Does the mTOR inhibitor everolimus influence the course of epilepsy in children with tuberous sclerosis complex?

2013 ◽  
Vol 44 (02) ◽  
Author(s):  
F Mackel ◽  
B Fiedler ◽  
A Hahn ◽  
H Hartmann ◽  
P Hernaiz-Driever ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mtor Inhibitor

scholarly journals RARE-25. RETINAL ASTROCYTOMA mTOR INHIBITOR THERAPY IN TUBEROUS SCLEROSIS MOSAICISM

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii447-iii447
Author(s):  
Naomi Evans ◽  
Katherine Paton ◽  
Harinder Kaur Gill ◽  
Juliette Hukin
Keyword(s):  
Optic Nerve ◽  
Retinal Detachment ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mtor Inhibitor ◽  
Mammalian Target Of Rapamycin ◽  
Neovascular Glaucoma ◽  
Renal Angiomyolipoma ◽  
Gradual Reduction ◽  
Health Canada

Abstract INTRODUCTION Everolimus is an inhibitor of mTORC1 (mammalian target of rapamycin complex 1), it is Health Canada and FDA approved for SEGA and renal angiomyolipoma in the setting of tuberous sclerosis complex (TSC). There is little data available in regards to this treatment of TSC associated retinal astrocytoma (RA). Although the behaviour of RA is often indolent or slowly progressive, aggressive behaviour with retinal detachment and neovascular glaucoma requiring enucleation has been reported in several patients. Definite TSC diagnosis is established when either two major features or one major and two minor features are present. Probable TSC diagnosis is established when one major plus one minor feature is present. METHODS We report a child with probable TSC mosaicism, with negative serum NGS for TSC but RA and retinal achromic patch on the left. A left retinal peripapillary astrocytoma around optic nerve and very close to fovea was noted. There was concern that if it grew or there were to be any leakage it would cause visual impairment. This lead to therapy with everolimus 4.5 mg/m2/d aiming for level between 5 and 10 mcg/L. RESULTS This boy has had a gradual reduction of the RA over the last 29 months, with healthy retina in the region no longer occupied by the lesion and preserved vision. He has tolerated therapy well with occasional mouth ulcers. CONCLUSION mTORC1 inhibition is effective therapy to preserve vision in the setting of retinal astrocytoma and tuberous sclerosis mosaicism.

scholarly journals Frequency, Progression, and Current Management: Report of 16 New Cases of Nonfunctional Pancreatic Neuroendocrine Tumors in Tuberous Sclerosis Complex and Comparison With Previous Reports

2021 ◽  
Vol 12 ◽  
Author(s):  
Kate Mowrey ◽  
Hope Northrup ◽  
Peyton Rougeau ◽  
S. Shahrukh Hashmi ◽  
Darcy A. Krueger ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Neuroendocrine Tumors ◽  
Tuberous Sclerosis Complex ◽  
Clinical Management ◽  
Mtor Inhibitor ◽  
Mtor Inhibitors ◽  
Surgical Removal ◽  
Pancreatic Neuroendocrine Tumors ◽  
Serial Imaging ◽  
Pathogenic Variants

Background: Tuberous sclerosis complex (TSC) is a genetic condition that causes benign tumors to grow in multiple organ systems. Nonfunctional pancreatic neuroendocrine tumors (PNETs) are a rare clinical feature of TSC with no specific guidelines outlined for clinical management at this time. Our purpose is to calculate the frequency of nonfunctional PNETs as well as characterize the presentation, current clinical management, and assess the impact of systemic mammalian target of rapamycin (mTOR) on nonfunctional PNETs in TSC.Methods: This retrospective chart review was performed by a query of the TS Alliance's Natural History Database and the Cincinnati Children's Hospital TSC Database for patients with nonfunctional PNET. Clinical data from these two groups was summarized for patients identified to have a nonfunctional PNET and compared to previously reported cases with TSC and nonfunctional PNETs.Results: Our calculated frequency of nonfunctional PNETs is 0.65%. We identified 16 individuals, nine males and seven females, with a median age of 18.0 years (interquartile range: −15.5 to 25.5). Just over half (56.3%, n = 9) of the patients provided results from genetic testing. Six had pathogenic variants in TSC2 whereas three had pathogenic variants in TSC1. The average age at PNET diagnosis was 15.0 years (range: 3–46 years). Almost all individuals were diagnosed with a PNET during routine TSC surveillance, 56.3% (n = 9) by MRI, 12.5% (n = 2) by CT, 25% (n = 4) by ultrasound, and 6.2% (n = 1) through a surgical procedure. Follow up after diagnosis involved 68.8% (n = 11) having serial imaging and nine of the sixteen individuals proceeding with surgical removal of the PNET. Eight individuals had a history of using systemic mTOR inhibitors. Tumor growth rate was slightly less in individuals taking an mTOR inhibitor (−0.8 mm/yr, IQR: −2.3 to 2.2) than those without (1.6 mm/yr; IQR: −0.99 to 5.01, p > 0.05).Conclusions: Nonfunctional PNETs occurred at younger ages in our TSC cohort and more commonly compared to ages and prevalence reported for the general population. PNETs in patients on systemic mTOR inhibitors had lower rates of growth. The outcome of this study provides preliminary evidence supporting the use of mTOR inhibitor therapy in conjunction with serial imaging as medical management for nonfunctional PNETs as an alternative option to invasive surgical removal.

Potential therapeutic effect of curcumin, a natural mTOR inhibitor, in tuberous sclerosis complex

Phytomedicine ◽  
2019 ◽  
Vol 54 ◽  
pp. 132-139 ◽  
Author(s):  
Chu-Jen Kuo ◽  
Chi-Chen Huang ◽  
Szu-Yi Chou ◽  
Yu-Chun Lo ◽  
Tzu-Jen Kao ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Therapeutic Effect ◽  
Tuberous Sclerosis Complex ◽  
Mtor Inhibitor

Tuberous sclerosis complex 2 (TSC2) expression in hepatocellular carcinoma to predict responses to mTOR inhibitor.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e15628-e15628
Author(s):  
Jinhyun Cho ◽  
Ji Yun Lee ◽  
Kwai Han Yoo ◽  
Cheol Keun Park ◽  
Seung Tae Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mtor Inhibitor

TSC1 and TSC2: Tuberous Sclerosis Complex and Its Related Epilepsy Phenotype

2021 ◽  
Author(s):  
Claudia Di Napoli ◽  
Alessia Gennaro ◽  
Carmelania Lupica ◽  
Raffaele Falsaperla ◽  
Roberta Leonardi ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mtor Inhibitor ◽  
Autosomal Dominant ◽  
Treatment Strategies ◽  
Neurological Impairment ◽  
Drug Resistant ◽  
Autosomal Dominant Disorder ◽  
Mechanistic Target Of Rapamycin ◽  
Neuropsychiatric Manifestations

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a multisystemic involvement. In TSC, reduced function of TSC1 and TSC2 genes products (hamartin and tuberin, respectively) leads to an hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and to a consequent cell growth dysregulation. In TSC patients, neurological and neuropsychiatric manifestations, especially epilepsy and neuropsychiatric comorbidities such as autism or intellectual disability, represent the most disabling features. In particular, epilepsy occurrs up to 80% of patients, is often drug resistant and is frequently associated with neurological impairment. Due to the burden of this morbidity, different treatment strategies have been proposed with the purpose to make patients epilepsy free, such as the use of different antiepileptic drugs like vigabatrin, carbamazepine, valproic acid, and levetiracetam. More recently, a mTOR inhibitor (i.e. everolimus) has showed promising results in terms of seizures reduction.

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