Neuromuscular Disease Flashcards
Describe the functioning of the neuromuscular junction (NMJ).
- Action potential reaches presynaptic terminal of motor neuron.
- This opens presynaptic Ca channels which allow Ca to flow into the cell
- Ca triggers vesicular release of ACh into the synaptic cleft.
- ACh binds to an post synaptic ACh receptor on the muslce fibre.
- This causes muscle fibre depolarisation which contracts the muscle.
What condition of the neuromuscular junction affects presynaptic channels? Which channel does it affect?
Lambert Eaton Myasthenic Syndrome
Presynaptic Ca channels
What causes Lambert Eaton Myasthenic Syndrome?
Autoantibodies produced by body or small cell lung cancer attack presynaptic Ca channels, damaging the neuromuscular junction and preventing muscle contraction.
How does Lambert Eaton Myasthenic Syndrome present?
Intially lower limb weakness
With possible autonomic features (dry mouth, postural hypotension, dysphagia)
Later, may get eye symptoms (ptosis, diplopia)
In a patient with risk factors (smoking, family history, other autoimmunity)
How do you diagnose Lambert Eaton Myasthenic Syndrome?
Nerve conduction study
consider autoantibodies but often negative
How do you treat Lambert Eaton Myasthenic Syndrome?
Amifampridine
IV Ig if severe
What condition of the neuromuscular junction affects postsynaptic channels? Which channel does it affect?
Myasthenia Gravis
Post synaptic ACh receptors
What causes myasthenia gravis?
Autoantibodies (AChR, MuSK) attack postsynaptic ACh receptor, damaging the neuromuscular junction and preventing contraction.
How does myasthenia gravis present?
Starts with facial muscle weakness
(ptosis, diplopia)
(mastication weakness, dysphagia)
Fatigue improves with rest, worst at end of day
Generalised limb weakness later
How do you diagnose myasthenia gravis?
Autoantibody testing (AChR/MuSK)
EEG if clinical suspicion but negative for autoantibodies
How do you treat myasthenia gravis?
Pyridostigmine (+/- steroids)
Thymectomy
What is myasthenic crisis and how do you treat it?
Worsening of myasthenia gravis causing respiratory failure
IV immunoglobulin
What drug should be avoided in myasthenia gravis and why?
Gentamicin
Can cause myasthenic crisis
What are the main differences between Lambert Eaton Myasthenic Syndrome (LEMS) and Myasthenia Gravis (MG) in terms of
- pathophysiology?
- presentation?
- treatment?
1.
LEMS caused by autoimmune/paraneoplastic (SSLC) damage to presynaptic Ca channels.
MG caused by autoimmune damage to postsynaptic ACh channels
2.
LEMS starts with limb weakness (autonomic features) and progresses onto ocular symptoms.
MG starts with ocular symptoms (and fatigue) and progresses onto limb weakness
3.
LEMS - Amifampridine
MG - Pyridostigmine
What causes myotonic dystrophy?
Autosomal dominant tri-nucleotide repeat causing myotonia and muscle wasting
How does mytonic dystrophy present?
In mid 20s Distal limb myotonia and weak neck Muscle wasting Cataract Frontal balding
What is motor neuron disease and what characterises it?
Neurodegenerative condition
Upper AND lower motor neuron signs
What gene is associated with motor neuron disease
C9orf72
Risk factors for motor neuron disease.
Family history
Smoking
Professional athletes (and military service)
What investigation is diagnostic of motor neuron disease?
None
MND is a clinical diagnosis.
Name 4 upper and lower motor neurons signs that you may see in motor neuron disease.
Upper
- stiffness
- spasticity
- hyper-reflexia
- painful spasms
Lower
- weakness (foot/head drop)
- muscle atrophy (split hand sign)
- increased lumbar lordosis (axial weakness)
- dyspnoea (diaphragm weakness)
Commonest form of motor neuron disease.
Amyotrophic lateral sclerosis
What neurons are affected in amyotophic lateral sclerosis (ALS)?
Upper motor neurons (somatosensory cortex)
Lower motor neurons (ventral horn of spinal cord)
Patient with motor neuron disease has cognitive decline.
- what form of MND do they have?
- what is causing cognitive decline?
- what test might you consider?
Amyotrophic lateral sclerosis
Frontotemporal dementia
C9epo72 gene testing (associated with ALS-frontotempoeral dementia)
