Neuropathology: Past, Present, and Future Flashcards by Lucy G

Name the 3 traditional neuropathology methods

Post-mortem
Surgical samples
Cytology samples

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Name the 2 types of traditional cytology samples

Intraoperative smears

CSF cytology

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What are the steps of brain cutting?

Weigh
External examination
Examine base
Examine hindbrain
Examine ventricles
Slice in coronal sections

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What is the purpose of fixation?

Cross-links proteins - prevents enzymatic degradation

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What is haematoxylin and eosin used for?

General stain

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What is a Nissl stain used for?

Myelination

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What is a Golgi stain used for?

No longer used

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Name the main categories of neuronal cytological abnormalities

Acute cell stress
Swollen neurons
Neuronal inclusions
Abnormal storage material
Amyloid
Axonal swelling

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What are the characteristics of acute cell stress?

Due to reversible/irreversible injury

Eosinophilic neurons - pink - damaged

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What are the characteristics of swollen neurons?

Due to axotomy

Material accumulation in neuronal body

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Name 5 neuronal inclusions

Lewy body
Marinesco body
Viral inclusion
Hirano body
Ferruginated neuron

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Where are Marinesco bodies found and what is the effect of eosin/haematoxylin staining?

Intranuclear

Eosinophilic

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Where and when are Marinesco bodies found and what is the effect of eosin/haematoxylin staining?

In hippocampus - with ageing - increased in AD

Eosinophilic

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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

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What is abnormal storage material in neurons due to?

Defective protein degradation - due to metabolic disorders

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What is lipofuscin and what condition is it involved in?

Ageing pigment

Neuronal ceroid lipofuscinosis - lipofuscin abundant in young patient

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Where is amyloid found?

Extracellular - in parenchyma and blood vessels

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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