Mediating effects of sleep quality between clinical characteristics and quality of life in children with epilepsy: A cross-sectional study from Southwest China.

BACKGROUND: Although sleep quality (SQ) reportedly affects the health-related quality of life (QOL) of patients with epilepsy, little is known about the potential association between SQ and QOL, particularly in children with epilepsy (CWE). Our study aimed to investigate the mediating effect of SQ on the QOL of CWE to obtain more information for the prevention and treatment of epilepsy in children. METHODS: We collected general demographic and clinical data of 212 CWE and 79 controls (children who visited the Health Examination Department), and their guardians were instructed to answer the Children's Sleep Habits Questionnaire (CSHQ) and the optimized Quality of Life in Childhood Epilepsy Questionnaire-16 (QOLCE-16). The t-test, analysis of variance, chi-square test, and Fisher's exact test were used for between group comparisons. The Pearson correlation was used to analyze the correlation between variables. The direct, indirect, and total effects of predictors on the QOL of CWE were estimated based on an adjusted mediation model. RESULTS: CWE had significantly smaller long-term urban residence rates, less educated guardians, higher total CSHQ score, higher incidence of poor SQ, higher bedtime resistance, more sleep anxiety, worse sleep-disordered breathing, increased parasomnia, more daytime sleepiness, more frequent night waking, and greater sleep onset delay than controls (P < 0.05 for all). The univariable analysis showed significant differences in total CSHQ scores between CWE with different seizure frequency in the last month, whether or not drug-resistant epilepsy (DRE), and with different video electroencephalogram (VEEG) findings (P < 0.05 for all). Differences in QOLCE-16 scores between CWE with different guardian's employment status, age at diagnosis, number of anti-seizure medication (ASM) types, seizure frequency in the last month, DRE status, seizure type, VEEG findings, neuropsychological evaluation findings, magnetic resonance imaging (MRI) findings, and etiology were statistically significant (P < 0.05 for all). The correlation study indicated that the total CSHQ score was negatively correlated with the QOLCE-16 score (P < 0.05). The mediation analysis showed that DRE and VEEG abnormalities had a standardized direct effect on the QOL. Seizure frequency in the last month, DRE, and VEEG abnormalities had an indirect effect on the QOL through SQ, and their mediating effect values of SQ were 31.61 %, 13.45 %, and 14.35 %, respectively. CONCLUSION: Our findings uncovered the relationship of some clinical characteristics with SQ and QOL and characterized the nature of factors affecting the QOL of CWE. SQ could be a key factor in the prognosis of CWE experiencing epileptic seizures, and more attention should be paid on the management of SQ in interventions for epilepsy.

Evaluating the performance of the language model ChatGPT in responding to common questions of people with epilepsy.

OBJECTIVE: People with epilepsy desire to acquire accurate information about epilepsy and actively engage in its management throughout the long journey of living with seizures. ChatGPT is a large language model and we aimed to assess the accuracy and consistency of ChatGPT in responding to the common concerns of people with epilepsy and to evaluate its ability to provide emotional support. METHODS: Questions were collected from the International League against Epilepsy and the China Association against Epilepsy. The responses were independently assessed by two board-certified epileptologists from the China Association against Epilepsy, and a third reviewer resolved disagreements. The reviewers assessed its ability to provide emotional support subjectively. RESULTS: A total of 378 questions related to epilepsy and 5 questions related to emotional support were included. ChatGPT provided "correct and comprehensive" answers to 68.4% of the questions. The model provided reproducible answers for 82.3% questions. The model performed poorly in answering prognostic questions, with only 46.8% of the answers rated as comprehensive. When faced with questions requiring emotional support, the model can generate natural and understandable responses. SIGNIFICANCE: ChatGPT provides accurate and reliable answers to patients with epilepsy and is a valuable source of information. It also provides partial emotional support, potentially assisting those experiencing emotional distress. However, ChatGPT may provide incorrect responses, leading users to inadvertently accept incorrect and potentially dangerous advice. Therefore, the direct use of ChatGPT for medical guidance is not recommended and its primary use at present is in patients education.

Clinical and electroencephalographic characteristics of 34 infant with onset of epileptic spasms before three months of age.

Epileptic spasms (ES) occur mostly between age 3 months and 24 months. ES beginning before 3 months of age were called early-onset ES in previous studies. The aim of this study was to identify clinical and electroencephalographic characteristics of patients with ES onset before 3 months of age. In total, 34 ES patients were retrospectively identified at Children's Hospital of Chongqing Medical University from January 1, 2020 to October 1, 2022. Our patients had diverse etiologies, including genetic (32.3 %), genetic-structural (11.8 %), structural-acquired (11.8 %), structural-congenital (8.8 %), and metabolic (5.9 %), with 29.4 % of patients having unknown etiology. Some patients experienced ES in clusters (either symmetrical or flexional) that occurred most often during awakening after sleep, and a minority of ES were characterized as isolated or asymmetrical, occurred during sleep, and could also manifest as relatively subtle. Approximately 35.3 % of patients also experienced other seizure types concurrently, including 10 focal seizures and 2 generalized seizures, and only half of the focal seizures had structural causes. The other seizure types occurred alone or sequentially with ES. Interictal electroencephalography revealed hypsarrhythmia or its variants, multifocal discharge, or burst suppression. 18 patients had no seizures lasting for more than 2 months, however, at the last follow-up visit, 5 of them had relapsed. All patients had different degrees of psychomotor retardation.

Quantitative muscle ultrasound in children with Duchenne muscular dystrophy: Comparing to magnetic resonance imaging.

OBJECTIVE: There is a need today for favorable biomarkers to follow up on the disease progression and therapeutic response in patients with Duchenne muscular dystrophy (DMD). This study evaluates whether quantitative muscle ultrasound (QMUS) or magnetic resonance imaging (MRI) is more suitable for the assessment of DMD in China. METHODS: Thirty-six boys with DMD, who were treated with prednisone from baseline to month 12, were enrolled in this longitudinal, observational cohort study. Muscle thickness and echo intensity on QMUS and T1-weighted MRI grading were measured in the right rectus femoris. RESULTS: Scores for muscle thickness and echo intensity in QMUS and T1-weighted MRI grading showed significant correlations with the clinical characteristics of muscle strength, timed testing, and quality of life (p < 0.05). Scores for muscle thickness and echo intensity on QMUS also showed good correlations with T1-weighted MRI grading (p < 0.05). However, 15 of 36 boys with DMD did not undergo MRI examinations for various reasons. CONCLUSIONS: QMUS and MRI can be used as biomarkers for tracking DMD to some extent. Both have strengths and weaknesses and the specific needs and goals of the clinical or research project are what make one preferable to the other.

Anti-GFAP Antibody-Associated Hypertrophic Pachymeningitis.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an inflammatory central nervous system (CNS) disorder that usually presents as steroid responsive encephalitis, meningitis, myelitis, or meningoencephalomyelitis. Hypertrophic pachymeningitis (HP) is an uncommon disorder that causes a localized or diffuse thickening of the dura mater. Depending on the etiology, HP can be idiopathic or secondary to a wide variety of other diseases. There are no reports of autoimmune GFAP astrocytopathy presenting as HP. METHODS: In this case report, we describe a rare case of pediatric HP possibly associated with anti-GFAP antibody. RESULTS: A 13-year-old previously healthy girl presented with headache for nearly 8 months with left-sided peripheral facial palsy and left-sided abductor nerve palsy in the second month of course. Magnetic resonance imaging (MRI) of the brain revealed contrast enhancement of hypertrophic dura mater. Anti-GFAPα antibodies were positive in serum and cerebrospinal fluid. The patient improved clinically after steroid treatment with partial resolution of abnormal intracranial MRI lesions. CONCLUSION: The present study suggests that HP may be one of the clinical phenotypes for autoimmune GFAP astrocytopathy or GFAP antibody is a biomarker for HP.

Clinical and electroencephalography characteristics of 41 children with epileptic spasms onset after 1 year of age.

The incidence of epileptic spasms (ES) that begin after the first year of life is much lower than that before 1 year of age. The aim of this study was to identify clinical and electroencephalography (EEG) characteristics, etiologies, treatments, and prognoses in pediatric patients with ES onset after 1 year of age. Forty-one children were retrospectively identified in Children's Hospital of Chongqing Medical University between January 1, 2020 and December 1, 2021. ES onset after 1 year of age have diverse presentations. Although most occur in clusters, are symmetrical and flexional, and occur frequently during awakening, some are characterized as isolated and asymmetrical, have a tonic component, and can also occur during sleep. The hypsarrhythmia variants and focal or multifocal discharges occur alternately in the interictal period, and the focal spikes and slow waves predominated in the unilateral temporal or frontotemporal areas. These patients had diverse etiologies, including structural (51.2 % of patients) and genetic (22.0 %) ones, and 11 patients (26.8 %) had an unknown etiology. No patients in our study had an infectious or immune-mediated etiology. Forty-eight percent of patients responded to hydrocortisone and/or adrenocorticotropic hormone. The efficacy of antiepileptic drug therapy was lower in patients who did not receive concurrent steroid therapy. However, ES onset after 1 year of age caused by a tumor, brain malformation, or other focal lesions, may be cured by focal cortical resection despite a lack of clearly localized EEG surface anomalies. Delays in motor, language, and cognitive development, or behavioral problems were observed in all but three patients.

Prognostic factors for the recurrence of afebrile seizures after benign convulsions associated with mild gastroenteritis.

OBJECTIVE: The overall prognosis of benign convulsions associated with mild gastroenteritis (CwG) is favorable, and the incidence of afebrile seizure recurrence with or without gastroenteritis (ASwGI and ASwoGI, respectively) is low. In this study we investigated the prognostic factors associated with afebrile seizure (AS) relapse after the first CwG episode. METHODS: A hospital-based cohort with an initial CwG episode from January 2012 to October 2019 was followed for at least 19 months. The relapse types were divided into ASwGI and ASwoGI. Logistic regression analysis was performed to identify the independent prognostic factors for the recurrence of AS after the initial CwG episode. Furthermore, the clinical characteristics between ASwGI and ASwoGI were compared. RESULTS: Among the 868 patients enrolled, 67 (7.7%) experienced a second AS and 71% (48/67) showed gastroenteritis-associated recurrence. Except for five patients with subsequent epilepsy (0.6%), only eight (0.9%) experienced three seizure episodes. The independent predictive factors for the subsequent recurrence of AS were age less than 18 months at onset (odds ratio [OR]: 2.93, 95% confidence interval [CI]: 1.53-5.63), repeated seizures over 24 h (OR: 4.09, 95% CI: 2.19-7.65), and absence of fever (OR: 2.33, 95% CI: 1.26-4.33) during the first CwG episode. The probability of recurrence of AS for those with one, two, and three predictive factors was 3.23%, 13.35%, and 22.85%, respectively. In addition, the age at onset was significantly lower in the ASwoGI group than in the ASwGI group during the first episode (p < .05). SIGNIFICANCE: The risk of AS relapse after the initial CwG episode is low, and the majority of patients presented with gastroenteritis. The risk can be predicted by age at onset, repeated seizures over 24 h, and absence of fever during the first CwG episode.

Childhood ischaemic stroke in the basal ganglia can lead to fine motor and anxiety disorders: a retrospective analysis and follow-up of 109 cases.

BACKGROUND: Stroke in children easily causes long-term dysfunction. Whether the prognoses of motor and anxiety disorders are related to the affected stroke area has not been reported. METHODS: One hundred nine cases of children with ischaemic stroke were reviewed and divided into three groups: lenticular nucleus lesions only (lenticular nucleus group), lenticular nucleus and caudate head lesions (caudate head group), and lenticular nucleus and thalamus lesions (thalamus group). Overall prognosis was evaluated by the mRS score. The SCAS-P was used to evaluate anxiety in children aged ≥6 years. RESULTS: mRS scores were ≤ 2 points (mean: 0.62), no significant difference among groups. 3/21 (14.2%) patients in the caudate head group changed handedness, which is significantly higher than other groups. Patients with lesions in thalamus group had significantly higher SCAS-P scores. CONCLUSIONS: The overall prognosis of children with basal ganglia ischaemic stroke is good. However, hand preference changes and anxiety disorders may develop. Patients in the caudate head groups are more likely to suffer from fine motor disorders and changes in handedness. Patients within the thalamus group are more prone to anxiety than patients in the other groups. Anxiety disorders should be noted in children with basal ganglia stroke.

A retrospective study of 92 children with new-onset refractory status epilepticus.

Little is known of the etiology, course, and treatment of new-onset refractory status epilepticus (NORSE) in children. Here we identified etiologies, electroencephalography (EEG) characteristics, and neuroimaging findings among pediatric patients with NORSE and among two patient subgroups, febrile infection-related epilepsy syndrome (FIRES) group and non-FIRES group. We also examined treatments and risk factors related to poor prognosis. Ninety-two children with NORSE were identified in Children's Hospital of Chongqing Medical University between January 1, 2010 and September 1, 2020. The end date was chosen to guarantee at least a 6-month follow-up. Our results indicated that patients with FIRES account for 90% of pediatric patients with NORSE. The clinical, EEG, and neuroimaging results and prognosis were not significantly different between the FIRES group and non-FIRES group of individuals. 68.5% of our patients had unknown etiology, and viral etiology was the most common identified cause (26.1%). Electroencephalography might have a certain diagnostic value for NORSE. A gradual increase in seizure burden was obvious from the onset of disease, and continuous or recurrent ictal discharge lasting ≥ 30 min was quite common in our study. The mortality was 22.8% in our study. Among the 71 surviving patients, the outcome at discharge was poor but improved during follow-up, and 68.5% had good or fair outcomes at their last follow-up. A poor outcome was observed in 39 of 92 cases (42%), with 43.9% and 30% of individuals in the FIRES group and non-FIRES group, respectively, having a poor outcome. The presence of super refractory status epilepticus (SRSE), electrographic seizures and nonconvulsive status epilepticus (NCSE), and diffuse cortical edema and multifocal abnormality may be related to a poor prognosis. Our analysis did not indicate that prognosis was directly related to etiology or treatment. Management of NORSE is challenging, and the role of immunotherapy warrants further investigation.

Natural history of spinal muscular atrophy in children: an analysis of 117 cases. / 117ä¾‹å„¿ç«¥è„Šé«“æ€§è‚ŒèŽç¼©ç—‡è‡ªç„¶ç— å²åˆ†æž.

OBJECTIVES: To study the natural history of spinal muscular atrophy (SMA) in Chongqing and surrounding areas, China, and to provide a clinical basis for comprehensive management and gene modification therapy for SMA. METHODS: A retrospective analysis was performed on the medical data and survival status of 117 children with SMA. RESULTS: Of the 117 children, 62 (53.0%) had type 1 SMA, 45 (38.5%) had type 2 SMA, and 10 (8.5%) had type 3 SMA, with a median age of onset of 2 months, 10 months, and 15 months, respectively. Compared with the children with type 2 SMA or type 3 SMA, the children with type 1 SMA had significantly shorter time to onset, consultation, and confirmed diagnosis (P<0.05) and a significantly shorter diagnostic time window (age from disease onset to consultation) (P<0.05). Pneumonia as the initial symptom, weakness in head control, crying weakness, and eating difficulty were more commonly observed in children with type 1 SMA (P<0.05). Scoliosis and lower limb joint contracture were more common in children with type 2 SMA than in those with type 1 SMA (P<0.05). All 117 SMA children (100%) had homozygous deletion of the SMN1 gene, and the homozygous deletion of exon 7 was the most common type (68.4%, 80/117). The 6-year survival rate of children with type 1 SMA was only 10%±5%, which was significantly lower than that of children with type 2 or 3 SMA (P<0.05). Age of onset ≤3 months, pneumonia as the initial symptom and weakness in head control were the risk factors for death in children with type 1 SMA (P<0.05). The children with type 2 SMA had non-linear regression of motor ability. CONCLUSIONS: There are differences in clinical manifestations and survival rates among children with different types of SMA. The children with type 1 SMA have a low survival rate, and those with type 2 SMA may have non-linear regression of motor ability. Early identification and management of SMA should be performed in clinical practice.

Risk factors for mechanical ventilation in children with Guillain-Barré syndrome.

BACKGROUND: We assessed clinical predictors of mechanical ventilation in children with Guillain-Barré syndrome (GBS) to help identify patients who require mechanical ventilation. METHODS: We retrospectively collected the clinical, laboratory, and electrophysiological data of 103 children with GBS. Patients were categorized into two groups based on the requirement for mechanical ventilation. Variables that were significantly different between the two groups in univariate analysis were analyzed by multivariate logistic regression models. RESULTS: Time from symptom onset to admission (P = .002), facial or bulbar weakness (P = .001), and axonal type (P = .005) were associated with mechanical ventilation in univariate analysis. In multivariate analysis, facial or bulbar weakness (odds ratio [OR], 7.936; P = .013) and axonal type (OR, 4.582; P = .022) were independent predictors for mechanical ventilation. CONCLUSIONS: Facial or bulbar weakness and axonal type were associated with increased risk for mechanical ventilation in children with GBS.

Prednisolone/prednisone as adrenocorticotropic hormone alternative for infantile spasms: a meta-analysis of randomized controlled trials.

AIM: To compare the efficacy and safety of prednisolone/prednisone and adrenocorticotropic hormone (ACTH) in the treatment of infantile spasms using a meta-analysis of randomized controlled trials (RCTs). METHOD: In a systematic literature search of electronic databases (MEDLINE, Embase, the Cochrane Library), we identified RCTs that assessed prednisolone/prednisone compared with ACTH/tetracosactide in patients with infantile spasms. The electroclinical response and adverse events were evaluated. RESULTS: Six RCTs (616 participants) were included in the meta-analysis. Compared with prednisolone/prednisone, ACTH/tetracosactide was not superior in terms of cessation of spasms at day 14 (relative risk 1.19, 95% confidence interval [CI] 0.74-1.92), day 42 (relative risk 1.02, 95% CI 0.63-1.65), and resolution of hypsarrhythmia on electroencephalogram (relative risk 1.14, 95% CI 0.71-1.81); the incidences of common adverse reactions caused by ACTH/tetracosactide were not lower than that of prednisolone/prednisone for irritability (relative risk 0.79, 95% CI 0.57-1.10), increased appetite (relative risk 0.78, 95% CI 0.57-1.08), weight gain (relative risk 0.86, 95% CI 0.56-1.32), and gastrointestinal upset (relative risk 0.60, 95% CI 0.35-1.02), though it seemed less frequent. INTERPRETATION: Prednisolone/prednisone elicits a similar electroclinical response as ACTH for infantile spasms, which indicates that it can be an alternative to ACTH for treating infantile spasms. What this paper adds Prednisolone/prednisone is as effective as adrenocorticotropic hormone (ACTH) in electroclinical response of infantile spasms. Prednisolone/prednisone and ACTH cause similar and tolerable adverse effects, whose incidences are comparable. High-dose prednisone/prednisolone might be preferable to low dose for achieving freedom from spasms.

Prednisolona/prednisona como alternativa a la hormona adrenocorticotrópica para los espasmos infantiles: un metanálisis de ensayos controlados aleatorios OBJETIVO: Comparar la eficacia y seguridad de la prednisolona/prednisona y la hormona adrenocorticotrópica (ACTH) en el tratamiento de los espasmos infantiles mediante un metanálisis de ensayos controlados aleatorios (ECA). MÉTODO: En una búsqueda sistemática en la literatura de bases de datos electrónicas (MEDLINE, Embase, Cochrane Library), identificamos ECA que evaluaban prednisolona/ prednisona en comparación con ACTH/tetracosactida en pacientes con espasmos infantiles. Se evaluaron la respuesta electro clínica y los eventos adversos. RESULTADOS: Seis ECA (616 participantes) se incluyeron en el metanálisis. En comparación con la prednisolona/prednisona, la ACTH/tetracosactida no fue superior en términos de cese de espasmos en el día 14 (riesgo relativo 1,19, intervalo de confianza del 95% [IC] 0,74-1,92), día 42 (riesgo relativo 1,02, IC del 95% 0,63- 1,65), y la resolución de la hipsarritmia en el EEG (riesgo relativo 1,14, IC 95% 0,71-1,81); la incidencia de reacciones adversas comunes causadas por ACTH/tetracosactida no fue inferior a la de prednisolona/prednisona para irritabilidad (riesgo relativo 0,79, IC 95% 0,57-11,10), aumento del apetito (riesgo relativo 0,78, IC 95% 0,57-1,08), aumento de peso (riesgo relativo 0,86; IC del 95%: 0,56-1,32) y malestar gastrointestinal (riesgo relativo 0,60; IC del 95%: 0,35-1,02), aunque parecía menos frecuente. INTERPRETACIÓN: La prednisolona/prednisona provoca una respuesta electro clínica similar a la ACTH para los espasmos infantiles, lo que indica que puede ser una alternativa a la ACTH para el tratamiento de los espasmos infantiles.

Prednisolona/predinisona como hormônio adrenocorticotrópico alternativo para espasmos infantis: uma metanálise de estudos randomizados controlados OBJETIVO: Comparar a eficácia e segurança da prednisolona/ prednisona e hormônio adrenocorticotrópio (HACT) no tratamento de espasmos infantis usando uma metanálise de estudos randomizados controlados (ERCs). MÉTODO: Em uma busca sistemática da literatura em bases de dados eletrônicas (MEDLINE, Embase, Biblioteca Cochrane), identificamos ERCs que avaliaram a prednisolona/ prednisona em comparação com o HACT/ tetracosactídeo em pacientes com espasmos infantis. A resposta eletroclínica e eventos adversos foram avaliados. RESULTADOS: Seis ERCs (616 participantes) foram incluídos na metanálise. Comparado com a prednisolona/ prednisona , o HACT/ tetracosactídeo não foi superior em termos de cessação dos espasmos no dia 14 (risco relativo 1,19, intervalo de confiança [IC] a 95% 0,74-1,92), dia 42 (risco relativo 1,02, IC 95% 0,63-1,65), e resolução da hipsarritimia no EEG (risco relativo 1,14, IC 95% 0,71-1,81); as incidências de reações adversas comuns causadas pelo HACT/ tetracosactídeo não foram menores que as da prednisolona/ prednisona para irritabilidade (risco relativo 0,79, IC 95% 0,57-1010), aumento do apetite (risco relativo 0,78, IC 95% 0,57-1,08), ganho de peso (risco relativo 0,86, IC 95% 0,56-1,32), e mal-estar gastrointestinal (risco relativo 0,60, IC 95% 0,35-1,02), embora parecessem menos frequentes. INTERPRETAÇÃO: A prednisolona/ prednisona /prednisone elicia resposta eletroclínica similar ao HACT para espasmos infantis, o que indica que pode ser uma alternativa ao HACD para tratar espasmos infantis.

Efficacy and safety of levetiracetam in the off-label treatment of neonatal seizures.

Background: Treatment of neonatal seizures includes etiotropic and anticonvulsant treatments. However, anticonvulsant use in neonates is off-label and requires ethical review.Objective: To investigate the efficacy and safety of levetiracetam for neonatal seizures and to establish a predictive model.Methods: We retrospectively analyzed 125 neonatal seizure cases (phenobarbital 66 cases, levetiracetam 59 cases). The efficacy, safety and tolerability of levetiracetam were evaluated by cox regression survival analysis and a regression tree prediction model for the 16-week time point.Results: There was no significant difference between phenobarbital and levetiracetam treatment group in short-term efficacy (p > 0.05). But the cumulative survival function suggested that levetiracetam treatment group was better than phenobarbital (p = 0.026) in long-term efficacy evaluation. Neurodevelopmental assessments at 16 weeks showed that levetiracetam had better effect on the neurodevelopmental level (Gesell scores in response) than phenobarbital (p = 0.011). The main adverse events with levetiracetam were irritability and anorexia. According to the regression tree prediction model, the top three factors influencing the therapeutic effect were pre-treatment seizure frequency, age of onset and etiological classification.Conclusion: Levetiracetam shows good efficacy, safety and tolerability for the long-term neonatal seizure treatment.

Dynamic Changes of Astrocytes and Adenosine Signaling in Rat Hippocampus in Post-status Epilepticus Model of Epileptogenesis.

It is of great importance to explore the development of epileptogenesis, and the adenosine and adenosine kinase (ADK) system seems to play a key role in this process. The aim of this study is to explore the dynamic changes of astrocytes and adenosine signaling during epileptogenesis in rat hippocampus in a post-status epileptogenesis (SE) model. Rat SE models were built and killed for experiments at 1 day (acute phase of epileptogenesis), 5 days (latent phase), 4 weeks (chronic phase), and 8 weeks (late chronic phase of epileptogenesis) after SE induction. Immunofluorescence staining, high-performance liquid chromatography, and Western blotting were performed to assess changes of astrocytes, adenosine, ADK, and ADK receptors (including A1R, A2aR, A2bR, and A3R) in hippocampus. The expression level of glial fibrillary acidic protein significantly increased from latent to late chronic phase. The concentration of adenosine sharply increased in acute phase and gradually decreased in the remaining phases of post-SE, being significantly lower than in the control group in late chronic phase. Protein levels of A1R and A2aR in post-SE models increased in acute phase, whereas A2bR and A3R protein expression decreased in latent phase, chronic phase, and late chronic phase following post-SE epileptogenesis. Protein expression of ADK significantly increased during latent phase, chronic phase, and late chronic phase of post-SE epileptogenesis. In conclusion, the levels of adenosine and protein expression of A1R and A2R significantly increased during acute phase of post-SE. During the remaining phases of post-SE epileptogenesis, there was imbalance among astrocytes, adenosine, adenosine receptors, and ADK. Regulation of the ADK/adenosine system may provide potential treatment strategies for epileptogenesis.

[An interpretation of the expert consensus on standards for the management of patients with primary mitochondrial disease from the Mitochondrial Medicine Society].

Primary mitochondrial disease is the most common inborn error of metabolism and is highly heterogeneous in terms of clinical manifestations and inheritance pattern. It has high mortality and disability rates. Multiple systems are often involved in this disease, and it is necessary to perform comprehensive evaluation and multidisciplinary management. The Mitochondrial Medicine Society issued the standard for the management of patients with primary mitochondrial disease: consensus statements from the Mitochondrial Medicine Society in 2017. The statements provided recommendations based on such consensus to guide the management and care of patients. This article interprets and summarizes the screening of organs and systems commonly involved in primary mitochondrial disease and the management of patients according to the consensus.

New multiplex real-time PCR approach to detect gene mutations for spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is the most common autosomal recessive disease in children, and the diagnosis is complicated and difficult, especially at early stage. Early diagnosis of SMA is able to improve the outcome of SMA patients. In our study, Real-time PCR was developed to measure the gene mutation or deletion of key genes for SMA and to further analyse genotype-phenotype correlation. METHODS: The multiple real-time PCR for detecting the mutations of survival of motor neuron (SMN), apoptosis inhibitory protein (NAIP) and general transcription factor IIH, polypeptide 2 gene (GTF2H2) was established and confirmed by DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). The diagnosis and prognosis of 141 hospitalized children, 100 normal children and further 2000 cases of dry blood spot (DBS) samples were analysed by this multiple real-time PCR. RESULTS: The multiple real-time PCR was established and the accuracy of it to detect the mutations of SMN, NAIP and GTF2H2 was at least 98.8 % comparing with DNA sequencing and MLPA. Among 141 limb movement disorders children, 75 cases were SMA. 71 cases of SMA (94.67 %) were with SMN c.840 mutation, 9 cases (12 %) with NAIP deletion and 3 cases (4 %) with GTF2H2 deletion. The multiple real-time PCR was able to diagnose and predict the prognosis of SMA patients. Simultaneously, the real-time PCR was applied to detect trace DNA from DBS and able to make an early diagnosis of SMA. CONCLUSION: The clinical and molecular characteristics of SMA in Southwest of China were presented. Our work provides a novel way for detecting SMA in children by using real-time PCR and the potential usage in newborn screening for early diagnosis of SMA.

Effect of Sodium Valproate on Cognitive Function and Hippocampus of Rats After Convulsive Status Epilepticus.

BACKGROUND The aim of this study was to explore the effect and possible mechanism of sodium valproate (VPA) on the cognitive function and the hippocampus of rats after convulsive status epilepticus (CES). MATERIAL AND METHODS A rat model of CES was established and the Morris water maze was used to observe changes in the cognitive function of the rats after the administration of VPA. Acute hippocampal slices were made to detect field excitatory postsynaptic potential. Western blot analysis was used to test for the expression of CaMKII and p-CaMKII. RESULTS (1) CSE caused no spatial reference memory (SFM) or spatial working memory (SWM) damage to 15-day-old (P15) rats, but caused significant SRM and SWM damage to 35-day-old (P35) rats. VPA damaged the SRM and SWM of P15 rats in both the CSE and control groups. However, VPA improved the memory damage caused by CSE in P35 rats. (2) VPA treatment in vivo increased the induced success rate and the sustainable time of long-term potentiation (LTP) in P35 rats, and also inhibited the expression of CaMKII and p-CaMKII in both P15 and P35 rats. CONCLUSIONS VPA significantly improved spatial cognitive dysfunction in a CSE model of P35 rats, and damaged the spatial memory of normal P15 and P35 rats. Improvements after administration of VPA were closely related to the increase of induced success rate and the prolongation of the sustainable time of LTP. VPA treatment in vivo, which inhibited expression and phosphorylation of CaMKII, showed no obvious inhibition on LTP, which may be related to the elution effect of VPA.

Daily prednisone treatment in Duchenne muscular dystrophy in southwest China.

INTRODUCTION: In this study we aimed to determine the influence of daily prednisone treatment in Duchenne muscular dystrophy (DMD) by performing a prospective, randomized, placebo-controlled trial in southwestern China. METHODS: Sixty-six children with DMD (4-12 years of age) were divided randomly into prednisone and placebo groups. Efficacy and safety of daily prednisone at 0.75 mg/kg/day were evaluated over 12 months by muscle strength and function, quality of life (QoL), quantitative muscle ultrasound (QMUS), and side effects. RESULTS: Significant improvements in muscle strength and function, QoL, and QMUS were observed in the prednisone group compared with the placebo-treated group (P < 0.05). Changes in body weight, height, body mass index, and diastolic blood pressure were similar in both groups (P > 0.05). CONCLUSIONS: This pilot study in southwestern China found that daily prednisone at 0.75 mg/kg/day is suitable for children with DMD. It slowed disease progression and improved QoL and QMUS. Moderate side effects were generally well tolerated.

Serum miR-206 and other muscle-specific microRNAs as non-invasive biomarkers for Duchenne muscular dystrophy.

Creatine kinase has been utilized as a diagnostic marker for Duchenne muscular dystrophy (DMD), but it correlates less well with the DMD pathological progression. In this study, we hypothesized that muscle-specific microRNAs (miR-1, -133, and -206) in serum may be useful for monitoring the DMD pathological progression, and explored the possibility of these miRNAs as potential non-invasive biomarkers for the disease. By using real-time quantitative reverse transcription-polymerase chain reaction in a randomized and controlled trial, we detected that miR-1, -133, and -206 were significantly over-expressed in the serum of 39 children with DMD (up to 3.20 ± 1.20, 2(-ΔΔCt) ): almost 2- to 4-fold enriched in comparison to samples from the healthy controls (less than 1.15 ± 0.34, 2(-ΔΔCt) ). To determine whether these miRNAs were related to the clinical features of children with DMD, we analyzed the associations compared to creatine kinase. There were very good inverse correlations between the levels of these miRNAs, especially miR-206, and functional performances: high levels corresponded to low muscle strength, muscle function, and quality of life. Moreover, by receiver operating characteristic curves analyses, we revealed that these miRNAs, especially miR-206, were able to discriminate DMD from controls. Thus, miR-206 and other muscle-specific miRNAs in serum are useful for monitoring the DMD pathological progression, and hence as potential non-invasive biomarkers for the disease. There has been a long-standing need for reliable, non-invasive biomarkers for Duchenne muscular dystrophy (DMD). We found that the levels of muscle-specific microRNAs, especially miR-206, in the serum of DMD were 2- to 4-fold higher than in the controls. High levels corresponded to low muscle strength, muscle function, and quality of life (QoL). These miRNAs were able to discriminate DMD from controls by receiver operating characteristic (ROC) curves analyses. Thus, miR-206 and other muscle-specific miRNAs are useful as non-invasive biomarkers for DMD.

A 1-year analysis from a natural history study in Chinese individuals with Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a disabling and life-threatening, X-linked recessive disorder caused by mutations in dystrophin. Natural history studies can inform the disease characteristics of DMD, and data from these studies can be used to plan and design clinical trials and as external controls for long-term studies. We report 12-month results from the largest natural history study of individuals with DMD in China receiving standard of care treatment. Methods: This ongoing, multicentre, prospective, single-cohort study (ClinicalTrials.gov: NCT03760029) was conducted in Chinese male participants with DMD (ambulatory aged <6 years [Group 1; n = 99]; ambulatory aged ≥6 years [Group 2; n = 177], and non-ambulatory of any age [Group 3; n = 36]. The follow-up period is ≥24 months, with some participants followed for 30 months. The primary endpoint was time to clinical milestones due to DMD disease progression, and motor, pulmonary, and cardiac function. Secondary endpoints were quality of life (QoL) assessments. Findings: Mean (standard deviation [SD]) age at screening was 3.4 (1.2), 8.6 (2.0), 12.3 (2.7) and 7.4 (3.5) years in Groups 1, 2, 3 and total respectively. Mean (SD) North Star Ambulatory Assessment (NSAA) total score at baseline was 21.2 (5.8) in Group 1, 19.5 (8.3) in Group 2 and 20.0 (7.7) in ambulatory total. Overall, the time to clinical milestones due to DMD disease progression was consistent with previous findings, in which loss of ambulation occurred at 13 years. There was a trend towards a decline over 12 months in NSAA and timed motor function from age 6 years, with the greatest reductions observed thereafter. There were no consistent trends in measures of QoL, although participants of any age generally had poorer outcomes at Month 12 versus their domain scores at baseline. Interpretation: This study improves the understanding of DMD progression according to the current standards of care in the Chinese DMD population and may inform selected endpoints and patient populations in clinical trials. Funding: Pfizer Inc.