Myasthenia gravis (N) Flashcards
Define myasthenia gravis.
Chronic autoimmune disorder of the post-synaptic membrane at the neuromuscular junction in skeletal muscle, characterised by generalised muscle weakness
What does the pathophysiology of myasthenia gravis involve?
Elevated serum autoantibodies against post-synaptic nicotinic ACh receptors (AChR) at the neuromuscular junction, or muscle-specific tyrosine kinase (MuSK)
What antibodies are found in the most common form of myasthenia gravis?
Autoantibodies against post-synaptic nicotinic AChR at the NMJ, which interferes with the neuromuscular transmission via depletion of post-synaptic receptor sites
What other diseases is myasthenia gravis associated with? (2)
- thymomas (tumour of anterior mediastinum) - may cause SVC obstruction
- thymic hyperplasia
Which demographic is myasthenia gravis most commonly seen in?
Women
What are some risk factors for myasthenia gravis?
- Fx/Hx other autoimmune conditions
- genetic markers
- cancer-targeted therapy
- beta-blockers - for myasthenic crisis
What is Lambert-Eaton Syndrome (myasthenia gravis)?
Paraneoplastic subtype of myasthenia gravis caused by autoantibodies against pre-synaptic calcium channels, leading to impairment of ACh release
What can myasthenia gravis be? (2)
- paraneoplastic (from lung cancer)
- autoimmune
Name another autoimmune condition that myasthenia gravis is associated with?
Pernicious anaemia
What are the clinical features of myasthenia gravis? (9)
- muscle strength fatiguability/weakness - worsens with activity and improves on rest (patients typically complain of it being worse at end of day)
- ptosis (droopy eyelid)
- diplopia (double vision)
- dysphagia (difficulty swallowing)
- dysarthria (changes in speech)
- facial paresis
- proximal limb weakness
- respiratory muscle weakness (may lead to dyspnoea)
- bulbar palsy symptoms (CN IX-XII, medulla oblongata):
- facial weakness (myasthenic snarl)
- disturbed hypernasal speech (dysarthria)
- difficulty smiling, chewing, swallowing
Describe the order of muscle weakness/fatiguability in myasthenia gravis. (6)
- extraocular
- bulbar
- face
- neck
- limb girdle
- trunk
How does muscle weakness differ in Lambert-Eaton Syndrome compared to myasthenia gravis?
Muscle weakness improves after repeated use (vs worsens in MG)
What are the features of bulbar palsy (CN IX-XII - medulla oblongata) in myasthenia gravis?
- facial weakness (myasthenic snarl)
- disturbed hypernasal speech (dysarthria)
- difficulty smiling, chewing, swallowing
What are the clinical features of thymoma (associated with myasthenia gravis)? (3)
Thymoma: tumour of anterior mediastinum
- distended head and neck veins - SVC obstruction
- SOB
- chest pain
What might be seen on examination of myasthenia gravis? (5)
- ocular signs: ptosis, diplopia, complex ophthalmoplegia, check for ocular fatigue
- ice on eyes test - placing ice packs on closed eyelids for 2min can improve NM transmission and reduce ptosis
- bulbar signs - dysarthria/nasal speech + dysphagia
- facial paresis
- limbs - power before and after repeated use
How do we check for ocular fatigue in myasthenia gravis?
Ask patient to sustain an upward gaze for 1 min and watch the progressive ptosis that develops
What might you see on examination of Lambert-Eaton Syndrome (myasthenia gravis)? (3)
- gait difficulty before eye signs
- autonomic involvement (dry eyes, constipation)
- hyporeflexia and weakness that improves after exercise - decreased tendon reflexes as less NT released, but reflexes may increase after maximum voluntary contractions due to build up of NT in synaptic cleft
What are the classes of myasthenia gravis?
- class I (mild) - any eye muscle weakness; possible ptosis; all other muscle strength normal
- class II (mild) - mild weakness of any other muscles; may have eye muscle weakness of any severity
- IIa - predominantly limb or axial muscles or both
- IIb - predominantly oropharyngeal or respiratory muscles or both
- class III (moderate) - moderate weakness of other muscles; may have eye muscle weakness of any severity
- IIIa - predominantly limb or axial muscles or both
- IIIb - predominantly oropharyngeal or respiratory muscles or both
- class IV (severe) - severe weakness of other muscles; may have eye muscle weakness of any severity
- IVa - predominantly limb or axial muscles or both
- IVb - predominantly oropharyngeal or respiratory muscles or both
- class V (severe) - intubation needed to maintain airway
What medication can make symptoms of myasthenia gravis worse?
Beta-blockers –> can cause FVC to drop
What are the first-line investigations for myasthenia gravis? (3)
- serum AChR antibody analysis (+ve)
- muscle-specific tyrosine kinase (MuSK) antibodies (+ve)
- serial pulmonary function tests
What is the main diagnostic test for myasthenia gravis?
Serum AChR antibody analysis - positive in 90% & most specific
(If seronegative, look for MuSK antibodies)
What might serial pulmonary function tests show in myasthenia gravis?
- especially if SOB or suspected myasthenic crisis
- low FVC, low NIF
What is the most sensitive test for myasthenia gravis?
EMG - shows decremental response to repetitive nerve stimulation
What test can we do to rule out thymoma in myasthenia gravis?
CT thorax
Thymoma/lung malignancies found in 20% of MG patients
What investigation can help reduce muscle weakness in myasthenia gravis?
Tensilon test - IV edrophonium given to reduce muscle weakness temporarily (not used much now due to risk of cardiac arrhythmia)
What are some differential diagnoses for myasthenia gravis? (4)
- Lambert-Eaton Syndrome: prominent proximal leg and arm weakness accompanied by diminished muscle stretch reflexes which improve with brief exercise, autonomic symptoms, SCLC association, anti-VGCC
- botulism - hypotension, bradycardia, diarrhoea–>constipation, urinary retention, blurred vision
- penicillamine-induced MG: anti-AChR antibody test with different properties to idiopathic MG
- primary myopathies - progressive muscle weakness that is not fatigable
What is the management plan for myasthenia gravis? (3)
- 1st line: pyridostigmine (long-acting acetylcholinesterase inhibitor)
- if Sx not resolved, add corticosteroid (prednisolone)
- consider azathioprine (immunosuppressant)
What drug may be used in muscle-specific tyrosine kinase (MuSK)-myasthenia gravis?
Rituximab
What can happen if too much pyridostigmine is taken for myasthenia gravis?
Cholinergic crisis
How would you manage an acute myasthenic crisis? (3)
- intubation and mechanical ventilation
- plasma exchange/plasmapheresis
- IV immunoglobulins (IVIG)
Myasthenic crisis is a complication of myasthenia gravis characterized by worsening of muscle weakness, resulting in respiratory failure that requires intubation and mechanical ventilation.
What surgery is considered in myasthenia gravis?
Thymectomy - may minimise the need for immunosuppressants
May be effective without thymoma too if AChR antibody positive
What medication should be avoided in myasthenia gravis?
Beta blockers e.g. bisoprolol
What is eculizumab and when is it used in myasthenia gravis?
- inhibits complement activation
- useful in patients with treatment-resistant generalised MG and AChR antibodies
What are some complications of myasthenia gravis? (5)
- myasthenic crisis
- respiratory failure
- impaired swallowing
- acute aspiration
- secondary pneumonia
What drug-induced adverse reactions can happen in myasthenia gravis? (3)
- pyridostigmine-induced adverse reactions - muscarinic adverse effects can be decreased by also giving glycopyrronium, alternatively loperamide when persistent diarrhoea
- plasma exchange-induced adverse reactions - coagulopathy, thrombocytopenia, electrolyte disturbance, arrhythmias, hypotension
- IVIG-induced adverse reactions - prophylactic administration of paracetamol/NSAID and diphenhydramine may reduce acute side effects e.g. fever, chills, headache and back pain
Describe the prognosis of myasthenia gravis.
Most, but not all, patients enjoy a good QoL and normal lifespan due to advances in diagnosis and immunosuppressive treatment
