The Use of Deep Brain Stimulation in Tourette's Syndrome

Janine Rotsides, B.S; Antonios Mammis, M.D.

Disclosures

Neurosurg Focus. 2013;35(5):e4 

In This Article

Abstract and Introduction

Abstract

Tourette's syndrome (TS) is a childhood neuropsychiatric disorder characterized by multiple involuntary motor and vocal tics. It is commonly associated with other behavioral disorders including attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, depression, and self-injurious behaviors. Tourette's syndrome can be effectively managed with psychobehavioral and pharmacological treatments, and many patients experience an improvement in tics in adulthood. However, symptoms may persist and cause severe impairment in a small subset of patients despite available therapies. In recent years, deep brain stimulation (DBS) has been shown to be a promising treatment option for such patients. Since the advent of its use in 1999, multiple targets have been identified in DBS for TS, including the medial thalamus, globus pallidus internus, globus pallidus externus, anterior limb of the internal capsule/nucleus accumbens, and subthalamic nucleus. While the medial thalamus is the most commonly reported trajectory, the optimal surgical target for TS is still a topic of much debate. This paper provides a review of the available literature regarding the use of DBS for TS.

Introduction

In 1885, Georges Gilles de la Tourette described 9 patients who suffered from "a neurological condition characterized by motor incoordination accompanied by echolalia and coprolalia."[30] Charcot later named the condition Tourette's syndrome (TS).[30] Tourette's syndrome is a complex childhood neuropsychiatric disorder characterized chiefly by the presence of tics. Tics are sudden, involuntary, repetitive muscle contractions (motor tics) or phonic productions (vocal tics). Tics are usually preceded by premonitory sensory urges with feelings of relief after execution of the tic.[31] Once thought to be rare, recent studies suggest that TS is more common than previously believed. The prevalence of TS differs among studies due to variations in age, sex, diagnostic criteria, and assessment methods, but is estimated at 0.77% in children and is considered to be 4 times more common in males than in females.[28]

Symptoms of TS typically develop during the 1st decade of life, with a mean age of onset of 7 years. Initial symptoms commonly manifest as simple motor tics of the head and face, with vocal tics appearing 1–2 years later.[31] Motor tics can be characterized as abrupt in onset, fast, and brief (clonic) or slow and sustained (dystonic or tonic). Simple tics involve only a single muscle or group of muscles, such as eye blinking, grimacing, sniffing, or throat clearing, while complex tics involve the coordinated action of multiple muscles to produce seemingly voluntary motor movements; examples include throwing, hitting, head shaking, or uttering phrases.[25] Symptoms wax and wane throughout its course, with tics changing in character, frequency, and location over time. Tics typically become more frequent and severe during periods of excitement, stress, or fatigue or when the patient is alone. On the other hand, tics may improve during times of relaxation and selective attention.[10] It has been reported that tics can be voluntarily suppressed for brief periods of time, but results in increased inner tension and a rebound period.[18] Patients with TS typically experience worsening symptoms during prepubescent years, peaking around age 10, with improvement during adolescence. An estimated 59%–85% of patients with TS experience a decline in the severity and number of tics in adulthood.[21] Complete remission of tics in adulthood has also been documented in several studies.[8,43]

A diagnosis of TS is based on clinical evaluation. Diagnostic criteria for TS, as outlined in the Diagnostic and Statistical Manual of Mental Disorders-IV,[3] require the presence of both multiple motor tics and 1 or more vocal tics, not necessarily simultaneously. Symptoms must develop before the age of 18 years and tics must occur multiple times per day nearly every day or intermittently for at least 1 year, with no more than 3 consecutive tic-free months. The tics must not be due to the direct physiological effects of a substance or general medical condition.[3] Other than the presence of tics, the neurological examination is typically normal. Currently, there are no laboratory tests or imaging studies that can definitively diagnose TS, but these may be useful in ruling out other diseases.[57]

Tourette's syndrome is frequently associated with other psychiatric disorders. Attention-deficit/hyperactivity disorder (ADHD) is the most common comorbidity, found in 21%–90% of TS patients. Obsessive-compulsive disorder has been reported in 11%–80% of TS patients, and self-injurious behavior is found in approximately 33% of TS patients. Other psychiatric comorbidities include anxiety, depression, and personality disorders.[47] The severity of tics and psychiatric disorders, and their impact on the life of patients with TS, ranges from mild to severe. Higher tic severity is generally associated with greater functional impairment.[12] However, psychiatric and behavioral symptoms may be more problematic and have a greater impact on quality of life than tics.[16]

Much of the pathophysiology of TS still remains unclear, but dysfunction of the basal ganglia and parallel striatal-thalamic-cortical circuits are believed to play a major role in the disorder.[19] The striatum and subthalamic nucleus receive excitatory input from the cortex and serve as the major inputs to the basal ganglia. The globus pallidus internus (GPi) and the substantia nigra pars reticulata serve as the major output, with inhibitory projections to the thalamus and midbrain that modulate motor patterns of the cerebral cortex and brainstem.[40] Inappropriate activation of striatal neurons with inhibitory projections to the GPi and substantia nigra pars reticulata have been suggested in TS. Abnormal inhibition of the GPi and substantia nigra pars reticulata can lead to increased thalamocortical drive, resulting in unwanted motor patterns and the execution of tics.[39] Aberrant action of dopamine has also been implicated in the pathophysiology of TS. Dopamine-mediated long-term potentiation of striatal neurons can cause excessive activity modulating cortical-striatal transmission.[40] This theory is supported, in part, by the relative efficacy of neuroleptics in treating TS.[25] Dysfunction in excitatory thalamostriatal loops are also believed to play a role. These loops involve the centromedian-parafascicular (CM-Pf) complex of the thalamus and project to the motor striatum and midline thalamic nuclei (substantia periventricularis [Spv]), toward the limbic part of the striatum.[50]

Due to its complex and variable clinical presentation, a multifactorial approach is often taken in the treatment of TS. It is important to assess the individual needs of the patient and treat the most debilitating symptoms. In patients with milder forms of TS, psychobehavioral therapy is often an effective form of treatment and aims to teach patients how to control environmental factors that affect their tics. These therapies include relaxation training, cognitive behavioral therapy, habit reversal training, and comprehensive behavioral intervention for tics.[56] For patients with moderate to severe TS, pharmacological treatment may be necessary. Standard tic-suppressing medications include α2-adrenergic agonists, typical and atypical neuroleptics, benzodiazepines, and botulinum toxin injections into muscle groups responsible for debilitating tics.[38,56] In some cases, symptoms of associated behavioral disorders can be more debilitating than tics and must be treated.[16] Despite previous conceptions that stimulant medications for ADHD can worsen tics, recent evidence suggests that methylphenidate, α2 agonists, desipramine, and atomoxetine can effectively treat patients with TS and ADHD without worsening tics.[7] Comorbid obsessive-compulsive disorder (OCD) can be treated with cognitive behavioral therapy, selective serotonin reuptake inhibitors (SSRIs), and typical and atypical neuroleptics.[38] Despite available behavioral and pharmacological treatments, there is a small subset of patients with TS who fail to show clinical improvement or experience potentially life-threatening tics or self-injurious behavior ("malignant TS").[11] If symptoms remain severe and cause marked impairment in functioning, surgical intervention may be warranted.

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