INTRAVENTRICULAR HEMORRHAGE

Definition and Incidence

Hemorrhage into the periventricular subependymal germinal matrix (SEH) with subsequent extension into the ventricles (IVH) is a common cause of death and morbidity in the preterm neonate less than 32 weeks gestation. Most vulnerable is the extremely low birth weight infant of less than 26 weeks gestation. In infants weighing 500-750g, IVH occurs in about 45%.

The incidence of hemorrhage in infants weighing less than 1500 gm was reported to be approximately 40‑50% in the early 1980's and decreased to approximately 20% in the late 1980s. That number has remained relatively unchanged since that time. In 2010, the incidence of SEH/IVH at UTMB was ~20% in infants <1500 gm birth weight.

Neuropathology

The primary lesion is bleeding from small vessels, principally capillaries, in the area of the subependymal germinal matrix. In most infants the hemorrhage originates in the matrix at the level of the head of the caudate nucleus and foramen of Monro. In extremely premature infants of less than 28 weeks, the lesion often is at the level of the body of the caudate.

In about 80% of cases, the hemorrhage ruptures through the ependyma and into the ventricular system.  Blood spreads through the ventricles, then passes through the medial and lateral apertures of the fourth ventricle (the foramen of Lushka and Magendie) and collects in the basilar cisterns of the posterior fossa.  Subsequent to the hemorrhage, an obliterating posterior fossa arachnoiditis may occur and cause obstruction to CSF flow with resultant post-hemorrhagic hydrocephalus.

In particularly severe hemorrhages, the periventricular hemorrhage appears to extend into the cerebral parenchyma and frequently leads to the development of porencephalic cysts. These parenchymal hemorrhages are not extensions of matrix bleeding, but areas of concurrent hemorrhagic infarction in the parenchyma that occur prior to or near the time of the IVH.  This extensive infarction may well account for the severe neurological deficits observed on follow‑up.

Pathogenesis

The factors that must be considered in the pathogenesis of IVH are:

1. Intravascular Factors. This includes the anatomic and physiologic determinants of the distribution and regulation of cerebral blood flow and blood pressure within the germinal matrix area. 

a. Distribution of Cerebral Blood Flow to the Periventricular Region. The vascular supply to the germinal matrix area is particularly prominent from 24 to 32 weeks gestation.   A rich arterial supply to this region is derived principally from the anterior cerebral artery via Heubner's artery and from the middle cerebral artery via the deep lateral striate arteries.  Before 32‑34 weeks gestation a disproportionately larger blood flow goes to the germinal matrix area than to the cerebral cortex.   Therefore, any factors that cause increased cerebral blood flow will preferentially tend to overperfuse the periventricular area.

b. Regulation of Cerebral Blood Flow. Cerebral blood flow in the premature infant, particularly the infant who sustains some degree of asphyxia, is pressure‑passive. That is, cerebral blood flow varies directly with arterial pressure, and blood flow to the matrix area will be very sensitive to changes in arterial blood pressure. This pressure‑passive nature of cerebral blood flow is very important because elevations in blood pressure, blood flow, or both have been observed during a number of situations. Blood pressure increase in the first minutes after delivery, with motor activity (either spontaneous or associated with handling), and during seizures, colloid infusions, exchange transfusions, apnea, and asphyxia. Recent studies have shown the importance of fluctuating arterial blood pressure in the pathogenesis of IVH.

Asphyxia is an event that may particularly increase risk of hemorrhage for 3 reasons. First, hypercapnia with increased cerebral blood flow and perivascular acidosis; second, the diving reflex with preferentially increased cerebral blood flow; and third, arterial hypertension with loss of ability to autoregulate cerebral blood flow.

Certain therapeutic maneuvers may also cause marked increase in cerebral blood flow - rapid infusion of volume expanders, use of hyperosmolar solutions (i.e., glucose or bicarbonate), and use of pressor agents.

c. Cerebral Venous Pressure and Flow. Increased venous pressure may cause increase in pressure within the periventricular capillaries. This may occur with hypoxic cardiac failure or with positive pressure ventilation. Elevated venous pressure then may promote rupture of vessels and subsequent hemorrhage.

2. Germinal Matrix Vasculature. The capillary bed in the matrix area is relatively immature and vulnerable to rupture. The endothelial cells are dependent on oxidative metabolism and are readily injured by hypoxia.

3.  Extravascular Factors. The germinal matrix area is a gelatinous region that provides poor support for the small vessels that course through it. It also contains an excessive amount of fibrinolytic activity which may explain the frequent extension of the hemorrhage. 

Clinical Features of IVH

The time of onset is most often at some time within the first 2 to 4 days of life, although the occurrence may be much later.   In one large series the median age of onset was 38 hours. The occurrence of hemorrhage may be accompanied by two basic clinical syndromes.

The first is catastrophic collapse consisting of neurological deterioration that evolves in minutes or hours and consists of stupor or coma, respiratory abnormalities, seizures, unreactive pupils, flaccid quadraparesis, and absent extraocular movements. This is accompanied by falling hematocrit, bulging fontanelle, systemic hypotension, bradycardia, temperature instability, metabolic acidosis, glucose abnormalities.

The second syndrome is more subtle and follows a somewhat saltatory course. There is a change in level of alertness (either stupor or an irritable, hyperalert state).   A clue to the occurrence of IVH may be a falling hematocrit or failure of the hematocrit to rise after transfusion.

Diagnosis of IVH

At the present time, the most reliable and convenient method of diagnosis is by portable ultrasound scanning using a transducer applied to the skin over the anterior fontanelle. By manipulating the transducer over the fontanelle, various sections of brain can be examined in both coronal and sagittal planes.

CT or MRI scanning are also excellent means of diagnosing hemorrhage but much less convenient because the infant must be transported to the scanner.

CSF examination may be useful as well. Elevated RBC count, xanthochromia and elevated protein content suggest bleeding. Glucose usually becomes very low within 5‑15 days of the hemorrhage (hypoglycorrhacia).

No uniform grading system has been agreed upon. There are at least 3 grading systems in use. This had led to much confusion in terms of categorizing the severity of the hemorrhage in relation to immediate and long term outcome. The grading system we have found most useful is the one originally described by Papile and coworkers.

Grade I ‑ Subependymal germinal matrix hemorrhage only

Grade II ‑ Extension of hemorrhage into the ventricles without ventricular dilatation

Grade III ‑ Intraventricular hemorrhage with ventricular dilatation

Grade IV - Grade III plus parenchymal involvement.  Sometimes, only parenchymal involvement is noted initiall .

Prognosis of IVH

The outcome of IVH is not uniformly grim. Over the short‑term, there is a distinct relationship between the severity of hemorrhage by CT or US and the prognosis.  With mild hemorrhage, most babies survive, and hydrocephalus is relatively uncommon.  Even with moderate bleeds, survival is the rule and risk of hydrocephalus is relatively low. Severe lesions carry the worst prognosis for death or hydrocephalus or long-term neurologic impairment.

Grade I and II hemorrhages appear to carry no increased risk for major handicap. Grade III and IV hemorrhages are associated with increased risk of major disability.

Management of IVH

1. Prevention

  1. Prenatal medical intervention ‑ certain drugs may reduce the incidence of IVH. The  administration of magnesium sulfate during premature labor is associated with decreased risk of IVH.   In addition use of steroids antepartum may reduce the incidence or severity of RDS and hence decrease the likelihood of IVH.
  2. Transportation in utero ‑ very low birth weight babies born outside perinatal centers and transported have higher risk of IVH than infants born at such centers. If at all possible, potentially high risk mothers and fetuses should be transferred before delivery.
  3. Postnatal drug therapy - Phenobarbital is occasionally used to decrease agitation,but has no direct effect on the incidence of IVH.
  4. Avoidance of cerebral hyperperfusion ‑ careful attention to cerebral perfusion and avoidance of events that lead to sudden increases in cerebral perfusion are crucial.  IVH has been shown to occur with fluctuations in blood pressure, after rapid volume expansion, following blood transfusion, and after pneumothorax.   In fact, a striking association between pneumothorax and IVH has been documented and is perhaps related to increases in cerebral blood flow velocity and blood pressure occurring at the time of pneumothorax.

2. Acute Management. Once hemorrhage occurs, initial therapy is primarily supportive. The major aspect is maintenance of cerebral perfusion by maintaining adequate arterial blood pressure. Other important aspects of care include:

a. Maintain adequate ventilation/oxygenation          

b. Maintain blood pressure

c. Maintain glucose homeostasis

d. Control seizures

e. Correct acidosis

f. Maintain hematocrit

g. Maintain fluid and electrolyte balance

h. Decrease intracranial pressure

3. Post hemorrhagic hydrocephalus. In surviving infants, the incidence of hydrocephalus has been estimated at 15-22%

a. Prevention ‑ at present no prophylactic intervention for post-hemorrhagic hydrocephalus is known. In one study, serial lumbar punctures instituted at the time of diagnosis of hemorrhage were not found to be effective in prevention of subsequent hydrocephalus.

b. Natural history‑ in a multi-center study in the 1990s of 87 infants of <1500 grams who had severe IVH, 20 developed early rapidly progressive hydrocephalus or death; 47 developed no hydrocephalus; 20 developed ventriculomegaly with normal intracranial pressure.  Of the 20 with progressive hydrocephalus, 9 exhibited arrest of the progression within 31 days and 11 of the 20 developed progressive hydrocephalus after a stabile period of up to 12‑84 days.   Thus, observation is necessary for many weeks after the hemorrhage, and ventricular size should be serially assessed by ultrasound.  

A more recent report from 1999-2008 found that 29% of infants with severe IVH developed symptomatic post hemorrhagic hydrocephalus requiring surgical intervention and 21% required shunt placement. Of note is that not all infants with ventriculomegaly progress to hydrocephalus (Limbrick et al, 2010).

(Source: Limbrick DD Jr, Mathur A, Johnston JM, Munro R, Sagar J, Inder T, et al. Neurosurgical treatment of progressive posthemorrhagic ventricular dilation in preterm infants: a 10-year single-institution study. J Neurosurg Pediatr. 2010; 6:224-230.)

c. Treatment options.

i. Serial ventricular punctures may be effective in management and are often temporary solutions until the CSF protein declines to acceptable levels. At that time, an Omaya reservoir or ventriculostomy is typically placed until the infant is large enough for a VP shunt (~2 kg).   Serial lumbar punctures are seldom successful because communication must exist between the lateral ventricles and the lumbar subarachnoid space. It is also necessary that adequate volume of CSF be removed ‑ in the range of 10‑20 cc per LP.

ii. Drugs that decrease CSF production such as isosorbide, glycerol, or acetazolamide are occasionally used.

iii. Placement of a ventriculostomy or ventriculoperitoneal shunt carries a variety of complications, including infection and malfunction.  An additional problem with VP shunts in small premies is ulceration of the scalp overlying the shunt.

4. Screening Ultrasound Examinations

A screening cerebral ultrasound examination should be done on all preterm infants of <1500 gm or of 31 weeks gestation or less who are admitted to the ISCU. The initial examination should be done at 7 days of age, or anytime (earlier or later), if hemorrhage or hydrocephalus is suspected. If periventricular or intraventricular hemorrhage is present, sonography should be repeated in 7‑10 days and at regular intervals thereafter if evidence of ventricular dilatation is present.

Older prematures (over 31 weeks) and term babies should have ultrasonography done as indicated based on their individual clinical histories, problems, and course. Indications in term babies include: abnormally increased or increasing head circumference, clinical signs of major CNS malformation, infection ‑ congenital (calcifications) or ventriculitis, suspected A‑V malformation, and severe trauma.

CT scan should be considered for situations where ultrasound is normal and a peripheral lesion (subdural hemorrhage, etc.) is suspected. Other indications include asphyxia, seizures, tumor, situations where contrast is required, and situations where ultrasound is normal and neurological signs are present.

References

Wilson-Costello D, Friedman H, Minich N, Fanaroff AA, Hack M. Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. Pediatrics. 2005; 115 :997-1003.

Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500gm. J Pediatr. 1978; 92: 529-534.

Philip AG, Allan WC, Tito AM, Wheeler LR. Intraventricular hemorrhage in preterm infants: declining incidence in the 1980s. Pediatrics. 1989; 84 :797-801.


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