Clinical Vignette

A 12-year-old boy presented to the neurology clinic with approximately 1 year of excessive eye blinking. He was accompanied by his parents. He was a full-term infant and reached all developmental milestones appropriately. Schoolwork has been average; he frequently loses pencils and articles of clothing. He also has difficulty finishing his homework. During the past year, his parents have noted increased frequency of eye blinking. The patient is aware of the blinking and has been told by his classmates that he “squints” and “makes funny faces.” He is embarrassed by the movements. His neurologic exam was notable for eye blinking, sniffing, nose wrinkling, and contraction of the platysma. He was able to suppress the movements volitionally. He was prescribed clonidine. After 8 weeks, he returned to the office with his parents. He reported lessening of his tics. His parents felt he was performing better at school.

Phenomenology and Classification

Tics are sudden, relatively quick, stereotyped movements (motor tics) or sounds (phonic tics) which are repeated at irregular intervals. Tics are often preceded by a premonitory urge or inner sensory stimulus, and can be suppressed at will. They are, therefore, referred to as semivoluntary, or unvoluntary, movements.

Tics are categorized as simple or complex (Box 39-1). Simple motor tics involve only one group of muscles and are characterized by quick, jerk-like movements. Usually they are abrupt in onset and brief (clonic tics) but they can also be slower and sustained (dystonic tics). Examples of simple motor tics include eye blinking, nose twitching, and shoulder shrugging. Simple phonic tics include sniffing, throat clearing, and grunting. Complex motor tics are sequenced and coordinated movements that can resemble gestures or fragments of normal behavior, e.g., kicking, jumping, and, rarely, inappropriate behavior, e.g., showing the middle finger. Complex phonic tics have a semantic basis, including words, parts of words, and obscene words (coprolalia).

It is important to distinguish tics from other hyperkinetic movement disorders. For example, simple motor tics can resemble myoclonus. However, clonic tics are stereotyped, rather than random, are suppressible, and are typically accompanied by a premonitory sensation.

The most common tic disorder is Tourette syndrome (TS), which is characterized by motor and phonic tics. The Tourette Syndrome Classification Study Group has formulated diagnostic criteria for TS that include the presence of both motor and phonic tics, though not necessarily concurrently; the presence of tics for at least 1 year; fluctuation in tic type, frequency, and severity; and onset before age 21 years. Tics of duration less than a year are classified as transient tic disorder. When only one category of chronic tics can be identified, the terms chronic motor tic disorder or chronic vocal tic disorder are used.

Causes Of Tic Disorders

Tic disorders can be primary or secondary (Box 39-2). Primary tic disorders are discussed in the previous section and include transient tic disorder, chronic motor tic disorder, chronic vocal tic disorder, and Tourette syndrome. Less commonly, tics can be secondary to other causes, including neurodegenerative illnesses (i.e., Huntington disease, neuroacanthocytosis), infection (i.e., viral encephalitis), global developmental syndromes (i.e., static encephalopathy, autism spectrum disorders), and drugs (i.e., amphetamines, lamotrigine). Secondary causes should always be considered in adult-onset tic disorders.

The pathogenesis of tic disorders is unknown but biochemical, neuroimaging, and genetic data suggest an abnormality in the cortico-striato-thalamo-cortical circuits and their neurotransmitter systems. One hypothesis suggests that there is disinhibition of excitatory neurons in the thalamus resulting in hyperexcitability of the cortical motor areas. Dysfunction of dopamine neurotransmission has been implicated, with recent evidence suggesting excessive dopaminergic activity via abnormal presynaptic terminal function, dopamine hyperinnervation, and/or dopamine receptor supersensitivity.

Clinical Course and Natural History of Tourette Syndrome

In TS, symptoms typically begin in childhood, usually by age 7 years. Early in the course, tics frequently involve the face, head, and neck (Fig. 39-1). Vocal tics tend to start later (ages 8–15 years). The frequency and severity of tics fluctuate over time, with peak severity occurring at about 10 years of age. The anatomic locations and complexity of tics also tend to change over time. The vast majority of TS patients (85%) experience reduction in tics during and after adolescence. Tics can be exacerbated by stress, fatigue, CNS stimulants, and caffeine. Alleviation of tics can occur with focused mental and physical exercise, relaxation, and exposure to nicotine and cannabinoids.

Figure 39-1 Common Motor Tics.

Tic disorders are frequently associated with a wide range of neuropsychiatric disorders. Approximately 50% of patients with TS have obsessive–compulsive disorder (OCD), and 50% exhibit attention deficit hyperactivity disorder (ADHD). In addition, affective disorders, impulse control disorders, anxiety, and rage attacks can be seen in patients with TS.

Therapies

There are both nonpharmacologic and pharmacologic treatments for tics. It is important to recognize that the mere presence of tics does not necessarily imply a need to initiate pharmacologic treatment. One initially needs to determine the degree to which tics are interfering with functioning at school, at work, or at home and any disability associated with tics. In addition, comorbidities such as ADHD, OCD, and mood disorders need to be assessed. If tics are mild, educational and psychosocial interventions can be implemented for treatment of tics. If tics are more severe and disabling, medication treatment should be considered (Box 39-3).

The alpha agonists clonidine and guanfacine have moderate efficacy in treating tic disorders and are often considered as first-line treatments because of their relatively low side effect burden. In addition, they can be effective in treating concomitant ADHD.

Dopamine receptor–blocking drugs are the most potent drugs for treatment of tics. These drugs include both typical (haloperidol, fluphenazine, pimozide) and atypical (risperidone, olanzapine) neuroleptics. Although these drugs are often highly effective, they can cause numerous side effects, including sedation, weight gain, metabolic syndrome, and tardive dyskinesia. The atypical neuroleptics quetiapine and clozapine are associated with low risk of tardive syndrome but they tend to be less effective in treating tics.

Tetrabenazine, a dopamine-depleting agent, has also shown efficacy in treatment of tics. Common side effects include depression, apathy, parkinsonism, and sedation.

Other agents that have tic-suppressing effects include clonazepam, dopamine agonists (low-dose ropinirole and pergolide), and levetiracetam.

Botulinum toxin can be considered for simple motor tics, especially dystonic tics. Many patients who have had botulinum toxin treatment for tics report decrease in premonitory urges to tic.

The role of deep brain stimulation (DBS) in the treatment of tic disorders is being studied as a possible treatment for severe, disabling, medication-refractory tic disorders. A number of different anatomic locations are targeted, including the medial portion of the thalamus, the globus pallidus internus, the nucleus accumbens, and the anterior limb of the internal capsule. Inclusion and exclusion criteria to determine suitable TS candidates for DBS have been devised and are listed in Box 39-4. Further controlled trials of DBS in TS will need to be done to confirm the efficacy of DBS in TS and the optimal surgical target.