Lectures Psychiatric and
Neurological Disorders
MINOR BIOMEDICAL TOPICS IN HEALTH CARE
Content
Introduction ...................................................................................................................................................................... 1
Brain MRI........................................................................................................................................................................... 1
Depression: clinical aspects ............................................................................................................................................ 11
Depression: preclinical research ..................................................................................................................................... 20
Obsessive compulsive disorders ..................................................................................................................................... 25
Preclinical models of compulsive drug use ..................................................................................................................... 32
Autism spectrum disorder .............................................................................................................................................. 36
Brain tumors ................................................................................................................................................................... 39
ADHD: clinical and preclinical aspects ............................................................................................................................ 44
Multiple Sclerosis: clinical aspects .................................................................................................................................. 50
Multiple Sclerosis: preclinical aspects ............................................................................................................................ 58
Parkinson’s disease: clinical aspects ............................................................................................................................... 64
Parkinson’s disease: preclinical aspects.......................................................................................................................... 70
Parkinson’s disease: rehabilitation ................................................................................................................................. 76
Dementia: diagnostics and treatments........................................................................................................................... 80
Dementia: preclinical aspects ......................................................................................................................................... 86
Cerebrovascular accident (stroke) and rehabilitation .................................................................................................... 91
Neurorehabilitation program........................................................................................................................................ 103
Site visit Leo Polak and dementia care ......................................................................................................................... 109
,Introduction
The human brain
- 100.000.000.000 neurons
- With 7000 synapses on average
- Multiple neurotransmitters
- Glial cells
With all these connections and cells, a lot can go wrong → ending up in a certain brain disease (1 in 4 people)
These also play a role in the immune system of the brain
Aim NPD
Acquire knowledge on diagnostics, therapies, biological mechanisms underlying psychiatric/neurological disorders
- ADHD, brain tumors & CVAs, Alzheimer’s disease, OCD, MS, autism, Parkinson’s disease, depression,
neuroimaging
Course content
- Lectures
- Group sessions/debate (Sept 28)
- Project assignment and presentation (Oct 12, 14) (30% final mark)
- Virtual site visit nursing home (date to be set, Oct 5-9) → Leo Polakhuis
- Exam, open and multiple-choice questions (Oct 22) → materials: literature and lectures (70% final mark)
Project assignment
The main goal of the project assignment is to describe and provide arguments for the pros and cons of
pharmacological and non-pharmacological therapies used for one of the disorders presented in the course.
The subjects that should be focussed upon with each project group are:
- Background of the disease
- What is the target therapy?
- E.g. body, mind, tissue, cell, molecule, process; is the treatment curative or palliative?
- How easily can the therapy be applied?
- E.g. route of administration, strain for the patient both physically and mentally, what are the cost
aspects, is informal care essential?
- What is the effect size of the therapy?
- E.g. medically and socially, evidence from epidemiological studies
- Are there any side effects associated with the therapy? (medically or socially)
- Conclusion and therapy recommendations
Brain MRI
Learning objectives
- Understand application/possibilities of neuroimaging in clinic and research
- Recognize abnormalities on brain scans
- Understand their underlying pathology
- Understand application of different MRI sequences/techniques in MS
Neuroanatomy
Every lobe has a different function, which is very important in brain
imaging, because the different types of damage and disorders that you
see in the brain, affect the patient’s differently depending on where the
damage is located
1
,Anatomical planes:
Remember: right is left, and left is right!!
- Axial/transverse: from top to bottom
- Coronal: from back to front
- Sagittal: from right to left
Neuroimaging: why?
- Clinic
- Diagnosis/prognosis
- CT, MRI, MRA, MRS, angiography, X-ray
- Research
- Improve diagnostics
- Prediction
- Post-mortem MRI & histopathology
- Understand biological processes (using advanced imaging techniques)
Neuroimaging – clinic
Stroke/cerebrovascular accident (CVA)/stroke:
- When blood flow to a part of your brain is stopped either by a blockage (ischemic) or the rupture
(hemorrhagic) of a blood vessel
- Often very acute, CT-scans are used because these are faster (look at the amount of damage)
- Loss of brain function due to disturbance in blood supply
- Hemorrhage/hematoma
- Bleeding trauma
- 20% of cases
- Ischemia
- Lack of blood flow (non-bleeding trauma)
- 80% of cases
- Transient ischemic attack (TIA) → symptoms disappear <24h
- Reversible ischemic neurological deficit (RIND) → symptoms disappear between 24h
and 6 weeks
Hemorrhage
2
,Epidural hematoma (rupture a. meningea media)
- Delayed onset of symptoms
- Slight pressure against brain tissue
- Between dura mater and skull
- Acute (trauma) → because it’s usually associated with skull fracture
- CT instead of MRI (faster and you don’t need very detailed pictures)
- ‘Lens-shaped’
- Symptoms: loss of consciousness (disappears), progressive headache (because of build up of pressure and
blood), nausea, fluid draining from nose or ears (CSF) (it has nowhere else to go)
Subdural hematoma (rupture cortical veins)
- Between dura mater and arachnoid
- More often than epidural
- This does not originate from arteries, but from veins → bridging veins
- Slow build-up of blood
- Acute (<24 hours), subacute (<10 days) and chronic (>10 days)
- Acute subdural hematoma is the most fatal, as there is a rapid development of blood build-up and
pressure, and they are usually larger than the other two types
- Intracranial pressure (unconsciousness; stiff pupil)
- Pressure on the left side, shift towards the right side
Herniation
Pressure because of the bleeding, therefore the brain starts to move
Depending on the cause there are different types of herniations:
1. Uncal herniation → downwards toward the cerebellum
2. Central → third ventricle is being compressed
3. Cingulate → compression of one ventricle towards the other
4. Transcalvarial → the brain tissue herniates outside of the skull, this happens
when you have a skull fracture
5. Upward cerebellar
6. Downward cerebellar → this is fatal, because the brain stem is pressured
(which regulates very basic functions)
3
,Other causes of bleeding
- Hypertension (high blood pressure)
- Aneurysm (enlargement of an artery caused by weakness in the arterial wall)
- Arteriovenous malformation (AVM) (tangle of abnormal blood vessels connecting arteries and veins in the
brain)
- Often intracerebral/intraparenchymal hemorrhage
Aneurysm
- Acute headache (‘something snaps’)
- Nausea
- Loss of consciousness → in severe cases these can
lead to a coma
- The walls of a blood vessel becomes thinner, a little
balloon is formed (aneurysm), this balloon has very
thin walls and therefore breaks open → results in
bleeding into the surrounding brain tissue
AVM: conventional T2 SE MRI
This is an abnormal connection between arteries and veins
It’s asymptomatic, if there are symptoms it depends on the location (headaches, epilepsy)
AVM: TOF-MRA (MIP reconstruction)
TOF = time of flight; MRA = magnetic resonance angiography; MIP = maximum
intensity projection
This image makes blood flow visible by using magnification, there is no contrast
required in this scan
The asymmetry is clearly shown in this image
Difference between AVM and aneurysm
The right picture is an aneurysm (there is a little balloon
and the cells look quite organised)
The left picture looks a bit messier and is therefore an
AVM
You can also see that the arteries and veins are not
properly connected with each other
4
, Ischemic stroke
An ischemic stroke occurs when a vessel supplying blood to the brain is obstructed
Causes
- Blood vessels:
- Atherosclerosis (thickening artery wall) → because of cholesterol, smoking, diabetes, obesity
- Hypertension (vasospasm; vasoconstriction) → thickened artery walls
- Carotid stenosis (narrowing of arteries) → less blood flow to the brain
- Vasculitis (blood vessel inflammation)
- Blood:
- Thrombocytosis (more thrombocytes → blood clotting)
- Cardial:
- Embolism (blockage of artery/vein by blood clot)
Brain tumors
- Give rise to different neurological deficits, these are very dependent on the locations in the brain
- Symptoms as a result of increased intracranial pressure (herniation) → the mass of carcinogenic cells, there
is no blood involved
- Epilepsy
- Headache in the morning (after lying down for hours) & vomiting without nausea
- Origin in neurons or glia cells
- Benign: meningioma (arise in the meninges), pituitary tumors
- Malignant: glioma (tumor of the glia cells), lymphoma (tumor of white blood cells)
- Treatment: resection (cut off the part of the brain that has the tumor), radiation, chemotherapy
- These three treatments are usually combined
→ very large brain tumor (midline shift, herniation)
Hematoma is quite even, whereas a tumor also affects a lot of the surrounding tissue
Neuroimaging – research
- Qualitative
- Standard clinical practice
- Look for pathology (not measuring, but looking at pressure, herniation, tumors, etc.)
- Quantitative
- Numbers as output
- Understand biological mechanisms
- Compare patient groups to healthy controls
5
Neurological Disorders
MINOR BIOMEDICAL TOPICS IN HEALTH CARE
Content
Introduction ...................................................................................................................................................................... 1
Brain MRI........................................................................................................................................................................... 1
Depression: clinical aspects ............................................................................................................................................ 11
Depression: preclinical research ..................................................................................................................................... 20
Obsessive compulsive disorders ..................................................................................................................................... 25
Preclinical models of compulsive drug use ..................................................................................................................... 32
Autism spectrum disorder .............................................................................................................................................. 36
Brain tumors ................................................................................................................................................................... 39
ADHD: clinical and preclinical aspects ............................................................................................................................ 44
Multiple Sclerosis: clinical aspects .................................................................................................................................. 50
Multiple Sclerosis: preclinical aspects ............................................................................................................................ 58
Parkinson’s disease: clinical aspects ............................................................................................................................... 64
Parkinson’s disease: preclinical aspects.......................................................................................................................... 70
Parkinson’s disease: rehabilitation ................................................................................................................................. 76
Dementia: diagnostics and treatments........................................................................................................................... 80
Dementia: preclinical aspects ......................................................................................................................................... 86
Cerebrovascular accident (stroke) and rehabilitation .................................................................................................... 91
Neurorehabilitation program........................................................................................................................................ 103
Site visit Leo Polak and dementia care ......................................................................................................................... 109
,Introduction
The human brain
- 100.000.000.000 neurons
- With 7000 synapses on average
- Multiple neurotransmitters
- Glial cells
With all these connections and cells, a lot can go wrong → ending up in a certain brain disease (1 in 4 people)
These also play a role in the immune system of the brain
Aim NPD
Acquire knowledge on diagnostics, therapies, biological mechanisms underlying psychiatric/neurological disorders
- ADHD, brain tumors & CVAs, Alzheimer’s disease, OCD, MS, autism, Parkinson’s disease, depression,
neuroimaging
Course content
- Lectures
- Group sessions/debate (Sept 28)
- Project assignment and presentation (Oct 12, 14) (30% final mark)
- Virtual site visit nursing home (date to be set, Oct 5-9) → Leo Polakhuis
- Exam, open and multiple-choice questions (Oct 22) → materials: literature and lectures (70% final mark)
Project assignment
The main goal of the project assignment is to describe and provide arguments for the pros and cons of
pharmacological and non-pharmacological therapies used for one of the disorders presented in the course.
The subjects that should be focussed upon with each project group are:
- Background of the disease
- What is the target therapy?
- E.g. body, mind, tissue, cell, molecule, process; is the treatment curative or palliative?
- How easily can the therapy be applied?
- E.g. route of administration, strain for the patient both physically and mentally, what are the cost
aspects, is informal care essential?
- What is the effect size of the therapy?
- E.g. medically and socially, evidence from epidemiological studies
- Are there any side effects associated with the therapy? (medically or socially)
- Conclusion and therapy recommendations
Brain MRI
Learning objectives
- Understand application/possibilities of neuroimaging in clinic and research
- Recognize abnormalities on brain scans
- Understand their underlying pathology
- Understand application of different MRI sequences/techniques in MS
Neuroanatomy
Every lobe has a different function, which is very important in brain
imaging, because the different types of damage and disorders that you
see in the brain, affect the patient’s differently depending on where the
damage is located
1
,Anatomical planes:
Remember: right is left, and left is right!!
- Axial/transverse: from top to bottom
- Coronal: from back to front
- Sagittal: from right to left
Neuroimaging: why?
- Clinic
- Diagnosis/prognosis
- CT, MRI, MRA, MRS, angiography, X-ray
- Research
- Improve diagnostics
- Prediction
- Post-mortem MRI & histopathology
- Understand biological processes (using advanced imaging techniques)
Neuroimaging – clinic
Stroke/cerebrovascular accident (CVA)/stroke:
- When blood flow to a part of your brain is stopped either by a blockage (ischemic) or the rupture
(hemorrhagic) of a blood vessel
- Often very acute, CT-scans are used because these are faster (look at the amount of damage)
- Loss of brain function due to disturbance in blood supply
- Hemorrhage/hematoma
- Bleeding trauma
- 20% of cases
- Ischemia
- Lack of blood flow (non-bleeding trauma)
- 80% of cases
- Transient ischemic attack (TIA) → symptoms disappear <24h
- Reversible ischemic neurological deficit (RIND) → symptoms disappear between 24h
and 6 weeks
Hemorrhage
2
,Epidural hematoma (rupture a. meningea media)
- Delayed onset of symptoms
- Slight pressure against brain tissue
- Between dura mater and skull
- Acute (trauma) → because it’s usually associated with skull fracture
- CT instead of MRI (faster and you don’t need very detailed pictures)
- ‘Lens-shaped’
- Symptoms: loss of consciousness (disappears), progressive headache (because of build up of pressure and
blood), nausea, fluid draining from nose or ears (CSF) (it has nowhere else to go)
Subdural hematoma (rupture cortical veins)
- Between dura mater and arachnoid
- More often than epidural
- This does not originate from arteries, but from veins → bridging veins
- Slow build-up of blood
- Acute (<24 hours), subacute (<10 days) and chronic (>10 days)
- Acute subdural hematoma is the most fatal, as there is a rapid development of blood build-up and
pressure, and they are usually larger than the other two types
- Intracranial pressure (unconsciousness; stiff pupil)
- Pressure on the left side, shift towards the right side
Herniation
Pressure because of the bleeding, therefore the brain starts to move
Depending on the cause there are different types of herniations:
1. Uncal herniation → downwards toward the cerebellum
2. Central → third ventricle is being compressed
3. Cingulate → compression of one ventricle towards the other
4. Transcalvarial → the brain tissue herniates outside of the skull, this happens
when you have a skull fracture
5. Upward cerebellar
6. Downward cerebellar → this is fatal, because the brain stem is pressured
(which regulates very basic functions)
3
,Other causes of bleeding
- Hypertension (high blood pressure)
- Aneurysm (enlargement of an artery caused by weakness in the arterial wall)
- Arteriovenous malformation (AVM) (tangle of abnormal blood vessels connecting arteries and veins in the
brain)
- Often intracerebral/intraparenchymal hemorrhage
Aneurysm
- Acute headache (‘something snaps’)
- Nausea
- Loss of consciousness → in severe cases these can
lead to a coma
- The walls of a blood vessel becomes thinner, a little
balloon is formed (aneurysm), this balloon has very
thin walls and therefore breaks open → results in
bleeding into the surrounding brain tissue
AVM: conventional T2 SE MRI
This is an abnormal connection between arteries and veins
It’s asymptomatic, if there are symptoms it depends on the location (headaches, epilepsy)
AVM: TOF-MRA (MIP reconstruction)
TOF = time of flight; MRA = magnetic resonance angiography; MIP = maximum
intensity projection
This image makes blood flow visible by using magnification, there is no contrast
required in this scan
The asymmetry is clearly shown in this image
Difference between AVM and aneurysm
The right picture is an aneurysm (there is a little balloon
and the cells look quite organised)
The left picture looks a bit messier and is therefore an
AVM
You can also see that the arteries and veins are not
properly connected with each other
4
, Ischemic stroke
An ischemic stroke occurs when a vessel supplying blood to the brain is obstructed
Causes
- Blood vessels:
- Atherosclerosis (thickening artery wall) → because of cholesterol, smoking, diabetes, obesity
- Hypertension (vasospasm; vasoconstriction) → thickened artery walls
- Carotid stenosis (narrowing of arteries) → less blood flow to the brain
- Vasculitis (blood vessel inflammation)
- Blood:
- Thrombocytosis (more thrombocytes → blood clotting)
- Cardial:
- Embolism (blockage of artery/vein by blood clot)
Brain tumors
- Give rise to different neurological deficits, these are very dependent on the locations in the brain
- Symptoms as a result of increased intracranial pressure (herniation) → the mass of carcinogenic cells, there
is no blood involved
- Epilepsy
- Headache in the morning (after lying down for hours) & vomiting without nausea
- Origin in neurons or glia cells
- Benign: meningioma (arise in the meninges), pituitary tumors
- Malignant: glioma (tumor of the glia cells), lymphoma (tumor of white blood cells)
- Treatment: resection (cut off the part of the brain that has the tumor), radiation, chemotherapy
- These three treatments are usually combined
→ very large brain tumor (midline shift, herniation)
Hematoma is quite even, whereas a tumor also affects a lot of the surrounding tissue
Neuroimaging – research
- Qualitative
- Standard clinical practice
- Look for pathology (not measuring, but looking at pressure, herniation, tumors, etc.)
- Quantitative
- Numbers as output
- Understand biological mechanisms
- Compare patient groups to healthy controls
5
