NS 12: Neuropathology

Question 1

3 possible routes for microorganisms to get into the CNS?

Answer 1

direct spread e.g. middle ear infection, spread to mastoid process and can cause a temporal lobe abscess, and base of skull fracture.
blood borne- cross BB barrier, e.g. infective endocarditis- streptococccus viridans or staph aureus
iatrogenic- e.g. following lumbar puncture, ventriculo-peritoneal shunts for hydrocephalus, surgery

Question 2

what is meningitis the inflammation of?

Answer 2

meninges- specifically the leptomininges= arachnoid mater and pia mater.

Question 3

in what 2 ways can meningitis cause death

Answer 3

rasied IC pressure

septicaemia- SHOCK- inadequate perfusion to vital tissues

Question 4

what is seen histologically in the brain with meningitis?

Answer 4

neutrophil infiltration= multi-lobed nuclei

Question 5

causes of meningitis in neonates?

Answer 5

E coli

listeria monocytogenes

Question 6

cause of meningitis in children aged between 2 and 5?

Answer 6

Haemophilus influenzae B
less likely now following 5 in 1 vaccine immunisation programme= diptheria, tetanus, polio, pertusis- whooping cough and Hib- H influenzae.

Question 7

cause of meningitis in those aged between 5 and 30?

Answer 7

Neisseria meningitidis

Question 8

cause of meningitis in those aged over 30?

Answer 8

Strep pneumoniae

Question 9

cause of chronic meningitis

Answer 9

M.TB- granulomatous inflammation- caseous necrosis, chronic inflammation= fibrotic meninges- causes nerve entrapment
tends to present with headaches and cranial nerve symptoms, may be weight loss and general malaise due to TB

Question 10

complications of meningitis?

Answer 10

death-swelling within rigid cranium causes raised ICP
cerebral infarction-STROKE, causing neurological defecit
cerebral abscess
subdural empyema
epilepsy- part. in children if brain parenchyma damaged as epileptogenic focus created= origin of high frequency electrical impulses discharged episodically in epilepsy, causing seizures.

systemic- septicaemia

Question 11

what is infected in encephalitis?

Answer 11

the brain parenchyma= neurones, neuronal bodies undergo cell death and get viral inclusions, causing neurone death.

Question 12

what is encephalitis typically caused by?

Answer 12

viral infection

Question 13

example of a virus which can infect the temporal lobe to cause encephalitis?

Answer 13

Herpes virus

tends to occur in children and immunocompromised individuals

Question 14

what doe the polio virus infect?

Answer 14

spinal cord motor neurone cell bodies

Question 15

what virus causes infection of brainstem?

Answer 15

rabies

varicella in children- causes chickenpox, but can cause encephalitis and pneumonitis

Question 16

what happens histologically with encephalitis?

Answer 16

lymphocytic infiltration- chronic inflammatory reaction, lymphocytes form perivascular cuffs.

Question 17

what inclusions occur with cytomegalovirus infection?

Answer 17

Owl’s eye

Question 18

why are pregnant women told to avoid cats in pregnancy?

Answer 18

cats may carry toxoplasma gondii, found in their faces, and infection of the mother=toxoplasmosis, can cause teratogenic effects

Question 19

when might toxoplasma cause problems?

Answer 19

pregnant women= teratogenic effects

immunocompromised- toxoplasma can become uncontrolled and cause encephalitis e.g. in chemotherapy patients.

Question 20

what are prions?

Answer 20

proteins, normal constituents of neuronal synapse

if mutated can cause prion disease= mutated proteins aggregate together and interfere with synaptic transfer.

Question 21

how can people get a mutated prion protein?

Answer 21

ingested
sporadic
inherited

Question 22

how does prion disease come about?

Answer 22

mutated prion protein can induce a conformational change in a normal prion protein of the neuronal synapse. can then aggregate together and disrupt neuronal transmission.
aggregates cause neurone death and holes in gray matter= spongiform encephalopathy
prion protein= very stable

Question 23

how is dementia separated from delerium?

Answer 23

dementia= no impairment of consciousness

Question 24

why are sulci and gyri more prominent in dementia?

Answer 24

have lost cortical neurones- death of neurones is accelerated

Question 25

2 causes of increased neuronal death in alzheimer's disease?

Answer 25

neurofibrillary tangles | senile plaques

Question 26

how do neurofibrillary tangles cause damage in alzheimer's disease?

Answer 26

= IC twisted filament of Tau protein= normal protein which usually binds and stabilises microtubules, but protein becomes hyperphosphorylated so clumping occurs as the proteins stick together, posionous to neurone causing cell death= tauopathy.

Question 27

example of genetic familial cause of alzheimer's disease, which subsequently occurs early in life e.g. in 30s?

Answer 27

Down's syndrome 3 genes related to amyloid protein on chromosome 21 Amyloid precusor protein (APP) gene, Presenilin (PS) genes 1 and 2 code for components of secretase enzyme, Leads to incomplete breakdown of APP and amyloid is deposited.

Question 28

how do senile plaques cause damage in alzheimer's disease?

Answer 28

Foci of enlarged axons,synaptic terminals and dendrites, amyloid deposition in vessels in centre of plaque.

Question 29

pressure normally exerted by CSF?

Answer 29

minimal, up to 10mmHg | coughing can increase it to 20mmHg

Question 30

compensation of brain to raised ICP?

Answer 30

less blood sent to brain- reduce blood volume reduced CSF volume= these 2 take hrs to days brain atrophy= occurs over much longer time period rasied ICP only significant if maintained for several mins

Question 31

for what ICP can vascular mechanisms maintain cerebral b.flow?

Answer 31

Vascular mechanisms maintain cerebral blood flow as long as ICP <60mmHg *t occur, and survival instinct- try and get brain below heart to get blood into it.

Question 32

what structures stop the brain from moving, causing problems with raised ICP in expanding SOLs?

Answer 32

rigid skull falx cerebri tentorium cerebelli= infolded layers of the meningeal layer of the dura mater

Question 33

causes of raised ICP?

Answer 33

``` tumour haematoma abscess infarction= oedema of surrounding tissues =expanding focal lesions infection e.g. meningitis, encephalitis= inflammatory oedema trauma = global increase in brain mass ```

Question 34

what is subfalcine herniation?

Answer 34

cingulate gyrus pushed under free edge of falx cerebri occurs on same side of mass compromises blood flow through anterior cerebral artery from ICA, so ischaemia of medial parts of the frontal and parietal lobe and corpus callosum= infarction

Question 35

false localising sign in tentorial herniation?

Answer 35

pupil dilation= makes you think lesion on 1 side of brain e.g. stroke, when in fact whole brain experiencing increase in ICP.

Question 36

what happens in tentorial hernitation?

Answer 36

uncus pushed through tentorial notch Damage to the occulomotor nerve on the same side Occlusion of blood flow in posterior cerebral and superior cerebellar arteries Frequently fatal because of secondary haemorrhage into the brainstem, resulting in Duret haemorrhage Common mode of death in those with large brain tumours and intracranial haemorrhage, and meningitis and encephalitis, brainstem centres compressed so ptnt stops breathing.

Question 37

prodromal features in ptnt with raised IC pressure?

Answer 37

headache- worse on walking, lying down and 1st thing on a morning vomiting papilloedema- optic disc swelling

Question 38

what happens in acute phase of raised ICP?

Answer 38

Occulomotor nerve compression = dilation of the pupil Compression of the brain stem = coma alongside, getting compression of cerebral peduncles= hemiparesis, and compression of vital bstem structures causing apnoea and cardiac arrest.

Question 39

what happens in coning?

Answer 39

cerebellar tonsils pushed into foramen magnum, compressing brainstem

Question 40

what would very high BP and weak pulse indicate in a patient previously experiencing headaches worse on a morning and walking, and vomiting?

Answer 40

Cushing's reflex following raised ICP compressing brainstem centres very high BP as body trying to pump blood to brain, and bradycardia

Question 41

most common benign tumour of brain?

Answer 41

meningioma

Question 42

origin of malignant tumours in brain which originate in brain?

Answer 42

astrocytes astrocytoma (grade 1 to grade 4) grade 1= well differentiated, 4=anaplastic – Spread along nerve tracts and through sub arachnoid space often presents with a spinal secondary *malignant of brain never metastasise to out of CNS

Question 43

most common tumour in brain?

Answer 43

result of metastasis common metastases to brain= breast cancer, lung cancer, bladder cancer, kidney cancer

Question 44

why are MRIs done following new onset epilepsy?

Answer 44

check for brain tumours- causing a focus

Question 45

primary damage in head trauma?

Answer 45

physical damage to brain: Focal damage – Bruising and laceration of the brain as it hits the inner surface of the skull – Tearing of blood vessels and nerves as the brain moves causing haemorrhage and blood is an irritant to brain, causes vasoconstriction. Diffuse – Direct tearing to axons - Diffuse Axonal Injury (DAI) white matter and grey matter accelerate and decelerate at different times

Question 46

types of damage in focal damage when primary damage occurs in head injury?

Answer 46

``` coup= focal damage at site if impact contrecoup= damage on opposite side of brain, often of greater severity ```

Question 47

what happens with diffuse injury (diffuse axonal injury DAI) in primary damage in head trauma?

Answer 47

Micro-tears to axons at sites of differing densities of brain substance e.g. junction of white and gray matter Tearing of nerves and small vessels Tearing of the pituitary stalk Severity proportional to the degree of force (especially rotational), often persistent vegetative state Heals by gliotic scarring- damage is permanent*

Question 48

how does a stroke differ from a TIA?

Answer 48

TIA- symptoms last for <24 hrs, and complete recovery occurs following this time. stroke= residual neurological defecit e.g. difficulty moving, difficulty with speech.

Question 49

what do lacuna infarcts commonly affect?

Answer 49

basal ganglia

Question 50

2 different types of haemorrhagic strokes?

Answer 50

``` intracerebral haemorrhage (10%) SAH (5%) ```

Question 51

characteristics of IC haemorrhagic strokes?

Answer 51

Associated with hypertensive vessel damage Charcot-Bouchard aneurysms, artery usually around basal ganglia May be assoc. with deposition of amyloid around cerebral vessels in the elderly May be inherited Produces space occupying lesion – RICP

Question 52

characteristics of SA haemorrhagic strokes?

Answer 52

Rupture of ‘berry’ aneurysms Pathogenesis poorly understood – Male sex-inherited – Hypertension- aneurysm more likely to burst if high BP – Atheroma – Links to other diseases Sited at branching points in the Circle of Willis occur at base of brain, high pressure arterial blood thunderclap headache sentinel headache- occur before big headache= intermittent bleeding of aneurysms before rupture Loss of consciousness Often instantly fatal Arterial spasm - ischaemia and infarction