Session 8 Neuropathology Flashcards
(40 cards)
How can microorganisms gain entry to the CNS?
Direct spread (from middle ear, basal skull fracture, even through ethmoid bone)
Blood-borne in sepsis or infective endocarditis
Iatrogenic (post neurosurgery, ventriculoperitoneal shunt, lumbar puncture
What is meningitis?
Potentially life threatening condition
Inflammation of leptomeninges (pi-arachnoid)
+/- septicaemia (remember that non-blanching rash is a sign of meningococcal septicaemia, not meningitis per se)
What are the common causative organisms of meningitis in different groups of people?
Neonates – E. coli, L. monocytogenes
2-5 years old – H. influenza
5-30 years – N. meningitidis (‘meningococcus’)
Immunocompromised patients – a variety of organisms e.g. fungi
What is ‘chronic’ meningitis caused by?
What syndrome can occur as a complication?
Caused by M. tuberculosis • Granulomas • Meningeal fibrosis • Cranial nerve entrapment • Bilateral adrenal haemorrhage (Waterhouse Friederichsen syndrome) can occur as a complication
What are the local and systemic complications of meningitis?
Local
- Death due raised intracranial pressure
- Cerebral infarction (stroke)
- Cerebral abscess
- Subdural empyema
- Epilepsy (due to direct irritation of brain)
Systemic
* Resulting from septicaemia
What is encephalitis?
usually viral
Inflammation of BRAIN PARENCHYMA not meninges (but can occur as a complication of meningitis)
What happens in encephalitis?
Which areas of the brain are affected by what?
Virus kills neurones causing inflammation and presence of intracellular viral inclusions. Lymphocytic infiltrate is typical
• Temporal lobe affected by Herpesviruses (most common)
• Spinal cord affected by polio (now eradicated)
• Brainstem affected by rabies (very rare)
What is the Prion Protein (PrP)?
a normal protein found in synapses (unknown function)
Following sporadic mutation of PrP what can it turn into?
can transform into PrPsc = abnormal form!
can also get this from familial inheritance or following ingestion of PrPsc itself
What makes PrPsc dangerous?
It is extremely stable and resistant to disinfectants and irradiation
It is not susceptible to immune attack as it is essentially a ‘self’ protein
How does PrPsc cause damage?
PrPsc causes damage by forming aggregates which destroy neurones and cause the brain to take on a sponge-like (spongiform) appearance
What are some examples of spongiform encephalopathies?
- Scrapie in sheep
- BSE in cows (‘mad cow’ disease)
- Kuru in New Guinean tribes (due to cannibalism and
ingestion of PrPsc) - Creutzfeld Jacob disease (CJD)
= Variant CJD (vCJD) which is strongly linked to BSE through ingestion of
prions
How is the variant CJV different from the classical CJV?
Essential difference compared to classical CJD is that there seems to be a much higher prion load associated with earlier age at death and more prominent psychiatric symptoms
What is dementia?
Acquired global impairment of intellect, reason and personality without impairment of consciousness
What is Alzheimer’s disease?
What does it lead to in the brain and what is the damage caused by?
Loss of cortical neurones
o Leading to .. cortical atrophy and decreased brain weight
o Damage caused by … neurofibrillary tangles and amyloid plaques
What are ‘tangles’?
What leads to tangle formation?
= Intracellular twisted filaments of Tau protein • Tau normally binds to microtubules • Hyperphosphorylation of tau is thought to lead to tangle formation
What are plaques?
- Foci of enlarged axons, synaptic terminals and dendrites
- Amyloid deposition in centre of plaque associated with vessels
- Trisomy 21 associated with Alzheimer’s disease (amyloid precursor protein (APP) found on this chromosome hence extra ‘dose’ of gene in patients with Down’s syndrome
What are some associated gene mutations associated with Alzheimer’s disease?
- APP
* Presenelin genes
What pathologies can lead to raised intracranial pressure?
- coughing and straining
- space occupying lesion e.g. tumour
- brain tumours
What is normal ICP? What can coughing/straining increase it to?
normal = 0-10mmHg coughing = 20 mmHg
What level must ICP be under to maintain cerebral blood flow?
<60 mmHg
What is brain herniation?
space occupying lesions cam displace midline structures and cause brain herniation where parts of the brain protrudes through a wall that normally contains it
What happens in subfalcine herniation?
Cingulate gyrus is pushed under the free edge of the
falx cerebri
Herniated brain can become ischaemic due to compression of anterior cerebral artery (which normally loops up around corpus callosum and can get pinched)
What happens in tentorial herniation?
Medial temporal lobe (classically the uncus) pushed
down through the tentorial notch (free edge of tentorium cerebelli)
Can compress ipisilateral oculomotor nerve and ipsilateral cerebral peduncle causing ipsilateral third nerve palsy but contralateral UMN signs in limbs
Can be complicated by secondary brainstem haemorrhage (Duret haemorrhage) – often fatal
Usual mode of death for those with large brain tumours or severe intracranial haemorrhage
