PND1 - Disease Burden in Epilepsy Associated with Tuberous Sclerosis Complex: Systematic Review

Abstract

To summarize literature on the burden of epilepsy in tuberous sclerosis complex (TSC); TSC is a genetic disease characterized by behavioral disorders, benign tumors in multiple organs, and neurological manifestations including epilepsy. A systematic search of keywords for TSC and burden of illness was conducted in MEDLINE- and EMBASE-indexed publications from 5/2000-1/2013, and non-indexed materials. In total, 83 articles on TSC-associated epilepsy were included. Up to 93% of TSC patients have epilepsy, with severe forms more common than in non-TSC epilepsy patients (infantile spasms, 35-57% vs. 9%; generalized tonic-clonic or grand mal seizures, 37% vs. 7%; complex focal seizures, 87% vs. 33%). Seizure onset is early (median age: 7 months, 82% by age 3). TSC2 gene mutations and cortical tubers, common brain malformations in TSC, are risk factors for early onset and greater severity of seizures. TSC-epilepsy patients have significant disabilities, including high rates of autism spectrum disorders (13-30%) and cognitive impairment/delay (62-80%). Although data are not available on long-term outcomes, early seizure control may reduce cognitive impairment and autism symptoms. Vigabatrin is a first-line treatment option for TSC-associated infantile spasms and focal seizures in infants, but poses a risk of serious retinal toxicity. Other anti-epileptic drugs are available as second-line options; most patients still require polytherapy, and 62% have refractory epilepsy that can necessitate surgery. With high rates of medication use, hospitalizations, and surgeries, TSC-epilepsy patients may consume substantial health care resources, particularly during the first 5 years post-diagnosis. Longitudinal trends in resource use, direct and indirect costs, and treatment patterns for TSC-epilepsy are largely absent from the literature. TSC-epilepsy is common and may be severe, with presentation early in childhood and long-term morbidity. True disease burden to patients, caregivers, and payers remains unknown given substantial data gaps in longitudinal clinical outcomes, treatment patterns, and costs.