Introduction to Neuropathology Flashcards
1
Q
What commensal organisms are present in the CNS?
A
None - it is normally sterile
2
Q
How might microorganisms gain entry to the CNS?
A
- Direct spread
- Blood-bourne
- Iatrogenic
3
Q
GIve two examples of where infection might spread to the CNS by direct spread
A
- Middle ear infection
- Base of skull fracture
4
Q
How are patients with a basal skull fracture managed?
A
Aseptically, with prophylactic antibiotics
5
Q
What infections might spread to the CNS by the blood bourne route?
A
- Sepsis
- Infective endocarditis
6
Q
How does infective endocarditis spread to the CNS?
A
An emboli from the infected heart valves travels to the brain
7
Q
What are the iatrogenic causes of CNS infection?
A
- V-P shunt
- Surgery
- Lumbar puncture
8
Q
What is meningitis?
A
Inflammation of the leptomeninges
9
Q
How does meningitis spread?
A
In the blood
10
Q
Does meningitis present with septicaemia?
A
Can present with or without
11
Q
What is essential in meningitis?
A
Prompt diagnosis and treatment
12
Q
What are the causative organisms of meningitis in neonates?
A
- E.coli
- L. monocytogenes
13
Q
What are the causative organisms of meningitis in 2-5 year olds?
A
H. influenzae type B
14
Q
What are the causative organisms of meningitis in 5-30 year olds?
A
N. Meningitidis
15
Q
What are the causative organisms of meningitis in people over 30 years?
A
S. pneumoniae
16
Q
What organism causes chronic meningitis?
A
M. tuberculosis
17
Q
What are the features of chronic meningitis?
A
- Granulomatous inflammation
- Fibrosis of meninges
- Nerve entrapment
18
Q
What are the local complications of meningitis?
A
- Death
- Cerebral infarction
- Cerebral abscess
- Subdural empyema
- Epilepsy
19
Q
How does meningitis cause death?
A
Swelling leads to raised intracranial pressure, leading to death
20
Q
What does cerebral infarction in meningitis lead to?
A
Neurological deficit
21
Q
When do systemic complications of meningitis occur?
A
If it is associated with septicaemia
22
Q
Is encephalitis caused by viruses or bacteria?
A
Classically viral
23
Q
What is affected in encephalitis?
A
The parenchyma, not the meninges
24
Q
What does the virus cause in encephalitis?
A
Neuronal cell death
25
What is neuronal cell death in encephalitis characterised by?
Inclusion bodies
26
What causes temporal lobe encephalitis?
Herpes virus
27
What causes spinal cord motor neurones encephalitis?
Polio
28
What causes brain stem encephalitis?
Rabies
29
What kind of inflammatory reaction can cause encephalitis?
Lymphocytic
30
What is a prion?
A protein that is a normla constituent of the synapse, but of unkown function
31
How can mutated PrP (prion protein) be obtained?
* Sporadic
* Familial
* Ingested
32
What effect does mutated PrP have?
It interacts with normal PrP to undergo post translocation conformational change
33
What is the result of PrPSC being extremely structurally stable?
It accumulates and aggregates
34
What is the result of the accumulation and aggregation of PRPSC?
Causes neuronal death and 'holes' in grey matter
35
What kind of neuropathology are caused by prions?
Spongiform encephalopathies
36
Give two examples of human spongiform encephalopathies
* Kuru
* Variety Creutzfeld-Jacob disease (vCJD)
37
Is vCJD different from classical CJD?
Yes
38
What is unique about each case of vCJD?
It has a unique genetic prion sequence
39
What supports the association between vCJD and BSE?
Strong laboratory and epidemiological evidence
40
How long does vCJD incubate for?
15+ years
41
What is the difficulty of eradicating vCJD?
Prions are not eradicated by traditional sterilisation
42
What is the difference between classic CJD and vCJD in terms of median age of death?
* Classic = 68 years
* Variant = 28 years
43
What is the difference between classic CJD and vCJD in terms of median duration of illness?
* Classic = 4-5 months
* Variant = 13-14 months
44
What are the clinical signs and symptoms of classic CJD?
Dementia and early neurologic signs
45
What are the clinical signs and symptoms of vCJD?
* Prominent psychiatric/behavioural symptoms
* Painful dyesthesiasis
* Delayed neurologic signs
46
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
47
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
48
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
49
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
50
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
51
What is dementia defined as?
Acquired global impairment of intellect, reason, and personality, without impairment of consciousness
52
What are the types of dementia?
* Alzheimer's
* Vascular dementia
* Lewy body
* Picks disease
53
What % of cases of dementia are caused by Alzheimer's?
* 50%
54
What is Alzheimer's disease?
A disease characterised by exaggerated ageing process
55
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
56
What can cause neuronal damage in Alzheimers?
* Neurofibrillary tangles
* Senile plaques
57
What are neurofibrillary tangles?
Intracellular twisted filaments of Tau protein
58
What does Tau normally do?
Binds and stabilises microtubules
59
What happens to Tau in Alzheimers?
It gets hyperphosphorylated
60
What are senile plaques?
Foci of enlarged axons, synaptic terminals, and dendrites with amyloid deposition in vessels in the centre of the plaque
61
What condition can predispose to Alzheimers?
Down's syndrome - *leads to early onset AD*
62
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*
63
Why does mutation of PS genes 1 and 2 lead to Alzheimers?
It leads to incomplete breakdown of APP, and amyloid deposition
64
What is the normal intracranial pressure (ICP)?
0-10mmHg
65
When might ICP be increased physiologically?
During coughing and straining - *increase to 20mmHg*
66
When is a rise in ICP significant?
If the increase in maintaned for several minutes
67
What is employed to maintain a normal ICP?
Compensation mechanisms
68
What are the compensation mechanisms aiming to reduce ICP?
* Reduced blood volume
* Reduced CSF volume
* Brain atrophy
69
At what ICP can vascular mechanisms maintain cerebral blood flow?
\<60mmHg
70
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
71
What is a hernia?
A protrusion of an organ or part of an organ through a wall that normally contains it
72
What are the types of brain herniation?
* Subfalcine
* Tentorial
* Tonsilar
73
Do subfalcine haemorrhages occur on the same side, or the opposite side, of the mass?
Same side
74
What happens in a subfalcine herniation?
The cingulate gyrus is pushed under the gree edge of the falx cerebri
75
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
76
What happens in a tentorial herniation?
The uncus/medial part of the parahippocampal gyrus herniate through the tentorial notch
77
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
78
Why is a tentorial herniation frequently fatal?
Because of secondary haemorrhage into the brainstem, leading to duret haemorrhage
79
Where is tentorial herniation a common mode of death?
In those with large brain tumours and intracranial haemorrhage
80
What happens in a tonsillar herniation?
Cerebellar tonsils are pushed into the foramen magnum, compressing the brainstem
81
What origin to benign CNS tumours have?
Meningeal origin
82
What is a benign tumour of the meninges called?
Meningioma
83
What is the origin of malignant CNS tumours?
Astrocytes
84
What are malignant tumours of astrocytes called?
Astrocytomas
85
How do astrocytomas progress?
They spread along the nerve tracts, and through the subarachnoid space
86
How do astrocytomas often present?
WIth a spinal secondary
87
Give three examples of other CNS tumours
* Neurofibromas
* Ependyomas
* Neuronal tumours, e.g. medullobastoma
88
What is the most common form of CNS tumour
Metastasis from other tissues
89
What is a stroke?
A sudden event producing a disturbance of CNS function due to vascular disease
90
What do the clinical features of strokes depend on?
Site and type of lesion
91
What are the categories of strokes?
* Cerebral infarction *(85%)*
* Cerebral haemorrhage *(15%)*
92
What risk factors are related to stroke?
* Hyperlipidaemia
* Hypertension
* Diabetes mellitus
93
What are the potential pathogenesis' of stroke?
* Embolism *(most common)*
* Thrombosis
94
What can cause embolisms leading to strokes?
* Atrial fibrillation
* Mural thrombus
* Atheromatous debris from carotid atheroma
* Thrombus over ruptured atheromatous plaque
* Aneurysm
95
What are the types of infarct in stroke?
* Regional
* Lacuna
96
What is a regional infarct?
One that originates from a named cerebral artery, or carotid
97
What is a lacuna infarct?
An infarct that is less than 1cm
98
What are lacuna infarcts associated with?
Hypertension
99
Where do lacuna infarcts commonly affect?
Basal ganglia
100
What causes cerebral haemorrhages?
They are spontaneous, *i.e. non-traumatic*
101
What are the types of cerebral haemorrhages?
* Intracerebral *(10% of all strokes)*
* Subarachnoid haemorrhages *(5% of all strokes)*
102
What are intracranial haemorrhages associated with?
Hypertensive vessel damage
103
What are Charcot-Bouchard aneurysms?
Aneurysms that occur in small blood vessels, which are a common cause of intracerebral haemorrhage
104
What can predispose to intracerebral haemorrhages?
Deposition of amyloid around cerebral vessels in the elderly
105
How do intracerebral haemorrhages cause brain pathology?
They produce a space occupying lesion, causing RICP
106
What happens in subarachnoid haemorrhages?
There is rupture of 'berry' aneurysms
107
What are the risk factors for subarachnoid haemorrhages?
* Male sex
* Hypertension
* Atheroma
* Links to other diseases
108
Where are subarachnoid haemorrhages sited?
At branching points in the Circle of Willis
109
What are the symptoms of subarachnoid haemorrhages?
* Sudden severe headache
* Sentinel headache
* Loss of consciousness
* Often instantly fatal*
