Mariangela Gulisano

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.

Increased antistreptococcal antibody titers and anti-basal ganglia antibodies in patients with Tourette syndrome: controlled cross-sectional study.

The association between Tourette syndrome, attention-deficit hyperactivity disorder (ADHD), and obsessive-compulsive disorder following streptococcal infections has been documented, but with conflicting reports. We thus felt it was important to investigate this association in a group of Italian patients not previously documented. We took blood on 69 patients with Tourette syndrome and 72 age- and sex-matched tic-free controls. Laboratory staff were blind to the diagnostic status of the subjects. Evidence of recent streptococcal infection was defined using antistreptolysin titers. Anti-basal ganglia antibodies were determined using human basal ganglia sections. Statistical analysis was conducted using analysis of variance and chi-square tests. Raised antistreptolysin titers were found in 41 of 69 (59%) patients with Tourette syndrome and 14 of 72 (19%) controls (P = .000). Positive anti-basal ganglia antibodies were found in 22 of 69 (32%) subjects with Tourette syndrome compared with 7 of 72 (10%) controls, which was also significant (P = .002). Raised antistreptolysin titers were detected in 18 of 22 (82%) patients with Tourette syndrome with positive anti-basal ganglia antibodies and 22 of 47 (47%) patients with negative anti-basal ganglia antibodies (P = .01). These results support the reported association between streptococcal infection and anti-basal ganglia antibodies and some patients with Tourette syndrome.

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.

Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large European Cohort

BACKGROUND Gilles de la Tourette syndrome (GTS) is a complex neuropsychiatric disorder with a strong genetic influence where copy number variations are suggested to play a role in disease pathogenesis. In a previous small-scale copy number variation study of a GTS cohort (n = 111), recurrent exon-affecting microdeletions of four genes, including the gene encoding arylacetamide deacetylase (AADAC), were observed and merited further investigations. METHODS We screened a Danish cohort of 243 GTS patients and 1571 control subjects for submicroscopic deletions and duplications of these four genes. The most promising candidate gene, AADAC, identified in this Danish discovery sample was further investigated in cohorts from Iceland, the Netherlands, Hungary, Germany, and Italy, and a final meta-analysis, including a total of 1181 GTS patients and 118,730 control subjects from these six European countries, was performed. Subsequently, expression of the candidate gene in the central nervous system was investigated using human and mouse brain tissues. RESULTS In the Danish cohort, we identified eight patients with overlapping deletions of AADAC. Investigation of the additional five countries showed a significant association between the AADAC deletion and GTS, and a final meta-analysis confirmed the significant association (p = 4.4 × 10(-4); odds ratio = 1.9; 95% confidence interval = 1.33-2.71). Furthermore, RNA in situ hybridization and reverse transcription-polymerase chain reaction studies revealed that AADAC is expressed in several brain regions previously implicated in GTS pathology. CONCLUSIONS AADAC is a candidate susceptibility factor for GTS and the present findings warrant further genomic and functional studies to investigate the role of this gene in the pathogenesis of GTS.

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.

ADHD and epilepsy in children with Tourette syndrome: a triple comorbidity?

Tourette Syndrome (TS) is an inherited neurodevelopmental disorder most commonly diagnosed in childhood or early adolescence, characterized by multiple motor tics and one or more phonic tics, which last for more than a year. Tics may be simple or complex in nature and vary in number, frequency and severity over time. TS is not a unitary condition and can be disaggregated into more homogeneous symptom components. With a prevalence of about 1%, TS is no longer considered a rare condition. TS has a multifactorial aetiology, in which genetic, immunological and hormonal factors interact to establish vulnerability. TS is associated with several comorbid disorders which are often the major source of impairment for affected children. Comorbidity between TS and ADHD is high even if the genetic relationship between ADHD and TS has not been fully established (1). The comorbidity of TS and epilepsy is rarely reported. In this paper, we report a series of eight young patients with TS who were followed up for at least 7 years, presenting comorbid mild ADHD symptoms and easily controlled seizures. Our series includes eight patients (seven males and one female) with a median age of 14.8 years (range 10–17) with definite diagnosis of TS according to Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revised (DSM-IV-TR) criteria, assessed at the Neuropediatric Unit of Catania University, Italy, and followed up for a period of at least 7 years. Full personal and family histories were obtained with particular reference to epilepsy and TS-related disorders. For the definition of epilepsy, we considered the presence of at least two afebrile seizures; for the ADHD definition, we considered excessive inattention, hyperactivity and impulsivity either alone or in combination. All the patients underwent a complete physical and neurological examination, routine laboratory examinations, awake electroencephalogram (EEG) and cerebral magnetic resonance imaging (MRI). Patients’ assessment was carried out using the National Hospital Interview Schedule for Gilles de la Tourette Syndrome, the Yale Global Tic Severity Rating Scale (YGTSS), the physician rated Diagnostic Confidence Index. The Conners’ Parents Scale, Child Behaviour Checklist and DSMIV-TR criteria were used to evaluate the severity of ADHD and to define its subtype. Psychiatric comorbidities were also evaluated by the following scales: the Children’s YaleBrown Obsessive Compulsive Scale, the Wechsler Intelligence Scale for Children, the self-report Child Depression Inventory and the Multidimensional Anxiety Scale for Children. Clinical findings of our eight patients are summarized in Table 1. Soft neurological signs such as incoordination and clumsiness were present in three patients. There was a positive family history for either tics or TS in four patients. All the patients had a typical onset of TS, presenting firstly motor tics at the age of 6.4 years (range 6–10 years), followed by vocal tics at the age of 9.8 years (range 8–13 years). One of them presented also obsessive compulsive disorder. Neuropsychological findings showed a normal IQ in six of eight patients. Three patients had mild tics and did not require any medications. TS was pharmacologically treated in five patients who presented high YGTSS’ scores (>20) with severe impairment in their daily life; three patients received pimozide and two risperidone, obtaining an improvement of the symptoms and a reduction in YGTSS’ score (p value: 0.005). All of them are still under pharmacological treatment. Acta Pædiatrica ISSN 0803–5253

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).

Clinical pharmacology of comorbid attention deficit hyperactivity disorder in Tourette syndrome.

Attention deficit hyperactivity disorder (ADHD) is the most common comorbid condition in people with Tourette syndrome (TS), reported in 60-80% of TS clinical samples. The comorbidity between TS and ADHD appears to have a complex pathogenesis and genetic factors can be implicated. Even if the etiological relationship between TS and ADHD is unclear, it is clear that individuals with both TS and ADHD are at a much greater risk for a variety of poor outcomes. It has been largely reported that the presence of comorbid symptoms seems to have a more significant influence on the patients quality of life than the presence of tics alone, and therefore it can be associated with a major need for pharmacological interventions. Nonpharmacological interventions, including psychotherapy, should be tried in patients with TS and comorbid ADHD before considering pharmacological treatment of ADHD symptoms. Available evidence suggests that the alpha 2-agonists should be the first-line treatment, followed by immediate release or sustained release psychostimulants as second choice, and atomoxetine as third-line treatment. Monitoring of emergence or worsening of tics is particularly recommended during a treatment course of psychostimulants.