Predictors of Drug-Resistant Epilepsy in Tuberous Sclerosis Complex

Abstract

Utilizing the multicenter Tuberous Sclerosis Complex (TSC) Natural History Database including 2034 subjects, this study aimed to identify predictors of drug-resistant epilepsy in TSC. Basic epilepsy data were available for 1965 individuals in the database. Supplemental data were further collected from 1546 of these subjects through directed site queries, addressing additional epilepsy characteristics including the presence of drug-resistant epilepsy, therapies trialed, and outcomes of specific therapies. Epilepsy was reported in 86.4% of individuals with TSC. Infantile spasms were reported in 45.2% of individuals and focal seizures were reported in 84.4% of individuals. In those with focal epilepsy, drug-resistance was reported in 59.6%, with focal seizure onset prior to age 1 year (OR 1.9, CI 1.4–2.5, p<0.001), infantile spasms (OR 2.0, CI 1.5–2.5, p<0.001), and infantile spasms incompletely responsive to therapy (OR 47.6, CI 6.7–333.3, p<0.001) being associated with an increased likelihood of drug-resistance.

Current concepts on epilepsy management in tuberous sclerosis complex

“…Similarly, Jeong, Nakagawa, and Wong (2017) Both typical and variant hypsarrhythmia have been reported in children with TSC, while ictal EEG of epileptic spasms is often characterized by fast rhythms, often preceded by focal or multifocal spikes (Liu et al, 2012).…”

Early developmental electroencephalography abnormalities, neonatal seizures, and induced spasms in a mouse model of tuberous sclerosis complex

“…Tuberous sclerosis complex (TSC) is a relatively common genetic cause of epilepsy, attributed to mutations in the TSC1 or TSC2 genes leading to excessive activation of the mechanistic target of rapamycin (mTOR) pathway 1,2 . Seizures occur in up to 90% of TSC patients and are often intractable to medication and nonmedical treatments 3 . The typical age of onset of epilepsy in TSC is during infancy or early childhood, with a majority of TSC patients having their first seizure within the first year of life 4 .…”

Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex

“…In fact, 80-96% of patients have epilepsy with two thirds refractory to existent therapies [1,9]. Failure to control seizures in TSC patients is highly correlated with an early onset of seizures, before the age of 1 year old, in the form of focal epilepsy and infantile spasms [10]. Epilepsy is frequently associated with tuberous sclerosis associated neuropsychiatric disorders (TAND), such as autism spectrum disorder, present in 40-50% of patients, and intellectual disability, present in 30% [9,11].…”

“…The importance of seizure control is further reinforced by its positive impact on developmental outcomes and quality of life assessments [12,13]. Nonetheless, despite the availability of some treatment options, due to the high heterogeneity of manifestations and TSC phenotype, not all individuals respond to the currently available therapies and new options are needed to attend to the patients' needs [10,14,15].…”