Ling Shan

Core Symptoms of Autism Improved After Vitamin D Supplementation

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. Among the environmental factors, vitamin D3 (cholecaliferol) seems to play a significant role in the etiology of ASD because this vitamin is important for brain development. Lower concentrations of vitamin D3 may lead to increased brain size, altered brain shape, and enlarged ventricles, which have been observed in patients with ASD. Vitamin D3 is converted into 25-hydroxyvitamin D3 in the liver. Higher serum concentrations of this steroid may reduce the risk of autism. Importantly, children with ASD are at an increased risk of vitamin D deficiency, possibly due to environmental factors. It has also been suggested that vitamin D3 deficiency may cause ASD symptoms. Here, we report on a 32-month-old boy with ASD and vitamin D3 deficiency. His core symptoms of autism improved significantly after vitamin D3 supplementation. This case suggests that vitamin D3 may play an important role in the etiology of ASD, stressing the importance of clinical assessment of vitamin D3 deficiency and the need for vitamin D3 supplementation in case of deficiency.

Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis

Vitamin D may play an important role in the etiology of Autism Spectrum Disorders (ASD). Vitamin D is regarded as a neuroactive steroid affecting brain development and function. It plays an essential role in myelination, which is important for connectivity in the brain. Studies have shown that decreased vitamin D levels in patients, decreased maternal vitamin D levels during pregnancy, and decreased exposure to solar UVB might increase the risk for ASD. In addition, autism symptoms and global functioning may improve after vitamin D supplementation. Here, we sought to aggregate information from previous publications on vitamin D levels and ASD, in order to achieve a higher statistical power and thereby to determine the validity of vitamin D deficiency as a risk factor for ASD. For this meta-analysis, 11 studies met the inclusion and exclusion criteria, accounting for a total of 870 ASD patients and 782 healthy controls. Levels of serum 25(OH) D in participants with ASD were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD.

Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder

Objective: High prevalence of vitamin D deficiency was previously reported in children with Autism Spectrum Disorder (ASD), but little is known about the efficacy of vitamin D3 treatment in ASD, although data from pilot studies seem promising. We hypothesized that serum vitamin D levels are reduced in ASD and correlate with the severity of disease. Also, we hypothesized that vitamin D3 treatment may be beneficial for a considerable portion of children with ASD. Methods: In total, 215 children with ASD and 285 healthy control children were recruited in our study. Thirty seven of 215 ASD children received vitamin D3 treatment. The Autism Behaviour Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were used to assess autism symptoms. High-performance liquid chromatography was used to assess the serum 25-hydroxyvitamin D [25(OH) D] level. Evaluations of ABC, CARS, and serum 25(OH) D levels were performed before and after 3 months of treatment. Results: Serum levels of 25(OH) D were significantly lower in ASD children than typically developing children. Levels of serum 25(OH) D were negatively correlated with ABC total scores and language subscale scores. After vitamin D3 supplementation, symptom scores were significantly reduced on the CARS and ABC. In addition, the data also suggest that treatment effects were more pronounced in younger children with ASD. Conclusion: Vitamin D deficiency might contribute to the aetiology of ASD. Supplementation of vitamin D3, which is a safe and cost-effective form of treatment, may significantly improve the outcome of some children with ASD, especially younger children (identifier ChiCTR-CCC-13004498). Clinical Trial Registration: The trial ‘Association of Polymorphisms of Vitamin D Metabolism-Related Genes With Autism and the Treatment of Autism with Vitamin D’ has been registered at www.chictr.org/cn/proj/show.aspx? proj=6135 (identifier ChiCTR-CCC-13004498).

A Pilot Study on the Combination of Applied Behavior Analysis and Bumetanide Treatment for Children with Autism

OBJECTIVE The purpose of this study was to investigate the therapeutic effects of combined bumetanide and applied behavior analysis (ABA) treatment in children with autism. METHODS Sixty children diagnosed with autism according to the International Classification of Diseases, Tenth Revision (ICD-10) criteria (mean age of 4.5 years) were randomly divided into two groups: A single treatment group (n=28) and a combined treatment group (n=32). The combined treatment group received ABA training combined with oral bumetanide (0.5 mg twice a day). The single treatment group received ABA training only. Autism symptoms were evaluated with the Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS), whereas severity of disease (SI) and global improvement (GI) were measured with the Clinical Global Impressions (CGI). Assessment of ABC, CARS, and CGI was performed immediately before and 3 months after initiation of the treatment(s). RESULTS Prior to intervention(s) no statistically significant differences in scores on the ABC, CARS, SI, or GI were found between the two groups. Total scores of the ABC, CARS, and SI were decreased in both groups after 3 months (p<0.05) compared with the scores prior to treatment. The total scores of the ABC and the CGI were significantly (p<0.05) lower in the combined treatment group than in the single treatment group. Although the total and item scores of the CARS in the combined treatment group were lower than in the single treatment group after a 3 month intervention, they did not reach statistical significance. No adverse effects of bumetanide were observed. CONCLUSIONS Treatment with bumetanide combined with ABA training may result in a better outcome in children with autism than ABA training alone.

A Prospective Case-Control Study of Radial Extracorporeal Shock Wave Therapy for Spastic Plantar Flexor Muscles in Very Young Children With Cerebral Palsy.

AbstractTo assess the effects of radial extracorporeal shock wave therapy (rESWT) on plantar flexor muscle spasticity and gross motor function in very young patients with cerebral palsy (CP).The design was case-control study (level of evidence 3).The setting was the Department of Pediatric Neurology and Neurorehabilitation, First Hospital of Jilin University, Changchun, China.Those with a diagnosis of CP and spastic plantar flexor muscles were recruited between April 2014 and April 2015.According to the parents’ decision, patients received 1 ESWT session per week for 3 months, with 1500 radial shock waves per ESWT session and leg with positive energy flux density of 0.03 mJ/mm2, combined with traditional conservative therapy (rESWT group) or traditional conservative therapy alone (control group).The Modified Ashworth Scale (MAS) (primary outcome measure) and passive range of motion (pROM) measurements were collected at baseline (BL), 1 month (M1), and 3 months (M3) after BL. The Gross Motor Function Measure (GMFM)-88 was collected at BL and M3.Sixty-six patients completed the final review at 3 months and were included in the study. Subjects ranged in age from 12 to 60 months (mean age 27.0 ± 13.6 months; median age 22.0 months; 33.3% female). For the rESWT group (n = 34), mean MAS grades at BL, M1, and M3 were 2.6, 1.9, and 1.5 on the left side and 1.9, 1.7, and 1.2 on the right side. For the control group (n = 32), mean MAS grades at BL, M1, and M3 were 2.5, 2.4, and 2.1 on the left side and 1.8, 1.8, and 1.5 on the right side. The within-subject effects time × side and time × treatment were statistically significant (P < 0.01). Similar results were found for the improvement of mean pROM. GMFM-88 improved from BL to M3, but showed no statistically significant difference between the groups. There were no significant complications.This study demonstrates that the combination of rESWT and traditional conservative therapy is more effective than traditional conservative therapy alone in the treatment of spasticity in very young patients with CP.

Effects of ultra-low frequency transcranial magnetic stimulation on motor function and intelligence of children with spastic cerebral palsy: study protocol for a randomized parallel-cohort controlled trial

Background: Ultra-low frequency transcranial magnetic stimulation is a novel transcranial magnetic stimulation method that was developed based on the biological resonance principle and has been used in combination with an encephalofluctuograph. It can be used to treat brain diseases by regulating the brain electrical activity of various neurotransmitters, thereby overcoming the shortcomings of conventional transcranial magnetic stimulation. Nevertheless, stimulation intensity, frequency, protocol, and curative effects should be considered. Ultra-low frequency transcranial magnetic stimulation has been widely used to treat insomnia and several studies have reported on the use of ultra-low frequency transcranial magnetic stimulation for the treatment of cerebral palsy. Methods/Methods: This is a randomized, parallel-cohort controlled trial. Patients with spastic cerebral palsy, aged 2-4 years, are included in this trial and assigned to two groups. In the control group, conventional rehabilitative treatment methods, including exercise therapy, Chinese traditional manipulation, and muscle fiber excitation are used. In the treatment group, in addition to routine rehabilitative treatment methods, ultra-low frequency transcranial magnetic stimulation is used. After 1 and 3 months of treatment, the outcomes are evaluated. The primary outcomes of the trial include Gross Motor Function Measure (GMFM) scores, Fine Motor Function Measure (FMFM) scores, and Wechsler Intelligence Scale for Children (WISC) scores. Discussion: The trial will provide clinical scale data for the use of ultra-low frequency transcranial magnetic stimulation to improve motor function and intelligence in child patients with spastic cerebral palsy. Trial registration: Chinese Clinical Trial Registration identifier: ChiCTR-TRC-14004706; registered on 26 May 2014. Ethical issues: This trial was approved by the Medical Ethics Committee, First Hospital, Jilin University, China (approval No. 100818-062). Signed written informed consent will be obtained from each subject.

Infra-low Frequency Transcranial Magnetic Stimulation Effectively Improves theMotor Function in Children with Spastic Cerebral Palsy

Background: Cerebral palsy (CP) is one of the major diseases that lead to severe disability and seriously impacts the quality of life of children. Infra-low frequency transcranial magnetic stimulation (ILF-TMS) is a new technique of noninvasive brain stimulation that exactly regulates the power of specific neurotransmitters through a special magnetic field. Our study was in order to investigate the efficacy of ILF-TMS treatment in children with spastic cerebral palsy. Methods: 113 spastic cerebral palsic children were randomly divided into two groups: conventional rehabilitation group and ILF-TMS treatment group, Healthy control group was established at the same time. In conventional rehabilitaion group, children were treated with conventional rehabilitation treatment; In ILF-TMS treatment group were treated with ILF-TMS in addition to conventional rehabilitation treatment. Neurotransmitter in the brain was recorded with encephalofluctuograph (EFG) before and after ILF-TMS treatment. Gross Motor Function Measure (GMFM), Fine Motor Function Measure (FMFM) and Gesell development scale (GDS) were used to comprehensively evaluate the motor function in children with spastic cerebral palsy. Results: The results showed that the relative power of γ-aminobutyric acid (GABA) in spastic cerebral palsy was lower than that in healthy controls and was increased significantly after ILF-TMS treatment for 3 months. The relative power of glutamate (Glu) in spastic cerebral palsy was higher than that in healthy controls and was reduced significantly after ILF-TMS treatment for 3 months. After 3 months training period there was significant improvements on the GMFM (dimension B, dimension C and dimension D), FMFM (dimension A and dimension B) and GDS (gross motor DA and gross motor DQ) in the ILF-TMS treatment group when compared to conventional rehabilitation group. Conclusions: These findings indicate that GMFM is a sensitive indicator to assess the treatment efficacy in children with spastic cerebral palsy and ILF-TMS treatment can improve the motor function through regulating neurotransmitters in brain.

Bench to bedside review: Possible role of vitamin D in autism spectrum disorder

Autism spectrum disorder (ASD) is a group of dysfunctions in social interaction, communication, and behaviors. Studies have demonstrated that vitamin D deficiency during pregnancy and in individuals increased the risk of ASD. A genetic polymorphism study has pinpointed that genotype AA/A-allele of GC rs4588 in children is associated with ASD, which encodes the vitamin D binding protein. Translating the mentioned points into clinical practice, several clinical trials have demonstrated that vitamin D supplementation can improve the core symptoms in children with ASD. One paper also showed that possible prophylactic effect for the reoccurrence of ASD by vitamin D supplement during pregnancy and early childhood. Herein, this review aims to address the recent advances in this field and to clarify the possible role of vitamin D in ASD.

Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children: Three cases report

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complicated interactions between genetic and environmental factors. Clinical trials, including case reports, case–control studies, and a double-blinded randomized clinical study, have suggested that high-dose vitamin D3 regimens may ameliorate the core symptoms of ASD. Vitamin D3 supplementation was effective in about three-quarters of children with ASD. To further investigate the relationship between vitamin D and ASD symptoms in vitamin D-responsive autistic children, changes in symptoms were assessed in three children with ASD who were given vitamin D3 supplementation followed by a long interruption. The core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL. Overall, these results showed that the core symptoms of ASD fluctuated in severity with changes in serum 25(OH)D levels in children, indicating that maintaining a responsive 25(OH)D level is important for treating ASD. Maintaining a serum 25(OH)D level between 40.0 and 100.0 ng/ml may be optimal for producing therapeutic effects in vitamin D-responsive individuals with ASD.

Does early injection of mouse nerve growth factor affect motor and cognitive abilities in high-risk infants? study protocol for a randomized parallel-controlled trial

Background and objectives: Newborns with perinatal risk factors and abnormal general motor quality assessment are at high risk of developing cerebral palsy. The treatment is earlier, the prognosis is better. This trial will investigate whether, combined with conventional early interventional therapy, the use of mouse nerve growth factor in high-risk infants can improve their motor and cognitive abilities. Design: This is a prospective, single-center, randomized, parallel, controlled, clinical trial. Methods: This trial will be conducted in the Department of Developmental Behavioral Pediatrics, the First Hospital of Jilin University, China. One hundred high-risk infants meeting the inclusion criteria will be recruited and randomized into control and treatment groups. Only participants in the treatment group will undergo the early treatment of mouse nerve growth factor via gluteus maximus injections, 20 μg per dose, once a day, 10 consecutive days per month. The treatment will last for 6 months. Both groups will receive standard early intervention therapies. Outcome measures: The primary outcome measure is the incidence of the developmental disorders cerebral palsy and non-cerebral palsy at the actual age or corrected age of 12 months. The secondary outcome measures are Gesell Developmental Schedule scores at the actual age or corrected age of 12 months, Gross Motor Function Measure score at 6 and 12 months of treatment, and adverse events during the trial. Discussion: If treatment with mouse nerve growth factor is found to be safe and effective for the high-risk infants, new options for the early-stage clinical treatment for such infants may be developed. Ethics and dissemination: This trial has been approved by the Ethics Committee of First Hospital of Jilin University of China [approval number: 2017 (2017-290)]. This trial was designed in August 2017. Ethics approval was done in October 2017. This trial was registered in November 2017. The recruitment of subjects began in December 2017. Data analysis will be finished in December 2021. The results of the trial will be reported in a scientific conference or disseminated in a peer-reviewed journal. Anonymized trial data will be available indefinitely at www.figshare.com. Trial registration: This trial has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-17012774). Protocol version (2.0).