Tourette

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. If the physician examines a

previously