2015年 · 第53卷第10期

The development of pediatric neurology in China can be traced back to the 1950s. With the support of Professor Zhu Futang, then Director of the Department of Pediatrics of Beijing Medical College, and Professor Qin Zhenting, then Director of the Department of Pediatrics, Dr. Zuo Qihua went to the Soviet Union from 1957 to 1960 to pursue an associate doctorate degree in pediatric neurology. After returning to China, he established the first pediatric neurology professional group in Beijing Medical College in 1961 to carry out clinical and basic research and popularization work. According to the medical research plan put forward by the Ministry of Health in 1978, professors Zuo Qihua, Guo Di, Wang Meixian and other professors joined forces with 14 experts from Beijing, Shanghai, Tianjin, Liaoning, Heilongjiang, Shaanxi, Guangxi Zhuang Autonomous Region, Zhejiang and other places engaged in pediatric neurology, development, health care, psychology and other aspects, and set up the Children's Intelligent Development and Pediatric Epilepsy Collaborative Group in Shanghai from July 4 to 11, 1979. Among them, doctors engaged in pediatric neurology include Zuo Qihua, Wang Meixian, Li Shuchun, Yang Baozhen, Lin Qing, He Guangzu, Wang Tianzhu, Wu Baomin, Ye Qifen, Shui Quanxiang, Liang Yazhen, etc., which started the initial stage of pediatric neurology development and school group construction in China.

Mitochondrial disease is one of the common genetic metabolic diseases in childhood, with an incidence of at least 1/5 000^[1]。 Due to the wide distribution of mitochondria, multiple organ involvement is the clinical feature of this disease, which often involves the brain, skeletal muscle, eyes, ears, digestion, endocrine, cardiovascular, kidney and blood system, etc. Mitochondria are "energy processing factories", which provide more than 90% of ATP for the human body. Tissue with large energy requirements such as brain, skeletal muscle, liver, myocardium and retina have more mitochondria. On the contrary, mitochondria have less mitochondria, resulting in heterogeneity of mitochondria tissue distribution. The genetic pattern of mitochondrial disease is complex, involving maternal inheritance of mitochondrial gene (mtDNA) and Mendelian inheritance of nuclear gene (nDNA). The genetic heterogeneity is strong, which brings great difficulties to genetic diagnosis. The general diagnostic process includes clinical manifestations, biochemical metabolism and imaging examinations, and genetic testing is required when mitochondrial disease is highly suspected. When the genetic test is negative, the clinical evaluation should be re-evaluated, and when mitochondrial disease is still suspected, muscle or skin biopsy, pathological analysis and respiratory chain enzymology tests are required, together with genetic analysis of tissue specimens.

China Birth Defect Prevention and Treatment Report (2012) pointed out that congenital heart disease, polydactyly (toe) and cleft lip (palate) are the top three high-incidence malformations of perinatal infants in China, among which congenital heart disease ranks first. Although the level of diagnosis has improved significantly, the detection rate of prenatal congenital heart disease remains low in areas with relatively backward medical care. Simple cardiac malformations and some critical congenital heart diseases can achieve a better prognosis if active intervention is given in the early postnatal period; However, some complex congenital heart diseases such as left heart dysplasia syndrome still cannot be cured, and the prognosis is poor. Prenatal cardiac malformation screening can prevent the occurrence of severe malformation, reduce the disability rate, and improve the prognosis of some children with congenital heart disease, which has great social significance. The level of diagnosis and treatment of fetal congenital heart disease in China is uneven, and the bearing capacity of children and their families is different, which makes it difficult to carry out single management. At the same time, doctors in different regions and different specialties have different levels of understanding of congenital heart disease. All these problems make the diagnosis and treatment of fetal heart disease in China more complicated than that in western countries. Therefore, the Cardiovascular Group of Pediatrics Branch of Chinese Medical Association, the Expert Committee of Congenital Heart Disease of Pediatrics Branch of Chinese Medical Doctors Association and the Editorial Committee of Chinese Journal of Pediatrics jointly formulated the "Expert Consensus on Diagnosis and Perinatal Management of Fetal Congenital Heart Disease"^[1]。

congenital heart disease (CHD) mainly refers to the disorder of heart and large blood vessels formation in the early stage of embryonic development (8 to 12 weeks of gestation), or the local anatomical structure of the heart and large blood vessels caused by the failure to close the channel that should be closed after birth. The former Ministry of Health "China Birth Defect Prevention and Treatment Report (2012)" pointed out that CHD ranked first among birth defects, accounting for 26.7% of all detected cases (2011), and there were more than 130,000 new children with CHD every year in China^[1]。 The incidence of fetal CHD is higher when intrauterine death, termination of pregnancy, and stillbirth are included. Since 1990s, a large number of clinical epidemiological data have shown that early diagnosis of CHD is beneficial to eugenics and postnatal care, and early intervention can significantly improve the prognosis of neonatal CHD^[2,3]。 It has important clinical value and far-reaching social significance to improve the quality of prenatal diagnosis and give reasonable prenatal consultation and obstetric management to pregnant women. Based on the status of diagnosis and treatment of fetal CHD in China, combined with foreign standards and guidelines in this field, this consensus reached a consensus on the diagnosis methods, prenatal consultation and follow-up, and perinatal management of fetal CHD after discussion by multi-center and multi-disciplinary experts, so as to further standardize the diagnosis and perinatal management of fetal CHD in China.

Epilepsy is one of the common neurological diseases in children. Oral antiepileptic drugs are the main treatment for most children with epilepsy. The principle of drug treatment is to standardize the selection of appropriate drugs according to the type of epileptic seizure and the classification of epileptic syndrome^[1,2]。 The concept of long-term management of childhood epilepsy is to pay attention to the whole process of diagnosis and treatment, among which the initial drug selection is very important, and the efficacy and safety of antiepileptic drugs should be considered in order to improve the long-term treatment retention rate^[3]。 In order to improve the standardized medication level of children's epilepsy in China, the Neurology Group of Pediatrics Branch of Chinese Medical Association took the lead in organizing more than 50 children's epilepsy experts from top three hospitals in 26 provinces, municipalities and autonomous regions across the country to formulate this consensus. Reference to 2010 International Alliance Against Epilepsy (ILAE) revised recommendations for the terminology of the Seizure and Epilepsy Classification Framework^[4]The questionnaire covered 22 common childhood seizure types or epileptic syndromes; It involves 13 antiepileptic drugs (arranged in alphabetical order of Chinese Pinyin) and a few special therapeutic drugs, including vigabatrin (VGB), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), valproate (VPA), carbamazepine (CBZ), lamotrigine (LTG), clonazepam (CZP), topiramate (TPM), nitrazepam (NZP), ethosuximide (ESM), levetiracetam (LEV), zonisamide (ZNS), adrenocorticotropic hormone (ACTH) and prednisone, etc.

Clinical studies have found that about half of newly diagnosed children with epilepsy are seizure-free after treatment with the first antiepileptic drug^[1,2]And it is particularly important for the standardized treatment of newly diagnosed children with epilepsy. In order to improve the standardized medication management level of children's epilepsy in China, the "Expert Consensus on Initial Monotherapy of Newly Diagnosed Children's Epilepsy", led by the Neurology Group of Pediatrics Branch of Chinese Medical Association, summarizes the clinical medication experience of experts in children's epilepsy, and will provide help for the selection of medication for initial monotherapy of common newly diagnosed children's epileptic seizure types and epileptic syndromes in China.

The child, 15 minutes old, was transferred from the delivery room of Liuzhou Maternal and Child Health Hospital to the neonatology department in December 2014 due to "swelling and bruising of the left lower limb for 15 minutes after birth". It was the first birth of the mother, with a gestational age of 40 weeks and vaginal birth, without a history of asphyxia and resuscitation. Immediately after birth, the left lower limb was found to be bruised and swollen, and the left lower abdomen and right instep saw flaky bleeding spots and ecchymosis, which was admitted to the neonatology department. Physical examination at admission: temperature 36.5 ℃, pulse 142 beats/min, breathing 40 beats/min, blood pressure 70/43 mmHg (1 mmHg =0.133 kPa), weight 3.4 kg. The mind is clear, the reaction is good, there are no obvious abnormalities in heart and lung auscultation, the abdomen is soft and not distended, the intestinal sounds are normal, the left lower limb is swollen, bruised, slightly hard, and the color does not fade when pressed, the skin of the toes and soles of the feet is still rosy, and the left lower abdomen and right instep of the foot can be seen with flaky bleeding spots and ecchymates (Figure 1), the movement of the left lower limb was reduced, the movement of the rest of the limbs was OK, and the muscle tone was normal. Blood gas analysis showed no obvious abnormalities in heart, liver, kidney function and electrolyte; Rapid blood sugar normal; Blood routine: white blood cell count 18.69×10⁹/L, platelets 52.0×10⁹/L, neutrophils 0.548, lymphocytes 0.352, red blood cell count 3.81×10¹²/L, hemoglobin 130.0 g/L; C-reactive protein (CRP)<5.0 mg/L. Coagulation function: prothrombin time (PT) 14.3 s, international normalized ratio (INR) 1.15, activated partial prothrombin time (APTT) 53.3 s, thrombin time (TT) 20.3 s, fibrinogen (FIB – C) 1 370 mg/L, D – D mer 15.38 mg/L. Five items of immunity : IgA 0.05 g/L, IgG 10.02 g/L, IgM 0.12 g/L, C3 0.773, C4 0.089 g/L. B-ultrasound of head, liver, gallbladder, spleen, pancreas and kidney showed no obvious abnormalities. B-ultrasound images of femoral vasculature of left lower limb showed no obvious abnormalities. Orthogonal radiographs of both lower limbs (Figure 2): The soft tissue of the left leg is swollen and the layers are blurred. Enhanced magnetic resonance scan of left lower limb 3 d after birth [cross-sectional (T₁Weighted image, T₁WI), sagittal plane T₁WI, coronal plane T₁WI (Figure 3)]: Enhanced scan of left lower limb showed partially irregular T in subcutaneous soft tissue of left lower limb₁, T₂The high signal showed heterogeneous cluster-like sheet-like strengthening, in which T₁Low, T₂The low signal partition showed uneven enhancement, the deep fascia was clear and the continuity was acceptable, and there was no obvious abnormal enhancement in the muscle and bone tissue of the left lower limb. The hemoglobin was 119.0, 139.0 and 106.0 g/L, and the platelet count was 50.0×10, respectively⁹/L, 55.0×10⁹/L and 47.0×10⁹/L. The family refused to complete the biopsy and was discharged automatically on the 4th day after birth.

1999, Lubs et al.^[1]An X-linked family of intellectual disabilities is described, with 5 affected males presenting with intellectual disabilities, dysphagia, gastroesophageal reflux, recurrent respiratory infections, hypotonia and peculiar face: oblique eye cleft, wide eye distance, low nasal bridge and short nose. CT of 2 older children showed cerebral atrophy. Three female carriers had an IQ of less than 80. The syndrome was named Lubs syndrome (LS, OMIM#300260) in 2000. The syndrome has since been confirmed by many reports, and it has been demonstrated that the genetic disease causing the syndrome is due to repeat or triple repeat mutations in the methyl-CpG binding protein 2 (MECP2) gene located on chromosome Xq28^[2,3,4,5]。 In 2010, some scholars named it MECP2 duplication syndrome^[6], because the MECP2 gene is located in the X chromosome long arm 2 region 8 band (Xq28), also known as Xq28 duplication syndrome^[7]。 Methylated CpG-binding protein 2 (MeCP2) was developed in 1992 by Lewis et al.^[8]Purification and identification, it is mainly combined with a single methylated CpG to regulate gene expression, and is a very important gene for brain development. 1999 Amir et al.^[9]MECP2 was found to be the causative gene of Rett syndrome (RS, OMIM#312750). RS is one of the causes of severe intellectual disability in women. The latest research progress of MECP2 duplication syndrome is reviewed.

acute bilirubin encephalopathy (ABE) is a serious complication of hyperunconjugated bilirubinemia. The characteristic clinical manifestations such as convulsion, increased muscle tone, opistonus, cervical resistance, and high and sharp crying are the basis for the diagnosis of ABE. Permanent central nervous system damage can occur in children with ABE, but recent studies have found that bilirubin-mediated nerve damage can still be reversed if aggressive treatment is given, and children with normal neurological development^[1]。 Therefore, the clinical manifestation of any of the above ABE is an indication for transfusion therapy^[2,3]。

"Do you want to be a pediatric neurologist or a pediatric neurologist?" This is a question I keep in mind, and it has played the most important role in my study, work and career. The questioner is my supervisor, Professor Wu Xiru. She has been educating her students and young doctors: an excellent pediatric neurologist must not only have good clinical ability, but also do research, be rigorous, realistic and innovative, so as to understand the disease more deeply, form a virtuous circle, reach a higher level, and thus promote the development of the discipline. Of course, it takes more hard work to become such a person, and Teacher Wu is such a model.

Clinical research in the field of pediatrics is often limited by various realistic conditions, and it is difficult to conduct randomized controlled clinical trials (RCTs). Due to the advantages of less ethical issues involved in real-world research (RWR), wider scope of research objects and good feasibility of research, the voice and demand of real-world clinical research in pediatrics field are increasing in recent years. So how do you conduct a real-world clinical study?