DISORDERS OF THE NEUROMUSCULAR JUNCTION Flashcards
What is the underlying pathology of in myasthenia gravis?
Antibodies directed against the postsynaptic acetylcholine receptor, which results in a reduction in overall stimulation by acetylcholine on the postsynaptic membrane.
Which muscles groups are most commonly affected by myasthenia gravis?
Proximal limb muscles
Ocular muscles
Bulbar muscles
An abnormality in which organ is often associated with myasthenia gravis?
Thymus - thymus hyperplasia is found in 70% of myasthenia gravis patients below the age of 40
What are the two distinct groups of patients who develop myasthenia gravis (in terms of demographic)?
Young women (20-35) Older men (60-75)
What are the feature of myasthenia gravis associated with young women as opposed to myasthenia gravis associated with older men?
Acute, severely fluctuating, more generalised condition, with increased association HLA-B8 and HLA-DR3.
What are the features of myasthenia gravis associated with older men as opposed to myasthenia gravis associated with young women?
Oculobulbar presentation
What are the ocular symptoms of myasthenia gravis?
Ptosis
Diplopia
What are the symptoms of myasthenia gravis with cranial nerve involvement?
Ptosis Diplopia Weak face and jaw Dysarthria - speech problems Dysphonia - impairment of voice Dysphagia - swallowing
What are the muscle groups of the limbs affected by myasthenia gravis?
Usually proximal - hips and shoulders
Neck flexion and extension - difficulty lifting their head
What are the symptoms associated with myasthenia gravis?
Ptosis Diplopia Weak face and jow Dyarthria Dysphonia Dysphagia Proximal muscle weakness Shortness of breath
What is the key feature of the all of the muscle weakness associated with myasthenia gravis?
Fatiguability
How can fatiguability be demonstrated in someone with myasthenia gravis?
Get a patient to keep their head still and look downward for a period. Then instruct them look up at an object. The eye lids will twitch on the way up.
What happens to the reflexes in someone with myasthenia gravis?
Normal at first but will then fatigue on repeated testing.
What are the signs of myasthenia gravis seen during a neurological examination?
Reduced power with fatiguability
Reduced reflexes with fatiguability
Some degree of muscle wasting (later disease)
Sensory normal
What investigations might you do for someone that presents with the signs and symptoms of myasthenia gravis?
Ice test
Edrophonium test
Look for serum acetylcholine receptor antibody
Look for anti-MUSK (muscle specific kinase) antibodies
Electromyography
Thymus imaging
Look for other autoantibodies
What is the edrophonium test, an investigations used for patients with suspected myasthenia gravis?
An investigations used for patients with suspected myasthenia gravis. Edrophonium is a fast-acting anticholinesterase. Upon giving this as a bolus, patients who do have myasthenia gravis will notice improvements within seconds.
What proportion of generalised myasthenia gravis patients are seropositive for the highly specific acetylcholine receptor antibody?
85%
What proportion of patients with ocular myasthenia gravis are seropositive for the highly specific antibody acetylcholine receptor antibody?
About 50%
What proportion of myasthenia gravis patients who are seronegative for the antibody acetylcholine receptor antibody are seropositive for the muscle specific kinase antibody (MUSK)?
About 50%
What will electromyography show in a patient with myasthenia gravis?
A progressive decrement in amplitude (fatigue) of the compound muscle action potential following repetitive stimulation.
Increased jitter using a single-fibre electrode.
Why do you need to image the thymus of myasthenia gravis patients?
Thymus hyperplasia has been associated with myasthenia gravis and therefore imaging the thymus to decide whether or not it is worth removing it is necessary. Removing the thymus can improve the condition in some patients. Removal of thymomas do not tend to improve symptoms, but is useful anyway to prevent malignant transformation of thymomas.
What are the treatment options for someone diagnosed with myasthenia gravis?
Oral acetylcholinesterases
Thymectomy
Immunosuppression
What are the anti-acetylcholinesterases used in the management of myasthenia gravis? What is the standard dose?
Pyridostigmine - 60mg three times a day
What is the ice test, used in diagnosis of myasthenia gravis?
Placed a latex glove containing crushed ice over the eye affected by ptosis. If myasthenia gravis is the pathology then improvement will be seen. 90% sensitivity and specificity.
What other autoimmune diseases is myasthenia gravis associated with?
A lot of them: Thyroid diseases Rheumatoid arthritis Pernicious anaemia Systemic lupus erythematosus (SLE)
In the treatment of myasthenia gravis, is thymectomy only useful in those with a thymus hyperplasia?
No. But there isn’t a lot of evidence either way.
What methods of immunosuppression are used in the management of myasthenia gravis patients?
Corticosteroids
Azathioprine
Mycophenalate
Ciclosporin
Plasmapheresis
IVIg
What is the underlying pathology in Lambert-Eaton myasthenic syndrome?
Antibodies against the presynaptic voltage gated calcium channels at the neuromuscular junction cause a failure in the release of acetylcholine into the synaptic cleft.
What condition is Lambert-Eaton myasthenic syndrome associated with?
It is a non-metastatic manifestation of malignancy
Small-cell carcinoma of the lung
What are the clinical features of Lambert-Eaton myasthenic syndrome?
Weakness of the proximal limb muscles, especially in the lower limbs
Fatiguability
Paradoxical initial improvement after exercise.
Autonomic involvement is most common in LEMS associated with underlying malignancy
What signs might be elicited on examination of someone with Lamber-Eaton myasthenic syndrome?
Absent reflexes, which return with use of the muscle
This is called post-tetanic potentiation
What will electromyographic testing show in someone with Lambert-Eaton myasthenic syndrome?
Incremental increase in compound muscle action potential after repetitive stimulation - opposite to myasthenia gravis
What would you look in the blood of someone with suspected Lambert-Eaton myasthenic syndrome?
Voltage gated calcium channel antibodies
What are the management options for someone with Lambert-Eaton myasthenic syndrome?
Guanethidine hydrochloride
4-aminopyridine
Plasmapheresis
IVIg
What is the drug that can induce myasthenia gravis?
Penicillamine
