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(See also Seizure Disorders.)
Neonatal
seizures are abnormal electrical discharges in the CNS of neonates
usually manifesting as stereotyped muscular activity or autonomic
changes. Diagnosis is confirmed by EEG; testing for causative conditions
is indicated. Treatment depends on cause.
Seizures occur in up to 1.4% of term infants and 20% of premature infants. Seizures may be a serious neonatal problem and require immediate evaluation. Most neonatal seizures are focal, probably because in neonates generalization of the electrical activity is impeded by lack of myelination and incomplete formation of dendrites and synapses in the brain. Some neonates undergoing EEG for assessment of symptoms of encephalopathy (eg, hypoactivity, decreased responsiveness) are found to have clinically silent seizures (epileptiform electrical activity during an EEG but without any visible seizure activity). Occasionally, clinically silent electrical activity is continuous and persists for > 20 min; at that point, it is defined as electrical status epilepticus.
Etiology
The abnormal CNS electrical discharge may be caused by a primary intracranial process (eg, meningitis, ischemic stroke, encephalitis, intracranial hemorrhage, tumor) or may be secondary to a systemic problem (eg, hypoxia-ischemia, hypoglycemia, hypocalcemia, hyponatremia). 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. Such seizures may be severe and difficult to treat, but they tend to abate after about 3 to 4 days.
Ischemic
stroke is more likely in neonates with polycythemia or with thrombophilia due to a genetic disorder but may also occur without any risk factors. Stroke typically occurs in the middle cerebral artery distribution or watershed zones. Seizures resulting from stroke tend to be focal and may cause apnea.
Infections such as meningitis and sepsis may cause seizures; in such cases, seizures are usually accompanied by other symptoms and signs. Group B streptococcus and gram-negative bacteria are common causes of such infections in neonates. Encephalitis due to cytomegalovirus, herpes simplex virus, rubella virus, Treponema pallidum
, or Toxoplasma gondii can also cause seizures.
Hypoglycemia is common among neonates whose mothers have diabetes, who are small for gestational age, 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, including subarachnoid, intracerebral, and intraventricular hemorrhage, may cause seizures. Intraventricular hemorrhage, which occurs in premature infants, results from bleeding in the germinal matrix (a region adjacent to the ventricles that gives rise to neurons and glial cells during development).
Hypernatremia or hyponatremia may cause seizures. Hypernatremia can result from accidental oral or IV NaCl overload. Hyponatremia can result from dilution (when too much water is given po or IV) or may follow Na loss in stool or urine.
Hypocalcemia (serum Ca level < 7.5 mg/dL [< 1.87 mmol/L]) is usually accompanied by a serum P level of > 3 mg/dL (> 0.95 mmol/L) and can also be asymptomatic. Risk factors for hypocalcemia include prematurity and a difficult birth.
Hypomagnesemia is a rare cause of seizures, which may occur when the serum Mg 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 Ca therapy.
Inborn
errors of metabolism (eg, amino or organic aciduria) can cause neonatal seizures. Rarely, pyridoxine deficiency or dependency causes seizures; it is readily treated.
Other
causes include CNS malformations. Maternal substance abuse (eg, cocaine, heroin, diazepam ) is an increasingly common problem; seizures can occur with acute withdrawal after birth. Neonatal seizures may be familial; some have genetic causes.
Symptoms and Signs
Neonatal seizures are usually focal and may be difficult to recognize. Migratory clonic jerks of extremities, alternating hemi-seizures, or primitive subcortical seizures (which cause respiratory arrest, chewing movements, persistent eye deviations or nystagmoid movements, episodic changes in muscle tone) are common. 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.
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. Seizures occur spontaneously, and motor activity is felt even when the limb is held still.
Diagnosis
Evaluation begins with a detailed family history and a physical examination. EEG (waking and sleep) is essential, especially when it is difficult to determine whether the neonate is having seizures; EEG is also helpful for monitoring response to treatment. EEG should capture periods of active and quiet sleep and thus may require ≥ 2 h of recording. A normal EEG with expected variation during sleep is a good prognostic sign; an EEG with diffuse severe abnormalities (eg, suppressed voltage or burst suppression pattern) is a poor one.
Other tests should include pulse oximetry; measurement of plasma glucose, Na, K, Cl, HCO3, Ca, and Mg; and lumbar puncture for CSF analysis (cell count and differential, glucose, protein) and culture. Urine and blood cultures are obtained. The need for other metabolic tests (eg, arterial pH, blood gases, serum bilirubin, urine amino or organic acids) or tests for commonly abused drugs (passed to the neonate transplacentally or by breastfeeding) depends on the clinical situation.
Most infants should have a head CT because it can detect intracranial bleeding and some brain malformations. Cranial ultrasonography may detect intraventricular bleeding but not subarachnoid bleeding; it may be preferred as a bedside test for very sick infants who cannot be moved to radiology. Diffusion-weighted MRI may detect ischemic tissue within a few hours but is usually done after the 2nd day to look for parenchymal damage.
Prognosis
About 50% of neonates with seizures due to hypoxia-ischemia develop normally. Most neonates with seizures due to subarachnoid hemorrhage, hypocalcemia, or hyponatremia do well. Those with severe intraventricular hemorrhage have a high morbidity rate. For idiopathic seizures or seizures due to malformations, earlier onset is associated with higher morbidity and mortality rates.
Whether neonatal seizures cause damage beyond that caused by the underlying disorder is unknown, although there is concern that the metabolic stress of prolonged nerve cell firing during lengthy seizures may cause additional brain damage. When caused by 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 from other causes may be more persistent in the neonatal period.
Treatment
Treatment focuses primarily on the underlying disorder and secondarily on seizures.
For low plasma glucose, 10% dextrose 2 mL/kg IV is given, and plasma glucose level is monitored; additional infusions are given as needed. For hypocalcemia, 10% Ca gluconate 1 mL/kg IV (9 mg/kg of elemental Ca) is given; this dose can be repeated for persistent hypocalcemic seizures. Rate of Ca gluconate infusion should not exceed 50 mg/min; continuous cardiac monitoring is necessary during the infusion. Extravasation should be avoided because skin may slough. For hypomagnesemia, 0.2 mL/kg of a 50% Mg sulfate solution is given IM. Bacterial infections are treated with antibiotics.
Anticonvulsants are used unless seizures stop quickly after correction of hypoglycemia, hypocalcemia, hypomagnesemia, hyponatremia, hypernatremia, or other underlying disorders. Phenobarbital is the drug of choice; a loading dose of 20 mg/kg IV is given. If seizures continue, 5 mg/kg can be given q 30 min until seizures cease or until a maximum of 40 mg/kg is given. Maintenance therapy is started about 12 h later at 1.5 to 2 mg/kg bid and increased to 2.5 mg/kg bid based on clinical or EEG response or serum drug levels. Phenobarbital is continued IV, especially if seizures are frequent or prolonged. When seizures are controlled, phenobarbital can be given orally. Therapeutic serum levels of phenobarbital are 15 to 40 μg/mL (65 to 170 μmol/L).
If a 2nd drug is needed, fosphenytoin or phenytoin is used. The loading dose is 20 mg PE ( phenytoin equivalents)/kg IV. It is given over 15 min to avoid hypotension or arrhythmias. A maintenance dose is then started at 2 to 3 mg/kg q 12 h and adjusted based on clinical response or serum levels. Therapeutic serum levels for phenytoin are 10 to 20 μg/mL (40 to 80 μmol/L).
Lorazepam 0.1 mg/kg IV may be used for resistant seizures and repeated at 5- to 10-min intervals, up to 3 doses in any 8-h period.
Neonates given IV anticonvulsants are closely observed; overmedication may result in respiratory depression.
Last full review/revision November 2005
Content last modified November 2005
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