TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study

Abstract

BackgroundMost evidence for TSC-associated neuropsychiatric disorders (TAND) to date have come from small studies and case reports, and very little is known about TAND in adults. We explored baseline TAND data from the large-scale international TOSCA natural history study to compare childhood and adult patterns, describe age-based patterns, and explore genotype-TAND correlations.ResultsThe study enrolled 2216 eligible participants with TSC from 170 sites across 31 countries at the data cut-off for the third interim analysis (data cut-off date: September 30, 2015). The most common behavioural problems (reported in > 10% of participants) were overactivity, sleep difficulties, impulsivity, anxiety, mood swings, severe aggression, depressed mood, self-injury, and obsessions. Psychiatric disorders included autism spectrum disorder (ASD, 21.1%), attention deficit hyperactivity disorder (ADHD, 19.1%), anxiety disorder (9.7%), and depressive disorder (6.1%). Intelligence quotient (IQ) scores were available for 885 participants. Of these, 44.4% had normal IQ, while mild, moderate, severe, and profound degrees of intellectual disability (ID) were observed in 28.1, 15.1, 9.3, and 3.1%, respectively. Academic difficulties were identified in 58.6% of participants, and neuropsychological deficits (performance <5th percentile) in 55.7%. Significantly higher rates of overactivity and impulsivity were observed in children and higher rates of anxiety, depressed mood, mood swings, obsessions, psychosis and hallucinations were observed in adults. Genotype-TAND correlations showed a higher frequency of self-injury, ASD, academic difficulties and neuropsychological deficits in TSC2. Those with no mutations identified (NMI) showed a mixed pattern of TAND manifestations. Children and those with TSC2 had significantly higher rates of intellectual disability, suggesting that age and genotype comparisons should be interpreted with caution.ConclusionsThese results emphasize the magnitude of TAND in TSC and the importance of evaluating for neuropsychiatric comorbidity in all children and adults with TSC, across TSC1 and TSC2 genotypes, as well as in those with no mutations identified. However, the high rates of unreported or missing TAND data in this study underline the fact that, even in expert centres, TAND remains underdiagnosed and potentially undertreated.

Assessment of Tuberous Sclerosis-Associated Neuropsychiatric Disorders Using the MINI-KID tool: A Pediatric Cohort Study

“…We found that ADHD, social anxiety disorder, panic disorder and speci c phobia are the most common in this group. The incidence of ADHD in our cohort was signi cantly higher than that in the TOSCA cohort (51.58% vs. 22.4%) [21], and we suggest the following possible reasons: (1) The age distribution of children in the TOSCA cohort was 0-18 years old, while the age distribution of children in our cohort was 6-16 years old, which was consistent with the high incidence age of ADHD diagnosis. (2) Our cohort included TSC patients from all over the country.…”

Best use of the tuberous sclerosis complex‐associated neuropsychiatric disorders (TAND) checklist

“…They found that 88% of participants had at least one TAND manifestation endorsed and that 78% had four or more manifestations, but without identifying any specific TAND profile. Intellectual disability was present in 47% of the sample, similar to most findings in the literature . Difficulties in mathematics were most commonly observed (62%) out of all academic challenges and dual‐task deficits were most common (44%) of all neuropsychological deficits .…”

Epilepsy in tuberous sclerosis complex: Findings from the TOSCA Study

“…10,38 Finally, the surgery as a rare recourse in the therapy arsenal should be further investigated and a closer interaction with expert centers for epilepsy surgery should be encouraged. Our aim was to increase awareness on the disease and to present a picture of patients' characteristics and interventions in a very large number of centers dedicated for TSC care around the world.…”

“…However, standardized neuropsychological and psychiatric assessment is still lacking in many countries, even in reference centers, and this should be better addressed and implemented. 10,38 Finally, the surgery as a rare recourse in the therapy arsenal should be further investigated and a closer interaction with expert centers for epilepsy surgery should be encouraged.…”