Defined by anatomical location, and circumstance:

• arterial, capillary, or venous
• intravascular hypertension, thrombosis, breakdown of vessel integrity following infarction or trauma
• location of infarct partly dictated by developmental stage
  • subdural, subarachnoid
  • intracortical, white matter
  • choroid plexus
  • brainstem/cerebellar
  • periventricular - from germinal matrix or white matter
  • intraventricular - from ganglionic eminence or choroid plexus

Subventricular zone = subependymal zone = subependymal matrix = germinal matrix

Ganglionic eminence: large aggregate of cells of the subventricular zone along the wall of the lateral ventricle, especially over the immature caudate nucleus

Epidemiology

• In utero bleeding rare
• autopsy studies are biased to worst outcome
  • small sub dural, subarachoid and intracerebral hemorrhages are common (20-30% livebirths)
  • large intraventricular and posterior fossa hemorrhages - 10-15% livebirths
• choroid plexus hemorrhage usually at >35wks GA and not as severe
• decreasing incidence over time
• incidence of intraventricular/periventricular hemorrhage is inversely proportional to gestational age at birth
  • 40-50% infants born at < 26wks GA
  • 20% at 26-32 wks
  • < 5% at > 32wks
• severity also worse in those of lower GA
• incidence of asymptomatic small subdural/subarachnoid (50%) and choroid plexus (30%) hemorrhages detected on MRI following uncomplicated term births are much higher than symptomatic intracranial hemorrhage (2.7%)
• 60% hemorrhages occur within first 24 hours of life, most within 3-4 days
• highest risk periods are first 3 hours of life, day 2, and day 10 of life
• Risk factors:
  • mainly prematurity, with associated RDS
  • IUGR
  • maternal/fetal sepsis, PPROM, chorioamnionitis
  • inconsistent relationship with maternal HTN and preeclampsia
  • traumatic delivery is risk factor for subdural hemorrhage

Embryology

• ventricular zone lines fetal ventricle
• ganglionic eminence is C-shaped collection of proliferating cells in the subventricular zone, below the caudate nucleus, along the ventricles down the temporal horns towards the amygdala
• neuronal precursor cells (especially GABAergic interneurons) are produced up to 18 wks GA, then glial precursors
• volume of subventricular zone peaks at 23-25 wks GA
• largely involutes by 38-40 wks GA leaving some cells in the subependymal region
• ciliated ependymal cells appear as the ventricular zone involutes
• large veins in the ganglionic eminence are the source of hemorrhage

Clinical features

• usually clinically occult
• if severe, can be irritable, have decreased LOC, tense fontanel (incr ICP), low HCT (bleed), seizures
• mortality for birth weight < 1500g (30 wks GA) is 30%
• morbidity is 25% of abnormal neurological outcome
• morbidities include:
  • hydrocephalus
  • cerebral palsy (hemiplegic)
  • cognitive delay
• effects difficult to differentiate with PVL
• subdural hematomas have grave consequences if incr ICP or in the posterior fossa

Imaging

• primary diagnostic tool - screening recommended
• grading system based on CT, but not recommended due to radiation effects
• Papile grading system
  Grade I: isolated subependymal hemorrhage (SEH)
  Grade II: SEH with IVH, no ventricular enlargement
  Grade III: IVH with enlarged ventricles
  Grade IV: IVH and SEH with extension into brain beyond the ganglionic eminence
• this grading system is now used with U/S
• other grading systems exist
  • Three grade system differentiating extent of parenchymal damage:
    Grade 1: focal SEH
    Grade 2: extension into basal ganglia
    Grade 3: extension laterally or superiorly into cerebrum
  • germinal matrix vs. white matter hemorrhage
    B1 - isolated GMH or choroid plexus hemorrhage
    B2 - GMH with IVH, without ventricular enlargement
    B3 - GMH with IVH and ventricular enlargement
    W1-W4 - white matter hemorrhage from PVL
  • MRI findings are more sensitive for small foci of hemorrhage

Laboratory tests

• imaging most important
• screening for etiology, e.g., clotting parameters, antiplatelet antibodies (neonatal alloimmune thrombocytopenia)
• CSF may be bloody, and cytokine levels in the umbilical cord may have some predictive value

Macroscopy

• most useful in acute cases
• subdural and subarachnoid hemorrhages usually thin
  
  
• germinal matrix hemorrhage located in the anterior ganglionic eminence over the caudate, often unilateral and asymmetric, associated with IVH
  
  
• hemorrhagic conversion of ischemic lesions more bilateral and symmetric in posterior white matter
• IVH seldom due to extension of white matter hemorrhage
• large intraventricular blood degrades slowly
• progresive hydrocephalus in 20%
• lateral extension of germinal matrix hemorrhage can damage maturing brain parenchyma
• resolution of the hematoma (few months) results in focal, smooth-walled cyst adjacent to lateral ventricle

Histopathology

• blood cells intermingle with with parenchyma, especially noncohesive germinal matrix cells
• identification of disrupted blood vessel helps understand process, but not diagnosis
• hemorrhaging conversion of ischemic lesion - petechial hemorrhages, not usually hematoma
• hemosiderin apparent as early as day 3 after bleed
• reactive astroglial and microglial changes are subtle, inflammation mild
• surrounding necrotic tissue if hematoma large enough to cause secondary infarction
• after 1 month, only outer 1-2mm of a hematoma will have organized
• after months, residual hemosiderin and mineralization may be seen in the ventricle wall
• hydrocephalus in aborted fetuses
  - careful investigation for blood blocking cerebral aqueduct important for counselling

Experimental models

• studies of immature rabbits, dogs, cats, and sheep help us understand the mechanism of germinal matrix hemorrhage
• showed that fluctuations in arterial and venous blood pressure, and not asphyxia alone, can cause periventricular hemorrhage

Pathogenesis

• differs between types of bleeds
• in premature babies, germinal matrix hemorrhage occurs at thin-walled veins running through the germinal matrix, which does not offer good structural support to the vessels
• rupture can be due to mechanical distortions, but more frequently from fluctuations in intravascular and intracranial pressures
• endogenous fibrinolytic activity in the germinal matrix may contribute to the vascular fragility
• blockage of the aqueducts usually resolve, but if scarring occurs, there can be progressive ventricular enlargment
• bleeding can also be due to arterial reperfusion following ischemia
• also due to distal occlusion by thrombus or hematoma
• focal subarachnoid hemorrhage from rupture of small vessels of rare clinical significance
• clinically significant subdural hematomas tear into the falx cerebri, tentorium, or sinuses