Quality of life and its predictors in adults with tuberous sclerosis complex (TSC): a multicentre cohort study from Germany

Abstract

Background: Tuberous sclerosis complex (TSC) is a monogenetic, multisystemic disease characterised by the formation of benign tumours that can affect almost all organs, caused by pathogenic variations in TSC1 or TSC2. In this multicentre study from Germany, we investigated the influence of sociodemographic, clinical, and therapeutic factors on quality of life (QoL) among individuals with TSC.

Methods: We assessed sociodemographic and clinical characteristics and QoL among adults with TSC throughout Germany using a validated, three-month, retrospective questionnaire. We examined predictors of health-related QoL (HRQoL) using multiple linear regression analysis and compared the QoL among patients with TSC with QoL among patients with other chronic neurological disorders.

Results: We enrolled 121 adults with TSC (mean age: 31.0 ± 10.5 years; range: 18-61 years, 45.5% [n = 55] women). Unemployment, a higher grade of disability, a higher number of organ manifestations, the presence of neuropsychiatric manifestations or active epilepsy, and a higher burden of therapy-related adverse events were associated with worse QoL, as measured by two QoL instruments (EuroQoL-5 dimensions [EQ-5D] and Quality of Life in Epilepsy Patients [QOLIE-31]). Neuropsychiatric and structural nervous system manifestations, the number of affected organs, and therapy-related adverse events were also associated with higher depression, as measured by the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). In multiple regression analysis, more severe therapy-related adverse events (large effect, p < 0.001), active epilepsy (large effect, p < 0.001), and neuropsychiatric manifestations (medium effect, p = 0.003) were independently associated with worse HRQoL, explaining 65% of the variance (p < 0.001). The HRQoL among patients with active TSC-associated epilepsy was worse than that among patients with drug-refractory mesial temporal lobe epilepsy (p < 0.001), and the generic QoL among patients with more than three TSC organ manifestations was similar to those of patients with severe migraine and uncontrolled asthma.

Conclusions: Active epilepsy, neuropsychiatric manifestations (such as anxiety and depression), and therapy-related adverse events are important independent predictors of worse quality of life among adults with TSC. Generic quality of life in TSC with several manifestations is similar to uncontrolled severe chronic diseases and significantly negatively correlates with TSC severity.

Trial registration: DRKS, DRKS00016045 . Registered 01 March 2019.

Keywords: EQ-5D; Epilepsy; Organ manifestations; QOLIE-31; Quality of life; Rare disease; Seizure; TSC; Tuberous sclerosis complex; mTOR inhibitor.

Fig. 1

Correlation between health-related quality of life and other factors in TSC. Health-related quality of life (HRQoL) in adult individuals with tuberous sclerosis complex (TSC), as assessed by the Quality of Life in Epilepsy Inventory-31 items (QOLIE-31) overall score was significantly correlated with A) the number of affected organ systems, B) the grade of disability, and C) the overall Liverpool Adverse Events Profile (LAEP) score, which measures therapy-related adverse events. D: HRQoL in adults with TSC was also significantly correlated with the perceived burden of illness, which was calculated as an index of 20 possible TSC-associated problems (possible range of 0–4 for each item)

Fig. 2

Health-related quality of life in our TSC cohort compared with other cohorts with epilepsy. A: Comparison of health-related quality of life (HRQoL), as assessed by the Quality of Life in Epilepsy Inventory-31 items (QOLIE-31) between a study on patients with drug-refractory mesial temporal lobe epilepsy and individuals from our tuberous sclerosis complex (TSC) cohort with active epilepsy (defined as experiencing seizures within the last 12 months). The TSC patients in our cohort demonstrated a lower overall health status compared with temporal lobe epilepsy patients, as measured by the visual analogue scale (VAS) component of the QOLIE-31. Fatigue was higher among TSC patients than temporal lobe epilepsy patients. B: Comparison of patients with TSC, both with and without epilepsy, between the TOSCA registry and our overall cohort. The QOLIE-31 overall quality of life subscore was significantly worse in the TOSCA cohort, seizure worry was higher, emotional well-being was worse, and medication effects were higher among the TOSCA cohort compared with our cohort, with all other categories demonstrating similar values. #Standard deviation for the VAS scale of the questionnaire was not reported by Jansen et al. Independent samples t-tests, * = p < 0.05, ** = p < 0.01, *** = p < 0.001

Fig. 3

Generic quality of life (EQ-5D) among TSC patients compared with patients with other chronic disorders. Comparison of quality of life (QoL), as assessed by the EuroQoL-5 dimensions (EQ-5D), between a study (Lucas et al., [38]) including 69 patients with severe asthma and 249 patients with severe migraine and our cohort of tuberous sclerosis complex (TSC) individuals, stratified by the number of TSC manifestations. A large difference in QoL between lightly and more severely affected TSC individuals is evident, with more severely affected individuals exhibiting QoL similar to patients with other severe chronic disorders