Neonatal Seizure Disorders

The abnormal central nervous system (CNS) electrical discharge may be caused by a

Seizures resulting from an intracranial process usually cannot be differentiated from seizures resulting from a systemic problem by their clinical features (eg, focal vs generalized).

Hypoxia-ischemia, the most common cause of neonatal seizures, may occur before, during, or after delivery (see Overview of Perinatal Respiratory Disorders Overview of Perinatal Respiratory Disorders Extensive physiologic changes accompany the birth process (see also Neonatal Pulmonary Function), sometimes unmasking conditions that posed no problem during intrauterine life. For that reason... read more ). Such seizures may be severe and difficult to treat, but they tend to abate after about 3 to 4 days. When neonatal hypoxia is treated with therapeutic hypothermia (usually whole-body cooling), seizures may be less severe but may recur during rewarming.

Ischemic stroke Ischemic Stroke Ischemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes... read more is more likely to occur in neonates with polycythemia Perinatal Polycythemia and Hyperviscosity Syndrome Polycythemia is an abnormal increase in red blood cell mass, defined in neonates as a venous hematocrit ≥ 65%; this increase can lead to hyperviscosity with sludging of blood within vessels... read more , thrombophilia due to a genetic disorder, or severe hypotension but may occur in neonates without any risk factors. Stroke occurs typically in the middle cerebral artery distribution or, if associated with hypotension, in watershed zones. Seizures resulting from stroke tend to be focal and may cause apnea.

Neonatal infections Overview of Neonatal Infections Neonatal infection can be acquired In utero transplacentally or through ruptured membranes In the birth canal during delivery (intrapartum) From external sources after birth (postpartum) Common... read more such as meningitis Neonatal Bacterial Meningitis Neonatal bacterial meningitis is inflammation of the meninges due to bacterial invasion. Signs are those of sepsis, central nervous system irritation (eg, lethargy, seizures, vomiting, irritability... read more and sepsis Neonatal Sepsis Neonatal sepsis is invasive infection, usually bacterial, occurring during the neonatal period. Signs are multiple, nonspecific, and include diminished spontaneous activity, less vigorous sucking... read more may cause seizures; in such cases, seizures are usually accompanied by other symptoms and signs. Group B streptococci and gram-negative bacteria are common causes of such infections in neonates. Encephalitis due to cytomegalovirus Congenital and Perinatal Cytomegalovirus Infection (CMV) Cytomegalovirus infection may be acquired prenatally or perinatally and is the most common congenital viral infection. Signs at birth, if present, are intrauterine growth restriction, prematurity... read more , herpes simplex virus Neonatal Herpes Simplex Virus (HSV) Infection Neonatal herpes simplex virus infection is usually transmitted during delivery. A typical sign is vesicular eruption, which may be accompanied by or progress to disseminated disease. Diagnosis... read more , rubella virus Congenital Rubella Congenital rubella is a viral infection acquired from the mother during pregnancy. Signs are multiple congenital anomalies that can result in fetal death. Diagnosis is by serology and viral... read more , Treponema pallidum Congenital Syphilis Congenital syphilis is a multisystem infection caused by Treponema pallidum and transmitted to the fetus via the placenta. Early signs are characteristic skin lesions, lymphadenopathy... read more , Toxoplasma gondii Congenital Toxoplasmosis Congenital toxoplasmosis is caused by transplacental acquisition of Toxoplasma gondii. Manifestations, if present, are prematurity, intrauterine growth restriction, jaundice, hepatosplenomegaly... read more , or Zika virus Zika Virus (ZV) Infections The Zika virus is a mosquito-borne flavivirus that is antigenically and structurally similar to the viruses that cause dengue, yellow fever, and West Nile virus. Zika virus infection is typically... read more can also cause seizures.

Hypoglycemia Neonatal Hypoglycemia Hypoglycemia is difficult to define in neonates but is generally considered a serum glucose concentration < 40 mg/dL (< 2.2 mmol/L) in symptomatic term neonates, < 45 mg/dL (< 2... read more is common among neonates whose mothers have diabetes Diabetes Mellitus in Pregnancy Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy ( 1)... read more , who are small for gestational age Small-for-Gestational-Age (SGA) Infant Infants whose weight is < the 10th percentile for gestational age are classified as small for gestational age. Complications include perinatal asphyxia, meconium aspiration, polycythemia... read more , or who have hypoxia-ischemia or other stresses. Seizures due to hypoglycemia tend to be focal and variable. Prolonged or recurrent hypoglycemia may permanently affect the CNS.

Intracranial hemorrhage Intracranial Hemorrhage The forces of labor and delivery occasionally cause physical injury to the infant. The incidence of neonatal injury resulting from difficult or traumatic deliveries is decreasing due to increasing... read more , including subarachnoid Subarachnoid hemorrhage The forces of labor and delivery occasionally cause physical injury to the infant. The incidence of neonatal injury resulting from difficult or traumatic deliveries is decreasing due to increasing... read more , intracerebral, and intraventricular hemorrhage Intraventricular hemorrhage and/or intraparenchymal hemorrhage The forces of labor and delivery occasionally cause physical injury to the infant. The incidence of neonatal injury resulting from difficult or traumatic deliveries is decreasing due to increasing... read more , may cause seizures. Intraventricular hemorrhage, which occurs more commonly in preterm infants Preterm Infants An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more , results from bleeding in the germinal matrix (an area that is adjacent to the ventricles and that gives rise to neurons and glial cells during development).

Hypernatremia Neonatal Hypernatremia Hypernatremia is a serum sodium concentration > 150 mEq/L (> 150 mmol/L), usually caused by dehydration. Signs include lethargy and seizures. Treatment is cautious hydration with IV saline... read more can result from accidental oral or IV sodium chloride overload.

Hyponatremia Neonatal Hyponatremia Hyponatremia is a serum sodium concentration < 135 mEq/L (< 135 mmol/L). Significant hyponatremia may cause seizures or coma. Treatment is cautious sodium replacement with IV 0.9% saline... read more can result from dilution (when too much water is given orally or IV particularly in the setting of hypovolemia, which, when severe enough, leads to increased antidiuretic hormone [ADH] levels despite the low serum osmolarity [nonosmotic ADH release]) or may follow sodium loss in stool or urine.

Hypocalcemia Neonatal Hypocalcemia Hypocalcemia is a total serum calcium concentration < 8 mg/dL (< 2 mmol/L) in term infants or < 7 mg/dL (< 1.75 mmol/L) in preterm infants. It is also defined as an ionized calcium... read more (serum calcium level < 7.5 mg/dL [< 1.87 mmol/L]) is usually accompanied by a serum phosphorus level of > 3 mg/dL (> 0.95 mmol/L) and can be otherwise asymptomatic. Risk factors for hypocalcemia include prematurity and a difficult birth. Hypocalcemia can also be a manifestation of DiGeorge syndrome DiGeorge Syndrome DiGeorge syndrome is thymic and parathyroid hypoplasia or aplasia leading to T-cell immunodeficiency and hypoparathyroidism. Infants with DiGeorge syndrome have low-set ears, midline facial... read more (22q11.2 deletion syndrome).

Hypomagnesemia Hypomagnesemia Hypomagnesemia is serum magnesium concentration < 1.8 mg/dL (< 0.70 mmol/L). Causes include inadequate magnesium intake and absorption or increased excretion due to hypercalcemia or drugs... read more is a rare cause of seizures, which may occur when the serum magnesium level is < 1.4 mEq/L (< 0.7 mmol/L). Hypomagnesemia often occurs with hypocalcemia and should be considered in neonates with hypocalcemia if seizures continue after adequate calcium therapy.

Inborn errors of metabolism Introduction to Inherited Disorders of Metabolism Most inherited disorders of metabolism (also called inborn errors of metabolism) are caused by mutations in genes that code for enzymes; enzyme deficiency or inactivity leads to Accumulation... read more (eg, amino or organic aciduria Overview of Amino Acid and Organic Acid Metabolism Disorders The kidneys actively reabsorb significant amounts of amino acids. Defects of amino acid transport in the renal tubule include cystinuria and Hartnup disease, which are discussed elsewhere. Amino... read more ) can cause neonatal seizures. Rarely, pyridoxine dependency Vitamin B6 Deficiency and Dependency Because vitamin B6 is present in most foods, dietary deficiency is rare. Secondary deficiency may result from various conditions. Symptoms can include peripheral neuropathy, a pellagra-like... read more causes seizures; however, it must always be considered in neonates with refractory seizures. Pyridoxine dependency is readily treated with pyridoxine.

CNS malformations Overview of Congenital Neurologic Anomalies Congenital brain anomalies usually cause severe neurologic deficits; some may be fatal. Some of the most serious neurologic anomalies (eg, anencephaly, encephalocele, spina bifida) develop in... read more can also cause seizures.

Maternal recreational substance use Social and Illicit Drugs During Pregnancy Drugs are used in over half of all pregnancies, and prevalence of use is increasing. The most commonly used drugs include antiemetics, antacids, antihistamines, analgesics, antimicrobials, diuretics... read more (eg, of cocaine, heroin, or diazepam) is an increasingly common problem; seizures can accompany acute withdrawal after birth.

Neonatal seizures may be familial; some have genetic causes. Benign familial neonatal convulsion is a potassium channelopathy inherited in an autosomal dominant pattern. Early infantile epileptic encephalopathy (Ohtahara syndrome) is a rare disorder associated with a variety of mutations.

Neonatal seizures are usually focal and may be difficult to distinguish from normal neonatal activity because they may manifest as chewing or bicycling movements. Common manifestations include migratory clonic jerks of extremities, alternating hemiseizures, and primitive subcortical seizures (which cause respiratory arrest, chewing movements, persistent eye deviations or nystagmoid movements, and episodic changes in muscle tone). Generalized tonic-clonic seizures are uncommon.

Clinically silent electrical seizure activity is often present after a hypoxic-ischemic insult (including perinatal asphyxia or stroke) and in neonates with CNS infections, especially after initial antiseizure medication treatment, which is more likely to stop clinical manifestations than electrical seizure activity.

Evaluation begins with a detailed family history and a physical examination.

Jitteriness (alternating contraction and relaxation of opposing muscles in the extremities) must be distinguished from true seizure activity. Jitteriness is usually stimulus-induced and can be stopped by holding the extremity still; in contrast, seizures occur spontaneously, and motor activity is felt even when the extremity is held still.

Treatment of neonatal seizures is focused primarily on the underlying disorder and secondarily on seizures.

Prognosis depends on the etiology:

It is suspected, but not proved, that prolonged or frequent neonatal seizures may cause damage beyond that caused by the underlying disorder. There is concern that the metabolic stress of prolonged nerve cell firing during lengthy seizures may cause additional brain damage. When caused by acute injuries to the brain such as hypoxia-ischemia, stroke, or infection, neonates may have a series of seizures, but seizures typically abate after about 3 to 4 days; they may recur months to years later if brain damage has occurred. Seizures due to other conditions may be more persistent during the neonatal period.