Neuropathology (1) Flashcards
(43 cards)
What are the subdivisions of primary and secondary events of head injuries?
Primary divided into neural and vascular
Secondary divided into ischaemia, oedema and infection
What are common characteristics of a contusional injury?
focal symptoms
contre-coup injury = injury showing lesion opposite to impact
common in frontal and temporal lobes
Cause: burst lobe, intracerebral haemorrhage and post traumatic epilepsy
What is TAI?
traumatic axonal injury
- Diffuse axonal injury is the most severe
- high velocity acceleration/deceleration with torsion are major causes of persistent vegetative state
Clinical effects are immediate but cellular effects evolve over hours
Axon bulbs form when axons rupture - 24 hours
Beta-APP present in 2-3 hours
Petechiae in corpus callosum, brainstem
Gliding contusions =haemorrhage in parasagittal WM, often bilateral but usually asymmetrical
What are the 3 types of traumatic vascular damage?
1) diffuse vascular damage - widespread petechial haemorrhages - death soon after injury
2) damage to arteries -in neck or intra-cranially causing infarction or focal ischaemia
3) intracranial haemorrhage
What are the different types of traumatic intracranial haemorrhage ?
1) Extradural - arterial, sometimes no associated cerebral damage, lucid interval
2) subdural - acute: from damage to underlying brain or bridging veins; chronic: from bridging veins; RF: cerebral atrophy, coagulation dysfunction, anticoagulation therapy, alcoholism
3) subarachnoid - damage to vertebral arteries in neck, or shearing of intracranial arteries
4) Intracerebral - often from contusions, may occur hours or even a day or 2 after injury
What is a damaged brain more sensitive to?
more sensitive to hypoxia and hypercapnia/hypercarbia (co2 retention)
- hypoxia can occur due to compromised airway or chest injuries
What are causes of an ischaemic brain?
reduced circulation due to:
- hypotension, hypovolemia, e.g. surgical shock
- raised intracranial pressure
What are the different types of infarction in the brain due to ?
damage to an artery:
- intra-cranial compartment
- extracranially - carotid, vertebral arteries
What are the causes of raised intracranial pressure?
1) Cerebral oedema - perfusions/circulatory problem, reaction to haemotoma, direct reaction to rapid deceleration
2) mass effect of haematoma
What are the causes of infection?
1) meningitis - a) compound depressed fracture of the skull, b) fracture of base of skull, through air sinuses, middle ear
2) cerebral abscess - same routes
When does head injury occur due to post traumatic epilepsy?
early (first week/mnth) = about 4-5%
Late = 40% within 6 mnths, 50% <1 year
early PTE gives rise to 25% risk of late pte
incidence relates to severity of injury therefore absence of intracranial haematoma, contusional damage or depressed fracture, risk of PTE is 1%
What is chronic traumatic encephalopathy?
neurodegenerative disorder in people with repetitive brain trauma e.g. contact sports
delayed onset with progression over time
Tauopathy / dementia puglistica- distinct from AD as it is mainly frontotemporal atrophy and there is no beta-amyloid
What occurs in protein misfolding?
involved in neurodegeneration
- incorrect folding into a tertiary structure is likely the cause of catalytic enzyme resistance- it is these molecules which form inert fibrils
- prefibrillar intermediate forms are also formed - cause toxicity e.g. in HD
Why does protein misfolding occur?
Due to endoplasmic reticulum dysfunction - also plays a role in hypoxic damage
What is the incidence of dementia?
5% @ 70-74 years
20% @ 75-80 years
40% > 90 years
What are the causes of dementia?
vascular disease - mainly atheroma
alcohol
hydrocephalus
metabolic - hepatic and thyroid disease, b12 deficiency, poryphyria, anaemia, hypoxic
cerebral tumours and paraneoplastic syndrome
autoimmune limbic encephalitis
chronic traumatic encephalopathy
MS
infections: Herpes simplex encephalitis, HIV/AIDS, neurosyphilis, progressive multifocal leucoencephalopathy, subacute sclerosing pan encephalitis
What are the common conditions that cause dementia?
AD - 65-70% Vascular dementia - 15-20% Lewy body dementia - 10% Frontotemporal dementia - 5% other <1%
What are the key characteristics of AD?
Cerebral atrophy- mainly frontotemporal
neuritic plaques
neurofibrillary tangless
amyloid angiopathy - increases risk of haemorrhaging
basal nuclei affected - loss of cholinergic input to the cortex
What is the pathogenesis of AD?
Similar features to normal ageing
NFT density correlates with severity - increased density = increased severity
Neuritic plaques only found in AD, LBD and ageing
- amyloid in these plaques - amyloid depositis are formed by beta-amyloid protein derived from beta amyloid precursor protein
What are the risk factors for AD?
age, head injury, low educational status (but not socioeconomic status)
What factors reduce risk of AD?
Cardioprotective lifestyle, statin therapy, active and socially integrated lifestyle, arthritis and IBD
What are the genetic factors relating to AD?
Down’s syndrome - earlier onset (40s)
Autosomal dominant forms- mutations in:
- BAPP gene (chr21)
- presenillin-1 - onset 30-50 and is commonest form
- presenillin -2
common factor is they affect the processing of BAPP
What are the treatments for AD?
arricept (Donezepil) - anticholinergic agents
Immunization against amyloid B peptide - reduced plaques but no clinical improvement and induced encephalitis in some pts
What is the link between apolipoprotein E?
5 alleles, E4 has an increased risk of dementia (x3 increased risk with one E4 allele; homozygotes for e4 = x8 increased risk) +
- higher rate of fatal M
- poor outcome after head injury, cardiac bypass surgery, cerebral haemorrhage
- greater psychological impairment
