Near - Motor neurone diseases

Question 1

Where are the upper neurones?

Answer 1

Cortex and brainstem

Question 2

Where are the lower neurones?

Answer 2

Brainstem and spinal cord

Question 3

What are the 6 signs of upper motor neurone damage?

Answer 3

Loss of dexterity - loss of close control of hand movement and finger movement
Babinski sign - requires upper motor neurones for a full reflex (goes to the upper motor neurones before descending back down onto the lower motor neurones)
Loss of superficial reflexes
Muscle weakness, no atrophy
Hyperreflexia to deep tendon reflexes
Pseudobulbar palsy

Question 4

What are the 6 signs of lower motor neurone damage?

Answer 4

Flaccid paralysis
Muscle atrophy
Hyporeflexia to deep tendon reflexes
Superficial reflexes often unchanged
Fasciculations (muscle twitch)
Muscle hypotonicity

Question 5

Describe pseudobulbar palsy - which nerves are damaged and which part of the brain?

Answer 5

Damage to cranial nerves 9-12 upper motor neurone lesion of corticobulbar tracts - mid pons (neurones passing through here become lesioned in some way)

Question 6

What are the 7 symptoms of pseudobulbar palsy

Answer 6

Slow and indistinct speech
Dysphagia
Small, stiff and spastic tongue
Brisk jaw jerk
Dysarthria
Labile affect
Gag reflex may be normal, exaggerated or absent

Question 7

Describe bulbar palsy

Answer 7

Also damage to cranial nerves 9-12 (after they have left the CNS) but lower motor neurone lesion at nuclei/fasci or lesion of cranial nerves outside medulla

Question 8

What does bulbar mean?

Answer 8

To do with the medulla oblongata (hind brain)

Question 9

What are the 9 symptoms of bulbar palsy

Answer 9

Dysphagia
Dysphonia
Dysarthria
Tongue atrophy, fasciculations
Difficulty chewing
Nasal regurgitation
Slurring of speech - often nasal monotonic
Choking on liquids, dribbling, no gag reflex
Jaw jerk reflex is normal or absent

Question 10

What are the symptoms of amytotrophic lateral sclerosis (ALS)

Answer 10

Begins at 30-60 years
Degeneration of anterior horn cells
Muscle denervation, split finger and muscle wasting in the tongue
90-95% sporadic, 5-10% familial
Sporadic form may be due to glutamate excitotoxity
Progressive and fatal in 3-5 years

Question 11

What is thought to be the cause of ALS?

Answer 11

Glutamate excitotoxicity is suggested as the damage to and loss of neurones.
Too much glutamate in the synaptic cleft either from reduced glutamate uptake into astroglia or by increase release from presynaptic neurone leads to too much glutamate in the synaptic cleft which cause increased intracellular calcium, leading to increased oxidative stress and mitochondrial dysfunction.

Question 12

What would an MRI of ALS patient show?

Answer 12

Number of effects of functional and structure.

changes in N-acetylaspartate and myoinsoitol concentrations
Thnning and loss of grey matter
White-matter tract damage
Changes to receptors

Question 13

What are the two hypothesizes in ALS

Answer 13

Dying forward hypothesis - glutamate excitotoxicity causes death in the upper MS and the changes cause the death in the lower MNs
Other is the dying back hypothesis - problem is not necessarly the glutamate excitotoxicity but may be because of motor neurotropic factor becomes deficent which leads to the death of the lower motor neurone first and in turn causes death of the upper MN

Question 14

Is primary lateral sclerosis upper or lower MN?

Answer 14

Upper

Question 15

Is progressive muscular atrophy upper or lower MN?

Answer 15

Lower

Question 16

Is progressive bulbar palsy upper or lower MN?

Answer 16

Lower

Question 17

What are the symptoms of primary lateral sclerosis?

Answer 17

Rare
Affects upper MN only
Onset 50+
Usually lower limbs first sometimes the tongue or hands
balance problems clumsiness, foot-dragging from muscle weakness
Spasticity of extremities
Dysphonia
Dysphagia
Hyperreflexia
Babinki's
Labile affect
Sometimes minor cognitive changes

Question 18

What are the symptoms of progressive muscular atrophy?

Answer 18

Rare - 5% of MND
Lower MN only
Onset 40+
Usually lower limbs first
Progressive weakness
Fasciculations
Atrophy
None of the UMN signs

Question 19

What are the symptoms of progressive bulbar palsy?

Answer 19

Rare
Lower MN
Onset 50-70
Bulbar symptoms
Some inherited mutations of SOD1

Question 20

Is CMT disorder inherited?

Answer 20

Yes

Question 21

Is CMT a single disorder or a group of disorders?

Answer 21

Group of disorders recognised by 3 neurologists Charcot, Marie and Tooth

Question 22

Is CMT homogenous?

Answer 22

Yes

Question 23

What is type 1 CMT?

Answer 23

Demyelination - get Schwann cell infiltrating the area and laying down another myelin sheath but get further demyelination and another cell etc
End up with several layers of Schwann cells around the axon giving an ‘onion bulb’ appearance
Thin myelination but thickening of the nerve due to Schwann cell

Question 24

What is type 2 CMT?

Answer 24

Axonal degeneration

Get changes to the mitochondria - don’t look normal in some cases they are swollen or lots of them aggregated together

Question 25

How many genes have been identified as being mutated in CMT?

Answer 25

70+

Question 26

What are the symptoms of CMT?

Answer 26

Slowly progressive
Present in 2nd decade - earlier/later onset can occur
Steppage gait
Sensory deficit
Lower limb amyotrophy
Unilateral muscle wasteage on one side
Loss of deep tendon reflexes
Balance impairment
Hammertoes
Later problems with upper limbs - claw-like hand, occasionally musculoskeletal pain and scoliosis

Question 27

How can you tell if someone has type 1 or 2 CMT?

Answer 27

Measure the electrophysiological changes in motor nerve conduction velocity, compound action potential, and sensory nerve action potential.

Normally above 45m/s but type 1 is slower at less than 38 and type 2 is above 45 (with decreased CMAP/SNAP)

Question 28

Mutations in what 6 proteins can lead to CMT disease?

Answer 28

Proteins affected are very diverse but include:
Dyamin
Dyein
Kinesin
tRNA synthase
TrpV4
Myelin