Disorders of the Motor Unit

Question 1

what does a motor unit comprise of?

Answer 1

The α- Motoneurone- A specific subset of neurones of the NS through which all commands from the brain are relayed to skeletal muscles

Skeletal Muscle- The only effector organ through which the brain expresses itself to the outside world

The Neuromuscular Junction- The site of communication between the motoneurone and muscle

Question 2

what are the 2 classifications of motor neurones?

Answer 2

Upper Motoneurones
Lower Motoneurones
These are arranged strictly in-series

Question 3

what happens when either of the 2 classifications of motor neurones are damaged?

Answer 3

Damage to any aspect of the Lower Motoneurone will lead to:
– “Lower Motoneurone Signs”
Damage to any aspect of the Upper Motoneurone will lead to:
– “Upper Motoneurone Signs”

Question 4

define innervation
what does the alpha motor neurone innervate?

Answer 4

nerve supply to a muscle or other target.
alpha-motoneurone (lower motor neurones) innervate skeletal muscle

Question 5

what are motor neurone diseases?

Answer 5

a class of disease that target cell bodies of motoneurons
Loss or damage of the motor neuron cell body will lead to death of the neuron
so muscle is left without innervation
it becomes denervated => neural dysfunction

Question 6

what is denervation of muscle and what does it lead to?

Answer 6

Denervation- loss of nerve supply
denervation of muscle can result in the death of the muscle as the neurone provides the muscle with trophic factors which keeps it alive.

Question 7

what is re-innervation?

Answer 7

When a nerve dies there may be a regrowth of that nerve (or a new nerve) to re-supply the muscle

Question 8

is re-innervation always successful? why?

Answer 8

no
most nerves often lose their way and re-innervate an effector organ that is DIFFERENT from its original target.
This leads to emergence of lots of unexpected results – e.g. crocodile tears syndrome (wrong reestablishment of innervation with tear ducts leads to crying when eating)

Question 9

what does death or dysufunction of a muscle give rise to?
how is this problematic when being identified?

Answer 9

Death or dysfunction of the muscles gives rise to neurological signs similar to lower motor neurone signs.
Lower motor neurone disorders will present different symptoms to upper motor neurone disorders.
This is problematic to trainees because there are 2 sources of dysfunction that are possible when a set of LMN disorder symptoms are present.

Question 10

what is polio myelitis?

Answer 10

Also known as infantile paralysis
It is a communicable infection caused when an individual is infected with the polio virus
Leeds to toxic infection of cell bodies of the lower motor neurones which are located in the the ventral horn.
Any motor neurones of the spinal cord are susceptible to this virus

Question 11

what does toxic infection lead to in polio myelitis?

Answer 11

This usually causes the death of the cell bodies.
Because they are post mitotic they can not be replaced so very serious.
Death of motor neurones leads to denervation hence paralysis of muscles they supply

Question 12

in the 1990s, what was used to treat polio myelitis?

Answer 12

Until early 1990 Iron lungs were used to keep people suffering from polio alive as they lost control of their respiratory muscles.

Question 13

what is given to prevent polio myelitis?

Answer 13

Immunisation programmes are effective at preventing this disease. Boosters given every 10 years. However still very apparent in developing world

Question 14

compare the two images

Answer 14

Healthy (left) vs damaged (right) (atrophy of ventral horn – bottom left) spinal cord

Question 15

how common is polio myelitis now?

Answer 15

Wiped out by immunization in developed countries
It is now largely a disease of the developing world
Global air-travel means that it can still be acquired when holidaying in the disease’s hotspots after immunity has lapsed (usually after 10 years after innoculation)

Question 16

what is a motor neurone disease characterised by?

Answer 16

Characterised by apoptosis (genetically programmed death) of motor neurones of the body

Question 17

what are the 3 variants of a motor neurone disease?

Answer 17

1. The disease simultaneously kills both upper motoneurone and lower motoneurons.
2. The disease targets only the lower motor neurone.
3. The disease only targets upper motor neurones

Question 18

give examples of diseases that affect the upper motor neurone ONLY

Answer 18

Progressive supranuclear palsy
Lou Gherig’s disease (also known as ALS)
ALS - amyotrophic (without muscle support) lateral sclerosis

Question 19

what is another cause of MND?

Answer 19

damage to axon – more forgiving than damage to cell bodies bc axons can regrow
HOWEVER– only possible if damage is distal – if it is closer to cell body damage to axon can result in death of whole motor neurone leading to denervation of muscle.

Question 20

are all motor neurones susceptible to MND?

Answer 20

No, some motor neurones of the body do not undergo apoptosis under motor neurone disease

Question 21

what motor neurones are not susceptible to MND?

Answer 21

These are as follow:
Motoneurone that supply extraocular muscles (this is why Stephen Hawkings could communicate with his eyes)
Motor neurones supplying the anal sphincter – neural root value s2-s4

Question 22

explain the case of Stephen Hawking as an example of motor neurones not being susceptible to MND

Answer 22

Professor Stephen Hawking suffered from motoneurone disease
it affected the motorneurone that supplied the extraocular muscles
His ability to communicate by coded eye movements is because some motoneurones of the body do not undergo apoptosis under MD

Question 23

how does trauma to the NS tissue cause motor neurone death?

Answer 23

Infection of the ventral horn of the grey matter of the cord would lead to death of motoneurones (rare)
Crushing injuries to the spinal cord damage the grey matter

Question 24

how can complete transection (tear) of axons of a motor nerve be caused by?

Answer 24

crushing injuries to limbs
stabbing injuries – severe axons
usually accidental
If the axon that is severed supplies a muscle it will result in denervation of muscle.

Question 25

what disorders lead to demyelination of the motor & sensory neurones?

Answer 25

Guillain-Barre Syndrome
Peripheral Neuropathies

Question 26

what is Guillain-Barre syndrome and what does it lead to?

Answer 26

is an acquired complication of a viral infection e.g. common cold
leads to demyelination of axons on both motor and sensory neurones

Question 27

what does diabetic neuropathy lead to?

Answer 27

leads to demyelination of axons on both motor and sensory neurones.

Question 28

what happens when curing disorders that lead to demyelination?

Answer 28

Clinical signs reverse when the condition is cured or goes into remission
but can return in a relapse.

Question 29

where is the NMJ in the motor unit?

Answer 29

It is the tissue interface
between the:
Motoneurone & Muscle
* It is a synaptic interface
* It is a special synapse
* It is also called the end-plate

Question 30

what are the classes of diseases that target the NMJ?

Answer 30

Botulinum Toxin
Nerve gases
Myasthenia Gravis

Question 31

what can lead to botulinum toxin?

Answer 31

Unskilled preservation of cooked food can lead to accidental culturing of the botulinum toxin
Badly preserved tinned foods are commonest cause of botulism
Ingestion of food laced with the toxin would lead to paralysis of muscles of the body
This is often an emergency as it can lead to death

Question 32

how does the botulinum toxin damage the NMJ?

Answer 32

The botulinum toxin inhibits exocytosis of ACh by the presynaptic neurone at NMJ.
It can also bind to NACh receptor and remains bound so receptors become unavailable.
Cosmetic use of “Botox” – paralysis of facial muscles to prevent wrinkles on skin.

Question 33

what are nerve gases?

Answer 33

Widely used during the first and second world wars – nerve agents e.g. chlorine gas
Still used as weapons of mass destruction
Nerve agents are a class of phosphorus-containing organic chemicals (organophosphates)
Organophosphates are used in formulation of common pesticides – they interrupt the NMJ in insects.

Question 34

how do nerve gases damage the NMJ?

Answer 34

It acts by blocking acetylcholinesterase from breaking down Ach in the our NMJ => muscle weakness
Also affects autonomic aspects of the nervous system
This can encourage glands to secret a lot of a hormone than usual.

Question 35

what is Myasthenia gravis?

Answer 35

Myasthenia gravis is a rare genetic disease of the neuromuscular junction
It affects any neuromuscular junction of the body in affected individuals

Question 36

how does Myasthenia graves damage the NMJ?

Answer 36

Nicotinic receptors of the post-synaptic membrane of the NMJ are selectively destroyed by the person’s immune system
It brings about flaccid weakness of the affected muscles – e.g. weakening of eyelid
It can cause respiratory failure if muscles of respiration are affected

Question 37

what does disorder of the skeletal muscle lead to?

Answer 37

The skeletal muscle is part of the motor unit
Any diseases or disorders of muscle would inevitably lead to lower motoneurone signs of myogenic origin

Question 38

what is an example of a disorder that affects the skeletal muscle?

Answer 38

Duchenne Muscular Dystrophy
Genetic- causes defects in muscle proteins
Results in progressive muscle weakness and eventual death of muscle tissue and then eventual death of the affected individual

Question 39

what are lower motor neurone signs?

Answer 39

Lesions of lower motoneurones (damage to cell body, axon, muscles or NMJ) lead to characteristic impairments of movements – known as LMN signs
Lower motoneurone signs are very different from upper motoneurone signs