Lifetime risk of seizures is highest in the neonatal period, and seizures are one of the most common neurologic complications encountered by the pediatric practitioner. In addition, seizure burden in the neonatal period can be associated with significant morbidity and mortality. Because many of the etiologies of seizures are treatable and may be life threatening, prompt identification and treatment are critical.
Neonatal seizures are relatively common and are estimated to occur in approximately 2 to 5 per 1,000 live births in the United States.1,2 In this population, seizures are most likely to occur within the first 10 days of postnatal life.3 Although neonatal seizures share some common etiologies with seizures occurring later in childhood, the majority are caused by conditions unique to the neonatal period.
Seizures are caused by excessive synchronous neuronal depolarization. Neuronal depolarization occurs via influx of sodium (Na+), and repolarization occurs via efflux of potassium (K+). This repolarization is driven by an adenosine triphosphate (ATP)-dependent pump that exchanges Na+ for K+. Certain common pathologic conditions in the neonatal period, such as hypoglycemia and hypoxic ischemic encephalopathy, result in failure of this Na+/K+ ATPase pump and destabilization of the membrane potential, resulting in seizures. The increased incidence of seizures in the neonatal period is thought to be due to a combination of excessive excitatory and deficient inhibitory neuronal activity. The neonatal brain contains elevated levels of excitatory neurotransmitters, particularly glutamate, which are important for activity-dependent synaptogenesis but also increase likelihood of seizures.4,5 Additionally, the primary inhibitory neurotransmitter, gamma-aminobutyric acid, is relatively less prevalent and exhibits an excitatory rather than inhibitory effect on the developing brain.5
Neonatal seizures have unique clinical characteristics compared to older infants, children, and adults. This is due to neuroanatomical differences. The neonatal brain is incompletely myelinated, which impairs seizure propagation. As a result, neonatal seizures tend to have a focal or multifocal onset without secondary generalization, especially across hemispheres. As such, they tend to be brief, often subtle, and nonspecific in appearance, and can be misinterpreted as normal neonatal movements. Thus, an electroencephalogram (EEG) is always recommended in cases where seizure activity is suspected due to poor reliability of the clinical examination alone. Neonatal seizures are classified into five categories: focal clonic, focal tonic, myoclonic, subtle (motor or autonomic), and generalized tonic (Table 1).3,4
Main Types of Neonatal Seizures
Focal clonic seizures are characterized by slow, rhythmic jerking of one or more extremities or rhythmic twitching of the face. Movements in different extremities or sides of the body may occur simultaneously. These movements are nonsuppressible, which may help distinguish them from nonepileptic etiologies such as jittery movements, limb clonus, or benign sleep myoclonus. Jittery movements generally involve all extremities and are characterized by short, rapid tremors that resolve with restraint or repositioning of the infant. Benign jittery movements occur when the infant is awake and in an alert state. Limb clonus is generally restricted to a single joint, characteristically the ankle, and is characterized by short bursts of jerking that can be elicited by stretching the affected tendon and suppressed by releasing the stretch on the tendon.
Focal tonic seizures are characterized by slow, sustained stiffening of a limb or limbs, often with associated posturing of the limb and asymmetric posturing of the trunk. Seizures do not terminate with tactile stimulation or repositioning of the limb and cannot be induced by stimulation. They may also be associated with sustained eye and head deviation.
Myoclonic seizures are characterized by rapid, single jerks of one or more extremities or the extremities and trunk. They may be repetitive but do not necessarily occur in a rhythmic manner. Unlike benign sleep myoclonus, which occurs exclusively during sleep, myoclonic seizures generally occur while neonates are awake.
Subtle seizures can be divided into motor and autonomic subsets. Subtle motor seizures are brief, stereotyped movements of the face or extremities such as eye deviation, blinking, nystagmus, tongue thrusting, chewing movements, “swimming” movements of the arms, or bicycling of the legs. Subtle autonomic seizures involve rapid, brief changes in heart rate (generally tachycardia), hypertension, and/or apnea. Subtle seizures occur more frequently in preterm infants, although apnea in the full-term infant is more commonly associated with subtle seizures than in the preterm infant.4
Epileptic spasms are a rare type of neonatal seizure. Spasms in the neonatal period have similar electroclinical characteristics as infantile spasms.6 Clinically, spasms are observed as brief flexion and/or extension of extremities lasting seconds and frequently occurring in clusters. The duration of extension and/or flexion is longer than myoclonus and shorter than tonic seizures.7
Generalized tonic seizures are associated with trunk and limb posturing, either in flexion or extension. They may be provoked or intensified with tactile stimulation and will generally terminate with restraint or containment. These sustained episodes do not generally correlate with epileptiform discharges on EEG and are thus felt to be a “brainstem release phenomenon” rather than true seizures.8
The differential diagnosis for neonatal seizures is broad and includes traumatic or structural causes, infectious and metabolic etiologies, drug withdrawal or intoxication, and neonatal epilepsy syndromes (Table 2).
Etiology of Neonatal Seizures
Hypoxic Ischemic Encephalopathy
The most common cause of neonatal seizures is hypoxic ischemic encephalopathy (HIE), accounting for up to 50% to 60% of cases. HIE results in decreased blood flow and oxygen delivery to the brain and generally occurs immediately prior to, during, or immediately after birth. Seizures caused by HIE generally present before 24 hours of postnatal life with highest frequency occurring between age 12 and 24 hours,1,4 as well as during the rewarming period. Due to the high risk of acute seizures, long-term EEG monitoring is recommended for all neonates undergoing therapeutic hypothermia.
Vascular lesions are the second most common etiology for seizures. This category includes ischemic stroke, hemorrhage, thrombosis, and congenital vascular anomalies of the brain (ie, vein of Galen malformation). Ischemic stroke can occur in arterial, venous, or watershed distributions, and they account for 10% to 20% of seizures in the neonatal period. Most of these strokes occur prenatally, and seizures tend to present after age 12 hours in an otherwise alert and well-appearing infant. Seizures are the presenting feature in up to 97% of cases and are often the only symptom.4 Cerebral sinus venous thrombosis is associated with venous infarct and has a high risk of hemorrhagic conversion.1 Although less common than ischemic stroke, it affects up to 1 in 8,000 infants.4
Intracranial hemorrhage is the most frequent hemorrhagic cause of seizures in infants. High-grade intraventricular hemorrhage in the preterm neonate may result in seizures in about 15% of cases.1,2 Less common causes include subarachnoid and subdural hemorrhage, and in these cases, seizures are often the result of underlying cerebral contusion rather than the bleed itself. These bleeds may result due to normal birth trauma, but neonates presenting after the first days of postnatal life should be evaluated for non-accidental trauma.
Congenital Brain Malformations
Congenital brain malformations can result in seizures that present at any point in the neonatal or infantile period due to inherent alterations in the cortical structure. These include focal (focal cortical dysplasia and schizencephaly) and diffuse (polymicrogyria, lissencephaly) lesions.
Bacterial, fungal, and viral infections of the central nervous system are a serious cause of seizures that require urgent treatment to prevent death and long-term neurodevelopmental impairment. The most common bacterial etiologies of seizure are meningitis caused by Group B streptococci and Escherichia coli. Seizures related to these pathogens generally occur around or after the later part of the first week after birth. Seizures related to herpes simplex virus generally occur within 7 days of birth in a previously healthy newborn. Seizures may also be a sequela of other congenital infections. Congenital infections that are associated with seizures include toxoplasmosis, rubella, syphilis, cytomegalovirus, coxsackie virus, and others viral causes. Seizures associated with congenital infections typically occur in the first days of postnatal life and are generally accompanied by findings such as hydrocephalus or calcifications on head imaging.
Metabolic derangements represent a treatable and reversible cause of seizures; thus, prompt recognition is critical. These include hypoglycemia, hypocalcemia, hypomagnesemia, hypophosphatemia, hypoor hypernatremia, as well as certain inborn errors of metabolism.
Hypoglycemia is most common in infants who are growth restricted or small for gestational age, as well as infants of mothers with diabetes. Hypoglycemia may cause jitteriness, lethargy, apnea, and seizures. Duration of hypoglycemia is most closely correlated with neurologic manifestations, and hypoglycemia severe enough to cause seizures is generally associated with persistent deficits.1
Hypocalcemia has two peak incidences in the neonatal period. The first occurs in the 2 to 3 days after birth and is most common in infants who are preterm, growth restricted, and small for gestational age, and in infants whose mothers have diabetes. The hypocalcemia is generally transient and responds well to calcium replacement. The second peak occurs between ages 4 and 28 days and has a wider differential diagnosis, including hypoparathyroidism (transient or congenital), congenital heart disease, DiGeorge syndrome, or nutritional deficits (vitamin D deficiency or high consumption of formula low in calcium). Symptomatic hypocalcemia presents with hyperreflexia, ankle, knee and jaw clonus, jitteriness, and focal seizures.
Cofactor and vitamin deficiencies, although rare, represent another potentially treatable metabolic cause of refractory neonatal seizures. These include pyridoxamine 5'-phosphate oxidase (PNPO) deficiency, pyridoxine-dependent epilepsy (PDE), and biotinidase deficiency.4 Seizures generally present in the first hours after birth, although intrauterine seizures have been described. These disorders present with a variety of seizure types, including infantile spasms, that are refractory to antiepileptic medications. These conditions should be suspected in a neonate that presents with intractable seizures soon after birth that fail to respond to multiple antiepileptic medications. In these conditions, the associated encephalopathy is typically progressive and results in death if not recognized and treated. Seizure control is achieved with cofactor or vitamin replacement, but neurodevelopmental outcomes are generally poor.
Inborn Errors of Metabolism
Many inborn errors of metabolism may present with seizures in the neonatal or infantile period. Inborn errors should be suspected in an infant with encephalopathy who presents within a few days of birth after an uncomplicated pregnancy and delivery. Affected neonates will be asymptomatic at birth and then experience a clinical deterioration within the first days to weeks after delivery. Excessive irritability or crying, recurrent apnea, lethargy, poor feeding, and hiccups may precede seizure activity. Unlike other causes of seizures, neonates will generally not return to a normal neurologic baseline but instead remain encephalopathic between seizures. Family history may reveal consanguinity or a history of neonatal deaths. Infants may have elevated ammonia levels and may have profound metabolic acidosis. The most common inborn errors presenting with seizures in the neonatal period include the organic acidemias, urea cycle defects, nonketotic hyperglycinemia, and aminoacidopathies.3
Neonatal Drug Withdrawal
Neonatal drug withdrawal, particularly from opiates/opioids, is a rare cause of neonatal seizures, although its incidence is increasing due to the rise in maternal drug use and postnatal opiate exposure. The substances most frequently associated with seizures are narcotics, benzodiazepines, barbiturates, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors. Fetal exposure to cocaine, alcohol, and tricyclic antidepressants has also been implicated in neonatal seizures. Infants with neonatal abstinence syndrome may manifest a variety of abnormal movements such as exaggerated Moro reflex, myoclonic jerks, and tremors, so EEG is recommended to identify true seizure activity. Seizures generally begin within the first few days after birth and may require antiepileptic therapy until the withdrawal symptoms have resolved.
Neonatal Epilepsy Syndromes
Unlike the above etiologies, the neonatal epilepsy syndromes represent unprovoked causes of seizure activity in the neonate. Three syndromes are recognized by the International League Against Epilepsy: benign familial neonatal epilepsy (BFNE), early (neonatal) myoclonic encephalopathy (EME) and early infantile epileptic encephalopathy (Otahara syndrome).
BFNE, as its name implies, is a relatively benign condition generally associated with excellent neurologic outcomes. This autosomal dominant condition is classified by seizures that begin within the first week of life and generally resolve by age 1 to 12 months. Seizures may be tonic, clonic, or associated with apneic spells. Development is generally normal although 10% to 15% of infants may go on to develop epilepsy later in life.4 Diagnosis is typically made based on characteristic EEG findings as well as genetic testing. BFNE is associated with mutations in potassium channel genes KCNQ2 and KCNQ3 on chromosome 20q and 8q respectively. These potassium channels control neuronal connectivity, and mutations in the channel result in hyperexcitability of the neuron.4
Epileptic encephalopathies such as EME and Otahara syndrome are both devastating conditions characterized by severe, intractable seizures with failure to gain developmental milestones. Both are characterized by significantly abnormal background EEG activity, frequently with suppression-burst activity on EEG. EME is generally caused by an underlying metabolic disorder, most commonly nonketotic hyperglycinemia, although it can also be due to amino acid or organic acid disorders. Otahara syndrome is most often due to structural brain malformations; however, several genetic causes have been identified for both conditions.8
After a thorough history is obtained and physical examination is completed, with special focus on the neurologic component, initial testing should focus on identification of potentially treatable etiologies such as infectious and metabolic derangements. Early laboratory testing should include a rapid point of care glucose level, serum chemistry panel, complete blood count, and blood culture. Clinicians should maintain a low threshold for obtaining cerebral spinal fluid (CSF) for gram stain and culture, chemistry, and cell counts to rule out infectious etiologies. If an infectious cause is suspected, then HSV testing should be performed, including HSV CSF polymerase chain reaction testing. Based upon the infant's history, it may be beneficial to obtain a C-reactive protein level, urinalysis, urine culture, and urine toxicology. If a congenital infection (ie, TORCH [Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, and Herpes simplex] infection) needs to be ruled out, then the appropriate diagnostic tests should be ordered. Additional testing should include blood gas, lactate, pyruvate, and ammonia levels. Newborn screen results should be obtained if available. In regard to radiologic studies, cranial ultrasound can be a useful rapid bedside tool, but brain magnetic resonance imaging is the gold standard for head imaging. If the above fails to yield a diagnosis, more extensive metabolic and genetic testing may be indicated, such as urine organic acids, plasma amino acids, vitamin levels, CSF neurotransmitters, and a comprehensive epilepsy genetic panel.
Seizures in the neonatal period are frequently brief, subtle, and clinically nonspecific. It can be difficult for the bedside provider to distinguish clinical seizure from normal movements. In addition, up to 80% to 90% of neonatal seizures are electrographic without clinical correlate.9 Thus, an EEG is recommended in the detection of seizure activity.
Electrographic seizure is defined as repetitive and rhythmic pattern of at least 10 seconds in duration (Figure 1). EEG with video is important in helping distinguish seizures from nonepileptic movements.9 Moreover, in neonatal seizures, treatment of clinical seizures with anticonvulsants often results in subsequent persistent electrographic seizures without clinical correlate (called “electroclinical dissociation”). Therefore, continuous video EEG monitoring (cEEG) is recommended to characterize seizures, quantify seizure burden, and assess response to treatment.6,9 In addition, it is recommended to continue video EEG until the patient is seizure free for 24 hours.
Neonatal electroencephalogram (EEG) findings. (A) Normal awake neonatal EEG from a 3-day-old infant born at 38 weeks gestational age with episodes of apnea and desaturations. Note the continuous background with variable frequency. Occasional frontal sharp transients (asterisk symbol) are normal. (B) Multifocal sharp discharges and discontinuity. This is from a 1-month-old infant with congenital heart disease on extra-corporeal membrane oxygenation (ECMO). Background is discontinuous with diffuse voltage attenuation (down arrow symbol) and excessive sharp discharges (double dagger symbol). (C, D) Electrographic seizures with multifocal onset from a 4-day-old infant with hypoglycemia, hyperammonemia, and body jerking concerning for seizure. (C) EEG demonstrates focal low voltage monomorphic rhythmic activity (right arrow symbol) localized in right central region. (D) This same patient had focal seizure arising from left central region (left arrow symbol) then another seizure arising independently from right central region. Both seizures were electrographic without clinical correlation.
Although cEEG is the diagnostic test of choice, there are many barriers to accessing EEG in institutions. As a result, amplitude-integrated EEG (aEEG) is a bedside tool that is increasingly implemented in the neonatal intensive care unit due to ease of application and interpretation by a neonatologist.10 aEEG uses limited EEG signals that are filtered, processed, and displayed in timecompressed scale, often in conjunction with raw EEG signal to provide assessment of background as well as to assist in detecting neonatal seizures. Importantly, it allows neonatologists a timely and convenient instrument for neuromonitoring. However, it is important to note that aEEG has limitations. There is potential of overdiagnosis of seizures attributed to mistaking artifact for seizure activity.10 It is also less accurate compared to cEEG in detecting seizures that are brief (<90 seconds in duration) and low voltage,9,10 which are common features in neonatal seizures. As a result, there is also a potential for underdiagnosing seizure frequency. Finally, aEEG interpretation is largely dependent on user experience. Nonetheless, the specificity and sensitivity for seizure detection can be up to 85% in an experienced user.10,11 Despite its limitations, studies have shown that aEEG has resulted in improved decision-making and better neurological outcomes.9 Therefore, although cEEG is the gold standard for seizure detection, aEEG is a useful screening tool until conventional EEG can be obtained.
The first priority in treating neonatal seizures is to manage airway, breathing, and circulation. This is followed by correction of any metabolic derangements that may be the underlying cause of the seizures. In the case of ongoing seizure activity, antiepileptics are used to control persistent seizures (Figure 2). Phenobarbital is the most frequently used first-line antiepileptic agent. Seizures are controlled in approximately 50% to 70% of neonates once a therapeutic level of phenobarbital, about 40 mcg/mL, is reached.2,4,12 Phenobarbital is generally administered in sequential loading doses until seizure control is reached, then maintenance dosing is started. Levels are generally checked 1 to 2 hours after each load, and periodically during maintenance therapy. There is concern in the animal model for neuronal apoptosis with phenobarbital, although human studies have failed to consistently demonstrate this.11,13,14 Choice of second-line agents is variable among providers but is generally split between levetiracetam or fosphenytoin. Fosphenytoin demonstrated equivalent efficacy to phenobarbital in a randomized controlled trial,15 but also has been shown to cause neuronal apoptosis in an animal model.14 There is emerging evidence that levetiracetam may be a safer and equally efficacious treatment option.16,17 although optimal dosing regimens and randomized controlled efficacy data are lacking. Seizures refractory to multiple loading doses of the above medications may respond to continuous infusion of a benzodiazepine, 18,19 which can be titrated based on cEEG monitoring. Lidocaine is used in some centers, although its use carries risk of arrhythmia so duration of treatment is limited.
Treatment algorithm for neonatal seizures. BID, two times daily; IV, intravenous; TID, three times daily.
Neonatal seizures carry an increased risk of mortality and neurodevelopmental disability that vary greatly depending upon etiology and prompt recognition/management. Overall, mortality rates are about 15% to 20%.20,21 In survivors, there is an increased risk of cerebral palsy, developmental delay, and epilepsy. Risk of cerebral palsy is 25% to 45%, risk of global developmental delay is about 50%, and risk of epilepsy is about 20% to 30%.21–24 Risk of cerebral palsy and epilepsy is increased in preterm infants, infants with low Apgar scores, severe encephalopathy, severe parenchymal injury, cerebral dysgenesis, status epilepticus, and abnormal background EEG activity.20–24
Close follow-up of the neonate with seizures is important, as well as prompt and aggressive early intervention therapies as indicated to address specific neurologic deficits. Infants should, at minimum, be observed by neurology as an outpatient, as well as physical, occupational, and speech therapies as indicated. Infants with concern for an underlying genetic etiology may need outpatient follow-up with a geneticist at discharge.
- Natarajan N, Gospe S. Neonatal seizures. In: Gleason CA, Juul SE, eds. Avery's Diseases of the Newborn. 10th ed. Philadelphia, PA: Elsevier, 2018:961–970.
- Abend NS, Jensen FE, Inder TE, Volpe JJ. Neonatal seizures. In: Volpe JJ, ed. Volpe's Neurology of the Newborn. 4th ed. Philadelphia, PA: WB Saunders; 2001:275–321.
- Olson DM. Neonatal seizures. Neoreviews. 2012;13(4):e213–e223. doi:10.1542/neo.13-4-e213 [CrossRef]
- Martin RJ, Fanaroff AA, Walsh MC. Fanaroff and Martin's Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 10th ed. Philadelphia: Elsevier/Saunders; 2015.
- Jensen FE. Developmental factors in the pathogenesis of neonatal seizures. J Pediatr Neurol. 2009;7(1):5–12. PMID:20191097
- Silverstein FS, Jensen FE. Neonatal seizures. Ann Neurol. 2007;62(2):112–120. doi:10.1002/ana.21167 [CrossRef] PMID:17683087
- Kliegman RM. Nelson's Textbook of Pediatrics. 21st ed. St. Louis, MO: Elsevier; 2019.
- Pellock J, Nordli D, Sankar R, Wheless J. Pellocks's Pediatric Epilepsy: Diagnosis and Therapy. 4th ed. New York, NY. Demos Medical Publishing; 2016.
- Abend NS, Wusthoff CJ. Neonatal seizures and status epilepticus. J Clin Neurophysiol.2012;29(5):441–448. doi:10.1097/WNP.0b013e31826bd90d [CrossRef] PMID:23027101
- Glass HC, Wusthoff CJ, Shellhaas RA. Amplitude-integrated electroencephalography: the child neurologist's perspective. J Child Neurol. 2013;28(10):1342–1350. doi:10.1177/0883073813488663 [CrossRef] PMID:23690296
- Meyn DF Jr, Ness J, Ambalavanan N, Carlo WA. Prophylactic phenobarbital and whole-body cooling for neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2010;157(2):334–336. doi:10.1016/j.jpeds.2010.04.005 [CrossRef] PMID:20553847
- Spagnoli C, Seri S, Pavlidis E, Mazzotta S, Pelosi A, Pisani F. Phenobarbital for neonatal seizures: response rate and predictors of refractoriness. Neuropediatrics. 2016;47(5):318–326. doi:10.1055/s-0036-1586214 [CrossRef] PMID:27458678
- Dilena R, De Liso P, Di Capua M, et al. Influence of etiology on treatment choices for neonatal seizures: a survey among pediatric neurologists. Brain Dev. 2019;41(7):595–599. doi:10.1016/j.braindev.2019.03.012 [CrossRef] PMID:30954359
- Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A. 2002;99(23):15089–15094. doi:10.1073/pnas.222550499 [CrossRef] PMID:12417760
- Painter MJ, Scher MS, Stein AD, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med.1999;341(7):485–489. doi:10.1056/NEJM199908123410704 [CrossRef] PMID:10441604
- Abend NS, Gutierrez-Colina AM, Monk HM, Dlugos DJ, Clancy RR. Levetiracetam for treatment of neonatal seizures. J Child Neurol.2011;26(4):465–470. doi:10.1177/0883073810384263 [CrossRef] PMID:21233461
- Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: safety and efficacy in neonatal seizures. Eur J Paediatr Neurol.2011;15(1):1–7. doi:10.1016/j.ejpn.2010.10.003 [CrossRef] PMID:21094062
- Castro Conde JR, Hernández Borges AA, Doménech Martínez E, González Campo C, Perera Soler R. Midazolam in neonatal seizures with no response to phenobarbital. Neurology. 2005;64(5):876–879. doi:10.1212/01.WNL.0000152891.58694.71 [CrossRef] PMID:15753426
- Claassen J, Hirsch LJ, Emerson RG, Bates JE, Thompson TB, Mayer SA. Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology. 2001;57(6):1036–1042. doi:10.1212/WNL.57.6.1036 [CrossRef] PMID:11571331
- Glass HC, Shellhaas RA, Wusthoff CJ, et al. Neonatal Seizure Registry Study Group. Contemporary profile of seizures in neonates: a prospective cohort study. J Pediatr. 2016;174:98.e1–103.e1. doi:10.1016/j.jpeds.2016.03.035 [CrossRef] PMID:27106855
- Uria-Avellanal C, Marlow N, Rennie JM. Outcome following neonatal seizures. Semin Fetal Neonatal Med.2013;18(4):224–232. doi:10.1016/j.siny.2013.01.002 [CrossRef] PMID:23466296
- Glass HC, Numis AL, Gano D, Bali V, Rogers EE. Outcomes after acute symptomatic seizures in children admitted to a neonatal neurocritical care service. Pediatr Neurol. 2018;84:39–45. doi:10.1016/j.pediatrneurol.2018.03.016 [CrossRef] PMID:29886041
- Ronen GM, Buckley D, Penney S, Streiner DL. Long-term prognosis in children with neonatal seizures: a population-based study. Neurology.2007;69(19):1816–1822. doi:10.1212/01.wnl.0000279335.85797.2c [CrossRef] PMID:17984448
- Glass HC, Grinspan ZM, Shellhaas RA. Outcomes after acute symptomatic seizures in neonates. Semin Fetal Neonatal Med. 2018;23(3):218–222. doi:10.1016/j.siny.2018.02.001 [CrossRef] PMID:29454756
Main Types of Neonatal Seizures
|Focal clonic seizures
||Slow, rhythmic jerking
||Occurs while awake; not suppressible; common manifestation in term neonates
|Focal tonic seizures
||Slow, sustained limb or trunk posturing
||Not suppressible; common manifestation in term neonates
||Rapid, single jerks, may be repetitive but generally not rhythmic
||Occurs while awake; may be provoked by stimulation
|Subtle motor seizures
||Blinking, sucking, chewing, tongue protrusions
||May be provoked or intensified by stimulation
|Subtle autonomic seizures
||Tachycardia, apnea, hyper-tension
||Occurs more frequently in preterm infants
||Brief flexion, extension, or mixed flexor/extension
||May occur in clusters; not suppressible; rare
|Generalized tonic seizures
||Slow, sustained posturing of limbs and trunk
||May be provoked by stimulation; suppressible
Etiology of Neonatal Seizures
|Cause of seizure
|Hypoxic ischemic encephalopathy (50%–60%)
||Generally occur within 12 to 24 hours of birth
|Vascular lesions (10%–20%)
Congenital vascular anomaly
||Includes venous sinus thrombosis, arteriovenous malformation, venous malformations
|Congenital brain malformations (5%–10%)
||Focal: agenesis of the corpus callosum, Dandy-Walker malformation
Diffuse: holoprosencephaly, lissencephaly, polymicrogyria
Congenital Infections (ie, TORCH)
||Can present early (first 72 hours of life) or late (after 7 days of life)
Seizures often prolonged and difficult to treat
||Reversible causes of neonatal seizures include electrolyte abnormalities as well as cofactor and vitamin deficiencies
|Drug intoxication or withdrawal (∼1%)
||Most common drugs include narcotics, benzodiazepines/barbiturates, tricyclic anti-depressants, cocaine, and alcohol
|Neonatal epilepsy syndromes (∼1%)
Benign familial neonatal epilepsy
Benign nonfamilial neonatal convulsions
Early myoclonic encephalopathy/Otahara syndrome
||Very rare, family history may reveal this etiology although many mutations are de novo