Neuropathology: Past, Present, and Future Flashcards
Name the 3 traditional neuropathology methods
Post-mortem
Surgical samples
Cytology samples
Name the 2 types of traditional cytology samples
Intraoperative smears
CSF cytology
What are the steps of brain cutting?
Weigh External examination Examine base Examine hindbrain Examine ventricles Slice in coronal sections
What is the purpose of fixation?
Cross-links proteins - prevents enzymatic degradation
What is haematoxylin and eosin used for?
General stain
What is a Nissl stain used for?
Myelination
What is a Golgi stain used for?
No longer used
Name the main categories of neuronal cytological abnormalities
Acute cell stress Swollen neurons Neuronal inclusions Abnormal storage material Amyloid Axonal swelling
What are the characteristics of acute cell stress?
Due to reversible/irreversible injury
Eosinophilic neurons - pink - damaged
What are the characteristics of swollen neurons?
Due to axotomy
Material accumulation in neuronal body
Name 5 neuronal inclusions
Lewy body Marinesco body Viral inclusion Hirano body Ferruginated neuron
Where are Marinesco bodies found and what is the effect of eosin/haematoxylin staining?
Intranuclear
Eosinophilic
Where and when are Marinesco bodies found and what is the effect of eosin/haematoxylin staining?
In hippocampus - with ageing - increased in AD
Eosinophilic
What are ferruginated neurons and where and when are they found?
Neurons encrusted in iron and calcium mineral deposits
In cortex after early-life hypoxic brain damage
What is abnormal storage material in neurons due to?
Defective protein degradation - due to metabolic disorders
What is lipofuscin and what condition is it involved in?
Ageing pigment
Neuronal ceroid lipofuscinosis - lipofuscin abundant in young patient
Where is amyloid found?
Extracellular - in parenchyma and blood vessels
Which stain shows amyloid and which colour is it stained?
Congo red stain
Apple-green
What do axonal swellings consist of?
Neurofilaments
Where and when are corpora amylacea found?
In astrocytes
With ageing
Where are Rosenthal fibres found and what could be they a part of?
In astrocytes
Could be part of tumour
What are the physiological roles of astrocytes?
Stem cell source BBB regulation K+ homeostasis Release gliotransmitters Glutamate regulation
What are the pathological roles of astrocytes?
Glial scar formation - proliferation and hypertrophy
Neurotransmission - spreading depolarisation waves
Release pro-inflammatory cytokines
BBB breakdown
Neurodegenerative diseases
Source of tumours - astroglioma
Which marker is specific for oligodendrocyte progenitor cells?
NG2
What marker is specific for mature oligodendrocytes?
NogoA
What are the pathological roles of oligodendrocytes?
Reduced number - in Multiple Sclerosis
Source of tumours - oligodendroglioma
How do microglia respond to dying neurons?
Surround
Release inflammatory cytokines
How is CNS microvasculature altered in ageing and what is the effect of this?
Tortuous vessels and venous collagenosis
Decreases perfusion
Cognitive effects
What are the effects of brain atherosclerosis?
Weakens vessel walls - increases haemorrhage risk
Impedes bloodflow - increases stroke risk
What could the cause of vascular dementia be?
Lacunar infarcts - occlusion of small arteries in deep brain
What is subcortical laminar heterotopia and what causes it?
Grey matter band under cortex - 6 cortical layers not distinct
Impaired neuronal radial migration
Caused by mutant doublecortin
What are focal cortical malformations and what causes them?
Enlarged neurons in abnormal position - restricted to one area
Somatic mTOR pathway mutations
What is the effect of a somatic mTOR mutation in an early developmental mitotic cycle on focal cortical Malformation severity?
Severe widespread malformation
What is the effect of a somatic mTOR mutation in a late developmental mitotic cycle on focal cortical malformation severity?
Small FCD focus
What is classical microglia activation?
Become M1 microglia
Pro-damage
What is alternative microglia activation?
Become M2 microglia
Pro-repair, anti-inflammatory
What causes autoimmune encephalitis and what are its symptoms?
Autoantibodies target neuronal antigens
Memory deficits, seizures, psychiatric symptoms
What is traumatic axonal injury, what causes it, and which brain area is most vulnerable?
Shearing of axons - interferes with axonal transport - swelling before shear site
Caused by head injury involving rotation
Corpus callosum vulnerable
What causes chronic traumatic encephalopathy?
Repetitive head trauma
What are the symptoms of chronic traumatic encephalopathy?
Memory decline
Parkinsonism
Behavioural changes
Where does tau accumulate in chronic traumatic encephalopathy?
Superficial cortical layers In astrocytes Around blood vessels Around ventricles Patchy distribution in frontal and temporal cortices
What is a prion?
Proteinaceous infectious agent
What histology is seen in prion disease?
Neuronal loss
Gliosis
PrP deposition
Which molecular feature can be used to distinguish high and low grade CNS tumours?
DNA methylation profile
