Motor Neurone Disease

Question 1

MND- ALS or Lou Gehrigs disease

Answer 1

1:400 lifetime risk (1.6 M : 1 F)
•	5 000 people in the UK
•	Life expectancy 2-4 years
•	10% of people > 10 yrs
•	60-80 years peak, all ages
•	~10% genetic component

Question 2

Disease of what system

Answer 2

Motor system - motor neurones come out at different levels and innervates roughly the same area it comes from

Question 3

Motor neurone pathway that results in contraction

Answer 3

Dorsal Horn > Dorsal root > Root ganglion> Sensory/motor Fibre > Muscle > contraction

Question 4

Motor system hierachy

Answer 4

Motor cortex> Medulla> Spinal cord

Question 5

what area causes contraction of the Oropharyngeal muscles

Answer 5

Medulla

Question 6

Bulbar motor neuron is associated with what area

Answer 6

Cervical spinal cord

Question 7

motor innervation for the limb muscles originates

Answer 7

Thoracic spinal cord

Question 8

Somatic Motor Neuron

Answer 8

Lumbar spinal cord

Question 9

MND

Answer 9

• Degeneration (think excess AGEING) of upper motor neurons and lower motor neurons
• Can have……
UMN pathology – primary lateral sclerosis
LMN pathology – progressive muscular atrophy
Mixture of both – Amyotrophic lateral sclerosis (90%)

Question 10

Presentations

Answer 10

•Limb onset (75%)
•Bulbar onset (20%)- refers to medullar( lower part of brainstem)
•Respiratory onset (5%)
•Associated with
– Frontotemporal dementia
•Language or behavioural variant
– Other neurodegenerative diseases
Weakness in intrinsic hand muscles or foot/leg – initial signs
Visible muscle weakness – shown in first dorsal interossei

Question 11

Limb symptoms-• Upper motor neurone symptoms

Answer 11

– Weakness

– Spasticity- increase of tone

Question 12

Limb Symptoms - • Lower motor neurone symptoms

Answer 12

• Lower motor neurone symptoms

Question 13

Bulbar symptoms

Answer 13

• Progressive, relentless
• Oropharyngeal muscles
• Dysarthria
• Dysphagia
• Jaw spasms/bruxism (deep grinding)
• Emotional lability

Question 14

Other symptoms

Answer 14

•	Respiratory failure
–	Appetite reduced
–	Weight loss
–	Sleep disturbance
–	Fatigue
•	General fatigue

Question 15

Extra motor features

Answer 15

• Frontotemporal Dementia (5%)
• Cognitive problems (50%)
• Parkinsonism
• Autonomic nervous system
• And later: sensory pathways, hippocampus, substantia nigra
• The oculomotor and Onuf’s nucleus are motor neurones unaffected in ALS

Question 16

incidence of death

Answer 16

75-80% die within 5 years

Question 17

Causes of Death

Answer 17

 Respiratory failure
 Bronchopneumonia
 Bulbar dysfunction

Question 18

Incidence of survival

Answer 18

 20% survive 5 years

 10% survive 10 years

Question 19

Multiple hit theory

Answer 19

• Multiple genes contributing

- Couple of mutations and env increase chance of MND

Question 20

Treatment

Answer 20

Multidisciplinary

Question 21

Methods to improve survival and quality of life

Answer 21

– Riluzole (approximately 3 months gain in 18 month trial) only approved medication
– Non-invasive ventilation
– Multi-disciplinary specialist care

Question 22

Respiratory failure in MS

Answer 22

• Frequent nocturnal awakening
• Nocturia
• Unrefreshed sleep
• Morning headaches
• Day time sleepiness
• Poor appetite
• Lethargy
• Weight loss
• Loss of strength

Question 23

Riluzole

Answer 23

Small but significant increase in survival

Question 24

Antisense Oligonucleotides

Answer 24

Reduce toxic protein 
•	ASO- short synthetic nucleic acid
–	Modified to increase stability and potency of binding
–	Binds to target mRNA and promotes degradation by RNaseH
–	Intrathecal administration
–	Phase 1 trial in Sheffield for SOD-1
–	New trials in c9orf72, alpha-synuclein
–	....Monoclonal antibodies to Tau

Question 25

C9ORF72- what disease does its mutation cause ?/

Answer 25

intronic GGGGCC expansion
Normally it produces GGGGCC
-ALS