Clinical and molecular spectrum of tuberous sclerosis complex in a regional cohort: an efficacy and outcome study with antiseizure medication plus mTOR inhibitor therapy

Objective: Tuberous sclerosis complex (TSC) is a genetic, multisystemic disease that causes severe and drug-resistant epilepsy. In this rectrospective cohort study, we aimed to determine the clinical and molecular spectrum of TSC in a regional cohort. Methods: Fifty-five patients who had been followed at least one year follow-up after the initial diagnosis enrolled in the study with using Revised Diagnostic Criteria for Tuberous Sclerosis Complex. Clinical demographics ( seizure semiology, seizure-onset age, antiseizure medication-ASM, mTOR therapy, seizure control rate, drug-refractory epilepsy-DRE, co-morbidities including autism and ADHD, and cognitive levels), EEG characteristics, MRI findings, and molecular spectrum were evaluated. Results: Active epilepsy was defined as 89.1% (n=49) in the study group. Other co-morbities were intellectual disability ( 63.6%), ADHD ( 47.2%) and autism ( 16.3%). Genetic analysis (n=18) revealed a pathogenic mutation (n=14, 78%) in the TSC1 (28%) or TSC2 gene (50%). Active epilepsy was defined with 80% in TSC1 mutation (+) patients and with 88.9% in TSC2 mutation (+) patients. DRE was defined in 47% (n=23) of patients with active epilepsy. Vigabatrin was selected as first ASM in 30% (n=15) of patients with active epilepsy and DRE occurred with 33.3% . Combined therapy (VGB plus mTOR therapy) was performed in 28 (57%) of the cohort with a favorable outcome in 46.2% (n=12). Non-pharmacologic therapy (ketogenic diet and VNS ) was applied in 6 (12.2%) patients with DRE.

Conclusion: A favorable seizure and overall outcome might be obtainable with early antiepileptic treatment of active epilepsy in patients with TSC.
Keywords: Tuberous sclerosis complex; epilepsy; anti-seizure drugs; mTOR inhibitor; intellectual disability