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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↗

Assertiveness training in the treatment of a child's tics.

Tic activity has long been an area for clinical intervention by behavior therapists. Most techniques have involved approaches that require direct focusing on the tic itself (e.g. habit reversal). For some people, however, such a direct focus may not be clinically appropriate. This article describes a child who, in addition to suffering from tics, was also extremely unassertive. It was observed that unassertive behavior often preceded tic activity. Assertiveness training provided the child with a self-control technique with which he was able to control and eventually eliminate his tic activity.

Assertiveness↗

Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome.

OBJECTIVE: A previous study showed no effect of 1Hz repetitive transcranial magnetic stimulation (rTMS) on tics in Gilles de la Tourette Syndrome (GTS). We modified the rTMS protocol in order to investigate some of the possible methodological reasons for the negative outcome in that study. METHODS: In a single blinded placebo-controlled cross-over study in five GTS patients without obsessive compulsive disorder we probed whether longer trains (1800 stimuli) of 1 Hz pre-motor cortex rTMS at 80% of active motor threshold and application to both hemispheres can improve tics in GTS. This was measured with the Yale Global Tic severity rating scale, the MOVES self-rating scale and video analysis. RESULTS: We found no significant effect of either left pre-motor cortex stimulation alone, or left pre-motor followed by right pre-motor cortex stimulation. CONCLUSIONS: These results suggest that the rTMS protocol used in this study is not useful for the treatment of tics in GTS. SIGNIFICANCE: rTMS protocols need to be modified substantially in order to explore their potential for the treatment of tics in GTS.

Adult↗

Amisulpride related tic-like symptoms in an adolescent schizophrenic.

Tic disorders can be effectively treated by atypical antipsychotics such as risperidone, olanzapine and ziprasidone. However, there are two case reports that show tic-like symptoms, including motor and phonic variants, occurring during treatment with quetiapine or clozapine. We present a 15-year-old girl schizophrenic who developed frequent involuntary eye-blinking movements after 5 months of amisulpride treatment (1000 mg per day). The tic-like symptoms resolved completely after we reduced the dose of amisulpride down to 800 mg per day. However, her psychosis recurred after the dose reduction. We then placed her on an additional 100 mg per day of quetiapine. She has been in complete remission under the combined medications for more than one year and maintains a fair role function. No more tic-like symptoms or other side effects have been reported. Together with previously reported cases, our patient suggests that tic-like symptoms might occur in certain vulnerable individuals during treatment with atypical antipsychotics such as quetiapine, clozapine, or amisulpride.

Adolescent↗

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↗

Tourette syndrome. Clinical rating and quantitative assessment of tics.

An adequate rating scale for the measurement of tic severity must account for the multiple motor and phonic tics that increase and decrease over time. Available rating scales for Tourette syndrome have used historical information, direct observation, or both. Videotapes provide an objective means to quantify tics over time in a controlled environment. Videotapes also can be viewed multiple times for careful review of tic frequency and distribution. A unified rating scale, which integrates all elements of tic assessment is being developed, but is not currently available.

Humans↗

Tics and Tourette's syndrome in childhood.

Childhood tics are multidimensional in nature. The dimensions run along various continuums, including duration of symptoms (from fewer than 1 year to lifelong), intensity of symptoms (from mild to severe), frequency of symptoms (from rare to constant), variety of symptoms (from single motor groups/single phonic tic to multiple occurrences of both types), complexity of tics (from simple motor/phonic tic to multiple motor groups or the production of multiple sounds, including involuntary phrases), response to treatment (from good to minimal or no response), and comorbid psychiatric disorders (from none to multiple). This review describes these dimensions and their relationships to the current diagnostic scheme for tic disorders.

Child↗

Stuttering and tics in twins.

A total of 63 twin pairs (22 MZ and 41 DZ), with one or both members affected by not organic stuttering and/or tics, have been drawn out of the Mendel Institute's twin file. Concordance of stuttering was observed in 10:12 MZ, but only in 2:19 DZ twin pairs; concordance of tics in 6:10 MZ and in 2:22 DZ twin pairs. Stuttering did not come out significantly associated either with other disturbances of language or with an IQ under the average; almost always it was possible to find out a precipitating factor. Significant relations between stuttering and tics could not be stated. Sex ratio, obtained regarding any affected subject separately, clearly turned in favour of males both in stuttering (32:12) and in tics (27:12). Stutterers and left-handers incidence in the families of stuttering subjects appeared significant in comparison with families of subjects with tics.

Adolescent↗

[Transcranial magnetic stimulation in child and adolescent psychiatry: excitability of the motor system in tic disorders and/or attention deficit hyperactivity disorders].

Motor system excitability can be investigated in vivo by means of single and paired pulse transcranial magnetic stimulation (TMS). Whereas the cortical silent period reflects the general degree of inhibitory mechanisms mainly within the sensorimotor loop, intracortical excitability measures the focused degree of inhibitory and facilitatory mechanisms within the motor cortex. In child and adolescent psychiatric disorders with uncontrollable motor behavior such as tics in tic disorder or motoric hyperactivity in attention deficit hyperactivity disorder (ADHD), different dysfunctional patterns of motor system excitability could be demonstrated compared to age-matched healthy controls: (1) In tic disorder, a shortened cortical silent period was observed, providing evidence of deficient inhibitory mechanisms within the sensorimotor loop, probably primarily at the level of the basal ganglia. (2) In ADHD, a decreased intracortical inhibition was found, probably reflecting deficient inhibitory mechanisms within the motor cortex (but enhancement of intracortical inhibition after oral intake of 10 mg methylphenidate). In order to investigate neurophysiological aspects of comorbidity, (3) motor system excitability was also measured in children with combined ADHD and tic disorder. The findings of a reduced intracortical inhibition as well as a shortened cortical silent period in these comorbid children provide evidence of additive effects at the level of motor system excitability. These decreased inhibitory mechanisms within the entire sensorimotor loop and especially the motor cortex could be essential neurobiological substrates of the deficient inhibitory motor control and regulation, respectively, in tic disorder and ADHD.

Adolescent↗

Methylphenidate in hyperactive boys with comorbid tic disorder: II. Short-term behavioral effects in school settings.

In this study, 11 prepubertal hyperactive boys with tic disorder received placebo and three doses of methylphenidate (0.1, 0.3, and 0.5 mg/kg) for 2 weeks each, under double-blind conditions. Each boy was observed for approximately 20 hours in the school setting (classroom seatwork activities, lunchroom, and playground). Results showed that methylphenidate effectively suppressed hyperactive/disruptive behaviors in the classroom and physical aggression in the lunchroom and on the playground. Methylphenidate also reduced the occurrence of vocal tics in the classroom and the lunchroom. None of the motor tic measures revealed drug effects, but the lowest mean rate of motor tics occurred on the 0.3 mg/kg dose. On an operationally defined minimal effective dose, only one boy experienced motor tic exacerbation.

Attention Deficit Disorder with Hyperactivity↗

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↗

Trigeminal numbness and tic relief after microvascular decompression for typical trigeminal neuralgia.

OBJECTIVE: After most operative treatments for trigeminal neuralgia, long-term tic relief is closely correlated with postoperative numbness in the trigeminal distribution. Microvascular decompression (MVD) is proposed to relieve tic through a nontraumatic mechanism. We investigated the relationship between postoperative trigeminal numbness and tic relief in a large, prospectively followed cohort of patients treated with MVD for typical trigeminal neuralgia. METHODS: Of 1204 patients who underwent MVD for typical tic during a 20-year period, 522 had single MVDs on a single side, had not undergone ablative trigeminal procedures before or after MVD, and were still being followed in 1994. In 1994, patients graded facial numbness using a questionnaire (response rate, 92%) with a 5-point scale. Multivariate Cox and logistic regression methods were used. The analyses were adjusted for the time that had passed between the performance of MVD and the completion of the questionnaire (minimum, 2 yr). RESULTS: Seventeen percent of patients reported some degree of persistent facial numbness. Decompression of a vein at MVD (odds ratio, 2.5) and failure to find compression by the superior cerebellar artery (odds ratio, 2.0) independently predicted postoperative facial numbness, which in turn predicted postoperative burning and aching facial pain (odds ratio, 5.2-5.9). A trend toward worse outcome was noted in patients with numb faces (P = 0.3). Similar findings were noted in subgroups of patients in whom the superior cerebellar artery was decompressed at MVD (n = 381) and in whom a superior cerebellar artery with no vein was found (n = 120). In the latter subgroup, facial numbness (5.8% of patients) significantly predicted worse long-term outcome (P = 0.03). CONCLUSION: We found no evidence that postoperative trigeminal numbness predicts relief of typical tic after MVD. Trigeminal numbness was related to operative findings at MVD and predicted postoperative burning and aching facial pain. To minimize postoperative facial dysesthesia, trauma to the trigeminal root during MVD should be avoided when possible.

Decompression, Surgical↗

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↗

Personal constructs associated with tics.

Thirteen subjects experiencing chronic tics kept diaries noting frequency, intensity and degree of control of their tic during their daily routines for one week. Three examples of high-, medium- and low-risk situations were chosen as elements and, using a modified form of Kelly's repertory grid, bipolar constructs were elicited by comparing the three types of situations. Principal dimensions extracted from INGRID analyses differed across individuals but related to three principal areas; self-image, degree of task involvement and type of task demand. Feelings of impatience and frustration frequently accompanied tic onset. Subjects' cognitive evaluations of their tic situations may be important in tic management.

Adult↗

The relationship between eye-winking tics, frequent eye-blinking and blepharospasm.

A family is reported in which three generations were affected with eye-winking tics and/or blepharospasm. The proband developed eye-winking tics in childhood and then developed excessive blinking progressing to blepharospasm by the age of 21 years. His mother presented with Meige's syndrome and spasmodic torticollis at the age of 59 years; his uncle had blinked excessively from his early forties. His eldest son developed an eye-winking tic with facial grimacing at the age of 8 years, and in another son, a self-limiting period of eye-blinking occurred at the age of 4 years. The recovery cycle of the blink reflex was abnormal in all three generations. Three other children with eye-winking tics have a parent or close relative with frequent eye-blinking or blepharospasm. Five patients with adult-onset blepharospasm or Meige's syndrome are also described who had excessive eye-blinking dating back to childhood. It is suggested that eye-winking tics, frequent blinking and blepharospasm may share common pathophysiological mechanisms; the clinical expression may be age-related.

Adolescent↗

A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.

OBJECTIVE: This study evaluated the efficacy and safety of guanfacine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). METHOD: Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. RESULTS: Thirty-four medication-free subjects (31 boys and three girls with a mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, guanfacine was associated with a mean improvement of 37% in the total score on the teacher-rated ADHD Rating Scale, compared to 8% improvement for placebo. Nine of 17 subjects who received guanfacine were blindly rated on the Clinical Global Improvement scale as either much improved or very much improved, compared with none of 17 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 27% in the guanfacine group and 21% in the placebo group, not a significant difference. On the Continuous Performance Test, commission errors decreased by 22% and omission errors by 17% in the guanfacine group, compared with increases of 29% in commission errors and of 31% in omission errors in the placebo group. Tic severity decreased by 31% in the guanfacine group, compared to 0% in the placebo group. One guanfacine subject with sedation withdrew at week 4. Guanfacine was associated with insignificant decreases in blood pressure and pulse. CONCLUSIONS: Guanfacine appears to be a safe and effective treatment for children with tic disorders and ADHD.

Adolescent↗

A placebo-controlled study of lofexidine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.

This study evaluated the efficacy and safety of Lofexidine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with lofexidine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. Fourty-four medication-free subjects (41 boys and three girls; mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, lofexidine was associated with a mean improvement of 41% in the total score on the teacher-rated ADHD Rating Scale compared to 7% improvement for placebo. Eleven of 22 subjects who received lofexidine were blindly rated on the Clinical Global Scale-Improvement as either much improved or very much improved compared to none of 22 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 29% in the lofexidine group and 18% in the placebo group, which was not a significant difference. On the Continuous Performance Test, commission errors decreased by 25% and omission errors by 20% in the lofexidine group, compared with increases of 33% in commission errors and of 36% in omission errors in the placebo group. Tic severity decreased by 27% in the lofexidine group, compared to 0% in the placebo group. One lofexidine subject with sedation withdrew at week 4. Lofexidine was associated with insignificant decreases in blood pressure and pulse. Lofexidine appears to be a safe and effective treatment for children with tic disorders and ADHD.

Adolescent↗

Occurrence of tics in Asperger's syndrome and autistic disorder.

Asperger's syndrome is a condition in the autistic spectrum in which language development is normal. Patients with Asperger's syndrome frequently exhibit repetitive movements (stereotypies), and can have motor and phonic tics in addition to other behavioral abnormalities. We present 12 patients with autistic spectrum disorders who were referred to our Movement Disorders Clinic for evaluation of tics. Eight of the 12 had normal language development and therefore met criteria for Asperger's syndrome. All patients exhibited stereotypic movements; in addition, seven had tics and six of these met diagnostic criteria for Tourette syndrome. Of the six patients with clinical features of both Asperger's syndrome and Tourette syndrome, three had severe congenital sensory deficits. The autistic patients in our series were clinically heterogeneous and though tics were clearly present, other aberrant movements demonstrated by them were harder to classify. Our series confirms the wide range of clinical manifestations in Asperger's syndrome and autism, including tics and other features of Tourette syndrome. Furthermore, it suggests that sensory deprivation contributes to the development of adventitious movements in this population.

Adolescent↗