neuropathology

Question 1

What are ways in which infection can spread in the CNS

Answer 1

oCNS normally sterile
oMicroorganisms can gain entry via
- Direct spread (from middle ear, basal skull fracture, even through ethmoid bone)
- Blood-borne in sepsis or infective endocarditis
- Iatrogenic (post neurosurgery, ventriculoperitoneal shunt, lumbar puncture

Question 2

What is meningitis

Answer 2

• Meningitis –
inflammation of the leptomeninges (pi-arachnoid) 
• With or without
septicaemia (remember that non-blanching rash is a sign of meningococcal septicaemia, not meningitis per se)
• Prompt diagnosis and
treatment is life saving
Can have organism
causing sepsis without
much meningitis
Need to give empirical
treatment before you
know what the
organism is sometime -
havent got time to wait.
Need to give antibiotics

Question 3

What are causative organisms of meningitis

Answer 3

• Neonates – E. Coli, L. monocytogenes
• 2 -5 years – H. influenzae type B (HiB)
• 5 -30 years – N. Meningitides (types)
• Over 30 years – S. pneumoniae

• Various in immunocompromised individuals - variety of organimss eg fungi

Question 4

What is chronic meningitis

Answer 4

“Chronic Meningitis”
• Chronic clinical
course
• M. tuberculosis
– Granulomatous
inflammation
– Fibrosis of meninges
– Nerve Entrapment
-- Bilateral adrenal haemorrhage (Waterhouse-Friederichsen syndrome) can occur as a complication

slow in development.
Not same symptoms.
Photophobia, neck
stiffness
Thick material
at edge of brain . Biros is can pick of cranial nerves.
caseous material building up and leading to fibrosis.

Question 5

What are complictaions of meningitis

Answer 5

• Local:
– Death (swelling -> RICP)
– Cerebral Infarction -> neurological deficit
– Cerebral abscess
– Subdural empyema (pus)
– Epilepsy (due to direct irritation of brain)

• Systemic (if associated with septicaemia)
If sepsis - die from
systemic effects of
infection NOT Ricp.

Question 6

What is encephalitis

Answer 6

• Classically viral not bacterial
• Inflammation of brain parenchyma not meninges (but can occur as a complication of meningitis)
• Virus kills neurones causing inflammation and presence of intracellular viral inclusion bodies in neuroens.
Lymphocytic infiltrate typical
•Temporal lobe affected by Herpesviruses (most common) - often in immunocompromosed people
•Spinal cord affected by polio (now eradicated)
•Brainstem affected by rabies (very rare)
– Lymphocytic inflammatory reaction

Question 7

What is cytomegalovirus

Answer 7

ss

Question 8

what is prion protein

Answer 8

Prion protein (PrP) is a normal protein found in synapses (unknown function)
- PrP can transform into PrPsc (abnormal form) following sporadic mutation, familial inheritance of mutated gene or following ingestion of PrPsc itself
•PrPsc can convert PrP into itself (i.e. induce a conformational change) by protein-protein interactions alone
•PrPsc is extremely stable (resistant to disinfectants, irradiation) and not susceptible to immune attack as it is essentially a ‘self’ sprotein

Question 9

How does PrPsc cause damage

Answer 9

PrPsc causes damage by forming aggregates which destroy neruones and cause the brain to take on a sponge-like (spongiform) appearance
•Spongiform encephalopathiesoScrapie in sheepoBSE in cows (‘mad cow’ disease)oKuru in New Guinean tribes (due to cannibalism and ingestion of PrPsc)
- Creutzfeld Jacob disease (CJD)
- Variant CJD (vCJD)

Question 10

Describe variant cjd

Answer 10

• First described in 1996•Different from ‘classical’ CJD
• Strongly linked to BSE through ingestion of prions
• Essential difference compared to classical CJD is that there seems to be a much higher prion load associated with earlier age at death and more prominent psychiatric symptoms

Question 11

Are prion diseaseas an infecion?

Answer 11

Unclear as to whether this is an infection as does not completely fulfil all of Koch’s postulates:

Question 12

What is dementia

Answer 12

DementiaAcquired global impairment of intellect, reason and personality without impairment of consciousnessAlzheimer’s disease (50% of cases)
•Loss of cortical neurones
- Leading to cortical atrophy and decreased brain weight
- Damage caused by neurofibrillary tangles and amyloid plaques

Question 13

Describe amyloid deposition in AD

Answer 13

• Amyloid deposition central to pathogenesis

• Down’s syndrome
– Trisomy 21
– Early onset AD

• Mutations of 3 genes 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 14

What is normal ICP

Answer 14

• 0 -10mmHg
• Coughing and straining increase to 20mmHg
• Only significant if the increase maintained
for several minutes
• Compensation mechanisms maintain normal
pressure
– Reduced blood volume
– Reduced CSF volume
– Spatial - brain atrophy if cronically elevated
• Vascular mechanisms maintain cerebral
blood flow as long as ICP <60mmHg

Question 15

What changes does a SOL cause

Answer 15

Space occupying lesions (e.g. tumour)
•Deforms or destroys surrounding brain
•Displaces midline structures – loss of symmetry, midline shift
•Can cause brain herniation where part of the brain protudes though its containing wallp

Question 16

What is subfalcine herniation

Answer 16

Subfalcine herniation
- Cingulate gyrus is pushed under the free edge of the falx cerebri
- Herniated brain can become ischaemic due to compression of anterior cerebral artery (which normally loops up around corpus callosum and can get pinched)
Initially , not many symptoms, only as it expands do you get more and then infarction

Question 17

What is subfalcine herniation

Answer 17

Subfalcine herniation
- Cingulate gyrus is pushed under the free edge of the falx cerebri
- Herniated brain (medial parts of the frontal
and parietal lobe and corpus callosum) can become ischaemic due to compression of anterior cerebral artery (which normally loops up around corpus callosum and can get pinched)
Initially , not many symptoms, only as it expands do you get more and then infarction

Question 18

What is tentorial herniation

Answer 18

• Medial temporal lobe (classically the uncus) pushed down through the tentorial notch (free edge of tentorium cerebelli)
• Can compress ipisilateral oculomotor nerve and ipsilateral cerebral peduncle causing ipsilateral third nerve palsy but contralateral UMN signs in limbs
• Occlusion of blood flow in posterior cerebral and superior cerebellar arteries
• Can be complicated by secondary brainstem haemorrhage (Duret haemorrhage) – often fatal
• Usual mode of death for those with large brain tumouss or sever intercranial haemorrhage

Question 19

What is tonsillar herniation

Answer 19

Cerebellar tonsils
pushed into the
foramen magnum
compressing the
brainstem

Question 20

Describe benign vs malignant brain tumours

Answer 20

Benign
•Meningioma (from meninges)

Malignant
•Astrocytoma
oLow grade slow growing but difficult to remove
oHigh grade aka glioblastoma multiforme
oDirect spread along white matter pathways
oCan also spread to distant parts of CNS via CSF
oDoesnt matastasie clasically but can get mets

Question 21

What are other types of brain tumour

Answer 21

Others
•Neurofibroma (from Schwann cells of peripheral or cranial nerve)
•Ependymoma (from ependymal cells lining ventricular system)
•Neuronal tumours (from neurones, extremely rare) eg medulloblastoma common in children
•From non-CNS tissues
oLymphomas
oMetastases (most common of all brain tumours

Question 22

What is a stroke

Answer 22

• A sudden event producing a disturbance of CNS function due to vascular disease
• 2 per 1000 of general population per year but more frequent in elderly
• A variety of described syndromes depending on which parts of brain affected
• Risk factors include hyperlipidaemia, hypertension, smoking, diabetes,

Question 23

Whgat are 2 broad categories of stroke

Answer 23

Two broad categories:
– Cerebral infarction - 85%
– Cerebral haemorrhage - 15%

Question 24

Descrieb the pathogenesis of stroke

Answer 24

• Embolism (Most common)
– Heart - atrial fibrillation, mural thrombus
– Atheromatous debris (carotid atheroma)
– Thrombus over ruptured atheromatous plaque
– Aneurysm

• Thrombosis
– Over atheromatous plaque

Question 25

What are 2 types of cerebral infarciron

Answer 25

• Regional
– Named cerebral artery or carotid
MCA commonly

• Lacuna
– Less than 1cm
– Associated with hypertension
– Commonly affect the basal ganglia and internal capsule

Question 26

Give an overview of cerebral haemorrhage

Answer 26

• 15% of all strokes
• Spontaneous i.e. Non-traumatic
• Intracerebral haemorrhage 10% of all
strokes
• Subarachnoid haemorrhage 5% of all
strokes

Question 27

What is intracerebral haemorrhage

Answer 27

• Associated with hypertensive vessel
damage
• Charcot-Bouchard aneurysms
• Deposition of amyloid around cerebral
vessels in the elderly - Walls more prone to lead to
haemorrhage
• May be inherited
• Produces space occupying lesion – RICP

Question 28

what is a subarachnoid haemorrhage

Answer 28

Subarachnoid haemorrhage (5% of all strokes)Rupture of berry aneurysms, usually found at branch points in circle of Willis
- Blood in subarachnoid space can cause secondary spasm of cerebral arteries
-Associations
•Male
•Hypertension
•Atherosclerosis
•Linked to other diseases (e.g. connective tissue disorders, congenital weakness in vessel walls?

Question 29

What are the symptoms of SAH

Answer 29

• Sudden severe headache – Thunderclap
• Sentinel headache
• Loss of consciousness
• Often instantly fatal