Release time ：2022-08-10
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Autism spectrum disorder (ASD) is a kind of neurodevelopmental disorder that starts in the early stage of development and is mainly characterized by continuous social interaction and social communication ability defects, restricted and repetitive behavior patterns, interests or activities[1].
Men are more likely to suffer from this disorder. It is usually a chronic lifelong disease course, which often seriously damages the social function of patients. It is one of the most important diseases leading to children's mental disability and leads to a serious disease burden. In recent years, it has attracted common attention all over the world.
Autism spectrum disorder starts in the early stage of development, mostly within 36 months. Among them, about 2/3 of the children developed disease gradually after birth, and about 1/3 of the children have degenerative onset after 1 ~ 2 years of normal development.
ICD-11 and DSM-5 divide the core symptoms of autism spectrum disorders into two areas, namely, persistent defects in social interaction and social communication ability, and restricted and repetitive behavior patterns, interests or activities.
In addition to the above main clinical manifestations, children with autism spectrum disorder often have other psychiatric symptoms, such as emotional instability, hyperactivity, impulsivity, self-injury, etc. Most patients suffer from other mental disorders, including mental retardation, attention deficit hyperactivity disorder, anxiety disorder, obsessive-compulsive disorder, affective disorder, eating disorder, etc. Some children have some somatic symptoms or somatic comorbidities, including gastrointestinal dysfunction, epilepsy, tuberous sclerosis, cerebral palsy, etc. There may also be chromosomal abnormalities, such as fragile X syndrome, trisomy 21 syndrome, etc.
According to the latest "Report on the Development of China's Autism Education and Rehabilitation Industry Ⅲ" released by the Wucailu Autism Research Institute in 2019, the incidence of autism has increased year by year. According to the report, the incidence rate of autism in China is 0.7%, and there are currently more than 10 million people with autism spectrum disorders, of which more than 2 million are children under 12 years old.
The etiology and pathogenesis of autism spectrum disorder are still unclear. A large number of studies have shown that autism spectrum disorder is a neurodevelopmental disorder caused by biological factors. Genetic factor is the most important factor, and the heritability is 0.7 ~ 0.9. In addition, environmental factors can increase the risk of individual disease. The interaction between genetic factors and environmental factors can also lead to abnormal brain development. Besides, some neurotransmitter systems (such as serotonin system) or neuropeptides (such as oxytocin) are also abnormal.
For children with suspicious symptoms of autism spectrum disorder, the following examinations and assessments are recommended: Physical and nervous system examination; Mental examination; Developmental level and intelligence assessment; Laboratory examination; EEG and brain imaging examination (cranial MRI and CT); Genetic examination; Screening and diagnostic evaluation of autism spectrum disorder.
The treatment principles of autism spectrum disorder are early diagnosis and early intervention, use scientific and effective treatment methods to intervene, intervention with comprehensive treatment methods and adhere to long-term treatment.
TMS is a non-invasive neuromodulation technology. The time-varying pulsed magnetic field can penetrate the skull non-invasively, act on the central nervous system, generate induced currents, and cause a series of physiological and biochemical reactions, thereby affecting metabolism and neuronal excitability in the brain so that improve and treat mental and neurological diseases.
In general, high-frequency stimulation increases the cortical excitability, whereas low-frequency stimulation has inhibitory control on the neural circuits. High-frequency rTMS (>5 Hz) produces an excitatory effect on neural tissue by inducing a form of long-term potentiation (LTP) that increases efficacy at the synapse that can last beyond the duration of a treatment session. Lowfrequency rTMS (≤1 Hz) produces an inhibitory effect on neural tissue via a long-term depression(LTD)-like mechanism.
International consensus statement on the potential of rTMS in the treatment of ASD in 2018[2]: Data from existing rTMS studies on ASD indicate that rTMS has therapeutic potential. Large, multi-site, double-blind, sham-controlled trials still need to be carried out in order to have a deeper understanding of the neurophysiological heterogeneity of ASD, so as to determine the appropriate treatment options and maximize the clinical outcomes.
A literature review on rTMS in the treatment of autism published in 2018 collected the literature data of rTMS in the treatment of autism from June 2016 to January 2018[3]. The results showed that:
Stimulation method：Most studies use traditional rTMS protocols.
Stimulation site：The goal of most studies is to stimulate the dorsolateral prefrontal cortex (DLPFC) on both sides or in the left hemisphere using low-frequency stimulation (0.5-1 Hz).
Stimulation sessions: Most studies were stimulated once a week or twice a week, but some studies performed daily treatment for 5-29 consecutive days.
Stimulation coil：Except for Enticott et al. (2014) using H-shaped coils and Annios et al. (2016) using specially designed helmets (containing up to 122 coils), all studies used traditional figure-of-eight coils.
The results of this meta-analyses showed that rTMS has a significant but moderate impact on repetitive and stereotyped behaviors, social behavior, and the number of errors in executive function tasks, but not other outcomes.
| Disease | Stimulation site | Stimulation frequency (Hz) | Stimulation intensity | Stimulation time (s) | Interval time (s) | Total number of pulses |
| ASD | DLPFC | 1 | 90%MT | 10 | 20 | 180 |
In October 2018, the consensus meeting promoted and supported by the International Federation of Clinical Neurophysiology (IFCN) proposed the 2020 safe application guide of transcranial magnetic stimulation[5]. The safety report on the application of transcranial magnetic stimulation in children in the guide is as follows:
（1）It is safe to use single-pulse and paired-pulse TMS for children 2 years and older when suitable hearing protection is used.
（2）For children younger than two years, data about risk for acoustic injury are not available, and therefore specialized hearing protection may be required.
（3）In addition, for children age one year and younger, due to the lack of safety data, it will be necessary to obtain TMS data on hearing safety first.
（4）According to current research reports, the larger number of children, including healthy children, now have undergone sTMS, ppTMS and rTMS, which also provides a reassurance for the safety of these technologies.
When TMS is given to children, it is necessary to strictly follow the contraindications of TMS. In addition, special attention should be paid to a series of changes due to the development of children's central nervous system. The following questions need to be considered: Closure of the fontanelle; Development of external auditory canal and seizures.
Considering these factors, children younger than 2 years old should use it with caution. It is recommended to use it for children over 3 years old.
Reference
[1] 精神障礙診療規范（2020年版）
[2] Cole, E. J. , Enticott, P. G. , Oberman, L. M. , Frampton, G. M. , Casanova, M. F. , & Jackson, S. , et al. (2018). The potential of repetitive transcranial magnetic stimulation for autism spectrum disorder: a consensus statement. Biological Psychiatry, 85, S0006322318315920-.
[3] Barahona-Corrêa J. Bernardo, Ana, V. , Ana, C. , Ricardo, L. , & Oliveira-Maia, A. J. . (2018). Repetitive transcranial magnetic stimulation for treatment of autism spectrum disorder: a systematic review and meta-analysis. Frontiers in Integrative Neuroence, 12, 27-.
[4] Kang, J. , Song, J. , Casanova, M. F. , Sokhadze, E. M. , & Li, X. . (2019). Effects of repetitive transcranial magnetic stimulation on children with low‐function autism. CNS Neuroscience & Therapeutics, 25(11).
[5] Sr, A. , Aab, C. , Sb, D. , Mb, E. , Cb, F. , & Jb, G. , et al. (2020). Safety and recommendations for tms use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: expert guidelines - sciencedirect. Clinical Neurophysiology.
