Lecture 1: Brain Imaging
- Understand application/possibilities of neuroimaging in clinic and research
o Clinic
Diagnosis/prognosis
CVA
CT/MRI/MRS/angiography/X-ray
CT fast acute conditions
o Research
Improve diagnostics
Prediction
Post-mortem MRI & histopathology
Understand biological processes (using advanced imaging techniques)
Qualitative
Standard clinical practice eg MS
Look for pathology
Quantitative
“numbers as output
Understand biological mechanisms
Compare patient groups to healthy controls
Structural MRI
o Brain volumes (atrophy)
o White matter integrity diffusion tensor imaging
Functional MRI
o Brain activation during cognitive/motor task
o Functional connectivity
- Recognize abnormalities on brain scans & understand their underlying pathology
o Hemorrhage
Epidural hematoma between dura mater & skull
Acute (trauma) CT
Lens-shaped
Symptoms delayed
o Loss of consciousness disappears
o Progressive headache
o Nausea
o Fluid (cerebrospinal fluid) draining from nose/ears
Arteries
Tissue pushed inside
Subdural hematoma between dura mater and arachnoid
More often than epidural
Bridging veins
Slow buildup of blood
3 types
o Acute <24 h (worst prognosis)
o Subacute <10 days
o Chronic >10 days
Midline shift
Intercranial pressure consciousness decreases; stiff pupil
Intracerebral hematoma
o Herniation occurs when something inside the skull produces pressure that moves the
brain tissues
Different types
o Hypertension
1
, o Aneurysm
Thin wall of blood vessel
Balloon forms (aneurysm)
Aneurysm pops bleeds
Balloon is clipped off
o Arteriovenous malformation (AVM)
Asymptomatic or headaches/epilepsy
Arteries and veins not connected correctly
Conventional T2 SE MRI
TOF-MRA (MIP reconstruction
o Intracerebral/intraparenchymal hemorrhage
o Stroke
CT darker
MRI white
MRA decrease in blood flow
o Brain tumor
T2 weighted MRI white
- Understand application of different MRI sequences/techniques in MS
o MRI magnetic resonance imaging
Uses magnetism and radiofrequency signals to acquire images
50,000 times more powerful than magnetic field of earth
Conventional MRI sequences
T1-weighted scan
o Contrast fat/water
o Anatomy
T2-weighted scan
o Contrast water/tissue (T tWo water=white)
o pathology
o MS lesions
T2 bright white spots
Advantages
Highly sensitive in detection of lesions
Reflects disease duration
Disadvantages
Lack of histopathological specificity
Moderate correlation with clinical disability clinic-radiological paradox
o Acute inflammation white (old lesions dark)
Disruption BBB
Acute inflammation 2-8 weeks
May coincide with relapse
Intravenous gadolinium
T1 weighted images
Best seen 15-30 min p.i.
“black holes” (letterlijk op T1 scan) disease severity (no remyelination)
o Typical locations
Juxtacortical
Corpus callosum
o Cortical lesion detection
Double inversion recovery (DIR)
o T2 scan
Number of lesions on baseline MRI predicts
Conversion to clinically definite MS
Development of new lesions
Development of mild to moderate disability
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,Lecture 2: Clinical aspects of depression
- Classification of unipolar depressive disorders DSM-V
o Major Depressive Disorder 2 weeks
o Persistent Depressive Disorder 2 years
o Symptoms 5/9 for at least 2 weeks (including core symptoms) many different
combinations
Depressed mood
Loss of interest or pleasure in activities
Changes in weights or appetite
Insomnia or hypersomnia
Psychomotor agitation/retardation
Fatigue
Feelings of guilt/self-reproach
Concentration problems
Suicidal thought
- Prevalence rates
o US
18-25
Women>men
Difference in ethnicity
o NL
Women> men
Lower prevalence than US
No data > 65 years old
Lifetime & 12-month prevalence
Lifetime ¼ women
12-month ±5%
65+ (LASA)
Depressive symptoms higher percentage
o Depends on setting
Urban> rural
Higher in population with somatic problems
o Average age of onset mid 20s
Duration
Average: 4-6 months
50% over 1 year
10-20% persistent or chronic depression influences prevalence rates
Recurrence
50% has recurrent episodes
After 2nd or 3rd episode risk for recurrence 70% or 90%
- High societal burden, but undertreatment
o Years lived with disability (YLD)
Prevalence * loss of health (disability weight)
o Disability Adjusted Life Years
YLD + years of life lost (YLL)
o YLS & DALYs increased in the last decades
o 2020 depression is expected to be the second leading cause of disability
But: of 80/1000 depressed people, who consult GP, 49 are not recognized as
depressed
If recognized ¼ / 1/5 are referred to secondary mental health services
- Pathophysiology
o Complex many factors
o Etiology epigenetics
3
, Genetics
G1/G2/G3 etc.
Environment
Stress/trauma/interpersonal dynamics etc
o Pathophysiology all interact with each other strong/medium evidence
Neurotransmitters 5-HT/NE/DA/Glu
Inflammation
HPA axis hyperactivity
Reduced neuroplasticity
PFC-limbic altered connectivity
o Clinical phenotype
Domains
Negative salience
Reward sensitivity
Motor activity
Impulsivity
Sleep/arousal
Symptoms
Sadness/guilt
Anhedonia
Psychomotor agitation/retardation
Suicidality
sleeplessness
o Recurrence Neuroprogressive nature of major depressive disorder
Medication continuation
o Connectivity problems areas not reached well
Hypoconnectivity Frontoparietal Network cognitive control & attentions &
emotion regulation
Hyperconnectivity Default Network internally oriented and self-referential
thought
Hypoconnectivity Affective Network processing emotions or salience
- Treatment
o Antidepressants help with higher Hamilton scores then there is a difference between
placebo and real medication
Don’t give everybody medication
o Guidelines
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