Li-Ping Zou

A possible association of responsiveness to adrenocorticotropic hormone with specific GRIN1 haplotypes in infantile spasms.

Aimu2002 Adrenocorticotropic hormone (ACTH) has been used as the major therapy for infantile spasms since 1958 because it effectively suppresses seizures; it also normalizes the electroencephalogram in the short‐term treatment of infantile spasms. G protein‐regulated inducer of neurite outgrowth 1 (GRIN1, also known as N‐methyl‐d‐aspartate receptor 1, NMDAR1), a glutamate receptor, is the main component of functional N‐methyl‐d‐aspartic acid receptors that are involved in the glucocorticoid‐induced neuronal damage. Thus, it may be a candidate gene to be tested for responsiveness to ACTH in infantile spasms. In the present study, polymorphisms in the GRIN1 gene in infantile spasms were investigated using a case–control design.

Effect of Acupuncture on the Brain in Children With Spastic Cerebral Palsy Using Functional Neuroimaging (fMRI)

We study the effect of acupuncture on brain activation patterns in children with cerebral palsy using functional magnetic resonance imaging (fMRI). fMRI of the whole brain was performed in 11 children with cerebral palsy and 10 healthy children during stimulation of a common acupoint in Traditional Medicine [Liv3 (Taichong)] on the left foot. We use both twisting and nontwisting methods with a blocked paradigm on a 2.0 Tesla MRI scanner. Functional data were analyzed by using Statistical Parametric Mapping software (SPM 99). Both signal increase and decrease in various regions of the brain were found in both groups of children. However, the pattern was different for the 2 groups, especially with decreases in signal regions. We suggest that the observed differences between children with cerebral palsy and healthy children with the stimulation of acupoint Liv3 might be due to blockage of the liver meridian in children with cerebral palsy.

Electro-acupuncture protects against hypoxic–ischemic brain-damaged immature rat via hydrogen sulfide as a possible mediator

We investigated whether hydrogen sulfide (H(2)S) may be a mediator of electro-acupuncture (EA) stimulation treatment for hypoxic-ischemic brain-damage (HIBD). We studied a HIBD 7-day-old rat model with 4 types of treatments: (1) 14 sessions of EA; (2) hydroxylamine (HA), an inhibitor of cystathionine-β-synthase (CBS), the key enzyme of H(2)S generation; (3) both EA and HA; or (4) no treatment. Sham-treated rats with or without EA were also studied. Regional cerebral blood flow (rCBF) was monitored before, during and after EA at different periods of treatment (d1, 7 and 14 sessions). We evaluated motor function, H(2)S levels and CBS expression in the cerebral cortex and prepared cerebral pathomorphological images after 14 sessions of treatment. EA stimulation could increase local blood circulation and improve motor function in HIBD rats. HIBD significantly increased H(2)S levels of brain tissue as compared with sham treatment, and EA treatment could decrease the H(2)S generation. Rats with HIBD receiving both EA and HA therapy showed greatly recovered motor function and brain morphology. H(2)S might be a mediator of EA treatment of HIBD in rats.

Functional Magnetic Resonance Imaging Activation of the Brain in Children: Real Acupoint Versus Sham Acupoint

The purpose was to examine the brain activation patterns with acupuncture using real acupoint (Liv3) versus sham acupoint in healthy, sedated children using functional magnetic resonance imaging (fMRI). Functional magnetic resonance imaging scans of the brain for 10 healthy, sedated children were taken during stimulation of real acupoint (Liv3 [Taichong]) and a nearby sham acupoint in a randomized order, employing twisting and nontwisting methods using a blocked paradigm using a 2.0-T scanner. The functional data were analyzed by using SPM 99. Various regions of the brain were activated in 2 acupoints. However, the pattern was different for the 2 acupoints. We suggest specific cerebral activation patterns with acupuncture might explain some of its therapeutic effect.

ACTH receptor (MC2R) promoter variants associated with infantile spasms modulate MC2R expression and responsiveness to ACTH.

Objective Adrenocorticotropin hormone (ACTH) has been the standard treatment to infantile spasms (IS). However, the mechanism of ACTH therapy is still unclear. ACTH exerts the function via melanocortin 2 receptor (MC2R). Our previous study showed a common 4-single nucleotide polymorphism (SNP) haplotype TCCT at the MC2R promoter was strongly associated with responsiveness to ACTH therapy, where these 4 SNPs [rs1893219, rs1893220, rs2186944, and a novel SNP (T>C)] were mapped at position −853, −759, −7, and −2u2009bp based on the transcription start site of the MC2R gene. In this study, we further elucidated functional significances of the TCCT haplotype. Methods To evaluate whether the TCCT haplotype influences MC2R transcription levels, the luciferase reporter vector was used by a transient transfection. Expression of rat MC2R cDNA driven by the TCCT-carrying or TCCC-carrying promoter was detected by the real-time quantitative reverse transcription-PCR. These assays were performed on cell lines cultured in absence or presence of ACTH. Results In the baseline, the light intensity of the luciferase reporter assay driven by the TCCT promoter was four times higher than that by the TCCC promoter. The intensity was dramatically increased in the pGL3-TCCT after ACTH stimulation, compared to that in the pGL3-TCCC. MC2R expression assay showed a 5-fold increase in the TCCT promoter in presence of ACTH, compared with that in absence of ACTH. Conclusion The results showed that the haplotype TCCT in MC2R promoter significantly led to increased MC2R expression and strong responses to ACTH, providing evidence of the molecular mechanism of ACTH therapy in IS.

Risk Factors for Arterial Ischemic and Hemorrhagic Stroke in Childhood

This study assessed potential etiologies of arterial ischemic stroke and hemorrhagic stroke among children of Mainland China. From January 1996-June 2006, 251 patients with consecutive childhood stroke (aged 1 month through 16 years) were admitted to Beijing Childrens Hospital. Arterial ischemic stroke accounted for the majority of cases (62.5%). Idiopathic stroke (32.5%) was more common than cardiac stroke (8.9%), vascular or arteriopathic stroke (21.0%), hematologic disorder-associated stroke (10.8%), and other etiologies (26.8%). Vitamin K deficiency was a major etiology in 72 of 94 hemorrhagic strokes (76.6%), most of which occurred in breastfeeding infants (80.6%) and those who received no vitamin K after birth (73.6%). Arteriovenous malformation (6.4%) was a frequent etiology in the remaining hemorrhagic stroke cases. We found that ischemic stroke in children is more common than hemorrhagic stroke, and many cases of ischemic stroke are idiopathic. Vitamin K deficiency was a major etiology in these young infants who experienced hemorrhagic stroke.

Randomized controlled trial of traditional Chinese medicine (acupuncture and tuina) in cerebral palsy: part 1--any increase in seizure in integrated acupuncture and rehabilitation group versus rehabilitation group?

OBJECTIVEnThe objective of this study was to observe for any change in baseline seizure frequency with acupuncture in children with cerebral palsy.nnnMETHODSnA randomized controlled study was conducted: Group I consisted of integrated acupuncture, tuina, and rehabilitation (physiotherapy, occupational therapy, and hydrotherapy) for 12 weeks; and Group II consisted of rehabilitation (physiotherapy, occupational therapy, and hydrotherapy) for 12 weeks. After a washout period of 4 weeks, Group II then received acupuncture and tuina for 12 weeks. Each subject received 5 daily acupuncture sessions per week for 12 weeks (total = 60 sessions). All children were assessed for any change in seizure frequency during treatment.nnnRESULTSnOne hundred and sixteen (116) children were recruited and randomized into Group I (N = 58) and Group II (N = 58). Thirty-three (33) children withdrew (9 from Group I and 24 from Group II). Of the remaining 83 children, Group I consisted of 49 and Group II of 34 children. For baseline, 5 children (6%; 5/83) had seizures. During phase 1 (12 weeks) of integrative treatment and subsequent 4-week follow-up, 3 children in Group I had seizures. Among those 3 children with seizures, 1 child with prior history of recurrent febrile seizure had 3 more recurrent febrile seizures during acupuncture treatment and 2 children without any prior history of seizures had new-onset seizures (1 with 3 recurrent febrile seizures and 1 with afebrile seizure). For Group I, 2 children with epilepsy had no increase in seizure frequency during acupuncture treatment. For Group II during the phase 2 acupuncture period, none had increase in seizure frequency. In both groups, 4 of 5 children (80%; 2 in Group I and 2 in Group II) with seizures had no increase in seizure frequency during acupuncture treatment and follow-up.nnnCONCLUSIONSnThe risk of increasing seizure is not increased with acupuncture treatment for cerebral palsy.

Role of TNF-α Gene Variation in Idiopathic Childhood Ischemic Stroke: A Case-Control Study

Etiology of the idiopathic childhood stroke remains unknown. In previous studies, the immunologic process may be involved in the idiopathic stroke. Tumor necrosis factor— alpha (TNF-α), an important immune mediator, may contribute to the initiation and progression in the stroke. The main purpose of this study was to investigate correlation of TNF-α genetic variation and idiopathic childhood ischemic stroke. Using the direct DNA sequencing method, polymorphisms in the TNF-α promoter region were genotyped in 67 Chinese patients with idiopathic childhood stroke and 70 controls. Among totally 7 single nucleotide polymorphisms identified in the TNF-α promoter region, the variant of the -863C/A is associated with increased risk of idiopathic childhood ischemic stroke in our study group. TNF-α molecule may have genetically as well as functionally an important role in the pathogenesis of idiopathic childhood ischemic stroke in the Chinese population.

Effectiveness of the First Antiepileptic Drug in the Treatment of Pediatric Epilepsy

Most previous studies on the effectiveness of the first antiepileptic drug have dealt with adults. The present retrospective study of 520 patients was designed to investigate the interaction among efficacy, tolerability, and overall effectiveness of the first antiepileptic drug in children with newly diagnosed epilepsy. A total of 344 patients became seizure-free with the first prescribed antiepileptic drug. A lower proportion of patients with symptomatic epilepsy (60.3%) or cryptogenic epilepsy (61.5%) became seizure-free, compared with patients with idiopathic epilepsy (73.8%), and more patients with symptomatic or cryptogenic epilepsy changed their treatments owing to intolerable side effects. Most patients (95.6%) received sodium valproate (n = 234), topiramate (n = 143), or carbamazepine (n = 120). The majority of seizure-free patients required only a moderate daily dose. Patients who took carbamazepine (16.7%) or topiramate (11.9%) had a higher incidence of adverse events, necessitating a change of treatment, compared with patients treated with valproate (4.3%), and fewer of them became seizure-free. Overall, 66.2% of the patients became seizure-free with the first-ever antiepileptic drug, and most of them at a moderate dose. Moreover, tolerability was as important as efficacy in determining overall effectiveness.

Comparison of the GMFM‐66 and the PEDI Functional Skills Mobility domain in a group of Chinese children with cerebral palsy

BACKGROUNDnPrevious research has suggested there is a high level of comparability between the Gross Motor Function Measure-66 (GMFM-66) and the Pediatric Evaluation of Disability Inventory (PEDI) Functional Skills Mobility domain. However, there are only a few studies that have examined the correlations between these instruments. The purpose of this study was to determine the correlation between the GMFM-66 and the PEDI Functional Skills Mobility domain scaled scores in a group of Chinese children with spastic cerebral palsy, at the ages of 12-70 months, in order to explore the feasibility of using them interchangeably.nnnMETHODSnSecondary data analysis was conducted of data collected during a prospective international collaborative study that used the GMFM-66 and the PEDI to examine the impact of treatment. This study examined the Pearson correlations between the GMFM-66 and the PEDI Functional Skills Mobility domain at six time points over the course of 28 consecutive weeks for 115 Chinese children who participated at baseline.nnnRESULTSnPearson correlations between the GMFM-66 and the PEDI Functional Skills Mobility domain ranged from 0.83 to 0.90 for the six time points of data collection, with statistically significant P-values <0.0001 for each correlation.nnnCONCLUSIONSnThese results support previous research that the GMFM-66 and the PEDI Functional Skills Mobility domain are complementary assessments that may be used interchangeably when it is not possible to administer both.