Session 12 - Pathology of the Brain Flashcards
Give three ways infections can enter the CNS
o Direct Spread
E.g. middle ear infection, base of skull fracture
o Blood Borne
Sepsis, infective endocarditis
o Iatrogenic
Ventriculoperitoneal Shunt, lumbar puncture
What can cause a cerebral abscess?
Temporal lobe abscesses can result from an untreated middle ear infection.
What is meningitis?
Meningitis is inflammation of the Leptomeninges (Pia and Arachnoid Mater). It presents with a severe headache, neck stiffness, aversion to bright lights and a non-blanching rash.
Give two ways in which meningitis is classified?
Acute or Chronic and as Bacterial or Non-Bacterial.
Give causes on meningitis at neonates 2-5 5-30 >30 Immunocompromised individuals
o Neonates E. Coli, L. Monocytogenes o 2 – 5 years H. Influenzae type B (HiB) o 5 – 30 years N. Meningitides (A, B and C types – B&C have vaccinations available) o > 30 years S. Pneumoniae o Immunocompromised individuals Various
What is the course of chronic meningitis
patients presenting with sub-acute headaches, increasing confusion and neurological signs.
What is the classical causative organism of chronic meninigitis and what does it cause?
The classic causative organism is Mycobacterium Tuberculosis, leading to Granulomatous inflammation and fibrosis of the meninges, which leads to the entrapment of cranial nerves.
Give five complications of meninigitis
o Death
Swelling and raised intracranial pressure
o Cerebral Infarction
o Cerebral Abscess
o Subdural Empyema
Infection and pus in-between Dura and Arachnoid Mater
o Epilepsy – particularly in children if it has caused a focal brain lesion
What is encephaliis
. It is infection of the brain tissue itself (parenchuma), not the meninges. Consequently the brain cells and becomes very haemorrhagic.
What causes encephalitis
Herpes virus/poli/rabies
What can be damaged in encephalitis
o Neuronal cell death due to virus o Temporal Lobe Herpes Virus Children can present with this and become rapidly unwell o Spinal Cord Motor Neurones Polio o Brain Stem Rabies o Lymphocytic Inflammation Reaction Perivascular cuffing with lymphocytes in Virchow-Robin Space (the spaces around vessels in the brain)
Give one distinct histological cause of encephalitis (tyep of virus)
Cytomegalovirus (CMV)
o Owls eye inclusions
Viral replication taking over the cell body machinery
o Eventual cell body destruction and neuronal death
What is toxoplasmosis caused by?
o Caused by the intracellular protozoan parasite Toxoplasm Gondii, which lives in the guts of cats. Humans are infected via contaminated cat faeces
What is the pathology of toxoplasmosis?
o Toxoplasms in cell bodies
o Destruction of cell body and death of neurone
o Particularly common cause of death in AIDs
What is a prion protein and how can it go awry?
o Prion protein (PrP) is a normal constituent of the synapse
o Mutated PrP can occur sporadically, familially or be ingested
How do mutated PrPs cause damage?>
o Mutated PrP interacts with normal PrP to undergo a post translational conformational change
Mutated PrP creates more mutated PrP
o Acts like an infection, but isn’t an infection
Mutated PrP forms aggregates, which causes neuronal death and “holes” in grey matter – Spongiform Encephalopathies
Define dementia
Acquired global impairment of intellect, reason and personality without impairment of consciousness”
Give four most common causes of dementia with % for first two
o Alzheimer’s – 50% Sporadic/Familial Early/Late o Vascular Dementia – 20% o Lewy Body o Pick’s disease
What occurs in alzheimerers and what causes it?
o Increased loss of cortical neurones Decreased brain weight Cortical atrophy o Due to neuronal damage Neurofibrillary tangles – Intracellular twisted filaments of Tau Protein Senile plaques – Amyloid deposition
What two proteins cause alzheimers?
Neurofibrillary tangles – Intracellular twisted filaments of Tau Protein
Senile plaques – Amyloid deposition
What are the three contributors to ICP
Brain
Blood
Cerebrospinal fluid
What must happen for ICP to remain stable when onechanges?
Therefore, for intracranial pressure to remain stable a change in the volume of any one of them must be accompanied by an equal and opposite change in the other two.
What is normal ICP and when is it raised physiologically, and to what level?
Normal Intracranial Pressure is 0-10mmHg and rises to 20mmHg when coughing and straining.
What three compensation mechanisms maintain normal ICP
Compensation mechanisms maintain normal pressure
o Spatial – brain atrophy
o Reduced blood volume
o Reduced CSF volume
Up to what pressure of ICP can blood flow to brain be maintaind?
Compensation mechanisms maintain normal pressure
o Spatial – brain atrophy
o Reduced blood volume
o Reduced CSF volume
Give four causes of raised ICP
Haemorrhage
Tumours Meningitis
Cerebral infarction
What does massivwely raised ICP cause?
). Increasing pressure within the closed box of the skull results in compression and herniation of key parts of the brain. Three areas are involved:
o The Cingulate Gyrus
o The Uncus
o The Cerebellar Tonsils
Give a main cause of raised ICP
Expanding lesion
What does an expanding lesion do when causing raised ICP (4)
o Deformation or destruction of the brain around the lesion
o Sulci flattened against the skull
o Displacement of midline structures – loss of symmetry
o Brain shift resulting in internal herniation of parts of the brain
Define herination
– A protrusion of an organ or part of an organ through wall that normally contains it.
What two structures divide the brain up?
o Falx Cerebri – In the midline between the two cerebral hemispheres
o Tentorium Cerebelli – Lies on the superior face of the cerebellum
Name four herniations
Subfalcine
Central (tentorial) herniation
uncal herniation
Tonsilar herniation
What occurs in 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 -> Infarction
What occurs in uncal herniation?
Uncus/medial part of the parahi[ppocampal gyrus through the tentorial notch
Damage to the oculomotor nerve on the same side
Occlusion of blood flow in posterior cerebral and superior cerebellar arteries
Frequently fatal because of secondary haemorrhage into brainstem -> Duret haemorrhage
Common mode of death in those with large brain tumours and intracranial haemorrhage
What happens in tonsillar herniation?
Cerebellar tonsils pushed into the foramen magnum, compressing the brainstem
What are three stages of raised ICp?
Prodromal phase
Acute phase
Compression of peduncles
What occurs in prodromal phase of raised ICP 3
o Headache
o Vomiting
o Papilloedema
What two thing soccur in acute phase of raised icp
o Occulomotor nerve compression – Dilation of pupil
o Compression of brain stem – Coma
What occurs in compression of trhe cerrebral peduncles
Hemiparesis
Name a benign tumour of the brain
o Meningioma
Give four malignant tumours of brain
Astrocytoma
Neurofibroma
Ependymoma
Neuronal
Outline course of astrocytoma
Grade 1 Grade 4 (Grade 4 are extremely aggressive, life expectancy of a few months)
Spread along nerve tracts and through sub-arachnoid space
Often presents with a spinal secondary
Never metastasise outside of the CNS
What is a common cause of brain tumour/
Secondary metastases (lung, breast)
What are two phases of head injury
Primary damage
Secondary damage
What is focal primary damage?
Bruising and laceration of the brain as it hits the inner surface of the skull
Tearing of blood vessels and nerves as the brain moves, leading to haemorrhage
Coup – Damage at site of impact
Contracoup – Damage on opposite side of the brain, often of greater severity
What is diffuse primary damage?
Direct tearing to axons – Diffuse Axonal Injury (DAI)
Micro-tears to axons at sites of differing densities of brain substance, e.g. junction of white and grey matter
Tearing of nerves and small vessels
Tearing of the pituitary stalk
Heals by gliotic scarring
What is secondary damage?
Reaction of the primary damage makes the injury worse
What can occur as secondary damage
Extradural haemorrhage
Subdural haematoma
Stroke
What is extradural haemorrhage
o Classically due to a Pterion Fracture
o Bleeding from the Middle Meningeal Artery
Under Arterial Pressure
Rapid increase in Intracranial Pressure
What is the pterion?
The Pterion is a ‘H-shaped’ junction of 4 bones, which lies on the lateral aspect of the skull and is the thinnest part of the Calveria. Bone fragments from fractures may rupture the Middle Meningeal Artery, leading to an Extradural Haemorrhage. The bones that make up the Pterion are: o Frontal o Parietal o Sphenoidal (greater wing) o Temporal
What occurs in subdural haematoma?
o Bridging veins from surface of the cerebral hemispheres connect with vessels in the dura
o These bridging veins are susceptible to tearing as they pass through the subdural space
o Brain floats freely within the CSF, but the vessels are fixed
Sudden brain movement will tear the bridging veins
Venous Bleeds
Blood accumulates much more slowly, therefore no sudden increase in intracranial pressure
What two groups are susceptible to subdrual haematomas
o The elderly and alcoholics are particularly susceptible due to shrinking of the brain
Give two broad categories of stroke and their relative incidence/
- Two broad categories
o Cerebral infarction – 85%
o Cerebral haemorrhage – 15%
Three main stroke risk factors
o Hyperlipidaemia
o Hypertension
o Diabetes mellitus
Give two causes of stroke/
- Embolism o Atrial fib, mural thrombus o Atheromatous debris o Thrombus over ruptured atheromatous plaque (often in basilar artery) o Aneurysm - Thrombosis o Over plaque
What is a tia
o Fibrin emboli from atheroma in carotids
o Lasts <24hrs and completely resolved
o Mary precede full stroke
Give two types of haemorrhagic stroke
o Intracerebral Haemorrhage (directly into the brain) – 10% of all strokes
o Subarachnoid Haemorrhage (into the subarachnoid space) – 5% of all strokes
What is intracerebral haemorrhage?
Bleeding directly into brain as a result of hypertensive vessel damage
Blow out lesion – “blood blows straight out”
Rapid death (“dead before you hit the floor
How can subarachoid haemorrhage occur?
o Rupture of Berry Aneurysms
Can be inherited – Congenital abnormalities of blood vessels
Associated with polycystic kidney disease
In non inherited patients linked to Atheroma
Sited at branching points in the Circle of Willis
How does subarachnoid haemorrhage occur?>
o Sudden, severe Thunderclap headache
o Sentinel headache (slowly worsening headache for a few days previously, aneurysm starting to rupture)
o Loss of consciousness
o Often instantly fatal
What is MS?
MS is a chronic, autoimmune, T-cell mediated inflammatory disorder of the CNS. Multiple plaques of demyelination occur throughout the white matter of the brain and spinal cord, occurring sporadically over years.
Give three main clinical patterns of MS
Relapsing remitting MS
Secondary progressive MS
Primary progressive MS
What is remitting relapsing MSF and how common is it?
85-95% of MS
Symptoms occur in attacks, with onset over days and recovery over weeks
What is secondary progressive MS?
Late stage of MS consisting of gradually worsening disability, progressive slowly over years
75% of patients with relapsing-remitting MS will eventually progress to secondary progressive MS
What is primary progressive MS?
The least common form of MS (10-15%)
Characterised by gradually worsening disability without relapses or remission
Typically presents later
Associated with fewer inflammatory changes on MRI
Give 7 symptoms of MS
o Visual changes o Sensory Symptoms Sensation of water trickling down the skin Reduced vibration sensation o Ataxia o Bladder hyper-reflexia causing urinary urgency and frequency o Neuropathic pain is common o Fatigue o Spasticity o Temperature Sensitivity Uhthoff’s Phenomenon Temporary worsening of pre-existing symptoms with increases in body temperature E.g. after exercise or a hot bath
Give two consequences to the CNS of supressed immunity
o Meningitis
Vulnerability to unusual organisms
o HIV
May cause neuropathy and rarely encephalopathy
