ALS second half Flashcards
What happens as a result of cortical motor cells dissapearing?
Retrograde axonal loss and gliosis in the corticospinal tract
What does gliosis cause?
White matter changes
Effect of ALS on SC?
The SC becomes atrophic, ventral roots become thin and there is a loss of myelinated fibres in motor nerves
First step in pathogenic mechanisms of ALS?
Glutamate excitotoxicity–> if glutamate stays in the synapse for too long it is toxic. Usually astrocytes take excess glutamate up but in ALS there is too much glutamate
What does excess glutamate cause in the post N?
Excessive Ca2+
What does excessive Ca2+ in the post n cause?
Mitochondrial dysfunction
Effect of mitochondrial dysfunction?
ATP production is affected, also superoxides are produces (oxidative stress)
What happens as a result of oxidative stress and mitochondrial dysfunction?
Aggregation of SOD1 and TPD proteins which are responsible for decreasing oxidative stress
What causes neuroinflammation?
Release of inflammatory mediators by microglia
How can neuroinflammation affect RNA metabolism?
Mutation of gene expression which can dysregulate RNA metabolism
How does ALS cause axonal transport defects?
Neurofilaments that are meant to be present along the axon begin to accumulate–> too much of them
Which tools are used to diagnose ALS?
El Escorial Criteria–> set of diagnostic guidelines
Why is electromyography key in diagnosing MND?
It detects electrical activity in muscles and can reveal abnormalities indicative of motor neuron involvement e.g. denervation patterns and spontaneous muscle activity
Four steps in El Escorial criteria?
Definite ALS, Probable ALS, Probable ALS, lab results supported, possible ALS
Possible ALS criteria?
Presence of upper motor neuron and lower motor neuron signs in one region or upper motor neuron signs in 2/3 regions
