Pathology - CNS & Eye Flashcards
Common locations of saccular aneurysms in the cerebral circulation
90% near major arterial branch points, more common at anterior circulation around the Circle of Willis
- ACA & ACoA 40%
- MCA & AChoroidalA 34%
- ICA & PCoA 20%
- Basilar & PCoA
Multiple in 20-30% cases at autopsy
Risk factors for saccular aneurysm rupture
- Size: > 10 mm with 50% risk of rupture per year
- Acute increase in ICP (straining at stool, orgasm)
Pathological sequelae of SAH
Acute - ischaemic injury (stroke) from vasospasm
Late - meningeal fibrosis and scarring, obstruction of CSF flow and absorption
Death
Morphology of berry aneurysm
Medial muscular layer thins as approaching the aneurysm’s neck and gets thickened hyalinised intima, covered with normal adventitia
Natural history of a ruptured berry aneurysm
- Acute onset of headache, ALOC
- Initial mortality 25-50%
- Rebleeding is common
- Vasospasm in vessels other than the bleeding site -> secondary ischaemic injury
- During healing, meningeal fibrosis and scarring -> secondary hydrocephalus
Causes of ischaemic cerebral infarction
Arterial thrombosis
Cerebral emboli
Lacunar infarcts from small vessels
Cerebral arteritis
Arterial dissection
Venous infarction
Sources of cerebral thromboemboli
Left atrium/ventricle thrombus Valvular vegetations Carotid plaque PFO with paradoxical emboli
Main pathological processes causing ischaemic stroke
Thrombus - atherosclerosis
Embolism - AMI with mural thrombus, valvular heart disease, AF, vascular surgery/shower embolism, fat embolism, endocarditis
Vasculitis - infective vasculitis, autoimmune vasculitis, primary angiitis of CNS
Arterial dissection
Venous infarction - venous sinus thrombosis
Drugs - amphetamines, cocaine, heroin
Hypercoagulable state
Distinguishing pathological features of haemorrhagic and non-haemorrhagic stroke?
Haemorrhagic (red) - multiple, confluent, petechial haemorrhages associated with emboli, secondary to reperfusion via collaterals or dissolution of materials, greater risk if anticoagulated
Non-haemorrhagic (pale/bland anaemic) - usually associated with thrombosis
Importance of stroke pathology in relation to stroke thrombosys
- Complications higher with embolic/haemorrhagic CVAs
- In non-haemorrhagic CVA, little macroscopic change can be seen within the first 6 hours
- Reversible ischaemic penumbra
- Early treatment leads to better outcome and less haemorrhagic risk
Types of cerebral ischaemic injury
Global (e.g. hypoxic encephalopathy) - generalised reduction of cerebral perfusion
Focal - reduction of blood flow to a localised area of the brain
Pathological effects of HTN on brain
Lacunar infarcts (lenticular nucleus, thalamus, internal capsule, deep white matter, caudate nucleus, pons)
Massive ICH
Hypertensive encephalopathy
Slit haemorrhages
Pathological mechanisms of cerebral oedema
Vasogenic - BBB disruption, incr vasc perm, fluid shift from intravascular to intercellular space
Cytotoxic - neuronal/glial/endothelial injury, from hypoxic or ischaemic insults or metabolic damage, leads to cellular swelling and intracellular oedema
Interstitial or ependymal oedema from high pressure hydrocephalus
Morphological findings of generalised cerebral oedema
- Flattened gyri
- Narrowing of sulci
- Compression of ventricles and basal cisterns
- Herniation
Major brain herniation locations
Subfalcine - cingulate gyrus under the falx cerebri
Transtentorial - medial aspect of the temporal lobe against the free margin of the tentorium
Tonsillar - cerebellar tonsils through the foramen magnum
Causes of dementia
- Alzheimer
- FTD
- Vascular
- Parkinson
- Creutzfeld-Jakob
- Neurosyphilis
- Toxins (heavy metals, alcohol)
Pathogenesis of Alzheimer
- Lysis of transmembrane protein Amyloid Precursor Protein (APP) by beta and gamma secretases produce Aβ and C-terminal portion of APP
- Aβ peptides aggregate into amyloid fibrils and can be directly neurotoxic
- C-terminal portion of APP is involved in cell signalling and transcription regulation
- Severity of AD is related to the loss of synapses
Main pathophysiological causes of spontaneous intracerebral haemorrhage
- Hypertension
- Cerebral amyloid
- Other: coagulopathy, neoplasm, vasculitis, aneurysm, vascular malformation
Areas of brain where hypertensive intracerebral haemorrhages most commonly occur
- Putamen 50-60%
- Thalamus
- Pons
- Cerebellum
Pathophysiology of cerebral amyloid angiopathy
- Deposition of amyloidogenic peptides in the walls of medium and small calibre meningeal and cortical vessels
- Results in weakening of the vessel wall and risk of haemorrhage
Types of intracranial bleeding in head injury
Extradural
Subdural
Subarachnoid and intraventricular
Intra-parenchymal
Sequence of events in extradural haemorrhage
- Dural artery tear (middle meningeal), usually associated with skull fracture
- Strips off the dura from the skull
- May be a lucid period before ALOC
Define concussion and clinical features
Altered consciousness secondary to a head injury, with
- transient neurological dysfunction
- transient respiratory arrest
- transient loss of reflexes
Features: headache, amnesia, n & v, concentration and memory impairment, perseveration, irritability, behaviour/personality change, dexterity loss, neuropsychiatric syndromes
Types of meningitis. Common organisms of bacterial meningitis in different age groups.
bacterial, viral, fungal, chemical/drug induced, chronic (TB, carcinomatous)
Neonate: E coli, GBS
Children: S pneumoniae, H influenzae
Adolescent/young adult: Neisseria meningiditis, S pneumoniae
Older adults: S pneumoniae,, Listeria
By organisms:
E coli & GBS: neonates
Pneumococci and Meningococci: all age groups beyond neonates
Haemophilus: children but decreased incidence with immunisation
Listeria: extremes of age
Unusual organisms: staph post neurosurgery, G neg in immunocompromised
CSF findings in acute bacterial meningitis
- raised pressure
- turbid
- raised protein
- decreased glucose
- raised neutrophils
- positive gram stain or culture
Difference in CSF findings between acute bacterial and viral meningitis
Bacterial: cloudy, high pressure, more neutrophils, raised protein, reduced glucose
Viral: lymphocytes, moderately raised protein, normal glucose
Common viral causes of meningitis
Echovirus, Coxachievuris (non polio enteroviruses)
HSV
VZV
mumps
measles
HIV
Arboviruses (WNV, JEV)
Non paralytic polio
Clinical features of MS
- distinct episodes of neurological deficits separated by time
- myriad of presentations as white matter lesions separated by space
- relapsing-remitting course
- unilateral visual impairment from optic neuritis
Pathogenesis of MS
Autoimmune, demyelinating disorder, to white matter lesions separated in space
Cellular immune response inappropriately directed against components of myelin sheath
Genetic linkage, environmental influences, microbial/viral trigger, CD4+ Th1 cells react against myelin antigens, release cytokines, activate macrophages
Inflammatory cells create plagues
CSF findings in MS
- elevated protein
- pleocytosis
- increased proportion of gamma globulin
- oligoclonal bands
Clinical features of Parkinsonism
- diminished facial expression
- stooped posture
- slowed voluntary movement
- festinating gait
- rigidity
- pill rolling tremors
Causes of Parkinsonism
Conditions that cause damage to nigrostriatal dopaminergic system
- PD
- post encephalitis
- familial forms
- trauma
- drugs: dopamine antagonists, toxins, pesticides
- multiple system atrophy, progressive supranuclear palsy
Pathogenesis of PD
No unifying pathogenic mechanism identified
- misfolded protein/stress response triggered by alpha-synuclein aggregation
- defective proteosomal function due to the loss of E3 ubiquitin ligase parkin
- altered mitochondrial function by loss of DJ-1 and PINK1
- damage to dopaminergic cells from toxins, drugs, autoimmune conditions
Process of peripheral nerve repair following injury
- death of distal part
- axonal cone of growth 1-2 mm per day
- growth through Schwann cell structure
- regenerating clusters
Changes in spinal cord after traumatic injury
Acute phase: haemorrhage, necrosis, axonal swelling in the surround 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
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
Nuclear changes
- chromatin condensation and fragmentation
- pyknosis, karyorhexis, karyolysis
Acute consequences of cervical spinal cord injury
- complete or incomplete
- spinal shock: quadriplegia, flaccid paralysis, total anaesthesia, areflexia
- if above C4, respiratory compromise from diaphragmatic paralysis
- neurogenic shock: hypotension, bradycardia, warm dry skin
- incomplete syndromes (anterior cord, central cord etc)
Genetic risk factors for saccular aneurysms
Generally unknown, not congenital
Linked to:
Polycystic kidney
EDS type 4
NF1
Marfan
FMD
Aortic coarctation
