Motor Neuron Disease

Question 1

What does Motor Neuron Disease refer to?

Answer 1

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

Question 2

Lower motor neurons

Answer 2

Those that have cell bodies in the cranial nerve nuclei or in the anterior horn of the spinal cord and synapse directly on muscle

Question 3

Upper motor neurons

Answer 3

Those that have cell bodies in the brain and synapse on lower motor neurons

Question 4

Motor Neuron Diseases of the UMN

Answer 4

Primary Lateral Sclerosis
Psuedobulbar palsy

Question 5

Motor Neuron Diseases of the LMN

Answer 5

Progressive muscular atrophy
Spinal muscular atrophy
Progressive bulbar palsy
Kennedy disease

Question 6

Motor neuron diseases of the UMN and the LMN

Answer 6

Amyotrophic Lateral Sclerosis

Question 7

What does Amyotrophic mean?

Answer 7

No muscle nourishment

Question 8

What does lateral mean?

Answer 8

Refers to the areas in person’s spinal cord where portions of the nerve cells that signal and control the muscle are located

Question 9

What is sclerosis?

Answer 9

Scarring of the affected tissue

Question 10

Progression of ALS

Answer 10

Gradually muscles under voluntary control are affected
Individuals lose strength, ability to sleep, eat, move and breath.
Most people with ALS die of respiratory failure within 3 to 5 years of onset

Question 11

ALS affects nerve cells responsible for controlling _ muscle movement

Answer 11

Voluntary
Motor neurons are the link between the brain and voluntary muscles.

Question 12

What happens to upper and lower MN in ALS?

Answer 12

They degenerate and die
Unable to function, the muscles degenerate

Question 13

ALS subtypes

Answer 13

Classical ALS
Primary Lateral Sclerosis (PLS)
Progressive Muscular Atrophy (PMA)

Question 14

Symptoms of ALS caused by UMN

Answer 14

Hyperreflexia (twitching)
Spasticity (muscles are stiff and hard to move)
Slowing of movements

Question 15

Symptoms of ALS caused by LMN

Answer 15

Weakness
Muscle atrophy
Fasciculations (spontaneous contraction or relaxation of muscles)

Question 16

Established ALS risk factors

Answer 16

Age and family history

Question 17

Proposed risk factors for ALS

Answer 17

Cigarette smokers
labourers engaged in agricultural work
factory work
heavy manual labour
exposure to welding or soldering
work in the plastics industry

Question 18

Pathology of ALS

Answer 18

Cortical motor cells disappear, leading to retrograde axonal loss and gliosis in the corticospinal tract.
This gliosis results in the bilateral white matter changes
The spinal cord becomes atrophic.
The ventral roots become thin, and there is a loss of large, myelinated fibres in motor nerves.
The affected muscles show denervation atrophy.

Question 19

Pathogenic mechanisms of ALS

Answer 19

1. Glutamate excitotoxicity
2. Mitochondrial dysfunction
3. Protein aggregation
4. Oxidative stress
5. Neuroinflammation
6. RNA metabolism dysregulation
7. Axonal transport defects
8. Epigenetic alterations

Question 20

El Escorial Criteria Overview

Answer 20

A set of diagnostic guidelines developed for the diagnosis of amyotrophic lateral sclerosis (ALS)

Question 21

El Escorial Criteria

Answer 21

• Possible ALS (U+LMN signs in 1 region OR UMN signs in ≥ 2 regions)
• Probable ALS (UMN signs in ≥ 1 region AND LMN signs in ≥ 2 regions)
• Possible ALS (U+LMN signs in 2 regions with at least one UMN sign rostral to LMN signs)
• Definite ALS (U+LMN signs in 3 regions)

Question 22

What is the role of electromyography in MND

Answer 22

Detects electrical activity in muscles, revealing abnormalities indicative of motor neuron involvement, such as denervation patterns and spontaneous muscle activity

Question 23

What is the importance of genetic testing in MND?

Answer 23

Diagnosing familial forms of MND, identifying specific mutations associated with the disease, which can inform prognosis and guide management strategies for affected individuals

Question 24

How to diagnose ALS?

Answer 24

• Clinical and neurological exams
• MRI
• Myelogram of cervical spine
• Muscle and/or nerve biopsy
• Electromyography (EMG) and nerve conduction velocity (NCV) to measure muscle response to nervous stimulation

Question 25

How is riluzole thought to reduce glutamate-induced excitotoxity?

Answer 25

• inhibition of glutamic acid release
• noncompetitive block of NMDA receptor mediated responses
• direct action on the voltage-dependent sodium channel

Question 26

Drawbacks of Riluzole

Answer 26

Limited efficacy, only extends survival 2-4 months
Common adverse effects (50%)
Serious risks like liver dysfunction
High discontinuation rates because of risks
No improvement in function only survival

Question 27

Side effects of Riluzole

Answer 27

Gastrointestinal disturbances (nausea, vomiting, diarrhea)
Fatigue
Dizziness.

Question 28

Emerging gene therapies for ALS

Answer 28

Innovative gene therapies targeting specific genetic mutations associated with MND are under investigation, personalized treatment options?.

Question 29

Enhanced supportive care models for ALS

Answer 29

Nutritional management and respiratory support etc, are crucial for maintaining quality of life and prolonging survival in MND patients.

Question 30

Exosome-based therapies for MND

Answer 30

Novel strategy
Using exosomes from LPS-stimulated macrophages to skew microglia towards M2 phenotype

Question 31

Microglial depletion and repopulation for MND

Answer 31

Inducing microglial replacement to restore homeostatic functions

Question 32

Targeting specific molecules for MND

Answer 32

• Nicotinamide phosphoribosyl transferase (NAMPT) to inhibit pro-inflammatory microglia
• Long noncoding RNA H19 to modulate HDAC-dependent M1 microglial polarization