Neuropathology Flashcards
What are the three possible routes of which microorganisms can enter the CNS?
Direct spread - middle ear infections, basal skull fractures
Blood-borne - sepsis, infective, endocarditis
Iatrogenic - V-P-shunt, surgery, lubar puncture
What is meningitis?
Meningitis is inflammation of the leoptomeninges
With or without septicaemia (sepsis is the more dangerous bit)
Prompt diagnosis and treatment is lifesaving. (Sometimes treat before knowing exact organism)
What are the common causative organisms of bacterial meningitis?
Neonates - E. Coli, L. Monocytogenes
2-5yrs - H. Influenzae type B
5-30 - N. Meningitides (types)
Over 30 - S. pneumoniae
Various in immunocompromised patients
What is the most common causative organism of chronic meningitis? How does it present?
Chronic clinical course
Not complain of some types of symptoms - more subtle.
M. Tuberculosis most common cause.
Granulomatous inflammation
Fibrosis of meninges
Nerve entrapment
What are the complications of meningitis?
Local: Death (swelling - RICP) Cerebral infarction - neurological deficit Cerebral abscess Subdural empyema Epilepsy
Systemic - associated with sepsis
What is encephalitis?
Classically viral not bacterial
It affects the parenchyma not meninges
Neuronal cell death by virus - inclusion bodies.
Virus kills neurones causing inflammation and presence of intracellular viral inclusions. Lymphocytic infiltrate typical
How does the organism change the area of the brain affected by encephalitis?
Temporal lobe - Herpes
Spinal cord motor neurones - Polio (eradicated)
Brainstem - Rabies (rare)
What are prions?
Misfolded proteins.
The key component of prions is the prion protein (PrP)
Normal constituents of synapses?
How do you get mutated prion proteins?
Mutated PrP can be sporadic, familial or ingested.
Mutated PrP interacts with normal PrP to undergo a post translational conformation change.
This is an extremely stable structure.
What happens in a dense caused by Prions? What diseases are caused by prions?
PrPsc aggregates - neuronal death and holes in great matter.
Spongiform encephalopathies: Scrapie in sheep BSE in cows Kuru in tribes of New Guinea Variant Creutzfeld-Jacob disease (vCJD)
What is vCJD?
Variant Creutzfeld-Jacob disease
First described in 1996 in UK
Different from classical CJD
Each case has unique prion sequence
Strong lab and epidemiological evidence of causal association of vCJD with BSE. -caused by eating meat of cows infected with BSE.
What is dementia?
Acquired global impairment of intellect reason and personality without impairment of consciousness.
What are the common types of dementia?
Alzheimer’s
Vascular dementia
Lewy body
Pick’’s disease
What is Alzheimer’s disease
Exaggerated ageing process
Loss of cortical neurones -decrease brain weight and cortical atrophy.
Die to increased neuronal damage - neurofibrillary tangles and senile plaques.
What are neurofibrillary tangles?
Intracellular twisted filaments of Tau proteins.
Tau normally binds and stabilises microtubules.
Tau becomes hyperphosphorylated
“Taupathy”
What are senile plaques?
Foci of enlarged axons, synaptic terminals and dendrites.
Amyloid deposition in vessels in centre of plaque.
How is amyloid deposition related to Alzheimer’s Demetia?
Amyloid deposition is central to pathogenesis not just of early onset Dementia but Down’s as well.
This is because it is related to mutations of 3 genes on chromosome 21 which leads to incomplete breakdown of Amyloid precursor protein (APP) and so amyloid is deposited.
What is normal intercranial pressure?
0-10mmHg
Describe some physiological reasons for increase in ICP
Coughing
Straining
But, this is only significant if this increase is maintained for several minutes.
What compensation mechanisms do we have to maintain normal ICP?
Reduced blood volume
Reduced CSF volume
Spatial - brain atrophy
Vascular mechanisms maintain cerebral blood flow as long as ICP <60mmHg.
What happens if you have an expanding lesion in the brain?
Deformation or destruction of the brain around the lesion
Displacement of midline structures - loss of symmetry
Brain shift resulting in internal herniation.
What is 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 lobes and Corpus Callosum due to compression of anterior cerebral artery - infarction
What is tectorial herniation?
This is when the uncus or medial part of the parahippocampal gyrus goes through the tectorial notch.
Damage the oculomotor nerve on the same side and occlusion of blood flow in the posterior cerebral and superior cerebellar arteries.
It is frequently fatal because of secondary haemorrhage into the brainstem (Duret haemorrhage).
Common mode of death in those with large brain tumours and inter cranial haemorrhage.
What is a tonsilar herniation?
Cerebellar tonsils pushed into the foramen magnum compressing the brainstem.
What types of tumours can you get in the brain?
Meningioma (benign)
Malignant: Astocytoma (low grade, slow growing but difficult to remove) Neurofibroma Ependymomas Medulloblastomas Lymphoma
But, metastasis form other areas in the body is the most common.
What is a stroke?
Sudden event producing a disturbance of CNS function due to vascular disease.
Last for over 24hours.
What are the two broad categories of stroke?
Cerebral infarction - 85%
Cerebral haemorrhage - 15%
What risk factors are often associated with strokes?
Hyperlipidaemia
Hypertension
Diabetes mellitus
What causes a stoke? (pathogenesis)
Embolism Heart -AF, mural thrombus Atheromatous debris Thrombus over ruptured atheromatous plaque Aneurysm
Thrombus
Over atheromatous plaque
What are the types of infarct?
Regional - named cerebral artery or carotid
Lacuna - less than 1cm, associated with hypertension, commonly affect the basal ganglia.
What are the two types of cerebral haemorrhage?
Two types - intracerebral and subarachnoid
What is an intercerebral haemorrhage?
Associated with hypertensive vessel damage
Charcot-Bouchard aneurysms.
Deposition of amyloidaround cerebral vessels in the elderly.
May be inherited.
Produced space occupying lesion (RICP)
What is a subarachnoid haemorrhage?
Rupture of berry aneurysm
Pathogenesis poorly understood:
- Males
- Hypertension
- Atheroma
- Links to other diseases
Sited at branching points in the Circle of Willis
How does a subarachnoid haemorrhage present?
Sudden severe headache - Thuderclap
Sentinel headache
Loss of consciousness
Often instantly fatal
What is neuropathology?
Integrates fundamental pathological principles with neuro anatomy and physiology to understand aetiology prevention and treatment.
