Neonatal Convulsions

Neonatal convulsion, postnatal 0-28. It is the most common clinical sign in neurological diseases of infants. 80% of newborn seizures occur in the first 2 days of life. The fact that convulsions seen in the neonatal period are generally associated with serious diseases and require specific treatment, disrupt the respiratory-circulatory integrity, and adversely affect the long-term prognosis of uncontrolled seizures by causing severe brain damage necessitate urgent diagnosis and treatment (1,2). They differ from convulsions in other age groups in terms of clinical, treatment and prognostic factors (1,3). Although clinical diagnosis of these seizures is not easy, there are difficulties in diagnosis and treatment (1,3,4). The true frequency of neonatal seizures is difficult to determine due to the uncertainty of clinical descriptive features; according to clinical observations, it varies between 2/1000 live births and 50/1000 as birth weight decreases (1).

II.ETIOLOGY

Etiological diagnosis of neonatal convulsions is based on clinical features and laboratory findings. The frequency of etiological causes varies according to the onset time of the seizures and the gestational age of the babies.

Hypoxic Ischemic Encephalopathy (HIE)

Hypoxic ischemic encephalopathy is the most common clinical condition known as the cause of acute neurological disorder and seizure in the neonatal period. Despite advances in antenatal and neonatal care today, acute neonatal encephalopathy following significant intrapartum asphyxia is still the most important cause of acute and chronic morbidity and mortality in these infants. Hypoxia is mostly due to insufficient feto-maternal gas exchange due to uteroplacental blood flow arrest or sudden occlusion of the umbilical cord. The fetus responds to this situation by increasing the perfusion of the brain and heart with its stimulated adrenergic system. However, the prolongation of this situation initiates a series of biochemical events that will lead to impaired cerebral perfusion and oxygenation, and release of neurotoxic mediators. Cell death after hypoxia and ischemia occurs either in the form of apoptosis or necrosis. If the severity of the initial event is high, necrosis is seen, if it is less, apoptosis is seen. The negative effect of HIE is mostly on the central nervous system (CNS). Neuropathological lesions associated with hypoxic ischemic encephalopathy differ in term and preterm infants. While injury occurs mostly in gray matter, cortical and subcortical regions in term infants, intraventricular hemorrhage and white matter destruction and some specific neuronal injury are prominent in premature infants (34). Seizures in HIE mostly occur within 4-24 hours after birth, and 60% of the patients in this picture have seizures up to 12 hours (34). Seizures are often isolated at first. They tend to intensify and recur within 12-24 hours after birth and may develop as status. The prognosis of convulsions seen in this period is also quite poor (34).

Intracranial Hemorrhage

It constitutes an important cause of neonatal convulsions. In many studies, it has been reported that intracranial hemorrhage is seen in 15-25% of cases (1,3,10). It often occurs due to birth trauma, rarely bleeding disorders and congenital vascular anomalies. Types of intracranial hemorrhage in the newborn are: subdural, subarachnoid, intracerebellar, intraventricular and intraparenchymal. Common clinical findings; swelling in the fontanel, decreased suction, bradycardia, changes in respiratory depth and frequency, apnea, hypotonicity, pallor, and convulsions. Ultrasonography is required as a screening method, and CT and/or MRI are required to confirm the diagnosis (42). The diagnosis of GM-IVK is made in the first day at a rate of 50% and in the first 3 days at a rate of 80-90%. Bleeding continues to progress in 20-40% of these babies. Although clinical convulsions were reported in 17% of GM-IVK cases (40), IVH and periventricular hemorrhagic infarction were found in 45% of infants with EEG findings in studies performed with electroencephalographic examination (44). The most common type of seizure seen in these infants is generalized tonic seizures.

Intracranial Infections

Bacterial or non-bacterial intracranial infections are responsible for 5%-10% of convulsions occurring in the neonatal period. Among bacterial infections, meningitis due to group B streptococci and E.coli constitute the most common group. In these patients, convulsions are often observed after the first 3 days of life. non-bacterial infections; includes encephalitis following toxoplasma, herpes simplex virus, rubella and cytomegalovirus. Convulsions can be seen in the first 3 days of life in intrauterine toxoplasma and cytomegalovirus infections (1).

Cerebrovascular Disorders

It can be demonstrated with advanced imaging methods. It has been determined as a convulsion factor at a rate of 5-6%. Thromboembolic events are especially of maternal origin. Depending on tumors, it may develop intrauterine and lead to fetal strokes, or it may be seen secondary to sepsis and dehydration in the neonatal period. Hereditary coagulation disorders should be considered in these cases, and the mother and child should be evaluated in this regard. Vascular malformations and related neurological findings may also occur with convulsions, neuroradiological examinations are instructive.

Developmental Cerebral Anomalies

Clinical findings are variable depending on the function of the affected area. Epilepsy, motor-mental retardation and focal neurological problems are the most important clinical findings. Epilepsy is often chronic and consists of partial and generalized attacks depending on the spread of the lesion. Developmental anomalies constitute approximately 50% of patients sent to epilepsy surgery centers due to unstoppable seizures (46). Seizures are frequently seen in the early period of life and are responsible for 5%-10% of seizures in the neonatal period. Clinically, seizures are often observed as myoclonus or infantile spasms, but focal clonic seizures or insidious attacks are also observed(5). Electroencephalography (EEG) is useful for the diagnosis of epilepsy due to cortical dysplasia in 75% of patients, but the findings are not specific. Two different EEG patterns have been described. The first is specific high-amplitude rhythmic rapid activity, the second is a low-amplitude focal interictal sharp or spike wave. Although clinical seizures are not described, epileptic disorders can be recorded in the EEG. Therefore, EEG recording should be performed even if there is no clinical seizure (47).

Metabolic Disorders

In this general category, especially glucose and serum electrolyte (sodium, calcium, magnesium) disorders as well as amino acid metabolism disorders (especially nonketotic hyperglycinemia), organic acidemias, mitochondrial (pyruvate dehydrogenase, cytochrome-c oxidase) and peroxisomal (zellweger syndrome, neonatal adrenoleukodystrophy) diseases, pyridoxine and folinic acid dependence, glucose transport disorder can be counted.

a) hypoglycemia; The most common metabolic disorder that can cause severe sequelae in the neonatal period is hypoglycemia. Especially babies with low birth weight and gestational week and babies of diabetic mothers are at high risk. Kovisto et al. stated that the most critical determinants in the development of neurological symptoms are the duration of hypoglycemia and the time to start treatment (48). Regardless of the cause, early and recurrent convulsions occur in hypoglycemia. In addition to convulsions, jitteriness, apnea, and hypotonia are also common among neurological symptoms. In a study, it was reported that 80% of infants with hypoglycemia and younger gestational age had neurological symptoms and 50% had seizures. In these babies, hypoglycemia developed in the early period (usually on the 2nd day of life) (1,5). hypoglycemia; It is very difficult to determine the role of hypoglycemia in the seizures of these babies, as it may be associated with clinical conditions such as hypocalcemia, perinatal asphyxia, sepsis and intracranial hemorrhage. Although Volpe described the frequency of seizures as 9% due to isolated hypoglycemia without any other metabolic defect, this rate was reported as 3% in recent studies (1,3). b) Hypocalcemia; It occurs in two different time periods as early and late hypocalcemia in the neonatal period. Early hypocalcemia observed in the first 2nd and 3rd days of life in premature and low birth weight infants; in infants of diabetic mothers; It is a common finding in infants who have experienced neonatal distress for any reason, especially hypoxic injury. Early hypocalcemia is therefore dependent on other potential etiological factors that play a fundamental role in the occurrence of convulsions and should be considered an additional condition rather than the main cause of convulsions (1). As a matter of fact, the failure of calcium treatment alone to stop seizures and the fact that babies with early hypocalcemia have a more severe prognosis than babies with late hypocalcemia support this view (1,5). Late hypocalcemia occurs at the beginning of the second week in term infants fed large amounts of formulas containing suboptimal phosphorus-calcium and phosphorus-magnesium ratios. The excessive phosphate load contained in these formulas may cause functional hypoparathyroidism due to the limited ability of the immature kidney to excrete phosphorus (5). It is clinically characterized by recurrent, well-formed focal and multifocal seizures in an infant who is restless, hyperactive, and often with a high appetite. Treatment response and prognosis in late hypocalcemia are very good (1,5). Although the frequency of hypocalcemia in neonatal seizures was reported as 13% in the 1970s, the association of hypocalcemia with other etiological factors was emphasized here. Today, the incidence of isolated hypocalcemia in neonatal convulsions has been reported as 3% (3). It is known that hypomagnesemic convulsions are rare and occur quite late. Magnesium absorbs In addition to ion disorder, hypomagnesemia can also be seen with autosomal recessive inheritance (10).

c) Pyridoxine addiction; are among the rare causes. Decrease in GABA synthesis and increase in glutamate amount as a result of abnormal binding of pyridoxal-5-phosphate to glutamic acid decarboxylase are involved in the pathophysiology of cortical excitation and epilepsy (49). Pyridoxine dependence is classically characterized by early-onset, resistant seizures that respond dramatically to pyridoxine therapy and may recur within a few days if treatment is discontinued. Seizures usually develop as generalized tonic-clonic and can be so effective that they can last for hours. EEG may not always give definite findings. If an EEG finding appears, it is almost always a multifocal spike slow wave chaotic finding resembling infantile spasm. Although the EEG finding is hypsarthymia, the seizure is not in the form of flexion or extension spasm and is almost always generalized clonic, suggesting pyridoxine dependence (10). Response to intravenous 50-100 mg pyridoxine is obtained within minutes. Intravenous pyridoxine should definitely be tried in all resistant cases of unknown cause and presenting with seizures up to the first 18 months, except in the neonatal period (5,49). d) Other metabolic causes: hyponatremia; It occurs as a result of inappropriate secretion of antidiuretic hormone due to meningitis, intracranial hemorrhage or hypoxia. Hypernatremia is seen due to excessive dehydration and excessive bicarbonate administration. The probability of both conditions to primarily cause seizures is very low (5,10). Some aminoacidurias and organic acidurias may cause seizures in the neonatal period, but these are very rare conditions. These diseases include nonketotic hyperglycinemia, sulfide oxidase deficiency, multiple carboxylase deficiency, glutaric aciduria type 2 and urea cycle defects. In these cases, convulsions usually occur 5-10 days after the start of feeding. They are often associated with important symptoms such as hyperammonemia, acidosis, and lethargy. Seizures in nonketotic hyperglycinemia are myoclonic and hiccups. The diagnosis is made when the CSF glycine level is higher than the blood glycine level, and the prognosis is quite poor.

A recently identified glucose transport disorder is called De Vivo’s syndrome. Prompt diagnosis and treatment will contribute to both stopping convulsions and improving neurological development. Seizures occur in the first 2 months of life in approximately 25% of cases. Although the blood glucose level is normal, the CSF glucose level is low and the lactate level is normal or low. The CSF/blood glucose level ratio is approximately 37%. Impaired glucose transport is associated with a defect in GLUT-1, which is responsible for the proper diffusion of glucose across the blood brain barrier and neural plasma membrane. A ketogenic diet constitutes a suitable metabolic fuel for brain energy metabolism and is not transported by GLUT-1. Ketogenic diet therapy prevents seizures, neurodevelopmental disorder and acquired microcephaly in these cases (50).

Toxic Causes

Seizure due to local anesthetic intoxication has been reported in the United States. It occurs as a result of accidentally injecting local anesthetic into the baby’s scalp during paracervical, pudendal or epidural blockade. A low APGAR score, hypotonia, bradycardia, and hypoventilation occur. Seizures are seen in the first 6 hours and have a good prognosis when treated appropriately (1). drug-induced convulsions; Although it is frequently seen in developed industrial societies, it is rare in our country. It can occur as a result of intoxication or withdrawal. Maternal narcotic analgesic dependence during pregnancy causes irritability and tremor in the first 24 hours of life. Seizures occur in only 1.2% to 3% of cases. A similar effect is experienced in infants of mothers addicted to short-acting barbiturates and alcohol (5).

Epileptic Syndromes in the Neonatal Period

International Epilepsy Association; In the classification of epilepsy and epileptic syndromes, there are four tables belonging to the neonatal period. These syndromes seen in the neonatal period can be listed as follows:

Selim Familial Neonatal Convulsions: It is a rare type of convulsion. Its onset is between the 2nd and 15th days after birth in most patients, but it is most commonly observed on the 2nd and 3rd days. It is of short duration (1-2 minutes) but repetitive (20-30 days). Seizures begin with tonic motor activity, apnea develops in a short time, besides vocalization, ocular findings, automatism are added. The clonic component appears asymmetrically or unilaterally at the end of the seizure. The postictal period is short-lived and uncertain. Interictal EEG is normal. In this type of epilepsy with autosomal dominant inheritance; The link shown by Leppert et al. in 1989 with the mutation of one of the potassium channel genes (EBN1) located on the long arm of chromosome 20 was also proven by later studies. following year Later, Steinlein et al. determined other family pedigrees in which the connection with the 20th chromosome was excluded, and they detected a second locus (EBN2) on the 8th chromosome (5). The diagnosis is made by excluding other causes of convulsions and obtaining a family history of similar seizures in the neonatal period. All biochemical, hematological, metabolic disease screening tests and cranial imaging are normal. The prognosis is good, it is recommended to discontinue the drug treatment as soon as 3-6 months. The risk of developing epilepsy in advanced ages is between 11% and 15% (51).
Benign Idiopathic Neonatal Convulsions: The prevalence of this syndrome, which occurs in the first week of life, mostly on the 4th-6th days of life, and is therefore called the 5th day seizures, is between 2-7% in newborn seizures (4). Attacks are usually in the form of multifocal clonic or apnea attacks and tonic seizures are not observed. It has been stated that seizures tend to status and, if status develops, lasts an average of 20 hours. Interictal EEG recordings showed that physiological activity was preserved and sleep organization was not impaired. It usually expires within 15 days. Although the etiology is unknown, term delivery, a normal pregnancy and delivery process, APGAR score higher than 8, onset on the 4th-6th days, normal neurological status in the interictal period, normal laboratory findings are necessary criteria for diagnosis and are positive prognostic indicators (52).
Early Infantile Epileptic Encephalopathy (EIEE): It is the earliest age-specific epileptic syndrome, first described by Ohtahara et al. in 1976. Its prevalence varies between 0.04% and 0.2%. Although seizures occur in the first months of life (0-3 months), they occur within the first month in 75% of cases. In its etiology, mostly structural cerebral anomalies; Although porencephaly, lissencephaly, Aicardi syndrome, olivery-dentate dysplasia, focal cortical dysplasia, hemimegalencephaly have been found, metabolic causes such as cytochrome oxidase deficiency, Leigh encephalopathy, pyridoxal-5-phosphate defect have also been reported rarely. Seizures are in the form of tonic spasms of less than 10 seconds, in clusters of 10-40, at intervals of 5-15 seconds. While the frequency of seizures can be up to 300 per day in isolated seizures, it can be 10-20 times in clusters. Displaced motor seizures, unilateral clonic or generalized asymmetric tonic seizures are also observed in 1/3 of the cases. While the burst suppression pattern on EEG is typical for this disease, periodic burst suppression is also observed on interictal EEG. Paroxysmal activity discharges with marked decrease in activity and even electrographically silent periods are observed. Paroxysmal discharges consist of an irregularly intertwined mix of spikes, silent waves, sharp and slow waves. It differs from hypsarthymia by the absence of sleep-wake difference in EEG pattern. Many clinicians view Ohtahara syndrome as an early variant of age-specific encephalopathies (West syndrome, Lennox Gastaut syndrome). However, it is also known that infantile spasms do not occur in some cases (53). West syndrome develops in 3-6 months in 75% of cases. Mortality is especially high in the early period, and severe motor-mental retardation is observed in survivors (51.53).
Early Myoclonic Epilepsy (EME): It was first described by Aicardi and Goutieres in 1978. It is a syndrome characterized by frequent myoclonias that begin in the first months of life, partial seizures, and the persistence of the stable burst suppression pattern on the EEG after the 2nd week (54). This syndrome results from unspecified metabolic defects and cerebral malformations. The clinical and EEG features of EME are similar to nonketotic hyperglycinemia, a glycine amino acid metabolism disorder. Propionic acidemia, Menkes disease, molybdenum cofactor deficiency sometimes occur with EME. Seizures occur in the first 3 months, most often in the first 10 days. Multifocal irregular myoclonias and partial seizures that recur many times a day are seen. It differs from EIEE by the prominence of multifocal irregular myoclonus and the late onset of tonic spasms. Myoclonic encephalopathy may continue after 1 year of age and may change to West Syndrome or multifocal independent thorn-focused severe epilepsy in 4-5 months. Mortality is very high. Almost half of the patients die before the age of 2 years. Severe neuromotor involvement is present in survivors (55).

III. PATHOPHYSIOLOGY

Neonatal seizures show a very different semiological structure from other seizures in childhood. On the other hand, the semiology of seizures in premature babies is quite different from that of term babies(10,11). Energy metabolism disorder is the most important factor in the acute development of neonatal convulsions. In newborns, both cerebral blood flow and oxygen and glucose use of the brain tissue are higher than in adults. Convulsions occur as a result of a series of biochemical events. The decrease in ATP and phosphokeratin, the energy substance of the brain, is due to energy loss. negatively affects ion pumping. This event, which also negatively affects glucose production, causes a decrease in the level of GABA made from glucose. Glucose deficiency and decreased GABA levels lead to both seizure formation and recurrence of seizures. The insufficiency of energy stores in preterm babies compared to term babies is important at this point. On the other hand, with the onset of convulsion, ATP is converted to Adenosine diphosphate (ADP) and a phosphorus is released. At the same time, glucose is burned and broken down into CO2 and pyruvate. The released phosphorus and pyruvate are excreted as lactate together with nicotinamide adenine dinucleotide (NADH) at the cytoplasm level. Excess lactate, especially hydrogen ion (H) has a good effect, causing local vasodilation and increased cerebral blood flow. This is achieved by the presence of a well-functioning autocerebrovascular mechanism in the newborn. In these events, the brain glucose level drops rapidly within the first 5 minutes with the onset of convulsions. If the uncorrected glucose level continues for 30 minutes, the brain lactate level increases and forms the basis of hypoxic ischemic brain injury (20)

IV. CLINICAL FEATURES AND PROGNOSIS

Classification of Neonatal Seizures

Convulsions can be seen in many different ways in the neonatal period. Since the maturation (axonal and dendritic formations) is not completed in the nervous system and synaptic connections are not developed in the neonatal period, generalized tonic-clonic convulsions are not expected to be observed. The postictal period is often poorly defined. With long-term EEG monitoring, simultaneous video and examination, and the introduction of many technical opportunities into neonatal units, innovations in classification have become inevitable. In some cases, since the electrical activity during the convulsion does not reach the superficial EEG electrodes, the EEG findings cannot be detected despite clinical convulsions (clinical seizure). In some cases, although there is an EEG finding, there is no clinical finding (electrographic seizure). If there are both clinical and EEG findings, this situation is called an electroclinical seizure. Volpe divides neonatal convulsions into 4 classes according to the basic clinical features; Subtle, clonic, tonic and myoclonic seizures. The distinction of subgroups is made according to the focal generalized and multifocal convulsions. In the definition of multifocal, asynchronous and usually migratory manifestation of clinical seizure activity in more than one area is described. The term generalized refers to the bilateral, diffuse and synchronized but not migratory characteristic of clinical activity.

Subtle Seizures: It is the most common seizure type in the neonatal period. This definition is used for seizures in which the definition of clonic, tonic and myoclonic cannot be made based on the motor, behavioral or autonomic features of the seizure. Studies based on EEG recordings or direct observations have shown that subtle seizures are more common in preterms than in term infants, and some clinical phenomena observed in term infants are unrelated to EEG activity (1,27,28). The most common common subtle seizure changes in preterm and term babies are ocular findings. While fixed eye movements are most common in premature infants, it is mostly horizontal eye movements in term infants (1). Apneic convulsions are common, rarely the only finding. It is often associated with ocular or autonomic findings. Fenichel et al. showed that bradycardia accompanying non-epileptic apneas, especially those longer than 20 seconds, in premature infants does not accompany epileptic apneic seizures. Clonic Seizures: Appear as rhythmic contractions that can involve any part of the body. Two subtypes have been defined, focal and multifocal. focal clonic seizures; It can be seen as facial, lower and upper extremity movements or axial structure (neck and trunk) disorders. Multifocal seizures, on the other hand, are mostly observed in a few parts of the body with their wandering characters. Several segments may be involved at the same time, but the contractions are not synchronous, although rapid displacement can roughly mimic a generalized seizure. Clonic seizures may be due to metabolic disorders in the newborn. They generally show compatibility with EEG activity (28,30). Tonic Seizures: Tonic seizures are divided into focal and generalized, and the generalized type is more common than the focal type. Focal tonic seizures consist of asymmetrical posture of one limb and flexion of the trunk towards the affected side. Mizrahi and Kellaway classify horizontal eye movements as focal tonic seizures. Unlike generalized seizures, EEG changes are seen in focal tonic seizures. Generalized seizures are often accompanied by tonic extension of all extremities or rarely with flexion of the upper extremities and extension of the lower extremities. However, 15% have electrical seizure activity (28). Myoclonic Seizures: These are rare seizures in which no EEG activity is observed, such as tonic seizures. They usually involve the flexor muscle groups and It differs from clonic seizures with its rapid formation characteristics. Myoclonic seizures; It is divided into three as focal, multifocal and generalized. Focal myoclonic seizures typically occur in the flexor muscle group of the upper extremity. In a study by Mizrahi and Kellaway, they showed that only 3 of 41 focal myoclonic seizures had EEG findings (28,31). Generalized myoclonic seizures are characterized by bilateral flexor contractions of the upper and lower extremities. While electrographic association is rare in focal and multifocal seizures, electrographic association is present in approximately 50% of generalized myoclonic seizures. EEG changes were also observed in 58 generalized myoclonic seizures studied by Mizrahi and Kellaway (31). All three types of myoclonic seizures can be seen in neonatal epileptic and nonepileptic syndromes. It is accepted by many authors that the prognosis of neonatal convulsions improves due to improvements in perinatal and neonatal care. Volpe collected the results of 2000 cases from studies published before and after 1969 and determined that mortality had decreased from 40% to 15%. Despite the decrease in mortality, no decrease was observed in the rate of neurological sequelae in surviving infants (1). Mental retardation, cognitive disorders, cerebral movement disorders and ongoing epileptic seizures are the leading neurological sequelae in newborn convulsions. The etiology of the convulsion determines the poor prognosis. Birth weight, gestational age, APGAR score, onset time, type and duration of convulsion are other factors affecting prognosis. The prognosis is relatively worse in presence of status, onset of seizures in the first 72 hours, and myoclonic convulsions. In hypoxic ischemic encephalopathy, intracranial hemorrhage and meningitis, mortality is 20%-70%, sequelae are 10%-40%, and the probability of recovery without sequelae is only 10%-35%. The prognosis is best in hypocalcemia and benign familial neonatal seizures. EEG gives very reliable information in determining the prognosis of neonatal convulsions. In clinical studies, it has been reported that background rhythm abnormalities rather than ictal and interictal abnormalities of EEG are important in determining the prognosis. While the prognosis is expected to be normal in infants with normal EEG, the probability of normal neurodevelopment is low in severe background rhythm abnormalities. The worst prognosis is expected in neonates with diffuse amplitude depression and burst suppression pattern (74,75).

V.LABORATORY FEATURES

Although the diagnosis of neonatal convulsions is difficult, investigations for the etiology should be initiated immediately following emergency treatment. First of all, a detailed history of the prenatal period and birth should be taken. Regarding pregnancy; Gestational age, drug use, maternal infections, bleeding or trauma, preeclampsia, eclampsia, characteristics of amniotic fluid are learned. Regarding the birth; Information about duration of labor and presence of complications, presence of meconium of amniotic fluid, aspiration, need for oxygen or presence of resuscitation, prolonged or too fast delivery, trauma, Apgar score, cord blood gas are collected. In the family history, consanguineous marriage, the presence of an individual in the family who had convulsions especially in the newborn period, and the history of sibling death should definitely be questioned. Then the baby should be examined; vital signs, weight, height, head circumference, fontanelle dimensions, camber, murmur, skin, eye signs, skin color should be noted. In neurological examination; state of consciousness, relationship with the environment, spontaneous movements and tone, cranial nerve examination, tendon reflexes, primitive reflexes should be checked, especially in terms of side difference. Although it is recommended to decide on a patient basis for laboratory tests, blood glucose level, blood count, urine analysis, blood and urine culture, serum electrolytes, cranial ultrasonography should be performed. If the etiology cannot be determined, serological tests and metabolic tests should be planned, and if the seizure continues, computed tomography and magnetic resonance imaging should be performed even if the cranial ultrasonography is normal (4,59). Electroencephalogram (EEG) is a reliable method used in the evaluation of cerebral functions. Especially in the detection of atypical stereotyped movements in the newborn, it is of great benefit in detecting seizures, distinguishing convulsive apnea from apnea due to other causes, demonstrating amorphous ‘subtle’ seizures, and predicting prognosis (60). However, it should be kept in mind that clinical seizures will not always be accompanied by electrical discharges, and on the other hand, electrical seizure activity may occur without any clinical symptoms, as in low-weight preterms. EEG diagnosis can be confirmed only in 10% of cases where neonatal seizures are suspected. Interictal background activity provides important clues regarding the presence, severity and extent of CNS pathology associated with seizures. If the EEG remains normal continuously in a newborn with convulsions, or If there is a significant normalization in the EEG in a short time, this is considered an important prognostic improvement (61,62).

VI.DIFFERENTIAL DIAGNOSIS

Some reflexes, tremors, withdrawals, jumps and athetosis-like movements of the newborn can often be confused with convulsions. Tremors can be seen in the jaw, upper and lower extremities. They are of short duration and have low amplitudes, whereas in clonies the amplitudes are larger and slower. Tremors can occur with voluntary stimuli, appear in the first days of life and disappear by 3-4 months.

“Jitterines” can also be seen frequently in the neonatal period, although it is generally considered benign; It may accompany hypocalcemia, asphyxia and sometimes convulsions. Its most important feature is that the movement can be stopped actively (4,56). Another condition that can be confused with convulsions is benign neonatal sleep myoclonus. The rapid eye movement (REM) phase of sleep in infants is the active phase. In this period, twitching of the eyelids, retractions around the mouth and multifocal beats in the extremities can be seen. This condition can often be confused with convulsions, sometimes sleep myoclonus may be quite pronounced. While falling asleep after feeding, repetitive, high-frequency myoclonic beats that can last for seconds to minutes can be seen in the arms and legs. If the child wakes up, the attack ends, they are not seen outside of sleep. These attacks usually disappear on their own when the child is 4-6 months old. The baby’s development is normal, and the sleep EEG is also normal. Treatment is unnecessary (56). Asphyxia, especially in newborns exposed to hypoxemia, can often be interpreted as seizures. In hypoxic conditions where the cortex is significantly suppressed, paroxysms originating from the brain stem, non-epileptic, eye glitches, tongue smacking, pedaling, and irregular body movements can be seen. These are rarely accompanied by discharges on EEG and are considered as convulsions. It can be seen especially in patients who have been ventilated for a long time in the intensive care unit. EEG monitoring is recommended for differential diagnosis. Antiepileptic drugs have no effect on these non-epileptic movements (56). Hyperekplexia is a very rare condition that can be confused with resistant convulsions in the neonatal period. It is an excessive response to environmental stimuli as a result of incomplete maturation of inhibitory glycine receptors in the brain. At the time of the attack, the child contracts tonic, cannot breathe during this period and cyanosis can be added to the picture. Especially if an attack starts with a warning during feeding, aspiration may occur. In severe attacks, the heart may stop. As the child grows, the severity and frequency of attacks decreases, spasms disappear, but sudden jumps may continue. Low-dose benzodiazepines and valproic acid are highly effective. There may be autosomal dominant and recessive inheritance (57,58). These conditions, which can easily be confused with seizures in the neonatal period, should always be considered in the differential diagnosis, and the event may need to be clarified with video-EEG when necessary (56).

VII. TREATMENT

In neonatal seizures, the mainstay of treatment is to provide adequate ventilation and blood glucose level, to stop the convulsion with immediate and effective treatment, to prevent its recurrence, and to determine the underlying cause and, if possible, to eliminate it (4).

The literature agrees that etiology is the most important indicator of prognosis in infants with neonatal seizures. For this reason, it is essential to detect and treat the etiological factor or factors immediately (1,5). Clinical features should be carefully examined in the determination of epileptic and non-epileptic phenomena, and if the neonatal intensive care unit has long-term EEG and video-EEG monitoring opportunities, it should be utilized at the maximum level. However, it should be noted that not all clinical seizures will have electrographic signatures. First of all, the airway of the newborn who has a seizure is kept open, oxygen is given, and blood samples are taken for biochemical tests by opening the vascular access (76).

GLUCOSE
PHENOBARBITAL
PHENHYTOIN
BENZODIAZEPINES
LIDOCAINE
PARALDEHYDE
VALPROIC ACID
CALCIUM AND MAGNESIUM
pyridoxine

Treatment Time

The optimum duration for the treatment of neonatal convulsions has not been determined, and specific principles have not been established in this regard. After acute treatment, it is recommended to make a decision based on the baby’s neurological examination, etiological reasons and EEG records. For example, in two separate studies conducted in asphyxia infants, it has been shown that the risk of recurrence of seizures is 50% in the presence of abnormal neurological examination (83). Etiology is also important for the decision to continue treatment. While the expected recurrence of seizures in asphyxiated infants is around 30%, this rate rises to 100% in the presence of cerebral dysgenesis. In the presence of hypocalcemia, which is one of the temporary metabolic disorders, there is no risk of recurrence of seizures. If the EEG background rhythm is normal or minimally disrupted in newborn convulsions, the probability of seizure recurrence is low, moderate or heavy background activity a normality, this probability is higher (68,84). The duration of treatment is decided by a careful evaluation of the factors mentioned above. Volpe summarized the general approach in treatment as follows: After acute treatment, if the baby’s neurological examination is normal and the etiology is one of transient metabolic disorders, anticonvulsant therapy can be terminated. If the baby’s neurological examination is abnormal and/or there are abnormal findings in the EEG, anticonvulsant treatment is continued according to the baby’s seizure intensity. It would be appropriate to discharge the patient, preferably with a single drug, and to be evaluated by neurological examination and EEG examination in the 1st month. The general approach is to gradually discontinue the treatment within 3 months if there are normal examination and EEG findings. If convulsion persists, anticonvulsant therapy is continued and treatment is supplemented with old and new anticonvulsant drugs when necessary. Surgical treatment options for cortical lesions (focal cortical dysplasia, hemimegalencephaly, Sturge Weber Syndrome) are recommended as an option during infancy and childhood (1).