Intracranial hemorrhage in the term preterm infant

Intracranial Hemorrhage in the Term & Preterm Infant Whit Walker, MD, MS Clinical Associate Professor Division of Neonatology Greenville Hospital System September 2011 Major Types of Intracranial Hemorrhage in the Term Infant  Subdural Hemorrhage  Primary Subarachnoid Hemorrhage  Intracerebellar Hemorrhage  Intraventricular Hemorrhage  Miscellaneous Intraparenchymal hemorrhage Incidence of Asymptomatic Intracranial Hemorrhage A large series of cranial ultrasounds in 1000 healthy, consecutively born term infants revealed that intracranial hemorrhage is not uncommon with 3.5% of these infants having detectable bleeds: subependymal locus in 2%, choroid plexus locus in 1.1% and parenchymal locus in 0.4% Heibel M et al Early diagnosis of perinatal cerebral lesions in apparently normal full-term newborns by ultrasound of the brain Neuroradiology 35:85-91, 1993 Significance of Term Infant Intracranial Hemorrhage Type of Hemorrhage Maturation of infant Relative Frequency Usual Clinical Gravity Subdural Full term > premature Uncommon Serious Primary subarachnoid Premature > full term Common Benign Intracerebellar Premature > full term Uncommon Serious Intraventricular Premature > full term Common Serious Miscellaneous Intraparenchymal + multiple sites Full term > premature Uncommon Variable Neuropathology of Subdural Hemorrhage Source of Bleeding Location of Hematoma Tentorial Laceration Infratentorial (posterior fossa) or supratentorial Straight sinus, vein of Galen, transverse sinus and infratentorial veins Occipital Osteodiastasis Infratentorial (posterior fossa) Occipital sinus Falx Laceration Longitudinal cerebral fissure Inferior sagittal sinus Superficial Cerebral Veins Surface of cerebral convexity Pathogenesis of Neonatal Subdural Hemorrhage Is most commonly a traumatic lesion with the vast majority of infants affected being full-term infants Many predisposing factors exist: At risk Predisposing Factors Mother Primaparous Older multiparous Small birth canal Large full-term infant Premature infant (unusually compliant skull) Precipitous Prolonged Breech extraction Foot, face, brow presentation Difficult forceps or vacuum extraction Difficult rotation Infant Labor Delivery Clinical Presentation of Subdural Hemorrhages Rapidly Lethal Syndromes: Usually a tentorial laceration with massive infratentorial hemorrhage is associated with neurological disturbances from time of birth Infant typically presents with stupor or coma, unequal pupils, nuchal rigidity, retrocollis and/or opisthotonic posturing Can rapidly progress to stupor, fixed and dilated pupils, bradycardia and ataxic respirations Occipital osteodiastasis is a prominent traumatic injury associated most commonly with breech presentations and includes traumatic separation of cartilagenous joint between squamous and lateral portions of the occipital bone, laceration of the cerebellum as well as rupture of occipital sinuses Less Malignant Posterior Fossa Subdural Hematomas: Clinically present in phases: (1) no neurological signs for for several hours to 3-4 days (2) progression to increased intracranial pressure with full fontanelle, irritability and lethargy and (3) signs of brainstem compromise with respiratory abnormalities, apnea, bradycardia and oculomotor abnormalities Seizures will occur in the majority of these infants Clinical Presentation of Subdural Hemorrhages Falx Laceration: When symptoms present, they are usually bilateral based on the loci of the lesion Striking neurological signs not usually occur unless the clot extends infratentorially Cerebral Convexity Subdural Hemorrhage: With minor hemorrhage, minimal-to-no clinical symptoms may occur Focal symptoms may occur, usually on the 2nd or 3rd day of life Seizures are the most common presentation and are usually focal The most distinctive neurological sign is dysfunction of the third cranial nerve on the side of the hematoma (a nonreactive or poorly reactive, dilated pupil) Another possible presentation of subdural hemorrhage with few initial clinical signs is the development of chronic subdural effusion over the first few months of life Major Causes of Increased Blood Pressure or Cerebral Blood Flow in the Premature Infant Related to “Physiological” Events Postpartum Rapid Eye Movement Sleep Related to Caretaking Procedures Noxious stimulation Motor activity: spontaneous or with handling Tracheal suctioning Instillation of mydriatics Related to Systemic Complications Pneumothorax Rapid volume expansion: exchange transfusion, other rapid colloid infusions Early ligation of patent ductus arteriosus Related to Neurological Complications Seizures Asphyxia Effects of Changes in Cerebral Blood Flow with Changes in Mean Arterial Pressure Short-Term Outcome of Intraventricular Hemorrhage Severity of Mortality Progressive Hemorrhage Rate (%) Vent Dilation (% survivors) Mild (IVH Grade I-II) Moderate (Grade II) 10 Severe (Grade III) 20 Severe + periventricular hemorrhagic infarction 20 55 50 80 Post Hemorrhagic Hydrocephalus Etiology: Acute (blood clot) Chronic (obliterative arachnoiditis and aqueductal obstruction) Temporal Features: progresses 1-3 weeks post bleed Rapid evolution related to severity of bleed Head growth or signs of elevated intracranial pressure follow ventricular dilation by days or weeks Posterior horns more affected than anterior horns Long-Term Developmental Outcome following IVH in Premature Infants Severity of Hemorrhage Grade Grade Grade Grade I II III IV Incidence of Definite Neurological Sequelae (%) 5% 15% 35% 90% Prevention of GMH-IVH: Prenatal Interventions Prevention of Premature Birth Transportation in utero Prenatal Pharmacological Interventions Phenobarbital Vitamin K Glucocorticoids * Magnesium sulfate Optimal Management of Labor & Delivery * The only clearly effective prenatal protective intervention Effect of Antenatal Steroids on Severe IVH Prevention Prevention of GMH-IVH: Postnatal Interventions Newborn resuscitation Correction of fluctuating cerebral blood flow velocity Muscle paralysis - pancuronium appears effective Correction or prevention of other hemodynamic disturbances Correction of abnormalities of coagulation Fresh frozen plasma Vitamin K Pharmacological interventions Phenobarbital - marginally beneficial Indomethacin - confirmed beneficial Ethamsylate Vitamin E Indomethacin Mechanism s of Effect in Preventing IVH Indomethacin is a specific inhibitor of prostaglandin biosynthesis This results in specific increases in cerebral vascular resistance and decreases in cerebral blood flow by 20% - 30% at doses of 0.05 - 0.2 mg/kg Blockade of the prostaglandin cyclo-oxygenase pathway also decreases production of free radicals And finally, indomethacin appears to enhance maturation of neuronal microvessels (increased laminin deposition in basement membranes) Decreases in infant CBF begin within minutes and last for hours As a cautionary note, high doses of indomethacin have been shown to decrease cerebral oxygen consumption and produce coma in animal models Summary Effects of Prophylactic Indomethacin Trials to Prevent Severe (Grade III-IV) Intraventricular Hemorrhage Ment Regimen of Prophylactic Indomethacin to Prevent Severe IVH Patient Population Most Likely to Benefit: Those infants < 1250 grams birth weight Dosing Regimen: 0.1 mg/kg once per day times days intravenously Typically given slowly (over 1-2 hours) First dose to be administered between 6-12 hours of age Conveniently closes the ductus arteriosus in 95% of treated patients Side Effects of Prophylactic Indomethacin Therapy Short Term: Decreased urine output Caution in using in patients with: thrombocytopenia (platelet count < 50,000) significant hyperbilirubinemia Use of postnatal steroids and indomethacin at the same time is associated with increased risk of intestinal perforation (2-3 fold higher risk) Long Term: Conflicting reports of benefit-to-harm ratio on neurodevelopmental outcome Prevention of GMH and IVH: Summary Prevent premature delivery If premature delivery is inevitable, assure optimal fetal environment, provide antenatal steroids, consider Cesarean delivery for most premature infants Provide skilled personnel in the delivery room Prevention of GMH and IVH: Summary First days of life is most critical in infants < 32 weeks: Administer vitamin K Limit fluid intake Control blood pressure: avoid fluctuating or increased BP, hypercarbia, hypoxemia, acidosis, hyperosmolar fluids, rapid volume expansion, pneumothorax and seizures Control acid-base status Consider prophylactic Indomethacin Begin screening for IVH at days of age [...]... originates from the choroid plexus (vs the germinal matrix in the preterm infant) However, in asymptomatic infants, the blood just as frequently originates from the subependymal germinal matrix as from the choroid plexus In the largest series of term infants with symptomatic IVH, the majority of these infants had accompanying bleeding noted in the thalamus In addition, the majority of these infants (75%)... shunting Most term infants will have some handicaps; most handicaps are motor and not cognitive Intraventricular Hemorrhage in the Term Infant A small minority of these hemorrhages are caused by intraventricular expansion of blood from major hemorrhagic infarctions, ruptured vascular lesions (AVMs, aneurysms), tumors or coagulopathies In term infants, symptomatic blood in the ventricles typically originates... commonly at the aqueduct of Sylvius or more diffusely at the level of the arachnoid villi Intraventricular Hemorrhage Imaging and Pathology Parenchymal Hemorrhage in the Premature Infant  These are very serious events occuring in 315% of all hemorrhages  The blood seen in these events originates from probable infarction of periventricular white matter venous drainage The possibility of ischemic injury... subependymal and subpial germinal matrices Extension from intraventricular hemorrhage Intracerebellar Hemorrhage via CT Imaging Prognosis in Intracerebellar Hemorrhage The outcome in premature infants is uniformly poor In term infants, the outcome is more variable Many will need surgery (especially those whose neurological condition continues to deteriorate) Nearly one-half of term infants will develop hydrocephalus... of the terminal vein or its precursors Germinal Matrix Blood Supply Germinal Matrix Hemorrhage (GMH)  Most GMH arise in the region of the caudate nucleus (over the body of the caudate nucleus in more immature infants and over the head of the caudate with more mature infants)  Subependymal cysts can develop post GMH  GMH events are not usually associated with adverse neurodevelopmental outcomes Intraventricular... deliveries (however, 25% of these infants did not have difficult deliveries and were not asphyxiated) Intraventricular Hemorrhage in the Term Infant: Clinical Features and Outcome In early onset symptomatic IVH, apnea, irritability, stupor and seizures usually focal are noted Other features can include fever, jitterness, and signs of increased intracranial pressure 50% of infants may present between... Intraventricular Hemorrhage (IVH)  GMH events rupturing through the ependyma into the floor of the lateral ventricles are referred to as IVH  Blood can fill part or all of the entire ventricular system spreading through the Foramen of Monro, the 3rd ventricle, the aqueduct of Sylvius, the 4th ventricle, and the foramina of Luschka and Magendie to collect around the brainstem in the posterior fossa... children in Jackson Hole, Wyoming USA Intraventricular Hemorrhage in the Premature Infant The Germinal Matrix The germinal matrix is an abundantly distributed mass of immature blood vessels, neuroblasts and glioblasts overlying the caudate nucleus and periventricular zones of the ventricular system The neural components of this tissue undergo rapid mitotic activity and migrate to other parts of the cerebrum... that withblood in the CSF, the most common source is intraventricular blood and not subarachnoid blood The primary source of blood is presumed to be small vascular channels derived from leptomeningeal arteries present during brain development or bridging veins within the subarachnoid space Primary Subarachnoid Hemorrhage: Clinical Presentation The most common presentation is minor to no clinical symptoms... typically GOOD (90% normal) Intracerebellar Hemorrhage This lesion is more common in premature infants However, it is more frequently diagnosed at autopsy in both premature and term infants (it is difficult to see on CT scan) There are 4 major types of intracerebellar bleeds: Primary intracerebellar hemorrhage Venous (hemorrhagic) infarction Extension into cerebellum of intraventricular or subarachnoid ... typically originates from the choroid plexus (vs the germinal matrix in the preterm infant) However, in asymptomatic infants, the blood just as frequently originates from the subependymal germinal matrix... from the choroid plexus In the largest series of term infants with symptomatic IVH, the majority of these infants had accompanying bleeding noted in the thalamus In addition, the majority of these... Types of Intracranial Hemorrhage in the Term Infant  Subdural Hemorrhage  Primary Subarachnoid Hemorrhage  Intracerebellar Hemorrhage  Intraventricular Hemorrhage  Miscellaneous Intraparenchymal