Tourette syndrome: Difference between revisions
→Experimental treatments: changed it to tetrahydrocannabinol b/c THC stands for too many articles |
→Experimental treatments: add what THC is |
||
Line 101: | Line 101: | ||
===Experimental treatments=== |
===Experimental treatments=== |
||
[[Nicotine]] showed preliminary promise in case reports, but these effects were not reproduced in well-controlled trials several years later. <ref name=Swerdlow2005>Swerdlow, NR. Tourette Syndrome: Current Controversies and the Battlefield Landscape. ''Curr Neurol Neurosci Rep''. 2005, 5:329-331. PMID 16131414</ref> Studies of nicotine derivatives ([[mecamylamine]], [[inversine]]) also showed that they were not effective as monotherapy for the symptoms of Tourette's.<ref>Silver AA, Shytle RD, Sheehan KH, et al. Multicenter, double-blind, placebo-controlled study of mecamylamine monotherapy for Tourette's disorder. ''J Am Acad Child Adolesc Psychiatry''. 2001 Sep;40(9):1103-10. PMID 11556635</ref> [[Deep brain stimulation]] has been used in treating a few patients with severe Tourette's, but is regarded as an experimental and dangerous procedure that is unlikely to become widespread.<ref>Tourette Syndrome Association. [http://web.archive.org/web/20050226093006/http://www.tsa-usa.org/news/DBS-Statement.htm Statement: Deep Brain Stimulation and Tourette Syndrome] Accessed 26 Feb 2005.</ref> [[Complementary and alternative medicine]] approaches, such as dietary modification, allergy testing and allergen control, and [[neurofeedback]], have popular appeal, but no role has been proven for any of these in the treatment of Tourette syndrome.<ref name=Swerdlow2005/><ref name=Zinner2004>Zinner SH. Tourette syndrome—much more than tics. ''Contemporary Pediatrics''. Aug 2004;21(8):22-49. [http://tsa-usa.org/research/images/cntped0804_022-036%20T1R2.pdf Part 1][http://tsa-usa.org/research/images/cntped0804_038-049%20T2R1.pdf Part 2]</ref> Case reports found that [[marijuana]] helped reduce tics, but validation of these results requires longer, controlled studies on larger samples.<ref>Sandyk R, Awerbuch G. Marijuana and Tourette's syndrome. ''J Clin Psychopharmacol''. 1988 Dec;8(6):444-5. PMID 3235704</ref><ref>Muller-Vahl KR, Kolbe H, Dengler R. [Gilles de la Tourette syndrome. Effect of nicotine, alcohol and marihuana on clinical symptoms] ''Nervenarzt''. 1997 Dec;68(12):985-9. German. PMID 9465342</ref> A six-week controlled study on treating TS with [[Dronabinol]], synthetic [[Tetrahydrocannabinol]] (brand name [[Marinol]]®)on 24 patients showed the patients taking Marinol® had a significant reduction in tic severity without serious adverse effects, and more significant reduction in tic severity was reported with longer treatment.<ref>Muller-Vahl KR, Schneider U, Prevedel H, et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. ''J Clin Psychiatry''. 2003 Apr;64(4):459-65. PMID 12716250</ref> The researchers reported a trend towards improvement in cognitive functioning in the people with TS taking Marinol, before and after treatment.<ref>Muller-Vahl KR, Prevedel H, Theloe K, et al. Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance. ''Neuropsychopharmacology''. 2003 Feb;28(2):384-8. PMID 12589392</ref> |
[[Nicotine]] showed preliminary promise in case reports, but these effects were not reproduced in well-controlled trials several years later. <ref name=Swerdlow2005>Swerdlow, NR. Tourette Syndrome: Current Controversies and the Battlefield Landscape. ''Curr Neurol Neurosci Rep''. 2005, 5:329-331. PMID 16131414</ref> Studies of nicotine derivatives ([[mecamylamine]], [[inversine]]) also showed that they were not effective as monotherapy for the symptoms of Tourette's.<ref>Silver AA, Shytle RD, Sheehan KH, et al. Multicenter, double-blind, placebo-controlled study of mecamylamine monotherapy for Tourette's disorder. ''J Am Acad Child Adolesc Psychiatry''. 2001 Sep;40(9):1103-10. PMID 11556635</ref> [[Deep brain stimulation]] has been used in treating a few patients with severe Tourette's, but is regarded as an experimental and dangerous procedure that is unlikely to become widespread.<ref>Tourette Syndrome Association. [http://web.archive.org/web/20050226093006/http://www.tsa-usa.org/news/DBS-Statement.htm Statement: Deep Brain Stimulation and Tourette Syndrome] Accessed 26 Feb 2005.</ref> [[Complementary and alternative medicine]] approaches, such as dietary modification, allergy testing and allergen control, and [[neurofeedback]], have popular appeal, but no role has been proven for any of these in the treatment of Tourette syndrome.<ref name=Swerdlow2005/><ref name=Zinner2004>Zinner SH. Tourette syndrome—much more than tics. ''Contemporary Pediatrics''. Aug 2004;21(8):22-49. [http://tsa-usa.org/research/images/cntped0804_022-036%20T1R2.pdf Part 1][http://tsa-usa.org/research/images/cntped0804_038-049%20T2R1.pdf Part 2]</ref> Case reports found that [[marijuana]] helped reduce tics, but validation of these results requires longer, controlled studies on larger samples.<ref>Sandyk R, Awerbuch G. Marijuana and Tourette's syndrome. ''J Clin Psychopharmacol''. 1988 Dec;8(6):444-5. PMID 3235704</ref><ref>Muller-Vahl KR, Kolbe H, Dengler R. [Gilles de la Tourette syndrome. Effect of nicotine, alcohol and marihuana on clinical symptoms] ''Nervenarzt''. 1997 Dec;68(12):985-9. German. PMID 9465342</ref> A six-week controlled study on treating TS with [[Dronabinol]], a synthetic version of [[Tetrahydrocannabinol]], the main psychoactive chemical in cannibus (brand name [[Marinol]]®), on 24 patients showed the patients taking Marinol® had a significant reduction in tic severity without serious adverse effects, and more significant reduction in tic severity was reported with longer treatment.<ref>Muller-Vahl KR, Schneider U, Prevedel H, et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. ''J Clin Psychiatry''. 2003 Apr;64(4):459-65. PMID 12716250</ref> The researchers reported a trend towards improvement in cognitive functioning in the people with TS taking Marinol, before and after treatment.<ref>Muller-Vahl KR, Prevedel H, Theloe K, et al. Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance. ''Neuropsychopharmacology''. 2003 Feb;28(2):384-8. PMID 12589392</ref> |
||
== Research directions and controversies == |
== Research directions and controversies == |
Revision as of 04:48, 17 February 2006
- "Tourette's" redirects here. For the Nirvana song, see Tourette's (song).
Tourette syndrome | |
---|---|
Specialty | Neurology ![]() |
Tourette syndrome (also called Tourette's syndrome, Tourette's disorder, Gilles de la Tourette syndrome, GTS or TS) is an inherited neurological disorder with onset in childhood, and characterized by the presence of multiple motor tics and at least one phonic tic, which characteristically wax and wane. Tourette syndrome was once considered a rare and bizarre syndrome. It is no longer considered rare, but is often undetected because of the wide range of severity, with most cases classified as mild.
The eponym was bestowed by Jean-Martin Charcot after and on behalf of his resident, Georges Albert Édouard Brutus Gilles de la Tourette, (1859 - 1904), a French physician and neurologist, who published an account of nine patients with Tourette's in 1885. Another French doctor, Jean Marc Gaspard Itard, reported the first case of Tourette syndrome in 1825, describing Marquise de Dampierre, an important woman of nobility in her time. [1]
Description
The hallmark of Tourette's syndrome are repetitive, involuntary movements (motor tics) and utterances (phonic tics) that constantly change in number, frequency, severity, and anatomical location. The Tourette Syndrome Association describes tics as movements or sounds "that occur intermittently and unpredictably out of a background of normal motor activity".[2]
Motor tics are movement-based tics affecting discrete muscle groups. Phonic tics are involuntary sounds produced by moving air through the nose, mouth, or throat. They may be alternately referred to as verbal tics or vocal tics. The tics of Tourette's characteristically wax and wane. Waxing and waning — a natural increase and decrease in severity and frequency of tics — occurs differently in each individual. Tics are described as occurring in "bouts of bouts", which vary for each person.[3]
Coprolalia (the spontaneous utterance of socially-objectionable or taboo words or phrases) is the most publicized symptom of Tourette's syndrome, but it is not required for a diagnosis of Tourette's. Fewer than 15% of TS patients exhibit coprolalia.[4]
In contrast to the stereotyped movements of some other movement disorders (e.g.; choreas, dystonias, myoclonus, and dyskinesias), the tics of Tourette's are temporarily suppressible and preceded by a premonitory urge.[3] Immediately preceding tic onset, most individuals with TS are aware of a premonitory urge,[5] which is similar to the need to sneeze or scratch an itch. Individuals describe the need to tic as the buildup of tension in a particular anatomical location,[6] which they consciously choose to release, as if the subject "had to do it".[7] Some examples of this premonitory urge are the feeling of having something in one's throat, or a localized discomfort in the shoulders, leading to the need to clear one's throat or shrug the shoulders. The actual tic may be felt as relieving this tension or sensation, similar to scratching an itch. Another example is blinking to relieve an uncomfortable sensation in the eye. These urges and sensations, preceding the expression of the movement or vocalization as a tic, are referred to in Tourette's subjects as "premonitory sensory phenomena". Some published descriptions of the tics of Tourette's identify sensory phenomena as the core symptom of TS, even though it is not included in the diagnostic criteria.[8][9]
Due to the sensory nature of tics, they can be described as semi-voluntary or "unvoluntary", because they may be experienced as a voluntary response to an unwanted, premonitory urge. Tics are experienced as irresistible and must eventually be expressed. People with TS are sometimes able to suppress their tics to some extent for limited periods of time, but doing so often results in an explosion of tics afterward. The control which can be exerted (from seconds to hours at a time) may merely postpone and exacerbate the ultimate expression of the tic. People with TS may seek a secluded spot to release their symptoms after suppressing them in school or at work. Some people with TS may not be aware of the premonitory urge. Children may be less aware of the premonitory urge associated with tics than are adults, but their awareness tends to increase with maturity. They may have tics for several years before becoming aware of premonitory urges. Children may suppress tics while in the doctor's office, so they may need to be observed while they are not aware they are being watched. The ability to suppress tics varies among individuals, and may be more developed in adults than children.[10]
Typically, tics increase as a result of stress or high energy emotions, which can include negative emotions, such as anxiety, but positive emotions as well, such as excitement or anticipation. Relaxation may result in a tic decrease or a tic increase (for example, tics may increase when one relaxes watching television), while concentration in an absorbing activity often leads to a decrease in tics.[11] [12] Neurologist and writer Oliver Sacks [13] describes a physician with severe TS, (Canadian Mort Doran, M.D., a pilot and surgeon in real life, although a pseudonym was used in the book), whose tics remit almost completely while he is performing surgery.
Tourette syndrome patients may exhibit symptoms of other conditions along with their motor and phonic tics. Associated conditions include attention-deficit hyperactivity disorder (ADD and ADHD), Obsessive-Compulsive Disorder (OCD), learning disabilities and sleep disorders.[12] Disruptive behaviors, overall functioning, and cognitive function in patients with co-occurring Tourette's syndrome and ADHD may be accounted for by the comorbid ADHD, highlighting the importance of identifying and treating comorbid conditions when they are present.[14][15][16][17]
Diagnosis
According to the DSM-IV-TR, TS is indicated when a person exhibits both multiple motor and one or more vocal tics (although these do not need to be concurrent) over the period of 1 year, with no more than 3 consecutive tic-free months. Previous versions of the DSM included a requirement for distress or impairment in social, occupational, or other important areas of functioning, but this requirement has been removed from the most recent version of the DSM, in recognition that not everyone with the diagnosis has distress or impairment to functioning. The onset must have been before the age of 18, and cannot be attributed to the use of a substance or another medical condition.[18] Hence, other medical conditions which include tics or tic-like movements (such as autism) must be ruled out before conferring a Tourette's diagnosis.
Although there is no such thing as a "typical" case, and each individual is different, Tourette's syndrome follows a fairly typical and reliable course in terms of age of onset and the natural time course of severity of symptoms. Tics may appear up to the age of 18, but the most typical age of onset is six or seven, with the most common first-presenting tics being eye blinking, facial movements, sniffing and throat clearing. Tics most frequently present initially in midline body regions where there are many muscles: the head, neck and facial region. [10] This can be contrasted with the stereotyped movements of other disorders (e.g.; stims and stereotypies) which tend to have an earlier age of onset, are more symmetrical, and involve extremities (e.g.; flapping hands) [19] The most common tics to appear early in the course of the condition are frequently confused with other conditions: examples are allergies, asthma, and vision problems.[10] The ages of statistical highest tic severity are 8 to 12, average 10, with tics steadily declining for most patients as they pass through adolescence.[20]
There are no medical or screening tests which can be used in diagnosing Tourette's disorder. The diagnosis is made based on a history of symptoms, and after ruling out other conditions which can include tics.[4] If a physician believes that there may be another condition present which could explain tics, some tests may be ordered as necessary to rule out those other conditions. An example of this would be when diagnostic confusion between tics and seizure activity exists, which would call for an EEG, or if there are indications that an MRI is warranted to rule out a brain tumor. However, most cases are diagnosed by merely observing a history of tics, and medical tests are not always called for.[10][4]
Because co-occurring conditions like OCD or attention-deficit hyperactivity disorder can be more impairing than tics, these conditions should be included in an evaluation of patients presenting with tics.[10][21] "It is critical to note that the comorbid conditions may determine functional status more strongly than the tic disorder." [10]
Differential diagnosis
Dystonias, choreas, other genetic conditions, and secondary causes of tics should be ruled out[21] in the differential diagnosis for Tourette's syndrome. Other conditions which may manifest tics or stereotyped movements include developmental disorders (autism spectrum disorders) and Stereotypic movement disorder [22]; other genetic conditions such as Huntington's disease, Neuroacanthocytosis, Hallervorden-Spatz disease, Idiopathic dystonia, Duchenne's disease, Tuberous sclerosis, Chromosomal disorders, Down syndrome, Klinefelter's syndrome, XYY karyotype, and Fragile X syndrome; Wilson's disease or Syndenham's chorea; and secondary or acquired causes of tics, such as drug-induced tics, head trauma, encephalitis, stroke, and carbon monoxide poisoning. Secondary causes of tics (not related to inherited Tourette's syndrome) are commonly referred to as tourettism. [21][23] The symptoms of Lesch-Nyhan syndrome may also be confused with Tourette syndrome. Most of these conditions are rarer than tic disorders, and a thorough history and examination may be enough to rule them out, without a lot of medical or screening tests. [10]
Prognosis
Tourette's syndrome is a spectrum disorder, which means that the severity of the condition can range along a continuum from mild to severe. However, it should be emphasized that "the majority of cases can be categorized as mild." [24] Those with mild cases may be minimally impacted by symptoms, to the extent that casual observers might not know of their condition. Severe cases (which are the rare minority in adulthood) can inhibit or prevent the individual from engaging in common activities such as holding a job or having a fulfilling social life.
Regardless of symptom severity, individuals with TS can expect to live a normal life span. Although TS symptoms may be lifelong and chronic for some, it is not a degenerative condition and is not life-threatening. Life span and intelligence are normal, although learning disabilities may be present.[4]
Multiple studies have demonstrated that the condition in most children improves with maturity. Tics may be at their highest severity at the time that they are brought to diagnostic awareness, and often improve with understanding of the condition. The statistical age of highest tic severity is typically between 8 and 12, with most individuals experiencing steadily declining tic severity as they pass through adolescence. The same studies have shown no correlation with tic severity and the onset of puberty. In many cases, complete remission of tic symptoms occurs after adolescence.[20] [25][26]
It is not uncommon for parents of affected children to be unaware that they, too, may have had tics as children. Because Tourette's syndrome tends to remit or subside in severity as one matures, and because milder cases of Tourette's are now more likely to be recognized, the first realization that a parent had tics as a child may not come until their offspring are diagnosed. It is not uncommon for several members of a family to be diagnosed together, as parents bringing children to a physician for an evaluation of tics come to the realization that "I did that, too, as a child."
Children with Tourette's may suffer socially if their tics are viewed as "bizarre". If a child has disabling tics, or tics which interfere with social or academic functioning, supportive psychotherapy or school accommodations can be helpful. [4] Because co-occurring conditions (such as ADHD or OCD) can cause more impact on overall functioning than tics, a thorough evaluation for co-occurring conditions is called for when symptoms and impairment warrant. [21]
A supportive environment and family generally gives one skills to manage the disorder. Persons with Tourette's syndrome may learn to camouflage socially inappropriate tics or channel the energy of their tics into some other endeavor, to their advantage. Among people with Tourette's syndrome are accomplished musicians, athletes, and public speakers, and professionals from all walks of life. Author and neurologist Oliver Sacks[13] describes the case of a drummer with TS, who uses his tics to give him a certain 'flair' or 'special sound' to his drumming.
There is currently no reliable means of predicting the outcome for any individual. The gene or gene(s) for Tourette's syndrome have not been identified, and there is no potential "cure".[4]
Discussions with adults who have Tourette syndrome reveal that not everyone wants treatment or a "cure", especially if that means they may "lose" something else in the process. Some believe that there may even be latent advantages associated with the genetic vulnerability. [3]
Prevalence
It was previously believed that Tourette's syndrome was a rare disorder, with about 5 to 10 people in 10,000 having Tourette's Syndrome.[10] However, multiple studies published since 2000 demonstrate that the prevalence is much higher than previously thought, and that Tourette's syndrome can no longer be considered rare. Contemporary prevalence estimates range from 1 to 3 per 1,000[27] to 10 per 1,000.[28] A large, community-based study suggested that over 19% of school-age children have tics, with almost 4% of children in regular education fulfilling the diagnostic criteria for Tourette's Syndrome. The children with tic disorders in that study were usually undiagnosed.[29] As many as 1 in 100 people may experience some form of tic disorder, which includes transient tics, chronic tics, or Tourette's Syndrome.[12] Males are affected 3 to 4 times more often than females.[12][24] The disorder is frequently misdiagnosed or underdiagnosed, partly because of the wide expression of severity, ranging from mild (the majority of cases) or moderate, to severe (the rare, but more widely-recognized and publicized cases). Because the tics of Tourette's syndrome tend to remit or subside with maturity, such that a diagnosis may no longer be warranted for many adults, prevalence rates in pediatric populations are higher than those in adult populations.[20]
Causes and origins: genetic and epigenetic factors
Tourette syndrome is found among all social, racial and ethnic groups.[12][30]
Genetic studies have proven that the overwhelming majority of cases of Tourette's syndrome are inherited, although the exact mode of inheritance is not yet known. [30] The spectrum of tic disorders, including TS, have long been thought to be inherited as an autosomal dominant gene. Recent research challenges the autosomal dominant hypothesis, and suggests an additive model involving multiple genes.[10][21] The inherited vulnerability to tic disorders may produce varying symptoms in different family members: Tourette's is a condition of variable penetrance, meaning even family members with the same genetic makeup may show different levels of symptom severity, and not everyone who inherits the genetic vulnerability will show symptoms at all. Inheriting the gene or genes does not necessarily mean that symptoms will be displayed.
Studies suggest that non-genetic, environmental, infectious, or psychosocial factors — while not causing Tourette's — can impact upon the expression of the severity of the disorder.[10] As one example of non-genetic factors, twin studies have shown that the lower birth weight twin is the one more likely to display more symptoms.[31] Other perinatal events, such as maternal stress[32] and obstetric complications[33] may also impact upon the severity of the expression of the inherited genetic vulnerability. Autoimmune processes may affect tic onset and exacerbation in some cases: the unproven and contentious hypothesis that pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, P.A.N.D.A.S., plays a role in the onset of tic disorders and OCD is a current focus of research.
A person with TS has about a 50% chance of passing the gene(s) to one of his/her children. However, the gene(s) may express as TS, as a milder tic disorder, or as obsessive compulsive symptoms with no tics at all.[4] Gender appears to have a role in the expression of the genetic vulnerability. [10] Only a minority of the children who inherit the gene(s) will have symptoms severe enough to ever require medical attention.[4] There is currently no way to predict the symptoms a child may display, even if the gene(s) are inherited.
While it is known that Tourette's is genetic, the exact mechanism affecting the inherited vulnerability has not been established. Research presents considerable evidence that abnormal activity of the brain chemical, or neurotransmitter, dopamine, is involved. Other neurotransmitters may also be involved.[4] Neuroanatomic models implicate failures in circuits connecting the brain's cortex and subcortex.[10]
Some forms of OCD may be genetically linked to Tourette's.[34] Genetic studies show an increased rate of tics and obsessive-compulsive behaviors or OCD in relatives of patients with Tourette's, and "reinforce the idea that at least some forms of OCD are etiologically related to TS, and may, therefore, be a variant expression of the same etiologic factors that are important for the expression of tics." [19] Further evidence supporting that OCD and Tourette's are alternative expressions of a common genetic vulnerability is that males inheriting the genetic vulnerability are more likely to display tics, while females are more likely to display obsessive-compulsive traits. [21]
The genetic relationship of ADHD to Tourette's syndrome is less clear, with some evidence to suggest no genetic linkage, and some evidence to suggest that some forms of Tourette's syndrome may be genetically related to ADHD. [3] Not all persons with Tourette's syndrome will have ADHD or OCD, although in clinical populations, a high percentage of patients presenting for care do have ADHD. [21] The high co-occurrence of ADHD observed in tertiary, referred populations may be an artifact of clinical ascertainment bias. Further study is needed to elucidate the genetic relationship between ADHD and Tourette's.[3]
In some cases, tics may not be inherited; these cases are identified as "sporadic" TS (also known as tourettism) because a genetic link is missing.[23]
Recent research at Yale University suggests that a small number of Tourette Syndrome cases may be caused by a defect on chromosome 13 of gene SLITRK1. Some cases of tourettism (tics due to reasons other than inherited Tourette's syndrome) can be caused by mutation.[23] The finding of a chromosomal abnormality appears to apply to a very small minority of cases (1 - 2%), and studies to locate all of the genes implicated in Tourette's syndrome are ongoing.[35]
Treatment
Knowledge and understanding are the best treatments available for tics. The majority of people with TS require no medication, but medication is available to help when symptoms interfere with functioning. There are no medications specifically designed to target the tics of Tourette's, none of the medications used are effective for all patients, and most available medications are associated with adverse effects. Because children with tics often present to physicians when their tics are at their highest severity, and because of the waxing and waning nature of tics, it is recommended that medication not be started immediately or changed often. Frequently, the tics subside with understanding of the condition and a supportive environment. When medication is necessary, pharmaceutical intervention should be targeted at the most impairing symptoms, taking into account co-occurring conditions such as ADHD or OCD, which when present, may warrant treatment even when tics are mild. [10]
The classes of medications with the most proven efficacy in treating tics — typical and atypical neuroleptics — can have long- and short-term adverse effects.[21] The antihypertensive agents, clonidine (Catapres®) and guanfacine (Tenex®), are also used to treat tics. Stimulants and other medications may be useful in treating ADHD when it co-occurs with tic disorders. Drugs from several other classes of medications can be used as alternatives when stimulant trials fail. Clomipramine (Anafranil®), a tricyclic antidepressant, and SSRIs, a class of antidepressants including Prozac, Zoloft, and Luvox, may be prescribed when a TS patient also has symptoms of Obsessive-compulsive disorder.
Cognitive Behavioral Therapy (CBT) is a useful treatment when OCD is present, and there is increasing evidence supporting the use of habit reversal in the treatment of tics. Relaxation techniques, such as exercise, yoga or meditation, may also be useful in relieving stress that may aggravate tics.
Treatment of tics
There are no medications specifically designed to target tics. Medications which are used as primary treatment in other conditions are used with some success in treating tics. Neuroleptic medications (antipsychotics), such as haloperidol (brand name Haldol®) or pimozide (brand name Orap®), have historically been and continue to be the medications with the most proven efficacy in controlling tics. These medications work by blocking dopamine receptors. However, these drugs are associated with a high adverse effects profile. The traditional antipsychotic drugs are associated with tardive dyskinesia when used long-term, and parkinsonism, dystonia, dyskinesia, and akathesia when used short-term. Additional side effects can be school phobia, depression, weight gain, and cognitive blunting. Another traditional antipsychotic used in treating Tourette's are fluphenazine (brand name Prolixin®), although the empirical support for its use is less than that of haloperidol and pimozide.
Newer neuroleptics, the atypical neuroleptics, are an alternative to the traditional medications used for treating tics. These medications have more selective dopamine blocking effects, or block serotonin with some blocking of dopamine. The medications in this class used to treat tics include risperidone (brand name Risperdal®), olanzapine (brand name Zyprexa®), ziprasidone (brand name Zeldox®), quetiapine (brand name Seroquel®), clozapine (brand name Clozaril®), tiapride, and sulpiride. They seem to have lower risks of neurological side effects (such as tardive dyskinesia]) when used short-term, but longer trials are needed to confirm this. Some of the side effects associated with these medications are insomnia, weight gain, and school phobia. Abnormalities in metabolism, cardiac conduction times, and increased risk of diabetes are concerns with these medications. There is good empirical support for the use of risperidone, and less support for the others.
The α2-adrenergic receptor agonists (antihypertensive agents) show some efficacy in reducing tics, as well as other comorbid features of some people with Tourette's. The evidence for their safety and efficacy is not as strong as the evidence for some of the standard and atypical neuroleptics, but there is fair supportive evidence for their use, nonetheless.[36] This class of medication is often the first tried for tics, as the antihypertensives have a lower side effect profile than some of the medications which more proven efficacy. Clonidine (brand name Catapres®) works on tics for about half of people with TS. [37][38] Maximal benefit may not be achieved for 4 - 6 months. A small number of patients may worsen on clonidine.[30] Guanfacine (brand name Tenex®) is another antihypertensive that is used in treating TS. Originally developed to treat high blood pressure, these medications could be a safer alternative to neuroleptic medications for the people with TS that respond to them. Side effects can include sedation, dry mouth, fatigue, headaches and dizziness. Sedation can be problematic when treatment is first initiated, but may wear off as the patient adjusts to the medication. This class of medication takes about six weeks to begin to work on tics, so sustained trials are warranted. Because of the blood pressure effects, antihypertensive agents should not be discontinued suddenly.
Other medications that can be used to treat tics include pergolide (brand name Permax®), botulinum toxin, and with less empirical support for efficacy, tetrabenazine and baclofen.
Treatment of ADHD in the presence of tic disorders
The treatment of attention-deficit hyperactivity disorder (ADHD) in the presence of tic disorders has long been a controversial topic. Referred (clinical) populations of patients with Tourette's have a high rate of comorbid ADHD, so the treatment of ADHD co-occurring with tics is often part of the clinical treatment of Tourette's. Past medical practice held that stimulants could not be used in the presence of tics, due to concern that their use might exacerbate underlying tic disorders.[22] However, multiple lines of research have shown that stimulants can be cautiously used in the presence of tic disorders.[39][40][41][42]Several studies have shown that stimulants do not exacerbate tics any more than placebo does, and suggest that stimulants may even reduce tic severity.[43] Controversy remains, and the PDR still carries a warning that stimulants should not be used in the presence of tic disorders, so physicians may be reluctant to use stimulants. Others are comfortable using them and even advocate for a stimulant trial when ADHD co-occurs with tics, because the symptoms of ADHD can be more impairing than tics.[10][22] The stimulants are the first line of treatment for ADHD, with proven efficacy, but they do fail in up to 20% of cases, even in patients without tic disorders. Current prescribed stimulant medications include: methylphenidate (Ritalin®, Metadate®, Concerta®), dextroamphetamine (Dexedrine®), and mixed amphetamine salts (Adderall®). Other medications can be used when stimulants are not an option. These include the alpha-2 agonists (clonidine and guanfacine), tricyclic antidepressants (desipramine and nortriptyline), and newer antidepressants (bupropion, venlafaxine and atomoxetine). There have been case reports of tic exacerbations with bupropion (brand name Wellbutrin®). There is good empirical support for the use of desipramine, bupropion and atomoxetine (brand name Strattera®). Atomoxetine is the only non-controlled FDA approved drug for the treatment of ADHD, but is less effective than stimulants for ADHD; is associated with individual cases of liver damage; carries an FDA black box warning regarding suicidal ideation; and controlled studies show increases in heart rate, decreases of body weight, decreased appetite and treatment-emergent nausea.[44]
Experimental treatments
Nicotine showed preliminary promise in case reports, but these effects were not reproduced in well-controlled trials several years later. [45] Studies of nicotine derivatives (mecamylamine, inversine) also showed that they were not effective as monotherapy for the symptoms of Tourette's.[46] Deep brain stimulation has been used in treating a few patients with severe Tourette's, but is regarded as an experimental and dangerous procedure that is unlikely to become widespread.[47] Complementary and alternative medicine approaches, such as dietary modification, allergy testing and allergen control, and neurofeedback, have popular appeal, but no role has been proven for any of these in the treatment of Tourette syndrome.[45][48] Case reports found that marijuana helped reduce tics, but validation of these results requires longer, controlled studies on larger samples.[49][50] A six-week controlled study on treating TS with Dronabinol, a synthetic version of Tetrahydrocannabinol, the main psychoactive chemical in cannibus (brand name Marinol®), on 24 patients showed the patients taking Marinol® had a significant reduction in tic severity without serious adverse effects, and more significant reduction in tic severity was reported with longer treatment.[51] The researchers reported a trend towards improvement in cognitive functioning in the people with TS taking Marinol, before and after treatment.[52]
Research directions and controversies
The direction of current and future research in Tourette's syndrome was delineated well in a 2005 paper, "Tourette Syndrome: Current Controversies and the Battlefield Landscape",[45] by the outgoing chairman of the TSA Scientific Advisory Board. Swerdlow outlines the research landscape by dividing issues into five broad questions about Tourette's: "what is it, who has it, what causes it, how do we study it, and how do we treat it"?
According to Swerdlow,[45] "we still lack consensus on the definition of TS." He calls this "the 'core' TS conundrum" that has "a direct impact on critical issues, from prevalence estimates to inclusion/exclusion criteria in genetic, neuro-imaging, and treatment studies". Since vocal tics result from a "motor event (ie, a contracting diaphragm moving air through the upper airways)", TS could be defined as a disorder of motor tics, eliminating the distinction between TS and the other tic disorders. Because "individuals with tics alone may not be functionally impaired", should TS, as currently defined, be a DSM diagnosis? Swerdlow highlights the importance of studies in new areas, such as behavioral techniques, and that "the whole-cloth dismissal of psychologic forces in the pathobiology of TS was a strategic error". Questions remain about whether co-occurring conditions should be part of the core definition, and why sensory phenomena, which are a core part of Tourette's, are not part of the diagnostic criteria.
Dropping the criteria for impairment from the diagnosis resulted in higher prevalence estimates for TS (the question of "who has it?"). With TS prevalence estimates at 1% to 2%, the condition is cast in an entirely new light.
Discovering "what causes TS" may resolve the questions of what it is and who has it. Research has been affected by the problem of referred samples, which may not reflect broader populations of persons with Tourette's. Probabilistic models may yield better results in finding the cause, as the autosomal dominant inheritance model has not been validated. The P.A.N.D.A.S. controversy remains contentious.
Expanding criteria for the diagnosis, and increasing awareness of the impact of co-occurring diagnoses result in further questions of how to study Tourette's. Developing and applying standardized instruments, along with awareness of ascertainment bias in recruitment sources, will be important in genetic studies. We don't know if "we lose both signals and are just adding noise to the experimental outcome"[45] when co-occurring conditions, such as OCD or ADHD, are included or excluded from study samples, or samples include/exclude children or adults, or patients with severe symptoms.
In terms of how to treat it, Tourette's is a heterogeous condition, with waxing and waning symptoms. The inherent changing nature of its core symptoms complicates research design. Results from case studies may not be borne out by controlled studies, stimulants may be under utilized, and behavioral therapies are understudied. High profile media coverage focuses on treatments that do not have established safety or efficacy e.g.; deep brain stimulation.
Sociological and cultural aspects
With the increased knowledge of the full range of symptomatology of Tourette's syndrome, it has shifted from a condition only recognized in its most severe and impairing forms, to being recognized as a condition which is often mild, and which may be associated with some advantages and disadvantages. There are many individuals with Tourette's, living and deceased, recognized in their fields, or for whom obsessive-compulsive tendencies associated with Tourette's may have helped fuel their success. An example of a person who may have used obsessive-compulsive traits to advantage is Dr Samuel Johnson, lexicographer, who certainly had Tourette syndrome as evidenced by the writings of James Boswell. Johnson wrote A Dictionary of the English Language in 1747, and was a prolific writer, poet, and critic. Andre Malraux, the French author, adventurer and statesman, also had Tourette syndrome. Prominent athletes diagnosed with Tourette syndrome include Mahmoud Abdul-Rauf (formerly Chris Jackson), a former NBA player who incorporates his tics into his basketball playing; Jim Eisenreich, a former major league baseball player; Tim Howard, a goalkeeper for Manchester United Football Club; Mike Johnston, a relief pitcher for the Pittsburgh Pirates; and Jeremy Stenberg, a motocross rider nicknamed "Twitch". Recognized muscians with Tourette syndrome include Tobias Picker, a composer; Nick Tatham, a singer/songwriter; and Michael Wolff, a Jazz musician.
Speculation about recognized people who may have Tourette syndrome
Benjamin Simkin, M.D., argued in Medical and Musical Byways of Mozartiana, that Mozart had Tourette syndrome.[53][54] Dr. Simkin is an endocrinologist, not a psychiatrist or a neurologist, the medical fields specializing in Tourette syndrome. Letters Mozart wrote to his cousin Maria Anna Thekla ("Bäsle") between 1777 and 1781 contain scatological language and he wrote canons titled Leck mich im Arsch ("Lick my ass") or variations thereof (including the pseudo-Latin Difficile lectu mihi mars). This alone is not indicative of Tourette syndrome, and there are alternative explanations for his use of language. Oliver Sacks, neurologist and author, published an editorial disputing Simkin's claim.[55][56] No Tourette's syndrome expert, organization, psychiatrist or neurologist has published concurrence that there is credible evidence to conclude that Mozart had Tourette's. One TS specialist stated that, "although some web sites list Mozart as an individual who had Tourette's and/or OCD, it's not clear from the descriptions of his behavior that he actually had either."[57]
References in the entertainment industry
The entertainment industry often depicts those with TS as being social misfits whose only tic is coprolalia, which has furthered stigmatization and the general public's misunderstanding of persons with Tourette's as "people who can't help yelling swear words a lot".
Several documentaries have attempted, with varying levels of success, to portray Tourette's syndrome accurately and to advocate for greater understanding of persons with Tourette's. I Have Tourette's but Tourette's Doesn't Have Me, was produced by HBO in conjunction with the Tourette Syndrome Association, featuring children between the ages of 6-13. It is available in a format that includes information for teachers, and has become a useful tool for advocating for tolerance and understanding of children with Tourette syndrome in the classroom. Video clips from that documentary are on CBS News and News 10 Now. John's not Mad is a 1989 documentary about a Scottish teenager who has severe Tourette's and coprolalia. The Discovery Health Channel produced a documentary on Tourette's Syndrome in the UK. Twitch and Shout examines a society that is quick to judge a person who strays outside the limits of conventional behavior, won numerous awards, and was nominated for an Emmy.
A movie released on video, The Tic Code, stars Gregory Hines as a saxophone player with TS who befriends a 10 year old boy with TS. It was written by Polly Draper, and produced with her husband, jazz musician Michael Wolff, who has Tourette's and on whose life the script was loosely based. The UK movie, Dirty Filthy Love, tells the story of Mark Furness (Michael Sheen) with Obsessive Compulsive Disorder (OCD) and Tourette's negotiating his way through divorce, matchmaking efforts, and a woman who introduces him to therapy and unconditional love.
Tourette syndrome is good fodder for radio and television talk show ratings. Some talk shows (e.g.; Oprah) have focused on accurate and sympathetic portrayals of people with Tourette's, while others (e.g.; Dr. Phil), have furthered stigmatization, focusing on rare and sensational aspects of the condition, or promoting misinformation. An infamous incident of disinformation about coprolalia and Tourette's involved Dr. Laura Schlessinger. Garrison Keillor, radio show host of NPR's A Prairie Home Companion, produced a segment in 2006, titled "Broadway Tourette's" about segregating people with stereotypical Tourette's from other passengers on a cruise ship, prompting a press release from the Tourette Syndrome Association. TSA on PHC
Many television shows have addressed the topic of Tourette's, but only a few of them have helped to advance understanding of Tourette's. A 1981 episode of the television show, Quincy, M.E., "Seldom Silent, Never Heard", was a seminal moment in the history of Tourette's. It was perhaps the first television representation of Tourette's syndrome, and its portrayal led to many undiagnosed people with tics recognizing their symptoms and getting a correct diagnosis. Other television shows which helped advance understanding of and advocacy for Tourette's include LA Law, The Practice and 7th Heaven.
However, even more television and film productions are not accurate representations of persons with Tourette's, and many of them have used misconceptions about coprolalia as a plot device or portrayed people with Tourette's as being dangerously out of control. For example, in an episode of Ally McBeal, Anne Heche portrays a woman with Tourette's who gets a sudden leg tic that causes her to run over and kill her boyfriend. She plays a simpleton who expresses no remorse for the killing. An episode of Touched by an Angel, "An Angel on my Tree", was about a father who committed manslaughter in an angry "rage" reaction to an event that involved his son, both with Tourette's. In an episode of The Simpsons, Ms Krabappel is recounting all the diseases and illnesses Bart has claimed to have to excuse himself for a test. She says, "and that unfortunate case of Tourette's Syndrome", and Bart tries to pretend he still might have it by cursing and rambling. Other examples are The Big White, Deuce Bigalow: Male Gigolo, Niagara, Niagara, Not Another Teen Movie, Wedding Crashers, The Wedding Singer, The West Wing and What About Bob. In Matchstick Men, the protagonist (Nicolas Cage) is a neurotic con artist with Tourette's and OCD.
The UK Britpop band Manic Street Preachers recorded a song on the Gold Against The Soul album titled "Symphony Of Tourette", the lyric being sung from the perspective of a person with Tourette's. The album sleeve also contains a brief description of the condition and its symptoms following the lyrics for the song. Nirvana recorded a song on the In Utero album titled "Tourette's", sung with the lyrics intensely shouted, perhaps to mimic the syndrome. A musical about Tourette's, In My Life, was a resounding flop on Broadway, opening in October, 2005, and closing quickly to dismal reviews.
External links
- The Tourette Spectrum Disorder Association - A California based advocacy group not affiliated with the TSA.
- The Tourette Syndrome Association, Inc. - A USA advocacy group for Tourette's, with chapters nationwide.
- Tourette Syndrome Plus - A website on Tourette Syndrome plus comorbid conditions.
- Tourette's Syndrome: minimizing confusion - A Tourette's Syndrome blog written by RD Freeman, a professional advisory board member of Tourette Syndrome Foundation of Canada, and former member of the TSA Medical Advisory Board (MAB).
References
- ^ Kushner, HI. A Cursing Brain? : The Histories of Tourette Syndrome. Harvard University Press, 1999.
- ^ Tourette Syndrome Association. Definitions and Classification of Tic Disorders. Accessed 22 Mar 2005.
- ^ a b c d e Leckman JF, Cohen DJ. Tourette's Syndrome—Tics, Obsessions, Compulsions: Developmental Psychopathology and Clinical Care. John Wiley & Sons, Inc., New York, 1999.
- ^ a b c d e f g h i Tourette Syndrome Association. Tourette Syndrome: Frequently Asked Questions Accessed 8 Feb 2006.
- ^ Cohen AJ, Leckman JF. Sensory phenomena associated with Gilles de la Tourette's syndrome. J Clin Psychiatry. 1992 Sep;53(9):319-23. PMID 1517194
- ^ Bliss J. Sensory experiences of Gilles de la Tourette syndrome. Arch Gen Psychiatry. 1980 Dec;37(12):1343-7. PMID 6934713
- ^ Kwak C, Dat Vuong K, Jankovic J. Premonitory sensory phenomenon in Tourette's syndrome. Mov Disord. 2003 Dec;18(12):1530-3. PMID 14673893
- ^ Scahill LD, Leckman JF, Marek KL. Sensory phenomena in Tourette's syndrome. Adv Neurol. 1995;65:273-80. PMID 7872145
- ^ Miguel EC, do Rosario-Campos MC, Prado HS, et al. Sensory phenomena in obsessive-compulsive disorder and Tourette's disorder. J Clin Psychiatry. 2000 Feb;61(2):150-6. PMID 10732667
- ^ a b c d e f g h i j k l m n Zinner SH. Tourette disorder. Pediatr Rev. 2000;21(11):372-383. PMID 11077021
- ^ Packer, L. Tourette Syndrome "Plus". Accessed 12 Feb 2006.
- ^ a b c d e National Institutes of Health (NIH). Tourette Syndrome Fact Sheet Accessed 23 Mar 2005.
- ^ a b Sacks O. The Man Who Mistook His Wife For A Hat: And Other Clinical Tales. Touchstone, New York, 1998.
- ^ Sukhodolsky DG, Scahill L, Zhang H, et al. Disruptive behavior in children with Tourette's syndrome: association with ADHD comorbidity, tic severity, and functional impairment. J Am Acad Child Adolesc Psychiatry. 2003 Jan;42(1):98-105. PMID 12500082
- ^ Hoekstra PJ, Steenhuis MP, Troost PW, et al. Relative contribution of attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic severity to social and behavioral problems in tic disorders. J Dev Behav Pediatr. 2004 Aug;25(4):272-9. PMID 15308928
- ^ Carter AS, O'Donnell DA, Schultz RT, et al. Social and emotional adjustment in children affected with Gilles de la Tourette's syndrome: associations with ADHD and family functioning. Attention Deficit Hyperactivity Disorder. J Child Psychol Psychiatry. 2000 Feb;41(2):215-23. PMID 10750547
- ^ Spencer T, Biederman J, Harding M, et al. Disentangling the overlap between Tourette's disorder and ADHD. J Child Psychol Psychiatry. 1998 Oct;39(7):1037-44. PMID 9804036
- ^ Behavenet.Tourette's disorder. Accessed 10 Mar 2005.
- ^ a b Cohen, DJ, Jankovic J, Goetz CG, (eds). Advances in Neurology, Vol. 85, Tourette Syndrome. Lippincott, Williams & Wilkins, Philadelphia, PA, 2001.
- ^ a b c Leckman JF, Zhang H, Vitale A, et al. Course of tic severity in Tourette syndrome: the first two decades. Pediatrics. 1998;102(1 Pt 1):14-19. PMID 9651407
- ^ a b c d e f g h Bagheri MM, Kerbeshian J, Burd L. Recognition and management of Tourette's syndrome and tic disorders. Am Fam Physician. 1999; 59:2263-2274.
- ^ a b c Freeman, RD. Tourette's Syndrome: minimizing confusion. Accessed 8 February 2006.
- ^ a b c Mejia NI, Jankovic J. Secondary tics and tourettism. Rev Bras Psiquiatr. 2005;27(1):11-7. PMID 15867978
- ^ a b Tourette Syndrome Association. What is Tourette syndrome? Accessed 11 Feb 2005.
- ^ Bloch MH, Peterson BS, Scahill L, et al. Adulthood outcome of tic and obsessive-compulsive symptom severity in children with Tourette syndrome. Arch Pediatr Adolesc Med. 2006;160(1):65-69. PMID 16389213
- ^ Burd L, Kerbeshian PJ, Barth A, et al. Long-term follow-up of an epidemiologically defined cohort of patients with Tourette syndrome. J Child Neurol. 2001;16(6):431-437. PMID 11417610
- ^ Scahill L, Tanner C, Dure L. The epidemiology of tics and Tourette syndrome in children and adolescents. Adv Neurol. 2001;85:261-71. PMID 11530433
- ^ Kadesjo B, Gillberg C. Tourette's disorder: epidemiology and comorbidity in primary school children. J Am Acad Child Adolesc Psychiatry. 2000 May;39(5):548-55. PMID 10802971
- ^ Kurlan R, McDermott MP, Deeley C, et al. Prevalence of tics in schoolchildren and association with placement in special education. Neurology. 2001 Oct 23;57(8):1383-8. PMID 11673576
- ^ a b c Robertson MM. Tourette syndrome, associated conditions and the complexities of treatment. Brain. 2000;123 Pt 3:425-462. PMID 10686169
- ^ Hyde TM, Aaronson BA, Randolph C, et al. Relationship of birth weight to the phenotypic expression of Gilles de la Tourette's syndrome in monozygotic twins. Neurology. 1992 Mar;42(3 Pt 1):652-8. PMID 1549232
- ^ Leckman JF, Dolnansky ES, Hardin MT, et al. Perinatal factors in the expression of Tourette's syndrome: an exploratory study. J Am Acad Child Adolesc Psychiatry. 1990 Mar;29(2):220-6. PMID 1969861
- ^ Santangelo SL, Pauls DL, Goldstein JM, et al. Tourette's syndrome: what are the influences of gender and comorbid obsessive-compulsive disorder? J Am Acad Child Adolesc Psychiatry. 1994 Jul-Aug;33(6):795-804. PMID 8083136
- ^ Pauls DL, Towbin KE, Leckman JF, et al. Gilles de la Tourette's syndrome and obsessive-compulsive disorder. Evidence supporting a genetic relationship. Arch Gen Psychiatry. 1986 Dec;43(12):1180-2. PMID 3465280
- ^ Schmidt, William (19 Oct 2005). Genetic mutation is linked to Tourette's. Yale Daily News.
- ^ Leckman JF, Hardin MT, Riddle MA, et al. Clonidine treatment of Gilles de la Tourette's syndrome. Arch Gen Psychiatry. 1991 Apr;48(4):324-8. PMID 2009034
- ^ Leckman JF, Cohen DJ, Detlor J, et al. Clonidine in the treatment of Tourette syndrome: a review of data. Adv Neurol. 1982;35:391-401. PMID 6756089
- ^ Leckman JF, Detlor J, Harcherik DF, et al. Short- and long-term treatment of Tourette's syndrome with clonidine: a clinical perspective. Neurology. 1985 Mar;35(3):343-51. PMID 3883235
- ^ Palumbo D, Spencer T, Lynch J, et al. Emergence of tics in children with ADHD: impact of once-daily OROS methylphenidate therapy. J Child Adolesc Psychopharmacol. 2004 Summer;14(2):185-94. PMID 15319016
- ^ Kurlan R. Tourette's syndrome: are stimulants safe? Curr Neurol Neurosci Rep. 2003 Jul;3(4):285-8. PMID 12930697
- ^ Law SF, Schachar RJ. Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder? J Am Acad Child Adolesc Psychiatry. 1999 Aug;38(8):944-51. PMID 10434485
- ^ Nolan EE, Gadow KD, Sprafkin J. Stimulant medication withdrawal during long-term therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder. Pediatrics. 1999 Apr;103(4 Pt 1):730-7. PMID 10103294
- ^ Tourette's Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002 Feb 26;58(4):527-36. PMID 11865128
- ^ Allen AJ, Kurlan RM, Gilbert DL, et al. Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. Neurology. 2005 Dec 27;65(12):1941-9. PMID 16380617
- ^ a b c d e Swerdlow, NR. Tourette Syndrome: Current Controversies and the Battlefield Landscape. Curr Neurol Neurosci Rep. 2005, 5:329-331. PMID 16131414
- ^ Silver AA, Shytle RD, Sheehan KH, et al. Multicenter, double-blind, placebo-controlled study of mecamylamine monotherapy for Tourette's disorder. J Am Acad Child Adolesc Psychiatry. 2001 Sep;40(9):1103-10. PMID 11556635
- ^ Tourette Syndrome Association. Statement: Deep Brain Stimulation and Tourette Syndrome Accessed 26 Feb 2005.
- ^ Zinner SH. Tourette syndrome—much more than tics. Contemporary Pediatrics. Aug 2004;21(8):22-49. Part 1Part 2
- ^ Sandyk R, Awerbuch G. Marijuana and Tourette's syndrome. J Clin Psychopharmacol. 1988 Dec;8(6):444-5. PMID 3235704
- ^ Muller-Vahl KR, Kolbe H, Dengler R. [Gilles de la Tourette syndrome. Effect of nicotine, alcohol and marihuana on clinical symptoms] Nervenarzt. 1997 Dec;68(12):985-9. German. PMID 9465342
- ^ Muller-Vahl KR, Schneider U, Prevedel H, et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry. 2003 Apr;64(4):459-65. PMID 12716250
- ^ Muller-Vahl KR, Prevedel H, Theloe K, et al. Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance. Neuropsychopharmacology. 2003 Feb;28(2):384-8. PMID 12589392
- ^ Simkin, Benjamin. Medical and Musical Byways of Mozartiana. FITHIAN PRESS.
- ^ Simkin B. Mozart's scatological disorder. BMJ. 1992 Dec 19-26;305(6868):1563-7. PMID 1286388
- ^ Tourette Syndrome Association:Did Mozart really have TS? Accessed online 14 Aug 2002.
- ^ Sacks O. Tourette's syndrome and creativity. BMJ. 1992 Dec 19-26;305(6868):1515-6. PMID 1286364
- ^ Packer, L. School Behavior.com - Famous People with Tourette's Syndrome or Obsessive-Compulsive Disorder. Accessed online 12 February 2006.