Introduction
The first description of a patient with tics and behaviors that characterize the Tourette
syndrome (TS), occurred in 1825, by the French doctor Jean Marc Gaspard Itard, that
diagnosed the curse of tics in the Marquis of Dampierre[1].
However, only in 1884, this pathology received the name of syndrome of Gilles de La
Tourette (TS), when the student Gilles de La Tourette, in the Hospital de La Salpêtrière,
reported the pathology as a disorder characterized by multiple tics, including the
involuntary use or inappropriate of obscene words (coprolalia) and the involuntary
repetition of a sound, word or phrase from another (echolalia), based in report of
Itard itself[2]
[3].
There were times where the TS were like a curse, and whoever had it was doomed to
manifest bizarre behaviors until the end of his life. Still is seen today, as a disorder
that causes integration difficulties and sometimes unsuitability of its bearers in
many contexts[4]. Children and teenagers that suffer from the disease are frequently discriminated
and have disadvantages in terms of psychosocial development. This condition can contribute
for a chronicity of symptoms, so as to the appearance of others personality disorders[5].
The TS consists in a neuropsychiatry pathology from the beginning of childhood, characterized
by the psychological and social commitment of the affected ones, causing more impact
in the life of the carriers and family[3]
[6]. She is generally associated still in a great variety of behaviors and emotional
problems[7]. Is classified in CID-10 in the group of Emotional and Behavioral Disorders with
the beginning usually in Childhood and Adolescence, with code F95.2 and described
as Disorder of multiple vocal and motor tics combined
[8].
Until recently, this pathology was considered a rare condition, with very low rate
of incidence in the world population (0,5/1000, in 1984)[9]. This fact was probably undiagnosed cases, since this disorder, in most of the times,
it is of a light intensity and many patients don't even search for help[10]. However, it is been observed that, today, through the prevalence studies, the increase
of its incidence in the last years[6]
[11]
[12]
[13].
Recente studies showed that the prevalence rate can variate from 1% to 2,9% in some
groups[14]
[15]. International statistical data show that the syndrome is found in many countries,
independent of social class or ethnicity, affecting about three to four times more
the males than the females[16]
[17]
[18]. Studies show that the prevalence of TS is ten times bigger in children and teenagers,
of which, when tics are considered separately, the frequency approximated varies from
1% to 13% in boys and 1% to 11% in girls[3]. The reason for such increase in the detection in the world incidence of TS seems
to be because of the improvement in the disclosure and the awareness of the clinical
characteristics of TS, among the health professionals[3]
[6]
[19].
Considering that the TS represents a paradigm for a better understanding of the close
relationship existent between the emotional-cognitive activity and the motor function,
the present study proposes to approach, broadly, many aspects of the TS, including
its definition and etiology, physiopathology, clinical picture, associated pathologies,
diagnostic approach, differential diagnoses and treatment.
Definition and etiology
The TS is a genetic disorder, from a neuropsychiatry, characterized by compulsive
phenomenon, that, many times, result in a sudden series of multiple motor tics in
one or more vocal tics, during at least a year, starting before 18 years old[20]
[21]
[22]
[23]. These tics can be classified as motor and vocal, subdividing, still, In simple
and complex. Usually, patients with TS present, initially, simple tics, evolving to
more complexes; however, the clinical picture can vary from patient to patient[24]
[25].
The tics are defined as abnormal movements, chronic, brief, quick, without purpose
and irresistible. Are exacerbated by situations of anxiety and emotional tension;
alleviated by rest and by situations that requires concentration. Can be suppressed
by will (for seconds or hours), soon followed by secondary exacerbations. Others manifestations,
like, echolalia, echopraxia, coprolalia and copropraxia can, also, be present[26].
As knowledge about the TS expands, it becomes more and more obvious that is not only
a movement disorder that manifests merely through motor and vocal tics, but also is
characterized by complexes neurobehavioral alterations. The association of Attention
Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD) is relatively
common. This way, what is frequently presented as a clinical manifestation by the
patients, represents only the tip of the iceberg[26]
[27].
Since the sixties, researchers in the entire world have described new aspects of this
disease. It is known today that this condition is associate to neurophysiologic alterations
and neuroanatomical of etiology, however, still unknown. There is the numerous gaps
to be cleared such as: a precise neurobiological model, the way of genetic transmission
and the clinic spectrum of the disorder[28].
During the last decade, has been possible to observe significant progress in the genetic
investigation of the etiology of TS. Chromosomal Anormalities in individuals and families
suffering with TS has been studied, in order to indentify the genes like the A gene
of monoamine-oxidase (MAOA)[29] and chromosomal regions like 18q22[30], 17q25 and 7q31[29], that seems to be involved in this pathology[31].
In this process of identification, evidences suggests that the TS is a genetic disorder
of autosomal dominant, since the frequency of tic cases and manifestations obsessive-compulsive
between the family of the patients, observed in multicenter studies[3]
[16]
[17]. Until now, it was not possible to identify the genetic marker in a definitive way
for the TS[29].
The degree of concordance between the pair of monozygotic twins is bigger than 50%,
while that in dizygotic twins is of 10%. If include twins with chronic motor tics,
the degree of concordance increases to 77-90% between the monozygotic and 30% for
the dizygotics. The differences between the degrees of concordances in the pair of
monozygotic twins and dizygotic indicates that the genetic factors play a important
role in the origin of the syndrome of Gilles de la Tourette[9].
Other factors have been associated to the pathogenesis of TS, such as, the possible
role of the streptococcal infections in the emergence of the tics. In some cases,
the affected for the second time for the Streptococcus are directly associate with the recurrence of neuropsychiatric symptoms[32]. Recent studies suggest that a inflammatory process, because of the acute or chronic
infection, or even from a self immune post-infectious, can be involved in the TS pathogenesis.
Researches about the function of the immune system in the TS, are found in the growth
of production of antibodies against the basal ganglia, including the antibodies antiphospholipid
and antineural, a possible connection with the genesis of the syndrome[33].
There are possible indications of the involvement of infections not-streptococcal
in the TS etiology, as the temporal relationship between the viral respiratory infections
and exacerbation of tics[32]. According to researches, the tics can appear or be found in the acute Lyme disease,
infections by Mycoplasma pneumonia, or even a regular cold. Besides, was observed the attenuation or remission of them
after the antibiotic therapy. These findings suggest that infectious agents can contribute
for the disease pathogenesis[34]. However, studies are still being made to determine the direct relation between
the infectious pictures of TS[3].
The traumatic brain injury, the intoxication by carbon monoxide, the abuse of cocaine,
the withdrawal of opiates or the pharmacological treatment with neuroleptic can also
associate to the syndrome genesis. There are evidences that the long-term treatment
with neuroleptic, can elevate the risk of development of tics in some patients. They
are called “Touret”or secondary tics[9].
Pre or post events can also be connected to TS, where the gravity of the stressors
during the pregnancy has been analyzed like factors that could contribute to the development
of tic disorders and the pathogenesis of the disease[9]
[17]. This way, because of the fact of not be determined, still, all the involved factors
in the abnormal neurological condition of TS, it cannot exclude the possibility of
the same to be a syndrome of multiple causes.
Physiopathology
Regarding to the physiopathology of the syndrome, important advances have occurred
in the last years, thanks to the information from researches involving neural anatomy,
neural biology and functional studies in vivo through Magnetic resonance imaging (RMI)[35].
There is an agreement that, at brain level, it is distinguished several parallel neuronal
circuits, that leads the information from the cortex until the subcortical structures
(basal ganglia) and return to the cortex passing through the thalamus, known as cortico-striatal-thalamic-cortical
(CSTC) circuit; they are responsible to intermediate the activity of motor, sensory,
emotional and cognitive. We thought that the patients with TS have a deficiency in
the inhibition of these circuits, that in a motor level it expresses like hyper sensibility
to the stimulation from both internal and external environment[10]
[35].
The studies of neural imaging has enabled a better understanding about the neural
base of TS, such as, its probable pathogenesis[36]. Many evidences of the involvement from the cortico-striatal-thalamic-cortical circuit
and their neurotransmission systems, associated to the clinical characteristics and
comorbidities present in the TS, have been widely disclosed in the literature[7]
[22].
The suppression of the tics in patients submitted to leucotomoy and thalamotomies,
by the interruption of the CSTC circuit, point to the direct involvement of them in
the TS, and so this fact it is observed through the functional visualization of MRI,
from the analysis of the measures of the area of the corpus callous and by the metabolism
of the glucose and blood flow in the cortical areas[3]
[7].
Abnormalities in the volume of the basic ganglia in the callous body also were observed
in the TS carriers[3]. Studies of neural imaging in adults with the syndrome, without the realization
of the treatment with long-term antipsychotics, revealed volumes significantly smaller
in the caudate nucleus, lenticular and globus pallidus when compared with the control
group, both the right side and the left side. Similar results were found in other
studies, when comparing children with TS and control groups, observing the important
difference of the volume of the left globus pallidus and lenticular asymmetry[37].
Researches involving emission tomography have revealed still hypo metabolism and hypo
perfusion in regions of the frontal cortex and temporal, in the cingulated, striate
and thalamus of patients with TS. These researches of metabolism analysis of glucose
and blood flow in the cortico-striatal region have identified abnormalities, mainly
involving the basal ganglia and cortical areas of these individuals[3]
[9]. These findings confirm that the morphological disorders and functional of the basal
ganglia and CSTC circuit, are key factors for the persistency from both the tics and
the obsessive-compulsive symptoms[37].
In the neurochemical point of view, many hypothesis suggest the involvement from the
system dopaminergic in the pathogenesis of TS, since the neuroleptic, dopamine antagonists,
are considered effective in the treatment of this disease, because promote great reduction
of the tic. By the other hand, the stimulants like the methylphenidate, the cocaine,
the pemoline and the L-dopa cause exacerbation of tics[3]
[7].
Immunohistochemical studies have been lately performed in the TS, particularly the
ones that refer to the dopaminergic system, noradrenergic and serotonergic[9]. With base in the data, the literature suggest a few mechanisms by which the system
dopaminergic could be involved, such as, abnormalities in the liberation of dopamine,
hyper innervations dopaminergic and presence of hyper sensitive dopaminergic receptors[7]
[29].
The first hypothesis, hyper sensibility of D2, was not confirmed, in other words,
was not demonstrated that the homovanillic acid, main metabolite of dopamine, is reduced
in the cerebrospinal fluid (CSF). The second, hyper innervations dopaminegic of the
striated, would lead to the increase in the concentration of dopamine[9]. A recent study, involving post-mortem analysis of tissues from the frontal cortex
and striated, showed elevated density from the dopaminergic receptor D2 in the pre-frontal
region of patients with TS[3]. This way, the hyper innervations would lead to a increased stimulation in the circuit
of CSTC, suggesting so, that the TS is associated to the lack of inhibition from the
mini circuits of CSTC. In this context, the obsessions and the obsessive need for
symmetries and precision would be the result of the lack of inhibition from pre-frontal
mini circuits[12]
[13].
The role of others neurotransmitters, such as, acetylcholine, gaba, endogenous opioid
system, serotonin and norepinephrine[13]
[17]
[23] has been studies, since we cannot discard the involvement of others neurotransmitters
inside the circuit of the CSTC[23].
The evidence of involvement from the noradrenergic system in the physiopathology of
the syndrome is based in the good benefits of clonidine and guanfacine, which are
traditionally selective agonists from the D2 receptor adrenergic. The studies in the
CSF of patients with TS, have evidenced reduction of the main metabolite of serotonin,
the hydroxy-indoleacetic acid. In post-mortem tissues, preview studies have also showed
that the serotonin is globally reduced in the basal ganglia. This metabolic alteration,
however, is related to the patients with OCD[9]
[22].
Clinical Picture
The clinical Picture can be split into three categories: motor tics, vocal tics and
sensitive tics.
The tics are defined as abnormal movements, clonic, brief, fast, sudden, without purpose
and irresistible, that persist through the sleep. Are exacerbated by situations of
anxiety and emotional tension; attenuated by rest, relaxation and for situations that
demand concentration. Can be suppressed by will (for seconds or hours), soon followed
by secondary exacerbations[3]
[38].
The tics happen daily, usually presenting in settings, occurring many times in a single
day, although they can present itself in a intermittent way through the year[3]. There is a periodic variation in the number, the frequency, in the type and localization
of the tics, being that the intensity from the symptoms also have a fluctuating character,
may even disappear for weeks or a few months[11]
[12]
[39].
Besides the notable social prejudice caused by the presence of the tics, in a work
performed by Miranda (1999)[35], was observed a case of retinal detachment because of the cervical dystonic tics
and fractured ribs because complex motor tics, where the patient struck severely his
chest. Besides can occur also orthopedic problems (by flexing his knees, excessively
turn the neck or the head) and skin problems (by pinching himself).
The begin of the symptoms usually appear through childhood or youth, eventually reaching
to stages classified as chronicle. But, in the pass by of adult life, frequently,
the symptoms go to the softening and gradually decreasing[3]
[40]
[41].
Motor Tics
The motor tics are classified as simple and complex. The first involves contractions
of muscles groups functionally related (ex: blink the eyes and make movements like
twisting the nose and mouth), are abrupt, fast, repeated and without purpose, usually
noticed as involuntary[3]. Are included in this classification the complex tics, however, they are more slow,
involve muscle groups non related functionally, seems to be purposeful and they are,
sometimes, noticed as involuntary. The complex motor tics include imitation of gestures
of others, even if they are common (echokinesis) or obscene (echopraxia), besides
the realization of obscene gestures (copropraxia).[35].
The simple motor tics most frequent are: blinking the eyes, deviations of the eyeball,
funny faces, spin the head, movements like twisting the nose and mouth, click the
jaw, clenching, hunch, movements of the fingers, kicks, abdominal contraction or other
parts from the body, shakes of the head, neck, or other parts of the body. The most
found complex motor tics are: facial gestures, stretch of the tongue, maintenance
of certain looks, hand gestures, clap the hands, throw an object, push, touch people
or things, jump, hit the foot, crouching, little jumps, bend, twirling or spinning
when walking, spin, twist, dystonic posturing, eye deviations, licking hands, fingers
or objects, touch, hit in or analyze part of the bodies, from other person or objects,
kiss, arrange, pinch, write the same letter or word, go back on the same steps, hit
with the head, bit the mouth, the lips or other part of the body, echopraxia and copropraxia[5]
[8]
[10]
[26]
[28]
[35].
In most of the cases, the Carrier patients of La Tourette Syndrome present, initially,
simple tics, evolving to more complexes ones. But, the clinical picture can vary from
patient to patient[3].
Vocal Tics
The vocal tics also are divided into simple and complex. The simple include the emission
of sounds, like, hawk, grunt, snuffle and even screams. The complex are of involunatary
use and inappropriate use of obscene words (coprolalia), repetition of words or phrases
(palilalia) and repetition involuntary of the phrases of other person (echolalia)[27]
[39]. It is observed, yet, the repeated use of random words, characterized by complex
sonority or exotic, arbitrarily placed in the between or in the middle of phrases[42].
Among the main simple vocal tics are scratching the throat, spit, click the tongue,
cluck, snore, sizzle, whistle, scream, grunt, gurgle, groan, howl, hiss, fizz, aspirate
and many other sounds. The act of uttering syllables, words or phrases out of the
context or inappropriate, short phrases and complexes, the palilalia, coprolalia and
echolalia, besides other abnormalities of speech as a block of speech, are the complex
vocal tics most common[2]
[8]
[10]
[28]
[35].
Sensitive Tic
The sensitive tic is defined as a somatic sensation at the articulations, in the bones
and muscles (weight, lightness, empty, cold or hot), that make the patient to execute
a voluntary movement to obtain relieve. Its presence it is not obligatory for the
diagnosis[3].
Associated Pathologies
Researches have shown that individuals with TS present more psychiatric comorbidities
and consequently higher operating damages[40]
[41].
The symptoms more commonly associate to the La Tourette Sydrome are obsessions and
compulsions. In a clinical study of 58 cases made by Fen (2001)[28], was found association with the Obsessive Compulsive Disorder in 39,6% of the cases.
Hyperactivity and distraction also are relatively common, and many patients with TS
present initially symptoms of the Attention Deficit Hyperactivity Disorder (ADHD).
This way, it is necessary distinguish if the symptoms of ADHD occur in the context
of TS or if exist a comorbiditie from TS with ADHD[4].
Impulsivity and social discomfort with the sensation of being observed by others,
shame and depressed humor also can manifest ate together with the TS[3].
The presence of self aggressiveness can reach 30% of the patients and the patients
with TS exhibit a greater incidence of phobias, anxiety disorders and panic than the
general population[10].
Besides all the foregoing, the social functioning, academic or ocupational can be
damaged, because of the rejection by others or anxiety into having the tics in social
situations, so, the syndrome also can be associated to the Learning Disorder[9]
[35].
Diagnosis
The diagnosis of the Syndrome de La Tourette is eminently clinical, not existing today,
no specific laboratorial test that confirm this pathology[3]. But, the American Association of Psychiatry (2002)[38], in order to systematize and make easier for the diagnosis, created the following
criteria:
-
Multiple motor tics and one or more vocal tics had been present in some moment of
the disease, although not necessary at the same time.
-
The tics occur many times per day (usually in strikes) almost every day or intermittently
during a period of over a year, and during this period there were not even a phase
free of tics superior to three consecutive months.
-
The beginning is before 18 years old.
-
The disturbance is not because of the physiological effects of a substance (for ex..
stimulants) or a general medical condition (like: Huntington disease or post viral
encephalitis).
The diagnosis of TS must be done carefully, because 10% of children present some tic
in a moment of their life[3]
[4]. And so, although the complementary exams (EEG, tomography or blood analysis) are
not useful to affirm the diagnosis of TS, they can be of great value in the differential
diagnosis, once they contribute for the exclusion of other disorders that have similar
symptoms[43].
Although the neural image exam are not used for the certain diagnosis of TS, a study
that did not make a long use of anti psychotic, have showed decreased volume in the
caudate nuclei and lenticular, compared to the control group. The volume of the caudate
nuclei demonstrated, yet, have a predictive value in relation to the severity of the
tics in children[33]
[34].
Differential Diagnosis
The Huntington Disease, the brain vascular accident, the Lesch Nyhan syndrome, Wilson
disease, Sydenham's chorea, multiple sclerosis, post-viral encephalitis and traumatic
brain injury are medical conditions that can come accompanied of abnormal movements
that must be differentiated from the presented tics in the TS. Besides those pathologies,
direct toxic effects of a substance also can simulate the presence of tics[38]
[44]
[45].
The tics also must be differentiated from the stereotyped movements seen at the Stereotyped
Movements Disorder and in Pervasive Developmental Disorders. The difference is not
always easy, but usually, the stereotyped movements seem to be more directed and intentional,
while the tics present a involuntary quality and are not rhythmic[38].
The TS also can be differentiated from the Obsessive Compulsive Disorder (OCD), more
complex pathology, where the movements are executed in respond to a obsession or according
to rules that must be strictly followed[28]. The compulsions are preceded by persistent worries, while the tics are preceded
by physical tension transients in a part of the body. But, is valid to point that
the association of two pathologies is not uncommon, so, if there is symptoms of both
the disorders, the two diagnosis can be justified in case the clinical picture fits
the criteria of diagnosis in each one of them[4].
Certain motor tics or vocal present in the syndrome also must be differentiated from
the behavior disorganized or catatonic from Schizophrenia.
Other tics disorders, (Motor Tic Disorder or Chronic Vocal, Transient Tic Disorder
and Tic Disorder Without Further Specification) are also included in the differential
diagnosis of TS[38].
These co-occurrences of symptoms can lead to a diagnostic confusion. And so, must
be attempt to the peculiarities of the clinical picture and private developments of
each disease and, still, have the knowledge that some of them can be a co-morbiditie[40]
[41].
Treatment
Because of the notable sociocultural and educational implications that govern the
TS, is important that the treatment is instituted the fastest as possible, to minimize
or avoid damage to the patient.
The choice of kind of treatment must be appropriated to each carrier of the TS, and
can include a pharmacological and psychological approach[3]. This last one is of a great importance, once that, besides the psychotherapeutic
treatment for the patient, guide parents, family and people next to them, about the
characteristics of the disease and the best way to deal with the affected individual[4].
The TS do not have a cure, and so, the pharmacological treatment is used only to relieve
and control the presented symptoms. Because of the considerable number of collateral
effects, the pharmacological approach must be considered only when the benefits of
intervention were superior than the adverse effects[3]. Besides, most of the patients do not need a specific treatment for the tics, being
enough to explain the nature of the picture and the good prognosis of most of the
cases, for the family and the teachers and people next to the patients[35].
But, when is relevant the use of drugs, the most used are the receptor antagonists
of dopamine, once that many studies suggest that the block of dopaminergic receptors
type 2 is the main point for the efficacy of the treatment[3]
[34].
The Haloperidol, is one of the medications most used for the treatment of TS, presents
many collateral effects, like extrapyramidal symptoms from parkinsonian characteristics,
sedation, dysphoria, hyperphagia with weight gain and late dyskinesia. The pimozide
has similar efficacy to the haloperidol without the inconvenient of the extra pyramidal
effects, but present collateral effects involving the cardiovascular system, including
sedation and cognitive dysfunction[3]
[10].
Today, there is a tendency to substitute the tipical antagonists of dopaminergic receptors
(ex: haloperidol, pimozide), by the atypical antagonists (ex: risperidone, olanzapine
and quetiapine) or for antagonists of receptors alpha-2-adrenergic (ex: clonined and
guanfacine), because they present a smaller profile of collateral effects[3]
[33]
[34]
[42].
The risperidone has as main collateral effect the sedation, increase of appetite and
elevation of the prolactin levels. The olanzapine is a good alternative for the control
of the aggressive symptoms and does not have severe collateral effects, but patients
with cardiovascular problems and of epilepsy must used with caution, and patients
with glaucoma must avoid him[3]
[33]
[34]
[42].
The clonidine and guanfacine, have been showing very effective in the treatment of
the TS, but, because they are antihypertensive agents, must be done an accompaniment
of blood pressure[3]
[33]
[34]
[42].
The ministrated doses of each drug must be individualized to attend the need of the
patient, causing the less number of collateral effects possible.
A few studies show that the injection of botulinic toxin can be a good therapeutic
option for the treatment of motor tics and in some cases for the vocal tics[39]. Recent experiments discuss yet the use of immune modulating therapy and anti-inflammatory,
also the use of magnetic stimulation repetitive transcranial, profound brains stimulation
and electroconvulsive therapy for the treatment of TS[33]
[34].
