rapid introduction or increase in corticosteroids
- Anemia
- Imbalance in electrolytes
- Certain medications- e.g. phenytoin, carbamazepine, hydroxychloroquine (rest on a separate flashcard)
What are some examples of drugs that interfere with neuromuscular transmission and that increase muscle weakness?
DRUGS THAT INTERFERE WITH NEUROMUSCULAR DAMAGE:
Phenytoin, carbamazepine
Aminoglycosides e.g. gentamicin, neomycin, clindamycin
Fluoroquinolone
Antimuscarinic agents
Procainamide, lidocaine
lithium, chlorpromazine
hydroxychloroquine
DRUGS THAT INCREASE MUSCLE WEAKNESS:
Magnesium
Benzodiazepines
Beta-blockers
Diuretics
Verapamil
Statins
What is the usual symptomatic treatment of MG (including doses, side effects)?
- ACETYLCHOLINESTERASE INHIBITORS:
Usually Pyridostigimine,
Dose: Start 15mg QDS with food (to reduce GI side effects) - Typical maintenance is 30-120mg divides into 4-6 daily doses
ADVERSE EFFECTS:
- Nicotinic effects- muscle and abdominal cramps
- Muscarinic- Gut hyper mobility- cramps, diarrhoea
- Increased sweat, saliva, lacrimation
- Hypotension
- Bradycardia
- Urinary incompetence
- Tachypnoea
- Increased bronchial secretions
To manage these side effects:
- Take with food- reduce GI effects
- If bad diarrhoea- use Loperamide
- Can co-prescribe anti-cholinergic drugs (anti-muscarinics) e.g. Glycopyrronium, Propantheline. These have no effects at the nicotinic receptors so won’t cause muscle weakness but can hep with side effects
Why may muscarinic antagonists (anti-muscarinic) be given alongside acetylcholinesterase inhibitors in MG treatment?
Anti-muscarinics e.g. Atropine
- Blocks acetylcholine at muscarinic receptors- idk can’t find online
