Presentation about ALS, includes brief description and Pathophysiology

1. AMYOTROPHIC LATERAL
SCLEROSIS

2. DEFINITION
ALS, also known as Lou Gehrig’s disease, leads to the
neuro degeneration of motor nerve cells. This affects muscle
cells, and will eventually lead to the total paralysis of the
diagnosed subject

3. ABOUT ALS
The most widespread degenerative disease of motor nerves
Fatal, with up to 3 years of survival period
1st discovered in 1869 by French neurologist Charcot
5% of the cases point at genetic origins, and 61% give proof
of heredity.

4. DISEASE OVERVIEW
Classic: affects LMNs of the anterior horn of the spinal cord
and the UMNs of the pericentral gyrus.
Progressive Muscular Atrophy: affects the LMNs that lead to
muscle cell degeneration
Familial ALS: ALS cases that involve autosomal propagation
of the disease. (Still a very recent branch of ALS research)

5. PATHOPHYSIOLOGY
Not the result of 1cascade, rather the product of several
cascades that all contribute to the degeneration of motor
nerve cells
Extensive research into the disease describes the following
as contributing to the development of ALS.

6. PATHOPHYSIOLOG
Y
Motor nerve degeneration is triggered by the death of the
neuron cell body.
Death of cell body leads to the degeneration of the axon.
When axons die, the remaining must therefore innervate
bigger muscle fibers, leading to the atrophy of muscle cells.

8. PATHOPHYSIOLOGY
Oxidative Stress: imbalance
between reactive oxygen species
and the body’s ability to detoxify
the reactive intermediates
(undergo reduction).
Leads to the synthesis of free
radicals, that react with cell
components: proteins, lipids, DNA
etc… Disrupting cell functions
leading to its death

9. PATHOPHYSIOLOGY
Mitochondrial disfunction: failure of the mitochondria to
deliver the required energy for the cell to carry its processes,
leading to cell disfunction and later on cell death.
Caused by mostly genetic inheritance: autosomal recessive
transmission of nDNA or dominant transmission of affected
mtDNA. Random large deletions in mtDNA also could lead
to disfunction.

10. PATHOPHYSIOLOGY
Motor nerve cells apoptosis: caused by the initiation of auto-destructive
kinases, eg: phosphoinositide 3 kinase, mitogen
activated kinases, that are activated by the immune system.
The causes behind apoptosis are very widespread, from
genetic defects to prions (free roaming DNA) infection.

11. PATHOPHYSIOLOGY
Abnormal levels of VE growth
factor: affects the capillary
density in the spinal cord,
meaning that the nerves and
surrounding cells are less
irrigated. The major cause of
low VEGF is a mutation of
what is now know as the ALS2
gene.

12. PATHOPHYSIOLOGY
Glutamate excitotoxicity AKA Nervous Strokes: over
secretion of Glutamate, one of the major excitatory NTs, in
the synaptic cleft disrupts the cell processes of the post
synaptic neurons: mitochondrial defection, nitrogen free
radicals and reactive oxygen species. ROS in turn act as a
signal on surrounding microglia (+ve feedback) who then
release cytokines and more ROSs, who in turn activate cell
apoptosis.

13. PATHOPHYSIOLOGY
The previously mentioned mechanisms and pathways may
seem individually simple in theory, however when it comes
to ALS, we have seen how most of them are interconnected,
where one leads to the other or vice versa. This makes ALS
a complicated maze of research topics.

14. DIAGNOSIS
Auto diagnosis starts when the subject feels muscle fatigue,
and abnormalities in his muscles: smaller muscle tension,
decrease of muscle size… Note that unexplained skeletal
muscle contractions are so far not related to ALS.

15. DIAGNOSIS
Clinical diagnosis goes as follows:
Physicians look for signs through the following techniques: MRI
scans, blood and urine hormone level, muscle and nerve biopsy and
electrodiagnostics for muscle tension, nerve conductance, and
correlation between the two.
Clinically definite ALS: UMN and LMN signs in at least 3 body
segments
Clinically probable ALS: UMN and LMN signs in at least 2 body
segments with some UMN signs in a segment above the LMN signs
Clinically probable, laboratory-supported ALS: UMN and LMN signs
in 1 segment or UMN signs in 1 region coupled with LMN signs by
electromyography (EMG) in at least 2 limbs
Clinically possible ALS: UMN and LMN signs in 1 body segment,
UMN signs alone in at least 2 segments, or LMN signs in segments
above UMN signs
Clinically suspected ALS (carried forward from the original El
Escorial criteria): Pure LMN syndrome with other causes of LMN
disease adequately excluded

16. FAMOUS CASES OF ALS:
Lou Gehring: former NY Yankees baseball player, after
whom the disease is currently named.
Stephen Hawking: Theoretical physicist.
Mao Zedong: Chinese dictator responsible for the rise of
Marxism and Communism in China.