Neuromuscular Junction Disease Flashcards
What is myasthenia gravis?
An autoimmune condition associated with the production of antibodies against nicotinic receptors at the NMJ causing fluctuating and fatiguing muscle weakness
What antibodies are involved in myasthenia gravis?
Anti-ACh receptor
Anti MuSK
What is the pathophysiology of myasthenia gravis?
Antibodies act at the NMJ to reduce the overall number of functional receptors leading to muscle weakness and fatiguability
What conditions are associated with myasthenia gravis?
Disease of the thymus
SLE
Rheumatoid arthritis
In myasthenia gravis what is the muscle weakness worsened by?
Pregnancy
Emotion
Exercise
Drugs: beta blockers, opiates, gentamicin, tetracyclines
Who presents with myasthenia gravis?
F>M
2 peaks of incidence: women - early 30s, men - 6-7th decades
What is the main clinical feature of myasthenia gravis?
Muscle weakness that gets worse throughout the day and with repeated use of the muscle
What order are the muscle groups affected in myasthenia gravis?
Ocular
Bulbar
Face
Neck, limb girdles, trunk, laryngeal muscles
What are the ocular symptoms of myasthenia gravis?
Double vision
Ptosis
What are the bulbar symptoms of myasthenia gravis?
Dysphagia
Difficulty chewing
Dysarthria
What are the facial symptoms of myasthenia gravis?
Drooping of facial muscles
Snarled expression with smiling
What are the neck, limb girdles, trunk, laryngeal muscle symptoms of myasthenia gravis?
Trunk involvement - difficulty breathing
Laryngeal muscles - quietening of voice
Difficulty holding up head
What do you see on examination in myasthenia gravis?
Snarled expression Ptosis Peek sign - sclera shows when patients close their eyes Normal sensation and reflexes Normal muscle appearance and tone
What investigations are done in myasthenia gravis?
Immunoloy (anti-AChR, anti-MuSK)
Neurophysiology - single fibre EMG
CT thorax to assess for thymoma
What is seen on single fibre EMG in myasthenia gravis?
Single fibre jitter
Low amplitude action potentials
Decremental decrease in muscle twitches with repeated stimulation
What is the management of myasthenia gravis?
Pyridostigmine (anti-cholinesterase)
Thymus abnormality - thymectomy
Relapses - prednisolone
How does Pyridostigmine work for management of myasthenia gravis?
Works by reducing the rate of ACh breakdown in the synapse and therefore increases activity of ACh
Help weakness but do not alter course of disease
What are the side effects of Pyridostigmine?
Diarrhoea Colic pain (reduced by an anti-muscarinic)
What is a myasthenic crisis?
Severe relapse of myasthenia gravis resulting in weakness of respiratory muscles and difficulty breathing
What is the management of a myasthenic crisis?
Ventilatory support
Immunoglobin or plasmaphoresis
What is Lambert-Eaton Myasthenic Syndrome?
A rare disease of pre-synaptic calcium channels resulting in muscle weakness
What is the pathophysiology of Lambert-Eaton Myasthenic Syndrome?
Reduced function of calcium channels limits the amount of ACh that can be released from presynaptic terminals
What are the causes of Lambert-Eaton Myasthenic Syndrome?
Autoimmune - anti P/Q CGCC antibodies Paraneoplastic syndromes (esp small cell lung cancer)
What is the presentation of Lambert-Eaton Myasthenic Syndrome?
Muscle weakness similar to myasthenia gravis
How is Lambert-Eaton Myasthenic Syndrome differentiated from myasthenia gravis?
Improvement with exercise
Primarily limb symptoms leading to gait disturbance
Autonomic involvement (dry mouth, constipation, impotence)
Hyporeflexia (again improves with exercise)
What investigations are done for Lambert-Eaton Myasthenic Syndrome?
Immunology (anti P/Q CGCC antibodies)
Neurophysiology
CT CAP screen for malignancy
What is seen in neurophysiology in Lambert-Eaton Myasthenic Syndrome?
Low frequency muscle action potentials
Increase in twitch amplitude with exercise
Increase in abductor digiti minimi fasciculation with exercise
What is the management for Lambert-Eaton Myasthenic Syndrome?
3,4 Diaminopyradine
IV immunoglobulins
What is botulism?
Infection with clostridium botulinum
What are associated with acquiring botulism?
IVDU
Penetrative wounds
How does clostridium botulinum cause symptoms?
Toxin blocks the release of ACh in presynaptic terminals
What is the presentation of botulism?
Afebrile
Flaccid paralysis
Rapid onset (hours)
Weakness without sensory loss
What is the management of botulism?
Anti-toxin
Improves on its own in about 12 weeks
