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The effect of mTOR inhibition on obstructive hydrocephalus in patients with tuberous sclerosis complex (TSC) related subependymal giant cell astrocytoma (SEGA)

  • Clinical Study
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Abstract

Purpose

Mammalian target of rapamycin inhibitors (mTORi) are known to effectively reduce the size of subependymal giant cell astrocytomas (SEGAs), which are benign brain lesions associated with Tuberous Sclerosis Complex (TSC) that commonly cause obstructive hydrocephalus (OH). This retrospective case series reviews an institutional experience of the effect of mTORi on OH in patients with TSC-related SEGA.

Methods

Thirteen of 16 identified patients with TSC-related SEGA treated with mTORi from October 2007 to December 2018 were included. Serial magnetic resonance imaging (MRI) and clinical charts were reviewed to correlate symptoms and signs of increased intracranial pressure (iICP) with ventriculomegaly on MRI. A proposed ventriculomegaly scale was used: none (< 7 mm), mild (7–10 mm), moderate (11–30 mm), and severe (> 30 mm). OH was defined as moderate or severe ventriculomegaly, based on the largest measurement.

Results

Patients’ median age at start of mTORi was 13 (6–17) years and five (38%) patients were female. Eight patients had OH at the time of mTORi initiation, five of whom were asymptomatic. Six patients had improvement of hydrocephalus on serial MRI imaging with mTORi therapy, while seven patients had no change based on the ventriculomegaly scale used. All three patients who presented with symptoms of iICP and had OH also had papilledema. None had worsening of hydrocephalus or required shunt placement. Out of five patients with symptoms of iICP, four avoided surgery.

Conclusion

Most patients had asymptomatic OH at the time of diagnosis, and ventricular enlargement was not correlated with iICP symptoms. mTORi was successful for treatment of OH from TSC-related SEGA, even in the setting of acute symptoms of iICP.

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Abbreviations

CSF:

Cerebrospinal fluid

EI:

Evans’ index

iICP:

Increased intracranial pressure

MRI:

Magnetic resonance imaging

mTOR:

Mammalian target of rapamycin

mTORi:

Mammalian target of rapamycin inhibitor

OH:

Obstructive hydrocephalus

SEGA:

Subependymal giant cell astrocytoma

TSC:

Tuberous sclerosis complex

VPS:

Ventriculoperitoneal shunt

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Authors and Affiliations

  1. Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, M5G 1X8, Canada

    Danielle R. Weidman, Eric Bouffet & Ute Bartels

  2. Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Canada

    Sunitha Palasamudram & Manohar Shroff

  3. Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada

    Maria Zak, Robyn Whitney & Blathnaid McCoy

  4. Division of Neurosurgery, Department of Surgery, The Hospital for Sick Children, Toronto, Canada

    Michael Taylor

  5. University of Toronto, Toronto, Canada

    Danielle R. Weidman, Sunitha Palasamudram, Robyn Whitney, Blathnaid McCoy, Eric Bouffet, Michael Taylor, Manohar Shroff & Ute Bartels

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  1. Danielle R. Weidman
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Correspondence to Ute Bartels.

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The authors declare that they have no conflict of interest.

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This research study was conducted retrospectively from data obtained for clinical purposes. Institutional Research Ethics Board approval was obtained at The Hospital for Sick Children (REB number: 1000060201).

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Weidman, D.R., Palasamudram, S., Zak, M. et al. The effect of mTOR inhibition on obstructive hydrocephalus in patients with tuberous sclerosis complex (TSC) related subependymal giant cell astrocytoma (SEGA). J Neurooncol 147, 731–736 (2020). https://doi.org/10.1007/s11060-020-03487-8

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  • DOI: https://doi.org/10.1007/s11060-020-03487-8

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