Tic disorders (TD) are complex, chronic neuropsychiatric disorders that begin in childhood and adolescence and are characterized by rapid, involuntary, sudden, repetitive, non-rhythmic, stereotyped, single or multi-site muscle motor twitches or (and) vocal twitches. According to the age of onset, duration of the disease, clinical manifestations and the presence of vocal tics, there are three clinical types of transient tic disorder, chronic motor or vocal tic disorder and Tourette’s syndrome.
I. Clinical characteristics
1. General characteristics: The age of onset is 2 to 21 years old, with 5 to 10 years old being the most common. The disease is usually most severe at the age of 10 to 12 years; males are significantly more than females, and the ratio of males to females is 3 to 5:1.
2. Twitching: an involuntary, purposeless, rapid and stereotyped muscle contraction. The performance of twitching is complex and varied. The motor twitch is an involuntary, sudden, rapid contraction of the muscles of the head and face, neck and shoulders, trunk and limbs; the vocal twitch is actually a contraction of the mouth, nose, throat and respiratory muscles, which vocalize through the airflow of the nose, mouth and throat. Motor tics or vocal tics can be further divided into two categories: simple and complex, and sometimes the two are not easily distinguished. Unlike other movement disorders, twitching occurs in the presence of normal motor function and is non-persistent. At the beginning of the disease, twitching symptoms usually start in the face and progress to the head, neck, and shoulder muscles, and then spread to the trunk and upper and lower extremities. The form of twitching can change from one form to another, with new forms of twitching constantly emerging. The frequency and intensity of twitching fluctuate significantly during the course of the disease, and new twitching symptoms may replace or superimpose on top of the old twitching symptoms. In children with a long course of the disease, the appearance of a twitch or vocalization is sometimes quickly followed by another movement in an attempt to mask it, further complicating the clinical picture. Twitching symptoms often come and go, and may resolve temporarily or spontaneously over time, or may be exacerbated or reduced by certain triggers. Factors that commonly aggravate tics include stress, anxiety, anger, shock, excitement, fatigue, infection, and being reminded of the tics. Forty to 55% of children with motor or vocal twitches are preceded by localized physical discomfort, called sensory twitches, which are considered aura symptoms (prodromal symptoms), especially in older children, including pressure, itching, pain, heat, cold or other unusual sensations. Motor or vocal twitches are likely to be associated with relief of local discomfort.
Co-morbidity: About half of the children have one or more psychological behavior disorders, including attention deficit hyperactivity disorder (ADHD), learning difficulties, obsessive-compulsive disorder, sleep disorders, mood disorders, self-injurious behavior, conduct disorder, and rage attacks. There are gender differences in the occurrence of TD co-morbidities, with ADHD, learning difficulties, conduct disorder, and rage attacks usually occurring more frequently in males, while obsessive-compulsive disorder and self-injurious behavior occur more frequently in females than in males. Co-morbidity further increases the complexity and severity of the disorder, affecting the child’s learning, social adjustment, personality and healthy development of psychological qualities, and adding many difficulties to treatment and management”.
Diagnosis
1. Diagnostic methods: There is a lack of specific diagnostic indicators. At present, the diagnosis is mainly made by clinical descriptive diagnostic methods, based on the child’s tic symptoms and related concomitant psychiatric behavioral manifestations. Therefore, a detailed history is the prerequisite for a correct diagnosis, and physical examination including psychiatric examination and necessary auxiliary examinations are also necessary to exclude other diseases. EEG, neuroimaging and laboratory tests are generally not characteristically abnormal. A few children may have nonspecific changes, such as background slowing or asymmetry in a few children on EEG; non-specific structural changes such as small volume of the caudate nucleus, slightly thin frontal and occipital cortices, mild enlargement of the ventricles, and deepening of the lateral fissure in a few children on cranial CT or MRI. Wilson’s disease) and other organic extrapyramidal diseases.
2, clinical typing: according to the clinical characteristics and duration of the disease, the disease can be divided into three types: transient TD, chronic TD and Tourette syndrome (TS). Transient TD is the most common type with the mildest disease, manifesting as one or more motor tics and/or vocal tics, and the duration of the disease is within 1 year. TS, also known as multiple tic disorder, is a relatively severe form of the disease, showing both motor and vocal tics, but not necessarily both at the same time, with a duration of more than 1 year. In the past, the term “Tourette’s syndrome” was not appropriate, because the incidence of obscenities was less than one-third, and obscenities were not a necessary condition for the diagnosis of Ts, and it had an obvious pejorative meaning. Transient TD can be converted to chronic TD, and chronic TD can be converted to Ts.
Some patients cannot be classified in any of these categories and belong to other types of TD that have not yet been defined, such as TD with adult onset (late-onset TD). Refractory TD is a new concept that has gradually developed in pediatric neurology and psychiatry in recent years, which refers to children with TD who have been treated with conventional anti-TD drugs such as haloperidol and thiopride for more than 1 year in adequate amounts and have not recovered from the disease. A variety of organic diseases can also cause TD, i.e. secondary TD, which should be excluded clinically. There are many causes of secondary TD, including genetic factors (such as Down syndrome, fragile X syndrome, tuberous sclerosis, neuroborreliosis, etc.), infectious factors (such as streptococcal infection, encephalitis, neurosyphilis, Creutzfeldt-Jakob disease, etc.), toxic factors (such as carbon monoxide, mercury, bee poisoning, etc.), and drug factors (such as methylphenidate, pemoline, amphetamine, cocaine, carbamazepine, phenobarbital, phenytoin, lamotrigine, etc.). phenytoin, lamotrigine, etc.) and other factors (such as stroke, head trauma, developmental disorders, neurodegenerative diseases, etc.).
3. Assessment of disease: According to the severity of the disease, it can be divided into mild, moderate and severe. Mild (mild) means that the tic symptoms are mild and do not affect the child’s life, learning or social activities; moderate means that the tic symptoms are heavy but have less impact on the child’s life, learning or social activities; severe (serious) means that the tic symptoms are heavy and significantly affect the child’s life, learning or social activities. Objective and quantitative assessments can also be made based on tic severity scales, such as the Yale Comprehensive Tic Severity Scale. In addition, the more co-morbidities associated with TD, the more severe the condition.
4. Diagnostic criteria: It can be based on the International Classification of Diseases, 10th edition, the Diagnostic and Statistical Manual of Mental Disorders, 4th revision (DSM-IV-TR) H. and the Chinese Standard for Mental Disorders and Diagnosis, 3rd edition (CCMD.III). At present, most scholars at home and abroad tend to adopt the diagnostic criteria in DSM I 1V-TR, which are briefly described as follows.
1) Transient TD.
①One or more motor twitches and/or vocal twitches
② multiple episodes of twitching in 1 d, with almost daily episodes lasting at least 4 weeks, but not more than 1 year
③No previous history of chronic TD or Ts; ④Onset before 18 years of age
⑤TD symptoms were not directly caused by certain drugs (e.g. stimulants) or medical diseases (e.g. Huntington’s chorea or post-viral infection encephalitis).
2) Chronic TD.
①One or more motor twitches or vocal twitches that do not occur simultaneously in the course of the disease
②Twitches may occur several times a day, either daily or intermittently, but the intermittent period lasts no more than 3 months, and the duration of the disease is more than 1 year
③Onset before 18 years of age; ④TD symptoms are not caused by certain drugs (such as stimulants) or medical diseases (such as Huntington’s chorea or post-viral infection encephalitis).
3) TS.
① with multiple motor twitches and one or more vocal twitches during the course of the disease, without having to appear at the same time
②Twitching can occur several times a day (usually clustered) or intermittently, but the interval does not exceed 3 months, and the duration of twitching is more than 1 year
③The location, number, frequency, intensity and complexity of the twitches change over time.
④Onset before the age of 18; ⑤Twitching symptoms are not directly caused by certain drugs (such as stimulants) or medical diseases (such as Huntington’s chorea or post-viral encephalitis).
5. Diagnostic process: Clinical diagnosis relies on detailed history, physical examination and relevant auxiliary examinations. The child should be interviewed directly to observe the twitching and general behavioral manifestations, and to clarify the priority, scope, evolution pattern and sequence of symptoms. It should be noted that the child’s symptoms can be self-controlled for a short period of time and can be easily overlooked and missed. At the same time, TD is also easily misdiagnosed because of the frequent co-morbidity of ADHD and obsessive-compulsive disorder. Attention should be paid to exclude rheumatic chorea, hepatomegaly, epilepsy, pharmacogenic tics, psychogenic tics and other extrapyramidal disorders.
III. Treatment
Before treatment, the target symptom should be identified, i.e., the symptom that has the greatest impact on the child’s daily life, learning or social activities. Twitching is usually the target symptom for treatment, while some children have co-morbid symptoms, such as hyperactive impulsivity and obsessive-compulsive thoughts. The principle of treatment is to give equal emphasis to pharmacological and psychological-behavioral treatment, and to focus on individualization of treatment.
1.Medication: For children with moderate to severe TD that affects daily life, learning or social activities, if the effect of psycho-behavioral treatment alone is not good, additional medication is needed, including dopamine receptor blockers, ā receptor agonists and other drugs. Medication should be given for a certain duration and at an appropriate dose, and should not be changed or stopped prematurely.
1) Commonly used drugs: Effective communication with the parents of the child should be conducted before using the drugs, and attention should be paid to monitoring the adverse effects of the drugs. Commonly used drugs mainly include the following four categories.
①Dopamine receptor blockers: they are the classic drugs for TD treatment. Commonly used drugs are as follows: haloperidol is commonly used at a therapeutic dose of 1-4 mg/d, 2-3 times/d, usually with equal doses of benzhexol (Antan) to prevent possible pharmacogenic extrapyramidal reactions caused by haloperidol; thiopride, also known as Tebrile, is commonly used at a therapeutic dose of 150-500 mg/d, 2-3 times/d, with few and mild side effects, including dizziness, weakness, drowsiness, gastrointestinal reactions, etc; The common treatment dose of sulpiride is 200-400 mg/d, 2-3 times/d, with sedation and mild extrapyramidal reactions more common; the common treatment dose of risperidone is 1-3 mg/d, 2-3 times/d, with common side effects such as insomnia, anxiety, irritability, headache and weight gain; aripiprazole has been tried in the treatment of children with TD, with good efficacy, and the recommended treatment dose is 5-20 mg/d, l-2 times/d. The recommended therapeutic dose is 5-20 mg/d, l-2 times/d. Common side effects are nausea, vomiting, headache, insomnia, drowsiness, irritability, and anxiety. There are many other drugs in this category, such as perphenazine, olanzapine, quetiapine, ziprasidone, sertindole, piquantone, butalbitalazine, fluphenazine and trifluoperazine, all of which have certain anti-twitch effects and are not much used in pediatric clinics.
② Central ā receptor agonist: commonly used colistin system d receptor agonist, especially for children with TD who have co-morbid ADHD; the commonly used therapeutic dose is 0.1-0.3 mg/d, 2-3 times/d; for those who have poor tolerance to oral preparations, colistin patch treatment can be used; the drug has less side effects, some children appear sedated, a few children appear dizziness, headache, Weakness, dry mouth, irritability, occasional postural hypotension and prolonged P-R interval. Guanfacine is also a first-line drug used for TD+ADHD treatment, and there is little experience in domestic pediatrics. The commonly used therapeutic dose is 1-3 mg/d, 2-3 times/d. Common side effects include mild sedation, fatigue and headache.
③ selective 5 hydroxytryptamine reuptake inhibitors: new antidepressants, such as fluoxetine, paroxetine, sertraline, fluvoxamine, etc., have anti-twitch effects; combined with risperidone can produce synergistic effects; also used for TD + obsessive-compulsive disorder treatment.
④Other drugs: clonazepam, sodium valproate, topiramate and other drugs have anti-TD effects, of which clonazepam treatment dose is 1-2 mg/d, 2-3 times/d, common side effects are drowsiness, dizziness, weakness, vertigo, etc.; sodium valproate treatment dose is 15-30 mg/(kg-d), pay attention to side effects such as liver function impairment; topiramate treatment dose is 1-4 mg∥(kg-d ), attention should be paid to side effects such as loss of appetite, weight loss, sweating disorder and cognitive impairment. For children with refractory TD, they should be promptly referred to psychiatry or functional neurosurgery for further pharmacological or neuromodulatory treatment. The application of multi-receptor modulating drugs in combination or the exploration of new drugs has become a trend in the treatment of refractory TD.
2) Drug treatment options.
①Preferred drugs: thiopride, permethrin, sulpiride, aripiprazole, colistin, guanfacine, etc. can be used. Start from the lowest dose and gradually increase the dose slowly (once every 1~2 weeks) to the target therapeutic dose.
②Intensive therapy: After the condition is basically controlled, the treatment dose needs to be continued for at least 1 to 3 months and intensive therapy is given.
The purpose of intensive and maintenance treatment is to consolidate the therapeutic effect and reduce relapse.
④Discontinuation: After the maintenance treatment phase, if the disease is completely controlled, the drug can be considered to be gradually reduced and discontinued for at least 1 to 3 months. If the symptoms recur or worsen, resume the medication or increase the dose. ⑤ Combined medication: When the use of a single drug can only partially improve the symptoms, or when there are co-morbidities, consider asking for a neurological consultation and consider combined medication; refractory TD also requires combined medication.
2.Non-pharmacological treatment
1) Psycho-behavioral therapy: It is an important means to improve tic symptoms, intervene in co-morbidities and improve social functions. For mild children with good social adjustment ability, most of the psycho-behavioral treatment alone can be effective. First, through psychological counseling for the child and parents, the child’s psychological state can be adjusted to eliminate the sense of stigma, and through health education, the child, parents and teachers can be instructed to understand the disease correctly, not to pay too much attention to the child’s tic symptoms, and to reasonably arrange the child’s daily life and reduce the school burden. At the same time, appropriate behavioral treatment can be given, including habit reversal training, exposure and response prevention, relaxation training, positive reinforcement, self-monitoring, fading exercises, and cognitive behavioral therapy. Among them, habit reversal training and exposure and response prevention are the first-line behavioral treatments.
2) Neuromodulation therapy: neuromodulation therapy such as repetitive transcranial magnetic stimulation, electroencephalographic biofeedback and transcranial microcurrent stimulation can be tried for the treatment of children with drug-refractory TD. Deep brain stimulation has more definite efficacy, but it is invasive and invasive treatment, which is mainly applicable to the treatment of drug-refractory TD in older children (above 12 years old) or adults.
3.Co-morbidity treatment
I) Co-morbid ADHD (TD+ADHD): It is the most common clinical co-morbidity. An ā agonist, such as colistin, may be preferred, with both anti-twitch and attention-improving effects. Tomoxetine does not induce or exacerbate twitching and is also indicated for children with TD with co-morbid ADHD. There is a potential risk of exacerbating or inducing tics with central stimulants, but clinical evidence is inconsistent, and there are successful experiences of using methylphenidate for TD+ADHD treatment in clinical practice. The use of conventional doses of dopamine receptor blockers (e.g., thiopirid) in combination with small doses of central stimulants (e.g., methylphenidate, 1/4 to 1/2 of the conventional dosage) is now generally advocated for the treatment of children with TD+ADHD, which can effectively control ADHD symptoms and has insignificant effects on tic symptoms in most children.
2) Co-morbidities of other behavioral disorders: such as learning difficulties, obsessive-compulsive disorders, sleep disorders, mood disorders, self-injurious behaviors, conduct disorders, etc., should be treated with educational training, psychological interventions, combined medication and other therapies along with TD, and timely referral to child psychiatry for comprehensive treatment.