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Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge-Weber Syndrome

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Review

Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge-Weber Syndrome

Carl E Stafstrom et al. Front Neurol.

Abstract

Neurocutaneous disorders are multisystem diseases affecting skin, brain, and other organs. Epilepsy is very common in the neurocutaneous disorders, affecting up to 90% of patients with tuberous sclerosis complex (TSC) and Sturge-Weber syndrome (SWS), for example. The mechanisms underlying the increased predisposition to brain hyperexcitability differ between disorders, yet some molecular pathways overlap. For instance, the mechanistic target of rapamycin (mTOR) signaling cascade plays a central role in seizures and epileptogenesis in numerous acquired and genetic disorders, including several neurocutaneous disorders. Potential routes for target-specific treatments are emerging as the genetic and molecular pathways involved in neurocutaneous disorders become increasingly understood. This review explores the clinical features and mechanisms of epilepsy in three common neurocutaneous disorders-TSC, neurofibromatosis type 1, and SWS.

Keywords: Sturge–Weber syndrome; epilepsy; mechanistic target of rapamycin; neurocutaneous disorder; neurofibromatosis; seizure; tuberous sclerosis complex.

Figures

Figure 1
Figure 1
Examples of brain MRI scans in patients with neurocutaneous disorders. (A) 8-year-old boy with tuberous sclerosis complex. (A1) Axial fluid attenuation inversion recovery (FLAIR) and (A2) coronal contrast-enhanced T1-weighted images show multiple cortical/subcortical, partially calcified mixed FLAIR-hyper/hypointense tubers in the right front parietal lobes (arrows, A1), FLAIR-hyperintense migration lines (triangle, A1), and a homogeneously enhancing, round subependymal giant cell astrocytoma within the right foramen of Monro (arrow, A2). (B) 16-year-old girl with neurofibromatosis type 1. (B1) Axial FLAIR and T1 post-contrast images showing a large expansile lesion centered at the right precentral gyrus (*) indicating a low-grade glioma. (B2) Axial T2 FLAIR image reveals focal areas of signal intensity (arrows) in the right globus pallidus and putamen and similar but to a lesser extent on the contralateral side, representing nonspecific unidentified bright objects. (C) 21-month-old boy with Sturge–Weber syndrome. (C1) Axial T1-weighted post-contrast image showing left hemisphere atrophy with prominent choroid plexus glomus (arrow). (C2) Coronal T1-weighted post-contrast image with occipital-parietal leptomeningeal enhancement (arrow).
Figure 2
Figure 2
Molecular pathways involved in three common neurocutaneous disorders— tuberous sclerosis complex (TSC), neurofibromatosis type 1, and SturgeWeber syndrome. As elaborated in the text, this diagram indicates unique sites of dysfunction as well as interactive and overlapping pathways that might serve as target-specific interventions.
Figure 3
Figure 3
Possible contributors to cellular hyperexcitability and seizures in three common neurocutaneous disorders—tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and SturgeWeber syndrome (SWS).

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