ALS

Question 1

Describe clinical presentation of ALS

Answer 1

• Muscle atrophy and spasticity
• Weakness of the limbs, trunk, tongue and respiratory muscles
• Usually distal muscles initially
• Bulbar signs - impaired swallowing and speech
• No impairment of bladder, bowl, sexual, oculomotor, sensory and autonomic function all spared
• Can be a decline in cognitive function (15%)

Question 2

Early diagnostic tests used

Answer 2

Muscle biopsy and electromyogram

• Biopsy shows grouped atrophic fibres
• Motor unit degeneration associated with re-innervation
• Wide precentral gyrus and atrophy of sulci in 3DMRI

Question 3

Describe treatment of MRI

Answer 3

• Speech therapist
• Occupational therapist
• NG tube, PEG
• Oxygen, assisted ventilation
• Treat cramps /muscle spasm
• To slow disease progression riluzole can be used, extends survival by around 3 months

Question 4

What is ALS characterised by?

Answer 4

• Motor neuron loss
• Corticospinal tract degeneration
• Ubiquitinated inclusions in neuronal cell bodies and proximal axons (immunoreactive LMN with filamentous or compact inclusions)

Question 5

What is a ubiquitinated protein?

Answer 5

• Post translational modification by a small 76aa regulatory protein, ubiquitin

Question 6

Describe genetics of ALS

Answer 6

• Familial ALS is 10% of cases, this is where gene discoveries have been made
• Abnormalities in RNA binding proteins, proteostasis and cytoskeletal proteins