Neuropathology Flashcards
The CNS is normally sterile.
What are 3 ways microorganisms can gain entry
Direct spread (From middle ear, basal skull fracture, ethmoid bone)
Blood-borne: (Sepsis, Infective endocarditis)
Iatrogenic: (Post neurosurgery, lumbar puncture)
Describe the pathophysiology of Meningitis (Potentially life threatening)
- Inflammation of leptomeninges
- May have septicaemia
(Non-balancing rash is a sign of meningococcal septicaemia, not meningitis)
Which organisms cause Meningitis in;
- Neonates
- 2-5 years old
- 5-30 years old
- 30+
- Immunocompromised patients
Neonates: E. coli, L. monocytogenes
2-5: H. influenza
5-30: N. meningitidis
30+: S. pneumoniae
Immunocompromised: Various organisms (E.g fungi)
Describe 5 features of Chronic Meningitis
- Caused by M. tuberculosis
- Granulomas
- Meningeal fibrosis
- Cranial nerve entrapment
- Bilateral adrenal haemorrhage (Waterhouse-Friederichsen syndrome) as a complication
List 5 complications of Meningitis
- Death due to raised ICP
- Cerebral infarction
- Cerebral abscess
- Subdural Empyema
- Epilepsy (due to direct irritation of brain)
(Systemic complication- Septicaemia)
Encephalitis is usually viral and causes inflammation of brain parenchyma
Describe the pathophysiology
Virus kills neurones causing Inflammation and presence of Intracellular viral inclusions
Lymphocytic infiltrate is typical
Which parts of the CNS are affected by;
- Herpes
- Polio (Eradicated)
- Rabies
- Herpes affects Temporal lobe
- Polio affects Spinal cord
- Rabies affects Brainstem
Prion protein (PrP) is a normal protein found in synapses
What can cause PrP to transform into PrPsc (abnormal form)
- Sporadic mutation
- Familial inheritance of mutated gene
- Ingestion of PrPsc
List 3 features of PrPsc
- Able to convert PrP into PrPsc by protein-protein interactions (induce a conformational change)
- Extremely stable (Resistant to radiation, disinfectants)
- Not susceptible to immune attack (is essentially a ‘self’ protein)
How does PrPsc cause damage?
PrPsc aggregates cause neuronal death, leading to ‘holes’ in grey matter
(Brain takes on a spongiform/ sponge-like appearance)
List 5 Spongiform Encephalopathies
- Scrapie (in sheep)
- BSE (in cows, ‘mad cow disease’)
- Kuru (in some tribes due to cannibalism)
- CJD (Creutzfeld Jacob disease)
- vCJD (Variant CJD)
Variant CJD is strongly linked to BSE.
How does it differ from ‘classical’ CJD?
Higher prion load associated with;
- Earlier age at death
- More prominent psychiatric/ behavioural symptoms
In Dementia, is consciousness impaired?
No
Describe the Pathophysiology of Alzheimer’s
Loss of cortical neurones-> Cortical atrophy and reduced brain weight
Damage caused by Neurofibrillary Tangles and Amyloid Plaques
Describe what Neurofibrillary tangles are
Intracellular twisted filaments of Tau protein
Tau normally binds and stabilises microtubules, becomes hyperphosphorylated in in Alzheimer’s
Describe what Amyloid Plaques are
- Foci of enlarged axons, dendrites and synaptic terminals
- Amyloid deposition in vessels in centre of plaque
What is Trisomy 21 associated with?
How?
- Alzheimer’s
- Amyloid Precursor Protein (APP) gene is found on this chromosome (hence extra dose of gene)
What are 2 gene mutations associated with Alzheimer’s
- APP gene
- Presenelin gene (Produce secretase which breaks down APP)
What is the normal ICP?
What can coughing/ sneezing raise it to?
0-10mmHg
10-20mmHg
(Only significant if raised for several minutes)
Suggest 2 mechanisms to compensate for raised ICP
Up to what ICP can cerebral flow be maintained?
- Reduced blood and CSF volume
- Brain atrophy if chronically elevated
Upto 60mmHg
Suggest 3 effects of a Space Occupying Lesion in the brain
- Deforms/ destroys around lesion
- Displacement of midline structures
- Can cause brain herniation
Describe a Subfalcine herniation as well as its possible effects
(One of the first herniations to occur)
- Cingulate Gyrus pushed under Falx Cerebri
- Herniated brain can become ischaemic due to compression of ACA
Describe a Tentorial herniation as well as its possible effects
- Medial Temporal Lobe (Uncus, typically) pushed through Tentorial Notch
Compression of;
- Ipsilateral CNIII-> CNIII Palsy
- Ipsilateral Cerebral Peduncle-> Contralateral UMN signs in limbs
Occlusion of Posterior Cerebral and Superior Cerebellar arteries
Duret haemorrhages are associated with Tentorial Herniation
What is it?
Secondary brainstem haemorrhage
What is a Tonsilar herniation?
Cerebellar tonsils pushed into Foramen Magnum-> Brainstem compression
Name a Benign brain tumour
Meningioma
List 5 Malignant brain tumours
not including Metastases which are the most common of all brain tumours
- Astrocytoma
- Neurofibroma (Schwann cells)
- Ependymoma (Ependymal cells)
- Neuronal tumours (Neurones)
- Lymphoma
List some features of Astrocytomas
- Low grade, slow growing, difficult to remove
- High grade ones known as Glioblastoma Multiforme
- Direct spread along white mater pathways
- Can also spread to distant CNS via CSF
Strokes are more frequent in the elderly.
List 4 risk factors
- Hyperlipidaemia
- Hypertension
- Smoking
- Diabetes
Strokes can be caused by an Embolism or Thrombus
What are the 2 broad categories of Stroke?
What percentage of all strokes do they each make up?
- Cerebral Infarction (85%)
- Cerebral Haemorrhage (15%)
Compare the 2 types of cerebral infarction
Regional;
- Large
- Worse prognosis
Lacunar;
- Small
- Associated with hypertension
- Commonly affect Basal Ganglia and Internal Capsule
Cerebral haemorrhages are usually spontaneous.
What are the 2 types of cerebral haemorrhage?
- Intracerebral haemorrhage (10% of all strokes)
- Subarachnoid haemorrhage (5% of all strokes)
List features of Intracerebral haemorrhage
- Associated with Age, Hypertensive vessel damage and Amyloid deposition in vessels
- Charcot-Bouchard aneurysms seen
- May be inherited
- Produces a Space Occupying Lesion
List features of Subarachnoid haemorrhage
- Rupture of Berry aneurysms, usually at branching points in Circle of Willis
- Blood in Subarachnoid space-> Spasm of cerebral arteries
What are 4 associations/ risk factors of Subarachnoid haemorrhage
- Male
- Hypertension
- Atherosclerosis
- Other diseases (CT disorders, Polycystic Kidney disease)
List 4 symptoms of Subarachnoid haemorrhage
- Thunderclap headache
- May be preceded by a ‘Sentinel headache’
- Loss of consciousness
- Often instantly fatal
