S8) Neuropathology Flashcards
The CNS is normally sterile. However, microorganisms gain entry by 4 possible routes.
Identify them
- Direct spread e.g. middle ear infection, base of skull fracture, air sinuses
- Blood-borne e.g. sepsis, infective endocarditis
- Iatrogenic e.g. ventricular-peritoneal shunt, surgery, lumbar puncture
- peripheral nerves eg HZV, viruses
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
- will see lots of lymphocytes
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 (protein) aggregates leading to neuronal death and holes in grey matter
→ lose synapses
→ lack if inflammation
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
- Infarction of medial parts of frontal lobe, parietal lobe and ischemia of corpus callosum due to compression of anterior cerebral artery → infarction
normla on left and abnormal on right
What occurs in a trans-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 = ischameia
- Often fatal due to secondary haemorrhage into the brainstem (duret haemorrhage)
- pushes onto the cerebellum
What occurs in a tonsillar herniation?
In a tonsillar herniation, the cerebellar tonsils (at the bottom) are pushed into the foramen magnum compressing the brainstem
CNS tumours are very rare.
Regardless, identify some
- Benign – meningioma
- Malignant – astrocytoma
- Others – neurofibroma, ependymoma, neuronal e.g. medulloblastoma
What is a stroke?
A stroke is a sudden event producing a disturbance of CNS function due to vascular disease
What are the two broad categories of strokes?
- Cerebral infarction (85%) Ischaemic (thrombotic or embolitic)
- Cerebral haemorrhage (15%)
Identify three risk factors for stroke
- Hyperlipidaemia
- Hypertension ( due to arteriosclerosis → walls thicken)
- Diabetes mellitus
Describe the pathogenesis of a stroke from an embolism (most common)
CAN COME FROM:
- Heart – atrial fibrillation, mural thrombus
- Atheromatous debris (carotid atheroma)
- Thrombus over ruptured atheromatous plaque
- DVT from patent foramen ovale
- Aneurysm
Describe the pathogenesis of a stroke from a thrombosis
Thrombosis – over atheromatous plaque inside the brain
→ carotid bifurcation, Middel cerebral artery, basil artery
→ fragments can break off and spread to distal sites
Identify and describe two types of infarct in the brain
- Regional – named cerebral artery or carotid
- Lacuna – Associated with hypertension (commonly affect the basal ganglia)
What are the two types of intracerebral haemorrhages?
- Intracerebral haemorrhage (10% of all strokes)
- Subarachnoid haemorrhage (5% of all strokes)
Describe the occurrence of intracerebral haemorrhages
- Associated with hypertensive vessel damage
- Deposition of amyloid around cerebral vessels in the elderly
- Produces space occupying lesion
Describe how a subarachnoid haemorrhage usually presents
- Sudden severe headache
- Loss of consciousness
- Often instantly fatal
→ sudden raise in ICP
Describe the pathogenesis of subarachnoid haemorrhages
Pathogenesis poorly understood:
- Male sex
- Hypertension
- Atheroma
- loose tissue
- Links to other diseases
What causes a subarachnoid haemorrhage?
A subarachnoid haemorrhage is caused by the rupture of ‘berry’ aneurysms
→ shearing of meningeal blood vessels
TRAUMATIC: basal skull fractures
SPONTANEOUS: berry, amyloid angiopathy, vertebral artery dissection
normally in anterior circulating area
what are the causes of raised ICP
→ heamatoma
→ tumours
→ space occupying lesions
→ cerebral oedema
→ infections
what do you observe with raised ICP
→ destruction of brain tissue around lesions
→ displacement of midline structures
→ brain shifts
swelling, loss of sulcus and gyri are expanded
what is a duret haemmorage
lots of small bleeds accumulating together in the midbrain and pons => rapidly developing brain herniation
what is an extradural/epidural haematoma
→ damage to the middle meningeal artery
→ trauma to the side of the head and temporal bone
→ blood accumulates between the dura and the skull
→ lucid intervals (takes a while for the dura mater to break away from the skull and for the blood to peel away the dura)
subdural haematoma
→ shearing of bridging veins
→ between the dura and the arachnoid
ACUTE: traumatic and rapid blood accumulation
CHRONIC: elderly and chronic alcoholics (brain atrophy so more space between the two layers)
→ check if the elderly are on warfarin or anticoagulants
→ a lot of blood can develop before clinical signs develop
ischemic stroke / cerebral infraction
→ damage is limited if there is collateral blood supply
→ watershed areas: areas that lie most distal to portion of the artery territory
which artery is most effected by emboli in the brain
→ middle cerebral as its a direct extension from the internal carotid artery
histology of cerebral ischaemia
spontaneous intracerebral haemmorage common sites
→ basal ganglia
→ thalamus
→ pons and cerebellum
in diagram there is extension into the ventricular system
what is cerebral amyloid angiopathy
→ advancing age
→ lobar haemmorages involving cerebral cortices and tiny microharmmorages
→ Amyloid deposition in walls of meningeal vessels
what are amyloids
→ build up of abnormal protein
→ can cause blockage of vessels
→ can be strained with Congo red dyes
what are arteriovenous and cavernous malformations likely to cause
intracerebral haemorrhage
- Arteriovenous malformations: very common, worm like and tangled subarachnoid vessels that can break
- Cavernous malformations: losse vascular channels, distended and thin walled in the cerebellum and the pons
what are some examples of CNS tumours
- primary → arises from the brain
- secondary → arises from elsewhere, breast or lungs
Gliomas
what are three complications of infections in the CNS
- meninges damaged
- aggregates of acute inflammation
- brain parenchyma
how can you test for meningitis
→ take a lumbar puncture and test the CSF
- see raised proteins (neutrophils), increased pressure, reduced glucose
- CT scans
histology of prions disease
shouldn’t see any of these white spaces
features of neurodegenerative disease
Alzheimer’s disease
→ caused from abnormal deposits of amyloid plaques and tau tangles in brain
→ altered mood, forget, can’t communicate (severe)
Parkinson’s disease
→ loss of dopaminergic neurones in the substantia nigra pars compacts
→ due to lewys bodies
→ hypokinesia
picture shows a lewys body
Huntingdon’s disease
→ effects the basal ganglia
→ hyperkinesia
→ autosomal dominant
→ mutant protein is broken down into aggregates of Huntingdon protein
- picture shows loss of white matter and the broadening of the sulcus
