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. If the physician examines a
previously