L11 - Neuropathology

Question 1

How do microorganisms gain entry to the CNS

Answer 1

Direct spreads:

• middle ear infections
• basilar skull fractures

Blood bourne:

• sepsis
• infective endocarditis

Iatrogenic:

• VP shunt
• surgery
• lumbar puncture

Question 2

Meningitis

Answer 2

Inflammation of the leptomeninges
With or without septicaemia
Non blanching rash

Question 3

Effects of meningitis

Answer 3

Rapid oedema
Blood vessel congestion’s
Invasion by neutrophils
Raised intracranial pressure

Question 4

Causative organism of meningitis in neonates

Answer 4

Ecoli

Monocytogenes

Question 5

Causative organism of meningitis in 2-5 year olds

Answer 5

Haemophilus influenzae type B

Rare due to vaccines

Question 6

Causative organism of meningitis in 5 - 30 yr olds

Answer 6

Neisseria meningitidis

Question 7

Causative organism of meningitis in over 30 yr olds

Answer 7

Streptococcus pneumoniae

Question 8

What causes chronic meningitis

Answer 8

Mycobacterium tuberculosis
Causes granulomatous inflammation
Fibrosis of meninges due to chronic inflammation
Nerve entrapment

Question 9

Complications of meningitis

Answer 9

Death
Cerebral infarcts
Cerebral abscess 
Subdural empyema
Epilepsy

Question 10

Encephalitis

Answer 10

Neuronal cell death by virus
Inclusion bodies aggregate
Parenchyma affected
Lymphocytic inflammatory reaction

Question 11

Causes of encephalitis

Answer 11

Temporal lobe:
- herpes virus - shingles can cause epilepsy

Spinal cord motor neurones:
- polio

Brainstem
- rabies

Question 12

How to treat encephalitis

Answer 12

Normally self limiting in younger patients

Can cause death

Question 13

Prions

Answer 13

Normal protein constituent of synapses

Question 14

Prions disease

Answer 14

1. Mutated prion protein can come in to contact with normal prion proteins
2. Normal prion proteins undergo a post translational confirmation change into the mutated form
3. Mutated prions aggregate inside cells and are difficult to remove
4. Cell apoptosis - neurones in brai.

Question 15

How are mutated prions obtained

Answer 15

Sporadic mutation
Familial condition
Ingested

Question 16

What can prions disease cause?

Answer 16

Spongiform encephalopathies:

• scrabies - sheep
• kuru
• bovine spongiform encephalopathy- cows
• variant creutzfeld Jacob disease - vCJD

Question 17

Difference between variant and classic CJD

Answer 17

Variant:

• younger age of death (28)
• longer duration of illness (13- 14months)
• prominent psychological/ behavioural changes
• painful dyesthesiasis
• delayed neurological signs
• presence of florid plaques
• accumulation of protease resistant prions

Classic CJD:

• older age of death (68)
• shorter duration (4-5 months)
• dementia
• early neurological signs

Question 18

Dementia

Answer 18

Acquired global impairment of intellect, reasoning and personality without impairment of consciousness

Question 19

Alzheimer’s disease

Answer 19

Exaggerated ageing process

Cortical atrophy due to increased neuronal damage by neurofibrillary tangoes and senile amyloid plaques

Question 20

Neurofibrillary tangles

Answer 20

Intracellular twisted filaments of Tau proteins
Tau proteins become hyperphosphorylated and insoluble
The build up of irregular tau proteins cause cell death

Question 21

Tau protein

Answer 21

Normally binds and stabilises microtubules

Question 22

Senile plaques

Answer 22

Foci of enlarged axons and dendrites fused together that aggregate

Amyloid deposition in the vessel in the middle of the plaque, reduced blood flow to the brain and can cause ischaemia

Question 23

How was amyloid discovered to be involved in Alzheimer’s disease

Answer 23

People with Down’s syndrome - trisomy 21 has early onset Alzheimer’s disease

They were found to have mutations of:

• amyloid precursors protein gene
• presenilin genes 1 and 2

Therefore there was incomplete breakdown of the amyloid precursor protein and increased amyloid deposition

Question 24

Presenilin genes

Answer 24

Codes for components of the secretase enzyme that normally breaks down amyloid plaques

Question 25

Normal intracranial pressure

Answer 25

0-10 mmHg Normally above 0 Coughing and straining e.g. the Valsava manoeuvre can increase ICP to 20 mmHg

Question 26

Compensatory mechanism to maintain ICP

Answer 26

Reduced blood volume Reduced CSF volume Brain atrophy

Question 27

ICP at which vascular mechanisms can maintain cerebral blood flow

Answer 27

Below 60 mmHg

Question 28

Types of space occupying lesions in the brain

Answer 28

Tumour Haemorrhage Oedema

Question 29

Effects of space occupying lesions

Answer 29

Deformation and destruction of the brain around the lesion Asymmetry Displacement of midline structures Herniation

Question 30

Types of brain herniation

Answer 30

Subfalcine Central Tentorial Tonsillar

Question 31

Subfalcine herniation

Answer 31

Cingulate gyrus pushed under the falx cerebri Compression of the anterior cerebral artery Ischaemia of medial parts of the frontal and parietal lobe and corpus callosum leading to an infarct Can be secondary to stroke

Question 32

Tentorial herniation

Answer 32

The uncus or medial part of the parahippocampal gyrus herniated through the tentorial notch of the tentorijm cerebellum - damages the ipsilateral occulomotor nerve - down and out pupil - occlusion of the posterior cerebral artery and superior cerebellar artery causing ischaemia and infarction Often fatal due to secondary haemorrhage into the brainstem - Duret haemorrhage

Question 33

Tonsilar herniation

Answer 33

Cerebellar tonsils are pushed down through the foramen magnum and compresses the medulla Causes the Cushing’s reflex: Early sign - raised BP - hypertension Compression of respiratory centre - irregular breathing Reflex bradycardia - low HR - low pulse

Question 34

Benign brain tumours

Answer 34

Meningioma - can get sudden development of epilepsy | - grow outwards and is not invasive

Question 35

Malignant brain tumour

Answer 35

Astrocytoma - spreads along nerve tracts and through the subarachnoid space - can include spinal cord as secondary - can occur in all ages but grade 1 commonly in younger patients and has a better prognosis

Question 36

Metastasising tumours

Answer 36

More common - Lymphoma - renal cell carcinoma

Question 37

Stroke

Answer 37

Sudden event producing a CNS disturbance due to a vascular disease

Question 38

Categories of stroke

Answer 38

Cerebral infarction - 85% | Cerebral haemorrhage -15%

Question 39

Risk factors of stroke

Answer 39

Hypertension Hyperlipidaemia Diabetes

Question 40

Causes of embolism

Answer 40

- Heart - atrial fibrillation or mural thrombus - atheromatous debris - carotid atheromatous - thrombus over ruptured atheromatous plaque - aneurysm

Question 41

Types of infarct

Answer 41

Regional - dependent on what artery infarcted Lacuna: - small less that 1cm - associated with hypertension - commonly affects the basal ganglia

Question 42

Types of cerebral haemorrhage

Answer 42

Intracerebral haemorrhage - 10% of strokes | Subarachnoid haemorrhage - 5%

Question 43

Intracerebal haemorrhage

Answer 43

Associated with chronic hypertension Charcot - Bouchard aneurysms - affecting the lenticulostriate vessels of the basal ganglia Associated with amyloid deposition around the cerebral vessels in the elderly Can have an inherited disposition - blow out haemorrhage

Question 44

Subarachnoid haemorrhage

Answer 44

``` Rupture of berry aneurysms Thunderclap headache Sentinel headaches - small bleeds before major event Loss of consciousness Often instantly fatal ```

Question 45

Berry aneurysms

Answer 45

Aneurysms that commonly occur at the burfications of the circle of Willis

Question 46

Risk factors of subarachnoid haemorrhages

Answer 46

Male Hypertension Atheromatous Poly cystic ovary disease