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Treatment of Tourette syndrome

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Tourette syndrome (also Tourette's syndrome or TS) is an inherited neuropsychiatric disorder with onset in childhood, characterized by the presence of motor and phonic tics. Treatment of Tourette syndrome has the goal of managing symptoms to achieve optimum functioning, rather than eliminating symptoms; not all persons with Tourette's require treatment, and there is no cure or universally effective medication.[1][2][3] Explanation and reassurance alone are often sufficient treatment;[2] education is an important part of any treatment plan.[4]

Tourette syndrome patients may exhibit symptoms of other comorbid conditions along with their motor and phonic tics. Associated conditions include attention-deficit hyperactivity disorder (ADD or ADHD), obsessive-compulsive disorder (OCD), learning disabilities and sleep disorders.[3] Patients who have ADHD along with Tourette's may also have problems with disruptive behaviors, overall functioning, and cognitive function. Co-occurring OCD can also be a source of impairment, necessitating treatment. Not all persons with tics will also have other conditions and not all persons with tics require treatment, but when comorbid disorders are present, they often require treatment.

Stimulants (such as Adderall and Ritalin) are underused in the treatment of ADHD when tics are also present because of fears that they increase tics.[5][6] Experimental treatments such as deep brain stimulation, nicotine, cannabis and complementary and alternative medicine approaches have widespread appeal but unproven safety and efficacy.

Treatment priority[edit]

Treatment of Tourette syndrome can be divided into treatment of tics, and treatment of co-occurring conditions, which, when present, are often a larger source of functional impairment than the tics themselves.[6]

There is no cure for Tourette's and no medication which works universally for all individuals without significant adverse effects;[3] knowledge and understanding are the best treatments available for tics.[2][4] Management of the symptoms of Tourette's may include pharmacological, behavioral and psychological therapies. While pharmacological treatment is reserved for more severe symptoms, other types of treatments may help avoid or improve symptoms of depression or social isolation, and improve supportive family functioning. Educating the patient, family, and surrounding community (school, church, friends, etc.) is a key part of treatment.[1]

The majority of people with TS require no medication, but medication is available to help when symptoms interfere with functioning.[3] 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, medication is not usually started immediately or changed often. Frequently, the tics subside with understanding of the condition and a supportive environment.[1] 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.[2]

The classes of medication with the most proven efficacy in treating tics—typical and atypical neuroleptics including risperidone (trade name[7] Risperdal), ziprasidone (Geodon), haloperidol (Haldol), pimozide (Orap) and fluphenazine (Prolixin)—can have long-term and short-term adverse effects.[6] The antihypertensive agents, clonidine (Catapres) and guanfacine (Tenex), are also used to treat tics; studies show variable efficacy, but a lower side effect profile than the neuroleptics.[1] 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 when stimulant trials fail, including guanfacine (Tenex), atomoxetine (Strattera) and tricyclics. Clomipramine (Anafranil), a tricyclic antidepressant, and SSRIs—a class of antidepressants including fluoxetine (Prozac), sertraline (Zoloft), and fluvoxamine (Luvox)—may be prescribed when a Tourette's patient also has symptoms of obsessive–compulsive disorder.[6]

Treatment of tics[edit]

Space-filling representation of a haloperidol molecule. Haloperidol is an antipsychotic medication sometimes used to treat severe cases of Tourette's.

There are no medications specifically designed to target tics, although some antipsychotics (for example, pimozide) have been FDA-approved for treating Tourette's. 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, and are associated with a high side effect profile. The traditional antipsychotic drugs are associated with tardive dyskinesia when used long-term; and parkinsonism, dystonia, dyskinesia, and akathisia when used short-term. Additional side effects can be school phobia (a form of separation anxiety), depression, weight gain, and cognitive blunting (dulling of cognitive ability). Another traditional antipsychotic used in treating Tourette's is fluphenazine (brand name Prolixin), although the evidence supporting its use is less than that of haloperidol and pimozide.[6]

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 Geodon), 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.[6]

Clonidine (or the clonidine patch) is one of the medications typically tried first when medication is needed for Tourette's.

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. Originally developed to treat high blood pressure, these medications are a safer alternative to neuroleptic medications for the people with TS that respond to them. 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. 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.[8] 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. Clonidine (brand name Catapres) works on tics for about half of people with TS.[9][10] Maximal benefit may not be achieved for 4–6 months. A small number of patients may worsen on clonidine.[11] Guanfacine (brand name Tenex) is another antihypertensive that is used in treating TS. 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.[6]

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.[6]

Treatment of ADHD in the presence of tic disorders[edit]

Stimulants (such as Adderall and Ritalin) are underused in the treatment of ADHD when tics are also present.

Patients with Tourette's who are referred to specialty clinics have a high rate of comorbid attention-deficit hyperactivity disorder (ADHD), so the treatment of ADHD co-occurring with tics is often part of the clinical treatment of Tourette's. Patients who have ADHD along with Tourette's may also have problems with disruptive behaviors, overall functioning, and cognitive function, accounted for by the comorbid ADHD, highlighting the importance of identifying and treating other conditions when present.[12]

The treatment of ADHD in the presence of tic disorders has long been a controversial topic. Past medical practice held that stimulants (such as Ritalin) could not be used in the presence of tics, due to concern that their use might worsen tics;[13] however, multiple lines of research have shown that stimulants can be cautiously used in the presence of tic disorders.[14] Several studies have shown that stimulants do not exacerbate tics any more than placebo does, and suggest that stimulants may even reduce tic severity.[15] Controversy remains, and the PDR continues to carry a warning that stimulants should not be used in the presence of tic disorders, so physicians may be reluctant to use them. 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.[2][13]

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.[6] Current prescribed stimulant medications include: methylphenidate (brand names 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). A retrospective case series published in 1993 suggested that treatment with bupropion (trade name Wellbutrin) can worsen tics,[16] but there is no data from placebo-controlled trials to support this.[17] There is good empirical support for the use of desipramine, bupropion and atomoxetine (brand name Strattera).[6] Atomoxetine is the only non-controlled Food and Drug Administration (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.[18]

Behavioral treatments[edit]

Cognitive behavioral therapy (CBT) is a useful treatment when OCD is present.[19]

Other behavioral therapies including habit reversal training (HRT)/comprehensive behavioral intervention (CBIT) and exposure and response prevention (ERP) are first-line interventions,[20] subject to some limitations: children younger than ten may not understand the treatment, people with severe tics or ADHD may not be able to suppress their tics or sustain the required focus to benefit from behavioral treatments, and there is a lack of therapists trained in behavioral interventions.[21]

Massed negative practice, biofeedback, relaxation, hypnosis and other behavioral approaches are proposed as alternative treatments of tics, but few have been well assessed.[22] Relaxation techniques, such as exercise, yoga or meditation, may be useful in relieving stress that may aggravate tics, but the majority of behavioral interventions (such as relaxation training and biofeedback, with the exception of habit reversal) have not been systematically evaluated and are not proven therapies for Tourette's.[23]

Experimental treatments[edit]

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.[24][25] While a balanced diet may aid in overall health, and avoidance of caffeine may help minimize tics for some children,[26] no particular diet or alternative therapy (vitamin or diet) is supported by scientific evidence.[24][22] As of 2018, in spite of no evidence base supporting dietary approaches to management of TS symptoms, anecdotal reports indicate that parents, caregivers, and individuals with TS are using dietary approaches and nutritional supplements nonetheless.[24]

Regular exercise can help reduce stress and improve a child's sense of accomplishment and self-esteem, but the effect of exercise on symptoms remains unstudied.[26]

Administration of nicotine via transdermal patches was found beneficial,[27] in preliminary case studies, but these effects were not reproduced in well-controlled trials several years later.[5] Studies of nicotine derivatives (mecamylamine, inversine) also showed that they were not effective as a single therapy for the symptoms of Tourette's.[28]

Limited evidence suggests that tetrahydrocannabinol (THC), the main psychoactive ingredient of cannabis, may help reduce tics in adults.[29] More research is needed to confirm this low-quality evidence for the effects of THC.[30] There is insufficient evidence for other cannabis-based medications in the treatment of Tourette's.[29]

Deep brain stimulation has been used to treat adults with severe Tourette's that does not respond to conventional treatment, but is regarded as an experimental and dangerous procedure that is unlikely to become widespread.[31][32][33] [34] The procedure is well tolerated, but complications include "short battery life, abrupt symptom worsening upon cessation of stimulation, hypomanic or manic conversion, and the significant time and effort involved in optimizing stimulation parameters".[35] As of 2006, there were five reports in patients with TS; all experienced reduction in tics and the disappearance of obsessive-compulsive behaviors.[35] Robertson reports that DBS had been used on 55 adults as of 2011, remains an experimental treatment,[32] and "should only be conducted by experienced functional neurosurgeons operating in centres which also have a dedicated Tourette syndrome clinic".[32] According to Malone et al (2006), "Only patients with severe, debilitating, and treatment-refractory illness should be considered; while those with severe personality disorders and substance abuse problems should be excluded."[35] Du et al (2010) say that "As an invasive therapy, DBS is currently only advisable for severely affected, treatment-refractory TS adults".[33] Singer (2011) says that "pending determination of patient selection criteria and the outcome of carefully controlled clinical trials, a cautious approach is recommended".[31] Viswanathan A et al (2012) say that DBS should be used in patients with "severe functional impairment that can not be managed medically".[36]

Practice guidelines[edit]

In 2019, the American Academy of Neurology (AAN) published practice guidelines, "Treatment of tics in people with Tourette syndrome and chronic tic disorders", including 46 recommendations based on a systematic review by nine physicians, two psychologists, and two patient representatives. The panel assigned three levels of recommendations corresponding to the strength of the evidence supporting the recommendation:[29]

  • A: "rare because they are based on high confidence in the evidence and require both a high magnitude of benefit and low risk".
  • B: "common because the requirements are less stringent but still based on the evidence and benefit–risk profile".
  • C: "lowest allowable recommendation level that the AAN considers useful within the scope of clinical practice and accommodates the highest degree of practice variation".

The panel attached a helping verb to each level of recommendation: A = must; B = should, and C = may.[29]

Description Recommendation per American Academy of Neurology 2019 practice guidelines[29] Clinicians
A: Must B: Should C: May
Counseling Inform individuals and caregivers about the natural course of tic disorders
☑Y
Counseling Evaluate tic-related impairment in functioning
☑Y
Counseling Inform about watchful waiting for those who do not experience impairment
☑Y
Counseling Initially prescribe Comprehensive Behavioral Intervention for Tics (CBIT) for those who are motivated and without functional impairment
☑Y
Counseling Periodically re-evaluate need for any prescribed medications for tics
☑Y
Psychoeducation Refer teachers and peers to resources for education about TS
☑Y
ADHD assessment and management Assess for comorbid ADHD
☑Y
ADHD assessment and management Evaluate impairment from symptoms of ADHD
☑Y
ADHD assessment and management Ensure ADHD is treated when it is causing impairment
☑Y
OCD assessment and management Assess for comorbid OCD
☑Y
OCD assessment and management Ensure OCD is treated when it is present
☑Y
Other comorbid disorders Screen for comorbid anxiety, mood, and disruptive behavior disorders
☑Y
Other comorbid disorders Inquire about suicidal ideation and recommend resources if present
☑Y
Tic severity assessment Measure severity of tics using a validated assessment scale
☑Y
Treatment expectations Inform that treating tics rarely leads to complete cessation of tics
☑Y
Behavioral treatments For those who have access to it, prescribe CBIT initially relative to other behavioral interventions
☑Y
Behavioral treatments Offer CBIT initially relative to medication
☑Y
Behavioral treatments If face-to-face CBIT is not available, prescribe CBIT via Internet, or prescribe other behavioral interventions
☑Y
α agonist treatment Inform individuals with comorbid ADHD that α2 agonists may treat both tics and ADHD
☑Y
α agonist treatment Prescribe α2 agonists when benefits outweigh risks
☑Y
α agonist treatment Inform individuals treated about side effects of α2 agonists
☑Y
α agonist treatment In those treated with α2 agonists, monitor heart rate and blood pressure
☑Y
α agonist treatment For those taking extended release guanfacine, monitor QTc interval as indicated
☑Y
α agonist treatment Gradually taper α2 agonists when discontinuing them
☑Y
Antipsychotic treatment Prescribe antipsychotics when benefit outweighs risks
☑Y
Antipsychotic treatment Inform patients about adverse effects (extrapyramidal, hormonal, and metabolic) of antipsychotics
☑Y
Antipsychotic treatment Prescribe lowest effective dosage of antipsychotics when using them
☑Y
Antipsychotic treatment When using antipsychotics, use evidence-based monitoring for drug-induced movement disorders and adverse effects
☑Y
Antipsychotic treatment When prescribing certain antipsychotics, monitor QTc interval and perform elecrocardiography
☑Y
Antipsychotic treatment Gradually taper (over weeks to months) antipsychotics when discontinuing
☑Y
Botulinum toxin injections Prescribe botulinum toxin injections for localized simple motor tics to adolescents and adults when benefits outweigh risks
☑Y
Botulinum toxin injections Prescribe botulinum toxin injections for aggressive or disabling vocal tics to adolescents and adults when benefits outweigh risks
☑Y
Botulinum toxin injections Inform individuals that temporary effects of botulinum toxin injections of hypophonia and weakness may occur
☑Y
Topiramate treatment Prescribe topiramate when benefits outweigh risks
☑Y
Topiramate treatment Inform individuals when prescribing topiramate of adverse effects
☑Y
Cannabis-based treatment When individuals are using cannabis as self-medication for tics, direct them to appropriate medical supervision
☑Y
Cannabis-based treatment For "treatment-resistant adults with clinically relevant tics", consider cannabis-based products where legislation permits it.
☑Y
Cannabis-based treatment For adults who already self-medicate tics with cannabis-based products, consider cannabis-based medication where legislation permits it.
☑Y
Cannabis-based treatment When prescribing cannabis-products where legislation permits it, use lowest effective dose
☑Y
Cannabis-based treatment When prescribing, inform individuals that cannabis-based products can affect driving
☑Y
Cannabis-based treatment When prescribing, provide ongoing re-evaluation of need
☑Y
Deep brain stimulation treatment Employ multidisciplinary evaluation of benefits versus risks
☑Y
Deep brain stimulation treatment Exclude secondary causes of tic-like movements and confirm TS diagnosis when considering deep brain stimulation
☑Y
Deep brain stimulation treatment Screen for psychiatric disorders and follow deep brain stimulation subjects post-operatively
☑Y
Deep brain stimulation treatment Before prescribing, assure that multiple classes of medications have been tried
☑Y
Deep brain stimulation treatment Consider deep brain stimulation for "severe, self-injurious tics"
☑Y

Notes[edit]

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  2. ^ a b c d e Zinner SH. Tourette disorder. Pediatr Rev. 2000;21(11):372–383. PMID 11077021
  3. ^ a b c d Tourette Syndrome Fact Sheet. National Institute of Neurological Disorders and Stroke/National Institutes of Health (NINDS/NIH), February 14, 2007. Retrieved on May 14, 2007.
  4. ^ a b Peterson BS, Cohen DJ. The Treatment of Tourette's Syndrome: Multimodal, Developmental Intervention. J Clin Psychiatry. 1998;59 Suppl 1:62–72; discussion 73–4. PMID 9448671 Full text, archived May 25, 1998. "Because of the understanding and hope that it provides, education is also the single most important treatment modality that we have in TS."
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  6. ^ a b c d e f g h i j Scahill L, Erenberg G, Berlin CM Jr, Budman C, Coffey BJ, Jankovic J, Kiessling L, King RA, Kurlan R, Lang A, Mink J, Murphy T, Zinner S, Walkup J; Tourette Syndrome Association Medical Advisory Board: Practice Committee. Contemporary assessment and pharmacotherapy of Tourette syndrome (PDF). NeuroRx. 2006 Apr;3(2):192–206. doi:10.1016/j.nurx.2006.01.009 PMID 16554257
  7. ^ Medication trade names may differ between countries. In general, this article uses North American trade names.
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    * 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
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  14. ^ 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. doi:10.1542/peds.103.4.730 PMID 10103294
  15. ^ 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
  16. ^ Spencer T, Biederman J, Steingard R, Wilens T. Bupropion exacerbates tics in children with attention-deficit hyperactivity disorder and Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 1993 Jan;32(1):211–4. doi:10.1097/00004583-199301000-00030 PMID 8428875
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  18. ^ 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. doi:10.1212/01.wnl.0000188869.58300.a7 PMID 16380617
  19. ^ Coffey BJ, Shechter RL. "Treatment of co-morbid obsessive compulsive disorder, mood, and anxiety disorders". Adv Neurol. 2006;99:208–21. PMID 16536368
  20. ^ Fründt O, Woods D, Ganos C. "Behavioral therapy for Tourette syndrome and chronic tic disorders". Neurol Clin Pract. 2017 Apr;7(2):148–56. doi:10.1212/CPJ.0000000000000348 PMID 29185535
  21. ^ Ganos C, Martino D, Pringsheim T. "Tics in the pediatric population: Pragmatic management". Mov Disord Clin Pract. 2017 Mar–Apr;4(2):160–72. doi:10.1002/mdc3.12428 PMID 28451624
  22. ^ a b Singer HS. "Tourette's syndrome: from behaviour to biology". Lancet Neurol. 2005 Mar;4(3):149–59. doi:10.1016/S1474-4422(05)01012-4 PMID 15721825
  23. ^ Woods DW, Himle MB, Conelea CA. Behavior therapy: other interventions for tic disorders. Adv Neurol. 2006;99:234–40. PMID 16536371
  24. ^ a b c Ludlow AK, Rogers SL. "Understanding the impact of diet and nutrition on symptoms of Tourette syndrome: A scoping review". J Child Health Care. 2018 Mar;22(1):68–83. doi:10.1177/1367493517748373 PMID 29268618
  25. ^ Zinner SH. "Tourette syndrome—much more than tics". Contemporary Pediatrics. Aug 2004;21(8):22–49. Part 1 PDF Part 2 PDF
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  27. ^ Sacco KA, Bannon KL, George TP. Nicotinic receptor mechanisms and cognition in normal states and neuropsychiatric disorders. J. Psychopharmacol. (Oxford) Dec 2004, 18(4):457–74 doi:10.1177/0269881104047273 PMID 15582913
  28. ^ 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
  29. ^ a b c d e Pringsheim T, Okun MS, Müller-Vahl K, et al. "Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders". Neurology. May 6 2019;92(19):896–906. PMID 31061208 doi:10.1212/WNL.0000000000007466
  30. ^ Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA 2015;313(24): 2456-2473. doi:10.1001/jama.2015.6358 PMID 26103030
  31. ^ a b Singer HS. "Tourette syndrome and other tic disorders". Handb Clin Neurol. 2011;100:641–57. doi:10.1016/B978-0-444-52014-2.00046-X PMID 21496613. Also see Singer HS. "Tourette's syndrome: from behaviour to biology". Lancet Neurol. 2005 Mar;4(3):149–59. doi:10.1016/S1474-4422(05)01012-4 PMID 15721825.
  32. ^ a b c Robertson MM. "Gilles de la Tourette syndrome: the complexities of phenotype and treatment". Br J Hosp Med (Lond). 2011 Feb;72(2):100–7. PMID 21378617
  33. ^ a b Du JC, Chiu TF, Lee KM, et al. "Tourette syndrome in children: an updated review". Pediatr Neonatol. 2010 Oct;51(5):255–64. doi:10.1016/S1875-9572(10)60050-2 PMID 20951354
  34. ^ Statement: Deep Brain Stimulation and Tourette Syndrome. Tourette Syndrome Association. Retrieved on February 26, 2005.
  35. ^ a b c Malone DA Jr, Pandya MM. Behavioral neurosurgery. Adv Neurol. 2006;99:241–7. PMID 16536372
  36. ^ Viswanathan A, Jimenez-Shahed J, Baizabal Carvallo JF, Jankovic J. Deep brain stimulation for Tourette syndrome: target selection. Stereotact Funct Neurosurg. 2012;90(4):213–24. PMID 22699684 doi: 10.1159/000337776

External links[edit]