Session 8 L3: Neuropathology Flashcards
(51 cards)
1
Q
How do microorganism gain entry to the brain?
A
- Direct spread e.g. middle ear infection (cerebral abscess), base of the skull fracture (predisposed to infection spread), cribriform plate
- Blood borne e.g. sepsis, infective endocarditis
- Iatrogenic e.g. V-P shunt, surgery, lumbar puncture
2
Q
What is meningitis?
A
- Inflammation of the leptomeninges (PIA+ARACHNOID)
- Can happen with or without septicaemia
3
Q
What are causative organism in meningitis?
A
Neonates – E.coli, L.monocytogenes 2-5 years – H.Influenzae type B 5-30 years – N.Meningitidis Over 30 years – S.pneumoniae Various in immunocompromised individuals
4
Q
What is a common cause of chronic meningitis?
A
- Caused by M tuberculosis commonly.
- Results in granulomatous inflammation, fibrosis of meninges and nerve entrapment
5
Q
What are the complications of meningitis?
A
Local
- Death (swelling leading to RICP)
- Cerebral Infarction leading to neurological deficit
- Cerebral abscess
- Subdural empyema
- Epilepsy
Systemic
6
Q
What is classically the cuase of encephalitis?
A
- Classically viral and not bacterial
- Affects the parenchyma not meninges
7
Q
What are lobes affected by viruses?
A
Temporal lobe - Herpes virus
Spinal cord motor neurons - Polio
Brain stem - Rabies
8
Q
What are prions?
A
- Key is prion protein (PrP)
- Normal constituent of synapse
9
Q
How are prions transmitted?
A
- Sporadic mutation
- Familial
- Ingested
10
Q
How do mutated PrP affect normal PrP?
A
- Mutated PrP interacts with normal PrP to undergo a post translational conformational change
- Extremely stable structure
11
Q
How do prions cause disease?
A
PRPsc aggregates lead to neuronal death and holes in grey matter
12
Q
What are examples of Prion disease?
A
- Spongiform encephalopathies
- Scrapie in sheep
- BSE in cows
- Kuru in tribes of New Guinea
- Variant Creutzfeld-Jacob disease
13
Q
What is vCJD?
A
- Different from classical CJD
- Each case has unique genetic prion sequence
- Strong laboratory and epidemiological evidence of causal association of vCJD with BSE
- Prolonged incubation period 15+ years
- Link to tradition butchery in area in 1980s
- Prions not eradicated by traditional sterilization
14
Q
What are the characteristic features of classical CJD?
A
- Median age of death is 68 years
- Median duration of illness is 4-5 months
- Periodic sharp waves on EEG often present
- Presence of florid plaques on neuropathology is rare or absent
- Immunohistochemical analysis of brain tissue shows variable accumulation
- Agent isn’t detected readily in lymphoid tissue
15
Q
What are the characteristic features of classical CJD?
A
- Median age at death is 28 years
- Median duration of illness is 13-14 months
- Periodic sharp waves on EEG is often absent
- Presence of florid plaques on neuropathology is present in large number
- Immunohistochemical analysis of brain tissue shows marked accumulation of protease resistance prion protein
- Agent is detected readily in lymphoid tissue
16
Q
What are the signs and symptoms of classic CJD?
A
- Dementia
- Early neurological signs
17
Q
What are the signs and symptoms of vCJD?
A
- Prominent psychiatric/behavioural symptoms
- Painful dyesthesiasis
- Delayed neurological signs
18
Q
What are some cause of dementia?
A
Alzheimer’s – sporadic/familial, early/late
Vascular dementia – gradual ischaemic damage so gradual degeneration of neurones
Lewy body
Picks disease
19
Q
What is dementia?
A
Acquired global impairment of intellect, reason and personality without impairment of consciousness
20
Q
What are the features of brain in Alzheimer’s disease?
A
- Loss of cortical neurones so decrease in brain weight and cortical atrophy
- Exaggerated agin process
21
Q
What are the microscopic features of Alzheimer’s disease?
A
- Neurofibrillary tangles
- Senile plaques
22
Q
What are neurofibrillary tangles?
A
- Intracellular twisted filaments of Tau protein
- Tau normally binds and stabilises microtubules
- Tau becomes hyperpolarised in AD causing Tauopathy
23
Q
What are senile plaques?
A
- Foci of enlarged axons, synaptic terminals and dendrites
- Amyloid deposition in vessels in centre of plaque
- Amyloid deposit is central to pethogenesis
24
Q
Which condition is Alzheimer’s disease more early onset?
A
- Down’s Syndromes
- Trisomy 21
- Familial Alzheimer’s is more common
- Mutation of 3 genes on chromosome 21 is the cause
25
What are are the 3 genes on chromosome 21 that are implicated to cause Alzheimer's?
- Amyloid precursor protein gene
- Presenilin (PS) genes 1 and 2 code for components of secretase enzyme
- Leads to incomplete breakdown of APP and amyloid is deposited
26
Which processes increase the intracranial pressure?
- Coughing and straining increase to 20 mmHg
| - Only significant if the increased main for several minutes
27
How can increased in ICP be compensated?
Compensation mechanism maintain normal pressure by:
- Reducing blood volume
- Reduced CSF volume
- Spatial such as brain atrophy
28
What is the effect of expanding lesions?
- Deformation or destruction of the brain around the lesion
- Displacement of midline structures – loss of symmetry
- Brain shift result in internal herniation. Brains squished against bony structures and extrudes through foramina
29
What is a hernia
Protrusion of an organ or part of an organ through wall that normally contains it
30
What are the different types of herniation?
- Subfalcine
- Tentorial
- Tonsilar
31
What is a subfalcine herniation?
- Same side as mass
- Cingulate gyrus pushed under the free edge of the falx cerebri
- Ischaemia of medial parts of the frontal and parietal lobe and corpus callosum due to compression of anterior cerebral artery leading to infarction
32
What is a tentorial herniation?
- Uncus/medial part of the parahippocampal gyrus through the tentorial notch
- Damage to the oculomotor nerve on the same side (clinical sign)
- Occlusion of blood flow in posterior cerebral and superior cerebellar arteries
33
Why is a tectorial herniation often fatal?
- Frequently fatal because of secondary haemorrhage into the brainstem leading to duret haemorrhage
- Common mode of death in those with large brain tumours and intracranial haemorrhage
34
What is a tonsillar herniation?
-Cerebellar tonsils pushed through into the foramen magnum compressing the brainstem
35
What are cancers of the brain?
- Meningioma (benign)
- Astrocytoma (malignant)
- Neurofirbroma
- Ependymoma
- Neuronal e.g medulloblastoma
- Tumors from non CNS
36
What is a meningioma?
Tumour from a meningeal origin
37
What is an astrocytoma?
- Astrocyte origin to astrocytoma (grade 1 to grade 4)
- Spread along nerve tracts and through sub arachnoid space often presents with a spinal secondary
- Grade 1 is more common in children
- Grade 4 is very aggressive and spreads through CNS very well. Interrupt the somatic systems
38
What are tumours from non-CNS origin?
- Lymphoma
| - Metastasis – the most common
39
What is a stroke?
Sudden event producing a disturbance of CNS function due to vascular disease.
40
What are the 2 broad categories of stroke?
Cerebral infarction – 85 % of strokes
| Cerebral haemorrhage – 15% of strokes
41
What are risk factors for stroke?
- Hyperlipidaemia
- Hypertension
- Diabetes mellitus
- Vascular disease
42
What is the pathogenesis of a stroke?
- Embolism
| - Thrombosis
43
What are common causes of an embolism to the brain?
- Heart – atrial fibrillation, mural thrombus
- Atheromatous debris (carotid atheroma)
- Thrombus over ruptured atheromatous plaque
- Aneurysm
44
What are the types of infarct?
- Regional
| - Lacuna
45
What can cause regional infarct?
Occlusion to Named cerebral artery or carotid
46
What can cause lacuna infarcts?
- Less than 1cm
- Associated with hypertension
- Commonly affect the basal ganglia
47
What are the features of intracerebral aneurysms?
- Associated with hypertensive vessel damage
- Charcot-Bouchard aneurysms
- Deposition of amyloid around cerebral vessels in the elderly
- May be inherited
- Produces space occupying lesion – RICP
48
What are the common causes of sub arachnoid haemorrhages?
Rupture of Berry Aneurysms
49
What are risk factors involved in the pathogenesis of sub arachnoid haemorrhages?
- Male sex
- Hypertension
- Atheroma
- Links to other diseases
50
What are the symptoms of a subarachnoid haemorrhage?
- Sudden severe headache – thunderclap
- Sentinel headache
- Loss of consciousness
- Often instantly fatal
51
Where does a berry aneurysm commonly occur?
Sited at branching points in the Circle of Willis
