Two rare cases of myelin oligodendrocyte glycoprotein antibody-associated disorder in children with leukodystrophy-like imaging findings.

BACKGROUND: Children with acquired demyelinating syndromes (ADS) whose sera are positive for myelin oligodendrocyte glycoprotein (MOG) immunoglobulin (IgG) can be diagnosed with MOG-IgG associated disorder (MOGAD). Cases with leukodystrophy-like imaging findings with recurrent MOGAD have rarely been reported. CASE PRESENTATION: Two children with MOGAD, whose onset age was 6 months and 3 years, respectively, were admitted to the hospital due to fever and altered consciousness. In both children, MOG-IgG was detected in the serum using live cell-based assay. Brain magnetic resonance imaging (MRI) revealed leukodystrophy-like lesions with diffuse bilateral white matter. Cerebrospinal fluid (CSF) analysis showed mild pleocytosis with normal or slightly increased protein levels and no oligoclonal bands. Metabolic and inflammatory blood/CSF markers were all negative. Full exon gene testing revealed normal results, and nuclear and mitochondrial DNA were normal. Despite regular immunotherapy and reduction of lesions based on brain MRI results, the patients repeatedly relapsed and had residual neurological dysfunction at 3-4 years of follow-up. CONCLUSIONS: Although MOGAD is a monophasic and benign condition, certain MOGAD patients can experience multiple relapses and residual neurologic deficits. The spectrum of clinical manifestations in MOGAD is wider in children than in previously reported cases, including cases with leukodystrophy-like imaging findings. Such imaging findings along with MOG-IgG may occur recurrently and result in severe neurological prognosis. Patients with extensive and confluent white matter lesions should undergo early testing of MOG-IgG to ensure early therapy. In refractory cases, MOGAD treatment may need to be escalated beyond the current therapy, which means second-line immunotherapy should be performed as early as possible and hormone levels should not be rapidly reduced. Early diagnosis and appropriate treatment may improve the prognosis of children with MOGAD.

Whole exome sequencing facilitated the diagnosis in four Chinese pediatric cases of Joubert syndrome related disorders.

OBJECTIVES: Joubert syndrome is a spectrum of rare genetic disorders, mainly characterized by a distinctive cerebellar and brain stem malformation called the "molar tooth sign" (MTS), hypotonia, and intellectual disability/developmental delay. METHODS: In this study, 4 pediatric cases with developmental delay and oculomotor abnormities were recruited, and submitted to a clinical evaluation and magnetic resonance imaging (MRI) examination. Afterwards, genetic detection with whole exome sequencing (WES) was conducted on the 4 patients. RESULTS: Imaging results demonstrated cerebellar dysplasia in all probands, yet the MTS findings varied in severity. WES detected diagnostic variations in all four probands, which were distributed in four genes, namely CC2D2A, NPHP1, AHI1, and C5orf42. Two variants were novelly identified, which were the CC2D2A: c.2444delC (p.P815fs*2) and the AIH1: exon (15-17) del. In silico analysis supported the pathogenicity of the variations in this study. CONCLUSIONS: Our findings expanded the mutation spectrum of Joubert syndrome related disorders, and provided solid evidence to the affected families for further genetic counseling and pregnancy guidance.

Compound Heterozygous Variants in a Surviving Patient With Alkuraya-Kucinskas Syndrome: A New Case Report and a Review of the Literature.

Background: Alkuraya-Kucinskas syndrome is an autosomal recessive disorder characterized by brain abnormalities associated with cerebral parenchymal underdevelopment, arthrogryposis, club foot, and global developmental delay. Most reported cases were cases of premature termination of pregnancies or neonatal deaths. To date, limited studies of nine surviving patients with global developmental delay and intellectual disability have been reported. In this study, we report another surviving patient. Methods: Whole-exome sequencing was utilized for the proband, and variants were filtered, annotated, and classified. Candidate variants were validated by Sanger sequencing of the proband and his family. The literature was reviewed; the prognosis among different regions and the variant type was analyzed. Results: A non-synonymous variant [NM_015312.3: exon29: c.4892C>G (p.Pro1631Arg)] was identified and validated in the patient's father. A frameshift duplication [NM_015312.3: exon62: c.10872dupA (p.Arg3625Lysfs*5)] that caused early translation termination was identified in his mother. The literature was reviewed, variants were classified into three regions of KIAA1109, and their survival status was summarized. Conclusion: We reported another survival proband with Alkuraya-Kucinskas syndrome driven by KIAA1109. Our case expands the genotypic spectrum of Alkuraya-Kucinskas syndrome and explored the relationship between the variant region and survival.

Clinical analysis of myelin oligodendrocyte glycoprotein antibody-associated demyelination in children: A single-center cohort study in China.

BACKGROUND AND PURPOSE: Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are detected at a high rate in childhood of acquired demyelinating syndrome (ADS), but the spectrum and characteristics of MOG-Abs-associated disorders (MOGAD) in children are to be determined. This study aimed to identify clinical features in Chinese children with MOGAD. METHODS: Of 48 children in whom MOGAD were diagnosed in our hospital, we analyzed the manifestations, laboratory test results, imaging characteristics, autoimmune antibodies in cerebrospinal fluid and serum, and response to treatment. We used a cell transfection immunofluorescence assay to test for MOG-Abs in serum. RESULTS: Of the 48 children, the most common phenotypes were acute disseminated encephalomyelitis (ADEM) (20/48, 41.7%) and optic neuritis (ON) (13/48, 27.1%). The onset ages of ON were significantly higher than those of ADEM (8.68±2.86 & 4.80±2.77, P<0.01). Cerebral lesions manifested as ADEM-like, leukodystrophy-like and other patterns. All children received first-line immunomodulatory therapy and some of them received second-line drugs, whose acute clinical symptoms were alleviated to some extent. 34 patients (34/48,70.8%) experienced one episode, the main phenotypes were ADEM (19/34,55.9%) and encephalitis (9/34,26.5%), and 14 children (14/48,29.2%) had two or more episodes, the primary expressions were ADEM-ON (8/14,57.1%) and recurrent ON (3/14,21.4%). During our follow-up, 8 patients suffered relapsed, but the MOG-Ab titers were not increase during acute stages. 4 patients (4/9,44.4%) of ADEM with ON were developed cognitive impairment, epilepsy and other sequelae, and 2 patients (2/3, 66.7%) of repeated ON suffered visual impairment. CONCLUSION: The clinical phenotypes of MOGAD are age-dependent, the onset ages of ADEM are significantly younger than those of the ON children, and leukodystrophy-like pattern could occur in infancy. Cerebral lesions of MRI were extensive and various, manifested as ADEM-like, leukodystrophy-like, ON and other patterns. The titers of MOG-Ab should not be used as the only basis for recurrence and long-term immunoregulatory treatment. Most children had a good prognosis, however, the phenotype of ADEM-ON at onset was tend to relapse, sometimes with cognitive impairment, epilepsy, and other sequelae. Repeated ON could cause visual impairment.

Succinic anhydride-based chemical modification making laccase@Cu3(PO4)2 hybrid nanoflowers robust in removing bisphenol A in wastewater.

To prepare a robust biocatalyst and enhance the removal of bisphenol A in wastewater, succinic anhydride was reacted with laccase to obtain succinic anhydride-modified laccase (SA-laccase) and then co-crystallized with Cu3(PO4)2 to form SA-laccase@Cu3(PO4)2 hybrid nanoflowers (hNFs). The activity of SA-laccase@Cu3(PO4)2 reached 5.27 U/mg, 1.86-, 2.88- and 2.15-fold those of bare laccase@Cu3(PO4)2, laccase@Ca3(PO4)2 and laccase@epoxy resin, respectively. Compared with free laccase, the obtained hNFs present enhanced activity and tolerance to pH and high temperature in the removal of BPA. Under the optimum conditions of pH 6.0 and 35 °C, BPA removal reached 93.2% using SA-laccase@Cu3(PO4)2 hNFs, which was 1.21-fold of that using free laccase. In addition, the obtained SA-laccase@Cu3(PO4)2 hNFs retained nearly 90% of their initial catalytic activity for BPA removal after 8 consecutive batch cycles. This efficient method for preparing immobilized laccase can also be further developed and improved to acquire green biocatalysts for removing persistent organic pollutants in wastewater.

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR-135a-5p to prevent the progression of epilepsy.

Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR-135a-5p, as well as those between miR-135a-5p and 3' untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual-luciferase reporter gene assay. The expression of miR-135a-5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR-135a-5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv-shGAS5 and Lv-miR-135a-5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR-135a-5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR-135a-5p. After the treatment of Lv-shGAS5 and Lv-miR-135a-5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR-135a-5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.

High quantum yield ZnO quantum dots synthesizing via an ultrasonication microreactor method.

Green emission ZnO quantum dots were synthesized by an ultrasonic microreactor. Ultrasonic radiation brought bubbles through ultrasonic cavitation. These bubbles built microreactor inside the microreactor. The photoluminescence properties of ZnO quantum dots synthesized with different flow rate, ultrasonic power and temperature were discussed. Flow rate, ultrasonic power and temperature would influence the type and quantity of defects in ZnO quantum dots. The sizes of ZnO quantum dots would be controlled by those conditions as well. Flow rate affected the reaction time. With the increasing of flow rate, the sizes of ZnO quantum dots decreased and the quantum yields first increased then decreased. Ultrasonic power changed the ultrasonic cavitation intensity, which affected the reaction energy and the separation of the solution. With the increasing of ultrasonic power, sizes of ZnO quantum dots first decreased then increased, while the quantum yields kept increasing. The effect of ultrasonic temperature on the photoluminescence properties of ZnO quantum dots was influenced by the flow rate. Different flow rate related to opposite changing trend. Moreover, the quantum yields of ZnO QDs synthesized by ultrasonic microreactor could reach 64.7%, which is higher than those synthesized only under ultrasonic radiation or only by microreactor.

[Changes of body weight and galanin in epileptic children treated with topiramate].

OBJECTIVE: Topiramate is a new broad-spectrum anti-epileptic drug. Decreased body weight and appetite are common side effects of topiramate. The side effect affects the growth and development in children greatly. Little is known about the mechanisms of topiramate-induced weight loss and decreased appetite in children with epilepsy in China and abroad. galanin is one of factors that affect appetite. It is a neuroendocrine peptide and play an important role in the control of appetite and body weight in the mechanism of hormone release. The purpose of this study was to explore the mechanism of topiramate-induced weight loss in children with epilepsy and the relation of weight loss with change of galanin, thereby to provide evidences for improvement of quality of life, compliance to treatment and reduce side effects of growth and development in children with epilepsy. METHODS: Totally 61 patients with especial epilepsy were enrolled into this study and the disease was defined by clinical manifestations and electroencephalography (EEG). Among them 32 cases had generalized seizures and 29 had local seizures. Sixteen normal children were enrolled as control group. The patients' age ranged from 0.5 to 14 (4.76 +/- 4.05) years and the patients were instructed to take 0.5 - 1 mg/kg of topiramate per day, with 0.5 - 1 mg/kg every 3 - 5 d increased to maximum of 3 - 8 mg/kg per day. Patients continued receiving the doses for 4 months. All patients' serum galanin levels and body height and weight and hepatic function were detected before and after antiepileptic drugs treatment. The galanin was detected by using radioimmunoassay. RESULTS: After treatment with topiramate (61 cases) for 4 months, plasma galanin [(22.01 +/- 8.12) pg/ml] declined as compared with baseline [(26.56 +/- 9.35) pg/ml, t = 2.85, P < 0.01] in children with epilepsy. Twenty-two of 61 patients lost weight, their plasma galanin concentration was significantly lower [(26.51 +/- 10.00) pg/ml vs. (20.45 +/- 8.09) pg/ml, t = 2.91, P < 0.01], but there was no significant change in the weight-gained patients (39/61) and control group (n = 16). In children with epilepsy, the mean value of body weight decreased as compared with the pre-treatment values, but the difference was not significant; however, the body-mass index (BMI) was significantly lower than that obtained before treatment (t = 8.628, P < 0.01). Eighteen of 22 patients who lost weight had decreased appetite, but only five of 39 patients who gained weight showed decreased appetite (chi(2) = 28.50, P < 0.001). The mean value of plasma galanin declined after treatment in patients (23 cases) with decreased appetite [(18.35 +/- 7.80) pg/ml vs. (27.28 +/- 6.90) pg/ml, t = 4.84, P < 0.001]; while plasma galanin did not change significantly after treatment in patients (38 cases) without decreased appetite [(24.23 +/- 7.66) pg/ml vs. (26.12 +/- 5.49) pg/ml, t = 1.04, P > 0.05]. CONCLUSION: Topiramate treatment may lower the body weight and reduce appetite in part of children with epilepsy which may be mediated by the reduced plasma galanin level.