TUBEROUS SCLEROSIS COMPLEX: ROLE OF RADIOLOGY AS AN INVALUABLE TOOL IN MANAGEMENT AND FOLLOW-UP

Abstract Background: Rhabdomyoma is the most common cardiac tumour in children. It is usually associated with tuberous sclerosis complex caused by mutations in TSC-1 or TSC-2 genes. This tumour typically regresses by unknown mechanisms; however, it may cause inflow or outflow obstruction that necessitates urgent surgery. Here we investigate the clinical features and the genetic analysis of patients with tuberous sclerosis complex presenting with large rhabdomyoma tumours. We also investigate the potential role of autophagy and apoptosis in the pathogenesis of this tumour. Methods: All the patients with cardiac rhabdomyoma referred to Aswan Heart Centre from 2010 to 2018 were included in this study. Sanger sequencing was performed for coding exons and the flanking intronic regions of TSC1 and TSC2 genes. Histopathological evaluation, immunohistochemistry, and western blotting were performed with P62, LC3b, caspase3, and caspase7, to evaluate autophagic and apoptotic signaling. Results: Five patients were included and had the clinical features of tuberous sclerosis complex. Three patients, who were having obstructive tumours, were found to have pathogenic mutations in TSC-2. The expression of two autophagic markers, P62 and LC3b, and two apoptotic markers, caspase3 and caspase7, were increased in the tumour cells compared to normal surrounding myocardial tissue. Conclusion: All the patients with rhabdomyoma were diagnosed to have tuberous sclerosis complex. The patients who had pathogenic mutations in the TSC-2 gene had a severe disease form necessitating urgent intervention. We also demonstrate the potential role of autophagy and apoptosis as a possible mechanism for tumourigenesis and regression. Future studies will help in designing personalised treatment for cardiac rhabdomyoma.

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The effect of sirolimus on angiomyolipoma is determined by decrease of fat-poor compartments and includes striking reduction of vascular structures

Scientific Reports ◽

10.1038/s41598-021-87930-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Elieser Hitoshi Watanabe ◽

Fernando Morbeck Almeida Coelho ◽

Hilton Leão Filho ◽

Bruno Eduardo Pedroso Balbo ◽

Precil Diego Miranda de Menezes Neves ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Blood Vessels ◽

Tuberous Sclerosis Complex ◽

Hounsfield Unit ◽

Mtor Inhibitors ◽

Volume Reduction ◽

Tumor Reduction ◽

Vascular Structures ◽

Remarkable Reduction

AbstractRenal angiomyolipomas hemorrhage is associated with their size and vascular constitution. The effects of sirolimus on different components of angiomyolipomas was analyzed in patients with tuberous sclerosis complex, sporadic lymphangioleiomyomatosis and multiple sporadic angiomyolipomas. Thirty angiomyolipomas from 14 patients treated with sirolimus were retrospectively evaluated. A Hounsfield-unit threshold was used to classify angiomyolipomas in fat-rich, fat-poor and intermediate-fat tumors, and to categorize tumor compartments in fat rich, fat poor, intermediate fat and highly vascularized. Diameter variations were measured to assess the effects on aneurysmatic/ectatic vascular formations. Volume reduction following treatment with sirolimus was higher in fat-poor than fat-rich angiomyolipomas. Tumor reduction was mainly determined by decrease of the fat-poor and highly-vascularized compartments while the volume of the fat-rich compartment increased. Broad liposubstitution was observed in some tumors. A median reduction of 100% (75 to 100) in the diameter of aneurysmatic/ectatic vascular structures was observed. Our study showed that sirolimus reduces the size of angiomyolipomas by decreasing primarily their highly-vascularized and fat-poor compartments. This effect is associated with a remarkable reduction of tumoral aneurysms/ectatic vessels, revealing the likely mechanism responsible for the risk-decreasing effect of mTOR inhibitors on angiomyolipoma bleeding. These findings support the role of mTOR in the development of angiomyolipoma blood vessels.

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Long-term outcomes of resective epilepsy surgery after invasive presurgical evaluation in children with tuberous sclerosis complex and bilateral multiple lesions

Journal of Neurosurgery Pediatrics ◽

10.3171/2014.10.peds14107 ◽

2015 ◽

Vol 15 (1) ◽

pp. 26-33 ◽

Cited By ~ 32

Author(s):

Ravindra Arya ◽

Jeffrey R. Tenney ◽

Paul S. Horn ◽

Hansel M. Greiner ◽

Katherine D. Holland ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Epilepsy Surgery ◽

Tuberous Sclerosis Complex ◽

Refractory Epilepsy ◽

Full Scale ◽

Secondary Outcome ◽

Resective Surgery ◽

Class 1 ◽

Medically Refractory Epilepsy

OBJECT Tuberous sclerosis complex (TSC) with medically refractory epilepsy is characterized by multifocal brain abnormalities, traditionally indicating poor surgical candidacy. This single-center, retrospective study appraised seizurerelated, neuropsychological, and other outcomes of resective surgery in TSC patients with medically refractory epilepsy, and analyzed predictors for these outcomes. METHODS Patients with multilesional TSC who underwent epilepsy surgery between 2007 and 2012 were identified from an electronic database. All patients underwent multimodality noninvasive and subsequent invasive evaluation. Seizure outcomes were classified using the International League Against Epilepsy (ILAE) scale. The primary outcome measure was complete seizure remission (ILAE Class 1). Secondary outcome measures included 50% responder rate, change in full-scale IQ, electroencephalography improvement, and reduction in antiepileptic drug (AED) burden. RESULTS A total of 37 patients with TSC underwent resective surgery during the study period. After a mean follow-up of 5.68 ± 3.67 years, 56.8% achieved complete seizure freedom (ILAE Class 1) and 86.5% had ILAE Class 4 outcomes or better. The full-scale IQ on follow-up was significantly higher in patients with ILAE Class 1 outcome (66.70 ± 12.36) compared with those with ILAE Class 2 or worse outcomes (56.00 ± 1.41, p = 0.025). In 62.5% of the patients with ILAE Class 2 or worse outcomes, the number of AEDs were found to be significantly reduced (p = 0.004). CONCLUSIONS This study substantiates the evidence for efficacy of resective epilepsy surgery in patients with bilateral multilesional TSC. More than half of the patients were completely seizure free. Additionally, a high proportion achieved clinically meaningful reduction in seizure burden and the number of AEDs.

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Epilepsy surgery in tuberous sclerosis complex: the BC Children’s Hospital experience

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.88 ◽

2015 ◽

Vol 42 (S1) ◽

pp. S14-S14

Author(s):

C Wilbur ◽

C Sanguansermsri ◽

H Chable ◽

A Mihaela ◽

P Steinbok ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Epilepsy Surgery ◽

Tuberous Sclerosis Complex ◽

Chart Review ◽

Retrospective Chart Review ◽

Seizure Outcome ◽

Corpus Callosotomy ◽

Age At Surgery ◽

Second Resection

Background: Epilepsy occurs in up to 90% of patients with Tuberous Sclerosis Complex (TSC) and is often refractory to medications. Our objective was to assess the safety and outcome of epilepsy surgery in children with TSC at our institution. Methods: We performed a systematic, retrospective chart review of children with TSC who underwent epilepsy surgery at our institution. Patients were identified through epilepsy and clinical neurophysiology databases. Results: 19 patients (out of 81 with TSC) underwent surgery between 1995-2014. Median age at surgery was 4.2 (Range 1.1-15.6) years, with patients having failed a median 4 (Range 0-10) anti-seizure medications. Surgery comprised corpus callosotomy in 2 and resection of one or more tubers in 17. 2 patients had a subsequent second resection. Minor neurologic deficits occurred after 14% of surgeries. Median follow-up was 2.4 years (Range 0.3 -13.8 years) following surgery . At last follow-up, 47% were seizure free, including 2 patients off anti-seizure medication. Conclusions: Epilepsy surgery is safe and effective in carefully selected TSC patients, with the majority having a good seizure outcome. Children with epilepsy secondary to TSC should be referred for epilepsy surgery assessment.

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