Paola V. Calì

Quality of life in young people with Tourette syndrome: a controlled study

Quality of life (QoL) may be adversely affected by Tourette syndrome (TS). Although the core symptoms of this complex neurodevelopmental disorder are tics, patients often present with an array of behavioural difficulties, such as co-morbid obsessive compulsive disorder (OCD) or attention deficit hyperactivity disorder (ADHD). In this study we investigated whether young people with TS exhibited poorer QoL in comparison to healthy individuals and an epilepsy control group. We also analysed whether greater tic severity or co-morbid OCD and\or ADHD led to greater differences in perceived QoL. The Youth Quality of Life Instrument-Research Version (Edwards et al. in J Adolesc 25:275–286, 2002) was used to assess QoL and a range of clinical scales were administered to assess anxiety, depression and other behavioural symptoms. TS was associated with significant differences in aspects of QoL related to home and social activities, involving peer and family interactions. Patients with more severe tics reported a greater negative impact on QoL. Patients with TS and no associated diagnoses (pure TS) presented with lower QoL scores in the environment domain, poorer perceived QoL in general, and depressive features. Co-morbid OCD appeared to exert a greater impact on self and relationship QoL domains. The presence of both OCD and ADHD as co-morbidities led to more widespread problems. In conclusion, TS can be associated with poorer perceived QoL. Although social aspects of QoL may be more vulnerable to TS in general, co-morbid conditions make an important contribution in determining which aspects of QoL are most affected in the individual.

Clinical Correlates of Quality of Life in Tourette Syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder involving tics, which is frequently accompanied by comorbid obsessive compulsive (OCD) or attention deficit hyperactivity disorder (ADHD). Individuals with TS often report poor quality of life (QoL) in comparison with the general population. This study investigated the clinical correlates of QoL in young people with TS using a self‐report multidimensional QoL measure, and a range of clinical scales used to assess tic severity and the symptoms of anxiety, depression, OCD, ADHD and other emotional and behavioral symptoms. Symptoms of depression, OCD, and ADHD appeared to have a widespread negative impact on QoL, but poorer QoL was not associated with increased tic severity. Greater emotional and behavioral difficulties, including symptoms of OCD, were among the best predictors of poor QoL in young people with TS.

Parent and self-report health-related quality of life measures in young patients with tourette syndrome

Tourette syndrome is a neurodevelopmental disorder characterized by tics and comorbid behavioral problems. This study compared child- and parent-reported quality of life and everyday functioning. We assessed 75 children with Tourette syndrome, of which 42 (56%) had comorbid conditions (obsessive-compulsive disorder = 25; attention-deficit hyperactivity disorder = 6; both comorbidities = 4). All patients completed psychometric instruments, including the Gilles de la Tourette Syndrome–Quality of Life Scale for Children and Adolescents (child report) and the Child Tourette’s Syndrome Impairment Scale (parent report). Data were compared for patients with pure Tourette syndrome, Tourette syndrome + obsessive-compulsive disorder, Tourette syndrome + attention-deficit hyperactivity disorder, and Tourette syndrome + both comorbidities. There were no group differences in quality of life. However, there were differences for total, school, and home activities impairment scores. Children and parents may not share similar views about the impact of Tourette syndrome on functioning. The measurement of health-related quality of life in Tourette syndrome is more complex in children than adults.

Quality of life in young people with treatment-responsive epilepsy: A controlled study

OBJECTIVE Quality of life (QoL) has been shown to be lower in individuals with epilepsy than the general public. However, few studies have investigated the QoL of individuals with well-controlled epilepsy. This study investigated the effects of epilepsy on QoL in persons with treatment-responsive seizures, beyond factors directly related to the presence of seizures. METHODS Fifty young patients with controlled epilepsy and 102 healthy controls completed a generic, multidimensional, self-report QoL instrument, along with standardized scales assessing anxiety, depression, and other emotional or behavioral difficulties. RESULTS Young people with epilepsy reported increased anxiety (P=0.037) and more emotional and behavioral difficulties (P<0.001). Though there were was no difference between the groups in Total QoL score, treatment-responsive epilepsy was associated with lower QoL within the Self domain (P=0.016). CONCLUSIONS Epilepsy may exert a negative influence on QoL in relation to thoughts and feelings about the self in the context of complete seizure remission. Future research should investigate the therapeutic value of interventions targeting detrimental changes to self-perception in young people living with controlled epilepsy.

The Gilles de la Tourette Syndrome-Quality of Life Scale for children and adolescents (C&A-GTS-QOL): development and validation of the Italian version.

Background: Gilles de la Tourette syndrome (GTS) is a chronic childhood-onset neuropsychiatric disorder with a significant impact on patients’ health-related quality of life (HR-QOL). Cavanna et al. (Neurology 2008; 71: 1410–1416) developed and validated the first disease-specific HR-QOL assessment tool for adults with GTS (Gilles de la Tourette Syndrome-Quality of Life Scale, GTS-QOL). This paper presents the translation, adaptation and validation of the GTS-QOL for young Italian patients with GTS. Methods: A three-stage process involving 75 patients with GTS recruited through three Departments of Child and Adolescent Neuropsychiatry in Italy led to the development of a 27-item instrument (Gilles de la Tourette Syndrome-Quality of Life Scale in children and adolescents, C&A-GTS-QOL) for the assessment of HR-QOL through a clinician-rated interview for 6–12 year-olds and a self-report questionnaire for 13–18 year-olds. Results: The C&A-GTS-QOL demonstrated satisfactory scaling assumptions and acceptability. Internal consistency reliability was high (Cronbach’s alpha > 0.7) and validity was supported by interscale correlations (range 0.4–0.7), principal-component factor analysis and correlations with other rating scales and clinical variables. Conclusions: The present version of the C&A-GTS-QOL is the first disease-specific HR-QOL tool for Italian young patients with GTS, satisfying criteria for acceptability, reliability and validity.

Tourette Syndrome and Comorbid Conditions A Spectrum of Different Severities and Complexities

To investigate clinical correlates of Tourette syndrome and to identify the impact of comorbidities, we retrospectively recruited 92 young people affected by Tourette syndrome compared with 102 healthy controls. Neuropsychological assessment included: Youth Quality of Life–Research, Multidimensional Anxiety Scale for Children, Children’s Depression Inventory, and Conner’s and Child Behavior Checklist; moreover, Tourette syndrome patients completed the Yale Global Tic Severity Rating Scale and the Yale-Brown Obsessive Compulsive Scale. Four clinical subgroups were identified: pure Tourette syndrome (49.8%), Tourette syndrome plus attention-deficit hyperactivity disorder (ADHD) (22.2%), Tourette syndrome plus obsessive-compulsive disorder (21.5%), and Tourette syndrome plus ADHD plus obsessive-compulsive disorder (6.5%). Our findings suggested that emotional lability appeared in all Tourette syndrome subgroups, independently from comorbidities, representing a clinical feature of Tourette syndrome itself. Moreover, our data suggested that all 4 clinical subgroups had higher statistically significant behavioral problems compared with the healthy controls (P = .000), whereas affective and anxiety symptoms were overrepresented in Tourette syndrome plus comorbidities subgroups. Finally, Tourette syndrome patients had a lower quality of life compared with the healthy controls. These differences were statistically significant between the pure Tourette syndrome subgroups and Tourette syndrome plus comorbidities subgroups, as well as Tourette syndrome plus comorbidities subgroups and healthy controls.

Metabolic Effects of Aripiprazole and Pimozide in Children With Tourette Syndrome

This study assessed the metabolic effects of aripiprazole and pimozide in pediatric Tourette syndrome, a neurodevelopmental condition characterized by multiple motor and phonic tics. Patients receiving aripiprazole (n = 25) or pimozide (n = 25) were compared with medication-free patients (n = 25). Body mass index, glycemia, triglyceridemia, and cholesterolemia were monitored at baseline and 12 and 24 months after commencing treatment. The aripiprazole group demonstrated significant increases in cholesterolemia. The pimozide group demonstrated significant increases in glycemia. Both groups demonstrated elevations in triglyceridemia not significantly different from those in unmedicated control subjects. The effect of aripiprazole on cholesterol was apparent after 12 months, but leveled off during year 2 of treatment. Longitudinal studies are required to evaluate the full extent of glycemic alterations with pimozide. Both agents appear relatively safe for use in pediatric Tourette syndrome. These findings will help guide medication selection in patients with specific medical vulnerabilities.

Premonitory Urges in Patients with Gilles de la Tourette Syndrome: An Italian Translation and a 7-Year Follow-up

OBJECTIVE Premonitory sensations or urges (PUs) are described as characteristic sensory phenomena preceding tics, which are often described as unpleasant. They occur in 90% of patients affected by Gilles de la Tourette Syndrome (GTS). They may be localized (around the area of tic) or generalized (covering a wide area of the body). The PUs can be measured by the Premonitory Urge for Tics Scale (PUTS). In this study we translated the PUTS scale into Italian and then assessed children and adolescents/young people (CYP) with GTS using the scale. METHODS GTS patients were assessed at the initial interview and after 7 years to evaluate the PUs, and the correlations of the PUTS scores with tic severity, severity of comorbid disorders (obsessive-compulsive disorder [OCD], attention-deficit/hyperactivity disorder [ADHD]), and a variety of coexisting psychopathologies. RESULTS A total of 95 patients were studied. We successfully translated the PUTS into Italian, and our results indicated that our translated version had good psychometric properties. Results demonstrated that the CYP had PUs at both interviews, but that older CYP were more consistent in reporting PUs than younger CYP (i.e., PUTS scores increased with age). We found no correlations between PUTS score and tic severity at either interview. We found a statistical significant correlation between PUTS score and obsessive-compulsive symptoms (OCS) at both interviews; Moreover both the PUTS and Childrens Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores increased significantly, whereas the Yale Global Tic Severity Rating Scale (YGTSS) score decreased significantly. We found no relationships between PUTS scores and anxiety, depression, ADHD, and externalizing/internalizing behavioral scores. CONCLUSIONS Our results suggest the the Italian translation of the PUTS has good psychometric properties. Although both younger (<10 years of age) and older CYP (≤ 10 years of age) reported PUs, the scores at the initial interview were statistically significantly lower than at follow-up. Moreover, in CYP >10 years of age, the PUs correlated with obsessions and compulsions (CY-BOCS scores).

Mandatory electrocardiographic monitoring in young patients treated with psychoactive drugs.

The pharmacotherapy for the management of tic and obsessive–compulsive disorder in Tourette syndrome relies on neuroleptics and selective serotonin reuptake inhibitors, which have been associated with electrocardiographic abnormalities, including QTc interval prolongation and increased risk of sudden cardiac death (SCD) in patients taking these drugs. Congenital long QT syndrome (LQTS) is an inherited condition characterized by a prolonged QT interval, and consequently is a major risk factor for torsades de pointes and SCD. We reported a case of critical QTc prolongation due to pimozide and fluoxetine therapies in a 10-year-old boy with Tourette syndrome and obsessive–compulsive disorder and unknown QT long syndrome. The patient’s family history was not contributory; no family member had a history of sudden death, syncope, or congenital heart disease. Pregnancy and developmental milestones during infancy were normal. At the age of 6 years, he began to present motor tics. A few years later, he started to present obsessions and compulsions, and for this reason, he was referred to us for our expert opinion. Both general and neurological examinations were normal. Mental state examination showed an intact cognitive state. During the visit, we observed the following motor and phonic tics: eye blinking, nose movements, lip licking, finger movements, echolalia, and echopraxia. Neuropsychological evaluation gave the following results: Yale Global Tic Severity Scale (YGTSS) 30; YaleBrown Obsessive Compulsive Scale (Y-BOCS) 38; Diagnostic Confidence Index, 80 %. Routine investigations to date have been normal, including brain magnetic resonance imaging and surface ECG (QTc: 418 ms). We prescribed pimozide at a dosage of 4 mg/day with marked improvement either in tics or in obsessions–compulsions. His global severity score on the YGTSS dropped to 22, and his global severity score on the Y-BOCS dropped to 28. After 3-month follow-up, the patient underwent a repeat routine investigation and surface ECG that showed an increase of QTc length (478 ms). We stopped pimozide, and in 15 days, the QTc was within the normal range (418 ms). Without any pharmacological treatment, his symptoms worsened concerning either tics or obsession– compulsion. His YGTSS was 22 and Y-BOCS was 36. We then prescribed fluoxetine at the dosage of 20 mg/ day, and after 3-month follow-up, he showed an improvement in symptoms; his scores in the neuropsychological scales were as follows: YGTSS 18; Y-BOCS 28. We repeated surface ECG which again showed an increase of QTc length (471 ms). We stopped the treatment and repeated the ECG, which then showed QTc length normalization after 15 days and worsening of Tourette symptoms. During the drug administration, the boy never presented with syncope or orthostatic hypotension. R. Rizzo (&) M. Gulisano P. V. Cali Section of Child Neuropsychiatry, Dipartimento di Scienze Mediche e Pediatriche, Catania University, Via Santa Sofia 78, 95123 Catania, Italy e-mail: rerizzo@unict.it

Oculogyric crisis: a rare extrapyramidal side effect in the treatment of Tourette syndrome.

While extrapyramidal adverse effects are generally rare when neuroleptics are used for the treatment of Tourette syndrome (TS) [1], still acute dystonic reactions occurring within the first 7 days of starting or rapidly increasing neuroleptic dose may occur. Acute dystonic reaction consists of sustained, often painful muscular spasms, producing twisting abnormal postures. Signs of neuroleptic-induced acute dystonia may include retrocollis, torticollis, trismus, grimacing or jaw-gaping, oculogyric crisis (characterized by spasmodic deviations of the eyes, most commonly upwards but occasionally downwards or oblique), laryngeal-pharyngeal constriction, dysphagia, dysphonia, tongue protrusion or tongue swelling, dysarthria, and opisthotonus or bizarre positions of the limbs or trunk [2]. The movements may fluctuate over hours and typically last minutes to hours without treatment. Aripiprazole is a novel atypical antipsychotic with high affinity for D2/D3 receptors. Moreover, it shows long elimination half-life and, at clinical doses, occupies a high fraction of its target receptor everywhere in the brain. Its dissociation from those receptors is very slow, and receptors remain nearly saturated for as long as 1 week after the last dose [3]. Aripiprazole is metabolized via the hepatic cytochrome P450 enzyme system, specifically the isoenzymes CYP2D6 and CYP3A4. Inhibition or induction of these enzymes—for example, through comedication— leads to predictable changes in aripiprazole serum concentrations [4]. We report a case of oculogyric crisis possibly associated with aripiprazole therapy in a 21-year-old woman with TS. Her family history is not contributory. Pregnancy and developmental milestones during infancy were normal. At the age of 5 years, she began to present motor tics (eye blinking). A few months later, she started to present simple phonic tics (sniffing). She had mild TS symptoms that did not require any medications until the age of 18 years when her tic symptoms worsened; tiapride (100 mg/day) and paroxetine (10 mg/day) were prescribed. After 1 year, she also developed marked phonic tics (screaming). Consequently, she was given sertraline (50 mg/day), although without success, and thus she was referred to us for our opinion. Both general and neurological examinations were normal. Mental state examination showed an intact cognitive state. However, she showed anxiety assessed with Beck Anxiety Inventory that scored 21. During the visit, we observed the following motor and phonic tics: eye blinking, nose movements, facial grimaces, lip licking, finger movements, abdominal contractions, touching of things, smelling, repeating vocalizations such as ‘ih, uh, ah’, inappropriate voice fluctuations, and echopraxia. To assess the severity of tics and obsessive compulsive disorder symptoms, the Yale Global Tic Severity Scale (YGTSS) and the Yale Brown Obsessive Compulsive Scale (with global impairment) (Y-BOCS) were used and respectively scored 39 and 26. Diagnostic Confidence Index for TS (DCI) scored 75 %. Routine investigations were normal, including brain magnetic resonance imaging. We prescribed aripiprazole after tapering and then stopped R. Rizzo (&) M. Gulisano P. V. Calı̀ Section of Child Neuropsychiatry, Dipartimento diScienze Mediche e Pediatriche, Catania University, Via Santa Sofia 78, 95123 Catania, Italy e-mail: rerizzo@unict.it