8.3 Neuropathology

Question 1

How can microorganisms gain entry into the sterile CNS?

Answer 1

Direct spread - basilar fracture, ear infection
Blood-borne - sepsis, infective endocarditis
Iatrogenic - lumbar puncture, surgery

Question 2

What is meningitis?

Answer 2

Inflammation of the leptomeninges with or without septicaemia. A condition requiring urgent diagnosis and treatment.

Question 3

What is empirical treatment and give an example of a condition it might be used in?

Answer 3

Treatment prior to diagnosis. For example, a broad spectrum antibiotic might be used to treat meningitis before it is officially diagnosed.

Question 4

What are the common causative organisms for meningitis in different age groups?

Answer 4

Neonates = E.coli, L.monocytogenes
2-5 yrs = H.influenzae type B
5-30 yrs = N. meningitides
30+ yrs = S. pneumoniae

Question 5

Infection with which organism may lead to chronic meningitis? How does this present?

Answer 5

M. tuberculosis
Does not present in the same way to normal acute meningitis - granulomatous inflammation, fibrosis of the meninges, nerve entrapment…

Question 6

Why are cerebral abscesses hard to treat?

Answer 6

Accumulation of bacteria, which is very difficult for antibiotics to fully penetrate and treat it.

Question 7

What is encephalitis?

Answer 7

Often virally-caused disorder of the parenchyma (neurons and glia). Results in neuronal cell death. Different regions of encephalitis arise from different conditions e.g. Polio affects the temporal lobe. Rabies affects the brainstem.

Question 8

How does Prion disease develop?

Answer 8

Mutated prion protein (PrP) is acquired sporadically, through family, or ingested.
It interacts with normal PrP so is not recognized by the body as foreign protein.
PrPsc aggregates leading to neuronal death and holes in grey matter.

Question 9

Give 3 examples of prion disease.

Answer 9

1. Spongiform encephalopathies
2. BSE in cows
3. vCJD (variant Creutzfeldt- Jakob disease) - strongly linked to BSE in cows, linked to butchery… ‘mad cow disease’

Question 10

What is dementia?

Answer 10

A condition of acquired global impairment of intellect, reason and personality without the impairment of consciousness.
Includes: Alzheimer’s, Vascular dementia, Lewy body dementia, and Pick’s disease (frontotemporal dementia)

Question 11

List some characteristic pathological hallmarks of Alzheimer’s disease.

Answer 11

1. Exaggerated ageing
2. Loss of cortical neurons / advanced brain atrophy
3. Increased presence of neurofibrillary tangles and senile plaques.

Question 12

What are neurofibrillary tangles?

Answer 12

In AD these are twisted filaments of Tau protein, which becomes hyperphosphorylated so cannot fulfill its job in stabilizing microtubules. This means the brain can accumulate damage.

Question 13

What are senile plaques?

Answer 13

In AD these are formed when pathological amyloid (amyloid beta) in deposited in vessels of the brain leading to plaque formation.

Question 14

Down Syndrome studies showed mutations of 2 genes being important in AD pathogenesis, what 2 genes are these?

Answer 14

1. Amyloid precursor protein (APP)
2. Presenillin (1+2) - encode secretase enzymes important for the correct breakdown of APP.
   (if breakdown is incorrect, the amyloid produced is deposited in neurons)

Question 15

Name some compensation mechanisms that can help achieve normal intracerebral pressure.

Answer 15

1. Reduced blood volume
2. Reduced CSF volume
3. Brain atrophy
   These mechanisms maintain cerebral blood flow so long as ICP <60mmHg.

Question 16

What occurs in a subfalcine herniation?

Answer 16

On the same side as the mass, the cingulate gyrus gets pushed under the free edge of falx cerebri. This leads to compression of the anterior cerebral artery and ischaemia of medial parts of the frontal and parietal lobes (and corpus callosum)

Question 17

What occurs in a tentorial herniation?

Answer 17

The uncus / medial parahippocampal gyrus herniates through the tentorial notch. Get damage to ipsilateral occulomotor nerve (Down and out sign), as well as occlusion to blood flow in the posterior cerebral and superior cerebellar arteries.
Frequently fatal = secondary haemmorhage into brainstem ‘duret haemmorhage’

Question 18

What occurs in a tonsillar herniation?

Answer 18

Cerebellar tonsils pushed into foramen magnum, compressing the brainstem.

Question 19

Give some examples of tumours affecting the brain and CNS.

Answer 19

1. Meningioma = benign, may compress brain –> herniation.
2. Astrocytoma = benign when grade 1, but can still grow and kill patient. Higher grades can appear as gross, necrotic tumours.
3. Neurofibroma
4. Ependymoma (kids only)
5. Medulloblastoma (neuronal)

Question 20

What is a stroke?

Answer 20

Sudden event producing a disturbance of CNS function due to vascular disease (symptoms last longer than 24hrs)

Question 21

What are the two main categories of stroke?

Answer 21

Ischaemic (85%) cases

Haemmorhagic (15%) cases

Question 22

What pathologies increase the risk of a stroke?

Answer 22

AF
Atheromatous debris (carotid atheroma)
Thrombus over ruptured atheromatous plaque
Aneurysm

Question 23

What are the two types of infarct involved in ischaemic strokes?

Answer 23

1. Regional - occludes named cerebral artery, or carotid
2. Lacunar - less than 1cm, blockage of any of the arteries arising from The Circle of Willis. Commonly affect the basal ganglia.

Question 24

What are the two types of haemmorhage involved in haemmorhagic stroke?

Answer 24

1. Intracerebral (10%) - associated with hypertensive vessel damage, Charcot-Bouchard aneurysms. Produces space occupying lesion.
2. Subarachnoid (5%) - rupture of berry aneurysms, sited at branching points in the Circle of Willis. Sudden severe (sentinel) headache. Associated with LOC. Often instantly fatal.