1880 | TSC defined as a disorder of the brain [19] |
1908 | Description of the ‘triad of impairment’ which included seizures/epilepsy, intellectual disability and facial angiofibromas [20] |
1911 | The term ‘epiloia’ coined to describe epilepsy combined with ‘anoia’ (intellectual disability) in individuals with TSC [21] |
1932 | First descriptions of behaviours suggestive of autism, behavioural manifestations and different intellectual levels in individuals with TSC [22] |
1967 | First set of diagnostic criteria for TSC—not including any TAND manifestations or reference to seizures/epilepsy [23] |
1983 | First systematic research on behavioural aspects of TSC [24,25,26] |
1987 | Exploration of infantile spasms and its relationship with behavioural manifestations in TSC (e.g. autism, hyperkinetic behaviour, psychosis and aggression) [27] |
1991 | Consideration of neuropsychological deficits in TSC, in relation to memory, attention and executive functions [29] |
1993 | Further exploration of links between TSC and varied behavioural problems and identification of risk markers of behavioural manifestations [28] |
1998 | First International TSC Consensus Conference to develop revised diagnostic criteria and clinical management guidelines with little consideration of TAND [32, 33] |
2005 | TSC Behaviour Consensus Panel publish clinical guidelines for the assessment of cognitive and behavioural problems in TSC: recommendations of comprehensive assessment during all key developmental phases to identify emerging TAND and urgent assessment in case of sudden or unexpected change [36] |
2007 | Molecular hypothesis for the causes of TAND: the GRIPP hypothesis proposed that there is a direct molecular pathway from gene disruption to psychopathologies and that molecularly targeted treatments may reverse these deficits [42] |
2008 | First animal models of TSC2+/- showing reversal of learning deficits in response to mTORi [45] |
2011 | First human findings to show improvement in memory and executive deficits in humans with TSC after mTORi in an open-label trial [44] |
2012 | Second International TSC Consensus Conference to revise diagnostic criteria, as well as surveillance and treatment guidelines for TSC [8] The term ‘TAND’ was coined, and the recommendation was made to screen for TAND on an annual basis [9]. |
2012 | Establishment of the TuberOus SClerosis registry to increase Awareness (TOSCA) consortium: the first large-scale international collaboration to study physical and TAND manifestations [49,50,51] |
2015 | Pilot validation and publication of the TAND Checklist [14, 17] with subsequent translation and authorisation in 19 languages (http://www.tandconsortium.org) |
2016 | Inclusion of TAND in Research Strategic Plan for TSC [52] |
2017 | First publication of randomised controlled trial findings on TAND from everolimus and sirolimus clinical trials [47] |
2018 | First description of natural TAND clusters [53] |
2019 | Launch of the TANDem project and establishment of the TAND consortium (http://www.tandconsortium.org) |
2020 | Replication of natural TAND clusters [54] |
2021 | Updated TSC Diagnostic Criteria and Surveillance and Management Recommendations including consensus guidelines for the identification and treatment of TAND [12] |