Hypoxic ischemic encephalopathy (HIE)

What is perinatal encephalopathy?

Perinatal damage of the nervous system in newborns is a number of conditions and diseases of the brain, spinal cord and peripheral nerves united into a general group by the time of exposure of damaging factors. Perinatal period includes the antenatal, intranatal and early neonatal periods. The antenatal period begins from week 22 of fetal life and ends with an act of delivery. The intranatal period includes the act of delivery from the start of labor until birth. The neonatal period consists of early neonatal (corresponds to the first week of life) and late neonatal (from day 8 to day 28 of life inclusively) periods.

What is the cause of perinatal encephalopathy?

Perinatal encephalopathy is a frequent complication of abnormal pregnancy and labor. This condition is usually due to oxygen deficiency of the central nervous system that occurs in a problematic course of perinatal period which is complex for a child. Perinatal brain damages account for over 60 % of all pathologies of the nervous system in infants. They are responsible for such diseases as infantile cerebral palsy, epilepsy and minimal cerebral dysfunction. Various outcomes of perinatal encephalopathy depend on the damage extent of the central nervous system and correct and timely treatment: one third of patients usually need minimal rehabilitation support to get well, one third of them requires serious treatment including drug therapy, and one third of patients will have health problems in future even if medical aid was rendered properly and for a long time.

Among the reasons for perinatal brain damages, the leading position is occupied by the prenatal and intranatal (at labor) fetal hypoxia, and the second position is given to mechanical trauma of a child during labor. The latter is usually accompanied by previous intrauterine hypoxia of some intensity. Infectious (including viral) and toxico-metabolic types of nervous system damages are also included into the structure of etiopathogenetic factors of perinatal pathology. Thus, the factors that lead to perinatal damage of the CNS include the following ones:

• intrauterine hypoxia (deficiency of oxygen) in a fetus;

• fetal hypoxia at labor;

• mechanical trauma at labor;

• infectious (viral) factors;

• toxic factors;

• hereditary factors;

• a combination of the factors mentioned above.

Among the risk factors of perinatal encephalopathy in children, a greater relative weight belongs to maternal morbidity. According to numerous studies, it does not only disturb the preconceptional health (the health responsible for the birth of healthy offspring and parents) but also produces a direct negative effect on the fetus.

When studying the structure of the general pathology in pregnant women during the last five years, a significant growth of their morbidity is noted. It is mainly due to the increased rate of diabetes and thyroid diseases. During pregnancy, these diseases lead to placental insufficiency, disturbed nutrient absorbability and uptake via the placenta, and deficiency in oxygen and carbon dioxide transport manifested as fetal growth retardation, intrauterine hypertrophy, immaturity of the lungs and surfactant. It is established that decreased uteroplacental blood flow is an objective index of hypoxic damage of the brain.

How is perinatal encephalopathy manifested?

Perinatal encephalopathy is clinically manifested through some complexes of symptoms. The most frequent of them are motor and mental retardation, hypertension-hydrocephalic syndrome, syndrome of muscular dystonia, and syndrome of brain stem damage.

What is psychomental retardation and how is it treated?

Infancy is the most complicated period in a child’s life. Infants have a rapid rate of growth and development. When a child is born, development of his/her organs and tissues is not completed yet. They constantly progress after the birth and look like the organs of an adult person by the structure and functions. That’s why all pediatric doctors need to study the basic development peculiarities of an infant in detail. Tracing a child’s development from infancy to 1 years of age, doctors pay attention to anthropometric data, psychomotor development (motor activity), speech development, formation of skills and abilities in a child.

Considering the features of a healthy newborn child’s psychomotor status and tracing extinction of congenital reflexes and acquisition of motor and social skills, it can be estimated whether an infant is developing properly.

Retardation of psychomotor development and motor skills is observed in various hereditary diseases, in children with the central nervous system pathology, resulting in persistent motor disturbances including infantile cerebral paralysis. Retardation is developmental delay for 2 and over months. Children with regress of previously acquired motor and psychoverbal skills should be given particular attention as this can be a sign of neurodegenerative diseases.

Mild developmental arrest is often found in premature children, in chronic non-neurological diseases and rickets. Moderate and severe developmental arrests require special examination and treatment.

Non-drug management of psychomotor arrest in infants includes as follows:

Physical rehabilitation: different kinds of therapeutic massage, therapeutic gymnastics, position treatment (setup, braces, collars, etc.), Vojta therapy, water exercises and hydromassage; dry immersion (weightlessness imitation); physiotherapy (alternating magnetic field, sinusoidal modulated currents, electrophoresis, paraffin therapy, laser therapy, light and color therapy).

Psychological and pedagogical management: correction (conductive) education, psychotherapeutic correction in the pair of a mother and a child (skin-to-skin, kangaroo-type contacts); music therapy, esthetic therapy, tactile and kinesthetic stimulation. It is especially recommended to use a combination of two or three soft methods of physical effect with psychoemotional and psychosensory management. It helps gaining an effect of the so-called sensory rooms used during rehabilitation of elder patients.

Drug therapy utilized by neurologists to manage the motor and mental development during the first year of life is mainly represented by peptide drugs. The drugs launch endogenous mechanisms of compensation and bring a child’s development back to normal.

What is a syndrome of muscular dystonia and how it should be treated?

In an infant, tonus disturbances can be local (associated with one group of muscles) or general (associated with several groups of muscles). According to the change type in the muscular tonus, they are subdivided into hypotonus (decreased tonus) and dystonia (improper combination of increased and decreased tonus).

Infantile torticollis is the most common local tonus disturbance.

Torticollisis usually due to mild underdevelopment of traumatic injury to the sternocleidomastoid muscle and roots running from C5 – C6 segments of the spinal cord or accessory nerve. Torticollis usually disappears by the age of 6–9 months. However, mild symptoms of torticollis can be found in elder children, too. Resistance is felt when the head is rotated toward the opposite side of the affected muscles.

Treatment can include applications, electrophoresis, Traumeel injections, Viburcol rectal suppositories, right positioning of the head using a special pillow.

Muscular hypotonia (floppy baby syndrome) is mainly manifested through reduced resistance to passive movements and increased range of motions (laxity of joint). In severe cases, hypotonia influences a child’s posture: frog position is a diagnostic clinical finding of diffuse muscular hypotonia. A floppy baby syndrome can be seen in a wide spectrum of diseases: severe neurological disorders, rickets, severe perinatal hypoxia (oxygen lack) and birth trauma leading to cerebral palsy, metabolic disorders, neuromuscular diseases, developmental abnormalities and degenerative diseases of the nervous system, chromosomal syndromes and some forms of endocrine pathology.

Diffuse muscular hypotonia is often found in a congenital pathology. It can be accompanied by a slight body weight and height gain, epileptic seizures, and acute cerebrovascular accidents. Premature children often have severely decreased muscular tone. By the age of 3–6 months, hypotonia can be transformed into a spastic syndrome.

Severe persistent muscular hypotonia combined with delay in psychomotor development requires regular rehabilitation courses (massage, exercise therapy, physiotherapy, hydro- and balneotherapy, acupuncture, lessons with a speech therapist, drug therapy).

Muscular hypertonia can range from mild (not inhibiting movements and development) to severe including spastic syndrome (extreme form of hypertonia). Increased muscular tone can accompanied by activated tonic reflexes and delay in extinction of unconditioned reflexes.

Tonic reflexes combined with an increased muscular tone produce a pathological effect on a child. The picture is often observed in premature and immature children or in infantile cerebral palsy. In the last case, unconditioned reflexes can even be more intense.

Dystonia and hyperkinesis (wrong, excessive and superfluous movements) are often delayed and seen after 3–6 months of age or after birth.

Hyperkinesis usually characterize affection of cerebral basal ganglia often combined with other neurological symptoms (for instance, with diminished hearing). Hypertonia and dystonia are long-term effects of bad posture leading to skeletal deformities in children. Thus, in case of motor disturbances, a child must be examined not only a neurologist, but also by an orthopedist.

Diagnosis is followed by restorative treatment. Restorative treatment (if there are no cardiovascular, respiratory adverse events, epileptic seizures, etc.) includes massage, exercise therapy, orthopedic positioning, physiotherapeutic treatment, hydro- and balneotherapy, acupuncture, lessons with speech therapists, working in sensory rooms.

Methods of infant development and drug therapy are patient-specific and depend on intensity of the syndrome and its combination with delay in development, hyperkinetic and dystonic syndromes.

Drug therapy given to manage the muscular tone in children under one year of age consists of agents decreasing muscular tone (anti-spastic medicines) and agents that manage muscular hypotonia.

What is a hypertension – hydrocephalic syndrome and how it must be treated?

By 1 year of age, normal growth in head circumference is 11–12 cm:

• within the first trimester, head circumference is increased by 4 cm (1.5 cm per month);

• it is increased by 3 cm within the second trimester (1 cm per month);

• within the third trimester, head circumference is increased by 3–4 cm (0.5 cm per month).

Pathological growth in head circumference as a symptom of hydrocephaly is due to obstruction of liquor passages at various levels and disturbed relations between production and absorption of spinal fluid.

Hydrocephalus:

Congenital hydrocephaly is formed in a fetus during pregnancy and is present at birth. Principal causes of congenital hydrocephaly: development defects; in rare cases, intrauterine infection; in very rare cases, ventricular hemorrhage in a fetus.

Acquired hydrocephaly is developed after the child is born, sometimes at the most early stages of life. Causes of acquired hydrocephaly: intraventricular hemorrhages, infection damaging the central nervous system such as meningitis, encephalitis, craniocerebral trauma, cerebral traumas.

Clinical symptoms of intracranial hypertension:

• changes in a child’s behavior: anxiety, frequent and monotonous crying, head lag, frequent regurgitation;

• delay in mental, motor and psychoverbal development;

• sagittal suture is wider than 0.5 cm, bulging anterior fontanel;

• change in the cranial shape with a high forehead (acrocephaly) or outstanding occipital prominence in combination with a rapid increase in head circumference, predominance of head circumference over chest circumference;

• graefe's sign, congestive changes in the fundus;

• increased muscular tone, predominantly in the hands and feet;

• tremor of hands with their opening.

Apart from hydrocephalus, children with a dome-shaped head may be diagnosed as follows:

• rickets;

• children born with big heads;

• infants with syndrome-based conditions and inherited diseases.

To provide an adequate assessment, the head circumference must always be compared to the chest circumference, head dimensions of the child’s parents must be assessed, results of additional methods of examination must be taken into account (fundus examination, neurosonography, CT, MRI).

Drug therapy to manage the hydrocephalus syndrome at the first year of age mainly includes diuretic and vascular agents.

Hydrocephalus is treated not by a neurologist, but by a neurosurgeon. A neurologist can’t decide on hydrocephalus treatment without being consulted by a neurosurgeon. If surgical treatment of hydrocephalus is not possible due to any reasons, the patient must be observed by both a neurologist, and a neurosurgeon.

Insufficient increase in the head circumference is observed in progressive congenital degenerative diseases, severe organic lesions (secondary microcephaly, when not growing brain slows down the growth of the skull), and in craniostenosis (cranial bone pathology that needs to be treated by a neurosurgeon).

It is of note that the rate of anterior fontanel occlusion differs and is probably rather associated with the features of mineral metabolism than with the nervous system pathology. A presence of an anterior fontanel by the end of the second six months of life and absence of neurological complaints are not the reasons for concern. The same goes for a rapid occlusion of the anterior fontanel which is not a reason to stop the planned prevention of rickets in an infant.

What is a convulsive disorder and how it can be treated?

During practice, a pediatric neurologist comes across many conditions that arise on a sudden, exist for a short term and terminate all at once. Epileptic seizures usually accompanied by loss of consciousness are examples of paroxysms. However, loss of consciousness is developed not in all paroxysms; some of them have unusual symptoms leading to diagnostic mistakes.

Detection and differentiation of various paroxysmal conditions in infants is especially difficult. In order to choose a proper treatment, we need to differentiate between paroxysmal conditions of epileptic and non-epileptic origin. Only an experienced neurologist-epileptologist can name the cause of paroxysms and give a prognosis.

Breath-holding spell is a short-term interruption of breathing when crying with a child turning pale or blue. Breath-holding spells need to be differentiated from the syndrome of apnoe (arrest of breathing) which frequently occurs in premature or immature infants and in children with cardiovascular, respiratory and brain stem pathology. Polysomnography, which records your brain waves, heart rate and breathing and determines what causes difficulty breathing in a child, is done to ensure strict differentiation. Breath-holding spells are not epileptic but are more likely to transform into epilepsy.

Paroxysmal sleep disturbances unite a large group of conditions which must be differentiated from non-neurological disorders and epileptic paroxysms. Nightmares when a child starts crying and yelling without awakening or not reacting to what is around him/her are typical examples of paroxysmal sleep disturbances. Frequently occurring nightmares show that there are mental problems.

Febrile convulsions belong to the most common type of paroxysmal conditions in children. Febrile convulsions (FC) include paroxysms of various duration in the form of seizures that occur in infants and younger children whose body temperature is 37,8–38,5 °C. There is a high risk that FC can be transformed into epilepsy.

We differentiate between typical and atypical FC. Typical FC are short-term (to 15 minutes) and generalized (all limbs are involved, short-term loss of consciousness is developed); values of a child’s psychomotor development conform to the age, EEG shows no typical changes. In atypical FC, an attack lasts over 15 minutes (to several hours), limbs on one side are involved; attacks are sometimes followed by Todd's paresis or transient muscular weakness in the convulsive limbs (in 0.4 % of cases), EEG shows common epileptic focal changes.

Neonatal seizures (NS) are developed within the first 4 weeks of life in a mature newborn (from day 1 to day 28) and later in immature ones. It is very difficult to differentiate between neonatal seizures and good movements based on clinical features only. Electroencephalographic (EEG) monitoring and video recording is required. Myoclonic attacks have the most severe prognosis. They can show there is an onset of early severe epilepsy.

Epilepsy is a chronic brain disorder characterized by recurrent provoked convulsive seizures causing impaired motor, sensory, vegetative, intellectual or mental functions which occur due to excessive neuron discharge in the brain cortex. Among children epilepsy is seen in 10 cases per 1,000.

Epilepsy is a very unpleasant but very common neurological disease, especially in childhood. Apart from life threatening conditions in continuous and complicated seizures in infants, epilepsy leads to remote negative consequences disturbing the cognitive, psycho-social and motor development of a child. Novel anti-seizure medications control many forms of epilepsy, but parents are afraid to use the medications due to negative experience of an older generation who used the agents and came across adverse effects. Discuss your worries with a specialist. Do not deprive your child of healthy future because of prejudices.

What are the symptoms of brain stem lesions and how they can be treated?

The brainstem (or brain stem) is the posterior part of the brain, continuous with the spinal cord.

It contains vitally important centers responsible for respiration, swallowing, cardiac activity, concordant movements of the eye, etc. In newborns with neurological problems, the centers can be not properly formed or damaged. Underestimation of brain stem lesion symptoms can result in critical consequences.

Bulbar and pseudobulbar disturbances in children with an injury to the nervous system are found since their birth. They appear as weak suckling ability, choking with saliva, food, water, passage of food through the nose, changed tone of the tongue, disturbed speech development.

Oculomotor disorders are very typical of infants with CNS pathology. Possible disturbances include nystagmus (rapid and repetitive movement of the eyes) and different types of heterotropy. Vision impaired patients are related to a very important group as in them, oculomotor disturbances can be the first symptoms of visual function disturbance (for example, the floating nystagmus of the blind). The patient need to be observed by a neurologist and ophthalmologist.

Disturbed restoration and cardiac rhythm are also typical of patients with the disturbed function of brain stem structures. Premature infants and infants with low weight are at risk for respiratory disturbances, apnea and arrhythmia. In this situation, differential diagnostics of neurological and non-neurological (cardiological, respiratory) causes of the found disturbances is crucial. These patients require proper diagnostics and need to be examined by a neurologist, pulmonologist, cardiologist and ENT specialist.

Do not forget to ask doctors about brainstem disturbances in your child. The consequences can be very severe (for instance, apnea type respiration disturbances result in the sudden infant death syndrome, while disturbed swallowing and chronic choking lead to severe aspiration pneumonia). However, correct and proper care (correct posture of a child while sleeping, feeding with a raised head and special diet) enables to avoid the difficulties even without additional drug intake.

Do all deviations in a child’s development require a special therapy?

During the first year of life, the following events are considered as normal variants:

• Physiological tremor is a rapid transient tremor found in the limbs and sometimes the chin during crowing or feeding. It can be found in a half of children not elder than 3 months of age. In premature infants, tremor can be observed until they are 6 months old.

• Physiological astasia-abasia is inability of 2- to 5-month-old children to bear some weight on their legs when supported. As their legs are tucked under, no stepping motions are present due to extinction of support reflexes.

• Jactation is a tossing or shaking of the body and/or head, especially before sleeping. They are typical of parentless children.

• Animation complex includes various chaotic movements of a child experiencing positive emotions. They are especially common for children with immobilized limbs (for instance, receiving treatment with gypsum or orthopedic appliances).

Thus, all children with perinatal encephalopathy need long-term dynamic observation by specialists and individually -tailored recurrent courses of restorative treatment with at least 3-month break and regular control of its effectiveness within the first year of life at out-patient rehabilitation centers, in-patient facilities and district polyclinics.

It is not enough to involve healthcare specialists in the rehabilitation process. A child’s family members must participate as well. Professionals interested in products of their labor will be glad to teach mothers basic exercise therapy, early swimming and methods of early infant development. Albeit the entrenched view, restorative treatment of children with the perinatal lesion of the nervous system must be initiated soon after diagnosis and terminated when the child is equal to his/her peers considering physical, motor and psychoverbal development.

O. V. Bykova

Doctor of Med. Sc., Principal Researcher of the Centre for Applied Research in Pediatric Psychoneurology

of Moscow Health Department