Disorders of peripheral nerves, NMJ and muscles Flashcards
neuromuscular junction disorders
What are the elements of the motor unit
The motor unit consists of:
- the LMN cell body in the ventral horn of the spinal cord
- the peripheral nerve
- neuromuscular junction
- muscle it innervates
What is the neuromuscular junction
The neuromuscular junction is the point at which the axon terminal of the motor neuron is in apposition to a specialized area of the muscle fiber membrane known as the motor end plate
Explain the mechanism of muscle contraction
The release of acetylcholine into the synaptic cleft is triggered by the influx of calcium into the distal nerve axon (via the opening of voltage-gated calcium channels) in response to the arrival of an action potential
Vesicles containing two molecules of ACh fuse with the cell membrane releasing the neurotransmitter into the synaptic cleft
These two molecules then attach to each ACh receptor on the sarcolemma, causing a channel to open in the receptor
Sodium and potassium ions then flow through this channel according to electrochemical concentration gradients, triggering an “end-plate potential”
- if there are sufficient numbers of end-plate potentials created at the motor end plate, then an action potential will spread through the entire muscle causing contraction
Once the impulse has finished residual ACh is then deactivated by hydrolysis into choline and acetic acid that are recycled by the distal nerve axon
What would be your differentials for junctionopathies in cats
Myasthenia gravis
Tick paralysis
Snake envenomation
Organophosphate and carbamate toxicity
Botulism (very uncommon)
What are the key features for tick paralysis
Signs are typically seen 4-5 days after tick attachment
Typically, weakness develops in the pelvic limbs, and the cat develops a grunting respiratory pattern
- acute, rapidly progressive ascending flaccid paralysis that can quickly progress to tetraparesis
Dysphonia, regurgitation and loss of the gag reflex are also commonly seen in more severe cases
- unlike dogs, cats often have dialted pupils
Hyperimmune canine tick antiserum can be used but with a potential risk of anaphylaxis
Prolonged supportive care is often needed and some patients require assisted ventilation
What are the key features of snake envenomation
Toxin acquired via bites of the Tiger and Brown snakes may cause a blockade of the neurmuscular junction by the depletion of acetylcholine vesicles at the presynaptic membrane
Hemolysis and coagulopathy may also be observed
CK levels are generally elevated
Provision of snake antivenom and supportive care are the mainstay of treatment
What is the mode of action of organophosphate and carbamate
Organophosphate and carbamate act at the NMJ via inhibition of cholinesterase
acute signs of intoxication can be attributed to increased activity of acetylcholine at parasympathomimetic, sympathomimetic and neuromuscular junctions
How would you explain the delayed polyneuropathy that may be seen after organophosphate intoxication
Delayed polyneuropathy may be explained by degenerescence of the axons of peripheral and central nerve fibers
What are the key features about myasthenia gravis in cats
Congenital MG is rarely reported in cats
- affected patients are < 6 months of age
- it is thought to arise from a developmental problem of the nicotinic acetylcholine receptors
- first identified in the Devon rex and Sphynx cats
Acquired MG is relatively unfrequent
- it is characterized by immune-mediated destruction of AChRs and is commonly seen in conjunction with thymoma
Most forms of MG induce signs of generalized musculoskeletal weakness
- however localized forms exist
Diagnosis is achieved via the demonstration of anti-AChR antibodies in serum
- traditionally, an edrophonium-response test was used
- specific findings with electrophysiological testing may also be suggestive
Treatment aims at:
- treat any predisposing conditions
- administration of anticholinesterase drugs such as pyridostigmine (0.5 mg/kg, PO, q12h)
- immunosuppression
Can you give an example of drug associated myasthenia gravis
A form of acquired MG has been associated with administration of methimazole in hyperthyroid cats due to the drug’s immunomodulating effects
- clinical signs develop 2 to 4 months after beginning treatment foor hyperthyroidism
What breeds of cats seem predisposed to acquired myasthenia gravis
The Abyssinian and the Somali breed are at the highest relative risk for MG
