What are the two potential causes for neuromuscular junction disease?
A failure of the NMJ to release sufficient ACh, or a failure of the muscle to respond to this ACh
What is the consequence of failure to release or respond to ACh in neuromuscular junction disease?
Reduced/absent muscle contraction
What are some ways to recognise muscle weakness caused by neuromuscular junction disease?
It is usually bilateral, and gets worse with repeated use
What is the motor end plate?
The synapses formed between motor neurones and muscles
What is curare? This is toxic if given how?
A plant like compound which occupies the same position as the ACh receptor but it does not open ion channels so there is no muscle contraction / IV or IM
What is Botulism? Who is it often seen in?
An organism present in soil causing food and wounds to become infected / IVDU
What are the two main pre-synaptic NMJ diseases?
Botulism and Lambert-Eaton syndrome
What is the clinical presentation of Botulism?
Rapid onset weakness without sensory loss
What is the pathophysiology behind Lambert-Eaton syndrome?
There are antibodies to pre-synaptic Ca++ channels which leads to less vesicle (containing ACh) release
Lambert-Eaton syndrome is often a paraneoplastic syndrome. It has a strong association with what?
Small cell lung cancer
How will patients with Lambert-Eaton syndrome present?
Proximal weakness, affecting the lower and then upper limbs
How is Lambert-Eaton syndrome treated?
3,4-diaminopyridine
What autoantibodies are seen in myasthenia gravis?
Postsynaptic ACh receptors
What is the only postsynaptic NMJ disorder?
Myasthenia gravis
Describe the two peak incidences of myasthenia gravis?
Young females in the 3rd decade of life, or males in the 6th/7th decades of life
What happens to the incidence of antibody positive myasthenia gravis?
It increases with age and is more common in males
ACh autoantibodies are found in what % of people with myasthenia gravis? If these are not found, what other autoantibody can you look for?
80-90% / Anti-musc
What is a clinical feature which is closely associated with myasthenia gravis and may be the cause behind the pathology?
Thymus problems e.g. hyperplasia or thymoma
What is the typical clinical feature of myasthenia gravis?
Typically fluctuating weakness which gets worse throughout the day
What are some of the most common muscles/muscle groups that myasthenia gravis would present in?
Extraocular, facial and bulbar weakness
Give some examples of how the muscle weakness in myasthenia gravis might present?
Eye shutting by the end of the day, speech that becomes slurred with talking, inability to finish a meal because of difficulty swallowing/chewing
If limb weakness occurs in myasthenia gravis, is it typically distal or proximal?
Proximal
Describe the acute treatment of myasthenia gravis?
ABCDE if required, ACh inhibitor (pyridostigmine), IV immunoglobulins and thymectomy
What are some long term treatment options for myasthenia gravis?
Steroids (prednisolone) or steroid sparing agents (azathioprine)
What are some emergency treatment options for myasthenia gravis?
Plasma exchange or immunoglobulin
What is a myasthenic crisis? What are some things that can trigger one?
A severe, acute exacerbation of symptoms / infection, drugs (gentamicin/anti-arrhythmics), pregnancy and stress
If myasthenia gravis was to cause death in a patient, what would be some potential causes for this?
Respiratory failure or aspiration pneumonia, side effects of immunosuppression in the elderly
The smallest contractile unit is the muscle fibre, these are each surrounded by a thin layer of what?
Endomysium
20-80 muscle fibres are grouped together to form a what? This is then surrounded by what?
Fascicle / perimysium
A large number of fascicles are ensheathed by what?
Epimysium
What are fasciculations? These are usually a sign of disease where?
Visible spontaneous switches of muscle / the motor neurone
What is myotonia?
The failure of a muscle to relax after use
What are some signs that might be seen in dermatomyositis?
Shawl sign, heliotrope rash, Gottron’s papules on knuckles and extensor surfaces
What marker is raised in poly and dermatomyositis? What medication do they respond to?
CK / steroids
In inclusion body myositis, there is characteristic sparing of what part of the body?
Thumb
How is myotonic dystrophy inherited? How are most muscular dystrophies inherited?
Autosomal dominant / X linked recessive
Duchenne and Becker muscular dystrophy are both associated with defects in what?
Dystrophin
Which drugs are the most likely to cause problems with the muscles?
Steroids and statins
What happens in rhabdomyolysis?
Damage to the skeletal muscle causes leakage of toxic intracellular contents into the plasma which can cause renal failure and DIC
What is the triad of rhabdomyolysis?
Myalgia, muscle weakness and myoglobinuria