VIVA: Pathology - CNS and eye Flashcards
What are the causes of ischaemic cerebral infarction?
- Arterial thrombus*
- Cerebral emboli
- Lacunar infarcts from small vessels
- Cerebral arteritis
- Arterial dissection
- Venous infarction
*needed to pass + 1 other
Where are some sources of cerebral thromboemboli?
2 to pass:
- Left atrium / ventricle thrombus
- Valvular vegetations
- PFO causing paradoxical emboli
- Carotid plaque
What are the distinguishing pathological features of haemorrhagic and non-haemorrhagic ischaemic cerebral infarcts?
Haemorrhagic (red *):
- Multiple, sometimes confluent, petechial haemorrhages typically associated with embolic * events
- Thought to be secondary to reperfusion * either via collaterals or dissolution of materials
- Greater risk if anticoagulated
Non-haemorrhagic (pale/bland anaemic *):
- Usually associated with thrombosis *
*needed to pass
How are the pathological processes involved in haemorrhagic vs non-haemorrhagic ischaemic infarcts important in relation to stroke thrombolysis?
- Complications are higher with embolic/haemorrhagic CVAs
- Aim is to reverse injury in ischaemic penumbra *
- In non-haemorrhagic CVA, little macroscopic change can be seen within the first 6hrs: earlier treatment leads to better outcome and less haemorrhagic risk
*needed to pass + concept
What are the types of cerebral ischaemic injury?
- Global cerebral ischaemia * (ischaemic/hypoxic encephlopathy):
- Generalised reduction of cerebral perfusion - Focal cerebral ischaemia *:
- Follows reduction of blood flow to a localised * area of the brain
*needed to pass
What are the pathological effects of HTN on the brain?
Needed to pass:
- Lacunar infarcts (in lenticular nucleus, thalamus, internal capsule, deep white matter, caudate nucleus, pons)
- Slit haemorrhages
- Hypertensive encephalopathy
- Massive intracerebral haemorrhage
Describe the pathological mechanisms which cause cerebral oedema
- Vasogenic *:
- BBB disruption with increased vascular permeability
- Fluid shift intravascular to intercellular spaces of brain
- May be generalised or localised (inflammation or neoplasm) - Cytotoxic *:
- Increased intracellular fluid due to neuronal, glial, or endothelial injury (e.g. generalised hypoxic/ischaemic insult or metabolic damage)
- Interstitial or ependymal oedema around lateral ventricles due to high pressure of hydrocephalus
*needed to pass or basic understanding of 2 mechanisms
What are the morphological findings of generalised cerebral oedema?
3/4 to pass:
- Flattened gyri
- Narrowing of sulci
- Compression of ventricles and/or basal cisterns
- Herniation
Describe the major herniation locations associated with raised ICP
2/3 to pass with correct description:
1. Subfalcine:
- Asymmetric expansion of cerebrum displaces the cingulate gyrus under the falx cerebri
2. Transtentorial/uncal:
- Medial aspect of the temporal lobe is compressed against the free margin of the tentorium
3. Tonsillar:
- Displacement of the cerebellar tonsils through the foramen magnum
What are the main pathophysiological causes of spontaneous intracerebral haemorrhage?
- HTN and cerebral amyloid are the main causes *
- Other causes include systemic coagulation disorders, neoplasms, vasculitis, aneurysms, and vascular malformations
*1/2 needed to pass + 2 others
Which areas of the brain do hypertensive intracerebral haemorrhages most commonly occur?
Hypertensive intracerebral haemorrhage may originate in the putamen (50-60% of cases), thalamus, pons, and rarely the cerebellar hemispheres *
*2 needed to pass, basal ganglia and brainstem also accepted
Describe the pathophysiology of cerebral amyloid angiopathy
There is deposition of amyloidogenic peptides in the walls of medium- and small-calibre meningeal and cortical vessels
This deposition can result in weakening of the vessel wall and risk of haemorrhage
What are the different types of meningitis?
- Bacterial *
- Viral
- Others: Rickettsial, chemical/chemo, autoimmune, TB, syphilis, carcinomatous/lymphomatous, fungi
*needed to pass + 1 other
What are the common organisms that cause bacterial meningitis in different age groups?
3/4 groups with 2 examples of each to pass:
1. Neonates:
- E. coli
- Pseudomonas
- Listeria
- Group B streptococcus
- Staphylococcus aureus
2. Children:
- Strep pneumoniae
- Haemophilus influenzae B
- Neisseria meningitidis
3. Adolescents and young adults:
- Neisseria meningitidis
- Strep pneumoniae
4. Older adults:
- Listeria
- Strep pneumoniae
- Neisseria meningitidis
What are the complications of meningitis?
3 to pass:
Acute:
- DIC
- Septic shock
- Loss of limbs
- Seizures
- Raised ICP
- CVA
- Hyponatraemia
- Death
Chronic:
- Hearing loss
- Learning difficulties/concentration problems
What is the likely diagnosis based off these CSF results, and why?
- Turbid
- Low sugar
- High protein
- Pleiocytosis with neutrophil predominance
- No bacteria
Acute bacterial meningitis
What changes occur in the spinal cord after a traumatic injury?
- Acute phase *:
- Haemorrhage
- Necrosis
- Axonal swelling in surrounding white matter at level of injury - Late phase *:
- Area of neuronal destruction becomes cystic and gliotic
- Secondary Wallerian degeneration involving long white matter tracts
- Liquefactive necrosis often seen in CNS
*1 example from each to pass
What are the features of irreversible injury at the cellular level?
- Mitochondrial damage *:
- Failure of oxidative phosphorylation -> ATP depletion * -> failure of energy-dependent cellular functions - Membrane damage *:
- Plasma membrane -> loss of osmotic balance
- Lysosomal membrane -> enzyme leakage * -> cell necrosis
*3/4 to pass
What are the acute clinical consequences of a cervical spinal cord injury?
Complete:
- Spinal shock: quadriplegia * / flaccid paralysis, total anaesthesia, areflexia
- If above C4, respiratory compromise * due to diaphragmatic paralysis
- Neurogenic shock: hypotension, bradycardia, warm dry skin
Incomplete:
- E.g. anterior cord, central cord etc
*needed to pass
Which type of vessels have been damaged to produce a subdural haematoma?
- Subdural blood comes from damage to bridging veins between the brain and the venous sinuses * (displacement of the brain with trauma can tear the veins at the point where they penetrate the dura to enter the sinuses)
- Results in blood between the dura and the arachnoid *
*needed to pass
Which groups of patients are most at risk for SDH and why?
- Elderly *:
- Veins stretched and more movement due to brain atrophy - Infants:
- Thin-walled bridging veins
*needed to pass
How does an extradural haematoma occur?
Extradural haematoma occurs with rupture of a meningeal artery *, usually associated with a skull fracture, leading to accumulation of arterial blood between the dura and the skull *
*needed to pass
Define and describe diffuse axonal injury
Where in the cerebral circulation are saccular (berry) aneurysms commonly located?
90% near major arterial branch points *:
- ACA with ACommA (40%) *
- MCA with AChoroidalA (34%)
- ICA with PCommA (20%)
- Basilar artery with PCA
- Multiple in 20-30% of cases at autopsy
*needed to pass
What factors increase the likelihood of rupture of these aneurysms?
- Increased likelihood with size * (>10mm carries 50% risk of rupture per year)
- May occur anytime but in about 1/3 are associated with acute increases in ICP * (e.g. straining at stool, orgasm)
*needed to pass
What are the pathological sequelae of subarachnoid haemorrhage?
Acute events (hours to days):
- Ischaemic injury (stroke) from vasospasm * (especially basal SAH)
- Raised ICP
Late events (healing process):
- Meningeal fibrosis and scarring *
- Obstruction of CSF flow * and/or to CSF absorption
- Death
*2/3 to pass
What is the morphology of a berry aneurysm?
Medial muscular layer thins as it approaches the neck of the aneurysm, thickened hyalinised intima, covered with normal adventitia
What is the natural history of a ruptured berry aneurysm?
3/4 to pass:
- Acute onset of severe headache, often with loss of consciousness (25-50% die at the time)
- Rebleeding is common
- Vasospasm in vessels other than the bleeding site can cause secondary ischaemic injury
- In the healing phase, meningeal fibrosis and scarring can cause secondary hydrocephalus
What are the main pathological processes causing ischaemic stroke?
- Thrombotic occlusion *:
- Atherosclerosis * most common - Embolism *:
- E.g. AMI, mural thrombus, valvular heart disease, AF, vascular surgery and shower embolism, fat embolism, endocarditis - Inflammatory process leading to luminal narrowing:
- E.g. infectious vasculitis, autoimmune vasculitis, primary angiitis of the CNS
*needed to pass + at least 2 causes of embolism + 1 other (embolic or inflammatory)
What are the causes of focal cerebral infarction?
- Emboli:
- From cardiac mural thrombi, arterial thromboemboli (especially carotid), paradoxical association with cardiac anomalies, tumour/fat/air embolus - Thrombotic arterial occlusion/in situ thrombosis:
- Large vessel disease - Vasculitis:
- Small vessel disease - Infectious:
- Immunosuppression and aspergillus, CMV encephalitis, syphilis, TB - Non-infectious:
- Polyarteritis nodosa, primary angiitis - Other:
- Amphetamines, cocaine, heroin
- Dissecting aneurysm of extracranial arteries
- Hypercoaguable states
What are some of the causes of dementia?
- Alzheimer’s disease (commonest) *
- Frontotemporal dementia
- Multi-infarct (vascular) dementia
- Parkinson’s disease (Lewy bodies)
- Creutzfeld-Jakob disease
- Neurosyphilis, toxins etc
*needed to pass + 2 others
Describe the pathogenesis of Alzheimer’s disease
- Lysis of transmembrane protein Amyloid Precursor Protein by beta and gamma secretases produces Amyloid-beta and C-terminal portion of APP *
- Amyloid-beta peptides aggregate into amyloid fibrils and can be directly neurotoxic
- C-terminal portion of APP involved in cell signalling and transcription regulation
- Severity of Alzheimer’s disease is related to loss of synapses *
*needed to pass
What types of intracranial bleeding can be seen in a patient with a head injury?
3/4 to pass:
- Extradural
- Subdural
- Subarachnoid (including intraventricular)
- Intraparenchymal
What sequence of events occur in an extradural haemorrhage?
- Dural artery (e.g. middle meningeal) tear, usually associated with a skull fracture *
- Strips off dura from skull
- May be a lucid period before loss of consciousness
*needed to pass
Define concussion and what are its clinical features
Definition:
- Altered consciousness secondary to a head injury *
- Transient neurological dysfunction *
- Transient respiratory arrest
- Transient loss of reflexes
- Pathogenesis unclear, may be dysregulation of reticular activating system
Clinical features:
- Headache
- Amnesia
- Nausea and vomiting
- Concentration and memory issues
- Perseveration
- Irritability
- Behaviour/personality changes
- Dexterity loss
- Neuropsychiatric syndromes
*needed to pass + 3 clinical features
What are the typical CSF findings in acute bacterial meningitis?
- Raised pressure
- Turbid
- Raised protein
- Low glucose
- Raised neutrophils *
- Bacteria on Gram stain or culture *
*needed to pass + 1 other
How do the CSF findings typically differ between acute bacterial and viral meningitis?
Bacterial:
- Turbid
- Higher pressure
- More neutrophils *
- Raised protein *
- Low glucose *
Viral:
- Lymphocytes *
- Moderately raised protein *
- Normal glucose *
*needed to pass
What are the typical CSF findings in viral meningitis?
3/4 to pass:
- Lymphocytes
- Normal glucose
- Mildly elevated protein
- No bacteria on Gram stain or culture
What are the common viral causes of viruses?
2/4 to pass:
- Echovirus
- Coxsackie (enteroviruses)
- Non-paralytic poliovirus
- Others (HSV, VZV, HIV)
What are the clinical features of multiple sclerosis?
- Distinct episodes of neurological deficits separated by time *
- Myriad of presentations as lesions separated by space
- Unilateral visual impairment (optic neuritis) is common
- Brainstem and cord lesions
*needed to pass
What is the pathogenesis of multiple sclerosis?
- Exact aetiology not established
- Autoimmune demyelinating disorder * resulting in white matter lesions separated in space
- Cellular immune response inappropriate directed against components of myelin sheath *
- CD4+ TH1 cells react against myelin antigens, release cytokines and activate macrophages
- Inflammatory cells create plaques
- Genetic and environmental influences (greater incidence in first degree relatives, ? microbial / viral triggers)
*needed to pass
What might be found in CSF of a patient with MS?
2 needed to pass:
- Mildly elevated protein
- Moderate pleiocytosis (33%)
- Increased proportion of gamma globulin
- Oligoclonal bands (reflects B cell proliferation)
Describe the clinical features of Parkinsonism
3/6 to pass:
- Diminished facial expression
- Stooped posture
- Slowness of voluntary movement
- Festinating gait (progressively shortened, accelerated steps)
- Rigidity
- “Pill-rolling” tremor
What are the causes of Parkinsonism?
Conditions that cause damage to the nigrostriatal dopaminergic system *:
- Parkinson’s disease
- Post-encephalitic
- Familial forms (rare; autosomal dominant and recessive)
- Trauma/injuries
- Drugs (e.g. dopamine antagonists, toxins, pesticides)
- Multiple system atrophy
- Progressive supranuclear palsy
*needed to pass + 2 examples
Outline the possible pathogenesis of Parkinson’s disease
No unifying pathogenic mechanism identified but possible pathogenesis involves:
- Misfolded protein/stress response triggered by alpha-synuclein aggregation
- Defective proteosomal function due to the loss of the E3 ubiquitin ligase parkin
- Altered mitochondrial function caused by loss of DJ-1 and PINK1
- Genetic variants with gene defects
- Possible damage to dopaminergic cells from toxins, drugs, autoimmune conditions
Describe the process of peripheral nerve repair following traumatic injury
- Death of distal part (+/- some of proximal)
- Axonal cone of growth 1-2mm per day
- Growth through Schwann cell structure
- Regenerating clusters
What is the most frequent cause of subarachnoid haemorrhage?
- Rupture of an aneurysm *
- Less common causes include extension of traumatic haemorrhage, hypertensive intracerebral bleed into ventricular system, AVM, bleeding disorders, tumour
*needed to pass
What are the genetic risk factors for saccular aneurysms?
Generally unknown, not “congenital”
Some genetic risk conferred by (2/6 to pass):
- Polycystic kidney
- Ehlers Danlos type 4
- Neurofibromatosis type 1
- Marfan’s
- Fibromuscular dysplasia
- Aortic coarctation
Predisposing factors:
- Smoking
- HTN
Define and describe diffuse axonal injury
Axonal microscopic injury *:
- Microscopic findings include axonal swelling and focal haemorrhagic lesions *
- Believed to damage the integrity of the axon at the node of Ranvier * -> alterations in axoplasmic flow *
- Commonly found with “coma” but no cerebral contusions *
*needed to pass
