Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders and Parental Stress: Findings from a National, Prospective TSC Surveillance StudyFunding This work was supported by the German Tuberous Sclerosis Foundation (Deutsche Tuberöse Sklerose Stiftung) (PNR 05/15) and Novartis (FPJ 0716), both to S. M. The authors confirm complete independence from the sponsors. The sponsors did not have any influence on either the content of the article or the conceptualization/design, methodology, investigation, supervision/oversight, data curation, and formal analysis of this study. The authors exclusively wrote this article. The study participants did not receive any compensation for their participation in the study.
30 March 2019
17 May 2019
02 July 2019 (eFirst)
Aim To assess the role of the TAND (tuberous sclerosis complex [TSC] associated neuropsychiatric disorders) checklist as a screening tool for neuropsychiatric pathology, to evaluate behavioral and psychiatric symptoms and related parental stress in children with TSC, and to analyze associations between parental stress, TAND findings, and TSC pathology.
Method This is a prospective cohort study including 22 individuals from a national TSC surveillance study in Germany using demographic and clinical data, the TAND checklist, the Child Behavior Checklist (CBCL), and the Parenting Stress Index (PSI).
Results Mean (standard deviation) age at follow-up was 4 years (3 years 9 months), and 13/22 of patients were male. Seventeen children had epilepsy (focal: 9; generalized: 4; infantile spasms: 4). Developmental delay was diagnosed in 12/22 patients. The most prevalent TAND items were anxiety and mood swings in 10/22 children. At least one TAND item was reported by 17/22 patients, internalizing symptoms by 10/22, and externalizing symptoms by 11/22. In contrast, only one patient had a clinically relevant score in the CBCL scales. Of 22 parents, 12 reported clinically relevant parental stress due to both child and parenting factors. Higher total parental stress was associated with a higher TAND externalizing score (r = 0.49; p = 0.028) and TAND total score (r = 0.51; p = 0.016), a higher CBCL total score (r = 0.59; p = 0.005), and the number of antiepileptic drugs (r = 0.50; p = 0.017). Developmental delay was correlated with child stress factors (r = 0.48; p = 0.023).
Interpretation The TAND checklist appears to be a promising screening tool for neuropsychiatric problems in very young children with TSC. Parental stress in children with TSC is modified by TSC-related pathology, both neuropsychiatric and neurological.
Keywordstuberous sclerosis complex - TAND - neuropsychiatric symptoms - parental stress - epilepsy - behavior
Ethics Approval and Consent to Participate
The study was approved by the Institutional Review Board of Saarland, Germany (file no. 219/14). Patients or their guardians provided informed consent to their participating in the study including to publication of the results.
All authors made substantial contributions. Daniel Ebrahimi-Fakhari, Justine Hussong, and Sascha Meyer wrote the manuscript to which all coauthors contributed as well. Daniel Ebrahimi-Fakhari wrote the first draft of the manuscript, performed descriptive statistics, designed all tables, and contributed to conceptualization/design, methodology, investigation, data curation, and formal analysis and resources. Justine Hussong performed statistical analysis and contributed to formal analysis. Marina Flotats-Bastardas and, Darius Ebrahimi-Fakhari and Alexander von Gontard contributed to formal analysis and critical revision of the manuscript. Sascha Meyer was the chief investigator and contributed to conceptualization/design, methodology, investigation, supervision/oversight, funding acquisition, data curation, formal analysis, and resources. All authors read and approved the final manuscript.
# Daniel Ebrahimi-Fakhari, Justine Hussong, and Sascha Meyer contributed equally to this manuscript.
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