Disorders of the neuromuscular junction Flashcards
What are the 2 main categories of neuromuscular junction disorder?
Pre-synaptic
Post-synaptic
What are some examples of pre-synaptic neuromuscular junction disorders?
Botulism
Lambert-Eaton myasthenia syndrome (LEMS)
What is an example of a post-synaptic neuromuscular junction disorder?
Myasthenia gravis
What bacteria causes botulism?
Clostridium botulinum
Where is C. botulinum found?
Soil
Contaminated food
Contaminated wounds
Contaminated street heroin
How does C. botulinum affect the neuromuscular junction?
It releases a potent exotoxin, which enters the presynaptic terminal to modify snare protein, which are involved in the docking of vesicles containing ACh, preventing ACh release across the synapse
How can botulinum toxin be used medically?
Low dose botulinum haemaglutin complex can be administered IM to treat overactive muscles (dystonias) and also ‘botox’ for wrinkles
Presentation of botulism
- Rapid onset (over hours) motor weakness, without sensory loss
- Typically ascending paralysis
What investigations are used in botulism?
Detection of toxin in serum, urine, stool, vomit/gastric fluid
Management of botulism
Mostly supportive - Treat respiratory failure, will improve
Antitoxin available from public health but anaphylaxis risk is common
What is Lambert-Eaton myasthenic syndrome?
A paraneoplastic manifestation of small cell bronchial carcinoma in which there is defective ACh release at the neuromuscular junction
Describe the pathophysiology of LEMS
Antibodies against voltage-gated Ca2+ channels in the motor neurone terminal results in reduced Ca2+ entry in response to depolarisation, causing reduced ACh release
How does LEMS present?
- Proximal limb muscle weakness, sometimes with ocular/bulbar muscles, some absent tendon reflexes
- Weakness tends to improve after a few minutes of muscular contraction (exertion), and absent reflexes return
What investigations are required in LEMS?
- Repetitive nerve stimulation
- Detection of underlying malignancy
What are the pharmacological managements available in LEMS? (Surgery is also available)?
- Potassium channel blockers (e.g. 3,4-diaminopyridine aka amifampridine) increase the release of ACh by prolonging the action potential in the motoneurone terminal
- Immunosuppression recommended for severe cases - prednisolone and a steroid-sparing agent e.g. azathioprine