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Elizabeth A Thiele - One of the best experts on this subject based on the ideXlab platform.
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sporadic facial angiofibroma and sporadic angiomyolipoma mimicking Tuberous Sclerosis Complex
Journal of Medical Genetics, 2021Co-Authors: Katarzyna Klonowska, Elizabeth A Thiele, Joannes M Grevelink, Aaron R Thorner, David J KwiatkowskiAbstract:Tuberous Sclerosis Complex (TSC) is a genetic syndrome due to mutations in either TSC1 or TSC2, leading to the development of hamartomatous tumours at multiple body sites, including facial skin (facial angiofibroma (FAF)), brain (cortical tubers) and kidney (angiomyolipoma (AML)). In this report, we describe an individual with minimal TSC clinical features, who had ‘no mutation identified’ (NMI) by prior genetic testing in a clinical laboratory. Our massively parallel sequencing (MPS) analysis of multiple samples from different body sites and tumours (including blood, saliva, normal skin, AML and FAF) revealed an extraordinary situation in which FAF and AML had completely independent inactivating biallelic variants in TSC2, not present in other matched samples. This suggests that the two different lesions (AML and FAF) are not due to the same underlying germline or mosaic mutation, rather both are likely sporadic events. This case demonstrates the relevance of thorough clinical examination, high-coverage MPS of multiple tumours and matched normal tissues, and appropriate genetic counselling for individuals with marginal TSC features and possible TSC1 or TSC2 mosaicism.
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cerebellar lesions are associated with tsc2 mutations in Tuberous Sclerosis Complex a retrospective record review study
Developmental Medicine & Child Neurology, 2017Co-Authors: Susana Boronat, Elizabeth A Thiele, Paul A CarusoAbstract:Aim Cerebellar lesions are present in approximately 30% of patients with Tuberous Sclerosis Complex. Although several prior studies have characterized these lesions, our study provides the first description of the specific distribution of these lesions within the cerebellum and the first genotype–phenotype correlation yet to be published. Method We retrospectively reviewed magnetic resonance images from 220 paediatric and adult patients with Tuberous Sclerosis Complex (95 males, 125 females; mean age 22.7y, range 9mo–81y). Sex, age, and genotype of patients with cerebellar lesions were recorded and specific characteristics, including signal intensity, number, shape, presence of enhancement, calcification or haemorrhage, and location within the cerebellar lobules were noted. Results Fifty-eight patients (26.4%) had 106 cerebellar lesions (62 right, 44 left). The mean number of cerebellar lesions per patient was 1.8 (range 1–6). Enhancement was present in 42.4% of lesions and folial retraction in 84%. Calcification was detected in 86.8% of lesions. Patients with calcified lesions were older (mean age 21.6y) than patients without calcification (11.5y). TSC2 mutations were detected in 41/42 (97.6%) of patients with cerebellar tubers who had genetic testing and one patient had no mutation identified. None of the patients had TSC1 mutation. Interpretation We provide new information regarding cerebellar lesions in Tuberous Sclerosis Complex: cerebellar lesions are significantly much more frequent in patients with TSC2 mutations than TSC1 mutations or patients with no mutation identified, and Crus II is the most frequent location of cerebellar lesions. New studies are needed to assess the clinical significance of these lesions.
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cerebellar lesions are associated with tsc2 mutations in Tuberous Sclerosis Complex a retrospective record review study
Developmental Medicine & Child Neurology, 2017Co-Authors: Elizabeth A Thiele, Susana Boronat, Paul A CarusoAbstract:Aim Cerebellar lesions are present in approximately 30% of patients with Tuberous Sclerosis Complex. Although several prior studies have characterized these lesions, our study provides the first description of the specific distribution of these lesions within the cerebellum and the first genotype–phenotype correlation yet to be published. Method We retrospectively reviewed magnetic resonance images from 220 paediatric and adult patients with Tuberous Sclerosis Complex (95 males, 125 females; mean age 22.7y, range 9mo–81y). Sex, age, and genotype of patients with cerebellar lesions were recorded and specific characteristics, including signal intensity, number, shape, presence of enhancement, calcification or haemorrhage, and location within the cerebellar lobules were noted. Results Fifty-eight patients (26.4%) had 106 cerebellar lesions (62 right, 44 left). The mean number of cerebellar lesions per patient was 1.8 (range 1–6). Enhancement was present in 42.4% of lesions and folial retraction in 84%. Calcification was detected in 86.8% of lesions. Patients with calcified lesions were older (mean age 21.6y) than patients without calcification (11.5y). TSC2 mutations were detected in 41/42 (97.6%) of patients with cerebellar tubers who had genetic testing and one patient had no mutation identified. None of the patients had TSC1 mutation. Interpretation We provide new information regarding cerebellar lesions in Tuberous Sclerosis Complex: cerebellar lesions are significantly much more frequent in patients with TSC2 mutations than TSC1 mutations or patients with no mutation identified, and Crus II is the most frequent location of cerebellar lesions. New studies are needed to assess the clinical significance of these lesions.
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rib and vertebral bone fibrous dysplasia in a child with Tuberous Sclerosis Complex
American Journal of Medical Genetics Part A, 2015Co-Authors: Alexandra L Geffrey, Susana Boronat, Ignasi Barber, Brian E Grottkau, Elizabeth A ThieleAbstract:Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems, primarily the skin, brain, heart, kidneys, lungs, and eyes. The skeletal system is commonly affected in patients with TSC, but these bone lesions are generally asymptomatic and have not been well characterized. We present clinically significant bone growth in two ribs and vertebrae in an 8-year-old male patient with TSC and discuss the effects of mammalian target of rapamycin (mTOR) inhibitors as a possible treatment for these osseous abnormalities. This report suggests that skeletal lesions may hold more clinical significance than previously assumed and that further research should be directed toward understanding bone involvement in TSC.
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rib and vertebral bone fibrous dysplasia in a child with Tuberous Sclerosis Complex
American Journal of Medical Genetics Part A, 2015Co-Authors: Susana Boronat, Alexandra L Geffrey, Ignasi Barber, Brian E Grottkau, Elizabeth A ThieleAbstract:Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems, primarily the skin, brain, heart, kidneys, lungs, and eyes. The skeletal system is commonly affected in patients with TSC, but these bone lesions are generally asymptomatic and have not been well characterized. We present clinically significant bone growth in two ribs and vertebrae in an 8-year-old male patient with TSC and discuss the effects of mammalian target of rapamycin (mTOR) inhibitors as a possible treatment for these osseous abnormalities. This report suggests that skeletal lesions may hold more clinical significance than previously assumed and that further research should be directed toward understanding bone involvement in TSC. © 2015 Wiley Periodicals, Inc.
Susana Boronat - One of the best experts on this subject based on the ideXlab platform.
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cerebellar lesions are associated with tsc2 mutations in Tuberous Sclerosis Complex a retrospective record review study
Developmental Medicine & Child Neurology, 2017Co-Authors: Elizabeth A Thiele, Susana Boronat, Paul A CarusoAbstract:Aim Cerebellar lesions are present in approximately 30% of patients with Tuberous Sclerosis Complex. Although several prior studies have characterized these lesions, our study provides the first description of the specific distribution of these lesions within the cerebellum and the first genotype–phenotype correlation yet to be published. Method We retrospectively reviewed magnetic resonance images from 220 paediatric and adult patients with Tuberous Sclerosis Complex (95 males, 125 females; mean age 22.7y, range 9mo–81y). Sex, age, and genotype of patients with cerebellar lesions were recorded and specific characteristics, including signal intensity, number, shape, presence of enhancement, calcification or haemorrhage, and location within the cerebellar lobules were noted. Results Fifty-eight patients (26.4%) had 106 cerebellar lesions (62 right, 44 left). The mean number of cerebellar lesions per patient was 1.8 (range 1–6). Enhancement was present in 42.4% of lesions and folial retraction in 84%. Calcification was detected in 86.8% of lesions. Patients with calcified lesions were older (mean age 21.6y) than patients without calcification (11.5y). TSC2 mutations were detected in 41/42 (97.6%) of patients with cerebellar tubers who had genetic testing and one patient had no mutation identified. None of the patients had TSC1 mutation. Interpretation We provide new information regarding cerebellar lesions in Tuberous Sclerosis Complex: cerebellar lesions are significantly much more frequent in patients with TSC2 mutations than TSC1 mutations or patients with no mutation identified, and Crus II is the most frequent location of cerebellar lesions. New studies are needed to assess the clinical significance of these lesions.
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cerebellar lesions are associated with tsc2 mutations in Tuberous Sclerosis Complex a retrospective record review study
Developmental Medicine & Child Neurology, 2017Co-Authors: Susana Boronat, Elizabeth A Thiele, Paul A CarusoAbstract:Aim Cerebellar lesions are present in approximately 30% of patients with Tuberous Sclerosis Complex. Although several prior studies have characterized these lesions, our study provides the first description of the specific distribution of these lesions within the cerebellum and the first genotype–phenotype correlation yet to be published. Method We retrospectively reviewed magnetic resonance images from 220 paediatric and adult patients with Tuberous Sclerosis Complex (95 males, 125 females; mean age 22.7y, range 9mo–81y). Sex, age, and genotype of patients with cerebellar lesions were recorded and specific characteristics, including signal intensity, number, shape, presence of enhancement, calcification or haemorrhage, and location within the cerebellar lobules were noted. Results Fifty-eight patients (26.4%) had 106 cerebellar lesions (62 right, 44 left). The mean number of cerebellar lesions per patient was 1.8 (range 1–6). Enhancement was present in 42.4% of lesions and folial retraction in 84%. Calcification was detected in 86.8% of lesions. Patients with calcified lesions were older (mean age 21.6y) than patients without calcification (11.5y). TSC2 mutations were detected in 41/42 (97.6%) of patients with cerebellar tubers who had genetic testing and one patient had no mutation identified. None of the patients had TSC1 mutation. Interpretation We provide new information regarding cerebellar lesions in Tuberous Sclerosis Complex: cerebellar lesions are significantly much more frequent in patients with TSC2 mutations than TSC1 mutations or patients with no mutation identified, and Crus II is the most frequent location of cerebellar lesions. New studies are needed to assess the clinical significance of these lesions.
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rib and vertebral bone fibrous dysplasia in a child with Tuberous Sclerosis Complex
American Journal of Medical Genetics Part A, 2015Co-Authors: Alexandra L Geffrey, Susana Boronat, Ignasi Barber, Brian E Grottkau, Elizabeth A ThieleAbstract:Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems, primarily the skin, brain, heart, kidneys, lungs, and eyes. The skeletal system is commonly affected in patients with TSC, but these bone lesions are generally asymptomatic and have not been well characterized. We present clinically significant bone growth in two ribs and vertebrae in an 8-year-old male patient with TSC and discuss the effects of mammalian target of rapamycin (mTOR) inhibitors as a possible treatment for these osseous abnormalities. This report suggests that skeletal lesions may hold more clinical significance than previously assumed and that further research should be directed toward understanding bone involvement in TSC.
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rib and vertebral bone fibrous dysplasia in a child with Tuberous Sclerosis Complex
American Journal of Medical Genetics Part A, 2015Co-Authors: Susana Boronat, Alexandra L Geffrey, Ignasi Barber, Brian E Grottkau, Elizabeth A ThieleAbstract:Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems, primarily the skin, brain, heart, kidneys, lungs, and eyes. The skeletal system is commonly affected in patients with TSC, but these bone lesions are generally asymptomatic and have not been well characterized. We present clinically significant bone growth in two ribs and vertebrae in an 8-year-old male patient with TSC and discuss the effects of mammalian target of rapamycin (mTOR) inhibitors as a possible treatment for these osseous abnormalities. This report suggests that skeletal lesions may hold more clinical significance than previously assumed and that further research should be directed toward understanding bone involvement in TSC. © 2015 Wiley Periodicals, Inc.
Katarzyna Kotulska - One of the best experts on this subject based on the ideXlab platform.
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Brain lesions in Tuberous Sclerosis Complex. Review
2016Co-Authors: Wiesława Grajkowska, Katarzyna Kotulska, Elżbieta Jurkiewicz, Ewa MatyjaAbstract:A b s t r a c t Tuberous Sclerosis Complex (TSC) is an autosomal dominant, multisystem disease characterized by the development of multiple hamartomas and benign or rarely malignant neoplasms distributed at various sites throughout the body, especially in the brain, skin, retina, kidney, heart, and lungs. Brain lesions in TSC include: cortical/subcortical glioneu-ronal tubers, subependymal glial nodules (SENs), and subependymal giant cell astrocytomas (SEGAs). Cortical tubers are characterized by a markedly disorganized cortical lamination with dysplastic aggregates of abnormal glial and neuronal elements, including giant cells. SENs consist of large cells, somewhat similar to the giant cells seen in tubers, accompanied by elongated glial cells. SENs are typically covered by a layer of ependyma and can grow over time and develop into subependymal giant cell astrocytomas. SEGAs consist of a mixed cell population of large ganglioid-like cells, spindle and giant cells with nuclear pleomorphism. Mitotic activity and necrosis might be observed in SEGAs but they should not be considered as features of malignancy. The clinical presentations of TSC result from mutations in either of two tumour suppressor genes: TSC1 (located on 9q34) or TSC2 (located on 16p13). The proteins encoded by TSC1 and TSC2 genes, hamartin and tuberin, respectively, form a heterodimer which suppresses the mammalian tar-get of rapamycin (mTOR), a major cell growth and proliferation controller. Oral rapamycin therapy may induce regres-sion of astrocytomas associated with TSC. In this review, the clinicopathological features of TCS and recent advan
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management of epilepsy associated with Tuberous Sclerosis Complex tsc clinical recommendations
European Journal of Paediatric Neurology, 2012Co-Authors: Paolo Curatolo, Eleonora Aronica, Lieven Lagae, Rima Nabbout, Jose C Ferreira, Martha Feucht, Christoph Hertzberg, Anna Jansen, Floor E Jansen, Katarzyna KotulskaAbstract:Tuberous Sclerosis Complex (TSC) is a leading genetic cause of epilepsy. TSC-associated epilepsy generally begins during the first year of life, and is associated with neurodevelopmental and cognitive problems. Management is challenging and seizures tend to persist in a large proportion of patients despite pharmacological and surgical treatment. This report summarizes the clinical recommendations for the management of TSC-associated epilepsy made by a panel of European experts in March 2012. Current treatment options and outstanding questions are outlined.
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effective everolimus treatment of inoperable life threatening subependymal giant cell astrocytoma and intractable epilepsy in a patient with Tuberous Sclerosis Complex
European Journal of Paediatric Neurology, 2012Co-Authors: Marta Perekpolnik, Sergiusz Joźwiak, Elzbieta Jurkiewicz, Danuta Perek, Katarzyna KotulskaAbstract:We present successful everolimus treatment of a huge subependymal giant cell astrocytoma in a 10-year old boy with Tuberous Sclerosis Complex. The patient underwent several partial tumor resections complicated by intraoperative cardiac arrest. The tumor has been regrowing and produced severe clinical symptoms. Everolimus treatment resulted in marked tumor regression, significant improvement in patient's ambulation and cessation of seizures. Moreover, the therapy was well tolerated. These findings indicate that everolimus treatment should be considered as a therapeutic option alternative to surgery in patients with Tuberous Sclerosis Complex.
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Tuberous Sclerosis Complex tumors and tumorigenesis
International Journal of Dermatology, 2011Co-Authors: Julita Borkowska, Katarzyna Kotulska, Robert A Schwartz, Sergiusz JozwiakAbstract:Tuberous Sclerosis Complex (TSC) is an inherited disorder characterized by hamartomas in different body organs, mainly in the brain, skin, kidney, liver, lung, and heart. The clinical manifestations of TSC are the result of a mutation of one of two tumor suppressor genes, TSC1 and TSC2. Cutaneous findings in TSC should be regarded as cutaneous signs of a pivotal systemic disease. The authors elucidate the variety of neoplasms seen in TSC patients, along with their clinical significance, and suggest suitable evaluation and management strategies.
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Tuberous Sclerosis Complex advances in diagnosis genetics and management
Journal of The American Academy of Dermatology, 2007Co-Authors: Robert A Schwartz, Katarzyna Kotulska, Geover Fernandez, Sergiusz JoźwiakAbstract:Tuberous Sclerosis Complex (TSC) is an autosomal dominant multisystem neurocutaneous syndrome characterized by the development of multiple hamartomas distributed throughout the body, skin, brain, heart, kidneys, liver, and lungs. Two-thirds of patients represent sporadic mutations. The classic triad is seizures, mental retardation, and cutaneous angiofibromas. However, the full triad occurs in only 29% of patients; 6% of them lack all three of them. Two tumor suppressor genes responsible for TSC have been identified: TSC1 gene on chromosome 9 and TSC2 on chromosome 16. This article highlights the most recent significant advances in the diagnosis and genetics of TSC, along with a discussion on the limitations and the usefulness of the revised 1998 clinical criteria for the Tuberous Sclerosis Complex. The "ash leaf" macule often comes in other shapes, such as round; most are polygonal, usually 0.5 cm to 2.0 cm in diameter, resembling a thumbprint. Since the death of its describer, Thomas Fitzpatrick, we call each a "Fitzpatrick patch." Special attention is paid in this work to TSC treatment options, including therapeutic trials with rapamycin, also known as sirolimus. Learning objective After completing this learning activity, participants should familiar with Tuberous Sclerosis Complex, its cutaneous signs and systemic findings stratified by patient age, its genetics, and the potential for meaningful therapeutic intervention.
Thomas N. Darling - One of the best experts on this subject based on the ideXlab platform.
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Clinical Characteristics of Connective Tissue Nevi in Tuberous Sclerosis Complex With Special Emphasis on Shagreen Patches
JAMA Dermatology, 2017Co-Authors: Michelle A. Bongiorno, Neera Nathan, Oyetewa Oyerinde, Ji-an Wang, Chyi-chia Richard Lee, G. Thomas Brown, Joel Moss, Thomas N. DarlingAbstract:Importance Patients with Tuberous Sclerosis Complex (TSC) frequently develop collagenous connective tissue nevi. The prototypical lesion is a large shagreen patch located on the lower back, but some patients only manifest small collagenomas or have lesions elsewhere on the body. The ability to recognize these variable presentations can be important for the diagnosis of TSC. Objective To describe the clinical characteristics of connective tissue nevi on the trunk and extremities of patients with Tuberous Sclerosis Complex. Design, Setting, and Participants A retrospective analysis of patient medical records and skin photography was performed; 104 adult patients with TSC were enrolled in an observational cohort study that was enriched for those with pulmonary lymphangioleiomyomatosis, and was therefore composed mostly of women (99 women, 5 men). All patients included were examined at the National Institutes of Health (NIH) in Bethesda, Maryland, from 1998 to 2013. Connective tissue nevi were categorized per anatomic location and size. Lesions less than 1 cm in diameter were termed collagenomas. Shagreen patches were characterized as small (1 to Main Outcome and Measures Frequency, anatomic location, size, and histological appearance of connective tissue nevi in patients with TSC. Results Overall, 58 of 104 patients (median [range] age, 42 [19-70] years) with TSC (56%) had at least 1 connective tissue nevus on the trunk or thighs; of these, 28 of 58 patients (48%) had a solitary lesion, and 30 of 58 patients (52%) had 2 or more lesions. Overall, 120 lesions from 55 patients were classified by size; 46 lesions (38%) were collagenomas; 39 lesions (32%) were small shagreen patches; 21 lesions (18%), medium shagreen patches; and 14 lesions (12%), large shagreen patches. The distribution of lesions was 9% (n = 11), upper back; 29% (n = 35), middle back; 51% (n = 61), lower back; and 11% (n = 13), other locations. All 26 shagreen patches that were analyzed histopathologically had coarse collagen fibers and 24 of 26 stained with Miller elastic stain had decreased elastic fibers. On immunoblot analysis, fibroblasts grown from shagreen patches expressed higher levels of phosphorylated ribosomal protein S6 than paired fibroblasts from normal-appearing skin. Conclusions and Relevance Tuberous Sclerosis Complex–related connective tissue nevi are not limited to the lower back, and occasionally present on the central or upper back, buttocks, or thighs. Elastic fibers are typically decreased. Recognition of these variable presentations can be important for TSC diagnosis.
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dermatologic and dental aspects of the 2012 international Tuberous Sclerosis Complex consensus statements
JAMA Dermatology, 2014Co-Authors: Joyce M C Teng, Edward W Cowen, Mari Watayakaneda, Elizabeth S Gosnell, Patricia M Witman, Adelaide A Hebert, Greg Mlynarczyk, Keyoumars Soltani, Thomas N. DarlingAbstract:Importance The 2012 International Tuberous Sclerosis Complex Clinical Consensus Conference was convened to update the last consensus statement in 1998. Skin and dental lesions are common in Tuberous Sclerosis Complex (TSC) and are a frequent concern for patients. Recognition of these lesions is imperative for early diagnosis, given the treatment advances that may improve patient outcomes. Objective To detail recommendations for the diagnosis, surveillance, and management of skin and dental lesions in TSC. Evidence Review The TSC Dermatology and Dentistry Subcommittee, 1 of 12 subcommittees, reviewed the relevant literature from 1997 to 2012. Findings A consensus on skin and dental issues was achieved within the Dermatology and Dentistry Subcommittee before recommendations were presented, discussed, and agreed on in a group meeting of all subcommittees from June 14 to 15, 2012. Conclusions and Relevance Skin and dental findings comprise 4 of 11 major features and 3 of 6 minor features in the diagnostic criteria. A definite diagnosis of TSC is defined as the presence of at least 2 major features or 1 major and 2 or more minor features; in addition, a pathological mutation in TSC1 or TSC2 is diagnostic. Skin and oral examinations should be performed annually and every 3 to 6 months, respectively. Intervention may be indicated for TSC skin or oral lesions that are bleeding, symptomatic, disfiguring, or negatively affecting function. Options presented include surgical excision, laser(s), or use of a mammalian target of rapamycin inhibitor.
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ct of sclerotic bone lesions imaging features differentiating Tuberous Sclerosis Complex with lymphangioleiomyomatosis from sporadic lymphangioleiomymatosis
Radiology, 2010Co-Authors: Nilo A Avila, Thomas N. Darling, Andrew J Dwyer, Antoinette Rabel, Chienhui Hong, Joel MossAbstract:Sclerotic bone lesions evident at CT are more common and numerous in patients with Tuberous Sclerosis Complex (TSC) or TSC with lymphangioleiomyomatosis (LAM) than in patients with sporadic LAM.
Darcy A Krueger - One of the best experts on this subject based on the ideXlab platform.
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lymphangioleiomyomatosis association with underlying genotype in patients with Tuberous Sclerosis Complex
Annals of the American Thoracic Society, 2020Co-Authors: Xinlun Tian, David J Kwiatkowski, Darcy A Krueger, David Neal Franz, Jennifer Glass, Alexander J Towbin, Kristen L Sund, Francis X Mccormack, Nishant GuptaAbstract:Rationale: Lymphangioleiomyomatosis (LAM) is a female-predominant lung disease caused by mutations in the Tuberous Sclerosis Complex (TSC) genes TSC1 and TSC2.Objectives: To examine the association...
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pilot study of neurodevelopmental impact of early epilepsy surgery in Tuberous Sclerosis Complex
Pediatric Neurology, 2020Co-Authors: Leslie E Grayson, Mustafa Sahin, Jurriaan M Peters, Tarrant Mcpherson, Darcy A Krueger, Hope Northrup, Brenda E Porter, Gary Cutter, Sarah Okelley, Jessica KreftingAbstract:Abstract Background To determine if early epilepsy surgery mitigates detrimental effects of refractory epilepsy on development, we investigated surgical and neurodevelopmental outcomes in children with Tuberous Sclerosis Complex who underwent surgery before age two years. Methods Prospective multicenter observational study of 160 children with Tuberous Sclerosis Complex. Surgical outcome was determined for the seizure type targeted by surgery. We obtained Vineland Adaptive Behavior Scales, Second Edition (Vineland-II); Mullen Scales of Early Learning; and Preschool Language Scales, Fifth Edition, at age three, six, nine, 12, 18, 24, and 36 months. Surgical cases were compared with children without seizures, with controlled seizures, and with medically refractory seizures. Results Nineteen children underwent surgery (median age 17 months, range 3.7 to 21.3), and mean follow-up was 22.8 months (range 12 to 48). Surgical outcomes were favorable in 12 (63%, Engel I-II) and poor in seven (37%, Engel III-IV). Nine (47%) had new or ongoing seizures distinct from those surgically targeted. All children with seizures demonstrated longitudinal decline or attenuated gains in neurodevelopment, the surgical group scoring the lowest. Favorable surgical outcome was associated with increased Mullen Scales of Early Learning receptive and expressive language subscores compared with the medically refractory seizure group. A nonsignificant but consistent pattern of improvement with surgery was seen in all tested domains. Conclusions These pilot data show neurodevelopmental gains in some domains following epilepsy surgery. A properly powered, prospective multicenter observational study of early epilepsy surgery is needed, using both surgical and developmental outcome metrics.
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improvement in renal cystic disease of Tuberous Sclerosis Complex after treatment with mammalian target of rapamycin inhibitor
The Journal of Pediatrics, 2017Co-Authors: Brian J Siroky, Alexander J Towbin, Andrew T Trout, Hannah Schafer, Anna R Thamann, Karen Agricola, Cynthia Tudor, Jamie K Capal, Bradley P Dixon, Darcy A KruegerAbstract:Renal cysts occur in approximately 50% of patients with Tuberous Sclerosis Complex, but their clinical significance and response to treatment are unknown. Abdominal imaging of 15 patients with Tuberous Sclerosis Complex-associated renal cystic disease who had received mammalian target of rapamycin inhibitor therapy for other Tuberous Sclerosis Complex-related indications was evaluated. Reductions in cyst number, sum diameter, and volume were observed.
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Tuberous Sclerosis Complex diagnostic criteria update recommendations of the 2012 international Tuberous Sclerosis Complex consensus conference
Pediatric Neurology, 2013Co-Authors: Hope Northrup, Darcy A KruegerAbstract:BACKGROUND: Tuberous Sclerosis Complex is highly variable in clinical presentation and findings. Disease manifestations continue to develop over the lifetime of an affected individual. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment. Although significant advances have been made in the past 15 years in the understanding and treatment of Tuberous Sclerosis Complex, current clinical diagnostic criteria have not been critically evaluated or updated since the last clinical consensus conference in 1998. METHODS: The 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 subcommittees, each led by a clinician with advanced expertise in Tuberous Sclerosis Complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important diagnostic implications and was charged with reviewing prevalence and specificity of diseaseassociated clinical findings and their impact on suspecting and confirming the diagnosis of Tuberous Sclerosis Complex. RESULTS: Clinical features of Tuberous Sclerosis Complex continue to be a principal means of diagnosis. Key changes compared with 1998 criteria are the new inclusion of genetic testing results and reducing diagnostic classes from three (possible, probable, and definite) to two (possible, definite). Additional minor changes to specific criterion were made for additional clarification and simplification. CONCLUSIONS: The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of Tuberous Sclerosis Complex in affected individuals.
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Tuberous Sclerosis Complex surveillance and management recommendations of the 2012 international Tuberous Sclerosis Complex consensus conference
Pediatric Neurology, 2013Co-Authors: Darcy A Krueger, Hope NorthrupAbstract:BACKGROUND: Tuberous Sclerosis Complex is a genetic disorder affecting every organ system, but disease manifestations vary significantly among affected individuals. The diverse and varied presentations and progression can be life-threateningwithsignificantimpactoncostandqualityoflife.Currentsurveillanceandmanagementpracticesare highly variable among region and country, reflective of the fact that last consensus recommendations occurred in 1998 and an updated, comprehensive standard is lacking that incorporates the latest scientific evidence and current best clinical practices. METHODS: The 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 separate subcommittees, each led by a clinician with advanced expertise in Tuberous Sclerosis Complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important clinical management implications and was charged with formulating key clinical questions to address within its focus area, reviewing relevant literature, evaluating the strength of data, and providing a recommendation accordingly. RESULTS: The updated consensus recommendations for clinical surveillance and management in Tuberous Sclerosis Complex are summarized here. The recommendations are relevant to the entire lifespan of the patient, from infancy to adulthood, including both individuals where the diagnosis is newly made as well as individuals where the diagnosis already is established. CONCLUSIONS: The 2012 International Tuberous Sclerosis Complex Consensus Recommendations provide an evidence-based, standardized approach for optimal clinical care provided for individuals with Tuberous Sclerosis Complex.
