125 Years of Tourette Syndrome: The Discovery, Early History and Future of the Disorder

Kevin St. P. McNaught, Ph.D., Executive Vice President, Medical and Scientific Programs, Tourette Association of America

The 19th century was a remarkable period for neurology because it was during this period that many of the brain disorders known today were either discovered, recognized as disease entities or were clearly documented in the medical literature. Many physicians and scientists contributed to this work, but much credit is attributed to Jean-Martin Charcot (1825-1893), a brilliant and prolific French neurologist who is often considered to be the father of modern neurology1. While working at the famous Salpêtrière hospital in Paris, France, Dr. Charcot studied and lectured on nervous system disorders, and attended to patients with a wide range of neurological illnesses1. Dr. Charcot later became director of the Salpêtrière hospital and his strong reputation in neurology attracted many students whom he would train and mentor. These included Sigmund Freud, a famous pioneer in the fields of psychology and psychiatry, and Georges Albert Édouard Brutus Gilles de la Tourette, who would later be credited with describing the symptoms of the neurological disorder that now bears his name.

The early years

Gilles de la Tourette was born on October 30, 1857, in the small town of Saint-Gervais-les- Trois-Clochers, France2. Little is known about his early life, but he began his medical studies during 1873-1876 in Poitiers and Paris, France. In 1884, Gilles de la Tourette began training under Dr. Charcot’s guidance at the Salpêtrière hospital. Initially, Gilles de la Tourette studied various medical conditions, such as hysteria, hypnosis and ataxia (a neurological disorder causing poor movement coordination), all of which were of interest to his mentor. Later, however, Dr. Charcot asked him to turn his attention to paroxysmal movement disorders, which are neurological illnesses characterized by sudden outbursts of emotion and/or action. It was at this point in his career in 1884, while still in training, that Gilles de la Tourette probably first encountered the disorder that now bears his name.

The landmark publication

In his most famous article, published in the January 1885 issue of the medical journal Archives de Neurologie3, at the age of 28 years old, Gilles de la Tourette described a bizarre neurological condition that he referred to as “maladie des tics.’ The article was based on the observation of 9 individuals with a condition that had various features, including childhood-onset, hereditability, waxing and waning, stereotyped movements, premonitory sensation, echolalia and coprolalia. Gilles de la Tourette speculated that the disorder had a degenerative cause wherein the afflicted inherited a nervous system that was weakened by the immoral behaviors of previous generations. Indeed, during this period, many people believed that mental illnesses were caused by wrong deeds, possession by evil spirits, etc. Dr. Charcot later renamed the disorder in honor of his student, Gilles de la Tourette, and is now widely referred to as Tourette syndrome (TS) or Tourette disorder (TD).

Gilles de la Tourette qualified as a doctor around 1886 after his famous publication. He continued to work on hypnotism, hysteria, neurological conditions and experimental therapies at a number of institutions where he held various positions4. He wrote and published extensively on a wide range of medical and other matters of personal interest (e.g. art, literature and law)4.

Tragically in 1893, both Gilles de la Tourette’s son and his mentor, Jean-Martin Charcot, died. During that very same year, Gilles de la Tourette was shot in the head, but not killed, by an apparently psychotic woman (Rose Kamper) who claimed that she had been hypnotized at the Salpêtrière hospital and was now incapable of making a living. Ironically, Gilles de la Tourette himself later developed psychiatric (probably depression and dementia) and neurological (neurosyphilis) illnesses and, in 1901-1902, he was forced to leave his hospital appointment and was admitted to a hospital for mental illnesses in Lausanne, Switzerland. His condition deteriorated significantly and shortly thereafter he died on May 22, 1904.

Was Tourette syndrome described previously?

It is noteworthy that, while Gilles de la Tourette is credited with the discovery of the disorder that bears his name, there is evidence to suggest that this condition was previously described by other clinicians1,5. Notably, Jakob Sprenger and Heinrich Kraemer in their book, published in 1498 and entitled “Maleus maleficarum (Witches hammer), described a priest who had motor and vocal tics that were thought to be the result of possession by the devil, witchcraft, or exorcism6. In 1825, a French doctor, Jean Marc Gaspard Itard (1775-1838), reported that the Marquise de Dampierre, an important woman of the Parisian aristocracy, suffered from a disorder that was characterized by involuntary movements associated with sudden vocalizations and outbursts of obscenities7. Incidentally, she was one of the 9 patients that Gilles de la Tourette described in his 1885 publication on the disorder. An 1873 publication of the famous French physician Armand Trousseau’s (1801-1867) monograph also described several patients with motor and vocal tics8. Interestingly, Gilles de la Tourette in his 1885 publication briefly mentioned and was mildly critical of Trousseau’s earlier observations. Moreover, Hughlings-Jackson (1835-1911), an English neurologist, reported in Clinical Lectures and Reports to the London Hospital a single case of the disorder in 18849. Despite these earlier reports of tics, it was Gilles de la Tourette who clearly reported the many features of the condition and thus he set the stage for the recognition of TS as a distinct neurological disorder. Indeed, given that Gilles de la Tourette was junior and relatively inexperienced at that time, it is likely that the study and description of the cases presented in the 1885 article were to a great extent the work/influence of his mentor, Dr. Charcot.

After Gilles de la Tourette

Following Gilles de la Tourette’s death and up to the early 1960s, there was relatively little interest in studying TS compared to other neurological conditions such as Parkinson’s disease and Alzheimer’s disease, which were recognized as medical conditions during the same period. This began to change in the 1960s-1970s when Shapiro and colleagues demonstrated that the neuroleptic drug haloperidol could be useful in treating TS symptoms10. This observation began to call into question the psychosocial/psychoanalytic view (e.g., having tics relates to sexual feelings and expressions) and the approach to treating the disorder which was proposed by the Hungarian psychoanalyst Sandor Ferenczi (1873-1933) in 1921 which had prevailed during the previous decades11.

The establishment of the national Tourette Syndrome Association in the US in 1972 coincided with and stimulated significant interest in the disorder during the 1970s and subsequent decades12. Indeed, the provision of research grant awards by the Tourette Association (beginning in 1984) and later other organizations across the world served to encourage many research scientists and clinicians to investigate the causes and to seek improved treatments for the disorder. Today, we benefit from a much better understanding of TS and therefore we are able to apply various therapeutic strategies to better treat individuals with the condition.

Tourette syndrome: Where are we now?

Clinical expression

It is now clear that, in addition to TS, there are other tic disorders, referred to as ‘Chronic Motor or Vocal Tic Disorder’ and ‘Provisional Tic Disorder (formerly Transient Tic Disorder)’ as outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM)13. It is also evident that up to half of those with TS will develop varying degrees of one or more psychiatric illnesses, in particular obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and problems with anger and impulse management14. Thus, TS can present solely as a movement disorder, or as a complex array of motor dysfunction and abnormal behaviors. These observations underscore the ongoing debate as to whether or not TS should be classified as a neurological, psychiatric or neuropsychiatric/neurobehavioral illness. More recently, there have been proposals to classify TS as a ‘Neurodevelopmental Disorder’ in the forthcoming edition of the DSM-5, but this consideration remains tentative13.

Occurrence

The first reports of the frequency of TS in the literature suggest that the condition was rather obscure during and before the 1800s. Although it is not known whether the numbers of individuals affected by TS have actually increased since then, today it is clear that medical professionals are better able to diagnose TS and that the general public is much more aware of the condition. Even though the worldwide prevalence of TS has been reported to range from 0.3% to 0.8% of all children, some epidemiological studies suggest that up to 24% of children may have tics sometime during their childhood, and up to 2-3% of all children may develop some features of TS15. A recent study by the Centers for Disease Control and Prevention (CDC) reported that, in the US, 3 in every 1000 children of school age (6-17) have the disorder16. As Gilles de la Tourette noted in his report, the condition manifests largely during childhood, and is now known to affect more boys than girls. Tics typically emerge between the ages of 4 and 6, then increase in severity, and peak between the ages of 10 and 12. Thereafter, tics tend to decline during adolescence and, by early adulthood, most individuals will experience markedly reduced tics or be tic-free14.

Cause(s)

The cause of TS remains elusive. Gilles de la Tourette (and Trousseau) noted that the condition occurred in families, and suggested that it might have been passed down from generation to generation as a consequence of their “immoral behaviors.” Today, it is clear that TS is hereditary17. Spearheaded by the Tourette Association, there have been intense, international, efforts aimed at finding the gene defects that cause or contribute to the disorder. These remain unknown, except for findings of very rare mutations in a few families with the condition18.19. There are suggestions that other factors, such as environmental agents and infections, might play a role in the development of TS, but these theories remain unproven and require further study20.

Brain changes

There continues to be significant interest in determining the precise changes that occur in the brain of people with TS. This knowledge will be valuable for the rational development of more effective therapies for tics and associated psychiatric conditions. Imaging of the brain using sophisticated scanning equipment and other kinds of biomedical studies suggest that changes in the basal ganglia, an interconnected group of structures in the brain that control movements, play an important role in TS21. In particular, there is evidence to suggest that overactivity of nerve cells that release a chemical called dopamine contributes to the expression of tics. Moreover, there is increasing evidence indicating that alterations in other nerve cells (e.g. cells containing the chemicals serotonin, glutamate and histamine) and brain areas (e.g. limbic structures and corpus callosum), contribute to the cause of tics and other symptoms in TS21.

Treatments

Since TS was first described, a variety of therapeutic approaches have been examined. The work by the physician Arthur Shapiro and colleagues in the 1960s-70s, which showed that the dopamine activity blocker, haloperidol, could reduce tic severity, led to the examination of many other drugs for TS22. At present, there are a variety of drugs that can interact with dopamine and non-dopamine systems in the brain that can be administered to people with TS22. However, for some people, several of these mediations have poor benefit and are associated with unpleasant side effects that further limit their usefulness. Thus, there continues to be a great need for more effective and safer medicines for treating tics and other features of TS.

Surgical approaches to TS

notably the electrical stimulation of specific regions of the brain using implanted probes, are under investigation as a potential therapy for very severe and drug-resistant cases of the disorder23. Some patients who have already received this therapy have experienced significant benefit, but many others have failed to show improvement. Thus, deep brain stimulation (DBS) remains an investigational but potentially effective therapy for otherwise difficult to manage cases of TS.

In recent years, there has been much interest in behavioral therapy as a treatment for TS. In a recent article published in JAMA, it was shown that cognitive behavioral intervention for tics (CBIT) was as effective as drugs for treating some people with the disorder24. This promising therapy will undergo further development and testing in the years ahead, and could become a treatment option for people with TS.

Interestingly, some individuals with TS have reported that ‘complementary and alternative therapies’ such as acupuncture, dietary supplements and homeopathic remedies have provided varying degrees of reduction in their tics25. While some of these approaches could benefit specific individuals, these interventions have not yet been confirmed in rigorous clinical trials involving many patients.

Conclusion: The future for Tourette syndrome

It is now 125 years since Gilles de la Tourette clearly described the disorder that bears his name. Research into the condition was delayed for many decades, but interest began to increase from the 1960s and, today, many scientists and clinicians around the world are studying the disorder. Although there has been progress in many areas, such as differential diagnosis, increased awareness and availability of therapies for some cases, there remain many mysteries and unmet needs in TS. For example, the cause(s) and precise brain changes underlying the disorder remain unknown, and there continues to be a lack of highly effective and safe medications for many with the condition. In the years ahead, we expect that research will continue to address the many unanswered questions and thus unravel the many mysteries surrounding the disorder. We also look forward to the development of more effective therapies, perhaps even hope for a cure.

Original atricle (without bibliography) appeared in the Quarterly Newsletter of the Tourette Association, Winter 2010, Vol. 38, No. 3