Intraventricular Hemorrhage

Most common variety of neonatal intracranial hemorrhage
Characteristic of the premature infant
The incidence of IVH has declined, but the overall number of premature infants who survive with IVH is increasing because > 85% of infants 700-1500 grams survive.

Neuropathology

Subependymal germinal matrix
source of cerebral neuroblasts at 10-20 weeks
richly vascularized
converging veins with sharp "U-turn" (free communication)
Neuropathological consequences of IVH

Germinal matrix destruction
Periventricular hemorrhagic infarction
Hydrocephalus

acute
subacute-chronic

taken from: Volpe JJ. Mental Retardation and Developmental Disabilities Research Reviews;3:3-13(1997) p.5

Pathogenesis - multifactorial
- Intravascular factors
  - fluctuating cerebral blood flow
    1. ventilated preterm infant with RDS (much improved with the synchronized ventilators)
    2. hypovolemia
    3. hypercarbia
    4. "restlessness"
    5. PDA
    6. high FiO2
  - Increase in cerebral blood flow
    - systemic hypertension - pressure-passive circulation (auto reg in stable pre-term infants and not in sick pre-term infants)
      1. REM
      2. inadvertent noxious stim
      3. abdominal exam
      4. handling
      5. mydriatics
      6. tracheal suctioning
      7. pneumothorax
      8. exchange transfusion
      9. seizures
    - rapid volume expansion
    - hypercarbia
    - decreased hematocrit
    - decreased blood glucose
  - Increase in Cerebral Venous Pressure
    - Venous anatomy - U-turn in direction of venous flow
    - Labor and vaginal delivery
      1. skull deformation and venous obstruction
      2. length of labor (>10-12 hrs)
    - asphyxia
    - Respiratory disturbance
      1. high peak pressures on the vent
      2. pneumothorax
      3. tracheal suctioning
      4. asynchrony with vent
  - Decrease in cerebral blood flow (followed by reperfusion)
    - systemic hypotension: pressure-passive circulation
      1. perinatal hypoxia-ischemia
      2. apnea-bradycardia
  - Platelet and coagulation disturbance
    - appears significant only in certain patients
    - plts < 100,000 - especially important in infants <1500 g.
    - unclear role of abnormal coags
- Vascular factors
  - Tenuous capillary integrity
    - involuting, remodeling capillary bed
    - deficient vascular lining
    - large vascular and luminal area
      - pre-term infants born to mothers with pre- ecclampsia have lower incidence (2.5%)of IVH than age matched infants whose mothers did not have pre ecclampsia (17%) - thought to be secondary to advanced maturation of all tissues
  - Vulnerability of matrix capillaries to hypoxic-ischemic injury
    - vascular border zones
    - high requirements for oxidative metabolism
    - free-radical damage - role of SOD in prevention
- Extravascular factors
  - Deficient vascular support - deficient astrocyte development (early signs - 27-31wks)
  - Fibrinolytic activity - proteolysis active secondary to remodeling phenomenon in a non-permanent structure -allows extension of lesions
  - Postnatal decrease in extravascular tissue pressure
    - no good evidence
Characteristics and presentation
- premature infant with respiratory distress requiring mechanical ventilation
- 50% of IVH occur in first 24 hours
- 90% of IVH occur by 72 hours
Diagnosis
- Cranial ultrasound
- Clinical signs and symptoms
- Routine screening
  - >90% of hemorrhages occur by 4-5 days of life
  - most extensions of lesion occurs 3-5 days after the initial bleed
- criteria at Children's Hospital-St. Paul
  - < 30 wks GA and/or < 1500 g or older infants who require extreme ventilation and/or hemodynamic support (i.e. PPHN)
  - Initial scan 5-7 days
  - repeat at one month if grade I or normal
  - repeat in one week if > grade II or other anomalies
  - final exam at 35-36 weeks to look for PVL
- Able to follow regression, progression and/or accompanying features - PVL etc.
- Grading system (Papille)
  - I - germinal matrix only
  - II - germinal matrix with intraventricular blood
  - III - germinal matrix with intraventricular blood resulting in dilated vents
  - IV - intraparenchymal bleeding which may or may not include any of the other 3 findings.
- CT/MRI not practical in the early days of prematurity - temperature control and instability prevent these from being used early on (used pre-shunt placement)
Management
- Prevention - Prenatal interventions
  - prevention of premature birth
  - transportaion in utero
  - prenatal pharmacologic interventions (steriods, magnesium?)
  - optimal management of labor and delivery
- Prevention - Postnatal interventions
  - avoid rapid colloid infusion, hypertonic soln (Na bicarb), hypoxia, hypercarbia
  - synchronized ventilation
  - "minimal stimulation" as much as possible
  - normal blood clotting studies optimal
  - pharmacologic interventions
    - indomethacin
      1. decreases incidence of IVH in babies < 1300 grams
      2. may or may not decrease incidence of severe IVH
      3. mechanisms - decreased cerebral blood flow by inhibiting prostaglandin biosynthesis, inhibition of free radicals and accelerated maturation of germinal max microvessels
    - Vitamin E ?
      - conflicting studies - some show decrease in IVH or degree of IVH (Chiswick and colleagues) while others show increase in IVH incidence (Phelps and associates)
      - need more studies
      - mechanism
        
        free radical scavenger - antioxidant for germinal matrix to protect from HI injury
Hydrocephalus

65% have no prog. dilation
Progressive dilatation occurs for some time prior to signs and symptoms (i.e. - marked increase in OFC, bulging fontanel, split sutures)

Brain injury and ventricular dilatation
- cerebral white matter
  - axonal stretching, subsequent axonal loss and gliosis
  - decreased cerebral blood flow and decreased energy metabolism
serial ultrasounds
slowly progressive (>4 wks) - follow, ?LP's, ?diamox - many will stabilize
rapidly progressive - ventricular drainage (reservoir, VP shunt)
arrested progression and then resolution of dilatation - 5% develop hydrocephalus even at 6 years or older and nearly all require VP shunt at that time

Prognosis
- Long-term outcome - spastic motor deficits and major cognitive deficits
- degree of parenchymal injury is a key component to assessing the severity of outcome

(taken from: Vople JJ. Mental Restardation and Developmental Disabilities Research Reviews.3:3-12 (1997) )

Periventricular Leukomalacia
- Most severe and frequent cause of cerebral palsy in children surviving preterm birth.
- Poor correlation with postnatal events and PVL suggests that it may be antenatal events that trigger the cascade which results in PVL.
- Necrosis of the white matter in a characteristic distribution ("around the ventricles").
- Area is particularly vulnerable to changes in perfusion because of "watershed blood supply" and high metabolic rate due to differentiation of brain cell and supportive tissue in that area.
- Risk factors for PVL (Zupan et al Dev Med and Chil Neur 1996, 38, 1061-1067)
  1. 27-30 weeks gestation was highest incidence
  2. lower in the VLBW infants who were less than 27 weeks
  3. PROM more than 12 hours before delivery
  4. intra-uterine infection
  5. combination of PROM and intra-uterine infection was the highest incidence (22/98 babies = 22%)
- Inflammatory mediators may be playing a major role - may explain high correlation with infection
  - IL-6 levels in amniotic fluid have been looked at in embryo mice model
  - other inflammatory markers (TNF and endotoxins)
- Postnatal factors did not appear to be very significant except gastrointestinal processes such as NEC and volvulus - ? enteric pathogens with endotoxin release?
- Outcomes for PVL - depends on the ultrasound characteristic. Need to collect data regarding predisposing factors and combine this with early ultrasound findings to better counsel parents when the infants are initially being managed.
  - transient periventricular echodensities
    - at risk for minor handicaps - new info because initially thought that if it disappeared then it was not clinically significant
  - cystic PVL
    1. very high risk for cerebral palsy especially if the lesions extend front to back.
    2. cognitive delays occur in the children who are most affected on ultrasound and who have spastic quadriplegia
    3. higher incidence of mortality under the age of two in some studies - (Rogers et al J. Peds vol 125, 1, s1-s8) (Ringelberg and van de Bor Neuropediatrics, 24, 1993, 269-273) (Fawer et al, Arch Dis Chil 1987, 62, 30-36)