Kimberly A. Lynch

Course of tic severity in Tourette syndrome : The first two decades

Objective. Prevalence studies indicate a 10-fold higher rate of Tourette syndrome (TS) among children compared with adults. The purpose of this investigation was to examine the course of tic severity during the first 2 decades of life. Method. A birth-year cohort of 42 TS patients followed at the Yale Child Study Center was recontacted an average of 7.3 years after their initial clinical evaluation. Data concerning the onset and course of tic severity until 18 years of age were available on 36 TS patients. A variety of statistical techniques were used to model aspects of the temporal patterning of tic severity. Results. Mean (SD) tic onset at 5.6 (2.3) years of age was followed by a progressive pattern of tic worsening. On average, the most severe period of tic severity occurred at 10.0 (2.4) years of age. In eight cases (22%), the frequency and forcefulness of the tics reached a severe level during the worst-ever period such that functioning in school was impossible or in serious jeopardy. In almost every case this period was followed by a steady decline in tic severity. By 18 years of age nearly half of the cohort was virtually tic-free. The onset of puberty was not associated with either the timing or severity of tics. Conclusions. A majority of TS patients displayed a consistent time course of tic severity. This consistency can be accurately modeled mathematically and may reflect normal neurobiological processes. Determination of the model parameters that describe each patients course of tic severity may be of prognostic value and assist in the identification of factors that differentially influence the course of tic severity.

Guanfacine Treatment of Comorbid Attention-Deficit Hyperactivity Disorder and Tourette's Syndrome: Preliminary Clinical Experience

OBJECTIVE Many children with Tourettes syndrome (TS) are handicapped more by difficulties with inattention, impulsivity, and hyperactivity than by their tics. However, stimulant medications used to treat attention-deficit hyperactivity disorder (ADHD) can exacerbate tics. Guanfacine is an alpha 2-adrenergic agonist that may have beneficial effects on attention, without the hypotensive or sedative effects of clonidine, which is often used as an alternative to stimulants. METHOD An open-label study of guanfacine was performed in 10 children with TS+ADHD, aged 8 to 16 years. The duration of follow-up was 4 to 20 weeks, and the majority of subjects were treated with 1.5 mg/day. Ratings of tic severity and ADHD symptoms were obtained using the Yale Global Tic Severity Scale (YGTSS), the Tic Symptom Self Report (TSSR), and the Conners Parent Rating Scale. In addition, blind Continuous Performance Tests (CPTs) were performed at baseline and at two follow-up intervals in eight subjects. RESULTS Guanfacine was associated with significant decreases in both commission errors (p < .02) and omission errors (p < .01) on the CPT. In addition, guanfacine caused a significant decrease in severity of motor (p < .02) and phonic (p < .02) tics as measured by the TSSR and the YGTSS, respectively. The most common side effects were transient sedation and headaches. CONCLUSION Guanfacine may provide a safe alternative therapy for children with ADHD in the presence of tics. Future double-blind, controlled trials should be undertaken.

Risperidone Treatment of Children and Adolescents with Chronic Tic Disorders: A Preliminary Report

OBJECTIVE The purpose of this trial was to investigate the short-term safety and efficacy of risperidone in the treatment of chronic tic disorders in children and adolescents. METHOD This was an 11-week open-label trial and included seven subjects (five boys and two girls) with a mean age of 12.9 +/- 1.9 years. The sample included five patients with Tourettes syndrome and two with chronic motor tic disorder. The children were seen at baseline and for two follow-up visits. Three children had a comorbid diagnosis of obsessive-compulsive disorder (OCD). RESULTS Clinical response, as measured by the Yale Global Tic Severity Scale and the Childrens version of the Yale-Brown Obsessive Compulsive Scale, revealed a statistically significant reduction in tic scores ranging from 26% [corrected] to 66%. One of three children with comorbid OCD showed substantial improvement; the other two subjects showed no change. The most frequent side effect was weight gain, which ranged from 8 to 14 lb. CONCLUSIONS Risperidone, a neuroleptic with both serotonin- and dopamine-blocking properties, appears to be effective in reducing tic frequency and intensity in children and adolescents with chronic tic disorders.

A preliminary study of tryptophan depletion on tics, obsessive-compulsive symptoms, and mood in Tourette's syndrome

Tourettes syndrome (TS) is a chronic neuropsychiatric disorder of childhood onset characterized by motor and phonic tics that wax and wane in severity, as well as by symptoms of obsessive-compulsive disorder (OCD) (Pauls and Leckman 1986; Leckman et a1 1992). There have been conflicting reports regarding altered tryptophan (TRP) metabolism and abnormalities in the serotonin (5-HT) system in TS. In one study of 7 TS subjects and 10 normal controls, no group differences in whole blood TRP were seen (Dursun et a1 1994); however, in two larger studies, whole blood TRP was lower in the TS group (Leckman et a1 1984; Comings 1990). Cerebrospinal fluid (CSF) levels of TRP have also been reported to be slightly but nonsignificantly lower in TS subjects, while within the TS group, CSF TRP was inversely related to tic severity (Leckman et a1 1995). Finally, a postmortem study found lower TS group mean levels of 5-HT and 5-hydroxy indoleacetic acid (5-HIAA), the major metabolite of 5-HT, in nearly all subcortical brain regions examined (Anderson et a1 1992). A role for altered TRP metabolism or underactivity of the brain 5-HT system in the pathophysiology of TS is also suggested by the emergence of transient motor tics in a patient with OCD participating in an acute TRP depletion study (Goodman WK, personal communication). In addition, there is a report of the successful treatment of stimulant-induced tics with oral TRP (Chandler et a1 1989). We therefore elected to systematically study the effects of acute TRP depletion in a group of subjects with TS.