L8- Neurodegenerative Disease, ALS

Question 1

ALS, aka (1), is caused by (2)

Answer 1

1- amyotrophic lateral sclerosis, Lou Gehrig’s, motor neuron disease

2- death of LMN in spinal cord, brainstem + death of UMN in motor cortex

Question 2

describe the effect of losing LMNs in ALS

Answer 2

denervation of muscles –> muscle atrophy (amyotrophy), weakness, fasciculations

Question 3

describe the effect of losing UMNs in ALS

Answer 3

• paresis
• spasticity
• hyperreflexia
• babinski sign

Note- degeneration of lateral portion of corticospinal tract = lateral sclerosis

Question 4

describe the non-motor effects of ALS (include what is unaffected)

Answer 4

• intellect, sensation, sphincter control, eye movements intact
• cognition may be affected in later stages

Question 5

ALS:

• (1) mostly males or females
• (2) average age of onset
• (3) life expectancy at time of Dx
• (4) mostly familial or sporadic cause

Answer 5

1- M > F
2- 40s
3- 2-5 yrs
4- sporadic; ~10% familial

Question 6

ALS clinical features:

• (1) initial signs
• (2) main progression
• (3) most common cause of death

Answer 6

1- subtle asymmetrical distal extremity weakness

2- dec in muscle strength and bulk + fasciculations (involuntary contractions)

3- recurrent bouts of pulmonary infections

Question 7

ALS:

• (1) is thought to be involved in the pathogenesis
• (2) and (3) are the possible genetic components that can contribute

Answer 7

1- abnormal RNA and or protein processing

2- superoxide dismutase
3- chr.9 hexanucleotide repeat (C9orf72)

Question 8

ALS gross appearance

Answer 8

• neuronal loss in anterior horn of spinal cord (roots appear thinner in comparison to posterior / sensory roots)
• motor cortex mildly atrophic due to UMN loss

Question 9

ALS microscopic features

Answer 9

-Anterior horn: dec in neurons + reactive gliosis

• cytoplasmic inclusions containing TDP43 in some cases
• abnormal SOD-1