ALS

Question 1

What does MND refer to?

Answer 1

A heterogenous group of conditions characterised by degeneration of lower motor neurons and/or upper motor neurons

Question 2

Where are the upper motor neurons?

Answer 2

Cortex and brainstem

Question 3

Where are the lower motor neurons?

Answer 3

SC

Question 4

Which upper motor neurons can be affected by MND?

Answer 4

Ones that synapse with lower motor neurons

Question 5

Which diseases involve upper motor neuron defects?

Answer 5

Primary lateral sclerosis, pseudobulbar palsy

Question 6

Which diseases involve lower motor neuron diseases?

Answer 6

Progressive muscular atrophy, spinal muscular atrophy, progressive bulbar palsy, Kennedy disease

Question 7

What is a common symptom between all MNDs involving lower motor neurons?

Answer 7

Muscular atrophy/loss of muscle function

Question 8

Which disease is associated with upper and lower motor neuron dysfunction?

Answer 8

Amyotrophic lateral sclerosis

Question 9

When was ALS first described in a publication?

Answer 9

1869

Question 10

ALS stands for?

Answer 10

Amyotrophic lateral sclerosis

Question 11

Amyotrophic meaning?

Answer 11

No muscle nourishment

Question 12

Sclerosis meaning?

Answer 12

Scarring of muscle

Question 13

Main cause of death as a result of ALS?

Answer 13

Respiratory failure

Question 14

Signs that upper motor neurons are affected negatively?

Answer 14

Hyperreflexia, spasticity, slowing of movements

Question 15

What is hyperreflexia?

Answer 15

Reflexes are frequent and happen in an uncontrolled way

Question 16

Muscle spasticity?

Answer 16

Muscles become thinner and lose the stiffness

Question 17

Signs that lower motor neurons are affected?

Answer 17

Weakness, muscle atrophy, fasciculations

Question 18

What is fasiculations?

Answer 18

Uncontrolled, rapid movements

Question 19

Why is drooling seen in ALS?

Answer 19

Upper motor neurons (brainstem etc) is affected–> muscles that control saliva cannot be controlled correctly

Question 20

Established risk factors for ALS?

Answer 20

Family history and age

Question 21

What % of ALS patients have inherited a mutation associated with the disease from their parents?

Answer 21

10%

Question 22

Lifestyle choices which may be associated w/ ALS?

Answer 22

Manual labour, smoking, excessive exercise, exposure to toxic chemicals

Question 23

Why could heavy exercise contribute to ALS?

Answer 23

Overuse of muscles which could lead to muscle injuries and damage of neuons

Question 24

What happens as a result of cortical motor cells dissapearing?

Answer 24

Retrograde axonal loss and gliosis in the corticospinal tract

Question 25

What does gliosis cause?

Answer 25

White matter changes

Question 26

Effect of ALS on SC?

Answer 26

The SC becomes atrophic, ventral roots become thin and there is a loss of myelinated fibres in motor nerves

Question 27

First step in pathogenic mechanisms of ALS?

Answer 27

Glutamate excitotoxicity--> if glutamate stays in the synapse for too long it is toxic. Usually astrocytes take excess glutamate up but in ALS there is too much glutamate

Question 28

What does excess glutamate cause in the post N?

Answer 28

Excessive Ca2+

Question 29

What does excessive Ca2+ in the post n cause?

Answer 29

Mitochondrial dysfunction

Question 30

Effect of mitochondrial dysfunction?

Answer 30

ATP production is affected, also superoxides are produces (oxidative stress)

Question 31

What happens as a result of oxidative stress and mitochondrial dysfunction?

Answer 31

Aggregation of SOD1 and TPD proteins which are responsible for decreasing oxidative stress

Question 32

What causes neuroinflammation?

Answer 32

Release of inflammatory mediators by microglia

Question 33

How can neuroinflammation affect RNA metabolism?

Answer 33

Mutation of gene expression which can dysregulated RNA metabolism

Question 34

How does ALS cause axonal transport defects?

Answer 34

Neurofilaments that are meant to be present along the axon begin to accumulate--> too much of them

Question 35

Which tools are used to diagnose ALS?

Answer 35

El Escorial Criteria--> set of diagnostic guidelines

Question 36

Why is electromyography key in diagnosing MND?

Answer 36

It detects electrical activity in muscles and can reveal abnormalities indicative of motor neuron involvement e.g. denervation patterns and spontaneous muscle activity

Question 37

Four steps in El Escorial criteria?

Answer 37

Definite ALS, Probable ALS, Probable ALS, lab results supported, possible ALS

Question 38

Possible ALS criteria?

Answer 38

Presence of upper motor neuron and lower motor neuron signs in one region or upper motor neuron signs in 2/3 regions

Question 39

Probable ALS, lab results supported criteria?

Answer 39

Presence of upper motor neuron and lower motor neuron signs in one region with evidence by EMG of lower motor neuron involvement in another region

Question 40

Probable ALS criteria?

Answer 40

Presence of upper and lower motor neuron signs in at least two regions with UMN sign rostral to LMN sign

Question 41

Definite ALS criteria?

Answer 41

Presence of upper motor neuron and lower motor neuron signs in three anatomical regions

Question 42

How is a myelogram carried out?

Answer 42

A dye is injected into the spinal canal--> dyes areas and then does a CT scan. Look to see where the dye has deposited

Question 43

Which exams can be used to diagnose ALS?

Answer 43

MRI, Myelogram, muscle and/or nerve biopsy

Question 44

What do the three separate mechanisms of riluzole all do?

Answer 44

Reduce glutamate induced exciotixicity

Question 45

How does riluzole work?

Answer 45

It inhibits glutamic acid release, noncompetitive block of NDMA receptor mediated response, direct action on the voltage dependent sodium channel

Question 46

Drawbacks of riluzole?

Answer 46

Only extends survival rate by 2-3 months, 50% of patients experience side effects

Question 47

Side effects of riluzole?

Answer 47

gastrointestinal disturbances (nausea, vomiting, diarrhea), fatigue, and dizziness

Question 48

Serious risks of riluzole?

Answer 48

Neutropenia, liver dysfunction

Question 49

Formulation issues w/ riluzole?

Answer 49

Patients cannow swallow