Neuropathology Flashcards
What are the 3 routes by which microorganisms can gain entry to the CNS?
- Direct Spread from a physical breach- e.g. middle ear infection, base of skull fracture
- Blood-borne - sepsis, infective endocarditis
- Iatrogenic (by medical professionals) - e.g. V-P shunt, surgery, lumbar puncture
What is meningitis, what are the consequences of it if left untreated?
Meningitis is inflammation of the leptomeninges (pia + arachnoid mater). Can occur with/ without septicaemia
Untreated causes rapid influx of oedema, neutrophil influx causes pus → raises ICP leading to death if not quickly treated
What are the main causative organisms of meningities in the age groups:
Neonates
2-5 years
5-30 years
Over 30s
Neonates - E.coli, L. monocytogenes
2-5 years - H. influenzae type B (HiB) - vaccinated against
5-30 years - N. Meningitides types A,B+C
Over 30s - S.pneumoniae
What organism causes chronic meningitis?
What are the effects of having chronic meningitis?
Mycobacterium Tuberculosis
- Granulomatous inflammation
- Fibrosis of the meninges
- Nerve entrapment
- facial nerve palsy
- headache
What are the some the local and systemic complications of meningitis
Local:
- Death (swelling raises ICP)
- Cerebral infarction → neurological deficit
- Cerebral abcess
- Subdural empyema → chronic pus
- Epilepsy
Systemic: if associated with speticaemia
What is Encephalitis?
Inflammation of the parenchyma (not the meninges) in the brain - affects neuronal cell bodies
What type of microorganisms cause encephalitis affecting different areas of the brain:
- Neuronal cell death
- Temporal lobe
- Spinal cord motor neurones
- Brain Stem
Mainly viral not bacterial
- Neuronal cell death - inclusion bodies (build up of virus)
- Temporal lobe - Herpes Virus
- Spinal cord motor neurones - Polio
- Brain Stem - Rabies
How do you treat encephalitis?
Often self limiting in young patients as long as they’re not immunocompromised
What are prions?
Prions are proteins we all have that are a part of synpases
What is prion disease?
- Mutation in prion proteins that are either sporadiac, familial or ingested
- Mutated PrP interacts with normal PrP to induce post translational conformational change
- Makes an extremely stable striucture that aggregates and cannot be elimited
- Causes neuronal death and holes in grey matter → spongiform encephalopathies
Name some types of spongiform encephalopthies
- Scrapie in sheep
- BSE in cows
- vCJD- Variant Creutzfeld- Jacob Disease - strongly associated with BSE
- Kuru in tribes of New Guinea
There are 2 forms of vCJD, classic and variant. What are the different clinical features of each?
Why is prion diease not classed as infection?
- Infectious agents should not be found in healthy organisms which prions are
- Microorganisms must be isolated and grown in pure culture- proteins cannot be grown
What is dementia?
Name the most common types
Aquired global impairment of intellect, reason and personality without impairment of conciousness
- Alzehimer’s (50%)- Sporadic/ Familial, Early/ Late
- Vascular dementia (20%)
- Lewy body
- Pick’s disease (Fronto-temporal dementia)
What happens to the brain in Alzheimer’s Disease?
- Brain undergoes an exggerated aging process
- Loss of cortical neurones
- decreased brain weight- greater sulci/ gyri definition
- cortical atrophy (thinner cortex)
- Neurofibrillary tangles and senile plaques cause increased neuronal damage
What are neurofibrillary tangles?
- Found in Alzheimer’s Disease
- Intracellular twisted filaments of Tau protein
- Tau, normally binds and stabilies microtubules
- Tau becomes hyperphospharylated and starts to aggregate
- Cell can’t function and produce energy → death
What are senile plaques?
- Plaques found in Alzheimer’s Disease
- Foci of englarged axons, synaptic terminals and dendrites
- Amyloid deposition in vessels in the centre of the plaque- buolds up around blood vessels causing ischemia
- Look like balls of cotton wool
What is the link between amyloid deposition and chromosome 21?
- Down’s syndrome (trisomy 21) will have early onset AD
- Mutation in 3 genes on trisomy 21 throught to be ivolved
- Amyloid precursor protein (APP) gene
- Presenlin genes 1 and 2 make secretase (enzyme that breaks down amyloid)
- Leads to incomplete breakdown of APP and amyloid is deposited
What is normal brain ICP?
0-10 mmHg
(may increase to 20mmHg during coughing and straining)
What compensatory mechanisms happen to maintain noraml brain ICP?
- Recued blood volume
- Reduced CSF volume
- Spatial → brain atrophy (if raised ICP is chronic)
Mechanisms work as long as ICP is <60 mmHg
If ICP raises too much it will cause herniation. What are the different types of herniation?
- Subfalcine
- Tentorial
- Tonsilar
Explain what happens in a subfalcine herniation
- The cingulate gyrus on the same side of the SoL is pushed under the free edge of the falx cerebri
- Causes ischemia of medial parts of the frontal & parietal lobes and the corpus callosum due to compression of the anterior cerebral artery → infarction
What happens in tentorial herniation?
- The uncus (medial part of the parahippocampal gyrus) is pushed through the tentorial notch
- Can cause damage to the occulomotor nerve (on the same side)
- Occlusion of blood flow in posterior cerebral and uperior cerebrallar arteries
- Frequently fatal due to secondary haemorrhage into the brainstem (Duret Haemorrhage- of the midbrain & pons)
What happens in tonsilar herniation?
- Cerebellar tonsisl are pushed into the foramen magnum compressing the brainstem
- Early on- blood can’t get to brain so systemic blood pressure rises to compensate
- After time- brainstem herniation depresses cardio respiratory centres
- Cushing’s reflex : High BP and Bradycardia
How common are tumours of the brain?
Primary tumours are rare, will more commonly see secondary tumours from other sites
Which tumours commonly metastasise to the brain?
- Renal Cell Carcinoma
- Malignant Melanoma
What is a menangioma?
A benign tumour of meningeal origin
Often found incidentally- can present as new onset epilepsy
What is an astrocytoma?
A maligant tumour of astrocyte origin (Grades 1-4)
Lower grades more common in younger people, in adults usually very aggressive 3-4 month survival
Won’t metastasise outside the CNS → spread along nerve tracts and through sub arachnoid space often present as spinal accessory
What is a stroke?
A sudden event producing a distrubance of CNS function due to Vascular disease
2 broad categories: Cerebral infarction 85%
Cerebral haemorrhage 15%
What types of infarct can you get in stroke?
Regional - names agter the cerbral artery or carotid
Lacuna - less than 1cm, associated with hypertension, commonly affects the basal ganglia
How do subarachnoid haemorrhages occur?
Rupture of berry aneurysms usually at bifuraction points of the circle of Willis
Pathogenesis poorly understood; male sex, hypertension, atheroma, links to other disease
What symptoms would you associate with a subarachnoid haemorrhage?
- Severe sudden onset headache - thunderclap
- Sentinal headaches (small bleeds before main headache)
- Loss of conciousness
- Often instantly fatal
