Developmental profile and diagnoses in children presenting with motor stereotypies

Introduction: Motor stereotypies represent a typical example of the difficulty in distinguishing non-clinical behaviors (physiological and transient) from symptoms or among different disorders (“primary stereotypies”, associated with Autistic Spectrum Disorder, Intellectual Disabilities, genetic syndromes, sensory impairment). Aim of this study was to get an accurate analysis on the relationship between stereotypies and neurodevelopmental disorders. Methods: We studied 23 children (3 girls) aged 36 to 95 months, who requested a consultation due to the persistence or the increase severity of motor stereotypies. None of patients had a previous diagnosis of ASD. The assessment included the Motor Severity Stereotypy Scale (MSSS), the Repetitive Behavior Scale-Revised (RBS-R), the Raven’s Colored Progressive Matrices (CPM), the Child Behavior Checklist for ages 1 ½ -5 or 4-18 (CBCL), the Social Responsiveness Scale (SRS) and the Autism Diagnostic Observation Schedule- Second edition (ADOS 2). Results: All patients were showing motor stereotypies for periods of time varying from 6 to 77 months. The MSSS showed each child had a limited number of stereotypies; their frequency and intensity were mild; the interference of stereotypies was variable; the impairment in the daily life was mild. The RBS-R scores resulted positive for the subscale of “Stereotypic behaviors” in all children; moreover, several children presented other repetitive behaviors, mainly “Ritualistic behavior” and “Sameness behavior”. All patients showed a normal cognitive level. The CBCL evidenced behavioral problems in 22% of the children: Internalizing problems, Attention and Withdrawn were the main complaints. On the SRS, all but one of the tested patients obtained clinical scores in the clinical range at least in one area. On the ADOS 2, four patients obtained scores indicating a moderate level of ASD symptoms, four had a mild level and fifteen showed no or minimal signs of ASD. Discussion: Motor stereotypies in children with normal cognitive level represent a challenging diagnostic issue for which a finely tailored assessment is mandatory in order to define a precise developmental profile. Notably, a careful and cautious use of standardized tests is warranted to avoid misdiagnosis. Furthermore, it is hard to consider motor stereotypies, even the primary ones, exclusively as a movement disorder

Developmental motor profile in preschool children with primary stereotypic movement disorder

Aim. Different neuropsychological dysfunctions have been described in children with primary Stereotypic Movement Disorder (SMD), mainly attention or motor coordination problems. Up to now with no study has evaluated psychomotor functions in preschoolers primary SMD. The aim of this observational study was to gather information on the motor profiles of SMD patients in this age range in comparison with typically developing children. Patients and Methods. Twenty-six children (four girls) aged 36 to 76 months (mean= 53 ±10) with primary SMD were assessed by a structured evaluation including the Movement Assessment Battery for Children-Second Edition (MABC-2), the Beery-Buktenica Developmental test of Visual-Motor Integration (VMI), the Repetitive Behaviour Scale-Revised (RBS-R), the Motor Severity Stereotypy Scale (MSSS), and the Child Behaviour Checklist (CBCL). The diagnoses of Intellectual Disability or Autism Spectrum Disorder were exclusion criteria from the study. A comparison group of twenty-seven (four girls) typically developing children without stereotypies aged 36 to 59 months (mean= 48 ±7) was also examined. Results. The MABC-2 total score was lower than 15th percentile in fifteen children with SMD (58%); the worst performances were observed in Balance and Manual Dexterity subtests. The motor coordination score of VMI was lower than 15th percentile in ten children (38%). The majority of the children with low scores at MABC-2 also had low scores at the motor coordination subscale of VMI. MABC-2 standard scores of the clinical group were significantly lower than those of controls on MABC-2 Total, Balance, and Ball Skills subtests. Conclusion. The finding of widespread dysfunction of gross and fine motor abilities in preschoolers with primary SMD seems to delineate a peculiar phenotype and could provide new approaches to the management of this neurodevelopment disorder

Health-related quality of life in patients with Gilles de la Tourette syndrome at the transition between adolescence and adulthood

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental condition characterised by tics and comorbid behavioural problems, affecting predominantly male patients. Tic severity typically fluctuates over time, with a consistent pattern showing improvement after adolescence in a considerable proportion of patients. Both tics and behavioural co-morbidities have been shown to have the potential to affect patients’ health-related quality of life (HR-QoL) in children and adults with persisting symptoms. In this study, we present the results of the first investigation of HR-QoL in patients with Gilles de la Tourette syndrome at the transition between adolescence and adulthood using a disease-specific HR-QoL measure, the Gilles de la Tourette Syndrome-Quality of Life-Children and Adolescents scale. Our results showed that patients with GTS and more severe co-morbid anxiety symptoms reported lower HR-QoL across all domains, highlighting the impact of anxiety on patient’s well-being at a critical stage of development. Routine screening for anxiety symptoms is recommended in all patients with GTS seen at transition clinics from paediatric to adult care, to implement effective behavioural and pharmacological interventions as appropriate

Self-concept and self-esteem in patients with chronic tic disorders::A systematic literature review

Chronic tic disorders are neurodevelopmental conditions characterized by the presence of motor and/or phonic tics and often accompanied by co-morbid behavioral problems. Chronic tic disorders can negatively affect the level of functioning of young patients across social and family domains, with possible repercussions on their self-perception. We conducted a systematic literature review to assess the clinical correlates of both components of self-perception (self-concept, i.e. what patients think about themselves, and self-esteem, i.e. how they feel about their self-concept) in patients with chronic tic disorders. Reported levels of self-perception varied widely across studies, partly due to the methodological heterogeneity of the reviewed literature. Poor self-concept and self-esteem appeared to be more strongly related to the presence of psychiatric co-morbidities (especially obsessive-compulsive disorder, attention-deficit and hyperactivity disorder, and anxiety disorders) than to tic severity. Poor peer relationship, social difficulties, as well as problems with parents' acceptance were identified as further risk factors for low self-perception. Finally, the reviewed studies highlighted a link between self-perception and quality of life in patients with chronic tic disorders, alongside the protective role of good social adjustment. This information can therefore assist treating clinicians in the choice of tailored therapeutic interventions for this patient population, including behavioral management techniques that can improve self-concept and self-esteem through increased self-efficacy

Clinical precursors of tics: an EMTICS study

Background: Children with Tourette syndrome (TS) often have comorbid disorders, particularly attention-deficit/ hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). While subtle premorbid symptoms have been described in various psychiatric disorders, the presence of clinical precursors that may exist before the onset of tics is unknown. This longitudinal study aimed to find clinical precursors of tics by assessing a range of clinical characteristics prior to tic onset in comparison with children without onset of tics. Methods: A sample of 187 3- to 10-year-old first-degree unaffected relatives of children with TS were followed up to 7 years in the European Multicentre Tics in Children Study (EMTICS). We investigated whether clinical characteristics assessed at baseline predicted tic onset, comparing 126 children without tic onset to 61 children who developed tics. We used the least absolute shrinkage and selection operator (LASSO) method, a penalised logistic regression approach. We also explored sex differences and repeated our analyses in an age- and sex-matched subsample. Results: Children with tic onset were more frequently male (b = 0.36), had higher baseline severity of conduct problems (b = 0.23), autism spectrum disorder symptoms (ASD; b = 0.08), compulsions (b = 0.02) and emotional problems (b = 0.03) compared to children without tic onset. Conduct and ASD problems were male-specific predictors, whereas severity of compulsions and oppositional (b = 0.39) and emotional problems were female-specific predictors. Conclusion: This study supports the presence of clinical precursors prior to tic onset and highlights the need of sex-specific monitoring of children at risk of developing tics. This may aid in the earlier detection of tics, particularly in females. We moreover found that tics most often persisted one year after tic onset, in contrast to the common belief that tics are mostly transient

Hair cortisol-a stress marker in children and adolescents with chronic tic disorders? A large European cross-sectional study

Background There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. Methods Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3–16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3–10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. Results There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. Conclusion A link between HCC and TDs is not supported by the present result

Clinical variability at the mild end of BRAT1‐related spectrum: Evidence from two families with genotype–phenotype discordance

Biallelic mutations in the BRAT1 gene, encoding BRCA1-associated ATM activator 1, result in variable phenotypes, from rigidity and multifocal seizure syndrome, lethal neonatal to neurodevelopmental disorder, and cerebellar atrophy with or without seizures, without obvious genotype-phenotype associations. We describe two families at the mildest end of the spectrum, differing in clinical presentation despite a common genotype at the BRAT1 locus. Two siblings displayed nonprogressive congenital ataxia and shrunken cerebellum on magnetic resonance imaging. A third unrelated patient showed normal neurodevelopment, adolescence-onset seizures, and ataxia, shrunken cerebellum, and ultrastructural abnormalities on skin biopsy, representing the mildest form of NEDCAS hitherto described. Exome sequencing identified the c.638dup and the novel c.1395G>A BRAT1 variants, the latter causing exon 10 skippings. The p53-MCL test revealed normal ATM kinase activity. Our findings broaden the allelic and clinical spectrum of BRAT1-related disease, which should be suspected in presence of nonprogressive cerebellar signs, even without a neurodevelopmental disorder

Tic disorders in children and adolescents: does the clinical presentation differ in males and females? A report by the EMTICS group

Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (n = 709, 23.3% females) recruited as part of the European Multicenter Tics in Children Study (EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females

Association of Group A Streptococcus Exposure and Exacerbations of Chronic Tic Disorders

Objective: To examine prospectively the association between group A Streptococcus (GAS) pharyngeal exposures and exacerbations of tics in a large multicenter population of youth with chronic tic disorders (CTD) across Europe. Methods: We followed up 715 children with CTD (age 10.7 ± 2.8 years, 76.8% boys), recruited by 16 specialist clinics from 9 countries, and followed up for 16 months on average. Tic, obsessive-compulsive symptom (OCS), and attention-deficit/hyperactivity disorder (ADHD) severity was assessed during 4-monthly study visits and telephone interviews. GAS exposures were analyzed using 4 possible combinations of measures based on pharyngeal swab and serologic testing. The associations between GAS exposures and tic exacerbations or changes of tic, OC, and ADHD symptom severity were measured, respectively, using multivariate logistic regression plus multiple failure time analyses and mixed effects linear regression. Results: A total of 405 exacerbations occurred in 308 of 715 (43%) participants. The proportion of exacerbations temporally associated with GAS exposure ranged from 5.5% to 12.9%, depending on GAS exposure definition. We did not detect any significant association of any of the 4 GAS exposure definitions with tic exacerbations (odds ratios ranging between 1.006 and 1.235, all p values >0.3). GAS exposures were associated with longitudinal changes of hyperactivity-impulsivity symptom severity ranging from 17% to 21%, depending on GAS exposure definition. Conclusions: This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD. Specific workup or active management of GAS infections is unlikely to help modify the course of tics in CTD and is therefore not recommended

Yale Global Tic Severity Scale (YGTSS): Psychometric Quality of the Gold Standard for Tic Assessment Based on the Large-Scale EMTICS Study

The Yale Global Tic Severity Scale (YGTSS) is a clinician-rated instrument considered as the gold standard for assessing tics in patients with Tourette's Syndrome and other tic disorders. Previous psychometric investigations of the YGTSS exhibit different limitations such as small sample sizes and insufficient methods. To overcome these shortcomings, we used a subsample of the large-scale “European Multicentre Tics in Children Study” (EMTICS) including 706 children and adolescents with a chronic tic disorder and investigated convergent, discriminant and factorial validity, as well as internal consistency of the YGTSS. Our results confirm acceptable convergent and good to very good discriminant validity, respectively, indicated by a sufficiently high correlation of the YGTSS total tic score with the Clinical Global Impression Scale for tics (rs = 0.65) and only low to medium correlations with clinical severity ratings of attention deficit/hyperactivity symptoms (rs = 0.24), obsessive–compulsive symptoms (rs = 27) as well as internalizing symptoms (rs = 0.27). Internal consistency was found to be acceptable (Ω = 0.58 for YGTSS total tic score). A confirmatory factor analysis supports the concept of the two factors “motor tics” and “phonic tics,” but still demonstrated just a marginal model fit (root mean square error of approximation = 0.09 [0.08; 0.10], comparative fit index = 0.90, and Tucker Lewis index = 0.87). A subsequent analysis of local misspecifications revealed correlated measurement errors, suggesting opportunities for improvement regarding the item wording. In conclusion, our results indicate acceptable psychometric quality of the YGTSS. However, taking the wide use and importance of the YGTSS into account, our results suggest the need for further investigations and improvements of the YGTSS. In addition, our results show limitations of the global severity score as a sum score indicating that the separate use of the total tic score and the impairment rating is more beneficial