Development of the Brain

Question 1

The brain begins to develop in the ____(a)____ week of development. The neural tube develops from the neuroectoderm. The cranial broad 2/3 of the neural tube represents the brain and the caudal narrow 1/3 represents the spinal cord. The cranial neuropore closes on the ____(b)____ day and the caudal neuropore closes on the ____(c)____ day. Neurulation is then complete and the CNS is represented by by a closed tubular structure. After closure of the neuropores, the brain shows three primary vesicles namely: the forebrain (prosencephalon), midbrain (mesencephalon) and hindbrain (rhombencephalon). During the ____(d)____ week, the forebrain partly divides into two secondary brain vesicles, the ____(e)____ and ____(f)____. The midbrain does not divide. The hindbrain partly divides into two secondary vesicles: the ____(g)____ and ____(h)____.

Answer 1

(a) 3rd
(b) 25th
(c) 27th
(d) 5th
(e) telencephalon [and] (f) diencephalon
(g) metencephalon [and] (h) myelencephalon

[Diagram]

Question 2

Primary and Secondary Brain Flexures
Primary: fold ventrally, Secondary: fold dorsally

During the fifth week, the embryonic brain grows rapidly and bends ventrally with the head fold. The bending produces the ____(1)____ flexure in the midbrain region and the ____(2)____ flexure at the junction of the hindbrain and spinal cord. Later, unequal growth of the brain between these flexures produces the ____(3)____ flexure in the opposite direction between the metencephalon and myelencephalon.

Answer 2

(1) midbrain/cephalic (primary flexure)
(2) cervical (primary flexure)
(3) pontine (secondary flexure)
[Diagram]

Question 3

State 4 differences between development of brain and spinal cord.

Answer 3

1. Alar and basal plates are recognizable only in the midbrain and hindbrain. In the forebrain alar plates are increased and basal plates disappear. The alar and basal plates are present throughout the developing spinal cord.
   [Picture: alar and basal plates]
   [Diagram: alar and basal plates]
2. The pontine flexure causes thinning of the roof of the hindbrain and movement of nuclei of medulla and pons; sensory nuclei move laterally and motor nuclei move medially. In the spinal cord, sensory nuclei are dorsal to motor nuclei.
   [Diagram: effects of pontine flexure]
3. Migration of neuroblasts causes grey mater to present mainly on the surface of the cerebrum and cerebellum (cerebral and cerebellar cortices), whereas in the spinal cord grey mater is central and surrounded by white mater.
4. Flexions as well as evaginations and protruberances explain why the final form of the brain differs from the simple linear tube. The brain undergoes flexions that fit it more compactly into the skull.

Question 4

1. The pontine flexure divides the hindbrain into caudal myelencephalon and rostral metencephalon. The myelencephalon becomes the ____(a)____ and the metencephalon becomes the ____(b)____.
2. State three consequences of the development of the pontine flexure on the development of the medulla.

Answer 4

1. (a) medulla oblongata
   (b) pons and cerebellum
2. The pontine flexure causes:
   - the lateral walls of the medulla to move laterally [hence the cavity of the myelencephalon (4th ventricle) becomes diamond shaped]
   - the roof plate to become stretched and greatly thinned
   - the alar plates become lateral to the basal plates; sensory nuclei develop lateral to motor nuclei.
   [Diagram: effects of pontine flexure]

Question 5

Choroid plexuses and cerebrospinal fluid
The stretched roof plate of the medulla consists of a single layer of ependymal cells covered by vascular mesenchyme, the pia mater. The ependyma and pia combined are known as ____(a)____. A number of vascular invaginations project into the cavity of the 4th ventricle. These tuft-like invaginations form the ____(b)____ which ____(c)____ [function of (b)].

Answer 5

(a) tela choroidea
(b) choroid plexus
(c) secretes cerebrospinal fluid

Question 6

The pons contains pontine nuclei originated from ____(a)____ plates. Axons of pontine nuclei grow transversely to enter the developing cerebellum forming the ____(b)____ and ____(c)____ [which cerebellar peduncle?].

Answer 6

(a) alar
(b) transverse pontine fibres
(c) middle cerebellar peduncle
(d) [Diagram]: Transverse Pontine Fibres

Question 7

The cerebellum develops from the ____(a)____, two thickenings of the dorsal parts of the alar plates of the metencephalon. ____(a)____ enlarge and fuse in the midline to form the ____(b)____. Lateral expansions of the ____(a)____ form the ____(c)____.

Answer 7

(a) rhombic lips
(b) vermis
(c) cerebellar hemispheres
[Diagram]

Question 8

The Midbrain
The basal plates of the midbrain contain two groups of cranial nerve motor nuclei: General Somatic Efferent neurons e.g. ____(a)____ nuclei and General Visceral Efferent neurons e.g. the ____(b)____ nucleus. Neuroblasts from the basal plates give rise to groups of neurons in the tegmentum in the midbrain e.g. ____(c)____ (3).

Cerebral peduncles are formed by fibres growing and descending from the cerebral cortex e.g. ____(d)____ fibres which pass through the ventral marginal layer of the developing midbrain to lower centres in the brainstem and spinal cord.

Answer 8

(a) oculomotor and trochlear nuclei
(b) Edinger-Westphal nucleus
(c) red nucleus, reticular nuclei, substantia nigra
(d) corticopontine, corticospinal and corticobulbar

Question 9

The prosencephalon (forebrain)
During the ____(a)____ week of development, a lateral diverticulum appears on each side of the prosencephalon (forebrain) named ____(b)____. The part of the prosencephalon cranial to the optic vesicles is the telencephalon and the rest forms the diencephalon.

Answer 9

(a) fourth
(b) optic vesicles
[Diagram]

Question 10

Briefly describe the development of the diencephalon.

Answer 10

The diencephalon develops from the median portion of the forebrain and consists of a roof plate and two alar plates but lacking basal and floor plates. The alar plates forming the lateral walls of the diencephalon proliferate and show three swellings that develop into the epithalamus, thalamus and hypothalamus.
Floor of the diencephalon gives rise to the posterior pituitary gland.

Question 11

At birth the brain is about 25% its adult volume. Postnatal growth of the brain is due to: ________________ (4 contributing factors).

Answer 11

1. increase in neuronal sizes
2. proliferation of neuronal processes
3. proliferation of astrocytes
4. myelination of nerve fibres

Question 12

Briefly discuss the following congenital malformations of the brain:
(a) cranium bifidum (encephalocele)
(b) anencephaly
(c) microcephaly

Answer 12

(a) cranium bifidum (encephalocele): This refers to a herniation of intracranial contents resulting from a defect in the cranium. The hernia may contain meninges (meningocele), meninges and part of the brain (meningoencephalocele), or meninges, part of the brain and part of the ventricular system (meningohydroencephalocele).
(b) anencephaly: most of the brain and skull vault are missing. It resluts from failure of closure of the rostral neuropore. Infants survive for only a few hours after birth.
(c) microcephaly/microencephaly: small cranial vault due to small brain; growth of calvaria is largely dependent on growth of the brain. The facial skeleton is of normal size. Causes may be genetic (autosomal recessive), teratogenetic (exposure to rubella virus, cytomegalovirus, toxoplasmosis, ionizing radiation and maternal alcohol abuse, or due to premature closure (synostosis) of the sutures of the skull. Microcephaly can be detected in utero by ultrasound.

Question 13

Hydrocephalus
(a) causes
(b) varieties (and explain)

Answer 13

(a) abnormal accumulation of CSF within ventricular system of the brain due to:
☑ impaired circulation
☑ impaired absorption
☑ increased secretion (by choroid adenoma)

(b) varieties:
☑ Obstructive (non-communicating) hydrocephalus: blockage of CSF flow is within the ventricular system, mainly due to aqueductal stenosis
☑ Non-obstructive (communicating) hydrocephalus: obliteration of the CSF circulation is in the subarachnoid space beyond the ventricular system and all ventricles are enlarged

Question 14

Briefly discuss Holoprocencephaly. Clinical presentations? [Holoprosencephaly is a disorder of regionalisation]

Answer 14

Forebrain fails to split into its two hemispheres during fetal development. It results in structural abnormalities in the brain and facial characteristics. Genetic factors, maternal diabetes and alcohol abuse can destroy embryonic cells of the median plane resulting in failure of the forebrain to invaginate or evaginate.
[Picture] [Diagram]
As you can observe from some of the images, the associated facial abnormalities include:
✓ anophthalmia and absence of the nose
✓ hypotelorism (closely set eyes) or cyclopia, a single central incisor tooth

Further notes:
There are are several forms of holoprosencephaly.
✓ alobar holoprosencephaly
✓ lobar holoprosencephaly (here, the midline structures e.g. thalami are fused)
✓ semilobar holoprosencephaly

Question 15

Hydranencephaly: description and cause

Answer 15

The brain’s cerebral hemispheres are largely absent, and the remaining cranial cavity is filled with cerebrospinal fluid. The brainstem is intact. Infants appear normal at birth; however the head grows excessively after birth due to excessive accumulation of CSF. There is failure of mental and cognitive development. The cause of this rare and severe anomaly is occlusion of blood flow to areas supplied by the internal carotid artery. It may also be caused by rubella virus.
[Picture 1] [Picture 2]

Question 16

____________________ is a group of disorders that affect a person’s ability to move and maintain balance and posture. Some of its symptoms include: poor coordination, stiff or loose muscles, tremors, abnormal or exaggerated reflexes, difficulty in speaking, excessive drooling …. It is caused by abnormal development or damage to the parts of the brain that control movement, balance, and posture.

Answer 16

Cerebral palsy

Question 17

State the 4 phases of CNS development.

Answer 17

1. Dorsal induction (entails neurulation: primary neurulation, 3rd to 4th week, primary NT and neural crest. Secondary neurulation is not complete until 8th week)
2. Ventral induction during 4th to 5th week (induction of rostral neural tube to form the different brain vesicles)- Primary goal: patterning of the forebrain.
3. Neuronal proliferation and migration
4. Myelination

Question 18

derivatives of optic vesicle

Answer 18

☯︎ Neural retina
☯︎ Retinal pigment epithelium
☯︎ Optic nerve

Question 19

Identify the developmental anomaly and state its embryological basis: [Image].

Answer 19

Lissencephaly: abnormal neuronal migration leading to a marked reduction or absence of the convolutional patter of the cerebral hemispheres.
[Radiograph]

Question 20

Identify the developmental anomaly: [Image].

Answer 20

Dandy-Walker Syndrome

Further notes:
It presents with cystic dilatation of the fourth ventricle as well as complete or partial agenesis of the vermis.
Symptoms of Dandy-Walker include slow motor development and large head size. Most of those affected develop hydrocephalus within the first year of life, which can present as increasing head size, vomiting, excessive sleepiness, irritability, downward deviation of the eyes and seizures.
Additional images: [Image 2] [Image 3]

Question 21

[Image]:
(a) State the name of this sign.
(b) What does this sign indicate?

Answer 21

(a) Sunset eye sign
(b) The Sunset eye sign is a clinical phenomenon encountered in infants and young children with raised intracranial pressure hence is often associated with hydrocephalus.