Perinatal Disorders (Gianani)

Question 1

Asphyxia and Hypoxic-Ischemic Encephalopathy (HIE) - when danger, differences betw. term and premature infants

Answer 1

• narrow window of a few days before and after birth = high risk of dying or suffering brain damage.
• caused by cerebral hypoxia and ischemia

term infants: HIE involves primarily the cerebral cortex and deep nuclei;

premature infants: affects more severely the white matter and is partially to blame for intraventricular hemorrhage (IVH).

• most common in the perinatal period, but may occur earlier in fetal life.

Question 2

When HIE pathology develops

Answer 2

when cerebral perfusion and oxygenation fall below a critical level

Infants with certain types of congenital heart disease (hypoplastic left heart syndrome, transposition of great vessels) who are chronically hypoxic in utero, have diffuse white matter loss, cortical abnormalities, and microcephaly at birth.

lesser degrees of hypoxia may cause subtle diffuse brain damage, and raises the issue that similar brain damage may develop in other related settings, e.g., placental insufficiency.

Question 3

asphyxia =

Answer 3

absence of pulse

Question 4

asphyxia and neonatal encephalopathy describe

Answer 4

an irritable or comatose newborn infant with low Apgar scores, apnea, poor feeding, hypotonia, acidosis, and, frequently, seizures.

Causes: intracranial hemorrhage, CNS infections, hyperbilirubinemia, severe CNS malformations, or metabolic disorders, but MOST- perinatal HIE.

Some die in the neonatal period; others –> intellectual disability, cerebral palsy, microcephaly.

Question 5

green placenta suggests

Answer 5

chorioamnitis

Question 6

knot in the umbilical cord suggestis

Answer 6

perinatal hypoxic lesion

Question 7

In our CIS case, Pre-eclampsia complicated by abruptio placentae with massive vaginal bleeding .
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Answer 7

Periventricular leukomalacia (preliminary stage- around the ventricles where most susceptible to ischemic damage) followed by multicystic encephalopathy.

Question 8

In our CIS case of E. Coli sepsis complicated secondary to Acute Chorioamnionitis.
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Answer 8

Asphyxia and Hypoxic-Ischemic Encephalopathy (HIE)

Question 9

what astrocytes do in damaged white matter

Answer 9

form a scar

.e.g. in infant with periventricular leukomalacia

Question 10

calcifications

Answer 10

An added feature of PVL and other necrotic brain lesions in fetuses and neonates is calcification, which makes lesions appear as whitish spots in the periventricular white matter. Large necrotic lesions cavitate in 2-4 weeks and remain cystic (cystic PVL). Small necrotic lesions do not cavitate at all or form small cysts that collapse into glial scars (non-cystic PVL).

Question 11

white matter necrosis with ischemic injury

Answer 11

Bilateral, roughly symmetric foci of white matter necrosis develop around the lateral ventricles, especially in the frontal and occipital lobes. The evolution of these lesions is similar to infarcts, i.e. liquefaction, phagocytosis, cavitation, and gliosis. Axonal damage is evident by the presence of axonal swellings, which may be obvious on H&E stains or detected with immunostains to Beta Amyloid Precursor Protein.

Question 12

The clinical manifestations of PVL

Answer 12

spastic diplegia or tetraplegia due to damage of corticospinal tract axons, visual impairment due to damage of the optic radiations, cognitive deficits, and seizures. The clinical deficits of PVL are not apparent initially. They are only fully appreciated months or years after the injury occurs.

• • PVL is the substrate of cerebral palsy (CP). The leading risk factor in 75% of CP is prematurity and the underlying pathology in most of CP is PVL.
• *

Question 13

In mature infants, severe perinatal HIE can cause

Answer 13

the cortex and white matter to melt away.. In other cases, destruction of cortex and white matter results in the formation of multiple cavities traversed by a web of delicate glial strands. The cavities contain fluid, debris, and macrophages. This entity is called cystic encephalomalacia or multicystic encephalopathy.

Question 14

The outcome of neonatal encephalopathy correlates with

Answer 14

the topography of the lesions. Brainstem injury usually causes death in the newborn period, because of damage of vital centers of respiration and cardiac function. Infants with cortical lesions survive but have intellectual disability and cerebral palsy. Given the central role of the thalamus in cognition and consciousness, severe injury leads into a persistent vegetative state.

Question 15

Porencephaly

Answer 15

fluid-filled cavity in the brain

Question 16

Schizencephaly

Answer 16

something missing from the brain

Question 17

hydranencephaly

Answer 17

the cerebral hemispheres are replaced by a thin-walled, fluid-filled cyst. The aqueduct is usually atretic, and increased fluid pressure causes the cyst (and the head) to enlarge. There is variable preservation of the inferior frontal, temporal, and occipital lobes, and of the basal ganglia and diencephalon. The brainstem and cerebellum are usually preserved. Hydranencephaly is not a malformation, but a disruption caused probably by ischemia in utero in the territories of the carotid arteries. Some cases of perinatal HIE come close to hydranencephaly. Babies with hydranencephaly may appear normal initially because the brainstem is intact. The empty cranial cavity transilluminates.

Question 18

GERMINAL MATRIX HEMORRHAGE

Answer 18

is a frequent lesion in premature babies who also have hyaline membrane disease and the respiratory distress syndrome.

It is much more frequent in babies weighing 500-750 gm. It is a major cause of morbidity and mortality in the newborn period and of cerebral palsy and mental retardation later on.

Question 19

BILIRUBIN ENCEPHALOPATHY

Answer 19

• Kernicterus (Bilirubin encephalopathy) is an acquired metabolic encephalopathy of the neonatal period.
  Its etiology and pathogenesis overlap to some extent with HIE.

Kernicterus is caused by unconjugated hyperbilirubinemia that develops either as a result of hemolytic disease (Rh incompatibility, hereditary spherocytosis, other hemolytic disorders) or because of inability of the liver to conjugate bilirubin. The latter is seen in a rare defect of glucuronyl transferase, the Crigler-Najjar syndrome.

Unbound, unconjugated, circulating bilirubin crosses the blood-brain barrier and, because it is lipid soluble, it penetrates neuronal and glial membranes.

Question 20

Babies with bilirubin encephalopathy are

Answer 20

are lethargic, hypotonic or hypertonic, and have a high pitched cry, opisthotonus, seizures, and may die if bilirubin is not lowered. The MRI shows high T2 signal in the globus pallidus. Patients surviving kernicterus have severe permanent neurologic symptoms (choreoathetosis, spasticity, hearing loss, ataxia, mental retardation). Less severe injury is associated with mild neurological abnormalities, including hearing loss, which may be the only abnormality.