= HIE = HYPOPERFUSION INJURY
Frequency: 2–9÷1,000 live births
Cause:
- in utero← interruption of placental blood flow + gas exchange:
- fetal factors: fetomaternal hemorrhage, thrombosis, bradycardia, disrupted umbilical circulation (tight nuchal cord, cord prolapse)
- inadequate placental perfusion: maternal hypotension, preeclampsia, placental abruption, chronic vascular disease
- impaired maternal oxygenation: asthma, pulmonary embolism, pneumonia, CO poisoning, severe anemia
- postnatally: severe hyaline membrane disease, pneumonia, meconium aspiration, CHD
- older child: cardiac arrest, near drowning, asphyxiation (strangling), barbiturate intoxication → circulatory / respiratory failure
Pathophysiology:
⇓cerebral blood flow (= ischemia) and ⇓ blood oxygenation (= hypoxemia) → shift in metabolism from oxidative phosphorylation to inefficient anaerobic oxidation → rapid energy depletion, acidosis, release of inflammatory mediators and excitatory neurotransmitters (particularly glutamate), free radical formation, calcium accumulation, lipid peroxidation → necrosis → cell death
- low Apgar score (0–3) at birth, multiorgan dysfunction
- profound metabolic acidosis in cord blood
- seizures, coma, hypotonia, abnormal EEG
Prognosis:
- full recovery
- neonatal death (20%)
- significant neurologic sequelae (25%): one of the most common causes of cerebral palsy (spastic quadriplegia, diplegia)
DDx: metabolic encephalopathy from inborn errors of metabolism (congenital lactic acidosis, urea cycle disorder, amino aciduria), congenital + neonatal CNS infections, congenital malformations, severe birth trauma
Temporal evolution and optimal imaging modality:
US:
- increased parenchymal echogenicity in days 2–10
CT:
- parenchyma of low attenuation in days 1–7
MR:
- immediate ⇑ lactate (spectroscopy most useful within hours) → pseudonormalization ~ 24 hours after birth
- restricted diffusion (DWI in days 1–5 most sensitive test) → pseudonormalization 5 days after birth
- T1WI and T2WI (most useful after day 2):
- T2 prolongation ← edema
- T2 shortening ← mineral deposition
Hypoperfusion Injury in Older Child
Location:
- mild HIE: watershed zones
- severe HIE: gray matter of cerebral cortex, basal ganglia, hippocampi + sparing of brainstem and cerebral white matter
CT:
- decreased attenuation of cortical gray matter (diffuse edema)
- loss of normal gray matter–white matter differentiation
- bilateral decreased attenuation of basal ganglia and thalami
- “reversal” sign = higher attenuation of white matter
- “white cerebellum” sign = lower attenuation of supratentorial brain with relative sparing of cerebellum + brainstem
MR:
- increased signal intensity on DWI (after 2 hours)
- subtle increased intensity + swelling of affected areas (after >24 hours)
- diffuse T2 prolongation in subcortical white matter (= delayed postanoxic leukoencephalopathy)
Hypoperfusion Injury in Preterm Infant
Gestational age:<36 weeks
Frequency: 5% of infants born <32 weeks EGA
Location:
- periventricular white matter (mild hypotension)
- thalami, brainstem, cerebellum = metabolically most active tissue (severe hypotension)
Consequence:
- Germinal matrix hemorrhage
- Periventricular leukomalacia
US:
- globular hyperechoic change = PVL (early)
- localized anechoic / hypoechoic lesions = cystic PVL (2–6 weeks later)
- progressive periventricular necrosis + ventricular enlargement = end-stage PVL
MR:
- hyperintense areas on T1WI within larger hyperintense area on T2WI (early)
- ventricular enlargement with irregular margins of body + trigone of lateral ventricles (later):
- loss of periventricular white matter with ↑ T2 signal
- thinning of corpus callosum
Prognosis: germinal matrix hemorrhage upon reperfusion to ischemic tissues
Cx: cerebral palsy in up to 19% of infants <28 weeks EGA
- 50% of cerebral palsy cases occur in infants born prematurely
Hypoperfusion Injury in Term Infant
Gestational age:≥36 weeks
Location:
Mild to moderate hypoxic-ischemic injury causes lesions in watershed areas, parasagittal cortex, and subcortical white matter, while sparing brainstem, cerebellum, deep gray matter structures.
Severe hypoxic-ischemic injury involves the lateral + ventral thalamus, posterior putamen, perirolandic sensorimotor cortex, and corticospinal tracts.
Injury pattern:
- peripheral pattern (= parasagittal, watershed / borderzone) - more common
MR:- restricted diffusion in parasagittal cortex and underlying subcortical white matter
- cortical thinning + diminution of underlying white matter
- ex vacuo dilatation of adjacent lateral ventricles in trigones and occipital horns
- basal ganglia–thalamus pattern
MR:- bilateral abnormal T1 hyperintensity (days 3–7) in posterolateral putamen, ventrolateral thalamus, corticospinal tract
- absent posterior limb sign = loss of normal mildly hyperintense T1 focus in posterior limb of internal capsule
- indistinct / abnormally iso- or hyperintense T2 foci relative to adjacent gray matter instead of normal hypointense foci in posterolateral putamen, posterior limb of internal capsule, ventrolateral thalamus
Prognosis: 15–20% of neonatal mortality; significant developmental deficits in 25%