Understanding TAND over time: The TANDem-2 study

About this study

TSC-associated neuropsychiatric disorders (TAND) affect more than 90% of people living with Tuberous Sclerosis Complex (TSC). TAND includes a wide range of challenges with behaviour, learning, attention, mental health, sleep, emotions and daily functioning. Despite their significant impact on quality of life, TAND symptoms all too often remain under-recognised and undertreated.

The international TANDem-2 study aims to:

• Improve understanding of how TAND changes over time
• Identify factors that influence these changes 
• Explore whether supporting caregiver wellbeing can also improve outcomes for people with TSC. 

NOTE: This study is currently recruiting participants and so no results or outcomes are yet published. 

How the study is being conducted

Recruitment to the study is currently underway. The researchers are hoping to recruit 500 participants who will be caregivers of children and adults living with TSC or adults who are themselves living with TSC. Participants from around the world are being recruited through TSC patient support organisations. 

Participants use the TAND Toolkit web-based App to complete questionnaires every 3 months over a 12-month period. These questionnaires will collect information about TAND symptoms, medical history, treatments and wellbeing.

Design of the study

Previous research by the same team has provided early findings about TAND that shaped the design of TANDem-2. These include:

• TAND symptoms do not appear to follow the same pattern for everyone. Some people’s symptoms improve over time, some remain stable, while others worsen.
• Caregivers frequently experience high levels of stress, with many reporting significant impacts on family relationships, community participation and employment.
• Preliminary analysis suggests caregiver wellbeing may influence TAND severity, indicating that supporting caregivers could potentially benefit both caregivers and the person living with TSC.

Importance of the study

The researchers believe TANDem-2 has the potential to answer several important questions that have not previously been studied.

By following participants over time rather than assessing them only once, the study hopes to identify different TAND “trajectories” and better understand why some people experience improvements, while others develop increasing challenges.

The researchers also hope to determine whether improving caregiver wellbeing could become an important part of managing TAND, rather than focusing only on the person living with TSC.

TANDem-2 could have significant benefits for the global TSC Community. The study may:

• Improve understanding of how TAND changes throughout life
• Help clinicians identify people who may be at higher risk of worsening TAND symptoms
• Establish the TAND Toolkit App as a practical way to monitor TAND over time
• Provide evidence for incorporating caregiver wellbeing into routine TSC care
• Support the development of effective, accessible online wellbeing programs for caregivers
• Improve future clinical research by providing a reliable way to measure changes in TAND.

Ultimately, the researchers hope this work will lead to earlier recognition of TAND, better support for families, and more effective interventions that improve quality of life both for people living with TSC and those who care for them.

DISCLAIMER

This information is intended to provide some insights into recent TSC-related research.  It is not intended to, and it should not, constitute medical or other advice.  Readers are warned not to take any action without first seeking medical advice.

de Vries PJ, Chambers N, Campbell E, Gutierrez-Lafrentz L, Heunis TM, Schlebusch L, Beaure d’Augères G, Bissell S, Byars A, Capal J, Cardozo L, Cukier S, Davis P, Epstein NB, Fladrowski C, Flinn J, Gipson T, Goy SL, Kingswood JC, Krueger D, Little F, Lubbe S, Mitchell R, Rozenberg M, Sahin M, Silva M, Smith C, Srivastava S, Takei M, van Eeghen A, Vasseghi M, Wagenaar JP, Waltereit R, De Waele L, Jansen AC. Closing the Gap to Interventions for Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND): Protocol for a Longitudinal Study of TAND Severity, Predictors, and Caregiver Well-Being (TANDem-2). JMIR Res Protoc. 2026 May 5;15:e91726. doi: 10.2196/91726. PMID: 42085697; PMCID: PMC13187705.
https://pmc.ncbi.nlm.nih.gov/articles/PMC13187705/