00:02
When children are weak,
sometimes the problem is in the motor nerve.
00:06
In this lecture, we'll talk about specific
motor nerve disorders that could occur
in pediatrics.
00:13
Let's start with Spinal Muscular
Atrophy or SMA.
00:18
SMA is
often a very debilitating condition.
00:22
it's autosomal recessive
in that it may travel in families.
00:26
and have unaffective carriers.
00:29
The defect is on the survival
motor neuron gene or the SMN gene
It results in a degeneration
of the anterior horn cells
of the spinal cord.
00:40
resulting in weakness.
00:43
There are three main types of SMA.
00:46
I, II and III.
00:47
SMA I is very severe.
00:50
It usually affects infants and is often
life threatening.
00:54
SMA II is more moderate
and SMA III is quite mild.
01:01
All of the SMAs, the problem is that small
muscles are not innervated.
01:06
The larger ones still have
innervations.
01:09
So, in muscle biopsy it will show a patchy
appearance.
01:13
Much like this.
01:14
Patients will present with a
progressive symmetrical proximal weakness.
01:20
Remember this is a lower
motor neuron disease.
01:23
So, they will be floppy
and may have absent deep tendon reflexes.
01:29
You may see muscle fasciculation
as well.
01:31
And it is often seen easily in the tongue.
01:35
But remember, it is just
the motor neurons.
01:37
These patients will have normal
cognition.
01:41
Let's review the natural progression of disease without any effective therapy,
which has only recently been discovered and instituted in the last 15 years.
01:49
Type one results in severe hypotonia in children.
01:53
Death before the age of 2 is common without therapy.
01:55
These patients will die of respiratory complications if untreated.
01:59
In Type II disease, they may have the
ability to sit
but often will not have
the ability not walk.
02:06
This typically presents a little
later
around 6-18 months of age.
02:10
And it requires nutrition and respiratory
support.
02:15
In Type III disease,
patients may lose the ability
to ambulate around 10 years of age.
02:22
It often presents after a year
an a half of age
and typically we will involve
Physical therapy and orthopedics
for braces or things like that
so to they can function as long
and as well as possible.
02:36
So, the diagnosis of SMA is made
by a genetic test of the SMA I gene.
02:43
We'll send it for sequencing and look for
deletions.
02:48
New treatments have come out for SMA including two new treatment options —
a gene replacement therapy called Zolgensma and a drug called nusinersen.
02:59
SMA gene therapy is a one-time infusion that replaces the defective or missing SMN1 gene with a working copy.
03:07
This new gene increases survival motor neuron (SMN) protein levels,
which improves motor neuron function and increases the likelihood of survival.
03:15
Recently, the FDA approved this treatment for children less than 2 years of age with SMA.
03:21
A child must have the SMN1 mutation that causes this disease to receive this therapy.
03:26
The FDA approved the use of this drug for all types of SMA with an SMN1 mutation,
from infant-onset SMA type 1 to adult-onset SMA type 4.
03:37
Nusinersen uses synthetic (man-made) genetic material called antisense oliigonucliotide
to improve the splicing of the SMN2 gene.
03:47
This helps children to make more SMN protein needed for healthy motor neurons.