Tourette syndrome

Clinic

• TS is a common neurodevelopmental disease that begins in childhood or adolescence.
• It is characterized by behavioral and Motor / Vocal / Phonic tic
• It is commonly believed that pathologies involving limbic, associative and motor circuits of the basal ganglia
• Tourette syndrome and OCD are caused by dysfunction of the non-motor loops of basal ganglia circuits
• Common tics are blinking, coughing, throat clearing, sniffing, and facial movements.
• Tourette's is at the more severe end of a spectrum of tic disorders. The tics often go unnoticed by casual observers.

• Tourette's was once regarded as a rare and bizarre syndrome and has popularly been associated with coprolalia

Related disese

• ADHD
• OCD

Characteristics

• TS's tics are nonrhythmic, often preceded by an unwanted urge or sensation in the affected muscles and can sometimes be suppressed temporarily,
• Its tics are characteristically change in location, strength, and frequency.
• In 90% tic are similar to the urge to sneeze or scratch an itch.
• Tics are described as semi-voluntary or "unvoluntary", rather than specifically involuntary; they may be experienced as a voluntary, suppressible response to the unwanted premonitory urge.

• Complex speech tics:
  • Coprolalia is the spontaneous utterance of socially objectionable or taboo words or phrases. (10%)
  • Palilalia (Repeating one's own words)
• Complex motor tics include
  • Copropraxia (Obscene / Forbidden gestures, or inappropriate touching)
  • Echopraxia (Repetition or imitation of another person's actions)
  • Palipraxia (Repeating one's own movements)

Onset and progression

There is no typical case of Tourette syndrome, but the age of onset and the severity of symptoms follow a fairly reliable course. Although onset may occur anytime before eighteen years, the typical age of onset of tics is from five to seven, and is usually before adolescence. A 1998 study from the Yale Child Study Center showed that tic severity increased with age until it reached its highest point between ages eight and twelve. Severity declines steadily for most children as they pass through adolescence, when half to two-thirds of children see a dramatic decrease in tics.

In people with TS, the first tics to appear usually affect the head, face, and shoulders, and include blinking, facial movements, sniffing and throat clearing. Vocal tics often appear months or years after motor tics but can appear first. Among people who experience more severe tics, complex tics may develop, including "arm straightening, touching, tapping, jumping, hopping and twirling". There are different movements in contrasting disorders (for example, the autism spectrum disorders), such as self-stimulation and stereotypies.

The severity of symptoms varies widely among people with Tourette's, and many cases may be undetected. Most cases are mild and almost unnoticeable; many people with TS may not realize they have tics. Because tics are more commonly expressed in private, Tourette syndrome may go unrecognized, and casual observers might not notice tics. Most studies of TS involve males, who have a higher prevalence of TS than females, and gender-based differences are not well studied; a 2021 review suggested that the characteristics and progression for females, particularly in adulthood, may differ and better studies are needed.

Most adults with TS have mild symptoms and do not seek medical attention. While tics subside for the majority after adolescence, some of the "most severe and debilitating forms of tic disorder are encountered" in adults. In some cases, what appear to be adult-onset tics can be childhood tics re-surfacing.

Co-occurring conditions

André Malraux (center) was a French Minister of Culture, author and adventurer who may have had Tourette syndrome. Because people with milder symptoms are unlikely to be referred to specialty clinics, studies of Tourette's have an inherent bias towards more severe cases. When symptoms are severe enough to warrant referral to clinics, ADHD and OCD are often also found. In specialty clinics, 30% of those with TS also have mood or anxiety disorders or disruptive behaviors. In the absence of ADHD, tic disorders do not appear to be associated with disruptive behavior or functional impairment, while impairment in school, family, or peer relations is greater in those who have more comorbid conditions. When ADHD is present along with tics, the occurrence of conduct disorder and oppositional defiant disorder increases. Aggressive behaviors and angry outbursts in people with TS are not well understood; they are not associated with severe tics, but are connected with the presence of ADHD. ADHD may also contribute to higher rates of anxiety, and aggression and anger control problems are more likely when both OCD and ADHD co-occur with Tourette's.

Compulsions that resemble tics are present in some individuals with OCD; "tic-related OCD" is hypothesized to be a subgroup of OCD, distinguished from non-tic related OCD by the type and nature of obsessions and compulsions. Compared to the more typical compulsions of OCD without tics that relate to contamination, tic-related OCD presents with more "counting, aggressive thoughts, symmetry and touching" compulsions. Compulsions associated with OCD without tics are usually related to obsessions and anxiety, while those in tic-related OCD are more likely to be a response to a premonitory urge. There are increased rates of anxiety and depression in those adults with TS who also have OCD.

Among individuals with TS studied in clinics, between 2.9% and 20% had autism spectrum disorders, but one study indicates that a high association of autism and TS may be partly due to difficulties distinguishing between tics and tic-like behaviors or OCD symptoms seen in people with autism.

Not all people with Tourette's have ADHD or OCD or other comorbid conditions, and estimates of the rate of pure TS or TS-only vary from 15% to 57%; in clinical populations, a high percentage of those under care do have ADHD. Children and adolescents with pure TS are not significantly different from their peers without TS on ratings of aggressive behaviors or conduct disorders, or on measures of social adaptation. Similarly, adults with pure TS do not appear to have the social difficulties present in those with TS plus ADHD.

Among those with an older age of onset, more substance abuse and mood disorders are found, and there may be self-injurious tics. Adults who have severe, often treatment-resistant tics are more likely to also have mood disorders and OCD. Coprolalia is more likely in people with severe tics plus multiple comorbid conditions.

Neuropsychological function

There are no major impairments in neuropsychological function among people with Tourette's, but conditions that occur along with tics can cause variation in neurocognitive function. A better understanding of comorbid conditions is needed to untangle any neuropsychological differences between TS-only individuals and those with comorbid conditions.

Only slight impairments are found in intellectual ability, attentional ability, and nonverbal memory—but ADHD, other comorbid disorders, or tic severity could account for these differences. In contrast with earlier findings, visual motor integration and visuoconstructive skills are not found to be impaired, while comorbid conditions may have a small effect on motor skills. Comorbid conditions and severity of tics may account for variable results in verbal fluency, which can be slightly impaired. There might be slight impairment in social cognition, but not in the ability to plan or make decisions. Children with TS-only do not show cognitive deficits. They are faster than average for their age on timed tests of motor coordination, and constant tic suppression may lead to an advantage in switching between tasks because of increased inhibitory control.

Learning disabilities may be present, but whether they are due to tics or comorbid conditions is controversial; older studies that reported higher rates of learning disability did not control well for the presence of comorbid conditions. There are often difficulties with handwriting, and disabilities in written expression and math are reported in those with TS plus other conditions.

Causes

• The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved. Genetic epidemiology studies have shown that Tourette's is highly heritable, and 10 to 100 times more likely to be found among close family members than in the general population. The exact mode of inheritance is not known; no single gene has been identified, and hundreds of genes are likely involved. Genome-wide association studies were published in 2013 and 2015 in which no finding reached a threshold for significance; a 2019 meta-analysis found only a single genome-wide significant locus on chromosome 13, but that result was not found in broader samples. Twin studies show that 50 to 77% of identical twins share a TS diagnosis, while only 10 to 23% of fraternal twins do. But not everyone who inherits the genetic vulnerability will show symptoms. A few rare highly penetrant genetic mutations have been found that explain only a small number of cases in single families (the SLITRK1, HDC, and CNTNAP2 genes).

Psychosocial or other non-genetic factors—while not causing Tourette's—can affect the severity of TS in vulnerable individuals and influence the expression of the inherited genes. Pre-natal and peri-natal events increase the risk that a tic disorder or comorbid OCD will be expressed in those with the genetic vulnerability. These include paternal age; forceps delivery; stress or severe nausea during pregnancy; and use of tobacco, caffeine, alcohol, and cannabis during pregnancy. Babies who are born premature with low birthweight, or who have low Apgar scores, are also at increased risk; in premature twins, the lower birthweight twin is more likely to develop TS.

Autoimmune processes may affect the onset of tics or exacerbate them. Both OCD and tic disorders are hypothesized to arise in a subset of children as a result of a post-streptococcal autoimmune process. Its potential effect is described by the controversial hypothesis called PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), which proposes five criteria for diagnosis in children. PANDAS and the newer pediatric acute-onset neuropsychiatric syndrome (PANS) hypotheses are the focus of clinical and laboratory research, but remain unproven. There is also a broader hypothesis that links immune-system abnormalities and immune dysregulation with TS.

Some forms of OCD may be genetically linked to Tourette's, although the genetic factors in OCD with and without tics may differ. The genetic relationship of ADHD to Tourette syndrome, however, has not been fully established. A genetic link between autism and Tourette's has not been established as of 2017.

Mechanism

Cortico-striato-thalamo-cortical (CSTC) circuits, or neural pathways, provide inputs to the basal ganglia from the cortex. These circuits connect the basal ganglia with other areas of the brain to transfer information that regulates planning and control of movements, behavior, decision-making, and learning. Behavior is regulated by cross-connections that "allow the integration of information" from these circuits. Involuntary movements may result from impairments in these CSTC circuits, including the sensorimotor, limbic, language and decision making pathways. Abnormalities in these circuits may be responsible for tics and premonitory urges.

The caudate nuclei may be smaller in subjects with tics compared to those without tics, supporting the hypothesis of pathology in CSTC circuits in Tourette's. The ability to suppress tics depends on brain circuits that "regulate response inhibition and cognitive control of motor behavior". Children with TS are found to have a larger prefrontal cortex, which may be the result of an adaptation to help regulate tics. It is likely that tics decrease with age as the capacity of the frontal cortex increases. Cortico-basal ganglia (CBG) circuits may also be impaired, contributing to "sensory, limbic and executive" features. The release of dopamine in the basal ganglia is higher in people with Tourette's, implicating biochemical changes from "overactive and dysregulated dopaminergic transmissions".

Histamine and the H3 receptor may play a role in the alterations of neural circuitry. A reduced level of histamine in the H3 receptor may result in an increase in other neurotransmitters, causing tics. Postmortem studies have also implicated "dysregulation of neuroinflammatory processes".