To discuss Tourette syndrome, one has to know what doctors meanby "tics." A tic is a brief, unwanted movement or noise thatsomeone performs repeatedly, usually many times a day. Ticscan be held back for a period of time, but this often bringsa sense of building pressure to repeat the tic. Blinking, headshaking, and loud sniffing are common simple tics. More complexactions such as touching the floor or saying words can alsobe tics. Tics are very common: about a quarter of young childrenwill have a tic for a short period of time, and about 1 childin each elementary school classroom has tics that last for ayear or more. If a patient has both motor and vocal tics thatstarted in childhood or teens, have lasted for at least a year,and do not have an identifiable specific cause, the patientreceives a diagnosis of Tourette syndrome (TS).
By this accepted definition, TS is relatively common. Studiesin which a large number of children are examined carefully fortics find that about 1 in 200 (0.5%) have TS. However, onlyabout half that number (0.3%) have ever received the TS diagnosis.Only about a quarter of patients with TS describe their symptomsas moderate or severe.1 Thus most people with TS have fairlymild symptoms and are best managed with education and nonspecificsupportive treatment.2
For others, however, TS is a daily battle. The problems canbe many. There may be social problems like bullying in schoolor unfair treatment in job interviews. Children may have troubleconcentrating in school because of tics or from focusing onholding tics back. Some patients have tics that are violentenough to cause injuries. It is appropriate to provide treatmentfor patients with any of these problems.
Fortunately, there are a variety of treatments for tics. Noavailable treatment cures TS, but 2 classes of treatment haveproven effective after careful study. The first class consistsof medicines that were originally developed to treat hallucinations.Recent drugs from this class, including risperidone, ziprasidone,olanzapine, and aripiprazole, reduce tics by about 50% on average.They are better tolerated than older drugs. The second kindof carefully studied effective treatment is a type of behaviortherapy. This was originally called habit reversal therapy andnow, with changes, is called CBIT (Comprehensive BehavioralIntervention for Tics).3
Other treatments are available; in fact, more than 20 differentkinds of treatment have been shown to be better than a placeboor "sugar pill." However, some patients with severe tics donot benefit enough or have side effects. For such patients eveninvasive treatments may be appropriate. One that has drawn muchinterest lately is deep brain stimulation (DBS).
Deep brain stimulation refers to placing very thin wires throughthe skull and into specific places in the brain, then sendingelectrical pulses through the wires to affect the activity ofthose brain regions. In other movement disorders, such as essentialtremor or Parkinson disease, there is now good evidence thatDBS is effective and relatively safe. This has led to the applicationof DBS to other movement disorders including TS.
Our state of knowledge regarding DBS for tics is no longer inits infancy but at best is still in the toddler stage.4 Forone thing, it is not yet clear where in the brain the wiresshould be placed for best effect. The 2 best sites seem to bethe internal globus pallidus (GPi) and the centromedian-parafascicularnuclei of the thalamus, near the middle of the brain (CM-Pf).Second, only a handful of patients with TS have participatedin controlled studies of DBS, where active stimulation treatmentis compared to sham or "pretend" treatment.5,6 Finally, littleinformation is available on the long-term effects of DBS fortic disorders.7 The current study from Italy and the UK in thisissue of Neurology® reports information on long-term DBStreatment in adults with TS.8
Investigators examined 18 patients, aged 17–46 years,with severe TS that had not responded to simpler treatments.The patients had 2 years of DBS in the left and right CM-Pf.Two patients had asked for the DBS to be stopped. One neededa second surgery with DBS in a different location. The authorsreport on how DBS may have influenced thinking and behaviorin the remaining 15 patients. In addition to tics, patientswith TS may have other behaviors including mood and anxietyproblems. The authors used rating scales to assess the severityof tics, obsessions, compulsions, anxiety, depression, and socialproblems. They performed testing of attention, memory, and language.Information was collected monthly, but this report focuses onresults at the 24-month visit compared to before surgery.
The 15 patients remaining in the study showed improvement intics, obsessive-compulsive symptoms, depression and anxiety,and all but 1 had better scores on social functioning. Noneof the cognitive or "thinking" tests showed a bad effect ofDBS, and in fact there was improvement in a measure of attention.
These results are good news for adults with severe TS who havenot responded adequately to medications or behavior therapy.They suggest that the majority of patients treated with DBSin the CM-Pf will have improved symptoms without cognitive sideeffects after 2 years of treatment.
As the authors are careful to note, however, this report doesnot answer all questions about DBS for TS. It may not be successfulin every patient. The 3 patients who dropped out of the studypresumably did not have similar improvement. A few patientshave been reported to have psychological side effects of DBS.It is considered a "Class IV" level of evidence (see "Aboutlevels of evidence").
When thinking of any treatment for TS, some important factsmust be considered. None of the available tic treatments, includingDBS, cures TS. Thus any treatment requires a careful weighingof the risks and benefits. Although DBS is relatively safe,it does carry some small risk of bleeding, infection, or injury.Half of children and teenagers with tics get better as theyget older, to the point that as adults they no longer noticeany tics. Furthermore, tics change in severity over time. SinceDBS would probably be used when tics are at their worst, someimprovement would be expected with or without DBS. However,the patients studied here had had severe tics for long periodsof time, so improvement without treatment may be less likely.
For all these reasons, at this point DBS should be consideredonly for a small fraction of patients with TS. The TouretteSyndrome Association makes several recommendations about DBS:1) Patients need to have full information about risks and benefitsof DBS and about other available treatments. 2) Patients needa very thorough evaluation before surgery at centers with specialexpertise, to make sure that DBS is the most appropriate choicefor each patient. 3) Until more information is available, mostDBS for TS should be done in a clinical research setting inwhich the results will be shared quickly and widely.9
Future controlled studies are needed, but this report emphasizesthat most patients with TS who receive treatment will have agood response without psychological side effects after 2 yearsof treatment with CM-Pf DBS.
The article on deep brain stimulation for Tourette syndrome(Neurology 2009;73:1375–1380) is considered a Class IVstudy. All studies in Neurology® are now rated on "levelsof evidence." This allows the reader of the article to quicklyget information about the quality of the study and to understandwhat problems might interfere with finding the "true answer"to a study question.
Doctors review scientific studies very carefully. There aremany different kinds of studies. Although all of them can provideimportant information about medical illnesses, studies differin the way that they are conducted. Some studies collect informationin strict ways. The most stringent studies are referred to asrandomized clinical trials or RCTs and provide the least biasedinformation. These are referred to as Class I. Trials that arenot so strict still provide helpful information yet have beencategorized with a lower class ranking (figure).
Figure Classification scheme requirements for therapeutic questions
Class I:
Referred to as RCTs, this kind of study is the most strict.People are selected for the study based on rigorous criteriathat are developed even before the study begins. In this kindof study, patients are assigned randomly (in a sense, by "cointoss") to either a specific medical treatment or placebo (sometimescalled a "sugar pill"). The person or team who rates how wellpatients do with the treatment cannot know whether the patientreceived the treatment or placebo: this is called "blinding."If the assessment team knows whether a patient is on placeboor treatment, it may influence their ratings. For example, theymay (consciously or unconsciously) expect that patients on treatmentwill do better and patients on placebo will do worse. This couldmake a treatment appear better than it really is.
For instance, if a person’s illness was improving, thetreatment team may automatically—perhaps subconsciously—thinkthat the treatment was successful because the patient receivedthe treatment and not placebo. In other words, the fact thatthe treatment team does not know who received treatment takesaway any influence that this knowledge could have on their assessments.
The treatment team must not be aware which treatment the nextstudyparticipant will receive until the participant has beenenrolledand treatment has been assigned by someone else.
The studyteam must decide their main question in advance ofthe study.
Theremust be clear rules for who is included in the study andwhocannot participate.
At least 80% of people who enter the studymust complete it.
If a treatment is being compared to an existing"standard" treatment,certain strict rules must be followed.
Class II:
A study that would be Class I except
It lacks 1 of the above 5 points OR.
It is a study that compares2 groups of people that are similarexcept that 1 group receiveda treatment and the other did not.In this class, the treatmentdecision was made by the person’sdoctor and not randomly(not by "coin toss"). The person orteam who rates how wellpatients did with the treatment shouldnot know what treatmentthe patient received ("blinded").
Class III:
Studies of all other types where the person or team rating theoutcome is unaware of what treatment the person received ("blinded")or the outcome of the treatment can easily be measured in astandard way (for example, with a number) that does not requiremuch judgment.
Class IV:
Studies that do not meet the above rules including expert opinions.
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Woods DW, Piacentini JC, Chang SW, et al. Managing Tourette Syndrome: A Behavioral Intervention: Parent Workbook. New York: Oxford University Press;
Ackermans L, Temel Y, Visser-Vandewalle V. Deep brain stimulation in Tourette’s syndrome. Neurotherapeutics 2008;5:339–344.[Medline]
Maciunas RJ, Maddux BN, Riley DE, et al. Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg 2007;107:1004–1014.[Medline]
Welter ML, Mallet L, Houeto JL, et al. Internal pallidal and thalamic stimulation in patients with Tourette syndrome. Arch Neurol 2008;65:952–957.[Abstract/Free Full Text]
Maddux B, Riley D, Whitney CM, Maciunas RJ. Double-blind trial of thalamic DBS for Tourette syndrome: one-year follow-up. Neurology 2007;68(suppl 1):A155. Abstract.
Porta M, Brambilla A, Cavanna AE, et al. Thalamic deep brain stimulation for treatment-refractory Tourette syndrome: two-year outcome. Neurology 2009;73:1375–1380.[Abstract/Free Full Text]
Mink JW, Walkup J, Frey KA, et al. Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome. Mov Disord 2006;21:1831–1838.[Medline]
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