Histopathology - Cerebral Pathology Flashcards
What is a stroke?
A clinical syndrome characterised by rapidly developing focal/global neurological deficit lasting > 24 hrs (of presumed vascular origin)
How long does a TIA last for?
- <24hrs with complete resolution of Sx
- Most = 1-5mins
-1/3 lead to strokes after 5 years if untreated
What is the most common modifiable RF for all kinds of strokes?
HTN
What is ischaemia?
A lack of oxygen supply to tissue
What is an infarction?
An area of tissue death due to lack of oxygen
What is a the most common cause of brain infarction?
Cerebral atherosclerosis
What percentage of strokes are caused by infarctions?
70-80%
What are some causes of brain infarctions?
- Embolism from intra/extra-cranial plaques
- Cerebral atherosclerosis
What are an important future predictor of strokes?
TIAs
What is the epidemiology and clinical presentation of a stroke?
Epi:
- 100,000 new strokes/yr in UK
Sx:
- Sudden onset
- FAST
- Numbness
- Loss of vision
- Dysphagia
What vascular territories are commonly affected in strokes?
- Anterior vs posterior territory
- Most common = MCA
What are the investigations and management of a stroke?
Ix:
- CT/MRI (infarct vs haemorrhage)
- Ix for vascular risk (BP, FBC, ESR, U+E, Glucose, Lipids, ECG, Carotid doppler)
Mx:
- Aspirin +/- dipyridamole
- Thrombolytics (IF <3hr from event)
- +/- carotid endarterectomy
- Long term: Treat HTN, Lower Lipids, Anticoag
What are the causes/RFs for strokes + TIAs?
- Smoking
- DM
- HTN
- FHx
- Prev. TIAs
- OCP
- PVD
- Increased ethanol usage
- Hyperviscosity (e.g. sickle cell, polycythaemia)
What is the epidemiology and clinical features of TIAs?
Epi:
- 0.4/1000 /yr
- 15% of 1st strokes preceded by TIAs
Sx:
- Sx last <24hrs
- Amaurosis fugax
- Carotid bruit
What vascular territories are commonly affected by TIAs?
Any
- Characteristically embolic atherogenic debris from carotid artery travels to ophthalmic branch of internal carotid
What are the investigations and management for TIAs?
Ix:
- Carotid US
- Ix for vascular risk (BP, FBC, ESR, U+E, Glucose, Lipids, CXR, Carotid doppler)
Mx:
- Aspirin + dipyridamole
- +/- carotid endarterectomy
- Long term: Treat HTN, Lower lipids, Anticoag
What are some stroke syndromes when caused at the ACA (anterior cerebral artery)?
- Contralateral leg paresis
- Sensory loss
- Cognitive defects (e.g. apathy, confusion + poor judgement)
What are some stroke syndromes when caused at the MCA (Middle cerebral artery)?
Proximal occlusion:
- Contralateral weakness + sensory loss of face + arm
- Cortical sensory loss
- ?Contralateral homonymous hemianopia/quadrantanopia
- IF Dominant (left) hemisphere: asphasia
- IF non-dominat (right) hemisphere: neglect
- Eye deviation towards side of lesion + away from weak side
What are some stroke syndromes when caused at the PCA (posterior cerebral artery)?
- Contralateral hemianiopia/quadrantanopia
- Midbrain findings: CN III + IV aplsy/pupillary changes, hemiparesis
- Thalamus findings: Sensory loss, amnesia, decreased level of consciousness
- IF Bilateral: Cortical blindness/prosopagnosia
- Hemiballismus
What are some stroke syndromes when caused by lacunar infarcts?
- Pure motor hemiparessi (posterior limb of internal capsule): contralateral arm, leg + face
- Pure sensory loss (ventral thalamic): hemisensory loss
- Ataxic hemiparesis (ventral pons or internal capsule): ipsilateral ataxia + leg paresis
- Dysarthria-clumsy hand syndrome (ventral pons/genu of internal capsule): dysarthria, facial weakness, dysphagia, mild hand weakness + clumsiness
What are lacunar infarcts?
- Deep hemispheric white matter
- Involving deep penetrating arteries of MCA, circle of Willis, basilar, + vertebral arteries
What percentage of strokes are caused by haemorrhagic causes?
20%
What are the non-traumatic haemorrhages?
- Intraparenchymal haemorrhage
- Subarachnoid haemorrhage
What are some features of an intraparenchymal haemorrhage, including its most common site?
- 50% due to HTN
- Abrupt onset
- Can cause Cahrcot-bouchard microaneurysms (likely to rupture)
- Common site: Basal Ganglia
What is the most common cause of haemorrhagic strokes?
HTN
What are some features of subarachnoid haemorrhages, including some buzzwords?
- 85% from ruptured berry aneurysms
- Most at internal carotid bifurcation (+ posterior communicating artery)
- F>M, <50yrs
- Thunderclap headache, vomiting + LoC
- Increased risk in APKD, Ehler’s Danlos + Aortic coarctation
- BUZZWORDS: HYPERATTENUATION AROUND CIRCLE OF WILLIS
What are some rare non-traumatic haemorrhagic causes of stroke?
- AV malformations (young people <50yrs)
- Cavernous angiomas (recurrent low pressure bleeds)
- Capillary telengiactasias
- Connective tissue disorders (e.g. Ehlers-Danlos)
What are some traumatic haemorrhages?
- Extradural haemorrhge
- Subdural haemorrhage
- Traumatic parenchymal injury
What are some features of an extradural haemorrhage?
- Skull fracture from truama (usually at pterion)
- Most common site = MIDDLE MENINGEAL ARTERY
- Rapid arterial bleed, lucid interval then LoC
- Buzzword = Lemon shape
What are some features of a subdural haemorrhage?
- Previous history of minor head trauma
- Damaged bridging verins with slow venous bleed
- Often elderly/alcoholic/on anticoagulation
- A/w gradual headache, fluctuating consciousness + behavioural changes
- Buzzword: Banana/crescent shape
What are the different types of traumatic parenchymal injury?
- Traumatic brain injury
- Concussion
- Contusions
- Diffuse axonal injury
- Skull fractures
What is a concussion?
Transient LoC + paralysis, recovery in hours/days
What is a contusion?
Collision between brain + skull
- Coup = where impact occurs
- Contracoup = opposite region of impact
What are some features of a diffuse axonal injury?
- Occurs at moment of injury due to shear tensile forces breaking axons apart
- Commonest cause of coma
- Midline strictures like Corpus Callosum, rostral brainstem + septum peelucidum affected
- Causes vegetative state + post-traumatic dementia
What should be looked out for when skull fractures occur (in terms of brain injury)?
- Otorrhea/rhinorrhoea
- Buzzword = STRAW-COLOURED FLUID = CSF + Battle’s sign
What is a Battle’s sign
Haemorrhage on mastoid process
What is the single largest cause of death in under 45s?
Traumatic brain injury
What are some causes of raised ICP?
- Oedema
- Space occupying lesion (e.g. tumour/abscess)
What can raised ICP lead to?
Brain herniation
What are the three main types of brain herniation and their features?
Subfalcine:
- Hernation of singular corex beneath flax (midline fold of dura)
Transtentorial/uncal:
- Herniation of medial temporal lobe under tentorium (horizontal dura mater between parietal lobes + cerebellum)
Tonsillar herniation:
- Hernation of cerebellum through foramen magnum
- Compresses brainstem leading to cardiorespiratory arrest + death (risk if doing LP with raised ICP)
What is oedema and its types?
Excess accumulation fo fluid in brain parenchyma
- Vasogenic = disruption of blood brain barrier permeability
- Cytotoxin = secondary to cellular injury (e.g. ischaemc or hypoxic)
What is hydrocephalus?
An increase in CSF + enlargement fo ventricular system
What are three types of hydrocephalus and the differences between them?
Communicating:
- Obstruction in outflow of CSF
- E.g. in neonates, lateral ventricles obstruct cerebral aqueduct causing build-up of CSF in lateral ventricles leading to enlarging brain + ventricles
Non-communicating:
- Reduced absorption of CSF into sinus veins
- E.g. in meningitis the meninges can become fibrous which reduces absorption
Normal pressure:
- Gait disturbances
- Urinary incontinence
- Confusion
What is the normal flow of CSF?
- Produced by choroid plexus
- Flows through interventricular forament into 3rd ventricle
- Flows via cerebral aqueduct into 4th ventricle
- Goes to sub-arachnoid space
- Goes to spinal cord + brain
- Reabsorption via superior sagittal sinus into venous system
Where do primary brain tumours originate?
CNS
What are the two types of primary brain tumours and where do they originate/the type of tumour?
Extra-axial:
- Cranium
- Soft tissue
- Meninges
- Nerves
- BENIGN
Intra-axial:
- Glial
- Neurones
- Neuroendocrine cells
- MALIGNANT
What are secondary brain tumours?
Metastatic lesions from other parts of the body
What are some features of secondary brain tumours?
- Commonest form of adult brain tumours
- Most common sources = lung, breast, malignant melanoma
- Located at grey-white matter junction
- Well demarcated, solitary or multiple with surrounding oedema
- VERY POOR PROGNOSIS
What are some RFs for brain tumours?
- Previous tumours
- Radiotherapy to head + neck
- Neurofibromatosis 1+2
- Tuberous sclerosis
- FHx of brain cancer
What are some signs + Sx of brain tumours?
Raised intracranial pressure:
- Headache
- Vomiting
- Change in mental state
Supratentorial:
- Focal neurological deficit
- Seizures
- Personality changes
Infratentorial:
- Ataxia
- Long tract signs = spasticity, hyperreflexia
- Cranial nerve palsies
What are some neuroimaging techniques?
- MRI
- CT
- Functional MRI
- MR-spectroscopy
- PET-SCAN
What is the management of a brain tumour?
- Surgical resection
- Radiotherapy +/- chemotherapy
What is the WHO classification of CNS tumours?
Tumour type: Cell of origin/lineation of differentiation:
- Astrocytes = astrocytomas
- Oligodendrocytes = oligodendrocytomas (FRIED EGG APPEARANCE)
- Ependyma = Ependyoma (VENTRICULAR TUMOUR, HYDROCEPHALUS)
- Meningothelial cells = meningioma
Tumour grade: predicted natural clinical behaviour (e.g. survival time)
- Grade 1 = benign (well differentiated)
- Grade 2 = 5yrs + survival
- Grade 3 = 1-5yrs survival
- Grade 4 = <1yr survival (poorly differentiated)
Molecular profiling
- Genetics
- Molecular markers
What are the three different types of astrocytic brain tumours?
- Pilocytic astrocytoma (G1)
- Diffuse glioma (G2-3)
- Glioblastoma multiforme (G4 = BAD)
What age group does a pilocytic astrocytoma arise, what are its histological features, associated mutations and buzz words?
Age:
- 0-20 yrs
Histology:
- Piloid HAIRY CELLS
- Rosenthal fibres
- Slow mitotic divisions
Mutation:
- BRAF in 70%
Buzzwords:
- INDOLENT
- CHILDHOOD
What age group does a diffuse glioma arise, what are its histological features and associated mutations?
Age:
- 20-40yrs
Histology:
- Low-moderate cellularity
- Low mitotic activity
- No vascular proliferation
Mutation:
- IDH A/W longer surivival + better response to chemo + radiotherapy
What age group does a glioblastoma multiforme arise, what are its histological features, associated mutations and buzz words?
Age:
- 50+ yrs
- Median survival = 8mths
- MOST COMMON, AGGRESSIVE PRIMARY TUMOUR IN ADULTS
Histology:
- High cellularity
- High mitotic activity
- Microvascular proliferation
- Necrosis
Mutation:
- IDH wildtype
Buzzwords:
- AGGRESSIVE
- POOR PROGNOSIS
What age group does a meningioma arise, what are its histological features, location and buzz words?
Age:
- Increased incidence with age
Histology:
- PSAMMOMA BODIES (calcifications)
- Mitotic activity determines grading
Location:
- Meninges
- Arachnoid cells
Buzzwords:
- NF2
What age group does a medulloblastoma arise, where is it found and its buzz words?
Age:
- 2nd most common brain tumour in children after astrocytoma
Location:
- Cerebellum
Buzzwords:
- Squint
Where are ependyomas found?
- Posterior fossa
- Tuberous sclerosis
Where are craniopharyngiomas and pituitary tumours found?
- Pituitary sella
What are some familial syndromes associated with CNS tumours, and their features?
Von Hippel- Lindau
- Hemangioblastoma of cerebellum, brainstem + spinal cord
- Retina
- Renal cysts
- Phaeochromocytoma
Tuberous sclerosis:
- Giant cell astrocytoma
- Cortical tuber
- Supependymal nodules + calcifcations on CT
NF1:
- Optic glioma
- Neurofibroma
- Astrocytoma
NF2:
- Vestibular schwannoma
- Meningioma
- Ependymoma
- Astrocytoma
Multiple endocrine neoplasia type 1 (MEN1):
- Pituitary adenoma
