Lecture 12 - Neuropathology Flashcards
What can maintained increased intracranial pressure cause?
Destruction of brain tissue
Displacement of midline structures
Brain shifts
Cerebral oedema
What are some compensatory mechanisms for regulating normal intracranially pressure?
Reduce venous blood volume
Reduce CSF volume
Brain atrophy
What is the normal intracranial pressure?
What pressure can coughing and straining lead to?
Normal = 0-10mmHg
Inc = max of 20mmHg
What can cause raised intracranial pressure?
Haematoma / Haeamorrhages
Tumours
Space occupying lesions
Cerebral oedema
Infections
How does a brain appear with cerebral oedema?
Loss of sulci
Widening of gyro
What is a subfalcine herniation?
The herniation of cingulate gyrus under the falx cerebri
What consequences can a subfalcine herniation cause on the brain?
Infarction of medial parts of frontal or parietal lobes or the corpus callosum
Why can a subfalcine herniation cause ischaemia of the corpus callosum?
Compression of the anterior cerebral artery
What is a Transtentorial herniation? (uncal herniation)
Herniation of medial part of the temporal lobe (uncus) into the tentorium cerebelli
What is a tonsillar herniation?
Cerebellar tonsils herniates through the Foramen magnum
Label slide 6 on herniations
In slide 7, what is the structure that is being compressed in this subfalcine herniation?
Lateral ventricle
What Cranial Nerve is most commonly damaged in an uncal herniation (trans-tentorial herniation)?
Occulomotor nerve (CN III)
What blood vessels can be occluded in a trans-tentorial herniation (uncal herniation)?
Posterior cerebral and superior cerebellar arteries causing ischaemia
What is a duret haemorrhage?
Secondary haemorrhage down into the brainstem from a transtentorial (uncal) haemorrhage
What is the consequence of tonsillar herniation (cerebellar tonsils)?
Pushed into Foramen magnum compressing brainstem
What are the 3 dural layers?
Dura mater
Arachnoid mater
Pia mater
Go to slide 11 and label the image
What blood vessel is normally ruptured leading to an extra dural haemorrhage?
Middle meningeal artery
What bone does the middle meningeal artery run behind?
Pterion
Where does blood accumulate in an Extradural haemorrhage?
Between the skull and the dura mater
How does the middle meningeal artery enter into the skull??
Foramen spinosum
What does the middle meningeal artery branch from?
Branches from maxillary artery
Which branches from external carotid artery
How does an extra dural haemorrhage present?
Lucid interval (hrs when fine) which then leads to drowsiness then neurological deficits
What causes a subdural haemorrhage?
What layers does the blood accumulate between?
The shearing of bridging veins (venous blood) on the way to the dural venous sinuses (likely the superior Sagittal sinus)
Between the dura mater and arachnoid mater
What causes acute subdural Haematoma?
Trauma leading to rapid blood accumulation
Who often have chronic subdural Haematoma and why?
Elderly and chronic alcoholics
Brain atrophy leading to increased tension on the bridging veins
How do subdural Haematomas present?
Assaults
Falls
RTCs
Minor head injuries (elderly)
Have to be careful of anticoagulant therapy or liver cirrhosis.
How do subdural haemorrhages appear on CT head?
Banana shape
(Branching Banana)
What is the cause of a subarachnoid haemorrhage?
Shearing of meningeal blood vessels
Usually caused by basal skull fractures and contusions
What is a contusion?
Brain bruises
What are some spontaneous causes of a subarachnoid haemorrhage?
Ruptured berry aneurysm
Amyloid angiography
Vertebral artery. Dissection
Arteriovenous malformation
Where does blood accumulate in a subarachnoid haemorrhage?
In the subarachnoid space where CSF is
Blood forced into subarachnoid space
What are the symptoms of a subarachnoid haemorrhage?
Sudden onset headache (worst ever/thunderclap headache)
Rapid neurological deterioration
Sudden collapse
What part of circulation do subarachnoid haemorrhages occur in due to a berry aneurysm?
Anterior circulation of circle of Willis
What conditions increase the risk of forming berry aneurysms in the circle of Willis?
Erhrlos Danlos syndrome (connective tissue)
Polycystic kidney disease
What is a stroke?
Sudden event producing a disturbance of CNS function due to vascular disease
What are the 2 categories of stroke?
Ischaemic stroke
Haemorrhagic stroke
What are the 2 types of ischaemic stroke?
Thrombotic occlusion
Embolic occlusion
What are the 2 types of haemorrhagic stroke?
Intracerebral haemorrhage
Subarachnoid haemorrhage
What are the risk factors for stroke?
Hyperlipidaemia
Hypertension
Diabetes Mellitus
What is an ischaemic stroke?
Obstruction of blood supply leads to ischaemia
Why are the basal ganglia, thalamus and deep white mater at increased risk of ischaemic stroke?
Has no collateral supply of blood
What is an example of a watershed area of the brain?
Border of the middle cerebral artery supply and anterior cerebral arertry supply
Can get wedge shaped necrosis here
Label the blood supply to the brain on slide 19
What are some causes of Embolic stroke?
Cardiac murmur thrombi (AF)
Atherosclerosis
(DVT through patent Foramen ovale)
Septic Embolic (infective endocarditis)
What blood vessel is most commonly affected by emboli leading to a stroke?
Why?
Middle cerebral artery
Where ICA comes in and branches to circle of Willis
What are some thrombotic causes of stroke?
Carotid bifurcation
Origin of MCA
Basilar artery
Lacunae infarcts
What is gliosis?
Fibrosis in the brain
What is seen on histology in cerebal ischaemia?
Neutrophils start to migrate since inflammation
Gliosis
What is spontaneous intracererbral haemorrhage (stroke) commonly caused by?
Hypertension
Cerbreral amyloid angiography
Arteriovenous and cavernous malformations
Tumours
What effects does hypertension have on the body?
Systemic effects - brain,heart, vessels and kidneys
Arteriosclerosis (artery walls thicken):
Arteries to:
Basal ganglia and thalamus
White matter
Brainstem
What does cerebal amyloid angiopathy cause?
Lobar haemorrhages involving the cerebral coritccecs and tiny microhaemorrhages
In cerebral amyloid angiopathy, what vessels do amyloid deposits end up in?
Meningeal and coritcal vessels
What are Arteriovenous malformations?
Subarachnoid vessels to brain causing wormlike tangles
What part of the brain are affectd in cavernous malformations?
Cerebellum and pons
What are some examples of Primary CNS tumours?
Gliomas (stroma)
Parenchymal
Meningeal
Neuronal
Poorly differentiated
What are some symptoms of CNS tumours?
Seizures
Headaches
Focal neurological deficits
Raised ICP (nausea and vomiting)
What is the most common type of glioma?
Astrocytoma
What is more aggressive?
Astrocytoma or glioblastoma multiforme?
Glioblastoma multiforme.
What is an ependymoma a cancer of?
Tumor of ventricular system often spreading to CSF
What infection is lymphoma associated with?
EBV
What is a meningioma?
Benign tumour derived from arachnoid meningiothelilal cells
Can compress important structures
What are the 4 methods by which infections can spread to the CNS?
Direct local spread (air sinuses, osteomyelitis from fractures, middle ear infections, infected teeth)
Haematogenous (retrograde venous spread through anstomoses and venous sinuses of skull)
Iatrogenic (lumbar puncture)
Peripheral nerves (Herpes zoster, viruses)
What can infections of the CNS affect?
Meninges
Accumulation of aggregates of acute inflammation like abcesses
Brain parenchyma (functional tissue)
What is meningitis?
Inflammation of the leptomeninges (arachnoid mater + Pia mater)
What are teh different types of meningitis?
Acute pyogenic (bacterial)
Aseptic (viral)
Chronic
Carcinomatosis (lots of tumour deposits in meninges)
What symptoms can someone have with meningitis?
May be septic (Neisseria meningitidis)
Headache
Photophobia
Stiff neck
Altered consciousness
Focal neurological impairment
What are some investigations done for meningitis?
CT scans
Lumbar puncture (will have neutrophils and other inflammatory mediators in)
What are some complications of meningitis?
Cerebral oedema
Cerebral infarction
Cerebral abscess
Empyema
Epilepsy
Meningoencephalitis
Septicaemia
What is the most common cause of bacterial acute pyogenic meningitis in infants?
Escherichia coli
What is the most common cause of bacterial acute pyogenic meningitis in young adults (5-30)?
Neisseria meningitidis
What is the most common cause of bacterial acute pyogenic meningitis in adults (30+)?
Streptococcus pneumoniae
What is the most common cause of bacterial chronic meningitis?
Mycobacterium tuberculosis
What is a cerebal abscess?
Acute inflammation and bacterial build up in cerebrum
What is encephalitis??
What type of eof organism most commmonly causes it?
Infection of the brain parenchyma
Viral > bacterial
What white blood cell will be elevated most commonly with encephalitis?
Lymphocytes since normally viral
What white blood cell will be elevated most commonly with encephalitis?
Lymphocytes since normally viral
What white blood cell will be elevated most commonly with encephalitis?
Lymphocytes since normally viral
What virus typically cases encephalitis of the temporal lobe?
Herpes Zoster virus
What virus typically cases encephalitis of the spinal cord?
Polio
What virus typically cases encephalitis of the brainstem?
Rabies
What virus commonly causes encephalitis in foetuses and those who are immunocomprimised?
Cytomegalovirus
What are prion disease?
Diseases that lead to abnormal cellular protein accumulations
How t prion diseases cause damage?
Neurone cell death
Synapse loss
Spongiform microvacuolations
Lack of inflammation
What are some examples of prion diseases?
Creutzfeldt-Jakobs disease (CJD)
Scrapie’s (sheep)
Bovine spongiform encephalopathy BSE (Mad cow disease)
What is the pathophysiology of prion disease like Creutzfeldt-Jakobs disease?
Normally protiens in alpha helices structure
When mutation or infection by prion occurs they undergo conformational change to B pleated sheets
B pleated sheets much more resistant to proteolysis so build up causing damage
Also affect nearby proteins to change to B pleated sheet structure
What are some symptoms of Creutzfelt-JaKobs disease?
Subtle changes in memory
Cerebal polar ataxia
Global dementia
Behavioural issues
What is the basis for neurodegenerative diseases?
Loss of neurones due to accumulation of protein aggregates
What are some changes with neurodegenerative disease if they affect the hippocampus and cerebral cortices?
Cognitive changes
Alteration in memory,behaviours and language
What lobes does Alzheimer’s disease affect?
Frontal, temporal and parietal
What are the proteins that build up causing Alzheimer’s?
Alpha beta plaques
Neurofibrillary tangles (tau)
What is the pathophysiology of Alzhemiers disease?
Transmembrane protein cleared to amyloid
Amyloid broken down to Alpha Beta (AB) monomers
AB monomers -> AB aggregates -> AB fibrils -> AB plaques build up
Tau can aggregates out of cells forming neurofibrillary tangles due to being hyperphosphorylated and being unable to bind to microtubules
What are the signs and symptoms of Alzheimer’s?
Impaired intellectual function
Impaired memory
Altered mood and behaviour
Disorientated
What gives you an increased risk of Alzheimer’s and why?
Down syndrome
Trisomy of Chromosome 21
The amyloid precursor protein found on chromosome 21
What causes Parkinson’s?
Loss of dopaminergic neurones from the substantia migrate
How does Parkinson’s disease present?
Hypokinesia
Rigidity
Brady Kinesia
Instability
Tremor
What part of the brain is affected in Huntingtons disease?
Basal ganglia
What type of inheritance is Huntingtons disease?
What causes it?
Autosomal dominatn
CAG trinucleotide repeats
These accumulate leading to cell injury, death and gliosis
How does Huntingtons present?
Hyperkinesia (involuntary jerky movements)
