The article presents the results of a survey of 85 patients with neonatal seizures (NS). The issues of pathogenesis and therapy of these conditions are discussed, the importance of modern instrumental examination methods and the most frequent long-term consequences of NS are shown.
Modern approach to the understanding and treatment of neonatal seizures
Article conducted the results of the survey 85 patients with neonatal seizures (NS). Discussed questions the pathogenesis and treatment of these conditions, the importance of modern instrumental methods of examination and the most frequent long-term consequences of NA.
Despite the fact that neonatal seizures (NS) are the result of many reasons, the main ones, according to most researchers, are ischemic-hypoxic encephalopathy, intracranial hemorrhage, infections and congenital malformations. All of these diagnoses are very generalized and do not meet the requirements of the modern classification of perinatal lesions of the nervous system. Despite the fact that neonatal seizures are credibly considered a sign of serious neurological damage to the brain, they cause a lot of scientific controversy about the pathogenesis. For example, is NS a consequence of brain damage, or is what is called seizures damaging the brain? Unfortunately, the risk factors for NA are still not well understood. Neonatal seizures are frequent and may be the first manifestations of neurological dysfunction after various injuries. Seizures in newborns are clinically significant, primarily because very few are idiopathic. Further research leading to timely diagnosis of the underlying condition is important because an early start can improve the prognosis.
Neonatal seizures lead to non-physiological apoptosis, but it is not clear whether this leads to further clinically significant neuronal damage in all types of seizures, whether it is possible to prevent negative consequences with the help of ongoing therapy. Therefore, many clinicians are unsure when to treat seizures and how to assess the adequacy of treatment.
An immature brain seems more prone to seizures; they are more common during the neonatal period than at any other time in life. This may indicate an earlier development of excitatory synapses, prevailing over inhibitory influences, in the early stages of maturation. The prevalence of clinical seizures in infants born at term is 0.7-2.7 per 1000 live births. The incidence is higher in premature infants - from 57.5 to 132 per 1000 live births (birth weight<1500 г).
In 75% of patients, epilepsy debuts in childhood. Thus, in the future, in most cases, neurologists observe the evolution of epilepsy. Therefore, the most significant time is the onset of epilepsy, its adequate therapy with the main goal of avoiding the transformation of some epileptic seizures into others, having achieved their maximum control.
Neonatal seizures are reliably recognized as one of the main neurological syndromes in children during the first 4 weeks of life. Today it is one of the most controversial problems in neurology, starting with the definition. If we assume that NS is a generalized reaction of the neonatal nervous system to various neurological, somatic, endocrine and metabolic disorders, then we can treat them as a transient symptom that does not require therapy, which is very widely represented in neonatology. Many other definitions of neonatal seizures are known. Unfortunately, none of them requires either a search for the causes or a study of the consequences of the NA. We give preference to the point of view of most neurologists, who consider NS to be the first reliable sign of severe brain damage in a newborn, with the exception of idiopathic seizures, which are much less common. A large scatter in statistics most often indicates its imperfection for many objective reasons. The minimum incidence of NS is most typical for underdeveloped countries, where NS often go unnoticed by either neonatologists or parents of newborns, and diagnostic methods are imperfect. It is very important for clinicians and little-known fact that latent seizures are more typical for newborns, they are also called electrographic seizures. Most electrical seizures are not accompanied by clinical correlates. At the same time, not all clinical seizures correlate with EEG changes. Neonatal seizures differ in clinical description from seizures in adults, and seizures in premature infants differ from seizures in infants born at term. The organization of the cerebral cortex, synaptogenesis and myelination of efferent neurons are poorly developed in newborns, which rarely leads to bisynchronous propagation of excitation. Therefore, fragmented seizures are more common in newborns, and electrical activity may not propagate to the surface of the EEG electrodes. Only with the help of such a research method as video-EEG monitoring is it possible to make differential diagnostics of various types of apnea. The phenomenon of electroclinical disconnection is most often determined in newborns with fragmented seizures, generalized tonic and focal myoclonic paroxysms, which may not be accompanied by simultaneous EEG correlates.
An analysis of the literature of recent decades shows that the majority of authors both in Russia and abroad are inclined towards hypoxic-ischemic brain lesions in the perinatal period as the main cause of the occurrence of NA. J.M. Rennie (1997) believes that seizures represent a common brain response to a stroke. D. Evans, M. Levene (1998) pay special attention to the importance of hypoxia-ischemia of moderate severity and severe, when NS appear in the first 24 hours of a child's life and have an unfavorable prognosis. And H. Tekgul, K. Gauvreau et al (2006), having conducted a study of 89 children with NS, indicate that in 82% of cases in newborns of this group, global cerebral hypoxia-ischemia was detected, which led to death in 7% of children and in 28%, gross neurological changes at the age of 12-18 months. The generally accepted term in the literature of hypoxic-ischemic brain damage is sometimes replaced by the outdated concept of "hypoxic-ischemic encephalopathy". One way or another, the criteria for this most frequent and life-threatening condition in perinatology have not yet been determined. This is a set of indicators, which include the Apgar score not only at birth, but also after 5 minutes, the severity of acidosis, the need for mechanical ventilation, convulsions, and others. The causes of NS are many pathological processes of the mother and the child, including metabolic disorders, congenital cortical malformations, infections, of which bacterial meningitis is most common.
The relevance of the study of neonatal seizures is determined not only by their insufficient knowledge, but also to a greater extent by their severe neurological consequences, which include motor impairments, cognitive deficits, social maladjustment and the formation of late epilepsy. Many scientific studies are devoted to the search for risk factors for the development of NS, which could contribute to improving the algorithm for managing a patient with NS, depending on the cause of the onset, neurological symptoms in the first hours of life, indicators of the energy balance of the newborn's body and instrumental research methods.
Taking into account the symptomatic nature of most neonatal seizures, we set ourselves the main task - to determine the proportion of perinatal brain pathology and, in particular, intranatal pathology, in the development of NS. It is equally important to us to evaluate modern approaches to the observation and treatment of patients with NS in practical health care. We consider the creation of an algorithm for the management of a newborn with NA as one of the tasks.
Materials and methods... The study included 85 children aged 1 month to 17 years who had suffered neonatal convulsions. The exception was newborns with idiopathic NS. A thorough assessment of the obstetric and early postnatal history was combined with a neurological examination of the child. Patients aged 1 month. up to 1 year old there were 33 (1st group), from 1 to 5 years old - 40 (2nd group) and from 5 to 17 years old - 12 (3rd group).
In the 1st age group, in 76% of patients in the first days of life, except for NS, grade II-III cerebral ischemia was verified, and in 24% of newborns it was combined with intraventricular hemorrhage and in 18% - with CNS depression syndrome. It is customary to talk about the neurological consequences of perinatal brain pathology by the age of 12-18 months. By 1 year of age, 52% of patients with NS were diagnosed with epilepsy, and 71% developed a persistent neurological deficit. In all infants, according to the USDG results, blood flow disturbances were combined with signs of previous hypoxia. Neuroimaging (MRI and CT) is an indisputable generally accepted algorithm for examining newborns with NS in the world. None of the newborns of the children of the first group examined by us had neuroimaging in the first month of life. In 29% of the examined children with recurrent epileptic seizures, according to MRI and CT, gross changes were revealed - by the age of 1 year, the picture of internal ventricular hydrocephalus and cystic-atrophic changes in the cerebral hemispheres prevailed. NSH, as the most accessible diagnostic method, was performed in 60% of patients with NS. In 9 examined children, periventricular cysts prevailed, in 4 - intraventricular hemorrhages, in 5 more - signs of intraventricular hydrocephalus. The data of ophthalmoscopy, carried out in 65% of patients, showed partial atrophy of the optic nerves in 30%, and in 70% - phenomena of retinal angiopathy of varying severity.
When analyzing the data of the anamnesis of patients of the 2nd age group (1 year - 5 years), we did not note large statistical differences in the symptoms of the first days of life. Later, infantile cerebral palsy developed in 60% of children, in 22% of patients it was combined with symptomatic focal epilepsy and in 18% with symptomatic West syndrome. That is, by the age of 5, more than a third (40%) of children who underwent NS suffered from epilepsy. According to MRI data, performed in 13 out of 40 children, 13% had mixed ventricular hydrocephalus, 10% had cystic-atrophic changes, and 7% had an abnormality in the development of the brain, in particular, hypoplasia of the corpus callosum. According to the results of USDG, in 30% of patients, asymmetry of blood flow through the vertebral arteries prevailed, and in 20% of them it was combined with severe venous dystonia, in 7% of patients signs of previous hypoxia were described.
All 12 patients of the 3rd group (5-17 years old) had cerebral ischemia of the II-III degree during the neonatal period; In our opinion, 100% indicator of ischemic disorders in this group has no objective reasons, but once again it allows us to note the high frequency of hypoxia-ischemia in newborns with NS. The degree of ischemia prevailed in very premature infants, as well as the frequency of neurological sequelae. The data of neurological examination and instrumental research methods did not differ from the two previous groups, which allowed us to draw a conclusion about the formation of neurological outcomes by the age of 12-18 months in children with NS. We consider the frequency of headaches (73%) and cognitive impairments in the form of decreased memory, perception, concentration of attention in 62% of patients tested by a psychologist as a significant difference between the 3rd age group and the first two. It is in this group of patients that one can reliably judge the long-term consequences of neonatal seizures. And the most common of the late complications were cephalalgia, in fact, perinatally caused, and attention deficit disorder.
The diagnosis of epilepsy today requires mandatory EEG monitoring, that is, continued EEG recording. Unfortunately, we found that even a routine EEG is not performed for all patients with NS, neither in the first days of life, nor during its first year. The reason for this study was only the onset of seizures, which required differentiation from epileptic seizures. Continuous EEG is recommended for children with perinatal CNS and NA pathology, so as not to miss convulsions in case of their visual absence, to determine the frequency and duration of seizures. Unfortunately, access to EEG monitoring is limited in most clinics, and interpretation is largely dependent on the specialist performing the EEG, requiring considerable experience. The detection of interictal abnormalities in the baseline EEG is useful for determining the prognosis in both term and preterm infants. The worst prognosis is associated with the “flash-suppression” pattern and persistence of persistent low-amplitude waves.
33 patients with NS at the age of 3 months. up to 17 years old in a hospital, video-EEG monitoring was carried out. When monitoring wakefulness in the background recording, organic changes were registered on the EEG in 60.6% of cases (20 people). In the vast majority - 72.7% of patients (24 people), epileptiform activity was registered during the study. In 15.2% (5 people) hospitalized in the department of infants and young children with lesions of the central nervous system and mental disorders diagnosed with symptomatic West syndrome, there were electroencephalographic changes characteristic of various variants of modified hypsarrhythmia.
In symptomatic focal and multifocal epilepsy, regional and multiregional epileptiform changes were recorded in 51.5% (17 people) of cases, in 3% of cases (1 person), complexes resembling benign epileptiform patterns of childhood were noted. In one child, the EEG recorded inhibition of cortical rhythm.
Video-EEG monitoring was carried out in 21 patients after receiving the results of routine EEG. During the initial routine EEG, epileptiform disorders were detected in 23.8% of children with a history of neonatal seizures. Video-EEG monitoring of wakefulness and sleep revealed epileptiform activity in 85.7% of cases, and in 61.9% of cases epileptiform activity was detected for the first time only during an EEG monitoring examination, that is, a routine EEG method using a standard technique for recording bioelectrical activity of the brain did not reveal epileptiform disorders. In isolation, only in a state of sleep, epileptiform activity was detected in 28.6% of cases, which increases the importance of EEG monitoring studies in this physiological state.
The main goal in the therapy of neonatal seizures is to relieve the symptoms of the underlying disease and maintain optimal respiratory parameters, glucose-electrolyte blood composition and thermal regime. The biggest debate is the question - to treat or not to treat NS? Prolonged or poorly controlled neonatal seizures are associated with poorer outcomes than infrequent or easily controlled seizures, but the severity of the underlying disorders can lead to poor seizure control and poor outcome. There are no clinical data that show that anticonvulsant treatment alters neurological outcome while controlling underlying neurological disorders. Many of the most commonly used AED regimens are ineffective in relieving all seizures, clinical or electrical. Abnormal EEG activity persists in a significant proportion of newborns, which show a clinically positive response to AED.
It may be necessary to try to control frequent or prolonged seizures, especially if homeostasis, ventilation and blood pressure are impaired. It is considered necessary to prescribe AED if there are three attacks per hour or more, or if one attack lasts 3 minutes or more. After clinical seizure control, persistent EEG seizures are rarely treated because they are usually brief and fragmentary — further dose escalation increases the risk of side effects. Many anticonvulsants inhibit respiration and impair myocardial function. The duration of therapy also raises considerable debate, but when seizures are controlled within a week and the neurological status is normal, AED is usually canceled.
The drug of first choice in neonatal practice is still phenobarbital (PB) at a dose of 20-40 mg / kg / day in 2 divided doses. At the same time, recent studies show that FB relieves only the clinical component of seizures and does not affect the frequency and duration of "electrical seizures", that is, the phenomenon of electroclinical disconnection is formed. The second-line drug of choice is diphenin at a dose of 10-20 mg / kg / day. Recent studies have shown a good effect of valproate at a dose of 20 mg / kg / day. There is evidence of the positive effect of topiramate in neonatal practice. To date, no reliable comparative data on the advantage of a certain AED in the treatment of NA have been obtained.
conclusions
1. Neonatal seizures in most cases are a consequence of perinatal brain damage of the newborn, and most often hypoxia-ischemia.
2. Most of the NS is not visualized and manifests itself only in latent, "electrical" attacks.
3. To date, there is no algorithm for managing patients with NS. EEG monitoring and neuroimaging are extremely rare in the first days and months of a child's life.
4. Treatment of NA is being discussed, but requires, first of all, the elimination of the cause of the development of NA, starting from the first minutes of life.
5. The consequences of NS are persistent neurological deficits, cognitive impairments, epilepsy.
E.A. Morozova
Kazan State Medical Academy
Morozova Elena Aleksandrovna - Candidate of Medical Sciences, Associate Professor of the Department of Pediatric Neurology
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To determine the further prognosis, the etiological factors of seizures play the greatest role. For example, in children whose seizures developed against the background of congenital brain abnormalities, hypoxia-ischemia, or postnatal, the prognosis is worse compared to children with minor subarachnoid hemorrhages or transient hypocalcemia.
EEG is also a valuable prognostic criterion in newborns with seizures. Moreover, for the prognosis, the main background of bioelectric activity is more important than the nature of epileptiform changes. Children with frequent and prolonged seizures usually have a worse prognosis than children with infrequent seizures. However, there are exceptions: children with benign familial neonatal seizures have frequent seizures and an excellent prognosis. Finally, children with normal neurological status during seizure periods have a better prognosis than children with neurological disorders.
Benign familial neonatal seizures
Unlike older children, fewer epileptic syndromes have been described in newborns because not all neonatal seizures are symptomatic. More often, neonatal seizures develop in response to acute cerebrovascular accident. However, five epileptic syndromes are known in newborns and infants, three of which have a good prognosis and two have a poor prognosis: benign familial neonatal seizures (also called familial neonatal seizures), benign neonatal seizures, benign partial epilepsy of infancy, early infantile epileptic seizures ), early myoclonic epileptic encephalopathy (EMEE).
The diagnosis of benign familial neonatal seizures in neonates with seizures is based on five criteria:
- normal neurological status;
- lack of other reasons for seizures;
- normal further development and normal intelligence;
- positive familial anamnesis for seizures in newborns or infants;
- the onset of seizures during neonatal or infancy.
In many children, seizures will debut in the first week of life, and only in a small number of cases later. This condition is one of several hereditary neonatal epileptic syndromes. Linkage analysis in large families of patients with benign neonatal seizures revealed two disease loci located on chromosomes 20ql3.3 and 8q24. These genes code for voltage-dependent potassium channels expressed in the brain (KCNQ2 and KCNQ3). Attacks, usually frequent in the first days of life, then stop. Children are usually completely healthy between attacks. The most common type of seizure is clonic seizures, focal or multifocal, but there are also generalized seizures. Generalized seizures are short, lasting no more than 1-2 minutes, but can develop frequently, up to 20-30 times a day.
The interictal EEG is of little help in diagnosing benign familial neonatal seizures because it can be normal or pathological. No specific diagnostic changes were found on the EEG. If any abnormalities are detected on the EEG, they are usually transient. The ictal EEG is characterized by a flattening of the basic rhythm, and then bilateral changes occur in the form of spikes and sharp waves. These changes may be correlated with generalized seizure.
The most common cause of neonatal seizures, hypoxic-ischemic encephalopathy. Many other diseases can cause neonatal seizures, including metabolic diseases, infections, trauma, abnormalities in brain structure, hemorrhage, embolism, and maternal disease. Since seizures in the neonatal period can indicate a serious, potentially dangerous and potentially reversible condition, it is necessary to organize a timely and competent approach to the examination of newborns with seizures.
Detailed study The neurological status of the newborn may reveal the cause of the seizures. Fundus examination may reveal signs of chorioretinitis, suggesting intrauterine infection. In this case, the determination of titers of antibodies to pathogens of congenital infections (TORCH) in mother and child is shown. Ecardi's syndrome, which is diagnosed only in girls, includes a number of features: iris coloboma, retinal lacunae, resistant epileptic seizures, and absence of the corpus callosum. On examination of the skin, one can see hypopigmented spots characteristic of tuberous sclerosis, or typical crusted vesicular rashes with pigment incontinence syndrome. Both neurocutaneous syndromes are associated with generalized myoclonic seizures onset at an early age. Unusual body odor suggests a congenital metabolic disorder.
Needed analyzes blood to determine the concentration of glucose, calcium, magnesium, electrolytes and urea nitrogen. If hypoglycemia is suspected, serum testing with a Dextrostix test strip is indicated so that treatment can begin immediately. Hypocalcemia can occur in isolation or in combination with hypomagnesemia. Decreased serum calcium levels are often associated with birth injury or stroke (hypoxic-ischemic encephalopathy) during the perinatal period. Other causes of neonatal seizures include maternal diabetes, prematurity, DiGeorge syndrome, and high dietary phosphorus. Hypomagnesemia (< 1,5 мг/дл) часто сочетается с гипокальциемией и обычно наблюдается у младенцев, рожденных от матерей пониженного питания. В этой ситуации судороги резистентны к терапии кальцием, однако эффективно внутримышечное введение магния в дозе 0,2 мл/кг 50% раствора сульфата магния (MgS04).
Study electrolytes serum curvy can reveal severe hyponatremia (serum sodium< 135 ммоль/л) или гипернатриемию (уровень натрия в сыворотке >150 mmol / L), which can cause seizures in newborns.
LP indicated for almost all newborns with seizures, if the cause of the seizures is not associated with metabolic disorders, such as gypsum glycemia or secondary hypocalcemia due to a high content of phosphates in the diet; in the latter case, in the interictal period, the child's condition is normal and a quick effect is observed with adequate therapy. LP results may indicate bacterial meningitis or aseptic encephalitis. Rapid diagnosis and adequate therapy improve the prognosis in these children.
Blood in CSF indicates trauma to the choroid plexus during puncture or subarachnoid / intraventricular hemorrhage. Examination of the cerebrospinal fluid after centrifugation can help in the differential diagnosis of other conditions. A clear supernatant indicates vascular injury (pathway blood), while the xanthochromic color allows the diagnosis of subarachnoid hemorrhage. However, healthy infants with moderate physiologic jaundice may have a yellowish CSF tint, making the supernatant test less reliable in the neonatal period.
Numerous congenital metabolic disorders can cause seizures in newborns. Because these conditions are often inherited in an autosomal recessive or X-linked recessive pattern, a detailed family history must be taken to determine if there have been early seizures or death among siblings and close relatives of the patient. Determination of serum ammonium levels is important for detecting abnormalities of the urea cycle (Krebs cycle), such as ornithine transcarbamylase, argininosuccinate lyase, and carbamoyl phosphate synthetase deficiencies. In addition to generalized clonic seizures, in the first days of life, newborns with these diseases have lethargy, progressing to coma, anorexia, vomiting, and a bulging fontanelle. If anionic deficiency and metabolic acidosis with hyperammonemia are detected in the study of the gas composition of blood, an urgent determination of the level of organic acids in urine is necessary to exclude methylmalonic or propionic acidemia.
Maple syrup disease urine should be suspected if metabolic acidosis is associated with generalized clonic seizures, vomiting, and increased muscle tone (muscle rigidity) in the first week of life.
Result screening a test using 2,4-dinitrophenylhydrazine, which detects keto derivatives in urine, is positive for this disease. Other metabolic diseases that can cause seizures in newborns include non-ketotic hyperglycemia (severe fatal illness, marked elevated plasma and CSF glycine levels, persistent generalized seizures, and lethargy that rapidly progresses to coma), ketotic hyperglycemia (in which seizures are associated with vomiting, electrolyte disturbances, and metabolic acidosis), Lee's disease (which can be assumed with an increase in blood lactate and CSF levels or an increase in lactate / pyruvate ratio). Biotinidase deficiency must also be ruled out.
In case of violation technicians local anesthesia during childbirth, it is possible to accidentally inject a local anesthetic into the fetus, which can provoke severe tonic convulsions. The condition of newborns in these cases is often regarded as a consequence of traumatic childbirth; at birth, muscle hypotension, impaired stem reflexes, signs of respiratory disorders, sometimes requiring mechanical ventilation, are noted. On examination, you can see the puncture site of the skin and the rupture of the soft tissues of the head. An increase in the level of anesthetic in the plasma of the newborn confirms the diagnosis. Treatment includes supportive care and forced diuresis through intravenous fluid administration, combined with monitoring to prevent excess fluid intake.
Benign familial newborns are characterized by an autosomal dominant mode of inheritance; convulsions debut on the 2-3rd day of life, the frequency reaches 10-20 seizures per day. In the interictal period, the pathology is not detected. Convulsions spontaneously stop at 1-6 months of life. The so-called fifth day seizures occur on the 5th (4-6th) day of life in healthy newborns without any neurological disorders. The seizures are multifocal in nature. They last only during the day (24 hours), the prognosis is favorable.
Pyridoxine dependence- a rare disease that must be excluded in newborns with signs of fetal distress (pathological condition of the fetus during intrauterine hypoxia, asphyxia), if generalized clonic seizures debut soon after childbirth. Seizures are resistant to traditional anticonvulsants such as phenobarbital and phenytoin. When collecting anamnesis, it is possible to assume that seizures of this nature occurred in utero. In some cases, symptoms of pyridoxine dependence appear later - in infancy or early childhood. The disease is inherited in an autosomal recessive manner. Although the exact biochemical defect in this disease is unknown, pyridoxine is required for the synthesis of glutamate decarboxylase, which is involved in the synthesis of GABA. Infants with this condition need high doses of pyridoxine to maintain adequate levels of GABA synthesis.
At suspicion for pyridoxine-dependent convulsions, intravenous administration of pyridoxine at a dose of 100-200 mg is recommended during EEG recording. If the diagnosis of pyridoxine dependence is correct, the seizures cease shortly after pyridoxine administration and the EEG returns to normal within a few hours. However, this effect from the first intravenous administration of pyridoxine is not observed in all cases of pyridoxine dependence. Oral administration of pyridoxine at a dose of 10-20 mg / day for 6 weeks. recommended for newborns in cases where suspicion of pyridoxine dependence persists after the lack of effect from intravenous administration of pyridoxine. In the future, the study of the level of pyridoxal-5-phosphate in the blood and CSF may be a more accurate diagnostic method to confirm pyridoxine dependence. Patients with pyridoxine dependence require lifelong pyridoxine replacement therapy (orally at a dose of 10 mg / day). In general, the earlier the diagnosis is made and pyridoxine therapy is started, the better the prognosis. Children not receiving therapy have persistent, refractory seizures and inevitably develop mental retardation.
Convulsions as a manifestation of drug dependence can occur in the first days of life, but sometimes develop only after a few weeks due to the lengthening of the period of elimination (excretion) of the drug in newborns. The reason for seizures may be the mother's intake of barbiturates, benzodiazepine drugs, heroin and methadone during pregnancy. Infants may experience irritability, lethargy, myoclonus, or clonic seizures. The mother of the child may refuse to take these drugs, but a blood or urine test can help identify the drug that is causing the child's seizures.
In infants children with focal seizures with suspected stroke or intracranial hemorrhage and severe abnormalities in the structure of the brain, including lisencephaly and schizencephaly (without clinical manifestations or manifested in the form of microcephaly), MRI or CT are indicated. Neuroimaging is recommended for newborns and in cases where seizures cannot be explained by changes in glucose, calcium and electrolyte disturbances in blood tests. Newborns with chromosomal abnormalities and ALD are at high risk of developing seizures. These patients should be tested for serum karyotype and serum long-chain fatty acids, respectively.
Treatment of neonatal seizures... Antiepileptic therapy should be given to newborns with seizures resulting from hypoxic-ischemic encephalopathy or acute intracranial hemorrhage. Doses and recommendations for taking phenobarbital, diazepam and other drugs used in the treatment of neonatal seizures. The anticonvulsant activity of phenytoin and phenobarbital is equivalent, but is not high enough in newborns and makes it possible to achieve control over seizures in less than 50% of cases. The widespread use of EEG in newborns with atypical neonatal seizures has revealed many patients with pathological motor activity of a non-epileptic nature.
They belong to rare forms of epilepsy; to date, less than 200 cases have been described. Equally often in boys and girls, in 100% of cases - hereditary burden with similar attacks during the neonatal period.
What Causes Benign Familial Idiopathic Neonatal Seizures:
The autosomal dominant mode of inheritance has been proven. The gene is mapped on the long arm of chromosome 20, locus 20q13.2, the second gene on the long arm of chromosome 8, locus 8q24.
Symptoms of Benign Familial Idiopathic Neonatal Seizures:
The age of onset is the 1st-7th day of life, most often the 2nd-3rd day.
Attacks reach a frequency of up to 3-6 per day, lasting 1-8 minutes. Convulsions are linked to the sleep-wake rhythm, more often during sleep. The seizures are more often focal in nature: mildly flowing short-term seizures such as apnea or clones, tonic manifestations, ocular symptoms are characteristic (fixation of the gaze of wide-open eyes, deviation of the eyes, upward, nystagmoid twitching, blinking of the eyelids, pupil dilation), oroautomatics (orofacial), oroalimentary. The period of persistence of seizures is up to several weeks.
The psyche is unremarkable.
Neurology was normal.
Diagnosis of Benign Familial Idiopathic Neonatal Seizures:
The basis for diagnosis is the nature of the seizures, the specified etiological factors and EEG data, although they, of course, are not well understood. The very low amplitude of activity at this age is comparable to the "noise" level of the encephalograph itself. The interictal EEG does not contain specific phenomena. During an attack - bilateral symmetric suppression of the amplitude for 5-19 s (tonic phase with apnea), then - rhythmic bursts of "steep" slow waves, interrupted by high-amplitude polyspikes and sharp waves (clonic phase).
Differential diagnosis
It is performed with metabolic disorders, perinatal injuries and brain abnormalities, benign idiopathic seizures of newborns ("fifth day seizures"), infections, cholecalciferol deficiency.
Forecast
The attacks stop spontaneously after a few weeks of life (68% - in the first 6 weeks), without consequences. In some children, convulsions recur at 3-4 months. life, 10-15% are transformed into epilepsy.
Treatment for Benign Familial Idiopathic Neonatal Seizures:
Phenobarbital 5 mg / kg / day
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A. E. Ponyatishin, A. B. Palchik,
V. N. Berezin, V. L. Parshina
CONFUSIONS OF NEWBORNS. ESTABLISHED, DISPUTED AND UNRESOLVED ISSUES
Department of Psychoneurology FPK and PP of the St. Petersburg State Pediatric Medical Academy; Children's City Hospital of St. Olga, St. Petersburg
A complication, and sometimes the only clinical manifestation of a number of neurological diseases and pathological conditions in newborns, is "neonatal seizures" (NS), the development of which is reliably correlated with unfavorable outcomes. In newborns, there is limited
a repertoire of neurological symptoms, while seizures are the most outlined clinical phenomenon indicating acute cerebral dysfunction, ie, in fact, NS are a nonspecific response of an “immature” brain to a damaging effect. Only in rare cases can neonatal convulsions be correlated with the onset of epilepsy as a nosologically independent disease. There are three age-dependent epileptic syndromes of the neonatal period included in the international classification of epilepsies (1989, 2001) - "benign familial NS", "early myoclonic" and "early infantile" epileptic encephalopathies. The definition of "epilepsy" to "idiopathic non-familial NS" ("convulsions of the 5th day"), according to J. Engel (2006), is optional.
Traditionally, "neonatal seizures" are defined as pathological, stimulus-independent, repeated, relatively short-term clinical phenomena that manifest paroxysmal changes in the main
neurological functions of the newborn and are the result of excessive discharges of neurons in the cerebral cortex. In this case, NS can be accompanied by impaired consciousness and are manifested not only by convulsive contractions of the limb muscles, but often by unusual motor, behavioral automatisms, ocular and autonomic reactions. Currently, it is recommended to use the term "convulsions" with caution and to use the definition of "epileptic seizures" more broadly, since this more accurately reflects the clinical and electrographic manifestations in newborns. In many intensive care units, a tactic for diagnosing HC is adopted, based solely on clinical criteria, that is, without EEG confirmation. However, the data revealed in recent decades indicate that often with paroxysmal phenomena, which are traditionally considered NS, there are no ictal (attack) electrographic correlates. On the other hand, in critically ill newborns, sometimes the EEG registers "attack" activity without the presence of paroxysmal manifestations at that moment. The established facts present difficulties in correct diagnosis of epileptic paroxysms, interpretation of electrographic changes, choice of optimal treatment tactics and prognosis of outcomes.
It is known that seizures in newborns are more common than in the population of older children, and their diagnosis is often difficult, since epileptic seizures in infants are phenomenologically not so well-formed and structurally organized. Underestimation of the severity of the condition of newborns can be the reason for underdiagnosis of convulsive syndrome, late initiation of treatment and, accordingly, an increase in the risk of developing persistent neurological deficit.
The need for early diagnosis of NA is determined by the following aspects:
1) convulsions in newborns are usually caused by serious intracranial disorders, and in some cases - life-threatening conditions, the timely diagnosis of which requires specific treatment;
2) the status course of seizures requires the provision of adequate support for the functioning of the child's internal organs and systems;
3) it is assumed that seizures "by themselves" can cause damage to the child's brain;
4) the diagnosis of NA in combination with the establishment of the etiology is an important clinical criterion for the prognosis of the development of children.
Often, the opposite process occurs - overdiagnosis of convulsive syndrome, followed by unreasonable prescription of anticonvulsants, which theoretically can lead to adverse consequences.
Despite the large number of studies devoted to the study of NS, until now there is
There are many unidentified, controversial, and often contradictory views on almost all aspects of the problem.
Etiology of neonatal convulsions and neonatal epilepsies
Neonatal seizures as a clinical symptom are a nonspecific response of the immature brain of a child to adverse factors. In more than 90% of cases, seizures in newborns are, in fact, symptomatic and only 5-7% meet the criteria for idiopathic, that is, genetically determined or of unknown etiology. Almost all the variety of pathological intracranial processes, a number of somatic, endocrine and metabolic disorders occurring in young children can lead to the development of convulsive syndrome. Many of them are unique and only significant during the neonatal period. Neonatal seizures are more often a symptom of an acute transient cerebral stroke, for example, asphytic encephalopathy, intracranial hemorrhage, etc., but they can also be the clinical debut of a number of static neurological diseases - cerebral dysgenesis, phakomatosis, and some genetic and chromosomal syndromes. Hypoxic-ischemic encephalopathy is the main (50-60%) cause of symptomatic seizures in mature newborns, while in premature infants these are intraventricular hemorrhages. Hypoglycemic conditions and electrolyte imbalances are common in newborns, but are relatively rare as the sole root cause of seizures.
"Benign familial neonatal seizures" is a form of neonatal epilepsy transmitted in an autosomal dominant manner. This is a genetically determined disease, which is an illustrative example, a kind of clinical model of "canalopathies". The genes encoding the synthesis of proteins necessary for the functioning of voltage-dependent neuronal potassium channels are located on the long arm of the 20d (KSKr2 gene) and 8d (KSKr3 gene) chromosomes. The corresponding gene mutations lead to the development of a characteristic clinical picture. The etiology of "benign nonfamilial neonatal seizures" is unknown. There are facts indicating low levels of zinc in the cerebrospinal fluid. It is assumed that the development of the disease is associated with rotavirus infection. Cases of sporadic mutations in the KSKr2 gene in children with “benign NS” without a family history have been described, which may bring together the etiopathogenetic mechanisms of benign “familial” and “nonfamilial” forms of neonatal epilepsy.
"Early infantile epileptic encephalopathy" (Otahar syndrome) is a polyetiological disease, the development of which is associated in 90-95% of cases
with cerebral structural and morphological disorders of various origins, for example, with cortical malformations, with cystic-atrophic changes in the brain and with phakomatosis. In children with a cryptogenic variant of the syndrome, a mutation of the BTXVR1 gene, encoding the function of synaptic release and transport of excitatory neurotransmitters, has been described. The etiology of early myoclonic encephalopathy (EME) often remains unclear. In recent years, reports have appeared that show the relationship between the development of the disease and congenital metabolic defects (non-ketonic hyperglycinemia, propionic aciduria, pyridoxine-dependent conditions, etc.). In a number of children with RME, a gene mutation in the 11p15.5 chromosome, encoding the function of release and transport of mitochondrial glutamate, was isolated.
Clinically grounded use of neuroimaging methods, biochemical, immunological, cerebrospinal fluid, and, if necessary, genetic and histological studies can diagnose most of the neurological diseases in newborns. However, even in modern conditions, in 3-10% of cases, it is not possible to establish the cause of neonatal seizures.
PATHOPHYSIOLOGICAL ASPECTS OF NEONATAL CONSUSIONS AND NEONATAL EPILEPTIC SYNDROMES
The pathogenesis of neonatal seizures, like epilepsy in general, is complex and not fully understood. It is believed that the physiological basis for the development of seizures is excessive depolarization of the membranes of nerve cells, which leads to the occurrence of a hypersynchronous electrical discharge in the pool of neurons in the cerebral cortex. Normally, the dynamic processes of depolarization and repolarization provide a stable membrane potential of the neuron.
Clinicians have long known that seizures are more common in newborns than in older children and adults. The fine molecular-membrane age-dependent (transient) mechanisms of the functioning of the cell membrane of an "immature" neuron, discovered in recent years, have partly brought closer to understanding the phenomenon of an increased tendency of the "developing" brain to seizures. The following age-dependent features can contribute to an imbalance of ionic equilibrium at the cell membrane:
1) the predominance of the chloride cotransporter KKSS1 over KSS2 in newborns, which leads to an increase, in comparison with the “mature” neuron, in the intracellular concentration of C1- ions. Activation of GABA-ergic membrane receptors under these conditions does not cause C1-entry into the cell (hyperpolarization), as occurs in the “mature brain,” but, on the contrary, along the concentration gradient, release of C1-into the extracellular space (depolarization). Accordingly, the "inhibitory" neuro-
the GABA mediator in the first weeks / months of children's life has a paradoxical, "exciting" effect;
2) significant expression in comparison with the mature brain of "excitatory" glutamatergic membrane receptors - NMDA and AMPA;
3) delayed maturation in the neonatal brain of the anti-convulsant GABA system in the substantia nigra. Under these conditions, exposure to trigger factors (hypoxia-ischemia, metabolic disorders, etc.) can lead to excessive depolarization of the "immature" neuron.
The pathogenesis of "benign familial neonatal seizures" is associated with potassium "canalopathy". Gene mutations KCNQ2-Q3 lead to dysfunction of neuronal potassium channels, as a result, the transport of K + ions to the extracellular space decreases, which leads to excessive depolarization on the neuron membrane. Potassium channels are diffusely and unevenly represented in the cerebral cortex, which may be one of the explanations for the predominance of multifocal epileptic seizures in DSS. It remains not entirely clear why the clinical manifestations of the disease are limited to a strictly defined, relatively short period of a child's life. Two hypotheses are considered. It is assumed that dysfunction of neuronal potassium channels alone cannot cause seizures in a child. For the development of epileptic seizures, it is necessary to combine "canalopathy" with an imbalance between excitatory and inhibitory neurotransmitters, which is the physiological "norm" in young children. Within weeks / months, the disappearance of the neurodiator imbalance is noted, which is clinically expressed by the self-limiting of the epileptic syndrome. Another explanation for this fact is associated with different expression of potassium channels at different periods of early cortical ontogenesis.
There are currently no convincing experimental models to study the pathogenesis of neonatal epileptic encephalopathy - “early myoclonic encephalopathy” and “early infantile epileptic encephalopathy”.
Unlike adults and older children, seizures in newborns rarely have a detailed clinical picture and are more often represented by abortive or focal seizures. It is believed that the phenomenological "immaturity" of the NS is associated with the ontogenetic features of the fetal brain - this is, first of all, incompleteness by the time of birth of the cortical-neuronal organization, synaptogenesis and myelination of brain structures; insufficiently developed commissural interhemispheric connections; the limbic system of the brain and its connections with the stem structures are relatively well formed; uneven representation of ion channels in the cortex. The noted anatomical and physiological features of the immature brain partly explain the predominance of focal
seizures, a tendency to develop fragmented seizures, the absence of the occurrence of primary generalized tonic-clonic seizures and the absence in some cases of registration of epileptiform discharges on the EEG at the time of clinical paroxysm. On the other hand, it is generally accepted that any paroxysmal clinical phenomenon is, in fact, epileptic if it develops as a result of a hypersynchronous discharge of a large number of neurons in the cerebral cortex. This definition implies that epileptic activity is initiated in the cerebral cortex and, accordingly, should be recorded on the convexital EEG at the time of clinical paroxysm. However, the use of video EEG monitoring showed that in newborns in 2/3 of cases there is no strict correlation between the clinical phenomena traditionally considered seizures and the registration of seizure epileptiform activity. This condition has been described as "clinical" or "electrographically unconfirmed seizures." Quite often the opposite situation occurs, when on the EEG of a child in critical condition, an onset of epileptiform activity is recorded in the absence at this moment of any clinical paro-xizmal manifestations ("electrographic convulsions"). These conditions are defined by the term "clinical-electrographic dissociation (QED)". In connection with the discovery of the QED phenomenon in recent years, the question of what is generally considered seizures in newborns and what should be the tactics of managing children with "clinical" and "electrographic" seizures has been discussed in recent years.
The following explanations are proposed for the development of "clinical seizures" in newborns, that is, seizures without EEG compliance:
1) these phenomena are epileptic, however, the generation of paroxysmal activity comes from the nuclei of the brain stem, subcortical formations and / or deep sections of the temporal lobes, and due to incomplete myelination, epileptic activity does not extend to the surface and is not recorded on the EEG;
2) an alternative point of view suggests that non-epileptic mechanisms underlie some of the paroxysmal phenomena, which were previously considered a priori seizures. In fact, these are primitive reflexes that manifest as a result of functional depression of the cerebral cortex and the "release" of stem structures from under its inhibitory influence, ie, the realization of the "stem release phenomenon".
"Electrographic seizures", ie, cases when the EEG registers seizure activity without clinical manifestations, also represents an unresolved problem of interpretation and choice of optimal treatment tactics. This electrographic phenomenon occurs: 1) in children who use muscle relaxants to synchronize their breathing with a ventilator; 2) in a newborn with initially epileptic
stupas receiving anticonvulsant therapy; 3) in children with diffuse cerebral insults, who are in a pre- or comatose state. Thus, it is assumed that "electrographic convulsions" are a reflection of functional or drug suppression of clinical manifestations, and their development is based on the same fundamental pathophysiological processes as in true epileptic seizures. The frequency of neo-natal "electrographic seizures" is unknown. M. Scher et al. (2002) noted this EEG phenomenon in newborns significantly more often than cases of complete clinical and electrographic coincidence. According to some authors, these electrographic phenomena should be considered as a kind of "epileptic seizures1" with appropriate treatment tactics and predicting outcomes. However, their diagnosis is possible only when registering an EEG in the neonatal period.
Until now, the question of how high are the roles of the seizures themselves in damage to the brain of newborns remains unresolved and, accordingly, how much advisable is the long-term prophylactic treatment of convulsive syndrome. Experimental studies have shown that repeated seizures with a tendency to protracted course as a result of systemic hemodynamic and metabolic disorders can lead to changes in cerebral blood flow, a decrease in ATP levels, activation of glutamatergic mechanisms and the initiation of apoptosis processes, and ultimately, to neuronal death. Later experiments have challenged this theory. It has been shown that the "immature brain" maintains sufficient "energy levels" during status epilepticus. It has been suggested that newborns are relatively resistant to the damaging effects of isolated seizures. On the other hand, studies completed in recent years indicate that convulsions in newborns, if they do not lead directly to the death of neurons, can, as a result of activation of complex molecular-biochemical processes, cause a decrease in protein synthesis, a violation of glial proliferation, cell migration, altered neuronal synaptogenesis, and delayed cerebral myelination. Experimentally induced convulsions in newborn rat pups reliably correlated with subsequent difficulties in their learning.
The use of antiepileptic drugs in newborns with paroxysmal clinical phenomena without EEG confirmation of their epileptic genesis raises the question of how this can affect the subsequent development of children. In clinical observations, it has been shown that the side effects of traditional anticonvulsants can be the cause of the subsequent development of cognitive and behavioral disorders in children. In addition, it was shown under experimental conditions that
phenobarbital, phenytoin, clonazepam, valproate are capable of activating the mechanisms of apoptosis, in contrast to topiramate. Thus, adverse neurological consequences in newborn infants with seizures are due to primary brain damage in infants as a result of exposure to etiological factors; mediated damaging effects of seizures on the brain of newborns; side effects of long-term use of anticonvulsants.
EPIDEMIOLOGY
The true frequency of occurrence of NS has not been established, which is associated with clinical polymorphism, difficulties and controversial concepts of electroclinical diagnostics, various methodological approaches to the inclusion of children with seizures in the analysis, as well as with a change in the spectrum of cerebral pathology in newborns that has occurred in recent decades. The lack of an accurate and comprehensive definition of neonatal seizures complicates epidemiological studies and correct comparison of the results.
In studies based on clinical diagnostic criteria, it was indicated that seizures occur in 0.5-0.8% of full-term newborns, reaching 22.7% in children with an extremely short gestational age. More recent epidemiological studies have shown that "clinical seizures", ie, without EEG confirmation, occur in 0.2% of term infants and 1.1% of preterm infants. In developing countries, the incidence of "clinical seizures" in the neonatal population can be as high as 12%.
Electrographically confirmed convulsions are noted much less often - in 0.7-2.7 cases per 1000 children born alive. In a population study, M. Carrascosa et al. (1996) in the group of term infants, EEG-confirmed seizures were diagnosed in 0.14% of cases. At the same time, among newborns of 3236 weeks of gestation, the frequency of convulsive syndrome was 1.3%, and among children with an extremely short gestation period, a complete clinical and electrographic correlation was found in 2.8% of cases.
Thus, despite the different approaches to the diagnosis of HC, the data presented reflect a general trend towards a decrease in the incidence of seizures, depending on the increase in the gestational age of newborns.
CLASSIFICATION AND CLINICAL
Phenotypes of neonatal convulsions
Despite the variety of clinical manifestations, there are four main types of seizures that occur in newborns - fragmented, clonic, tonic and myoclonic. E. Mizrahi, P. Kellaway (1987) suggest isolating "epileptic spasms". Currently, there is no generally accepted classification of NS. In many neonatal centers
The popular classification proposed by I. Walpe (1989), which includes clinical phenomena traditionally considered "neonatal seizures," that is, the author a priori considers them "epileptic" in terms of genesis.
There are significant phenomenological differences between NA and the types of seizures that occur in older children. Newborns do not have generalized tonic-clonic seizures, absences, psychomotor seizures. At the same time, the author identifies a number of clinical phenomena that are unique in their own way and characteristic of young children.
Fragmented seizures (AF) are the most common seizure in newborns. At the same time, they often cause difficulties in diagnosis, since they are disguised as non-epileptic phenomena. Paroxysmal conditions that, based on clinical manifestations, cannot be clearly classified as clonic, tonic, or myoclonic seizures, are referred to as fragmentary seizures. AF is more often observed in newborns at the onset of extensive intraventricular hemorrhages or in diffuse cerebral strokes. Accordingly, AF is often associated with poor outcomes. In the diagnosis and differentiation of AF with non-epileptic phenomena, video EEG monitoring becomes relevant. However, it has been shown that in case of fragmentary seizures in 7585% of cases it is not possible to register “attack” activity on the EEG. According to a number of authors, the absence of ictal correlation is a criterion for excluding the epileptic genesis of paroxysm.
Clonic seizures (CS) are rhythmic, prolonged contractions of the limbs and / or facial muscles with an average frequency of 1-4 per second. Phenomenologically formed CS are found in newborns older than 34-36 weeks of gestation. Insufficiently developed cortical-neuronal organization in children less than 28-30 weeks of gestation explains the low incidence of CS in premature infants. There are focal CSs, which correlate with unilateral cerebral pathology, and multifocal CSs, which occur in diffuse strokes. Primary generalized CS in newborns does not occur. In the overwhelming majority of cases with CS, there is an ictal electrographic correlation - registration at the moment of an attack of focal or multifocal rhythmic "peak-wave" activity.
Tonic convulsions (TS) are manifested by short-term, symmetrical tension of the limbs (generalized TS) or tension of one of the limbs and / or adversion of the head and eyes (focal TS). Primary generalized tonic-clonic seizures, starting from the tonic phase and turning into clonic, do not occur in newborns and children in the first months of life, which is associated with anatomical and functional
the immaturity of the infant's brain. On the EEG in the onset period of focal TS, regional, continued flashes of rhythmic theta / delta waves or "peak-wave" complexes are almost constantly recorded. With generalized TS, in most cases, there is no ictal pattern on the EEG, while the background activity is often sharply suppressed. Some authors consider HCS as a manifestation of primitive reflexes in the structure of the "stem release" phenomenon, while the prognosis is considered extremely unfavorable.
Myoclonic seizures (MS) are serial tremors of the limbs and trunk with the involvement of the facial muscles. Distinguish between focal, multifocal and generalized myoclonic seizures. Myoclonic seizures must be differentiated from pathological hyperkinesis ("spinal", "subcortical" myoclonus), as well as from "benign neonatal sleep myoclonus". The most common causes of MS in young children are cerebral malformations, metabolic defects, and genetic syndromes. Myoclonias are often noted in the structure of neonatal withdrawal symptoms. However, it is not always possible to establish their epileptic genesis. MS is an obligate clinical symptom of the age-dependent form of epilepsy - "Early myoclonic encephalopathy". Prospective observations have shown, in most cases, a poor prognosis in children with MS at an early age. With multifocal MS on EEG, the ictal pattern is not recorded in all cases. With generalized MS on EEG, diffuse discharges of acute activity of high amplitude are recorded.
Epileptic spasms (ES) are a rare type of epileptic seizures in children in the neonatal period, which is represented by serial paroxysms in the form of short-term (<10 с), диффузных тонических напряжений конечностей, мышц шеи и туловища. ЭС могут быть флексорными, экстензорными или смешанными. Эпилептические спазмы являются облигатным видом приступов в структуре синдрома Отахара . На ЭЭГ в момент эпилептического спазма регистрируется генерализованная амплитудная депрессия ритма и/или диффузная вспышка низкоамплитудной быстрой активности .
The description of the phenomenon of "clinical and electrographic dissociation" raised a number of questions and, in particular, what should be considered as neonatal convulsions, on the basis of which criteria to diagnose NS - only clinical or only electrographic? Taking into account modern concepts of the origin of "neonatal seizures" (epileptic and non-epileptic genesis of some clinical phenomena that are considered a priori "seizures"), E. Mizrahi, R. Kellaway (1987), depending on the registration on the EEG of "seizure" epileptiform activity in comparison with clinical
clinical manifestations of neonatal seizures were proposed.
1. "Clinical convulsions." Clinical phenomena, often without ictal electrographic confirmation, are the main part of AF, generalized TS, and focal and multifocal MS.
2. "Electroclinical convulsions". Clinical phenomena with continuous EEG confirmation. These are all types of CS, focal TS, generalized MS, epileptic spasms, seizures manifested by deviation of the eyeballs, and isolated apnea.
3. "Electrographic convulsions". Cases when a child has an "onset" epileptiform activity in the absence of clinical manifestations at that moment.
According to the authors, it is fundamentally important to diagnose and distinguish between these conditions, since this determines the tactics of treatment in the acute period (the appointment of anticonvulsants for "electroclinical" and "electrographic seizures" and the inexpediency of treatment for "clinical") and the prognosis of the child's development (the most unfavorable outcomes in children with "clinical" and "electrographic convulsions").
DIAGNOSTIC EEG SIGNIFICANCE IN NEWBORN CHILDREN WITH CONSULS
EEG and its modifications remain the main, objective methods of diagnosis and differentiation of epileptic and non-epileptic paroxysms in children, including newborns. Various disturbances in the background activity are nonspecific markers of infant brain dysfunction and reliable predictors of the prognosis of psychomotor development. A number of electrographic patterns of the background EEG of newborns with seizures, for example, "persistent amplitude depression", "flash-depression" and others, are often correlated with unfavorable long-term outcomes of the development of children.
Morphologically epileptiform sharp waves on the neonatal EEG are, on the one hand, a characteristic and frequent finding, and, on the other hand, the most difficult problem of interpretation, especially in children with convulsions in the inter-seizure period. Acute waves on the neonatal EEG can be a manifestation of both normal ("frontal acute waves", "sporadic adhesions", etc.) and pathological, but non-epileptic activity (for example, "positive Rolandic adhesions"). Registration of acute waves on the EEG in older children and adults with epilepsy is often a criterion for confirming the diagnosis in the interictal period. However, pathological, single acute waves are often found in newborns who have never had seizures. In addition, pathological “acute” activity often has focal / multifocal localization, which does not coincide with the focus of “onset” epileptiform activity in newborns.
with convulsions. According to E. Mizrahi et al. (2005), single, irregular sharp waves, as well as short (less than 10 s) "runs" of focal rhythmic sharp waves recorded in newborns in the interictal period of seizures should not be considered in the context of epileptiform activity. In this case, the diagnostic value of pathological activity is considered to be a nonspecific marker of parenchymal damage. Accordingly, according to the authors, only the detection of a seizure pattern is an unconditional electrographic criterion for the diagnosis and confirmation of convulsive syndrome in newborns.
Ictal activity on a neonatal EEG is significantly different from that in older children. Primary generalized epileptiform activity is extremely rare, if at all, in newborns. Most often, electrographic paroxysm has a (multifocal) onset over the central or temporal regions and spreads along the cerebral hemispheres, changing morphology and other characteristics as the clinical picture unfolds. Often, there are two or more independent foci of pathological activity. The morphology and localization of "attack" activity can differ significantly in one child with the same type of clinical paroxysmal phenomena. Ictal activity on a neonatal EEG is most often represented by a (multifocal) pattern in localization that differs from the background activity in morphology, amplitude and frequency in the form of a rhythmic burst of activity lasting more than 10 seconds with a distinct beginning and end.
M. Scher (2002) identifies four ictal patterns on the neonatal EEG: focal rhythmic "acute" activity against a changed and unchanged background; multi-focal rhythmic activity; focal / multifocal rhythmic pattern in the range of basic rhythms (pseudo-alpha / beta / theta / delta activity). Primarily generalized outbreaks of epileptiform complexes occur only in generalized myoclonic seizures. A little more often on the neonatal EEG, the phenomenon of "secondary bilateral synchronization" is noted, that is, the sequential diffuse spread of epileptiform activity from the primary focus.
Ictal activity may correlate with a clinical paroxysmal phenomenon, however, it is more often recorded without clinical correspondence ("electrographic convulsions"). The average duration of one isolated "electrographic epileptic seizure" in newborns, as a rule, does not exceed 2-3 minutes, but their cumulative duration can be significant. "Neonatal electrographic status epilepticus" is usually defined if continuous epileptiform activity is recorded for more than 20-30 minutes or its total duration
ness is more than 50% of the total EEG recording time. It is believed that the prognosis of a child's psychomotor development largely depends not so much on the registration of "seizure" epileptiform activity, but rather correlates with the degree of disturbances in the background EEG.
Technical and organizational difficulties during long-term EEG monitoring of newborns required the selection of a cohort of children at risk for the development of "electroclinical" and "electrographic" NS in order to optimize further examination and confirm the diagnosis. Studies of N. barola e! a1. (1998) showed that when registering significant changes in background activity on a routine EEG in newborns in the first hours of life, the risk of developing "electrographic seizures" in the next 24 hours reaches 80-90%. E.V. Gumennik (2007) identified 3 groups of newborns with hypoxic-ischemic encephalopathy, who have a high risk of developing "electrographic seizures", who need EEG monitoring. These are children: 1) with gross violations of the background activity on the short-term EEG; 2) when registering epileptiform activity on a routine EEG; 3) children with severe asphyxia or in a pre- / coma.
Due to the fact that urgent EEG monitoring is often difficult due to technical difficulties, in recent years the technique of "monitoring of cerebral function" or amplitude-integrative EEG (aEEG) has become popular in the intensive care units of newborns. Interpretation and assessment of aEEG data is quite simple and possible by practicing neonatologists. The use of a small number of electrodes allows for many hours or even daily observations. A high correlation was shown between the results of standard EEG and aEEG, especially when assessing normal and grossly pathological background activity. The effectiveness of the aEEG technique in the diagnosis of "electrographic seizures" is slightly lower in comparison with the standard EEG. Due to the small number of electrodes used and the electrographic picture significantly "compressed" in time, focal seizures other than Roland (leads C3-C4), localization, as well as low-amplitude (< 2030 мкВ) и кратковременная (< 30 с) «приступная» эпилеп-тиформная активность . Совмещение двух методик (стандартная ЭЭГ и аЭЭГ) многократно увеличивает диагностические возможности электрографического исследования новорожденных.
According to I. Walpe (2001), visual observation and assessment of the paroxysmal phenomenon are sufficient for the diagnosis of NA followed by immediate initiation of treatment. At present, tactics are becoming popular before the start of the introduction of anticonvulsants.
a significant EEG confirmation of the epileptic genesis of the paroxysmal phenomenon, i.e., only the registration of ictal activity. This is the only and necessary condition for the diagnosis of "neonatal seizures". Most authors agree that the immediate and long-term prognosis of children with NA is largely determined by the etiology. In this regard, there is some skepticism about the prospect of improved outcomes despite successful treatment of seizures. On the other hand, the damaging effect of seizures "by themselves" on the developing brain of the infant has been shown. Accordingly, the treatment of NS should be started immediately after their correct electroclinical diagnosis.
Phenobarbital, phenytoin and benzodiazepines are still the first-line drugs for the treatment of seizure syndrome in newborns. A recent observational and analytical study has shown that currently there is no convincing data proving a greater efficacy in the treatment of NS of other drugs than traditional anticonvulsants.
Standard treatment regimens can stop clinical manifestations in 70-90% of cases. However, the video EEG monitoring technique has shown that complete clinical and electrographic control over the NS with the use of traditional drugs is achieved only in 20-40% of cases. It was found that the preservation of epileptic activity on the EEG even in the absence of clinical manifestations has no less damaging effect on the brain of newborns. Accordingly, in the context of medical practice, judgment based only on clinical outcomes may create a false impression of the effectiveness of the treatment of neonatal seizures. R. Sancar, M. Painter (2005) make a rhetorical remark in the title of the article: "After so many years of using traditional anticonvulsants, we still love what doesn't really work!" ...
There are isolated studies conducted on a small contingent of newborns indicating the effectiveness of valproate, carbamazepine, topiramate. These facts require further study and confirmation.
Experimental studies have shown that the "inhibitory" neurotransmitter GABA in the first weeks of postnatal life has a paradoxical, exciting effect. This partly explains the low efficacy of phenobarbital and benzodiazepines in the treatment of NS, since these drugs stimulate GABAergic receptors. In recent years, the question has been raised about the need to search for fundamentally new anticonvulsants in the treatment of neonatal seizures. For example, currently there is an active study of the effectiveness of the drug bumetanide, which is used in the United States as a diuretic. Bumetanide blocks the entry of Cl- ions into the intracellular space
state of the "immature" neuron, reducing and leveling its intracellular concentration, thereby reducing the paradoxical, age-dependent, "exciting" effect of GABA. Early experiments in animal models have shown promising results.
The question of the duration of prophylactic treatment of NS remains unresolved. It is proposed to use antiepileptic drugs for several days in cases where seizures do not recur and there are no changes in the child's neurological status. While maintaining a depressed state, the duration of therapy continues for a month of life and, in rare cases, up to three months of age. On the other hand, a low risk (8%) of recurrence of epileptic seizures in newborns after early withdrawal of anticonvulsants is shown. There are also reports that the risk of developing epilepsy in children with NS in the next two to three years does not statistically correlate with the duration of treatment for convulsive syndrome in the neonatal period. It should be borne in mind that long-term use of anticonvulsants, in particular phenobarbital, also has a damaging effect on the developing brain of the infant.
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