Neonatal seizures geotar. Modern approach to understanding and treating neonatal seizures

To determine the further prognosis, the etiological factors of attacks play the greatest role. For example, children whose seizures develop due to congenital brain abnormalities, hypoxia-ischemia, or postnatal cerebral anomalies have a worse prognosis compared to children with small subarachnoid hemorrhages or transient hypocalcemia.

EEG is also a valuable prognostic criterion in neonates with seizures. Moreover, the basic background of bioelectrical activity is more important for prognosis 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 seizures have a better prognosis than children with neurological impairment.

Benign familial neonatal seizures

Unlike older children, not many epileptic syndromes have been described in newborns, since not all neonatal seizures are a symptom. More often, neonatal seizures develop in response to acute cerebrovascular accident. However, there are five known epileptic syndromes in newborns and infants, three of which have a favorable prognosis and two have an unfavorable prognosis: benign familial neonatal seizures (also called familial neonatal seizures), benign neonatal seizures, benign partial epilepsy of infancy, early infantile epileptic encephalopathy of infancy (EIEE). ), early myoclonic epileptic encephalopathy (EMEE).

The diagnosis of benign familial neonatal seizures in newborns with seizures is based on five criteria:

• normal neurological status;
• absence of other causes for seizures;
• normal further development and normal intelligence;
  • positive family anamnesis for seizures in newborns or infants;
• onset of seizures during neonatal or infancy.

In many children, seizures begin in the first week of life, and in a small number of cases later. This condition is one of several inherited neonatal epileptic syndromes. Linkage analysis in large families of patients with benign neonatal seizures identified two disease loci located on chromosomes 20ql3.3 and 8q24. These genes encode voltage-gated potassium channels expressed in the brain (KCNQ2 and KCNQ3). The attacks, usually frequent in the first days of life, then stop. During the period between attacks, children are usually completely healthy. The most common type of seizure is clonic convulsions, focal or multifocal, but generalized ones also occur. Generalized attacks are short, lasting no more than 1-2 minutes, but can develop frequently, up to 20-30 times a day.

Interictal EEG is not of much help in diagnosing benign familial neonatal seizures because it can be either normal or abnormal. No specific diagnostic changes were found on the EEG. If any abnormalities are detected on the EEG, they are usually transient. Ictal EEG is characterized by a flattening of the underlying rhythm, followed by bilateral changes in the form of spikes and sharp waves. These changes may correlate with a generalized seizure.

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A. E. Ponyatishin, A. B. Palchik,

V. N. Berezin, V. L. Parshina

NEWBORN SEIZURES. ESTABLISHED, CONTROVERSIAL AND UNRESOLVED ISSUES

Department of Psychoneurology FPK and PP 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 adverse outcomes. Newborns have limited

a repertoire of neurological symptoms, with seizures being the most well-defined clinical phenomenon indicating acute cerebral dysfunction, i.e., in fact, NS are a nonspecific response of the “immature” brain to a damaging effect. Only in rare cases can neonatal seizures 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 epilepsy”, “early myoclonic” and “early infantile” epileptic encephalopathies. The definition of “epilepsy” to “idiopathic non-familial NS” (“5th day seizures”), according to J. Engel (2006), is optional.

Traditionally, “neonatal seizures” are defined as pathological, stimulus-independent, repeated, relatively short-term clinical phenomena that manifest as paroxysmal changes in the main

neurological functions of the newborn and are a consequence of excessive discharges of neurons in the cerebral cortex. In this case, NS can be accompanied by a disturbance of consciousness and is manifested not only by convulsive contractions of the muscles of the limbs, but often by unusual motor and behavioral automatisms, ocular and autonomic reactions. Currently, it is recommended to use the term “convulsions” with caution and to use the definition “epileptic seizures” more widely, since this more accurately reflects the clinical and electrographic manifestations in newborns. In many intensive care units, the tactics for diagnosing NS have been adopted, based solely on clinical criteria, i.e., without EEG confirmation. However, data revealed in recent decades indicate that often with paroxysmal phenomena, which are traditionally considered NS, there are no ictal (paroxysmal) electrographic correlates. On the other hand, in newborns who are in a critical condition, sometimes “paroxysmal” activity is recorded on the EEG without the presence of paroxysmal manifestations at this moment. Established facts present difficulties in correctly diagnosing epileptic paroxysms, interpreting electrographic changes, choosing optimal treatment tactics and predicting 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 phenomenologically epileptic seizures in infants are not so well formed and structurally organized. Underestimation of the severity of the condition of newborns may be the reason for underdiagnosis of convulsive syndrome, late initiation of treatment and, accordingly, an increased risk of developing persistent neurological deficit.

The need for early diagnosis of NS is determined by the following aspects:

1) seizures in newborns are usually caused by serious intracranial disorders, and in some cases by life-threatening conditions, the timely diagnosis of which requires specific treatment;

2) the status of seizures requires providing 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) diagnosis of NS in combination with the establishment of etiology is an important clinical criterion for the prognosis of children's development.

Often the reverse 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 remains

There are many unidentified, controversial, and often contradictory ideas on almost all aspects of the problem.

ETIOLOGY OF NEONATAL SEIZURES AND NEONATAL EPILEPSY

Neonatal seizures as a clinical symptom are a nonspecific response of the immature brain of a child to the influence of unfavorable factors. In more than 90% of cases, seizures in newborns are essentially symptomatic and only 5-7% meet the criteria for idiopathic, i.e. genetically determined or unknown etiology. Almost all the variety of pathological intraranial processes, a number of somatic, endocrine and metabolic disorders found in young children can lead to the development of convulsive syndrome. Many of them are unique and are significant only in the neonatal period. Neonatal seizures are often a symptom of acute transient cerebral stroke, for example, asphyxtic encephalopathy, intracranial hemorrhages, etc., but they can also be the clinical debut of a number of static neurological diseases - cerebral dysgenesis, phakomatoses, some genetic and chromosomal syndromes. Hypoxic-ischemic encephalopathy is the main (50-60%) cause of symptomatic seizures in mature newborns, while in premature infants it is intraventricular hemorrhages. Hypoglycemic conditions and electrolyte imbalances are common in newborns, however, they are relatively rarely the sole underlying cause of seizures.

“Benign familial neonatal seizures” is one of the forms of neonatal epilepsy, transmitted in an autosomal dominant manner. This is a genetically determined disease, which is a clear example, a kind of clinical model of “channelopathies”. 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. A connection between the development of the disease and rotavirus infection is assumed. Cases of sporadic mutations in the KCKr2 gene have been described in children with “benign NS” without a family history, which may bring together the etiopathogenetic mechanisms of benign “familial” and “non-familial” forms of neonatal epilepsy.

“Early infantile epileptic encephalopathy” (Otahara syndrome) is a polyetiological disease, the development of which in 90-95% of cases is associated with

with cerebral structural and morphological disorders of various origins, for example, with cortical malformations, with cystic-atrophic changes in the brain and with phakomatoses. In children with the cryptogenic variant of the syndrome, a mutation of the BTXBP1 gene has been described, encoding the function of synaptic release and transport of “excitatory” neurotransmitters. The etiology of “early myoclonic encephalopathy” (EME) often remains unknown. In recent years, reports have appeared showing the connection between the development of the disease and congenital metabolic defects (non-ketonic hyperglycinemia, propionic aciduria, pyridoxine-dependent conditions, etc.). A number of children with RME have a gene mutation on chromosome 11p15.5, which encodes the function of release and transport of mitochondrial glutamate.

Clinically justified use of neuroimaging methods, biochemical, immunological, liquorological, and, if necessary, genetic and histological studies make it possible to diagnose most 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 SEIZURES AND NEONATAL EPILEPTIC SYNDROMES

The pathogenesis of neonatal seizures, as well as 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 nerve cell membranes, which leads to the occurrence of 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 subtle molecular membrane age-dependent (transient) mechanisms of functioning of the cell membrane of an “immature” neuron, discovered in recent years, have partly brought us closer to understanding the phenomenon of the increased susceptibility of the “developing” brain to seizures. The following age-dependent features may contribute to ionic imbalance on the cell membrane:

1) the predominance of the chloride cotransporter KKCC1 over KCC2 in newborns, which leads to an increase, in comparison with a “mature” neuron, in the intracellular concentration of C1- ions. Activation of GABAergic membrane receptors under these conditions does not cause the entry of C1- into the cell (hyperpolarization), as occurs in the “mature brain,” but, on the contrary, along the concentration gradient, the release of C1- into the extracellular space (depolarization). Accordingly, the “inhibitory” neuro-

the GABA mediator has a paradoxical, “stimulating” effect in the first weeks/months of children’s lives;

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. Exposure to trigger factors (hypoxia-ischemia, metabolic disorders, etc.) under these conditions can lead to excessive depolarization of the “immature” neuron.

The pathogenesis of “benign familial neonatal seizures” is associated with potassium “channelopathy”. Gene mutations KCNQ2-Q3 lead to dysfunction of neuronal potassium channels, as a result of which the transport of K+ ions into the intercellular 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 explanation for the predominance of multifocal epileptic seizures in DSNS. It remains not entirely clear why the clinical manifestations of the disease are limited to a strictly defined, relatively short-term period of a child’s life. Two hypotheses are considered. It is assumed that neuronal potassium channel dysfunction alone cannot cause seizures in a child. For the development of epileptic seizures, a combination of “channelopathy” with an imbalance between excitatory and inhibitory neurotransmitters is necessary, which is the physiological “norm” in young children. Within weeks/months, the neurotransmitter imbalance disappears, which is clinically expressed by the self-limitation of the epileptic syndrome. Another explanation for this fact is associated with different expression of potassium channels during different periods of early cortical ontogenesis.

Convincing experimental models that allow studying the pathogenesis of neonatal epileptic encephalopathies - “early myoclonic encephalopathy” and “early infantile epileptic encephalopathy” - do not currently exist.

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 characteristics of the fetal brain - this is, first of all, the incompleteness at the time of birth of the cortical-neuronal organization, synaptogenesis and myelination of brain structures; commissural interhemispheric connections are underdeveloped; the limbic system of the brain and its connections with 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 recording 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 essentially epileptic if it develops as a result of 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 has shown that in 2/3 of newborns there is no strict correlation between clinical phenomena traditionally considered seizures and registration of seizure epileptiform activity. This condition will be described as "clinical" or "electrographically unconfirmed seizures." Often the opposite situation occurs when the EEG of a child in a critical condition records paroxysmal epileptiform activity in the absence of any clinical paroxysmal manifestations (“electrographic convulsions”) at that moment. These conditions are defined by the term “clinical-electrographic dissociation (CED)”. In connection with the discovery of the phenomenon of CED in recent years, the question of what is generally considered to be considered convulsions in newborns and what should be the tactics for managing children with “clinical” and “electrographic” convulsions has been discussed.

The following explanations are offered for the development of “clinical seizures” in newborns, i.e. seizures without EEG correspondence:

1) these phenomena are epileptic, but the generation of paroxysmal activity comes from the nuclei of the brain stem, subcortical formations and/or deep parts of the temporal lobes, and due to incomplete myelination, epileptic activity does not spread to the surface and is not recorded on the EEG;

2) an alternative point of view suggests that non-epileptic mechanisms underlie some paroxysmal phenomena that were previously a priori considered to be seizures. In essence, these are primitive reflexes that manifest as a result of functional depression of the cerebral cortex and the “release” of stem structures from its inhibitory influence, i.e. the implementation of the “stem release phenomenon”.

“Electrographic seizures,” i.e. cases where seizure activity is recorded on the EEG without clinical manifestations, also represents an unresolved problem of interpretation and selection of optimal treatment tactics. This electrographic phenomenon occurs: 1) in children who use muscle relaxants to synchronize breathing with a ventilator; 2) in a newborn with initially epileptic symptoms;

stupas receiving anticonvulsant therapy; 3) in children with diffuse cerebral strokes who are in a pre- or comatose state. Thus, it is assumed that “electrographic seizures” 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 paroxysms. The frequency of neonatal "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 only possible by recording EEG in the neonatal period.

Until now, the question of how high the role of seizures themselves in brain damage in newborns is and, accordingly, to what extent it is advisable to carry out long-term preventive treatment of seizure syndrome remains completely unresolved. Experimental studies have shown that repeated seizures, which tend to be protracted 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 apoptotic processes, and ultimately, to the death of neurons. Later experiments cast doubt on this theory. It has been shown that the “immature brain” maintains sufficient “energy levels” in conditions of status epilepticus. It has been suggested that newborns are relatively resistant to the damaging effects of isolated seizures. On the other hand, studies carried out in recent years indicate that convulsions in newborns, if they do not directly lead to the death of neurons, can, as a result of the activation of complex molecular-biochemical processes, cause a decrease in protein synthesis, disruption of glial proliferation, cell migration, changes in neuronal synaptogenesis and delay in cerebral myelination. Experimentally induced seizures in newborn rat pups were significantly correlated with subsequent learning difficulties.

The use of antiepileptic drugs in newborns with paroxysmal clinical phenomena without EEG confirmation of their epileptic genesis raises the question of how this may affect the subsequent development of children. Clinical observations have shown that the side effects of traditional anticonvulsants can cause the subsequent development of cognitive and behavioral disorders in children. In addition, under experimental conditions it was shown that

phenobarbital, phenytoin, clonazepam, valproate are capable of activating apoptosis mechanisms, unlike topiramate. Thus, adverse neurological consequences in newborns with seizures are due to primary damage to the infant's brain as a result of exposure to etiological factors; indirectly damaging effects of seizures on the brain of newborns; side effects of long-term use of anticonvulsants.

EPIDEMIOLOGY

The true incidence of NS has not been established, which is associated with clinical polymorphism, difficulties and controversial concepts of electroclinical diagnosis, various methodological approaches to including children with seizures in the analysis, as well as changes in the spectrum of cerebral pathology in newborns that have occurred in recent decades. The lack of an accurate and comprehensive definition of neonatal seizures makes epidemiological studies and correct comparison of results difficult.

Studies based on clinical diagnostic criteria have 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”, i.e. without EEG confirmation, occur in 0.2% of term and 1.1% of preterm newborns. In developing countries, the incidence of “clinical seizures” in the neonatal population can be as high as 12%.

Electrographically confirmed seizures are observed much less frequently - in 0.7-2.7 cases per 1000 children born alive. In a population-based study by M. Carrascosa et al. (1996) in a group of full-term children, EEG-confirmed seizures were diagnosed in 0.14% of cases. Moreover, among newborns of 3236 weeks of gestation, the frequency of convulsive syndrome was 1.3%, and among children with an extremely short gestation period, complete clinical and electrographic correlation was detected in 2.8% of cases.

Thus, despite the different approaches to the diagnosis of NS, the data presented reflect the general trend of a decrease in the frequency of seizures depending on the increase in the gestational age of newborns.

CLASSIFICATION AND CLINICAL

PHENOTYPES OF NEONATAL SEIZURES

Despite the variety of clinical manifestations, there are four main types of seizures that occur in newborns - fragmentary, clonic, tonic and myoclonic. E. Mizrahi, P. Kellaway (1987) propose to distinguish “epileptic spasms”. Currently, there is no generally accepted classification of NS. In many neonatal centers

pax, the classification proposed by I. Bo1re (1989) is popular, which includes clinical phenomena traditionally considered “neonatal seizures,” i.e., the author a priori considers them “epileptic” in genesis.

There are significant phenomenological differences between NS and the types of seizures that occur in older children. Generalized tonic-clonic seizures, absence seizures, and psychomotor seizures do not occur in newborns. 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 (FS) are the most common type of seizure in newborns. However, they often cause diagnostic difficulties because they disguise themselves as non-epileptic phenomena. Fragmented seizures include those paroxysmal conditions that, based on clinical manifestations, cannot be clearly classified as clonic, tonic or myoclonic seizures. AF is more often observed in newborns at the onset of extensive intraventricular hemorrhages or with diffuse cerebral strokes. Accordingly, AF is often associated with adverse outcomes. When diagnosing and differentiating AF from non-epileptic phenomena, video-EEG monitoring becomes relevant. However, it has been shown that during fragmented seizures, in 75-85% of cases, the EEG fails to register “seizure” activity. According to some authors, the absence of ictal correlation is a criterion for excluding the epileptic genesis of paroxysm.

Clonic convulsions (CS) are rhythmic, continuous contractions of the limbs and/or facial muscles with an average frequency of 1-4 per second. Phenomenologically formed CS occur 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 CS, which correlate with unilateral cerebral pathology, and multifocal CS, which occur with diffuse strokes. Primary generalized CS do not occur in newborns. In the vast majority of cases with CS, ictal electrographic correlation is noted - registration at the time 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 convulsions, 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

natural immaturity of the baby's brain. On the EEG during the attack period of focal TS, regional, continuous bursts of rhythmic theta/delta waves or peak-wave complexes are almost constantly recorded. In generalized TS, in most cases there is no ictal pattern on the EEG, while background activity is often sharply suppressed. Some authors consider HTS as a manifestation of primitive reflexes in the structure of the implementation of the “trunk release” phenomenon, while the prognosis is considered extremely unfavorable.

Myoclonic spasms (MS) are serial jerks of the limbs and trunk involving the facial muscles. There are focal, multifocal and generalized myoclonic seizures. Myoclonic convulsions 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. Myoclonia is often observed in the structure of neonatal abstinence syndrome. However, it is not always possible to establish their epileptic genesis. MS is an obligate clinical symptom of an age-dependent form of epilepsy - “Early myoclonic encephalopathy”. Prospective observations showed in most cases an unfavorable prognosis in children who had MS at an early age. With multi-/focal MS, the ictal pattern is not recorded on the EEG in all cases. In generalized MS, diffuse discharges of pointed activity of high amplitude are recorded on the EEG.

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-electrographic dissociation” raised a number of questions and, in particular, what is considered to be neonatal convulsions, on the basis of what criteria to diagnose NS - only clinical or only electrographic? Taking into account modern ideas on the origin of “neonatal seizures” (epileptic and non-epileptic genesis of some clinical phenomena that are a priori considered “convulsions”), E. Mizrahi, R. Kellaway (1987) depending on the registration on the EEG of “seizure” epileptiform activity in comparison with clinical

Based on their clinical manifestations, they proposed an electro-clinical classification of neonatal seizures.

1. “Clinical seizures.” Clinical phenomena that often do not have ictal electrographic confirmation are the bulk of AF, generalized TS, and focal and multifocal MS.

2. "Electroclinical convulsions." Clinical phenomena with constant 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 spasms." Cases when a child exhibits “paroxysmal” epileptiform activity in the absence of paroxysmal clinical manifestations at that moment.

According to the authors, it is fundamentally important to diagnose and distinguish between these conditions, since this determines treatment tactics in the acute period (prescription of anticonvulsants for “electroclinical” and “electographic seizures” and the inappropriateness of treatment for “clinical”) and the prognosis of the child’s development (the most unfavorable outcomes in children with “clinical” and “electographic seizures”).

DIAGNOSTIC VALUE OF EEG IN NEWBORN CHILDREN WITH SEIZURES

EEG and its modifications remain the main, objective methods for diagnosing and differentiating epileptic and non-epileptic paroxysms in children, including newborns. Various disturbances in background activity are nonspecific markers of infant brain dysfunction and reliable predictors of the prognosis of psychomotor development. A number of electrographic patterns of background EEG of newborns with seizures, for example, “persistent amplitude depression”, “burst-suppression” and others, are often correlated with unfavorable long-term developmental outcomes in children.

Epileptiform morphologically pointed waves on the neonatal EEG are, on the one hand, a characteristic and common finding, and, on the other hand, the most difficult problem of interpretation, especially in children with seizures in the interictal period. Sharp waves on a neonatal EEG can be a manifestation of both normal (“frontal sharp waves”, “sporadic spikes”, etc.) and pathological, but non-epileptic activity (for example, “positive Rolandic spikes”). Registration of sharp 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 sharp waves often occur in newborns who have never had seizures. In addition, pathological “acute” activity often has a focal/multifocal localization, which does not coincide with the focus of “seizure” epileptiform activity in newborns

with convulsions. According to E. Mizrahi et al. (2005), single, nonrhythmic sharp waves, as well as short (less than 10 s) “runs” of focal rhythmic sharp waves recorded in newborns during 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 neonatal EEG differs significantly from that in older children. In newborns, primary generalized epileptiform activity is extremely rare, if at all. More often, electrographic paroxysm has a (multi-) focal onset over the central or temporal regions and spreads across 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 “paroxysmal” activity can differ significantly in one child with the same type of clinical paroxysmal phenomena. Ictal activity on the neonatal EEG is most often represented by a (multi-) focal pattern in localization, different from 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 neonatal EEG: focal rhythmic “acute” activity on a changed and unchanged background; multifocal rhythmic activity; focal/multifocal rhythmic pattern in the range of fundamental rhythms (pseudo-alpha/beta/theta/delta activity). Primary generalized outbreaks of epileptiform complexes occur only in generalized myoclonic seizures. Somewhat more often, the neonatal EEG shows the phenomenon of “secondary bilateral synchronization,” i.e., a 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 (“electographic seizures”). The average duration of one isolated “electographic epileptic seizure” in newborns, as a rule, does not exceed 2-3 minutes, but their total 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.

This is more than 50% of the total EEG recording time. It is believed that the prognosis of a child’s psychomotor development depends to a greater extent 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 in conducting multi-hour EEG monitoring in newborns required the identification of a cohort of children at risk for the development of “electroclinical” and “electographic” NS in order to optimize further examination and confirm the diagnosis. Research on N. brago1a e! a1. (1998) showed that when significant changes in background activity are recorded on routine EEG in newborns in the first hours of life, the risk of developing “electographic 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 “electographic seizures” and who require EEG monitoring. These are children: 1) with gross disturbances of background activity on short-term EEG; 2) when recording seizure epileptiform activity on a routine EEG; 3) children with severe asphyxia or in a pre-/comatose state.

Due to the fact that urgent EEG monitoring is often difficult due to technical difficulties, in recent years the technique of “cerebral function monitoring” or amplitude-integrative EEG (aEEG) has become popular in neonatal intensive care units. Interpretation and evaluation of aEEG data is quite simple and possible by practicing neonatologists. The use of a small number of electrodes allows long-term or even daily observations. A high correlation has been 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 diagnosing “electographic seizures” is slightly lower compared to standard EEG. Due to the small number of electrodes used and the electrographic pattern being significantly “compressed” in time, focal seizures other than the Rolandic (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. Bo1re (2001), visual observation and assessment of the paroxysmal phenomenon are sufficient for diagnosing NS with subsequent immediate initiation of treatment. Currently, the tactic is becoming popular before starting the introduction of anticonvulsants:

essential EEG confirmation of the epileptic genesis of the paroxysmal phenomenon, i.e. only registration of ictal activity. This is the only and necessary condition for diagnosing “neonatal seizures”. Most authors agree that the immediate and long-term prognosis of children with NS is largely determined by etiology. There is therefore some skepticism about the prospects for improved outcomes despite successful treatment of seizure disorders. On the other hand, the damaging effect of seizures “by themselves” on the developing brain of an infant has been shown. Accordingly, treatment of NS should be started immediately after their correct electroclinical diagnosis.

Phenobarbital, phenytoin and benzodiazepines still remain the first-line drugs for the treatment of convulsive syndrome in newborns. A recent review and analytical study showed that there is currently no convincing data proving that drugs other than traditional anticonvulsants are more effective in the treatment of NS.

Standard treatment regimens make it possible to stop clinical manifestations in 70-90% of cases. However, the video-EEG monitoring technique has shown that complete clinical and electrographic control of the nervous system when using traditional drugs is achieved only in 20-40% of cases. It has been established that the persistence of epileptic activity on the EEG, even in the absence of clinical manifestations, has no less damaging effects on the brain of newborns. Accordingly, in clinical settings, assessment based only on clinical results may give a false impression of the effectiveness of treatment for 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 like something that doesn’t really work!” .

There are isolated studies conducted on a small cohort of newborns indicating the effectiveness of valproate, carbamazepine, and topiramate. These facts require further study and confirmation.

Experimental studies have shown that the “inhibitory” neurotransmitter GABA has a paradoxical, excitatory effect in the first weeks of postnatal life. This partly explains the low effectiveness of phenobarbital and benzodiazepines in the treatment of AN, 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, the effectiveness of the drug bumetanide, which is used in the USA as a diuretic, is currently being actively studied. Bumetanide blocks the entry of Cl- ions into the intracellular space

the presence of an “immature” neuron, reducing and leveling its intracellular concentration, thereby reducing the paradoxical, age-dependent, “exciting” effect of GABA. Initial experiments on animal models showed encouraging results.

The question of the duration of preventive treatment for NS remains unresolved. It is suggested 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. If the depressed state persists, 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 resumption of epileptic paroxysms in newborns after early withdrawal of anticonvulsants has been shown. There are also reports that the risk of developing epilepsy in children with NS in the next two to three years is not statistically correlated with the duration of treatment for seizure syndrome in the neonatal period. It should be taken into account that long-term use of anticonvulsants, in particular phenobarbital, also has a damaging effect on the developing infant brain.

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Morozova T.M., Evtushenko S.K., Omelyanenko A.A., Balakhonova O.N., Donetsk National Medical University. M. Gorky

Resume

Neonatal seizures are often the first sign of neurological dysfunction and an important indicator of further cognitive impairment and developmental delay. This article presents the identification, clinical presentation, diagnosis, and specific (standard and alternative) treatment of neonatal seizures.

Keywords

seizures, newborns, treatment.

Neonatal seizures (NS) is a polyetiological clinical syndrome of the newborn period, which primarily indicates cerebral disorders.

NS occurs in the first 4 weeks of life of a full-term newborn (from the 1st to the 28th day). For prematurely born infants, this period corresponds to a postconception age of 44 weeks (postconception age is equal to the sum of the gestational period before birth and the duration of the postnatal period).

The frequency of NS ranges from 0.7 to 16 (L. Nirupama, 2000; M. Levene, 2002) per 1000 live births, which is explained by the difficulty of identification. NS is an ambiguous age-dependent phenomenon; seizures are often undeveloped, with a lack of secondary generalization, and, as a rule, go unnoticed and are not always distinguishable from normal activity. Seizures “evolve” through the process of myelination and synaptogenesis. In addition, so-called “latent” seizures are often recorded, that is, seizures without clinical manifestations, which are diagnosed only electroencephalographically (L. Nirupama, 2000; M.S. Scher, 2002; G.B. Boylan, 2002).

In most cases (over 90%) NS are symptomatic, and only about 10% are hereditarily determined (idiopathic NS). According to the observations of Mizrahi and Kellaway, hypoxic-ischemic encephalopathy (HIE) has the largest share (32%), intracranial hemorrhage (ICH) makes up 17%, intrauterine infections (IUI) with damage to the central nervous system - 14%, cerebral malformations - 7% , metabolic disorders - 6%, inborn errors of metabolism - 3%, phakomatoses - 2% and unknown causes - 10%.

Since the immature brain is highly epileptogenic, the presence of NS is often the first sign of neurological dysfunction. Seizures usually indicate the severity of the pathology and are the main symptom that predicts cognitive and motor deficits in the further development of the child. The prognosis of NS is unfavorable in most cases, the mortality rate ranges from 15 to 40%. 11-90% of surviving children have dramatic long-term consequences, manifested by epileptic encephalopathy with impaired cognitive functions, learning and communication difficulties, deviant behavior, and motor delay.

It has been proven that the resistance of the brain to the damaging effects of seizures in newborns is high during the first week of life, and then decreases (O. Cataltepe, 1995). An inverse relationship has been established between the degree of maturity of newborns and the incidence of seizures. Why are seizures dangerous for the developing brain?

An attack reduces the levels of ATP, phosphocreatine, glucose and increases the level of ADP, pyruvate, lactate => transition to glycolysis and anaerobic metabolism => glucose deficiency, hypoxia.

Increased lactate => local vasodilation and impaired autoregulation of cerebral blood flow => increased risk of bleeding (from the germinal matrix and into the penumbra of ischemic infarctions).

Despite the increased blood flow, the high metabolic demand due to the seizure is not compensated for, there is a decrease in protein metabolism/DNA synthesis, RKN and irreparable damage during cell division => slower neuronal differentiation and myelination, disruption of synaptic connections and apoptosis.

Thus, a seizure occurs when a large group of neurons undergoes excessive synchronized depolarization. Violation of the level of glutamate, aspartate, calcium influx, energy deficiency, development of hypoxia and loss of cerebral autoregulation of blood flow with its increase cause a secondary damaging effect. In this regard, there is a need for adequate diagnosis and treatment of NS from the first days of an infant’s life.

In the International Classification of Epilepsy (1989), NS is classified as age-dependent convulsive syndromes, but idiopathic NS is verified as forms of hereditary (familial) epilepsies that debut in the neonatal period.

As a polyetiological syndrome, NS has a fairly wide range of clinical manifestations and time of manifestation, which should be taken into account when making a diagnosis. Making a nosological diagnosis, the specific manifestation of which is NS, is determined by a whole set of criteria: gestational age, anamnestic family data, primarily prenatal history of development, intranatal situation and the nature of the course of early neonatal adaptation. Anamnesis and the clinical syndrome complex accompanying neonatal convulsions are important keys to uncovering the etiology of NS:

A family history of convulsions dating back to the neonatal period suggests that the infant has a genetic syndrome. Some of these syndromes are considered benign and often disappear within the neonatal period.

A detailed pregnancy history, a search for signs that suggest the possibility of TORCH infection, fetal distress, preeclampsia or maternal infection may also facilitate the etiological search.

The birth history is no less important: the type of delivery and the documented traumatic factor. The Apgar score also suggests an etiological factor. However, a low score without the need for resuscitation and subsequent intensive care is unlikely to be associated with UA.

The postnatal history is equally significant: UA in infants with an unprecedented prenatal history and delivery may be the result of postnatal causes. The presence of tremor may suggest delivery with analgesia or neonatal hypocalcemia. Unstable blood pressure and fever suggest infection or sepsis.

Taking into account the characteristics of the morphofunctional maturity of the central nervous system of a newborn, the following types of nervous system are distinguished:

Fragmentary NS:

• ophthalmic (ocular);

  oroalimentary;

  motor;

  vegetative.

Clonic NS:

• focal;

  multifocal;

  generalized (bilateral).

Myoclonic NS:

• focal;

  multifocal;

  generalized.

Tonic NS:

• focal;

  generalized.

Phenomenological classification of NS (J. Volpe, 2001) and their semiotics:

1. Fragmentary NS (soft, atypical, erased, abortive - subtle).

1.1. Ocular phenomena: a) tonic deviation; b) rhythmic nystagmoid twitching of the eyeballs);

c) blinking, opening the eyes, freezing the gaze. These attacks must be differentiated from manifestations of cerebrospinal fluid tension, paresis of the oculomotor nerves, metabolic encephalopathy (Leigch syndrome), and “dancing eyes” syndrome in latent neuroblastoma.

1.2. Oroalimentary (oral-buccal-lingual-facial) automatisms: a) chewing; b) swallowing movements; c) sucking movements; d) smacking; e) paroxysmal movements of the tongue; f) unusual grimaces, paroxysmal smile.

1.3. Motor phenomena: a) “pedaling,” “boxing,” or raking movements in the limbs with a short-term change in muscle tone; b) adverse cervical attacks; c) chaotic movements of the upper and lower extremities.

1.4. Attacks: a) going limp; b) fading; c) loss of consciousness; d) diffuse decrease in muscle tone; e) cessation of physical activity.

1.5. Autonomic reactions: short-term changes in: a) heart rate and blood pressure; b) skin color (cyanosis); c) drooling; d) hiccups.

1.6. "Convulsive" apneas.

Genesis: HIE, brain abnormalities, hereditary metabolic disorders, toxic-metabolic disorders, cerebral hemorrhages (infratentorial, parenchymal), IUI. Ictal EEG - slow waves and changes in the type of peak-wave complexes.

2. Clonic NS (CNS): rhythmic muscle twitching of individual parts of the torso, face and limbs, usually with a frequency of 1-3 per second. Occurs in children over 36 weeks of gestation.

2.1. Focal CNS: rhythmic clonic twitching of the face and limbs with clear laterization, combined with adversion of the head and eyes. In some cases, focal status epilepticus is formed. After an attack, transient mono- or hemiparesis of the limbs may develop.

Genesis: cerebral infarction, hematoma, bacterial meningitis, arteriovenous malformation, tumor, etc. The EEG shows focal foci of epileptic activity of the “peak-wave” complex type.

2.2. Multifocal CNS: convulsive seizures affecting individual muscle groups, unstable, fragmented, migrating from one limb to another and from one side of the body to the opposite. Combinations with apnea are common.

Genesis: electrolyte disturbances (hypomagnesemia, hypocalcemia), low pyridoxine levels, disturbances in cortical differentiation and migration. Rarely occur in the recovery phase after acute asphyxia.

2.3. Generalized CNS. Generalized clonic seizures in 95% of cases in newborns are of a focal nature with secondary generalization. When a generalized clonic attack has formed, loss of consciousness is noted; breathing rhythm disturbances with cyanosis and hypersalivation may occur. Such attacks indicate the maturity of the newborn’s brain and occur mainly in full-term infants.

Genesis: HIE, birth trauma, metabolic disorders.

3. Myoclonic NS (MNS).

3.1/3.2. Focal/multifocal MNS: a) axial MNS - lightning-fast flexion of the head and neck such as “pecks”, “nods” with a frequency of 1-8 per second or less, can be combined with autonomic-visceral disorders, dilated pupils; b) MNS of the limbs - rhythmic symmetrical flexion of the limbs, more often the arms, with a frequency of once per second or 1-2 per 10 seconds. The spontaneous Moro reflex is often imitated.

3.3. Generalized MNS - a combination of “pecking” with flexor flexion or extension of the limbs, nodding the head. Relatively symmetrical, synchronous myoclonic jerks.

Genesis: severe diffuse brain damage, terminal phase of asphyxia, hereditary metabolic diseases (HMD), hereditary degenerative diseases, cerebral malformations. In the future, myoclonic seizures may become part of the West, Otahara, Ajkardi, Lennox - Gastaut syndromes.

4. Tonic NS (TNS): indicate damage to the forebrain structures.

4.1. Focal TNS: a) stereotypical, often short-term tonic changes in position and muscle tone in one limb, tonic tension of the neck muscles, flexion or extension of one limb (imitation of an asymmetric cervical-tonic reflex); b) head adversion. Accompanied by apnea, tonic deviation of the eyeballs or gaze fixation.

4.2. Generalized TNS: a) attacks of the type of decerebrate rigidity lasting less than one minute, consisting of retraction of the neck muscles and extension of the arms and legs; b) flexion of the arms and extension of the legs according to the type of decortication pose. They are combined with upward deviation of the eyeballs and paroxysmal breathing disturbances, which resemble a prolonged inhalation.

Genesis: more common in the first day of life in low birth weight children with neonatal HIE and intraventricular hemorrhages. Ictal EEG: specific slow wave activity originating from brainstem structures and basal ganglia.

Idiopathic NS, or nosologically independent epileptic syndromes, are divided into benign idiopathic (among which there are two forms - benign familial NS and benign idiopathic NS) and malignant idiopathic NS (early myoclonic encephalopathy, early infantile epileptic encephalopathy, migratory partial epilepsy of young children).

Benign familial neonatal seizures (P. Plouin, 1985) are inherited in an autosomal dominant manner, the genetic marker is localized on the 8th or long arm of the 20th chromosome. Debut - 2-3 days of life against the background of relative well-being. Convulsions occur mainly during sleep with a frequency of 35 times a day. The duration of the attack is 1-3 minutes. Short multifocal clonic seizures are combined with apnea, ocular and autonomic phenomena, and oral automatisms. The duration of convulsions is from 5-7 days to 6 weeks, regardless of the prescription of anticonvulsants. Ictal EEG: amplitude suppression, generalized spike waves. Interictal EEG corresponds to the age norm.

Benign idiopathic neonatal seizures (“fifth day seizures”). The main reason is acute zinc deficiency. Occurs in full-term infants against the background of complete well-being. Apgar scale at 5 minutes - at least 9 points. Manifestation on the 5-7th day of life. The frequency of attacks is up to 15-20 per day or in the form of neonatal status epilepticus, generalized multifocal, less often focal clonic convulsions lasting up to 20 hours. Convulsions are resistant to therapy and are accompanied by apnea for up to 1 minute and cyanosis. Ictal EEG: θ - sharp waves or alternating bursts of θ waves. Prospectively, normal development.

Early myoclonic encephalopathy. Debut - first 28 days. There is a seriality of attacks up to continuous status epilepticus. Convulsions in the form of fragmented chaotic myoclonic twitching in the muscles of the face and limbs. Characteristic is the addition of focal phenomena (eye abduction, apnea, facial redness) and tonic extension of the limbs. EEG pattern: “flare-suppression” with modification into hypsarrhythmia and focal spikes after 3-5 months.

Early infantile epileptic encephalopathy (Ohtahara syndrome). Onset in the first 20 days of life. Seizures are tonic generalized or focal motor, serial (10-20 series), frequency 100-300 times per day. They occur both during sleep and while awake. Clonic convulsions and myoclonus are also observed. EEG pattern: "flash - depression". Severe neurological deficit.

Migrating partial epilepsy of young children. Debut - from 13 days to 7 months. Motor seizures with a vegetative component (apnea, cyanosis, facial hyperemia), secondary polymorphism with generalization, eye symptoms. Frequency - from 5 to 30 attacks several times a day or in periods of 2-5 days. EEG pattern: multifocal activity of predominantly temporal localization, slowing of background activity. Progressive neurological deficit.

Let's consider the main etiological factors of symptomatic NS.

Hypoxic-ischemic encephalopathy (35-56%). Pathological condition caused by severe hypoxemia and ischemia: Apgar score below 4 points, resuscitation measures from the first minutes of life. A decrease in PO2 level below 40 mm water column, excess CO2, and metabolic acidosis are recorded - blood pH below 7.2. Clinical manifestations: cerebral depression to coma, symptoms of increased ICP, cerebral edema. Convulsions in the 1st-3rd days of life, often recurring, generalized clonic, tonic, multifocal, atypical with a status course. Lack of sensitivity to anticonvulsants.

VCHK traumatic (10%). There is a documented precedent in childbirth. Catastrophic deterioration of the condition is observed on the 1st day, most often at the 3-8th hour of life. Noteworthy are changes in the nature of the cry and loss of communication skills, decreased muscle tone and motor activity, signs of progressive intracranial hypertension or acute hydrocephalus. Eye symptoms are important (ptosis, anisocoria, strabismus, fixed gaze, constant vertical and horizontal nystagmus, impaired oculocephalic reflex and decreased pupillary response to light, symptom of closed eyelids). Natal injury is accompanied by: metabolic acidosis, hypoxemia, progressive posthemorrhagic anemia, a decrease in hematocrit or the absence of its increase during infusion therapy. Convulsions: focal, clonic, generalized, tonic, apnea, tonic postures, respiratory disorders.

Intrauterine infections (5-10%). Symptoms debut in the early neonatal period: intrauterine growth retardation, hepatosplenomegaly, jaundice, exanthema, fever, respiratory distress, cardiovascular failure, focal neurological disorders, convulsions. Thrombocytopenia. Microcephaly, calcifications in the brain. IUI diagnostic standard:

Direct detection of the causative agent of the disease, its genome or antigens, direct methods - virological, bacteriological, PCR, DNA hybridization. Cerebrospinal fluid is used to diagnose lesions of the nervous system.

Detection of markers of a specific immune response (indirect diagnostic methods). Detection of specific antibodies to pathogen antigens in the child’s blood serum. Requirements: a) serological examination must be carried out before the administration of blood products (plasma, immunoglobulins, etc.); b) serological examination of newborns and children should be carried out with simultaneous serological examination of mothers; c) serological examination should be carried out using the “paired sera” method with an interval of 2-3 weeks. In this case, the study must be performed using the same technique in the same laboratory. Serological markers of the acute phase of the infectious process are IgM and low-avidity IgG. As the severity of the process subsides, the avidity of IgG antibodies increases, and high-avidity immunoglobulins are formed, which almost completely replace the synthesis of IgM.

Cerebral malformations (9-16%). NS occurs due to structural disorders of neuroontogenesis in the first 20 weeks of pregnancy. The nature of the attacks: short duration (no more than 1 minute), high frequency of automatisms in the initial phase, secondary generalization of attacks. Often demonstrative and unusual motor phenomena (pedaling, gestural automatisms), pronounced motor manifestations, including atypical postures such as bilateral or unilateral tonic postures and/or atonic episodes. Complex partial seizures with minimal impairment of consciousness. Between seizures, the EEG sometimes shows unusual and extremely active focal epileptic discharges in the form of repeated spike waves.

Standard for diagnosing cerebral malformations: 1) absence of obvious precedent, including severe hypoxia during childbirth; 2) convulsive syndrome resistant to therapy; 3) muscle hypotonia during the neonatal period; 4) focal neurological deficit; 5) delay in the rate of psychomotor development and disruption of the formation of postural reflexes; 6) radiological methods of studying the brain, confirming the malformation (MRI, PET); 7) specific immunological studies of cerebrospinal fluid to verify intrauterine encephalitis.

Hereditary metabolic diseases account for 3%. The NBO clinic is characterized by polymorphism, diagnosis is difficult, and treatment is often ineffective. However, this figure may be higher, given the 3% of newborns in whom convulsions are combined with hypoglycemia, metabolic acidosis, jaundice, malnutrition, diarrhea, vomiting, hepato- and splenomegaly, nystagmus, cataracts, and shortness of breath. A delay in diagnosing NBO is dangerous for the development of ICH, a septic process. Among the NBCOs debuting NSs, we can highlight:

arginine succinate lyase deficiency;

carbamoylphosphate synthetase deficiency;

non-ketotic hyperglycinemia;

illness that smells like maple syrup urine;

isovaleric acidemia;

propionic acidemia;

methylmalonic acidemia;

fatty acid acyl-CoA dehydrogenase deficiency;

Zellweger syndrome;

biotinidase deficiency;

ornithine carbamoyltransferase deficiency;

tyrosinemia type I;

tryptophanuria;

Hyperornithemia - Hyperammonemia - Homocitrullinuria (HHH) syndrome.

The diagnostic standard includes the history and clinical manifestations characteristic of the group of congenital metabolic defects:

The leading signs of NBO are: autosomal recessive type of transmission of the genetic defect, systemic nature of the lesion, steady progression.

Anamnestic data: genealogical history with the study of the pedigree - consanguineous marriage, neurological signs in one of the parents, absence of indications of pathology during pregnancy and childbirth, the presence of an interval of well-being between the day of birth and the first signs of illness. Particularly noteworthy are: fetal death, spontaneous abortion, fetal hyperactivity in utero, death of children in early childhood, sudden infant death syndrome, Reye's syndrome.

Neurodistress syndrome (syndrome of acute neurological disorders): increased excitability or depression of nervous system functions, anorexia, vomiting, weight loss, oculomotor disorders, unusual movements, muscle hypotonia, impaired consciousness (lethargy, coma), hypothermia, pyramidal syndrome, multiple organ changes , psychomotor retardation.

Seizures are polymorphic, multifocal, myoclonic, resistant to therapy, and prone to status.

Respiratory distress: disturbance of the respiratory rhythm (hyperpnea, apnea, shortness of breath or acidotic breathing), which is caused by a toxic effect on the respiratory center, in the absence of pathology of the heart and lungs.

Extraneural anomalies are combined with neurological symptoms. The multisystem nature of the lesion is manifested by facial dysmorphia, skin and hair abnormalities, skeletal disorders, cardiomyopathies, conduction disorders, arrhythmias, fibroelastosis, pulmonary anomalies, hepato- and splenomegaly, damage to the pancreas, kidneys, polycystic disease, and hearing impairment. Pathology of the visual analyzer (cataracts, glaucoma, optic nerve hypoplasia, retinal degeneration) and specific changes in the smell and color of urine are also characteristic.

The combination of two of the above symptoms should direct clinical thinking towards inborn errors of metabolism.

Phakomatoses (1.5-2%). The manifestation of NS in this case is variable, the clinical picture is polymorphic. The prognosis depends on the nature of the pathology. Among phakomatoses manifested by NS, the main place is occupied by tuberous sclerosis (TS) and encephalotrigeminal angiomatosis. Therapy is ineffective.

Seizures in TS are often in the form of generalized or focal clonic, less often - myoclonic atypical seizures. Skin manifestations are represented by depigmented oval spots of the “ash leaf” type. Neuroradiological signs are characterized by calcified subependymal and intracerebral tubers, which are usually detected in the second year of life.

NS in the form of focal clonic, less often tonic or atypical seizures, which are combined with a characteristic cavernous angioma on the head corresponding to the branches of the trigeminal nerve, glaucoma and sometimes contralateral hemiparesis, are characteristic signs of Sturge-Weber syndrome. Treatment and prognosis depend on the nature of morphological changes in the brain.

Metabolic and toxic-metabolic disorders are the cause of NS in 5-10% of cases. The leading role among them belongs to hypocalcemia, hypomagnesemia, hypoglycemia.

Hypocalcemia is a condition in which serum calcium levels fall below normal limits: total calcium is reduced< 2,2 ммоль/л, ионизированный < 1,18 ммоль/л. Гипокальциемия встречается с момента рождения ребенка, но поскольку расходование кальция в организме новорожденного очень экономное, клинические симптомы гипокальциемии в виде судорог, тетании появляются при снижении уровня общего кальция у недоношенных ≤ 1,5 ммоль/л, у доношенных - ≤ 1,75-1,5 ммоль/л. По времени возникновения гипокальциемии подразделяют на ранние - в первые 24-48-72 часа жизни и поздние, как правило, они возникают на 6-7-й день после рождения.

Iatrogenic causes of hypocalcemia: administration of barbiturates, steroid hormones, aminoglycosides, vincristine, amphotericin B, long-term use of furosemide, administration of soda, citrate, heparin. It must be emphasized that one of the main mechanisms of iatrogenic hypocalcemia is a decrease in magnesium levels, which leads to a decrease in PTH levels.

Reasons for a decrease in ionized calcium with normal levels of total calcium: administration of citrate during replacement blood transfusions, heparin, intravenous fat emulsions, alkalosis due to hyperventilation or with the administration of alkaline solutions. Based on duration, hypocalcemia is divided into transient and persistent.

Treatment of hypocalcemia in newborns

intravenous calcium gluconate 10% solution 1 ml/kg very slowly. In the case of hypocalcemia in low birth weight children, its correction is carried out at a rate of 1-1.5 mg/kg of elemental calcium per hour (only through the lineomat);

intramuscular magnesium sulfate 25% solution 0.2 ml/kg 2 times/day.

If there is no effect, although, as a rule, it develops “on the needle,” then after 15-60 minutes you can repeat the administration of calcium gluconate at the previous dose. It should be noted that most often the failure of calcium administration is caused by the fact that they forget to administer magnesium sulfate, but, unfortunately, they introduce Relanium or Seduxen, which do not have an effect. Their introduction is impractical! To further maintain normal calcium levels, calcium supplements are given orally at each feeding.

It must be remembered that 1 ml of 10% calcium gluconate solution is equal to 9 mg of elemental calcium. The presence of persistent hypocalcemia in a newborn is an absolute indication for consulting an endocrinologist and prescribing appropriate therapy.

Hypomagnesemia: decrease in magnesium level below 0.62 mmol/l (normal 0.62-0.91 mmol/l). Causes: persistent diarrhea, taking diuretics, administration of hyperosmolar glucose solutions, excessive amounts of calcium chloride and gluconate, impaired intake of magnesium from food, defective absorption in the intestine. Clinical symptoms: generalized and focal convulsions, hyperexcitability, tremor, muscle tremors, unusual cry, muscle hypotension, edema, bradycardia, respiratory rhythm disturbances.

Hypoglycemia: a decrease in glucose levels below 2.8 mmol/L in a full-term infant and 1.1 mmol/L in a premature infant.

Causes of hypoglycemia: pathology of pregnancy (placental anomaly, multiple pregnancy), prematurity and malnutrition, asphyxia, birth trauma, sepsis, meningitis, hyaline membrane disease, treatment of the mother with sulfonamides, administration of more than 6 g of glucose per hour to the mother during labor, sudden cessation of glucose administration newborn, late breastfeeding, adrenogenital syndrome, hemorrhage in the adrenal glands. Hyperinsulinism (adenoma and hyperplasia of the pancreas, diabetes mellitus in the mother). NBO - organic aciduria (propionic, methylmalonic, isovaleric, leucinosis, tyrosinemia), mitochondrial encephalomyopathy, glycogenosis. Beckwith-Wiedemann syndrome (exophthalmos, macroglossia, gigantism and pancreatic hyperplasia).

Clinic: convulsions, breast refusal, shrill crying, cyanosis, tachypnea and apnea, tachycardia, tremor, muscle hypotension.

Treatment of hypoglycemia: intravenous bolus of 10% glucose solution 2 ml/kg for 5-10 minutes, followed by drip administration of 6-8 mg/kg/min. Monitor blood glucose levels after 30 minutes. When subnormal levels are reached, switch to a 5% glucose solution.

Pyridoxine-dependent NS occurs when the level of pyridoxine and its coenzyme, pyridoxal-5-phosphate, in the blood is low. Pyridoxine and its coenzymes take part in the synthesis of antiepileptic substrates and inhibitory mediators in the central nervous system. Pyridoxine deficiency is observed in cases of nutritional deficiency and aminoacidopathy. Pyridoxine-dependent convulsions can occur in utero (in this case, the mother notes rhythmic clonic twitching) and in the first 72 hours of life. Clinically, pyridoxine-dependent NS is manifested by generalized clonic, myoclonic contractions of the “pecking” type and generalized winces. This type of nervous system is often combined with developmental delay. The EEG reveals specific slow-wave activity. To relieve attacks, pyridoxine is prescribed - at least 100 mg per day.

Among the toxic-metabolic disorders leading to NS are hyperbilirubinemia. The clinical picture of bilirubin encephalopathy consists of the classic symptom complex: lethargy, rigidity, opisthotonus, high-pitched scream, temperature and convulsions. NS caused by bilirubin damage to the brain (kernicterus) occurs on the 5-7th day of life and usually manifests itself as generalized tonic or fragmentary convulsions with the development of apnea and cyanosis.

NS caused by the toxic effects of anesthetics and medications. Local anesthetics used in parturient women during epidural anesthesia, paracervical block (lidocaine) or topically during episiotomy can penetrate the placental barrier. In this case, clinical manifestations resemble conditions caused by asphyxia: bradycardia, hypotension, apnea, impaired reflex activity, oculocephalic reflex and pupillary reactions, dilated pupils. Seizures develop in the first 6 hours of life and occur in the form of a tonic generalized attack. Often combined with apnea and pulmonary hypoventilation. Unlike infants with HIE, these newborns' condition spontaneously improves after 24-48 hours. Therapy is aimed at eliminating the drug by forced diuresis. The use of anticonvulsants is inappropriate.

A state of cerebral excitability (tremor, hypersensitivity to sensory stimuli, child excitability and motor restlessness, decreased sleep duration, increased muscle tone, autonomic disorders), turning into a convulsive attack, can be observed with the so-called withdrawal syndrome. Most often, these disorders are recorded in children of mothers who took drugs and medications during pregnancy. The substances that most often cause passive dependence in the fetus include: narcotic analgesics, alcohol, barbiturates, tricyclic antidepressants. Convulsions are accompanied by attacks of cyanosis, areflexia and can last up to 3-7 days. On the 4-6th day, gastrointestinal disorders begin (sluggish sucking, regurgitation, vomiting and diarrhea). The therapeutic effect is achieved by prescribing phenobarbital or diazepam (for gastrointestinal disorders).

Identifying the underlying etiological factor and properly differentiating seizures related to the neonatal period from non-epileptic events in this period is another task of differential diagnosis. Paroxysmal conditions of non-epileptic origin include: jitteriness, apnea of ​​respiratory and cardiac origins, ophthalmic non-convulsive phenomena, hyperexlexia, benign nocturnal neonatal myoclonus, tonic postures, Sandifer syndrome.

Jitteriness (hyperexcitability) - rapid generalized trembling of the whole body. Tremor can occur spontaneously or be provoked by tactile or sound stimulation and is not combined with ophthalmic and autonomic phenomena. Consciousness is preserved. Trembling decreases with passive flexion or repositioning of the limbs. Convulsions, unlike shaking tremor, are clonic, often associated with ophthalmic and autonomic phenomena, and do not respond to passive motor and sensory stimuli.

Other motor non-epileptic phenomena are: large-scale tremor, which appears when inducing an asymmetric cervical tonic reflex and is caused by the reaction of the red nucleus, paroxysms of extension with dorsiflexion of the thumbs, extension with tremor of the legs, spontaneous Babinski reflex (stretches), cyclic movements, grimaces. All these phenomena are causally determined, induced by external stimuli and, unlike myoclonic, tonic and clonic convulsions, are stopped by changing the child’s position or passive flexion of the limbs.

Apnea of ​​respiratory and cardiac origins should be distinguished from epileptic apnea, in which the heart rate is stable, and apnea is combined with autonomic phenomena, paroxysms of transient muscle hypotension and changes in the EEG.

Ophthalmic nonconvulsive phenomena: nystagmus, fixed gaze, deviation of the eyeballs, Graefe and Willi symptoms, opsoclonus. All these phenomena are usually causally determined and occur during vestibular loads. They are not accompanied by disturbances in breathing rhythm and motor stereotypic reactions. Ophthalmic convulsions are spontaneous, involuntary, occur at rest, are accompanied by attacks of apnea, autonomic reaction, and motor stereotypies.

Opsoclonus. Fast, conjugating, multidirectional movements of the eyeballs, intensifying with sound stimulation. In some cases, it is accompanied by myoclonic twitching of various muscle groups. Consciousness is not impaired. Opsoclonus is commonly observed in neonatal forms of degenerative diseases. In the future, when it is combined with myoclonus and ataxia, it is necessary to carry out differential diagnosis with an intracranial space-occupying process.

Hyperexflexion. A hereditary disease that occurs only in response to provocation, even minor stimuli. It is based on a pathological strengthening of the quadrigeminal “start reflex” of the midbrain. In severe cases, the child, picked up, stretches out, there is a diffuse increase in muscle tone, sometimes apnea and bradycardia. The tonic episode is relieved by forceful flexion of the neck or hips. The EEG is characterized by normal fundamental rhythms.

Benign nocturnal neonatal myoclonus. Rapid myoclonic twitching of various muscle groups. Myoclonus is bilateral, asynchronous, asymmetrical, often migrates from one part of the body to another and is observed during sleep. They make their debut in the first week of life. In contrast to myoclonus of epileptic origin, the duration of paroxysms of benign myoclonus is shorter (several minutes). Video monitoring and EEG do not show pathological epileptic patterns.

Tonic postures are associated with increased intracranial pressure, kernicterus, intracranial hypertension, irritation of the meninges, and decerebrate rigidity due to compression of midbrain structures. This kind of muscle tension is also causal. An indirect distinguishing feature is the strength of muscle tension - rigidity during tonic convulsions is pronounced and does not decrease in response to external influences, while tonic tension of non-epileptic origin decreases or increases with changes in the child’s body position.

Sandifer syndrome. With a hiatal hernia and gastroesophageal reflux, infants develop “dystonic” postures (torso twisting, head tilting, development of torticollis), which are associated with food intake and facilitate its passage from the esophagus to the stomach.

Thus, when diagnosing NS, it is necessary to take into account the presence in infants of certain conditions that are not related to convulsive phenomena and do not require specific treatment.

NS require close attention and strict monitoring in order to quickly establish the true genesis of a convulsive state in a newborn. The identification of metabolic disorders and infections of the central nervous system is urgent. It should be noted, however, that even with the full use of the entire modern arsenal of diagnostic tools, the causes of 10% of seizures remain unknown.

When determining treatment tactics, a number of fundamental questions arise: what is the genesis of NS, when should anticonvulsants be prescribed, the choice of the first drug and its dose, the need to change the antiepileptic drug, the use of polytherapy, and determining the time to discontinue treatment.

Therapy for convulsive conditions in the neonatal period is divided into standard (starting, traditional) and alternative. Alternative therapy is prescribed for resistant NS when there are risk factors for severe neurological deficit. In addition to combining different anticonvulsants, an alternative approach to the treatment of AN also includes a specific diet, enpits, vitamins or cofactors specific for inborn errors of metabolism.

If the status is, it is necessary to be able to perform mechanical ventilation and administer drugs intravenously:

Phenobarbital: 10 mg/kg, then from 1 mg/kg/hour to 40 mg/kg/day;

tonic and myoclonic nature of the NS;

high frequency, polymorphism of seizures, status and serial course;

Apgar score below 4 points, neonatal resuscitation;

mechanical ventilation for more than 7 days;

structural changes in the brain during neuroimaging;

resistance to initial anticonvulsant therapy;

cerebral malformations, NBO, phakomatoses.

It must be remembered that valproic acid is contraindicated in hyperammonemia and non-ketotic hyperglycinemia.

The answer to the question about the timing of therapy (several days before EEG normalization or within 4-6 months) requires taking into account the entire spectrum of causes of NS and the probability of recurrence, which is 4-20%. When the seizures are stopped, J.J. Volpe recommends taking a step-by-step approach to stopping anticonvulsants. And completely cancel them if the results of neurological studies are normal (interictal EEG is age-appropriate, there are no neurological symptoms, gross structural abnormalities). If the results are abnormal, it is necessary to consider the reasons and change the anticonvulsant drug, taking into account the semiotics and phenomenology of seizures. If the neurological status remains normal on follow-up examinations within 1 month, the anticonvulsant can be discontinued within 2 weeks. If neurological symptoms persist and there are no epileptic patterns on the EEG, treatment should be continued. If abnormal activity is present on the EEG, anticonvulsants are prescribed long-term. It is recommended to repeat the examination every 3 months.

When predicting the outcome of NS, it is necessary to take into account several factors: the genesis of NS (NBO, phakomatoses, brain abnormalities), the age of the baby at their manifestation, features of structural changes in the brain (cerebral malformations are the most unfavorable), the nature of NS (tonic and myoclonic), the presence of a family history of NS. epilepsy.

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Most common cause of neonatal seizures, hypoxic-ischemic encephalopathy. Neonatal seizures can be caused by many other conditions, including metabolic diseases, infections, trauma, brain disorders, hemorrhage, embolism, and maternal illness. Because seizures in the neonatal period may indicate a serious, potentially dangerous, and potentially reversible condition, a timely and intelligent approach to the evaluation of newborns with seizures is necessary.

Detailed study The neurological status of the newborn may reveal the cause of epileptic seizures. Fundus examination may reveal signs of chorioretinitis, suggesting intrauterine infection. In this case, determination of antibody titers to pathogens of congenital infections (TORCH) in mother and child is indicated. Ecardi syndrome, which is diagnosed only in girls, includes a number of features: iris coloboma, retinal lacunae, refractory seizures and absence of the corpus callosum. When examining the skin, you can see hypopigmented spots characteristic of tuberous sclerosis, or typical crusty vesicular rashes of pigment incontinence syndrome. Both neurocutaneous syndromes are associated with generalized myoclonic seizures that begin at an early age. An unusual body odor suggests an inborn error of metabolism.

Required tests 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 alone or in combination with hypomagnesemia. Decreased serum calcium levels are often associated with birth trauma or stroke (hypoxic-ischemic encephalopathy) in 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 Krivi may reveal severe hyponatremia (serum sodium level< 135 ммоль/л) или гипернатриемию (уровень натрия в сыворотке >150 mmol/l), which can cause neonatal seizures.

LP indicated in almost all newborns with seizures, unless the cause of the seizures is associated with metabolic disorders, such as gypsum glycemia or secondary hypocalcemia due to high phosphate in the diet; in the latter case, in the interictal period the child’s condition is normal and a rapid effect is observed with adequate therapy. LP results may indicate bacterial meningitis or aseptic encephalitis. Rapid diagnosis and adequate therapy improve the prognosis of these children.

Blood in CSF indicates injury to the choroid plexus during puncture or subarachnoid/intraventricular hemorrhage. Examination of the cerebrospinal fluid after centrifugation may help in the differential diagnosis of other conditions. A clear supernatant indicates vascular injury (passage blood), while a xanthochromic color allows the diagnosis of subarachnoid hemorrhage. However, healthy newborns with moderate physiologic jaundice may have a yellowish tint to the CSF, making the supernatant fluid 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, it is necessary to obtain a detailed family history and determine whether there has been a history of seizures or early death among the affected siblings. Determination of serum ammonium levels is important for identifying abnormalities of the urea cycle (Krebs cycle), such as ornithine tran-carbamylase, argininosuccinate lyase, and carbamoyl phosphate synthetase deficiencies. In addition to generalized clonic convulsions in the first days of life, newborns with these diseases experience lethargy, progressing to coma, anorexia, vomiting and bulging fontanel. If a blood gas study reveals anion deficiency and metabolic acidosis with hyperammonemia, an urgent determination of the level of organic acids in the urine is necessary to exclude methylmalonic or propionic acidemia.

Maple syrup disease urine should be suspected if metabolic acidosis is combined 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 may cause seizures in newborns include nonketotic hyperglycemia (a severe illness with a fatal outcome, markedly increased glycine levels in plasma and CSF, persistent generalized seizures and lethargy rapidly progressing to coma), ketotic hyperglycemia (in which seizures are combined with vomiting, electrolyte disturbances and metabolic acidosis), Leigh's disease (which can be suspected by increased lactate levels in the blood and CSF or an increase in the lactate/pyruvate ratio). It is also necessary to exclude biotinidase deficiency.

In case of violation technology Local anesthesia during childbirth may accidentally introduce 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 birth; At birth, muscle hypotonia, impaired brainstem reflexes, and signs of respiratory disorders are observed, sometimes requiring mechanical ventilation. Upon 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 neonatal plasma confirms the diagnosis. Treatment includes supportive care and forced diuresis through intravenous fluid administration, combined with monitoring to prevent excess fluid entering the body.

Benign familial newborns are characterized by an autosomal dominant type of inheritance; seizures debut on the 2-3rd day of life, the frequency reaches 10-20 seizures per day. In the interictal period, pathology is not detected. Seizures spontaneously stop between 1 and 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 nature of the seizures is multifocal. They last only for a day (24 hours), the prognosis is favorable.

Pyridoxine addiction- a rare disease that must be excluded in newborns with signs of fetal distress (pathological condition of the fetus due to intrauterine hypoxia, asphyxia), if generalized clonic convulsions debut soon after birth. Seizures are resistant to traditional anticonvulsants such as phenobarbital and phenytoin. When collecting anamnesis, it is possible to assume that convulsions 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 disorder require large doses of pyridoxine to maintain adequate levels of GABA synthesis.

At suspicion For pyridoxine-dependent seizures, intravenous administration of pyridoxine at a dose of 100-200 mg is recommended during EEG recording. If the diagnosis of pyridoxine dependence is correct, seizures stop soon after pyridoxine administration and the EEG returns to normal within a few hours. However, such an 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, testing 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 who do not receive therapy experience persistent, refractory seizures and inevitably develop mental retardation.

Convulsions as a manifestation of drug dependence, they can occur in the first days of life, but sometimes develop only after a few weeks due to the prolongation of the period of elimination (excretion) of the drug in newborns. The cause of seizures can be the mother's intake of barbiturates, benzodiazepine drugs, heroin and methadone during pregnancy. In newborns, irritability, lethargy, myoclonus, or clonic seizures may occur. The child's mother may deny taking 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, suspected stroke or intracranial hemorrhage and severe abnormal brain structure, including lissencephaly and schizencephaly (without clinical manifestations or manifested as microcephaly), MRI or CT is indicated. Neuroimaging is recommended in newborns and in cases where seizures cannot be explained by changes in glucose, calcium and electrolyte abnormalities in blood tests. Newborns with chromosomal abnormalities and ALD are at high risk of developing seizures. In these patients, karyotype and serum long-chain fatty acid levels, respectively, should be examined.

Treatment of neonatal seizures. Antiepileptic therapy should be prescribed to newborns with seizures due to 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 sufficiently high in newborns and allows achieving seizure control in less than 50% of cases. Widespread use of EEG in newborns with atypical neonatal seizures has identified many patients with pathological motor activity of a non-epileptic nature.

– syndrome of paroxysmal muscle contractions, debuting in the first 28 days after birth. It manifests itself as generalized or focal convulsions, accompanied by vegetative symptoms, sometimes with respiratory failure. The EEG shows a typical picture of an epileptic seizure, which, together with the history and clinical picture, confirms the diagnosis of neonatal seizures. The treatment is complex. Etiotropic therapy is carried out, anticonvulsants must be prescribed, and mechanical ventilation may be required. The prognosis is often unfavorable.

General information

Neonatal seizures are actually a type of symptomatic epilepsy associated with the neonatal period. The prevalence ranges from 1 to 16 cases per 1000 newborns, the pathology is more common in boys. The degree of full term of the child plays a role; in premature children, the frequency of occurrence is higher, and the course is more severe. Neonatal seizures occupy a special place in pediatrics, since the consequences of convulsive syndrome are irreversible, especially when it comes to a child in the first month of life. The mortality rate is 15-40%; among surviving children there is a high percentage of disability. The nosology has not been fully studied; with the current knowledge base, the causes of about 10% of cases of pathology remain unclear.

Causes and classification of neonatal seizures

The child’s brain at the time of birth is in an immature state; new neurons and interneuronal connections continue to form. This is due to his high convulsive readiness. As a consequence, the range of causes that can cause neonatal seizures is very wide. Most often, attacks are provoked by hypoxic-ischemic perinatal encephalopathy, which is a complication of pregnancy and childbirth. Also, seizures accompany brain injuries with intracranial hemorrhages, brain tumors, intrauterine infections and developmental abnormalities of the central nervous system.

Neonatal seizures may be associated not only with cerebral pathology. Often convulsive syndrome is caused by metabolic disorders. These may be hereditary pathologies of the metabolism of specific vitamins, minerals, etc., in particular - pyridoxine dependence, hypocalcemia, urea metabolism disorders, lysosomal storage diseases. Neonatal convulsions of toxic origin are rare, when children born to drug-addicted mothers experience a kind of withdrawal syndrome (neonatal withdrawal syndrome), manifested by convulsive seizures and other symptoms. A similar clinical picture is also typical in the case of taking tricyclic antidepressants and some other drugs during pregnancy.

Clinical classification is based on the type of seizure disorder. There are tonic, clonic, myoclonic and atypical seizures. The clinical picture varies depending on the cause, but different types of seizures can be observed under the influence of one etiological factor. Primary (hereditary) and symptomatic neonatal seizures are also distinguished. Only in 10% of cases, convulsive syndrome is observed in isolation. ICD-10 distinguishes between benign familial neonatal seizures and early myoclonic encephalopathy, which is a malignant variant of the pathology. In the remaining 90% of cases, convulsive syndrome is accompanied by other symptoms specific to each specific nosology.

Symptoms of neonatal seizures

The first clinical manifestations can be observed from the moment of birth or appear several days and even weeks after a period of well-being or against the background of a diagnosed disease. The time of onset of symptoms depends on the underlying diagnosis. Tonic seizures are more common in premature babies. At the same time, the child throws back his head, stretches his arms along the body, the eyeballs typically roll up, and sometimes breathing problems are observed. Neonatal seizures of this type indicate damage to the anterior structures of the brain and are usually observed in the first days and hours of a child’s life.

Most often in clinical practice, clonic and myoclonic neonatal convulsions occur, manifested by generalized or local twitching. The latter option is typical for trauma and hemorrhage. Myoclonic neonatal convulsions develop in almost any disease with a clinical picture of convulsive syndrome. Atypical manifestations, expressed in rhythmic twitching of the eyeballs, smacking, and vegetative attacks, are rare. There is a cyclical occurrence of symptoms. This type of neonatal seizures often accompanies mild abnormalities of brain development.

Diagnosis of neonatal seizures

Making a diagnosis is often difficult, since neonatal seizures can be caused by many different reasons, and the seizure syndrome does not always occupy a leading place in the clinic. Finding out the mother’s medical history plays an important role - existing somatic diseases and family history are taken into account. In addition, the pediatrician finds out the peculiarities of pregnancy and childbirth. There may be a diagnosed intrauterine infection, birth trauma of newborns, prematurity, etc. Different diseases are characterized by the onset of seizures at different times after birth, and this also makes it easier to make a specific diagnosis.

Pathological electrical activity in the brain is recorded using an EEG study. Typically, the encephalogram detects peak-wave complexes and slow waves. Outside of an attack, there is a complete absence of pathological changes on the EEG or minor changes. Brain abnormalities and tumors are confirmed using CT and MRI. Analysis of the cerebrospinal fluid of patients with neonatal seizures can identify abnormalities characteristic of intrauterine infections and also helps in the diagnosis of hemorrhages. Metabolic syndromes and storage diseases can be suspected by accompanying symptoms, and the diagnosis is confirmed by specific laboratory tests.

Treatment and prognosis of neonatal seizures

Treatment is carried out in the intensive care unit; constant observation and medical supervision are required; the child often requires respiratory support. Anticonvulsants are used in therapy. Such treatment is symptomatic, but its implementation is vital, since convulsive syndrome itself is extremely dangerous for the child’s life. The more attacks the baby suffers, the more severe the damage to his health and the worse the prognosis for later life. At the same time, etiotropic therapy is carried out: antibiotics and antiviral drugs, surgical treatment of injuries and tumors, dehydration therapy, specific drugs for the treatment of various metabolic syndromes, etc.

The prognosis is often unfavorable. The exception is benign familial neonatal seizures. Convulsive syndrome caused by hypocalcemia is well corrected. Any other disease, as a rule, has an irreversible damaging effect on the child’s central nervous system, which subsequently leads to impaired social adaptation, mental retardation (mental retardation, mental retardation) and disability. Mortality due to neonatal convulsions is high; deaths are more often observed in premature infants, with massive injuries and hemorrhages, gross developmental anomalies and septic complications. Neonatal seizures can be prevented only by timely treatment of the underlying disease.