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Summary Neurobiology of Disease

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Summary of Neurobiology of Disease

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  • 5 décembre 2024
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Neurobiology of disease
Oral- Open questions about disease mechanisms, not about disease or disease symptoms

Content
Stroke.....................................................................................................................................................2
Introduction........................................................................................................................................2
Causes and risk factors.......................................................................................................................3
Stroke symptoms................................................................................................................................4
Pathophysiology of stroke..................................................................................................................6
Molecular pathogenesis of cerebral ischemia and hemmorhagic........................................................6
Treatment of stroke.............................................................................................................................7
Secondary prevention & outcome after stroke....................................................................................8
ALS/FTD spectrum................................................................................................................................8
Clinical aspects of FTD......................................................................................................................8
Neuropathology of FTD.....................................................................................................................9
Genetics of FTD...............................................................................................................................10
Neurobiology of disease of FTD.......................................................................................................10
Muscular dystrophies ..........................................................................................................................12
Clinical features ...............................................................................................................................13
Duchenne muscular dystrophy ....................................................................................................13
Becker muscular dystrophy ..........................................................................................................13
Diagnostic examinations ..................................................................................................................13
Genetics and Protein function ..........................................................................................................14
Pathomechanism and animal models ...............................................................................................15
Therapies..........................................................................................................................................15
Dementia..............................................................................................................................................17
Multiple sclerosis (MS)........................................................................................................................22
Basics - clinic & pathology...............................................................................................................22
Epidemiology...................................................................................................................................24
Genetics & immunopathogenesis.....................................................................................................24
Animal model...................................................................................................................................24
Treatment..........................................................................................................................................25
Amyotrophic Lateral Sclerosis (ALS)..................................................................................................25
Clinical aspects of ALS....................................................................................................................25
Neuropathology of ALS....................................................................................................................26
Genetics of ALS...............................................................................................................................27
Neurobiology of disease of ALS.......................................................................................................27

,Charcot-Marie-Tooth disease................................................................................................................30
Clinical aspects.................................................................................................................................30
Genetics............................................................................................................................................30
Disease mechanisms.........................................................................................................................32
Potential new therapeutic strategies..................................................................................................33
Biomarkers...........................................................................................................................................34
Alzheimer's disease..........................................................................................................................34
ALS..................................................................................................................................................34
Chronic inflammatory demyelinating polyneuropathy (CIPD).........................................................34
Neuroanatomy and Parkinson’s disease................................................................................................36
Anatomical basics of the human brain - comparison with mouse brain............................................36
Motoric and sensoric systems...........................................................................................................36
Extrapyramidal motor system...........................................................................................................37
Anatomical correlatives of memory function and behaviour............................................................37
Parkinson’s disease...........................................................................................................................38


Stroke
Introduction
Stroke is a cerebrovascular accident. It is a sudden loss of neurological functions due to a problem
with cerebral circulation.
 Ischemic stroke (brain infarct) (80%)
o Arterial or venous occlusion arterial more common
o Permanent symptoms vs transient: TIA
 Hemorrhagic stroke (brain hemorrhage) (20%)
o Parenchymal hematoma
o Subarachnoid hemorrhage

Blood supply to the brain comes from the internal carotid artery bilaterally
(80%) and the basilar artery (20%). Internal carotid artery stems from common
carotid artery and the basilar artery stems from 2 vertebral arteries. Cerebral
arteries join in the circle of Willis. From there the anterior, middle, and posterior
cerebral arteries arise. The circle of Willis protects against ischemia, as the blood
supply can come from another artery. The external carotid arteries supply the
face and the internal the skull.
Circle of Wilis (incomplete in 20- 25%):
 Arteria communicans anterior (acomm): between both anterior cerebral artery (ACA)
 Posterior communicating artery (pcomm): between posterior cerebral artery (PCA) and
middle cerebral artery (MCA)
Leptomeningeal anastomoses connections between distal arterial branches use in case of
occluded/stenotic proximal artery
Collateral circulation will help during ischemia and its development depends on

,  Genetics
 Downstream reduced blood flow
 Angiogenetic factors secreted from infarction
 Chronic hypoperfusion
The venous circulation is vulnerable to occlusion because of slow flowing blood.

Causes and risk factors
Hypertension is the most important risk factor. Additionally, diabetes and hypercholesterolemia
(LDL) are also risk factors.
Mechanism of ischemic stroke
1. Local thrombosis
a. Mostly because of rupture of atherosclerotic plaque
b. Thrombosis outside the brain (large cerebropetal vessels) or at the large or small
intracerebral blood vessels
i. Small vessel disease: sometimes due to non-thrombotic pathology
c. Anterograde perfusion is limited due to blood vessel occlusion
2. Embolisation of thrombus (most frequent):
a. Usually from outside the brain
i. Atherosclerotic plaque in the neck vessels or heart
b. Embolus remains lodged in a smaller, more distal blood vessel and causes local loss of
perfusion
Radiological clues
 Occlusion of a large intracranial blood vessel: wedge-shaped infarct in cortical + subcortical
regions
o Local intracranial thrombosis or embolus
o and/or multiple infarcts in cortical and subcortical regions: embolus
 Lacunar infarct/small vessel disease: Occlusion of a small, penetrating blood vessel: small
infarct in deep brain regions in typical locations (perfusion territory of those small penetrating
arteries)
 Watershed infarct: infarct in the distal perfusion territory/territory of overlapping perfusion
between different blood vessels: caused by hypoperfusion (e.g. severe blood pressure drop,
severe extracranial stenosis)
Causes ischemic stroke
 Cardio-embolic sources 25%
o Atrial fibrillation (A-fib) no temporal relationship between stroke but might share
same risk factors
o Endocarditis infection inside the heart the lower the left ventricle output, the
higher the risk
 Cryptogenic stroke (unknown) 25%
o 30% have a-fib
o Loop recorders measures electrical field of the heart (battery is 3 years)
 Large vessel atherosclerosis 20%
o Hypoperfusion and watershedinfarction
o Distal embolisation
 Small vessel disease (arteriosclerosis/lipohyalinosis) 20%
o Can cause ischemic stroke 3 ways

,  Local thrombosis
 Lipohyalinosis/atheriosclerosis
 Accumulation of beta-amyloid in blood vessel wall in small perforating
arteries
o Lacunar stroke and accumulation of vascular lesions in WM (leukaraiosis)
 Other defined sources 10%
o Vasculitis
o Arterial dissection
o Venous sinus thrombosis
 Venous drainage is insufficient blood stands still (often bilateral)
 Increased intracranial pressure, venous infarction and venous haemorrhage
 Causes: thrombotic disorders, inflammation caused by contagious infection,
inflammatory disorder
o Paradoxal embolization
 Connection between two atria way for venous
thrombosis to travel to the brain or embolus via
RA to lung
o Genetic diseases

Causes hemorrhagic stroke
 Parenchymal (most common) bleeding in the brain
o Deep hemorrhage- hypertension
o Lobar hemorrhage- cerebral amyloid angiopathy and hypertension
 Subarachnoid bleeding outside the brain (subarachnoid space)
o Perimesencephalic hemorrhage venous origin (most likely)
o Trauma or aneurysm balloon like dilation of the blood vessels thin wall, can
rupture)
 Cerebral circulation thinner so lack in external lamina elastica and are
surrounded by CSF more risk for aneurysm
o Bifurcation turbulence and waterhammer effect more T-like bifurcation more risk
than Y shaped as waterhammer effect is stronger
o Woman suffer more from this

Stroke symptoms
 Ischemic stroke and intracranial hemorrhage
o Acute
o Focal neurological deficit
o Dependent on location
 Non-lacunar cortical symptoms
 Lacunar no cortical symptoms
o No test to separate ischemic or intracranial
 Subarachnoid hemorrhage
o Hyperacute
o Coma
o Neck stiffness
o Subarachnoid excites the dura, that have a lot of nerves headache and high
intercranial pressure passing out and can lead to sudden death
 Cerebral venous thrombosis
o Subacute

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