Lecture 22 - Motor Neurone Disease Flashcards
Give a brief description of MND
A group of diseases
• The most common of which is Amyotrophic lateral scerlosis
• Affects motor neurons
- Progressive
- Fatal
What are the symptoms of MND?
1. Loss of muscle function: • Muscle twitching • Muscle weakness • Difficulty speaking • Difficulty swallowing • Tripping, stumbling, dropping things • Progressive paralysis • Decreased respiratory function
- Loss of muscle mass
• Muscle atrophy
What are the two forms of motor neurons?
Which are affected in MND?
Upper motor neurons
• Originate in brain / brain stem
• Do not directly innervate muscle
Lower motor neurons
• Directly innervate muscle
• Originate in the spinal cord
Both are affected in MND
What is the average age of onset of MND?
45-60 years
Mid-late adulthood, after reproduction
What happens to sensory neurons in MND?
Usually spared
What happens to cognitive ability in MND?
Generally thought to be spared
May be some degeneration (?)
How is MND diagnosed?
Why is this so?
Diagnosis is purely clinical (no test)
• Process of exclusion
• Not easy to diagnose
• Much uncertainty about diagnosis
Hard to diagnose because the underlying causes are not known
What is the prognosis of MND?
- Progressive: continues getting worse
- Timeframe for symptom progression is variable
Generally:
• Confined to wheelchair within 1-2 years
• Death within 3-5 years
What normally causes death in MND?
Respiratory failure
What treatments are there at the moment for MND?
Riluzole
• Only drug on the market
• Moderate, controversial clinical efficacy
• Works by enhancing glutamate uptake from the synapse
What was seen in the RCT of Riluzole?
Not much of a correlate between dose and effect of drug.
With increasing dose, there was not an increased life expectancy
Only a small increase in life expectancy between drug and placebo
Why is there no good drug for MND?
The fundamental causes of the diseases are not known
What are the causes of MND?
90% of cases are sporadic
The 10% that aren't: 1. Genetic factors: Mutations in various genes: • SOD1 • TDP43 • Angiogenin • Optineurin etc. It is unclear whether the mutations are loss or gain of function
- Environmental factors:
• Head trauma
• Military service (Gulf war)
• Chemical toxins
What are some biochemical observations in MND?
NB not just motor neurons, but astrocytes & microglia as well
Astrocytes:
• Impaired glutamate uptake from synapse
Discuss in general mutations in Cu/Zn superoxide dismutase
Gene known to be commonly mutated in MND
Still not known how this affects pathogenesis