Hypoxic ischemic encephalopathy (HIE) is a noninfectious syndrome of foals characterized by CNS dysfunction. The condition is often considered a component of perinatal asphyxia syndrome associated with peripartum events such as dystocia or placental insufficiency. However, in many cases there is no obvious episode of hypoxia, and it appears that HIE may also result from in utero exposure to inflammatory cytokines, perhaps secondary to occult placentitis.
The precise etiology of HIE is unknown; however, hypoxia is thought to initiate metabolic cascades that result in decreased energy production, ion dysregulation, increased concentrations of excitatory neurotransmitters (especially glutamate and aspartate), and impaired protein synthesis. An increase in intracellular calcium concentration appears to play a prominent role in neuronal injury. Oxygen-free radicals, nitric oxide production, and pro-inflammatory cytokines are also implicated. When a hypoxic episode is not evident, exposure to inflammatory cytokines likely initiates a similar cascade of events.
Foals may be neurologically abnormal from birth but often appear normal initially and develop clinical signs over the first 24–48 hr. A poorly coordinated suckle reflex and loss of affinity for the mare are the most common signs, although not present in every case. Mentation may alternate between depression or stupor and hyperresponsiveness. Other clinical signs include hypotonia, opisthotonos, abnormal respiratory patterns, persistent tongue protrusion, abnormal jaw and facial movements, head pressing, and abnormal vocalization (hence “barker foals”). Seizures are relatively common and may range from mild, abnormal movement of the face and jaw to generalized seizures with recumbency and paddling. Clinical signs are often asymmetric and may include a head tilt, circling, and asymmetric pupillary reflexes.
Although signs related to CNS dysfunction are most common, other organ systems may be affected. The kidneys and GI tract appear particularly susceptible to injury, but the heart, lungs, liver, adrenal glands, and parathyroid glands may also be involved. Many foals with HIE have clinical signs of abnormal GI and renal function, including gastric reflux, bloat, meconium retention, colic, and persistent increases in creatinine concentration.
Diagnosis is based on compatible clinical findings and exclusion of differential diagnoses. A history of dystocia, premature placental separation, or placentitis may support a diagnosis of HIE. The CBC is usually normal unless sepsis is present. The serum chemistry may also be normal but often indicates organ dysfunction secondary to hypoxic or cytokine-mediated injury. CSF may be normal or have an increased RBC count and protein concentration. CNS necrosis, edema, and hemorrhage are found in some cases at necropsy; however, these findings are inconsistent.
Differential diagnoses for HIE include bacterial meningitis, equine herpesvirus 1 infection, metabolic abnormalities (eg, hypoglycemia, electrolyte derangements), acid-base disturbances, kernicterus subsequent to massive hemolysis (ie, neonatal isoerythrolysis), brain or spinal trauma, congenital defects (eg, hydrocephalus, hydranencephaly), and nutritional myodegeneration (white muscle disease). Some of the clinical signs of HIE may also occur in foals with severe sepsis (see Sepsis in Foals).
Treatment and Prognosis
Treatment of HIE is primarily supportive. Judicious IV fluid administration and intranasal O2 insufflation may be required to improve cardiac output and maintain cerebral perfusion and O2 delivery. Severely affected foals, especially those with concurrent sepsis, may need inotrope or vasopressor support; some require mechanical ventilation. If the foal is unable to nurse, nutrition can be supplied via an indwelling nasogastric tube. Total parenteral nutrition is indicated in foals with GI dysfunction. Self-trauma may occur during seizures; injury may be limited by providing a protected or padded environment. Trauma to the eye and corneal ulceration is particularly common; the eyes should be monitored closely and treatment implemented if necessary. In recumbent foals, ophthalmic lubricant may be used to reduce the chance of corneal injury.
Foals with HIE appear to be predisposed to sepsis. Whether this is due to an underlying infectious process, impaired immune function, or increased exposure to pathogens (ie, indiscriminant nursing behavior) is unclear. In addition, foals that are neurologically abnormal at birth often fail to nurse and commonly have failure of passive transfer. For these reasons, broad-spectrum antimicrobial treatment is indicated. Care should be taken when administering aminoglycosides because renal function may be compromised.
Isolated or infrequent seizures may be controlled with diazepam (0.10–0.44 mg/kg, IV). If seizures persist, phenobarbital should be administered (2–3 mg/kg, IV, bid-tid). Some clinicians have used continuous infusions of midazolam (0.1–0.2 mg/kg/hr) instead of phenobarbital or in foals with seizures that do not respond to pheno-barbital. Total IV anesthesia (eg, propofol infusion) may be necessary in foals with intractable seizures.
Many therapies have been used to treat CNS inflammation and edema and improve CNS function. These include dimethyl sulfoxide (1 g/kg as a 10% solution, IV, sid-bid), flunixin meglumine (1.1 mg/kg, IV, sid-bid), furosemide (1 mg/kg, IV, sid-bid), hypertonic saline (2 mL/kg 7.2% NaCl, IV, every 4 hr for 5 treatments), mannitol (0.5–1.0 g/kg as a 20% solution, IV, qid), magnesium sulfate (0.05 mg/kg/hr loading dose followed by 0.025 mg/kg/hr), thiamine (5 mg/kg, slow IV or SC, sid), and vitamins E (20 IU/kg, SC or PO, sid) and C (10 mg/kg, IV or PO, sid). Although these may have a sound theoretical basis and have been anecdotally beneficial, there are few clinical trials demonstrating their efficacy. There is no role for corticosteroids in the treatment of HIE.
Most foals with HIE have a good to very good prognosis. In uncomplicated cases, the survival rate is at least 75% with a full return to function. Sepsis and related complications adversely affect the prognosis, although the majority of these patients are discharged.
Last full review/revision July 2011 by Brett Tennent-Brown, BVSc, MS, DACVIM, DACVECC