Renata Rizzo

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce.

Epidermal nevus syndrome: a neurologic variant with hemimegalencephaly, gyral malformation, mental retardation, seizures, and facial hemihypertrophy.

The epidermal nevus syndrome (ENS) is a sporadic neurocutaneous disorder that consists of epidermal nevi and congenital anomalies involving the brain and other systems. From among over 60 patients with ENS presenting with neurologic manifestations, we identified 17 who had hemimegalencephaly based on pathologic or radiologic studies. Associated brain and neurologic abnormalities included gyral malformations in 12 of 12, mental retardation in 13 of 14, seizures in 16 of 17 (including 9 with infantile spasms), and contralateral hemiparesis in 7 of 12. All had ipsilateral epidermal nevi of the head, and several had ipsilateral facial hemihypertrophy. We concluded that these abnormalities comprise a recognizable neurologic variant of ENS that we believe represents the full expression of primary brain involvement. Several patients also had evidence of acquired brain lesions such as infarcts, atrophy, porencephaly, and calcifications, which are best explained by prior ischemia or hemorrhage. Given repeated observations of blood vessel anomalies in ENS patients, we hypothesize that underlying vascular dysplasia predisposes to these acquired lesions. The same cause may be invoked to explain the wide variety of neurologic symptoms reported in ENS patients without hemimegalencephaly. While the cause of ENS remains unknown, several observations suggest a somatic mutation.

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.

Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection

The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fishers exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection.

European clinical guidelines for Tourette Syndrome and other tic disorders. Part I: assessment

A working group of the European Society for the Study of Tourette Syndrome (ESSTS) has developed the first European assessment guidelines of Tourette Syndrome (TS). The available literature including national guidelines was thoroughly screened and extensively discussed in the expert group of ESSTS members. Detailed clinical assessment guidelines of tic disorders and their comorbidities in both children and adults are presented. Screening methods that might be helpful and necessary for specialists’ differential diagnosis process are suggested in order to further analyse cognitive abilities, emotional functions and motor skills. Besides clinical interviews and physical examination, additional specific tools (questionnaires, checklists and neuropsychological tests) are recommended.

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.

Neuropsychological aspects of Tourette syndrome: A review

Tourette syndrome (TS) is assumed to result from frontostriatal dysfunction, which would be expected to result in impairments in neuropsychological functions. This possibility has been explored in a number of studies that have assessed the performance of patients with TS within major cognitive domains and on tests involving executive functioning. We aim to summarize the main findings of these studies while evaluating the influence of task limitations and potentially critical confounding factors such as the presence of comorbidity. Although there is clearly a need for improved study design, we tentatively suggest that there is considerable evidence for cognitive impairment in a subgroup of patients, and that some difficulties seem to be intrinsic to TS. These impairments may reflect dysfunction of the anterior cingulate network within the frontostriatal pathway.

Support of the histaminergic hypothesis in Tourette Syndrome: association of the histamine decarboxylase gene in a large sample of families

Background Gilles de la Tourette Syndrome is a neurodevelopmental disorder that is caused by the interaction of environment with a complex genetic background. The genetic etiology of the disorder remains, so far, elusive, although multiple promising leads have been recently reported. The recent implication of the histamine decarboxylase (HDC) gene, the key enzyme in histamine production, raises the intriguing hypothesis of a possible role of histaminergic dysfunction leading to TS onset. Methods Following up on the finding of a nonsense mutation in a single family with TS, we investigated variation across the HDC gene for association with TS. As a result of a collaborative international effort, we studied a large sample of 520 nuclear families originating from seven European populations (Greek, Hungarian, Italian, Polish, German, Albanian, Spanish) as well as a sample collected in Canada. Results and Conclusions Interrogating 12 tagging SNPs (tSNP) across the HDC region, we find strong over-transmission of alleles at two SNPs (rs854150 and rs1894236) in the complete sample, as well as a statistically significant associated haplotypes. Analysis of individual populations also reveals signals of association in the Canadian, German and Italian samples. Our results provide strong support for the histaminergic hypothesis in TS etiology and point to a possible role of histamine pathways in neuronal development.

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.

Replication of association between a SLITRK1 haplotype and Tourette Syndrome in a large sample of families

Replication of association between a SLITRK1 haplotype and Tourette Syndrome in a large sample of families