PURPOSE: 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.
METHODS: 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.
KEY FINDINGS: 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.
SIGNIFICANCE: 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.