Introduction to Neuropathology Flashcards
What commensal organisms are present in the CNS?
None - it is normally sterile
How might microorganisms gain entry to the CNS?
- Direct spread
- Blood-bourne
- Iatrogenic
GIve two examples of where infection might spread to the CNS by direct spread
- Middle ear infection
- Base of skull fracture
How are patients with a basal skull fracture managed?
Aseptically, with prophylactic antibiotics
What infections might spread to the CNS by the blood bourne route?
- Sepsis
- Infective endocarditis
How does infective endocarditis spread to the CNS?
An emboli from the infected heart valves travels to the brain
What are the iatrogenic causes of CNS infection?
- V-P shunt
- Surgery
- Lumbar puncture
What is meningitis?
Inflammation of the leptomeninges
How does meningitis spread?
In the blood
Does meningitis present with septicaemia?
Can present with or without
What is essential in meningitis?
Prompt diagnosis and treatment
What are the causative organisms of meningitis in neonates?
- E.coli
- L. monocytogenes
What are the causative organisms of meningitis in 2-5 year olds?
H. influenzae type B
What are the causative organisms of meningitis in 5-30 year olds?
N. Meningitidis
What are the causative organisms of meningitis in people over 30 years?
S. pneumoniae
What organism causes chronic meningitis?
M. tuberculosis
What are the features of chronic meningitis?
- Granulomatous inflammation
- Fibrosis of meninges
- Nerve entrapment
What are the local complications of meningitis?
- Death
- Cerebral infarction
- Cerebral abscess
- Subdural empyema
- Epilepsy
How does meningitis cause death?
Swelling leads to raised intracranial pressure, leading to death
What does cerebral infarction in meningitis lead to?
Neurological deficit
When do systemic complications of meningitis occur?
If it is associated with septicaemia
Is encephalitis caused by viruses or bacteria?
Classically viral
What is affected in encephalitis?
The parenchyma, not the meninges
What does the virus cause in encephalitis?
Neuronal cell death
What is neuronal cell death in encephalitis characterised by?
Inclusion bodies
What causes temporal lobe encephalitis?
Herpes virus
What causes spinal cord motor neurones encephalitis?
Polio
What causes brain stem encephalitis?
Rabies
What kind of inflammatory reaction can cause encephalitis?
Lymphocytic
What is a prion?
A protein that is a normla constituent of the synapse, but of unkown function
How can mutated PrP (prion protein) be obtained?
- Sporadic
- Familial
- Ingested
What effect does mutated PrP have?
It interacts with normal PrP to undergo post translocation conformational change
What is the result of PrPSC being extremely structurally stable?
It accumulates and aggregates
What is the result of the accumulation and aggregation of PRPSC?
Causes neuronal death and ‘holes’ in grey matter
What kind of neuropathology are caused by prions?
Spongiform encephalopathies
Give two examples of human spongiform encephalopathies
- Kuru
- Variety Creutzfeld-Jacob disease (vCJD)
Is vCJD different from classical CJD?
Yes
What is unique about each case of vCJD?
It has a unique genetic prion sequence
What supports the association between vCJD and BSE?
Strong laboratory and epidemiological evidence
How long does vCJD incubate for?
15+ years
What is the difficulty of eradicating vCJD?
Prions are not eradicated by traditional sterilisation
What is the difference between classic CJD and vCJD in terms of median age of death?
- Classic = 68 years
- Variant = 28 years
What is the difference between classic CJD and vCJD in terms of median duration of illness?
- Classic = 4-5 months
- Variant = 13-14 months
What are the clinical signs and symptoms of classic CJD?
Dementia and early neurologic signs
What are the clinical signs and symptoms of vCJD?
- Prominent psychiatric/behavioural symptoms
- Painful dyesthesiasis
- Delayed neurologic signs
What is the difference between classic CJD and vCJD in terms of the electroencephalogram presentation?
With classic CJD, periodic sharp waves on the electroencephalogram are often present. With vCJD, these are often absent
What is the difference between classic CJD and vCJD in terms of the presence of ‘florid plaques’ on neuropathology?
In classic CJD, they are rare or absent. In vCJD, they are present in large numbers
What is the difference between classic CJD and vCJD in terms of immunohistochemical analysis of brain tissue?
In classic CJD, there is variable accumulation. In vCJD, there is marked accumulation of protease-resistance prion protein
What is the difference between classic CJD and vCJD in terms of the presence of agent in the lymphoid tissue?
In classic CJD, it is not readily detected. In variant CJD, it is readily detected
What criteria of infections do prion diseases not fulfill?
- The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms
- The microorganism must be isolated from a diseased organism, and grown in pure culture
- The cultured microorganism should cause a disease when introduced into a healthy organism
- The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being indentical to the original specific causative agent
What is dementia defined as?
Acquired global impairment of intellect, reason, and personality, without impairment of consciousness
What are the types of dementia?
- Alzheimer’s
- Vascular dementia
- Lewy body
- Picks disease
What % of cases of dementia are caused by Alzheimer’s?
- 50%
What is Alzheimer’s disease?
A disease characterised by exaggerated ageing process
What is the pathological process in Alzheimers disease?
There is a loss of cortical neurones due to increased neural damage, leading to decreased brain weight and cortical atrophy
What can cause neuronal damage in Alzheimers?
- Neurofibrillary tangles
- Senile plaques
What are neurofibrillary tangles?
Intracellular twisted filaments of Tau protein
What does Tau normally do?
Binds and stabilises microtubules
What happens to Tau in Alzheimers?
It gets hyperphosphorylated
What are senile plaques?
Foci of enlarged axons, synaptic terminals, and dendrites with amyloid deposition in vessels in the centre of the plaque
What condition can predispose to Alzheimers?
Down’s syndrome - leads to early onset AD
What mutations can predipose to Alzheimers?
3 mutations on chromosome 21;
- Amyloid precursor protein (APP) gene
- Presenilin (PS) genes 1 and 2, which code for components of secretase enzyme
Why does mutation of PS genes 1 and 2 lead to Alzheimers?
It leads to incomplete breakdown of APP, and amyloid deposition
What is the normal intracranial pressure (ICP)?
0-10mmHg
When might ICP be increased physiologically?
During coughing and straining - increase to 20mmHg
When is a rise in ICP significant?
If the increase in maintaned for several minutes
What is employed to maintain a normal ICP?
Compensation mechanisms
What are the compensation mechanisms aiming to reduce ICP?
- Reduced blood volume
- Reduced CSF volume
- Brain atrophy
At what ICP can vascular mechanisms maintain cerebral blood flow?
<60mmHg
What does an expanding lesion in the brain cause?
- Deformation or destruction of the brain around the lesion
- Displacement of the midline structures, leading to loss of symmetry
- Brain shift resulting in herniation
What is a hernia?
A protrusion of an organ or part of an organ through a wall that normally contains it
What are the types of brain herniation?
- Subfalcine
- Tentorial
- Tonsilar
Do subfalcine haemorrhages occur on the same side, or the opposite side, of the mass?
Same side
What happens in a subfalcine herniation?
The cingulate gyrus is pushed under the gree edge of the falx cerebri
What does a subfalcine herniation cause?
Ischaemia of the medial parts of the frontal and parietal lobe and corpus callosum due to compression of the anterior cerebral artery, leading to infarction
What happens in a tentorial herniation?
The uncus/medial part of the parahippocampal gyrus herniate through the tentorial notch
What does a tentorial herniation cause?
- Damage to the oculomotor nerve on the same side
- Occlusion of blood flow in the posterior cerebral and superior cerebellar arteries
Why is a tentorial herniation frequently fatal?
Because of secondary haemorrhage into the brainstem, leading to duret haemorrhage
Where is tentorial herniation a common mode of death?
In those with large brain tumours and intracranial haemorrhage
What happens in a tonsillar herniation?
Cerebellar tonsils are pushed into the foramen magnum, compressing the brainstem
What origin to benign CNS tumours have?
Meningeal origin
What is a benign tumour of the meninges called?
Meningioma
What is the origin of malignant CNS tumours?
Astrocytes
What are malignant tumours of astrocytes called?
Astrocytomas
How do astrocytomas progress?
They spread along the nerve tracts, and through the subarachnoid space
How do astrocytomas often present?
WIth a spinal secondary
Give three examples of other CNS tumours
- Neurofibromas
- Ependyomas
- Neuronal tumours, e.g. medullobastoma
What is the most common form of CNS tumour
Metastasis from other tissues
What is a stroke?
A sudden event producing a disturbance of CNS function due to vascular disease
What do the clinical features of strokes depend on?
Site and type of lesion
What are the categories of strokes?
- Cerebral infarction (85%)
- Cerebral haemorrhage (15%)
What risk factors are related to stroke?
- Hyperlipidaemia
- Hypertension
- Diabetes mellitus
What are the potential pathogenesis’ of stroke?
- Embolism (most common)
- Thrombosis
What can cause embolisms leading to strokes?
- Atrial fibrillation
- Mural thrombus
- Atheromatous debris from carotid atheroma
- Thrombus over ruptured atheromatous plaque
- Aneurysm
What are the types of infarct in stroke?
- Regional
- Lacuna
What is a regional infarct?
One that originates from a named cerebral artery, or carotid
What is a lacuna infarct?
An infarct that is less than 1cm
What are lacuna infarcts associated with?
Hypertension
Where do lacuna infarcts commonly affect?
Basal ganglia
What causes cerebral haemorrhages?
They are spontaneous, i.e. non-traumatic
What are the types of cerebral haemorrhages?
- Intracerebral (10% of all strokes)
- Subarachnoid haemorrhages (5% of all strokes)
What are intracranial haemorrhages associated with?
Hypertensive vessel damage
What are Charcot-Bouchard aneurysms?
Aneurysms that occur in small blood vessels, which are a common cause of intracerebral haemorrhage
What can predispose to intracerebral haemorrhages?
Deposition of amyloid around cerebral vessels in the elderly
How do intracerebral haemorrhages cause brain pathology?
They produce a space occupying lesion, causing RICP
What happens in subarachnoid haemorrhages?
There is rupture of ‘berry’ aneurysms
What are the risk factors for subarachnoid haemorrhages?
- Male sex
- Hypertension
- Atheroma
- Links to other diseases
Where are subarachnoid haemorrhages sited?
At branching points in the Circle of Willis
What are the symptoms of subarachnoid haemorrhages?
- Sudden severe headache
- Sentinel headache
- Loss of consciousness
- Often instantly fatal*
