Tourette's Syndrome: Diagnostic and Treatment Challenges

Tourette's syndrome (TS) is a neurodevelopmental disorder typically developing between ages 3 and 8.¹ Named after the pioneering French neurologist who first described this disorder, Georges Gilles de la Tourette, TS is more prevalent than previously assumed, is associated with numerous comorbidities, and is easily misdiagnosed.

Its hallmark symptoms (Table 1) include chronic repetitive motor and vocal tics that wax and wane. Motor tics can be simple (eg, eye blinks, face grimacing) or complex (eg, bending, twisting, hopping). Similarly, vocal tics can be simple (eg, sniffing, throat clearing, barking) or complex (eg, cursing, repeating words). The tics occur in varying cycles. For example, face grimacing may occur up to 30 times a minute, whereas complex vocal tics have longer cycles.

Complex tics often appear coordinated, voluntary, or purposeful. Some patients exercise inhibitory control for seconds to hours. This control, however, merely delays the outburst, which may be more extreme when voluntary control fails.² Tics often persist in all sleep stages?further proving their involuntary nature.³

Diagnosis

Symptoms of TS are easily confused with those of other disorders, including mental retardation, Wilson's disease, Meige's syndrome, Huntington's chorea, amphetamine abuse, schizophrenia, autism, and attention-deficit/hyperactivity disorder (ADHD).^4,5 Sudden withdrawal of medications (eg, neuroleptics) can lead to emergent tics.

Diagnostic criteria for Tourette's syndrome include the following:

• Multiple motor tics and at least 1 vocal tic occurring over the course of a year, although not necessarily simultaneously
• Symptoms that wax and wane, but no tic-free period longer than 3 months
• Onset prior to age 18^1,6

Diagnosis often is a process of elimination, employing laboratory work and computed tomography, electroencephalography, and magnetic resonance imaging scans. TS generally is diagnosed 2 to 3 years following symptom onset.¹

Prevalence and Clinical Course

The National Institute of Neurological Disorders and Stroke (NINDS) estimates that ~200,000 Americans have severe TS, but 1 in 100 individuals may exhibit milder symptoms. True prevalence remains elusive, partly because mild TS may go undiagnosed.⁵ Some experts estimate prevalence between 2% and 10% for milder variants of TS.¹ Males are affected 3 to 4 times more often than females.⁶

TS generally begins before age 8 with motor tics. Simple vocal tics follow, usually between ages 8 and 15, and then complex tics may start. Symptoms worsen progressively and peak between ages 8 and 11.^1,7 Up to 85% of patients report diminishing symptom severity at adolescence, although only 8% to 10% have complete remission in adulthood.⁷ Early tic severity is not predictive of adult tic severity.⁷ Stereotypes of TS patients disgorging obscenities or ethnic slurs incessantly are incorrect?fewer than 15% of cases include coprolalia.²

During periods of anger, excitement, or stress, symptoms typically intensify. They subside somewhat during periods of fatigue, calm, or focused activity or when sufferers concentrate on enjoyable events.⁶

Pathophysiology

TS is a neurologic disorder. Nevertheless, stereotypes persist suggesting that symptoms and etiology are psychiatric. The cortico-striatal-thalamocortical pathways are involved in TS, and evidence exists supporting cortical dysfunction as the underlying etiology.⁷ A neurotransmitter imbalance may underlie the pathology of TS, and domaminergic, glutamatergic, GABAergic, serotoninergic, cholinergic, noradrenergic, and opioid systems may be involved.⁷

A gene mutation responsible for TS has been identified. Among 174 TS sufferers, scientists found a consistent mutation pattern that was absent in 3600 control chromosomes.⁸ Identical twins are 85% concordant for serious tic disorders.⁷

Comorbid Conditions

Several neurobehavioral and psychological disorders are associated with TS:

• ADHD is diagnosed in approximately 50% of patients with TS
• Obsessive-compulsive behaviors occur in 20% to 60% of patients with TS
• Migraines occur in 10% to 13% of adults and in 2% to 10% of children with TS
• Mood and anxiety disorders occur in up to 25% of TS sufferers, and sleep disorders occur in 20% to 50%
• Approximately 33% to 44% of TS patients engage in self-injurious behaviors, possibly because of underlying mood disorders^3,7

Comorbid conditions may be more functionally disruptive than TS itself. For example, patients with TS test normal on intelligence scales. Severe symptoms, however?especially those from ADHD and obsessive-compulsive disorders?interfere with school performance. Up to 50% of TS-affected children experience school and learning difficulties.³ Social-adjustment problems and social isolation commonly occur. Many patients fear and/or experience peer rejection and ridicule because of embarrassing symptoms?leading to depression and anxiety.

Treatment Issues

Symptoms persist into adulthood for the majority of patients. Although TS is not a degenerative disorder, there is no cure. Symptom management, and ideally suppression, is the treatment goal. Treatment strategies and pharmacotherapy must occur in tandem with comorbidity-related treatment goals.

A 2-tiered treatment approach is recommended: nonneuroleptic agents for mild tics and typical and atypical agents for more severe symptoms (Table 2).^5,7 TS responds to significantly lower dosages than those used for psychiatric disorders, and practitioners recommend "start low, go slow."

In the first tier, the alpha-adrenergic agonists, which are used primarily for hypertension treatment, are effective, particularly clonidine and guanfacine. Children's doses are clonidine 0.3 mg daily and guanfacine 0.5 to 1.5 mg twice daily.^1,5,6 The NINDS reports that stimulant medications such as methylphenidate and dextroamphetamine can lessen ADHD symptoms in people with TS?noting, however, that product labeling advises against use in children with tic and TS disorders.⁶

The neuroleptics have been used the most for TS, with haloperidol and pimozide considered effective. Haloperidol 0.5 to 4 mg at bedtime is effective in ~70% of cases. Pimozide is effective at 1 to 8 mg, also taken at bedtime. Among the atypical neuroleptics, risperidone frequently is used, generally at 1 to 2 mg 2 or 3 times daily.¹ Side effects, particularly increased risk for tardive dyskinesia (TD), must be carefully considered. Olanzapine, which has a lower TD risk, generally is poorly tolerated by children, although 1 study found that children did well on doses of 1.25 to 2.5 mg daily.⁹

Because TS symptoms wax and wane and antipsychotics require several weeks for maximum impact, practitioners sometimes confuse response with natural symptom waning early in treatment. The majority of patients usually require medication for up to 2 years, and ~15% require long-term pharmacotherapy.¹ Once tics appear stable and/or suppressed, gradual dose reduction is recommended.

Researchers are exploring several other agents, and some studies report favorable findings with botulinum, the nicotine patch, and delta-9 tetrahydrocannabinol.¹ In highly unusual and severe cases, bimedial frontal leucotomy and anterior cingulotomy have been used.¹

Final Thoughts

Despite practitioners' limited understanding of the etiology of TS, sufferers continue to look to clinicians for symptom relief?and answers. As with many childhood disorders, the entire family is affected. Parents may agonize that they might have contributed to this disease in some unknowing manner, and often they need reassurance and support. Counseling frequently extends beyond the patient and pharmacotherapy.

Dr. Zanni is a psychologist and health-systems consultant based in Alexandria,Va. Views expressed in this article are those of the author and not those of any government agency.

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