As to causation, little is known. There is no consistent association with infection, trauma, or other disease except the putative connection to streptococcal infections discussed further on. Hyperactive children who have been treated with stimulants appear to be at increased risk of developing or exacerbating tics (Price et al) but a causal relationship has not been established beyond doubt (see comments regarding treatment below). MRI has shown no uniform abnormalities; functional imaging has demonstrated numerous but inconsistent abnormalities. Histopathologic changes have not been discerned in the few brains examined by the usual methods. However, Singer and coworkers (1991), who analyzed preand postsynaptic dopamine markers in postmortem striatal tissue, found a significant alteration of dopamine uptake mechanisms; more recently, Wolf and colleagues, have found that differences in D2 dopamine receptor binding in the head of the caudate nucleus reflected differences in the phenotypic severity of Gilles de la Tourette syndrome. These observations, coupled with the facts that L-dopa exacerbates the symptoms of the syndrome and that haloperidol, which blocks dopamine (particularly D2) receptors, is an effective treatment, support a dopaminergic abnormality in the basal ganglia, more specifically in the caudate. In this respect, instances of compulsive behavior in relation to lesions in the head of the caudate nucleus and its projections from orbitofrontal and cingulate cortices may be pertinent.
For delimited and benign tics, treatment is generally not necessary. Reassurance of the parents can be very helpful. Isolated or infrequent nonintrusive, motor tics in males beyond adolescence, generally an inherited trait, is often aided by clonazepam but may require some of the more potent medications named above.
Two classes of drugs are used in treatment of intractable and multiple tics; alpha agonists and antipsychosis medications. The alpha2-adrenergic agonists clonidine and guanfacine have been useful in several studies. These are not as potent as treatment with neuroleptic drugs, but their side effects are less severe and they are recommended as the first treatment. Guanfacine has the advantage over clonidine of daily dosing and less sedating effect. The initial dose is 0.5 to 1 mg given at bedtime and gradually increased as needed to a total dose of 4 mg. Clonidine is started as a bedtime dose of 0.05 mg and increased every several days by 0.05 mg until a total dose of about 0.1 mg three times daily. The neuroleptics haloperidol and pimozide, (and less frequently used sulpiride and tiapride) have proved to be effective therapeutic agents but should be used only in severely affected patients and usually after the adrenergic agents have been tried. Haloperidol is instituted in small doses (0.25 mg initially, increasing the dosage gradually to 2 to 10 mg daily). The atypical neuroleptics, such as risperidone, have also been used with some success. Pimozide, which has a more specific antidopaminergic action than haloperidol, may be more effective than haloperidol; it should be given in small amounts (0.5 mg daily) to begin with and increased gradually to 8 to 9 mg daily. The addition of benztropine mesylate (0.5 mg daily) at the outset of treatment may help to prevent the adverse motor effects of haloperidol. The potent agent tetrabenazine, a drug that depletes monoamines and blocks dopamine receptors, may be useful if high doses can be tolerated. Further details of the use of these drugs can be found in the reviews by Leckman and by Kurlan. According to a trial conducted by the Tourette’s Syndrome Study Group, the hyperactivity component of the Tourette syndrome can be treated safely with methylphenidate or clonidine without fear of worsening the tics.