Lecture 12: Motor Neuron Disease

Question 1

ALS breakdown

Answer 1

• Amytrophy: muscle wasting LMN

- Lateral sclerosis: loss of lateral corticospinal tract UMN

Question 2

Treatment

Answer 2

Riuzole

• increases lifespan by 3 months
• NMDA antagonist

Question 3

Features of MND

Answer 3

• characterised by upper +/- lower MN loss
• sensation is preserved
• Few groups of MN spared: sphincter control, extraocular muscles

Question 4

Symptoms

Answer 4

(-) muscle weakness, cramps, flaccid paralysis

(+) hyper reflexia, spastic paralysis

Question 5

Diagnosis

Answer 5

• Not definitive
• Rule out other diseases
• Motoneuronal degeneration determined by:
• clinical tests
• electrophysiological tests

Question 6

Types

Answer 6

• sporadic: 95%

- familial: 5%

Question 7

Sporadic

Answer 7

• middle-late onset
• Slight preference for males
• UMN +/- LMN loss
• muscle weakness, cramps, wasting, paralysis
• death within 2 yrs due to resp-related illnesses

Question 8

Spinal Muscular Atrophy

Answer 8

• progressive loss of LMNs
• Types: infantile and juvenile
• recessive mutation in SMN1

Question 9

Hypotheses on Causes of MND

Answer 9

1. genetics
2. excitotoxicity
3. oxidative stress

Question 10

Excitotoxicity

Answer 10

• Loss of glial glutamate transporters -> excessive glutamate -> act on NMDA receptors -> cell death
  Although:
• only some reports of decreased glutamate transporters and increased glutamate in CSF
• NMDA antagonist only extends like by 90 days:?

Question 11

Oxidative Stress

Answer 11

• SOD-1 scavenges free-radicals
  -> mutation in SOD-1 -> increase in free radicals -> cell injury
  Although:
• SOD1 mutation kill other cells too -> not specific to MN death as seen in MND