Tourettes Syndrome

Today the full-blown case of TS is unlikely to be confused
with any other disorder. However, only a decade ago TS was
frequently misdiagnosed as schizophrenia,
obsessive-compulsive disorder, Sydenham's chorea, epilepsy,
or nervous habits. The differentiation of TS from other tic
syndromes may be no more than semantic, especially since
recent genetic evidence links TS with multiple tics.
Transient tics of childhood are best defined in retrospect.
At times it may be difficult to distinguish children with
extreme attention deficit hyperactivity disorder (ADHD)
from TS. Many ADHD children, on close examination, have a
few phonic or motor tics, grimace, or produce noises
similar to those of TS. Since at least half of the TS
patients also have attention deficits and hyperactivity as
children, a physician may well be confused. However, the
treating doctor should be aware of the potential dangers of
treating a possible case of TS with stimulant medication.
On rare occasions the differentiation between TS and a
seizure disorder may be problematic. The symptoms of TS
sometimes occur in a rather sharply separated paroxysmal
manner and may resemble automatisms. TS patients, however,
retain a clear consciousness during such paroxysms. If the
diagnosis is in doubt, an EEG may be useful. We have seen
TS in association with a number of developmental and other
neurological disorders. It is possible that central nervous
system injury from trauma or disease may cause a child to
be vulnerable to the expression of the disorder,
particularly if there is a genetic predisposition. Autistic
and retarded children may display the entire gamut of TS
symptoms, but whether an autistic or retarded individual
requires the additional diagnosis of TS may remain an open
question until there is a biological or other diagnostic
test specifically for TS. In older patients, conditions
such as Wilson's disease, tardive dyskinesia, Meige's
syndrome, chronic amphetamine abuse, and the stereotypic
movements of schizophrenia must be considered in the
differential diagnosis. The distinction can usually be made
by taking a good history or by blood tests. Since more
physicians are now aware of TS, there is a growing danger
of overdiagnosis or over-treatment. Prevailing diagnostic
criteria would require that all children with suppressible
multiple motor and phonic tics, however minimal, of at
least one year, should be diagnosed as having TS. It is up
to the clinician to consider the effect that the symptoms
have on the patient's ability to function as well as the
severity of associated symptoms before deciding to treat
with medication. 
 
TABLE 1. RANGE OF SYMPTOMS OF TS
 
Motor
 
Simple motor tics: fast, darting, and meaningless.
 
Complex motor tics: slower, may appear purposeful 
 
Vocal
 
Simple vocal tics: meaningless sounds and noises.
 
Complex vocal tics: linguistically meaningful utterances
such as words and
 
phrases (including coprolalia, echolalia, and palilalia).
 
Behavioral and Developmental
 
Attention deficit hyperactivity disorder, obsessions and
compulsions, 

emotional problems, irritability, impulsivity,
aggressivity, and self-injurious
 
 behaviors; various learning disabilities 
 
Symptomatology
 
 The varied symptoms of TS can be divided into motor,
vocal, and behavioral manifestations (Table 2). Complex
motor tics can be virtually any type of movement that the
body can produce including gyrating, hopping, clapping,
tensing arm or neck muscles, touching people or things, and
obscene gesturing. At some point in the continuum of
complex motor tics, the term "compulsion" seems appropriate
for capturing the organized, ritualistic character of the
actions. The need to do and then redo or undo the same
action a certain number of times (e.g., to stretch out an
arm ten times 
 
Definitions of Tic Disorders
 
Tics are involuntary, rapid, repetitive, and stereotyped
movements of individual muscle groups. They are more easily
recognized than precisely defined. Disorders involving tics
generally are divided into categories according to age of
onset, duration of symptoms, and the presence of vocal or
phonic tics in addition to motor tics. Transient tic
disorders often begin during the early school years and can
occur in up to 15% of all children. Common tics include eye
blinking, nose puckering, grimacing, and squinting.
Transient vocalizations are less common and include various
throat sounds, humming, or other noises. Childhood tics may
be bizarre, such as licking the palm or poking and pinching
the genitals. Transient tics last only weeks or a few
months and usually are not associated with specific
behavioral or school problems. They are especially
noticeable with heightened excitement or fatigue. As with
all tic syndromes, boys are three to four times more often
afflicted than g! irls. While transient tics by definition
do not persist for more than a year, it is not uncommon for
a child to have series of transient tics over the course of
several years. Chronic tic disorders are differentiated
from those that are transient not only by their duration
over many years, but by their relatively unchanging
character. While transient tics come and go - with sniffing
replaced by forehead furrowing or finger snapping, chronic
tics - such as contorting one side of the face or blinking
- may persist unchanged for years. Chronic multiple tics
suggest that an individual has several chronic motor tics.
It is often not an easy task to draw the lines between
transient tics, chronic tics, and chronic multiple tics.
Tourette Syndrome (TS), first described by Gilles de la
Tourette, can be the most debilitating tic disorder, and is
characterized by multiform, frequently changing motor and
phonic tics. The prevailing diagnostic criteria include
onset before the age of 21; recurrent, involuntary, rapid,
purposeless motor movements affecting multiple muscle
groups; one or more vocal tics; variations in the intensity
of the symptoms over weeks to months (waxing and waning);
and a duration of more than one year. While the criteria
appear basically valid, they are not absolute. First, there
have been rare cases of TS which have emerged later than
age 21. Second, the concept of "involuntary" may be hard to
define operationally, since some patients experience their
tics as having a volitional component - a capitulation to
an internal urge for motor discharge accompanied by
psychological tension aefore writing, to even up, or to
stand up and push a chair into "just the right position")
is compulsive in duality and accompanied by considerable
internal discomfort. Complex motor tics may greatly impair
school work, e.g., when a child must stab at a workbook
with a pencil or must go over the same letter so many times
that the paper is worn thin. Self-destructive behaviors,
such as head banging, eye poking, and lip biting, also may
occur. Vocal tics extend over a similar spectrum of
complexity and disruption as motor tics ( The most socially
distressing complex vocal symptom is coprolalia, the
explosive utterance of foul or "dirty" words or more
elaborate sexual and aggressive statements. While
coprolalia occurs in only a minority of TS patients (from
5-40%, depending on the clinical series), it remains the
most well known symptom of TS. It should be emphasized that
a diagnosis of TS does not require that coprolalia is
present. Some TS patients may have a tendency to imitate
what they have just seen (echopraxia), heard (echolalia),
or said (palilalia). For example, the patient may feel an
impulse to imitate another's body movements, to speak with
an odd inflection, or to accent a syllable just the way it
has been pronounced by another person. Such modeling or
repetition may lead to the onset of new specific symptoms
that will wax and wane in the same way as other TS
symptoms. 
 
TABLE 2. EXAMPLES OF MOTOR SYMPTOMS
 
Simple motor tics
 
Eye blinking, grimacing, nose twitching, lip pouting,
shoulder shrugging, arm jerking, abdominal tensing,
kicking, finger movements, jaw snapping, tooth clicking,
frowning, tensing parts of the body, and rapid jerking of
any part of the body. 
 
Complex motor tics
 
Hopping, clapping, touching objects (or others or self),
throwing, arranging, gyrating, bending, "dystonic"
postures, biting the mouth, the lip, or the arm,
headbanging, arm thrusting, striking out, picking scabs,
writhing movements, rolling eyes upwards or side-to-side,
making funny expressions, sticking out the tongue, kissing,
pinching, writing over-and-over the same letter or word,
pulling back on a pencil while writing, and tearing paper
or books. 
 
Copropraxia
 
"Giving the finger" and other obscene gestures. 
 
Echopraxia
 
Imitating gestures or movements of other people. 
 
TABLE 3. EXAMPLES OF VOCAL SYMPTOMS
 
Simple vocal tics
 
Coughing, spitting, screeching, barking, grunting,
gurgling, clacking, whistling, hissing,
 
sucking sounds, and syllable sounds such as "uh, uh,"
"eee," and "bu." 
 
Complex vocal tics
 
"Oh boy," "you know," "shut up," "you're fat," "all right,"
and "what's that." 

or any other understandable word or phrase
 
Rituals
 
Repeating a phrase until it sounds "just right" and saying
something over 3 times. 
 
Speech atypicalities
 
Unusual rhythms, tone, accents, loudness, and very rapid
speech. 
 
Coprolalia
 
Obscene, aggressive, or otherwise socially unacceptable
words or phrases. 
 
Palilalia
 
Repeating one's own words or parts of words. 
 
Echolalia
 
Repeating sounds, words, or parts of words of others. 
 
The symptoms of TS can be characterized as mild, moderate,
or severe by their frequency, their complexity, and the
degree to which they cause impairment or disruption of the
patient's ongoingctivities and daily life. For example,
extremely frequent tics that occur 20-30 times a minute,
such as blinking, nodding, or arm flexion, may be less
disruptive than an infrequent tic that occurs several times
an hour, such as loud barking, coprolalic utterances, or
touching tics. There may be tremendous variability over
short and long periods of time in symptomatology,
frequency, and severity. Patients may be able to inhibit or
not feel a great need to emit their symptoms while at
school or work. When they arrive home, however, the tics
may erupt with violence and remain at a distressing level
throughout the remainder of the day. It is not unusual for
patients to "lose" their tics as they enter the doctor's
office. Parents may plead with a child to "show the doctor
what you do at home," only to be told that the youngster
"just doesn't feel like doing them" or "can't do them" on
command. Adults will say "I only wish you could see me
outside of your office," and family members will heartily
agree. A patient with minimal symptoms may display more
usual severe tics when the examination is over. Thus, for
example, the doctor often sees a nearly symptom-free
patient leave the office who begins to hop, flail, or bark
as soon as the street or even the bathroom is reached. In
addition to the moment-to-moment or short-term changes in
symptom intensity, many patients have oscillations in
severity over the course of weeks and months. The waxing
and waning of severity may be triggered by changes in the
patient's life; for example, around the time of holidays,
children may develop exacerbations that take weeks to
subside. Other patients report that their symptoms show
seasonal fluctuation. However, there are no rigorous data
on whether life events, stresses, or seasons, in fact, do
influence the onset or offset of a period of exacerbation.
Once a patient enters a phase of waxing symptomatology, a
process seems to be triggered that will run its course -
usually within 1-3 months. In its most severe forms,
patients may have uncountable motor and vocal tics during
all their waking hours with paroxysms of full-body
movements, shouting, or self-mutilation. Despite that, many
patients with severe tics achieve adequate social
adjustment in adult life, although usually with
considerable emotional pain. The factors that appear to be
of importance with regard to social adaptation include the
seriousness of attentional problems, intelligence, the
degree of family acceptance and support, and ego strength
more than the severity of motor and vocal tics. In
adolescence and early adulthood, TS patients frequently
come to feel that their social isolation, vocational and
academic failure, and painful and disfiguring symptoms are
more than they can bear. At times, a small number may
consider and attempt suicide. Conversely, some patients
with the most bizarre and disruptive symptomatology may
achieve excellent social, academic, and vocational
adjustments. 
 
Associated Behaviors and Cognitive Difficulties
 
As well as tics, there are a variety of behavioral and
psychological difficulties that are experienced by many,
though not all, patients with TS. Those behavioral features
have placed TS on the border between neurology and
psychiatry, and require an understanding of both
disciplines to comprehend the complex problems faced by
many TS patients. The most frequently reported behavioral
problems are attentional deficits, obsessions, compulsions,
impulsivity, irritability, aggressivity, immaturity,
self-injurious behaviors, and depression. Some of the
behaviors (e.g., obsessive compulsive behavior) may be an
integral part of TS, while others may be more common in TS
patients because of certain biological vulnerabilities
(e.g., ADHD). Still others may represent responses to the
social stresses associated with a multiple tic disorder or
a combination of biological and psychological reactions. 
 
Obsessions and Compulsions
 
Although TS may present itself purely as a disorder of
multiple motor and vocal tics, many TS patients also have
obsessive-compulsive (OC) symptoms that may be as
disruptive to their lives as the tics - sometimes even more
so. There is recent evidence that obsessive-compulsive
symptomatology may actually be another expression of the TS
gene and, therefore, an integral part of the disorder.
Whether this is true or not, it has been well documented
that a high percentage of TS patients have OC symptoms,
that those symptoms tend to appear somewhat later than the
tics, and that they may be seriously impairing. The nature
of OC symptoms in TS patients is quite variable.
Conventionally, obsessions are defined as thoughts, images,
or impulses that intrude on consciousness, are involuntary
and distressful, and while perceived as silly or excessive,
cannot be abolished. Compulsions consist of the actual
behaviors carried out in response to the obsessions or in
an effort to ward them off. Typical OC behaviors include
rituals of counting, checking things over and over, and
washing or cleaning excessively. While many TS patients do
have such behaviors, there are other symptoms typical of TS
patients that seem to straddle the border between tics and
OC symptoms. Examples are the need to "even things up," to
touch things a certain number of times, to perform tasks
over and over until they "feel right," as well as
self-injurious behaviors. 
 
Attention Deficit Hyperactivity Disorder (ADHD)
 
Up to 50% of all children with TS who come to the attention
of a physician also have attention deficit hyperactivity
disorder (ADHD), which is manifested by problems with
attention span, concentration, distractibility,
impulsivity, and motoric hyperactivity. Attentional
problems often precede the onset of TS symptoms and may
worsen as the tics develop. The increasing difficulty with
attention may reflect an underlying biological dysfunction
involving inhibition and may be exacerbated by the strain
of attending to the outer world while working hard to
remain quiet and still. Attentional problems and
hyperactivity can profoundly affect school achievement. At
least 30-40% of TS children have serious school performance
handicaps that require special intervention, and children
with both TS and ADHD are especially vulnerable to serious,
long term educational impairment. Attention deficits may
persist into adulthood and together with compulsions and
obsessions can seriously impair job performance. 
 
Emotional Lability, Impulsivity, and Aggressivity
 
Some TS patients (percentages vary greatly in different
studies) have significant problems with labile emotions,
impulsivity, and aggression directed to others. Temper fits
that include screaming, punching holes in walls,
threatening others, hitting, biting, and kicking are common
in such patients. Often they will be the patients who also
have ADHD, which makes impulse control a considerable
problem. At times the temper outbursts can be seen as
reactions to the internal and external pressures of TS. A
specific etiology for such behavioral problems is, however,
not well understood. Nevertheless, they create much
consternation in teachers and great anguish both to TS
patients themselves and to their families. The treating
physician or counselor is often asked whether those
behaviors are involuntary, as tics are, or whether they can
be controlled. Rather than trying to make such a
distinction, it is perhaps more helpful to think of such
patients as having a "thin barrier" between aggressive
thoughts and the expression of those thoughts through
actions. Those patients may experience themselves as being
out of control, a concept that is as frightening to
themselves as it is to others. Management of those
behaviors is often difficult and may involve adjustment of
medications, individual therapy, family therapy, or
behavioral retraining. The intensity of those behaviors
often increases as the tics wax and decreases as the tics
wane. Etiology The most intensive research in relation
to etiology has focused on neurochemical alterations in the
brain. Multiple neurochemical systems have been implicated
by pharmacologic and metabolic evidence. The most
convincing evidence for dopaminergic involvement has come
from the dramatic response to haloperidol and other
neuroleptics such as pimozide, flupenazine, and
penfluridol, as well as exacerbations produced by stimulant
medications. Findings of reduced levels of dopamine
metabolites in cerebrospinal fluid (CSF) have led
investigators to believe that TS results from a
hypersensitivity of postsynaptic dopamine receptors.
Serotonergic mechanisms have been suggested on the basis of
reduced CSF serotonin metabolites. Since systems relying on
neurotransmitters send projections to the substantia nigra
and the striatum, they could play an important role in the
pathophysiology of TS. Medications affecting that system
seem somewhat effective for obsessions but have
inconsistent effects on tics. The role of the cholinergic
system is clouded by contradictory reports. Enhancing
cholinergic function by use of physostigmine has been
associated both with the improvement and the worsening of
TS. Elevated levels of red blood cell choline have been
found in TS patients and their relatives, but the
significance is unclear. Investigation of the GABAergic
system suggests that it may be implicated. The proximity
and connections between the GABA and dopamine systems
support the possibility of an interrelationship. Response
to clonazepam (a GABAergic agent) has been positive in some
cases. Yet other GABAergic drugs such as diazepam do not
have such positive effects. Noradrenergic mechanisms have
been most persuasively implicated by observations that
clonidine, a drug that inhibits noradrenergic functioning
by the stimulation of an autoreceptor, may improve motor
and phonic symptoms. Noradrenergic involvement has also
been suggested by the exacerbation of the syndrome by
stress and anxiety. The use of functional neuroimaging
techniques such as positron emission tomography may help
clarify many physiologic relationships and identify
important anatomical areas in the near future. 
 
Stimulant Medications
 
A particularly important risk factor in tics and TS is the
use of stimulant medication. Over 25% of all TS patients in
some cohorts have had a course of stimulation medication
early in the emergence of their behavioral or tic symptoms
because they have been diagnosed as having ADHD. Over the
last several years, series of cases have been reported in
which the use of stimulants (methylphenidate,
dextroamphetamine, and pemoline) has been correlated with
the onset of motor and phonic tics. There is also chemical
evidence to support the observation that stimulants will
increase the severity of tics in 25-50% of TS patients. In
many cases, the tics associated with stimulant medication
will disappear with the reduction or termination of the
medication. It is more controversial whether stimulants can
actually trigger or produce prolonged chronic multiple tics
or TS that will persist following their termination.
However, cases have been reported in which that seems to
have occurred. Available information thus indicates that
stimulants should be used cautiously with ADHD children who
have a close relative with tics, should generally be
avoided with ADHD children with a first-degree relative
with TS, and should be terminated with the onset of tics in
children who previously were tic-free. Children and parents
should be educated concerning the risks versus benefits in
each case prior to being treated with stimulants.
Alternatives such as behavioral management, environmental
manipulation, and/or other types of medication should be
considered carefully. 
 
Epidemiology and Genetics
 
While once thought to be rare, TS is now seen as a
relatively common disorder affecting up to one person in
every 2,500 in its complete form and three times that
number in its partial expressions that include chronic
motor tics and some forms of obsessive-compulsive disorder.
The question of the familial transmission of TS was first
raised in the original 19th century descriptions of the
disorder, but a genetic basis for TS was not considered
seriously until recently. Several genetic studies have now
been reported and other rigorous studies are now well
enough along to draw several important conclusions. Those
studies have investigated many families in which TS and
other tic disorders have been transmitted over several
generations. Based on available information, it is now
clear that TS is a genetic disorder. The vulnerability to
TS is transmitted from one generation to another. When we
speak of "vulnerability," we imply that the child receives
the genetic or constitutional basis for developing a tic
disorder; the precise type of disorder or severity may be
different from one generation to another. That
vulnerability is transmitted by either mothers or fathers
and can be passed on to either sons or daughters. When one
parent is a carrier or has TS, it appears that there is
about a 50-50 chance that a child will receive the genetic
vulnerability from that parent. That pattern of inheritance
is described as autosomal dominant. However, not everyone
who inherits the genetic vulnerability will express any of
the symptoms of TS. There is a 70% chance that female gene
carriers will express any of the symptoms of TS. For a male
gene carrier, there is a 99% chance of showing some
clinical expression of the gene. The degree of expression
is described as penetrance. In males, the penetrance is
higher than in females; thus, males are more likely to have
some form of expression of the genetic vulnerability. There
is a full 30% chance of female gene carriers showing no
symptoms at all. For males, the figure is 1%. There is a
range of forms in which the vulnerability may be expressed
that includes full-blown TS, chronic multiple tics, and, as
most recently recognized, obsessive-compulsive disorder.
Some individuals have TS (or chronic tics) and
obsessive-compulsive disorder together; others may have the
conditions singly. There are also differences between the
sexes in the form of expression of the TS gene. Males are
more likely to have TS or tics; females are more likely to
have obsessive-compulsive disorder; however, both males and
females may have any combination or severity. The severity
of the disorder is also highly variable. Most individuals
who inherit the TS genetic vulnerability have very mild
conditions for which they do not seek medical attention.
Researchers are actively engaged in searching for the
chromosomal location of the TS gene of affected
individuals. At present, there is no genetic or biochemical
test to determine if a person with TS or an unaffected
individual carries the gene. There is no prenatal test for
the vulnerability to TS. When scientists succeed in
locating the gene, such tests may become available. 
 
Non-Genetic Contributions
 
The individual variations in character, course, and degree
of severity by which TS is manifested cannot be explained
by genetic hypotheses alone. Furthermore, it appears that
about 10-15% of TS patients do not acquire the disorder
genetically. Thus, non-genetic factors are also
responsible, both as causes and as modifiers of TS.
Non-genetic factors that have been implicated include such
stressful processes or events during the prenatal,
perinatal, or early life periods as fetal compromise and
exposure to drugs or other toxins. Findings from one study
in which decreased birth weights were observed in the
affected co-twins of discordant monozygotic pairs lend
further support to the influence of environmental factors. 
 
Clinical Assessment Of Tourette Syndrome
 
Assessment of a case of TS involves far more than simple
diagnosis. Since symptoms may fluctuate in severity and
character from hour to hour, a thorough understanding of
the patient may take a considerable amount of time. As the
patient becomes more comfortable with the doctor, there
will be less likelihood of symptom suppression or
inhibition. Only when there is confidence in the physician
is the patient likely to acknowledge the most frightening
or bizarre symptoms. The nature, severity, frequency, and
degree of disruption produced by the motor and vocal tics
need to be carefully assessed from the time of their
emergence until the present. Inquiries should be made about
factors that may have worsened or ameliorated their
severity. A critical question concerns the degree to which
the tics have interfered with the patient's social,
familial, and school or work experiences. In those respects
interviews with families may be revealing and informative.
During the evaluation of a patient with TS, the clinician
must assess all areas of functioning to fully understand
both difficulties and strengths. It is important to explore
the presence of attentional and learning disabilities, a
history of school and/or work performance, and
relationships with family and peers. Before receiving the
diagnosis, the patient and/or family may have thought he or
she "was going crazy." The patient may have become
extremely distressed by his or her own experiences and by
the often negative responses evoked. Parents may have
scolded, cajoled, ridiculed, threatened, and perhaps beaten
the child to stop the "weird" and embarrassing behavior,
and the emotional sequelae may affect the patient far
beyond the period of childhood. During the evaluation of a
child, therefore, family issues including parental guilt
need to be addressed. Relevant factors elicited through
careful diagnostic evaluation can be approached through
clarification, education, and therapeutic discussion with
the youngster and the family. Careful assessment of
cognitive functioning and school achievement is indicated
for children who have school problems. TS children with
school performance difficulties often do not have clearly
delineated learning disorders, and the average IQ of TS
patients is normal. Rather, their problems tend to lie in
the areas of attentional deployment, perseverance, and the
ability to keep themselves and their work organized. Many
have difficulties with penmanship (graphomotor skills) and
compulsions that interfere with writing. Determining
specific problem areas will help in the recommendation of
alternatives (e.g., extended periods of time for tests, the
use of a typewriter or the emphasis on oral rathe! r than
written reports). The neurological examination should
include documentation of neuromaturational difficulties and
other neurological findings. About half of TS patients have
non-localizing, so called "soft," neurological findings
suggesting disturbances in the body scheme and integration
of motor control. While such findings have no specific
therapeutic implications, they are worth noting as
"baseline" data since the use of medications such as
haloperidol may cloud the neurological picture. The EEG is
often abnormal in TS, but the EEG findings are nonspecific.
Computed tomography of the brain produces normal results in
people with TS. Thus, unless there is some doubt about the
diagnosis or some complicating neurological factors, an EEG
and a computed tomography are not necessary parts of the
clinical evaluation. Additional studies that may be
considered in the biological work-up include serum
electrolytes, calcium, phosphorous, copper, ceruloplasmin,
and liver function tests - all related to movement
disorders of various types. In practice, however, they are
rarely needed for the diagnosis. A behavioral pedigree of
the extended family, including tics, compulsions,
attentional problems and the like is useful. Previous
medications must be reviewed in detail during assessment.
If a child has received stimulant medications, it is
important to determine what the indications for the
medications were, whether there were any pre-existing tics
or compulsions, and the temporal relation between the
stimulants and the new symptoms. Catecholaminergic agonists
are contained in other drugs, such as in decongestant
combinations used in treating allergies and in medications
used for asthma. If a patient with TS is on a stimulant or
a drug containing an ephedrine like agent, discontinuation
should be strongly considered.