DEVELOPMENT

&
ANOMALIES
OF CENTRAL NERVOUS
SYSTEM

Asluf Amaan Dr.TESFAYE

GROUP 42.
12/06/2017
The central nervous system (CNS) is the part of the nervous system consisting of
the brain and spinal cord.

The central nervous system is so named because it integrates information it

receives from, and coordinates and influences the activity of all parts of the body
and it contains the majority of the nervous system.

Many consider the retina and the optic nerve (2nd cranial nerve), as well as the
olfactory nerves (1st) and olfactory epithelium as parts of the CNS, synapsing
directly on brain tissue without intermediate ganglia. Following this classification
the olfactory epithelium is the only central nervous tissue in direct contact with
the environment, which opens up for therapeutic treatments.

The CNS is contained within the dorsal body cavity, with the brain housed in the
cranial cavity and the spinal cord in the spinal canal. In vertebrates, the brain is
protected by the skull, while the spinal cord is protected by the vertebrae, both -
brain and spinal cord- enclosed in the meninges.

Development of the Central Nervous System

During early development of the vertebrate embryo, a longitudinal
groove on the neural plate gradually deepens and the ridges on either
side of the groove (the neural folds) become elevated, and ultimately
meet, transforming the groove into a closed tube called the neural
tube.

The formation of the neural tube is called neurulation. At this stage,

the walls of the neural tube contain proliferating neural stem cells in a
region called the ventricular zone. The neural stem cells, principally
radial glial cells, multiply and generate neurons through the process of
neurogenesis, forming the rudiment of the central nervous system.

The neural tube gives rise to both brain and spinal cord. The anterior
portion of the neural tube initially differentiates into three brain
vesicles : the prosencephalon at the front, the mesencephalon, and,
between the mesencephalon and the spinal cord, the
rhombencephalon.

(By six weeks in the human embryo) the prosencephalon then divides
further into the telencephalon and diencephalon; and the
rhombencephalon divides into the metencephalon and
myelencephalon. The spinal cord is derived from the posterior or
'caudal' portion of the neural tube.

As a vertebrate grows, these vesicles differentiate further still. The

telencephalon differentiates into, among other things, the striatum, the
hippocampus and the neocortex, and its cavity becomes the first and
second ventricles. Diencephalon elaborations include the subthalamus,
hypothalamus, thalamus and epithalamus, and its cavity forms the third
ventricle. The tectum, pretectum, cerebral peduncle and other
structures develop out of the mesencephalon, and its cavity grows into
the mesencephalic duct (cerebral aqueduct). The metencephalon
becomes, among other things, the pons and the cerebellum, the
myelencephalon forms the medulla oblongata, and their cavities
develop into the fourth ventricle.

Neural development
Neural development refers to the processes that generate, shape, and
reshape the nervous system, from the earliest stages of embryogenesis
to adulthood. The field of neural development draws on both
neuroscience and developmental biology to describe and provide
insight into the cellular and molecular mechanisms by which complex
nervous systems develop. Defects in neural development can lead to
malformations and a wide variety of sensory, motor, and cognitive
impairments, including holoprosencephaly and other neurological
disorders such as Rett syndrome, Down syndrome and intellectual
disability.
The mammalian central nervous system (CNS) is derived from the
ectodermthe outermost tissue layerof the embryo. In the third
week of human development the neuroectoderm appears and forms
the neural plate along the dorsal side of the embryo. The neural plate is
the source of the majority of neurons and glial cells of the CNS. A
groove forms along the long axis of the neural plate and, by week four
of development, the neural plate wraps in on itself to give rise to the
neural tube, which is filled with cerebrospinal fluid (CSF).

In the developing chordate (including vertebrates), the neural tube is

the embryo's precursor to the central nervous system, which comprises
the brain and spinal cord. The neural groove gradually deepens as the
neural folds become elevated, and ultimately the folds meet and
coalesce in the middle line and convert the groove into the closed
neural tube. In humans, neural tube closure usually occurs by the
fourth week of pregnancy (28th day after conception). The ectodermal
wall of the tube forms the rudiment of the nervous system. The centre
of the tube is the neural canal.

Four neural tube subdivisions each eventually develop into distinct

regions of the central nervous system by the division of neuroepithelial
cells: the forebrain (prosencephalon), the midbrain (mesencephalon),
the hindbrain (rhombencephalon) and the spinal cord.

The prosencephalon further goes on to develop into the

telencephalon (cerebrum) and the diencephalon (the optic
vesicles and hypothalamus).
The mesencephalon stays as the midbrain.
The rhombencephalon develops into the metencephalon (the
pons and cerebellum) and the myelencephalon (the medulla
oblongata).

For a short time, the neural tube is open both cranially and caudally.
These openings, called neuropores, close during the fourth week in
humans. Improper closure of the neuropores can result in neural tube
defects such as anencephaly or spina bifida.

The dorsal part of the neural tube contains the alar plate, which is
associated primarily with sensation. The ventral part of the neural tube
contains the basal plate, which is primarily associated with motor (i.e.,
muscle) control.

As the embryo develops, the anterior part of the neural tube forms a
series of bulges called vesicles, which become the primary anatomical
regions of the brain: the forebrain (prosencephalon), midbrain
(mesencephalon), and hindbrain (rhombencephalon). These simple,
early vesicles enlarge and further divide into the telencephalon (future
cerebral cortex and basal ganglia), diencephalon (future thalamus and
hypothalamus), mesencephalon (future colliculi), metencephalon
(future pons and cerebellum), and myelencephalon (future medulla).

The CSF-filled central chamber is continuous from the telencephalon to

the spinal cord, and constitutes the developing ventricular system of
the CNS. Because the neural tube gives rise to the brain and spinal cord
any mutations at this stage in development can lead to lethal
deformities like anencephaly or lifelong disabilities like spina bifida.
During this time, the walls of the neural tube contain neural stem cells,
which drive brain growth as they divide many times. Gradually some of
the cells stop dividing and differentiate into neurons and glial cells,
which are the main cellular components of the CNS. The newly
generated neurons migrate to different parts of the developing brain to
self-organize into different brain structures.

Once the neurons have reached their regional positions, they extend
axons and dendrites, which allow them to communicate with other
neurons via synapses. Synaptic communication between neurons leads
to the establishment of functional neural circuits that mediate sensory
and motor processing, and underlie behavior.

During early embryonic development the ectoderm becomes specified

to give rise to the epidermis (skin) and the neural plate. The conversion
of undifferentiated ectoderm to neuro-ectoderm requires signals from
the mesoderm. At the onset of gastrulation presumptive mesodermal
cells move through the dorsal blastopore lip and form a layer in
between the endoderm and the ectoderm. These mesodermal cells
that migrate along the dorsal midline give rise to a structure called the
notochord. Ectodermal cells overlying the notochord develop into the
neural plate in response to a diffusible signal produced by the
notochord. The remainder of the ectoderm gives rise to the epidermis
(skin). The ability of the mesoderm to convert the overlying ectoderm
into neural tissue is called neural induction.

The neural plate folds outwards during the third week of gestation to
form the neural groove. Beginning in the future neck region, the neural
folds of this groove close to create the neural tube. The formation of
the neural tube from the ectoderm is called neurulation. The ventral
part of the neural tube is called the basal plate; the dorsal part is called
the alar plate. The hollow interior is called the neural canal. By the end
of the fourth week of gestation, the open ends of the neural tube,
called the neuropores, close off.

Late in the fourth week, the superior part of the neural tube flexes at
the level of the future midbrainthe mesencephalon. Above the
mesencephalon is the prosencephalon (future forebrain) and beneath it
is the rhombencephalon (future hindbrain).

The optical vesicle (which eventually become the optic nerve, retina
and iris) forms at the basal plate of the prosencephalon. The alar plate
of the prosencephalon expands to form the cerebral hemispheres (the
telencephalon) whilst its basal plate becomes the diencephalon. Finally,
the optic vesicle grows to form an optic outgrowth.

Neuronal Formation
Within the brain and the spinal cord the fundamental organisation of
the neurons is into 'columns' or groupings of cells within both the
sensory and motor regions of the brain and within the grey matter of
the spinal cord. Groups of neurons with similar functions are able to
form 'nuclei'. Cranial nerve nuclei can include both motor and sensory
neurons and are able to undertake a wide variety of functions and
tasks. Cranial nerves can also convey fibres from multiple cranial nerve
nuclei. Within the spinal cord specific columns of neurones, or 'spinal
tracts' convey specific information to high centres in the brain.

Congenital anomalies.

Practically any part of the nervous system can show defects of

development, and these produce a wide variety of clinical signs and
symptoms. Only the common defects of the central nervous system are
considered here. Spina bifida, hydrocephalus, and anencephaly each
occur about 6 times per 1,000 births and are therefore the more
common congenital anomalys.

Spina Bifida
In spina bifida, the spines and arches of one or more adjacent vertebrae
fail to develop. The condition occurs most frequently in the lower
thoracic, lumbar, and sacral regions. Beneath this defect, the meninges
and spinal cord may or may not be involved to varying degrees. The
condition is a result of failure of the mesenchyme, which grows in
between the neural tube and the surface ectoderm, to form the
vertebral arches in the affected region. The types of spina bifida are as
follows:

Spina bifida occulta. The spines and arches of one or more

vertebrae, usually in the lumbar region, are absent, and the
vertebral canal remains open posteriorly. The spinal cord and
nerve roots usually are normal. The defect is covered by the
postvertebral muscles and cannot be seen from the surface. A
small tuft of hair or a fatty tumor may be present over the defect.
Most cases are symptomless and are diagnosed by chance when
the vertebral column is x-rayed.
Meningocele. The meninges project through the defect in the
vertebral arches, forming a cystic swelling beneath the skin and
containing cerebrospinal fluid, which communicates with the
subarachnoid space. The spinal cord and nerves usually are
normal.
Meningomyelocele. The normal spinal cord, or cauda equina, lies
within the meningeal sac, which projects through the vertebral
arch defect. The spinal cord or nerve roots are adherent to the
inner wall of the sac.
Myelocele. The neural tube fails to close in the region of the
defect. An oval raw area is found on the surface; this represents
the neural groove whose lips are fused. The central canal
discharges clear cerebrospinal fluid onto the surface.
Syringomyelocele. This condition is rare. A meningomyelocele is
present, and in addition, the central canal of the spinal cord at the
level of the bony defect is grossly dilated.

Spina bifida occulta is the most common defect. The next most
common defect is myelocele, and many afflicted infants are born dead.
If the child is born alive, death from infection of the spinal cord may
occur within a few days.
Most cases of spina bifida occulta require no treatment. A meningocele
should be removed surgically within a few days of birth. Infants with
meningomyelocele should also be treated surgically. The sac is opened,
and the spinal cord or nerves are freed and carefully replaced in the
vertebral canal. The meninges are sutured over the cord and the
postvertebral muscles are approximated.

As the result of advances in medical and surgical care, many infants

with the severe forms of spina bifida now survive. Unfortunately, these
children are likely to have lifelong disabilities and psychosocial
problems. The neurologic deficits alone may result in deformation of
the limbs and spine and in bladder, bowel, and sexual dysfunction.

Hydrocephalus
Hydrocephalus is an abnormal increase in the volume of cerebrospinal
fluid within the skull. The condition may be associated with spina bifida
and meningocele. Hydrocephalus alone may be caused by stenosis of
the cerebral aqueduct or, more commonly, by the normal single
channel being represented by many inadequate minute tubules.
Another cause, which is progressive, is the overgrowth of neuroglia
around the aqueduct. Inadequate development or failure of
development of the interventricular foramen, or the foramina of
Magendie and Luschka, may also be responsible.
In cases of hydrocephalus with spina bifida, the Arnold-Chiari
phenomenon may occur. During development, the cephalic end of the
spinal cord is fixed by virtue of the brain residing in the skull, and in the
presence of spina bifida, the caudal end of the cord may also be fixed.
The longitudinal growth of the vertebral column is more rapid and
greater than that of the spinal cord, and this results in traction pulling
the medulla and part of the cerebellum through the foramen magnum.
This displacement of the hindbrain downward obstructs the flow of
cerebrospinal fluid through the foramina in the roof of the fourth
ventricle.
Hydrocephalus may occur before birth, and if it is advanced, it could
obstruct labor. It usually is noticed during the first few months of life
because of the enlarging head, which may attain a huge size,
sometimes measuring more than 30 inches in diameter. The cranial
sutures are widely separated, and the anterior fontanelle is much
enlarged. The veins of the scalp are distended, and the eyes look
downward. Cranial nerve paralyses are common. The ventricles of the
brain become markedly dilated. This ventricular expansion occurs
largely at the expense of the white matter, and the neurons of the
cerebral cortex are mostly spared. This results in the preservation of
cerebral function, but the destruction of the tracts, especially the
corticobulbar and corticospinal tracts, produces a progressive loss of
motor function.

Anencephaly
In anencephaly, the greater part of the brain and the vault of the skull
are absent. The anomaly is caused by the failure of the rostral end of
the neural tube to develop, and as a consequence, its cavity remains
open. In place of the normal neural tissue, there are thin-walled
vascular channels resembling the choroid plexus and masses of neural
tissue. Although the eyes are present, the optic nerves are absent.

The condition commonly involves the spinal cord, and the neural tube
remains open in the cervical region. The condition is commonly
diagnosed before birth with sonography or x-ray studies. Most
anencephalic infants are stillborn or die shortly after birth.
 Prevention of Neural Defects With Folic Acid

The development and closure of the neural tube are normally

completed within 28 days. In practical terms, this means that neural
tube defects have occurred before many women are aware that they
are pregnant.

Extensive clinical research has demonstrated that environmental and

genetic factors have a joint role in the causation of neural tube defects.
The increased risk of neural defects in the lower socioeconomic groups
suggests that poor nutrition may also be an important factor. More
recent clinical research has demonstrated that the risk of recurrent
neural defects is significantly reduced among women who take 4,000
mg of folic acid daily compared with women who do not. Further
studies have shown that a daily dose that is 10 times lower is effective
in preventing the defect. These findings have stimulated much new
research to identify the genetic and biochemical bases of neural tube
defects.
Because as many as 50% of pregnancies in the United States are
unplanned and since the neural tube closes before most women know
that they are pregnant, physicians should strongly urge women capable
of becoming pregnant to consume at least 400 mg of folic acid per day,
preferably in a multivitamin supplement.