Pediatric Reye's Syndrome

Introduction to children's syndrome Reyes Syndrome (RS) is an acute progressive encephalopathy, also known as encephalopathy with visceral steatosis, Reye syndrome, viral infectious encephalopathy syndrome, hepatic massive steatosis - acute encephalopathy syndrome, vomiting, liver Lipidosis and the like. This syndrome is an unexplained syndrome with acute encephalopathy and hepatic steatosis as the main clinical features. It was first reported by Australian pediatric pathologist Reye in 1963. Reye syndrome is a critical illness, often preceded by a virus. Symptoms of encephalopathy such as acute intracranial hypertension, disturbance of consciousness, and convulsions after infection, often accompanied by severe cerebral edema, and abnormal liver function and metabolic disorders. In most cases, severe intracranial pressure and cerebral palsy cause death, or serious neurological sequelae. basic knowledge The proportion of illness: 0.002% Susceptible people: children Mode of infection: non-infectious Complications: arrhythmia cerebral palsy

The cause of children's Rei's syndrome

Infection (25%):

Common viral infections before the disease, manifested as respiratory or digestive tract symptoms, the pathogen may be influenza virus, chickenpox, parainfluenza, enterovirus, Epstein-Barr virus, etc.

Drugs (25%):

There is more evidence (such as epidemiology) that patients who take salicylate (aspirin) during viral infection are more likely to develop this disease later, and it has been confirmed to have multiple inhibitory effects on mitochondria. In recent years, the incidence of this disease has decreased in the United States, the United States and other countries to reduce or stop the application of salicylic acid. In addition, the anti-epileptic drug valproic acid can also cause the same symptoms as Reye's syndrome.

It has recently been reported that Reye syndrome usually occurs after flu or chickenpox, and if the incidence of aspirin is significantly increased, there is a significant correlation between the two, the Atlanta Center for Prevalence Control has been caused by oral administration of aspirin in chickenpox and flu. The same performance as Reye syndrome is called "aspirin syndrome". Aspirin Pharmaceuticals and Aspirin in the United States have been affixed to aspirin vials since 1985. Children with flu or chickenpox need to be approved by the physician before taking it. Warning label and delete the word flu as an indication for aspirin.

Toxin (30%):

Aflatoxin, organic phosphorus and organic oxygen and other insecticides, dirt and other contaminated foods or contact with it, may appear the same symptoms as this disease.

Genetic metabolic disease (15%):

Some children have a family history, some congenital metabolic abnormalities can cause the manifestation of Reye's syndrome, sometimes called Reye-like syndrome, such as systemic carnitine deficiency, liver enzyme damage and In the urinary circulation, ornithine transcarbamylase (OTC) and carbamyl phosphate synthase (CPS) deficiency caused by hyperammonemia, etc., with the advancement of genetic technology, there will be more Wright's synthesis A specific diagnosis of inherited metabolic diseases was obtained.

The above various reasons are also affected by the inherent susceptibility of the body. Lassick et al believe that this symptom is caused by the excessive release of tumor necrosis factor (TNF), which is known to be caused by viral infection, endotoxin and phagocytic cells. Increased release of activated macrophages, non-hormonal anti-inflammatory drugs can release macrophages to excessive concentrations of TNF, arterial experiments suggest that young animals are more sensitive to TNF, thus causing a hypothesis, namely Some specific young children treated with aspirin can increase TNF release leading to the development of Reye syndrome.

Pediatric Reyes syndrome prevention

The prevention of hereditary diseases mainly depends on genetic counseling and prenatal diagnosis. Since most cases of this syndrome are sporadic, the development of prenatal diagnosis is not currently widespread.

1. Prevent infections, especially viral infectious diseases, and do a variety of vaccination work.

2. Caution or use of certain drugs to infect children should stop taking salicylate, use anti-epileptic drug valproic acid with caution.

3. Avoid all kinds of toxins.

4. Do a good job in the prevention and treatment of hereditary diseases.

Pediatric Reye's syndrome complications Complications arrhythmia cerebral palsy

The disease is caused by multiple organs, and various clinical manifestations, such as liver enlargement, liver and spleen dysfunction, arrhythmia, heart failure, oliguria, anuria, etc., advanced brain damage or cerebral palsy may occur, and breathing may occur. Functional failure.

Symptoms of children's syndrome, common symptoms, hyperammonemia, respiratory failure, hepatomegaly, slumber, low fever, convulsions, sputum, full intracranial pressure, increased arrhythmia, diarrhea

The clinical manifestations of this symptom can be described as "four high, four low and one normal", four high:

1. Obvious acute intracranial hypertension;

2. The incidence of liver damage is high;

3. Hyperammonemia;

4. The mortality rate is high, four low:

5. Low age group;

6. The incidence of jaundice is low;

7. Go to the cerebral cortex or go to the brain to have less signs of rigidity;

8. Hypoglycemia, a normal means that the routine and biochemical examination of cerebrospinal fluid is normal.

1. Clinical manifestations The age of onset is more than 4 months to 5 years old, and can be seen at any age. Typical RS is characterized by "dual phase" disease. Children often have prodromal infections, such as respiratory or digestive tract. Symptoms of viral infection, accompanied by hypothermia, cough, runny, nausea, vomiting, diarrhea, etc., followed by personality changes, but these changes are often ignored, several days (sometimes very short) or 2 to 3 weeks after the acute Encephalopathy and abnormal liver function, vomiting is frequent and frequent with the progress of the disease, especially in children under 1 year old, sudden high fever after 3 to 7 days, frequent vomiting, convulsions and disturbance of consciousness (sleeping or coma), etc. Symptoms of encephalopathy, severe symptoms of central respiratory failure such as respiratory rhythm disorders, severe heart disease may occur to the cortex or to the brain tonic, often accompanied by circulatory disorders, hypoglycemia or diarrhea and other symptoms, often accompanied by liver enlargement, texture is tough or hard, Generally not accompanied by jaundice.

Clinical manifestations vary with age. Older children and adolescents often have frequent vomiting and less fever. Infancy is characterized by fever, convulsions and respiratory failure. Vomiting can last for several days, mainly when the intracranial pressure is increased. Stimulated, 24-48h mental state changes, drowsiness and paralysis, can appear cortical tonic or go tonic.

Vomiting is often brown, severe symptoms can cause dehydration, acidosis or electrolyte imbalance. If left untreated, the condition can continue to develop, and changes in consciousness disorders such as lethargy, disorientation, memory loss, and even excitement, hallucinations, paralysis, Stupor state or coma, mild or moderate cases can be terminated at this stage and gradually recover, but in most cases, the condition is worse, and the intracranial pressure is increased (such as anterior sputum fullness, fast breathing, deep, excessive Ventilation) and brain symptoms, beginning with diffuse cerebral cortical dysfunction, followed by brain stem dysfunction, one side of the pupil dilated or bilateral asymmetry, the last two sides of the pupil dilated, the limbs are de-cerebral toe, Tendon reflexes, Babinski sign positive, there are still III, VI brain nerve damage rhythm, further developed into limbs flaccid paralysis, no response to various stimuli, tendon reflex disappeared, heart rate first accelerated, after Slower, lower blood pressure, slower breathing, and eventually death.

Wright's syndrome is generally not associated with high fever, the focal signs of the nervous system and meningeal irritation are not obvious, the liver may have mild, moderate swelling, but liver dysfunction and jaundice are not obvious, most cases may appear in the course of the disease Various types of convulsions, deep coma have gastrointestinal bleeding, late case optic disc edema, or arrhythmia or cardiac insufficiency due to myocardial conduction system involvement, occasionally combined with acute renal insufficiency, combined with acute Pancreatitis can be associated with coagulopathy.

The symptoms vary from case to case, and those with mild or timely treatment can gradually recover in the early stage of the disease and recover gradually. In severe cases, they can die within a few days or even within 24 hours.

2. Grading According to the progress of the disease, the National Institutes of Health (NIH) divided the RS into 5 grades in 1982. See Table 1. Generally, the expression progresses from grade I to grade V within 1 to 2 days. The critically ill is more than the onset. After a few days of death, the heavy RS is fierce, rapid development, and even died within 24 hours. Survivors recover within 2 to 3 days after the condition improves, especially in infants. The sequela of encephalopathy can account for 1/3 to 2 /3, generally no liver sequelae.

Examination of children's syndrome

1. The blood picture examination showed that the total number of white blood cells was significantly increased, and granulocytes were the majority.

2. Urine examination The ketone body can appear in the urine and the dicarboxylic acid appears.

3. Blood tests for abnormal liver function, serum aspartate aminotransferase, alanine aminotransferase, and creatine phosphokinase (CPK) values increased significantly after the disease, returned to normal within 1 week, and blood ammonia increased significantly in the early stage of the disease, which could be increased by 300 g. Above /dl, it also returned to normal blood ammonia within 1 week, prothrombin decreased, other metabolic disorders showed a significant decrease in blood glucose, cholesterol and total blood lipids decreased, and free fatty acid concentration increased, infants often have hypoglycemia, may appear low Carnitineemia, hypocholesterolemia, hypolipoproteinemia and dicarboxylate blood (urine), dicarboxylic acid in serum, blood lactic acid in some children, increased pyruvate, decreased activity of mitochondrial enzyme complex.

4. Cerebrospinal fluid examination showed more pressure on cerebrospinal fluid. Most routine examination of cerebrospinal fluid was normal. The number of cells and protein were normal. If there was no hypoglycemia, the amount of sugar was normal. The glycemic content of hypoglycemia was correspondingly reduced. The lactic acid and pyruvate levels of cerebrospinal fluid in some children were decreased. Increased, the activity of the mitochondrial enzyme complex is reduced.

5. Liver biopsy can reveal typical RS liver changes.

6. EEG examination is normal early, abnormal after 2 years old, EEG is diffuse encephalopathy, see slow wave increase, irregular electrical activity, etc., can also have epileptiform discharge (spin wave), sleep spindle The wave disappears, the background wave is widely and slowly, and the degree of EEG changes is not completely consistent with the clinical manifestations.

7. Brain CT, MRI examination should be done brain CT examination, can be found cerebral edema, midline shift and other changes, showing frontal atrophy, corpus callosum dysplasia, brain stem narrowing, ventricle enlargement.

Diagnosis and identification of children's syndrome

diagnosis

According to the clinical characteristics combined with the relevant examinations and tests can make a diagnosis, because the clinical symptoms of the brain first, the liver enlargement is not obvious, generally no jaundice, it is easy to ignore.

1. Anyone who meets the following conditions can make a diagnosis

(1) Age is under 16 years old, especially infants and young children.

(2) History of a precursor infection or history of taking salicylate before the illness.

(3) Sudden onset, symptoms of cerebral edema and increased intracranial pressure, but no signs of the nervous system, cerebrospinal fluid examination, except for increased pressure, other normal.

(4) Blood ammonia exceeds the normal value by 1.5 times, serum transaminase exceeds the normal value by 3 times, blood sugar is lowered, prothrombin time is prolonged, and serum bilirubin is not high.

(5) Liver biopsy is of great significance for clinical diagnosis.

Partin's 2300 liver biopsy experience in 15 years is the only specific diagnostic marker for this disease, mainly including smooth endoplasmic reticulum proliferation, glycogen loss, peroxisome proliferative and hepatocyte mitochondrial changes. It is still not clear that the disease has been diagnosed by electron microscopy. Even if a liver biopsy is performed, it is still difficult to have a pathologist who is familiar with the electron microscopy technique.

2. Diagnostic Criteria Developed by the CDC The most commonly used standard in clinical practice is the diagnostic criteria established by the Centers for Disease Control and Prevention (CDC), which mainly include:

(1) Clinically diagnosed RS (CRS):

1 acute non-inflammatory encephalopathy: disturbance of consciousness, cerebrospinal fluid examination except for increased pressure, the rest are normal, except for central nervous system infection or histology confirmed.

2 laboratory examination: transient liver dysfunction, that is, transaminase, blood ammonia or prothrombin measurement normal value × 3, but should be seized at the time of the attack, or return to normal 2 to 7 days after the onset; blood Increased ammonia, acute fatty liver, may be associated with blood lactic acid, increased pyruvate, decreased prothrombin, increased CK, infants often have hypoglycemia.

3 Except other diseases: except for other similar diseases, such as acute poisoning, inherited metabolic diseases, acute severe hepatitis.

RS (CRS) called clinical diagnosis if liver biopsy or autopsy is not performed in accordance with the above clinical diagnostic criteria.

(2) Confirmed RS (DRS): If the liver biopsy or autopsy meets the RS diagnostic criteria, it is called a confirmed RS (DRS).

(3) Excluding some diseases: The symptoms of RS can occur in many diseases similar to RS, so it is necessary to identify a number of diseases, such as acute central nervous system infection, toxic encephalopathy, and genetic metabolic diseases.

Because the above-mentioned RS diagnostic criteria are non-specific, even the light microscopy is not specific for "acute fatty liver", so liver biopsy should be performed as much as possible, and changes in hepatocyte mitochondria should be observed under electron microscope to confirm the diagnosis. Liver biopsy It should be carried out within 4 to 5 days after the onset of the disease. The autopsy specimens are not suitable for mitochondrial morphology or related metabolic tests.

3. 1988 International Reye Syndrome Diagnostic Criteria The 1988 International Reye Syndrome Diagnostic Criteria Development Group proposed new diagnostic criteria, with 9 required standards, 8 supporting standards, and 7 exclusion criteria, as follows:

(1) Required standards:

1 Normal before birth and perinatal period.

2 6 months after birth (can be up to 18 months) mental exercise is normal.

3 The head circumference is normal at birth.

45 months to 4 years old, head growth slowed down.

From 56 months to 30 months, the skills of the purposeful hand that have been acquired are lost, and the ability of social interaction is declining.

6 The ability to express and understand language is severely impaired, and severe mental retardation develops.

Stereotypes of 7 hands, such as twisting hands, picking up hands, clapping, tapping, biting, washing hands, etc., appear after the purposeful hand movement disappears.

At 81 to 4 years old, there is an ataxia gait and physical disability.

9 until 2 to 5 years old, can make a tentative diagnosis.

(2) Supporting standards:

1 abnormal breathing, awake time to stop apnea, intermittently hyperventilation; breath holding, gaze; forced spit saliva, insufflation.

2 abnormal EEG, slow background wave or paroxysmal slow rhythm; epileptiform discharge with or without clinical seizures.

3 horror.

4 muscle contracture, associated with muscle disuse and dystonia.

5 peripheral vascular movement is abnormal.

6 scoliosis.

7 growth retardation.

8 atrophic small feet.

(3) Exclusion criteria:

1 intrauterine growth retardation.

2 increased internal organs or other signs of accumulated disease.

3 retinopathy or optic atrophy.

4 small head at birth.

5 perinatal acquired brain injury.

6 There is a metabolic disease or other progressive neuropathy.

7 serious infection or sequelae of head trauma.

Differential diagnosis

The disease has different clinical manifestations at different stages, especially in the early stage of the disease, with fewer signs and atypical symptoms. The disease is similar to other diseases due to severe secondary contracture, which is easy to cause misdiagnosis. The disease must be associated with purulent meninges. Inflammation, viral meningoencephalitis, toxic encephalopathy, encephalopathy after infectious disease or vaccination, intracranial tumor, no jaundice-type hepatitis differentiation, in addition, lack of vitamin B1 in infants (brain type); infectious mononuclear Cytomegaly, the lack of certain enzymes in the body and the lack of systemic carnitine, the most differential diagnosis is "baby fever".

1. Identification of autism is easy to mix with autism, the main points of identification of the two diseases.

2. The main difference between the central nervous system infection and the central nervous system infection (viral encephalitis, purulent meningitis) is that the cerebrospinal fluid has inflammatory changes.

3. The main difference between the identification of brain symptoms of viral hepatitis is that the brain symptoms of viral hepatitis have jaundice and persistent liver damage.

4. Acute toxic encephalopathy The so-called "acute toxic encephalopathy" is a group of syndromes whose diagnostic criteria are not very clear. The commonality with Reye's syndrome is often related to systemic infections. The clinical manifestations are also convulsions and disturbances of consciousness. Symptoms of increased intracranial pressure, pathology also have cerebral edema, no inflammation, the difference is that there is no mitochondrial lesions, without visceral steatosis, such as timely treatment, the general condition is lighter than Reye's syndrome.

5. Differentiation from Leigh's disease and brain-type infant beriberi is also required to distinguish from Leigh's disease and brain-type infant beriberi, both of which have the characteristics of Reye syndrome.

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