scholarly journals A retrospective analysis of the efficacy and tolerability of treatment with everolimus in treatment-refractory epilepsy associated with tuberous sclerosis

2020 ◽  
Vol 48 (1) ◽  
pp. 1-6
Author(s):  
A. V. Grigoryeva ◽  
M. Yu. Dorofeeva ◽  
V. S. Perminov ◽  
E. D. Belousova
Keyword(s):  
Tuberous Sclerosis ◽  
Mtor Inhibitor ◽  
Autosomal Dominant ◽  
Refractory Epilepsy ◽  
Subependymal Giant Cell Astrocytoma ◽  
Renal Angiomyolipoma ◽  
Multisystem Disorder ◽  
Epileptic Spasms ◽  
The Russian Federation ◽  
Refractory Seizures

Rationale: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by multiple multi-organ hamartomas. Medically refractory epilepsy (MRE) occurs in up to 60% of TSC patients. The results of the EXIST-3 study have shown the efficacy of MRE treatment with an mTOR inhibitor everolimus. In the Russian Federation, the drug has been approved since 2017 for the treatment of TSC-associated MRE in patients above 2 years of age. Aim: To assess the efficacy of everolimus for treatment of medically refractory seizures associated with TSC. Materials and methods: We retrospectively analyzed medical files from 89 patients with TSC who had been admitted with MRE to the Department of Psychoneurology and Epileptology, Research and Clinical Institute for Pediatrics (Moscow, Russia) from November 2016 to December 2018. The patients were divided into three groups depending on their indications for everolimus: 1) 17 patients received with MRE; 2) 64 patients with MRE and subependymal giant cell astrocytoma (SEGA) of > 1 cm in diameter; 3) 8 patients with MRE and renal angiomyolipoma (AML) of > 3 cm in diameter. Their median age was 7.9 year (range, from 2 to 34 years). There were 45 (50.6%) male and 44 (49.4%) female patients. Their treatment lasted from 6 months to 5 years; the dose of everolimus was 8 mg/m2 . Focal seizures were more prevalent than epileptic spasms: 60 (67.4%) and 29 (32.6%) patients, respectively. Results: There were 9/17 (52.9%) responders in the MRE group, 16/64 (25%) in the MRE + SEGA group, and 4/8 (50%) in the MRE + AML group. Mild to moderate stomatitis was the most frequent side effect (40.5%). Conclusion: Everolimus is a new important agent for MRE in TSC patients. Treatment with everolimus is safe and well tolerated.

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 Huge Renal Angiomyolipoma in a Child with Tuberous Sclerosis Complex: A Diagnostic and Therapeutic Dilemma

2021 ◽  
Vol 5 (0-2) ◽  
pp. 26
Author(s):  
Sharifah NurDurrah Binti Syed Mudzhar ◽  
Mohd Yusran Othman
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Left Kidney ◽  
Abdominal Distension ◽  
Bleeding Risk ◽  
Subependymal Giant Cell Astrocytoma ◽  
Renal Angiomyolipoma ◽  
Cardiac Rhabdomyoma ◽  
Contralateral Kidney ◽  
Life Threatening

Tuberous Sclerosis Complex (TSC) is a rare neuro-cutaneous disorder that is associated with the development of benign hamartomas including renal angiomyolipoma (RAML). TSC associated RAML are usually asymptomatic, but it carries a life-threatening bleeding risk. We are sharing a case of a 5-year-old girl who was diagnosed to have TSC with associated subependymal giant cell astrocytoma, cardiac rhabdomyoma and autism. She presented with a history of worsening abdominal distension over 3 weeks duration and clinically noted to be pale with a ballotable left flank mass. Ultrasound and CT scan found to have multiple RAML in both kidneys with a huge mass on the left side. The mass represented a huge RAML (8cm) with aneurysmal formation with suspicion of intratumoral bleeding. The option of conservative management with mammalian target of rapamycin inhibitor followed with partial nephrectomy has been questioned with its life-threatening risk of bleeding and inability to do biopsy to rule out the possibility of renal cell carcinoma. Decision for nephrectomy was then made clearer following a MAG-3 scan which revealed only 11% differential function of the left kidney. She underwent a total left nephrectomy uneventfully and intraoperatively noted to have an enlarging lesion as compared to the previous imaging; 15cm in largest diameter. Histopathological finding was consistent with multifocal angiomyolipoma with intratumoral haematoma. Decision for nephrectomy in TSC-associated RAML need to be justified carefully in view of its risk of losing the contralateral kidney following the disease progression which may end up with life-long renal replacement therapy.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S26

scholarly journals Tuberous Sclerosis Complex Associated Lymphangioleiomyomatosis Presenting with Spontaneous Pneumothorax and Renal Angiomyolipomas

2019 ◽  
Vol 48 (2) ◽  
pp. 51-54
Author(s):  
Mohammed Mirazur Rahman ◽  
Shish Mohammad Sarkar ◽  
Manzurul Ibrahim Musa ◽  
Farjana Binte Habib ◽  
Md Nazmul Hasan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Spontaneous Pneumothorax ◽  
Autosomal Dominant ◽  
Multisystem Disorder ◽  
Autosomal Dominant Disorder ◽  
Oxygen Inhalation ◽  
Lower Back ◽  
Thin Walled

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder manifested by involvement of multisystem including skin, central nervous system, heart, kidneys and eyes. Lymphangioleiomyomatosis (LAM) is also a multisystem disorder that primarily affects the lungs. We report a case of tuberous sclerosis complex associated lymphangio-leiomyomatosis (TSC-LAM) in a 26-year-old female patient who was presented with spontaneous pneumothorax and renal angiomyolipomas. In clinical examination; We found multiple angiofibromas over her face, shagreen patches over upper and lower back and ungual fibromas in both fingers and toes. HRCT of chest revealed right sided pneumothorax with multiple thin walled cysts in both lungs. Ultrasonogram (USG) and Computer Tomography (CT) scan of abdomen revealed bilateral angiomyolipomas. We managed her pneumothorax with intercostal chest tube drainage and oxygen inhalation. Bangladesh Med J. 2019 May; 48 (2): 51-54

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.

scholarly journals Case report on Tuberous Sclerosis

2014 ◽  
Vol 2 (4) ◽  
pp. 208-210
Author(s):  
Sushma Shrestha ◽  
Sabina Shrestha ◽  
Anil Raj Ojha
Keyword(s):  
Case Report ◽  
Early Diagnosis ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Late Childhood ◽  
Multisystem Disorder ◽  
Rare Genetic Disorder ◽  
Autosomal Dominant Fashion

Tuberous Sclerosis Complex is a rare genetic disorder inherited in autosomal dominant fashion. It is a multisystem disorder involving brain, skin, kidneys, heart, eyes and lungs which becomes apparent only in late childhood, limiting the usefulness of early diagnosis in infancy. Here, we report a case of an 11 year male child with tuberous sclerosis.DOI: http://dx.doi.org/10.3126/jkmc.v2i4.11798Journal of Kathmandu Medical CollegeVol. 2, No. 4, Issue 6, Oct.-Dec., 2013Page : 208-210

scholarly journals The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma

2017 ◽  
Vol 33 (1) ◽  
pp. 101-109 ◽  
Author(s):  
John J. Bissler ◽  
David N. Franz ◽  
Michael D. Frost ◽  
Elena Belousova ◽  
E. Martina Bebin ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Giant Cell ◽  
Pediatric Patients ◽  
Subependymal Giant Cell Astrocytoma ◽  
Renal Angiomyolipoma ◽  
Giant Cell Astrocytoma

scholarly journals Tuberous sclerosis complex

2012 ◽  
Vol 87 (2) ◽  
pp. 184-196 ◽  
Author(s):  
Daniela Araujo Rodrigues ◽  
Ciro Martins Gomes ◽  
Izelda Maria Carvalho Costa
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autosomal Dominant ◽  
Multisystem Disorder ◽  
Therapeutic Trials ◽  
Multiple Organs ◽  
Tissue Replacement ◽  
History Of ◽  
Neurocutaneous Syndrome ◽  
Made In

Tuberous Sclerosis Complex, also known as Epiloia or Bourneville-Pringle disease is an autosomal dominant neurocutaneous syndrome with variable clinical expression. It is a multisystem disorder that may be associated with hamartomas in multiple organs in an unpredictable manner. The dermatologist plays an essential role in the history of the disease, since skin manifestations represent the most prevalent clinical features, enabling early diagnosis and intervention in its natural course. This article aims to inform the scientific community about advances made in the study of genetics and molecular biology. Recent findings regarding stimulation of tumor growth have been changing the history of this condition, making therapeutic trials with topical and systemic drugs possible. Knowledge of these topics enables better management of the patients affected, since tissue replacement by tumors can result in significant morbidity and mortality.

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