Tuberous sclerosis complex (TSC) is associated with a wide range of physical manifestations for which international clinical recommendations for diagnosis and management have been established. TSC is, however, also associated with a wide range of TSC-Associated Neuropsychiatric Disorders (TAND) that are typically under-identified and under-treated yet associated with a profound burden of disease. The contemporary evidence base for the identification and treatment of TAND is much more limited and, to date, consensus recommendations for the diagnosis and management of TAND have also been limited and non-specific.
The TANDem project was launched with an international, interdisciplinary, and participatory consortium of 24 individuals, including TSC family representatives, from all World Health Organization (WHO) regions but one. One of the aims of the TANDem project was to generate consensus recommendations for the identification and treatment of TAND. At the time of this project, no internationally adopted standard methodology and methodological checklists existed for the generation of clinical practice recommendations. We therefore developed our own systematic procedure for evidence review and consensus-building to generate evidence-informed consensus recommendations of relevance to the global TSC community.
At the heart of the consensus recommendations are ten core principles surrounded by cluster-specific recommendations for each of the seven natural TAND clusters identified in the literature (autism-like, dysregulated behavior, eat/sleep, mood/anxiety, neuropsychological, overactive/impulsive, and scholastic) and a set of wraparound psychosocial cluster recommendations. The overarching recommendation is to \"screen\" for TAND at least annually, to \"act\" using appropriate next steps for evaluation and treatment, and to \"repeat\" the process to ensure early identification and early intervention with the most appropriate biological, psychological, and social evidence-informed approaches to support individuals with TSC and their families.
The consensus recommendations should provide a systematic framework to approach the identification and treatment of TAND for health, educational, social care teams and families who live with TSC. To ensure global dissemination and implementation of these recommendations, partnerships with the international TSC community will be important. One of these steps will include the generation of a \"TAND toolkit\" of \"what to seek\" and \"what to do\" when difficulties are identified in TAND clusters.

Current guidelines and regulations strongly discourage the use of valproic acid (VPA) in women of childbearing age because of the risk of congenital malformations and neurodevelopmental disability in children exposed to VPA in utero. Our goal was to establish the reasons for continued use of VPA in a cohort of women with epilepsy (WWE) and to characterize the subgroup of WWE who do not consent to withdraw VPA despite potential risks.
The study included consecutive adult premenopausal WWE who visited an outpatient epilepsy clinic between April 2017 and March 2018. Data on demographics (age, age at onset of epilepsy), characteristics of epilepsy (types and frequency of seizures), and its treatment were collected from medical records and seizure diaries. All WWE taking VPA were regularly informed about VPA-related risks and had the opportunity to discuss the withdrawal of VPA.
The study involved 353 WWE (mean age: 31.7 years). Focal epilepsy was diagnosed in 244 (69.1%) patients; 180 (51.0%) women had no seizures during last 12 months before the study visit, and 228 patients (64.6%) were on monotherapy. A total of 146 (41.3%) patients used VPA in the past, and 98 (27.8%) never used VPA. Of women who were currently on VPA (n = 109, 30.9%), 30 had concurrent severe disabilities that would make future pregnancy extremely unlikely, in further 15 patients, VPA was recommenced because of failure of alternative treatment and 64 women did not accept the plan of VPA withdrawal. Women currently on VPA were more likely to have genetic generalized epilepsy and to be on monotherapy (both p ≪ 0.001). Among 64 WWE who decided to continue therapy with VPA, 35 (55.5%) had generalized epilepsy and 35 (55.5%) were in remission, 27 (42.2%) had at least one child, 9 (14.1%) planned to have a child in the near future but only 15 (23.4%) used effective contraception.
Treatment with VPA is unavoidable in many WWE of childbearing age despite recent regulations. About 60% of WWE currently treated with VPA do not consent to withdraw VPA treatment after thorough consideration of potential risks and other 40% use VPA because pregnancy is highly unlikely and/or other treatments failed.