Myasthenia gravis Flashcards
What is the epidemiology of myasthenia gravis?
1/5000
Two main subgroups affected:
Young women, 20-35; associated with other autoimmune conditions and thymic hyperplasia
Older men, 60-75; associated with thymic atrophy/tumour, RA, SLE
What is the aetiology and pathophysiology of myasthenia gravis?
Unknown
Genetic link (as with most autoimmune disorders)
Autoimmune condition:
AutoAbs to post-synaptic nicotinic acetylcholine receptors (AChR) at NMJs
Their breakdown → affected neuromuscular transmission
B + T cells are implicated = produce the IgG autoAbs
How does myasthenia gravis present?
Relapsing/crisis/flare-up condition
Increasing muscular fatigue, worsened by: Pregnancy
Low K
Infection
Change of climate Emotion
Exercise
Drugs – gentamicin, opiates, quinine, beta blockers
Muscle groups affected in order:
extraoccular → ptosis, diplopia (sometimes can be confined to ocular if caught early)
bulbar → dysphagia, dysarthria
face → droopy, weak face, snarl on smiling
axial → neck/trunk + respiratory muscle weakness
proximal → shoulders + thighs
Tendon reflexes are normal or brisk
No sensory abnormalities
How do you investigate myasthenia gravis clinically?
Fatigability can be demonstrated by asking a patients to do a repetitive movement i.e. flap arms for 30-60s
Also report worsening of symptoms as day progresses – best times are mornings or post nap
Ptosis:
Improves after application of ice to the shut eyelid for >2mins
What bloods do you look for in myasthenia gravis?
Serum anti-AChR Abs are elevated in 90% of patients
If seronegative, look for MUSK Abs (muscle specific tyrosine kinase – much more common in women)
What other tests can you do in myasthenia gravis?
EMG:
Used to test how fatigable a muscle is
Single fibre EMGs are preferred
Electricity used to repeatedly stimulate a single motor unit (an alpha motor neuron and all the muscle fibres it innervates) → a ‘jitter’ is found
CT/MRI:
Head – structural brain disease?
Thymus – to look for hyperplasia
Spirometry:
Can give an indication of how badly the respiratory muscles are affected
TENSILON test:
Traditional but may not give clear answers and has dangers
Given 2 drugs – Edrophionium (prevents acetylcholine breakdown) and atropine (to prevent the cardiac side effects of the first drug)
Within seconds – there is a dramatic symptom reduction (that wears after a few minutes)
How do you decide where to manage myasthenia gravis?
Inpatient for early bulbar symptoms, low vital capacity, respiratory symptoms or progressive deterioration
Outpatient for ocular symptoms, mild/moderate limb weakness, mild bulbar symptoms
How do you manage as an inpatient?
Myasthenic crisis:
Weakness of respiratory muscles during a relapse
Can be life threatening
Monitor FVC
Potential need for ventilatory support
Immunosuppression:
High dose IV prednisolone ± azathioprine/methotrexate
Plasmapheresis or IVIg and identify cause for relapse
How do you treat myasthenia gravis as an outpatient?
Oral acetylcholinesterase inhibitors:
Pyridostigmine - 30mg QDS 2-4 days then 60mg QDS 5days then 90mg QDS 7 days if needed
To prevent destruction of ACh at the synaptic space
Cholinergic side effects: increased salivation,
lacrimation, sweats, vomiting, diarrhoea, miosis
Immunosuppression: 2nd line
Prednisolone ± azathioprine/methotrexate - decrease dose upon remission
Osteoporosis prophylaxis
Plasmapheresis or IVIg may be of use during severe exacerbation
What surgery may be indicated in myasthenia gravis?
Thymectomy
Consider if onset <50yrs and disease not easily controlled by medication
Also indicated for if thymoma
What is an important differential for MG and how does it present/differ?
Lambert-Eaton Myasthenic Syndrome:
A paraneoplastic condition, most often seen with small cell lung cancer
Causes defective ACh release at the neuromuscular junction
Proximal limb weakness with some absent reflexes
Weakness tends to improve after exercise - NO DECREMENT UNLIKE MG
Also have autonomic involvement – dry mouth, constipation, impotence
90% have anti-VGCC (antibodies to voltage gated calcium channels)
What drug can cause a myasthenic syndrome?
Treatment with D-penicillamine (e.g. for Wilson’s disease)
