Orphanet Journal of Rare Diseases | A Systematic Review of the Disease Burden of TSC-related Epilepsy

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This systematic review summarizes the disease burden of TSC-related epilepsy, including epidemiology, quality of life, medical costs, and resource utilization. The study highlights the high prevalence of epilepsy among TSC patients and its significant impact on the quality of life of both patients and caregivers. It also identifies the lack of high-quality epidemiological data and emphasizes the importance of early intervention.

 

Literature Overview

This article, titled 'Burden of illness in tuberous sclerosis complex-associated epilepsy: a systematic literature review of epidemiology, health-related quality of life, costs and resource use', published in the 'Orphanet Journal of Rare Diseases', reviews and summarizes the impact of TSC-related epilepsy on the quality of life, healthcare resource utilization, and disease costs for patients and caregivers. The article notes that TSC-related epilepsy is characterized by early onset and intractability, significantly increasing the disease burden for patients and families, and is closely associated with cognitive impairment, autism spectrum disorder, and neuropsychiatric conditions. The study also reveals that epilepsy significantly affects patients' quality of life, family functioning, and medical expenditures, with differences in prevalence across age groups. The article concludes with a call for higher-quality epidemiological data and the importance of early diagnosis and effective intervention in alleviating disease burden.

Background Knowledge

Tuberous Sclerosis Complex (TSC) is a rare autosomal dominant genetic disorder caused by mutations in the TSC1 and TSC2 genes, leading to the formation of hamartomas across multiple organ systems. TSC-related epilepsy is one of the most common and burdensome neurological manifestations of the disease, affecting approximately 60-80% of patients, with nearly half developing drug-resistant epilepsy. Epilepsy not only represents a key early neurodevelopmental issue in TSC patients but is also closely linked to declining cognitive function and increased risk of psychiatric disorders. Additionally, TSC2 mutations are more likely to result in epilepsy compared to TSC1 mutations, with more severe seizure manifestations and earlier diagnosis ages. Although drugs such as everolimus and cannabidiol have been approved, managing epilepsy effectively remains a clinical challenge. The current study aims to systematically assess the disease burden of TSC-related epilepsy, including epidemiology, quality of life, treatment patterns, and resource utilization, to provide reference for clinical and public health strategies.

 

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Research Methods and Experiments

The study follows the PRISMA statement for systematic literature review, searching major databases such as Medline, EMBASE, Cochrane Library, and conference websites up to April 2023. The inclusion criteria encompass studies focusing on the epidemiology, quality of life, medical costs, resource utilization, and treatment patterns of epilepsy in TSC patient populations. Exclusion criteria include non-neurological TSC manifestations and studies focusing on treatment efficacy and safety. Two researchers independently conducted the literature screening, and data were synthesized and summarized manually after extraction. No statistical analysis or bias assessment was performed, except for Cochrane bias evaluation of clinical trials. Epidemiological data were analyzed by calculating average incidence and prevalence, quality of life data by average scores, and cost data were presented as mean or total costs in original currencies.

Key Findings and Insights

• Global incidence of TSC ranges from 0.153–17.24 per 100,000 live births, with a prevalence of 0.6–12.7 per 100,000 population.
• The average prevalence of epilepsy in children with TSC is 79.8%, while it is 64.1% in adults, with approximately 45.5% of mixed-age patients developing drug-resistant epilepsy.
• Seizure frequency is significantly associated with a decline in quality of life for TSC patients and their caregivers, and has a negative impact on overall family functioning.
• Comorbidities such as autism spectrum disorder, attention deficit hyperactivity disorder, and behavioral disorders are more prevalent among epilepsy patients.
• Early-onset epilepsy is associated with more severe cognitive impairments and neurodevelopmental issues, and epilepsy surgery can significantly improve quality of life for some patients.
• Medical costs and resource utilization are significantly elevated among TSC-related epilepsy patients, with indirect costs such as caregiver career interruption and patient educational limitations being common.
• TSC2 mutations are associated with more severe epilepsy phenotypes, and epilepsy is one of the main contributors to increased mortality in TSC patients.

Significance and Future Directions

The review highlights the importance of TSC-related epilepsy in disease burden and emphasizes the critical role of early diagnosis and effective interventions in improving the quality of life for patients and families. It recommends that future studies should collect higher-quality epidemiological data, particularly in adult populations and long-term follow-ups. Additionally, standardized tools for quality of life assessment and systematic studies on the broader impact of TSC on family members are still needed.

 

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Conclusion

This study systematically reviews the disease burden of TSC-related epilepsy, covering epidemiology, quality of life, medical expenditures, and resource utilization. TSC-related epilepsy is characterized by early onset and intractability, significantly affecting the quality of life of patients and families, and increasing both medical and indirect social costs. Although approved medications exist, effective management of epilepsy remains a clinical challenge. The study calls for more high-quality epidemiological data and emphasizes the importance of early identification and intervention in reducing neurodevelopmental sequelae. Future research should focus on the burden of TSC-related epilepsy in adults, the development of standardized quality of life assessment tools, and the broader impact of TSC on family members.

 

Alexandra Furber, Alison Martin, Andrea Bertuzzi, Sally Bowditch, and Jamshaed Siddiqui. Burden of illness in tuberous sclerosis complex-associated epilepsy: a systematic literature review of epidemiology, health-related quality of life, costs and resource use. Orphanet Journal of Rare Diseases.