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My name is Pietro Fratta, and I'm
a neurologist and a researcher
at the UCL Institute of Neurology
and at the National Hospital
for Neurology and
Neurosurgery in London.
Today we'll be talking about the
pathogenesis and cell biology
of the neurodegenerative disorder
Amyotrophic Lateral Sclerosis, ALS.
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The fundamental feature of
ALS is that it's characterized
by the degeneration of both
upper and lower motor neurons.
Upper motor neurons
are in the brain,
and lower motor neurons
are in the brain stem
and in the spinal cord.
Other motor neuron diseases
involve either upper motor neurons,
such as progressive
lateral sclerosis
and hereditary spastic paraplegia,
or the lower motor neurons,
such as primary muscular
atrophy, spinobulbar
muscular atrophy, or
spinal muscular atrophy.
Clinically, the loss of both
upper and lower motor neurons
contributes to the
progressive weakness.
The loss of upper motor neurons
instead specifically causes
spasticity and brink reflexes,
whilst the loss of the lower motor
neurons causes fasciculations
and muscle wasting.
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So clinically, ALS has an
incidence of 2 in 200,000.
And this is uniform
across Western countries.
There's a lifetime
risk of 1 in 1,000.
And the age of onset is typically
between 55 and 65 years of age.
Onset can occur even
earlier, and 5% of cases
occur before the age of 30 years.
There's a prevalence of males,
with a male to female ratio
of 1.5 to 1.
And 5% of cases have also
positive family history.
Inheritance in these cases
is mostly autosomal dominant.
The onset most frequently
occurs in the limbs,
but a bulbar onset can occur in
a fourth to a third of patients.
All muscles are affected, with
the exception of the extraocular
muscles, and this means that all
major functions are impaired,
such as walking, the
use of the upper limbs,
swallowing, and breathing.
In 5% of cases, frontotemporal
dementia can occur.
And 50% percent of
patients indeed show
cognitive impairment,
although this is mild.
Death occurs typically three
to five years after onset,
mostly due to respiratory
insufficiency.
