S8 L3 Introduction to neuropathology

Question 1

What is meant by infections of the CNS?

Answer 1

CNS is normally sterile
No commensal bacteria
Immune privileged site

Question 2

How can micro-organisms gain access to the CNS?

Answer 2

1. Direct spread → Middle ear infection, base of skull fracture
2. Blood-borne → sepsis, infective endocarditis
3. Iatrogenic → VP shunt, surgery, lumbar puncture

Question 3

What is meningitis?

Answer 3

Inflammation of the leptomeninges → pia and arachnoid mater (inner layers)
With or without septicaemia- non blanching rash (sign of meningococcal septicaemia not meningitis)
Prompt diagnosis and treatment is life saving → acute inflammation, oedema, swells the brain, congestion of BV, neutrophils and pus → ↑ICP → death if not treated

Question 4

What are the causative organisms of bacteria meningitis?

Answer 4

Different age groups different prominent bacteria
Various ones in immunocompromised individuals e.g. fungi
DONT need to learn- just be aware
1. Neonates → E.Coli, L.monocytogenes
2. 2-5 years → H. influenzae type B (HiB)
3. 5-30 years → N. Meningitides (types)
4. Oer 30 years - S. pneumoniae

Question 5

What is chronic meningitis?

Answer 5

Rare disease 
Chronic clinical course 
M. tuberculosis 
→ Granulomatous formation 
→ Fibrosis of the meninges 
→ Nerve entrapment 
If left untreated or in immunocompromised patients→ more progression → cranial nerve problems

Question 6

What are the complications of meningitis?

Answer 6

Local
- Death (swelling → RICP)
- Cerebral infarction → neurological defect
- Cerebral abscess → bit of infection becomes walled off, antibiotics unable to reach it
- Subdural empyema → infection (pus) in potential space between meninges
- Epilepsy → damages particular areas of the brain
Systemic (if associated with septicaemia)

Question 7

What is encephalitis?

Answer 7

Classically viral not bacterial
Inflammation of the brain parenchyma not the meninges → can occur as a complication of meningitis
- Neuronal cell death by virus → inflammation and presence of inclusion bodies
- Lymphocytic infiltrate typical → chronic inflammation- swelling of the brain
- Different areas of the brain affected by different viruses
→ Temporal lobe affected by Herpesvirusus (most common)
→ Spinal cord affected by polio (now eradicated)
→ Brainstem affected by rabies (very rare)

Question 8

What is prions disease?

Answer 8

• Prion protein (PrP) → normally found in synapses (unknown function)
• Mutated PrP → PrPsc
• Sporadic, familial or ingested
• Mutated PrP (PrPsc) can interact with normal PrP - undergoes post translational conformational change by protein-protein interactions alone
• PrPsc is extremely stable - resistant to disinfectants, irradiation etc…, not susceptible to immune attacks- ‘self protein’
• Forms aggregates in the brain which results in damage

Question 9

What does prions disease result in?

Answer 9

Spongiform encephalopathies - brain looks like a sponge

• Scrapie in sheep
• BSE in cows
• Kuru in tribes of New Guinea
• Variant Creutzfeld-Jacob disease (vCJD)

Question 10

What is variant Creutzfeld-Jacob disease?

Answer 10

• Linked to ingestion of prions
• Much higher prion load compared to classical CJD
• Earlier age death (28 years)
• More prominent psychiatric symptoms
• Prolonged incubation period 15+ years

Question 11

Is prion disease an infection?

Answer 11

Unclear
Does not fulfil Koch’s postulate
- Microorganism must be found in abundance in all organisms suffering from disease but not found in healthy organisms
- Must be isolated from diseased organism and grown in pure culture
- Cultured microorganism should cause disease when introduced into a healthy organism
- Organisms must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent

Question 12

What is dementia?

Answer 12

Acquired global impairment of intellect reason and personality without impairment if consciousness

• AD → 50% → Sporadic/familial, early/late
• Vascular dementia → 20% → Not enough blood getting to the brain
• Lewy body
• Picks disease

Question 13

What is Alzheimers disease?

Answer 13

• Exaggerated aging process
• Loss of cortical neurones → ↓brain weight, cortical atrophy (shrinkage)
• Due to ↑neuronal damage → neurofibrillary tangles, senile plaques
• Amyloid deposition central to pathogenesis

Question 14

What is a tangle in Alzheimer’s disease?

Answer 14

• Intracellular twisted filament of Tau protein
• Tau normally binds and stabilises microtubules
• Tau becomes hyperphosphorylated in AD
• Tauopathy

Question 15

What is a senile plaque in AD?

Answer 15

• Foci of enlarged axons, synaptic terminals and dendrites
• Amyloid deposition in centre of plaque associated with BV
• Builds up around BV → abnormal and fragile → reduced blood flow to brain → ischaemia

Question 16

What is the familial cause of AD?

Answer 16

Trisomy 21 associated - Down syndrome
Early onset AD
Mutation in 3 genes in chromosome 21
- Amyloid precursor protein (APP) gene
- Presenilin (PS) genes 1 and 2 code for components of secretase enzyme
Incomplete breakdown of amyloid precursor protein → amyloid deposited → where they build up determines pathology

Question 17

What is normal intracranial pressure?

Answer 17

• 0-10mmHg
• Coughing/straining can increase it to 20mmHg
• Compensatory mechanism in place to deal with fluctuations
  → ↓blood flow
  → ↓ CSF volume
  → Chronic elevation → brain atrophy
• Cerebral blood flow can be maintained as long as the ICP < 60 mmHg

Question 18

What is a space occupying lesion?

Answer 18

e.g. tumour, haemorrhage
Deforms or destroys surrounding brain tissue
Displacement of midline structures - loss of symmetry, midline shift
Can result in brain herniation
- Subfalcine herniation
- Tentorial herniation

Question 19

What is a hernia?

Answer 19

Protrusion of an organ or part of an organ through wall that normally contains it

Question 20

What is subfalcine herniation?

Answer 20

• Cingulate gyrus pushed under the free edge of the falx cerebri
• Herniated brain can become ischaemic due to compression of anterior cerebral artery
• Normally loops up around the corpus callosum

Question 21

What is a tentorial herniation?

Answer 21

• Medial part of temporal lobe - uncus- pushed down through the tentorial notch - free edge of tentorium cerebelli
• Compress ipsilateral oculomotor nerve → down and out eye
• Ipsilateral cerebral peduncle causing ipsilateral third nerve palsy but contralateral UMN signs in limbs?????????
• Complicated by brainstem haemorrhage (Duret haemorrhage) → often fatal
• Usual mode of death for those with large brain tumours or severe intracranial haemorrhage

Question 22

What is a tonsilar herniation?

Answer 22

Cerebral tonsils pushed into the foramen magnum compressing the brainstem

Question 23

What is Cushing reflex?

Answer 23

• Physiological response to ↑ICP
• Blood vessels compressed so body unable to get -blood to brain
• Detects the ↑systemic pressure to try and push more and more blood to the brain → ↑ICP even more → sustainable for short period of time → herniation of brain
• Compress cardiorespiratory centres in the brainstem → Bradycardia
  Reflex bradycardia - ↑↑ BP ↓HR
  Brain coning

Question 24

What are brain tumours?

Answer 24

Generally rare
- Benign
→ Meningioma - meningeal origin, often accidental finding or develop epilepsy then find it
- Malignant
→ Astrocyte origin - astrocytoma (grade 1- 4)
Others
- Neurofibroma (Schwann cell origin PNS or cranial nerves)
- Ependymoma (ependymal cells lining ventricular system)
- Neuronal tumours (from neurones, extremely rare)
- Non-CNS tissue
→ Lymphoma
→ Metastases (most common of all brain tumours)

Question 25

What are the different types of astrocytoma?

Answer 25

Low grade → slow growing, difficult to remove
High grade → aka glioblastoma multiforme
Direct spread along white matter tracts
Can also spread to distant parts of CNS via CSF
Through subarachnoid space often present with a spinal secondary

Question 26

What is a stroke?

Answer 26

Sudden vascular event producing disturbances of CNS function due to vascular disease
2/1000 per year - more frequent in elderly
Clinical features depend on site and type of lesion

Question 27

What are the risk factors for stroke?

Answer 27

Hyperlipidaemia
Hypertension
Smoking
Diabetes

Question 28

What are the two broad categories of stroke?

Answer 28

Cerebral infarction - 85%

Cerebral haemorrhage- 15%

Question 29

What is the pathogenesis of stroke?

Answer 29

Embolism (most common)
- Various sources
→ Heart - AF, mural thrombus 
→ Atheromatous debris 
→ Thrombus over ruptured plaque 
→ Aneurysm 
Thrombosis 
- Over atheromatous plaque

Question 30

What are the different types of cerebral infarct?

Answer 30

85% of all strokes
Regional
- In the territory of a named cerebral artery
Lacunar
- Small <1cm affected
- Associated with hypertension
- Commonly affect basal ganglia and internal capsule

Question 31

What are the different types of cerebral haemorrhage?

Answer 31

15% of all strokes

1. Intracerebral haemorrhage (10% of all strokes)
2. Subarachnoid haemorrhage (5% of all strokes)

Question 32

What is a intracerebral haemorrhage?

Answer 32

• Associated with increased age, hypertensive vessel damage and amyloid deposition in/ around cerebral vessels
• Charcot-Bouchard aneurysms are seen (BV ruptured)
• Maybe inherited
• Produces space occupying lesions

Question 33

What is a subarachnoid haemorrhage?

Answer 33

• Rupture of berry aneurysms, usually found at branch points in the circle of Willis
• Blood in subarachnoid space can cause secondary spasm of cerebral arteries
• Associations
  → Male
  → Hypertension
  → Atherosclerosis
  → Linked to other disease (e.g. connective tissue disorders, congenital weakness in vessel wall)

Question 34

What are the symptoms of subarachnoid haemorrhage?

Answer 34

Thunderclap headache
May be preceded by ‘sentinel’ headache
Loss of consciousness
Often instantly fatal