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Background: Gilles de la Tourette syndrome (GTS) is a chronic neuropsychiatric disorder which has a significant detrimental impact on the health-related quality of life (HR-QOL) of patients. However, no patient-reported HR-QOL measures have been developed for this population. Objective: The development and validation of a new scale for the quantitative assessment of HR-QOL in patients with GTS. Methods: In stage 1 (item generation), a pool of 40 potential scale items was generated based on interviews with 133 GTS outpatients, literature review, and consultation with experts. In stage 2 (scale development), these items were administered to a sample of 192 GTS outpatients. Standard statistical methods were used to develop a rating scale satisfying criteria for acceptability, reliability, and validity. In stage 3 (scale evaluation), the psychometric properties of the resulting scale were tested in a second sample of 136 subjects recruited through the UK-Tourette Syndrome Association. Results: Response data analysis and item reduction methods led to a final 27-item GTS-specific HR-QOL scale (GTS-QOL) with four subscales (psychological, physical, obsessional, and cognitive). The GTS-QOL demonstrated satisfactory scaling assumptions and acceptability; both internal consistency reliability and test-retest reliability were high (Cronbach alpha ≥0.8 and intraclass correlation coefficient ≥0.8); validity was supported by interscale correlations (range 0.5–0.7), confirmatory factor analysis, and correlation patterns with other rating scales and clinical variables. Conclusions: The Gilles de la Tourette syndrome (GTS)–specific health-related quality of life (HR-QOL) scale (GTS-QOL) is proposed as a new disease-specific patient-reported scale for the measurement of HR-QOL in patients with GTS, taking into account the complexity of the clinical picture of GTS.

The effects of treatment with ropinirole (0.25 to 0.5 mg bid) were examined using an open-label design for 8 weeks in 15 subjects with Gilles de la Tourette syndrome (GdlT). All patients completed the study, and most showed an improvement in their tics during treatment. Low-dose ropinirole may improve the motor features in GdlT, but further controlled studies are necessary.

The growing awareness in women’s health issues in neurology has spawned a focus on the neurochemical modulatory effects of female sex hormones.1 Sex-specific variability in the expression of Gilles de la Tourette syndrome (GTS) is likely affecting men much more often than women. Several case reports and one questionnaire-based study have noted a premenstrual increase in tics thought to be secondary to low estrogen levels.2-4⇓⇓ No study has actually measured estrogen and progesterone levels through a menstrual cycle to correlate tic severity and hormonal activity. In families with motor tics, an associated behavioral manifestation, obsessive compulsive disorder (OCD), is also frequently seen in women. Further, men are more likely to present with tics (with or without OCD), and women are more likely to present with OCD (with or without tics).5 We hypothesized that menstruating women with GTS experience subjective and objective worsening of their tics and their OCD symptoms during the premenstrual period, during which both estrogen and progesterone are …

Objective: To identify common genetic variants associated with Gilles de la Tourette Syndrome (GTS). Background GTS is a highly heritable, neurodevelopmental disorder, though discovery of definitive GTS susceptibility genes has been challenging. Here, we report the first genome-wide association study (GWAS) of GTS in 1496 cases and 5249 unselected, ancestry-matched controls. Design/Methods: A multi-center case-control study was conducted with subjects of general European ancestry (EU), two European-derived population isolates, Ashkenazi Jews (AJ) and French Canadians (FC), and two closely-related Latin American population isolates from Antioquia, Colombia (ANT) and the Central Valley of Costa Rica (CVCR). Diagnoses were made using DSM-IV-TR criteria. 908 EU cases, all population-isolate cases, 298 EU controls and all FC and ANT controls were genotyped on the Illumina Hap610 platform. An additional 148 EU cases were genotyped on the IlluminaHap370, and remaining EU and AJ controls were previously genotyped on Illumina Hap550K and Hap1M arrays. Quality control (QC) was conducted in PLINK with specific focus on removing SNPs with differential performance across genotyping platforms. Ancestry-stratified case-control analyses were performed in PLINK using logistic regression. Case-weighted meta-analyses were conducted in METAL. Results: and Conclusions: In the primary meta-analysis of European-derived samples (EU, AJ, FC), no loci surpassed the threshold for genome-wide significance (p -8 ). However, the top 535 loci (p COL27A1 gene on chromosome 9 (rs7868992) with a genome-wide significant p-value =2.9 x 10 -8 . Additional neurodevelopmental genes of interest among the top signals included SLITRK6 , CNTN1 , and SEMA3G . Conclusions: Replication in additional samples is underway to validate the findings and to identify additional GTS susceptibility loci. Supported by: A grant from the Judah Foundation, NIH grants NS40024 to DLP and the Tourette Syndrome Association International Consortium for Genetics, NIH grant NS16648 and a grant from the Tourette Syndrome Association to DLP, NIH grant NS037484 to NBF, NIH grant NS043538 to AR-L, and an American Academy of Neurology Foundation grant and NIH grant MH085057 to JMS. Disclosure: Dr. Scharf has nothing to disclose. Dr. Yu has nothing to disclose. Dr. Mathews has nothing to disclose. Dr. Neale has nothing to disclose. Dr. Stewart has nothing to disclose. Dr. Fagerness has nothing to disclose. Dr. Scharf has nothing to disclose. Dr. Scharf has nothing to disclose. Dr. Scharf has nothing to disclose. Dr. Osiecki has nothing to disclose. Dr. Illmann has nothing to disclose. Dr. Cath has nothing to disclose. Dr. King has nothing to disclose. Dr. Dion has received personal compensation for activities with Biovail Pharma, Pfizer and Eli Lilly. Dr. Sandor has received personal compensation for activities with Psyadon, Shire, Solway, UCB Pharma, Janssen, Eli Lilly, Pfizer, and Prestwick. Dr. Barr has nothing to disclose. Dr. Budman has received research support from Psyadon Pharmaceuticals and Otsuka Pharmaceuticals. Dr. Lyon has nothing to disclose. Dr. Hoekstra has received personal compensation for activities with Desitin, Eli Lilly & Company and Shire. Dr. Singer has nothing to disclose. Dr. Jankovic has received personal compensation for activities with Allergan, Inc., Chelsea Therapeutics, Serono Inc., Merz Pharma, Lundbeck Research USA, Inc, Teva Neuroscience as a consultant. Dr. Jankovic has received personal compensation in an editorial capacity for Medlink: Neurology in Clinical Practice. Dr. Jankovic has received research support from Allergan, Inc, Allon Therapeutics, Ceregene, Inc., Chelsea Therapeutics; Diana Helis Henry Medical Research Foundation, Serono Inc., Huntington9s Disease Society of America, Huntington Study Group, Impax Pharmaceuticals, Ipsen Limited, Lundbeck Research USA, Inc. Dr. Gilbert has received personal compensation in an editorial capacity for Pediatrics Review and Education Program R11. Dr. Gilbert has received research support from Psyadon Pharmaceuticals and Otsuka Pharmaceuticals. Dr. Hoekstra has received personal compensation for activities with Desitin, Eli Lilly & Company and Shire. Dr. Heiman has nothing to disclose. Dr. Tischfield has nothing to disclose. Dr. State has nothing to disclose. Dr. Robertson has nothing to disclose. Dr. Kurlan has nothing to disclose. Dr. Ophoff has nothing to disclose. Dr. Gibbs has nothing to disclose. Dr. Cookson has nothing to disclose. Dr. Hardy has nothing to disclose. Dr. Singleton has nothing to disclose. Dr. Rodriguez has nothing to disclose. Dr. Rouleau has nothing to disclose. Dr. Heutink has nothing to disclose. Dr. Oostra has nothing to disclose. Dr. McMahon has nothing to disclose. Dr. Freimer has nothing to disclose. Dr. COX has nothing to disclose. Dr. Pauls has nothing to disclose.

Clinical and genetic observations of Gilles de la Tourette syndrome were carried out on members of 14 families from the Minneapolis area. An unusual number of the families were of Jewish and other Eastern European ancestry, and in all but one of these families multiple members were affected. These observations parallel our earlier findings based on 21 families from the New York City area. Together with recent evidence indicating relative instability of a specific enzyme in some patients, these observations suggest that there is a genetically determined form of Gilles de la Tourette syndrome.

Following 6 years of continuous chlorpromazine therapy for schizophrenia, a young woman developed multifocal tics and vocalizations characteristic of Tourette syndrome. These symptoms first appeared when chlorpromazine was withdrawn. They were permanent, although partially ameliorated by chronic haloperidol therapy. Because of her age and past history, these symptoms were attributed to chronic neuroleptic therapy analogous to neuroleptic-induced tardive dyskinesia, rather than to Tourette syndrome per se. These symptoms suggest that chronic receptor-site blockade can result in hypersensitivity of dopamine receptor sites, and that this may play a role in the pathophysiology of Gilles de la Tourette syndrome. This is the first evidence that hypersensitivity of dopamine receptors is involved in the pathophysiology of 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.