Diagnosis and Management of Functional Tic-Like Phenomena.

Over the past 3 years, a global phenomenon has emerged characterized by the sudden onset and frequently rapid escalation of tics and tic-like movements and phonations. These symptoms have occurred not only in youth known to have tics or Tourette syndrome (TS), but also, and more notably, in youth with no prior history of tics. The Tourette Association of America (TAA) convened an international, multidisciplinary working group to better understand this apparent presentation of functional neurological disorder (FND) and its relationship to TS. Here, we review and summarize the literature relevant to distinguish the two, with recommendations to clinicians for diagnosis and management. Finally, we highlight areas for future emphasis and research.

Pharmacologic Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Tourette and Tic Disorders.

A complete and comprehensive medical and psychiatric evaluation is necessary to delineate tic symptoms from attention-deficit/hyperactivity disorder, and to prioritize the most problematic symptoms for intervention. Stimulants are the recommended first-line pharmacotherapy to treat attention-deficit/hyperactivity disorder symptoms in patients with tic disorders. Comprehensive behavioral intervention for tics is an effective behavioral therapy that is generally considered the first-line treatment of persistent tic disorders. α-Agonists can be added to stimulants if tics increase or be used as monotherapy to target attention-deficit/hyperactivity disorder and tics. Atomoxetine is also an excellent option to treat attention-deficit/hyperactivity disorder and tics.

Tic disorders in children and adolescents: does the clinical presentation differ in males and females? A report by the EMTICS group.

Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (n = 709, 23.3% females) recruited as part of the European Multicenter Tics in Children Study (EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females.

Allopregnanolone: The missing link to explain the effects of stress on tic exacerbation?

The neurosteroid allopregnanolone (3α-hydroxy-5α-pregnan-20-one; AP) elicits pleiotropic effects in the central nervous system, ranging from neuroprotective and anti-inflammatory functions to the regulation of mood and emotional responses. Several lines of research show that the brain rapidly produces AP in response to acute stress to reduce the allostatic load and enhance coping. These effects not only are likely mediated by GABAA receptor activation but also result from the contributions of other mechanisms, such as the stimulation of membrane progesterone receptors. In keeping with this evidence, AP has been shown to exert rapid, potent antidepressant properties and has been recently approved for the therapy of moderate-to-severe postpartum depression. In addition to depression, emerging evidence points to the potential of AP as a therapy for other neuropsychiatric disorders, including anxiety, seizures, post-traumatic stress disorder and cognitive problems. Although this evidence has spurred interest in further therapeutic applications of AP, some investigations suggest that this neurosteroid may also be associated with adverse events in specific disorders. For example, our group has recently documented that AP increases tic-like manifestations in several animal models of tic disorders; furthermore, our results indicate that inhibiting AP synthesis and signalling reduces the exacerbation of tic severity associated with acute stress. Although the specific mechanisms of these effects remain partially elusive, our findings point to the possibility that the GABAergic activation by AP may also lead to disinhibitory effects, which could interfere with the ability of patients to suppress their tics. Future studies will be necessary to verify whether these mechanisms may apply to other externalising manifestations, such as impulse-control problems and manic symptoms.