Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy / 中华儿科杂志

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

Clinical features of 6 children with uridine-responsive developmental epileptic encephalopathy 50 caused by CAD gene variants / 中华儿科杂志

Objective: To analyze the clinical features of children with uridine responsive developmental epileptic encephalopathy 50 (DEE50) caused by CAD gene variants. Methods: A retrospective study was conducted on 6 patients diagnosed with uridine-responsive DEE50 caused by CAD gene variants at Beijing Children's Hospital and Peking University First Hospital from 2018 to 2022. The epileptic seizures, anemia, peripheral blood smear, cranial magnetic resonance imaging (MRI), visual evoked potential (VEP), genotype features and the therapeutic effect of uridine were descriptively analyzed. Results: A total of 6 patients, including 3 boys and 3 girls, aged 3.5(3.2,5.8) years, were enrolled in this study. All patients presented with refractory epilepsy, anemia with anisopoikilocytosis and global developmental delay with regression. The age of epilepsy onset was 8.5 (7.5, 11.0) months, and focal seizures were the most common seizure type (6 cases). Anemia ranged from mild to severe. Four patients had peripheral blood smears prior to uridine administration, showing erythrocytes of variable size and abnormal morphology, and normalized at 6 (2, 8) months after uridine supplementation. Two patients suffered from strabismus, 3 patients had VEP examinations, indicating of suspicious optic nerve involvement, and normal fundus examinations. VEP was re-examined at 1 and 3 months after uridine supplementation, suggesting significant improvement or normalization. Cranial MRI were performed at 5 patients, demonstrating cerebral and cerebellar atrophy. They had cranial MRI re-examined after uridine treatment with a duration of 1.1 (1.0, 1.8) years, indicating significant improvement in brain atrophy. All patients received uridine orally at a dose of 100 mg/(kg·d), the age at initiation of uridine treatment was 1.0 (0.8, 2.5) years, and the duration of treatment was 2.4 (2.2, 3.0) years. Immediate cession of seizures was observed within days to a week after uridine supplementation. Four patients received uridine monotherapy and were seizure free for 7 months, 2.4 years, 2.4 years and 3.0 years respectively. One patient achieved seizure free for 3.0 years after uridine supplementation and had discontinued uridine for 1.5 years. Two patients were supplemented with uridine combined with 1 to 2 anti-seizure medications and had a reduced seizure frequency of 1 to 3 times per year, and they had achieved seizure free for 8 months and 1.4 years respectively. Conclusions: The clinical manifestations of DEE50 caused by CAD gene variants present a triad of refractory epilepsy, anemia with anisopoikilocytosis, and psychomotor retardation with regression, accompanied by suspected optic nerve involvement, all of which respond to uridine treatment. Prompt diagnosis and immediate uridine supplementation could lead to significant clinical improvement.

Analysis of clinical and genetic characteristics of epilepsy associated with chromosome 16p11.2 microdeletion / 中华儿科杂志

Objective: To investigate the clinical and genetic characteristics of epilepsy associated with chromosome 16p11.2 microdeletion. Methods: The patients (n=10) with 16p11.2 microdeletion found in children with epilepsy treated in Beijing Children's Hospital Affiliated to Capital Medical University from January 2018 to January 2021 were collected. The clinical manifestations, gene variations and prognosis were analyzed retrospectively. Results: A total of 10 children's data were collected, including 5 male and 5 female. The onset age of epilepsy was 4.5 (4.1,5.0) months. Regarding the seizure types, 7 cases had focal seizures with secondary generalization, 2 cases had generalized seizures, and 1 case had tonic seizures and spasms. Nine cases had cluster seizure attacks and 3 cases had status epilepticus. Seven cases had focal or multifocal epileptiform discharges in interictal electroencephalogram (EEG), 3 cases had borderline or normal EEG. Brain magnetic resonance imaging showed polymicrogyria in 1 case, paraventricular leukomalacia in 1 case, delayed myelination of white matter in 3 cases, and no obvious abnormalities in the other 5 cases. The patients were followed up for 0.5-3.5 years, with 1-3 kinds of antiepileptic drugs taken orally. The case with polymicrogyria still had seizures, however the other 9 cases had seizures controlled. The age of the last seizure attack was 8 (6, 12) months. There were 6 cases with mental and motor developmental delay before epilepsy onset. During the follow-up, 7 cases were retarded to varying degrees, while 3 cases had normal development. Regarding the genetic detection methods, 7 cases underwent whole exome sequencing, 2 cases underwent whole genome copy number variation detection, and 1 case underwent whole genome sequencing. The length of the 16p11.2 deletion in 10 cases ranged from 525 to 951 kb, and all contained the PRRT2 gene intact. Six cases were de novo variants, 1 case was inherited from the mother who had a history of convulsions in early childhood, and the source of variant was not verified in 3 cases, none of whose parents had relevant phenotype. Conclusions: The epilepsy associated with 16p11.2 microdeletion is mainly induced by the heterozygous deletion of PRRT2 gene in this region, however the phenotype is usually severe, and often combined with developmental and epileptic encephalopathy. Detection of copy number variation should be emphasized in children whose etiology is considered genetic but second-generation sequencing result is negative.

Nucleophosmin modulates the alleviation of atopic dermatitis caused by the marine-derived compound dihydroaustrasulfone alcohol

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.

Survey of Rh Blood Type Phenotypes in Unpaid Blood Donors in Tongchuan Area of Shaanxi Province / 现代检验医学杂志

Objective To investigate the distribution of Rh blood type phenotype in unpaid blood donors in Tongchuan area and establish a Rh blood type phenotype database to provide a strong guarantee for clinical safe blood transfusion.Methods The Rh blood group antigens of 3 419 cases of blood donors samples were detected by the method of card column weak gel in the Tongchuan Blood Center from June 2015 to March 2017,and identification of RhD negative specimens were confirmed fordetermining the phenotype of its Rh blood group with indrect antiglobulin test.The cassification statistics were carried out and filed with computer.Rh distribution with other parts of the domestic distribution of blood type was compared using t test.Results The negative rate of RhD in 3 419 unrelated donors was 0.55％.The positive rates of other antigens in Rh were 99.45％,90.41％ in C,55.10％ in E,45.51％ in E and 92.19％ in E,respectively.D:0.921,C:0.673 7,c:0.320 7,E:0.275 5 and e:0.730 6.The distribution of Rh phenotype was:CCDee＞ CcDEe＞ CcDee＞ ccDEE＞ ccDEe＞ CcDEE＞ ccDee ＞ RhD negative.Statistical analysis showed that there was significant difference between the composition ratio of CCDee and ccDEE in Tongchuan and that in Nanning and Qiannan (x2 =21.552,P=0.016;x2=18.519,P=0.001).There was no significant difference between Shenyang,Xingtai and Tianjin Binhai (x2 =0.227～1.31,all P＞0.05).Conclusion The distribution of Rh phenotype in Tongchuan area has the characteristics of northern region[1～4].The RhD negative rate is in line with the distribution characteristics of Chinese Han population.Rh and Rh genotypes differ in southern and northern China,Phenotypic distribution of the investigation for the safety of blood transfusion is of great significance.

Follow-up study on the clinical characteristics and treatment effect of the different types of Guillain-Barré syndrome in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics and effects of immunoglobulin treatment in children with the different types of Guillain-Barré syndrome (GBS).</p><p><b>METHOD</b>Data of 108 patients hospitalized for GBS were retrospectively analyzed; 75 cases in this group were given acute high dose of gamma globulin (IVIG) 400 mg/(kg·d) intravenously for 5 d. Clinical and electrophysiological data and information on treatment and recovery of the children were collected during the follow-up and were analyzed.</p><p><b>RESULT</b>According to the clinical and electrophysiologic findings, 32 patients manifested acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 34 had acute motor axonal neuropathy (AMAN), 3 had acute motor and sensory axonal neuropathy (AMSAN), 4 were inexcitable, 2 were unclassified. The clinical progress of the AMAN was faster than the AIDP group. Except for sensory nerve involvement, there was no significant difference in the clinical feature and severity. The mean time of the muscle strength began to recover was (5.59±3.63) days in the AIDP group and (7.21±4.68) days in the AMAN group after IVIG treatment. The time of the AIDP group was shorter than the AMAN group, but the difference was not statistically significant (t=-1.5702, P>0.05). The mean time of the muscle strength increased one grade was (8.88±4.39) days in the AIDP group and (12.67±8.35) days in the AMAN group. The difference was statistically significant (t=-2.3689, P<0.05). No patients in this group died. Follow-up data showed that the complete recovery time was not significantly different (t=0.2041, P>0.05).</p><p><b>CONCLUSION</b>The clinical progress of the AMAN was faster than the AIDP group. Besides sensory nerve involvement, there was no significant difference in the clinical feature and severity. The AIDP group's clinical recovery was faster than AMAN's after the immunoglobulin treatment. The two groups were not significantly different in long-term prognosis.</p>

Effects of fluoride on the expression of vascular endothelial growth factor in fibroblast of mice / 中国地方病学杂志

Objective To observe the expression of vascular endothelial growth factor(VEGF) mRNA and protein in fluoride(F~-) treated fibroblast(FB) of mice in planar(2D) and FBs populated collagen lattice(3D) culture systems and to further explore the effects of VEGF on the osteogenic action of FB. Methods FB were divided into 0 (control group), 0.0001,0.0010,0.1000,1.0000,10.0000 and 20.0000 mg/L groups(F~-). The levels of VEGF mRNA and protein at 48 h were measured by using RT-PCR, ELISA and immunohistochemistry (IHC) methods. Results The expression of VEGF mRNA increased obviously in group of 0.1000 mg/L(1.08 ± 0.09) in 3D FB compared with the control group(0.93 ± 0.02, all P < 0.05). Fluoride increased the content of VEGF protein obviously in groups of 0.1000,1.0000,10.0000 mg/L(0.19 ± 0.02, 0.26 ± 0.01 and 0.32 ± 0.01 ), higher than that in 2D FB culture supematant in the control group(0.14 ± 0.01, all P < 0.05) ; and in groups of 0.1000, 1.0000 rag/L(0.59 ± 0.06 and 0.52 ± 0.03) it was higher than that in 3D FB culture supematant in the control group(0.37 ± 0.05, all P< 0.01 ). The IHC results showed that the VEGF positive staining cells increased significantly in group of 0.001 mg/L (0.45 ± 0.05) in 2D FB when it was compared with control group(0.36 ± 0.03, P< 0.05); and in groups of 0.0010, 0.1000, 1.0000 rag/L(0.62 ± 0.04,0.70 ± 0.06 and 0.65 ± 0.07) are it was higher than that in 3D FB control group (0.44 ± 0.04, P < 0.05 or < 0.01 ). Conclusions The higher expression of VEGF mRNA and protein in 2D and 3D FB induced by fluoride may play an important role in stimulating the osteogenesis ability in FB.

Clinical characteristics and diagnosis of neuronal migration disorders / 中华儿科杂志

<p><b>OBJECTIVE</b>Neuronal migration disorders (NMD) are a group of malformations of the brain which ultimately disrupt migrating neuroblasts from the germinal plate to the cerebral cortex, it consists of agyria-pachygyria, polymicrogyria, schizencephaly, hemimegalencephaly and heterotopia. This study aimed to investigate the clinical characteristics and diagnostic methods of NMD.</p><p><b>METHODS</b>The clinical data, cranial imaging and experimental examinations of 37 patients with NMD were analyzed. The patients consisted of 21 males and 16 females whose age of first hospital visit ranged from 2 months to 14 years and 6 months. Among the 37 cases, 18 were followed up.</p><p><b>RESULTS</b>Of the 37 patients, 21 were agyria-pachygyria, the main clinical manifestations were mental retardation (20 cases), epilepsy (14 cases), hemiparesis (6 cases), and 17 patients had microcephaly which was an important physical sign. Eight patients had agyria-pachygyria with other malformations, they presented mental retardation (6 cases), epilepsy (4 cases), and hemiparesis (2 cases). Of the 5 patients with heterotopia, 4 manifested epilepsy. 3 patients had schizencephaly and 2 presented with hemiparesis. EEG was performed in 16 cases. Generalized irregular sharp and slow wave complexes were present in 10 cases, focal spike and slow complex in one case, hypsarrhythmia in one case, and the normal EEG in 4 cases. Eighteen cases were followed-up from seven months to eight years and three months, 14 patients had epilepsy, and still had epileptic attacks with the treatment with anticonvulsives, motor development was improved but speech development delayed in 4 cases.</p><p><b>CONCLUSION</b>The results of this study suggest that NMD is characterized by mental retardation, epilepsy and hemiparesis. Cranial MRI is the best diagnostic method.</p>

Diagnosis of childhood narcolepsy and significance of HLA in its diagnosis / 中华儿科杂志

<p><b>OBJECTIVE</b>Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, and features of rapid eye movement (REM) sleep, such as cataplexy, sleep paralysis and hypnagogic hallucinations. The present study aimed to investigate the diagnostic basis of childhood narcolepsy and possible role of HLA Class II alleles in the onset of this disease.</p><p><b>METHODS</b>The clinical data of 40 narcoleptic children were analyzed. All patients received Multiple Sleep Latency Test (MSLT) and they were analyzed in combination with clinical features. Polymerase chain reaction/sequence specific primers (PCR/SSP) methods were used to detect the HLA-DRB1 and DQB1 alleles.</p><p><b>RESULTS</b>Narcolepsy was diagnosed in 40 children. The age range was 3 to 14 years (mean 8.5 +/- 2.5 years), 29 were male and 11 female. Their mean course of disease was 6.5 months, 14 patients (30%) were less than 3 months old, 21 patients (52%) were less than 6 months old. All the patients had excessive daytime sleepiness, cataplexy appeared in 37 cases, hypnagogic hallucination in 22 and sleep paralysis in 6. Mean sleep latency on MSLT was less than 5 min, the average number of sleep-onset rapid eye movement (SOREM) was 4.33 +/- 0.26 episodes (2-5 episodes), the latency of SOREM episodes were 4.0 +/- 1.8 min (0.25-4.9 min). Thirty-five patients were DRB1 1501 and DQB1 0602 positive (Pc < 0.01), 2 were DRB1 1502 and DQB1 0601 positive, while 3 were DRB1 15 and DQB1 6 negative.</p><p><b>CONCLUSIONS</b>Some pediatric patients with narcolepsy were different from adult patients in that the pediatric cases had a sudden onset and shorter disease course. Diagnosis of this disease was based on the clinical manifestations, MSLT and absence of any medical or psychiatric disorder that could account for the symptoms. The authors demonstrated that DRB1 1501 and DQB1 0602 were susceptibility genes for narcolepsy and those who were DRB1 15 negative could not be excluded.</p>