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Neurology > Neuromuscular junction disorders > Flashcards

Neuromuscular junction disorders Flashcards

1
Q

What is the neuromuscular junction important for?

A

Process of converting an action potential that terminated at the NMJ into a muscular contraction

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2
Q

Describe the normal neuromuscular physiology (9 steps)

A
  1. Presynaptic depolarisation
  2. Calcium ion influx - action potential activated the calcium channels and causes an influx of calcium which triggers fusion of the synaptic vesicles and release of neurotransmitter (ACh)
  3. Exocytosis - stored vesicles released into synaptic cleft
  4. ACh binds AChR on post-synaptic sarcolemma
  5. Confirmational change leads to sodium influx and depolarisation of the sarcolemma
  6. Sodium ions influx causing depolarisation of adjacent muscle
  7. T-tubules: depolarisation of the sarcolemma then travels down the t-tubules and ultimately causes release of calcium from the sarcoplasmic reticulum
  8. Influx of calcium causes contraction
  9. Unbound ACh in synaptic cleft defuses away or is hydrolysed by acetylcholinesterase (preventing further depolarisation)
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3
Q

What is myasthenia gravis?

Describe the pathophysiology

A

Auto-immune condition with. antibodies targeted against AChR and MuSK causing weakness and fatiguability
- AChR-Ab binds to ACh receptors at the NMJ and this prevents ACh binding and therefore, depolarisation needed for muscular contraction

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4
Q

What is the hallmark of myasthenia gravis

A

fatiguability - increased muscle weakness with repeated use

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5
Q

Does early onset MG affect young females or males >40 more commonly?

A

Young females

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6
Q

Does late onset MG affect young females or males >40 more commonly?

A

Males >40

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7
Q

85% of cases of myasthenia gravis are due to the formation of what?

A

ACh-R antibodies

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8
Q

What percentage of AChR need to be lost for symptoms of MG to occur?

A

60%

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9
Q

Difference between ocular MG and generalised MG

A

Ocular

  • weakness limited to eyelids and extra-ocular muscles
  • only 50% are seropositive for antibodies against ACh-R

Generalised

  • can affect numerous muscle groups including the neck, bulbar, limbs, respiratory and ocular
  • 85% patients are seropositive for antibodies against AChR
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10
Q

Main features of myasthenia gravis

ocular, respiratory, bulbar, limbs and neck

A

Ocular - more than 50% patients

  • diplopia
  • ptosis
  • opthalmoplegia - weak eye muscles
  • weak eye movements
  • pupillary sparing (normal reaction to light)

Bulbar - 15% patients

  • fatiguable chewing
  • dysarthria
  • dysphagia
  • nasal speech

Respiratory

  • most serious presentation as can lead to resp failure
  • breathlessness
  • weak breathing

Limbs and neck

  • dropped head
  • proximal affected more than distal
  • Arms > legs
  • worsened after prolonged and sustained muscle contraction (fatiguability)
  • expressionless face (myasthenic sneer)
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11
Q

What simple bedside tests can we do for myasthenia gravis?

A

Ice pack test - apply ice pack for 2 min to eye and if there is >2mm improvement in ptosis, positive test

Cogan’s lid twitch - ask patient to follow finger and when fingner going up, they will twitch when looking up

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12
Q

Serological markers for diagnosis of MG?

A

Antibodies - AChR positive in 85%

Anti MuSK positive in 10%

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13
Q

Neurophysiology testing for diagnosis of MG?

A

Electromyography - repetitive muscle stimulation results in decremental potential (the more you stimulate, the more the response declines)

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14
Q

Describe the association with MG and the thymus gland

A

In MG the thymus remains large and contains clusters of immune cells leading to cell-lymphoid hyperplasia

Thymus results in mal development of the immune system → autoimmunity to AChR → attacks the NMJ transmission

10-15% of patients with myasthenia gravis have a thymoma - 50% cases of thymoma have MG

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15
Q

What is a myasthenic crisis and what are the dangers?
What percentage of MG patients will experience myasthenic crisis?
What is the best investigation for crisis?

A
  • Medical emergency as:
    • Lead to respiratory failure requiring support
    • Impaired swallowing
    • Severe limb weakness
    • One or combination of all above meets the criteria for MG crisis
  • 10-15% patients with MG go into crisis within 2-3yrs post diagnosis
  • MuSK positive cases are likely to develop this
  • Increasing muscle weakness and diplopia
  • Sings / symptoms: Quiet breathing, reduced chest expansion, tachycardia, hypertension and suggests hypoxia
  • Saturations and ABG might be normal - best investigation if FVC (or single breath count)
  • If FVC <1L|or <15ml/kg needs ITU admission for close monitoring
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16
Q

What things might cause or precipitate a myasthenic crisis?

A
  • Stress
  • Infections
  • Withdrawal of cholinesterase inhibitors
  • Rapid reduction of steroids
  • Electrolyte imbalance (hypokalaemia, hypophosphatemia)
  • Anaemia
  • Antibiotics, anti-rheumatic, antihypertensive drugs, botulism toxin etc.
17
Q

Pharmacological management of MG?

A

Acetylcholine esterase inhibitors are first line - pyridostigmine (reduced muscle weakness)

Steroids - pred to inhibit immune response (given if ongoing symptoms with pyridostigmine)

Steroid sparing agent immunosuppressant (azathioprine offered first-line)( PMT, ciclosporin, methotrexate, mycophenate mofetil, rituximab)

Other management of MG

  • Plasma exchange in crisis
  • IV immunoglobulins
  • Benefit from both in MG crisis
  • Onset >65yrs, generalised MG, we can consider thymectomy
18
Q

Benefits of thymectomy in those with MG?

A
  • Less symptomatic
  • Possibility of prednisolone withdrawal increases from 30% to 60%
  • Those on prednisolone require a lower dose
  • Reduces azathiprine use from 40% to 15%
  • Has efficacy in those >40
  • Recommend in generalised MG: up to. 5yrs
  • UK - recommended for ocular up to 2yrs
19
Q

What is lambert eaton myasthenic syndrome?

A

Condition due to antibodies against voltage gated calcium channel on pre-synaptic ion channel in the NMJ.

20
Q

Pathophysiology of lambert eaton myasthenic syndrome?

A

Blockage of calcium channels by antibodies causes less calcium inside of the neuron and therefore, reduced acetylcholine released = muscle weakness

21
Q

50-60% of patients with lambert eaton myasthenic syndrome have underlying…?

A

malignancy

  • Small cell carinoma of the lung
  • Lymphoproliferative disorders (Hodgkin’s lymphoma)
22
Q

What are some non-cancer related LEMS associations?

A

T1DM

Hashimoto’s

23
Q

Difference in age presentation between non-cancer LEMS and cancer related LEMS?

A

Non-cancer related = any age

Cancer related = >50 yrs

24
Q

Clinical features of LEMS?

A
  • proximal weakness (hips, thighs, shoulder)
  • autonomic symptoms: sexual dysfunction, dry mouth, postural hypotension
  • potentiation: strength increases with repeated use
  • reflexes are diminshed or absent
25
Q

Diagnosis of LEMS?

A
  • Look for antibodies against voltage-gated calcium channels

- Once diagnosed, chest CT to look for evidence of underlying small cell lung cancer

26
Q

Management of LEMS

A

Cancer treatment if underlying cancer
AChR inhibitor treatments

3,4 diamino pyridine blocks potassium channels in the nerve terminal and potentiates action.

27
Q

What is congenital myasthenia syndrome

A

Disorder due to mutations in NMJ protein coding genes - not auto-immune disorder.

28
Q

What is neuromyotonia? What is the underlying pathophyisiology?
Clinical features of neuromyotonia?

A

Rare neuromuscular disorder characterised by progressive muscle stiffness, continuously contracting or twitching muscles (myokymia) and diminished reflexes.
Due to auto-antibody to VGKC on nerve terminal resulting in hyper-excitability.
- 80% acquired.

Clinical features

  • Cramps
  • Fasciculations
  • Hyperhydrosis - increased sweating
  • Myokymia
  • Fatigue
  • Exercise intolerance
  • Stiffness

Neurology (17 decks)

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