B.14 ALS

Question 1

General Info

Answer 1

-neurodegenerative disease
- affects upper and lower Motor Neurons
-focal weakness spreads
-upper motor Neurons: cortex, stiffness and spasticity
-lower motor Neurons: spinal cord and brain stem, twitching and electrical irritability
+muscular atrophy
- progressive paralysis
-higher pravelence in old age
-heterogenous presentation
-more men affected in sporadic form

Question 2

Subtypes

Answer 2

ALS: Amyotropic Lateral Sclerosis

PLS: primary Lateral Sclerosis

PMA: primary muscular atrophy

Question 3

Classification

Answer 3

Bulbar onset:
- aggressive
- you er population 
-FTD
Progressive bulbar palsy (lower motor Neurons)
->PMA

Spectrum: middle ALS with impaired cognition and flaing limbs

Spinal onset:
-slow progress
-older onset
- normal cognition
Upper motor Neurons 
->PLS

Question 4

Familial Forms

Answer 4

• 5-10% of which 70% Mendelian

- cures in mouse model

Question 5

Sporadic Forms

Answer 5

• also show heritability

-

Question 6

Genes Relevant to ALS

Answer 6

• SOD1
• TARDBP
• FUS
• C9orf72
• TDP-43

Question 7

Environmental Factors

Answer 7

• chemicals
• somatic mutations
• Smoking
• Asbestos
• sports
• drinking
• > generic load +predisposition > cell damage and exposure

Question 8

Neuroinflammation

Answer 8

-risk factor
-immuneresponse our of balance
Hypothesis:
Increased immunresponse in ALS leads to increase if TNF + interleukin and leads to toxicity and hyper immunresponse