Self-injurious behavior and tuberous sclerosis complex: Frequency and possible associations in a population of 257 patients
ABSTRACT Self-injurious behavior (SIB) has been observed in people with tuberous sclerosis complex (TSC), although the frequency of SIB in TSC is largely unknown. SIB is associated with intellectual and developmental disabilities, but there is no single cause of SIB. We retrospectively examined the frequency of SIB in a population of 257 patients with TSC and determined possible associations with SIB. We found a 10% frequency of SIB in our TSC population. When compared with patients without psychiatric symptoms, we identified a significantly higher rate of electroencephalographic interictal spikes in the left frontal lobe and a significantly lower number of tubers in the left occipital, parietal, and posterior temporal lobes. We also found that frequency of TSC2 mutation, history of infantile spasms, history of seizures, mental retardation, and autism are significantly associated with SIB.
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ABSTRACT: Background Tuberous Sclerosis Complex (TSC) is a multi-system disorder that includes a range of TSC-associated neuropsychiatric disorders (TAND). The lifetime prevalence rates of TAND are very high, yet surveys suggest that the majority of individuals with TSC never receive appropriate assessment or treatment for TAND. To aid systematic enquiry, a TAND Checklist was developed. Here we performed pilot validation of the TAND Checklist. Method Mixed-methods were used across two stages. In stage 1 we gathered feedback on the Checklist from TSC ‘expert professionals’ and ‘expert parents/caregivers’. The aim was to examine face and content validity. Stage 2 involved the administration of the refined TAND Checklist to 20 parents of individuals with TSC concurrently with four widely used, validated rating scales, in order to examine external validity and to obtain qualitative feedback on face-to-face administration of the Checklist. Results Twenty professionals and 62 parents/caregivers from 28 countries participated in the pilot. The TAND Checklist demonstrated good face and content validity with high overall mean and median scores. Qualitative analysis highlighted concerns about the likely use of the Checklist, suggesting that family members and individuals with TSC should drive usage. Stage 2 results showed moderate to very good external validity across TAND domain and key subdomains. Internal consistency of domains and subdomains was acceptable to very good. Ninety three percent of all participants (93%) reported 4 or more lifetime TAND behavioral difficulties. Conclusion The pilot validation suggested that the TAND Checklist could provide a useful screening tool in clinical settings.Pediatric Neurology 10/2014; 52(1). DOI:10.1016/j.pediatrneurol.2014.10.006 · 1.50 Impact Factor
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ABSTRACT: Research reporting prevalence rates of self-injurious and aggressive behaviour in people with tuberous sclerosis complex (TSC) is limited. No studies have compared rates of these behaviours in TSC with those in other syndrome groups matched for degree of disability or investigated risk markers for these behaviours in TSC. Data from the Challenging Behaviour Questionnaire were collected for 37 children, aged 4 to 15 years, with TSC. Odds ratios were used to compare rates of self-injury and aggression in children with TSC with children with idiopathic autism spectrum disorder (ASD), fragile X, Cornelia de Lange and Down syndromes. Characteristics were measured using the Mood Interest and Pleasure Questionnaire, the Activity Questionnaire, the Social Communication Questionnaire, the Repetitive Behaviour Questionnaire, the Wessex Behaviour Schedule and the revised Non-communicating Children Pain Checklist. Mann-Whitney U analyses were used to compare characteristics between individuals with self-injury and aggression and those not showing these behaviours. Rates of self-injury and aggression in TSC were 27% and 50%, respectively. These are high but not significantly different from rates in children with Down syndrome or other syndrome groups. Both self-injury and aggression were associated with stereotyped and pain-related behaviours, low mood, hyperactivity, impulsivity and repetitive use of language. Children who engaged in self-injury also had lower levels of interest and pleasure and showed a greater degree of 'insistence on sameness' than children who did not self-injure. Aggression was associated with repetitive behaviour. The majority of these associations remained significant when the association with level of adaptive functioning was controlled for. Behavioural profiles can be used to identify those most at risk of developing self-injury and aggression. Further research is warranted to understand the influence of such internal factors as mood, ASD symptomatology and pain on challenging behaviour in people with intellectual disability.Journal of Neurodevelopmental Disorders 05/2014; 6(1):10. DOI:10.1186/1866-1955-6-10 · 3.71 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
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ABSTRACT: The Food and Drug Administration (FDA) has approved two mechanism-based treatments for tuberous sclerosis complex (TSC)-everolimus and vigabatrin. However, these treatments have not been systematically studied in individuals with TSC and severe autism. The aim of this review is to identify the clinical features of severe autism in TSC, applicable preclinical models, and potential barriers that may warrant strategic planning in the design phase of clinical trial development. A comprehensive search strategy was formed and searched across PubMed, Embase and SCOPUS from their inception to 2/21/12, 3/16/12, and 3/12/12 respectively. After the final search date, relevant, updated articles were selected from PubMed abstracts generated electronically and emailed daily from PubMed. The references of selected articles were searched, and relevant articles were selected. A search of clinicaltrials.gov was completed using the search term "TSC" and "tuberous sclerosis complex". Autism has been reported in as many as 60% of individuals with TSC; however, review of the literature revealed few data to support clear classification of the severity of autism in TSC. Variability was identified in the diagnostic approach, assessment of cognition, and functional outcome among the reviewed studies and case reports. Objective outcome measures were not used in many early studies; however, diffusion tensor imaging of white matter, neurophysiologic variability in infantile spasms, and cortical tuber subcategories were examined in recent studies and may be useful for objective classification of TSC in future studies. Mechanism-based treatments for TSC are currently available. However, this literature review revealed two potential barriers to successful design and implementation of clinical trials in individuals with severe autism-an unclear definition of the population and lack of validated outcome measures. Recent studies of objective outcome measures in TSC and further study of applicable preclinical models present an opportunity to overcome these barriers.