Neurological and Psychiatric Disorders.
Introduction.
The human brain consist of 100.000.000.000 neurons, with 7000 synapses on average. In
these networks function multiple neurotransmitters.
The purpose of this course is to acquire knowledge on diagnostics, therapies, biological
mechanisms underlying psychiatric or neurological disorders.
Examples of disorders are ADHD, brain tumors, CVA’s, Alzheimer’s disease, OCD, MS,
autism, depression, and Parkinson’s disease.
Brain imaging.
The brain is divided into different lobes:
- Frontal; association, planning, motivation, attention, reward.
- Parietal; language processing, spatial awareness, reading.
- Temporal; visual memories, language comprehension, emotion.
- Occipital; visual processing, vision.
The motor cortex is in the frontal lobe, and the somatosensory cortex is in the parietal lobe.
The three anatomical planes are axial (transverse), coronal, and sagittal (sword).
Neuroimaging is used in the clinic for diagnosis and prognosis. Examples are CT, MRI, MRA,
MRS, angiography, and X-ray. In research, neuroimaging is used to improve diagnostics,
prediction, post-mortem MRI and histopathology, and to understand biological processes
(using advances imaging techniques).
A cerebrovascular accident (CVA), i.e. stroke, is the loss of brain function due to disturbance in
blood supply. There are two forms of CVA:
1. Haemorrhage: 20%, bleeding trauma.
2. Ischemia: 80%, lack of blood flow.
a. TIA (= transient ischemic attack): symptoms disappear < 24 hours.
b. RIND (= reversible ischemic neurological deficit): symptoms disappear between 24
hours and 6 weeks.
Haemorrhage, i.e. hematoma, can occur in three different ways.
Epidural: rupture a. meningea media (outside dura mater).
Subdural: rupture cortical veins (between dura mater and arachnoid).
Intracerebral: mainly in putamen and thalamus (within pia mater).
An epidural hematoma often is lens-shaped and very acute, so CT is used instead of MRI to
act fast. Symptoms are loss of consciousness, progressive headache, nausea, and CSF
draining from nose or ears.
An subdural hematoma occurs more often than an epidural hematoma. The blood slowly
builds up (bridging veins), leading to intracranial pressure (less consciousness, stiff pupil). This
can happen acute (< 24 hours), subacute (<10 days) or chronic (>10 days).
Herniation happens when the brain is being pushed against the dura mater or skull.
Other causes are hypertension, aneurysm, and arteriovenous malformation (AVM).
,Magnetic resonance angiography (MRA) uses time of flight (TOF) and usually a maximum
intensity projection (MIP).
An ischemic stroke can be caused by:
- Embolism: blockage of artery/vein by blood clot.
- Thrombocytosis: an increase in thrombocytes, leading to blood clotting.
- Atherosclerosis: thickening of the artery wall.
- Hypertension: vasospasm, vasoconstriction.
- Carotid stenosis: narrowing of arteries.
- Vasculitis: blood vessel inflammation.
Brain tumors origin in neurons or glia cells. Symptoms are neurological deficits, epilepsy,
headache in the morning, and vomiting without nausea, as a result of herniation.
Benign: meningioma, pituitary tumors.
Malignant: glioma, lymphoma.
Possible treatments for brain tumors are resection, radiation, and chemotherapy.
Qualitative research is used for standard clinical practice and focuses on pathology.
Quantitative research focuses on biological mechanisms and compares patients to controls.
Magnetic resonance imaging (MRI) uses magnetism and radiofrequency signals to acquire
images. It is based on density and spins of protons, and can detect different types of tissue
because of different intensities of white matter, grew matter, and CSF.
T1-weighted scan: used for anatomy, contrast fat/water (fat = white).
T2-weighted scan: used for pathology, contrast water/tissue (water = white).
Multiple sclerosis (MS) is a neurodegenerative disease, paired with inflammation of the CNS.
This is caused by the attack of white blood cells, leading to demyelination of neurons. As a
result, physical and cognitive problems arise.
MS lesions are seen as white spots, where the white matter is damaged. These lesions often
are near to or in the ventricles. Around the ventricles, there are aging caps.
MS is diagnosed on the basis of the McDonald criteria:
- dissemination in space (DIS).
- dissemination in time (DIT).
The McDonalds criteria should only be applied in patients with clinically isolated syndrome
(CIS). CIS presentations can be monofocal or multifocal, and typically involve the optic nerve,
brain stem/cerebellum, spinal cord, or cerebra hemisphere.
These McDonald criteria have resulted in earlier diagnosis of MS with a high degree of both
specificity and sensitivity, allowing for better counselling and earlier treatment.
Both asymptomatic gadolinium-enhancing and non-enhancing lesions are highly specific for
predicting early development of clinically definite MS (CDMS). However, T2 lesions will still be
required to establish DIT.
MRI can be used to detect MS lesions, because it is highly sensitive and it reflects the duration
of the disease (cumulative history, T2). However, it lacks histopathological specificity and there
is moderate correlation with clinical disability (clinic-radiological paradox).
Acute inflammation occurs in 2-8 weeks, and is associated with disruption of the blood brain
barrier (BBB). It may coincide with relapse. Intravenous gadolinium on T1-weighted images.
, Black holes are associated with tissue loss; no remyelination, leading to axonal damage. This
is literary seen as a black hole on T1-weighted images. For this reason, black holes do
measure the severity of the disease.
For DIS, 1 of more T2 lesions in at least 2 out of 4 regions of the CNS (periventricular,
juxtacortical, infratentorial, spinal cord) must be present. Lesions in the juxtacortical regions
are against the grey matter; involvement of U-fibers and lesions in corpus callosum.
Cortical lesions in the grey matter can be detected by double inversion recovery (DIR) or fluid-
attenuated inversion recovery (FLAIR).
DIR is a MRI pulse sequence which suppresses signal from the CSF as well as from the
white matter and hence enhances any inflammatory lesion.
FLAIR is an MRI sequence with an inversion recovery set to null fluids.
Indication for spinal cord imaging are:
no incidental cord lesions with ageing / hypertension.
cord presentation: rule out compression and confirm MS lesions.
Increased sensitivity.
Increased specificity: in patient with inconclusive brain MR (e.g. hypertension).
Post-mortem imaging:
- Tissue dissection.
- Matching histopathology and MRI.
- No color no myelin.
- End-stage atrophy.
Brain tumors.
In normal tissue, the rates of new cell growth and old cell death are kept in balance. Cancer
arises from a loss of normal growth control. This can be caused by the loss of a cell’s ability to
undergo apoptosis. The tumor suppression gene p53 plays a major role in this process.
Invasion is direct migration and penetration into neighbouring tissues. Metastasis happens
when cancer cells penetrate into lymphatic system and blood vessels.
Benign tumors generally do not spread by invasion or metastasis. Malignant tumors are
capable of spreading by invasion and metastasis.
Primary brain tumors are rare; 6.4 per 100,000. You can live approximately 7 years with low-
grade gliomas (20%) and 1-2 years with high-grade gliomas (80%). Low-grade astrocytomas
become secondary glioblastoma in 5-10 years. Surgery, radiotherapy and chemotherapy can
increase the life expectancy.
Gliomas origin in glial cells. Different forms are:
Astrocytomas: low mitotic index, diffuse invasion, high rate of transformation.
Oligodendrocytes + astrocytes oligoastrocytomas: grade 3.
Glioblastoma multiforme (GBM): grade 4, rapid proliferation, angiogenesis, diffuse
invasion, cellular necrosis.
Low-grade gliomas, high-grade gliomas, meningiomas and primary CNS lymphomas do have
different frequencies of symptoms. Examples are headache (especially high-grade gliomas),
seizure (especially low-grade gliomas), hemiparesis (especially high-grade gliomas), and
mental-status abnormalities (primary CNS lymphomas).
Introduction.
The human brain consist of 100.000.000.000 neurons, with 7000 synapses on average. In
these networks function multiple neurotransmitters.
The purpose of this course is to acquire knowledge on diagnostics, therapies, biological
mechanisms underlying psychiatric or neurological disorders.
Examples of disorders are ADHD, brain tumors, CVA’s, Alzheimer’s disease, OCD, MS,
autism, depression, and Parkinson’s disease.
Brain imaging.
The brain is divided into different lobes:
- Frontal; association, planning, motivation, attention, reward.
- Parietal; language processing, spatial awareness, reading.
- Temporal; visual memories, language comprehension, emotion.
- Occipital; visual processing, vision.
The motor cortex is in the frontal lobe, and the somatosensory cortex is in the parietal lobe.
The three anatomical planes are axial (transverse), coronal, and sagittal (sword).
Neuroimaging is used in the clinic for diagnosis and prognosis. Examples are CT, MRI, MRA,
MRS, angiography, and X-ray. In research, neuroimaging is used to improve diagnostics,
prediction, post-mortem MRI and histopathology, and to understand biological processes
(using advances imaging techniques).
A cerebrovascular accident (CVA), i.e. stroke, is the loss of brain function due to disturbance in
blood supply. There are two forms of CVA:
1. Haemorrhage: 20%, bleeding trauma.
2. Ischemia: 80%, lack of blood flow.
a. TIA (= transient ischemic attack): symptoms disappear < 24 hours.
b. RIND (= reversible ischemic neurological deficit): symptoms disappear between 24
hours and 6 weeks.
Haemorrhage, i.e. hematoma, can occur in three different ways.
Epidural: rupture a. meningea media (outside dura mater).
Subdural: rupture cortical veins (between dura mater and arachnoid).
Intracerebral: mainly in putamen and thalamus (within pia mater).
An epidural hematoma often is lens-shaped and very acute, so CT is used instead of MRI to
act fast. Symptoms are loss of consciousness, progressive headache, nausea, and CSF
draining from nose or ears.
An subdural hematoma occurs more often than an epidural hematoma. The blood slowly
builds up (bridging veins), leading to intracranial pressure (less consciousness, stiff pupil). This
can happen acute (< 24 hours), subacute (<10 days) or chronic (>10 days).
Herniation happens when the brain is being pushed against the dura mater or skull.
Other causes are hypertension, aneurysm, and arteriovenous malformation (AVM).
,Magnetic resonance angiography (MRA) uses time of flight (TOF) and usually a maximum
intensity projection (MIP).
An ischemic stroke can be caused by:
- Embolism: blockage of artery/vein by blood clot.
- Thrombocytosis: an increase in thrombocytes, leading to blood clotting.
- Atherosclerosis: thickening of the artery wall.
- Hypertension: vasospasm, vasoconstriction.
- Carotid stenosis: narrowing of arteries.
- Vasculitis: blood vessel inflammation.
Brain tumors origin in neurons or glia cells. Symptoms are neurological deficits, epilepsy,
headache in the morning, and vomiting without nausea, as a result of herniation.
Benign: meningioma, pituitary tumors.
Malignant: glioma, lymphoma.
Possible treatments for brain tumors are resection, radiation, and chemotherapy.
Qualitative research is used for standard clinical practice and focuses on pathology.
Quantitative research focuses on biological mechanisms and compares patients to controls.
Magnetic resonance imaging (MRI) uses magnetism and radiofrequency signals to acquire
images. It is based on density and spins of protons, and can detect different types of tissue
because of different intensities of white matter, grew matter, and CSF.
T1-weighted scan: used for anatomy, contrast fat/water (fat = white).
T2-weighted scan: used for pathology, contrast water/tissue (water = white).
Multiple sclerosis (MS) is a neurodegenerative disease, paired with inflammation of the CNS.
This is caused by the attack of white blood cells, leading to demyelination of neurons. As a
result, physical and cognitive problems arise.
MS lesions are seen as white spots, where the white matter is damaged. These lesions often
are near to or in the ventricles. Around the ventricles, there are aging caps.
MS is diagnosed on the basis of the McDonald criteria:
- dissemination in space (DIS).
- dissemination in time (DIT).
The McDonalds criteria should only be applied in patients with clinically isolated syndrome
(CIS). CIS presentations can be monofocal or multifocal, and typically involve the optic nerve,
brain stem/cerebellum, spinal cord, or cerebra hemisphere.
These McDonald criteria have resulted in earlier diagnosis of MS with a high degree of both
specificity and sensitivity, allowing for better counselling and earlier treatment.
Both asymptomatic gadolinium-enhancing and non-enhancing lesions are highly specific for
predicting early development of clinically definite MS (CDMS). However, T2 lesions will still be
required to establish DIT.
MRI can be used to detect MS lesions, because it is highly sensitive and it reflects the duration
of the disease (cumulative history, T2). However, it lacks histopathological specificity and there
is moderate correlation with clinical disability (clinic-radiological paradox).
Acute inflammation occurs in 2-8 weeks, and is associated with disruption of the blood brain
barrier (BBB). It may coincide with relapse. Intravenous gadolinium on T1-weighted images.
, Black holes are associated with tissue loss; no remyelination, leading to axonal damage. This
is literary seen as a black hole on T1-weighted images. For this reason, black holes do
measure the severity of the disease.
For DIS, 1 of more T2 lesions in at least 2 out of 4 regions of the CNS (periventricular,
juxtacortical, infratentorial, spinal cord) must be present. Lesions in the juxtacortical regions
are against the grey matter; involvement of U-fibers and lesions in corpus callosum.
Cortical lesions in the grey matter can be detected by double inversion recovery (DIR) or fluid-
attenuated inversion recovery (FLAIR).
DIR is a MRI pulse sequence which suppresses signal from the CSF as well as from the
white matter and hence enhances any inflammatory lesion.
FLAIR is an MRI sequence with an inversion recovery set to null fluids.
Indication for spinal cord imaging are:
no incidental cord lesions with ageing / hypertension.
cord presentation: rule out compression and confirm MS lesions.
Increased sensitivity.
Increased specificity: in patient with inconclusive brain MR (e.g. hypertension).
Post-mortem imaging:
- Tissue dissection.
- Matching histopathology and MRI.
- No color no myelin.
- End-stage atrophy.
Brain tumors.
In normal tissue, the rates of new cell growth and old cell death are kept in balance. Cancer
arises from a loss of normal growth control. This can be caused by the loss of a cell’s ability to
undergo apoptosis. The tumor suppression gene p53 plays a major role in this process.
Invasion is direct migration and penetration into neighbouring tissues. Metastasis happens
when cancer cells penetrate into lymphatic system and blood vessels.
Benign tumors generally do not spread by invasion or metastasis. Malignant tumors are
capable of spreading by invasion and metastasis.
Primary brain tumors are rare; 6.4 per 100,000. You can live approximately 7 years with low-
grade gliomas (20%) and 1-2 years with high-grade gliomas (80%). Low-grade astrocytomas
become secondary glioblastoma in 5-10 years. Surgery, radiotherapy and chemotherapy can
increase the life expectancy.
Gliomas origin in glial cells. Different forms are:
Astrocytomas: low mitotic index, diffuse invasion, high rate of transformation.
Oligodendrocytes + astrocytes oligoastrocytomas: grade 3.
Glioblastoma multiforme (GBM): grade 4, rapid proliferation, angiogenesis, diffuse
invasion, cellular necrosis.
Low-grade gliomas, high-grade gliomas, meningiomas and primary CNS lymphomas do have
different frequencies of symptoms. Examples are headache (especially high-grade gliomas),
seizure (especially low-grade gliomas), hemiparesis (especially high-grade gliomas), and
mental-status abnormalities (primary CNS lymphomas).
