avoiding hyperthermia For neonates encephalopathic immediately after birth, therapeutic hypothermia initiated within hours of life and continued for 72 hours is now an evidence-proven therapy that should be considered Parenteral fluids should be administered to ensure adequate cardiac output Metabolic derangements should be addressed in order to maintain serum sodium close to 140 to avoid exacerbations of cerebral edema, and hypoglycemia should be treated aggressively to avoid secondary neuronal injury Infants with evidence of trauma or increased intracranial pressure may need to have emergent neurosurgical interventions, and coagulation disturbances should be corrected to try and control intracranial hemorrhage Acute intoxication and/or IEM may present with worsening encephalopathy, and in certain circumstances, may require emergent dialysis to clear the offending metabolite CLINICAL PEARLS AND PITFALLS The neonatal neurologic examination can be challenging due to subtle changes in mental status in infants with underdeveloped CNSs Nonetheless, the neurologic examination can identify infants at high risk for brain injury and timely interventions, such as hypothermia, can result in neuroprotection In some circumstances, brainstem herniation can occur without bulging of the anterior fontanelle because of isolated increased pressure in the posterior fossa It is not uncommon for the infant to have waxing and waning of neurologic signs, and careful documentation and serial evaluations are important diagnostic and prognostic clues Perinatal hypoxia–ischemia is a major cause of neonatal encephalopathy, however, additional etiologies for late-onset or progressive encephalopathy must be evaluated Current Evidence Hypoxic–ischemic injury during the perinatal period is the most common identified cause of neonatal encephalopathy The pathophysiology of injury leading to cerebral edema, reperfusion injury, and neuronal cell death can also be applied to any acute asphyxial event in the neonatal period Brain injury in response to such an event continues to evolve over a period of hours to days, and can account for changes seen in the clinical examination