Brain Imaging and Diagnosing Hypoxic-Ischemic Encephalopathy (HIE) | Birth Injury Diagnosis
The Importance of Neonatal Brain Imaging in Diagnosing Hypoxic Ischemic Encephalopathy (HIE)
Neonatal encephalopathy (NE) is a brain injury that causes a baby to have signs and symptoms of brain dysfunction. Hypoxic ischemic encephalopathy (HIE) is a brain injury caused by a lack of oxygen (hypoxia) and/or a lack of blood flow (ischemia) in the brain. It is very important to recognize NE and HIE as soon as possible because early intervention improves outcomes. In cases of hypoxic-ischemic encephalopathy, hypothermia treatment must be given within 6 hours of the oxygen-depriving insult to help halt the cycle of brain injury and prevent death and cerebral palsy. Diagnosing hypoxic-ischemic encephalopathy and neonatal brain damage promptly is critical in preserving a baby’s ability to recover from a birth injury.
Prospective studies that utilize MRI (magnetic resonance imaging) techniques show that most cases (over 75%) of neonatal encephalopathy are caused by HIE brain injury that occurs during or near the time of birth (intrapartum).
The risk that hypoxic-ischemic injury will cause permanent problems such as cerebral palsy increases as the severity and duration of the hypoxic-ischemic insult increases. When there is a hypoxic-ischemic insult to the baby’s brain, the injury can evolve over a period of days and weeks.
Hypoxia (a lack of oxygen at the tissue level) and ischemia (a restriction of blood flow) both cause cell injury and brain damage, but ischemia is the more significant contributor to brain injury. Ischemia causes hypoxia and hypoxia can cause ischemia. Global ischemia is worse than hypoxia because it causes cellular energy failure and a build-up of lactic acid and other toxins that are very injurious to cells in a number of ways, including making it more difficult for the uptake of oxygen by the cells.
Certain parts of the brain are more vulnerable to hypoxic-ischemic insults than others. The severity and length of time of the insult as well as the condition of the fetus (fetal reserve) will determine the location and extent of the brain injury. Regions of the brain that have high metabolic activity (high neuronal excitation), such as the basal ganglia and thalamus, are the most vulnerable to sudden and severe insults, which usually last 30 minutes or less. The cerebral cortex is vulnerable to prolonged, less severe hypoxia/ischemia because when the brain is subjected to these conditions, blood gets shunted away from the cerebral cortex – which is the outermost layer of neural tissue – to the deeper structures of the brain. The watershed regions, which do not have a direct arterial blood supply, are also vulnerable due to the tenuous blood supply in these areas. The partial prolonged insult that causes damage to this region usually lasts 30 minutes or more.
There is almost always some degree of selective neuronal necrosis (death of neurons) in cases of hypoxic-ischemic encephalopathy (HIE). Of course, all the cells in the brain can be affected by a hypoxic-ischemic insult, but the neurons are the most vulnerable. Neurons process and transmit information via electrical and chemical signals, and they connect to each other and form the core of the nervous system.
The Causes of Hypoxic-Ischemic Encephalopathy (HIE) and Neonatal Brain Injury
Acute Near Total / Acute Profound Asphyxia
When the baby suffers severe or total hypoxia/asphyxia, the insult is called acute/profound or profound (near total) asphyxia. With very severe insults, there will usually be a central pattern of focal neuronal injury (deep gray nuclei injury) to many levels of the central nervous system, with diffuse and pronounced neuronal necrosis. When the insult is relatively abrupt and severe, there will be an injury to the deep nuclear structures, such as the basal ganglia, thalamus and brain stem, because total asphyxia prevents the adaptive mechanism of shunting. Thus the cerebral cortex will typically be spared from injury.
When a baby suffers an insult in which the oxygen deprivation/ischemia is moderate to severe and relatively prolonged, there is a cerebral deep nuclear pattern (injury to deep parts of the brain), and there might be at least some degree of shunting. These types of insults usually cause damage to the cerebral cortex and deep nuclear structures, especially the putamen and thalamus.
Partial Prolonged Asphyxia
Partial prolonged asphyxic insults, which usually last for more than 30 minutes, mainly lead to cortical injury in the watershed and parasagittal regions, with relative sparing of damage to the deep gray matter.
Partial prolonged asphyxia can be caused by Pitocin and Cytotec use, which are labor induction drugs that can cause contractions to be so strong and frequent that the blood vessels in the placenta are almost continuously restricted, thereby causing a decrease in the amount of oxygen-rich blood going to the baby. When these drugs cause contractions to be intense and fast, it is called hyperstimulation or tachysystole. When the uterus is essentially in a constant state of contraction, it is called hypertonus. Hyperstimulation, tachysystole and a hypertonic uterus can cause oxygen deprivation that gets progressively worse.
High and low blood pressure in the mother (hypertension and hypotension) can also cause the baby to experience partial prolonged asphyxia. Blood pressure problems can be caused by many conditions, including dehydration, a maternal infection, and drugs used with an epidural and anesthesia.
Other events that can cause partial prolonged asphyxia include umbilical cord compression caused by a nuchal cord (cord wrapped around the baby’s neck) or oligohydramnios, placental insufficiency and inadequate or delayed resuscitation of the baby at birth.
Mixed Injury Pattern
There also can be a mixed injury pattern whereby the baby experiences both profound asphyxia as well as partial prolonged asphyxia.
Progression of Brain Injury in Cases of Hypoxic-Ischemic Encephalopathy (HIE)
A brief overview of the brain injury cycle will help with the understanding of how brain damage is diagnosed with brain imaging studies.
When a condition (such as placental abruption) causes the oxygen saturation in the baby’s blood to drop, the brain may not be affected initially. However, when the oxygen supply gets too low, hypoxia develops. Hypoxia is a state of decreased oxygen supply and resultant anaerobic metabolism. Anaerobic metabolism is the creation of energy in the absence of oxygen, and the acidosis created by this process has a direct, harmful effect on neurons (brain cells).
Acidosis also can lead to a drop in fetal blood pressure that causes a reduced flow of blood in the brain, which leads to ischemia. Both hypoxia and acidosis cause reduced cerebral blood flow. Indeed, research shows that hypotension and resultant diminished brain perfusion are significant factors associated with neuronal injury and hypoxic-ischemic encephalopathy (HIE).
The cerebral damage that occurs during this hypoxic-ischemic phase is worsened by a reperfusion injury, which is an injury that occurs 2 – 6 hours after the primary insult. Reperfusion is damaging because as blood flow in the brain is restored, there is an increase in oxygen in the blood, which leads to free radical production that causes further cell damage and energy failure and more brain injury.
On a cellular level, each individual neuron can have a selective degree of injury. If the neuron – or any cell – is not getting the oxygen and glucose it needs, it will have difficulty completing its production of adenosine triphosphate (ATP). ATP is the main source of energy for most cell functions. ATP depletion leads to cellular injury. When the neuron dies right away (traumatic cell death), it is called neuronal necrosis.
Apoptotic cell death occurs when the brain cell is significantly injured and it begins a process of programmed cell death. The activation of this apoptotic cell pathway causes a release of inflammatory substances such as cytokines, and in this pathway, there are excitotoxic molecules created, such as neurotransmitters called glutamate. Glutamate causes reactions to occur that are very damaging to the cell. Reactive oxygen and nitrogen species are generated, and this leads to cell death. These secondary pathways occur hours to days after the initial hypoxic-ischemic injury.
Secondary insults that occur after a hypoxic-ischemic insult include reperfusion injury, edema, increased intracranial pressure (ICP), abnormalities of autoregulation and hemorrhage (brain bleeding).
What Happens to the Brain When Oxygen Deprivation Causes Hypoxic Ischemic Encephalopathy (HIE)?
Listed below is a timeline of some significant events that occur when the brain suffers from a lack of oxygen-rich blood. These are listed independently of the type of insult. Thus, for example, injury to the basal ganglia may occur with profound (near total) asphyxia and mixed injury patterns, but the basal ganglia will not be affected by a partial prolonged insult.
- 0 – 12 hours after hypoxic-ischemic insult (HII): During this time there can be prominent involvement of the basal ganglia, focal cerebral infarction (tissue death) and focal cerebral lesions.
- 12 – 24 hours after HII: Between 12 and 24 hours, basal ganglia damage occurs.
- 24 – 36 hours after HII: Major cell changes – observable cell swelling.
- 24 – 72 hours after HII: Signs of swelling and edema (fluid build up) occur during this time. In addition to swelling, there typically is increased ICP.
- 72+ hours after HII: After 72 hours, there is selective neuronal necrosis involving the deep nuclear structures (basal ganglia and thalamus) and brain stem.
Edema is a consequence of hypoxic-ischemic encephalopathy (HIE). When a woman had an uneventful pregnancy, the development of edema in the first day or so after birth is highly indicative of a brain insult that occurred during or near the time of delivery. As discussed earlier, the location and type of injury is indicative of what type of insult the baby experienced. At or after 24 hours, there are overt signs of cell necrosis, and in 3 – 5 days, the necrotic debris will be consumed and then a glial mat will form over the next several weeks. Severe lesions may result in cavity formation, especially in the cerebral cortex.
Diagnosing Hypoxic-Ischemic Encephalopathy and Brain Injury with Brain Imaging Techniques
Diagnosing Hypoxic Ischemic Encephalopathy (HIE) Using MRI
Magnetic Resonance Imaging (MRI) is the best imaging technique for diagnosis of babies with moderate to severe HIE and can be performed 12 – 24 hours after birth (edema and injury are usually evident by 24 hours on MRI). During an MRI, images are taken from the top of the skull down to the base, from the front to back, and from side to side. Each image represents a unique slice of the brain so all areas of the brain are captured and none are missed on the scan, allowing for each layer to be analyzed. High signal areas are areas of abnormal tissue (lesions). When the brain is damaged, a scar forms over the injury; parts of the brain that have lesions/scarring give off a high signal (hyperintense signal) that differentiates it from normal tissue. Indeed, MRI can accurately demonstrate the injury pattern as a hyperintense area one day after birth, sometimes sooner, and especially after day 4.
Diffusion-weighted imaging (DWI) allows identification of injury in the first 24 – 48 hours, and this sequence can show areas of edema (injured areas). DWI changes peak at 3 – 5 days of life, and it is also important to note that these changes may underestimate the extent of the damage due to the importance of apoptosis in the final extent of the injury.
Hypoxic-ischemic injuries, in general, show a 1, 2, 3, 4 sign on MRI:
- Increased signal intensity in the basal ganglia;
- Increased signal intensity in the thalamus;
- Absent or decreased signal intensity in the posterior limb of the internal capsule (white matter structure that carries information past the basal ganglia);
- Restricted water diffusion on diffusion-weighted images.
Profound (Near Total) Asphyxia
Typically, in a newborn baby with an acute profound injury, edema can be seen on MRI (T2 weighted imaging (WI)) by 24 hours. The major effects of edema resolve by the end of day 5 or the beginning of day 6. If there is significant edema in the central gray matter structures, the thalami, and basal ganglia, there will be compression of the third ventricle. When the injury is more extensive and additionally involves the rolandic cortex (motor area of the cerebral cortex), there may be compression of other ventricular areas as well (lateral ventricular compression). After 72 hours, compression of the ventricles may increase, depending on how extensive the injury process is. When the injury process is on day 3, going until day 6, compression of the ventricles resolves and they go back to their regular size. The increased signal intensity sometimes changes with the initial evolution of damage, and sometimes there is no change.
Edema subsides and injured tissue remains, and this alone can cause changes in signal intensity. There may be mineralization around necrotic debris (dead neurons) in the gray matter that’s more central. Due to the effects caused by calcifications at the site of injured neurons, there may be increased signal intensity on MRI (T1 WI). As the cycle of injury continues over weeks to months, depending on the amount of tissue involved, there is reabsorption of tissue, and this leads to localized softening of the brain (encephalomalacia) and scarring (gliosis), which results in degradation (atrophy) of areas of the brain. Gliosis appears on MRI as areas of increased signal intensity (T2 WI and FLAIR) because of the abnormally high water content. This change is best shown when the child is 18 months of age or older when the myelinated white matter appears hypointense on MRI and contrasts with the increased intensity of gliosis. When atrophy occurs, there is a decrease in tissue volume and the cerebral spinal fluid-filled spaces are abnormally large. Encephalomalacia becomes more evident over time, with more and more tissue reabsorption.
Partial Prolonged Asphyxia
Injuries in the watershed zones are typically gradual in onset and can involve both gray and white matter. These injuries are typically seen within 24 hours or later. As edema increases, the cortex will become more hypodense, and there will be a loss of differentiation between gray and white matter. This loss is seen most frequently in the parasagittal areas and there often is involvement of either the parietal-occipital lobes or frontal lobes or both. Injuries in the watershed zones can be in different areas; they can be on one side of the brain or more through the middle of the brain (anterior/posterior). When the partial prolonged asphyxia has a longer duration, the damage can extend beyond the watershed zones, into the adjacent cortical areas. This causes major edema, leading to the destruction of much of the lateral ventricles, and there typically is brain swelling that is greater than what it was at 24 hours, peaking at about 72 hours. Varying degrees of cerebral swelling can be seen at 36 hours and, to some extent, after 96 hours.
As edema subsides, the cortex will seem to appear again in the images at 8 days and later, and this represents visualization of cortical necrosis. There will be atrophy of the damaged cortex as tissue loss progresses, the subarachnoid space will be enlarged, and there will be shrinkage of some portions of the hemispheres that are involved in the injury process. Calcification sometimes is seen in the cortex, and subcortical cystic encephalomalacia is common. This represents a complete replacement of areas of white and gray matter by fluid-filled spaces that are cystic, all within regions of necrosis. The undersurface of a ridge on the cerebral cortex (gyrus) may have such compromised vasculature after the swelling that a mushroom-like structure appears beneath it. This structure, called ulegyria, is secondary to atrophy.
DWI is the best way to detect the earliest changes in watershed injury in partial prolonged asphyxia. The damage causes a restriction of the motion of water and it will be seen as high signal intensity (at a field strength of B1000). Twenty four hours after the hypoxic-ischemic insult, the cortex will lose its normal low signal intensity (on T2 WI) due to the edema causing increased brightness, making it indistinguishable from the bright white matter that is unmyelinated. The edema in the white and gray matter increases the size of this matter, which causes the ventricles to be compressed. As the edema subsides, cortical necrosis shows up as an increase in signal intensity (T1 WI). This high signal intensity disappears as the cortical reabsorption occurs. Cerebral volume loss (sometimes occurring as cystic encephalomalacia) will appear on the images, and gliosis (scarring) will appear as areas of increased signal intensity (T2 WI and FLAIR). Gliosis usually involves the subcortical white matter and cortex, and it can extend towards the ventricles, within the white matter.
When partial prolonged asphyxia is severe, the decreased blood flow and oxygenation lasts a sufficiently long time or to such a degree that the area of the cerebral cortical gray matter and subcortical white matter injury goes beyond the typical watershed regions. This is seen as a more extensive and homogenous pattern that includes edema (and the effects of edema), involving large areas of all the cerebral lobes. This will appear as increased intensity (T2 WI) by 24 hours after the insult, and even sooner on DWI. Maximal edema and edema that has subsided follow a similar time course as that of lesser degrees of partial prolonged asphyxia. Changes in the cortex that are indicative of cortical necrosis show up as increased density on non-enhanced imaging (T1 WI) as abnormal increased signal intensity. These changes occur frequently in this severe type of situation. As more and more reabsorption occurs, cystic encephalomalacia may occur as well as global cortical and subcortical atrophy. The ventricles and sulci are typically enlarged and there usually are extra-axial collections of fluid in chronic situations.
In mixed patterns, when energy substrates are depleted in partial prolonged asphyxia, there is further insult in the form of near total collapse. This is seen when there is sudden bradycardia superimposed on a decline in the baby’s heart rate that is more gradual. In addition to the injury from the partial prolonged asphyxia taking place in the watershed zones or beyond (in more severe insults), the severe bradycardic events cause damage to the putamina and thalamus, and sometimes the hippocampus, vermis, and brainstem. The progression of mixed injuries is similar to the others described earlier.
Very severe near total asphyxia may have the typical profound pattern of injury but with greater extent of cortical injury. This is typically seen when the baby’s bradycardia is really long. This is a profound asphyxia injury pattern with predominantly severe damage to the thalamus and basal ganglia.
It is also important to note that MRIs can also be combined with magnetic resonance spectroscopy (MRS), which can help medical practitioners understand not just the impact of hypoxia/ischemia on brain structure, but also on brain cells’ metabolism.
Diagnosing Hypoxic Ischemic Encephalopathy (HIE) Using Ultrasonography (Ultrasounds)
Cranial ultrasonography (ultrasound) has the benefit of being available at the baby’s bedside, but it has a low sensitivity for detecting the anomalies that can be seen with hypoxic-ischemic encephalopathy (HIE). Ultrasound does, however, have high sensitivity for showing hemorrhages and ventricle size. It can also show severe parasagittal white matter damage and prominent cystic lesions, but ultrasonography does not show the outer portion of the cerebral cortex or milder white matter abnormalities very well.
Ultrasonography can be used to detect cerebral edema within about 24 hours after the hypoxic-ischemic insult, and findings include a global increase of echogenicity. Obliteration of CSF containing spaces may be evident, and after few days, necrosis may show up as areas of echodensity.
Early Diagnosis of Hypoxic-Ischemic Encephalopathy (HIE) and Brain Injury
Early detection of brain injury and diagnosis of hypoxic-ischemic encephalopathy (HIE) is very important because early intervention is critical in minimizing the effects of a hypoxic-ischemic insult. Seizures frequently occur when a baby has HIE. If HIE is diagnosed very early, a baby may be more likely to be closely monitored for seizure activity. Close monitoring, which may include continuous EEG monitoring, is crucial because seizures often have no obvious signs and seizure activity causes brain injury. The sooner seizure treatment begins, the better the outcome for the baby.
Brain imaging studies are very important because they help clinicians determine if asphyxia caused the brain injury, and these studies also help pinpoint the timing of the brain insult. Timing is important because if a brain injury could have been prevented, the hospital and medical professionals responsible for the preventable injury should be held accountable so that the harmful behavior is deterred and the child and family can receive compensation to help pay for the child’s therapy, treatment, and housing and educational needs.
Reiter & Walsh, P.C. | Trusted Michigan HIE Attorneys and Brain Injury Lawyers
Birth injury is a difficult area of law to pursue due to the complex nature of medical records. The award-winning attorneys at Reiter & Walsh ABC Law Centers have decades of experience with brain injury, cerebral palsy and hypoxic-ischemic encephalopathy (HIE) cases. To find out if you have a case, contact our firm to speak with one of our award-winning attorneys. We handle cases throughout the U.S. We have numerous multi-million dollar verdicts and settlements that attest to our success; no fees are ever paid to our firm until we win your case. Email or call us at 888-419-2229.
- Hintz, Susan R., et al. “Neuroimaging and neurodevelopmental outcome in extremely preterm infants.” Pediatrics 135.1 (2015): e32-e42.
- Barnette AR, Horbar JD, Soll RF, et al. Neuroimaging in the evaluation of neonatal encephalopathy. Pediatrics 2014; 133:e1508.
- Executive summary: Neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians and Gynecologists’ Task Force on Neonatal Encephalopathy. Obstet Gynecol 2014; 123:896.
- Wu YW, Backstrand KH, Zhao S, et al. Declining diagnosis of birth asphyxia in California: 1991-2000. Pediatrics 2004; 114:1584.
- Graham EM, Ruis KA, Hartman AL, et al. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008; 199:587.
- Thornberg E, Thiringer K, Odeback A, Milsom I. Birth asphyxia: incidence, clinical course and outcome in a Swedish population. Acta Paediatr 1995; 84:927.
- Lee AC, Kozuki N, Blencowe H, et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res 2013; 74 Suppl 1:50.
- Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33:696.
- Ferriero DM. Neonatal brain injury. N Engl J Med 2004; 351:1985.
- Dammann O, Ferriero D, Gressens P. Neonatal encephalopathy or hypoxic-ischemic encephalopathy? Appropriate terminology matters. Pediatr Res 2011; 70:1.
Executive summary: Neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians and Gynecologists’ Task Force on Neonatal Encephalopathy. Obstet Gynecol 2014; 123:896.