CHAPTER 87 Surgery for Tourette’s Syndrome
Tourette’s syndrome (TS) is a disorder in which individuals randomly but repeatedly exhibit stereotyped behavior (tics) of any part of the body, including the phonic (sound production) apparatus.1 Such movements may be simple or complex and may include socially inappropriate behavior. Tics occur many times per day in bouts. Affected individuals commonly describe an irresistible “urge” that is relieved when the tic occurs. Attempts to suppress expression of tics are usually only transiently successful and commonly result in rebound flurries.
According to the widely accepted Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), the onset of TS occurs before the age of 18 years.2 The mean age at onset of symptoms is about 5 years, and the greatest tic severity occurs at approximately 10 years of age.3 TS was once thought to be rare, but studies in the past 20 years have documented prevalence rates as high as 1% to 2%,1 comparable to Parkinson’s disease. Males usually outnumber females by a factor of 3 to 4. TS occurs worldwide, and symptoms appear to be independent of culture or ethnic background. An association of TS with comorbid psychiatric disorders in pediatric patients is well described, including attention-deficit/hyperactivity disorder, obsessive-compulsive disorder (OCD), depression, and anxiety.1
Tic frequency and severity wax and wane with time and are reported to diminish by the age of 18 years. However, about half of all affected individuals continue to experience tic symptoms in adulthood.1 In a recent objective longitudinal study, 90% of individuals who had been videotaped as children still demonstrated tics when videotaped as adults, although a lower percentage reported that tics still occur.4 More than a quarter of these adult tic patients were disabled.4
Anatomic, Physiologic, and Pharmacologic Substrate of Tourette’s Syndrome
The etiopathology of TS is not yet clear. Genetic transmission is well documented,1,5 and a variety of genes have been explored. Some investigators have emphasized a possible role of infections and immune response in the development of TS and other “PANDAS” (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection),6 but this is not likely to be a major causative factor in most cases of TS.
The anatomic and physiologic substrate has long been believed to involve the basal ganglia and the corticostriatopallidothalamocortical (CSPTC) loop. By the late 1970s, it was apparent that antidopaminergic agents could suppress tics.7 The basal ganglia are a major target of the dopaminergic system projecting from the brainstem. Pathologic studies, anatomic imaging studies with magnetic resonance imaging, and functional neuroimaging studies consisting of functional magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography have revealed various abnormalities of the basal ganglia and frontal cortex.8–10
Models of basal ganglia interconnections and function have been evolving11–14 in an attempt to explain basal ganglia dysfunction in a variety of neurological diseases, including parkinsonism, chorea, dystonia, and TS. The basal ganglia are the target of a large set of parallel pathways arriving from all parts of the cerebral cortex, and the output pathways remain essentially segregated in channels through the thalamus and back to the cerebral cortex.11,13 Our understanding has expanded to include more appreciation of specific interconnections between the basal ganglia and midline thalamic nuclei.
In current concepts of normal basal ganglia function, the system is optimized to select desired movement programs and suppress competing or unwanted movements.13,14 In hyperkinetic movement disorders such as chorea, elements of motor programs may be inappropriately selected in a random and nonpatterned fashion. In tic disorders, the inappropriate behavior is stereotyped and may be elemental (simple) or highly organized (complex), thus suggesting a type of dysfunction distinct from that of chorea.
Because the system contains not only motor but also prefrontal and limbic pathways serving cognitive and emotional functions, dysfunction of the basal ganglia commonly results in behavioral and affective disturbances. Within the striatal circuitry, abnormalities in the interaction of these systems may lead to inappropriate expression of specific tic behavior13,14 and may explain the high incidence of obsessive-compulsive symptoms and behavior in the TS population.
Although the association of obsessive and compulsive symptoms and behavior in TS is well described, their clinical manifestation differs from the symptoms and behavior observed in pure OCD.1 In TS, compulsions commonly involve checking, ordering, counting, repeating, and getting things “just right.” In primary OCD, obsessional themes tend toward contamination, dirt, germs, and fear of becoming ill, and compulsions relate to cleaning and washing. Patients with tic disorders commonly experience sensory premonitions before their tics, whereas in primary OCD, the premonitions are cognitive and autonomic. These differences suggest separate pathophysiologic origins of TS and OCD.
Medical and Behavioral Treatment of Tourette’s Syndrome
Pharmacologic treatment of TS has focused on dopamine receptor blockers (e.g., haloperidol, pimozide, fluphenazine, and other typical neuroleptics), presynaptic catecholamine-depleting agents (e.g., reserpine, tetrabenazine), or central α2-adrenergic receptor blockers (e.g., clonidine).14 Tics are rarely eradicated entirely; the goal of medication is to achieve maximal control with minimal side effects. About 13% to 22% of adult individuals with TS must continue to take medications for tics.4 Some adult patients remain symptomatic with clinically disabling tics despite maximal medical therapy.
Several specific behavioral techniques, as well as alternative treatments, have been investigated; however, these methods are incompletely studied or of limited efficacy.14 Some individuals benefit from local injections of botulinum toxin, but this strategy can be applied to only a very limited distribution of tics. For medically refractory individuals, there is no satisfactory alternative for controlling symptoms. It is in these cases that consideration is given to palliative surgical therapy.
Surgical Treatment of Tourette’s Syndrome
A variety of neurosurgical lesioning procedures have been used in an effort to palliate the symptoms of severe, medically refractory TS. Many deep brain targets have been explored, such as the frontal lobes, the cingulate gyrus, the anterior limb of the internal capsule, the limbic system, and the subthalamic zona incerta (reviewed by Temel and Visser-Vandewalle15). Some success has been achieved in amelioration of the psychiatric aspects of TS when present, especially those involving manifestations of OCD. In contrast, control of motor and sonic tics has been more variable and less significant. Risk for adverse effects related to these lesioning procedures has been high.
Other surgeons have stereotactically targeted the thalamus and basal ganglia for therapeutic lesioning, with more beneficial results. Cooper reported on 6 patients with severe motor tics who received significant benefit from staged bilateral ventrolateral (VL) thalamotomies.16 Hassler and Dieckmann reported on 15 patients who achieved excellent, durable clinical results after undergoing bilateral thermocoagulation of the rostral intralaminar nuclei and medial thalamic nuclei.17 de Divitiis and coauthors described 3 patients who underwent unilateral right-sided radiofrequency lesioning of the dorsal medial and intralaminar nuclei; 2 achieved complete remission and 1 had a minimal reduction in tics.18 Korzen and associates reported on 1 patient who experienced an excellent, sustained benefit after bilateral VL thalamotomy.19
Deep Brain Stimulation for Tourette’s Syndrome
Limited data are available regarding the efficacy of DBS in patients with TS. A case series of three patients was reported in which the ventral thalamus was targeted bilaterally.20 The first of these patients had been reported previously by Vandewalle and coworkers.21 These authors carefully considered the existing lesion-based reports and determined that the targets of Hassler and Dieckmann were most likely to result in a reduction in the occurrence of tics, and they targeted this thalamic region bilaterally. They reported a reduction in tic frequency of 70% to 90% with the stimulator on as compared with the stimulator-off state.
At University Hospitals Case Medical Center, after appropriate informed consent had been obtained, we performed a sentinel DBS implantation in 2004 that targeted the thalamic regions reported by Hassler and Dieckmann17 and Visser-Vandewalle and colleagues20 in a 30-year-old individual who had TS since before the age of 5 years. Tic frequency and severity were reduced dramatically, as measured by a video scoring procedure.22 That individual continues to enjoy minimal symptoms from tics several years after initial activation of his stimulators.
Clinical Trials of Deep Brain Stimulation for Tourette’s Syndrome
Based on the information available in 2005, our group conducted a pilot trial of thalamic DBS in five individuals.23 Thus far, no other randomized, sham-controlled, double-blinded, prospective clinical trials of DBS for TS have been conducted.
