Abstracts

Rationale: Association of epilepsy with cognitive, neurobehavioral and psychiatric comorbidities in Tuberous Sclerosis Complex (TSC) has been noted in few small series and remains indeterminate.Methods: Using the TSC natural history dataset of 1657 patients (age = 1 month–81 years) with definite clinical and/or genetically confirmed diagnosis of TSC, we analyzed the relationship of epilepsy and neurobehavioral diagnoses. We also studied relationship to the TSC genotype.Results: Of 1657 patients, 1161 (70%) had epilepsy and 158 (9.5%) did not. Epilepsy status was unknown in 338 (20.5%). TSC 1 or 2 mutations were reported in 470 (470/1657; 28.3%) patients. Of 135 with TSC1 mutations (135/470; 29%), 107 (79%) had epilepsy. Of 335 with TSC 2 mutations (335/470; 71%), 304 (92%) had epilepsy suggesting higher frequency of epilepsy with TSC 2 mutations. There was a significant association between the ‘age of epilepsy onset’ and the frequency as well as the severity of intellectual disability (P < 0.001). 82% patients with age of epilepsy onset < 2 years, 80% with age of epilepsy onset between 2-5 years, and 53% with epilepsy onset > 5 years of age reported mild (IQ 51-70) to profound (IQ < 20) intellectual disability. There was a trend (R2=0.97) towards more frequent (29/99; 29%) and more severe (IQ < 35) disability in the age group with epilepsy onset < 2 years. Only 23% of TSC patients without epilepsy had intellectual disability, but all had mild to moderate degree. Presence or absence of Autism was reported in 982 patients (age 2–58y). Autism was reported in 23% of the patients (192/837) with epilepsy. Autism was not reported in any patient without epilepsy (0/145 patients; P-value < 0.0001). The diagnosis of autism showed no difference based on the frequency of TSC 1 vs. 2 mutations (P-value = 0.053). Presence or absence of ADHD was reported 961 patients (age 4-61y). ADHD was reported with significantly higher frequency in patients with epilepsy (18%, 149/817) compared to those without (0.1%, 10/144 patients; p = 0.0008). Again, ADHD diagnosis showed no difference based on the frequency of TSC 1 vs. 2 mutations (P-value 0.16). Presence or absence of anxiety was reported in 952 (age 8-69y) and depression in 944 (age 16-65y) TSC patients. 9% (85/952) had anxiety and 6% (53/944) were diagnosed with depression. There was no significant difference between the diagnoses of anxiety (P-value 0.12) and/or depression (P-value 0.23) based on the presence or absence of epilepsy. There was no difference between the frequency of TSC 1 vs 2 mutations for the diagnosis of anxiety (P-value 0.82) or depression (P-value 0.27).Conclusions: Epilepsy is more common in TSC2 mutations. Epilepsy is associated with intellectual disability, and when epilepsy begins before the age of 2 years the frequency and severity of intellectual disability is much higher. Epilepsy is also strongly associated with risk of autism and ADHD but not anxiety and depression. Prospective studies are needed to clarify if early and aggressive treatment of epilepsy may mitigate intellectual disability, autism and ADHD.