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Tourette’s Syndrome: Implications for a Moving Disorder

Submitted by Rebecca Hegel, MS, RN, FNP-C

Tags: Psychiatry Tourettes Syndrome treatment

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Tourette’s syndrome is a tic disorder which is defined by the American Psychological Association (APA) as an inheritable, childhood-onset neurological disorder marked by persistent multiple motor tics and at least one vocal tic (as cited in Kenney, Sheng, & Joohi, 2008). The disorder was first reported in 1885 by French neurologist George de la Tourette as a psychogenic disorder, and is commonly referred to as Tourette syndrome (TS). Later pharmacology research in the 1960’s changed perceptions of the disease from psychological origins to those of biological central nervous system mechanisms (Muller, 2007; Pountney, 2009).

Due to variances in research methodology, the prevalence of TS in the United States is uncertain, with ranges from 1 to 30 per 1,000 population. The disorder predominately affects males 4-5 times more often than females with an average age of onset at 7 years. Tics tend to peak in adolescence and decline in early adulthood. Approximately 50% of patients with TS have complete resolution of the disorder, for the other half, the disorder is usually life-long (Kenney, et al., 2008). TS is twice more likely to be found in non-Hispanic Whites than other racial groups, and has been reported in diverse ethnic groups (Centers for Disease Control and Prevention [CDC], 2009). Several researchers have found the disease to be associated with learning disorders as well as psychiatric co-morbidities such as obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD), and depression (APA,1994; Bloch, 2008; Kenney, et al., 2008; Muller, 2007).

Pathophysiology of Topic

A variety of genetic and environmental factors including birth-related problems have been researched to determine the cause of Tourette syndrome. Most of these factors are unknown and researchers continue their efforts to determine variables that contribute to this complex disorder. Scientists believe that tics result from changes in neurotransmitters that are responsible for producing and controlling voluntary movements.

Tics

The most cardinal feature of Tourette syndrome is the presence of tics. Although tics are a clinical manifestation of TS, they are also the defining physiological component of the disorder. The characteristic tics of TS are involuntary, sudden, rapid, recurrent, nonrhythmic, stereotypic movements (motor) or vocalizations (phonic) that can be temporarily suppressed (CDC, 2009). Approximately 80% of persons with TS describe a premonition-like feeling before a tic occurs; for example, a person might feel muscle tension before a shoulder shrug or discomfort before jaw opening (Kenney, et al., 2008). The sensation is relieved once the tic is expressed, thus a person will compulsively repeat a tic until they feel “just right” (Kenney, et al., 2008). Initially tics are simple in nature and begin with some type of facial tic such as eye blinking or nose twitching. As the disorder progresses, these tics are replaced or added to by other tics of that involve the neck, trunk, and limbs. These involuntary tics can become complicated and involve the entire body.

Tics occur in clusters and are not evenly distributed across periods of time. Several bouts may occur daily and tic free periods may only last for a few minutes to hours. Individuals with TS experience new tics or regain old tics as tics wax and wane over time. The character and severity of a tic can be variable; factors such as fatigue, stress, change in temperature or environment, and streptococcal infection can exacerbate a tic. Concentration absorbing activities such as sleep or playing an instrument can attenuate or diminish a tic (Bloch, 2008; Kenney, et al., 2008). Suppression of tics can lead to a burst of tics, for example when an individual returns home from a social activity they will experience a “release” of tic activity.

Tourette syndrome has been found to be the most common cause of tics (Bloch, 2008; Kenney, et al., 2008; & Pountney, 2009). Depending on the number of muscle groups involved, tics are categorized as motor or vocal, simple or complex. “Simple motor tics involve a single muscle or group of muscles and may be brief (clonic), prolonged (dystonic), or a sustained isometric (tonic) contraction” (Kenney, et al., 2008, p.651). These types of tics can frequently go unnoticed as they resemble voluntary movements. Likewise, simple phonic tics can be disguised as voluntary or meaningless noises. Comparatively, complex motor and phonic tics use more than one muscle group and are forceful, repetitive, and exaggerated. Complex tics frequently occur out of normal context and during inappropriate situations, thus calling attention to a person (Kenney, et al., 2008).

Coprolalia, a well-known complex phonic tic which produces involuntary swearing is present in only 10% of all cases of Tourette syndrome (Pountney, 2009). Table 1 provides a categorical list of common tic manifestations.

Table 1

Examples of Common Tics

Simple Motor	Complex Motor	Simple Phonic	Complex Phonic
Clonic Eye blinking Head jerking Nose twitching Dystonic Blepharospasm Blocking tic Bruxism Oculogyric movements Shoulder rotation Jaw opening Torticollis Tonic Abdominal contraction Blocking tic Limb extension Limb flexion	Burping Copropraxia Echopraxia Head shaking Hitting Jumping Kicking Retching Smelling objects Throwing Touching Trunk bending Vomiting	Blowing Coughing Grunting Hiccupping Screaming Sniffing Squeaking Sucking Throat clearing Whistling Barking	Coprolalia Echolalia Paliphrasia

Note: Definitions of terms: Bruxism-teeth grinding; Copropraxia-inappropriate obscene gestures; Echopraxia-imitating some one else’s gestures; Echolalia-echoing what others say; Oculogyric movements-eyeball spasm; Paliphrasia-repeating ones own utterances; Torticollis- A contracted state of the neck muscles that causes the neck to rotate and tilt sideways, forwards, or backwards.  Adapted from “Tourette Syndrome” by C. Kenney, H.K. Sheng, and & J.S. Joohi, 2008, American Family Physician, 77(5), p. 652.

Underlying Brain Function

Although the exact cause of Tourette’s syndrome is unknown, biologic and genetic features indicate a disturbance in underlying brain function (Pountney, 2009). Research indicates a probable cause of TS is a disorder of dopamine and serotonin uptake in the striatum of the basal ganglia.

The straitum of the brain is made up of the caudate nucleus, putamen and globus pallidus. The inferior portion of the basal ganglia is the substantia nigra which synthesizes dopamine and plays an important role in reward, addiction, and movement (McCance, Heuther, Brashers, & Rote, 2010).  Functionally, the basal ganglia are responsible for voluntary movements and postures. Tics are thought to be a result of aberrant activation of dopaminergic neurons in the striatum (Muller, 2007).

Note: Adapted from Google Images, original source http://brainmind.com/BasalGanglia.html

Genetic Factors

Studies indicate that Tourette’s syndrome is an inherited disorder caused by bilineal transmission. While the exact inheritance pattern of Tourette syndrome is unclear, a history of tics has been found in both maternal and paternal family members (CDC, 2007; Kenney, et al, 2008; Muller, 2007).

Among family members of an affected person, it is difficult to predict who else may be at risk of developing the condition. Muller (2007) found the frequency of developing TS in first-degree relatives ranges from 9.8 to15 percent. Monozygotic (identical) twins have shown concordant rates of TS from 55-77 percent compared to 23% in dizygotic twins. Additionally, relatives of patients with TS have increased rates of tics, OCD, and ADHD.

Mutations involving the SLITRK1 gene have been identified in a small number of people with Tourette syndrome (Kenney, et al., 2008).

This gene encodes a protein that is believed to influence dendritic growth. It is thought that the SLITRK1 protein plays a role in the development of communicative nerve cells including axons and dendrites. It is unclear how mutations in the SLITRK1 gene lead to TS, as the association has not been confirmed. Most people with Tourette syndrome do not have a mutation in the SLITRK1 gene. Researchers suspect other genes may be associated with Tourette syndrome (United States National Library of Medicine, 2010).

Inflammation and Immune Response

Acute and chronic inflammatory processes as well as postinfectious autoimmune responses have been well established in the development of TS (Bloch, 2008; Kenney, et al., 2008; Muller, 2007). Tics are exacerbated in acute strept infection, Lyme disease, and Mycoplasma pneumonia. Because antibiotic therapy has resulted in improvement of tics, there is a strong correlation that infectious agents contribute to the pathogenesis of tics and TS. The onset of Tourette symptoms can be the result of trauma or intoxication (Muller, 2007).

The belief that TS is a result of a poststrepotccoal autoimmune process can most accurately be described by the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) theory. PANDAS manifests as a sudden onset motor and vocal tic disorder that shares obsessive compulsive (OC) symptoms as in Tourette’s disorder. Research by Muller (2007), found that both TS and PANDAS patients have increased antibody titers to certain streptococcal proteins responsible for immune properties of a particular streptococci strain. The PANDAS concept has limitations as it is focused on children. There is no streptococci test required for the diagnosis which can lead to therapeutic consequences which may exacerbate tic symptoms (Muller, 2007).

In immune dysfunction, research has shown increased titers of antiphospholipid antibodies and increased IgE levels in children and adults with TS (Muller, 2007). Increased serum cytokines interleukin (IL)-12 and tumor necrosis factor (TNF-α) in adolescents with TS were found during tic exacerbations. Moreover, increased levels of cytokines and TNF-α demonstrate a relationship between tic severity and proinflammatory cytokines (Muller, 2007).

Environmental Factors

There is limited research on the incidence of environmental factors in the development of TS, but researchers suspect such factors may produce TS. Pregnancy and pre-birth problems such as premature low-birth weight children, smoking, and hyperemesis gravidarum during the first trimester are likely to be associated with Tourette syndrome (Pountney, 2009).

Clinical Manifestations

The clinical manifestations of Tourette syndrome can be variable. Each individual client will have a different set of clinical symptoms depending on severity of the disease and the presence of co-morbid conditions. The practitioner should have knowledge of tic manifestations as well as diagnostic criteria.

Psychological Co-morbidities

In 2007, the first national, population-based survey of TS of persons under 18 years of age was implemented by the Centers for Disease Control and Prevention. The National Survey of Children’s Health (NSCH) data found that more than 79% of individuals with TS are diagnosed with a psychiatric comorbidity. Of this population: approximately 64% with ADHD; 36% with depression; 40% with anxiety; and 43% with behavioral problems (CDC, 2009). Obsessive compulsive disorder has been reported in 40-90 percent of individuals with TS (Muller, 2007). Schizophrenia has similar pathogenic features as TS and can occur simultaneously with TS.

Patient Concerns

The symptoms and co-morbidities of TS can interfere with activities of daily living including academic, occupational, and social situations.

Children tend to become withdrawn and socially isolated due to embarrassment. Many feel ashamed because they have been ridiculed or teased by peers. Repetitive phonic tics and behavioral problems in school may lead to disciplinary action when the education system is not supportive or educated about the child’s disorder. As a result of the disorder, individuals with TS tend to be self-conscious which may contribute to the development of a personality disorder (Muller, 2007). Tourette syndrome patients suffer from a relentless self-perpetuating cycle of anger, sadness, social isolation, relationship difficulties, and tic-related injuries, eventually becoming outsiders in their families and peer groups.

Evaluation

A comprehensive history and assessment with attention to details of presence and severity of features is crucial in the management of patients with TS; tics and co-morbidities are interrelated and may influence each other (Kenney, et al., 2008). Thorough evaluation is necessary to determine aspects of the disorder which may be disabling and to formulate a treatment plan (National Tourette Syndrome Association, 2010).

Differential Diagnosis

The DSM-IV (1994) classifies Tourette syndrome as a tic disorder within a group of similar movement disorders. The other disorders in this class include: chronic motor or vocal tic disorder, transient tic disorder, and tic disorder not otherwise specified. The disorders can be distinguished from one another based on variation and duration of tics as well as age at onset of symptoms.

Tics should be differentiated from muscle spasms, synkinesis[1], and other disorders characterized by abnormal body movement. Tourette syndrome may be confused with secondary tics or other movement disorders. When diagnosing TS, other movement disorders such as Huntington’s disease, Sydenhams chorea, restless leg syndrome, dystonia, and myoclonus must be ruled out as they share similar phenomena as TS (Kenney, et al., 2008).

Pharmacological induced hyperkinesia caused by amphetamines or L-dopa (amino acid) may mimic Tourette symptoms. Antipsychotic drug therapies which induce tics or stereotypic movements are important to take into account. Neuroacanthocytosis, a group of genetic conditions which are characterized by movement disorders and abnormal red blood cells (acanthocytosis) may also show features of TS (Muller, 2007).

Diagnostic Features

According to the National Tourette Syndrome Association (TSA, 2010), there is no specific test for the diagnosis of Tourette syndrome. Diagnosis is made by evaluating the history of the onset of symptoms and ruling out other possible medical conditions. A diagnosis of TS can be difficult as these patients suffer from so many co-morbidities. Most individuals with TS have mild cases of the disorder that do not prompt medical attention; however patients that are seen have severe symptoms. Tourette syndrome can be classified into three types: pure Tourette’s; full-blown Tourette’s (features paliphrasia and echolalia); and Tourette’s plus which occurs with co-morbid ADHD & OCD (Muller, 2007). A diagnosis of TS is made by the following DSM-IV (1994) criteria:

Criterion A: Both multiple motor and one or more vocal tics have been present at some time during the illness. Criterion B: Tics occur many times a day (usually in bouts) nearly every day or intermittently throughout    a period of more than 1 year, and during this period there was never a tic free period or more than 3 consecutive months. Criterion C: The disturbance causes marked distress or significant impairment in social, occupational, or other important areas of functioning. Criterion D: The onset is before 18 years. Criterion E: The disturbance is not due to direct  physiological effects of a substance (e.g. stimulants) or a medical condition (e.g., Huntington’s disease or post-viral encephalitis). (p.103)   

History of Present Illness

During the health history, it is important to ask open-ended questions to help the client feel comfortable and give the examiner time to observe symptoms. According to Muller (2007), the suppression of tics by a patient when attention is focused on them, such as in a medical exam, is a diagnostic feature. As in any comprehensive health history, the examiner should inquire about familial, personal, social, and physical history. A thorough psychological history is necessary due to the various co-morbidities of TS. A careful evaluation of medications as well as alcohol and substance abuse is important as both may diminish or alleviate tics. Many patients suffering from TS describe their tics as compulsions, therefore details about behaviors and habits should be discussed. Communication and expression of feelings may be difficult because of poor emotional control. Specific questions about the frequency and type of tics the patient is experiencing will assist in determining treatment. Sample questions for the examiner to ask:  

• “At what age did your symptoms begin?”
• “Are you experiencing any repetitive behaviors such as washing your hands, etc?”
• “Can you describe any sensations or urges that you have before a tic occurs? If so do you experience a sense of relief?”
• “Do the urge and tic continue?”
• “Do your tics come and go, or have they been occurring continuously?”     
• “Please describe symptoms and length of time.”
• “Have you injured yourself as a result of tics, are the tics causing pain?”
• “Are you having problems concentrating, prioritizing tasks, or completing things?”

Past Medical History

Past medical history should include questions about trauma, recent streptococcal or other infection, and medical disorders which can be mistaken for Tourette’s syndrome. Other causes of symptoms such as medication or substance abuse should be explored as these can cause tics and mimic psychiatric co-morbidities.

Family History

There is a strong indication that Tourette syndrome is an inherited disorder, therefore questions about family members should be addressed. The examiner will need to establish the how many and which family members have TS or other mental health disorders.

Social History

Because of social isolation and co-morbid conditions such as depression, questions pertaining to school performance, peer relationships, hobbies, and substance abuse will provide insight about behavior, attention, and reoccurring tics. 

Physical Findings

The severity of tics decreases as children develop into adults, TS in adulthood is rare. Individuals with TS will attempt to suppress their tics during a physical exam, making it difficult for the examiner to observe symptoms. An individual may disguise a tic as picking something off of the floor or laughing.

The most common objective and subjective physical finding of individuals with TS is eye blinking (Schub & Grose, 2010). Except for the presence of tics, the neurological exam is normal. The examiner should assess for orthopedic or trauma injuries as motor tics can cause inadvertent physical injury. Careful attention to the integumentary system should be given as skin problems result from constant picking.

Diagnostic Testing

There is no blood test or type of neurological test that can confirm the diagnosis of Tourette syndrome. CT scan, MRI, and EEG may be ordered to evaluate abnormalities and rule out other conditions that may be confused with TS.

Radiological Studies

Neuroimaging studies of individuals with TS have shown symmetrical smaller caudate, lenticular, and globus pallidus volumes in the basal ganglia. Normally, these areas have asymmetrical volumes (Muller, 2007). Abnormal activity has been demonstrated in the basal ganglia and associated cortical areas during tic activity. MRI studies have revealed significantly higher frequencies of cortical and subcortical hyperintensities compared with controls; this is correlational to inflammatory processes. The hypothesis that TS is an inflammatory process is further demonstrated by brain studies which show increased white matter lesions in the basal ganglia and other brain regions (Muller, 2007).

Treatments

The National Tourette’s Association (2010) indicates the goal of treatment for individuals with TS should be to improve social functioning, self-esteem, and quality of life. Therapy should be geared at providing symptomatic relief and preventing complications. Emotional well being and education for the patient and family is a priority for these individuals. Treatment should be individually tailored as a combination of medications and therapy may be required. General principles for treatment include: identify the most disabling symptoms; determine if symptoms are severe enough to warrant treatment; determine if nonpharmacologic therapies apply; unless symptoms are florid, start with mildest medications; if stimulants worsen tics, initiate treatment of tics; do not start more than one agent at a time; have a high index of suspicion for comorbid OCD, ADHD, anxiety, and depression, and treat as necessary; assess for school or occupational modifications or accommodations are necessary (Kenney, et al., 2008).

Medications

Each medication should be chosen on the basis of specific target symptoms and potential side effects. Several pharmacologic options including α2-adrenergic receptor antagonists, typical and atypical antipsychotic drugs, and benzodiazepines are used in the treatment of TS. The decision to initiate pharmacological intervention needs to be balanced with risks of side effects and reassessed regularly. Selective Serotonin Uptake Inhibitors (SSRIs) and dopamine blocking agents have been shown to be effective in decreasing tics and co-morbid symptoms. Haloperidol has specifically been shown to decrease intensity and frequency of tics (Bloch, 2008; Muller, 2007; Schub, et al., 2010). Conversely, Clonidine is more effective in treating behavioral abnormalities. Anti-inflammatory therapies such as the use of COX-2 inhibitors (Celecoxib) have shown effectiveness in some cases. Botulinum (Botox) injections have demonstrated effectiveness in treating a single tic that causes severe functional impairment (Bloch, 2008).

Behavior Therapy

Bloch (2008) identified habit reversal therapy (HRT) as a promising method to reduce tic severity. Although TS can not be cured, psycho-therapeutic therapies such as relaxation therapy, awareness and assertive training, anger management, counseling, and learning alternative behaviors may reduce tic frequency and intensity.

Emerging Therapies

• Anti-inflammatory and immunomodulatory therapy. In cases of infectious Lyme-Borreliosis, Myocloplasma Pneumoniae, and streptococci, antibiotics have cured TS symptoms (Muller, 2007). Effective treatments with immunomodulatory substances including intravenous immunoglobulin G (IgG) and plasmapheresis have been effective in cases of children with PANDAS.     
• Repetitive transcranial magnetic stimulation. This therapy has been effective in treating depression and auditory schizophrenia. A recent study using low-frequency repetitive transcranial magnetic stimulation (rTMS) has shown to be useful in reducing tic severity. The sample size in this study was limited five people who reported tic improvement for 3 months after therapy (Bloch, 2008; Muller, 2007).
• Electroconvulsive therapy. Electroconvulsive therapy (ECT) is thought to work as an “indirect dopamine inhibitor by increasing serotonin concentrations in the brain” (Bloch, 2008, p. 328). There have been four cases in which subjects reported improvement of tic symptoms, OCD, and depression. Maintenance therapy of one treatment every 4-6 weeks is recommended. To date there have been no cases of using ECT in children (Bloch, 2008; Muller, 2007). 
• Deep brain stimulation. Deep brain stimulation (DBS) is a reversible, surgical technique that is used in other movement disorders.
  DBS is the preferred treatment for intractable tics. In one study, 62% of patients reported improvement of tics. DBS stimulation is effective when electrodes are placed at the globus pallidus interna and thalamus (Bloch, 2008; Kenney, et al., 2008; Muller, 2007).

Guidelines for Treatment

Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, Bloch (2008) identified the level of evidence supporting the use various pharmacological and emerging therapies in treating TS. Table 2 (p. 19-20) provides a comprehensive list of these treatments indicating dosage ranges, advantages and disadvantages.

Summary

Tourette syndrome is a disabling disease which impacts an individual’s daily living. There is no test or cure for TS and although progress has been made during last decade, the pathophysiology of Tourette syndrome remains unknown. Recent therapies and the role of inflammation have become the focus of research. Further research focusing on differentiating therapies during stages of inflammation may be useful in determining the etiology and treatments of TS. For accurate diagnosis and prognosis, it is imperative that the practitioner is aware of differential diseases which may mimic symptoms of TS. Because TS affects daily living, a supportive environment is invaluable for the patient and family dealing with TS. The National Tourette Syndrome Association of America provides resources for medical professionals, educators, and counselors.

References

1. American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4^th ed.). Washington, DC: Author.
2. Bloch, M.H. (2008). Emerging treatments for Tourette’s disorder. Current Psychiatry Reports, 10(4), 323-330.
3. Centers for Disease Control and Prevention. (2009). Prevalence of diagnosed Tourette syndrome in persons aged 6-17 years-United States, 2007. MMWR, Morbidity and Mortality Weekly Report, 58(21), 581-585.
4. Kenney, C., Sheng, H.K., & Joohi, J.S. (2008). Tourette’s syndrome. American Family Physician, 77(5), 651-658.
5. McCance, K.L., Huether, S.E., Brashers, V.L., & Rote, N.S. (6th Ed.). (2010). Pathophysiology: The biological basis for disease in adults and children. Maryland Heights, Missouri: Mosby.
6. Muller, N. (2007). Tourette’s syndrome: Clinical features, pathophysiology and therapeutic approaches. Dialogues in Clinical Neuroscience 9, 161-171.
7. National Tourette Syndrome Association. (2010). Guide to the diagnosis and treatment of Tourette syndrome. Retrieved from http://www.tsa-usa.org/index.html
8. Pountney, D. (2009). Identifying and managing tourette syndrome. British Journal of Neuroscience Nursing, 5(9), 416-418.
9. Schub, T., & Grose, S. (2010). Tourette’s syndrome. Cinahl Information Systems. Retrieved from Cinahl database.
10. United States National Library of Medicine, National Institutes of Health, Genetics Home Reference. (2010). SLITRK1. Retrieved from http://ghr.nlm.nih.gov/gene/SLITRK1