Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review

Abstract

Objectives:

Tuberous sclerosis complex (TSC) is a progressive genetic disorder characterized by pervasive benign tumor growth. We sought to assess the current understanding of burden of TSC-related neurological manifestations.

Methods:

We systematically searched MEDLINE- and EMBASE-indexed, English-language literature (5/2000−5/2010) and non-indexed materials.

Results:

In total, 119 articles were included, 115 on epidemiology and treatment. Recent prevalence estimates from Ireland and Taiwan report TSC in 1:14,000−25,000 individuals, below older estimates of 1:10,000. While neurological manifestations are common, treatment is largely unaddressed by guidelines and focuses on symptoms, with resection standard for subependymal giant cell astrocytomas (SEGAs) and common practice for refractory epilepsy. Antiepileptic drugs and mammalian target of rapamycin inhibitors safely, effectively minimize the need for surgery for severe epilepsy and SEGAs.

Conclusion:

Morbidity and treatment burden of prevalent neurological manifestations is significant, suggesting substantial economic and humanistic burden; however, these areas are poorly studied, indicating total disease burden is unknown. Future research should assess quality of life, caregiver burden, and costs.

Key words::

• Clinical
• Economic
• Humanistic
• Tuberous sclerosis

Transparency

Declaration of funding

This study was sponsored by Novartis Pharmaceuticals Corporation, US.

Declaration of financial/other relationships

Z.L. and J.V. have disclosed that they are employees of Novartis Pharmaceuticals Corporation and Novartis Biociências SA, respectively. Z.L. has also disclosed that she owns stock in Novartis. L.H., T.F., and M.B. have disclosed that they are employees of United BioSource Corporation, a company that received funding from Novartis to conduct this study.

Acknowledgements

The authors acknowledge with appreciation Jeanfrancois Baladi for his assistance in reviewing the manuscript.