I passed the exam with an 8.5
WIHTOUT stress and neuropsychiatry !
WIHTOUT what we learn from pathology (leukodystrophy) !
Clinics of OCD are RAW notes
> These lectures were excluded from our exam (2024/2025)
Week 1, Introduc/on ...................................................................................................................................... 3
Brain development ............................................................................................................................................. 3
Week 2, Leukodystrophies ............................................................................................................................ 18
An Introduc5on to Concepts ............................................................................................................................. 18
What we Learn from Pathology (not exam material) ....................................................................................... 29
To Study Disease Mechanisms, VWM as a Case Study ..................................................................................... 30
To Develop Outcome Measures in Clinical Trials and Clinometry ..................................................................... 41
What has Water Homeostasis to do with Them? MLCs .................................................................................... 53
Envision Therapies ............................................................................................................................................ 65
Envision Gene Therapy ..................................................................................................................................... 75
Week 3, Mul/ple Sclerosis ............................................................................................................................ 86
Clinical Features of MS ..................................................................................................................................... 86
Imaging............................................................................................................................................................. 92
E5ological mechanisms and neuropathology ................................................................................................... 99
Current therapy for MS ................................................................................................................................... 110
Cogni5ve dysfunc5on ..................................................................................................................................... 116
Networks in MS............................................................................................................................................... 125
Week 5, Parkinson’s Disease ....................................................................................................................... 133
Clinical Features of Parkinson’s Disease ......................................................................................................... 133
Brain Imaging ................................................................................................................................................. 139
Disease Mechanisms ...................................................................................................................................... 152
Current Therapy for Parkinson’s Disease ........................................................................................................ 173
Week 6, Neuropsychiatry ............................................................................................................................ 183
Clinics of OCD.................................................................................................................................................. 183
Stress and neuropsychiatry............................................................................................................................. 187
Brain circuits in OCD ....................................................................................................................................... 188
Circuit-based neuromodula5on rTMS, from disease to personalized targe5ng ............................................. 195
The depression paradox.................................................................................................................................. 208
Ins & outs of depression research ................................................................................................................... 213
Biological pathways of MDD .......................................................................................................................... 221
Week 7, Glioma .......................................................................................................................................... 230
Clinics of neuro-oncology................................................................................................................................ 230
Current therapy for glioma .......................................................................... Fout! Bladwijzer niet gedefinieerd.
,Week 1, Introduc/on
Brain 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 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 cogni6ve and motor impairment, as well
as neurological disorders such as au0sm, ReA syndrome, and intellectual disability
Learning objec0ves:
- Able to describe the landmarks in brain development
- Have knowledge of neurological disease resul0ng from failure in this process
- Have basic knowledge about pediatric neurological development
The human CNS follows a paAern of development Building the human CNS requires the
precise orchestra6on and coordina6on of myriad molecular and cellular processes across a
staggering array of cell types and over a long period of 6me.
• Dysregula0on of these processes affects the structure and func0on of the CNS and
can lead to neurological or psychiatric disorders.
• Recent technological advances and increased focus on human neurodevelopment
have enabled a more comprehensive characteriza0on of the human CNS and its
development in both health and disease.
summary of some key cellular processes in the developing prefrontal cortex and func0onal
milestones.
From 24 weeks postnatal a baby is kept alive.
,Processes of brain development
- Neurogenesis in the ventricular zone
- Neuronal migra0on
- Synaptogenesis
- Synap0c pruning
- Myelina0on
Growth of the brain can be followed from the outside by measuring head size.
- The volume inside the skull determines the head size
o Consis0ng of the brain and CSF
- 80% of its volume in the first two years of life and con0nues into adulthood
o Mostly neurogenesis and myelina0on cause the brain to grow
- Microcephaly:
o too small brain
o can be caused by hydrocephaly
Development and milestones
- Motor Development: Crawling, siWng, walking
- Communica0on: understanding words (at the age of 2 they can know 25 words)
- Cogni0ve: ini0a0on of smiles, symbolic play
- Social-emo0onal skills: 0me with caregiver, expressing emo0ons, being le[ alone
, 5 day old boy
- Muscle tone: passive tone in the muscles (not when it ac0vely uses the muscles)
o Flec0on tone: not laying flat (is what you want)
o Hyper tone: laying flat
o Asymmetric neck tone Reflex: head going to one side, one side flexion, one
side hyper tone (permea0ve reflex)
- No motor milestones so far
Permea0ve reflex: not conscious about, mostly from the brainstem, important to survive, in
first 6 months of life (this can reappear in neurodegenera0ve diseases.
- If these reflexes persist: neurodevelopmental disorder or disease
Baby at 3 months (first motor development of baby):
- Head balance
- Li[ing head
- Turning around from belly to back
Baby at 12 months
- Standing and Walking
- Pincher grasp reflex
*A lot of varia0on between children but there are limits on what is normal and what is not
Psychiatric and neurological disorders have discrete ages of onset
Indica0ve of the biological challenge of precisely regula0ng diverse molecular and cellular
processes over a protracted period of 0me and across myriad cell types and regions, the CNS
exhibits regionally and temporally dis0nct paAerns of vulnerability to various diseases and
insults
- intellectual disabili0es early in live
- Psychiatric disorders o[en at adolescence
- Neurodegenera0ve disease at the end of life
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