Nervous System: Neuropathology

Question 1

What are the routes than microorganisms can enter the CNS?

Answer 1

1. Direct spread: base of skull fracture most common (give prophylactic antibiotics), middle ear infection
2. Blood-bourne: sepsis, infective endocarditis embolus
3. Iatrogenic: Lumbar puncture, surgery, ventricle-peritoneal shunt

Question 2

What is the site of infection in meningitis?

Answer 2

Th leptomeninges (pia and arachnoid mata)

Question 3

What is the histological appearance of meningitis?

Answer 3

Oedematous and full of neutrophils

Question 4

What are the causative organisms of meningitis in different age groups?

Answer 4

Neonates - E Coli, L moncytogenes
2-5yrs - H influenzae
5-30yrs - N meningitides
30+ - Strep pneumoniae

Question 5

What is chronic meningitis?

Answer 5

Meningitis caused by slow growing M tuberculosis.
Dont get the acute clinical symptoms, get granulomatous inflammation, fibrosis of the meninges and nerve entrapment around the midbrain

Question 6

What are the potential complications of meningitis?

Answer 6

Local:

• death caused by RICP
• cerebral infarction
• cerebral abscess
• subdural empyema
• epilepsy

Systemic:
- sepsis

Question 7

What is encephalitis?

What are the causative organisms?

Answer 7

Infections of the neuronal cells in the grey matter, typically viral.

Temporal lobe can be infected by herpes virus and present with epilepsy, visual hallucintions.

Spinal cord motor neurones can be caused by polio

Brains stem can be affected by rabies

Question 8

What is the macroscopic appearance of encephalitis?

Answer 8

Brain appears red, haemorrhagic and swollen

Question 9

What is the pathophysiology of prion disease?

Answer 9

Prion proteins (PrP) are a normal constituent of synapse function however mutated PrPs can occur sporadically, be inherited or ingested.
Forms an extremely stable structure than is insoluble and can build up?

Question 10

What does prion disease cause?

Answer 10

Spongiform encephalopathies where there is neuronal death abd ‘holes’ in the grey matter

Question 11

What are the main differences between classic and variant creutzfeld - jacob disease?

Answer 11

Classic is sporadic, occurs around age 68 and lasts 4-5 months. Causes dementia.

Variant is caused by injested faulty prions, occurs aged 28 and lasts around a year. Causes prominent behavioural / psychiatric symptoms

Question 12

What are some of the common forms of dementia?

Answer 12

• 50% caused by Alzheimers which can be sporadic/familial, late/early onset (usually sporadic and late)
• 20% caused by vascular dementia
• Lewy body dementia
• Picks disease (a type of fronto-temporal dementia)

Question 13

What are the macroscopic features of a brain with Alzheimers?

Answer 13

There are a loss of cortical neurones resulting in cortical atrophy and decreased brain weight. The brain appears smaller with large sulci and small gyri.

Question 14

What is the microscopic appearance of a brain with alzheimers disease?

Answer 14

There are neurofibrillary tangles made up of Tau protein - becomes hyperphosphorylated and dissociates out of solution.

Also get senile plaques which are foci of enlarged axons, synapses and dendrites. There is amyloid deposits in the central BV

Question 15

What are some genetic predispositions to alzheimers disease?

Answer 15

Downs syndrome - trisomy 21, get early onset in 30s-40s (have 3 chromosome 21 so more amyloid produced)

Mutations of 3 genes on chromosome 21 - controls amyloid production.

Question 16

What are some of the compensatory mechanisms to maintain normal intracranial pressure?

Answer 16

Note - only useful for chronic changes eg a slow growing tumour.

• reduced blood volume
• reduced CSF volume
• brain atrophy

Question 17

What signs indicate that brain herniation is imminent?

Explain the mechanism

Answer 17

Severe hypertension (systolic 220) and bradycardia indicates severe RICP. 
Due to cushings reflex - when IC pressure is greater than arterial pressure blood cannot be pumped into the brain, therefore BP increases. This stimulates baroreceptors which cause bradycardia.

Question 18

What are the potential sites of brain herniation in RICP?

Answer 18

1. Subfalcine: occurs the same side as mass - the cingulate gyrus is pushed under the flax cerebri. Can compress anterior cerebral artery.
2. Tentorial: the uncus herniates through the tentorial notch - can damage oculomotor nerve so blown pupil on same side, can occlude posterior and superior cerebellar rteries. Freq fatal due to duret haemorrhage into brainstem.
3. Tonsilar: cerebellar tonsils herniate into foramen magnus and compress brainstem

Question 19

What are some types of primary brain tumours?

Answer 19

Benign - meningioma
Malignant - astrocytoma (grade 4 is v v aggressive 3 month prognosis)

Primary tumours very rare! Tumours almost always are metastases - lung breast colon

Question 20

What percentage of strokes are infarcts and haemorrhages?

Answer 20

Cerebral infarction 85%

Cerebral haemorrhage 15%

Question 21

What are some causes of cerebral infarcts?

Answer 21

Embolism is most common eg

• heart, AF
• atheromatous debris
• aneurysm

Thrombus can form over atheromatous plaque

Question 22

What are the 2 types of infarct seen in stroke?

Answer 22

• regional (named cerebral or carotid artery)

- lacuna (less than 1cm, commonly affect basal ganglia, associated with hypertension)

Question 23

What are the 2 types of haemorrhage seen in stroke?

Answer 23

Haemorrhage causes 15% of all strokes:

• intracerebral heamorrhage (10% of all strokes)
• subarachnoid haemorrhage (5% of all strokes)

Question 24

What can cause subarachnoid haemorrhage?

Answer 24

Rupture of berry aneurysms (usually sited at branching points of the circle of willis)
Risk factors inc: male, hypertension causing their rupture not formation, and atheroma

Question 25

What are the signs and symptoms of a subarachnoid haemorrhage?

Answer 25

• thunderclap headache
• loss of consciousness
• often instantly fatal