Differences in Tic Severity Among Adolescent Girls and Boys with Tourette Syndrome During the Pandemic.

Limited data are available regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on adolescents with Tourette syndrome (TS). We sought to compare sex differences in tic severity experienced by adolescents before and during the COVID-19 pandemic. We extracted from the electronic health record and retrospectively reviewed Yale Global Tic Severity Scores (YGTSS) from adolescents (ages 13 through 17) with TS presenting to our clinic before (36 months) and during (24 months) the pandemic. A total of 373 unique adolescent patient encounters (prepandemic: 199; pandemic: 173) were identified. Compared with prepandemic, girls accounted for a significantly greater proportion of visits during the pandemic (p < 0.001). Prepandemic, tic severity did not differ between girls and boys. During the pandemic, compared with girls, boys had less clinically severe tics (p = 0.003). During the pandemic, older girls, but not boys, had less clinically severe tics (ρ =- 0.32, p = 0.003). These findings provide evidence that, regarding tic severity assessed with YGTSS, the experiences of adolescent girls and boys with TS have differed during the pandemic.

Adolescent Gender Differences in Tic- and Non-Tic-Related Impairments in Tourette Syndrome.

We aimed to compare tic- and non-tic-related impairment experienced by adolescent girls and boys (ages 13 through 17) with Tourette syndrome and associations with age. We extracted from the electronic health record child and parental responses to the mini-Child Tourette Syndrome Impairment Scale (mini-CTIM) and other questionnaire data reflective of tic- and non-tic-related impairment of adolescents with Tourette syndrome presenting to our clinic over a 12-month period. We identified a total of 132 (49 female, 83 male) unique adolescent encounters. Mini-CTIM scores did not differ significantly between genders. Tic- and non-tic-related impairment were lower in older boys, but not older girls. Obsessive-compulsive symptoms correlated with parent-reported non-tic-related impairment experienced by adolescent girls but not boys. During adolescence, tic- and non-tic-related impairments may be less likely to improve with age in girls. Future longitudinal studies are needed to confirm this finding.

Pilot Testing Behavior Therapy for Chronic Tic Disorders in Neurology and Developmental Pediatrics Clinics.

Comprehensive Behavioral Intervention for Tics (CBIT) is an efficacious treatment with limited regional availability. As neurology and pediatric clinics are often the first point of therapeutic contact for individuals with tics, the present study assessed preliminary treatment response, acceptability, and feasibility of an abbreviated version, modified for child neurology and developmental pediatrics clinics. Fourteen youth (9-17) with Tourette disorder across 2 child neurology clinics and one developmental pediatrics clinic participated in a small case series. Clinician-rated tic severity (Yale Global Tic Severity Scale) decreased from pre- to posttreatment, z = -2.0, P < .05, r = -.48, as did tic-related impairment, z = -2.4, P < .05, r = -.57. Five of the 9 completers (56%) were classified as treatment responders. Satisfaction ratings were high, and therapeutic alliance ratings were moderately high. Results provide guidance for refinement of this modified CBIT protocol.

The prevalence of neuropsychiatric disorders in Sydenham's chorea.

Sydenham's chorea is a rare movement disorder associated with streptococcal infection. The co-occurrence of neuropsychiatric symptoms has raised the question of whether streptococcal infection could trigger these symptoms without chorea. This study evaluated the prevalence of behavioral diagnoses before, during, and after the onset of chorea in a cohort of children with a history of Sydenham's chorea for whom demographic and clinical data were available. In all, 28 Sydenham's chorea patients were evaluated, with a mean age of 10.3 years. Retrospective analysis was performed for subject demographics, streptococcal titers, and presence of arthritis and carditis. Structured diagnostic interviews were performed on 14 available patients and parents. Streptococcal titers and duration of treatment for chorea were compared between groups. The prevalence of attention deficit hyperactivity disorder before and after chorea was 30 and 37%, respectively. The proportion of children meeting combined, subthreshold, and suprathreshold criteria before, during, and after Sydenham's chorea was 71, 79, and 79% for anxiety and 19, 69, and 44% for depression. Streptococcal antibody titers and duration of treatment did not correlate with attention deficit hyperactivity disorder, depression, or anxiety disorders. During and after the diagnosis of Sydenham's chorea, clinicians should be vigilant for signs and symptoms of anxiety, depression, and attention deficit hyperactivity disorder.

Atomoxetine treatment of ADHD in Tourette syndrome: reduction in motor cortex inhibition correlates with clinical improvement.

OBJECTIVE: In children with attention deficit hyperactivity disorder (ADHD), clinical responses to the selective norepinephrine reuptake inhibitor atomoxetine (ATX) vary. We sought to determine in children with Tourette Syndrome (TS) whether clinical responses correlate with changes in short interval cortical inhibition (SICI). METHODS: Fourteen children, ages 8-16, with ADHD and TS were treated open-label with ATX for one month. ADHD rating scale scores and SICI, measured with paired-pulse transcranial magnetic stimulation (pTMS), were assessed blindly and independently at treatment onset and one month later. RESULTS: Eleven children, mean ADHD rating scale scores 31.8 (SD 8.2) at onset, completed the study. After one month, ADHDRS changes ranged from an increase of 4 points to a decrease (improvement) of 24 points (mean change -9.6, SD 9.1). The changes in ADHDRS scores correlated with reduction in SICI (r=.74, p=.010). CONCLUSIONS: In children with TS, one month of atomoxetine treatment appears to induce correlated improvements in ADHD and, paradoxically, further reductions in cortical inhibition. SIGNIFICANCE: PTMS-evoked SICI in ADHD with TS may be a biomarker of both deficiency and compensatory changes within cortical interneuronal systems. Effective atomoxetine treatment may augment compensatory processes and thereby reduce SICI.

Dopamine transporter genotype influences the physiological response to medication in ADHD.

Attention deficit hyperactivity disorder (ADHD) is a complex, multifactorial disorder characterized by physical hyperactivity and behavioural disinhibition. Short interval cortical inhibition (SICI), measured in motor cortex with transcranial magnetic stimulation, is reduced in ADHD and correlates with symptom severity. However, ADHD medication-induced changes in SICI vary widely among normal individuals and have not been well studied in children with ADHD. Therefore, we undertook this study to measure and compare effects of two ADHD medications, methylphenidate (MPH), a psychostimulant, and atomoxetine (ATX), a selective norepinephrine reuptake inhibitor, on SICI in children with ADHD. In addition, we wished to determine whether a genetic variation in the dopamine transporter (DAT1), a site of action of MPH, could influence the effects of MPH or ATX on SICI. We performed a randomized, double-blind, single-dose, crossover study comparing 0.5 mg/kg MPH with 1.0 mg/kg ATX in 16 children with ADHD, aged 8-17. Seven were homozygotes and 9 heterozygotes for the DAT1 variable number of tandem repeats 10-repeat allele. Medication and genotype effects on SICI were estimated with repeated measures, mixed model regression. We found that MPH and ATX had similar effects on SICI. However, medication effects differed significantly by DAT1 genotype [F(2,13) = 13.04, P = 0.0008]. Both MPH and ATX increased SICI in heterozygotes but not in 10-repeat homozygotes. In conclusion, MPH and ATX have similar effects on SICI in children with ADHD. A genetic variation in DAT1, previously linked to ADHD risk and MPH behavioural responses, influences the neurophysiological effects of both MPH and ATX.

Comparison of the inhibitory and excitatory effects of ADHD medications methylphenidate and atomoxetine on motor cortex.

Stimulant and norepinephrine (NE) reuptake inhibitor medications have different effects at the neuronal level, but both reduce symptoms of attention deficit hyperactivity disorder (ADHD). To understand their common physiologic effects and thereby gain insight into the neurobiology of ADHD treatment, we compared the effects of the stimulant methylphenidate (MPH) and NE uptake inhibitor atomoxetine (ATX) on inhibitory and excitatory processes in human cortex. Nine healthy, right-handed adults were given a single, oral dose of 30 mg MPH and 60 mg ATX at visits separated by 1 week in a randomized, double-blind crossover trial. We used paired and single transcranial magnetic stimulation (TMS) of motor cortex to measure conditioned and unconditioned motor-evoked potential amplitudes at inhibitory (3 ms) and facilitatory (10 ms) interstimulus intervals (ISI) before and after drug administration. Data were analyzed with repeated measures, mixed model regression. We also analyzed our findings and the published literature with meta-analysis software to estimate treatment effects of stimulants and NE reuptake inhibitors on these TMS measures. There were no significant pretreatment differences or effects of treatment order. Both agents produced a significant increase in facilitation and a decrease in inhibition. Effects of ATX and MPH did not differ significantly. Pooled estimates from published studies show similar results for stimulants and NE reuptake inhibitors. In conclusion, in healthy adults, both stimulant and nonstimulant medications for ADHD decrease cortical inhibition and increase cortical facilitation. Cortical inhibition, shown previously to be abnormal in ADHD, may play a key role producing behavioral pathology.

Transcranial magnetic stimulation-evoked cortical inhibition: a consistent marker of attention-deficit/hyperactivity disorder scores in tourette syndrome.

BACKGROUND: Prior case-control studies using Transcranial Magnetic Stimulation (TMS) to probe the neural inhibitory circuitry of Attention Deficit Hyperactivity Disorder (ADHD), Tourette Syndrome (TS), and Obsessive Compulsive Disorder (OCD), have yielded conflicting results. Using regression analysis in TS patients with tics, ADHD, and/or OCD symptoms, all ranging from none to severe, we previously found that TMS-evoked short interval intracortical inhibition (SICI) correlated inversely with ADHD scores. We sought to validate this observation. METHODS: We used regression to estimate the consistency of the association between ADHD symptom scores and TMS-evoked SICI at two separate visits in 28 children and adults with TS. RESULTS: ADHD scores correlated significantly and consistently with SICI, particularly in patients not taking dopamine receptor blockers (r=.60 and r=.58). Hyperactivity, not inattention, scores accounted for ADHD-related variance in SICI. CONCLUSIONS: SICI reliably reflects the severity of hyperactivity in children and adults with TS.

Tourette's Syndrome.

Tourette's syndrome is a childhood-onset neuropsychiatric disorder characterized by multiple motor and vocal tics, frequently accompanied by symptoms of obsessiveness and/or compulsiveness, anxiety, and behavioral impulsivity. Treatment of Tourette's syndrome symptoms should be considered when symptoms cause significant functional or social impairment or pain, as occurs with self-injurious tics. Because comorbid psychiatric disorders, particularly attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder often are present, clinicians must work with affected persons and families and prioritize treatment targets based on the specific disorder-related impairment. Treatment with alpha-2 adrenergic agonists may reduce tics and improve ADHD symptoms. Effective treatment of ADHD, even with stimulant medications, in most cases does not exacerbate tics. Treatment with selective serotonin reuptake inhibitors may reduce obsessive-compulsive and anxiety symptoms, secondarily reducing tics. Neuroleptics and atypical antipsychotics may be used for severe tics, but the risk of neurologic side effects and weight gain is significantly higher. Habit reversal treatment shows promise as a nonpharmacologic intervention. Use of deep brain stimulation has produced benefit in three severely affected adults but should still be considered experimental.