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Everything you need to know for the exam of Clinical Neurosciences (AM_1005)

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Vrije Universiteit Amsterdam (VU)

Everything you need to know for the exam of Clinical Neurosciences (AM_1005). All lectures included, explained, with supportive images. Course given in the master Neurosciences, at VU Amsterdam.

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Clinical Neurosciences

HC 1 – Introduction
Questions:

About: clinical characteristics and pathophysiology of brain disorders. Etiology and pathophysiology of
brain-related diseases/disorders. Working mechanisms of existing treatments. Develop new
treatments. Common and distinct pathological features across brain-related diseases/disorders.
Precision medicine. Predictive biomarkers (treatment and progression). Clinical neuroscience is
multidisciplinary.

On 21/11 or 24/11 group presentation;
- 3/4 students
- A recent and ground-breaking finding on chosen topic, with original data (e.g. no reviews) example
of clinical neuroscience (i.e. no clinical trials)
- 15 min presentation, 5 min discussion
- Upload your PP prior to presentation
- 5 sessions, 4 groups per session
- 30% of grade

Exam: MC and open questions. 70%.

HC 2 – Brain/neural development
Neural development refers to the processes that generate, shape, and reshape the nervous system,
from the earliest stages of embryogenesis to the final years of life. The study of neural development
aims to describe the cellular basis of brain development and to address the underlying mechanisms.
The field draws on both neuroscience and developmental biology to provide insight into the cellular
and molecular mechanisms by which complex nervous systems develop. Defects in neural
development can lead to cognitive and motor impairment, as well as neurological disorders such as
autism, Rett syndrome, and intellectual disability. Brain development can be categorized on a timeline
(Figure 1). First you have prenatal development, than growth that continues during childhood.
Neurogenesis (growth of brain) is very important in foetal development, together with ventricular
formation, neuronal migration. Building the human CNS requires the precise orchestration and
coordination of myriad molecular and cellular processes across a staggering array of cell types and over
a long period of time. Dysregulation of these processes affects the structure and function of the CNS
and can lead to neuro- logical or psychiatric disorders. Recent technological advances and increased
focus on human neurodevelopment have enabled a more comprehensive characterization of the
human CNS and its development in both health and disease.

The growth of the head reflects the growth of the brain, and/or the amount of spinal fluid. Growth of
the head in children is measured by the head circumference. Small head is microcephaly, large head
macrocephaly. Hydrocephaly; sometimes in the circulation of spinal fluid there is an obstruction, due
to this obstruction the pressure in the brain is too high, and the brain starts to grow.

You can look at the development of the child, and the milestones it gets (Figure 1); divided into 4
domains: sensorimotor (sensor and motor development), communication, social-emotional, cognitive.
Example of motor development test in new born baby; shining light in eyes, reacting to sounds;

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, Clinical Neurosciences

Figure 1 – Developmental stages of the Central Nervous System, together with developmental milestones.

reaction to stimuli. In 3 month old baby; child is more active, head up, rolls over. Rolling over is one of
the important motor milestones. This change is probably due to more myelinization and neurogenesis.
Child of 12 months; sits on its own, development of fine motor skills (e.g. pincher grasp; develops
between 10-12 months old), child develops dominant hand around the age of 3-4 years. If you see a
dominant hand earlier, it might be because of a problem in the system.

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, Clinical Neurosciences

Many diseases have their own time period in life that they appear (Figure 2). For child; developmental
problems, autism, concentration problems. For later in life anxiety and mental disorders.
Neurodegenerative diseases occur even later.

Figure 2 – Psychiatric and Neurological disorders have discrete ages of onset.

The human CNS exhibits the organizing principles and developmental pattern typical of all mammals;
it begins as a simple neural tube that breaks off from the embryonic ectoderm and gradually acquires
mature organizational features through immensely complex and strictly regulated molecular and
cellular processes. Studies of model organisms have provided fundamental insights into many human
neurodevelopmental processes Neurulation refers to the inductive events that occur on the dorsal
aspect of the embryo and results
in the formation of the brain and
spinal cord. The nervous system is
derived from the ectoderm—the
outermost tissue layer—of the
embryo. In the third week of
development the neuroectoderm
appears and forms the neural
plate along the dorsal side of the
embryo. This neural plate is the
source of the majority of neurons
and glial cells in the mature
human. A groove forms in the
neural plate and, by week four of
development, the neural plate
wraps in on itself to make a hollow
neural tube. Because this neural
tube later 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.

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Figure 3 – Neurulation.

, Clinical Neurosciences

Neurulation is the formation of the neural tube from the ectoderm of the embryo. It follows
gastrulation in all vertebrates. During gastrulation cells migrate to the interior of embryo, forming
three germ layers — the endoderm (the deepest layer), mesoderm and ectoderm (the surface layer)
— from which all tissues and organs will arise. In a simplified way, it can be said that the ectoderm
gives rise to skin and nervous system, the endoderm to the guts and the mesoderm to the rest of the
organs.

After gastrulation the notochord — a flexible, rod-shaped body that runs along the back of the embryo
— has been formed from the mesoderm. During the third week of gestation the notochord sends
signals to the overlying ectoderm, inducing it to become neuroectoderm. This results in a strip of
neuronal stem cells that runs along the back of the embryo. This strip is called the neural plate, and is
the origin of the entire nervous system. The neural plate folds outwards to form the neural groove.
Beginning in the future neck region, the neural folds of this groove close to create the neural tube (this
form of neurulation is called primary neurulation). The ventral (front) part of the neural tube is called
the basal plate; the dorsal (rear) 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 (the neuropores)
close off. 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.

Spina bifida: neural tube defect, the neural tube is not closed. This can lead to problems with paralysis,
motor skills (problems with muscles in the legs), sensory (e.g. blisters because they don’t feel
pressure), impaired reflexes (some reflexes are absent), autonomic dysfunction (dysfunction of the
bladder, hydrocephalus, and intestines). Because of the introduction of the 20-week ultrasound and
folic acid the prevalence has decreased a lot.

Neurofibromatosis; because the CNS was a part of the ectoderm, problems can arise in the skin (the
neural crest tissue is ‘left out’ when the neural tube forms). This is a genetic disease, that leads to small
tumours and formation of melanocytes of the skin, and in the brain dorsal (posterior) root ganglia,
enteric plexi, and chromaffin cells of the medulla. These individuals have intellectual disabilities.

Between the weeks 4 and 8, in the embryo there is
regionalization. In the fifth week, the alar plate of the
prosencephalon expands to form the cerebral
hemispheres (the telencephalon). The basal plate
becomes the diencephalon. The diencephalon,
mesencephalon and rhombencephalon constitute the
brain stem of the embryo. It continues to flex at the
mesencephalon. The rhombencephalon folds
posteriorly, which causes its alar plate to flare and
form the fourth ventricle of the brain. The pons and
the cerebellum form in the upper part of the
rhombencephalon, whilst the medulla oblongata
forms in the lower part.

Figure 4 – Regionalization.
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