Article
Clinical Neurology
Srinivas Chivukula, Omeed Modiri, Alon Kashanian, Diana Babayan, George M. Ibrahim, Alexander G. Weil, Albert Tu, Joyce Y. Wu, Gary W. Mathern, Aria Fallah
Summary: Patients with TSC2 mutations exhibit poorer seizure outcomes following surgical treatments, with a lower rate of seizure control compared to those with TSC1 mutations, highlighting the importance of genetic mutation in predicting surgical response in tuberous sclerosis complex.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2021)
Article
Neurosciences
Ines Serra, Ana Stravs, Catarina Osorio, Maria Roa Oyaga, Martijn Schonewille, Christian Tudorache, Aleksandra Badura
Summary: TSC1 mutations are associated with a rare disorder called tuberous sclerosis complex 1, which is also linked to autism spectrum disorder (ASD). The cerebellum, among other brain regions, plays a role in ASD development, and Tsc1 haploinsufficiency can affect cerebellar development and disrupt the mTOR pathway.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Anita Maasz, Timea Bodo, Agnes Till, Gabor Molnar, Gyoergy Masszi, Gusztav Labossa, Zsuzsanna Herbert, Judit Bene, Kinga Hadzsiev
Summary: "Impact of Early Genetic Testing and Antiepileptic Drug Therapy on Brain Development." This study presents a three-year follow-up of a patient with tuberous sclerosis complex (TSC) and a utero-detected rhabdomyoma. Genetic testing revealed a de novo variant in the TSC2 gene, and the pregnant mother was treated with everolimus to regress the fetal tumor. Early genetic testing, in utero treatment, and early medication intervention had a significant impact on the developmental delay of the patient.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Bei Liu, Jiaxi Zhang, Xue Meng, Shelly M. Xie, Fang Liu, Heli Chen, Demin Yao, Minglei Li, Minghui Guo, Haitao Shen, Xianghong Zhang, Lingxiao Xing
Summary: This study reveals that ETV4 activates mTORC1 in non-small cell lung cancer cells by controlling HK1 expression and glycolysis-lactate production. Furthermore, G3BP2 and HDAC6 play important roles in inhibiting mTORC1 through regulating TSC2. Therefore, the HDAC6-G3BP2 complex might represent a critical adaptive mechanism for cell survival under low-lactate challenges.
Article
Genetics & Heredity
Cong Luo, Ye Zhang, Yu-shi Zhang, Ming-Xin Zhang, Jun Ning, Min-Feng Chen, Yuan Li, Lin Qi, Xiong-Bing Zu, Yang-Le Li, Yi Cai
Summary: This study examines the relationship between genotype and renal phenotype in a Chinese cohort with Tuberous Sclerosis Complex (TSC) and provides guidance for clinical decision-making. The results showed that patients with TSC2 variants are more likely to develop severe renal angiomyolipomas (AML) and require nephrectomy/partial nephrectomy or mTOR medication.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Neurosciences
Victoria A. Riley, Jennie C. Holmberg, Aidan M. Sokolov, David M. Feliciano
Summary: Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations in TSC1 or TSC2 genes. Loss of TSC2 affects the development of olfactory bulb granule cells (GCs) and alters gene expression involved in neural circuit formation. These findings highlight the crucial role of TSC2 in neural development and the molecular and morphological characteristics of inhibitory GCs.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Ekaterina Bychkova, Marina Dorofeeva, Aleksandr Levov, Alexey Kislyakov, Kristina Karandasheva, Vladimir Strelnikov, Kirill Anoshkin
Summary: Patients with tuberous sclerosis complex display cognitive, behavioral, and psychiatric impairments linked to cortical tubers. These tubers are caused by mutations in TSC1 or TSC2 genes, resulting in overactivation of the mTOR pathway. However, the formation of cortical tubers may involve more complex molecular mechanisms that require further investigation.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Genetics & Heredity
Hirofumi Kashii, Shinya Kasai, Atsushi Sato, Yoko Hagino, Yasumasa Nishito, Toshiyuki Kobayashi, Okio Hino, Masashi Mizuguchi, Kazutaka Ikeda
Summary: The study found that double mutations in the TSC1 and TSC2 genes lead to the occurrence of autism spectrum disorder, similar to TSC2 mutations. The double mutations cause significant changes in gene expression and contribute to the genotype-phenotype correlations in TSC.
Article
Cell Biology
Muireann Ni Bhaoighill, Juan M. Falcon-Perez, Felix Royo, Andrew R. Tee, Jason P. Webber, Elaine A. Dunlop
Summary: This study investigates the role of extracellular vesicles (EVs) in modulating the tumor microenvironment and their impact on the development of TSC tumors. It shows that EVs secreted from TSC2-deficient cells contain a specific protein cargo that promotes cell viability, proliferation, and growth factor secretion in the tumor microenvironment. The study also demonstrates that rapamycin can alter the cargo of EVs and reduce their ability to promote cell proliferation.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Clinical Neurology
Ji-Hye L. Hwang, Olga S. Perloff, Stephanie E. Gaus, Camila Benitez, Carolina Alquezar, Celica Q. Cosme, Alissa L. Nana, Sarat C. Vatsavayai, Eliana M. Ramos, Daniel H. Geschwind, Bruce L. Miller, Aimee W. Kao, William W. Seeley
Summary: This study found that individuals with tuberous sclerosis complex (TSC) are at risk for a unique age-related tauopathy. The tauopathy pathogenesis may involve TSC1, TSC2, and related molecular pathways.
ACTA NEUROPATHOLOGICA
(2023)
Review
Neurosciences
Tanjala T. Gipson, D. Kimbrough Oller, Daniel S. Messinger, Lynn K. Perry
Summary: Tuberous Sclerosis Complex (TSC) is a neurocutaneous disorder associated with a high prevalence of autism spectrum disorder (ASD), affecting around 50% of individuals. Understanding language development in individuals with TSC is crucial, as it may also have implications for those with other causes of syndromic and idiopathic ASD.
FRONTIERS IN HUMAN NEUROSCIENCE
(2023)
Article
Behavioral Sciences
Elizabeth Shephard, Fiona S. McEwen, Thomas Earnest, Nina Friedrich, Isabelle Mortl, Holan Liang, Emma Woodhouse, Charlotte Tye, Patrick F. Bolton
Summary: TSC patients exhibit hypoconnectivity in neural networks, particularly in the alpha frequency during resting-state and theta, alpha frequencies during task execution, which may be linked to the occurrence of ASD and ADHD symptoms.
Article
Biology
Jasbir Singh Dalal, Kellen Diamond Winden, Catherine Lourdes Salussolia, Maria Sundberg, Achint Singh, Truc Thanh Pham, Pingzhu Zhou, William T. Pu, Meghan T. Miller, Mustafa Sahin
Summary: The study revealed that dysfunction of FMRP and its targets may lead to molecular alterations in neural cells in tuberous sclerosis complex, suggesting that treatments aimed at restoring the function of these pathways could be beneficial.
Article
Clinical Neurology
Viera Kutna, Valerie B. O'Leary, Ehren Newman, Cyril Hoschl, Saak Ovsepian
Summary: Tuberous sclerosis complex is a genetic disorder caused by mutations in TSC1 and TSC2 genes, resulting in uncontrolled cell growth and division leading to benign tumors. While human brains manifest a range of neuropsychiatric symptoms, rat brains show differences in pathology and behavior, suggesting incomplete understanding of the disease.
Article
Genetics & Heredity
Kaili Yin, Nan Lin, Qiang Lu, Liri Jin, Yan Huang, Xiangqin Zhou, Kaifeng Xu, Qing Liu, Xue Zhang
Summary: This study reports the clinical and molecular characteristics of 18 families with TSC. Through high-throughput DNA sequencing, 17 mutations were identified, with TSC-2 mutations being more common. Facial angiofibromas and epilepsy were the most prevalent clinical features. Treatment with anti-seizure medication or in combination with rapamycin showed clinical remission in most patients. Additionally, a correlation between TSC-1/TSC-2 mutations and age of onset and response to medication was observed.
Article
Audiology & Speech-Language Pathology
Alberto Maria Saibene, Emanuela Fuccillo, Giovanni Felisati, Giorgia Carlotta Pipolo, Valentina Chiesa, Maria Paola Canevini, Alberto Maccari, Martha De Gasperis, Nicole Pizzorni, Antonio Schindler
Summary: The aim of this study was to evaluate vocal outcomes in patients undergoing vagus nerve stimulation therapy for drug-resistant epilepsy. The results showed that VNS implantation led to laryngeal motility alterations and voice changes. Patients with intact vocal fold function at rest performed worse in acoustic voice analysis during VNS activation, and VNS activation resulted in overall worsening of the perceptual and acoustically analyzed voice quality.
Article
Genetics & Heredity
Marcello Niceta, Simone Pizzi, Francesca Inzana, Angela Peron, Somayeh Bakhtiari, Mathilde Nizon, Jonathan Levy, Cecilia Mancini, Benjamin Cogne, Francesca Clementina Radio, Emanuele Agolini, Dario Cocciadiferro, Antonio Novelli, Mustafa A. Salih, Maria Paola Recalcati, Rosangela Arancio, Marianne Besnard, Anne-Claude Tabet, Michael C. Kruer, Manuela Priolo, Bruno Dallapiccola, Marco Tartaglia
Summary: CNOT2 haploinsufficiency is the underlying cause of a rare neurodevelopmental disorder called Intellectual Developmental disorder with NAsal speech, Dysmorphic Facies, and variable Skeletal anomalies (IDNADFS, OMIM 618608). This disorder shares clinical similarities with chromosome 12q15 deletion syndrome, suggesting that CNOT2 haploinsufficiency plays a significant role in the latter. CNOT2 is a member of the CCR4-NOT complex, which regulates various cellular processes. The clinical profile of IDNADFS remains incompletely understood due to the limited number of reported cases.
Article
Clinical Neurology
Emanuele Cerulli Irelli, Enrico Cocchi, Georgia Ramantani, Antonella Riva, Roberto Horacio Caraballo, Alessandra Morano, Loretta Giuliano, Tulay Yilmaz, Eleni Panagiotakaki, Francesca F. Operto, Beatriz Gonzalez Giraldez, Simona Balestrini, Katri Silvennoinen, Sara Casciato, Marion Comajuan, Francesco Fortunato, Anna Teresa Giallonardo, Rimma Gamirova, Antonietta Coppola, Giancarlo Di Gennaro, Angelo Labate, Vito Sofia, Gerhard Josef Kluger, Antonio Gambardella, Dorothee G. A. Kasteleijn-NolstTrenite, Betul Baykan, Sanjay M. Sisodiya, Alexis Arzimanoglou, Pasquale Striano, Carlo Di Bonaventura
Summary: Based on age at epilepsy onset (AEO), this study identified three subtypes of objective epilepsy with eyelid myoclonia (EEM) and analyzed their distinct clinical features. Early onset EEM was associated with higher rates of intellectual disability, antiseizure medication refractoriness, and psychiatric comorbidities, while late onset EEM had the highest proportion of myoclonia involving body regions other than eyelids and generalized tonic-clonic seizures. Intermediate onset EEM had the lowest observed rate of additional findings. Family history of EEM was more frequent in the subtypes with intermediate and late onset. Patients with body-MYO showed higher rates of migraine and generalized tonic-clonic seizures.
Article
Biochemistry & Molecular Biology
Sara Perego, Valentina Alari, Gianluca Pietra, Andrea Lamperti, Alessandro Vimercati, Nicole Camporeale, Maria Garzo, Francesca Cogliati, Donatella Milani, Aglaia Vignoli, Angela Peron, Lidia Larizza, Tommaso Pizzorusso, Silvia Russo
Summary: This study investigated the MECP2 gene variants associated with different pathological phenotypes in Rett syndrome. iPSC-neurons were generated from the blood of Rett syndrome patients and compared with control neurons. Morphological and electrophysiological analyses revealed specific cellular phenotypes correlated with different MECP2 mutations. The findings suggest that these cellular markers could be used for drug testing and translational research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Psychiatry
Katherine Turner, Anna Castelnovo, Lampros Perogamvros, Robert C. Cloninger, Andrea Galbiati, Alessia Bertolotti, Paola Proserpio, Michele Terzaghi, Raffaele Manni, Luigi Ferini Strambi, Lino Nobili, Mauro Manconi, Maria Paola Canevini, Elena Zambrelli
Summary: This study aimed to compare the personality traits of children and adolescents with and without disorders of arousal (DOA). The results showed that patients with DOA had higher scores on assessment measures such as PADSS and SDSC, as well as higher scores on novelty seeking, harm avoidance, and self-transcendence subscales in the JTCI. They also had lower scores on the self-directedness subscale.
JOURNAL OF PSYCHIATRIC RESEARCH
(2023)
Article
Health Care Sciences & Services
Katherine Turner, Francesca La Briola, Aglaia Vignoli, Elena Zambrelli, Valentina Chiesa, Laura Fongoni, Olivia Baldi, Maria Paola Canevini
Summary: The study aims to characterize the behavioral profiles of adolescents with epilepsy, assess psychopathological disorders, and investigate the relationships between epilepsy, psychological functioning, and clinical variables. The findings reveal that 55.2% of adolescents with epilepsy have emotional disturbances, including body dissatisfaction, anxiety, interpersonal conflicts, family problems, uncertainty about the future, and self-esteem/well-being disorders. Gender and poor seizure control are associated with specific emotional features. Therefore, it is important to screen for emotional distress, recognize impairments, and provide appropriate treatment and follow-up for adolescents with epilepsy.
Article
Behavioral Sciences
G. Ferrera, E. Ricci, A. Vignoli, M. N. Savini, I. Vigano, V. Chiesa, D. Caputo, E. Zambrelli, F. La Briola, K. Turner, M. P. Canevini
Summary: This retrospective study aimed to evaluate the effects of highly purified, pharmaceutical-grade CBD on seizure frequency, quality of life (QoL), behavior, parental stress, and sleep in patients with drug-resistant epilepsy (DRE). The results showed that CBD decreased seizure frequency in 50% of the patients, with no serious adverse effects. CBD did not significantly affect sleep or parental stress, but it improved social interaction in QoL. These findings suggest that CBD is a safe and effective anti-seizure medication with potential benefits in other childhood disabilities.
EPILEPSY & BEHAVIOR
(2023)
Meeting Abstract
Clinical Neurology
P. Proserpio, E. Zambrelli, A. Lanza, A. Dominese, R. Di Giacomo, R. Quintas, I. Tramacere, A. Rubino, K. Turner, C. Colosio, F. Cattaneo, M. P. Canevini, A. D'Agostino, E. C. Agostoni, G. Didato
Proceedings Paper
Engineering, Electrical & Electronic
Stefania Coelli, Alessandra Calcagno, Eleonora Iascone, Ludovica Gaspari, Maria Paola Canevini, Anna Maria Bianchi
Summary: Electroencephalography (EEG) has been widely used for studying neurodevelopmental disorders like ADHD. In addition to traditional spectral measures, brain functional connectivity has become a focus of research. This study explored functional connectivity changes during cognitive tasks in ADHD and healthy children, finding that ADHD children had less efficient network integration.
2022 IEEE 21ST MEDITERRANEAN ELECTROTECHNICAL CONFERENCE (IEEE MELECON 2022)
(2022)
Meeting Abstract
Clinical Neurology
M. P. Canevini, O. Mecarelli, G. Di Gennaro, A. D'Aniello, A. T. Giallonardo, U. Aguglia, G. Assenza, A. Gambardella, G. Coppola, P. Veggiotti, V. De Giorgis, C. Cerminara, F. Vigevano, S. Goldman, A. Patten, P. Mansi, A. Milan, A. Gentile
Meeting Abstract
Clinical Neurology
A. Gambardella, G. Di Gennaro, A. D'Aniello, A. T. Giallonardo, O. Mecarelli, U. Aguglia, G. Assenza, M. P. Canevini, G. Coppola, P. Veggiotti, V. De Giorgis, C. Cerminara, F. Vigevano, S. Goldman, A. Patten, P. Mansi, A. Milan, A. Gentile
Meeting Abstract
Clinical Neurology
L. Turacchi, A. Lividini, V. Rovelli, K. Turner, E. Salvatici, G. Banderali, M. P. Canevini, E. Zambrelli
Article
Genetics & Heredity
Angela Peron, Maria Paola Canevini, Filippo Ghelma, Rosangela Arancio, Miriam Nella Savini, Aglaia Vignoli
Summary: Clinical manifestations and management of adult patients with Rett syndrome were assessed in this study. The results showed that adult patients with Rett syndrome still experience a range of symptoms and issues, such as epilepsy, sleep problems, and behavioral disorders. A transitional program and a multidisciplinary team are needed to optimize the clinical management of these patients.
JOURNAL OF MEDICAL GENETICS
(2022)