- Hypotonia: Flaccid paresis, floppy posturing, and abnormal reflexes may be present.
- Seizures (often subclinical): Respiratory or cardiac rhythm abnormalities, and muscle tone fluctuations may occur.
- Ophthalmoplegia: Sixth nerve paresis, conjugate deviations (seizures, hemiparesis), and sunsetting phenomenon may be seen.
- Posturing: Larger hemorrhages can present with further muscle tone changes and abnormal posturing.
- Irregularities in respiration and cardiac rhythms: Apnea, bradycardia, and hypotension can be seen after large IVH.
- Metabolic acidosis: Metabolic acidosis may be due to hypovolemia, maternal acidosis, congenital heart disease, or renal disease. It predisposes to intracerebral bleeding.
- Pupillary dilation: This is more often a sluggish reaction to light, rather than true mydriasis.
- Anemia: There may be an unexplained drop in hematocrit (>10%).
If the hemorrhage progresses to hydrocephalus, additional signs are as follows:
- Bulging fontanelle: This sign is very easy to assess but is not an objective measurement. Even a full but soft fontanelle can indicate active hydrocephalus.
- Separation of sutures: Neonatal sutures, still not fused, become splayed due to the separation of the cranial bones, as a result of the increased ICP.
- Distended scalp veins: There is unidirectional flow from intracranial to extracranial veins (Spalteholz valves). Increased ICP is transmitted to them.
- Sunsetting: Upward gaze palsy (“sunset” eyes sign) may be present.
- Increasing head circumference: A rapidly increasing head circumference that crosses the centile curves with a rate larger than 1.5 – 2 cm/week or 2 mm/day may be seen. Head growth of the premature infant is increased during the “catch up phase” when he/she is able to be fed adequately, and this growth has to be differentiated from an abnormal head circumference increase (42).
- CSF analysis Biochemical analysis for protein – glucose and microbiology for WBCs (neutrophils, lymphocytes) and RBCs. Due to the underdeveloped blood – CSF barrier in preterm neonates, higher rates and concentrations should be expected as normal, compared to findings in older children and-full term infants. Acceptable levels for testing of CSF in preparation for shunting are a WBCs count that is less than 15/mm3, a RBC count of up to 1000/mm3, a protein level below 150mg/dl and a glucose levels that is 2/3 of serum glucose concentration (20 – 70 mg/dl) (9).
Ultrasonography is a noninvasive, low-cost, and easily available examination in most neonatal intensive care units that can be done at the bedside.
- Accurate assessment: The cranial ultrasound has a very important role in the initial assessment and follow-up of premature infants. Performed through the open anterior fontanelle (and, occasionally, posterior fontanelle), it provides direct and accurate data about ventricular size, exact location and extension of the hematoma, cortical mantle thickness, and periventricular white matter condition. With today’s advanced hardware, cranial ultrasonography has a sensitivity and specificity greater than 91% each (5, 83, 91).
- Disadvantages: Poor imaging of the posterior fossa and operator dependency.
- Early detection of developing hydrocephalus: Combined with clinical evidence, ultrasound is used to detect initial hemorrhage, which occurs more often at the first antenatal week, and further ventricular dilation, which results in progressive hydrocephalus usually after the third week. This time interval is important because ventricular dilation can occur without clinical evidence and contributes to otherwise preventable brain damage.
- Detection of evolving hemorrhages – 1 examination per week: A primarily minor hemorrhage (grades I and II) can extend to a major one (grade IV) with subclinical evidence in an intubated and sedated infant. For these reasons many recommendations have been formulated focusing on the screening usage of ultrasound. Infants at greater risk (lower gestational age, lower birth weight) should be scanned more often. An initial ultrasound is obtained before day 5 of life, a second one during the second week (days 10–14) and a third on day 28. Generally at least one ultrasound per week should detect all cases of IVH and delineate the ventricular size status. If ventricular dilation is treated with surgical interventions (ventricular taps, reservoirs, drains, lumbar punctures), more frequent ultrasounds should be considered (48, 74, 75).
- Receding use due to MRI and ultrasound: Although CT scanning assisted the diagnostic workup of infants with IVH when first applied, it has been replaced by ultrasound and MRI to avoid exposure of the neonate to radiation. All the information that a CT scan can provide is more easily and accurately obtained by the latest ultrasound devices, especially when combined with MRI. The role of CT scanning is limited to cases of relative emergency and lack of ultrasound assistance.
In recent years MRI has been increasingly used to evaluate infants with IVH. Although it is difficult to transfer a critically ill preterm infant to the MR suite and maintain correct temperature and it is difficult for the infant to endure the examination, which lasts a long time, valuable information can be extracted. The exact condition of periventricular white matter can be clarified.
- PVL: PVL is demonstrated early by restricted diffusion in affected areas (DWI) and later by periventricular volume loss, ventriculomegaly, and gliosis. Neurodevelopmental outcome is grossly affected by such findings, and early consultation with parents can be more accurate.
- Hydrocephalus vs. encephalomalacia: MRI can contribute to distinguishing ventricular enlargement due to atrophy from ventricular dilation due to CSF accumulation. Round “ballooned” horns, periventricular high signal on T2-weighted MRI, and effaced subarachnoid spaces are typical findings of active hydrocephalus. Additional evidence can be elicited by more sophisticated techniques such as cerebral blood flow measurement and apparent diffusion coefficient (ADC) values registration (45).
- Compensated hydrocephalus: Distinction between progressive and compensated hydrocephalus is crucial in premature infants. It has been found that normal cerebral blood flow and low ADC values (measured by MRI) are associated with a compensated–arrested state and could support a conservative treatment approach. A similar theory was based on the Doppler ultrasound measurement of cerebral arterial flow, used mostly in the past. Arterial flow normalization after CSF drainage favored ventricular distension against “ex vacuo” ventriculomegaly.
Nuclear Medicine Tests
- PET scan: For research purposes, PET was used to demonstrate low cerebral blood flow in the periventricular region after the germinal matrix hemorrhage had occurred. Most likely this reflected the low perfusion seen in venous infarction (99).
- SEPs: SEPs have been used to identify neonates with progressive hydrocephalus. It was shown that the latency of SEPs in these patients correlated with CSF pressure and improved after treatment and CSF pressure decrease. Daily clinical application remains problematic (16).
- Not indicated: Typically, children with this condition are too young at the time of presentation to undergo such testing.
Correlation of Tests
Accelerated head growth and large ventricles on scanning: Abnormally fast head growth will typically trigger scanning, and the imaging will show enlarged ventricles as would be expected with developing hydrocephalus.