Neonatal hypoxic-ischemic encephalopathy

Introduction to neonatal hypoxic ischemic encephalopathy Hypoxic-ischemic encephalopathy of newborn (HIE) refers to neonatal brain injury caused by various causes of hypoxia and decreased cerebral blood flow. Brain tissue is characterized by edema, softening, necrosis and hemorrhage. It is one of the important complications of neonatal asphyxia and one of the common causes of neurological disability in children. In severe cases, there are sequelae, such as cerebral palsy, mental retardation, epilepsy, deafness, visual impairment, etc. This disease not only seriously threatens the life of newborns, but also is one of the most common causes of sick children after neonatal period. basic knowledge The proportion of illness: 0.001% Susceptible population: newborn Mode of infection: non-infectious Complications: aspiration pneumonia intracranial hemorrhage hydrocephalus

Causes of neonatal hypoxic ischemic encephalopathy

(1) Causes of the disease

There are many factors that cause neonatal hypoxic-ischemic brain damage:

Hypoxia

(1) Perinatal asphyxia: including prenatal, intrapartum and postpartum asphyxia, intrauterine hypoxia, abnormal placental function, umbilical cord prolapse, compression and around the neck; abnormal delivery such as urgency, delayed labor, abnormal fetal position; Dysplasia such as premature birth, overdue production and intrauterine growth retardation.

(2) apnea: repeated apnea can lead to hypoxic ischemic brain damage.

(3) Severe pulmonary infection: Newborns have serious respiratory diseases, such as severe lung infections.

2. Ischemia

(1) Severe circulatory diseases: sudden cardiac arrest and bradycardia, severe congenital heart disease, severe heart failure, etc.

(2) A large number of blood loss: a large amount of blood loss or shock.

(3) severe intracranial diseases: such as intracranial hemorrhage or cerebral edema.

Neonatal asphyxia is the leading cause of this disease in HIE, with prenatal and postpartum asphyxia accounting for 50% and 40%, respectively, and other causes account for about 10%.

(two) pathogenesis

1. Hemodynamic changes In the absence of oxygen, the body undergoes diving reflexes, in order to ensure the blood supply of important vital organs (such as brain, heart), cerebral vasodilation, non-significant organ vasoconstriction, this automatic regulation function makes the brain mild Short-term hypoxia is not damaged, such as hypoxia continues to exist, cerebral vascular autoregulation function decompensation, cerebral arterioles have reduced ability to respond to changes in perfusion pressure and CO2 concentration, forming a pressure-related passive cerebral blood flow regulation process When blood pressure is lowered, cerebral blood flow is reduced, causing ischemic damage to the edge of the artery.

2. Brain cell energy metabolism failure Intracellular oxidative metabolism disorder in hypoxia, can only rely on glucose anaerobic glycolysis to generate energy, while producing a large amount of lactic acid and accumulating in cells, leading to intracellular acidosis and brain edema, due to anaerobic leaven The energy produced by the solution is far less than that of aerobic metabolism, and must be compensated by increasing glycogenolysis and glucose uptake, thereby causing secondary energy failure, resulting in impaired ion pump function on the cell membrane, intracellular sodium, calcium and water. Increased, causing cells to swell and dissolve.

3. Reperfusion injury and oxygen free radicals Oxygen free radicals increase and decrease during hypoxia-ischemia, a large number of oxygen free radicals accumulate in the body, damage cell membranes, proteins and nucleic acids, resulting in destruction of cell structure and function, oxygen Hydroxyl radicals are the most harmful to free radicals in the free radicals. Xanthine oxidase and dehydrogenase are mainly concentrated in the endothelial cells of microvessels, resulting in damage to the vascular endothelium, destruction of the structure and integrity of the blood-brain barrier, and formation of vascular sources. Sexual brain edema.

4. When the Ca2 internal flow is hypoxia, the activity of the calcium pump is weakened, which leads to calcium influx. When the intracellular Ca2 concentration is too high, the enzyme regulated by Ca2 is activated, and the phospholipase is activated, which can decompose the membrane phospholipid and produce a large amount of arachidene. Acid, under the action of cyclooxygenase and lipoxygenase, forms prostacyclin, thromboxane and leukotriene, nuclease activation, can cause nucleic acid decomposition and destruction, protease activation, can catalyze the transformation of xanthine dehydrogenase into jaundice Oxidase, which catalyzes the hypoxanthine to become jaundice when restoring oxygen supply and blood flow, while generating free radicals, further aggravating nerve cell damage.

5. Neurotoxicity of excitatory amino acids Energy failure can cause damage to the sodium pump function, extracellular K accumulation, continuous depolarization of the cell membrane, presynaptic neurons release a large amount of excitatory amino acids (glutamate), accompanied by sudden Impaired post-touch glutamate damage, resulting in increased glutamate in the synaptic cleft, over-activation of postsynaptic glutamate receptors, non-N-methyl-D-aspartate (NMDA) receptors When activated, Na influx, Cl- and H2O also passively enter the cell, causing rapid death of neurons; when NMDA receptor is activated, Ca2 influx can lead to a series of biochemical chain reactions, causing delayed neuronal death .

6. Biphasic action of nitric oxide (NO) NO is also a gas radical that reacts with O2 to produce a peroxynitrite (ONOO-) and further decomposes into OH- and NO2-, when In the presence of metallic iron, ONOO- decomposes to generate free radicals NO2-, OH- and NO2- have a strong cytotoxic effect. In addition, NO can also mediate the toxic effects of glutamate, and can also damage mitochondria, proteins and DNA directly causes neuronal damage. In hypoxia-ischemia, Ca2 influx, when intracellular Ca2 accumulates to a certain level, activates nitric oxide synthase (NOS), synthesizes a large amount of NO, and NOS has three different types. Subtypes, neuronal and inducible NOS mediate early and late neurotoxic effects, respectively, while NO produced by endothelial cell type NOS can dilate blood vessels and play a neuroprotective role.

7. Apoptosis and delayed neuronal death In the past, neuronal injury after hypoxia-ischemia was caused by cell necrosis caused by acute energy failure, but it could not explain that children with asphyxia may have a transient relative normal period, but for several hours. After the appearance of delayed brain injury, studies have confirmed that hypoxia-ischemia can cause two different types of cell death, namely necrosis and apoptosis. Delayed neuronal death is essentially apoptosis, detected in animal models. To the expression of a series of apoptosis-related genes.

In short, the pathogenesis of HIE is very complex, and it is the result of a series of biochemical chain reactions caused by a combination of various mechanisms. A large number of studies have confirmed that most neurons do not die from hypoxia-ischemia, but die from hypoxia From hours to days after the blood, this delayed cell death can be prevented or alleviated by interventions that begin after hypoxia-ischemia.

The pathological changes of HIE are closely related to gestational age, the nature and extent of injury. There are mainly four pathological types. One is cerebral hemisphere damage on both sides: mainly found in term infants, asphyxia is incomplete, and the first blood division between organs ( Diving reflex) to ensure heart, cerebral blood supply, with hypoxia persistence, blood pressure drops, blood flow redistribution for the second time (brain shunt), that is, blood supply to the cerebral hemisphere is reduced due to vasoconstriction of the forebrain circulation, and the thalamus The blood supply to the brainstem and cerebellum increases due to vasodilation of the cerebral circulation. Therefore, the cerebral hemisphere is more susceptible to damage, often accompanied by severe cerebral edema, and the second is basal ganglia, thalamic and brain stem damage: complete asphyxia, twice The compensatory mechanism of redistribution of blood flow is invalid. Brain damage is mainly caused by thalamus and brainstem, while damage of extracranial organs and cerebral hemispheres is not serious, cerebral edema is mild, and third is white matter softening around the ventricles: mainly found in premature infants. Hypoxic-ischemic ischemia around the lateral ventricle leads to the death of deep white matter brain cells, which is often symmetrically distributed. Later, the lower extremity involvement may occur, and the fourth is the subventricular/intraventricular space around the ventricles. Blood: mainly seen in premature children, the subependymal germinal tissue bleeding, with intraventricular hemorrhage.

Neonatal hypoxic ischemic encephalopathy prevention

The prevention of this disease is more important than the prevention of perinatal asphyxia. It is necessary to continuously improve the obstetric technique, promptly handle intrauterine distress, and end the delivery as soon as possible. The babies who suffocate after birth should recover in time to reduce the occurrence of HIE.

Pregnant women should regularly perform prenatal examinations and find that high-risk pregnancies should be treated in time to avoid premature delivery and surgical delivery; improve obstetric techniques; provide fetal heart rate monitoring for high-risk pregnancies, and detect intrauterine distress in the early stage; Immediately after the head is delivered, the mucus in the nose and mouth is squeezed out, and after the birth, the mucus is again squeezed out or sucked out, the secretion of the nasopharynx is prepared, and all preparations for neonatal resuscitation are prepared.

Once the fetal distress is found, the mother is immediately given oxygen, and the newborn is resuscitated and oxygenated. The newborn should be supine after birth, with a slightly higher head and less disturbance.

(1) During the delivery process, the fetal heart rate should be closely monitored, and the fetal scalp blood pH and blood gas should be measured regularly. It is necessary to promptly give oxygen and intravenous glucose and other drugs in the intrauterine distress, and choose the best way to end the delivery as soon as possible.

(2) Newborns who suffocate after birth should strive to establish effective breathing and perfect circulation function within 5 minutes to minimize the damage of brain cells after hypoxia.

(3) Newborns after asphyxia resuscitation should closely observe neurological symptoms and monitor vital signs. Once abnormal neurological symptoms such as disturbance of consciousness, weakened limbs, and primitive reflexes are not easily elicited, the diagnosis of this disease should be considered. Treatment is given to reduce the incidence of sequelae in survivors.

Neonatal hypoxic ischemic encephalopathy complications Complications, aspiration pneumonia, intracranial hemorrhage, hydrocephalus

Often associated with aspiration pneumonia, often complicated by intracranial hemorrhage, cerebral edema, brain parenchymal necrosis and hydrocephalus, the short-term adverse prognosis of HIE is early neonatal death, long-term poor prognosis is mostly the sequela of cranial nerve damage, lacking in surviving cases The more severe the oxygen ischemia, the longer the symptoms of encephalopathy last, the more likely the sequelae will occur, and the more severe the sequelae, the sequelae are often stunted, mental retardation, spasticity, epilepsy, deafness, visual impairment.

Symptoms of neonatal hypoxic ischemic encephalopathy Common symptoms Reflex before disappearing full suffocation muscle tension reduced coma stagnation susceptibility disorder sinus fetal heart rate drowsiness

According to the condition, it is light, medium and heavy:

(1) Mild: excessive arousal state, irritability, excitement and high agitation (jitter, tremor), normal muscle tension, active hug reflex, normal sucking reflex, stable breathing, no convulsions, symptoms gradually disappear within 3 days The prognosis is good.

(2) Moderate: inhibited state, lethargy or shallow coma, low muscle tone, 50% of cases have seizures, apnea and hug, weakened sucking reflexes, lower limb muscle tension in full-term children is more severe than lower limbs, suggesting lesions involving sagittal In the sinus area, if the premature infants show lower limb muscle tension than the upper limbs, it suggests that the lesion is white matter softening around the ventricles. If the symptoms last for 7 to 10 days, there may be sequelae.

(3) Severe: the child is in a coma, the muscle tension is extremely low, soft, hugs the reflex, the sputum reflex disappears, the pupil is not large, the response to light is poor, the anterior condyle, the convulsions are frequent, the breathing is irregular or suspended, and even appears Respiratory failure, severe cases of high mortality, survivors often leave sequelae.

(1) Mostly suitable for full-term gestational age, with a history of obvious intrauterine distress or a history of asphyxia (Apgar score 1 minute <3, 5 minutes <6, spontaneous breathing after 10 minutes of rescue, or need to use Intratracheal intubation for positive pressure for more than 2 minutes).

(2) Disorder of consciousness is an important manifestation of this disease. Abnormal neurological symptoms appear after birth and last for more than 24 hours. Lightness is only irritating or lethargy; heavy consciousness is diminished, coma or stupor.

(3) Cerebral edema sign is a characteristic of perinatal HIE. The front sputum is full, the suture is separated, and the head circumference is enlarged.

(D) convulsions: more common in the middle, severe cases, convulsions can be atypical focal or multifocal, clonic and myotonic myoclonus, the number of attacks varies, more than 24 hours after birth, 24 hours The incidence of sequelae of internal authors increased significantly.

(5) Increased muscle tone, weakened or soft, and epilepsy may occur.

(6) Original reflection anomaly: If the hug reflection is excessively active, weakened or disappeared, the sucking reflex is weakened or disappeared.

Severe cases of central respiratory failure, respiratory rhythm, apnea, and nystagmus, pupillary changes and other brain stem damage.

The clinical symptoms of HIE are most important in the state of consciousness, changes in muscle tone and convulsions, and are the main indicators for distinguishing the severity and sequela of encephalopathy.

Examination of neonatal hypoxic ischemic encephalopathy

[Laboratory Inspection]

1. Biochemical indicators Determination of neuroenolase (NSE), S-100 protein (S-100) and brain creatine phosphokinase (CK-BB) are present in different parts of the nervous tissue, 6 to 72 h after HIE in the blood It is positively correlated with the increase in cerebrospinal fluid and the degree of brain damage, and can be sensitively used as a marker for early diagnosis and assessment of prognosis of HIE.

2. Others select arterial blood gas analysis according to the condition, blood glucose, electrolytes, urea nitrogen, platelets, prothrombin time, clotting time, fibrinogen and other tests.

[Auxiliary inspection]

1. Chest X-ray examination often has aspiration pneumonia.

2. Head CT examination

(1) Mild: scattered, focal low-density shadows distributed in 2 brain lobe.

(2) Moderate: The low-density shadow exceeds 2 brain leaves, and the white matter gray matter is blurred.

(3) Severe: diffuse low-density shadow, the gray matter white matter disappears, but the basal ganglia and cerebellum still have normal density. The middle and severe cases often have intracranial hemorrhage. Normal newborns, especially premature infants, have more brain water and myelin development. Mature, there may be a wide range of low density, so the low-density diagnostic CT value should be below 18, in the acute phase of HIE, cerebral edema is more obvious, may cover brain cell damage, and the condition is still changing, so early imaging The examination does not reflect the prognosis and needs to be reviewed after 2 to 4 weeks.

3. Brain ultrasound examination

(1) The general echo is enhanced, and the ventricles are narrowed or disappeared, suggesting brain edema.

(2) The high echo area around the ventricle is more common in the posterior corner of the lateral cerebral ventricle, suggesting that there may be white matter softening around the ventricles.

(3) scattered in the high echo area, caused by extensive dissemination of brain parenchymal ischemia.

(4) Localized hyperechoic area, indicating that there is ischemic damage in a region of a major cerebrovascular distribution.

4. Magnetic Resonance Imaging (MRI) MRI can not only detect the presence, distribution and severity of acute HIE, but also help to determine the prognosis, and can also find whether the myelination is delayed or abnormal to determine the development of the nerve.

5. Brain function check

(1) Electroencephalogram (EEG) examination: manifested as a rhythm disorder, a slow wave burst on a low-amplitude background wave or a sustained diffuse slow activity; "burst suppression", "low voltage" or even "electrical rest" It is severe HIE, the degree of abnormal EEG is parallel with the severity of the disease, the EEG is normal or single, the prognosis is good; the abnormal abnormality (equal potential, low potential, fast wave, burst suppression waveform, etc.) EEG, Especially periodic, multifocal or diffuse changes are signals of the sequelae of the nervous system.

(2) Brainstem auditory evoked potential (BAEP): manifested as efferent wave delay, prolonged latency, flattened amplitude and wave loss, dynamic observation of V wave amplitude and V/I amplitude ratio, if sustained low indicates nervous system damage .

(3) Doppler ultrasound cerebral blood flow velocity (CBV) measurement: help to understand cerebral perfusion, high CBV suggesting cerebral vasospasm and lack of autonomic regulation, low CBV suggesting extensive brain necrosis, hypoperfusion, or even no Perfusion.

6. Brain metabolism monitoring

(1) Magnetic resonance spectrum (MRS): MRS is a non-invasive method for detecting chemical components in the body (such as brain tissue ATP, phosphocreatine, lactic acid, etc.), which can measure the metabolism of brain tissue in vivo. It is more sensitive than MRI to reflect the degree of hypoxic-ischemic brain damage.

(2) Near-infrared spectroscopy (NIRS): NIRS is an emerging optical diagnostic technology in recent years. It can directly detect changes in oxyhemoglobin and reduced hemoglobin in brain tissue, and actually understand the oxygenation in the brain and indirectly reflect the brain. Hemodynamic status and intracellular biooxidation process.

Diagnosis and diagnosis of neonatal hypoxic ischemic encephalopathy

diagnosis

Clinical diagnosis basis:

(1) It has a clear history of perinatal asphyxia. Abnormal neurological symptoms such as disturbance of consciousness, changes in muscle tone, and abnormalities in the original reflex were seen within 12 hours or 24 hours after birth.

(2) Those who are critically ill have convulsions and respiratory failure.

Differential diagnosis

Pay attention to the identification of diseases such as intrauterine infection, central nervous system malformation and intracranial hemorrhage.

1. Neonatal intracranial hemorrhage can be confirmed as intracranial hemorrhage, which can clearly show the type, location, shape, size range, amount of bleeding and compression of surrounding brain tissue; and HIE pathological changes include brain edema, brain tissue necrosis And intracranial hemorrhage, these pathological changes can be confirmed by clinical manifestations and CT scans.

2. Congenital malformations of the skull and viral infections. If hypoxia-ischemia occurs several weeks or months before birth, the child may have no asphyxia or neurological symptoms at birth, but may appear in days or weeks. The performance of subacute or chronic encephalopathy is clinically difficult to distinguish from congenital brain malformation or intrauterine viral infection. CT examination can reflect the congenital malformation of the skull. Etiological and serum-specific antibody examination is beneficial to the identification of viral infectious diseases.

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