Treatment of Neonatal Seizures
When seizures occur in a baby, they must be treated immediately because even a single seizure can cause or worsen brain damage. Seizures can also be an indication of brain dysfunction – a sign that a baby suffered some type of brain damage. Furthermore, seizures cause permanent brain injuries, such as cerebral palsy and intellectual disabilities and developmental delays.
Treating the cause of seizures is critical to preventing further brain damage. This is especially true for seizures associated with metabolic disorders, such as hypoglycemia, hypocalcemia (low calcium) and hypomagnesemia (low magnesium), and with central nervous system problems or infections that travel to the baby’s brain. Furthermore, seizures may not be adequately controlled with antiepileptic drugs (AEDs) unless the underlying causes are treated.
Common Causes of Neonatal Seizures
- Intracranial hemorrhage. This includes intraventricular, intracerebral, subdural and subarachnoid hemorrhages. Treatment of intracranial bleeds mostly is supportive, although neurosurgical intervention may be necessary in certain instances (such as with the management of subdural hematomas).
- Hypoxic ischemic encephalopathy (HIE) and associated neonatal encephalopathy. This is the most common cause of neonatal seizures. Thus, every effort should be made to prevent HIE. When HIE occurs, the brain is deprived of oxygen, either due to a lack of blood flow or a lack of oxygen in the blood. When this happens, there is a cascade of events that causes excessive depolarization, which leads to uncontrolled electrical activity in the brain. Seizures resulting from HIE usually occur within the first 72 hours of life.
- The management of moderate to severe HIE should take place in a neonatal intensive care unit. Major goals include:
- Maintenance of physiological homeostasis (keeping the baby’s temperature, blood pressure and heart rate stable)
- Adequate ventilation (avoidance of too much or too little oxygen)
- Adequate blood flow to the brain and organs (blood pressure must be kept normal)
- Normal metabolic status (baby’s nutrition should be kept up; blood sugar status should be kept normal)
- Avoiding brain edema (fluid overload in the brain)
- The baby should be given hypothermia treatment. Hypothermia is the only effective neuroprotective therapy currently available for treatment of neonatal encephalopathy / HIE. With this type of treatment, the baby’s brain or body is cooled down to a few degrees below normal body temperature. The treatment should begin within 6 hours after birth (or after injury) and may last up to 3 days.
- The management of moderate to severe HIE should take place in a neonatal intensive care unit. Major goals include:
- Central nervous system infections. Infection of the central nervous system is a common cause of neonatal seizures and should be treated with broad spectrum antibiotics at doses sufficient to treat meningitis. These types of infections include meningitis, encephalitis (including herpes encephalitis (HSV)) and cytomegalovirus.
- Stroke . A stroke is caused by blood supply to the brain becoming blocked or restricted. Treatment of a stroke must occur immediately, followed by rehabilitation to ensure that further strokes, damage and complications do not arise. Physicians must take actions to ensure that the baby has adequate oxygen and good circulation. IV fluids and anti-clotting medications may be given to reduce the risk of a recurrent stroke. Hypothermia treatment may improve neurological outcome after a stroke, and this can help prevent seizures.
- Metabolic problems, such as hypoglycemia. Metabolic disturbances are a treatable common cause of neonatal seizures, and testing for these disturbances is very easy. Hypoglycemia should be corrected immediately with a glucose solution given through an IV. Maintenance glucose infusion can be given thereafter. Hypocalcemia is the presence of low calcium in the blood. This can be treated with calcium gluconate or calcium chloride. Hypomagnesemia occurs when the magnesium level in the baby’s blood is too low, and is often associated with hypocalcemia. The treatment is a solution of magnesium sulfate given by an injection into the muscle. This injection can be repeated every 12 hours until normal magnesium levels are achieved.
- Congenital abnormalities of the brain such as hydrocephalus. Hydrocephalus is swelling of the brain’s ventricles caused by too much cerebral spinal fluid (CSF). This can be treated by placing a shunt that directs flow from an area of CSF build up to the abdominal cavity, where it can be absorbed into the circulation. Magnesium sulfate also may help improve neonatal outcome in babies with hydrocephalus due to the fact that it increases circulation in the brain and has a neuroprotective effect.
Other Causes of and Risk Factors for Neonatal Seizures Include:
- Trauma to the baby’s brain during delivery. This can cause brain bleeds and hemorrhages, which are significant risk factors for seizures. Traumatic injury can occur when labor is prolonged, forceps or vacuum extractors are used, labor induction drugs, such as Pitocin and Cytotec are used, and the baby is in an abnormal position, such as breech or face presentation.
- Fetal distress. Anything that causes the baby to be deprived of sufficient oxygen can cause fetal distress, which is one of the main caused of seizures.
- Problems with the placenta or uterus, such as a ruptured uterus or placenta previa. The placenta contains the blood vessels that carry oxygen-rich blood to the baby through the umbilical cord. Anything that interferes with the baby receiving sufficient oxygen can cause HIE and seizures.
- Umbilical cord compression or nuchal cord. When the umbilical cord exits in front of the baby in the birth canal (compression) or is wrapped around the baby’s neck (nuchal cord), oxygen-rich blood to the baby can be severely diminished or stopped, which can cause HIE and seizures.
Treatments for Neonatal Seizures
It is imperative that medical staff treat the underlying cause of seizures. The physician must decide whether to initiate antiepileptic therapy (AED) after (1) managing airway and cardiovascular support and (2) identifying and treating the underlying cause of the seizures. The physician must also decide what AEDs to use. Factors to be taken into consideration include whether the seizure is epileptic in origin. If it is, the physician must examine seizure duration and severity.
AEDs are used to treat neonatal seizures of epileptic origin, but not those of nonepileptic origin. (Nonepileptic seizures mimic epileptic seizures, but do not involve abnormal, rhythmic discharge of neurons (cells) in the cortex of the brain.)
First-line treatment of epileptic seizures includes:
- Phenobarbital is usually the first drug of choice because it is relatively effective, the side effects are well appreciated, and the way it works is well understood for term and preterm infants. A loading (initial) dose of phenobarbital (20 mg/kg) will achieve a therapeutic level of approximately 20 µg/ml, which is not affected by birth weight or gestational age. The IV route is preferred because of the more rapid onset of action and more reproducible effects on blood levels. The maintenance dose of phenobarbital is lower in the first week of life (3.5 mg/kg/day) and increases to 5 mg/kg/day with increasing postnatal age. Phenobarbital is eliminated by the liver and kidneys. Thus, if a baby has impaired kidney or liver function, which often is the case with HIE, the standard dosing could be toxic. The younger the baby, the higher the likelihood of toxicity.
- Phenytoin is often the second drug of choice to be added when seizures are not controlled by phenobarbital alone. A loading dose of 20 mg/kg through IV will achieve therapeutic blood levels (approximately 15 µg/ml) and the maintenance dose is 5 mg/kg/day. However, maintenance doses must be extremely tailored for each baby due to such factors as wide variability with how each baby metabolizes (processes) the drug, and the fact that generic versions of phenytoin can work very differently on the brain.
- Fosphenytoin is often used as an alternative to phenytoin due to reports of less adverse effects when given as an initial dose to treat a sudden seizure.
- Lorazepam is useful for infants with “uncontrolled” seizures in spite of therapy with phenobarbital and phenytoin. The usual dose is 0.05 – 0.1 mg/kg per dose. Due to the possibility of respiratory depression (especially if phenobarbital is already in the baby’s system), the safest use of lorazepam is when the baby is on a breathing machine / ventilator. When respiratory depression occurs, the baby will either stop breathing, have periods of breathing cessation (apnea), or the breaths will be too shallow and infrequent to be effective and meet the baby’s metabolic demands.
When seizures are unresponsive to AEDs, pyridozine (a B vitamin (B6)) should be administered. If the baby does not respond to this, medical staff may administer folic acid (B9).
Standard practice consists of continuing acute (sudden onset) AED therapy until seizures are controlled. AEDs are typically withdrawn 2 weeks after the baby’s last seizure.
The Importance of Seizure Monitoring
Babies at risk of having seizures and that have had a seizure must be closely monitored. Sometimes the only sign of seizure is activity on an EEG (electroencephalography – brain activity monitoring). Cardiopulmonary monitoring devices may also alert the medical team that the baby may be having a seizure. One sign of a seizure is apnea, and monitoring devices can detect this. In addition, respiratory rate and heart rate may change during a seizure, which also can be detected on a monitor. Many times, a seizure can be observed. If anyone on the medical team witnesses signs of a seizure, such as the body going limp, the baby losing consciousness, or the baby staring and / or making bicycle “pedaling” movements, EEG monitoring and diagnosis of seizure activity must promptly take place. If a seizure is diagnosed, the underlying cause must be found and treated in a timely fashion.
Very close monitoring must also occur if AED therapy occurs because this treatment can be dangerous. In addition to standard monitoring, physicians must monitor blood levels of the drugs used, as well as liver and kidney function.
NEONATAL SEIZURES AND MEDICAL MALPRACTICE
Failure to diagnose and treat seizure activity in a timely fashion is negligence, and this includes failure to treat the seizure’s underlying cause, failure to properly monitor a baby on medication, and failure to properly administer seizure medications. If this negligence leads to injury in the baby, it is medical malpractice.
The birth injury attorneys at Reiter & Walsh ABC Law Centers have helped hundreds of families (in Michigan, Ohio, Washington, D.C., and throughout the U.S.) affected by seizures and other birth injuries. Partners Jesse Reiter and Rebecca Walsh are currently recognized as being two of the best medical malpractice lawyers in America by U.S. News and World Report 2015, which also recognized ABC Law Centers as being one of the best medical malpractice law firms in the nation. If your baby was injured during birth, call Reiter & Walsh at 888-419-2229.
- Gallagher RC, Van Hove JL, Scharer G, et al. Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy. Ann Neurol 2009; 65:550.
- Glass HC, Wirrell E. Controversies in neonatal seizure management. J Child Neurol 2009; 24:591.
- Painter MJ, Scher MS, Stein AD, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med 1999; 341:485.
- Volpe JJ. Hypoxic-ischemic encephalopathy: clinical aspects. In: Neurology of the Newborn, 5th, Volpe JJ (Ed), Saunders, Philadelphia 2008. p.400.
- Yager JY, Armstrong EA, Black AM. Treatment of the term newborn with brain injury: simplicity as the mother of invention. Pediatr Neurol 2009; 40:237.
- Okereafor A, Allsop J, Counsell SJ, et al. Patterns of brain injury in neonates exposed to perinatal sentinel events. Pediatrics 2008; 121:906.
- Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365:663.
Related Articles and Blogs from Reiter & Walsh ABC Law Centers
- “Seizures in newborns may indicate neurological birth injury.”
- “Delayed treatment of infant seizures can cause permanent brain damage.”
- “Revolutionary technology may be able to instantly detect seizures in babies and prevent brain damage.”
- “Hypoxic ischemic encephalopathy (HIE)/birth asphyxia and seizures.”