Myasthenia Gravis Flashcards
Define myasthenia gravis
An autoimmune disease mediated by antibodies to nicotinic acetylcholine receptors on the post synaptic side of the neuromuscular junction.
Is it more common in men or women?
Women
While anyone is susceptible, there are 2 main subgroups:
Young women 20-35 and older men 60-75
What is the general course of myasthenia gravis?
Periods of remission interrupted by crises
Some can predict when they are due a crisis and others find there is no pattern
What is the key feature?
Muscle fatigability - due to destruction of synapses there is decreased conduction at neuromuscular junctions
What four sets of muscles are particularly affected?
Ocular - ptosis, diplopia
Bulbar - dysphagia, dysphonia, dysarthria and weak / droopy face
Proximal muscles - shoulder and thigh weakness
Axial - neck and trunk, also muscles involved in respiration
Are there sensory abnormalities?
No
What are the limb reflexes like?
Normal or brisk
Describe the course of muscle weakness
Progressively weaker during periods of activity and slowly improve after periods of rest
How can the fatigability of muscles be demonstrated?
Ask patient to do repetitive movement e.g flap arms for 30 -60 seconds
Is muscle wasting present?
Usually not unless severe disease
Describe the pathophysiology
B and T cell mediated IgG autoantibodies created which attack post synaptic acetylcholine receptors at neuromuscular junction.
Antibodies prevent ACh binding to receptor, so nerve signal not fully transmitted - muscle weakness due to incomplete stimulation rather than inherent muscle disorder
Is ACh in synapse for short or long time?
Short - it is quickly broken down by acetylcholinesterase
Myasthenia gravis has a strong association with disorders of…
The thymus
In 75% there is hyperplasia of thymus and in 10% this becomes a thymoma
In men - thymic atrophy, thymic tumour
Other than an association with the thymus, what else is associated with MG?
Autoimmune disorders- pernicious anaemia, autoimmune thyroid disorders RA, SLE
What can exacerbate symptoms?
Pregnancy Low K Infection Change in climate Over treatment Emotion Exercise Antibiotics: Gentamicin , macrolides, quinolones, tetracyclines Opiates Lithium Phenytoin Beta blockers Quinine
What tests are done?
Antibodies: anti AChR in 90% , the remaining positive for muscle specific tyrosine kinase antibodies (MUSK)
Electomyography (EMG) decremental muscle response to repetitive nerve stimulation +/- single fibre jitter
CT thorax to exclude thyoma
CK is normal
Tensilon test (not done anymore due to cardiac arrhythmia risk)
How is it managed?
Long acting anti cholinesterase inhibitors e.g pyridostigmine
Immunosuppression- prednisolone for relapses
Azothioprine, ciclosporin, mycophenolate may be used
Thymectomy- has beneficial effects even in those without thymoma
What is a myasthenic crisis?
Life threatening weakness of respiratory muscles during relapse
Ventilator support may be needed
Treat with plasmapheresis, IV immunoglobulin
Identify and treat trigger for relapse e.g infection, medications
What cholinergic side effects can occur due to treatment?
Increased salivation and lacrimation, sweating, vomiting, miosis
What type of hypersensitivity reaction is it?
Type II
Causes cytotoxic injury - results in lysis of cells
