Neuro: Myasthenia Gravis and LEMS Flashcards
What is Myasthenia Gravis?
Myasthenia graves is an autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest.
At what ages do men tend to be affected by myasthenia gravis?
Men over 60 (60-80s)
At what ages do women tend to be affected by myasthenia gravis?
Women under 40, 20s-30s
What type of tumour is particularly associated with Myasthenia Gravis?
Thymoma
There is a strong link between thymoma (tumours of the thymus gland) and myasthenia gravis. 10-20% of patients with myasthenia gravis have a thymoma. 20-40% of patients with a thymoma develop myasthenia gravis.
How does a muscle contraction occur?
Motor nerves communicate with muscles at neuromuscular junctions.
Axons of motor nerves are situated across a synapse from the post synaptic membrane on the muscle cell
Axons release a neurotransmitter (acetylcholine) from the pre-synaptic membrane
Ach travels across the synapse and attaches to the receptors on the post-synaptic membrane, stimulation the receptors, and this signal leads to muscle contraction
What is the pathophysiology of Myasthenia Gravis (majority of cases)?
Immune system produced acetylcholine receptor antibodies
These bind to the postsynaptic neurotransmitter junction receptors, blocking them and preventing acetylcholine from being able to stimulate the receptor and rigger a muscle contraction
As the receptors are used more during physical activity more of them become blocked up hence less effective stimulation with increased activity hence more muscle weakness occurs on activity
These antibodies also activate the complement system within the neuromuscular junction, leading to damage to cells at the postsynaptic membrane, further worsening the symptoms
What are the two other antibodies which cause 15% of MG cases?
Antibodies against muscle-specific kinase and antibodies against low-density lipoprotein receptor-related protein 4
MuSK and LPR4 are important proteins for the creation and organisation of the acetylcholine receptor, so their destruction leads to inadqeuete acetylcholine receptors.
How does Myasthenia Gravis present?
Symptoms anywhere from mild to life threatening in severity
Symptoms minimal in morning and worsening towards the end of the day and with activity
Extraocular symptoms are usually the intital presenations
Proximal muscles and small muscles of head and neck most effected, leading to:
Diplopia
Pstosis
Weakness in facial movement
Slurred speech
Fatigue in jaw when chewing
Progressive weakness with repetitive movements
Difficulty swallowing
Thymic hyperplasia
How can you elicit fatiguability in the muscles of a patient with Myasthenia Gravis?
Repeated blinking to exaccerbate ptosis
Prolonged upward gazing will exacerbate diplopia on further eye movement testing
Repeated abduction of on arm 20 times will results in unilateral weakness when comparing both sides
How might you assess lung function in a patient with myasthenia gravis?
Test forced vital capacity (FVC)
What scar in particular might be seen on patient with Myasthenia Gravis?
Thymectomy scar
How can Myasthenia Gravis be diagnosed?
Diagnosis can be made testing directly for the relevant antibodies:
- Acetylcholine receptor (ACh-R) antibodies (85% of patients)
- Muscle-specific kinase (MuSK) antibodies (10% of patients)
- LRP4 (low-density lipoprotein receptor-related protein 4) antibodies (less than 5%)
- A CT or MRI of the thymus gland is used to look for a thymoma.
The edrophonium test can be helpful where there is doubt about the diagnosis.
What is the edrophonium test and how is it used to diagnose MG?
Patients are given an IV dose of edrophonium chloride (or neostigmine)
Normally cholinesterase enzymes in the neuromuscular junction break down acetylcholine, but these are blocked by the edrophonium test
The weakness is therefore relieved temporarily
Treatment options for Myasthenia Gravis
Reversible acetylcholinesterase inhibitors (usually pyridostigmine (oral) or neostigmine (oral and IV preperations)) increases the amount of acetylcholine in the neuromuscular junction and improve symptoms
Immunosuppression (e.g. prednisolone or azathioprine) suppresses the production of antibodies
Thymectomy can improve symptoms even in patients without a thymoma
Rituximab is a monoclonal antibody that targets B cells and reduces the production of antibodies. It is available on the NHS if standard treatment is not effective
IV immunoglobulin (acute decline or crisis, pts will respons in just over a week)
Plasmapherisis - removes AChR antibodies and short-term improvement - used in myasthenic crisis
What is Myasthenic crisis and its management?
Myasthenic crisis is a severe complication of myasthenia gravis. It can be life threatening. It causes an acute worsening of symptoms, often triggered by another illness such as a respiratory tract infection. This can lead to respiratory failure as a result of weakness in the muscle of respiration.
Presentation: slack facial muscles, weak neck, drooling, nasal speech, general weakness, unsafe swallow
Mx:
Patients may require non-invasive ventilation with BiPAP or full intubation and ventilation.
Medical treatment of myasthenic crisis is with immunomodulatory therapies such as IV immunoglobulins and plasma exchange.
Admission to ITU
Measure FVC as often as every two hours
Avoid exarrebating drugs (aminoglycosides, muscle relazents, lithium, phenytoin, betablockers CCB, statins, antihistamines, anticholinergics,Mg, IV contrast)
How would you investigate myasthenia gravis?
Serum antibodies: anti-Ach receptor (90% generalised MG 50% ocular MG)
MuSK antibodies - found in a small percentage of patients
Thyroid function and thyroid autoantibodies
EMG
Thymus scanning - CT chest
Electro diagnostics - repetitive nerve stimulation
Orthoptic investigations
What are the basic physiological steps behind sight?
Light enters eye
Focusing (cornea and lens)
Signal transfuction (retina)
Processing (optic nerve, tracts and cotrex)
What is the role of the retina?
Signal transduction
What structures are responsible for processing in sight?
Optic nerve
Optic Tracts
Optic cortex
What structures of the eye are responsible for cornea and lens?
Focusing cornea and lens
What is cataract?
Condition in chich the lens of the eye (responsible for focusing) becomes progressively opaque, resulting in blurred vision
Opacity or reduction in clarity of the crystaline lens
Symptoms of cataract?
Slowly progressive visual loss or blurring
Glare
Reduced colour sensitivity
Reduced night vision
Double vision