S8) Neuropathology

Question 1

The CNS is normally sterile. However, microorganisms gain entry by 3 possible routes.

Identify them

Answer 1

• Direct spread e.g. middle ear infection, base of skull fracture
• Blood-borne e.g. sepsis, infective endocarditis
• Iatrogenic e.g. ventricular-peritoneal shunt, surgery, lumbar puncture

Question 2

What is meningitis?

Answer 2

• Meningitis is the inflammation of the leptomeninges, with/without septicaemia
• Prompt diagnosis and treatment is life saving

Question 3

What are the causative organisms of meningitis in patients of various ages?

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

Question 4

Describe, in three steps, how chronic meningitis might occur

Answer 4

M. tuberculosis:

⇒ Granulomatous inflammation

⇒ Fibrosis of meninges

⇒ Nerve entrapment

Question 5

Identify five complications of meningitis

Answer 5

• Death (swelling → RICP)
• Cerebral Infarction → neurological deficit
• Cerebral abscess
• Subdural empyema
• Epilepsy

Question 6

What is encephalitis?

Answer 6

• Encephalitis is the classically viral inflammation of the brain parenchyma due to infection
• Neuronal cell death by virus occurs, with the inclusion bodies

Question 7

Identify the causative organisms for encephalitis in the following areas:

• Temporal lobe
• Spinal cord motor neurons
• Brain stem

Answer 7

• Temporal lobe e.g. herpes virus
• Spinal cord motor neurons e.g. polio
• Brain stem e.g. rabies

Question 8

How might mutated prion proteins enter the body?

Answer 8

• Sporadic mutation
• Familial mutation
• Ingested

Question 9

What is the effect of the mutated PrP on the body?

Answer 9

Mutated PrP interacts with normal PrP to undergo a post translational conformational change

Question 10

What occurs in prion disease?

Answer 10

PrP^SC aggregates leading to neuronal death and holes in grey matter

Question 11

What is dementia?

Answer 11

Dementia is the acquired global impairment of intellect, reason and personality without impairment of consciousnes

Question 12

Identify four common forms of dementia

Answer 12

• Alzheimer’s (50%)
• Vascular dementia (20%)
• Lewy body
• Picks disease

Question 13

Describe some defining features of Alzheimer’s Disease

Answer 13

Exaggerated aging process due to:

• Loss of cortical neurones – ↓ brain weight, cortical atrophy
• ↑ neuronal damage – neurofibrillary tangles, senile plaques

Question 14

In three steps, describe how neuronal damage occurs in AD due to neurofibrillary tangles

Answer 14

⇒ Intracellular twisted filaments of Tau protein

⇒ Tau normally binds and stabilises microtubules

⇒ Tau becomes hyperphosphorylated in AD

Question 15

In two steps, describe how neuronal damage occurs in AD due to senile plaques

Answer 15

⇒ Foci of enlarged axons, synaptic terminals and dendrites

⇒ Amyloid deposition in vessels in centre of plaque

Question 16

In Down’s syndrome, there is early onset AD.

Explain why

Answer 16

• Mutations of 3 genes on chromosome 21:

I. Amyloid precusor protein (APP) gene,

II. Presenilin (PS) genes 1 and 2 code for components of secretase enzyme

• Leads to incomplete breakdown of APP and amyloid is deposited

Question 17

What is the value for normal intracranial pressure?

Answer 17

0 - 10mmHg

Question 18

Which physiological mechanisms increase ICP?

Answer 18

Coughing and straining increase ICP to 20 mmHG

Question 19

Identify the three compensation mechanisms that maintain normal pressure

Answer 19

• Reduced blood volume
• Reduced CSF volume
• Spatial – brain atrophy

Question 20

How are vascular mechanisms affected by ICP?

Answer 20

Vascular mechanisms maintain cerebral blood flow as long as ICP < 60mmHg

Question 21

State the three effects of an expanding lesion in the brain

Answer 21

• Deformation/destruction of the brain around the lesion
• Displacement of midline structures – loss of symmetry
• Brain shift resulting in internal herniation

Question 22

What occurs in a subfalcine herniation?

Answer 22

• In a subfalcine herniation, the cingulate gyrus is pushed under the free edge of the falx cerebri
• Ischaemia of medial parts of frontal lobe, parietal lobe and corpus callosum due to compression of anterior cerebral artery → infarction

Question 23

What occurs in a tentorial herniation?

Answer 23

• In a tentorial herniation, the uncus / medial part of the parahippocampal gyrus herniates through the tentorial notch
• Ipsilateral occulomotor nerve damage and occlusion of posterior cerebral and superior cerebellar arteries
• Often fatal due to secondary haemorrhage into the brainstem (duret haemorrhage)

Question 24

What occurs in a tonsillar herniation?

Answer 24

In a tonsillar herniation, the cerebellar tonsils are pushed into the foramen magnum compressing the brainstem

Question 25

CNS tumours are very rare. Regardless, identify some

Answer 25

- **Benign** – meningioma - **Malignant** – astrocytoma - **Others** – neurofibroma, ependymoma, neuronal *e.g. medulloblastoma*

Question 26

What is a stroke?

Answer 26

A **stroke** is a sudden event producing a disturbance of CNS function due to vascular disease

Question 27

What are the two broad categories of strokes?

Answer 27

- Cerebral infarction (85%) - Cerebral haemorrhage (15%)

Question 28

Identify three risk factors for stroke

Answer 28

- Hyperlipidaemia - Hypertension - Diabetes mellitus

Question 29

Describe the pathogenesis of a stroke from an embolism (most common)

Answer 29

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

Question 30

Describe the pathogenesis of a stroke from a thrombosis

Answer 30

Thrombosis – over atheromatous plaque

Question 31

Identify and describe two types of infarct in the brain

Answer 31

- **Regional** – named cerebral artery or carotid - **Lacuna** – Associated with hypertension (commonly affect the basal ganglia)

Question 32

What are the two types of intracerebral haemorrhages?

Answer 32

- Intracerebral haemorrhage (10% of all strokes) - Subarachnoid haemorrhage (5% of all strokes)

Question 33

Describe the occurrence of intracerebral haemorrhages

Answer 33

- Associated with **hypertensive vessel damage** - Deposition of **amyloid** around cerebral vessels in the elderly - Produces **space occupying lesion**

Question 34

Describe how a subarachnoid haemorrhage usually presents

Answer 34

- Sudden severe headache - Loss of consciousness - Often instantly fatal

Question 35

Describe the pathogenesis of subarachnoid haemorrhages

Answer 35

Pathogenesis poorly understood: - Male sex - Hypertension - Atheroma - Links to other diseases

Question 36

What causes a subarachnoid haemorrhage?

Answer 36

A subarachnoid haemorrhage is caused by the rupture of **‘berry’ aneurysms**