neuropathology Flashcards
What are ways in which infection can spread in the CNS
oCNS normally sterile
oMicroorganisms can gain entry via
- Direct spread (from middle ear, basal skull fracture, even through ethmoid bone)
- Blood-borne in sepsis or infective endocarditis
- Iatrogenic (post neurosurgery, ventriculoperitoneal shunt, lumbar puncture
What is meningitis
• Meningitis – inflammation of the leptomeninges (pi-arachnoid) • With or without septicaemia (remember that non-blanching rash is a sign of meningococcal septicaemia, not meningitis per se) • Prompt diagnosis and treatment is life saving Can have organism causing sepsis without much meningitis Need to give empirical treatment before you know what the organism is sometime - havent got time to wait. Need to give antibiotics
What are causative organisms of meningitis
- Neonates – E. Coli, L. monocytogenes
- 2 -5 years – H. influenzae type B (HiB)
- 5 -30 years – N. Meningitides (types)
- Over 30 years – S. pneumoniae
• Various in immunocompromised individuals - variety of organimss eg fungi
What is chronic meningitis
“Chronic Meningitis” • Chronic clinical course • M. tuberculosis – Granulomatous inflammation – Fibrosis of meninges – Nerve Entrapment -- Bilateral adrenal haemorrhage (Waterhouse-Friederichsen syndrome) can occur as a complication
slow in development.
Not same symptoms.
Photophobia, neck
stiffness
Thick material
at edge of brain . Biros is can pick of cranial nerves.
caseous material building up and leading to fibrosis.
What are complictaions of meningitis
• Local:
– Death (swelling -> RICP)
– Cerebral Infarction -> neurological deficit
– Cerebral abscess
– Subdural empyema (pus)
– Epilepsy (due to direct irritation of brain)
• Systemic (if associated with septicaemia)
If sepsis - die from
systemic effects of
infection NOT Ricp.
What is encephalitis
• Classically viral not bacterial
• Inflammation of brain parenchyma not meninges (but can occur as a complication of meningitis)
• Virus kills neurones causing inflammation and presence of intracellular viral inclusion bodies in neuroens.
Lymphocytic infiltrate typical
•Temporal lobe affected by Herpesviruses (most common) - often in immunocompromosed people
•Spinal cord affected by polio (now eradicated)
•Brainstem affected by rabies (very rare)
– Lymphocytic inflammatory reaction
What is cytomegalovirus
ss
what is prion protein
Prion protein (PrP) is a normal protein found in synapses (unknown function) - PrP can transform into PrPsc (abnormal form) following sporadic mutation, familial inheritance of mutated gene or following ingestion of PrPsc itself •PrPsc can convert PrP into itself (i.e. induce a conformational change) by protein-protein interactions alone •PrPsc is extremely stable (resistant to disinfectants, irradiation) and not susceptible to immune attack as it is essentially a ‘self’ sprotein
How does PrPsc cause damage
PrPsc causes damage by forming aggregates which destroy neruones and cause the brain to take on a sponge-like (spongiform) appearance
•Spongiform encephalopathiesoScrapie in sheepoBSE in cows (‘mad cow’ disease)oKuru in New Guinean tribes (due to cannibalism and ingestion of PrPsc)
- Creutzfeld Jacob disease (CJD)
- Variant CJD (vCJD)
Describe variant cjd
- First described in 1996•Different from ‘classical’ CJD
- Strongly linked to BSE through ingestion of prions
- Essential difference compared to classical CJD is that there seems to be a much higher prion load associated with earlier age at death and more prominent psychiatric symptoms
Are prion diseaseas an infecion?
Unclear as to whether this is an infection as does not completely fulfil all of Koch’s postulates:
What is dementia
DementiaAcquired global impairment of intellect, reason and personality without impairment of consciousnessAlzheimer’s disease (50% of cases)
•Loss of cortical neurones
- Leading to cortical atrophy and decreased brain weight
- Damage caused by neurofibrillary tangles and amyloid plaques
Describe amyloid deposition in AD
• Amyloid deposition central to pathogenesis
• Down’s syndrome
– Trisomy 21
– Early onset AD
• Mutations of 3 genes on chromosome 21
– Amyloid precusor protein (APP) gene,
– Presenilin (PS) genes 1 and 2 code for components of
secretase enzyme,
– Leads to incomplete breakdown of APP and amyloid
is deposited.
What is normal ICP
• 0 -10mmHg
• Coughing and straining increase to 20mmHg
• Only significant if the increase maintained
for several minutes
• Compensation mechanisms maintain normal
pressure
– Reduced blood volume
– Reduced CSF volume
– Spatial - brain atrophy if cronically elevated
• Vascular mechanisms maintain cerebral
blood flow as long as ICP <60mmHg
What changes does a SOL cause
Space occupying lesions (e.g. tumour)
•Deforms or destroys surrounding brain
•Displaces midline structures – loss of symmetry, midline shift
•Can cause brain herniation where part of the brain protudes though its containing wallp
What is subfalcine herniation
Subfalcine herniation
- Cingulate gyrus is pushed under the free edge of the falx cerebri
- Herniated brain can become ischaemic due to compression of anterior cerebral artery (which normally loops up around corpus callosum and can get pinched)
Initially , not many symptoms, only as it expands do you get more and then infarction
What is subfalcine herniation
Subfalcine herniation
- Cingulate gyrus is pushed under the free edge of the falx cerebri
- Herniated brain (medial parts of the frontal
and parietal lobe and corpus callosum) can become ischaemic due to compression of anterior cerebral artery (which normally loops up around corpus callosum and can get pinched)
Initially , not many symptoms, only as it expands do you get more and then infarction
What is tentorial herniation
- Medial temporal lobe (classically the uncus) pushed down through the tentorial notch (free edge of tentorium cerebelli)
- Can compress ipisilateral oculomotor nerve and ipsilateral cerebral peduncle causing ipsilateral third nerve palsy but contralateral UMN signs in limbs
- Occlusion of blood flow in posterior cerebral and superior cerebellar arteries
- Can be complicated by secondary brainstem haemorrhage (Duret haemorrhage) – often fatal
- Usual mode of death for those with large brain tumouss or sever intercranial haemorrhage
What is tonsillar herniation
Cerebellar tonsils pushed into the foramen magnum compressing the brainstem
Describe benign vs malignant brain tumours
Benign
•Meningioma (from meninges)
Malignant
•Astrocytoma
oLow grade slow growing but difficult to remove
oHigh grade aka glioblastoma multiforme
oDirect spread along white matter pathways
oCan also spread to distant parts of CNS via CSF
oDoesnt matastasie clasically but can get mets
What are other types of brain tumour
Others
•Neurofibroma (from Schwann cells of peripheral or cranial nerve)
•Ependymoma (from ependymal cells lining ventricular system)
•Neuronal tumours (from neurones, extremely rare) eg medulloblastoma common in children
•From non-CNS tissues
oLymphomas
oMetastases (most common of all brain tumours
What is a stroke
- A sudden event producing a disturbance of CNS function due to vascular disease
- 2 per 1000 of general population per year but more frequent in elderly
- A variety of described syndromes depending on which parts of brain affected
- Risk factors include hyperlipidaemia, hypertension, smoking, diabetes,
Whgat are 2 broad categories of stroke
Two broad categories:
– Cerebral infarction - 85%
– Cerebral haemorrhage - 15%
Descrieb the pathogenesis of stroke
• Embolism (Most common)
– Heart - atrial fibrillation, mural thrombus
– Atheromatous debris (carotid atheroma)
– Thrombus over ruptured atheromatous plaque
– Aneurysm
• Thrombosis
– Over atheromatous plaque
What are 2 types of cerebral infarciron
• Regional
– Named cerebral artery or carotid
MCA commonly
• Lacuna
– Less than 1cm
– Associated with hypertension
– Commonly affect the basal ganglia and internal capsule
Give an overview of cerebral haemorrhage
• 15% of all strokes • Spontaneous i.e. Non-traumatic • Intracerebral haemorrhage 10% of all strokes • Subarachnoid haemorrhage 5% of all strokes
What is intracerebral haemorrhage
• Associated with hypertensive vessel damage • Charcot-Bouchard aneurysms • Deposition of amyloid around cerebral vessels in the elderly - Walls more prone to lead to haemorrhage • May be inherited • Produces space occupying lesion – RICP
what is a subarachnoid haemorrhage
Subarachnoid haemorrhage (5% of all strokes)Rupture of berry aneurysms, usually found at branch points in circle of Willis
- Blood in subarachnoid space can cause secondary spasm of cerebral arteries
-Associations
•Male
•Hypertension
•Atherosclerosis
•Linked to other diseases (e.g. connective tissue disorders, congenital weakness in vessel walls?
What are the symptoms of SAH
- Sudden severe headache – Thunderclap
- Sentinel headache
- Loss of consciousness
- Often instantly fatal
