Phenotypic characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease in children: a single-center, retrospective study.

Objective: To analyze the clinical characteristics and follow-up data of children with different clinical phenotypes of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: The basic demographic and clinical features, laboratory and imaging examination results, and follow-up data of 74 Chinese children with different phenotypes of MOGAD were retrospectively reviewed and analyzed. Results: The male-to-female ratio in this cohort was 1:1.39. The clinical phenotypes of MOGAD included acute disseminated encephalomyelitis (ADEM; n = 37), encephalitis (n = 11), optic neuritis (ON, n = 9), neuromyelitis optica spectrum disorder (NMOSD; n = 9), transverse myelitis (TM; n = 6), leukodystrophy-like manifestations (n = 1), and meningitis (n = 1). The mean age of disease onset was 86 months. The number of leukocytes in the cerebrospinal fluid of patients with ADEM was significantly higher than that in patients with ON but lower than that in patients with TM (p < 0.05). The pathogen detection rate among all patients was 36.5%. Recurrence occurred in 17 patients (23%), with the highest recurrence rate in patients with NMOSD and TM. Patients with recurrence had a significantly higher median age than those without any recurrence (109.00 vs. 82.44 months, p < 0.05). The male-to-female ratio in patients with recurrence was 1:4.67, which differed significantly from that at first onset (p < 0.05). Conclusion: The most common clinical phenotypes of MOGAD in this cohort were ADEM and encephalitis. Recurrence of MOGAD may be related to age and sex, with a higher recurrence rate observed in females. These findings provide a basis for further exploration of the characteristics of different MOGAD phenotypes.

Novel compound heterozygous mutation and phenotype in the tetratricopeptide repeat-like domain of the GEMIN5 gene in two Chinese families.

BACKGROUND: GEMIN5 is an RNA-binding protein that regulates multiple molecular functions, including splicing, localisation, translation, and mRNA stability. GEMIN5 mutations present a syndrome centred on cerebellar dysplasia, including motor dysfunction, developmental delay, cerebellar atrophy, and hypotonia. CASES: We report three patients from two families with novel compound heterozygous mutations in the tetratricopeptide repeat-like domain of the GEMIN5 gene who presented with motor dysfunction, developmental delay, and ataxia syndrome. Novel variants were identified: c.2551_c.2552delCT (Leu851Glufs*30) and c.2911 C > G (Gln971Glu) in Family 1, and c.3287 T > C (Leu1096Pro) and c.2882 G > C (Trp961 Ser) in Family 2, which were inherited from their parents. Moreover, infantile spasms syndrome(ISs) was diagnosed in the family. CONCLUSION: We report the first case of ISs caused by GEMIN5 gene mutations. Our cases expand on GEMIN5 variants and neurological phenotypes, reinforcing the crucial impact of tetratricopeptide repeat-like domain variants in the GEMIN5 gene.

Metagenomic next-generation sequencing and proteomics analysis in pediatric viral encephalitis and meningitis.

Introduction: Early and accurate identification of pathogens is essential for improved outcomes in patients with viral encephalitis (VE) and/or viral meningitis (VM). Methods: In our research, Metagenomic next-generation sequencing (mNGS) which can identify viral pathogens unbiasedly was performed on RNA and DNA to identify potential pathogens in cerebrospinal fluid (CSF) samples from 50 pediatric patients with suspected VEs and/or VMs. Then we performed proteomics analysis on the 14 HEV-positive CSF samples and another 12 CSF samples from health controls (HCs). A supervised partial least squaresdiscriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) model was performed using proteomics data. Results: Ten viruses in 48% patients were identified and the most common pathogen was human enterovirus (HEV) Echo18. 11 proteins overlapping between the top 20 DEPs in terms of P value and FC and the top 20 proteins in PLS-DA VIP lists were acquired. Discussion: Our result showed mNGS has certain advantages on pathogens identification in VE and VM and our research established a foundation to identify diagnosis biomarker candidates of HEV-positive meningitis based on MS-based proteomics analysis, which could also contribute toward investigating the HEV-specific host response patterns.

Case report: Pediatric anti-gamma aminobutyric acid-B receptor encephalitis with benign prognosis.

Objective: To explore the clinical characteristics of pediatric anti-gamma-aminobutyric acid-B receptor (GABABR) encephalitis to enhance the understanding and improve the diagnostic and therapeutic strategies for this disease. Methods: We report a rare case of a female pediatric patient with anti-GABABR encephalitis who was treated at the Children's Hospital of Zhejiang University School of Medicine. Literature search was performed to explore the clinical characteristics of pediatric anti-GABABR encephalitis. Results: The patient exhibited recurrent epileptic seizure, status epilepticus, and psychiatric symptoms at the age of 11 years and 10 months. Anti-GABABR antibodies were positive in cerebrospinal fluid and serum. Brain magnetic resonance imaging (MRI) exhibited abnormal signals in the left hippocampus. Symptoms and abnormality of brain MRI were improved after administration of immunosuppressants, anti-seizure and antipsychotic drugs. Two of pediatric anti-GABABR encephalitis with clinical data were identified through literature search. Analysis of these three cases suggested that the pediatric patients primarily experienced limbic encephalitis, with no tumor incidence. A favorable immunotherapy response was demonstrated with a superior prognosis in all the cases. Conclusions: We reported a pediatric anti-GABABR encephalitis case with early age of onset. Promt autoimmune antibody testing and tumor screening, as well as immunomodulatory treatment immediately after a definitive diagnosis are warranted to improve prognosis.

Hutchinson-Gilford progeria syndrome complicated with stroke: A report of 2 cases and literature review.

Background: Hutchinson-Gilford Progeria Syndrome (HGPS) is a ultrarare, fatal autosomal dominant disorder. The pathogenesis of the disease is a mutation in LMNA, which leads to the accumulation of progerin in cells, impairing the normal physiological functions. Stroke and transient ischemic attack seriously affect the survival rate and quality of life of HGPS children, although the literature of this aspect is limited. This study summarizes the clinical manifestations and related imaging features of HGPS children with stroke to improve pediatric clinicians' understanding of this disease. Case presentation: Both children have a de novo heterozygous mutation of LMNA [c.1824C > T ( p.G608G)]. Case 1. At the age of 4 years, the child had a cerebral infarction, which manifested as blurred vision and communication disturbance. Multiple abnormal signals were observed on the head MRI in the bilateral frontoparietal cortex, bilateral semiovale center, lateral ventricle, and deep frontal and parietal lobes. Multiple abnormal white matter signals on head MRA: bilateral internal carotid artery stenosis with basilar artery, and bilateral thickening of the posterior communicating artery. Case 2. At the age of 8.5 years, the child presented with cerebral infarction, which manifested as decreased muscle strength and choking after drinking water. MRI of the head showed that the bilateral frontal lobes were small with multiple abnormal signal shadows in the bilateral center of the semiovale and the lateral ventricle. Brain MRA revealed that the bilateral internal carotid arteries (C5-7) were narrow and uneven in thickness, and the A1 segment of the left anterior cerebral artery was narrower than the contralateral one. After symptomatic and supportive treatment, the two children improved. Conclusion: Hemiplegia and physical weakness are the most prevalent stroke symptoms in children with HGPS, followed by headache, epilepsy, dysarthria, and psychosis as the primary manifestation in some children. Stroke in children with HGPS is mostly ischemic cerebral infarction caused by an insufficient cerebral blood supply. Pediatric cerebral infarction mainly occurs in the large vascular area, involving all vascular areas, with the internal carotid artery and middle cerebral artery being the most commonly accumulated.

Proteomic profiling of cerebrospinal fluid in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system. METHODS: Extracted proteins from 34 cerebrospinal fluid (CSF) samples [patients with MOGAD (MOG group, n = 12); healthy controls (HC group, n = 12); patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases (IND group, n = 10)] were processed and subjected to label-free quantitative proteomics. Supervised partial least squares-discriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) models were also performed based on proteomics data. Functional analysis of differentially expressed proteins (DEPs) was performed using Gene Ontology, InterPro, and Kyoto Encyclopedia Genes and Genomes. An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD. RESULTS: Four hundred and twenty-nine DEPs (149 upregulated and 280 downregulated proteins) were identified in the MOG group compared to the HC group according to the P value and fold change (FC). Using the O-PLS-DA model, 872 differentially abundant proteins were identified with variable importance projection (VIP) scores > 1. Five proteins (gamma-glutamyl hydrolase, cathepsin F, interalpha-trypsin inhibitor heavy chain 5, latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1) overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired. Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades, cell adhesion, axon guidance, and glycosphingolipid biosynthesis compared to the HC group. CONCLUSION: The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.

Expanding the Phenotypic and Genotypic Spectrum of ARFGEF1-Related Neurodevelopmental Disorder.

Mono-allelic loss-of-function variants in ARFGEF1 have recently caused a developmental delay, intellectual disability, and epilepsy, with varying clinical expressivity. However, given the clinical heterogeneity and low-penetrance mutations of ARFGEF1-related neurodevelopmental disorder, the robustness of the gene-disease association requires additional evidence. In this study, five novel heterozygous ARFGEF1 variants were identified in five unrelated pediatric patients with neurodevelopmental disorders, including one missense change (c.3539T>G), two canonical splice site variants (c.917-1G>T, c.2850+2T>A), and two frameshift (c.2923_c.2924delCT, c.4951delG) mutations resulting in truncation of ARFGEF1. The pathogenic/likely pathogenic variants presented here will be highly beneficial to patients undergoing genetic testing in the future by providing an expanded reference list of disease-causing variants.

A novel SCN9A gene variant identified in a Chinese girl with paroxysmal extreme pain disorder (PEPD): a rare case report.

BACKGROUND: Paroxysmal extreme pain disorder (PEPD) is a rare autosomal dominant hereditary disease, characterized by paroxysmal burning pain in the rectum, eyes or mandible and autonomic nervous symptoms, including skin redness and bradycardia. PEPD is a sodium channel dysfunctional disorder caused by SCN9A gene variants. It occurs mainly in Caucasians and only one case has been reported in the Chinese population. Here, we report the second PEPD case in a Chinese indivisual. CASE PRESENTATION: A 2 years and 6 months old girl initially presented with non-epileptic tonic seizures at 7 days after birth. Her clinical symptoms in order of presentation were non-epileptic tonic seizures, harlequin color change and pain. Genetic analysis showed the patient carried a heterozygous variant c.4384T>A (p.F1462I) in the SCN9A gene, which was speculated to cause PEPD symptoms. After administrating carbamazepine, the symptoms were relieved and the patient's condition improved. However, the patient's mother, who carries the same SCN9A variant as her daughter, only showed bradycardia and sinus arrest but no PEPD-related pain. CONCLUSIONS: This is the second PEPD case reported in the Chinese population. With the discovery of a novel variant in SCN9A, we expanded the genotype spectrum of PEPD. This is the first case suggesting that the clinical presentations of SCN9A-associated PEPD may show inter familial phenotypic diversity. In the future of clinical diagnosis, patients with triggered non-epileptic tonic seizures or pain and harlequin color change should be considered for PEPD and proper and prompt treatment should be given.

Circulating MicroRNAs From Plasma Small Extracellular Vesicles as Potential Diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy.

Pediatric epilepsy is a neurological condition that causes repeated and unprovoked seizures and is more common in 1-5-year-old children. Drug resistance has been indicated as a key challenge in improving the clinical outcomes of patients with pediatric epilepsy. In the present study, we aimed to identify plasma small extracellular vesicles (sEVs) derived microRNAs (miRNAs) from the plasma samples of children for predicting the prognosis in patients with epilepsy and drug-resistant epilepsy. A total of 90 children clinically diagnosed with epilepsy [46 antiepileptic drug (AED)-responsive epilepsy and 44 drug-resistant epilepsy] and 37 healthy controls (HCs) were enrolled in this study. RNA sequencing was performed to identify plasma sEVs derived miRNAs isolated from the children's plasma samples. Differentially expressed plasma sEVs derived miRNAs were identified using bioinformatics tools and were further validated by reverse transcription-polymerase chain reaction and receiver operator characteristic (ROC) curve analysis. In the present study, 6 miRNAs (hsa-miR-125b-5p, hsa-miR-150-3p, hsa-miR-199a-3p, hsa-miR-584-5p hsa-miR-199a-5p, and hsa-miR-342-5p) were selected for further validation. hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-150-5p with area under curve (AUC) values of 0.846, 0.835, and 0.826, respectively, were identified as promising biomarkers of epilepsy. A logistic model combining three miRNAs (hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-199a-3p) could achieve an AUC of 0.883 and a six miRNAs model (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) could attain an AUC of 0.888. The predicted probability of multiple miRNA panels was evaluated for differentiating between drug-resistant children and drug-responsive children. The AUC of a six-miRNA panel (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) reached 0.823. We identified and confirmed plasma sEVs derived miRNA biomarkers that could be considered as potential therapeutic targets for pediatric epilepsy and drug-resistant epilepsy.

Acute Flaccid Myelitis in Children in Zhejiang Province, China.

In July-December 2018, an outbreak of polio-like acute flaccid myelitis (AFM) occurred in Zhejiang province, China. Enterovirus (EV)-D68 infection has been reported to be associated with AFM. This study aimed to investigate the clinical presentation, laboratory findings, and outcomes of AFM patients. We investigated the clinical and virologic information regarding the AFM patients, and real-time PCR, sequencing, and phylogenetic analysis were used to investigate the cause of AFM. Eighteen cases met the definition of AFM, with a median age of 4.05 years (range, 0.9-9 years), and nine (50%) were EV-D68 positive. Symptoms included acute flaccid limb weakness and cranial nerve dysfunction. On magnetic resonance imaging, 11 (61.1%) patients had spinal gray matter abnormalities. Electromyography results of 16 out of 17 patients (94.1%) were abnormal. Cerebrospinal fluid (CSF) pleocytosis was common (94.4%), while CSF protein concentration was normal in all patients. There was little improvement after early aggressive therapy. Phylogenetic analysis revealed that EV-D68 subclade B3 was the predominant lineage circulating in Zhejiang province in 2018.

A child with household transmitted COVID-19.

BACKGROUND: Although people of all ages are susceptible to the novel coronavirus infection, which is presently named "Coronavirus Disease 2019" (COVID-19), there has been relatively few cases reported among children. Therefore, it is necessary to understand the clinical characteristics of COVID-19 in children and the differences from adults. CASE PRESENTATION: We report one pediatric case of COVID-19. A 14-month-old boy was admitted to the hospital with a symptom of fever, and was diagnosed with a mild form of COVID-19. The child's mother and grandmother also tested positive for SARS-CoV-2 RNA. However, the lymphocyte counts were normal. The chest computed tomography (CT) revealed scattered ground glass opacities in the right lower lobe close to the pleura and resorption after the treatment. The patient continued to test positive for SARS-CoV-2 RNA in the nasopharyngeal swabs and stool at 17 days after the disappearance of symptoms. CONCLUSION: The present pediatric case of COVID-19 was acquired through household transmission, and the symptoms were mild. Lymphocyte counts did not significantly decrease. The RNA of SARS-CoV-2 in stool and nasopharyngeal swabs remained positive for an extended period of time after the disappearance of symptoms. This suggests that attention should be given to the potential contagiousness of pediatric COVID-19 cases after clinical recovery.

Insulin-Like Growth Factor-1 Down-Regulates the Phosphorylation of FXYD1 and Rescues Behavioral Deficits in a Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is a neurodevelopmental disease in children that is mainly caused by mutations in the MeCP2 gene, which codes for a transcriptional regulator. The expression of insulin-like growth factor-1 (IGF-1) is reduced in RTT patients and animal models, and IGF-1 treatment is a promising therapeutic strategy for RTT. However, the mechanism underlying the effects of IGF-1 remains to be further explored. FXYD1 is an auxiliary subunit of Na, K-ATPase. Overexpression of FXYD1 is involved in the pathogenesis of RTT. However, whether IGF-1 exerts its effect through normalizing FXYD1 is completely unknown. To this end, we evaluated the effect of IGF-1 on FXYD1 expression and posttranslational modification in a mouse model of RTT (MeCP2308) using both in vitro and in vivo experiments. The results show that FXYD1 mRNA and phosphorylated protein (p-FXYD1) were significantly elevated in the frontal cortex in RTT mice, compared to wild type. In RTT mice, IGF-1 treatment significantly reduced levels of FXYD1 mRNA and p-FXYD1, in parallel with improvements in behavior, motor coordination, and cognitive function. For mechanistic insight into the effect of IGF-1 on p-FXYD1, we found the decreased phosphorylated forms of PI3K-AKT-mTOR signaling pathway components in the frontal cortex of RTT mice and the normalizing effect of IGF-1 on the phosphorylated forms of these components. Interestingly, blocking the PI3K/AKT pathway by PI3K inhibitor could abolish the effect of IGF-1 on p-FXYD1 level, in addition to the effect of IGF-1 on the phosphorylation of other components in the PI3K/AKT pathway. Thus, our study has provided new insights into the mechanism of IGF-1 treatment for RTT, which appears to involve FXYD1.

[A genotyping study of 13 cases of early-onset Charcot-Marie-Tooth disease].

OBJECTIVE: To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT). METHODS: Children with a clinical diagnosis of early-onset CMT were selected for the study. Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed. RESULTS: A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (15%) had novel mutations. The new variant c.394C>G (p.P132A) of the MPZ gene was rated as "possibly pathogenic" and the new variant c.326A>G (p.K109R) of the MFN2 gene was rated as "pathogenic". CONCLUSIONS: Early-onset CMT is mainly caused by PMP22 gene duplication mutation and MPZ gene mutations. The clinical phenotype is mainly CMT type 1, among which Dejerine-Sottas syndrome accounts for a considerable proportion.

The Blood Levels of Trace Elements Are Lower in Children With Tic Disorder: Results From a Retrospective Study.

Background: Tic disorders (TD) are common neuropsychiatric disorders among children and adolescents. It is controversial that trace elements may participate in the pathogenesis of TD. Our study aimed to investigate the trace elements status of zinc (Zn), copper (Cu), iron (Fe), and magnesium (Mg) in children with TD, in comparison to healthy controls. Methods: The medical records of eligible TD children and normal healthy children from January 1 to December 31, 2018 in the outpatient clinic were retrospectively reviewed. The clinical information of all subjects were collected including age, gender, diagnosis, previous health records, and serum trace elements level (Cu, Zn, Fe, Mg) at the time of diagnosis before initiating treatment. Results: In total, 1204 TD children (7.63 ± 2.45 years) and 1,220 healthy children (7.27 ± 3.15 years) who were divided into two gender and three age groups (2-4years, 5-9years, ≥10 years) were reviewed in our study. Our study showed that TD children generally had lower whole blood levels of Zn, Cu, Fe than the normal controls (P < 0.01). No significant difference was observed in whole blood levels of Mg. After adjusting for gender, the trends still remained. Further analysis was performed according to age, the trends still remained in Zn and Fe in all age groups (P < 0.05). However, we observed an almost significantly (P = 0.055) lower level of Cu in TD of 2-4 years group while significant differences in other two groups (P < 0.01). Further multiple linear regression and point biserial correlation showed that the lower blood levels of Zn, Cu, and Fe were correlated with the incidence of TD. Conclusion: The present results indicated that lower blood levels of zinc, iron, copper were associated with TD. Trace elements may be used as an auxiliary treatment for TD and need to be further explored.

Clinical and molecular analysis of epilepsy-related genes in patients with Dravet syndrome.

Dravet syndrome is considered to be one of the most severe types of genetic epilepsy. Mutations in SCN1A gene have been found to be responsible for at least 80% of patients with Dravet syndrome, and 90% of these mutations arise de novo. The variable clinical phenotype is commonly observed among these patients with SCN1A mutations, suggesting that genetic modifiers may influence the phenotypic expression of Dravet syndrome. In the present study, we described the clinical, pathological, and molecular characteristics of 13 Han Chinese pedigrees clinically diagnosed with Dravet syndrome. By targeted-exome sequencing, bioinformatics analysis and Sanger sequencing verification, 11 variants were identified in SCN1A gene among 11 pedigrees including 7 missense mutations, 2 splice site mutations, and 2 frameshift mutations (9 novel variants and 2 reported mutations). Particularly, 2 of these Dravet syndrome patients with SCN1A variants also harbored SCN9A, KCNQ2, or SLC6A8 variants. In addition, 2 subjects were failed to detect any pathogenic mutations in SCN1A and other epilepsy-related genes. These data suggested that SCN1A variants account for about 84.6% of Dravet syndrome in our cohort. This study expanded the mutational spectrum for the SCN1A gene, and also provided clinical and genetic evidence for the hypothesis that genetic modifiers may contribute to the variable manifestation of Dravet syndrome patients with SCN1A mutations. Thus, targeted-exome sequencing will make it possible to detect the interactions of epilepsy-related genes and reveal their modification on the severity of SCN1A mutation-related Dravet syndrome.

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) associated with bacteria meningitis caused by listeria monocytogenes: A case report.

RATIONALE: Mild encephalitis/encephalopathy with a reversible splenial lesion is a clinico-radiological syndrome mainly triggered by viral infection. Bacteria, like listeria monocytogenes, are relatively rare pathogens. PATIENT CONCERNS: A two and a half years old girl with a 3-day history of fever and vomiting, complicated by a sudden seizure. She was in a coma after seizure. DIAGNOSES: Listeria monocytogenes was detected in cerebrospinal fluid cultures. Serum IL-6 remarkably elevated, and hyponatremia appeared on day 2 of hospitalization. Magnetic resonance imaging of the brain performed on day 3 of hospitalization showed right subdural effusion and a lesion in the central portion of the splenium of the corpus callosum. INTERVENTIONS: We administered antimicrobial therapy, intravenous mannitol and hypertonic fluid therapy. OUTCOMES: Her neurological symptoms improved gradually. The lesion in the splenium of the corpus callosum completely disappeared on magnetic resonance imaging on day 10 of hospitalization. LESSONS: We diagnosed this case as mild encephalitis/encephalopathy with a reversible splenial lesion caused by listeria monocytogenes. The patient recovered completely clinically and on imaging, without any specific immunomodulatory treatment. It also indicated IL-6 may play a role in the forms of hyponatremia in mild encephalitis/encephalopathy with a reversible splenial lesion.

Selective preservation of cholinergic MeCP2 rescues specific Rett-syndrome-like phenotypes in MeCP2stop mice.

RTT is a neurodevelopmental disorder characterized by growth regression, motor dysfunction, stereotypic hand movements, and autism features. Typical Rett syndrome (RTT) is predominantly caused by mutations in X-linked MeCP2 gene which encodes methyl-CpG-binding protein 2 (MeCP2). The brain-abundant MeCP2 protein mainly functions as a transcriptional regulator for neurodevelopment-associated genes. Specific functions of MeCP2 in certain neuron types remain to be known. Although cholinergic system is an important modulating system in brain, how MeCP2 in cholinergic neurons contribute to RTT has not been clearly understood. Here we use a mouse model with selectively activated endogenous MeCP2 in cholinergic neurons in otherwise MeCP2stop mice to determine the cholinergic MeCP2 effects on rescuing the RTT-like phenotypes. We found cholinergic MeCP2 preservation could reverse some aspects of the RTT-like phenotypes in mice including hypolocomotion and increased anxiety level, and delay the onset of underweight, instead of improving the hypersocial abnormality and the poor general conditions such as short lifespan, low brain weight, and increasing severity score. Our findings suggest that selective activation of cholinergic MeCP2 is sufficient to reverse the locomotor impairment and increased anxiety-like behaviors at least in early symptomatic stage, supporting future development of RTT therapies associated with cholinergic system.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with Mycoplasma pneumoniae infection.

BACKGROUND: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by transient mild symptoms of encephalopathy and a reversible lesion in the splenium of the corpus callosum on magnetic resonance imaging (MRI). It is often triggered by infection. The common pathogens of MERS are viruses, especially influenza virus. However, Mycoplasma pneumoniae (M.pneumoniae) are relatively rare pathogens for MERS. CASE PRESENTATION: Here we report two paediatric cases of M.pneumoniae infection-induced MERS. The diagnosis of M.pneumoniae infection was established based on polymerase chain reaction (PCR) and specific serum antibodies (IgM). Both of the two patients presented with mild encephalopathy manifestations and recovered completely within a few days. The initial MRI showed a lesion in the central portion of the splenium of the corpus callosum, which completely resolved on the seventh and eighth day after admission for case 1 and case 2. Lumbar puncture was performed in both patients, which revealed no pleocytosis. In case 1, the patient had hyponatremia, peripheral facial nerve paralysis, and rash. To the best of our knowledge, it is the first MERS case associated with peripheral nerve damage. In case 2, interleukin-6(IL-6) was moderately increased in the cerebrospinal fluid (CSF). It suggested that IL-6 may play a role in the pathogenesis of M.pneumoniae-induced MERS. CONCLUSION: Our study enriches the available information on the pathogens of MERS and provides valuable data for better understanding of this syndrome.

[Peroneal myoatrophy type 4H FGD4 new gene mutation in one case and literature review].

OBJECTIVE: To explore the clinical and gene mutation characteristics of children with peroneal myoatrophy FGD4 mutations. METHOD: The clinical data of a patient with peroneal myoatrophy with novel FGD4 gene mutations were collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center for Biotechnology Information and PubMed (up to December 2014) by using search terms"muscular disorders, atrophic""peripheral nervous system diseases""genes". The clinical features and treatment of the patients with FGD4 gene mutations were studied. RESULT: The patient was a 10-years-old boy, he was presented to our clinic due to lower extremity weakness for 3 years, worsening for one year with normal family history and birth history. When he was 6 years old, his feet turned inward as he walked, at 7 years of age, his toes pointed toward the ground, the heel could not touch the ground, the right foot was more serious. During the recent year his symptoms were worsened, manifested as clubfoot, foot drop, arched feet, crane legs, difficult in squatting, walking with swaying gait, easy to fall. He was brought to a number of domestic general hospitals' neurology clinic, he was clearly diagnosed as peroneal myoatrophy, but failed to make typing. Electromyography (EMG) showed neurogenic damage (peripheral neuropathy - motor and sensory fibers are involved). Target gene sequencing showed that the child had FGD4 genes compound heterozygous mutation: c. 338A> G and c. 1730G> A, where the former was inherited from his father, the latter inherited from his mother, it was a new mutation unreported previously. Literature search retrieved six reports (all in English literature) with FGD4 10 cases with mutations, which were expressed as peroneal myoatrophy, but were homozygous mutation. CONCLUSION: This study found the FGD4 4th and the 14th exons' c. 338A> G and c. 1730G> A heterozygous mutations, and this mutations may lead to peroneal myoatrophy.