L11 - Neuropathology Flashcards
How do microorganisms gain entry to the CNS
Direct spreads:
- middle ear infections
- basilar skull fractures
Blood bourne:
- sepsis
- infective endocarditis
Iatrogenic:
- VP shunt
- surgery
- lumbar puncture
Meningitis
Inflammation of the leptomeninges
With or without septicaemia
Non blanching rash
Effects of meningitis
Rapid oedema
Blood vessel congestion’s
Invasion by neutrophils
Raised intracranial pressure
Causative organism of meningitis in neonates
Ecoli
Monocytogenes
Causative organism of meningitis in 2-5 year olds
Haemophilus influenzae type B
Rare due to vaccines
Causative organism of meningitis in 5 - 30 yr olds
Neisseria meningitidis
Causative organism of meningitis in over 30 yr olds
Streptococcus pneumoniae
What causes chronic meningitis
Mycobacterium tuberculosis
Causes granulomatous inflammation
Fibrosis of meninges due to chronic inflammation
Nerve entrapment
Complications of meningitis
Death Cerebral infarcts Cerebral abscess Subdural empyema Epilepsy
Encephalitis
Neuronal cell death by virus
Inclusion bodies aggregate
Parenchyma affected
Lymphocytic inflammatory reaction
Causes of encephalitis
Temporal lobe:
- herpes virus - shingles can cause epilepsy
Spinal cord motor neurones:
- polio
Brainstem
- rabies
How to treat encephalitis
Normally self limiting in younger patients
Can cause death
Prions
Normal protein constituent of synapses
Prions disease
- Mutated prion protein can come in to contact with normal prion proteins
- Normal prion proteins undergo a post translational confirmation change into the mutated form
- Mutated prions aggregate inside cells and are difficult to remove
- Cell apoptosis - neurones in brai.
How are mutated prions obtained
Sporadic mutation
Familial condition
Ingested
What can prions disease cause?
Spongiform encephalopathies:
- scrabies - sheep
- kuru
- bovine spongiform encephalopathy- cows
- variant creutzfeld Jacob disease - vCJD
Difference between variant and classic CJD
Variant:
- younger age of death (28)
- longer duration of illness (13- 14months)
- prominent psychological/ behavioural changes
- painful dyesthesiasis
- delayed neurological signs
- presence of florid plaques
- accumulation of protease resistant prions
Classic CJD:
- older age of death (68)
- shorter duration (4-5 months)
- dementia
- early neurological signs
Dementia
Acquired global impairment of intellect, reasoning and personality without impairment of consciousness
Alzheimer’s disease
Exaggerated ageing process
Cortical atrophy due to increased neuronal damage by neurofibrillary tangoes and senile amyloid plaques
Neurofibrillary tangles
Intracellular twisted filaments of Tau proteins
Tau proteins become hyperphosphorylated and insoluble
The build up of irregular tau proteins cause cell death
Tau protein
Normally binds and stabilises microtubules
Senile plaques
Foci of enlarged axons and dendrites fused together that aggregate
Amyloid deposition in the vessel in the middle of the plaque, reduced blood flow to the brain and can cause ischaemia
How was amyloid discovered to be involved in Alzheimer’s disease
People with Down’s syndrome - trisomy 21 has early onset Alzheimer’s disease
They were found to have mutations of:
- amyloid precursors protein gene
- presenilin genes 1 and 2
Therefore there was incomplete breakdown of the amyloid precursor protein and increased amyloid deposition
Presenilin genes
Codes for components of the secretase enzyme that normally breaks down amyloid plaques
Normal intracranial pressure
0-10 mmHg
Normally above 0
Coughing and straining e.g. the Valsava manoeuvre can increase ICP to 20 mmHg
Compensatory mechanism to maintain ICP
Reduced blood volume
Reduced CSF volume
Brain atrophy
ICP at which vascular mechanisms can maintain cerebral blood flow
Below 60 mmHg
Types of space occupying lesions in the brain
Tumour
Haemorrhage
Oedema
Effects of space occupying lesions
Deformation and destruction of the brain around the lesion
Asymmetry
Displacement of midline structures
Herniation
Types of brain herniation
Subfalcine
Central
Tentorial
Tonsillar
Subfalcine herniation
Cingulate gyrus pushed under the falx cerebri
Compression of the anterior cerebral artery
Ischaemia of medial parts of the frontal and parietal lobe and corpus callosum leading to an infarct
Can be secondary to stroke
Tentorial herniation
The uncus or medial part of the parahippocampal gyrus herniated through the tentorial notch of the tentorijm cerebellum
- damages the ipsilateral occulomotor nerve - down and out pupil
- occlusion of the posterior cerebral artery and superior cerebellar artery causing ischaemia and infarction
Often fatal due to secondary haemorrhage into the brainstem - Duret haemorrhage
Tonsilar herniation
Cerebellar tonsils are pushed down through the foramen magnum and compresses the medulla
Causes the Cushing’s reflex:
Early sign - raised BP - hypertension
Compression of respiratory centre - irregular breathing
Reflex bradycardia - low HR - low pulse
Benign brain tumours
Meningioma - can get sudden development of epilepsy
- grow outwards and is not invasive
Malignant brain tumour
Astrocytoma - spreads along nerve tracts and through the subarachnoid space
- can include spinal cord as secondary
- can occur in all ages but grade 1 commonly in younger patients and has a better prognosis
Metastasising tumours
More common
- Lymphoma
- renal cell carcinoma
Stroke
Sudden event producing a CNS disturbance due to a vascular disease
Categories of stroke
Cerebral infarction - 85%
Cerebral haemorrhage -15%
Risk factors of stroke
Hypertension
Hyperlipidaemia
Diabetes
Causes of embolism
- Heart - atrial fibrillation or mural thrombus
- atheromatous debris - carotid atheromatous
- thrombus over ruptured atheromatous plaque
- aneurysm
Types of infarct
Regional - dependent on what artery infarcted
Lacuna:
- small less that 1cm
- associated with hypertension
- commonly affects the basal ganglia
Types of cerebral haemorrhage
Intracerebral haemorrhage - 10% of strokes
Subarachnoid haemorrhage - 5%
Intracerebal haemorrhage
Associated with chronic hypertension
Charcot - Bouchard aneurysms - affecting the lenticulostriate vessels of the basal ganglia
Associated with amyloid deposition around the cerebral vessels in the elderly
Can have an inherited disposition
- blow out haemorrhage
Subarachnoid haemorrhage
Rupture of berry aneurysms Thunderclap headache Sentinel headaches - small bleeds before major event Loss of consciousness Often instantly fatal
Berry aneurysms
Aneurysms that commonly occur at the burfications of the circle of Willis
Risk factors of subarachnoid haemorrhages
Male
Hypertension
Atheromatous
Poly cystic ovary disease
