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Basic Neurosciences - MRCPsych A > Neuropathology > Flashcards

Neuropathology Flashcards

1
Q

Name some macroscopic changes seen in Alzheimers?

A

Cortical atrophy (particularly over hippocampus, amygdala - frontal & parietal lobes effected most)

Flattened cortical sulci

Enlarged ventricles

Depigmentation of locus coerlus in face of persevered substantia nigra

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2
Q

Outline the microscopic changes seen in Alzheimer’s

A
  • Senile plaques
  • Neurofibrillary tangles
  • Hirano bodies
  • Astrocytic gliosis
  • Granulovascular degeneration (small vaculoses with central granules in cytoplasm of neurons - especially in the temporal lobes)
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3
Q

What are senile plaques made of and where are they located?

A

Senile plaques are made of insolube amyloid peptide deposites (Amyloid beta) peptide

They are located extracellularly and form a pleated sheet configuration

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4
Q

What enzymes cleave amyloid-beta precursor protein?

A

beta-secreatase and gamma-secretase cleave to form amyloid-beta.

Alpha-secretase prevents its formation

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5
Q

What two types of amyloid beta plaques exist and which are counted in neuropathological tests?

A

Neuritic plaques - counted in neuropathological tests
- Amyloid beta is in the form of amyloid fibrils - swollen dystrophic neurites are present within the plaque
- Eosinophillic mass appearance on haematoxylin and eosin stains
- Neuritic plaques contain a dense central core of amyloid
- Beta-pleated sheets give the neuritic plaque a green apple birefringence when Amyloid sensitive congo red stain is applied

Diffuse plaques - not counted in neuropathological tests:
- These are non-fibrillar extracellular amyloid beta and do not related to cognitive decline
- No pleated sheet appearance

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6
Q

What are neurofibrillary tangles made of?

A

Hyperphosphorylated Tau

Tau is a peptite used in the making of microtubules - microtubules help transport materials down an axon

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7
Q

Name some other Tauopathies apart from Alzheimer’s?

A

Down syndrome

Pick’s disease

Progressive supranuclear palsy

Corticobasal degeneration

Frontotemporal dementia with parkinsonism (FTDP-17)

Dementia pugilistica (punch-drunk syndrome)

Parkinson-dementia complex of Guam

Hallervorden-Spatz disease

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8
Q

Where is Tau located?

A

Intraneuronal - if there is neuronal breakdown it may appear in the extracellular space

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9
Q

What appearance are Tau?

A

Basophillic

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10
Q

Where does Tau initial develop?

A

Enterohinal cortex and CA1 field of the hippocampus before acculumating in density in other parts of the hippocampus, the medial temporal neocortex and other cortical regions (hypothalamus and thalamus).

Braak and Braak (1995) devised a staging for the degree of Tau related abnormalities

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11
Q

What are hirano bodies made of?

A

Rod-shaped eosinophillic bodies in the cytoplasm of neurons - when the neuron dies the hirano body may be in the extracellular space

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12
Q

What are hirano bodies made of?

A

Intracellular aggregates of actin and actin associated bodies

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13
Q

What is CAA?

A

Cerebral Amyloid Angiopathy:
- Affects 90% of those with Alzheimers and 30% in normal aging
- Deposition of amyloid beta plaques in the walls of blood vessels in the cerebral cortex and overlying leptomeninges
- Typically CAA causes superficial lobar bleeding that can spread into subarachnoid space.

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14
Q

What is the antibody for synapses and why is it relavent?

A

Synaptophysin is an antibody for presynaptic endings
- Neuropathological decline correlates well with declines in synapses

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15
Q

In Alzheimers where does neuronal loss occur in the hippocampus?

A

Subiculum and layers II and IV of enterohinal cortex

Neuronal loss isolates hippocampus from inputs and outputs (association cortex, hypothalamus, basal forebrain, thalamus) contributing to memory decline

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16
Q

Apart from Lewy Body Dementia name some other synculeopathies?

A

Parkinson’s
Multisystem atrophy

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17
Q

What antibody can be used to identify Lewy bodies?

A

Antibody to the protease ubiquitin

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18
Q

What do Lewy Bodies contain?

A

Alpha-synuclein - function is to accelerate reuptake of dopamine into neurons. The accelerated uptake in DLB and Parkinson’s may be toxic

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19
Q

How do Lewy bodies compare in Parkinson’s and DLB?

A

Parkinson’s confined to substantia nigra
DLB - present in many areas of cerebrum (frontal areas, temporal lobe, cingulate gyrus, dorsal motor nucleus of the vagus)

Lewy bodies are weak eosinophillic spherical, cytoplastic inclusions

20
Q

Apart from Lewy bodies name some other microsopic signs of DLB?

A

Lewy neurites - nerve cell processes that contain alpha synuclein (can also present in DLB/dementia of parkinsons and idiopathic parkinson’s disease)

Microvacuolation of the cerebral cortex (MTL - can mimic a prion disease)

21
Q

Outline the three type of underlying pathology in FTD?

A

Frontal lobe degeneration
- Spongiform or micovaculation of superificial neuropil in layers III and V of cortex
- Loss of large cortical nerve cells with minimal gliosis

Pick’s type:
- Loss of large nerve cells with abundant gliosis - occurs in frontotemporal regions
- Pick bodies - masses of cytoskeletal elements - argentophilic, tau and ubiquitin reactive filamentous inclusions
- Pick cell’s - loss of Nissl substance and peripherally displaced nucleus, oval shaped and swollen neuronal cells

Motor neurone disease type:
- Less shrinkage of cerebrum, limbic areas mostly intact
- Again loss of large cortical nerve cells, mild gliosis
- Ubquitinated but not tau-immunoreactive inclusions in frontal cortex and hippocampus
- Motor neurone disease pathology in anterior horn cells

22
Q

What pathology is seen in Huntingon’s dementia?

A
  • Atrophy of head of caudate and putamen –> loss of cells in caudate causes dilatation of the anterior horns of the lateral ventricles
23
Q

What does dissociative amnesia present with?

A

Loss of retrograde autobiographical memory (occurs usually after trauma)

24
Q

What stains are used in Pick’s disease and Alzheimer’s respectively?

A

Pick’s disease:
- Anti-ubiquitin and anti-tau

Alzheimers:
- Basic fibroblast growth factor
- Amyloid P
- Heparin Sulphate Glycoaminoglycan

25
Q

In what disease is there knife blade atrophy?

A
  • Pick’s disease –> selective atrophy of frontal lobe, if temporal lobe involved often most of superior temporal gyrus is spared
26
Q

Prominent pathology in the dorsal medial thalamus may suggest?

A

Wernicke-Korsakoffs syndrome

27
Q

in CJD the spongiform changes in brain tissue are secondary to what?

A

Neuropil vacuolation

28
Q

How does HIV enter the brain?

A

Through T-lymphocytes and monocytes as these can cross the BBB.

HIV first enters T-lymphocytes and monocytes by binding to CD4 and chemokine receptors

29
Q

What are the microscopic findings in CJD?

A

Spongiform encephalopathy due to vacolisation (formation of vacuoles - fluid filled cysts) secondary to neuropil (area of unmyelinated axons, dendrites with few cell bodies) vacuolisation.

30
Q

What accumulates in CJD?

A

Prion protein
- Normally encoded by chromosome 20 - in CJD it is converted to an abnormal form PrPc which is protease resistant. The build up triggers further conversion of prion protein.
- Prion protein is identified by immunoperoxidase staining

31
Q

What is 14-3-3?

A

An abnormal protein found in the CSF of CJD (50% of cases) however non-specific and found in viral encephalitis and not vCJD

32
Q

What sign is highly suggestive of vCJD?

A

Pulvinar sign posterior thalamic abnormality - detected using FLAIR MRI

33
Q

What polymorphism may influence susceptibility of CJD?

A

Polymorphism at codon 129 of PrP

34
Q

Compare and contrast Sporadic/Classical CJD with variant CJD

A

Sporadic/Classical:
- Genetic mutation cause
- Develops later in life > age 65
- Dementia and early neurological signs
- Characteristic EEG - biphasic and triphasic sharp waves (with generalised slowing)
- No pulvinar sign on EEG
- Tonsillar biopsy cannot isolate PrP
- Fewer plaques
- Tends to be shorter duration 5 months

Variant:
- Younger age of onset - 25 years
- Caused by infected meat products or passing abnormal PrP –> surgical equipment
- Psychiatric signs first anxiety/depression
- Pulvinar sign on MRI (poster thalamus)
- Less common EEG changes - sharp triphasic waves are rarer
- Plaques are larger numbers
- Tonsillar biopsy can isolate prion protein
- Methionine homozygosity on codon 129 is a possible susceptibility

35
Q

In mood disorders including depression and bipolar disorder what neuroimaging findings have been established?

A

White matter hyper-intensities in subcortical areas - periventricular area and basal ganglia (lesser extent)

  • Associated with vascular risk factors commonly
  • Confer a poor prognosis
36
Q

The following brain changes are associated with which condition?

Gliosis and small haemorrhages in:
- Mamillary bodies
- Hypothalamus
- Mediodorsal thalamic nuclei
- Colliculi
- Midbrain tegmentum

Cerebellar atrophy

A

Wernicke’s encephalopathy

37
Q

What is brain shrinkage in alcoholism (without complications) accounted for by?

A

Loss of white matter - may be reversible

The neuronal loss in alcohol occurs in specific areas - superior frontal association cortex, hypothalamus (supraoptic and paraventricular), cerebellum

38
Q

In ASD what brain changes have been shown?

A

Hypoplasia of cerebellar vermis

Decreased purkinje cell count in cerebellum

39
Q

Name the gross brain changes observed in Schizophrenia

A

Reduced tissue volume (thalamus, temporlimbic structures e.g. hippocampus, amygdala, parrahippocampal gyrsus)

Reduced white matter (hippocampus and parahippocampal gyrus)

Increased incidence of cavum septi pellucidi

Reversal of normal asymmetry noted in planum temporale (L normally > R)

Decrease in basal ganglia volume - however since neuroleptics have been used basal ganglia volume is actually larger

40
Q

What histological findings have been shown in Schizophrenia?

A

No astrogliosis

Decreased cell count predominately in hippocampus and DLPFC (glutamatergic neurons)

But increased in neuronal density (dendritic arborisation and decreased neuropil)

Decreased presynaptic marker decrements in DLPFC (excessive pruning)

In cingulate gyrus pruning of GABAergic neurons

Antipsychotics increase glial density - particularly in caudate and putamen

41
Q

In the brain what cells does HIV typically infect?

A

In theory can infect all cell types however commonly infects macrophages and microglial

42
Q

What is macrophage trophic?

A

Trophic changes of macrophages caused by HIV

A mutation in the region of gp120 the external glycoprotein of the virus

43
Q

Apart from trojan horse mechanism how else may HIV-1 enter the CNS?

A

Free transport between or transcytosis of endothelial cells

  • controversial as endothelial cells may not express CD4
44
Q

What is the mechanism for HIV neuropathology?

A

Direct effect of HIV infection OR
Indirect consequence of infection e.g. secretion of cytokines and neurotoxins

Macrophages and infected monocytes:
- Shed vital proteins
- Release pro-inflammatory cytokines and neurotoxins
- The pro-inflammatory cytokines (TAT and TNF-alpha) make the BBB more permeable to peripheral inflammatory mediators and neurotoxins

Toxic products e.g. platelet activating factor, quinolinic acid, nitric oxid, arachadonic acid may lead to apoptosis

45
Q

Give examples of biopsy findings in infected brain tissue?

A
  1. Infiltration of macrophages in CNS
  2. Neuronal loss (hippocampus, basal ganglia inc. caudate nucleus)
  3. Microglial activation - microglial nodules
  4. Myelin damage
  5. Accumulation of lipid macrophages (extreme cases)
46
Q

In AIDS what are the common psychiatric conditions?

A

Dementia

Depression

Psychosis is rarer (10%)

Basic Neurosciences - MRCPsych A (8 decks)

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