• HTN
• cardiac disease
• cigarette smoking
• HLD
• DM

• OCP's
• hematologic disease- sickle cell, PRV
• thrombotic coagulopathies
• vasculitis
• cerebral amyloid angiopathy
• hereditary angiopathy
  • CADASIL syndrome- causes brain infarcts and dementia
    • Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukocephalopathy
• dissecting aneurysm in extracranial bv's
• cocaine, heroin, amphetamines

• aerobic
• oxygen supplied via circulation
• oxygen is the limiting factor in cerebral metabolism
• cerebral blood flow subject to autoregulation over a wide range of arterial and ICP's

• causes
  • acute respiratory failure
  • CO poisoning
  • low environmental partial pressure of oxygen
• definition- blood flow normal but blood oxygen content reduced

• definition- oxygen content of blood normal, but blood flow reduced
• causes
  • cardiac arrest
  • hypovolemic shock

• ischemia more damaging because toxic metabolic wates accumulate
• most hypoxic conditions lead to depressed cardiac output, leading to ischemia
  • so usually, we end up with features of combined hypoxia and ischemia
• irreversible injury after a few minutes (less than 10 minutes) of oxygen deprivation

• neurons >> oligodendrocytes > astrocytes > blood vessels
• some neurons are more vulnerable than others
  • hippocampal pyramidal neurons in Sommer sector
  • pyramidal neurons of cerebral cortex (layers 3 and 5)
  • Purkinje cells of cerebellum

• decrease ATP
• increase excitatory NT's and receptor activation
  • glutamate
    • NMDA and kainate receptors
• increase intraneuronal calcium, sodium, water
• increase new gene products (ex: heat shock proteins)
• decrease protein synthesis with reperfusion
• increase destructive intracellular enzymes activated by calcium influx
  • proteases
  • lipases
  • endonucleases
• increase NO and free radicals
• damage to membranes, mitochondria, DNA
• inflammatory mediators released

• cortical supply via ACA, PCA, PCA
• deep supply via:
  • central vessels called the lenticulstriate vessels (supply basal ganglia, internal capsule)

• diencephalon (thalamus, hypothalamus)
• basal ganglia
• internal capsule

• most of the lateral surface of the cerebral hemispheres

• frontal tips
• anterior 2/3 of medial surface of cerebral hemisphere

• occipital tips
• posterior 1/3 of medial surface of cerebral hemispheres
• inferior and medial surfaces of temporal lobes

• blood oxygen and/or decrease CPP
• borderline perfusion may cause damaged neurons without damaging glia or blood vessels
  • could lead to neuronal injury (hypoxic/ ischemic)

• single arter or arterial branch occluded
• all tissue (neurons, glia, bv's) destroyed in distribution of blocked vessel
  • cerebral infarct

• zones at outer limit of vascular territories
  • at end of arterial distribution system
  • last area to be perfused
• zones most affected in global hypoxia/ischemia
• sustain neuronal or total parenchymal injury to global hypoxic/ischemic insults
  • total parenchymal injury = watershed infarct
• locations
  • junction of ACA and MCA territories
  • junction of MCA and PCA territories

• single cerebral bv occlusion by:
  • thrombosis (clot forms in situ in CNS vessel)
  • embolism (clot forms elsewhere, breaks off and lodge in CNS arterial branch pt or narrowed luminal segment)
• injured tissue zone conforms to distribution of blocked artery
  • ICA distribution (MCA + ACA distrubition)

• anemic (pale/bland/non hemorrhagic)
  • no reperfusion to necrotic area
  • characteristic of thrombotic infarcts
• hemorrhagic (red)
  • reperfusion of necrotic area
    • extravasation of blood from necrotic vesles
  • characteristic of embolic infarcts

• acute
  • 0-2 dys after infarct
  • subtle tissue softening
  • dusky gray matter discoloration
  • blurring of gray/white matter demarcation
• subacute
  • 2-4 dys after infarct
  • findings of acute stage more pronounced
  • swelling (edema) of tissue with mass effect
• chronic
  • 4 dys and following after infarct
  • early: liquefactive necrosis
  • late: cystic cavitation
    • brain lacks fibroblasts, so no fibrous scar can form

• acute
  • red neurons- neuronal cytoplasm shrink, turn pink, nucleus collapse and break up
  • neutrophils migrate from vessels at infarct edge
• subacute
  • red neurons break up (liquefactive necrosis) and disappear
  • neutrophils replaced by lymphocytes and phagocytic macrophages
• chronic
  • cavity replace liquefactive dead tissue, spanned by reactive astrocyte process and capillaries
  • reactive gliosis and partial tissue damage in surrounding non-necrotic parenchyma with neuronal encrustation
    • iron, calcium salts deposited on neurons in infarct rim

• etiology
  • infection
  • tumor invasion
  • thrombotic diathesis
• definition- thrombosis of dural venous sinus or cortical vein
• blocked drainage leads to (at drainage territory):
  • congestion
  • ischemia
  • hemorrhagic necrosis

• epidural- trauma
• subdural- trauma
• subarachnoid
  • trauma
  • saccular aneurysm rupture
  • AVM rupture
  • spread of intraventricular, intracerebral hemorrhage
• intracerebral
  • trauma
  • chronic HTN
  • hemorrhagic infarct
  • cerebral amyloid angiopathy
• intraventricular
  • extension of intracerebral hemorrhage that ruptures ventricular/ependymal lining

1. accelerated atheroscerosis in large vessels (circle of willis and proximal branches)
2. hyaline arteriosclerosis and lipohyalinosis in deep perforating central branches
   • vascular smooth muscle replaced by fibrocollagenous tissue
   • vessel wall thicker but weaker and less compliant- Charcot-Bouchard microaneurysms could occur
   • thickened arteriole with narrowed lumen and weakend wall:
     • thrombosis- small infarct (lacunar: located in basal ganglia/thalamus, pons, or deep cerebellum)
     • rupture, leading to intracranial hemorrhage

• brain regions supplied by perforating central arterioles
  • basal ganglia (esp. putamen) and thalamus
  • brainstem (esp. basal pons)
  • deep cerebellar white matter

• amyloid deposited in small and medium sized cortical and leptomeningeal bv's
• types
  • beta amyloid
  • cystatin
• thickened but weakened vessels subject to rupture

• beta amyloid (derived from APP)
  • widely distributed transmembrane glycoprotein or unknown function
    • neurons, platelets, heart, lung, kidney, spleen, intestines
  • pathogenesis- APP metabolized abnormally to produce smaller fragments polymerized and folded into amyloid
• cystatin
  • cysteine protease inhibitor
  • pathogenesis- single AA substitution in peptide sequence leads to abnormally shaped molecule polymerized and folded into amyloid

• cerebral hemorrhage more superfical than with HTN hemorrage
• lobar pattern (ganglionic with HTN)
• reflects involvement of leptomeningeal and superficial cortical vessels (instead of deep perforating central vessles like in HTN)
• may see several hemorrhages of different ages in different brain areas

• affected vessels have double barrel "vessel in vessel" appearance
• amyloid staining characteristics
  • H and E: pink
  • congo red in polarized light: apple green
  • congo red: orange or pink

• epidemiology- most common cause of non-traumatic subarachnoid hemorrhage
• etiology
  • Ehler-Danlos
  • Marfan's syndrome
  • fibromuscular dysplasia of extracranial arteries
  • cerebral vascular malformations (AVM)
  • aortic coarctation
  • ADPKD
  • neurofibromatosis I
• most common location: anterior circle of Willis
• growth and rupture promoted by what:
  • cigarrette smoking
  • HTN
  • turbulent flow in affected vessels

1. extrusion of vascular intima through weak or deficient media at arterial branch point of circle of Willis
2. rupture at dome
3. blood collect in subarachnoid space
   • with or without brain parenchyma
   • with or without ventricular system

complications of rupture

• vasospasm in circle of Willis exposed to subarachnoid blodo leading to infarct
  • arachnoid fibrosis leads to communicating hydrocephalus
    • communicating- obstruction in subarachnoid space, not ventricular system
    • non-communicating- blockage somewhere in ventricular system leading to CSF accumlation proximal to block

• arteriovenous malformations
• carvernous hemangioma (cavernoma)
• venous angioma
• capillary telangiectasia

• symptomatic (AVM, cavernoma)
  • intracerebral with or without subarachnoid hemorrhage
  • seizure disorder
• incidental radiographic/autopsy finding

• often involves MCA territory
• tortouous large caliber vascular tangle in parenchyma with or without subarachnoid space
• flow rates rapid
• direct AV shunt with no capillary bed
  • arterial vessels- smooth muscle, elastic lamina
  • venous vessels- smooth muscle, no elastic
  • arteriolized veins- thick fibrous walls
• brain tissue between abnormal vessles
• reactive change surrounds brain
  • hemosiderin
  • calcium
  • gliosis

• location
  • brainstem
  • cerebellum
  • cerebral subcortical white matter
• grossly resembles hematoma
• flow rates sluggish
• no smooth muscle, elastic
• abnormal vessels with thin fibrous walls without intervening brain tissue

• associated with:
  • chronic HTN
  • DM
  • cerebral atherosclerosis
• different types
  • multi-infarct dementia: bilateral infarcts destroy threshold volume of gray matter or functionally critical gray matter (thalamus, hippocampus)
  • diffuse white matter disease
    • arteriosclerosis leads to inadequate vascular support of white matter
      • myelin damage w/axonal loss
      • disconnect of brain association areas
    • subcortical arteriosclerotic leukoencephalopathy, Binswanger's disease

• closed head injury- skull and dura remain in tact
• open head injury- skull fractured with tearing of dura
  • penetrating injury: object pierce skull and brain and comes to rest
  • perforating injury: object pierce skull and brain and exits at site remote from entry
• displaced fracture- fractured skull fragment depressed by greater than its thickness
• diastatic fractures- fracture crossing bone suture line
  • fractures from later blows do not cross earlier fracture lines

Dura from base of skull must be stripped at autopsy to reveal basal skull fractures

1. skull fracture lacerates underlying dural artery
   • middle meningeal artery most often involved
2. blood under arterial P accumulates in potential space between skull and dura
3. hematoma mass effect may cause herniation

presentation

• may experience lucid interval between injury and neurologic deterioration
• medical emergency requiring prompt evacuation

1. tearing in bridging vein between cortical surface and dural sinus
   • cortical vein attached to brain
   • bridging bein tethered in dura
   • inertial movement of brain relative to skull/ dura shears bridging vein
2. venous blood accumulates between dura and arachnoid
3. organized by dural fibroblasts that form membranes (outer, inner) around hematoma
   • granulation tissue capillaries of organizing hematoma may rupture with minor trauma   (re-bleed)

• parenchymal contusions or lacerations bleeding through disrupted pia or ependyma
• basilar blodd vessles ruptured by basilar skull fractures
• dissectin aneurysm of vertebral arteries

• contusions
• lacerations

• contusions- parenchymal bruise from impact of brain with skull
• laceration- brain tear from penetrating or perforating injury

• brain edges close to skull (esp. prominences of inner table)
  • frontal, occipital, temporal poles of brain
• brain surfaces overlying rough regions of inner table
  • undersurfaces of frontal and temporal lobes
• brain surface adjacent to skull fracture

• tissue and vascular damage with hemorrhage
• impact greates on crown of gyri
• follows organizational sequence of intracerebral hemorrhage

• head falls or is stuck, brain develops inertia relative to skull
  • when resting head struck, skull moves slightly before brain
    • moving skull impacts stationary brain
• when falling head strikes surface, skull stops before brain
  • moving brain impacts arrested skull
  • brain may rebound against inner skull surface opposite impact site
• coup injury
  • parenchymal contusion at impact site
  • associated with blows to stationary head and falls
• contrecoup injury
  • associated with falls
  • parenchymal contusion 180 degrees opposite impact site due to rebound injury

• gross
  • small hemorrhages in corpus callosum, dorsal midbrain, dorsal pons
  • plus or minus contusions, lacerations
• microscopic
  • rounded swellings in white matter neuropil
  • stain with axon stains (ex: Bielschowsky silver)

1. etiology
   • may be seen with open or closed head injury
     • angular acceleration (shaking) without impact sufficient to produce diffuse axonal injury
2. stretching and shearing of axons in deep white matter
   • callosal and periventricular white matter
   • brainstem
3. axons severed at nodes of Ranvier
   • axoplasmic flow disrupted with intraaxonal accumulation proximal to sites of interruption
   • rounded axonal swellings seen in special stains for axons
4. presentation
   • patients unconscious from moment of injury without lucid interval
   • remains unconscious, vegetative, or disabled until death