3.2 Peripheral Nervous System Disorder Flashcards
Nerves are composed of fascicles, or bundles, of axonal fibers which can be damaged to varying degrees.
Extrinsic nerve injury (crush, stretch, transection, and inflammation) can occur in all individuals, but patients with underlying risk factors may be more susceptible to nerve damage. Regardless of etiology, nerve injury is typically classified by severity.
- In _________, the axon is intact, but there is impaired conduction of the nerve action potential conduction due to focal demyelination or ion channel dysfunction.
- In ___________, there is a break in the axon, resulting in Wallerian degeneration distally.
- The most severe form of nerve injury is ___________, in which there is discontinuity through the entirety of the nerve, including the epineurium and connective tissue.
neuropraxia;
axonotmesis;
neurotmesis
After a single axon is crushed, it then attempts to regenerate and reconnect with its target organ. This describes what happens after an Axon is disrupted with successful regeneration after.
- The first picture on the left shows the axon in pink, with the myelin sheath and Schwann cell in purple wrapped around it. There is a crush injury at the upper end of the axon in the picture. This completely interrupts the _____________.
- If we assume that the cell body of this axon is proximal to the crush injury, then the more distal part of the axon is separated from the cell body and will therefore degenerate. This is seen in (Fig B). The proximal stump of the axon is still attached to the cell body proximally, but the distal part of the axon has degenerated and __________________.
- At the same time, as shown in Fig C, there is proliferation of the ____________ through mitosis which induce the proximal stump of the axon to produce very fine axonal sprouts. For one axonal stump there are a few axonal sprouts. These are encouraged to grow down. Eventually if one of them connects with the target axon distally and forms synapses with the target, then all the other sprouts will immediately withdraw back into the stump,
- In Fig D, we can see the successful axon sprout quickly and become wider in diameter, acquiring a myelin sheath
- In Fig E, we can see that it eventually looks very much like the normal axon, with perhaps the only difference being that the _______________. This will mean that in fact, this regenerated axon will conduct at a slightly lower speed than normal.
axoplasm;
the myelin sheath has been infiltrated by macrophages which are gobbling up the degenerative material;
Schwann cells ;
internodal distances are shorter
There are a number of factors which affect the success of regeneration and reinnervation.
1) Firstly, the distance of the injury from the neuronal cell body. If the injury is __________________, then the nerve cannot sustain this kind of injury and there will be no regeneration there at all. However, if the injury is a reasonable distance away from the cell body then the axon does try to regenerate.
2) The second important factor is the type of injury.
- The most successful outcome is when the axons within the peripheral nerve have been compressed, but there is no ____________________. The endoneurium acts as a very good guide for each individual axon to grow back to its correct target.
- If there is tearing or complete cutting of the peripheral nerve, then the axons, although they will try to regenerate, may regenerate down the wrong endoneurium and end up in the wrong place (abnormal reinnervation). So, although regeneration may be quite successful reinnervation will not be.
3) The final factor which affects success is the _______________. If this distance is too great, then the axons may just not be able to regenerate.
very close to the neuron cell body;
tearing of the connective tissue sheath (endoneurium);
distance of the lesion from the target organ
There are various diagnostic techniques which can be used to try to diagnose peripheral nerve dysfunction, and if so, what sort of mechanism underlies that degeneration.
1) A nerve conduction test can be done. At the same time, usually an electromyography is performed.
- Nerve conduction test: This is where a peripheral nerve is stimulated at one end and then recorded from the other end. The ________________ is calculated.
- Electromyography: This gives us information regarding the ___________________. This helps to tell if the problem is primarily of the muscle or the peripheral nerves and can at times localize the level of the nerve injury.
Then there is the _____________ which can show various pathological changes in the nerve which can suggest either nerve axonal degeneration or demyelination or other specific features e.g. inflammation or inclusion bodies. A combination of these specialized techniques can be used to diagnose and evaluate nerve disorders.
speed of conduction and axon potential amplitude;
electrical activity of the muscles and integrity of the motor unit;
nerve biopsy
Guillain-Barre Syndrome
- ____________________ disorder where antibodies produced against the pathogen cross-reacts and damages myelin in PNS neurons, causing nerve conductance deficits.
- Motor, sensory and autonomic dysfunction
Post-infectious/inflammatory
Motor neuron disease
- Sporadic and familial neurodegenerative disorder
- Motor neuron disease impacts either the upper (__________________) or lower motor neurons (___________________) or combinations of both (_________________).
- _____________ for upper motor neuron lesions, __________________ for lower motor neuron lesions
- Usually chronic and progressive leading to respiratory and swallowing difficulties
- More than 20+ genes associated with familial ALS. Familial ALS is attributed to many genes including ____, ______, _______. Many of these lead to motor neuron deficits.
- For sporadic ALS, the aetiology for the disease is not well understood. Typically, it is chronic and progressive, leading to secondary muscle atrophy, fasciculations and cramps. Patients also suffer from mild cognitive impairments due to fronto-temporal dementia like symptoms.
Primary lateral sclerosis;
Progressive muscular atrophy;
amyotrophic lateral sclerosis, aka ALS;
Spasticity, hyperreflexia;
muscle atrophy and fasciculations;
c9orf72, Fuss, SOD
Poliomyelitis
- Viral infection causing destruction of the _____________________
- Segmental involvement leading to motor deficits
- Typically, viral infection can be cleared and polio victims can recover but in some cases, polio can lead to _____________ which results in permanent locomotor function deficits and paralysis of the limb innervated by the affected anterior horn cell levels. For example, infection and damage to anterior horn cells in the left lumbosacral cord would lead to lower motor neuron findings in the left lower limb. There is no sensory or autonomic involvement.
anterior horn cells in the spinal cord and brain stem;
lower motor neuron death
Horner’s syndrome
- Horner’s syndrome presents as __________ (drooping of eyelid) and _______ (failure of dilation of the pupil) due to loss of sympathetic tone. This is due to loss of sympathetic tone to the _________________of the eyelid and the _______________ of the iris.
- There is injury to the sympathetic fibres as it travels through the brainstem, to the apex of the neck, ascending through the cervical ganglion to the eye.
- Lateral medullary brainstem lesions, tumors or trauma at the neck or upper lung (Pancoast tumour) and carotid artery dissection are common causes. There is ptosis (drooping of eyelid) and meiosis (failure of dilation of the pupil) due to loss of sympathetic tone.
ptosis; meiosis;
superior tarsal muscle (Muller’s muscle) ; dilator pupillae;
Hereditary sensory and autonomic neuropathy (HSAN)
- HSAN is a group of genetic disease which result in peripheral and autonomic neuropathies. Many of HSAN diseases are associated with loss of myelinated and unmyelinated fibers which affect the somatic and autonomic responses.
- One example is the type III HSAN which is also known as _________. This class of disease has wide ranging symptoms during development including poor locomotor coordination and response, temperature regulation, poor growth, etc. Mutation in _____________ that is ubiquitously expressed in many cells including brain is involved in the pathogenesis of this disorder.
familial dysautonomia;
IKBKAP protein;
Adie tonic pupil
- A pupil with parasympathetic denervation where the _____________ is damaged resulting in loss of pupillary response to light stimulation.
- Most cases are idiopathic although inflammation and infection are potential causes. Interestingly, the syndrome effects more women than men and is not considered a life-threatening disease.
ciliary ganglion;
