Epilepsy in TSC: certain etiology does not mean certain prognosis

Prevalence and long-term outcome of epilepsy in tuberous sclerosis complex (TSC) is reported to be variable, and the reasons for this variability are still controversial.

We reviewed the clinical characteristics of patients with TSC who were regularly followed since 2000 at the San Paolo Multidisciplinary Tuberous Sclerosis Centre in Milan, Italy. From patient charts we collected data about age at epilepsy onset, seizure frequency and seizure type, history of infantile spasms (IS), epileptic syndrome, evolution to refractory epilepsy or to seizure freedom and/or medication freedom, electroencephalography (EEG) features, magnetic resonance imaging (MRI) findings, cognitive outcome, and genetic background.

Among the 160 subjects (120 adults and 40 children), 116 (72.5%) had epilepsy: 57 (35.6%) were seizure-free, and 59 (36.9%) had drug-resistant epilepsy. Most seizure-free patients had a focal epilepsy (89.5%), with 54.4% of them drug resistant for a period of their lives. Epilepsy onset in the first year of life with IS and/or focal seizures was characteristic of the drug-resistant group of patients, as well as cognitive impairment and TSC2 mutation (p < 0.05). A small group of patients (7 patients, 4.4%) experienced a seizure only once; all of them had normal cognition.

Although epilepsy management can be challenging in TSC, more than one third of patients had their seizures controlled: through monotherapy in 56% and by polytherapy in 32%. Moreover, 12% of the patients became seizure-free and were off medication. Identifying predictive features of epilepsy and cognitive outcome can ensure better management for patients with TSC and delineate genotype-phenotype correlations.