Neuropathology

Question 1

What are the 3 routes by which microorganisms can gain entry to the CNS?

Answer 1

1. Direct Spread from a physical breach- e.g. middle ear infection, base of skull fracture
2. Blood-borne - sepsis, infective endocarditis
3. Iatrogenic (by medical professionals) - e.g. V-P shunt, surgery, lumbar puncture

Question 2

What is meningitis, what are the consequences of it if left untreated?

Answer 2

Meningitis is inflammation of the leptomeninges (pia + arachnoid mater). Can occur with/ without septicaemia

Untreated causes rapid influx of oedema, neutrophil influx causes pus → raises ICP leading to death if not quickly treated

Question 3

What are the main causative organisms of meningities in the age groups:

Neonates

2-5 years

5-30 years

Over 30s

Answer 3

Neonates - E.coli, L. monocytogenes

2-5 years - H. influenzae type B (HiB) - vaccinated against

5-30 years - N. Meningitides types A,B+C

Over 30s - S.pneumoniae

Question 4

What organism causes chronic meningitis?

What are the effects of having chronic meningitis?

Answer 4

Mycobacterium Tuberculosis

• Granulomatous inflammation
• Fibrosis of the meninges
• Nerve entrapment
  
  • facial nerve palsy
  • headache

Question 5

What are the some the local and systemic complications of meningitis

Answer 5

Local:

• Death (swelling raises ICP)
• Cerebral infarction → neurological deficit
• Cerebral abcess
• Subdural empyema → chronic pus
• Epilepsy

Systemic: if associated with speticaemia

Question 6

What is Encephalitis?

Answer 6

Inflammation of the parenchyma (not the meninges) in the brain - affects neuronal cell bodies

Question 7

What type of microorganisms cause encephalitis affecting different areas of the brain:

• Neuronal cell death
• Temporal lobe
• Spinal cord motor neurones
• Brain Stem

Answer 7

Mainly viral not bacterial

• Neuronal cell death - inclusion bodies (build up of virus)
• Temporal lobe - Herpes Virus
• Spinal cord motor neurones - Polio
• Brain Stem - Rabies

Question 8

How do you treat encephalitis?

Answer 8

Often self limiting in young patients as long as they’re not immunocompromised

Question 9

What are prions?

Answer 9

Prions are proteins we all have that are a part of synpases

Question 10

What is prion disease?

Answer 10

• Mutation in prion proteins that are either sporadiac, familial or ingested
• Mutated PrP interacts with normal PrP to induce post translational conformational change
• Makes an extremely stable striucture that aggregates and cannot be elimited
• Causes neuronal death and holes in grey matter → spongiform encephalopathies

Question 11

Name some types of spongiform encephalopthies

Answer 11

• Scrapie in sheep
• BSE in cows
• vCJD- Variant Creutzfeld- Jacob Disease - strongly associated with BSE
• Kuru in tribes of New Guinea

Question 12

There are 2 forms of vCJD, classic and variant. What are the different clinical features of each?

Answer 12

Question 13

Why is prion diease not classed as infection?

Answer 13

• Infectious agents should not be found in healthy organisms which prions are
• Microorganisms must be isolated and grown in pure culture- proteins cannot be grown

Question 14

What is dementia?

Name the most common types

Answer 14

Aquired global impairment of intellect, reason and personality without impairment of conciousness

• Alzehimer’s (50%)- Sporadic/ Familial, Early/ Late
• Vascular dementia (20%)
• Lewy body
• Pick’s disease (Fronto-temporal dementia)

Question 15

What happens to the brain in Alzheimer’s Disease?

Answer 15

• Brain undergoes an exggerated aging process
• Loss of cortical neurones
  
  • decreased brain weight- greater sulci/ gyri definition
  • cortical atrophy (thinner cortex)
• Neurofibrillary tangles and senile plaques cause increased neuronal damage

Question 16

What are neurofibrillary tangles?

Answer 16

• Found in Alzheimer’s Disease
• Intracellular twisted filaments of Tau protein
• Tau, normally binds and stabilies microtubules
• Tau becomes hyperphospharylated and starts to aggregate
• Cell can’t function and produce energy → death

Question 17

What are senile plaques?

Answer 17

• Plaques found in Alzheimer’s Disease
• Foci of englarged axons, synaptic terminals and dendrites
• Amyloid deposition in vessels in the centre of the plaque- buolds up around blood vessels causing ischemia
• Look like balls of cotton wool

Question 18

What is the link between amyloid deposition and chromosome 21?

Answer 18

• Down’s syndrome (trisomy 21) will have early onset AD
• Mutation in 3 genes on trisomy 21 throught to be ivolved
• Amyloid precursor protein (APP) gene
• Presenlin genes 1 and 2 make secretase (enzyme that breaks down amyloid)
• Leads to incomplete breakdown of APP and amyloid is deposited

Question 19

What is normal brain ICP?

Answer 19

0-10 mmHg

(may increase to 20mmHg during coughing and straining)

Question 20

What compensatory mechanisms happen to maintain noraml brain ICP?

Answer 20

• Recued blood volume
• Reduced CSF volume
• Spatial → brain atrophy (if raised ICP is chronic)

Mechanisms work as long as ICP is <60 mmHg

Question 21

If ICP raises too much it will cause herniation. What are the different types of herniation?

Answer 21

• Subfalcine
• Tentorial
• Tonsilar

Question 22

Explain what happens in a subfalcine herniation

Answer 22

• The cingulate gyrus on the same side of the SoL is pushed under the free edge of the falx cerebri
• Causes ischemia of medial parts of the frontal & parietal lobes and the corpus callosum due to compression of the anterior cerebral artery → infarction

Question 23

What happens in tentorial herniation?

Answer 23

• The uncus (medial part of the parahippocampal gyrus) is pushed through the tentorial notch
• Can cause damage to the occulomotor nerve (on the same side)
• Occlusion of blood flow in posterior cerebral and uperior cerebrallar arteries
• Frequently fatal due to secondary haemorrhage into the brainstem (Duret Haemorrhage- of the midbrain & pons)

Question 24

What happens in tonsilar herniation?

Answer 24

• Cerebellar tonsisl are pushed into the foramen magnum compressing the brainstem
• Early on- blood can’t get to brain so systemic blood pressure rises to compensate
• After time- brainstem herniation depresses cardio respiratory centres
• Cushing’s reflex : High BP and Bradycardia

Question 25

How common are tumours of the brain?

Answer 25

Primary tumours are **rare**, will more commonly see secondary tumours from other sites

Question 26

Which tumours commonly metastasise to the brain?

Answer 26

* Renal Cell Carcinoma * Malignant Melanoma

Question 27

What is a menangioma?

Answer 27

A **benign tumour** of meningeal origin Often found incidentally- can present as new onset epilepsy

Question 28

What is an astrocytoma?

Answer 28

A maligant tumour of astrocyte origin (Grades 1-4) Lower grades more common in younger people, in adults usually very aggressive 3-4 month survival Won't metastasise **outside** the CNS → spread along nerve tracts and through sub arachnoid space often present as spinal accessory

Question 29

What is a stroke?

Answer 29

A sudden event producing a distrubance of CNS function due to **Vascular disease** 2 broad categories: **Cerebral infarction 85%** **Cerebral haemorrhage 15%**

Question 30

What types of infarct can you get in stroke?

Answer 30

**Regional** - names agter the cerbral artery or carotid **Lacuna** - less than 1cm, associated with hypertension, commonly affects the basal ganglia

Question 31

How do subarachnoid haemorrhages occur?

Answer 31

Rupture of **berry aneurysms** usually at bifuraction points of the **circle of Willis** Pathogenesis poorly understood; male sex, hypertension, atheroma, links to other disease

Question 32

What symptoms would you associate with a subarachnoid haemorrhage?

Answer 32

* Severe sudden onset headache - thunderclap * Sentinal headaches (small bleeds before main headache) * Loss of conciousness * Often instantly fatal