Know Your Brain: Tourette Syndrome
Background
Georges Gilles de la Tourette, circa 1870
After graduating from medical school in 1881, Georges Gilles de la Tourette moved to Paris to refine his medical knowledge by working under one of his idols (and one of the great figures in the history of neurology): Jean-Martin Charcot. While under Charcot’s supervision, Gilles de la Tourette began studying a class of ailments known as the paroxysmal movement disorders. These conditions are characterized by brief episodes of abnormal, involuntary movements (like an unintentional swinging of the arm up in the air). Gilles de la Tourette’s investigation led to the publication of a paper in which he described a particular affliction he called the maladie des tics.
In the paper, Gilles de la Tourette discussed nine patients who had a similar constellation of symptoms that centered around sudden uncontrolled movements or vocalizations. Soon after the publication of Gilles de la Tourette’s paper, Charcot suggested the maladie des tics be renamed after Gilles de la Tourette, leading to the modern-day designation of Tourette syndrome (TS).
Up until the past few decades, it was thought that TS was an exceedingly rare condition. More recent research, however, has identified cases of TS in every country studied. Prevalence estimates vary significantly due to differences in methodology, but the Centers for Disease Control and Prevention (CDC) estimate that around 3 out of every 1,000 children and adolescents aged 6-17 suffers from the condition. For reasons that are not completely clear, boys are about three times more likely to experience TS than girls.
Symptoms
As suggested by Gilles de la Tourette’s original name for the disorder, the hallmark sign of Tourette syndrome (TS) is the appearance of sudden involuntary actions called tics, which might consist of either movements or sounds. The tics are classified as simple or complex. Simple tics involve only one group of muscles (e.g. eye blinking, shoulder shrugging) or one type of sound (e.g. sniffing, throat clearing). Complex motor tics involve coordinated movements (e.g. reaching out to touch someone, bending over), and sometimes can consist of a series of simple tics (e.g. shoulder shrugging combined with a facial grimace). Complex vocal tics may involve the utterance of phrases or sentences, and describe the symptom most frequently linked to TS: coprolalia, or the involuntary use of obscene or inappropriate language. Despite the perception, however, coprolalia is thought to occur in less than 20% of TS cases.
For a patient to be diagnosed with TS, he must have experienced motor and vocal tics before the age of 18, and the tics must have lasted for at least one year after appearing. Typically, tics develop before the age of 10 and become most severe between the ages of 10-12. In most patients, the severity of tics begins to decline after reaching this peak, and by adulthood tics are usually occurring much less frequently or have disappeared altogether. In the most severe cases of TS, however, tics not only continue into adulthood but also may become more debilitating during this time. In some patients, these more severe tics can involve potentially self-harming actions like head-banging or eye-poking.
Tics are often accompanied by what are known as premonitory urges. These are uncomfortable sensations that precede the tic and make the patient feel like the tic is inevitable or necessary. For example, a patient might have the sensation that something is in his throat just before performing a throat-clearing tic. Premonitory urges are often compared to something like feeling the need to sneeze, and thus perhaps it’s not surprising that execution of the tic can cause patients to experience a short-lived sense of relief in satisfying the premonitory urge.
Unfortunately, more than half (and perhaps up to 90%) of patients with TS experience other psychiatric problems as well. The two most common disorders that TS patients suffer from are attention-deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD), although a number of other conditions (e.g. depression, anxiety, learning disability) may also occur simultaneously with TS, making TS that much more challenging to endure.
Basal ganglia (within red square).
The neuroscience of Tourette syndrome
What goes on in the brain to cause Tourette syndrome (TS) is not completely clear, but most hypotheses suggest an important role for a group of structures known as the basal ganglia. The term basal ganglia describes a collection of regions found deep within the cerebral hemispheres that include the: caudate, putamen, globus pallidus, substantia nigra, and subthalamic nucleus.
The basal ganglia form a network that is thought to be involved in a variety of cognitive, emotional, and movement-related functions. Relevant to our discussion of TS, many neuroscientists consider the basal ganglia to play an important role in suppressing unwanted actions, thoughts, and emotions. According to this perspective, there are inhibitory signals sent from select basal ganglia nuclei to the cerebral cortex (primarily by way of the thalamus). These signals work to inhibit a long list of unwanted actions—like your leg involuntarily kicking out in front of you or your head suddenly turning to one side for no apparent reason. But the inhibition can also be more complex, involving things like curbing the desire to have an unnecessary snack or suppressing the impulse to yell at your boss out of anger.
Simply put, inhibitory signaling from the basal ganglia is thought to be critical to ensuring that we don’t do things we don’t really want to do. But in TS, that mechanism of inhibition may become faulty. Neurons in the basal ganglia that are assigned to inhibit unwanted signals from reaching the cortex fail to do so, causing the execution of a habitual action (i.e. tic) that the patient would prefer to suppress.
This failed inhibition may also be coupled with increased activity in motor pathways that generate movements. Thus, TS patients might experience the particularly problematic combination of abnormally high motor activity that is aimed at generating habitual patterns of behavior, along with abnormally low inhibitory activity that typically keeps those patterns of behavior from being acted out.
Causes and treatment
As with most neurodevelopmental disorders, a full understanding of the factors that cause one child to develop TS while others do not remains elusive. Genetics do seem to play an important role, and having a first-degree relative with TS increases one’s risk of developing TS by anywhere from 10 to 100 times. The genetics of TS are complex, however, with a number of gene variants across the genome (rather than one clear TS-gene) being linked to an increased risk of developing the disorder.
But, as with most disorders that have some genetic basis, there are likely other non-genetic factors that play a critical role in the development of TS as well. One hypothesis that has some support suggests that environmental insults in early prenatal or perinatal development (e.g. infections, stress during pregnancy, smoking during pregnancy)— combined with genetic susceptibility—might prompt excessive immune responses that could impact brain development to increase the risk of developing TS. But researchers are still attempting to elucidate the details of this type of immune system interaction and what factors might be involved.
Scientists also continue to seek a cure for TS, but unfortunately at this point there is not even a treatment that is universally effective. Because TS can be very different in its presentation from patient to patient (as can the disorders, like ADHD and OCD, that often occur along with it), treatment typically needs to be adjusted to each individual patient’s needs. Still, there are a number of therapeutic approaches that can be beneficial.
For patients with mild tics, medication is often not necessary. Many of these individuals will respond to behavioral interventions that teach them to manage the symptoms of TS with things like: noticing premonitory urges and immediately engaging in an action that is contradictory (e.g. using muscles that make execution of the tic especially difficult), relaxation training, social support, etc.
Because most of the medications for TS have significant side effects, they are typically reserved for cases where behavioral interventions are ineffective or not viable, or where tics are severe enough to substantially disrupt quality of life. The most effective medications to treat TS tend to be antipsychotic drugs (e.g. risperidone), which typically inhibit dopamine activity (excessive dopamine activity in the basal ganglia may contribute to the symptoms of the disorder). These drugs are usually not the first course of treatment, however, because they are associated with problematic side effects ranging from movement disorders to weight gain (the specific side effects experienced depend on the medication).
Thus, the first-line pharmacological approach often instead involves the use of drugs that stimulate the alpha-2 adrenergic receptor, a receptor involved with sympathetic nervous system activation. Although they stimulate alpha-2 adrenergic receptors, these drugs actually cause decreased sympathetic nervous system activity, and may help to reduce tics in some patients. The effects, however, are not typically as potent as those seen with antipsychotic drugs.
There are a number of other drugs that can sometimes be effective in treating TS, and TS patients will often be prescribed additional medications to help with concurrent psychiatric disorders. Other treatment options continue to be explored as well, with the hope that one day the impact of this disorder on patients’ lives can be mitigated further.
References (in addition to linked text above):
Jahanshahi M, Obeso I, Rothwell JC, Obeso JA. A fronto-striato-subthalamic-pallidal network for goal-directed and habitual inhibition. Nat Rev Neurosci. 2015 Dec;16(12):719-32. doi: 10.1038/nrn4038. Epub 2015 Nov 4.
McNaught KS, Mink JW. Advances in understanding and treatment of Tourette syndrome. Nat Rev Neurol. 2011 Nov 8;7(12):667-76. doi: 10.1038/nrneurol.2011.167.
Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, Roessner V, Woods DW, Hariz M, Mathews CA, Črnčec R, Leckman JF. Gilles de la Tourette syndrome. Nat Rev Dis Primers. 2017 Feb 2;3:16097. doi: 10.1038/nrdp.2016.97.
