Hypoxic-Ischemic Encephalopathy(HIE)

Hypoxic ischemic encephalopathy (HIE), also called neonatal maladjustment syndrome, is a syndrome in the newborn foal that appears as a problem with the foal's mental function. Affected foals are said to be "dummy foals," "barker foals" and "wanderers."

Encephalopathy refers to a problem with the brain. Hypoxia is the scientific name for decreased oxygen, and ischemic means a decreased supply of blood. Thus, HIE indicates a lack of oxygen and blood to the brain resulting in a pathologic condition.

The severity of the symptoms is probably related to the amount of hypoxia and ischemia that occurs normally during the birth process. After this initial insult the brain responds by swelling. This swelling is called cerebral edema. As the brain swells, there is an increase in the intracranial pressure, and it is this pressure that is responsible for the development of the clinical signs.

What to Watch For

• Sudden loss of suckle reflex
• Wandering away from the mare
• Blindness
• Sleeping while standing up
• Repetitive circling around the mare
• Seizure
• Coma

The signs maybe present at birth or may occur in the first 72 hours of life. The foals with mild HIE, (lack of suckle) may recover in 24 to 48 hours. Foals that proceed to a more severe form of HIE (seizures and coma) may take 7 to 10 days of intensive support for full recovery to be achieved.

Veterinary Care

Veterinary care for the foal with HIE can be intensive and prolonged. It is focused on providing the foal with neurologic support in the way of seizure control and decreasing intracranial swelling of the brain. Anticonvulsants drugs and intravenous drugs that will reduce cerebral edema are used.

One needs to remember that it is highly likely that the HIE foal may not have suckled from his mother and thus has not obtained colostrum. It is important to provide the foal with protective antibodies through the administration of high quality colostrum, or if after 12 to 24 hrs, by administration of plasma intravenously. If the foal has not nursed and the mare has not dripped colostrum, then the mare should be hand milked and the colostrum given to the foal through a nasogastric tube, since the foal does not have a suckle reflex.

If the foal has lost his suckle reflex then he will not be able to feed himself. Nutrition must be administered through the use of an indwelling nasogastric tube. The tube is placed through the nose and into the stomach. It can be taped to the nose or sewn to the nostril so that the caretaker can administer milk on an hourly basis. A normal foal will eat 20 percent of his body weight in kilograms every day. This is essentially 9 to 12 liters of milk for the average sized foal. The total amount should be divided by 24 to give you the amount that you need to feed every hour. Initially, it may be difficult to administer this amount to a foal through a naso-gastric tube.

Recumbency – when the horse is lying down and cannot get up – may also create problems. It is important to keep the foal warm and dry. He will continue to urinate and defecate, and urine scalding can be a problem. It can be avoided by sponge bathing the foal, drying him and applying baby powder to the area. The baby powder absorbs the moisture.

Because foals do not have much body cushion in the way of fat, they are prone to developing pressure sores if they are unable to stand. The pressure sores develop over the bony prominences such as the elbow, the hock, the shoulder, the stifle and the hip. These pressure sore can develop quickly if the foal is on a hard surface. Even in deeply bedded stalls, the seizing foal will work his way down to the dirt floor. A soft cushion such as a lawn chair cushion helps to prevent this problem.

Home Care and Prevention

Careful observation of your newborn foal's behavior is important in the recognition of this problem. Newborn foals should show a desire to stay by their dam's side. They should be bright and aware of their surroundings. If they tend to wander away from the mare or don't suckle from the mare's udder then the foal is not showing appropriate behavior and you should begin to suspect that the foal may have HIE. This condition can change rapidly within hours so it is best that you alert your veterinarian as soon as you notice an abnormality.

In mild cases of HIE, the owner of the foal may wish to try and treat the foal at home. In more severe cases, this becomes difficult because the care is so labor intensive. It is difficult to provide the around-the-clock nursing care that the foal needs in order to survive. Referral to a hospital facility is usually the best decision for the foal's survival.

Because the hypoxic/ischemic event happens while the foal is still in the uterus or at birth, it is difficult to predict prior to birth which foal will be affected. Attended births may help in the delivery of foals that are distressed, thus decreasing the time that the lack of oxygen occurs. Sometimes during the delivery process, a red membrane appears at the vulva lips of the mare instead of the normal transparent amniotic sack. What you are seeing is actually the placenta coming out with the foal. This is called "red bag" and it caused by a premature separation of the placenta from the uterine wall. When this happens, the foal is unable to receive oxygen and nutrients from the mare. At the same time, the foal is still within the birth canal and cannot breath. This is an emergency situation. The red membrane must be cut open and the foal delivered as quickly as possible to minimize the amount of time that the foal is without oxygen.

If placentitis or twinning is suspected in your mare, then the mare should be sent to a facility that can provide care for the high-risk pregnancy. Mares that have had one foal with HIE are at higher risk of producing another. One should consider sending this mare to a hospital facility for foaling.

Hypoxic ischemic encephalopathy (HIE) describes the result of asphyxiation of a foal during the birth process. While the foal is in the uterus of the mare, he receives all of his oxygen and nutrients from the placental blood flow. If for some reason this blood flow is interrupted, the foal will suffer. For short periods of time, the foal may be able to send the oxygenated blood to his brain and heart preferentially. If it is interrupted for longer periods, the brain will become oxygen starved, which will result in the death of certain cells and the leakage of fluid into other cells in the brain tissue causing the brain to swell.

Because the brain is encased in the hard bones of the skull, it doesn't have much room to swell. This creates pressure and further destruction of nervous tissue. The pressure within the brain may cause some of the blood vessels going to the brain to narrow, further decreasing blood flow and oxygen to the brain.

Causes

• Severe maternal illness – colic, endotoxemia
• Placentitis – infection of the placenta
• Twinning
• Premature placental separation – "red bag"
• Labor induction
• Dystocia – difficulty foaling
• Excessive hemorrhage from the umbilical cord

A thorough history may be helpful to your veterinarian in making the diagnosis of HIE. For example if the foal and the placenta were expelled together at the birth or if you saw a "red bag" (premature placental separation) at the time of birth, then you could be fairly certain that the placenta had separated while the foal was in the uterus. If you have a foal that was malpositioned and took some time and force to deliver, then you might suspect that the foal suffered some hypoxia while in the birth canal.

The clinical signs of HIE may be singular and static, such as a lack of suckle reflex, or they may be progressive to seizure and coma. The progression is probably due to the continued swelling of the brain. The signs maybe full blown at birth or they may occur gradually over the first 72 hours of life. If the signs are progressive they may follow a pattern similar to the following scheme:

• After birth the foal stands and maybe nurses
• Within a few hours the foal may start to wander away from his dam
• The foal loses his ability to suckle
• The foal may then show signs of depression and becomes recumbent
• The foal may develop a vacant look in his eyes
• The foal can begin to have seizures. Seizures may be severe with the foal becoming rigid, throwing his head back (opisthotonus) and paddling his legs. They are generally unaware of their surroundings and will vocalize – sounding like a barking dog. More subtle seizures may be missed. They could present as roving eye movements, tongue movements, grimacing and repetitive blinking.

These signs may progress rapidly within a few hours or they may take a few days. If the foal recovers from this problem it usually does so in the reverse order of the appearance of the signs, taking sometimes up to a week to be neurologically normal again.

Disturbed mental function in the equine neonate can occur with other diseases besides HIE. Some of these include:

• Hypoglycemia. A foal with a blood glucose of less than 40 mg/dl will show similar signs of depression and may progress to seizures.
• Trauma. Occasionally mares are not as agile around their foals as they should be. Head trauma should be ruled out as a possible cause for mental dysfunction.
• Developmental abnormalities. Infrequently a foal is born with a congenital neurology problem, such as hydrocephalus.
• Septic meningoencephalitis. In equine neonatal septicemia, the widespread infection may spread to the brain and the covering of the brain (meninges).
• Tetanus. A foal with tetanus may be confused with a foal with seizures because they become very rigid.
• White muscle disease. This is a muscle disease caused by a deficiency in selenium and vitamin E that produces signs of weakness and recumbency.

In order to diagnose the specific cause of your foal's mental dysfunction, your veterinarian will need to do some basic blood work. This includes a complete blood count, a blood glucose, a chemistry profile and an immunoglobulin level. The complete blood count is usually normal in the foal with HIE whereas in the septic foal there may be a very low or high white blood cell count. A low blood glucose can be found in any foal that has not eaten. This could occur in both a septic foal and a foal with HIE. If the mental disturbance is secondary a low blood glucose then correction of it with intravenous glucose will correct the problem.

A chemistry profile will report on the status of the foal's kidney, liver and muscle functions and his electrolyte levels. In white muscle disease the muscle enzymes will be very high.

Other tests that may be performed at a hospital facility may include a cerebral spinal fluid (CSF) analysis and a CT or MRI study. The CSF analysis would generally be normal in the foal with HIE but would contain an elevated white cell count and protein in the foal with septic meningitis. The CT or MRI may be helpful in the diagnosis of developmental abnormalities such as hydrocephalus.

The goals of veterinary care for foals with HIE are centered on three different needs of the foal – the neurologic needs, the immunologic needs and the supportive needs.

• Neurologic needs. The treatment of the neurologic problem in the affected foals is focused on decreasing the seizure activity and decreasing the swelling in the brain. Seizure control is usually met through the use of anticonvulsants such as Valium and phenobarbital. Swelling of the brain (cerebral edema) if mild will correct itself with supportive fluids over a short period of time (1 to 2 days). Severe edema may need more aggressive therapy with drugs that decrease inflammation and fluid in the brain. These drugs include a substance called DMSO or a drug called mannitol. The use of these drugs is to try to draw fluid away from the brain at the same time that you are increasing the blood flow. It is important to maintain adequate blood flow to the brain or more hypoxic ischemic damage may occur.
• Immunologic needs. Many of the foals with HIE do not stand and nurse at birth. In severe cases, the neurologic signs are present at birth. It is very important to remember that this foal needs to receive a good quality and quantity of colostrum. If this does not happen then the foal should be treated as if he has the potential to become septic. He should receive a plasma transfusion if he is over 12 hours of age and has not received colostrum. Your veterinarian will often give protective antibiotics.
• Supportive needs. This is the biggest category of needs. Foals with HIE are unable to do anything for themselves and can be rather self-destructive in the process of their disease. It is important to provide the best supportive care in order to decrease the possible complications that can occur in a recumbent foal.

Because these foals are not mentally aware of their surroundings and have the potential to have seizures, they should have a personal 24-hour attendant. Human restraint is the best method of preventing the foal from self-inflicted trauma. Even when they are not seizing, these foals often struggle and throw themselves around. The attendant may need to hold the foal in his lap in order to prevent the foal from hurting himself. Wrapping the foal's legs and making a head protector or helmet out of a piece of foam may further protect the foal.

Foals with HIE will often cause trauma to their eyes during their seizure episodes. Careful examination of the eyes on a twice-daily routine is important. Your veterinarian may stain the eyes with a fluorescent dye to look for corneal ulcers or abrasions. Antibacterial ophthalmic ointments are often used as both a preventative and a treatment of corneal ulcers. Treatment should be applied every 4 to 6 hours.

These foals do not have a suckle reflex, so all of their nutrition and fluids must be provided for them by nasogastric tube or intravenously. It is best to feed the foal by utilizing the intestinal tract if it is working. So in an HIE foal with no intestinal complications it is best to feed them with the nasogastric tube. This is a small diameter plastic tube that is inserted through the foal's nose and passed down his throat and esophagus into the stomach. Because the foal needs to be fed every 1 to 2 hours, the tube is generally secured in place with tape or a suture through his nostril. A foal that is about 100 pounds should be receiving a total of 9 to 12 liters of mare's milk or foal formula per day. This works out to approximately 375 to 500 mls of fluid per hour.

If the foal is recumbent then he should be kept warm and dry. Urine scalding can create skin irritation. Frequent cleaning of the foal and application of baby powder will reduce the problem. Keeping the foal on a soft cushion is important in prevention of pressure sores. Even in deeply bedded stalls, the seizing foal will work his way down to the dirt floor. Pressure sores develop over the bony prominences such as the elbow, the hock, the shoulder, the stifle and the hip. It is important to palpate the skin over these areas daily. In the beginning the skin may feel slightly thicker. It then begins to take on the appearance of leather with a sharp demarcation between the normal and the affected skin. Soon the leathery skin will peel away leaving an open wound. Pressure sores can develop quickly if the foal is on a hard surface.

Once pressure sores develop then they need to be cleaned and bandaged. The bandage will provide some protection and cushioning to decrease the severity of the sore. It is easy to bandage the lower limbs but difficult to keep a bandage or cushion on the stifle, hip or shoulder. This can best be accomplished by placing sutures around the wound and lacing umbilical tape through the suture to hold a pad of sterile gauze over the wound.

Foals with uncomplicated HIE generally have a good prognosis. Recovery rate is approximately 70 to 75 percent. Their recovery is the reverse of the presentation of clinical signs. Recovery may be slow with a little progress each day. This is a typical recovery pattern.

• The seizures stop.
• The comatose foal begins to show response to stimuli.
• The foal becomes more aware of his surroundings.
• The recumbent foal makes successful attempts to stand.
• The foal may become more aware of his mother, nuzzling around for an udder.
• Finally the foal regains his suckle reflex. The suckle reflex appears to be the first reflex to be lost and the last to be regained.

The key to this type of recovery is uncomplicated HIE. As one can see, the HIE foal is at high risk for complications with the chance of failure to ingest a good quality and quantity of colostrum. This leads to all the associated problems of septicemia. It is sad to have a foal recover from HIE only to develop septic arthritis or pneumonia. Other complications, such as corneal ulceration or pressure sores, can prolong the foal's hospital stay.

Many owners are worried about the mental capacity of their foals after they recover from HIE. Studies that have gone back and questioned owners about their now adult horses that had HIE as foals have been very promising. These foals do not appear to have any training problems. They respond to their training the same as other foals of their age. Since it is difficult to measure the IQ of a horse, it is difficult to assess any subtle changes.