Tourette syndrome: clinical features, pathophysiology, and treatment

Abstract

Tourette syndrome is a chronic neurodevelopmental disorder characterised by motor and phonic tics that can substantially diminish the quality of life of affected individuals. Evaluating and treating Tourette syndrome is complex, in part due to the heterogeneity of symptoms and comorbidities between individuals. The underlying pathophysiology of Tourette syndrome is not fully understood, but recent research in the past 5 years has brought new insights into the genetic variations and the alterations in neurophysiology and brain networks contributing to its pathogenesis. Treatment options for Tourette syndrome are expanding with novel pharmacological therapies and increased use of deep brain stimulation for patients with symptoms that are refractory to pharmacological or behavioural treatments. Potential predictors of patient responses to therapies for Tourette syndrome, such as specific networks modulated during deep brain stimulation, can guide clinical decisions. Multicentre data sharing initiatives have enabled several advances in our understanding of the genetics and pathophysiology of Tourette syndrome and will be crucial for future large-scale research and in refining effective treatments.

Figure 1.. Variability of Tourette syndrome and associated comorbidities.

(A) Child with common simple motor and phonic tics (eg, shrugging shoulders and winking). (B) Adolescent with a combination of complex motor tics (eg, pulling hair) and complex phonic tics (eg, saying “donť trip”), and emerging behavioural features including attention deficit hyperactivity disorder (ADHD) depicted as swirling thoughts. (C) Although tics become less severe after adolescence in most cases, complex motor tics, phonic tics, and behavioural features can persist into adulthood in some individuals. This adult example experiences complex motor tics (eg, hand gestures, followed by snapping fingers and scatching their head) and phonic tics (eg, humming repetitively). (D) Psychiatric and behavioural comorbidities can be the primary symptoms (with or without tics) in some individuals and can include obsessive-compulsive disorder (eg, checking behaviours, as depicted in the thought cloud) or mood disorders (eg, depression or anxiety, depicted as darkness in the thought cloud). Although individuals of various ages are depicted, tics and comorbidities do not follow a single time course; the natural history of Tourette syndrome and the severities and types of symptoms differ widely among patients of various ages.

Figure 2.. Models of Tourette syndrome pathophysiology.

(A) Cortico-basal ganglia networks and Tourette syndrome clinical characteristics. Distinct cortico-basal ganglia networks are related to tics (sensorimotor network [orange]) and comorbidities (associative and limbic networks [grey]) in Tourette syndrome. (B) Neuropathological underpinnings of Tourette syndrome: stereological cellular count in post-mortem tissue revealed different cellular distributions in the basal ganglia of individuals with Tourette syndrome (3 patients, mean [SEM] age 42·0 [11·9] years) compared with controls (5 healthy controls, mean [SEM] age 60·0 [9·7] years; left panel), with fewer inhibitory GABAergic cells (red circle) and cholinergic cells (green hexagon) within the striatum in Tourette syndrome (5 patients, mean [SEM] age 43·0 [3·6] years) compared with 5 controls mean [SEM] age 61·8 [4·3] years (right panel). (C) Model of relationship between premonitory urges and tics: abnormal interoceptive information processing (insular cortex; blue area) and exteroceptive processing (sensorimotor cortex; pink areas) results in genesis of premonitory urges (insular cortex), leading to action initiation (via anterior cingulate cortex; green area) and subsequent tic execution (via cortico-basal ganglia sensorimotor network (as shown in A). Acc=anterior cingulate cortex. Ach+=cholinergic interneurons of the striatum. ADHD=attention deficit hyperactivity disorder. GABA Pav+=GABAergic parvalbumin-positive interneurons of the striatum. GPi=globus pallidus internus. GPe=globus pallidus externus. Ins=insular cortex. MSN=medium spiny neurons. OCD=obsessive-compulsive disorder. OFC=orbitofrontal cortex. SM=sensorimotor cortex. B (left) has been adapted from Kalanithi and colleagues and B (right) from Kataoka and colleagues.

Figure 3.. Neurosurgical targets for deep brain stimulation in Tourette syndrome and structural networks associated with tic improvement.

Adapted with permission from Johnson and colleagues.^, Active contact locations (represented by spheres) varied across patients with Tourette syndrome implanted with deep brain stimulation in (A) the pallidum (30 patients; yellow represents contacts targeted to amGPi and green pvGPi) and (B) the centromedian regions of the thalamus (33 patients; red contacts targeted to centromedian regions of the thalamus). (C) With pallidal deep brain stimulation (of either the amGPi or pvGPi), higher structural connectivity from the site of stimulation to limbic and associative networks was positively correlated with a reduction in tic severity (left). With thalamic deep brain stimulation, higher structural connectivity from the site of stimulation to sensorimotor networks was positively correlated with a reduction in tic severity (right). CM=centromedian nucleus. GPe=globus pallidus externus. GPi=globus pallidus internus. Pf=parafascicular nucleus. Voi=ventro-oralis internus.