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Tic disorders: from pathophysiology to treatment.

Tic disorders are stereotypic behaviours,more frequent than once believed, and therefore likely to be encountered by primary care physicians. Tics usually begin in childhood and are the clinical hallmark of Tourette Syndrome (TS), the most common cause of tics. TS is a relatively common neurobehavioural disorder with a spectrum of manifestations that wax and wane during its natural course. The pathophysiology of tics, at molecular and cellular level, is still unknown,whereas structural and functional neuroimaging studies have shown the involvement of the basal ganglia and related cortico-striato-thalamo-cortical circuits, and the dopaminergic neuronal system. Moreover, TS has a strong genetic background. The management of TS is often complicated by the presence of attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and other behaviour disorders. The correct diagnosis is a fundamental step for a proper management of these disorders, and a multimodal treatment is usually indicated. This approach includes educational and supportive interventions, as well as pharmacological treatments when tics are at their worst.

Humans↗

Randomized trial of parent management training in children with tic disorders and disruptive behavior.

Oppositional, defiant, and disruptive behaviors are common in clinical samples of children with tic disorders. In this study, we sought to evaluate the short-term efficacy of a structured parent training program in children with tic disorders accompanied by disruptive behavior. Children with tic disorders and at least a moderate level of disruptive behavior were randomly assigned to a 10-session structured parent management training program or to continue treatment as usual. Twenty-four children (18 boys and 6 girls) between the ages of 6 and 12 years (mean 8.9 +/- 2.0 years) were enrolled; 23 subjects completed the study. At baseline, subjects showed moderate to severe levels of oppositional and defiant behavior. Twenty subjects (83%) were on stable medication. The parent-rated Disruptive Behavior Rating Scale score decreased by 51% in the parent management training group compared with a decrease of 19% in the treatment as usual group (P < .05). On the Improvement scale of the Clinical Global Impression, a rater masked to treatment assignment classified 7 of 11 subjects who completed parent management training as much improved or very much improved compared with 2 of 12 subjects in the treatment as usual group (Fisher exact test, P < .05). These results suggest that parent management training is helpful for short-term improvement in disruptive behavior problems in children with tic disorders. Larger randomized clinical trials are needed.

Analysis of Variance↗

A functional-analytic approach to the diagnosis of a transient tic disorder.

The diagnostic utility of functional analyses has been demonstrated with a variety of behaviors including tics. Whereas previous analyses have focused on the discovery of maintaining variables to aid in treatment prescription, we employed a functional analysis to confirm a clinical diagnosis. An 11 year old male student, who had not been previously diagnosed with a tic disorder, exhibited multiple vocal tic-like behaviors which had persisted over a period of time. Teacher reports conflicted regarding the possible etiology of these behaviors. Hence, a functional analysis was conducted in the classroom to determine if the behaviors were maintained by operant variables. Our hypothesis stated that the occurrence of vocal behaviors across experimental conditions would strongly indicate the presence of a tic disorder. The functional analysis included the following conditions: attention, escape, alone, freeplay, and high sensory stimulation. We used a multi-element design to evaluate the effects of the different stimulus conditions on vocal-behavior frequency. Data indicated the student exhibited vocal behaviors in all conditions. However, the behaviors were partially exacerbated in the attention and escape conditions. Results supported the diagnosis of a transient tic disorder affected by operant variables.

Attention↗

Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome.

The aim of this study was to assess rates for tic disorders and obsessive compulsive psychopathology in families of children and adolescents with Gilles de la Tourette syndrome (TS). Diagnoses were based on the DSM III-R criteria. Obsessive compulsive psychopathology, that did not fulfill the criteria for obsessive compulsive disorder (OCD) was additionally assessed and termed obsessive compulsive symptoms (OCS). The authors hypothesized that comorbid OCD or OCS in TS patients predicts a higher familial loading with obsessive compulsive symptomatology. The study cohort included 87 patients with TS who were evaluated clinically and with the use of a structured psychiatric interview. All available parents (152/174; 87%), several sibs (49/93; 53%) and some second degree relatives (27/659; 4.1%) were also interviewed. For other first and second degree relatives the family history method was used. Familial rates for TS were clearly elevated. Rates for chronic tic disorders (CT) were considerably lower than in previous studies. Additionally, tic disorders not otherwise specified (TDNOS) were diagnosed in a substantial number of first degree (15/267; 5.6%) and second degree relatives (36/659; 5.5%). OCD in parents (4/174; 2.3%) did not occur in an above baseline rate. However, both OCD (14/87; 16.1%) and OCS (15/87; 17.2%) were frequently associated with TS in index patients. Interestingly, 10 of 16 fathers with OCS also had a tic disorder. Obsessive compulsive psychopathology clustered in families. It is concluded that genetic studies in TS could profit from adhering to a conservative diagnostic approach to both tic disorders and OCD. The familial clustering of OCS/OCD in conjunction with the elevated paternal rate for the co-occurrence of tic disorders and OCS might indicate heterogeneity of TS.

Adolescent↗

Tic disorders in childhood (and beyond).

Tic disorders are classified into three main categories: transient (duration more than 1 month but less than 1 year), chronic (duration more than 1 year), and Tourette's syndrome (multiple motor and vocal tics lasting more than 1 year to life). Typically, symptoms increase with emotional stress, diminish with distraction or concentration, and disappear during sleep. Because of the risks involved and the lack of any truly curative value, drug therapy should be used only when tics are seriously disabling. Haloperidol (Haldol), the most widely prescribed medication, is efficacious in about 80% of patients with Tourette's syndrome. Psychotherapy is not effective as a primary therapeutic strategy; it may, however, be indicated in selected cases to relieve the grief and frustration of parents and to help affected children deal with the disorder.

Adolescent↗

Regional cerebral blood flow in obsessive-compulsive patients with and without a chronic tic disorder. A SPECT study.

The main goal of the present study was to explore whether regional cerebral blood flow (rCBF) differs between obsessive-compulsive disorder (OCD) patients without chronic motor tic disorder and those OCD patients with a comorbid chronic tic disorder. Twenty-seven patients suffering from OCD (DSM-IV criteria), including 7 OCD patients who met DSM-IV criteria for simple chronic motor dic disorder, and 16 healthy volunteers were examined at rest using a high resolution SPECT. Seven regions of interest (ROIs) were manually traced and quantified as a percentage of the mean cerebellar uptake. Severity of obsessive-compulsive symptoms (OCS), anxiety and depressive symptoms and presence of motor tics were assessed with the Y-BOCS, HRS-A, HRS-D, MADRS, and Yale Global Tics Severity Scale, respectively. We found a significant relative decrease in rCBF in OCD patients without motor tics compared to healthy volunteers in the right orbitofrontal cortex (OCD without tics = 0.87; healthy volunteers = 0.94; p = 0.02). No significant differences in rCBF were seen when OCD patients with and without chronic tics were directly compared. A lower severity of OCS in OCD patients with chronic tics was found. These results are consistent with previous functional neuroimaging studies at rest that have widely involved the orbitofrontal cortex in the pathophysiology of the OCD. However, our results do not support the idea that OCD patients with chronic tics may constitute a biological subgroup within the OCD.

Adult↗

Clinical and psychological features distinguishing obsessive-compulsive and chronic tic disorders.

Medical and biogenetic research has suggested that obsessive-compulsive disorder and chronic (multiple) tic disorder may share a common etiology. This article reviews corresponding evidence for psychological similarities and differences between the two disorders. There are similarities in self-management strategies, psychological traits (both report high scores on different aspects of perfectionism) and in the ego-syntonic-ego-dystonic cycle of the impulsive-compulsive behavior. Situational cues likely to elicit or worsen the problem differ between the disorders as do associated emotions, comorbidity and background styles of action. In both disorders, cognitive factors, such as anticipations and appraisals of the problem, can play a role in onset and maintenance of the problem, and this raises the question as to whether cognitive or behavioral factors are best addressed in treatment. Psychological characteristics, such as lack of confidence, may contribute to apparent performance deficit. Psychological evaluation, particularly functional analysis, may aid in differential diagnosis between the two disorders, lead to improvement in treatment matching, and in understanding of the multidetermined etiology.

Adult↗

Associated psychopathology in children with both ADHD and chronic tic disorder.

OBJECTIVE: To examine the relation between severity of tic disorder and comorbid psychopathology in 47 prepubertal children with tic disorder who were referred for clinical evaluation of and treatment for attention-deficit hyperactivity disorder (ADHD), oppositional behaviors, and aggressive behaviors. METHOD: Parents and teachers completed the Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF) for each child. RESULTS: Seventy-five percent of the sample was in the clinical range in at least two categories of psychopathology. When the children were divided into two groups on the basis of tic severity, significantly higher scores were obtained for children with more severe tics on the narrow-band Depressed, Uncommunicative, Obsessive-Compulsive, and Aggressive scales, and the broad-band internalizing scale of the CBCL. The severity groups did not differ on TRF scores. Children who were more aggressive also received higher CBCL scores. CONCLUSIONS: The findings from this study suggest that the severity of chronic tics is a clinical indicator of complex psychopathology in children with ADHD who are referred for psychiatric evaluation.

Attention Deficit Disorder with Hyperactivity↗

Prevalence of tic disorders and Tourette syndrome in a Swedish school population.

The aim of the study was to find the epidemiological distribution of tic disorders and Tourette syndrome (TS) in Swedish school children aged 7 to 15 years. A total population of 4,479 children and their parents were asked to fill in a questionnaire covering both motor and vocal tics. A three-stage procedure was used: screening, interview, and clinical investigation. Two hundred and ninety-seven children (190 males, 107 females) were found to have tics. TS, according to DSM-IV criteria, was found in 0.6% of the total population, another 0.8% had chronic motor tics, and 0.5% had chronic vocal tics. Further, 4.8% of the children had transient tics. All together 6.6% of 7- to 15-year-old children currently had or had experienced some kind tic disorder during the last year. Prevalence of different tic disorders was higher among younger children and in males, and was highly associated with school dysfunction. The prevalence of TS was higher than was previously thought but other tic disorders were more common in this childhood population.

Adolescent↗

Elevated D8/17 expression on B lymphocytes, a marker of rheumatic fever, measured with flow cytometry in tic disorder patients.

OBJECTIVE: Elevated D8/17 expression on B lymphocytes is a known susceptibility marker of rheumatic fever. Previous studies have reported higher than usual D8/17 expression on B lymphocytes of patients with tic disorders. The purpose of this study was to assess D8/17 expression on B lymphocytes of tic disorder patients by using an objective method in which no operator variability was involved. METHOD: D8/17 expression on B lymphocytes was assessed with flow cytometry by using an immunoglobulin M (IgM) monoclonal D8/17-specific antibody in an unselected group of Dutch patients with tic disorders (N=33) and healthy volunteers (N=20). Binding of this monoclonal antibody was compared with binding of an irrelevant IgM monoclonal antibody, and the shift in mean fluorescence intensity of the D8/17-specific antibody compared to that of the irrelevant IgM monoclonal antibody was used as a measure of D8/17 overexpression. For the patients, Yale Global Tic Severity Scale scores were used to assess disease severity. RESULTS: D8/17 overexpression in the patient group (mean=16.8 arbitrary units, SD=30.5) was significantly higher than in the comparison group (mean=3.2, SD=3.0). A significant minority of the patients (N=13, 39.4%), however, had levels of D8/17 overexpression within the range of that of the healthy comparison subjects. Flow cytometric analysis did not indicate a separate subpopulation of D8/17-positive B cells. CONCLUSIONS: These data confirm the utility of D8/17 B cell overexpression as a peripheral blood marker in patients with tic disorders and are compatible with a streptococcus-related pathogenesis for at least a subgroup of patients with tic disorders.

Adolescent↗

The behavioral spectrum of tic disorders: a community-based study.

BACKGROUND: Tourette syndrome (TS) and related tic disorders are commonly associated with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). It has been argued, however, that any observed association between TS and these and other psychopathologies may be due to ascertainment bias in that individuals with multiple problems are more likely to be referred for medical evaluation. METHODS: In order to overcome the potential confounding by ascertainment bias, the authors conducted a community-based study of school children using direct interviews to determine the prevalence of tic disorders and any comorbid psychopathology. A standard psychiatric interview and standardized rating scales were utilized to diagnose childhood behavioral disorders. RESULTS: Of the 1,596 children interviewed, 339 were identified as having tics. The following psychopathologies were found more commonly (p < 0.05) in the children with tics: OCD, ADHD, separation anxiety, overanxious disorder, simple phobia, social phobia, agoraphobia, mania, major depression, and oppositional defiant behavior. CONCLUSION: The behavioral spectrum of tic disorders includes OCD, other anxiety disorders, a mood disorder, and attention-deficit and disruptive behavior disorders.

Adolescent↗

Increased seroreactivity in tic disorder patients to a 60 kDa protein band from a neuronal cell line.

In tic disorders, increased seroreactivity against neuronal antigens has been demonstrated, without performing molecular characterization of antigens. Here, unselected patients with a tic disorder were compared with healthy controls, autistic disorder (AD), and obsessive-compulsive disorder (OCD) patients. Seroreactivity against neuroblastoma cells was analyzed by Western blot. Anti-60 kDa binding occurred significantly more frequently in tic disorder patients (67.1%) than in AD (40.0%), OCD (40.0%) and healthy controls (41.9%). Sequence analysis of the 60 kDa protein band identified this as a ubiquitous heat shock protein. However, the involvement of other autoantigens with a molecular weight of 60 kDa cannot be excluded.

Adult↗

Tourette syndrome and other tic disorders. Diagnosis, pathophysiology, and treatment.

In this report, we discuss the definition, characteristics, pathophysiology, and treatment of tic disorders with a major emphasis on Tourette syndrome. Although the diagnosis of a tic disorder depends on the presence of motor and/or phonic tic(s), patients with these problems also have a variety of co-morbid features including obsessive-compulsive symptoms, attention-deficit hyperactivity disorder, behavioral difficulties, and learning disabilities. Conservative estimates for Tourette syndrome suggest a prevalence rate of 0.1-1.0 per 1000. This syndrome is inherited in a sex-influenced autosomal dominant pattern with either chronic multiple tic disorder or obsessive-compulsive disorder as alternative phenotypes of the putative gene. Current evidence continues to support a pathophysiologic mechanism involving synaptic neurotransmission, with the dopaminergic system as a primary candidate. Therapeutically, it is essential to clarify whether a patient's problems are related to tics or associated behavioral difficulties. Pharmacotherapy for motor and phonic tics is strictly symptomatic and should be reserved for those with functionally disabling symptoms. A comprehensive individualized treatment program is often required in the care of individuals with tic disorders.

Behavior↗

[Neuropsychological performance in ADHD and tic-disorders: a prospective 1-year follow-up].

Inhibitory deficits in the brain play a major role in the pathophysiology of ADHD and tic disorders. Impairment of executive functions (EF) may be directly linked to these abnormalities. Hence, parallel to an amelioration of symptomatology in ADHD and in tic disorders a decline of EF impairment should be observed. This phenomenon would indirectly suggest that there exist inhibitory deficits in these disorders. Age and IQ matched samples of boys one with ADHD (n = 15; age: M = 128 months SD = 16, IQ: M = 101 SD = 11), the other with tic disorders (n = 14; age: M = 132 months SD = 16; IQ: M = 101 SD = 10) have been compared with a group of controls (n = 23; age: M = 131 months SD = 13; IQ: M = 108 SD = 7). Reexamination has been performed after about one year. In ADHD EF deficits found at the beginning were decreased at the second testing after about one year when symptomatology had ameliorated. The boys with tic disorders revealed no differences compared to controls and no changes over time. The reduction of EF deficits with time in boys with ADHD is best explained by neuronal maturational processes, which are very intensive in the children with ADHD of this age.

Attention↗

A computer-aided diagnosis for distinguishing Tourette's syndrome from chronic tic disorder in children by a fuzzy system with a two-step minimization approach.

Tourette's syndrome, no longer considered as a rare and unusual disease, is the most severe tic disorder in children. Early differential diagnosis between Tourette's syndrome and chronic tic disorder is difficult but important because proper and early medical therapy can improve the child's condition. Brain single-photon emission computed tomography (SPECT) perfusion imaging with technetium-99m hexamethylpropylene amine oxime is a method to distinguish these two diseases. In this paper, a fuzzy system called characteristic-point-based fuzzy inference system (CPFIS) is proposed to help radiologists perform computer-aided diagnosis (CAD). The CPFIS consists of SPECT-volume processing, input-variables selection, characteristic-points (CPs) derivation, and parameter tuning of the fuzzy system. Experimental results showed that the major fuzzy rules from the obtained CPs match the major patterns of Tourette's syndrome and chronic tic disorder in perfusion imaging. If any case that was diagnosed as chronic tic by the radiologist but as Tourette's syndrome by the CPFIS was taken as Tourette's syndrome, then the accuracy of the radiologist was increased from 87.5% (21 of 24) without the CPFIS to 91.7% (22 of 24) with the CPFIS. All 17 cases of Tourette's syndrome, which is more severe than chronic tic disorder, were correctly classified. Although the construction and application process of the proposed method is complete, more samples should be used and tested in order to design a universally effective CAD without small sample-size concerns in this research.

Algorithms↗

[Study on the prevalence of tic disorders in schoolchildren aged 7-16 years old in Wenzhou].

OBJECTIVE: To study the epidemiological features of tic disorders (TD) among schoolchildren in Wenzhou area. METHODS: Stratified cluster sampling was carried out to investigate TD in 9742 schoolchildren aged 7 to 16 years old in Wenzhou. RESULTS: The average prevalence rate of TD among school-age children was 104/10 000 (166/10 000 for males, 29/10 000 for females). There was a significantly higher prevalence rate for males than that for females (chi(2) = 43.96, P < 0.001, prevalence ratio = 5.7, prevalence ratio 95% CI: 3.20 - 10.30). The prevalence rates of clinical subtypes in males was significantly higher than that of females while pupils was significantly higher than that in high school students (chi(2) = 11.33, P < 0.01, prevalence ratio = 2.2, prevalence ratio 95% CI: 1.37 - 3.43). Prevalence rate of transient tic disorders (TTD), chronic motor vocal tic disorder (CMVTD), tourette syndrome (TS) were 34/10 000, 27/10 000 and 43/10 000 respectively with the highest among 9-10 years old group. The mean onset age of TD was 8.5 +/- 2.8 years. The peak of onset was among 6-10 year olds. The rate of delayed diagnosis of the disorders was 69.3% and the median in delayed diagnosis was 1.0 year. CONCLUSION: TD is a common disease with high rate of misdiagnoses among schoolchildren in Wenzhou area. Physicians and population should be trained to identify the syndromes and to practice correct diagnosis and effective treatment as early as possible.

Adolescent↗

Infection: a stimulus for tic disorders.

The object of this study was to investigate the potential association of infections, especially group A hemolytic streptococcal infection, with the abrupt onset/exacerbation of tics or obsessive-compulsive behaviors. A structured clinical interview was used to evaluate 80 consecutive children, 5-17 years of age, with a diagnosis of tic disorder. Forty-two patients (53%) described a sudden, explosive onset or worsening of tic symptoms; 15 of these 42 had their exacerbation historically associated with an infection, nine of the 15 specifically with a streptococcal infection. Comparisons between those nine individuals and the remainder of the study population are presented. The results of this study reveal that descriptions of an abrupt tic onset or exacerbation are not uncommon in children with tic disorders; approximately 11% of children with tic disorders described abrupt changes of tic behavior within a 6-week period after a streptococcal infection.

Adolescent↗

Anticonvulsant medications: an iatrogenic cause of tic disorders.

A review of the relationship between anticonvulsant medications and tics is presented. Data on 5 patients in whom anticonvulsants, either caused tics or exacerbated existing tic disorders is discussed. Discontinuation of the medication resulted in a decrease in the frequency of tickings in all patients. The effects of anticonvulsants on the reticular system are discussed. It is felt that it may be important for clinicians to consider carefully the use of barbiturate anticonvulsants, especially phenobarbital, in children with tics or a family history of tics. Tic disorders caused or exacerbated by exposure to anticonvulsant medications appear to be more common than previously reported, and in some patients the tics may not remit with discontinuation of the medication.

Anticonvulsants↗