Burden of illness in tuberous sclerosis complex-associated epilepsy: a systematic literature review of epidemiology, health-related quality of life, costs and resource use

TL;DR

This study reviews the impact of epilepsy in tuberous sclerosis complex, highlighting its effects on quality of life, costs, and healthcare use.

Contribution

The study provides a systematic review of the burden of illness in TSC-associated epilepsy, focusing on areas not previously covered in recent literature.

Findings

TSC-associated seizures affect 64.1% of adults and 79.8% of children.

Seizures significantly reduce quality of life and increase healthcare costs.

TSC-associated epilepsy is linked to higher mortality and cognitive impairments.

Abstract

Tuberous sclerosis complex (TSC) is a rare genetic disorder resulting in hamartomas in multiple organs, causing varied manifestations with a substantial burden of illness (BOI) for patients and caregivers. A significant component of the BOI is the high prevalence of TSC-associated epilepsy. The objective of this systematic literature review is to provide an overview of the BOI in TSC-associated epilepsy, a focus not reported in the recent review by Zöllner et al. (2020).

Following a search of major databases and congress sites to April 2023, published studies covering epidemiology, quality of life (QOL) of patients and their caregivers, direct and indirect costs, resource use and treatment patterns in children and/or adults with TSC were included. Studies on efficacy and safety, and non-neurological TSC manifestations, were excluded. Relevant studies were manually reviewed, double screened and summarised/synthesised. No statistical analyses or bias assessments were conducted.

Relevant articles (n = 241) included 182 reporting global epidemiology data, revealing a wide range of TSC incidence per 100,000 live births (0.153–17.24) and prevalence per 100,000 general population (0.6–12.7). TSC-associated seizures were reported in a mean of 64.1% and 79.8% of adults and children, respectively. Patient-reported outcome (PRO) tools indicated that cognitive impairment and neuropsychiatric disorders (e.g. autism spectrum disorder) frequently occur with TSC-associated epilepsy. The reported BOI is substantial, impacting the QOL of patients, caregivers and the wider family. Additionally, TSC-associated seizures negatively impact QOL, elevate indirect and healthcare costs (e.g. £14,335 vs £4,448), resource use (e.g. hospital admissions, physician visits and impact on patients’ and caregivers’ careers) and risk of mortality (7.53% vs 3.68%) compared with the healthy population or patients with TSC without seizures.

This review summarises the BOI caused by the early onset and refractory nature of TSC-associated epilepsy. Limitations include a lack of recent prevalence data (> 2016), standardised PROs, formal statistical analysis, BOI data in adults and impact on wider family QOL. More robust epidemiological data are needed. Nevertheless, this review supports the importance of early identification and effective seizure management to improve the BOI of TSC-associated epilepsy for patients, caregivers and the wider family, and society.

The online version contains supplementary material available at 10.1186/s13023-025-03975-y.

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