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Neuropsychiatric comorbidities in tuberous sclerosis complex patients with epilepsy: results of the TAND checklist survey

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Abstract

Purpose

In addition to epilepsy, individuals with tuberous sclerosis complex (TSC) experience a wide range of behavioral, psychiatric, intellectual, academic, and psychosocial problems. They usually exert a large psychological burden on individuals with these illnesses.

Methods

This cross-sectional study used TSC-associated neuropsychiatric disorders (TAND) checklist interviews conducted at a single medical center. The enrollment of all subjects was > 6 years, and the comorbidities of neurodevelopmental disorders were assessed by clinical psychologists before enrollment. To assess the spectrum of TAND, the TAND checklist was applied as stated in the protocol, and the responses to the TAND checklist were evaluated by clinical psychologists.

Results

In the behavioral concerns of patients with TSC without epilepsy, those with epilepsy had excessive shyness, language delay, lack of eye contact, rigid behavior, inattentiveness, and restlessness. In psychiatric disorders, autism spectrum disorder and attention-deficit/hyperactivity disorder are significantly correlated with epilepsy history. Diminished academic skills, including reading, writing, and mathematics skills, are significantly associated with epilepsy history. For intellectual ability, TSC patients without epilepsy is associated normal intelligence level. Among neuropsychological skills, deficits in attention, dual tasking/multi-tasking, visuospatial tasking, and executive skills are significantly associated with epilepsy history.

Conclusions

Epilepsy in patients with TSC contributes to comorbid neuropsychiatric disorders. In addition to epilepsy evaluation, it is crucial to evaluate the heterogeneous spectrum of neuropsychiatric disorders using a standard checklist during the annual clinical follow-up of patients with TSC.

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Data availability

All the data are available in the result section.

References

  1. Tsai JD, Ho MC, Lee HY, Shen CY, Li JY, Weng JC (2021) Disrupted white matter connectivity and organization of brain structural connectomes in tuberous sclerosis complex patients with neuropsychiatric disorders using diffusion tensor imaging. MAGMA 34:189–200

    Article  CAS  PubMed  Google Scholar 

  2. Kaczorowska M, Jurkiewicz E, Domańska-Pakieła D, Syczewska M, Lojszczyk B, Chmielewski D et al (2011) Cerebral tuber count and its impact on mental outcome of patients with tuberous sclerosis complex. Epilepsia 52:22–27

    Article  PubMed  Google Scholar 

  3. Pitkänen A (2010) Therapeutic approaches to epileptogenesis—hope on the horizon. Epilepsia 51(Suppl 3):2–17

    Article  PubMed  PubMed Central  Google Scholar 

  4. Asato MR, Hardan AY (2004) Neuropsychiatric problems in tuberous sclerosis complex. J Child Neurol 19:241–249

    Article  PubMed  Google Scholar 

  5. de Vries PJ, Whittemore VH, Leclezio L, Byars AW, Dunn D, Ess KC, Hook D et al (2015) Tuberous sclerosis associated neuropsychiatric disorders (TAND) and the TAND Checklist. Pediatr Neurol 52:25–35

    Article  PubMed  Google Scholar 

  6. Toldo I, Brasson V, Miscioscia M, Pelizza MF, Manara R, Sartori S et al (2019) Tuberous sclerosis-associated neuropsychiatric disorders: a paediatric cohort study. Dev Med Child Neurol 61:168–173

    Article  PubMed  Google Scholar 

  7. Kingswood JC, d’Augères GB, Belousova E, Ferreira JC, Carter T, Castellana R et al (2017) TuberOus SClerosis registry to increase disease awareness (TOSCA)—baseline data on 2093 patients. Orphanet J Rare Dis 12:2

    Article  PubMed  PubMed Central  Google Scholar 

  8. Nabbout R, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P, TOSCA Consortium and TOSCA Investigators et al (2018). Epilepsy in tuberous sclerosis complex: findings from the TOSCA study. Epilepsia Open 4:73–84

    Article  PubMed  PubMed Central  Google Scholar 

  9. de Vries PJ, Hunt A, Bolton PF (2007) The psychopathologies of children and adolescents with tuberous sclerosis complex (TSC): a postal survey of UK families. Eur Child Adolesc Psychiatry 16:16–24

    Article  PubMed  Google Scholar 

  10. Gipson TT, Johnston MV (2017) New insights into the pathogenesis and prevention of tuberous sclerosis-associated neuropsychiatric disorders (TAND). F1000Res. 6:F1000 Faculty Rev-859

  11. Northrup H, Aronow ME, Bebin EM et al (2021) Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations. Pediatr Neurol 123:50–66

    Article  PubMed  Google Scholar 

  12. de Vries PJ, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P, TOSCA Consortium and TOSCA Investigators et al (2018) TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study. Orphanet J Rare Dis 13:157

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wong M (2019) The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex. J Neurodev Disord. https://doi.org/10.1186/s11689-019-9289-6

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wong M (2008) Mechanisms of epileptogenesis in tuberous sclerosis complex and related malformations of cortical development with abnormal glioneuronal proliferation. Epilepsia 49:8–21

    Article  PubMed  Google Scholar 

  15. Wong AM, Wang HS, Schwartz ES, Toh CH, Zimmerman RA, Liu PL et al (2013) Cerebral diffusion tensor MR tractography in tuberous sclerosis complex: correlation with neurologic severity and tract-based spatial statistical analysis. AJNR Am J Neuroradiol 34:1829–1835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tsai JD, Ho MC, Shen CY, Weng JC (2022) Assessment of disrupted brain functional connectome in tuberous sclerosis complex using resting-state fMRI. Medicine (Baltimore) 101:e29024

    Article  PubMed  Google Scholar 

  17. Miszewska D, Sugalska M, Jóźwiak S (2021) Risk factors associated with refractory epilepsy in patients with tuberous sclerosis complex: a systematic review. J Clin Med 10(23):5495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Crino PB (2015) mTOR signaling in epilepsy: insights from malformations of cortical development. Cold Spring Harb Perspect Med 5:a022442

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ruppe V, Dilsiz P, Reiss CS, Carlson C, Devinsky O, Zagzag D et al (2014) Developmental brain abnormalities in tuberous sclerosis complex: a comparative tissue analysis of cortical tubers and perituberal cortex. Epilepsia 55:539–550

    Article  CAS  PubMed  Google Scholar 

  20. Krueger DA, Northrup H; International Tuberous Sclerosis Complex Consensus Group (2013) Tuberous sclerosis complex surveillance and management: recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol 49:255–265

    Article  Google Scholar 

  21. Wei CC, Sheu JN, Liu JT, Yang SH, Chou IC, Tsai JD (2018) Trend of seizure remission in patients with tuberous sclerosis complex: a retrospective medical review. J Chin Med Assoc 81(8):724–728

    Article  PubMed  Google Scholar 

  22. Gupta A, de Bruyn G, Tousseyn S, Krishnan B, Lagae L, Agarwal N (2020) TSC natural history database consortium. epilepsy and neurodevelopmental comorbidities in tuberous sclerosis complex: a natural history study. Pediatr Neurol 106:10–16

    Article  PubMed  Google Scholar 

  23. Ding Y, Wang J, Zhou H, Li T, Zhou S, Wang Y (2021) Assessment of tuberous sclerosis-associated neuropsychiatric disorders using the MINI-KID tool: a pediatric case-control study. Orphanet J Rare Dis 16(1):181

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the grant (CSH-2021-A002) of Chung Shan Medical University Hospital, Taichung, Taiwan.

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Authors and Affiliations

  1. Department of Psychology, Chung Shan Medical University, Taichung, Taiwan

    Hom-Yi Lee

  2. School of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Hom-Yi Lee, Xing-An Wang & Jeng-Dau Tsai

  3. Room of Psychology, Chung Shan Medical University Hospital, Taichung, Taiwan

    Hom-Yi Lee

  4. School of Medicine, China Medical University, Taichung, Taiwan

    Chien-Heng Lin

  5. Department of Paediatrics, China Medical University Hospital, Taichung, Taiwan

    Chien-Heng Lin

  6. Department of Paediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan

    Xing-An Wang & Jeng-Dau Tsai

Authors
  1. Hom-Yi Lee
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  2. Chien-Heng Lin
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  4. Jeng-Dau Tsai
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Contributions

Hom-Yi Lee conceived and designed the experiments. Xing-An Wang and Chien-Heng Lin carried out the initial analysis the data. Jeng-Dau Tsai critically reviewed the manuscript, and approved the final manuscript as submitted.

Corresponding author

Correspondence to Jeng-Dau Tsai.

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None of the authors have any relevant conflicts of interest to disclose. We confirm that we have read the Journal’s position on issues related to ethical publication and affirm that this report is consistent with those guidelines.

Ethical approval

The studies involving human participants were reviewed and approved by Institute of Review Board (CSMUH No. CS12245), Chung Shan Medical University Hospital.

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Lee, HY., Lin, CH., Wang, XA. et al. Neuropsychiatric comorbidities in tuberous sclerosis complex patients with epilepsy: results of the TAND checklist survey. Acta Neurol Belg (2024). https://doi.org/10.1007/s13760-024-02510-3

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  • DOI: https://doi.org/10.1007/s13760-024-02510-3

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