Disorders of the neuromuscular junction Flashcards

1
Q

What are the 2 main categories of neuromuscular junction disorder?

A

Pre-synaptic
Post-synaptic

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2
Q

What are some examples of pre-synaptic neuromuscular junction disorders?

A

Botulism
Lambert-Eaton myasthenia syndrome (LEMS)

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3
Q

What is an example of a post-synaptic neuromuscular junction disorder?

A

Myasthenia gravis

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4
Q

What bacteria causes botulism?

A

Clostridium botulinum

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5
Q

Where is C. botulinum found?

A

Soil
Contaminated food
Contaminated wounds
Contaminated street heroin

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6
Q

How does C. botulinum affect the neuromuscular junction?

A

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

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7
Q

How can botulinum toxin be used medically?

A

Low dose botulinum haemaglutin complex can be administered IM to treat overactive muscles (dystonias) and also ‘botox’ for wrinkles

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8
Q

Presentation of botulism

A
  • Rapid onset (over hours) motor weakness, without sensory loss
  • Typically ascending paralysis
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9
Q

What investigations are used in botulism?

A

Detection of toxin in serum, urine, stool, vomit/gastric fluid

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10
Q

Management of botulism

A

Mostly supportive - Treat respiratory failure, will improve

Antitoxin available from public health but anaphylaxis risk is common

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11
Q

What is Lambert-Eaton myasthenic syndrome?

A

A paraneoplastic manifestation of small cell bronchial carcinoma in which there is defective ACh release at the neuromuscular junction

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12
Q

Describe the pathophysiology of LEMS

A

Antibodies against voltage-gated Ca2+ channels in the motor neurone terminal results in reduced Ca2+ entry in response to depolarisation, causing reduced ACh release

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13
Q

How does LEMS present?

A
  • 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
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14
Q

What investigations are required in LEMS?

A
  • Repetitive nerve stimulation
  • Detection of underlying malignancy
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15
Q

What are the pharmacological managements available in LEMS? (Surgery is also available)?

A
  • 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
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16
Q

What is myasthenia gravis?

A

Autoimmune disorder of neuromuscular junction transmission, characterized by weakness and fatiguability of proximal limb, bulbar and ocular muscles

17
Q

What is a condition that in many (75%) of patients can lead to myasthenia gravis?

A

Thymic hyperplasia/thymoma

18
Q

Describe the aetiology of myasthenia gravis?

A

Females - Most common in 3rd decade
Males - Most common in 6th-7th decades

19
Q

Describe the pathophysiology of myasthenia gravis

A

Autoantibodies agains nACh receptors in the endplate
Results in a reduction in the number of functional channels and so decreases the amplitude of the endplate potential

20
Q

How does myasthenia gravis present?

A
  • Fatiguable weakness of skeletal muscle
  • Most common presentation with extraocular weakness (60%), facial and bulbar weakness
  • In a small number may remain only ocular
  • Usually generalised
  • Limb weakness typically proximal
21
Q

What investigations are required in myasthenia gravis?

A
  • Serum AChR antibodies
  • Single fibre EMG
  • CT chest for thymoma
22
Q

What are some acute management options of myasthenia gravis?

A
  • ACh inhibitor - pyridostigmine
  • IV immunoglobin or plasma exchange
  • Thymectomy
23
Q

What are some long term management options of myasthenia gravis?

A
  • Steroids
  • Steroid sparing agents - azathioprine, mycophenolate
  • Emergency treatment with plasma exchange or immunoglobulin
  • Avoid certain drugs - anaethesia, gentamicin
24
Q
A