S8) Neuropathology Flashcards
The CNS is normally sterile. However, microorganisms gain entry by 3 possible routes.
Identify them
- Direct spread e.g. middle ear infection, base of skull fracture
- Blood-borne e.g. sepsis, infective endocarditis
- Iatrogenic e.g. ventricular-peritoneal shunt, surgery, lumbar puncture
What is meningitis?
- Meningitis is the inflammation of the leptomeninges, with/without septicaemia
- Prompt diagnosis and treatment is life saving
What are the causative organisms of meningitis in patients of various ages?
- Neonates – E. Coli, L. monocytogenes
- 2 - 5 years – H. influenzae type B (HiB)
- 5 - 30 years – N. Meningitides (types)
- Over 30 years – S. pneumoniae
Describe, in three steps, how chronic meningitis might occur
M. tuberculosis:
⇒ Granulomatous inflammation
⇒ Fibrosis of meninges
⇒ Nerve entrapment
Identify five complications of meningitis
- Death (swelling → RICP)
- Cerebral Infarction → neurological deficit
- Cerebral abscess
- Subdural empyema
- Epilepsy
What is encephalitis?
- Encephalitis is the classically viral inflammation of the brain parenchyma due to infection
- Neuronal cell death by virus occurs, with the inclusion bodies
Identify the causative organisms for encephalitis in the following areas:
- Temporal lobe
- Spinal cord motor neurons
- Brain stem
- Temporal lobe e.g. herpes virus
- Spinal cord motor neurons e.g. polio
- Brain stem e.g. rabies
How might mutated prion proteins enter the body?
- Sporadic mutation
- Familial mutation
- Ingested
What is the effect of the mutated PrP on the body?
Mutated PrP interacts with normal PrP to undergo a post translational conformational change
What occurs in prion disease?
PrPSC aggregates leading to neuronal death and holes in grey matter
What is dementia?
Dementia is the acquired global impairment of intellect, reason and personality without impairment of consciousnes
Identify four common forms of dementia
- Alzheimer’s (50%)
- Vascular dementia (20%)
- Lewy body
- Picks disease
Describe some defining features of Alzheimer’s Disease
Exaggerated aging process due to:
- Loss of cortical neurones – ↓ brain weight, cortical atrophy
- ↑ neuronal damage – neurofibrillary tangles, senile plaques
In three steps, describe how neuronal damage occurs in AD due to neurofibrillary tangles
⇒ Intracellular twisted filaments of Tau protein
⇒ Tau normally binds and stabilises microtubules
⇒ Tau becomes hyperphosphorylated in AD
In two steps, describe how neuronal damage occurs in AD due to senile plaques
⇒ Foci of enlarged axons, synaptic terminals and dendrites
⇒ Amyloid deposition in vessels in centre of plaque
In Down’s syndrome, there is early onset AD.
Explain why
- Mutations of 3 genes on chromosome 21:
I. Amyloid precusor protein (APP) gene,
II. Presenilin (PS) genes 1 and 2 code for components of secretase enzyme
- Leads to incomplete breakdown of APP and amyloid is deposited
What is the value for normal intracranial pressure?
0 - 10mmHg
Which physiological mechanisms increase ICP?
Coughing and straining increase ICP to 20 mmHG
Identify the three compensation mechanisms that maintain normal pressure
- Reduced blood volume
- Reduced CSF volume
- Spatial – brain atrophy
How are vascular mechanisms affected by ICP?
Vascular mechanisms maintain cerebral blood flow as long as ICP < 60mmHg
State the three effects of an expanding lesion in the brain
- Deformation/destruction of the brain around the lesion
- Displacement of midline structures – loss of symmetry
- Brain shift resulting in internal herniation
What occurs in a subfalcine herniation?
- In a subfalcine herniation, the cingulate gyrus is pushed under the free edge of the falx cerebri
- Ischaemia of medial parts of frontal lobe, parietal lobe and corpus callosum due to compression of anterior cerebral artery → infarction
What occurs in a tentorial herniation?
- In a tentorial herniation, the uncus / medial part of the parahippocampal gyrus herniates through the tentorial notch
- Ipsilateral occulomotor nerve damage and occlusion of posterior cerebral and superior cerebellar arteries
- Often fatal due to secondary haemorrhage into the brainstem (duret haemorrhage)
What occurs in a tonsillar herniation?
In a tonsillar herniation, the cerebellar tonsils are pushed into the foramen magnum compressing the brainstem
