8.3 Pathology of the brain Flashcards
how do microorganisms gain access to the CNS?
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?
Inflammation of leptomeninges (pi-arachnoid)
+/- septicaemia (remember that non-blanching rash is a sign of
meningococcal septicaemia, not meningitis per se)
what are the causative organisms of meningitis in neonates?
E. coli, Listeria monocytogenes
what are the causative microorganisms in infants?
haemophilus influenza
what are the causative microorganisms of meningitis in adults?
neisseria meningitidis (meningococcus)
what are the causative microorganisms of meningitis in immunocompromised patients?
variety of organisms such as fungi
what is the main causative microorganism in chronic meningitis?
mycobacterium tuberculosis
what are some of the complications of chronic meningitis?
- Granulomas
- Meningeal fibrosis
- Cranial nerve entrapment
- Bilateral adrenal haemorrhage (Waterhouse-Friederichsen syndrome) can occur as a complication
what are the local complications of meningitis?
Death due raised intracranial pressure Cerebral infarction (stroke) Cerebral abscess Subdural empyema Epilepsy (due to direct irritation of brain)
what are the systemic complications of meningitis?
result from septicaemia
- septic shock
- hypotension
- shortness of breath
- raised temp
what is encephalitis?
Inflammation of brain parenchyma not meninges (but can occur as a complication of meningitis)
Usually viral, and virus kills neurones causing inflammation and presence of intracellular viral inclusions. Lymphocytic infiltrate typical
what virus usually causes temporal lobe encephalitis?
herpes virus
what virus can cause spinal cord encephalitis?
polio virus
what virus can cause brainstem encephalitis?
rabies virus
what is the pathology of prion diseases?
Prion diseases are diseases caused by the destruction of neurones by abnormal prion proteins (PrPsc). 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’ protein. PrPsc causes damage by forming aggregates which destroy neruones and
cause the brain to take on a sponge-like (spongiform) appearance
give some examples of spongiform encephalopathies?
Scrapie in sheep BSE in cows (‘mad cow’ disease) Kuru in New Guinean tribes (due to cannibalism and ingestion of PrPsc) Creutzfeld Jacob disease (CJD)
what is Creutzfeld Jacob disease?
Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is a fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes, poor coordination, and visual disturbances.
how is the variant CJD different from the 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
why is it unclear whether or not prion diseases are infections?
does not completely fulfil all of
Koch’s postulates
what is deementia?
Acquired global impairment of intellect, reason and personality without impairment of consciousness
what is the most common form of dementia?
alzheimers disease
what is the underlying pathology of alzheimers disease?
Loss of cortical neurones leading to cortical atrophy and decreased brain weight. Damage caused by neurofibrillary tangles and amyloid plaques
what are tangles seen in alzheimers disease?
Intracellular twisted filaments of Tau protein. Tau normally binds to microtubules. Hyperphosphorylation of tau is thought to lead to tangle formation
what are the plaques seen in alzheimers disease?
senile plaques are foci of enlarged axons, synaptic terminals and dendrites. neurones become so abnormal they aggregate together. Amyloid deposition in vessels in centre of plaque. This reduces blood supply to the brain causing ischaemia and cell damage
why is downs syndrome associated with alzheimers syndrome?
Trisomy 21 associated with Alzheimer’s disease as amyloid precursor protein (APP) is found on this chromosome hence extra ‘dose’ of gene in patients with Down’s syndrome and greater development of amyloid plaques Also Presenilin (PS) genes 1 and 2 are mutated on chromosome 21. These presenilin genes code for components of secretase enzyme, – Leads to incomplete breakdown of APP and amyloid is deposited.
what are the associated gene mutations of alzheimers disease?
amyloid protein precursor
presenelin genes
what is normal intracranial pressure
0-10mmHg
Coughing/straining can increase it to 20mmHg
what are the compensatory mechanisms in place to compensate for increased
pressure?
reduces blood volume and CSF volume
brain atrophy if chronically elevated
at what pressure is cerebral blood flow compromised?
when ICP exceeds the 60mmHg
how do space occupying lesions in the cranium cause structural changes?
- Deforms or destroys surrounding brain
- Displaces midline structures – loss of symmetry, midline shift
- Can cause brain herniation where part of the brain protrudes through a wall that normally contains it
what is a 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)
what is a 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
Can be complicated by secondary brainstem haemorrhage (Duret haemorrhage) – often fatal
Usual mode of death for those with large brain tumours or severe intracranial haemorrhage
give an example of a benign brain tumour?
meningioma
Neurofibroma (from Schwann cells of peripheral or cranial nerve)
give an example of a malignant brain tumour?
astrocytoma
Ependymoma (from ependymal cells lining
ventricular system)
what is an astrocytoma?
a malignant cancer of the astrocytes
Low grade slow growing but difficult to remove
High grade aka glioblastoma
multiforme
Direct spread along white matter pathways
Can also spread to distant parts of CNS via CSF
what are the most common brain tumours?
metastasis from non-CNS tumours (lung, breast, colon, kidney and melanoma)
what is a stroke?
A sudden event producing a disturbance of CNS function due to vascular disease
what are the risk factors for stroke?
hyperlipidaemia
hypertension
smoking
diabetes
what is the most common cause of a stroke?
cerebral infarction (85%)
what are the 2 main pathologies that cause stroke?
embolism - likely from the - Heart (due to AF, mural thrombus) - Atheromatous debris (carotids) - Thrombus over ruptured plaque - Aneurysms thrombosis - over atheromatous plaque
What are the 2 broad classes of cerebral infarctions?
regional - In the territory of a named cerebral artery
Lacunar - Small (less than 1cm area affected). Associated with hypertension. Commonly affect basal ganglia and internal capsule.
what are some of the pathological factors associated with intracerebral haemorrhage?
increased age
hypertensive vessel damage
amyloid deposition in vessels
what are Charcot-Bouchard aneurysms?
Charcot-Bouchard aneurysms are minute aneurysms (microaneurysms) in the brain that occur in small penetrating blood vessels. The most common vessels involved are the lenticulostriate branches (LSA) of the middle cerebral artery (MCA)
how do intracerebral haemorrhages cause damage?
bleeding forms a space occupying lesion
what are subarachnoid haemorrhages?
Rupture of berry aneurysms, usually found at branch points in circle of Willis
Blood in subarachnoid space can cause secondary spasm of cerebral arteries
what are risk factors associated with subarachnoid haemorrhage?
- Male
- Hypertension
- Atherosclerosis
- Linked to other diseases (e.g. connective tissue disorders, congenital weakness in vessel walls?)
what are symptoms of a subarachnoid haemorrhage?
- Thunderclap headache
- May be preceded by a ‘sentinel’ headache
- Loss of consciousness
- Often instantly fatal
what are sentinel haedaches?
Sentinel headache (SH) is a kind of secondary headache that is characterized as sudden, intense, and persistent, preceding spontaneous subarachnoid hemorrhage (SAH) by days or weeks.
why is prompt treatment of meningitis life saving?
Because acute inflammation leads to influx of neutrophils causing oedema and congestion of the blood vessels (very engorged). Pus accumulating around the cerebral hemispheres. Raises intracranial pressure and rapidly cause death of the patient. Acute inflammation is activated and amplified very quickly - within 24 hours
what is the main causative microorganism in over 30s?
Streptococcus pneumoniae
what is a tonsillar herniation?
Cerebellar tonsils pushed into the foramen magnum
compressing the brainstem
how does a tonsilar herniation cause cushings reflex?
Blood cant be pushed into the brain as well as the brainstem is compressed. Systemic blood pressure begins increasing to overcome increased pressure. Brain becomes more swollen. Brainstem becomes herniated, compressing the respiratory and CVS centres, causing reflex bradycardia. Patients with high BP and low pulse = cushing’s reflex (often fatal)
what is cushings reflex?
a physiological nervous system response to increased intracranial pressure (ICP) that results in Cushing’s triad of increased blood pressure, irregular breathing, and bradycardia.
