seizure is generally associated with it due to involvement of motor cortex in middle cerebral artery region. intraventricular hemorrhage: it causes generally causes seizures in term infants except large hemorrhage involving injury to parenchyma. central nervous system infection: cns infection are found in 3-10% of neonates who seize, though exact incidence varies between studies. bacterial meningitis and viral meningoencephalitis are most prevalent, though fungal infections can occur in antenatal, perinatal and prenatal brain of neonates. infections caused due to late streptococcus b and herpes simplex virus often occur at any time during the neonatal period. lumbar puncture help in diagnosis of neonates suspected of it. in case of the infant is unstable for it, empirical treatment of meningoencephalitis is warranted. seizures related to it persist longer than those associated with hie or ich. congenital central nervous system malformations: lissencephaly, polymicrogyria, and tuberous sclerosis are specific entities known to cause seizures due to defects in brain tissue development. since prognosis is poor and often these disorders are genetic, identification of this etiology is of utmost importance to be able to counsel parents appropriately. inborn errors of metabolism: inborn errors of metabolism can cause physiologic conditions that result in seizures. these errors are genetic and often are accompanied by other symptoms such as lethargy, poor feeding, and low tone. diagnosis often involves specific laboratory tests of metabolic products as well as genetic tests. several classification systems exist for seizures caused by inborn errors of metabolism, one of which separates causes into problems with neurotransmitter metabolism, energy production, and biosynthetic substances crucial for brain formation. electrolyte abnormalities: metabolic abnormalities such as hypoglycemia, hyponatremia, and hypocalcemia can manifest as seizures. substance-related: neonatal abstinence syndrome occurs when maternal drug use before birth results in a fetal withdrawal syndrome. substances include alcohol, cocaine, narcotics, tricyclclic antidepressants, or other sedatives. seizures can be prevented from occurring if the symptoms of withdrawal are recognized and treated early. diagnosis a normal amplitude integrated eeg trace in a term infant who is several days old. the amplitude-integrated trace is in the top half of the screen displaying left- and right-sided traces. there is a normal baseline and upper limit, sleep-wake cycling, and no seizures. seizure activity in a neonate is difficult to diagnose, as many seizures have no clinical correlate. altered level of consciousness is often the only clue, and in a neonate this can be difficult to accurately assess. thus, diagnosis relies on attempting to directly measurement the abnormal electrical activity in the brain with electroencephalography (eeg). eeg is combined with video recording of the infant to correlate any seizure movements with eeg recordings. there are several modes of eeg that are commonly used in the nicu to diagnose neonatal seizures. conventional continuous multichannel conventional eeg is the gold standard for diagnosis of epileptiform activity, but requires expert interpretation. newer amplitude integrated eeg (aeeg) (also termed cerebral function monitoring, or cfm) allows easier monitoring of brain activity, but may not allow identification of short duration, low amplitude, or very high frequency seizure activity. often, both modes are displayed concurrently. determining the cause since many causes of seizures can be rapidly reversed and longterm sequelae prevented, evaluation of underlying cause is of utmost importance. evaluation for infection (with blood counts, lumbar puncture, and empiric treatment with antibiotics) often occurs during eeg monitoring. blood glucose and electrolyte testing can identify metabolic problems that can be corrected. further testing includes evaluation for genetic causes and other more rare metabolic causes. brain injury such as cerebral infarction or hemorrhage can be evaluated with imaging techniques such as magnetic resonance imaging (mri) and brain ultrasound to avoid unnecessary radiation exposure. differential diagnosis infants can exhibit stereotyped movements that may be hard to distinguish from seizure activity. since many of these non-seizure movements are not dangerous and require no treatment, differentiation from actual seizure activity is useful. jitteriness is common in the neonatal period and is seen in upwards of 2/3 of neonates. it is characterized by a tremor that is especially prominent during sleep or periods of agitation. gaze deviation or eye movements do not occur. benign neonatal sleep myoclonus (bnsm) is another common movement that can be mistaken for a seizure. it is characterized by jerking limb movements only during sleep, and stop with waking of the infant. bnsm typically occurs later in infancy, but can occur during the neonatal period. treatment once diagnosis is made, the goals of management are to identify the cause of the seizure, stop the seizure activity, and maintain physiologic parameters such as oxygenation, ventilation, blood glucose, and temperature. treatment greatly depends on the cause of the seizure. for example, infectious causes of seizures (meningitis, meningoencephalitis), are often treated with antimicrobials (antibiotic, antifungal, or antiviral medications). similarly, electrolyte or glucose abnormalities are treated by repleting or lowering the offending electrolyte or sugar. if the cause of the seizures are unlikely to be easily or quickly corrected, once diagnosis of a seizure is made, the mainstay of treatment is pharmacotherapy with anti-epileptic drugs. a 2013 systematic review found that most practitioners use phenobarbital or phenytoin. this study found that phenobarbital has the safest side effect profile and longest history of use in neonates.hence, phenobarbital is used for first-line of treatment. after just one dose of 20 mg/kg of it, seizures are in control, in approximately half of the patients diagnosed with acute symptomatic seizures. a neolev2 study was conducted in the year 2020 to compare the efficiency of levetiracetam and phenobarbital as the first line of therapy. 80% of patients who were administered phenobarbital became seizure-free in 24hrs whereas merely 28% patients became seziure free in case of levetiracetam administration. benzodiazepines are often used as second-line treatment if treatment with phenobarbital does not result in clinical improvement. almost 66% of patients with acute symptomatic seizures, don't have a complete response to the initial dose administered. this is valid for any type of medication selected. research is ongoing on the use of other anti-epileptics that are commonly used in older children and adults and are safe or efficacious to use in neonates. part of the challenge of anticonvulsant drug treatment during the neonatal period is that the immature excitatory and inhibitory neurotransmitter system results in few effective drug targets. there are some drugs that are effective in controlling seizures. "phenobarbitone remains the first-line treatment for seizures in most countries throughout the world, though off-label use of newer anticonvulsants is widespread in the usa". the united states prefers to use unprescribed drugs to help slow down neonatal seizures, but they also use prescribed drugs if needed. drugs are the only option infants are given, even though they are not 100% effective, they are the best option in helping take control of the seizures to stop them from occurring. the following table lists the dosage of the respective medicine: medicine dose phenobarbitone target level: 40mcg/ml maintenance dosage: 3–6 mg/kg/d loading dosage: intravenously 20 mg/kg, repeat once when required phenytoin target level: 10-20mcg/ml to be administered over ten minutes maintenance dosage: 2.5–5 mg/kg/d to be administered in two equal doses. loading dose: 20 mg/kg phenytoin equivalent intravenous over 20 minutes levetiracetam target level: unknown maintenance dosage: 30–60 mg/kg/d in three equal doses loading dosage: intravenously 40–60 mg/kg/d outcomes with earlier diagnosis and increasingly prompt diagnosis, mortality after diagnosis of neonatal seizures has decreased dramatically from an estimated 33% in the 1990s to around 10% in the 2010s. underlying cause of the seizure remains the greatest predictor of ongoing seizures and neurologic problems later in life. controversy remains with the extent of damage the seizures themselves cause. clinician consensus is that frequent or intractable seizures (status epilepticus) leads to neuronal damage and are associated with later neurodevelopment problems. developmental delay, cerebral palsy, and problems with vision and hearing are the most common poor outcomes following neonatal seizures. severity of impairment ranges greatly and many infants develop normally once the initial seizure cause is treated. studies have identified risk factors for poor outcomes after neonatal seizures. infants that are premature, have hypoxemic ischemic encephalopathy, cns infection, severe intraventricular hemorrhage, structural central nervous system defect, or severely abnormal eeg tracings tend to do worse than infants with focal strokes, transient metabolic issues (hypoglycemia, hypocalcemia), or clinical seizures without eeg abnormalities. there are many other risk factors for neonatal seizures. "some of the risk factors that we have detected, such as low apgar score, need for resuscitation at birth, and perinatal distress, were previously reported". an apgar score indicates how a baby is immediately after birth. perinatal distress is when a mother experiences a lot of stress during pregnancy. this shows how serious neonatal seizures really are, and not many people knew that. risk of epilepsy later during childhood is a common question asked by parents in the neonatal intensive care unit (nicu). unfortunately, the answer is rarely clear cut as it depends greatly on the underlying cause. for all infants with neonatal seizures regardless of cause, the rate of subsequent seizures during childhood is estimated between 10 and 20%. infants who survive severe global hie have the highest rate of epilepsy later in life. epidemiology it is difficult to determine the incidence of seizures in the neonatal period. estimations range between 1-5 per 1,000 live births, though the actual rate of seizures during this period may be higher due to a lack of accurate diagnosis of sub-clinical seizure activity without continuous eeg monitoring. the epidemiology moreover varies in high-income countries (hic) from that in low-income ones (lic). the incidence is estimated to be 1-3 per 1000 live births in hic whereas it ranges from 36 to 90 per live birth in lic. acute causes of seizures (hypoxemic ischemic encephalopathy, infection, intracranial hemorrhage, stroke, etc.) are more common than the first episode of neonatal epilepsy syndromes. watching the eeg monitor and detecting when a seizure occurs can help the preterm infant survive these seizures. "continuous monitoring and cranial imaging in the setting of neonatal seizures now compromise the standard of care at many centers, and these technologies are being used to guide management, diagnosis, and prognosis". as the monitoring devices for neonatal seizures become more advanced, the closer researchers are to finding how these seizures occur and how they can be stopped. seizures occur during the neonatal period at a higher rate than in any other period of life. seizures in the developing brain are more common than in a mature brain for several reasons. first, the developing brain is hyperexcitable due to excess in excitatory glutaminergic neurons and immaturity of inhibitory gamma-amino butyric acid (gaba) neurons. preterm infants are at especially high risk for seizures for this reason. research directions since interpretation of continuous eeg monitoring requires a trained neurologist, automated interpretation software has been proposed. algorithms and machine learning have been studied, however logistical and mathematic challenges remain.