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The broken brain Flashcards

1
Q

what does damage in the central nervous system cause?

A

irreversible changes to the structure of neurons

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2
Q

3 types of damage in the peripheral nervous system?

A

1.neurophaxia
2.axontomesis
3.neurotmesis

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3
Q

Neuropraxia

A

least severe, with no damage to axons or sheathing, often the result of stretching or compression
-demylineation
-reversible
-compression- myelin sheath is compacted

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4
Q

what happens if the soma of the cell is damaged

A

it cannot regenerate,
if the axon are damaged it can just grow it back

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4
Q

Axontomesis

A

moderate, axons damaged but sheathing intact
-dymelineation + axon lost but endonurim is entact meaning axon can grow back

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5
Q

Neurotmesis

A

most severe, partial or complete severance of axon and sheathing, likelihood of recovery dependant on type of cut (clean cut is better than twisted/ripped)
-dymelination and axon loss
-damage of endoneurium- there is a fear growth but not as well as if the endoneruium was enacted
-inolvement of perineurium if this is damaged -poor growth
-epineurium- damage in this there is no growth

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6
Q

Wallerian

A

degeneration of the distal portions of the axon and myelin after damage/compression

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7
Q

what do the 3 damages nerupaxia, axontomesis and neurotmesis lead to?

A

1.Wallerian
2.Axonal
Demyelination

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8
Q

axonal

A

progressive dying back of the neuron from distal to proximal regions

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9
Q

Demyelination

A

loss of oligodendroglial or Schwann cells

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10
Q

what is Transneuronal degeneration

A

describes the death of cells within the communication chain as they are no longer in use

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11
Q

what are the 2 types of transneruonal degeneration?

A
  1. anterograde (distal cells following the damaged cell)
    2.retrograde degeneration (dying back of axons - axonal degeneration or death of cells proximal to the site of damage).
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12
Q

head trauma

A

nything that results in damage to the head that can lead to raised intracranial pressure and changes in consciousness

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13
Q

example of head trauma

A

nything that results in damage to the head that can lead to raised intracranial pressure and changes in consciousness
less-expanding lesions e.g abcsess, cysts, meningitis

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13
Q

Brain Haemorrhage

A

rupture of arteries or veins

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14
Q

how to detect haemorrhage?

A

CT imaging as fresh blood is bright compared to the grey tissue.

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15
Q

what are the different bleeds of different layers of meninges and brain tissue

A

Subarachnoid haemorrhage:
.

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16
Q

Extradural (epidural) haemorrhage)

A

Following a blow to the head, blood from torn meningeal arteries accumulates between the outer dural layer of the meninges and the skull.

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17
Q

Subarachnoid haemorrhage

A

This kind of bleed usually follows the rupture of a cerebral aneurysm (a balloon in the blood vessel that is a point of weakness). Blood collects in the CSF beneath the arachnoid layer of the meninges.

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18
Q

Subdural haemorrhage

A

Following a blow that causes the brain to move within the skull, e.g. in boxing, blood collects in the subdural space following the rupture of a vein.

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19
Q

Intracerebral/intraparenchymal haemorrhage

A

results from the rupture of a vessel within the brain tissue itself.

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20
Q

how does diffuse axonal injury impact lesions?

A

small lesions (areas of damage), usually at the border of the grey and white matter (this transition point between cell bodies and axons is a weak spot), but these lesions can have devastating effect

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21
Q

Diffuse axonal injury

A

damage that results from a twisting or rotational force being applied to the brain (e.g in a crash it’s rare to get a direct impact on the head, the head is more likely to rotate and turn on impact).

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22
Q

Concussion

A

form of mild traumatic brain injury (mTBI)

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23
Contusion
bruises in the brain and tend to occur at more superficial levels of the cortex as the brain bumps during a traumatic event.
24
what are the 3 gradings of contusion?
1.mild:limited to the grey matter 2.moderate:involving grey and white matter 3.severe:haemorrhages coalesce
25
what are 2 indications of diffuse axonal injury?
1.scattered microhaemorrhages (small bleeds) 2.pockets of ischaemia in the white-grey matter border or in the white matter
26
Stroke
sudden onset of neurological symptoms due to either haemorrhage or ischaemia
27
acronym for identify someone is displaying stroke?
Face – has their face fallen on one side? Can they smile? Arms – can they raise both arms and keep them there? Speech – is their speech slurred? Time to call 999 if you see any one of these signs
28
what are TIA in strokes and what are they caused by?
mini strokes transient loss of blood supply, which resolve within 24 hours - small tremors you get before a big earthquake, they are a warning sign that must be heeded.
29
what are the 4 brain regions used to confirm diagnosis?
1.Amyloid plaques 2.Neurofibrillary tangles 3.Inclusions 4.Prion proteins
30
Amyloid plaques
aggregations of misfolded/fragmented proteins found in the extracellular matrix
31
what are 3 different proteins in amyloid plaques?
1.β-amyloid (fragments of the amyloid precursor protein) in 2.Alzheimer's Disease 3.α-synuclein (which mostly form fibrils) in Parkinson's Disease Prion proteins in Creutzfeldt Jakob Disease (CJD)
32
what amyloid plaques caused by?
protein phosphorylation, which leads to changes in protein folding and the formation of β-sheets
33
what do B sheets include?
sheet form insoluble fibres and toxic oligomers, which can clump together to form plaques
34
Neurofibrillary tangles
formed by the microtubule associated protein - Tau
34
what is Tau?
involved in the structural composition of microtubules which provide the transport system in a neuron
34
what does Hyperphosphorylation of tau lead to?
misfolding, which then causes the breakdown of the microtubules, β-sheet and fibril formation. These fibrils aggregate to form tangles
35
Inclusions
intracellular protein aggregations
36
what 2 things does inclusions lead to?
1.Lewy bodies 2.Pick cells
36
structure of inclusion?
-dense core of protein and a halo of surrounding filaments. The are the result of misfolded and ubiquitinated proteins
37
what other proteins can inclusion be made of?
1.ubiquitin 2.crystallin 3.neurofilament
37
what are inclusions made up of ?
α-synuclein
38
what role do prion protein play?
presynaptic transport and cell signalling (just like α-synuclein). Conformational changes as a result of changes in phosphorylation, leads to formation of β–sheets and fibrils
38
prion protein
infectious; they can cause other proteins to misfold as well as misfolding themselves
39
what are protein prions associated with?
mall pockets of cells death, so as well as the visible amyloid plaques you also see vacuolisation, which gives the brain tissue a spongiform appearance
40
Diabetic neuropathy(peripheral degenerative disorder)
principally axonal (‘dying back’) in form -Degeneration often symmetrical and starts at the extreme ends of the limbs, in the hands and feet, working back towards the body, giving the classic 'glove and stocking' pattern of loss
41
what can the poor circulation in diabetic neuropathy lead to?
suffer with pain and ulceration, but at early stages the damage to the nerves is often indicated by patients feeling tingling in the hands and feet and experiencing poor balance
42
in diabetic neuropathy why is there degeneration of the nerves?
result of the high glucose in the blood, causing microvascular disease and altering the local environment of the nerves
43
Motorneuron disease (MND)(Peripheral degenerative disorder)
spectrum of disorders encompassing degeneration throughout the motor system
44
use see astrocytosis in ALS , what is this?
(hypertrophy of astrocytes).
45
what is Amyotrophic lateral sclerosis (ALS) (peripheral degenerative disorder) caused by?
-form of MND 1/SOD1 gene leads to protein misfolding 2.reduced ROS (Reactive oxygen species) removal 3. increased cell damage and death
46
in ALS where does the loss of motor neurones occur?
-corticospinal tract -affecting the large Betz cells in the cortex and anterior horn cells in the spinal cord - leading to thinning of peripheral anterior roots and fibre pathways
47
in ALS what does Tonic atrophy mean?
wasted, fasciculating (twitching) muscles plus brisk reflexes
48
Friedreich's ataxia(peripheral degenerative disorder)-what is it and what is it caused by?
autosomal recessive disorder, caused by GAA triplet repeats in FXN gene (Frataxin), which leads to problems with iron metabolism
49
Ataxia
gait/movement)
50
what does fredreiches ataxia cause in the motor system?
loss of large myelinated fibres in the spinocerebellar tracts, dorsal root ganglia and posterior column. Later loss includes cerebellar mass and corticospinal tracts.
51
in fredreiches what can cardiomapathy cause?
changes in frataxin also impacts the pancreas leading to most patients also having diabetes mellitus
52
Guillain-Barré syndrome (GBS)(peripheral degenerative disorder)
demyelinating disorder and has several forms including Miller Fisher syndrome (MFS) which is an ocular form
53
what is GBS caused by?
suspected to be an autoimmune reaction, triggered by preceding viral/bacterial infection
54
symptoms of GBS?
rapid onset weakness and tingling that spreads through body. This normally starts in feet/legs and spreads upwards. Peak symptoms occur approx. 2-4 weeks after onset and it can lead to paralysis.
55
Multiple sclerosis (MS)(central degenerative disorder)
primary inflammatory, autoimmune disease causing demyelination in the CNS
56
How does MS impact?
presents with a single feature episode of blindness (commonly the result of optic neuritis), weakness or numbness
57
In MS what are the plaques made up of?
products of inflammation accumulate in the demyelinated areas, these can be seen as flares in white matter regions of CNS on scans
58
what is PD seen as a loss of?
loss of pigmented cells in Substantia Nigra (SN) - dopamine containing cells are black in nature
58
what signs do Parkinson's disease (PD) inlcude?(central degenerative disorder)
include: tremor, rigidity, reduced movement and instability), but can only really be confirmed post mortem
59
what 3 things can be seen in the neuronal/histological view in PD?
1.Loss of dopamine neurons in SN 2.Presence of Lewy Bodies in BG circuitry 3.Raised α-synuclein/parkin protein levels
60
in Parkinson's disease where are the 3 things you would see lewy bodies?
1.neocortex 2.cerebellum 3. basal ganglia.
61
Huntington's disease( central degenerative disorder)
genetic disorder affecting the basal ganglia, causing loss of GABA and changes in cholinergic function and astrocytosis -autosomal dominant disorder
61
what 3 things is Huntington disorder characterised by?
1.Choreiform movements - erratic, writhing, snake-like movements 2.Character alteration - personality changes, outbursts of anger 3.Psychotic behaviour - strange, erratic behaviours
62
what can be seen in post mortem in Huntington's disease?
arge degeneration of the caudate nucleus and putamen, two regions of the basal ganglia.
63
what is ex-vacuo dilatation and what is it caused by?
- ventricles are enlarged -caused by expansion of the ventricles due to loss of tissue, with CSF production increasing to effectively fill the void and support the brain tissue.
64
Spongiform encephalopathies(central degenerative disorder)
changes in prion proteins, causing them to alter from the soluble form, PrPc, to the insoluble PrPsc which forms sheets, fibrils and tangles.
65
Creutzfeldt-Jakob disease (vCJD)(example of degenerative disorder and caused by spongiform encephalopathies)
cross-species transmission via the food chain of infected ('mad') cows
66
what did patients with vCJD experience?
suffered progressive motor and cognitive dysfunction
67
what changes did the vCJD make to the cerebellum ?
showed spongiform changes and prion proteins could be detected in the GI tract.
68
what 3 things are there a deterioration in Dementia?
1.Cognition (Memory, Orientation, Concentration, Speech) 2.Behaviour 3.Personality
69
what are the 3 different forms of dementia?
1.Cortical - involving the surface regions of the brain 2.Subcortical - involving deeper regions, basal ganglia, brainstem and limbic system, 3.Mixed: Cortical and subcortical
70
Alzheimer's dementia
creasing cortical degeneration and progression involving the connectivity to deeper regions of the brain.
70
what are the 3 types of grading of cognitive impairment in AD?
1.Mild cognitive impairment 2.Mild to moderate dementia 3.Advanced dementia
71
what are things that occur at the histological level in AD?
1. β-amyloid plaques 2. neurofibrillary tangles are present throughout limbic and cortical areas
71
what are the 2 activities that happen in AD?
cortical atrophy ex-vacuo dilatation
72
Vascular dementia
cardiovascular disease and it's impact on cerebral blood flow
73
what are the 2 groups of vascular dementia?
1.Stroke-related dementia: Which can result from single-infarcts or, more commonly, multi-infarcts. 2.Small-vessel dementia (Binswanger's disease)
74
Dementia with Lewy Bodies (DLB)
it's presentation with both Alzheimer’s and Parkinson’s disease
75
what 3 symptoms does DLB have?
1.Parkinsonism 2.Visual hallucinations 3.Fluctuations in cognition
76
what is FTD characterised by at the gross pathological level?
by focal atrophy of frontal or temporal lobes
77
what are the 2 types of positive FTD can be ?
1.Tau positive 2. ubiquitin positive
77
Frontotemporal dementia (FTD)
includes Pick’s Disease, which is characterised by the inclusions known as Pick bodies.
77
what does a loss in DLB lead to?
loss of both dopaminergic and cholinergic neurons and is characterised histologically by the presence of Lewy bodies
78
histologically what are the Tau positive case characterised by?
presence of Pick cells (ballooned cells) and neuronal inclusions (Pick Bodies) formed by Tau protein.
79
Normal pressure hydrocephalus (NPH)
describes the situation where the ventricles are enlarged but the ICP is normal
80
on imaging what is NPH characterised by?
ventriculomegaly
81
what are the 2 subtypes of NPH?
1.NPH with preceding cause 2.Idiopathic NPH
81
what cardinal features does NPH present?
Gait disturbance Cognitive decline – subcortical pattern Urinary incontinence
82
what are the 3 stages in the timescale for stages of dementia?
1.acute(weeks) 2.subacute(months) 3.chronic(years)
82
what 2 ways can progression be seen in dementia
1.progresses you start to see neocortical/medial temporal lobe atrophy 2.hippocampus is one region that begins to degenerate at earlier stages and this may help you differentiate between AD and other forms of dementia, such as DLB where the hippocampus remains intact at earlier stage
83
how do you differentiate between the different types of dementia?
look at the timescale of cognitive decline
84
what is functional imaging in AD patients?
hypometabolism in the posterior cingulate and bilateral parieto-temporal regions
85
what can functional imaging show and what does it use?
-technique uses radioimaging with ioflupane iodine-123 injections to detect dopamine binding. -DaTSCANs shows characteristic reduced striatal DAT binding in DLB patients. -AD patients will show normal striatal activity
86
what can cholinesterase inhibitors increase?
increase levels of ACh to improve/prolong cognitive function
87
what inhibitors is used for mild to moderate dementia?
cholinesterase inhibitors
88
what are 3 examples of cholinesterase inhibitors ?
1.donepezil (Aricept) 2.galantamine 3.rivastigmine
89
what do cholinesterase inhibitors prevent?
breakdown of acetylcholine, which is the most affected neurotransmitter system in dementia.
90
what drug is used to treat moderate to severe dementia?
glutamate receptor (NMDA) antagonist memantine
91
what is the role of glutamate receptor (NMDA) antagonist memantine?
alter disease progression by interfering with glutamate mediated cell death by reducing Ca2+ entry into the cell via the NMDA receptor. If Ca2+ levels are too high in the cell this can lead to cell death, so blocking this receptor may be neuroprotective
92
how do antipsychotics treating dementia?
- they are dopamine antagonists hallucinations and manic behaviours associated with psychosis
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mental health + neurobiology (45 decks)

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