Yan Cheng, Zheng Guo, Qiu-Ju Feng, Lu-Jia Liu, Xue Li, You-Peng Wang

1. Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China

2. The second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150001, China

Keywords:Tic disorder Treatment Research progress

ABSTRACT Tic disorder is one of the common neuropsychiatric disorders that affect children’s physical and mental health. If it is not tested, diagnosed and treated early, it will have a serious impact on children themselves, their families, and even the whole society. Simple western medicine treatment methods include drugs, nerve regulation, psychological and behavioral therapy,but the results are not ideal. Traditional Chinese medicine takes systematic treatment based on syndrome differentiation and it uses methods of traditional Chinese medicine, massage and acupuncture to regulate five viscera and six bowels in order to harmonized Yin and Yang.These methods make up for the deficiencies of western treatment. In recent years, the clinical treatment of children with Tic disorders involving a variety of combined therapy has achieved significant results. As a result, the rehabilitation of children with Tic disorders has been significantly improved. By consulting the available literature at home and abroad in recent years, the author elaborates the etiology, pathogenesis and treatment of tic disorder in children,in order to further guide the clinical diagnosis and treatment.

1. Introduction

Tic disorder, (TD) mostly occurs in children and adolescents.In contrast with girls, boys are more vulnerable to the disease. [1].The main clinical manifestations are sudden twitches, movements,or sounds that people do repeatedly. The symptoms can be accompanied by various symptoms of neuropsychiatric disorders,such as attention deficit hyperactivity disorder, obsessive-compulsive movement, thought disorder, sleep disorder, conduct disorder,emotional disorder and so on. If the disease is not intervened in time and the disease gradually worsens, it will seriously affect the physical and mental health of children [1,2]. Western medicine divides children’s tic disorder into four types: transient tic disorder,chronic tic disorder, Tourette syndrome (TS) and other undefined tic disorders, among which TS is the most typical. The highest incidence rate in clinical classification is transient tic disorder.From the perspective of epidemiology, the total prevalence of TD in children of China can be as high as 6.1% at present, and the number is increasing year by year [2]. With the continuous development and progress of medical technology in our country, the methods of treating children with TD are gradually increasing. At present,western medicine mainly treats children with TD by drugs, immune regulation, neural regulation and psychological treatment. By contrast, traditional Chinese medicine mainly treats children with TD by traditional Chinese medicine, acupuncture and massage. At the same time, the combination of traditional Chinese and Western medicine shows good curative effect and advantages. In this paper,we summarized the research progress of this disease in recent years:

1. New progress of Western Medicine Research

1.1 Understanding of etiology and pathogenesis of TD in Western Medicine

At present, the etiological study of TD in western medicine has not been completely clear, and no one factor can fully explain the occurrence of TD at present. It needs further research and discussion. Some experts have proposed that the etiology of TD is complex, which may be related to biological factors (Genetics,immunity, neurobiochemistry, etc.), psychosocial factors (family atmosphere, education methods, etc.), drug factors, and many other factors. The disease may be caused by one or more these factors. [3].The mainstream hypothesis holds that the occurrence of TD may be closely related to the imbalance of a variety of neurotransmitters,among which the excessive activity of dopamine (DA) in striatum synapse or the hypersensitivity of DA receptor are considered as the key factors of TD [4]. In addition, the imbalance of trace element intake, cervical spine brain injury, various abnormalities during pregnancy, unreasonable food intake will also affect, aggravate or induce the occurrence of TD [5,6,7,8,]. The author believes that only through further study and discussion of the etiology and pathogenesis of TD, and by taking active prevention and treatment measures, can the incidence of TD in children be effectively reduced.

1.2 Dew progress in the treatment of TD with Western Medicine

1.2.1 Drug treatment

At present, the overall efficacy of western medicine is limited,and moreover there is no unified scheme for clinical drug selection in the world. Clinically, drug therapy can alleviate the symptoms of children with tic disorder by regulate the imbalance of neurotransmitters. Therapeutic drugs include dopamine receptor blockers [9,10], dopamine system stabilizers [11], selective monoaminergic antagonists [12], central α 2 receptor agonists [13],antiepileptic drugs [14], etc. Some clinical studies have shown that thiopride and sulpiride, the most commonly used drugs in clinic,have selective antagonistic effect on dopamine D2 receptor. They can significantly reduce the number of tic while having no bad effect on children’s cognitive function. At the same time, the adverse reactions are generally tolerable[9,10]. Aripiprazole, as a dopamine system stabilizer, is not only approved by FDA for the treatment of TS, but also used by Japanese experts as the first-line drug for the treatment of TD.Aripiprazole can partially activate dopamine D2 receptor and 5-hydroxytryptamine receptor, as well as antagonize serotonin receptor, and regulate the transmission of dopamine neurotransmitter in brain according to the activity of dopamine receptor [12].Aripiprazole can significantly reduce the frequency of tic symptoms in children with TD, especially movement and vocalization.Risperidone, as a selective monoaminergic antagonist, has a high affinity antagonistic effect on 5-hydroxytryptamine, dopamine D2 receptor, α 1 and α 2 adrenoceptors and histamine receptor,and it is more suitable for children with TD comorbid obsessivecompulsive disorder. European guidelines regard risperidone as the first choice for TD drug treatment [12]. However, its long-term efficacy and safety for children with TD are not very clear, which is why Japan, Canada and other countries have listed risperidone as the second-line drug for TD treatment at present. Except for antipsychotics, clonidine, an alpha agonist, is also widely used in children with TD comorbid attention deficit hyperactivity disorder[13]. As for antiepileptic drugs, due to the lack of high-quality clinical research evidence, they are not recommended as conventional treatment [15]. In addition, there are also reports on the clinical application of other drugs including cannabis drugs, botulinum toxin,nicotine in the treatment of children with refractory TD. As highquality research and unclear drug safety lacks, the clinical application should be carefully weighed. To sum up, there is no standardized treatment plan in the world, and high-quality research on children’s TD drug treatment should still focus on further development of the global standardized treatment plan of drug prescription. At the same time, clinicians should also specify comprehensive individualized treatment plan based on various medical conditions such as factors,disease severity, drug effectiveness and safety, so as to improve children’s TD curative effect.

1.2.2 Neuroregulatory treatmentNeural regulation is a treatment method to improve the function of central, peripheral or autonomic nervous system through the process of implantable and non implantable technology as well as electrical or chemical means. Some studies have suggested that compared with the children with drug-resistant tic disorder, we can try to use neuroregulation methods to treat them, such as EEG biofeedback,transcranial micro current stimulation, repeated transcranial magnetic stimulation, deep brain stimulation, etc. The results of transcranial micro current stimulation therapy (TCD) by Yang Lili et al [16]showed that the total score of YGTT decreased, IVA-CPT evaluation value increased, and the effect was significant. In addition, some studies have shown that EEG bio feedback and transcranial magnetic stimulation are noninvasive and safe. Although the effectiveness is confirmed, the two methods still lack a large number of follow-up observation and multi center double blind research evidence; Deep brain stimulation has significant effect on refractory TD in older children (over 12 years old), but the disadvantage is that this method is invasive therapy [17]. In conclusion, the effectiveness and safety of the treatment plan for children with tic need to be considered carefully at the same time. For children with drug-resistant tic disorder, neuromodulation therapy is a good choice after weighing the risk ratio of clinical benefits.

1.2.3 PsychotherapyBehavioral therapy (BT) is an important treatment method for TD in children. It has the function of improving the twitching, controlling comorbidity and improving social function. This treatment method has been written in the European and American guidelines for the treatment of tic[18]. BT includes habit reversal training (HRT),exposure and response prevention (ERP), relaxation training (RT),positive reinforcement, self-monitoring, retreat training, cognitive behavior therapy, etc, among which HRT and ERP have become the first-line treatment scheme[19]. At present, psycho-behavioral therapy has been widely used in children TD treatment, while light TD children can only use simple psychological behavior therapy. A large number of clinical studies have shown that in order to improve the symptoms of children with refractory cases, psychological behavior therapy and drug combined can be used[20,21]. In addition,other psychotherapy includes mental control training, comprehensive behavioral intervention therapy, cognitive behavior therapy, selfhypnosis, and family support therapy, etc. The author thinks that psychological behavior therapy can be accompanied with the treatment of the disease. The cooperation of parents and school teachers also helps children to eliminate psychological problems and even plays an important role in the rehabilitation of children with tic disorder.

2. New progress of traditional Chinese medicine research

2.1 TCM understanding of TD etiology and pathogenesis

The name “tic disorder” is not clearly recorded in ancient medical books. According to its clinical manifestations, it can be classified into five categories according to traditional Chinese medicine:“l(fā)iver wind syndrome”, “slow convulsion”, “convulsion”, “Pang”and “emotional disease”. The cause of TD includes congenital or acquired. Congenital factors include insufficient endowment and birth injury, while acquired factors are mostly related to external pathogen invasion, emotional and internal injury, improper diet,disease induction and so on. The main location of the disease is liver,and the other four viscera can also be involved. The key pathogenesis is wind phlegm cementation and hyperactivity of liver. As TCM has more and improved understanding of this disease, increasingly more doctors have put forward their own opinions on its TCM pathogenesis from aspects of different syndrome differentiation.The author summarizes the following points: first, Simultaneous liver and lung diseases, [22, 23]; second, the bright spirit is damaged,Endogenous Wind of Liver [24]; third, the kidney essence is deficient,and the liver Yang is unbalance [25]; fourth, the Yin and yang are imbalanced, and spleen deficiency and liver hyperactivity [26-28];Fifth, insufficiency of gallbladder qi causing timidity [29]; sixth, the marrow sea is not full, and the spirit is imbalanced [30]; seventh,wind-phlegm is Internal ambulation, and the Yin and yang are imbalanced [31,32], Eight, blood deficiency causing wind, and liver wind stirring up internally[33]; nine, sanjiao imbalance causes liver wind[34]; ten, liver wind damages tendons, and endogenous disturbance[35]. TCM doctors with years of clinical experience analyze the etiology and pathogenesis of tic disorder in children from different angles, which not only opens up the ideas of TCM treatment of tic disorder, but also reflects the characteristics and advantages of TCM emphasizing dialectical treatment.

2.2 New progress of TCM Treatment

2.2.1 Internal treatment of traditional Chinese MedicineTraditional Chinese medicine in the treatment of children with TD process, has significant efficacy and advantages. It pays attention to the whole concept and adopts the combination of disease differentiation and syndrome differentiation, which has a significant effect. Many doctors from different angles study the disease differentiation and treatment, and the author will now summarize them as follows.

2.2.1.1 treatment from viscera

The point of view that the location of the disease is mainly in the liver has become a consensus of doctors. However, traditional Chinese medicine pays attention to the concept of five viscera as a whole, and the treatment of the disease can not be treated by one viscera alone. Doctors have different opinions on the syndrome differentiation of viscera. According to the treatment of liver and lung, Liu Bichen [22] used various drugs of diffusing the lung and free coursing the liver to eliminate the external and internal wind,and achieved good clinical effect; Xu rongqian[23] took wind quenching and phlegm resolving as the basic rule for the treatment of this disease, and emphasized the importance of preventing colds to consolidate the curative effect of this disease and prevent the recurrence and aggravation of tic symptoms in children. According to the treatment of heart and liver, Professor Wang Lie [36] selected the modified Tiaoshen Decoction to treat the disease, and to achieve the effect of nourishing the heart and calming the mind, resolving phlegm and stopping movement; Han Fei [24] mainly focus on the heart,and she drew up her own tranquilizing and stopping movement formula to achieve the effect of calming the heart, the mind, the wind and resuscitation. According to the treatment of liver and kidney,Professor Zhang biao [25]selected the herbs of tonifying kidney and calming liver to play the role of tonifying kidney yin and Yang,softening liver and stopping spasm; Li Yaqun [37] self-made qiangzhi prescription to treat Tourette’s syndrome from the perspective of deficiency of tonifying kidney. According to the treatment of liver and spleen, Ma Rong [26] chose Tianma Gouteng Decoction and Ganmai Dazao Decoction to stabilize the liver and spleen; Professor Wang Sumei [28] took invigorating the spleen and resolving phlegm as the basis of treatment, and then used drugs for calming the liver and entering the collaterals to search the wind to treat the symptoms.Professor Xu rongqian [29] selected Wendan Decoction to relieve depression, clear the gallbladder and calm the nerves, so as to make the gallbladder Qi peaceful and smooth, and the convulsion peaceful.To sum up, the author believes that the treatment of TD in children has played an important role in regulating the relationship between the five Zang and six Fu organs and coordinating the function of Zang and Fu organs.

2.2.1.2 Treatment based on Qi, blood and body fluid

Syndrome differentiation of Qi, blood and body fluid is a dialectical method to judge the pathological changes of Qi, blood,body fluid and fluid according to the clinical manifestations of the disease by using the theory of Qi, blood and body fluid in the theory of viscera. Many doctors choose to treat the disease by syndrome differentiation of Qi, blood and body fluid, and have also achieved remarkable curative effect. According to the treatment of wind phlegm, Wang Shouchuan [31] made his own Fengning Decoction to eliminate phlegm and eliminate wind as the main method, combined with calming the liver and purging fire, eliminating phlegm and invigorating the spleen, nourishing the kidney and calming the heart to achieve the purpose of treating both the symptoms and the root causes; Han Xinmin [32] selected his own Xifeng Ditan Decoction to achieve the effect of resolving phlegm and calming the wind.Hu Tiancheng [38] chose Siwu Decoction Combined with Zhijing powder to promote blood circulation and stop spasm, while Li Yanyi[33] used Bergamot powder combined with Xue fu Zhu yu Decoction and Ganmai Dazao Decoction to eliminate blood circulation and wind. The author believes that the treatment of children tic disorder from the perspective of wind phlegm, blood deficiency, wind and other pathogenesis, not only has a unique idea, but also clinical verification shows that the curative effect is significant, which provides a new idea in addition to viscera syndrome differentiation.

2.2.2 Acupuncture therapyClinical studies have confirmed that acupuncture and moxibustion can relieve and improve the tic symptoms of children with tic disorder in different degrees. Professor Li Yingkun [39] combined the international standard scalp acupoints with the meridian theory of traditional Chinese medicine to create a “scalp acupoint treatment line” and applied it to children with TD, and achieved good results;Professor Liu zhe [40] applied the alternating acupuncture method of abdomen and back to the treatment of chronic tic disorder, and achieved obvious results; Professor Wu Xu [41] selected acupoints according to more than 40 years of clinical experience, paid attention to regulating liver effect acupoints, and took care of the spleen and stomach The main acupoints are Ganshu, Hegu, Fengchi and Taichong. The matching acupoints are Baihui, Zusanli, Yongquan and Sanyinjiao. The light and flexible acupuncture technique is used to treat children with TD. The curative effect is remarkable.At present, studies have shown that the efficacy and safety of acupuncture alone in the treatment of children with TD has been clinically confirmed. Therefore, in the clinical application of the treatment of this disease, it is of great significance to pay attention to acupuncture treatment, examine the syndrome and seek the cause, and dialectical acupuncture, so as to improve the cure rate of children with tic disorder.

2.2.3 Massage therapy

Massage therapy is a method that can dredge meridians by pressing acupoints and meridians. It plays a good auxiliary role in the treatment of TD in children. Professor Wang Xuefeng[42] used Anshen Ningzhi massage combined with traditional Chinese medicine in the treatment of 70 cases of TD children with hyperactivity of liver wind phlegm syndrome, which was clinically effective. Anshen Ningzhi massage can prevent exogenous diseases by pushing and saving bamboo, pushing kangong and kneading the sun, pushing and saving bamboo and Jingming to alleviate children’s eye symptoms, kneading Fengchi to achieve the effect of dispersing wind, tonifying Yuanqi according to Baihui and Sishencong, kneading Tiantu and Tanzhong, kneading Rub the chest and flank, knead the spine, hold the shoulder well to dredge the meridians, regulate qi and remove phlegm. A whole set of massage can regulate qi, blood, yin and Yang, calm the nerves and dredge the collaterals. In addition, studies have shown that the use of Tongdu abdominal massage method, Jianpi Anshen method, Xifeng Zhijing chiropractic massage and other massage techniques combined with traditional Chinese medicine in the treatment of children with TD,the effect is better. The author thinks that massage therapy, which is a green therapy without side effects, has its unique advantages in the treatment of this disease. Therefore, it is worthy of clinical application.

2.2.4 Others

Auricular point sticking and pressing brain point, Shenmen, liver,spleen, stomach, heart, kidney and other acupoints combined with Jianpi Zhidong decoction can achieve the effect of invigorating spleen and resolving phlegm, relieving wind and stopping spasm,and the clinical effect is better than simple internal treatment of traditional Chinese medicine [43]. Press needle to Hegu, Taichong,Sanyinjiao, Zusanli, Fenglong and other points combined with modified Ditan Decoction in the treatment of multiple tic disorder has definite clinical effect and small adverse reactions [44]. In addition, there are catgut embedding therapy, acupoint injection therapy, pricking therapy, sticking therapy and other treatment methods. Clinical research shows that it also has good effect on improving tic symptoms.

The combination of traditional Chinese and Western medicine has also achieved good results in the treatment of children with TD.Professors like Li Weiyuan [45]combined traditional Chinese and Western medicine and selected the ladder therapy with multiple treatment levels in treating children with TD. In the first level,Xiaoyao Powder and Guipi pill were taken orally as Chinese medicine decoction. In the second level, Chinese medicine decoction was combined with ear acupoints. In the third level, chiropractic needle was added on the basis of the second level, haloperidol and Antan were taken orally, and psychological intervention was carried out at all levels at the same time. The results showed that the condition before and after the treatment are diverse. The total effective rate was 96%. For parents who want to quickly control tic symptoms and do not want to accept high adverse reactions,integrated traditional Chinese and western medicine is an acceptable and effective treatment.

3. Summary and Prospect

In conclusion, TD is a kind of neuropsychiatric disease with unknown etiology and diverse manifestations. Children is vulnerable to the disease. And it harms children’s physical and mental health.There are many kinds of clinical treatment methods for children’s TD and they are constantly improving. Due to the complexity and variability of the pathological basis of TD in children, the clinical treatment of TD is more comprehensive. To sum up, it can be seen that the best treatment is the combination of systematic and personalized treatment. According to the author’s preliminary summary, the following points need to be paid extra attention:① The initial diagnosis of TD in children is difficult. At present,no specific diagnostic method has been found to diagnose TD.The main diagnostic method is clinical phenomenology. The early manifestations are easily ignored by parents or clinicians, and they are also easy to be covered by various symptoms. Therefore, in order to improve the treatment of TD, both parents and clinicians should test early and treat it early. ② The clinical symptoms of children with TD are diverse and the predisposing factors are complex. The effect of single therapy is often limited, and the disease needs early treatment in order to achieve good curative effect. Therefore, it is necessary to combine a variety of treatment methods in clinical practice. However, it is necessary to formulate individualized treatment plan based on the characteristics of TD children’s age, types of diseases, comorbidity types, disease severity and children’s physical type, to prevent poor treatment effect or aggravating the economic pressure of treating the disease.③Traditional Chinese medicine therapy, be it traditional Chinese medicine therapy, acupuncture and massage therapy or other traditional Chinese medicine therapy, has broad prospects in the treatment of children with TD. It can not only effectively control the occurrence of tic symptoms, but also reduce the recurrence of the disease. It has significant curative effect and less adverse reactions, and it is easy to be accepted by children and parents. The traditional Chinese medicine, as a characteristic medicine in China with a great development potential, has some obvious shortcomings.In order to solve the existing problems, it is necessary to carry out further research. Doctors formulate individualized therapy plan by conducting study in multiple centers and analyzing population-level samples. They take the advantages of both Chinese and western medicine to optimize the treatment plan and use combined methods to develop a new plan with higher cure rate and lower frequency. The combination plays a great role in protecting the physical and mental health of children with Tic. ④ The treatment and prevention of recurrence of children with TD is a long-term and arduous project.Parents of children should be positive and cooperate with doctors,and they should pay attention to the psychological treatment of children with TD to make children ready to participate in the society physically and psychologically.