Pilot Study of Neurodevelopmental Impact of Early Epilepsy Surgery in Tuberous Sclerosis Complex

Grayson, Leslie E.; Peters, Jurriaan M.; McPherson, Tarrant; Krueger, Darcy A.; Şahin, Mustafa; Wu, Joyce; Northrup, Hope; Porter, Brenda E.; Cutter, Gary; O’Kelley, Sarah; Krefting, Jessica; Stone, Scellig; Madsen, Joseph R.; Fallah, Aria; Blount, Jeffrey P.; Weiner, Howard L.; Bebin, E. Martina; Warfield, Simon K.; Goyal, Monisha; Pearson, Deborah A.; Williams, Marian E.; Hanson, Ellen; Bing, Nicole M.; Kent, Bridget; Filip-Dhima, Rajna; Dies, Kira; Bruns, Stephanie; Scherrer, Benoît; Murray, Donna S.; Roberds, Steven L.; Capal, Jamie K.

doi:10.1016/j.pediatrneurol.2020.04.002

Cited by 30 publications

(26 citation statements)

References 20 publications

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“…Epilepsy surgery should be considered for patients with refractory TSC, particularly after failing three medications. [114][115][116] Special consideration should be given to children at younger ages experiencing neurological regression, 117,118 and evaluation for surgery should be performed at specialized epilepsy centers with experience and expertise in TSC (Category 2A). Obtain an echocardiography every 1-3 years in asymptomatic pediatric patients until regression of cardiac rhabdomyomas is documented.…”

Section: Lungmentioning

confidence: 99%

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Northrup¹,

Aronow²,

Bebin³

et al. 2021

Pediatric Neurology

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305

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Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods: Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results: Only two changes were made to clinical diagnostic criteria reported in 2013: "multiple cortical tubers and/or radial migration lines" replaced the more general term "cortical dysplasias," and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSCassociated neuropsychiatric disorders, and new medication approvals. Conclusions: Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families.

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Section: Lungmentioning

confidence: 99%

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Northrup¹,

Aronow²,

Bebin³

et al. 2021

Pediatric Neurology

Self Cite

358

305

View full text Add to dashboard Cite

show abstract

“…Tubers form during embryonic development and are primarily found in the cortex and occasionally in other regions such as the cerebellum [37, 38]. Tubers or the peri-tuberal cortex can become seizure foci [39, 40] and may be surgically resected as a treatment for intractable epilepsy in TSC [41]. Approximately 80% of individuals with TSC develop benign growths emanating from the ventricular walls called subependymal nodules (SENs) [42].…”

Section: Mtoropathiesmentioning

confidence: 99%

Current Approaches and Future Directions for the Treatment of mTORopathies

Karalis

Bateup

2021

Dev Neurosci

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The mechanistic target of rapamycin (mTOR) is a kinase at the center of an evolutionarily conserved signaling pathway that orchestrates cell growth and metabolism. mTOR responds to an array of intra- and extracellular stimuli and in turn controls multiple cellular anabolic and catabolic processes. Aberrant mTOR activity is associated with numerous diseases, with particularly profound impact on the nervous system. mTOR is found in two protein complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which are governed by different upstream regulators and have distinct cellular actions. Mutations in genes encoding for mTOR regulators result in a collection of neurodevelopmental disorders known as mTORopathies. While these disorders can affect multiple organs, neuropsychiatric conditions such as epilepsy, intellectual disability, and autism spectrum disorder have a major impact on quality of life. The neuropsychiatric aspects of mTORopathies have been particularly challenging to treat in a clinical setting. Current therapeutic approaches center on rapamycin and its analogs, drugs that are administered systemically to inhibit mTOR activity. While these drugs show some clinical efficacy, adverse side effects, incomplete suppression of mTOR targets, and lack of specificity for mTORC1 or mTORC2 may limit their utility. An increased understanding of the neurobiology of mTOR and the underlying molecular, cellular, and circuit mechanisms of mTOR-related disorders will facilitate the development of improved therapeutics. Animal models of mTORopathies have helped unravel the consequences of mTOR pathway mutations in specific brain cell types and developmental stages, revealing an array of disease-related phenotypes. In this review, we discuss current progress and potential future directions for the therapeutic treatment of mTORopathies with a focus on findings from genetic mouse models.

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“…Epilepsy surgery in infants younger than 3 years of age, and even younger than the age of 1 year, has demonstrated encouraging outcomes in terms of epilepsy control and safety 19,21–33 . Other studies have stressed the improved cognitive outcome of patients undergoing early surgery 12,34,35 . Despite these results, epilepsy surgery in the young infant group (younger than the age of 3 months) is rarely described, with less than 50 cases altogether 12,34,36–42 .…”

Section: Introductionmentioning

confidence: 99%

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study

et al. 2021

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Summary Objective Drug‐resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on “ultra‐early” epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra‐early epilepsy surgery performed before the age of 3 months. Methods To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. Results Sixty‐four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty‐five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow‐up of 41 months (19–104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1–3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). Significance Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

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Pilot Study of Neurodevelopmental Impact of Early Epilepsy Surgery in Tuberous Sclerosis Complex

Cited by 30 publications

References 20 publications

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Current Approaches and Future Directions for the Treatment of mTORopathies

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study

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