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Drugs 2022 May 21. Epub 2022 May 21.

Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

Ganaxolone (ZTALMY; Marinus Pharmaceuticals) is a synthetic neuroactive steroid that acts as a positive allosteric modulator of the gamma-aminobutyric acid (GABA) receptor complex. Ganaxolone received its first approval in March 2022 in the USA for the treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients 2 years of age and older. Approval was based on the results of a multinational phase III trial, in which ganaxolone was effective in reducing seizure frequency in children and adolescents with CDD. Read More

Neurogenetics 2022 May 21. Epub 2022 May 21.

Mckusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.

Tuberous sclerosis complex (TSC) is mainly caused by variants in TSC1 and TSC2, which encodes hamartin protein and tuberin protein, respectively. Here, we report clinical and molecular characteristics of 18 families with TSC. High-throughput DNA sequencing was employed to detect variants in all the exons and flanking region of TSC1 and TSC2. Read More

PLoS One 2022 19;17(5):e0268597. Epub 2022 May 19.

Comprehensive Epilepsy Center, New York University School of Medicine, New York, New York, United States of America.

Background: Tuberous sclerosis complex (TSC) and some focal cortical dysplasias (FCDs) are associated with dysfunctional mTOR signaling, resulting in increased cell growth and ribosomal S6 protein phosphorylation (phospho-S6). mTOR inhibitors can reduce TSC tumor growth and seizure frequency, and preclinical FCD studies indicate seizure suppression. This pilot study evaluated safety of mTOR inhibitor everolimus in treatment resistant (failure of >2 anti-seizure medications) TSC and FCD patients undergoing surgical resection and to assess mTOR signaling and molecular pathways. Read More

Curr Rev Clin Exp Pharmacol 2022 May 17. Epub 2022 May 17.

Nephrology Section, Hospital Universitario Principe de Asturias, Alcala de Henares, Madrid, Spain.

Background: Autosomal dominant polycystic kidney disease (ADPKD) may coexist with other genetic disorders, such as tuberous sclerosis, when deletion in TSC2/PKD1 genes occurs. Recently, the effect of tolvaptan has been explored in ADPKD patients alone, but its safety and efficacy on TSC2/PKD1 contiguous gene syndrome is unknown.

Case Presentation: This report describes the case of an asymptomatic patient with TSC2/PKD1 contiguous gene syndrome that fulfills the imaging criteria for initiating the treatment with tolvaptan. Read More

Cell Rep 2022 May;39(7):110824

Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Electronic address:

The tuberous sclerosis complex (TSC) 1 and 2 proteins associate with TBC1D7 to form the TSC complex, which is an essential suppressor of mTOR complex 1 (mTORC1), a ubiquitous driver of cell and tissue growth. Loss-of-function mutations in TSC1 or TSC2, but not TBC1D7, give rise to TSC, a pleiotropic disorder with aberrant activation of mTORC1 in various tissues. Here, we characterize mice with genetic deletion of Tbc1d7, which are viable with normal growth and development. Read More

J Kidney Cancer VHL 2022 22;9(2):13-18. Epub 2022 Apr 22.

Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Renal angiomyolipomas (AMLs) are a subset of perivascular epithelioid cell neoplasms (PEComas) that are associated with tuberous sclerosis complex (TSC). Epithelioid angiomyolipomas (EAMLs) are a rare variant of AML with more aggressive propensities. EAMLs with malignant potential can be difficult to distinguish from relatively benign AMLs and other renal tumors. Read More

Epilepsy Behav 2022 May 14:108701. Epub 2022 May 14.

Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Trieste, Italy.

Front Neurol 2022 29;13:704978. Epub 2022 Apr 29.

Department of Neurology and Epileptology, Children's Memorial Health Institute, Warsaw, Poland.

Background: Epilepsy develops in 70-90% of children with Tuberous Sclerosis Complex (TSC) and is often resistant to medication. Treatment with mTOR pathway inhibitors is an important therapeutic option in drug-resistant epilepsy associated with TSC. Our study evaluated the antiepileptic effect of rapamycin in the pediatric population of patients diagnosed with TSC. Read More

Neurosurg Focus 2022 05;52(5):E1

4Department of Neurosurgery, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.

Neurosurg Focus 2022 05;52(5):E2

1Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

Objective: Neurocutaneous syndromes have variable multisystem involvement. The multiorgan involvement, potential pathologies, and various treatment options necessitate collaboration and open discussion to ensure optimal treatment in any given patient. These disorders provide quintessential examples of chronic medical conditions that require a lifelong, multidisciplinary approach. Read More

Neurosurg Focus 2022 05;52(5):E6

2Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and.

Objective: Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem neurocutaneous disorder associated with cortical tubers, brain lesions seen in nearly all patients with TSC, which are frequently epileptogenic. Seizures are often the earliest clinical manifestation of TSC, leading to epilepsy in over 70% of patients. Medical management with antiepileptic drugs constitutes early therapy, but over 50% develop medically refractory epilepsy, necessitating surgical evaluation and treatment. Read More

Cureus 2022 Apr 5;14(4):e23861. Epub 2022 Apr 5.

Department of Urology, Hospital General de Mexico, Mexico City, MEX.

Wünderlich syndrome (WS) is a spontaneous retroperitoneal hemorrhage confined to the subcapsular or perinephric space without a history of trauma. Since it is a rare condition with a significant mortality rate if not treated timely, it is essential to identify its risk factors and early clinical manifestations for a favorable outcome. Various conditions are associated, but the most common causes are benign and malignant renal neoplasms. Read More

Urol Case Rep 2022 May 26;42:102042. Epub 2022 Feb 26.

Department of Radiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang Province, China.

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a special classification of indolent kidney tumors newly discovered in recent years. It is extremely uncommon, with only a few clinical and pathological reports, and its imaging description are very rare. Here, we present a case of ESC RCC. Read More

Ann Dermatol Venereol 2022 May 5. Epub 2022 May 5.

Department of Dermatology, Montpellier University Hospital Center, 34295 Montpellier, France.

Background: Tuberous sclerosis complex (TSC) is a genetic disorder involving the TSC1 or TSC2 gene. Skin signs are prominent, but dermatological data are scarce. This study aims to describe the cutaneous signs of TSC with the genotype. Read More

Mod Rheumatol Case Rep 2022 May 5. Epub 2022 May 5.

Department of Rheumatology and Allergology, NHO Osaka Minami Medical Center, Kawachinagano, Japan.

A 26-year-old woman with tuberous sclerosis complex (TSC) received outpatient treatment for the complication of systemic lupus erythematosus (SLE) at our hospital. She visited our hospital with a chief complaint of pitting edema in bilateral lower legs for three days. The urinalysis showed massive proteinuria with a lot of WBC casts. Read More

Quant Imaging Med Surg 2022 May;12(5):2995-2999

Department of Radiology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.

Brain Dev 2022 Apr 29. Epub 2022 Apr 29.

Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan. Electronic address:

Introduction: Adrenocorticotropic hormone (ACTH) therapy is a first-line treatment for infantile spasms, which may rarely cause intracranial hemorrhage. However, the changes in blood coagulation during ACTH therapy are poorly understood, with little description in the management guidelines.

Objective: To assess the changes in blood coagulation during ACTH therapy. Read More

Epilepsy Behav 2022 Jun 29;131(Pt A):108704. Epub 2022 Apr 29.

Child Neurology Section, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States. Electronic address:

Front Neurosci 2022 13;16:806876. Epub 2022 Apr 13.

Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Autism spectrum disorder (ASD) is a basket term for neurodevelopmental disorders characterized by marked impairments in social interactions, repetitive and stereotypical behaviors, and restricted interests and activities. Subtypes include (A) disorders with known genetic abnormalities including fragile X syndrome, Rett syndrome, and tuberous sclerosis and (B) idiopathic ASD, conditions with unknown etiologies. Positron emission tomography (PET) is a molecular imaging technology that can be utilized for dynamic and quantitative research, and is a valuable tool for exploring pathophysiological mechanisms, evaluating therapeutic efficacy, and accelerating drug development in ASD. Read More

Actas Dermosifiliogr 2022 Apr 27. Epub 2022 Apr 27.

Servicio de Dermatología, Hospital Universitario de Pontevedra, España.

Cold Spring Harb Mol Case Stud 2022 04 28;8(3). Epub 2022 Apr 28.

Department of Pathology, University of Otago, Dunedin 9016, New Zealand.

Tuberous sclerosis complex (TSC) is an inheritable disorder characterized by the formation of benign yet disorganized tumors in multiple organ systems. Germline mutations in the (hamartin) or more frequently (tuberin) genes are causative for TSC. The malignant manifestations of TSC, pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipoma (AML), may also occur as independent sporadic perivascular epithelial cell tumor (PEComa) characterized by somatic mutations. Read More

Kidney Int 2022 Apr 25. Epub 2022 Apr 25.

Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address:

Ribosomal protein S6 (rpS6) phosphorylation mediates the hypertrophic growth of kidney proximal tubule cells. However, the role of rpS6 phosphorylation in podocyte hypertrophy and podocyte loss during the pathogenesis of focal segmental glomerulosclerosis (FSGS) remains undefined. Here, we examined rpS6 phosphorylation levels in kidney biopsy specimens from patients with FSGS and in podocytes from mouse kidneys with Adriamycin-induced FSGS. Read More

Actas Dermosifiliogr 2022 Feb 18. Epub 2022 Feb 18.

Servicio de Dermatología, Hospital Universitario de Pontevedra, Pontevedra, España.

Background: Cutaneous manifestations are complicated to treat in rare diseases. The main aim of this study was to analyze the impact of compounded drugs prepared by hospital pharmacists on the quality of life of patients with genodermatoses.

Material And Methods: We undertook a cross-sectional study of patients with genodermatoses treated with topical medications compounded and dispensed by the pharmacy at Complejo Hospitalario Universitario in Pontevedra, Spain. Read More

Microbiol Spectr 2022 Apr 25:e0186421. Epub 2022 Apr 25.

Medical School of Chinese PLA, Beijing, China.

Autism spectrum disorder (ASD), a highly hereditary and heterogeneous neurodevelopmental disorder, is influenced by genetic and environmental factors. Tuberous sclerosis complex (TSC) is a common syndrome associated with ASD. Cytomegalovirus (CMV) infection is an environmental risk factor for ASD. Read More

Neurol Clin 2022 May 31;40(2):405-420. Epub 2022 Mar 31.

Department of Neurological Surgery, The Ohio State University Wexner Medical Center, The Ohio State University, 410 West 10th Avenue, Doan Hall N1019, Columbus, Ohio 43210, USA.

Familial neoplastic syndromes commonly impact the central and peripheral nervous systems. The most common neoplastic syndromes clinically relevant to neurology and neurologic surgery, include neurofibromatosis type 1, neurofibromatosis type 2, and Von Hippel-Lindau disease. We define the epidemiology, genetics, clinical presentation, and manifestations, as well as screening recommendations and management paradigms for these syndromes and other familial neoplastic syndromes that affect the nervous system. Read More

Front Pharmacol 2022 8;13:802334. Epub 2022 Apr 8.

Royal Sussex County Hospital, Brighton, United Kingdom.

The TuberOus SClerosis registry to increase disease Awareness (TOSCA) Post-Authorization Safety Study (PASS) was a non-interventional, multicenter, safety substudy that assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) receiving everolimus for its licensed indications in the European Union (EU). This substudy also aimed to address TSC-associated neuropsychiatric disorders (TAND), sexual development, and male infertility. Eligible patients were enrolled from 39 sites across 11 countries in the EU. Read More

Genes (Basel) 2022 04 11;13(4). Epub 2022 Apr 11.

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Science, 117485 Moscow, Russia.

Our study reviewed abnormalities in spontaneous, as well as event-related, brain activity in syndromes with a known genetic underpinning that are associated with autistic symptomatology. Based on behavioral and neurophysiological evidence, we tentatively subdivided the syndromes on primarily hyper-sensitive (Fragile X, Angelman) and hypo-sensitive (Phelan-McDermid, Rett, Tuberous Sclerosis, Neurofibromatosis 1), pointing to the way of segregation of heterogeneous idiopathic ASD, that includes both hyper-sensitive and hypo-sensitive individuals. This segmentation links abnormalities in different genes, such as , and , that are causative to the above-mentioned syndromes and associated with synaptic transmission and cell growth, as well as with translational and transcriptional regulation and with sensory sensitivity. Read More

Children (Basel) 2022 Apr 2;9(4). Epub 2022 Apr 2.

Department of Neurosurgery, University Hospital of Basel, 4031 Basel, Switzerland.

Background: Due to advances in the treatment of pediatric brain tumors (PBT), an increasing number of patients are experiencing the transition from the pediatric to the adult health care system. This requires efficient transitional models.

Methods: We systematically reviewed the literature regarding PBT concerning different transitional models and aspects of the transitional period. Read More

Biomedicines 2022 Mar 31;10(4). Epub 2022 Mar 31.

Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.

Previous studies have suggested that the topical mechanistic target of rapamycin (mTOR) inhibitors may be effective in treating facial angiofibromas in patients with tuberous sclerosis complex (TSC). Various concentrations of topical sirolimus for TSC have been tested, but their comparative efficacy and safety remained unclear. To assess the effects of topical mTOR inhibitors in treating facial angiofibromas, we conducted a systematic review and network meta-analysis (NMA) and searched MEDLINE, Embase, and Cochrane Library for relevant randomized controlled trials on 14 February 2022. Read More

Neurobiol Dis 2022 Jul 20;169:105737. Epub 2022 Apr 20.

Department of Biology, University of Virginia, Charlottesville, VA 22904, USA; Department of Cell Biology, University of Virginia, Charlottesville, VA 22904, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA 22904, USA.

Altered mitochondrial DNA (mtDNA) occurs in neurodegenerative disorders like Alzheimer's disease (AD); how mtDNA synthesis is linked to neurodegeneration is poorly understood. We previously discovered Nutrient-induced Mitochondrial Activity (NiMA), an inter-organelle signaling pathway where nutrient-stimulated lysosomal mTORC1 activity regulates mtDNA replication in neurons by a mechanism sensitive to amyloid-β oligomers (AβOs), a primary factor in AD pathogenesis (Norambuena et al., 2018). Read More