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LECTURES CLINICAL NEUROSCIENCE
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Lecture 1 – Brain developmentD. Bakker
Learning objectives:
- Able to describe the landmarks in brain development
- Have knowledge of neurological disease resulting from a failure in this process
- Have basic knowledge about pediatric neurological development
Timeline:
- 28 days after conception, the neural tube is formed (first trimester)
- 22 weeks after conception, the brain looks smooth (absence of gyri and sulci)
- Myelination starts after birth. This gives the ability to learn how to move more smoothly (roll over)
- 24 weeks is the youngest age a newborn can be
given support to survive after birth
- Responses to touch and light already start
before birth
- Development of handedness start at 2-3 years
of age. If the child has a dominant hand very
early in life, this is an indication for a certain
cerebral malformation or an infarction around
birth.
- A child gives the first smile to their parents at
the age of 2-3 months.
Spina bifida:
This is a disease that occurs after neurulation (neural tube
formation) is not succeeded and the end of the neural tube is not
closed properly. An opening of the vertebrae with underlying
tissue is present in this disease. The neural tissue is exposed to
the outside world and hereby gets damaged. There is a decline in
the spina bifida incidence over the years, which has 2 causes:
1. First rapid decline: lack of folic acid in the diet mother’s diet
during the hongerswinter.
2. Second decline: The introduction of the 20th week ultrasound
where the spina bifida is detected and when the spina bifida is
present, the pregnancy is aborted.
1
,Neurofibromatosis:
The skin and the neural tube are both originated
from the ectoderm.
A mutation in the NF-1 gene → unequal
distribution of melanocytes in the skin. The
appearance of the skin gives a clue for the
neurological problems the child has. You can see
the abnormalities in the brain (hematomas in the
globus pallidus). This NF-1 gene mutation gives a
higher chance for forming gliomas in the optic
pathways. Also, problems in learning and
behavioural problems are related to this mutation.
The nerves in the skin have the tendency to make
fibromas (tumor like swellings on the skin).
Holoprosencephaly:
The gyri and sulci are not properly formed
in the frontal lobe. Also, the corpus
callosum is not properly formed, so there
is a bad connection between the two
hemispheres.
Neuronal migration:
Neuronal migration takes place between week 16 after conception and
birth. The neurons proliferate and originate from the ventricular zone. They
move to the cortex via glial cells. So, they pass the first layers that are
already formed. There are two ways to migrate:
1. Radial manner: from inside to outside
2. Tangential manner: in between the other layers.
2
,Neuronal migration related diseases:
F) Next to the ventricles (what used to be
the ventricular zone), you see some white
brain tissue with the same intensity as the
cortex. So here are neurons that were
supposed to migrate to the cortex but
failed. This is caused by a mutation in
filamin A.
D) The gyri are very big and
undifferentiated. Also, the cortex is very
thick. This is called lissencephaly, which is
caused by a mutation in the LIS1 gene.
E) There is a layer with the intensity of the
cortex. So there is gray matter in places
where you normally have white matter.
This is called the double-cortex-syndrome.
This is caused by a mutation in the DCX gene.
C) The cortex is very thin. The gyri and sulci are not formed properly. This is caused by a mutation in
the ARX gene.
Periventricular grey matter heterotopia:
This gives rise to a lot of seizures, spasticity and mental
disabilities.
3
, Temporal and spatial expression of morphogens:
There are specific expression profiles in each layer of the brain. So every layer of the brain has its
own expression profile. Also, these expression profiles change over time. For instance LM04 is highly
expressed in cortical areas and not in the ventricular zone.
CNS synaptogenesis:
Synaptogenesis starts before birth and continues until adolescence. This process is activity
dependent.
Myelination:
You can see in the 7-month-old human fetus that the myelination
in the motor cortex has started. Also, the structures in the brain
stem are myelinated first because these areas are important
already after birth (e.g. normal breathing, coordination etc.).
4
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