Lecture 31 - Amyotrophic Lateral Sclerosis (ALS)

Question 1

ALS incidence?

Answer 1

familial form is rare, fifth decade onset, death usually within 5yr

Question 2

Symptoms?

Answer 2

progressive wasting, wasting of limbs, dysphagia, dysarthria, increased reflexes and tone (spasticity), fibrillations and fasciculations

Question 3

Exempt symptoms?

Answer 3

no involvement of extraocular muscles, anal and bladdr sphincters and intellectual deficit

Question 4

Disease cause?

Answer 4

progressive degeneration of: alpha and gamma motoneurons of spine, brain stem mtoneurons (exc. III, IV and VI), ‘upper’ moto neurons (hence spasticity)

Question 5

Oxidative stress hypothesis?

Answer 5

mutation of superoxide dismutase, increase free radicals which damage motoneurons

Question 6

Excitotoxic hypothesis?

Answer 6

extracellular glutamate increase, reduces GluR2 subunit of AMPA, leading to higher Ca fluxes and excitotoxic damage

Question 7

TDP-43/FUS Mutation hypothesis?

Answer 7

RNA proteins typicaly in nucleus mutate and shift to cytoplasm, forming insoluble aggregates affecting neural function

Question 8

Treatment?

Answer 8

no efective drug treatment; Riluzole slows preogression, Baclophen reduces spasticity, Dexpramipexole imrpoves Mt function