Session 8 L3: Neuropathology Flashcards
How do microorganism gain entry to the brain?
- Direct spread e.g. middle ear infection (cerebral abscess), base of the skull fracture (predisposed to infection spread), cribriform plate
- Blood borne e.g. sepsis, infective endocarditis
- Iatrogenic e.g. V-P shunt, surgery, lumbar puncture
What is meningitis?
- Inflammation of the leptomeninges (PIA+ARACHNOID)
- Can happen with or without septicaemia
What are causative organism in meningitis?
Neonates – E.coli, L.monocytogenes 2-5 years – H.Influenzae type B 5-30 years – N.Meningitidis Over 30 years – S.pneumoniae Various in immunocompromised individuals
What is a common cause of chronic meningitis?
- Caused by M tuberculosis commonly.
- Results in granulomatous inflammation, fibrosis of meninges and nerve entrapment
What are the complications of meningitis?
Local
- Death (swelling leading to RICP)
- Cerebral Infarction leading to neurological deficit
- Cerebral abscess
- Subdural empyema
- Epilepsy
Systemic
What is classically the cuase of encephalitis?
- Classically viral and not bacterial
- Affects the parenchyma not meninges
What are lobes affected by viruses?
Temporal lobe - Herpes virus
Spinal cord motor neurons - Polio
Brain stem - Rabies
What are prions?
- Key is prion protein (PrP)
- Normal constituent of synapse
How are prions transmitted?
- Sporadic mutation
- Familial
- Ingested
How do mutated PrP affect normal PrP?
- Mutated PrP interacts with normal PrP to undergo a post translational conformational change
- Extremely stable structure
How do prions cause disease?
PRPsc aggregates lead to neuronal death and holes in grey matter
What are examples of Prion disease?
- Spongiform encephalopathies
- Scrapie in sheep
- BSE in cows
- Kuru in tribes of New Guinea
- Variant Creutzfeld-Jacob disease
What is vCJD?
- Different from classical CJD
- Each case has unique genetic prion sequence
- Strong laboratory and epidemiological evidence of causal association of vCJD with BSE
- Prolonged incubation period 15+ years
- Link to tradition butchery in area in 1980s
- Prions not eradicated by traditional sterilization
What are the characteristic features of classical CJD?
- Median age of death is 68 years
- Median duration of illness is 4-5 months
- Periodic sharp waves on EEG often present
- Presence of florid plaques on neuropathology is rare or absent
- Immunohistochemical analysis of brain tissue shows variable accumulation
- Agent isn’t detected readily in lymphoid tissue
What are the characteristic features of classical CJD?
- Median age at death is 28 years
- Median duration of illness is 13-14 months
- Periodic sharp waves on EEG is often absent
- Presence of florid plaques on neuropathology is present in large number
- Immunohistochemical analysis of brain tissue shows marked accumulation of protease resistance prion protein
- Agent is detected readily in lymphoid tissue
What are the signs and symptoms of classic CJD?
- Dementia
- Early neurological signs
What are the signs and symptoms of vCJD?
- Prominent psychiatric/behavioural symptoms
- Painful dyesthesiasis
- Delayed neurological signs
What are some cause of dementia?
Alzheimer’s – sporadic/familial, early/late
Vascular dementia – gradual ischaemic damage so gradual degeneration of neurones
Lewy body
Picks disease
What is dementia?
Acquired global impairment of intellect, reason and personality without impairment of consciousness
What are the features of brain in Alzheimer’s disease?
- Loss of cortical neurones so decrease in brain weight and cortical atrophy
- Exaggerated agin process
What are the microscopic features of Alzheimer’s disease?
- Neurofibrillary tangles
- Senile plaques
What are neurofibrillary tangles?
- Intracellular twisted filaments of Tau protein
- Tau normally binds and stabilises microtubules
- Tau becomes hyperpolarised in AD causing Tauopathy
What are senile plaques?
- Foci of enlarged axons, synaptic terminals and dendrites
- Amyloid deposition in vessels in centre of plaque
- Amyloid deposit is central to pethogenesis
Which condition is Alzheimer’s disease more early onset?
- Down’s Syndromes
- Trisomy 21
- Familial Alzheimer’s is more common
- Mutation of 3 genes on chromosome 21 is the cause
What are are the 3 genes on chromosome 21 that are implicated to cause Alzheimer’s?
- Amyloid precursor protein gene
- Presenilin (PS) genes 1 and 2 code for components of secretase enzyme
- Leads to incomplete breakdown of APP and amyloid is deposited
Which processes increase the intracranial pressure?
- Coughing and straining increase to 20 mmHg
- Only significant if the increased main for several minutes
How can increased in ICP be compensated?
Compensation mechanism maintain normal pressure by:
- Reducing blood volume
- Reduced CSF volume
- Spatial such as brain atrophy
What is the effect of expanding lesions?
- Deformation or destruction of the brain around the lesion
- Displacement of midline structures – loss of symmetry
- Brain shift result in internal herniation. Brains squished against bony structures and extrudes through foramina
What is a hernia
Protrusion of an organ or part of an organ through wall that normally contains it
What are the different types of herniation?
- Subfalcine
- Tentorial
- Tonsilar
What is a 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 lobe and corpus callosum due to compression of anterior cerebral artery leading to infarction
What is a tentorial herniation?
- Uncus/medial part of the parahippocampal gyrus through the tentorial notch
- Damage to the oculomotor nerve on the same side (clinical sign)
- Occlusion of blood flow in posterior cerebral and superior cerebellar arteries
Why is a tectorial herniation often fatal?
- Frequently fatal because of secondary haemorrhage into the brainstem leading to duret haemorrhage
- Common mode of death in those with large brain tumours and intracranial haemorrhage
What is a tonsillar herniation?
-Cerebellar tonsils pushed through into the foramen magnum compressing the brainstem
What are cancers of the brain?
- Meningioma (benign)
- Astrocytoma (malignant)
- Neurofirbroma
- Ependymoma
- Neuronal e.g medulloblastoma
- Tumors from non CNS
What is a meningioma?
Tumour from a meningeal origin
What is an astrocytoma?
- Astrocyte origin to astrocytoma (grade 1 to grade 4)
- Spread along nerve tracts and through sub arachnoid space often presents with a spinal secondary
- Grade 1 is more common in children
- Grade 4 is very aggressive and spreads through CNS very well. Interrupt the somatic systems
What are tumours from non-CNS origin?
- Lymphoma
- Metastasis – the most common
What is a stroke?
Sudden event producing a disturbance of CNS function due to vascular disease.
What are the 2 broad categories of stroke?
Cerebral infarction – 85 % of strokes
Cerebral haemorrhage – 15% of strokes
What are risk factors for stroke?
- Hyperlipidaemia
- Hypertension
- Diabetes mellitus
- Vascular disease
What is the pathogenesis of a stroke?
- Embolism
- Thrombosis
What are common causes of an embolism to the brain?
- Heart – atrial fibrillation, mural thrombus
- Atheromatous debris (carotid atheroma)
- Thrombus over ruptured atheromatous plaque
- Aneurysm
What are the types of infarct?
- Regional
- Lacuna
What can cause regional infarct?
Occlusion to Named cerebral artery or carotid
What can cause lacuna infarcts?
- Less than 1cm
- Associated with hypertension
- Commonly affect the basal ganglia
What are the features of intracerebral aneurysms?
- Associated with hypertensive vessel damage
- Charcot-Bouchard aneurysms
- Deposition of amyloid around cerebral vessels in the elderly
- May be inherited
- Produces space occupying lesion – RICP
What are the common causes of sub arachnoid haemorrhages?
Rupture of Berry Aneurysms
What are risk factors involved in the pathogenesis of sub arachnoid haemorrhages?
- Male sex
- Hypertension
- Atheroma
- Links to other diseases
What are the symptoms of a subarachnoid haemorrhage?
- Sudden severe headache – thunderclap
- Sentinel headache
- Loss of consciousness
- Often instantly fatal
Where does a berry aneurysm commonly occur?
Sited at branching points in the Circle of Willis
