Characteristics of cortical tubers in tuberous sclerosis

Туберозный склероз - орфанное аутосомно-доминантное наследственное заболевание, причиной которого являются инактивирующие мутации в генах TSC1 или TSC2, сопровождающиеся гиперактивацией сигнального пути mTOR, отвечающего за регуляцию роста, пролиферации, выживаемости клеток, а также аутофагии. Одним из основных клинических симптомов туберозного склероза является наличие туберов в головном мозге. Данные образования характеризуются нарушениями кортикальной ламинации, появлением аномальных нейронов и выраженным глиозом. Известно, что количество кортикальных туберов коррелирует с развитием нейропсихиатрических расстройств, в том числе фармакорезистентной эпилепсии. В данной статье освещены вопросы молекулярной генетики туберозного склероза, приведена гистопатологическая характеристика кортикальных туберов, рассмотрен молекулярный механизм морфогенеза кортикальных туберов, а также приведены данные о связи этих образований с развитием неврологических проявлений и методах их лечения. Tuberous sclerosis is an orphan autosomal dominant hereditary disease caused by inactivating mutations in the TSC1 or TSC2 genes, accompanied by hyperactivation of the mTOR signaling pathway, which is responsible for the regulation of growth, proliferation, cell survival, and autophagy. One of the main clinical symptoms of tuberous sclerosis is the formation of tubers in the brain. These formations are characterized by disorders of the cortical lamination, the appearance of abnormal neurons and severe gliosis. It is known that the presence of cortical tubers correlates with the development of neuropsychiatric disorders, including drug-resistant epilepsy. This article highlights the issues of molecular genetics of tuberous sclerosis, presents the histopathological characteristics of cortical tubers, considers mechanism of morphogenesis of cortical tubers, and also presents the data on relationship of these formations with the development of neurological manifestations and methods of their treatment.

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Retracted Tuberous sclerosis complex: molecular pathogenesis and animal models

Neurosurgical FOCUS ◽

10.3171/foc.2006.20.1.5 ◽

2006 ◽

Vol 20 (1) ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Leandro R. Piedimonte ◽

Ian K. Wailes ◽

Howard L. Weiner

Keyword(s):

Animal Models ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Conditional Knockout ◽

Signaling Complex ◽

Normal Functions ◽

Similar Disease ◽

The Central Nervous System ◽

Cortical Tubers ◽

The Brain

Mutations in one of two genes, TSC1 and TSC2, result in a similar disease phenotype by disrupting the normal interaction of their protein products, hamartin and tuberin, which form a functional signaling complex. Disruption of these genes in the brain results in abnormal cellular differentiation, migration, and proliferation, giving rise to the characteristic brain lesions of tuberous sclerosis complex (TSC) called cortical tubers. The most devastating complications of TSC affect the central nervous system and include epilepsy, mental retardation, autism, and glial tumors. Relevant animal models, including conventional and conditional knockout mice, are valuable tools for studying the normal functions of tuberin and hamartin and the way in which disruption of their expression gives rise to the variety of clinical features that characterize TSC. In the future, these animals will be invaluable preclinical models for the development of highly specific and efficacious treatments for children affected with TSC.

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Case Report on: Tuberous Sclerosis

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i52a33567 ◽

2021 ◽

pp. 140-147

Author(s):

Ruchira Ankar ◽

Archana Dhengare ◽

Arti Raut ◽

Seema Singh ◽

Samruddhi Gujar

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Genetic Disorder ◽

Hereditary Disease ◽

Chief Complaint ◽

Benign Tumors ◽

Surrounding Area ◽

Benign Tumours ◽

Intellectual Incapacity ◽

The Brain

Introduction: Tuberous sclerosis is a rare hereditary disease that creates noncancerous tumours in the brain, kidneys, heart, liver, eyes, lungs, and skin. Seizures, intellectual incapacity, developmental delays, and behavioral issues are just a few of the warning symptoms. Like Skin problems, and lung and kidney problems. A hereditary mutation in one of two genes causes TSC.TSC1 and TSC2 are two distinct TSC types. The proteins hemartin and tuberin, which act as tumour suppressors and govern cell proliferation and differentiation, are produced by these genes. [1]. Background: Tuberous sclerosis complex (TSC) is a rare genetic disorder that affects 1 in every 6,000 to 1 in every 18,000 people. It's a life-threatening condition caused by the formation of benign tumors/lesions in several organs. Tumors can affect organ growth and/or function and are frequent in the brain, heart, skin, kidneys, and lungs. The number of organs affected, as well as the size of tumours inside each organ, varies greatly. As a result, the disease's symptoms are extremely variable and unexpected [2]. Case Presentation: A 35-year old female admitted to AVBRH on date 25/11/2021 with the chief complaint of fever chills, nausea, vomiting and itching and back skin over mouth and eye surrounding area since in 10 days. History of Present Illness: Tuberous sclerosis, also known as tuberous sclerosis complex, is a rare genetic disease that causes non-cancerous (benign) tumours in the brain, skin, kidneys, heart, eyes, and lungs. A 35-yearold female admitted to hospital on date 25/11/2020 with the chief complaint was fever chills, nausea, vomiting and itching and back skin over mouth and eye surrounding area since in 4month. Interventions: The patient was treated the patient was started on Injection- Ceftriaxone, 1gm - Intravenous – BD- Antibiotic, Injection- Pan, 40mg – Intravenous- BD – Antacid, Injection- Livipril, 100mg – Intravenous- BD- Anticonvulsant, Injection- Paracetamol, 150mg – Intra muscular- SOS- Antipyretic. Conclusion: During hospital stay with the chief complaint of patient are fever chills, nausea, vomiting and itching and back skin over mouth and eye surrounding area since in 10 days. Her situation was critical, therefore she was brought to AVBR Hospital and treatment was started right away.

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Polymeric Nanoparticles for Brain Drug Delivery - A Review

Current Drug Metabolism ◽

10.2174/1389200221666200508074348 ◽

2020 ◽

Vol 21 (9) ◽

pp. 649-660

Author(s):

Subashini Raman ◽

Syed Mahmood ◽

Ayah R. Hilles ◽

Md Noushad Javed ◽

Motia Azmana ◽

...

Keyword(s):

Drug Delivery ◽

Surface Modification ◽

Polymeric Nanoparticles ◽

Drug Loading ◽

Preparation Methods ◽

Brain Drug Delivery ◽

Polymeric Nanoparticle ◽

Relationship Of ◽

The Relationship ◽

The Brain

Background: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery. Methods: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs. Results: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain. Conclusion: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

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Expression and cellular distribution of FGF13 in cortical tubers of the tuberous sclerosis complex

Neuroscience Letters ◽

10.1016/j.neulet.2021.135714 ◽

2021 ◽

Vol 749 ◽

pp. 135714

Author(s):

Kefu Wu ◽

Jiong Yue ◽

Kaifeng Shen ◽

Jiaojiang He ◽

Gang Zhu ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Cellular Distribution ◽

Cortical Tubers

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The relationship of morphometric changes of the brain with IL-6 levels, systemic inflammation and immune disturbances in the patients with schizophrenia

Procedia Computer Science ◽

10.1016/j.procs.2021.06.064 ◽

2021 ◽

Vol 190 ◽

pp. 553-559

Author(s):

Irina K. Malashenkova ◽

Vadim L. Ushakov ◽

Sergey A. Krynskiy ◽

Daniil P. Ogurtsov ◽

Nikita A. Khailov ◽

...

Keyword(s):

Systemic Inflammation ◽

Relationship Of ◽

The Relationship ◽

The Brain

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Neuron–Glia Interactions in Tuberous Sclerosis Complex Affect the Synaptic Balance in 2D and Organoid Cultures

Cells ◽

10.3390/cells10010134 ◽

2021 ◽

Vol 10 (1) ◽

pp. 134

Author(s):

Stephanie Dooves ◽

Arianne J. H. van Velthoven ◽

Linda G. Suciati ◽

Vivi M. Heine

Keyword(s):

Tuberous Sclerosis ◽

Glial Cells ◽

Tuberous Sclerosis Complex ◽

Neuronal Development ◽

Transmembrane Proteins ◽

Significant Burden ◽

Epidermal Growth ◽

And Control ◽

Egf Signaling ◽

The Brain

Tuberous sclerosis complex (TSC) is a genetic disease affecting the brain. Neurological symptoms like epilepsy and neurodevelopmental issues cause a significant burden on patients. Both neurons and glial cells are affected by TSC mutations. Previous studies have shown changes in the excitation/inhibition balance (E/I balance) in TSC. Astrocytes are known to be important for neuronal development, and astrocytic dysfunction can cause changes in the E/I balance. We hypothesized that astrocytes affect the synaptic balance in TSC. TSC patient-derived stem cells were differentiated into astrocytes, which showed increased proliferation compared to control astrocytes. RNA sequencing revealed changes in gene expression, which were related to epidermal growth factor (EGF) signaling and enriched for genes that coded for secreted or transmembrane proteins. Control neurons were cultured in astrocyte-conditioned medium (ACM) of TSC and control astrocytes. After culture in TSC ACM, neurons showed an altered synaptic balance, with an increase in the percentage of VGAT+ synapses. These findings were confirmed in organoids, presenting a spontaneous 3D organization of neurons and glial cells. To conclude, this study shows that TSC astrocytes are affected and secrete factors that alter the synaptic balance. As an altered E/I balance may underlie many of the neurological TSC symptoms, astrocytes may provide new therapeutic targets.

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Mood symptoms Associated with CADASIL Syndrome: A Case Report

CNS Spectrums ◽

10.1017/s1092852920002278 ◽

2021 ◽

Vol 26 (2) ◽

pp. 144-144

Author(s):

Asad Shaikh ◽

Joel Idowu

Keyword(s):

Case Report ◽

Clinical Symptoms ◽

Psychiatric Symptoms ◽

Small Vessel Disease ◽

Altered Mental Status ◽

Hereditary Disease ◽

African American Female ◽

Psychiatric Disturbance ◽

Rare Type ◽

Parietal Lobes

AbstractObjectiveTo discuss the psychiatric symptoms that are associated with CADASIL syndrome Abstract Cerebral:Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare type of hereditary disease involving the small cerebral vessels. The clinical symptoms are various and include recurrent ischemic strokes, migraine with aura, seizures with epilepsy, psychiatric problems such as mood disturbances, and progressive cognitive decline leading to dementia. This disease needs awareness amongst the psychiatrists even though it is discussed much more in neurology literature. Psychiatric symptoms are seen in 20–41% of patients with CADASIL syndrome (1, 2). Psychiatric symptoms are actually the initial presentation in 15% of the cases. (3) The psychiatric disturbance most reported are mood disturbances (9–41%) especially depression. Here a 42-year-old African American female was brought to the hospital emergency room after she was found wandering in the streets. Psychiatry was consulted for altered mental status. Upon evaluation by the psychiatric consult service she was only oriented to person, depressed, anxious and complaining of headaches. Initial CT scan showed marked small vessel disease and old lacunar infarcts in the basal ganglia and right corona radiata. Magnetic Resonance Imaging (MRI) of the brain showed acute infarcts in the right posterior frontal and right parietal lobes along with old infarcts. Her symptoms and findings on imaging were consistent with CADASIL syndrome. Once the diagnosis was confirmed and prior records were obtained patient was resumed on an antidepressant and anxiolytic.ConclusionThe purpose of this case report was to discuss psychiatric symptoms associated with CADASIL syndrome. Although there has been research showing a relationship between vascular disease and depression, a review of the literature suggests that there needs to be more research done to explore other psychiatric disturbances that may be seen with this syndrome. Psychiatric symptoms that are untreated can have the potential to further impact the quality of life therefore psychiatrists need to be aware of this syndrome in order to treat these patients promptly.References1 https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0778-8 2 http://dx.doi.org/10.32474/OJNBD.2018.01.000101 3 https://pdfs.semanticscholar.org/47f6/5952ee3c5dcf2a61345f704914b17fa8dc0d.pdf

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A novel TSC1 variant associated with tuberous sclerosis and sacrococcygeal teratoma

Human Genome Variation ◽

10.1038/s41439-020-00124-8 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Saba Ahmad ◽

Luis Manon ◽

Gifty Bhat ◽

Jerry Machado ◽

Alice Zalan ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Cellular Differentiation ◽

Autosomal Dominant ◽

De Novo ◽

Autosomal Dominant Disease ◽

Sacrococcygeal Teratoma ◽

Dominant Disease ◽

The Brain

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disease associated with tumors and malformed tissues in the brain and other vital organs. We report a novel de novo frameshift variant of the TSC1 gene (c.434dup;p. Ser146Valfs*8) in a child with TSC who initially presented with a sacral teratoma. This previously unreported association between TSC and teratoma has broad implications for the pathophysiology of embryonic tumors and mechanisms underlying cellular differentiation.

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