Catechol-O-methyltransferase and Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (TS) is a neuropsychiatric disorder characterized by both motor and vocal tics. Individuals with TS often have symptoms of obsessive compulsive disorder (OCD) and these symptoms are thought to be an alternative expression of the TS gene(s) in TS families. In this paper we test for linkage of the functional polymorphism in the catechol-O-methyltransferase (COMT) gene to TS and OCD in five multi-generational families ascertained through a TS proband. This polymorphism (valine to methionine at codon 158) has been previously reported to influence the activity of COMT by three to four-fold and has recently been reported to be associated with OCD.1 We tested for linkage using an autosomal dominant model with reduced penetrance and non-parametric methods. No significant evidence for linkage was found for the COMT gene and the TS/CMT, or OCD phenotypes in these pedigrees.     

Gilles de la Tourette syndrome in Oriental children.

Seventy-four cases of tic syndromes were classified into four groups: chronic multiple tics, subacute multiple tics, chronic simple tics and transient simple tics, and 37 cases of chronic multiple tics (Tourette syndrome) were investigated. Clinical evaluation suggested that a transition existed between the four groups. Posture abnormalities were found in 27% of Tourette syndrome and a relation to dystonia was implied. Clinical evaluation and studies of catecholamine blockers' effectiveness suggested the validity of subtyping Tourette syndrome into four groups whose topographical or biochemical abnormalities differ. It was argued that the neurochemical basis of Tourette syndrome might lie in a multiplicity of biochemical abnormalities including disturbances of dopaminergic and noradrenergic pathways.     

Oculomotor control in Gilles de la Tourette syndrome.

Saccadic eye movements, fixation and smooth pursuit were studied in 28 children with Gilles de la Tourette syndrome and found to be normal. A link has been postulated between Gilles de la Tourette syndrome and other movement disorders. The results obtained in the present series do not support this hypothesis.     

The treatment of Gilles de la Tourette syndrome by limbic leucotomy.

A patient with Gilles de la Tourette syndrome and severe self-injurious compulsions who had failed to respond to drug treatment and behavioural therapy obtained a complete and sustained resolution of his destructive behaviour and improvement in his tics following bilateral limbic leucotomy.     

Color vision deficiencies in Gilles de la Tourette syndrome.

Color perception was tested using the Farnsworth-Munsell 100-Hue Test in a sample of persons with Gilles de la Tourette syndrome (GTS), and compared to norms from three age cohorts in the early second, fourth and sixth decades. Red-green color errors on the Farnsworth-Munsell did not appear to change appreciably as a function of age or GTS. Blue-yellow error scores did, however, increase with age and were exaggerated in the GTS group. It is concluded that sensory and perceptual disturbances are present in GTS as in other basal cell ganglia disorders. The results are discussed in terms of converging retinal dopaminergic mechanisms also associated with Parkinson's and Huntington's diseases and even with normal aging. Suggestions are offered that daily activities and behavior may be affected by spatial and chromatic deficiencies.     

Hypoxanthine guanine phosphoribosyltransferase (HGPRT) in Gilles de la Tourette syndrome.

Hypoxanthine guanine phosphoribosyltransferase (HGPRT) and adenosine phosphoribosyltransferase (APRT) were examined from 11 individuals with Gilles de la Tourette syndrome, 10 of their first- or second-degree relatives, and 3 normal controls. It has been suggested that in some self-mutilating Tourette patients, HGPRT shows a time-related loss of activity at 4 degrees C, and an unusual isoelectrofocusing pattern. Although 3 patients experienced self-mutilation, no consistent abnormalities were found in the temperature-stability of their HGPRT at 4 degrees C and 70 degrees C, or in isoelectrofocusing of HGPRT purified by immunoprecipitation. An alteration of the purine metabolic pathway in Tourette syndrome has not been established.     

Georges Gilles de la Tourette. The man and his times

Georges Albert Edouard Brutus Gilles de la Tourette (1857-1904), one of Charcot's favourite pupils and his self-appointed amanuensis made several valuable contributions to medicine and literature. His most substantial achievements were in the study of hysteria and the medico-legal ramifications of hypnotism, but he was also a competent neuropsychiatrist with a particular interest in therapeutics. He was a dynamic, passionately outspoken man whose prodigious literary output reflected his own restless compulsions as well as the interests of his beloved chiefs Brouardel and Charcot. His love of Loudun, his ancestral home strongly influenced his subject matter which included a biography of Theophraste Renaudot and with his colleague Gabriel Legué a perceptive analysis of Soeur Jeanne des Anges' account of her hysterical illness induced by her unrequited love for the Loudun priest Urbain Grandier. In 1893 shortly after the tragic death of his young son and of his mentor Charcot, Gilles de la Tourette was shot by a deluded woman who had been a patient at the Salpêtrière. Her claims that she had been hypnotised by Gilles de la Tourette against her will causing her to lose her sanity bore a macabre resemblance to the accusation of Soeur Jeanne des Anges against Grandier. The bizarre episode became a "procès célèbre" seeming superficially to vindicate the Nancy School's views that criminal suggestion was possible under hypnotism, a view Gilles de la Tourette had vehemently rejected. Despite his colourful life and varied achievements only an incomplete biographical account by his friend Paul le Gendre, a few informative orbituaries and some caustic sketches by Leon Daudet exist.     

Gilles de la Tourette syndrome: further studies and thoughts.

A possible association between the Gilles de la Tourette and Lesch-Nyhan syndromes has recently been postulated. Fourteen patients with Tourette syndrome demonstrated no similarity to Lesch-Nyhan based upon patterns of inheritance, behavioral changes, or alterations of purine metabolism. Despite a strong male predominance, a sex-linked pattern of inheritance could not be confirmed. Self-mutilating behavior was found in 4 male patients but was readily differentiated from that characteristic of the Lesch-Nyhan syndrome. Quantitation of hypoxanthine-guanine phosphoribosyltransferase and isoelectric focusing of its isoenzymes produced results that were indistinguishable from those in controls. We speculate that, pathophysiologically, Tourette syndrome represents an imbalance between the central neurotransmitters dopamine and serotonin rather than an alteration in purine metabolism.     

Cassette EEG sleep recordings in Gilles de la Tourette syndrome.

Tourette syndrome (TS) patients often complain of sleep problems, and questionnaire studies indicate that sleep disturbance is frequent. Decreased slow wave sleep and increased awakenings have been reported in laboratory polysomnography in TS patients, and a serotoninergic disorder of arousal has been postulated. We recorded outpatient sleep in 20 patients newly diagnosed with TS utilizing a 4-channel cassette EEG system. The newly-diagnosed patients were predominantly male, and ranged in age from 10 to 36 years. Some had taken psychotropic medications in the past, but none had been treated systematically for TS. Seven patients had chronic tics only, 8 had tics and attention deficit-hyperactivity, and 5 had tics plus obsessions and compulsions. None had other medical, neurologic, or psychiatric disorders. All were nocturnal sleepers, and were recorded in their usual sleeping environments and routines. TS patients had reduced sleep, decreased sleep efficiency, increased awakenings, and decreased slow wave sleep. Tic patients had increased nocturnal awakenings and movements, particularly those who had tics during sleep. Sleep fragmentation and loss of slow wave sleep was most marked in TS patients with attention deficit-hyperactivity. Sleep latency was increased, REM sleep reduced, and REM sleep latency decreased in TS patients with obsessions and compulsions. These findings accord with previous reports of sleep disturbance in TS, and suggest that these disturbances may vary with TS symptoms. Chronic tics may persist in sleep and cause awakenings, TS with attention deficit may be associated with a disorder of arousal and alertness, and obsessions and compulsions may be manifestations of a biochemical disturbance involving paradoxical sleep.     

Abnormalities of the blink reflex in Gilles de la Tourette syndrome.

The blink reflex and it's recovery cycle were studied in 26 patients with Gilles de la Tourette syndrome and 10 controls. There was a significant increase in the mean duration of the R2 response. The amplitude of the R2 response following paired shocks (mean R2[T]/R2[C]%) was 11%, 40% and 52% of the conditioning stimulus with intervals of 200 ms, 500 ms and 1 second in the patients, compared with 10%, 17% and 32% respectively in the controls. Half the patients, however, had normal recovery cycles and voluntary suppression of tics and blinks reduced the amplitude of R2 in all patients. These results suggest increased excitability of brainstem interneurons in Gilles de la Tourette syndrome.     

Contingent negative variation in adults with Gilles de la Tourette syndrome.

Three deflections or waves of the Contingent Negative Variation (CNV): the Slow Negative Wave (SNW), the Terminal CNV (TCNV) and the Post Imperative Negative Variation (PINV) were studied in 18 adults with Gilles de la Tourette syndrome and in 15 controls. The patients showed a reduced SNW, a normal TCNV and an increased PINV. Moreover, at the right parietal region the patients demonstrated a decreased SNW, TCNV and PINV. The results are discussed in relation to behavioral and neuropsychological disturbances found in Gilles de la Tourette syndrome.     

Non-invasive assessment of autonomic nervous function in Gilles de la Tourette syndrome.

Autonomic nervous function was investigated in 18 Gilles de la Tourette (GTS) patients and in 23 controls, who matched the patients in age, sex, baseline blood pressure and baseline heart rate. Four heart rate tests were used (variation at rest, during deep breathing, following standing up and during a Valsalva manoeuvre), and two blood pressure tests (standing up and sustained handgrip). The only significant difference between the groups was found in the Valsalva test. This was due to the initial heart rate increase which was higher in the GTS group; the subsequent decrease did not differ between the groups. Increased sympathetic activity is a possible explanation for this finding, but no additional evidence in its favour was found. No signs of autonomic failure were found.     

A clinical study of Gilles de la Tourette syndrome in the United Kingdom.

The clinical features of 53 British-born patients with Gilles de la Tourette syndrome are described. The mean age at onset of body tics was seven years and for vocalisations 11 years. Coprolalia was present in 39%, copropraxia in 21%, echolalia in 46% and echopraxia in 21%. Complicated antics and mannerisms were also common, often involving the compulsive touching of objects or self-injurious behaviour. Forty-six per cent of cases had a family history of tics in a single close relative and in two individuals a further member of the family had Gilles de la Tourette syndrome. Focal dystonia was present in four patients who had never received neuroleptics drugs and chorea was seen in two other untreated patients. In three patients acoustic startle consistently induced brief eye blink followed by a whole body jerk or jump. Rapid repetitive movements of the hands increased the frequency and severity of tics in 13 patients, but the performance of mental arithmetic under time pressure had a much more unpredictable effect. Electroencephalographic abnormalities occurred in eight (13%) but no definite CT brain scan abnormalities were detected. The incidence of left handedness did not differ from that in the general population and no evidence to suggest organic impairment was found on neuropsychological testing. This study provides no support for the notion that Gilles de la Tourette syndrome is a degenerative disorder of the central nervous system but provides some evidence for heterogeneity.     

Gilles de la Tourette syndrome: patient's knowledge and concern of adverse effects.

The objective of this study was to assess awareness and concern of neuroleptic (NL)-induced side effects in Gilles de la Tourette syndrome (GTS) patients. Although NLs are effective tic suppressants, they can be associated with various side effects. Data on patient knowledge and concern about side effects can guide educational efforts. One hundred consecutive GTS patients or parents in a tertiary referral medical center responded to a standardized, in-person questionnaire. They were given a list of 15 side effects and asked which could be ascribed to NLs (9) or not (6). Side effect concern was rated on a 0 (none) to 10 (extreme) scale. The mean age for the 100 patients was 19.4+/-14 years; 55 had a history of NL use, and 45 were NL-naive. Less than half the cohort met criteria for being well informed. Only one third of the listed NL side effects were accurately identified by at least 75% of the respondents. Patients with past or current NL treatment were more accurate in identifying NL side effects but less concerned about them than NL-naive patients. The side effects of greatest concern were seizures, tardive dyskinesia, thinking and emotion disturbances, and cardiac irregularities. Overall, patient awareness of NL side effects is insufficient, and although past exposure to NLs enhances knowledge, it decreases concern.