Trial reportPediatric neurology2019
Longitudinal Effects of Everolimus on White Matter Diffusion in Tuberous Sclerosis Complex.
Trial report in Pediatric neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00411619 (Everolimus), which is not on this map. Cited by 19 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Everolimus (RAD001)Therapy of Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex
Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Systematic review of mTOR inhibitor treatment, biomarkers and prophylaxis for tuberous sclerosis complex-associated seizures.Clinical medicine (London, England) · 2022Pooled it
- Autism and Epilepsy in Patients With Tuberous Sclerosis Complex.Frontiers in neurology · 2020Pooled it
- ENT1 inhibitor J4 restores cognitive function and white-matter integrity in a mouse model of tuberous sclerosis complex.Journal of biomedical science · 2026Article
- Potential for Therapeutic Alteration of the Underlying Biology of Epilepsy.Biomedicines · 2025Review
- mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.Nature reviews. Neuroscience · 2024Review
- Inhibition of p70 Ribosomal S6 Kinase (S6K1) Reduces Cortical Blood Flow in a Rat Model of Autism-Tuberous Sclerosis.Neuromolecular medicine · 2024Article
- Is tuberous sclerosis complex-associated autism a preventable and treatable disorder?World journal of pediatrics : WJP · 2024Review
- Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy.Brain : a journal of neurology · 2023Review
- Synthetic MRI in children with tuberous sclerosis complex.Insights into imaging · 2022Article
- Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders.Frontiers in neurology · 2022Article
- Impaired myelin production due to an intrinsic failure of oligodendrocytes in mTORpathies.Neuropathology and applied neurobiology · 2021Article
- Detection of endophenotypes associated with neuropsychiatric deficiencies in a mouse model of tuberous sclerosis complex using diffusion tensor imaging.Brain pathology (Zurich, Switzerland) · 2021Article
- Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin.Science advances · 2021Article
- Editorial: Biomarkers to Enable Therapeutics Development in Neurodevelopmental Disorders.Frontiers in integrative neuroscience · 2020Article
- Tuberous Sclerosis Complex as Disease Model for Investigating mTOR-Related Gliopathy During Epileptogenesis.Frontiers in neurology · 2020Review
- The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex.Journal of neurodevelopmental disorders · 2019Review
- Early patterns of functional brain development associated with autism spectrum disorder in tuberous sclerosis complex.Autism research : official journal of the International Society for Autism Research · 2019Article
- White matter mean diffusivity correlates with myelination in tuberous sclerosis complex.Annals of clinical and translational neurology · 2019Article
- Everolimus for the treatment of refractory seizures associated with tuberous sclerosis complex (TSC): current perspectives.Therapeutics and clinical risk management · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveWe studied the longitudinal effects of everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), on callosal white matter diffusion tensor imaging (DTI) in patients with tuberous sclerosis complex (TSC).
methodsSerial imaging data spanning nine years were used from the open label, Phase I/II trial (NCT00411619) and open-ended extension phase of everolimus for the treatment of subependymal giant cell astrocytoma associated with TSC. From 28 patients treated with everolimus and 25 untreated control patients, 481 MRI scans were available. Rigorous quality control resulted in omission of all scans with diffusion weighted imaging data in less than 15 directions or more than eight artifacted volumes, and all postsurgical scans. We applied a linear mixed-effects model to the remaining 125 scans (17 treated, 24 controls) for longitudinal analysis of each DTI metric of manually drawn callosal regions of interest.
resultsOn a population level, mTOR inhibition was associated with a decrease in mean diffusivity. In addition, in treated patients only, a decrease of radial diffusivity was observed; in untreated patients only, an increase of axial diffusivity was seen. In patients below age 10, effect-sizes were consistently greater, and longer treatment was associated with greater rate of diffusion change. There was no correlation between DTI metrics and reduction of subependymal giant cell astrocytoma volume, or everolimus serum levels.
conclusionsEffects from mTOR overactivity on white matter microstructural integrity in TSC were modified through pharmacologic inhibition of mTOR. These changes sustained over time, were greater with longer treatment and in younger patients during a time of rapid white matter maturation.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.