CPAT NEURO Flashcards
What does the falx cerebri separate
right and left hemispheres
what does the tentorium cerebelli separate
forebrain and hindbrain
what are the 5 types of space occupying lesions
- haemorrhage -extradural, subdural, subarachnoid, intracerebral
- tumour
- infection
- edema.
- hydrocephalus (increase csf volume)
what are two conseqences of SOL which continue to grow - uncontrolled
midline shift
gyral flattening onto outside of skull. (narrowed sulci)
normally cerebral perfusion means
arterial pressure is greater than intracranial pressure causing a net flow into the brain.
if arterial pressure is less than or qual to intracranial pressure, no net flow into brain and brain death.
what is a sub falcine herniation
displacement of brain under falx cerebri
what is a transtentorial herniation
displacement of brain under tentorium cerebelli into hind brain.
what is a tonsilar herniation
displacement of brain through foramen magnum into spinal column.
what are some secondary pathologies of SOLs
- haemorrhage e.g. Duret haemorrhage
- compression of cranial nerves/arteries
- edema
- congestive brain swelling
what is Alzheimers disease characterised by
progressive loss of neurons (white matter) and a long disease course with amjor risk factor being age.
what is the characteristic pathologic feature of alzheimers disease
protein accumulation - tauopathies
protein inclusions
what are the forms of AD
inherited and sporadic/acquired.
what are some symptoms of AD
early loss of short term memory, cognitive impairment to e.g. loss of visuospatial skills
what are the macroscopic features of AD
Global atrophy (Except parietal and occipital lobe), widened sulci. atrophy begins in hippocampus, proceeds to temporla, then global
what are the microscopic features of AD
1/. plaques - extracellular, variable in size and structure, mostly composed of beta amyloid.
2.neurofibrillary tangles - intracellular, in cytoplasm of neurons. major component is hyperphosphorylated tau
what is the evolution of AB plaques
diffuse
neuritic (dystrophic neurites, tau +ve)
compact
where are neurofibrillary tangles usually found
hippocampus, medial temporal lobe
what do you see when there is overlap between tau (NFTs) and AB (plaques) pathology
neuritic plaques - central core of AB surrounded by distorted neuritic tau positive processes and glial cells.
what are the two pathways of amyloid precursor protein proteloysis
- non amyloidogenic - alpha secretase cuts peptide between AB so the AB fragment cant be formed
- amyloidogenic - beta and gamma secretase cut the peptide either side of AB so AB fragment is formed. AB42 is very sticky - causes fibrillisation and plaques
what are the mutations identified in familial AD
mutations to APP, preselin 1 and 2 (components of gamma secretase)
no mutations in tau protein yet identified
describe the amyloid cascade hypothesis for sporadic AD
- dysregulation of APP metabolism causes increase AB
2 interacts with neuronal receptor or membrane and changes conditions in neuron (ionic homeostasis/oxidative injury) - alterered kinase/phosphatase activity which causes hyperphosphorylated tau which leads to development of NFTs.
4 neuronal death/dysfunction.
what are risk factors for sporadic AD
e4 allele of APOE gene (has probable role in clearance of AB, has been shown in plaques)
what is a problems with the amyloid cascade hypothesis
- failure of AB therapies to halt cognitive decline (may just need to introduce therapy earlier)
parkinsons disease is apart of what disorder specturm
lewy body disorder spectrum (most common lewy body disorder)
what kind of proteinopathy does parkinsons exhibit
synucleinopathy - characterised by intra neuronal alpha synuclein inclusions.
what are the clinical features of PD
bradykinesia, tremor, ridgidity
may also exhibit stooped posture and asymmetric motor dysfunction.
treatment for PD
L-DOPA
what are the macroscopic features of PD
loss of cells in susbtantia nigra which contain a pigment called neuromelanin. loss of this pigment. neuromelanin is thought to be involved in handling the oxidisable biproducts of dopamine.
microscopic features of PD
loss of dopaminergic neurons and neuromelanin, nigral lewy bodies (inclusions in dopaminergic neurons)
what are the main component of lewy bodies
alpha synuclein (fibrillar)
how is PD staged
by the spread of lewy bodies. (Braak staging)
early stages - medullar and olfactory region
mid stages - midbrain and pons
late stages - neocortices (dementia)
what is the lewy body pathogenesis of PD
excess alpha synuclein forms oliogmers then fibrils then lewy bodies which eventually kills cell.
dopaminergic output in PD
In normal brain, dopamine activate the direct over indirect (reduced GPi output) and promotion of movement
With Parkinson’s disease there is loss of > 50% dopamine (DA) input to striatum
So indirect pathway favoured, thalamic inhibition increased, movement retarded
What about Tremor? – not only striatum deficit, may also involve cerebellum, red nucleus
describe monogenic forms of PD
rare, incolve mutatations in LRRK2, PINK1, Parkin - all invovled in mitochondrial function.
describe sporadic forms of PD
combinatino of genetic susceptibility ( from common polymorphisms) and environmental factors on a background of aging.
describe an example of environmental induced PD
MPTP )biproduct of methadone) crosses BBB and is converted into MPP+ by monoamine oxidase. MPP+ is a complex 1 inhibitor - this prevents oxidative phosphorylation and damages dopaminergic neurons.
what might be protective factor against PD
nicotine - by preventing alpha synuclein defibrilisation.
how is PD treated
LDOPA, deep brain stimulation.
what is multiple system atrophy
parkinsonism with autonomic dysfunction. alpha synuclein in oligodendricytes, cytoplasmic not intraneuronal protein inclusions.
what are the three types of stroke
- ischemic - large artery atherothrombosis, embolism
- haemorrhagic
- unknown
what are the main sites of larger artery atherothrombi
- extracranial vessels (most common) - internal carotid artery near common carotid bifurcation
- intracranial vessels - origin of middle cerebral artery and ends of basilar artery
what are the two major zones of injury during cerebral ischemia
- core ischemic zone
- ischemic penumbra - mild to moderate ischemic tissue remains viable for much longer due to blood supply from collateral arteries.
when does neuronal electrical failure develop during brain ischemia
at 30% cerebral blood flow, causes loss of sensation , movement, speech
when does neuronal membrane failure develop
at 5% cerebral blood flow - neurons die.
what are the molecular events occuring in acute ischemia
- glutamate release - in excess is toxic. causes increase in intracellular Ca, stimulates reactive intermediates leading to membrane and DNA damage.
- decreased energy production - leads to failure of ionic pumps, mitochondrial injury and production of free radicals.
- ischemic reperfusion injury - leukocyte infiltration etc causes damage.
what are macro features of acute brain infarct (< 2 days)
- softening/loss of tissue
- swelling and edema
- infiltration of neutrophils
- ischemic red cell neuronal change
what are macro features of subacute brain infarct (days-weeks)
- liquefication and cavitation
- foamy macrophages filled with myelin (lipid)
- reactive astrocytes form glial scar
what are macro features of remote brain infarct (weeks +)
- cavitation
- glial scar
- haemosiderin laden macrophages
what kind of stroke is a small penetrating artery occlusion
atherothrombotic stoke
where do small penetrating artery occlusions occur
lenticulostriate arteries coming off the middle cerebral arteries - these arteries are very susceptible to changes in bp.
what can occlusion of a small penetrating artery lead to
infarcts in striatum, internal capsule, basal ganglia, thalamus, brain stem - can be catastro[hic
what is small penetrating artery occlusion associated with
arterial hypertenstion
what does small penetrating artery occlusion often present as
transient ischemic attacks - may be clinically silent
describe an embolic stroke
the dislodging of a thrombus causing an emboli to move and lodge in vessel in brain.
what do embolic strokes usually present as
haemorhagic due to blood reflowing into area after lysis of emboli but damage to vessels leading to haemorrhagic embolic stroke. different to haemorhagic stroke.
where do most embolic strokes occur
middle cerebral artery territory
what are the most common sites for haemorhagic strokes
sub cortical structures - cerebellum, basal ganglia, brain stem.
what is a histologically feature of small vessel haemorrhagic stroke
slit haemorrhage lined with hemosidering laden macrophages
what is the major risk factor for strokes in subcortical regions
hypertension
what is a micro feature of lobar haemorhage
beta amyloid build up.
describe subarachnoid haemorrhage
occurs due to rupture of BV outside of brain on surface, usually caused by ruptured berry anuerism. sudden onset, thunderclap headaches, high mortality,
describe a berry aneurisum
stretched blood vessel which forms a pocket of blood. thin wall highly susceptible to rupture.
where to berry anuerisms usually occur
at areas where there is a change of blood flow from laminar to turbulent.
describe the stroke subtype - global ischemia
caused by infarcts between arterial territories
when are boundary zone infarcts seen
global ischemia when there is abrupt hypotension followed by rapid recovery.
where are global ischemic infarcts usually seen
between middle and anterior cerebral arteries and middle and posterior cerebral arteries.
what are the two kinds of primary traumatic brain injury
concussion, diffuse and focal
what are some examples of diffuse traumatic brain injury
global ischemia, diffuse vascular injury, brain swelling
what are some examples of focal brain injury
haemorrhage
describe diffuse brain injury
APP immunostaining - amyloid precursor protein indicative of axonal damage caused by injury.
focal brain injury: traumatic haemorrhage - what types
extradural - skull fracture
subdural
chronic subdural
subarachnoid (fatal, a result of major trauma)
what is traumatic intracerebral haemorhage
intraparenchymal haemorrhage, similar presentation as stroke but due to trauma. coupe and contre coupe injury. symmetrical injury to other side of brain.
secondary injury from TBI.
secondary damage due to inflammatory processes, glutamate buildup, ROS, BBB damage - leads to vascular and cytotoxic edema and swelling, most often COD.
what does raised intracerebreal pressure lead to
as intracerebral pressure rises and approaches arterial pressure, cerebral perfusion pressure decreases. at 30% blood flow electrical failure
15% blood flow =cell death
what are characteristic signs of secondary injury FROM TBI
damage first in CAI neurons of hippocampus, characteristic red neuron look.
what is treatment from secondary injury from TBI
monitor ICP, monitor brain o2, drainage, craniotomy.
describe subdural haemorrhage
bridging veins between arachnoid into dura are thinner and more suscptible to rupture following trauma.
what are some examples of sports related TBI
- concussion
- second impact syndrome - accumulative effect of multiple concussions - impaired attention, poor memory, depression
- post concussive syndrome - associated with single concussive event, leads to dizziness, impaired attention and poor memory
describe chronic traumatic encephalopathy(CTE)
caused by repetitive mild TBI or concussions, causes atrophy in white matter structures e.g. corpus collosum and causes NFT (no AB plaques like AD). may also see neuronal white matter loss in cerebellum and substantia nigra.
where are NFTS often seen in CTE
at the bottom of sulcus - change in tissue densisty
what are the amcroscopic features of CTE
diffuse brain volume loss, cavum septum pellucidum, cavum vergae, loss of white matter in corpus collosum.
what the microscopic features of CTE
degeneration of SNc, neuronal loss in cerebelllum, NFTS in cortex (Tauopathy)
what is creutzfeld jacob disease
an infectious, degenerative disease caused by a prion. also known as a transmissible spongiform encephalopathy.
what is the infectious protein in CJD
PrPsc - misfolded protein which survives very very long and hard to destroy. has as extended incubation period. begins as asymptomatic but then shows rapid degeneration.
what is sporadic CJD
most common form of CJD, unsure etiology, short duration, dementia, ataxia, wide posture. atrophy, spongiform encephalopathy due to a loss of cells/ neurons, increased vacuolation pattern, florid plaques.
what is the prion hypothesis
normal PRPC has 3% beta sheet. a conformational change causes it to switch to PRPSC which has 43% beta sheet. is resistant. comes into contact with normal protein and causes it to switch to PRPSC form which is infective.
what is iatrogenic CJD
induced CJD e.g. pituitary hromone exrtacts used to treat dawrfism, transplants etc.
what is MS
demyelinative disease, chronic inflammatory autoimmune disease of CNS. lesions can occur in any parts of cns including spinal cord.
risk factors for MS
gender - females, distance from equator.
HLADR2 halotype. MHC on chromosome 6P21 involved in presenting peptide to antigens.
what is the EAE model for MS
an immune rection against murine muelin basic protein induces MS
what is the course of MS
remitting relapsing
how is MS diagnosed
MRI - paraventricular lesions/plaques, other lesions sites include optic nerve, brain stem, cerebellum, spinal cord. shows well defined grey firm plaques in white matter.
what are the microscopic features of MS
myelin loss cause punched out lesions oftern around small veins, myelin debris in macrophages, loss of oligodendricytes. perivascular cuffing - perivascular inflammatory cells including lymphocytes, plasma cells, macrophages. reactive astrocytes.
what is pathogenesis of MS
- loss of myelin - slow/no neurotransmission
- asonal loss
- axonal destruction in chronic plaques (lack of support from oligodendricytes)
- loss of brain volume over time.
describe alcohol related brain damage
brain atrophy, white matter loss, minor neuronal loss in frontal cortex (not motor cortex)
what is the pathogenesis of alcohol related brain damage
- gluatamate toxicity and or oxidative damage
- decreased neurogenesis
- hepatic encephalopathy (NH3 and inflammation)
- malnutrition e.g. vitb12 deficiency
- polydrug use
what is wenicke korsakoff syndrome
caused by thiamine (VITB12) deficiency, usually caused by chronic alcoholism.
what are the acute presentations of wernicke korsakoff syndrome
oculomotor abnormalities, cerebellar dysfuntcion, confusion.
what are the histological features of acute wernicke korsakoff syndrome
periventricular haemorrhage, endothelial hypertrophy
what are the chronic presentations of wernicke korsakoff syndrome
may have retrograde amnesia (korsakoff psychosis
what are the histological features of chronic wernicke korsakoff syndrome
mamillary body shrinkage due to neuron loss, also neurons loss in anterior thalamus and anterior cerebral vermis - lose ability to recall memories, make new memories.
