Biochemical Characterisation of TSC1 and TSC2 Variants Identified in Patients with Tuberous Sclerosis Complex

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2010-07-01

autism -spectrum disorders. Mutations in either the TSC1 gene on chromosome 9q34 [van Slegtenhorst et al., 1997], or the TSC2 gene on chromosome 16p13.3...cell-based phospho-ERK assay for dopamine D2 and D3 receptors. Anal Biochem 2004; 333: 265–272. 14 Selkirk JV, Nottebaum LM, Ford IC et al: A novel cell

Imaging of tuberous sclerosis complex: a pictorial review

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Ranke, Felipe Mussi von; Faria, Igor Murad; Zanetti, Glaucia; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, (Brazil); Hochhegger, Bruno [Santa Casa de Porto Alegre, Porto Alegre, RS (Brazil); Souza Junior, Arthur Soares [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP) , SP (Brazil)

2017-01-15

Tuberous sclerosis complex (TSC) is a genetically determined hamartomatous neurocutaneous disease with high phenotypic variability. TSC is characterized by widespread hamartomas and benign, or rarely malignant, neoplasms distributed in several organs throughout the body, especially in the brain, skin, retina, kidney, heart, and lung. Common manifestations include cortical tubers, subependymal nodules, white matter abnormalities, retinal abnormalities, cardiac rhabdomyoma, lymphangioleiomyomatosis, renal angiomyolipoma, and skin lesions. The wide range of organs affected by the disease implies that TSC1 and TSC2 genes play important roles in the regulation of cell proliferation and differentiation. Although recent advances in treatment have improved morbidity, the prognosis remains quite poor and nearly 40% of patients die by the age of 35 years. Imaging is important in the evaluation of TSC because of its role not only in presumptive diagnosis, but also in defining the full extent of involvement. This information allows a better understanding of the behavioural phenotype, as related to lesion location. Imaging also contributes to treatment planning. This pictorial review describes common and uncommon imaging manifestations of TSC. (author)

Cortical dysplasia and autistic trait severity in children with Tuberous Sclerosis Complex : A clinical epidemiological study

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S.E. Mous (Sabine); I.E. Overwater (Iris); R. Vidal Gato (Rita); J. Duvekot (Jorieke); L.W. ten Hoopen (Leontine); M. Leguin (Maarten); M.C.Y. de Wit (Marie Claire); G.C. Dieleman (Gwen)

2017-01-01

textabstractTuberous Sclerosis Complex (TSC) is characterized by a high prevalence of autism spectrum disorders (ASD). Little is known about the relation between cortical dysplasia and ASD severity in TSC. We assessed ASD severity (using the Autism Diagnostic Observation Scale), tuber and radial

Dermatologic and dental aspects of the 2012 International Tuberous Sclerosis Complex Consensus Statements.

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Teng, Joyce M C; Cowen, Edward W; Wataya-Kaneda, Mari; Gosnell, Elizabeth S; Witman, Patricia M; Hebert, Adelaide A; Mlynarczyk, Greg; Soltani, Keyoumars; Darling, Thomas N

2014-10-01

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. To detail recommendations for the diagnosis, surveillance, and management of skin and dental lesions in TSC. The TSC Dermatology and Dentistry Subcommittee, 1 of 12 subcommittees, reviewed the relevant literature from 1997 to 2012. 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. 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.

Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex.

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Yanan Guo

Full Text Available Tuberous Sclerosis Complex (TSC is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or TSC2. We sought to generate a mouse model of one or more of these tumor types by targeting deletion of the Tsc1 gene to fibroblasts using the Fsp-Cre allele. Mutant, Tsc1ccFsp-Cre+ mice survived a median of nearly a year, and developed tumors in multiple sites but did not develop angiomyolipoma or lymphangioleiomyomatosis. They did develop a prominent skin phenotype with marked thickening of the dermis with accumulation of mast cells, that was minimally responsive to systemic rapamycin therapy, and was quite different from the pathology seen in human TSC skin lesions. Recombination and loss of Tsc1 was demonstrated in skin fibroblasts in vivo and in cultured skin fibroblasts. Loss of Tsc1 in fibroblasts in mice does not lead to a model of angiomyolipoma or lymphangioleiomyomatosis.

Metastatic Group 3 Medulloblastoma in a Patient With Tuberous Sclerosis Complex: Case Description and Molecular Characterization of the Tumor.

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Moavero, Romina; Folgiero, Valentina; Carai, Andrea; Miele, Evelina; Ferretti, Elisabetta; Po, Agnese; Diomedi Camassei, Francesca; Lepri, Francesca Romana; Vigevano, Federico; Curatolo, Paolo; Valeriani, Massimiliano; Colafati, Giovanna S; Locatelli, Franco; Tornesello, Assunta; Mastronuzzi, Angela

2016-04-01

Medulloblastoma is the most common pediatric brain tumor. We describe a child with tuberous sclerosis complex that developed a Group 3, myc overexpressed, metastatic medulloblastoma (MB). Considering the high risk of treatment-induced malignancies, a tailored therapy, omitting radiation, was given. Based on the evidence of mammalian target of rapamycin mTORC, mTOR Complex; RAS, Rat sarcoma; RAF, rapidly accelerated fibrosarcoma (mTOR) pathway activation in the tumor, targeted therapy was applied resulting in complete remission of disease. Although the PI3K/AKT/mTOR signaling pathway plays a role in MB, we did not find TSC1/TSC2 (TSC, tuberous sclerosis complex) mutation in our patient. We speculate that a different pathway resulting in mTOR activation is the basis of both TSC and MB in this child; H&E, haematoxilin and eosin; Gd, gadolinium. © 2015 Wiley Periodicals, Inc.

Epilepsy in Adults with TSC

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... Privacy Policy Sitemap Learn Engage Donate About TSC Epilepsy in Adults with TSC Individuals with tuberous sclerosis ... being well controlled for long periods of time. Epilepsy and Seizures Epilepsy is any brain disorder that ...

Rhinophyma in tuberous sclerosis complex: case report with brief review of literature

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Friedrich, Reinhard E.

2014-11-01

Full Text Available Tuberous sclerosis or tuberous sclerosis complex (TSC is an autosomal dominant inherited disease characterized by the triad epilepsy, hamartomas (angiofibroma and reduced intellectual capacity. Phenotype can vary considerably. Almost all patients with TSC have at least one characteristic dermatologic feature. Facial angiofibroma can cause severe disfigurement. It may involve the cheeks, perioral region and nose, resulting in thick layers of nodular and pustular skin. Aesthetic surgery of the face comprises an individually adapted ablation of the affected skin regions in order to improve physical appearance. Reports on the subject of surgery for nasal angiofibroma confirm the homogenous transformation of the connective tissues by this hamartoma. Hitherto there is only one report in the literature describing the typical epithelial alterations of the nasal skin compatible with a rhinophyma and adjacent angiofibroma. Here we report the successful electrosurgical treatment of a patient with TSC and extensive sebaceous glands giving rise to a rhinophyma in close association with angiofibroma.

Long-term Follow-up Assessing Renal Angiomyolipoma Treatment Patterns, Morbidity, and Mortality : An Observational Study in Tuberous Sclerosis Complex Patients in the Netherlands

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Eijkemans, Marinus J C; van der Wal, Willem; Reijnders, Leida J; Roes, Kit C B; van Waalwijk van Doorn-Khosrovani, Sahar Barjesteh; Pelletier, Corey; Magestro, Matthew; Zonnenberg, Bernard

2015-01-01

BACKGROUND: Long-term data from patients with tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (angiomyolipoma) are limited. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Adult patients with TSC treated at the University Medical Center Utrecht (the

The pathogenesis and imaging of the tuberous sclerosis complex

International Nuclear Information System (INIS)

Baskin, Henry J.

2008-01-01

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by the formation of hamartomatous lesions in multiple organ systems. It is the second most common neurocutaneous syndrome after neurofibromatosis type 1 and has been recognized since the late 1800s. Although the disease has complete penetrance, there is also high phenotypic variability: some patients have obvious signs at birth, while others remain undiagnosed for many years. In addition to skin lesions, TSC patients develop numerous brain lesions, angiomyolipoma (AMLs), lymphangiomyomatosis (LAM) in the lungs, cardiac rhabdomyomas, skeletal lesions, and vascular anomalies, all of which are well seen with medical imaging. Our knowledge of TSC genetics and pathophysiology has expanded dramatically in recent years: two genetic loci were discovered in the 1990s and recent elucidation of TSC's interaction with the mTOR pathway has changed how we manage the disease. Meanwhile, medical imaging is playing an increasingly important role in the diagnosis, management, and treatment of TSC. We provide an update on the genetics and pathophysiology of TSC, review its clinical manifestations, and explore the breadth of imaging features in each organ system, from prenatal detection of cardiac rhabdomyomas to monitoring rapamycin therapy to treatment of AMLs by interventional radiology. (orig.)

The pathogenesis and imaging of the tuberous sclerosis complex

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Baskin, Henry J. [Cincinnati Children' s Medical Center, Department of Radiology, Cincinnati, OH (United States)

2008-09-15

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by the formation of hamartomatous lesions in multiple organ systems. It is the second most common neurocutaneous syndrome after neurofibromatosis type 1 and has been recognized since the late 1800s. Although the disease has complete penetrance, there is also high phenotypic variability: some patients have obvious signs at birth, while others remain undiagnosed for many years. In addition to skin lesions, TSC patients develop numerous brain lesions, angiomyolipoma (AMLs), lymphangiomyomatosis (LAM) in the lungs, cardiac rhabdomyomas, skeletal lesions, and vascular anomalies, all of which are well seen with medical imaging. Our knowledge of TSC genetics and pathophysiology has expanded dramatically in recent years: two genetic loci were discovered in the 1990s and recent elucidation of TSC's interaction with the mTOR pathway has changed how we manage the disease. Meanwhile, medical imaging is playing an increasingly important role in the diagnosis, management, and treatment of TSC. We provide an update on the genetics and pathophysiology of TSC, review its clinical manifestations, and explore the breadth of imaging features in each organ system, from prenatal detection of cardiac rhabdomyomas to monitoring rapamycin therapy to treatment of AMLs by interventional radiology. (orig.)

Early onset epileptic encephalopathy or genetically determined encephalopathy with early onset epilepsy? Lessons learned from TSC

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Curatolo, P.; Aronica, E.; Jansen, A.; Jansen, F.; Kotulska, K.; Lagae, L.; Moavero, R.; Jozwiak, S.

2016-01-01

BACKGROUND: In tuberous sclerosis complex (TSC) a relationship has been shown between early and refractory seizures and intellectual disability. However, it is uncertain whether epilepsy in TSC is simply a marker in infants who are destined to develop an encephalopathic process or if seizures play a

Early onset epileptic encephalopathy or genetically determined encephalopathy with early onset epilepsy? Lessons learned from TSC

NARCIS (Netherlands)

Curatolo, Paolo; Aronica, Eleonora; Jansen, Anna; Jansen, Floor; Kotulska, Katarzyna; Lagae, Lieven; Moavero, Romina; Jozwiak, Sergiusz

2016-01-01

In tuberous sclerosis complex (TSC) a relationship has been shown between early and refractory seizures and intellectual disability. However, it is uncertain whether epilepsy in TSC is simply a marker in infants who are destined to develop an encephalopathic process or if seizures play a causal role

[Clinical analysis of 15 pediatric patients with tuberous sclerosis complex complicated by cardiac rhabdomyomas].

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Huang, Guo-Qiang; Zhai, Qiong-Xiang; Yu, Jun-Hao; Wang, Chun; Zhuo, Mu-Qing; Wang, Lin-Gan

2015-05-01

To investigate the clinical features in children with tuberous sclerosis complex (TSC)-associated cardiac rhabdomyomas (CRM). The clinical data of 15 children with TSC complicated by CRM were collected. The clinical features of the patients were analyzed, and TSC gene mutations were detected. Eleven cases (73%) developed multiple CRM. The majority of the tumors were located in the left and right ventricles. Most tumors presented as a round-like hyperechogenic mass with a clear margin on echocardiography. Arrhythmias occurred in 3 patients and 2 patients experienced heart failure. Gene mutation tests were performed in 2 patients, and pathogenic mutations were detected in both patients, which were TSC1 mutation and TSC2 mutation, respectively. Three patients were followed up for 6 to 38 months, and their CRM shrank or regressed spontaneously. TSC-associated CRM is generally multiple. Heart failure and arrhythmias may occur in some patients. Echocardiography is important for diagnosis of CRM. TSC-associated CRM has an inclination to spontaneous regression. TSC can be diagnosed at a molecular genetic level by TSC gene mutation detection.

Pulmonary choriostoma in a case of tuberous sclerosis complex

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S Spalgais

2015-01-01

Full Text Available A 52 years old lady was diagnosed to have Tuberous Sclerosis Complex (TSC on the basis of 2 major and one minor criterion. She had family history of similar complaints in her sister and two sons. There was involvement of kidney in the form of angiomyolipoma, skin in the form of facial angiofibroma and teeth with a dental pit. She had an unusual lung involvement in the form of multiple small choristomas. Choristoma was diagnosed on transbronchial lung biopsy and was present in the form of disorganised striated muscles. The reported pulmonary manifestations of TCS i.e. lymphangioleiomyomatosis (LAM and multifocal micronodular pneumocyte hyperplasia (MMPH are types of hamartomas. Hamartomas and choristomas are both types of disorganized tissue. ′Choristoma′of lung in TSC however is not reported. Clinopathological correlation of pulmonary hamartoma and choristoma, and treatment in TSC has been discussed.

Sun exposure causes somatic second-hit mutations and angiofibroma development in tuberous sclerosis complex

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Tyburczy, Magdalena E.; Wang, Ji-an; Li, Shaowei; Thangapazham, Rajesh; Chekaluk, Yvonne; Moss, Joel; Kwiatkowski, David J.; Darling, Thomas N.

2014-01-01

Tuberous sclerosis complex (TSC) is characterized by the formation of tumors in multiple organs and is caused by germline mutation in one of two tumor suppressor genes, TSC1 and TSC2. As for other tumor suppressor gene syndromes, the mechanism of somatic second-hit events in TSC tumors is unknown. We grew fibroblast-like cells from 29 TSC skin tumors from 22 TSC subjects and identified germline and second-hit mutations in TSC1/TSC2 using next-generation sequencing. Eighteen of 22 (82%) subjects had a mutation identified, and 8 of the 18 (44%) subjects were mosaic with mutant allele frequencies of 0 to 19% in normal tissue DNA. Multiple tumors were available from four patients, and in each case, second-hit mutations in TSC2 were distinct indicating they arose independently. Most remarkably, 7 (50%) of the 14 somatic point mutations were CC>TT ultraviolet ‘signature’ mutations, never seen as a TSC germline mutation. These occurred exclusively in facial angiofibroma tumors from sun-exposed sites. These results implicate UV-induced DNA damage as a cause of second-hit mutations and development of TSC facial angiofibromas and suggest that measures to limit UV exposure in TSC children and adults should reduce the frequency and severity of these lesions. PMID:24271014

Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

International Nuclear Information System (INIS)

Back, Susan J.; Andronikou, Savvas; Kilborn, Tracy; Kaplan, Bernard S.; Darge, Kassa

2015-01-01

Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

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Back, Susan J. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Andronikou, Savvas [University of the Witwatersrand, Radiology Department, Faculty of Health Sciences, Johannesburg (South Africa); Kilborn, Tracy [University of Cape Town, Red Cross War Memorial Children' s Hospital, Cape Town (South Africa); Kaplan, Bernard S. [The Children' s Hospital of Philadelphia, Division of Nephrology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Darge, Kassa [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States)

2015-03-01

Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

Rare lung manifestation of multifocal micronodular pneumocyte hyperplasia in a teenage girl with tuberous sclerosis complex

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Ha, Seung Mi; Yoon, Hye Kyung; Lee, Seung Koo [Kangwon National University Hospital, Chuncheon (Korea, Republic of)

2016-08-15

Multifocal micronodular pneumocyte hyperplasia (MMPH) is a relatively rare pulmonary disorder that can be associated with tuberous sclerosis complex (TSC). It has been rarely reported in children or adolescents. MMPH is a hamartomatous process of the lung with multiple small nodules, composed of type II pneumocytes. Plain radiography and chest CT in MMPH may demonstrate numerous small nodules measuring 1-10 mm in diameters, distributed randomly throughout both lungs. If MMPH is an initial presentation of TSC, and unless we are familiar with this lung manifestation of TSC, radiologic findings can mimic miliary tuberculosis or metastatic disease. We report a teenage girl with TSC and histologically confirmed MMPH which mimicked miliary tuberculosis at the initial presentation.

Rare lung manifestation of multifocal micronodular pneumocyte hyperplasia in a teenage girl with tuberous sclerosis complex

International Nuclear Information System (INIS)

Ha, Seung Mi; Yoon, Hye Kyung; Lee, Seung Koo

2016-01-01

Multifocal micronodular pneumocyte hyperplasia (MMPH) is a relatively rare pulmonary disorder that can be associated with tuberous sclerosis complex (TSC). It has been rarely reported in children or adolescents. MMPH is a hamartomatous process of the lung with multiple small nodules, composed of type II pneumocytes. Plain radiography and chest CT in MMPH may demonstrate numerous small nodules measuring 1-10 mm in diameters, distributed randomly throughout both lungs. If MMPH is an initial presentation of TSC, and unless we are familiar with this lung manifestation of TSC, radiologic findings can mimic miliary tuberculosis or metastatic disease. We report a teenage girl with TSC and histologically confirmed MMPH which mimicked miliary tuberculosis at the initial presentation

Tsc1 is a Critical Regulator of Macrophage Survival and Function

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Chunmin Fang

2015-07-01

Full Text Available Background/Aims: Tuberous sclerosis complex 1 (Tsc1 has been shown to regulate M1/M2 polarization of macrophages, but the precise roles of Tsc1 in the function and stability of macrophages are not fully understood. Here we show that Tsc1 is required for regulating the survival, migration and phagocytosis of macrophages. Methods: Mice with Tsc1 homozygous deletion in myeloid cells (LysMCreTsc1flox/flox; Tsc1 KO were obtained by crossing Tsc1flox/flox mice with mice expressing Cre recombinase under the control of Lysozyme promoter (LysMCre. The apoptosis and growth of macrophages were determined by flow cytometry and Real-time PCR (RT-PCR. The phagocytosis was determined using a Vybrant™ phagocytosis assay kit. The migration of macrophages was determined using transwell migration assay. Results: Peritoneal macrophages of Tsc1 KO mice exhibited increased apoptosis and enlarged cell size. Both M1 and M2 phenotypes in Tsc1-deficient macrophages were elevated in steady-state as well as in inflammatory conditions. Tsc1-deficient macrophages demonstrated impaired migration and reduced expression of chemokine receptors including CCR2 and CCR5. Phagocytosis activity and ROS production were enhanced in Tsc1-deficient macrophages. Furthermore, pharmacological inhibition of the mammalian target of rapamycin complex 1 (mTORC1 partially reversed the aberrance of Tsc1-deficient macrophages. Conclusion: Tsc1 plays a critical role in regulating macrophage survival, function and polarization via inhibition of mTORC1 activity.

Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is mediated via NPC1 and LDL-R.

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Filippakis, Harilaos; Alesi, Nicola; Ogorek, Barbara; Nijmeh, Julie; Khabibullin, Damir; Gutierrez, Catherine; Valvezan, Alexander J; Cunningham, James; Priolo, Carmen; Henske, Elizabeth P

2017-06-13

Tuberous sclerosis complex (TSC) is a multisystem disease associated with hyperactive mTORC1. The impact of TSC1/2 deficiency on lysosome-mediated processes is not fully understood. We report here that inhibition of lysosomal function using chloroquine (CQ) upregulates cholesterol homeostasis genes in TSC2-deficient cells. This TSC2-dependent transcriptional signature is associated with increased accumulation and intracellular levels of both total cholesterol and cholesterol esters. Unexpectedly, engaging this CQ-induced cholesterol uptake pathway together with inhibition of de novo cholesterol synthesis allows survival of TSC2-deficient, but not TSC2-expressing cells. The underlying mechanism of TSC2-deficient cell survival is dependent on exogenous cholesterol uptake via LDL-R, and endosomal trafficking mediated by Vps34. Simultaneous inhibition of lysosomal and endosomal trafficking inhibits uptake of esterified cholesterol and cell growth in TSC2-deficient, but not TSC2-expressing cells, highlighting the TSC-dependent lysosome-mediated regulation of cholesterol homeostasis and pointing toward the translational potential of these pathways for the therapy of TSC.

Mucocutaneous changes in tuberous sclerosis complex: A clinical profile of 27 Indian patients

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Ghosh Sudip

2009-01-01

Full Text Available Background: Tuberous sclerosis complex (TSC is an autosomal dominant neurocutaneous disease resulting in a wide array of clinical manifestations, primarily affecting the skin and central nervous system. Mucocutaneous features play a very important role in the recognition of this syndrome. Aims: To review the prevalence and patterns of cutaneous manifestations in tuberous sclerosis, in a group of patients from eastern India. Methods: Observational clinical study on twenty-seven consecutive patients of tuberous sclerosis collected during a period of four years. Results: Most were between 10-20 years of age; the male to female ratio was 2:1. Family history was found in two-thirds. The classical triad of tuberous sclerosis was present in only nine (33.3% patients. Adenoma sebaceum was the most common cutaneous feature (100%, followed by hypomelanotic macules (92.6%, connective tissue nevi (66.6%, and Koenen′s tumors (33.3%. Oral mucosal fibromas were seen in six (22.22% patients. Fibromatous plaque over forehead and scalp was seen in three patients. Limitation of the study was small size of study sample. Conclusion: Prominent mucocutaneous changes are extremely common manifestation of TSC, which may provide crucial diagnostic clues for primary care physicians.

An Australian tuberous sclerosis cohort: are surveillance guidelines being met?

NARCIS (Netherlands)

Chopra, M.; Lawson, J.A.; Wilson, M.; Kennedy, S.E.; Taylor, P.; Buckley, M.F.; Wargon, O.; Parasivam, G.; Camphausen, C.; Yates, D.; Mowat, D.

2011-01-01

AIM: This study aims to describe the phenotypic and genotypic characteristics of 45 Australian patients with tuberous sclerosis complex (TSC), to assess risk factors for intellectual disability, to compare patients with TSC1 and TSC2 mutations and to assess adherence to surveillance recommendations.

Clinical features and genetic analysis of tuberous sclerosis pedigrees

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LI Ya-qin

2012-06-01

Full Text Available Objective In order to understand tuberous sclerosis complex better, the clinical manifestation, imaging characteristics, and genetic characteristics of tuberous sclerosis complex from 3 pedigrees were investigated. Methods The clinical data of patients from 3 tuberous sclerosis families were collected. The gene mutation type of TSC2 of proband in pedigree one was determined by PCR and direct gene sequencing. Results All of the 3 probands went to our clinic for the reason of epilepsy. Brain imaging examination noted intracranial nodular calcification. EEG showed comprehensive spines and slow waves, sharp waves. The pedigree 1 has family history, two male patients and 3 female patients, all had facial angiofibromas and epilepsy. Gene mutation analysis of TSC2 demonstrated the c.1444-2A > C mutation in index patient. All the 3 index patients had mental retardation, autism and hypopigmented macule. Conclusion For infants and young children with epilepsy as the first symptom, accompanied by mental retardation, autism, facial angiofibromas or hypopigmented macule and other skin abnormalities, brain imaging examination noted intracranial nodular calcification are highly suggestive of tuberous sclerosis complex. TSC1 and TSC2 gene analysis contribute to the diagnosis of this disease, genentic counseling and prenatal diagnosis.

Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules.

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Armour, Eric A; Carson, Robert P; Ess, Kevin C

2012-08-15

Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia.

Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules

Science.gov (United States)

Armour, Eric A.; Carson, Robert P.

2012-01-01

Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia. PMID:22674026

Heterozygous loss of TSC2 alters p53 signaling and human stem cell reprogramming.

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Armstrong, Laura C; Westlake, Grant; Snow, John P; Cawthon, Bryan; Armour, Eric; Bowman, Aaron B; Ess, Kevin C

2017-12-01

Tuberous sclerosis complex (TSC) is a pediatric disorder of dysregulated growth and differentiation caused by loss of function mutations in either the TSC1 or TSC2 genes, which regulate mTOR kinase activity. To study aberrations of early development in TSC, we generated induced pluripotent stem cells using dermal fibroblasts obtained from patients with TSC. During validation, we found that stem cells generated from TSC patients had a very high rate of integration of the reprogramming plasmid containing a shRNA against TP53. We also found that loss of one allele of TSC2 in human fibroblasts is sufficient to increase p53 levels and impair stem cell reprogramming. Increased p53 was also observed in TSC2 heterozygous and homozygous mutant human stem cells, suggesting that the interactions between TSC2 and p53 are consistent across cell types and gene dosage. These results support important contributions of TSC2 heterozygous and homozygous mutant cells to the pathogenesis of TSC and the important role of p53 during reprogramming. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Anti-EGFR Antibody Efficiently and Specifically Inhibits Human TSC2−/− Smooth Muscle Cell Proliferation. Possible Treatment Options for TSC and LAM

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Lesma, Elena; Grande, Vera; Ancona, Silvia; Carelli, Stephana; Di Giulio, Anna Maria; Gorio, Alfredo

2008-01-01

Background Tuberous sclerosis complex (TSC), a tumor syndrome caused by mutations in TSC1 or TSC2 genes, is characterized by the development of hamartomas. We previously isolated, from an angiomyolipoma of a TSC2 patient, a homogenous population of smooth muscle-like cells (TSC2−/− ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of heterozygosity (LOH) and consequently, do not produce the TSC2 gene product, tuberin. TSC2−/− ASM cell proliferation is EGF-dependent. Methods and Findings Effects of EGF on proliferation of TSC2−/− ASM cells and TSC2−/− ASM cells transfected with TSC2 gene were determined. In contrast to TSC2−/− ASM cells, growth of TSC2-transfected cells was not dependent on EGF. Moreover, phosphorylation of Akt, PTEN, Erk and S6 was significantly decreased. EGF is a proliferative factor of TSC2−/− ASM cells. Exposure of TSC2−/− ASM cells to anti-EGFR antibodies significantly inhibited their proliferation, reverted reactivity to HMB45 antibody, a marker of TSC2−/− cell phenotype, and inhibited constitutive phosphorylation of S6 and ERK. Exposure of TSC2−/− ASM cells to rapamycin reduced the proliferation rate, but only when added at plating time. Although rapamycin efficiently inhibited S6 phosphorylation, it was less efficient than anti-EGFR antibody in reverting HMB45 reactivity and blocking ERK phosphorylation. In TSC2−/− ASM cells specific PI3K inhibitors (e.g. LY294002, wortmannin) and Akt1 siRNA had little effect on S6 and ERK phosphorylation. Following TSC2-gene transfection, Akt inhibitor sensitivity was observed. Conclusion Our results show that an EGF independent pathway is more important than that involving IGF-I for growth and survival of TSC−/− ASM cells, and such EGF-dependency is the result of the lack of tuberin. PMID:18958173

Clinical Characteristics of Connective Tissue Nevi in Tuberous Sclerosis Complex With Special Emphasis on Shagreen Patches.

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Bongiorno, Michelle A; Nathan, Neera; Oyerinde, Oyetewa; Wang, Ji-An; Lee, Chyi-Chia Richard; Brown, G Thomas; Moss, Joel; Darling, Thomas N

2017-07-01

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. To describe the clinical characteristics of connective tissue nevi on the trunk and extremities of patients with tuberous sclerosis complex. 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 connective tissue nevi in patients with TSC. 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

Coexistence of Autism Spectrum Disorders Among Three Children with Tuberous Sclerosis Complex; Case reports and review of literature

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Amna Al-Futaisi

2016-11-01

Full Text Available Tuberous sclerosis complex (TSC is a multisystem neurocutaneous disorder inherited in an autosomal dominant manner and characterised by benign tumours in the brain and other vital organs such as the heart, eyes, kidneys, skin and lungs. Links between autism spectrum disorder (ASD and TSC have been postulated for many decades, with TSC considered to be one of the main syndromic causes of ASD; however, precise confirmation of a relationship between these two disorders required validated diagnostic tools. Fortunately, accurate evaluation of this relationship is now possible with standardised criteria for ASD diagnosis. We report three children who presented to the Sultan Qaboos University Hospital, Muscat, Oman, between 2014 and 2015 with ASD and TSC. These cases demonstrate the spectrum of neuropsychiatric involvement in TSC and highlight the importance of screening children with TSC for ASD features in order to encourage the early enrolment of these children in educational and rehabilitation programmes.

Heterozygous inactivation of tsc2 enhances tumorigenesis in p53 mutant zebrafish

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Seok-Hyung Kim

2013-07-01

Tuberous sclerosis complex (TSC is a multi-organ disorder caused by mutations of the TSC1 or TSC2 genes. A key function of these genes is to inhibit mTORC1 (mechanistic target of rapamycin complex 1 kinase signaling. Cells deficient for TSC1 or TSC2 have increased mTORC1 signaling and give rise to benign tumors, although, as a rule, true malignancies are rarely seen. In contrast, other disorders with increased mTOR signaling typically have overt malignancies. A better understanding of genetic mechanisms that govern the transformation of benign cells to malignant ones is crucial to understand cancer pathogenesis. We generated a zebrafish model of TSC and cancer progression by placing a heterozygous mutation of the tsc2 gene in a p53 mutant background. Unlike tsc2 heterozygous mutant zebrafish, which never exhibited cancers, compound tsc2;p53 mutants had malignant tumors in multiple organs. Tumorigenesis was enhanced compared with p53 mutant zebrafish. p53 mutants also had increased mTORC1 signaling that was further enhanced in tsc2;p53 compound mutants. We found increased expression of Hif1-α, Hif2-α and Vegf-c in tsc2;p53 compound mutant zebrafish compared with p53 mutant zebrafish. Expression of these proteins probably underlies the increased angiogenesis seen in compound mutant zebrafish compared with p53 mutants and might further drive cancer progression. Treatment of p53 and compound mutant zebrafish with the mTORC1 inhibitor rapamycin caused rapid shrinkage of tumor size and decreased caliber of tumor-associated blood vessels. This is the first report using an animal model to show interactions between tsc2, mTORC1 and p53 during tumorigenesis. These results might explain why individuals with TSC rarely have malignant tumors, but also suggest that cancer arising in individuals without TSC might be influenced by the status of TSC1 and/or TSC2 mutations and be potentially treatable with mTORC1 inhibitors.

Repression of TSC1/TSC2 mediated by MeCP2 regulates human embryo lung fibroblast cell differentiation and proliferation.

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Wang, Yuanyuan; Chen, Chen; Deng, Ziyu; Bian, Erbao; Huang, Cheng; Lei, Ting; Lv, Xiongwen; Liu, Liping; Li, Jun

2017-03-01

Pulmonary fibrosis (PF) is a severe inflammatory disease with limited effective treatments. It is known that the transdifferentiation of human embryo lung fibroblast (HELF) cells from pulmonary fibroblasts into myofibroblasts, contributes to the progression of pulmonary fibrogenesis. The tuberous sclerosis proteins TSC1 and TSC2 are two key signaling factors which can suppress cell growth and proliferation. However, the roles of TSC1 and TSC2 in lung fibroblast are unclear. Here, we developed a PF model with bleomycin (BLM) in mice and conducted several simulation experiments in HELF cells. Our study shows that the expression of TSC1 and TSC2 in fibrotic mice lung was reduced and stimulation of HELF cells with TGF-β1 resulted in a down-regulation of TSC1 and TSC2. In addition, overexpression of TSC1 or TSC2 decreased cell proliferation and differentiation. Furthermore, we found that reduced expression of TSC1 and TSC2 caused by TGF-β1 is associated with the promoter methylation status of TSC1 and TSC2. MeCP2, controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis. We found that expression of TSC1 and TSC2 can be repressed by MeCP2, which regulates HELF cell differentiation and proliferation as myofibroblasts and lead to PF ultimately. Copyright © 2016. Published by Elsevier B.V.

Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

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Angelika Mühlebner

Full Text Available Tuberous Sclerosis Complex (TSC is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1 activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.

Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

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Mühlebner, Angelika; van Scheppingen, Jackelien; Hulshof, Hanna M; Scholl, Theresa; Iyer, Anand M; Anink, Jasper J; van den Ouweland, Ans M W; Nellist, Mark D; Jansen, Floor E; Spliet, Wim G M; Krsek, Pavel; Benova, Barbora; Zamecnik, Josef; Crino, Peter B; Prayer, Daniela; Czech, Thomas; Wöhrer, Adelheid; Rahimi, Jasmin; Höftberger, Romana; Hainfellner, Johannes A; Feucht, Martha; Aronica, Eleonora

2016-01-01

Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.

Resting and Task-Modulated High-Frequency Brain Rhythms Measured by Scalp Encephalography in Infants with Tuberous Sclerosis Complex

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Stamoulis, Catherine; Vogel-Farley, Vanessa; Degregorio, Geneva; Jeste, Shafali S.; Nelson, Charles A.

2015-01-01

The electrophysiological correlates of cognitive deficits in tuberous sclerosis complex (TSC) are not well understood, and modulations of neural dynamics by neuroanatomical abnormalities that characterize the disorder remain elusive. Neural oscillations (rhythms) are a fundamental aspect of brain function, and have dominant frequencies in a wide…

Clinical management of tuberous sclerosis complex over the lifetime of a patient

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Frost M

2015-08-01

Full Text Available Michael Frost,1 John Hulbert2 1Minnesota Epilepsy Group, PA, St Paul, MN, USA; 2Urologic Physicians, PA, Edina, MN, USA Abstract: Tuberous sclerosis complex (TSC is a genetic disorder characterized by nonmalignant tumors (hamartomas that can occur in various organ systems, including the brain, kidneys, lungs, skin, eyes, and heart. Clinical manifestations of TSC can occur at any age, thereby making the diagnosis difficult. No typical disease presentation is known, and the clinical presentation usually differs between pediatric and adult patients. Furthermore, variable penetrance of the genetic mutation causes a range of disease severity from very mild to severe, and affected individuals can go undetected for years because many of the clinical manifestations of TSC lack specificity. Once a diagnosis is made, TSC management strategies should be tailored to address the symptoms and risks most relevant to the age of the patient. Improved understanding of the genetic basis of TSC and of the central issue of mTOR overactivation has led to use of pharmacotherapies such as the mTOR inhibitors everolimus and sirolimus in the treatment of TSC disease. In Phase II and III studies, everolimus has demonstrated efficacy and safety in the treatment of both brain (subependymal giant cell astrocytoma and renal (angiomyolipoma manifestations associated with TSC. It is important to bear in mind that TSC is a lifelong condition, and for those diagnosed as children, a continuum of care will be needed as they transition from pediatric to adult health services. Clearly identifying the likely differences among diagnosis, monitoring, and management of pediatric and adult patients with TSC is an important step in enabling efficiencies to be maximized without compromising the care provided to patients. Keywords: mammalian target of rapamycin inhibitors, mTOR treatment, treatment strategies

Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin

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Seok-Hyung Kim

2011-03-01

Tuberous sclerosis complex (TSC is an autosomal dominant disease caused by mutations in either the TSC1 (encodes hamartin or TSC2 (encodes tuberin genes. Patients with TSC have hamartomas in various organs throughout the whole body, most notably in the brain, skin, eye, heart, kidney and lung. To study the development of hamartomas, we generated a zebrafish model of TSC featuring a nonsense mutation (vu242 in the tsc2 gene. This tsc2vu242 allele encodes a truncated Tuberin protein lacking the GAP domain, which is required for inhibition of Rheb and of the TOR kinase within TORC1. We show that tsc2vu242 is a recessive larval-lethal mutation that causes increased cell size in the brain and liver. Greatly elevated TORC1 signaling is observed in tsc2vu242/vu242 homozygous zebrafish, and is moderately increased in tsc2vu242/+ heterozygotes. Forebrain neurons are poorly organized in tsc2vu242/vu242 homozygous mutants, which have extensive gray and white matter disorganization and ectopically positioned cells. Genetic mosaic analyses demonstrate that tsc2 limits TORC1 signaling in a cell-autonomous manner. However, in chimeric animals, tsc2vu242/vu242 mutant cells also mislocalize wild-type host cells in the forebrain in a non-cell-autonomous manner. These results demonstrate a highly conserved role of tsc2 in zebrafish and establish a new animal model for studies of TSC. The finding of a non-cell-autonomous function of mutant cells might help explain the formation of brain hamartomas and cortical malformations in human TSC.

TOSCA - first international registry to address knowledge gaps in the natural history and management of tuberous sclerosis complex.

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Kingswood, John C; Bruzzi, Paolo; Curatolo, Paolo; de Vries, Petrus J; Fladrowski, Carla; Hertzberg, Christoph; Jansen, Anna C; Jozwiak, Sergiusz; Nabbout, Rima; Sauter, Matthias; Touraine, Renaud; O'Callaghan, Finbar; Zonnenberg, Bernard; Crippa, Stefania; Comis, Silvia; d'Augères, Guillaume Beaure; Belousova, Elena; Carter, Tom; Cottin, Vincent; Dahlin, Maria; Ferreira, José Carlos; Macaya, Alfons; Benedik, Mirjana Perkovic; Sander, Valentin; Youroukos, Sotirios; Castellana, Ramon; Ulker, Bulent; Feucht, Martha

2014-11-26

Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disorder with an estimated prevalence between 1/6800 and 1/15000. Although recent years have seen huge progress in understanding the pathophysiology and in the management of TSC, several questions remain unanswered. A disease registry could be an effective tool to gain more insights into TSC and thus help in the development of improved management strategies. TuberOus SClerosis registry to increase disease Awareness (TOSCA) is a multicentre, international disease registry to assess manifestations, interventions, and outcomes in patients with TSC. Patients of any age diagnosed with TSC, having a documented visit for TSC within the preceding 12 months, or newly diagnosed individuals are eligible. Objectives include mapping the course of TSC manifestations and their effects on prognosis, identifying patients with rare symptoms and co-morbidities, recording interventions and their outcomes, contributing to creation of an evidence-base for disease assessment and therapy, informing further research on TSC, and evaluating the quality of life of patients with TSC. The registry includes a 'core' section and subsections or 'petals'. The 'core' section is designed to record general information on patients' background collected at baseline and updated annually. Subsections will be developed over time to record additional data related to specific disease manifestations and will be updated annually. The registry aimed to enrol approximately 2000 patients from about 250 sites in 31 countries. The initial enrolment period was of 24 months. A follow-up observation period of up to 5 years is planned. A pre-planned administrative analysis of 'core' data from the first 100 patients was performed to evaluate the feasibility of the registry. Results showed a high degree of accuracy of the data collection procedure. Annual interim analyses are scheduled. Results of first interim analysis will be presented subsequent to

Clinical report: a rare co-occurrence of tuberous sclerosis complex and Rett syndrome in a girl with mental retardation, epilepsy and autism

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Belousova, Elena; Sukhorukov, Vladimir; Dorofeeva, Marina; Shagam, Lev; Vlodavetz, Dmitrii V.

2017-01-01

Introduction. There are some genetic disorders with combination of mental retardation, epilepsy and autism in which the abnormal mammalian Target of Rapamycin (m-TOR) signaling is implicated. The most important of them is tuberous sclerosis complex (TSC), but the disturbances of the m-TOR pathway can also be detected in Rett syndrome (RS), Fragile X syndrome and Down syndrome. We describe the rare case of co-occurrence of TSC and RS. Case study. The female child was born at term by normal de...

Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors

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Dabora Sandra L

2010-02-01

Full Text Available Abstract Background Tuberous Sclerosis Complex (TSC is an autosomal dominant tumor disorder characterized by the growth of hamartomas in various organs including the kidney, brain, skin, lungs, and heart. Rapamycin has been shown to reduce the size of kidney angiomyolipomas associated with TSC; however, tumor regression is incomplete and kidney angiomyolipomas regrow after cessation of treatment. Mouse models of TSC2 related tumors are useful for evaluating new approaches to drug therapy for TSC. Methods In cohorts of Tsc2+/- mice, we compared kidney cystadenoma severity in A/J and C57BL/6 mouse strains at both 9 and 12 months of age. We also investigated age related kidney tumor progression and compared three different rapamycin treatment schedules in cohorts of A/J Tsc2+/- mice. In addition, we used nude mice bearing Tsc2-/- subcutaneous tumors to evaluate the therapeutic utility of sunitinib, bevacizumab, vincristine, and asparaginase. Results TSC related kidney disease severity is 5-10 fold higher in A/J Tsc2+/- mice compared with C57BL/6 Tsc2+/- mice. Similar to kidney angiomyolipomas associated with TSC, the severity of kidney cystadenomas increases with age in A/J Tsc2+/- mice. When rapamycin dosing schedules were compared in A/J Tsc2+/- cohorts, we observed a 66% reduction in kidney tumor burden in mice treated daily for 4 weeks, an 82% reduction in mice treated daily for 4 weeks followed by weekly for 8 weeks, and an 81% reduction in mice treated weekly for 12 weeks. In the Tsc2-/- subcutaneous tumor mouse model, vincristine is not effective, but angiogenesis inhibitors (sunitinib and bevacizumab and asparaginase are effective as single agents. However, these drugs are not as effective as rapamycin in that they increased median survival only by 24-27%, while rapamycin increased median survival by 173%. Conclusions Our results indicate that the A/J Tsc2+/- mouse model is an improved, higher through-put mouse model for future TSC

mTOR Inhibition and Tuberous Sclerosis Prevention

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J Gordon Millichap

2013-09-01

Full Text Available Investigators at Children's Memorial Health Institute, Warsaw, Poland, report monozygotic twin sisters with tuberous sclerosis complex (TSC, one treated with the mTOR inhibitor everolimus since age 4 years.

Comparison of Color Fundus Photography, Infrared Fundus Photography, and Optical Coherence Tomography in Detecting Retinal Hamartoma in Patients with Tuberous Sclerosis Complex.

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Bai, Da-Yong; Wang, Xu; Zhao, Jun-Yang; Li, Li; Gao, Jun; Wang, Ning-Li

2016-05-20

A sensitive method is required to detect retinal hamartomas in patients with tuberous sclerosis complex (TSC). The aim of the present study was to compare the color fundus photography, infrared imaging (IFG), and optical coherence tomography (OCT) in the detection rate of retinal hamartoma in patients with TSC. This study included 11 patients (22 eyes) with TSC, who underwent color fundus photography, IFG, and spectral-domain OCT to detect retinal hamartomas. TSC1 and TSC2RESULTS: The mean age of the 11 patients was 8.0 ± 2.1 years. The mean spherical equivalent was -0.55 ± 1.42 D by autorefraction with cycloplegia. In 11 patients (22 eyes), OCT, infrared fundus photography, and color fundus photography revealed 26, 18, and 9 hamartomas, respectively. The predominant hamartoma was type I (55.6%). All the hamartomas that detected by color fundus photography or IFG can be detected by OCT. Among the methods of color fundus photography, IFG, and OCT, the OCT has higher detection rate for retinal hamartoma in TSC patients; therefore, OCT might be promising for the clinical diagnosis of TSC.

High-throughput drug screen identifies chelerythrine as a selective inducer of death in a TSC2-null setting.

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Medvetz, Doug; Sun, Yang; Li, Chenggang; Khabibullin, Damir; Balan, Murugabaskar; Parkhitko, Andrey; Priolo, Carmen; Asara, John M; Pal, Soumitro; Yu, Jane; Henske, Elizabeth P

2015-01-01

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome associated with tumors of the brain, heart, kidney, and lung. The TSC protein complex inhibits the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Inhibitors of mTORC1, including rapamycin, induce a cytostatic response in TSC tumors, resulting in temporary disease stabilization and prompt regrowth when treatment is stopped. The lack of TSC-specific cytotoxic therapies represents an important unmet clinical need. Using a high-throughput chemical screen in TSC2-deficient, patient-derived cells, we identified a series of molecules antagonized by rapamycin and therefore selective for cells with mTORC1 hyperactivity. In particular, the cell-permeable alkaloid chelerythrine induced reactive oxygen species (ROS) and depleted glutathione (GSH) selectively in TSC2-null cells based on metabolic profiling. N-acetylcysteine or GSH cotreatment protected TSC2-null cells from chelerythrine's effects, indicating that chelerythrine-induced cell death is ROS dependent. Induction of heme-oxygenase-1 (HMOX1/HO-1) with hemin also blocked chelerythrine-induced cell death. In vivo, chelerythrine inhibited the growth of TSC2-null xenograft tumors with no evidence of systemic toxicity with daily treatment over an extended period of time. This study reports the results of a bioactive compound screen and the identification of a potential lead candidate that acts via a novel oxidative stress-dependent mechanism to selectively induce necroptosis in TSC2-deficient tumors. This study demonstrates that TSC2-deficient tumor cells are hypersensitive to oxidative stress-dependent cell death, and provide critical proof of concept that TSC2-deficient cells can be therapeutically targeted without the use of a rapalog to induce a cell death response. ©2014 American Association for Cancer Research.

Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex.

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Jeong, Anna; Wong, Michael

2016-09-01

Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy. Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis. Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3-3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0-4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3-3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8-5.1, p epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0-3.5, p = 0.04) remained significantly associated with the presence of epilepsy. The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease prognostication and assist in the identification of individuals who may receive maximal benefit from potentially novel, targeted, preventative therapies. Wiley

Tuberous Sclerosis Complex in 29 Children: Clinical and Genetic Analysis and Facial Angiofibroma Responses to Topical Sirolimus.

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Wang, Senfen; Liu, Yuanxiang; Wei, Jinghai; Zhang, Jian; Wang, Zhaoyang; Xu, Zigang

2017-09-01

Tuberous sclerosis complex (TSC) is a genetic disorder and facial angiofibromas are disfiguring facial lesions. The aim of this study was to analyze the clinical and genetic features of TSC and to assess the treatment of facial angiofibromas using topical sirolimus in Chinese children. Information was collected on 29 patients with TSC. Genetic analyses were performed in 12 children and their parents. Children were treated with 0.1% sirolimus ointment for 36 weeks. Clinical efficacy and plasma sirolimus concentrations were evaluated at baseline and 12, 24, and 36 weeks. Twenty-seven (93%) of the 29 patients had hypomelanotic macules and 15 (52%) had shagreen patch; 11 of the 12 (92%) who underwent genetic analysis had gene mutations in the TSC1 or TSC2 gene. Twenty-four children completed 36 weeks of treatment with topical sirolimus; facial angiofibromas were clinically undetectable in four (17%). The mean decrease in the Facial Angiofibroma Severity Index (FASI) score at 36 weeks was 47.6 ± 30.4%. There was no significant difference in the FASI score between weeks 24 and 36 (F = 1.00, p = 0.33). There was no detectable systemic absorption of sirolimus. Hypomelanotic macules are often the first sign of TSC. Genetic testing has a high detection rate in patients with a clinical diagnosis of TSC. Topical sirolimus appears to be both effective and well-tolerated as a treatment of facial angiofibromas in children with TSC. The response typically plateaus after 12 to 24 weeks of treatment. © 2017 Wiley Periodicals, Inc.

Initial presentation with dilated cardiomyopathy in a patient of tuberous sclerosis: A rare case report

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Dharmendra Jain

2013-01-01

Full Text Available A 35-year-old man presented with dilated cardiomyopathy, an unusual association with tuberous sclerosis. Clinical history and examination were consistent with tuberous sclerosis including major features of tuberous sclerosis complex (TSC like facial angiofibroma, shagreen patch, subependymal nodules, and angiomyolipoma of kidney. The clinical manifestations, pathogenesis and evaluation of tuberous sclerosis are discussed.

Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex

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Adriaensen, M.E.A.P.M., E-mail: miraude@gmail.com [Department of Radiology, Atrium Medical Center Parkstad, Heerlen (Netherlands); Department of Radiology, University Medical Center Utrecht, Utrecht (Netherlands); Schaefer-Prokop, C.M. [Department of Radiology, Meander Medical Center, Amersfoort (Netherlands); Duyndam, D.A.C. [Department of Radiology, OLVG, Amsterdam (Netherlands); Zonnenberg, B.A. [Department of Internal Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Prokop, M. [Department of Radiology, University Medical Center Utrecht, Utrecht (Netherlands); Department of Radiology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)

2011-07-15

Aim: To determine the gender-specific prevalence of pulmonary cysts typical for lymphangioleiomyomatosis (LAM) in adult patients with known tuberous sclerosis complex (TSC). Materials and methods: A retrospective, cross-sectional study in a cohort of 206 adult TSC patients was performed. Institutional review board approval was obtained, and patient informed consent was waived. Patients had routinely undergone abdominal CT scanning between 1996 and 2006. All 186 patients (mean age 38 years; range 19-72 years; 91 (49%) male patients) in whom at least the lung bases were depicted on computed tomography (CT) were included. Images were reviewed for the presence of pulmonary thin-walled cysts. Descriptive statistics, two sample t-test to compare means, and {chi}{sup 2}-test to compare proportions were applied. Results: CT demonstrated pulmonary thin-walled cysts in the lung bases in 52 (28%) of 186 patients. Size varied from 2 mm in diameter to more than 2 cm. Pulmonary cysts were detected in 40 (42%) of 95 female patients and in 12 (13%) of 91 male patients (p < 0.001). In general, cysts were larger and more numerous in women than in men. Only minimal cystic changes were found in four women and two men, moderate cystic changes were seen in three women and seven men, but considerable cystic changes were seen almost exclusively in women (33 women versus three men). Conclusion: CT demonstrated thin-walled pulmonary cysts in the lung bases in 28% of 186 included patients with tuberous sclerosis complex. Female patients were more affected than male patients.

Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex

International Nuclear Information System (INIS)

Adriaensen, M.E.A.P.M.; Schaefer-Prokop, C.M.; Duyndam, D.A.C.; Zonnenberg, B.A.; Prokop, M.

2011-01-01

Aim: To determine the gender-specific prevalence of pulmonary cysts typical for lymphangioleiomyomatosis (LAM) in adult patients with known tuberous sclerosis complex (TSC). Materials and methods: A retrospective, cross-sectional study in a cohort of 206 adult TSC patients was performed. Institutional review board approval was obtained, and patient informed consent was waived. Patients had routinely undergone abdominal CT scanning between 1996 and 2006. All 186 patients (mean age 38 years; range 19-72 years; 91 (49%) male patients) in whom at least the lung bases were depicted on computed tomography (CT) were included. Images were reviewed for the presence of pulmonary thin-walled cysts. Descriptive statistics, two sample t-test to compare means, and χ 2 -test to compare proportions were applied. Results: CT demonstrated pulmonary thin-walled cysts in the lung bases in 52 (28%) of 186 patients. Size varied from 2 mm in diameter to more than 2 cm. Pulmonary cysts were detected in 40 (42%) of 95 female patients and in 12 (13%) of 91 male patients (p < 0.001). In general, cysts were larger and more numerous in women than in men. Only minimal cystic changes were found in four women and two men, moderate cystic changes were seen in three women and seven men, but considerable cystic changes were seen almost exclusively in women (33 women versus three men). Conclusion: CT demonstrated thin-walled pulmonary cysts in the lung bases in 28% of 186 included patients with tuberous sclerosis complex. Female patients were more affected than male patients.

Significance of tuber size for complications of tuberous sclerosis complex.

Science.gov (United States)

Pascual-Castroviejo, I; Hernández-Moneo, J L; Pascual-Pascual, S I; Viaño, J; Gutiérrez-Molina, M; Velazquez-Fragua, R; Quiñones Tapia, D; Morales Bastos, C

2013-01-01

Tuberous sclerosis complex (TSC) is one of the most frequent neurocutaneous disorders. Cortical tubers are the most common pathological changes in TSC and they are directly related to the disease's main clinical manifestations: seizures, mental retardation, and autistic behaviour. The aim of this study is to establish a correlation between tuber size and the severity of clinical features in TSC. We performed a retrospective study of the clinical and imaging findings from 45 TSC patients (22 females and 23 males) and compared the clinical features with the location, size, and number of the cortical tubers in each patient. Four patients had voluminous tubers located in 1 or both cerebral hemispheres. All of these patients had intractable seizures and severe mental retardation; 3 of these cases also presented with autistic behaviour, despite tubers having been resected in all 4 patients. Thirteen patients had tubers of large-to-average size, and all patients in this group showed intractable seizures and mental retardation. Nine patients who had experienced infantile spasms during the first year of life presented autistic behaviour. Multiple tubers of small to average size were found in 28 patients. In general, this group had seizures that responded well to antiepileptic drugs and a low prevalence of autism. In 3 patients who all presented good seizure control and normal intelligence, single cortical/subcortical tubers were located in the frontal or occipital lobes. Of the total of 45 patients, 13 had cerebellar as well as cerebral tubers; these were generally present in cases with more severe clinical features. Although large tubers are less common than small to medium-sized ones, they are much more likely to be accompanied by severe clinical symptoms (seizures, mental retardation and autistic behaviour), even when the smaller tubers are quite numerous. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Coincidence of tuberous sclerosis and systemic lupus erythematosus-a case report.

Science.gov (United States)

Carrasco Cubero, Carmen; Bejarano Moguel, Verónica; Fernández Gil, M Ángeles; Álvarez Vega, Jose Luis

2016-01-01

Tuberous sclerosis, also called Bourneville Pringle disease, is a phakomatosis with potential dermal, nerve, kidney and lung damage. It is characterized by the development of benign proliferations in many organs, which result in different clinical manifestations. It is associated with the mutation of two genes: TSC1 (hamartin) and TSC2 (tuberin), with the change in the functionality of the complex target of rapamycin (mTOR). MTOR activation signal has been recently described in systemic lupus erythematosus (SLE) and its inhibition could be beneficial in patients with lupus nephritis. We report the case of a patient who began with clinical manifestations of tuberous sclerosis complex (TSC) 30 years after the onset of SLE with severe renal disease (tipe IV nephritis) who improved after treatment with iv pulses of cyclophosphamide. We found only two similar cases in the literature, and hence considered the coexistence of these two entities of great interest. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Bilateral Giant Renal Angiomyolipoma in a Patient with Tuberous Sclerosis Complex: A Case Report

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Andika Afriansyah

2018-04-01

Full Text Available Tuberous sclerosis complex (TSC has several renal manifestations including angiomyolipomas (AML and renal epithelial neoplasms. A bilateral giant renal AML is extremely rare. We report a case of giant bilateral AML and discuss the diagnosis and treatment of it. The 22-year-old man was admitted due to bilateral flank pain, gross hematuria, and abdominal fullness. He had history of epilepsy, mental retardation, and delayed development during childhood. He had angiofibroma on his face since 10 years ago. Abdominal CT and MRI revealed large lobulated heterogeneous mass with fatty content. Based on those findings, we diagnosed the patient with bilateral giant renal AML. We gave conservative management for the patient and planned to total nephrectomy on the left kidney if the continued bleeding occurred. AML associated with TSC occur more frequently as multiple lesions and grows to larger size than idiopathic AML. Bilateral giant AML, which is very rare, could be treated with conservative management if no significant hemorrhage occurred.

Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.

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Wyatt B Potter

Full Text Available Tuberous sclerosis complex (TSC is a multisystem genetic disease that manifests with mental retardation, tumor formation, autism, and epilepsy. Heightened signaling through the mammalian target of rapamycin (mTOR pathway is involved in TSC pathology, however it remains unclear how other signaling pathways are perturbed and contribute to disease symptoms. Reduced long-term depression (LTD was recently reported in TSC mutant mice. We find that although reduced LTD is a feature of the juvenile mutant hippocampus, heightened expression of metabotropic glutamate receptor 5 and constitutively activated Erk signaling in the adult hippocampus drives wild-type levels of LTD. Increased mGluR5 and Erk results in a novel mTOR-independent LTD in CA1 hippocampus of adult mice, and contributes to the development of epileptiform bursting activity in the TSC2(+/- CA3 region of the hippocampus. Inhibition of mGluR5 or Erk signaling restores appropriate mTOR-dependence to LTD, and significantly reduces epileptiform bursting in TSC2(+/- hippocampal slices. We also report that adult TSC2(+/- mice exhibit a subtle perseverative behavioral phenotype that is eliminated by mGluR5 antagonism. These findings highlight the potential of modulating the mGluR5-Erk pathway in a developmental stage-specific manner to treat TSC.

PHAKOMATOSIS : INTRESTING CASES OF TUBEROUS SCLEROSIS WITH RETINAL ASTROCYTOMA

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Srinivasa Rao

2015-05-01

Full Text Available NTRODUCTION: Tuberous sclerosis complex (TSC or Morbus Bourneville - Pringle disease is an autosomal dominant phakomatosis, first described by Desiree - Magloire Bourneville in 1880. Tuberous sclerosis is a genetic disorder characterized by the growth of numerous benign tumours in many parts of the body caused by mutations on either of two genes, TSC1 and TSC2. This rare genetic disorder is usually associated with a triad of seizures, mental retardation and cutaneous lesions. Approximately one half of all patients affected by TS develop at least one retinal astrocytoma in one eye. PRESENTATION OF CASES: In the department of ophthalmology, G.S.L M edical C ollege, Rajahmundry, we came across 3 cases of tuberous sclerosis involving multi organ systems. Out of 3 cases, 2 cases were reported to be familial and 1case is sporadic, with a history of epilepsy with angiofibromatosis lesions over the face, multiple ash - leaf lesions over the abdomen, renal angiomyolipomas, multiple subependymal nodules in brain and retinal astrocytic hamartomas in the retina. CONCLUSION: It is important to be cognizant of the likely presence of systemic and ocular pathology in a child with mental retardation and skin lesions. Identification of retinal phakomatosis during ocular evaluation in any suspected case of Tuberous sclerosis can aid in the establishment of the diagnosis of the disease

Analysis of twenty pediatric cases of tuberous sclerosis complex: Are we doing enough?

Directory of Open Access Journals (Sweden)

Jyoti Nath

2015-01-01

Full Text Available Background: Tuberous sclerosis complex (TSC is a neuro-cutaneous disease characterized by hamartoma formation in various organs particularly the skin, brain, eye, kidney, heart and lungs. Patients usually have multisystem involvement and thus present to different medical specialties with varied complaints while the true nature of the disease and the hidden manifestations may remain unattended. A im: To assess the frequency and characteristics of various cutaneous and systemic manifestations in TSC and the total impact on different system in a cohort of pediatric patients. Methods: The study included 20 patients fulfilling the diagnostic criteria for TSC from dermatology, pediatrics, and neurology department. Detailed history, examination, and investigations such as chest X-ray, electrocardiography (ECG, ultrasonography (USG abdomen, echocardiography, fundoscopy, computed tomography (CT scan of brain and abdomen were done. Results: Dermatological manifestations included ash leaf macules, angiofibromas, shagreen patch, and fibrous plaque. Systemic findings observed were subependymal calcified nodules, subependymal giant cell astrocytoma, cortical tubers, renal cysts, angiomyolipomas, lung cyst, retinal hamartomas, mental deficits and epilepsy. Limitations: Wechsler′s Intelligence Scale for Children would have been more appropriate for assessing the intelligence. Dental check-up was not done in our group of patients. Conclusion: Our study highlights the wide variety of cutaneous and systemic manifestations of TSC. The study emphasizes the need for comprehensive multidisciplinary treatment and periodic follow-up which are necessary for appropriate management of this multisystem disorder. Counseling regarding education and rehabilitation of the patients and genetic counseling of parents are important.

Cross-sectional Imaging Review of Tuberous Sclerosis.

Science.gov (United States)

Krishnan, Anant; Kaza, Ravi K; Vummidi, Dharshan R

2016-05-01

Tuberous sclerosis complex (TSC) is a multisystem, genetic disorder characterized by development of hamartomas in the brain, abdomen, and thorax. It results from a mutation in one of 2 tumor suppressor genes that activates the mammalian target of rapamycin pathway. This article discusses the origins of the disorder, the recently updated criteria for the diagnosis of TSC, and the cross-sectional imaging findings and recommendations for surveillance. Familiarity with the diverse radiological features facilitates diagnosis and helps in treatment planning and monitoring response to treatment of this multisystem disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

(TSC) in Bulgaria: six novel mutations in the TSC1 and TSC2 genes

Indian Academy of Sciences (India)

G2-Trombo

Zdrave” str., ... Our data is similar to previous studies with .... The TSC1 and TSC2 protein products, hamartin (TSC1) with 1164 amino acids and tuberin ... cohort are missense, frameshift and nonsense mutations, while in the TSC1 gene most of ...

A novel TSC2 mutation in a Chinese family with tuberous sclerosis ...

Indian Academy of Sciences (India)

1Department of Medical Genetics, College of Basic Medical Science and 2Undergraduate Student Brigade, ... Recent studies in the TSC patients indicated that mutations ... Because of the low back pain he ... tein of 946 amino acids instead of a normal tuberin protein ... In the TSC cohort, more than 90% had skin lesions,.

Magnetic resonance imaging and diffusion-weighted imaging of normal-appearing white matter in children and young adults with tuberous sclerosis complex

International Nuclear Information System (INIS)

Arulrajah, Sahayini; Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M.; Jordan, Lori; Khaykin, Elizabeth; Izbudak, Izlem

2009-01-01

Patients with tuberous sclerosis complex (TSC) frequently present with neurocognitive deficits which may be related to impaired white matter maturation. The purposes of our study were (a) to evaluate the white matter maturation in children and young adults with TSC by comparing the apparent diffusion coefficient (ADC) values of normal-appearing white matter (NAWM) with age-matched healthy controls and (b) to determine the association of NAWM-ADC values with the severity of neurological symptoms in TSC patients. Twenty-three TSC patients who underwent magnetic resonance imaging/diffusion-weighted imaging between January 2000 and January 2009 were studied. ADC values of NAWM were measured in the frontal, parietal, occipital lobes, and in the pons. ADC data were compared with age-matched normative data derived from healthy controls. Patients were neurologically scored by a pediatric neurologist. Two-sample t tests and linear regression were conducted using STATA software. ADC values of NAWM were higher in TSC patients compared with healthy controls; the increase, however, only reached statistical significance in the frontal white matter and pons in the age group between 96 and 144 months and in the right parietal and occipital white matter in the age group above 144 months. There was no significant change in neurological severity score per unit increase in ADC measurement. ADC values of NAWM appear increased in TSC patients. The abnormal ADC values suggest that myelination may be delayed/impaired in TSC patients, which could explain global neurocognitive deficits. Larger prospective studies, including diffusion tensor imaging, are necessary to validate our results. (orig.)

Magnetic resonance imaging and diffusion-weighted imaging of normal-appearing white matter in children and young adults with tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Arulrajah, Sahayini; Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M. [Johns Hopkins Hospital, Division of Pediatric Radiology, Department of Radiology and Radiological Science, Baltimore, MD (United States); Jordan, Lori [Johns Hopkins School of Public Health, Division of Pediatric Neurology, Baltimore, MD (United States); Khaykin, Elizabeth [Johns Hopkins School of Public Health, Department of Mental Health, Baltimore, MD (United States); Izbudak, Izlem [Johns Hopkins Hospital, Division of Neuroradiology, Department of Radiology and Radiological Science, Baltimore, MD (United States)

2009-11-15

Patients with tuberous sclerosis complex (TSC) frequently present with neurocognitive deficits which may be related to impaired white matter maturation. The purposes of our study were (a) to evaluate the white matter maturation in children and young adults with TSC by comparing the apparent diffusion coefficient (ADC) values of normal-appearing white matter (NAWM) with age-matched healthy controls and (b) to determine the association of NAWM-ADC values with the severity of neurological symptoms in TSC patients. Twenty-three TSC patients who underwent magnetic resonance imaging/diffusion-weighted imaging between January 2000 and January 2009 were studied. ADC values of NAWM were measured in the frontal, parietal, occipital lobes, and in the pons. ADC data were compared with age-matched normative data derived from healthy controls. Patients were neurologically scored by a pediatric neurologist. Two-sample t tests and linear regression were conducted using STATA software. ADC values of NAWM were higher in TSC patients compared with healthy controls; the increase, however, only reached statistical significance in the frontal white matter and pons in the age group between 96 and 144 months and in the right parietal and occipital white matter in the age group above 144 months. There was no significant change in neurological severity score per unit increase in ADC measurement. ADC values of NAWM appear increased in TSC patients. The abnormal ADC values suggest that myelination may be delayed/impaired in TSC patients, which could explain global neurocognitive deficits. Larger prospective studies, including diffusion tensor imaging, are necessary to validate our results. (orig.)

Mechanism of Akt1 inhibition of breast cancer cell invasionreveals a protumorigenic role for TSC2

Energy Technology Data Exchange (ETDEWEB)

Liu, Hong; Radisky, Derek C.; Nelson, Celeste M.; Zhang, Hui; Fata, Jimmie; Roth, Richard A.; Bissell, Mina J.

2006-02-07

Akt1 is frequently upregulated in human tumors, and has been shown to accelerate cell proliferation and to suppress programmed cell death; consequently, inhibiting the activity of Akt1 has been seen as an attractive target for therapeutic intervention. Paradoxically, hyperactivation of the Akt1 oncogene can also prevent the invasive behavior that underlies progression to metastasis. Here we show that overexpression of activated myr-Akt1 in human breast cancer cells phosphorylates and thereby targets the tumor suppressor tuberous sclerosis complex 2 (TSC2) for degradation, leading to reduced Rho-GTPase activity, decreased actin stress fibers and focal adhesions, and reduced motility and invasion. Overexpression of TSC2 rescues the migration phenotype of myr-Akt1-expressing tumor cells, and high levels of TSC2 in breast cancer patients correlate with increased metastasis and reduced survival. These data indicate that the functional properties of genes designated as oncogenes or tumor suppressor genes depends on the context of the cell type and the tissues studied, and suggest the need for caution in designing therapies targeting the function of individual genes in epithelial tissues.

TSC1/2 mutations define a molecular subset of HCC with aggressive behaviour and treatment implication.

Science.gov (United States)

Ho, Daniel W H; Chan, Lo K; Chiu, Yung T; Xu, Iris M J; Poon, Ronnie T P; Cheung, Tan T; Tang, Chung N; Tang, Victor W L; Lo, Irene L O; Lam, Polly W Y; Yau, Derek T W; Li, Miao X; Wong, Chun M; Ng, Irene O L

2017-08-01

We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC -mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2 -mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment. Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The neuroanatomical phenotype of tuberous sclerosis complex: focus on radial migration lines

International Nuclear Information System (INIS)

Eeghen, Agnies M. van; Teran, Laura Ortiz; Johnson, Jason; Caruso, Paul; Pulsifer, Margaret B.; Thiele, Elizabeth A.

2013-01-01

The contribution of radial migration lines (RMLs) to the neuroanatomical and neurocognitive phenotype of tuberous sclerosis complex (TSC) is unclear. The aim of this study was to perform a comprehensive evaluation of the neuroradiological phenotype of TSC, distinguishing RMLs from normal-appearing white matter (NAWM) using diffusion tensor imaging (DTI) and volumetric fluid-attenuated inversion recovery imaging. Magnetic resonance images of 30 patients with TSC were evaluated. The frequencies of RMLs, tubers, and subependymal nodules (SENs) were determined for every hemispheric lobe. Cerebellar lesions and subependymal giant cell tumors were counted. DTI metrics were obtained from the NAWM of every hemispheric lobe and from the largest RML and tuber. Analyses of variance and correlations were performed to investigate the associations between neuroanatomical characteristics and relationships between RML frequency and neurocognitive outcomes. NAWM DTI metrics were compared with measurements of 16 control patients. A mean of 47 RMLs, 27 tubers, and 10 SENs were found per patient, and the frequencies of these lesions were strongly correlated (p < 0.001). RML fractional anisotropy and mean diffusivity were strongly inversely correlated (p = 0.003). NAWM DTI metrics were similar to the controls (p = 0.26). RML frequency was strongly associated with age of seizure onset (p = 0.003), intelligence outcomes (p = 0.01), and level of autistic features (p = 0.007). A detailed neuroradiological phenotype is presented, showing that RMLs are the most frequent neuroanatomical lesion, are responsible for white matter DTI abnormalities, and are strongly associated with age of seizure onset, intelligence outcomes, and level of autistic features. (orig.)

The neuroanatomical phenotype of tuberous sclerosis complex: focus on radial migration lines

Energy Technology Data Exchange (ETDEWEB)

Eeghen, Agnies M. van [Massachusetts General Hospital, Department of Neurology, Carol and James Herscot Center for Tuberous Sclerosis Complex, Boston, MA (United States); Erasmus Medical Centre, ENCORE, Expertise Centre for Neurodevelopmental Disorders, Department of Neuroscience, Rotterdam (Netherlands); Teran, Laura Ortiz; Johnson, Jason; Caruso, Paul [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States); Pulsifer, Margaret B. [Massachusetts General Hospital, Department of Psychiatry, Psychological Assessment Center, Boston, MA (United States); Thiele, Elizabeth A. [Massachusetts General Hospital, Department of Neurology, Carol and James Herscot Center for Tuberous Sclerosis Complex, Boston, MA (United States)

2013-08-15

The contribution of radial migration lines (RMLs) to the neuroanatomical and neurocognitive phenotype of tuberous sclerosis complex (TSC) is unclear. The aim of this study was to perform a comprehensive evaluation of the neuroradiological phenotype of TSC, distinguishing RMLs from normal-appearing white matter (NAWM) using diffusion tensor imaging (DTI) and volumetric fluid-attenuated inversion recovery imaging. Magnetic resonance images of 30 patients with TSC were evaluated. The frequencies of RMLs, tubers, and subependymal nodules (SENs) were determined for every hemispheric lobe. Cerebellar lesions and subependymal giant cell tumors were counted. DTI metrics were obtained from the NAWM of every hemispheric lobe and from the largest RML and tuber. Analyses of variance and correlations were performed to investigate the associations between neuroanatomical characteristics and relationships between RML frequency and neurocognitive outcomes. NAWM DTI metrics were compared with measurements of 16 control patients. A mean of 47 RMLs, 27 tubers, and 10 SENs were found per patient, and the frequencies of these lesions were strongly correlated (p < 0.001). RML fractional anisotropy and mean diffusivity were strongly inversely correlated (p = 0.003). NAWM DTI metrics were similar to the controls (p = 0.26). RML frequency was strongly associated with age of seizure onset (p = 0.003), intelligence outcomes (p = 0.01), and level of autistic features (p = 0.007). A detailed neuroradiological phenotype is presented, showing that RMLs are the most frequent neuroanatomical lesion, are responsible for white matter DTI abnormalities, and are strongly associated with age of seizure onset, intelligence outcomes, and level of autistic features. (orig.)

Tuberous Sclerosis

Science.gov (United States)

... National Institute of Neurological Disorders and Stroke (NINDS). Esclerosis tuberosa Order NINDS Publications Patient Organizations Child Neurology ... National Institute of Neurological Disorders and Stroke (NINDS). Esclerosis tuberosa Order NINDS Publications Definition Tuberous sclerosis (TSC) ...

Tsc2 Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during Gestational Immune Activation

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Dan Ehninger

2014-01-01

Full Text Available Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of syndromic autism, such as autism associated with tuberous sclerosis, a genetic disorder caused by heterozygous TSC1 or TSC2 mutations. Environmental risk factors, such as gestational viral infections, may, in some cases, also contribute to the pathogenesis of autism and related neuropsychiatric disorders. We have recently found that a heterozygous Tsc2 mutation and the poly I:C model of maternal immune activation (MIA interactively perturb fetal development and adult social behavior in mice, suggesting that these factors converge on shared pathways. TSC/mTOR signaling plays an important role in the modulation of immune responses, raising the possibility that the damage caused by MIA was greater in Tsc2+/− than in wildtype fetuses because of an exacerbated immune response in the mutants. Here, cytokine antibody arrays were employed to measure relative cytokine abundances in the fetal brain and the placenta during MIA. Cytokines were induced by gestational poly I:C but there was no obvious modulatory effect of Tsc2 haploinsufficiency. The data indicate that cytokine exposure during MIA is comparable in Tsc2 haploinsufficient and wildtype control fetuses, suggesting that downstream molecular and cellular processes may account for the interactive effects of Tsc2 haploinsufficiency and MIA.

Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice.

Science.gov (United States)

Zhang, Danqing; Kobayashi, Toshiyuki; Kojima, Tetsuo; Kanenishi, Kenji; Hagiwara, Yoshiaki; Abe, Masaaki; Okura, Hidehiro; Hamano, Yoshitomo; Sun, Guodong; Maeda, Masahiro; Jishage, Kou-ichi; Noda, Tetsuo; Hino, Okio

2011-04-01

Genetic crossing experiments were performed between tuberous sclerosis-2 (Tsc2) KO and expressed in renal carcinoma (Erc) KO mice to analyze the function of the Erc/mesothelin gene in renal carcinogenesis. We found the number and size of renal tumors were significantly less in Tsc2+/-;Erc-/- mice than in Tsc2+/-;Erc+/+ and Tsc2+/-;Erc+/- mice. Tumors from Tsc2+/-;Erc-/- mice exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen (Ki67) and TUNEL analysis, respectively. Adhesion to collagen-coated plates in vitro was enhanced in Erc-restored cells and decreased in Erc-suppressed cells with siRNA. Tumor formation by Tsc2-deficient cells in nude mice was remarkably suppressed by stable knockdown of Erc with shRNA. Western blot analysis showed that the phosphorylation of focal adhesion kinase, Akt and signal transducer and activator of transcription protein 3 were weaker in Erc-deficient/suppressed cells compared with Erc-expressed cells. These results indicate that deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 KO mice and inhibits the phosphorylation of several kinases of cell adhesion mechanism. This suggests that Erc/mesothelin may have an important role in the promotion and/or maintenance of carcinogenesis by influencing cell-substrate adhesion via the integrin-related signal pathway. © 2011 Japanese Cancer Association.

Targeted treatment trials for tuberous sclerosis and autism: no longer a dream.

Science.gov (United States)

Sahin, Mustafa

2012-10-01

Genetic disorders that present with a high incidence of autism spectrum disorders (ASD) offer tremendous potential both for elucidating the underlying neurobiology of ASD and identifying therapeutic drugs and/or drug targets. As a result, clinical trials for genetic disorders associated with ASD are no longer a hope for the future but rather an exciting reality whose time has come. Tuberous sclerosis complex (TSC) is one such genetic disorder that presents with ASD, epilepsy, and intellectual disability. Cell culture and mouse model experiments have identified the mTOR pathway as a therapeutic target in this disease. This review summarizes the advantages of using TSC as model of ASD and the recent advances in the translational and clinical treatment trials in TSC. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical features of tuberous sclerosis complex in children with epilepsy

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Dong LI

2014-12-01

Full Text Available Objective To explore the clinical features of tuberous sclerosis complex (TSC in children with epilepsy.  Methods The clinical data of 36 TSC children complicated with epilepsy were analyzed retrospectively.  Results All children had epilepsy as first symptom: 23 cases of seizures happened on age less than one year old (63.89%, 8 cases on age 1-3 years old (22.22%, and 5 cases on age more than 3 years old (13.89% . Main attack types were as follows: 12 cases with focal seizures (33.33% , 5 cases with generalized seizures (13.89% , 7 cases with spasms (19.44% and 12 cases (33.33% with mixed seizures. Mental retardation was found in 19 cases (67.86%. Among 30 cases who received brain MRI examination, all had subependymal nodules, 26 cases (86.67% were complicated with cortical and subcortical nodules, 2 cases (6.67% with subependymal giant cell astrocytoma (SEGA, one case (3.33% with pachygyria. EEG examination showed interictal epileptiform discharges in 34 cases (94.44% , including multifocal discharges in 12 patients (35.29% , generalized discharges in 8 patients (23.53% , focal discharges and hypsarrhythmia in 7 patients (20.59% respectively. Seizures were monitored in 8 patients, and the types included spasms in 4 cases, focal seizures in 3 cases, and myoclonic seizures in one case. Seventeen cases (47.22% took one single antiepileptic drug, 12 cases (33.33% took two drugs, and 7 cases (19.44% took three drugs, while one of them underwent surgical treatment. After 0.50-10 year follow-up, seizures free happened in 7 cases (19.44%, improved in 16 cases (44.44%, and invalid in 13 cases (36.11%.  Conclusions Epilepsy is the most common nervous system performance in children TSC, and most seizures begin to happen in infants. The main types of onset are partial seizures and spasms. Most of the patients get improved with antiepileptic drugs. doi: 10.3969/j.issn.1672-6731.2014.12.011

Role of CTGF in White Matter Development in Tuberous Sclerosis

Science.gov (United States)

2016-04-01

which lacks Tsc1 expression only in neurons . Here we show that, neurons lacking Tsc1 secrete excessive amounts of connective tissue growth factor...that, neurons lacking Tsc1 secrete excessive amounts of connective tissue growth factor (CTGF), which in turn blocks the maturation of...Columbia University Medical Center New York, NY 2015 Neuronal Connectivity in Tuberous Sclerosis / Keynote Stanley Manne Children’s Research Institute

six novel mutations in the TSC1 and TSC2 genes

Indian Academy of Sciences (India)

M. GLUSHKOVA

2018-04-30

Apr 30, 2018 ... RESEARCH ARTICLE ... nant disorder caused by inactivating TSC1 or TSC2 gene variants (Van ... premature protein truncation, while missense mutations are rare ..... TSC2 variants in our cohort are missense, frame-shift.

From mTOR to Cognition: Molecular and Cellular Mechanisms of Cognitive Impairments in Tuberous Sclerosis

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Ehninger, D.; de Vries, P. J.; Silva, A. J.

2009-01-01

Background: Tuberous sclerosis (TSC) is a multi-system disorder caused by heterozygous mutations in the "TSC1" or "TSC2" gene and is often associated with neuropsychiatric symptoms, including intellectual disability, specific neuropsychological deficits, autism, other behavioural disorders and epilepsy. Method: Here, we review evidence from animal…

Altered inhibition in Tuberous Sclerosis and Type IIb cortical dysplasia

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Talos, Delia M.; Sun, Hongyu; Kosaras, Bela; Joseph, Annelise; Folkerth, Rebecca D.; Poduri, Annapurna; Madsen, Joseph R.; Black, Peter M.; Jensen, Frances E.

2012-01-01

Objective The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early-life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered GABAA receptor (GABAAR)-mediated inhibition. Methods Expression of the GABAAR subunitsα1 and α4, the Na+-K+-2Cl− (NKCC1), and the K+−Cl− (KCC2) transporters in human TSC and FCD Type II specimens were analyzed by Western blot and double label immunocytochemistry. GABAAR responses in dysplastic neurons from a single case of TSC were measured by perforated-patch recording and compared to normal-appearing cortical neurons from a non-TSC epilepsy case. Results TSC and FCD Type IIb lesions demonstrated decreased expression of the GABAAR α1, increased NKCC1 and decreased KCC2 levels. In contrast, FCD Type IIa lesions showed decreased α4, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABAAR responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABAAR-mediated currents in normal neurons from non-TSC cortical slices. Interpretation Expression and function of GABAARs in TSC and FCD IIb suggests the relative benzodiazepine insensitivity and more excitatory action of GABA compared to FCD IIa. These factors may contribute to resistance of seizure activity to anticonvulsants that increase GABAergic function, and may justify add-on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD Type IIb related epilepsy. PMID:22447678

Tumor suppressors TSC1 and TSC2 differentially modulate actin cytoskeleton and motility of mouse embryonic fibroblasts.

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Elena A Goncharova

Full Text Available TSC1 and TSC2 mutations cause neoplasms in rare disease pulmonary LAM and neuronal pathfinding in hamartoma syndrome TSC. The specific roles of TSC1 and TSC2 in actin remodeling and the modulation of cell motility, however, are not well understood. Previously, we demonstrated that TSC1 and TSC2 regulate the activity of small GTPases RhoA and Rac1, stress fiber formation and cell adhesion in a reciprocal manner. Here, we show that Tsc1(-/- MEFs have decreased migration compared to littermate-derived Tsc1(+/+ MEFs. Migration of Tsc1(-/- MEFs with re-expressed TSC1 was comparable to Tsc1(+/+ MEF migration. In contrast, Tsc2(-/- MEFs showed an increased migration compared to Tsc2(+/+ MEFs that were abrogated by TSC2 re-expression. Depletion of TSC1 and TSC2 using specific siRNAs in wild type MEFs and NIH 3T3 fibroblasts also showed that TSC1 loss attenuates cell migration while TSC2 loss promotes cell migration. Morphological and immunochemical analysis demonstrated that Tsc1(-/- MEFs have a thin protracted shape with a few stress fibers; in contrast, Tsc2(-/- MEFs showed a rounded morphology and abundant stress fibers. Expression of TSC1 in either Tsc1(-/- or Tsc2(-/- MEFs promoted stress fiber formation, while TSC2 re-expression induced stress fiber disassembly and the formation of cortical actin. To assess the mechanism(s by which TSC2 loss promotes actin re-arrangement and cell migration, we explored the role of known downstream effectors of TSC2, mTORC1 and mTORC2. Increased migration of Tsc2(-/- MEFs is inhibited by siRNA mTOR and siRNA Rictor, but not siRNA Raptor. siRNA mTOR or siRNA Rictor promoted stress fiber disassembly in TSC2-null cells, while siRNA Raptor had little effect. Overexpression of kinase-dead mTOR induced actin stress fiber disassembly and suppressed TSC2-deficient cell migration. Our data demonstrate that TSC1 and TSC2 differentially regulate actin stress fiber formation and cell migration, and that only TSC2 loss promotes

Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference.

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Krueger, Darcy A; Northrup, Hope

2013-10-01

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-threatening with significant impact on cost and quality of life. Current surveillance and management practices are 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. 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. 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. 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. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

High gamma-aminobutyric acid level in cortical tubers in epileptic infants with tuberous sclerosis complex measured with the MEGA-editing J-difference method and a three-Tesla clinical MRI Instrument.

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Taki, Masako Minato; Harada, Masafumi; Mori, Kenji; Kubo, Hitoshi; Nose, Ayumi; Matsuda, Tsuyoshi; Nishitani, Hiromu

2009-10-01

The purpose of this study was to estimate the gamma-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) concentrations in the cortical tubers of patients with tuberous sclerosis complex (TSC) using the MEGA-editing J-difference method and a stimulated echo-acquisition mode with a short echo time, and to determine which abnormality was more dominant between GABA and Glx in patients with TSC with epilepsy. This study included six patients with TSC (mean age, 4.3 years) and seven control subjects (mean age, 4.8 years). Measurements were obtained with a three-Tesla apparatus and postprocessing was conducted with an LCModel. The GABA level in the cortical gray matter (cgGABA) was calculated as a result of segmentation in voxels and from the literature values for gray and white matter ratios for GABA. Increased GABA and myo-inositol (mI) concentrations and a decreased N-acetyl aspartate (NAA) concentration were observed in the cortical tubers. The cgGABA level, and cgGABA/NAA and cgGABA/Glx ratios were also higher in patients with TSC than in control subjects. No significant difference was found in Glx concentration between patients with TSC and control subjects. Although the number of patients with TSC in this study was small, the increase in GABA and no significant change in Glx were consistent with previous neurochemical studies and support the hypothesis that brain GABA plays a key role in the pathophysiology of epilepsy during the process of neuronal development.

Genetics Home Reference: tuberous sclerosis complex

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... 42. Citation on PubMed Northrup H, Koenig MK, Pearson DA, Au KS. Tuberous Sclerosis Complex. 1999 Jul ... Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007 Aug;57(2): ...

mTORC1 Inhibition Corrects Neurodevelopmental and Synaptic Alterations in a Human Stem Cell Model of Tuberous Sclerosis

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Veronica Costa

2016-04-01

Full Text Available Hyperfunction of the mTORC1 pathway has been associated with idiopathic and syndromic forms of autism spectrum disorder (ASD, including tuberous sclerosis, caused by loss of either TSC1 or TSC2. It remains largely unknown how developmental processes and biochemical signaling affected by mTORC1 dysregulation contribute to human neuronal dysfunction. Here, we have characterized multiple stages of neurogenesis and synapse formation in human neurons derived from TSC2-deleted pluripotent stem cells. Homozygous TSC2 deletion causes severe developmental abnormalities that recapitulate pathological hallmarks of cortical malformations in patients. Both TSC2+/− and TSC2−/− neurons display altered synaptic transmission paralleled by molecular changes in pathways associated with autism, suggesting the convergence of pathological mechanisms in ASD. Pharmacological inhibition of mTORC1 corrects developmental abnormalities and synaptic dysfunction during independent developmental stages. Our results uncouple stage-specific roles of mTORC1 in human neuronal development and contribute to a better understanding of the onset of neuronal pathophysiology in tuberous sclerosis.

Targeted treatment trials for tuberous sclerosis and autism: no longer a dream

OpenAIRE

Sahin, Mustafa

2012-01-01

Genetic disorders that present with a high incidence of autism spectrum disorders (ASD) offer tremendous potential both for elucidating the underlying neurobiology of ASD and identifying therapeutic drugs and/or drug targets. As a result, clinical trials for genetic disorders associated with ASD are no longer a hope for the future but rather an exciting reality whose time has come. Tuberous sclerosis complex (TSC) is one such genetic disorder that presents with ASD, epilepsy, and intellectual...

Distinctive MRI features of the epileptogenic zone in children with tuberous sclerosis

International Nuclear Information System (INIS)

Jahodova, A.; Krsek, P.; Kyncl, M.; Jezdik, P.; Kudr, M.; Komarek, V.; Jayakar, P.; Miller, I.; Resnick, T.

2014-01-01

Objective: Localization of the epileptogenic zone (EZ) is challenging in children with tuberous sclerosis complex (TSC). We sought to ascertain whether brain MRI could identify the EZ in TSC patients independent of the clinical and diagnostic data. Methods: Presurgical MRI's of 34 children with TSC who underwent epilepsy surgery at Miami Children's Hospital were retrospectively reevaluated by experts blinded to all other data. Changes typical of TSC (tubers, calcifications, cystic changes) and abnormalities of the perituberal cortex typical of focal cortical dysplasia (FCD) (increased cortical thickness, abnormal gyration, transmantle change, gray/white matter junction blurring) were identified and their localization was compared with the resection site. Sensitivity, specificity and accuracy of individual MRI features to localize the EZ were determined and statistically compared between postoperatively seizure-free and non-seizure-free patients as well as clusters of features typical of FCD and TSC. Results: MRI alone correctly localized the resection cavity in all 19 postoperatively seizure-free patients and 12 of 15 non-seizure-free subjects. Sensitivity, specificity and accuracy of MRI features typical of FCD to localize EZ (90%, 96% and 96%, respectively) were superior to those typical of TCS (79%, 75% and 75%, p < 0.0001). Increased cortical thickness and abnormal gyral formation outside tubers occurred only in the resection site. Resection sites were better predicted by MRI in seizure-free than in non-seizure-free patients. Conclusion: Thorough MRI evaluation identifies the EZ in a significant proportion of TSC patients. Epileptogenic regions were mostly characterized by “FCD-like” changes outside cortical tubers. The findings may have important practical consequences for surgical planning in TSC

Distinctive MRI features of the epileptogenic zone in children with tuberous sclerosis

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Jahodova, A., E-mail: a.jagoda@email.cz [Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Krsek, P., E-mail: pavel.krsek@post.cz [Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Kyncl, M., E-mail: martinkyn@seznam.cz [Department of Radiology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Jezdik, P., E-mail: jezdip1@feld.cvut.cz [Department of Measurement, Faculty of Electric, Czech Technical University Prague, Technicka 2, CZ 166 27 Prague 6 (Czech Republic); Kudr, M., E-mail: mat.kudr@gmail.com [Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Komarek, V., E-mail: vladimir.komarek@fnmotol.cz [Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, V Uvalu 84, Prague 5 150 06 (Czech Republic); Jayakar, P., E-mail: Prasanna.Jayakar@mch.com [Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children' s Hospital, 3200 S.W. 60th Court, Miami, FL (United States); Miller, I., E-mail: ian.miller@mchdocs.com [Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children' s Hospital, 3200 S.W. 60th Court, Miami, FL (United States); Resnick, T., E-mail: trevor.resnick@mch.com [Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children' s Hospital, 3200 S.W. 60th Court, Miami, FL (United States); Department of Neurology, University of Miami Miller School of Medicine, Miami, FL (United States); and others

2014-04-15

Objective: Localization of the epileptogenic zone (EZ) is challenging in children with tuberous sclerosis complex (TSC). We sought to ascertain whether brain MRI could identify the EZ in TSC patients independent of the clinical and diagnostic data. Methods: Presurgical MRI's of 34 children with TSC who underwent epilepsy surgery at Miami Children's Hospital were retrospectively reevaluated by experts blinded to all other data. Changes typical of TSC (tubers, calcifications, cystic changes) and abnormalities of the perituberal cortex typical of focal cortical dysplasia (FCD) (increased cortical thickness, abnormal gyration, transmantle change, gray/white matter junction blurring) were identified and their localization was compared with the resection site. Sensitivity, specificity and accuracy of individual MRI features to localize the EZ were determined and statistically compared between postoperatively seizure-free and non-seizure-free patients as well as clusters of features typical of FCD and TSC. Results: MRI alone correctly localized the resection cavity in all 19 postoperatively seizure-free patients and 12 of 15 non-seizure-free subjects. Sensitivity, specificity and accuracy of MRI features typical of FCD to localize EZ (90%, 96% and 96%, respectively) were superior to those typical of TCS (79%, 75% and 75%, p < 0.0001). Increased cortical thickness and abnormal gyral formation outside tubers occurred only in the resection site. Resection sites were better predicted by MRI in seizure-free than in non-seizure-free patients. Conclusion: Thorough MRI evaluation identifies the EZ in a significant proportion of TSC patients. Epileptogenic regions were mostly characterized by “FCD-like” changes outside cortical tubers. The findings may have important practical consequences for surgical planning in TSC.

Eye Involvement in TSC

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... 50% of the individuals with TSC have normal intelligence, and inasmuch as these individuals may become parents, ... of vision may be difficult or impossible. Since growth and change of TSC lesions in the eye ...

Parental Understanding of Tuberous Sclerosis Complex.

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Samia, Pauline; Donald, Kirsten A; Schlegel, Birgit; Wilmshurst, Jo M

2015-09-01

Tuberous sclerosis complex is a genetic disorder with multisystem involvement that poses significant challenges to the affected child and family. Caregiver knowledge in the South African population has not previously been reported. A prospective study of the parents of 21 children with tuberous sclerosis complex was undertaken. Median parental age was 38 (interquartile range 34.5-45) years. Parents were randomly allocated to receive written information about the condition, or to receive verbal counseling already established in clinic. A significant difference (P = .001) was observed in the change in the mean knowledge scores for the parent group that received written information (34.2 at baseline, 51.7 at the second visit. This impact was higher in parents with an education level of at least grade 8 (P = .003). Parental understanding of tuberous sclerosis complex can be improved by provision of written information and should be routinely available in a readily understandable format. © The Author(s) 2014.

Identification of NPM and DDX5 as Therapeutic Targets in TSC

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2017-12-01

Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited...9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort...complexes in TSC cells. 15. SUBJECT TERMS NPM, DDX5, TSC, chemical library , split-luciferase 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT

Attention Deficit Hyperactivity Disorder and Tuberous Sclerosis Complex

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... Privacy Policy Sitemap Learn Engage Donate About TSC Attention Deficit Hyperactivity Disorder and TSC What is ADHD? Attention Deficit Hyperactivity Disorder (ADHD) is a common neurobehavioral disorder. It is ...

Types of Seizures Affecting Individuals with TSC

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... Policy Sitemap Learn Engage Donate About TSC Epilepsy/Seizure Disorders Seizures remain one of the most common neurological ... TSC Brain and Neurological Function Brain Abnormalities Epilepsy/Seizure Disorders Infantile Spasms Epilepsy in Adults with TSC Epilepsy ...

Tuberous sclerosis complex: A case report

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Soumyabrata Sarkar

2016-01-01

Full Text Available Tuberous sclerosis complex is an unusual autosomal dominant neurocutaneous syndrome characterized by the development of benign tumors affecting different body systems affecting the brain, skin, retina, and viscera. It is characterized by cutaneous changes, neurologic conditions, and the formation of hamartomas in multiple organs leading to morbidity and mortality. The most common oral manifestations are fibromas, gingival hyperplasia, and enamel hypoplasia. The management of these patients is often multidisciplinary involving specialists from various fields. Here, we present a case report of a 26-old-year male patient with characteristic clinical, radiological, and histological features of tuberous sclerosis complex.

Time-dependent EQPET analysis of TSC

International Nuclear Information System (INIS)

Takahashi, Akito

2006-01-01

Time-dependent fusion rates for 2D and 4D reactions are calculated for squeezing of tetrahedral symmetric condensate (TSC) from about 100 pm size to its minimum size (about 10 fm), within about 75 fs squeezing motion. Life time of the minimum TSC state is yet to be studied. Time-averaged fusion rates are given by assuming the life time of minimum TSC state is negligible. Time-averaged 2D fusion rate was given as 2.9x10 -25 f/s/pair, and time-averaged 4D fusion rate was 5.5x10 -8 f/s/cl. These values are compared with 1.0x10 -20 f/s/pair for 2D and 1.0x10 -9 f/s/cl for 4D, respectively, of previously estimated values by electronic quasi-particle expansion theory/TSC models. Effective fusion time by the TSC squeezing motion was estimated as 0.014 fs: namely fusions may happen in very short time interval. (author)

White matter abnormalities in tuberous sclerosis complex

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Griffiths, P.D. [Sheffield Univ. (United Kingdom). Academic Dept. of Radiology; Bolton, P. [Cambridge Univ. (United Kingdom). Section of Developmental Psychiatry; Verity, C. [Addenbrooke`s NHS Trust, Cambridge (United Kingdom). Dept. of Paediatric Radiology

1998-09-01

The aim of this study was to investigate and describe the range of white matter abnormalities in children with tuberous sclerosis complex by means of MR imaging. Material and Methods: A retrospective cross-sectional study was performed on the basis of MR imaging findings in 20 cases of tuberous sclerosis complex in children aged 17 years or younger. Results: White matter abnormalities were present in 19/20 (95%) cases of tuberous sclerosis complex. These were most frequently (19/20 cases) found in relation to cortical tubers in the supratentorial compartment. White matter abnormalities related to tubers were found in the cerebellum in 3/20 (15%) cases. White matter abnormalities described as radial migration lines were found in relation to 5 tubers in 3 (15%) children. In 4/20 (20%) cases, white matter abnormalities were found that were not related to cortical tubers. These areas had the appearance of white matter cysts in 3 cases and infarction in the fourth. In the latter case there was a definable event in the clinical history, supporting the diagnosis of stroke. Conclusion: A range of white matter abnormalities were found by MR imaging in tuberous sclerosis complex, the commonest being gliosis and hypomyelination related to cortical tubers. Radial migration lines were seen infrequently in relation to cortical tubers and these are thought to represent heterotopic glia and neurons along the expected path of cortical migration. (orig.)

Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST-1 Study.

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David N Franz

Full Text Available Everolimus, a mammalian target of rapamycin (mTOR inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs and other manifestations of tuberous sclerosis complex (TSC. However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828.EXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m2/day titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years who received ≥1 dose of everolimus (median duration, 47.1 months, 57.7% (95% confidence interval [CI], 47.9-67.0 achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2% achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence suspected to be treatment-related were stomatitis (43.2% and mouth ulceration (32.4%.Everolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a

Comment on "A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation": building a model of the mTOR signaling network with a potentially faulty tool.

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Manning, Brendan D

2012-07-10

In their study published in Science Signaling (Research Article, 27 March 2012, DOI: 10.1126/scisignal.2002469), Dalle Pezze et al. tackle the dynamic and complex wiring of the signaling network involving the protein kinase mTOR, which exists within two distinct protein complexes (mTORC1 and mTORC2) that differ in their regulation and function. The authors use a combination of immunoblotting for specific phosphorylation events and computational modeling. The primary experimental tool employed is to monitor the autophosphorylation of mTOR on Ser(2481) in cell lysates as a surrogate for mTOR activity, which the authors conclude is a specific readout for mTORC2. However, Ser(2481) phosphorylation occurs on both mTORC1 and mTORC2 and will dynamically change as the network through which these two complexes are connected is manipulated. Therefore, models of mTOR network regulation built using this tool are inherently imperfect and open to alternative explanations. Specific issues with the main conclusion made in this study, involving the TSC1-TSC2 (tuberous sclerosis complex 1 and 2) complex and its potential regulation of mTORC2, are discussed here. A broader goal of this Letter is to clarify to other investigators the caveats of using mTOR Ser(2481) phosphorylation in cell lysates as a specific readout for either of the two mTOR complexes.

Recurrent meningitis associated with frontal sinus tuber encephalocele in a patient with tuberous sclerosis.

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Elbabaa, Samer K; Riggs, Angela D; Saad, Ali G

2011-07-01

Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder that commonly affects the CNS. The most commonly associated brain tumors include cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). The authors report an unusual case of recurrent meningitis due to a tuber-containing encephalocele via the posterior wall of the frontal sinus. An 11-year-old girl presented with a history of TSC and previous SEGA resection via interhemispheric approach. She presented twice within 4 months with classic bacterial meningitis. Cerebrospinal fluid cultures revealed Streptococcus pneumoniae. Computed tomography and MR imaging of the brain showed a right frontal sinus encephalocele via a posterior frontal sinus wall defect. Both episodes of meningitis were treated successfully with standard regimens of intravenous antibiotics. The neurosurgical service was consulted to discuss surgical options. Via a bicoronal incision, a right basal frontal craniotomy was performed. A large frontal encephalocele was encountered in the frontal sinus. The encephalocele was herniating through a bony defect of the posterior sinus wall. The encephalocele was ligated and resected followed by removing frontal sinus mucosa and complete cranialization of frontal sinus. Repair of the sinus floor was conducted with fat and pericranial grafts followed by CSF diversion via lumbar drain. Histopathology of the resected encephalocele showed a TSC tuber covered with respiratory (frontal sinus) mucosa. Tuber cells were diffusely positive for GFAP. The patient underwent follow-up for 2 years without evidence of recurrent meningitis or CSF rhinorrhea. This report demonstrates that frontal tubers of TSC can protrude into the frontal sinus as acquired encephaloceles and present with recurrent meningitis. To the authors' knowledge, recurrent meningitis is not known to coincide with TSC. Careful clinical and radiographic follow-up for frontal tubers in patients with TSC is

lessons from tuberous sclerosis complex

African Journals Online (AJOL)

intellectual disability, autism, specific learning disorders) and mental health disorders (e.g. depression, psychosis and anxiety disorders). The first lesson, therefore, is ... of an adolescent with TSC, facial angiofibromas and a presumed fat-poor ...

Fetal and Postnatal Magnetic Resonance Imaging of Unilateral Cystic Renal Dysplasia in a Neonate with Tuberous Sclerosis

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Vineet Tyagi

2016-10-01

Full Text Available Tuberous sclerosis (TS is an autosomal dominant condition associated with mutations in the TSC1 and/or TSC2 genes. Clinical manifestations are multisystemic, and they often include lesions in the brain, skin, heart, kidneys, and bones. TSC2 gene mutations can be seen concomitantly with autosomal dominant polycystic kidney disease gene mutations. We present a case of a fetus with prenatal diagnosis of TS that had unique asymmetrical distribution of renal cystic disease. We describe the extensive work up with both fetal and neonatal magnetic resonance imaging with correlating images of the unilateral polycystic renal disease in addition to typical TS brain findings.

pTSC: Data file editing for the Tokamak Simulation Code

International Nuclear Information System (INIS)

Meiss, J.D.

1987-09-01

The code pTSC is an editor for the data files needed to run the Princeton Tokamak Simulation Code (TSC). pTSC utilizes the Macintosh interface to create a graphical environment for entering the data. As most of the data to run TSC consists of conductor positions, the graphical interface is especially appropriate

Volumetric localization of epileptic activities in tuberous sclerosis using synthetic aperture magnetometry

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Xiao, Zheng [Hospital for Sick Children, Research Institute, Toronto (Canada); Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Xiang, Jing [Hospital for Sick Children, Research Institute, Toronto (Canada); Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Holowka, Stephanie; Chuang, Sylvester [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Hunjan, Amrita; Sharma, Rohit; Otsubo, Hiroshi [Hospital for Sick Children, Division of Neurology, Toronto (Canada)

2006-01-01

Magnetoencephalography (MEG) is a novel noninvasive technique for localizing epileptic zones. Tuberous sclerosis complex (TSC) is often associated with medically refractory epilepsy with multiple epileptic zones. Surgical treatment of TSC requires accurate localization of epileptogenic tubers. The objective of this study was to introduce a new MEG technique, synthetic aperture magnetometry (SAM), to volumetrically localize irritable zones and clarify the correlations between SAM, dipole modeling and anatomical tubers. Eight pediatric patients with TSC confirmed by clinical and neuroimaging findings were retrospectively studied. MEG data were recorded using a whole-cortex CTF OMEGA system. Sleep deprivation was employed to provoke epileptiform activity. Irritable zones were localized using both dipole modeling and SAM. MRI detected 42 tubers in the eight patients. Dipole modeling localized 28 irritable zones, and 19 out of the 28 zones were near tubers (19/42, 45%). SAM found 51 irritable zones, and 31 out of the 51 zones were near tubers (31/42, 74%). Among the 51 irritable zones determined by SAM, thirty-five zones were in 1-35 Hz, nine zones were in 35-60 Hz, and seven zones were in 60-120 Hz. The new method, SAM, yielded very plausible equivalent sources for patients who showed anatomical tubers on MRI. Compared to conventional dipole modeling, SAM appeared to offer increased detection of irritable zones and beneficial volumetric and frequency descriptions. (orig.)

The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial.

Science.gov (United States)

Randell, Elizabeth; McNamara, Rachel; Davies, D Mark; Owen-Jones, Eleri; Kirby, Nigel; Angel, Lianna; Drew, Cheney; Cannings-John, Rebecca; Smalley, Michelle; Saxena, Anurag; McDermott, Emer; Stockwell, Laura; de Vries, Petrus J; Hood, Kerry; Sampson, Julian R

2016-08-11

Tuberous sclerosis complex (TSC) is a genetic disorder affecting about 1 in 6000 people and is characterised by the development of tumours in many organs, including the skin and kidneys, and by a range of neurological and neuropsychiatric manifestations. TSC-associated neuropsychiatric disorders (TAND) occur in the majority of those with TSC, and they have a significant impact on patients and their families, given the everyday impact of TAND on education, employment, family and social life. The potential benefits of better treatment for TAND therefore include reduction in health care demands and wider benefits for patients and their carers. We have planned a single-centre, two-arm, individually randomised, phase II, double-blind, placebo-controlled trial of everolimus versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis. Everolimus is a licensed medicine in this patient group, but for a different target of effect. The present trial is a proof-of-principle study developed to provide effect size estimates which may be used to inform the design of subsequent trials. Forty-eight patients aged 16-60 years with tuberous sclerosis who have an IQ >60 and a significant deficit (at least -2 SD) in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to receive everolimus or placebo, respectively. Participants will be assessed for eligibility and then be started on study medication 4 weeks later. They will then be randomised and receive placebo or everolimus for 24 weeks. Neurocognitive and safety assessments will be carried out at baseline and weeks 4, 12, 24 and 36. This study is designed to determine the effect sizes of treatment with everolimus or placebo for 6 months on specific neurocognitive functions-recall memory (verbal and non-verbal) and executive function-in people affected by TSC who have significant deficits in these functions. These data will provide new evidence to determine whether

Results of ionospheric parameters measurements during injections of exhaust streams of TSC "Progress" OMS

Science.gov (United States)

Khakhinov, Vitaly; Alsatkin, Sergey; Medvedev, Andrey; Kushnarev, Dmitriy; Lebedev, Valentin; Potekhin, Alexander; Ratovsky, Konstantin; Shpynev, Boris

Since 2006 we have carried out active space experiments using the transport spacecraft (TSC) "Progress" and the ground-base Radio-Optic Complex of ISTP SB RAS including Irkutsk Incoherent Scatter Radar (IISR). Engine burns of TSC orbital maneuvering subsystem (OMS) were used as a source of ionospheric disturbances and changing radar signature characteristics of TSC. The flight altitudes were about 340 km. The amount of engine exhaust products was varied from 2 to 11 kg. The flow directions relative to IISR and amount of injected exhaust products were changed from flight to flight. The flows directed to IISR were almost parallel to the geomagnetic field line. For these cases the most pronounced effects were observed, the electron density depletion reached 20-40

[Tuberous sclerosis: clinical characteristics and their relationship to genotype/phenotype].

Science.gov (United States)

Monteiro, T; Garrido, C; Pina, S; Chorão, R; Carrilho, I; Figueiroa, S; Santos, M; Temudo, T

2014-11-01

Tuberous sclerosis (TS) is an inherited disorder with multisystemic involvement and a high phenotypic variability. There are two genes that cause this condition: TSC1 and TSC2. Our goal was to clinically characterize patients with TS followed up in the Pediatric Neurology Clinic of a tertiary hospital during the last 10 years, and correlate the genotype with the severity of neurological manifestations and imaging studies. Retrospective analysis of patients with TS, including review of medical records and available MRI imaging. We studied 35 cases with a median age at diagnosis of ten months. Seizures were the first manifestation in 91.4% of cases, with a predominance of epileptic spasms. Over 50% had cognitive impairment and 49% behavioral disorders. A genetic study was performed on 24 children, and TSC2 mutations identified in 58.3% of them. Of the 11 cases of refractory epilepsy, six had the TSC2 gene mutation. In the group of eight patients with moderate/severe cognitive deficits, five had TSC2 mutations. We reviewed 26 MRI scans, in which it was observed that 76.9% had diffuse involvement of cerebral lobes, which reflects a greater burden of injury. Of the patients who had an MRI scan performed and had TSC2 mutations, all had a high tuber load, and5 of them had refractory epilepsy. In our sample we observe a high percentage of mutations in the TSC2 gene. This mutation carries a worse neurological prognosis, with drug-resistant epilepsy and a more severe cognitive impairment. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Cell Type-Specific Contributions to the TSC Neuropathology

Science.gov (United States)

2017-08-01

AWARD NUMBER: W81XWH-16-1-0415 TITLE: Cell Type-Specific Contributions to the TSC Neuropathology PRINCIPAL INVESTIGATOR: Gabriella D’Arcangelo...AND SUBTITLE Cell Type-Specific Contributions to the TSC Neuropathology 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0415 5c. PROGRAM...how heterozygous and homozygous Tsc2 mutations affect the development of mutant excitatory neurons as well as other surrounding brain cells , in vivo

Conjunctival lymphangioma in a 4-year-old girl revealed tuberous sclerosis complex

Directory of Open Access Journals (Sweden)

Freiberg, Florentina Joyce

2016-09-01

Full Text Available Background: To present a case of conjunctival lymphangioma in a girl with tuberous sclerosis complex.Methods/results: A 4-year-old girl presented with a relapsing cystic lesion of the bulbar conjunctiva in the right eye with string-of-pearl-like dilation of lymphatic vessels and right-sided facial swelling with mild pain. Best-corrected vision was not impaired. Examination of the skin revealed three hypomelanotic macules and a lumbal Shagreen patch. Magnetic resonance imaging (MRI findings displayed minimal enhancement of buccal fat on the right side. Cranial and orbital MRI showed signal enhancement in the right cortical and subcortical areas. Genetic analysis revealed a heterozygous deletion encompassing exon 1 and 2 of the gene (tuberous sclerosis complex 1 gene, confirming the diagnosis of tuberous sclerosis complex.Conclusion: In conjunctival lymphangioma, tuberous sclerosis complex should be considered as the primary disease.

TSC mobile mining and extraction technology

Energy Technology Data Exchange (ETDEWEB)

Lavender, W.J. [TSC Company Ltd., Calgary, AB (Canada)

2001-11-01

This Power-Point presentation described an innovative mining and extraction technology developed by Calgary-based TSC Company Ltd. that has provided a major breakthrough in bitumen production from mineable oil sands. The presentation described the process and key mechanical components as demonstrated on oil sands leases. It also described the step change in cost structure and profitability. Oil sands mining provide a hugh resource base with no exploration costs and no decline in production. Despite these advantages, oil sands mining faces the challenge of high capital and operating costs and materials handling. Other challenges include the variability of the ore and environmental impacts. This paper described the fundamentals of the new technology called the Tar Sand Combine (TSC), a continuous mining machine, crusher, cyclone, tailings filter and stacker all in one mobile module. Several viewgraphs were included with the presentation to depict the recovery process as successfully demonstrated at a pilot project. Patent is pending on the process and components. The advantages of the TSC are reduced materials handling, and no tailings ponds are generated since tailings remain where they are mined. The final product is clean bitumen. The specifications of a commercial TSC are: 2000 ton/stream hour mining produce 25,000 bpsd bitumen at 12 per cent ore grade; mined ore bitumen recovery is greater than 95 per cent and the availability factor is 85 per cent. It was concluded that the TSC can maximize oil sands reserves, while providing significant cost savings and environmental benefits. 2 tabs., 24 figs.

Selective Activation of mTORC1 Signaling Recapitulates Microcephaly, Tuberous Sclerosis, and Neurodegenerative Diseases

Directory of Open Access Journals (Sweden)

Hidetoshi Kassai

2014-06-01

Full Text Available Mammalian target of rapamycin (mTOR has been implicated in human neurological diseases such as tuberous sclerosis complex (TSC, neurodegeneration, and autism. However, little is known about when and how mTOR is involved in the pathogenesis of these diseases, due to a lack of animal models that directly increase mTOR activity. Here, we generated transgenic mice expressing a gain-of-function mutant of mTOR in the forebrain in a temporally controlled manner. Selective activation of mTORC1 in embryonic stages induced cortical atrophy caused by prominent apoptosis of neuronal progenitors, associated with upregulation of HIF-1α. In striking contrast, activation of the mTORC1 pathway in adulthood resulted in cortical hypertrophy with fatal epileptic seizures, recapitulating human TSC. Activated mTORC1 in the adult cortex also promoted rapid accumulation of cytoplasmic inclusions and activation of microglial cells, indicative of progressive neurodegeneration. Our findings demonstrate that mTORC1 plays different roles in developmental and adult stages and contributes to human neurological diseases.

Attention-deficit hyperactivity disorder (ADHD) and tuberous sclerosis complex.

Science.gov (United States)

D'Agati, Elisa; Moavero, Romina; Cerminara, Caterina; Curatolo, Paolo

2009-10-01

The neurobiological basis of attention-deficit hyperactivity disorder (ADHD) in tuberous sclerosis complex is still largely unknown. Cortical tubers may disrupt several brain networks that control different types of attention. Frontal lobe dysfunction due to seizures or epileptiform electroencephalographic discharges may perturb the development of brain systems that underpin attentional and hyperactive functions during a critical early stage of brain maturation. Comorbidity of attention-deficit hyperactivity disorder (ADHD) with mental retardation and autism spectrum disorders is frequent in children with tuberous sclerosis. Attention-deficit hyperactivity disorder (ADHD) may also reflect a direct effect of the abnormal genetic program. Treatment of children with tuberous sclerosis complex with combined symptoms of attention-deficit hyperactivity disorder (ADHD) and epilepsy may represent a challenge for clinicians, because antiepileptic therapy and drugs used to treat attention-deficit hyperactivity disorder (ADHD) may aggravate the clinical picture of each other.

Facial Angiofibroma Severity Index (FASI): reliability assessment of a new tool developed to measure severity and responsiveness to therapy in tuberous sclerosis-associated facial angiofibroma.

Science.gov (United States)

Salido-Vallejo, R; Ruano, J; Garnacho-Saucedo, G; Godoy-Gijón, E; Llorca, D; Gómez-Fernández, C; Moreno-Giménez, J C

2014-12-01

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by the development of multisystem hamartomatous tumours. Topical sirolimus has recently been suggested as a potential treatment for TSC-associated facial angiofibroma (FA). To validate a reproducible scale created for the assessment of clinical severity and treatment response in these patients. We developed a new tool, the Facial Angiofibroma Severity Index (FASI) to evaluate the grade of erythema and the size and extent of FAs. In total, 30 different photographs of patients with TSC were shown to 56 dermatologists at each evaluation. Three evaluations using the same photographs but in a different random order were performed 1 week apart. Test and retest reliability and interobserver reproducibility were determined. There was good agreement between the investigators. Inter-rater reliability showed strong correlations (> 0.98; range 0.97-0.99) with inter-rater correlation coefficients (ICCs) for the FASI. The global estimated kappa coefficient for the degree of intra-rater agreement (test-retest) was 0.94 (range 0.91-0.97). The FASI is a valid and reliable tool for measuring the clinical severity of TSC-associated FAs, which can be applied in clinical practice to evaluate the response to treatment in these patients. © 2014 British Association of Dermatologists.

lessons from tuberous sclerosis complex

African Journals Online (AJOL)

lot by studying and treating rare disorders, sometimes with profound clinical consequences. A careful look will identify ... and high rates of Alzheimer's disease, which led to the discovery of the molecular basis of familial ... diagnosis, monitoring and treatment of TSC,[14,15] we set out to draft a clinical update summarising an ...

Eye Involvement in TSC

Science.gov (United States)

... eye involvement. Nonretinal and Retinal Eye Findings Facial angiofibromas may involve the eyelids of individuals with TSC, ... the hamartomas have many blood vessels (as are angiofibromas of the skin). Less than half of the ...

Sclerotic bone lesions at abdominal magnetic resonance imaging in children with tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Boronat, Susana [Massachusetts General Hospital, Department of Neurology, Boston, MA (United States); Universitat Autonoma de Barcelona, Department of Pediatric Neurology, Vall d' Hebron Hospital, Barcelona (Spain); Barber, Ignasi [Universitat Autonoma de Barcelona, Department of Pediatric Radiology, Vall d' Hebron Hospital, Barcelona (Spain); Pargaonkar, Vivek [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States); Chang, Joshua; Thiele, Elizabeth A. [Massachusetts General Hospital, Department of Neurology, Boston, MA (United States)

2016-05-15

Sclerotic bone lesions are often seen on chest CT in adults with tuberous sclerosis complex. To characterize bone lesions at abdominal MRI in children with tuberous sclerosis complex. This retrospective review included 70 children with tuberous sclerosis complex who had undergone abdominal MRI for renal imaging. An additional longitudinal study was performed in 50 children who had had two or more MRI scans. Abdominal CT (eight children) and radiographs (three children) were reviewed and compared with MRI. A total of 173 sclerotic bone lesions were detected in 51/70 children (73%; 95% confidence interval: 0.61-0.82) chiefly affecting vertebral pedicles. New lesions appeared in 20 children and growth of previous sclerotic bone lesions was documented in 14 children. Sclerotic bone lesions were more frequent in girls and in children with more extensive renal involvement. Sclerotic bone lesions are commonly detected by abdominal MRI in children with tuberous sclerosis complex. They usually affect posterior vertebral elements and their number and size increase with age. As current recommendations for tuberous sclerosis complex surveillance include renal MR performed in childhood, recognition of these lesions is useful. (orig.)

Sclerotic bone lesions at abdominal magnetic resonance imaging in children with tuberous sclerosis complex

International Nuclear Information System (INIS)

Boronat, Susana; Barber, Ignasi; Pargaonkar, Vivek; Chang, Joshua; Thiele, Elizabeth A.

2016-01-01

Sclerotic bone lesions are often seen on chest CT in adults with tuberous sclerosis complex. To characterize bone lesions at abdominal MRI in children with tuberous sclerosis complex. This retrospective review included 70 children with tuberous sclerosis complex who had undergone abdominal MRI for renal imaging. An additional longitudinal study was performed in 50 children who had had two or more MRI scans. Abdominal CT (eight children) and radiographs (three children) were reviewed and compared with MRI. A total of 173 sclerotic bone lesions were detected in 51/70 children (73%; 95% confidence interval: 0.61-0.82) chiefly affecting vertebral pedicles. New lesions appeared in 20 children and growth of previous sclerotic bone lesions was documented in 14 children. Sclerotic bone lesions were more frequent in girls and in children with more extensive renal involvement. Sclerotic bone lesions are commonly detected by abdominal MRI in children with tuberous sclerosis complex. They usually affect posterior vertebral elements and their number and size increase with age. As current recommendations for tuberous sclerosis complex surveillance include renal MR performed in childhood, recognition of these lesions is useful. (orig.)

Diagnóstico Tardio de Esclerose Tuberosa

Directory of Open Access Journals (Sweden)

Catarina Oliveira

2016-03-01

Full Text Available Tuberous sclerosis (also referred to as Tuberous Sclerosis Complex is an autosomal dominant neurocutaneous syndrome that can involve multiple organs such as the brain, heart, kidney, lung, liver, skin and eye. The diagnosis is clinical and most patients are identified during childhood, in the context of a severe epileptic or neuropsychiatric disorder. Here we report a case of TSC diagnosed in an adult woman with dermatological and vascular involvement that were only recognized as manifestations of TSC after the diagnosis of her infant daughter. This case highlights how important it is that physicians recognize the full spectrum of manifestations of TSC, including the most unusual, so not to miss the diagnosis

Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference.

Science.gov (United States)

Sahin, Mustafa; Henske, Elizabeth P; Manning, Brendan D; Ess, Kevin C; Bissler, John J; Klann, Eric; Kwiatkowski, David J; Roberds, Steven L; Silva, Alcino J; Hillaire-Clarke, Coryse St; Young, Lisa R; Zervas, Mark; Mamounas, Laura A

2016-07-01

On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program, and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. Here we summarize the outcomes from the extensive premeeting deliberations and final workshop recommendations, including (1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex, (2) the key gaps, needs, and challenges that hinder progress in tuberous sclerosis complex research, and (3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five to ten year time frame. Copyright © 2016 Elsevier Inc. All rights reserved.

Pancreatic tumors in children and young adults with tuberous sclerosis complex

International Nuclear Information System (INIS)

Koc, Gonca; Sugimoto, Sam; Kammen, Bamidele F.; Karakas, S.P.; Kuperman, Rachel

2017-01-01

Pancreatic neuroendocrine tumors are not included in the diagnostic criteria for tuberous sclerosis complex, although an association has been described. To investigate the association of pancreatic neuroendocrine tumor in children and young adults with tuberous sclerosis complex and define MRI characteristics of the tumor. We retrospectively evaluated the abdominal MRI scans of 55 children and young adults with tuberous sclerosis complex for the presence of a pancreatic mass. The scans were performed over a period of 7 years to monitor renal pathology. We obtained each patient's clinical history and treatment protocol from the hospital's electronic medical records. A solid pancreatic mass was identified in 5/55 (9%, 95% confidence interval [CI] 3-20%) patients (4 male) with a mean age of 12.6 years. Four of the lesions were located in the pancreatic tail and one in the pancreatic body. All of the lesions were solid, ovoid and well demarcated, with a mean diameter of 3.1 cm. The masses uniformly demonstrated T1 and T2 prolongation, but their diffusion behavior and post-contrast enhancement varied. The two surgically resected lesions were synaptophysin (+) non-functional pancreatic neuroendocrine tumors on pathology. Two of the patients who did not have surgery were treated with everolimus; one of the lesions has shown interval decrease in size and the other has remained stable. Pancreatic tumor is relatively common in children and young adults with tuberous sclerosis complex. (orig.)

Pancreatic tumors in children and young adults with tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Koc, Gonca [Erciyes University, School of Medicine, Department of Pediatric Radiology, Melikgazi, Kayseri (Turkey); Sugimoto, Sam; Kammen, Bamidele F.; Karakas, S.P. [UCSF Benioff Children' s Hospital, Department of Diagnostic Imaging, Oakland, CA (United States); Kuperman, Rachel [UCSF Benioff Children' s Hospital, Department of Pediatric Neurology, Oakland, CA (United States)

2017-01-15

Pancreatic neuroendocrine tumors are not included in the diagnostic criteria for tuberous sclerosis complex, although an association has been described. To investigate the association of pancreatic neuroendocrine tumor in children and young adults with tuberous sclerosis complex and define MRI characteristics of the tumor. We retrospectively evaluated the abdominal MRI scans of 55 children and young adults with tuberous sclerosis complex for the presence of a pancreatic mass. The scans were performed over a period of 7 years to monitor renal pathology. We obtained each patient's clinical history and treatment protocol from the hospital's electronic medical records. A solid pancreatic mass was identified in 5/55 (9%, 95% confidence interval [CI] 3-20%) patients (4 male) with a mean age of 12.6 years. Four of the lesions were located in the pancreatic tail and one in the pancreatic body. All of the lesions were solid, ovoid and well demarcated, with a mean diameter of 3.1 cm. The masses uniformly demonstrated T1 and T2 prolongation, but their diffusion behavior and post-contrast enhancement varied. The two surgically resected lesions were synaptophysin (+) non-functional pancreatic neuroendocrine tumors on pathology. Two of the patients who did not have surgery were treated with everolimus; one of the lesions has shown interval decrease in size and the other has remained stable. Pancreatic tumor is relatively common in children and young adults with tuberous sclerosis complex. (orig.)

Diagnosis, monitoring and treatment of tuberous sclerosis complex ...

African Journals Online (AJOL)

Diagnosis, monitoring and treatment of tuberous sclerosis complex: A South African consensus response to international guidelines. ... inhibitors to treat subependymal giant cell astrocytomas not amenable to surgery and renal angiomyolipomas larger than 3 cm, and as adjunctive treatment for refractory focal seizures.

Characterization of Ninjurin and TSC22 induction after X-irradiation of normal human skin cells

International Nuclear Information System (INIS)

Koike, Manabu; Ninomiya, Yasuharu; Koike, Aki

2008-01-01

The skin is an external organ that is most frequently exposed to radiation. It is important to elucidate the influence of radiation exposure on the skin at the molecular level. To identify radiation-responsive genes in human skin cells, we used microarray technology to examine the effects of irradiation on 641 genes in normal human epidermal keratinocytes at 4 h and 8 h postirradiation with a cytotoxic dose of X-ray (10 Gy). We found that 18 genes were upregulated and 35 genes were downregulated in keratinocytes at 4 h and/or 8 h postirradiation. Ninjurin, whose function remains unknown in keratinocytes, was induced most strongly by X-irradiation. Several known apoptosis-related genes, such as TSC22, were also upregulated. We characterized Ninjurin and TSC22 induction after X-irradiation of normal human skin cells. The induction of the expression of Ninjurin and TSC22 mRNA in keratinocytes following high-dose X-irradiation was confirmed by northern blot analysis. In dermal fibroblasts, Ninjurin, but not TSC22, was induced after X-ray irradiation. The dependence of both gene expression on the status of an apoptosis regulator, p53, was found. In addition, the expression of both mRNA was induced upon treatment with an apoptosis inducer, etoposide. On the other hand, TSC22, but not Ninjurin, was induced and accumulated in keratinocytes upon treatment with an apoptosis inducer, anisomycin. However, in transient expression assay, EYFP-TSC22, as well as EYFP-Ninjurin or EYFP alone, did not induce apoptosis in keratinocytes in contrast to EYFP-GADD45. Taken together, these findings have important implications on the understanding of the mechanism underlying the complex response of skin cells following X-irradiation. (author)

The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma.

Science.gov (United States)

Bissler, John J; Franz, David N; Frost, Michael D; Belousova, Elena; Bebin, E Martina; Sparagana, Steven; Berkowitz, Noah; Ridolfi, Antonia; Kingswood, J Christopher

2018-01-01

Patients with tuberous sclerosis complex (TSC) often have multiple TSC-associated hamartomas, particularly in the brain and kidney. This was a post hoc analysis of pediatric patients being treated for subependymal giant cell astrocytomas (SEGAs) during the phase 3, randomized, double-blind, placebo-controlled EXIST-1 trial. Patients were initially randomly assigned to receive everolimus 4.5 mg/m 2 /day (target blood trough 5-15 mg/dl) or placebo and could continue in an open-label extension phase. Angiomyolipoma response rates were analyzed in patients aged 20% increase in kidney volume from nadir, and angiomyolipoma-related bleeding ≥ grade 2. Tolerability was also assessed. Overall, this analysis included 33 patients. Renal angiomyolipoma response was achieved by 75.8% of patients (95% confidence interval, 57.7-88.9%), with sustained mean reductions in renal angiomyolipoma volume over nearly 4 years of treatment. In addition, most (≥80%) achieved clinically relevant reductions in angiomyolipoma volume (≥50%), beginning at week 24 and continuing for the remainder of the study. Everolimus was generally well tolerated in this subgroup, with most adverse events being grade 1 or 2 in severity. Although everolimus is currently not indicated for this use, this analysis from EXIST-1 demonstrates its long-term efficacy and safety for the treatment of renal angiomyolipoma in pediatric patients undergoing treatment for TSC-associated SEGA.

Epilepsy in Adults with TSC

Science.gov (United States)

... individual with TSC deserves the best quality of life possible, so they should work with the caregivers to reach a balance between seizure control and side effects of the medication. Treatment Options There are many ...

Resource utilization in children with tuberous sclerosis complex and associated seizures: a retrospective chart review study.

Science.gov (United States)

Lennert, Barb; Farrelly, Eileen; Sacco, Patricia; Pira, Geraldine; Frost, Michael

2013-04-01

Seizures are a hallmark manifestation of tuberous sclerosis complex, yet data characterizing resource utilization are lacking. This retrospective chart review was performed to assess the economic burden of tuberous sclerosis complex with neurologic manifestations. Demographic and resource utilization data were collected for 95 patients for up to 5 years after tuberous sclerosis complex diagnosis. Mean age at diagnosis was 3.1 years, with complex partial and infantile spasms as the most common seizure types. In the first 5 years post-diagnosis, 83.2% required hospitalization, 30.5% underwent surgery, and the majority of patients (90.5%) underwent ≥3 testing procedures. In 79 patients with a full 5 years of data, hospitalizations, intensive care unit stays, diagnostic testing, and rehabilitation services decreased over the 5-year period. Resource utilization is cost-intensive in children with tuberous sclerosis complex and associated seizures during the first few years following diagnosis. Improving seizure control and reducing health care costs in this population remain unmet needs.

Biomarkers of Renal Tumor Burden and Progression in TSC

Science.gov (United States)

2013-09-01

implications. Standard of care should include routine genotyping and regular creatinine measurement in all TSC patients to help guide clinical...pressure, serum chemistries, urinalysis and urine chemistries). (B) Measure soluble growth factors, angiogenesis factors and renal injury molecules in...ELISA was unacceptably limited compared to the standard curve. This limitation restricts its ability to discriminate between samples from TSC patients

Interdependence of clinical factors predicting cognition in children with tuberous sclerosis complex.

Science.gov (United States)

Overwater, I E; Verhaar, B J H; Lingsma, H F; Bindels-de Heus, G C B; van den Ouweland, A M W; Nellist, M; Ten Hoopen, L W; Elgersma, Y; Moll, H A; de Wit, M C Y

2017-01-01

Cognitive development in patients with tuberous sclerosis complex is highly variable. Predictors in the infant years would be valuable to counsel parents and to support development. The aim of this study was to confirm factors that have been reported to be independently correlated with cognitive development. 102 patients included in this study were treated at the ENCORE-TSC expertise center of the Erasmus Medical Center-Sophia Children's Hospital. Data from the first 24 months of life were used, including details on epilepsy, motor development and mutation status. Outcome was defined as cognitive development (intellectual equivalent, IE) as measured using tests appropriate to the patients age and cognitive abilities (median age at testing 8.2 years, IQR 4.7-12.0). Univariable and multivariable regression analyses were used. In a univariable analysis, predictors of lower IE were: the presence of infantile spasms (β = -18.3, p = 0.000), a larger number of antiepileptic drugs used (β = -6.3, p = 0.000), vigabatrin not used as first drug (β = -14.6, p = 0.020), corticosteroid treatment (β = -33.2, p = 0.005), and a later age at which the child could walk independently (β = -2.1, p = 0.000). An older age at seizure onset predicted higher IE (β = 1.7, p = 0.000). In a multivariable analysis, only age at seizure onset was significantly correlated to IE (β = 1.2, p = 0.005), contributing to 28% of the variation in IE. In our cohort, age at seizure onset was the only variable that independently predicted IE. Factors predicting cognitive development could aid parents and physicians in finding the appropriate support and schooling for these patients.

ESCLEROSIS TUBEROSA Y AFECCIÓN RENAL: REPORTE DE UN CASO CLÍNICO

Directory of Open Access Journals (Sweden)

Ciocchini M

2016-05-01

Full Text Available A 27 year-old woman was initially referred to the division of nephrology because of polyuria and the finding of renal cysts. She did not have nervous system manifestations. According to the "2012 International Tuberous Sclerosis Complex Consensus Conference" the diagnosis of Tuberous Sclerosis Complex (TSC was completed. TSC is an autosomal dominant inherited multisystem disease with nearly complete penetrance. Clinical manifestations can vary widely even in patients belonging to a same linage. The morbidity and mortality depends on renal or respiratory complications on adulthood. This report highlight the need of a high level of suspicions in patients with manifestations compatible with this disease and shows the importance of a multidisciplinary team working together to arrive to the appropriate diagnosis.

Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

Energy Technology Data Exchange (ETDEWEB)

Obayashi, Yoko, E-mail: youko_oobayashi@ajinomoto.com [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Campbell, Jean S.; Fausto, Nelson [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Yeung, Raymond S. [Department of Surgery, University of Washington School of Medicine, Seattle, WA (United States)

2013-07-19

Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.

Electrochemical behaviour of alkaline copper complexes

Indian Academy of Sciences (India)

Abstract. A search for non-cyanide plating baths for copper resulted in the development of alkaline copper complex baths containing trisodium citrate [TSC] and triethanolamine [TEA]. Voltammetric studies were carried out on platinum to understand the electrochemical behaviour of these complexes. In TSC solutions, the.

Understanding the Etiology of Tuberous Sclerosis Complex

Science.gov (United States)

2011-07-01

neurological symptoms (e.g. seizures), which are the most significant causes of disability and morbidity. Presently, there are no known cures for TSC and...diseases such as symptomatic epilepsy syndrome, fragile X syndrome, schizophrenia , and autism spectrum disorders (Orlova et al., 2010; Chu et al., 2009...hydramnios, megalencephaly, symptomatic epilepsy syndrome,  fragile X syndrome,  schizophrenia , and autism spectrum disorders  technical advance The

Diffusion tensor imaging in children with tuberous sclerosis complex: tract-based spatial statistics assessment of brain microstructural changes.

Science.gov (United States)

Zikou, Anastasia K; Xydis, Vasileios G; Astrakas, Loukas G; Nakou, Iliada; Tzarouchi, Loukia C; Tzoufi, Meropi; Argyropoulou, Maria I

2016-07-01

There is evidence of microstructural changes in normal-appearing white matter of patients with tuberous sclerosis complex. To evaluate major white matter tracts in children with tuberous sclerosis complex using tract-based spatial statistics diffusion tensor imaging (DTI) analysis. Eight children (mean age ± standard deviation: 8.5 ± 5.5 years) with an established diagnosis of tuberous sclerosis complex and 8 age-matched controls were studied. The imaging protocol consisted of T1-weighted high-resolution 3-D spoiled gradient-echo sequence and a spin-echo, echo-planar diffusion-weighted sequence. Differences in the diffusion indices were evaluated using tract-based spatial statistics. Tract-based spatial statistics showed increased axial diffusivity in the children with tuberous sclerosis complex in the superior and anterior corona radiata, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the uncinate fascicle and the anterior thalamic radiation. No significant differences were observed in fractional anisotropy, mean diffusivity and radial diffusivity between patients and control subjects. No difference was found in the diffusion indices between the baseline and follow-up examination in the patient group. Patients with tuberous sclerosis complex have increased axial diffusivity in major white matter tracts, probably related to reduced axonal integrity.

Diffusion tensor imaging in children with tuberous sclerosis complex: tract-based spatial statistics assessment of brain microstructural changes

International Nuclear Information System (INIS)

Zikou, Anastasia K.; Xydis, Vasileios G.; Tzarouchi, Loukia C.; Argyropoulou, Maria I.; Astrakas, Loukas G.; Nakou, Iliada; Tzoufi, Meropi

2016-01-01

There is evidence of microstructural changes in normal-appearing white matter of patients with tuberous sclerosis complex. To evaluate major white matter tracts in children with tuberous sclerosis complex using tract-based spatial statistics diffusion tensor imaging (DTI) analysis. Eight children (mean age ± standard deviation: 8.5 ± 5.5 years) with an established diagnosis of tuberous sclerosis complex and 8 age-matched controls were studied. The imaging protocol consisted of T1-weighted high-resolution 3-D spoiled gradient-echo sequence and a spin-echo, echo-planar diffusion-weighted sequence. Differences in the diffusion indices were evaluated using tract-based spatial statistics. Tract-based spatial statistics showed increased axial diffusivity in the children with tuberous sclerosis complex in the superior and anterior corona radiata, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the uncinate fascicle and the anterior thalamic radiation. No significant differences were observed in fractional anisotropy, mean diffusivity and radial diffusivity between patients and control subjects. No difference was found in the diffusion indices between the baseline and follow-up examination in the patient group. Patients with tuberous sclerosis complex have increased axial diffusivity in major white matter tracts, probably related to reduced axonal integrity. (orig.)

A genetic screen identifies Tor as an interactor of VAPB in a Drosophila model of amyotrophic lateral sclerosis

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Senthilkumar Deivasigamani

2014-10-01

Full Text Available Amyotrophic Lateral Sclerosis (ALS is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5–10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci – TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2 that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt and VAP(P58S, but in a contrasting manner. Reversal of VAP(P58S bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease.

A genetic screen identifies Tor as an interactor of VAPB in a Drosophila model of amyotrophic lateral sclerosis.

Science.gov (United States)

Deivasigamani, Senthilkumar; Verma, Hemant Kumar; Ueda, Ryu; Ratnaparkhi, Anuradha; Ratnaparkhi, Girish S

2014-10-31

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5-10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci - TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S) expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2) that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt) expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt) and VAP(P58S), but in a contrasting manner. Reversal of VAP(P58S) bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S) expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease. © 2014. Published by The Company of Biologists Ltd.

A 28-Year-Old Male Patient with Nail Tumors, Skin Lesions, and Epilepsy.

Science.gov (United States)

Balak, Deepak M W; Zonnenberg, Bernard A; Spitzer-Naaijkens, Juliette M J; Hulshof, Mieke M

2017-01-01

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of benign hamartomas in multiple organs. Most patients with TSC exhibit cutaneous manifestations. We report a 28-year-old patient with multiple pink papules at the proximal nail fold of several toes. Histopathological analysis of a biopsy of a papule was consistent with an ungual fibroma. Histopathological analysis of a biopsy of an elevated skin-colored plaque at the lower back was diagnostic for a Shagreen patch. These findings were consistent with a clinical diagnosis of TSC. This patient was subsequently referred to a multidisciplinary TSC clinic for further screening, which revealed a giant cell astrocytoma and multiple subependymal tubers. Annual monitoring was recommended. The skin lesions were treated with topical rapamycin ointment. Recognizing dermatological manifestations of TSC is of importance to allow early diagnosis. TSC should be considered as a differential diagnosis in the case of ungual fibromas, even in older patients.

A 28-Year-Old Male Patient with Nail Tumors, Skin Lesions, and Epilepsy

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Deepak M.W. Balak

2017-01-01

Full Text Available Background: Tuberous sclerosis complex (TSC is an autosomal dominant disorder characterized by the development of benign hamartomas in multiple organs. Most patients with TSC exhibit cutaneous manifestations. Methods: We report a 28-year-old patient with multiple pink papules at the proximal nail fold of several toes. Results: Histopathological analysis of a biopsy of a papule was consistent with an ungual fibroma. Histopathological analysis of a biopsy of an elevated skin-colored plaque at the lower back was diagnostic for a Shagreen patch. These findings were consistent with a clinical diagnosis of TSC. This patient was subsequently referred to a multidisciplinary TSC clinic for further screening, which revealed a giant cell astrocytoma and multiple subependymal tubers. Annual monitoring was recommended. The skin lesions were treated with topical rapamycin ointment. Conclusions: Recognizing dermatological manifestations of TSC is of importance to allow early diagnosis. TSC should be considered as a differential diagnosis in the case of ungual fibromas, even in older patients.

A Morpholino Strategy to Assess TSC Gene Function in Zebrafish

Science.gov (United States)

2006-11-01

Neurobiol 25:795-805. Kenerson H, Dundon TA, Yeung RS. 2005. Effects of rapamycin in the Eker rat model of tuberous sclerosis complex. Pediatr Res 57:67-75...hippocampal slice: a system for studying the pharmacology of seizures and for screening anticonvulsant drugs. Epilepsia 18:543-548. Onda H, Crino PB, Zhang...sclerosis in a 19-week fetus: immunohistochemical and molecular study of hamartin and tuberin. Pediatr Dev Pathol 5:448-464. Weiner HL, Ferraris N, LaJoie J

Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Chakraborty, Sanjukta; Mohiyuddin, SM Azeem; Gopinath, KS; Kumar, Arun

2008-01-01

Despite extensive research, the five-year survival rate of oral squamous cell carcinoma (OSCC) patients has not improved. Effective treatment of OSCC requires the identification of molecular targets and signaling pathways to design appropriate therapeutic strategies. Several genes from the mTOR signaling pathway are known to be dysregulated in a wide spectrum of cancers. However, not much is known about the involvement of this pathway in tumorigenesis of OSCC. We therefore investigated the role of the tumor suppressor genes, TSC1 and TSC2, and other members of this pathway in tumorigenesis of OSCC. Expression of genes at the RNA and protein levels was examined by semi-quantitative RT-PCR and western blot analyses, respectively. Loss of heterozygosity was studied using matched blood and tumor DNA samples and microsatellite markers from the TSC1, TSC2 and PTEN candidate regions. The effect of promoter methylation on TSC gene expression was studied by treating cells with methyltransferase inhibitor 5-azacytidine. Methylation status of the TSC2 promoter in tissue samples was examined by combined bisulfite restriction analysis (COBRA). The semi-quantitative RT-PCR analysis showed downregulation of TSC1, TSC2, EIF4EBP1 and PTEN, and upregulation of PIK3C2A, AKT1, PDPK1, RHEB, FRAP1, RPS6KB1, EIF4E and RPS6 in tumors. A similar observation was made for AKT1 and RPS6KB1 expression in tumors at the protein level. Investigation of the mechanism of downregulation of TSC genes identified LOH in 36.96% and 39.13% of the tumors at the TSC1 and TSC2 loci, respectively. No mutation was found in TSC genes. A low LOH rate of 13% was observed at the PTEN locus. Treatment of an OSCC cell line with the methyltransferase inhibitor 5-azacytidine showed a significant increase in the expression of TSC genes, suggesting methylation of their promoters. However, the 5-azacytidine treatment of non-OSCC HeLa cells showed a significant increase in the expression of the TSC2 gene only. In order

Interdependence of clinical factors predicting cognition in children with tuberous sclerosis complex

NARCIS (Netherlands)

I.E. Overwater (Iris); Verhaar, B.J.H.; H.F. Lingsma (Hester); G.C.B. Bindels-de Heus (Karen); A.M.W. van den Ouweland (Ans); M.D. Nellist (Mark); L.W. ten Hoopen (Leontine); Y. Elgersma (Ype); H.A. Moll (Henriëtte); M.C.Y. de Wit (Marie Claire)

2017-01-01

textabstractCognitive development in patients with tuberous sclerosis complex is highly variable. Predictors in the infant years would be valuable to counsel parents and to support development. The aim of this study was to confirm factors that have been reported to be independently correlated with

Perivascular Epithelioid Cell Tumor (PEComa of the Uterine Cervix in a Patient with Tuberous Sclerosis Complex: A Literature Review

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Handan ÇELİK

2018-01-01

Full Text Available Perivascular epithelioid cell tumors (PEComa are a rare type of mesenchymal tumor arising from perivascular epithelial cells. These tumor cells are a co-expression of both melanocytic and myogenic antigens, such as HMB 45 and smooth muscle actin, and at least in some patients, are located around vessels. PEComas has been reported at various sites, including visceral organs, soft tissue, the prostate gland and broad ligaments. In the female reproductive system, the uterine corpus is the most common site of involvement. Some cases are related to tuberous sclerosis complex. Cervical PEComa with tuberous sclerosis complex is presented in the case of a 41 year-old and the literature is reviewed. There have been only eight cases of cervical PEComas and only one other case associated with tuberous sclerosis complex reported to date.

Analysis of the quantitative dermatoglyphics of the digito-palmar complex in patients with multiple sclerosis.

Science.gov (United States)

Supe, S; Milicić, J; Pavićević, R

1997-06-01

Recent studies on the etiopathogenesis of multiple sclerosis (MS) all point out that there is a polygenetical predisposition for this illness. The so called "MS Trait" determines the reactivity of the immunological system upon ecological factors. The development of the glyphological science and the study of the characteristics of the digito-palmar dermatoglyphic complex (for which it was established that they are polygenetically determined characteristics) all enable a better insight into the genetic development during early embriogenesis. The aim of this study was to estimate certain differences in the dermatoglyphics of digito-palmar complexes between the group with multiple sclerosis and the comparable, phenotypically healthy groups of both sexes. This study is based on the analysis of 18 quantitative characteristics of the digito-palmar complex in 125 patients with multiple sclerosis (41 males and 84 females) in comparison to a group of 400 phenotypically healthy patients (200 males and 200 females). The conducted analysis pointed towards a statistically significant decrease of the number of digital and palmar ridges, as well as with lower values of atd angles in a group of MS patients of both sexes. The main discriminators were the characteristic palmar dermatoglyphics with the possibility that the discriminate analysis classifies over 80% of the examinees which exceeds the statistical significance. The results of this study suggest a possible discrimination of patients with MS and the phenotypically health population through the analysis of the dermatoglyphic status, and therefore the possibility that multiple sclerosis is genetically predisposed disease.

TSC response of irradiated CVD diamond films

CERN Document Server

Borchi, E; Bucciolini, M; Guasti, A; Mazzocchi, S; Pirollo, S; Sciortino, S

1999-01-01

CVD diamond films have been irradiated with electrons, sup 6 sup 0 Co photons and protons in order to study the dose response to exposure to different particles and energies and to investigate linearity with dose. The Thermally Stimulated Current (TSC) has been studied as a function of the dose delivered to polymethilmetacrilate (PMMA) in the range from 1 to 12 Gy with 20 MeV electrons from a linear accelerator. The TSC spectrum has revealed the presence of two components with peak temperatures of about 470 and 520 K, corresponding to levels lying in the diamond band gap with activation energies of the order of 0.7 - 1 eV. After the subtraction of the exponential background the charge emitted during the heating scan has been evaluated and has been found to depend linearly on the dose. The thermally emitted charge of the CVD diamond films has also been studied using different particles. The samples have been irradiated with the same PMMA dose of about 2 Gy with 6 and 20 MeV electrons from a Linac, sup 6 sup 0 ...

Prenatally Diagnosis and Outcome of Fetuses with Cardiac Rhabdomyoma ? Single Centre Experience

OpenAIRE

Bejiqi, Ramush; Retkoceri, Ragip; Bejiqi, Hana

2017-01-01

BACKGROUND: Cardiac rhabdomyoma (CRs) are the most common primary tumour of the heart in infants and children. Usually are multiple and, basing on the location can cause a haemodynamic disturbance, dysrhythmias or heart failure during the fetal and early postnatal period. CRs have a natural history of spontaneous regression and are closely associated with tuberous sclerosis complex (TSC). It has an association with tuberous sclerosis (TS), and in those, the tumour may regress and disappear co...

Mechanisms of Angiogenesis and Lymphangiogenesis in TSC Skin Tumors

Science.gov (United States)

2011-09-16

professional and personal life. I enjoyed tasting all the different cuisines as part of our birthday celebrations and also his Christmas decorations. I...associated with tuberous sclerosis complex, Am J Kidney Dis 2006, 48:e27-29 78. Hofbauer GF, Marcollo-Pini A, Corsenca A, Kistler AD, French LE, Wuthrich

TSC plasma halo simulation of a DIII-D vertical displacement episode

International Nuclear Information System (INIS)

Sayer, R.O.; Peng, Y.K.M.; Jardin, S.C.

1993-01-01

A benchmark of the Tokamak Simulation Code (TSC) plasma halo model has been achieved by calibration against a DIII-D vertical displacement episode (VDE) consisting of vertical drift, thermal quench and current quench. With a suitable halo surrounding the main plasma, the TSC predictions are in good agreement with experimental results for the plasma current decay, plasma trajectory, toroidal and poloidal vessel currents, and for the magnetic probe and flux loop values for the entire VDE. Simulations with no plasma halo yield much faster vertical motion and significantly worse agreement with the magnetics and flux loop data than do halo simulations. (author). 12 refs, 13 figs

The E3 ubiquitin ligase protein associated with Myc (Pam) regulates mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling in vivo through N- and C-terminal domains.

Science.gov (United States)

Han, Sangyeul; Kim, Sun; Bahl, Samira; Li, Lin; Burande, Clara F; Smith, Nicole; James, Marianne; Beauchamp, Roberta L; Bhide, Pradeep; DiAntonio, Aaron; Ramesh, Vijaya

2012-08-31

Pam and its homologs (the PHR protein family) are large E3 ubiquitin ligases that function to regulate synapse formation and growth in mammals, zebrafish, Drosophila, and Caenorhabditis elegans. Phr1-deficient mouse models (Phr1(Δ8,9) and Phr1(Magellan), with deletions in the N-terminal putative guanine exchange factor region and the C-terminal ubiquitin ligase region, respectively) exhibit axon guidance/outgrowth defects and striking defects of major axon tracts in the CNS. Our earlier studies identified Pam to be associated with tuberous sclerosis complex (TSC) proteins, ubiquitinating TSC2 and regulating mammalian/mechanistic target of rapamycin (mTOR) signaling. Here, we examine the potential involvement of the TSC/mTOR complex 1(mTORC1) signaling pathway in Phr1-deficient mouse models. We observed attenuation of mTORC1 signaling in the brains of both Phr1(Δ8,9) and Phr1(Magellan) mouse models. Our results establish that Pam regulates TSC/mTOR signaling in vitro and in vivo through two distinct domains. To further address whether Pam regulates mTORC1 through two functionally independent domains, we undertook heterozygous mutant crossing between Phr1(Δ8,9) and Phr1(Magellan) mice to generate a compound heterozygous model to determine whether these two domains can complement each other. mTORC1 signaling was not attenuated in the brains of double mutants (Phr1(Δ8,9/Mag)), confirming that Pam displays dual regulation of the mTORC1 pathway through two functional domains. Our results also suggest that although dysregulation of mTORC1 signaling may be responsible for the corpus callosum defects, other neurodevelopmental defects observed with Phr1 deficiency are independent of mTORC1 signaling. The ubiquitin ligase complex containing Pam-Fbxo45 likely targets additional synaptic and axonal proteins, which may explain the overlapping neurodevelopmental defects observed in Phr1 and Fbxo45 deficiency.

Phosphatidylcholine transfer protein interacts with thioesterase superfamily member 2 to attenuate insulin signaling.

Science.gov (United States)

Ersoy, Baran A; Tarun, Akansha; D'Aquino, Katharine; Hancer, Nancy J; Ukomadu, Chinweike; White, Morris F; Michel, Thomas; Manning, Brendan D; Cohen, David E

2013-07-30

Phosphatidylcholine transfer protein (PC-TP) is a phospholipid-binding protein that is enriched in liver and that interacts with thioesterase superfamily member 2 (THEM2). Mice lacking either protein exhibit improved hepatic glucose homeostasis and are resistant to diet-induced diabetes. Insulin receptor substrate 2 (IRS2) and mammalian target of rapamycin complex 1 (mTORC1) are key effectors of insulin signaling, which is attenuated in diabetes. We found that PC-TP inhibited IRS2, as evidenced by insulin-independent IRS2 activation after knockdown, genetic ablation, or chemical inhibition of PC-TP. In addition, IRS2 was activated after knockdown of THEM2, providing support for a role for the interaction of PC-TP with THEM2 in suppressing insulin signaling. Additionally, we showed that PC-TP bound to tuberous sclerosis complex 2 (TSC2) and stabilized the components of the TSC1-TSC2 complex, which functions to inhibit mTORC1. Preventing phosphatidylcholine from binding to PC-TP disrupted interactions of PC-TP with THEM2 and TSC2, and disruption of the PC-TP-THEM2 complex was associated with increased activation of both IRS2 and mTORC1. In livers of mice with genetic ablation of PC-TP or that had been treated with a PC-TP inhibitor, steady-state amounts of IRS2 were increased, whereas those of TSC2 were decreased. These findings reveal a phospholipid-dependent mechanism that suppresses insulin signaling downstream of its receptor.

In vivo synaptic transmission and morphology in mouse models of Tuberous sclerosis, Fragile X syndrome, Neurofibromatosis type 1 and Costello syndrome.

Directory of Open Access Journals (Sweden)

Tiantian eWang

2015-07-01

Full Text Available Defects in the rat sarcoma viral oncogene homolog (Ras/extracellular-signal-regulated kinase (ERK and the phosphatidylinositol 3-kinase (PI3K-mammalian target of rapamycin (mTOR signaling pathways are responsible for several neurodevelopmental disorders. These disorders are an important cause for intellectual disability; additional manifestations include autism spectrum disorder, seizures and brain malformations. Changes in synaptic function are thought to underlie the neurological conditions associated with these syndromes. We therefore studied morphology and in vivo synaptic transmission of the calyx of Held synapse, a relay synapse in the medial nucleus of the trapezoid body (MNTB of the auditory brainstem, in mouse models of Tuberous sclerosis (TSC, Fragile X syndrome (FXS, Neurofibromatosis type 1 (NF1 and Costello syndrome (CS. Calyces from both Tsc1+/- and from Fmr1 knock-out (KO mice showed increased volume and surface area compared to wild-type (WT controls. In addition, in Fmr1 KO animals a larger fraction of calyces showed complex morphology. In MNTB principal neurons of Nf1+/- mice the average delay between EPSPs and APs was slightly smaller compared to wild-type controls, which could indicate an increased excitability. Otherwise, no obvious changes in synaptic transmission or short-term plasticity were observed during juxtacellular recordings in any of the four lines. Our results in these four mutants thus indicate that abnormalities of mTOR or Ras signaling do not necessarily result in changes in in vivo synaptic transmission.

The cochaperone BAG3 coordinates protein synthesis and autophagy under mechanical strain through spatial regulation of mTORC1.

Science.gov (United States)

Kathage, Barbara; Gehlert, Sebastian; Ulbricht, Anna; Lüdecke, Laura; Tapia, Victor E; Orfanos, Zacharias; Wenzel, Daniela; Bloch, Wilhelm; Volkmer, Rudolf; Fleischmann, Bernd K; Fürst, Dieter O; Höhfeld, Jörg

2017-01-01

The cochaperone BAG3 is a central protein homeostasis factor in mechanically strained mammalian cells. It mediates the degradation of unfolded and damaged forms of the actin-crosslinker filamin through chaperone-assisted selective autophagy (CASA). In addition, BAG3 stimulates filamin transcription in order to compensate autophagic disposal and to maintain the actin cytoskeleton under strain. Here we demonstrate that BAG3 coordinates protein synthesis and autophagy through spatial regulation of the mammalian target of rapamycin complex 1 (mTORC1). The cochaperone utilizes its WW domain to contact a proline-rich motif in the tuberous sclerosis protein TSC1 that functions as an mTORC1 inhibitor in association with TSC2. Interaction with BAG3 results in a recruitment of TSC complexes to actin stress fibers, where the complexes act on a subpopulation of mTOR-positive vesicles associated with the cytoskeleton. Local inhibition of mTORC1 is essential to initiate autophagy at sites of filamin unfolding and damage. At the same time, BAG3-mediated sequestration of TSC1/TSC2 relieves mTORC1 inhibition in the remaining cytoplasm, which stimulates protein translation. In human muscle, an exercise-induced association of TSC1 with the cytoskeleton coincides with mTORC1 activation in the cytoplasm. The spatial regulation of mTORC1 exerted by BAG3 apparently provides the basis for a simultaneous induction of autophagy and protein synthesis to maintain the proteome under mechanical strain. Copyright © 2016 Elsevier B.V. All rights reserved.

Heat-Mirror Spectral Profile Optimization for TSC Hybrid Solar Conversion

Science.gov (United States)

Soule, D. E.; Wood, S. E.

1986-09-01

The efficiencies for total solar cogeneration (TSC) can be optimized by tailoring the transparent heat-mirror (HM) beam splitter spectral profile shape. The entire output is cogenerated by photovoltaic/photothermal conversions into three energy forms: electricity (PV) 18V d.c./module, high-temperature heat (HT) 400°C, and low-temperature heat (LT) 70°C. The emphasis is to maximize the high-quality energy sum PV + HT, while maintaining PV at a high level. A generalized 5-parameter double Fermi model for the HM spectral profile is investigated allowing for a wide parametric range and profile asymmetry. The projected optimized TSC conversion efficiencies are: PV = 14.3%, HT = 43.5%, and LT = 42.2% with a high-quality energy sum of PV + HT = 57.8%. The approach to this optimum HM spectral profile by experimental HM films such as ITO are discussed.

Giant renal artery pseudoaneurysm caused by rupture of renal angiomyolipoma following pregnancy: Endovascular treatment and review of the literature

Directory of Open Access Journals (Sweden)

Ilkay S Idilman

2014-01-01

Full Text Available Renal angiomyolipoma is a hamartomatous, benign tumor composed of blood vessels, fatty tissue and smooth muscle cells, and is often detected incidentally. It can also be associated with the tuberous-sclerosis complex (TSC. Pregnancy and use of oral contraceptives are known to be associated with an increased risk of tumoral rupture and bleeding. Herein, we report a unique case of renal angiomyolipoma associated with TSC who presented with hypovolemic shock as a result of spontaneous rupture of a giant renal pseudoaneurysm, immediately after pregnancy. Emergency endovascular treatment was successful with sparing of most of the affected kidney as demonstrated by follow-up computed tomography imaging.

Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.

Science.gov (United States)

Weston, Matthew C; Chen, Hongmei; Swann, John W

2014-01-01

The Pten and Tsc1 genes both encode proteins that repress mechanistic target of rapamycin (mTOR) signaling. Disruption of either gene in the brain results in epilepsy and autism-like symptoms in humans and mouse models, therefore it is important to understand the molecular and physiological events that lead from gene disruption to disease phenotypes. Given the similar roles these two molecules play in the regulation of cellular growth and the overlap in the phenotypes that result from their loss, we predicted that the deletion of either the Pten or Tsc1 gene from autaptic hippocampal neurons would have similar effects on neuronal morphology and synaptic transmission. Accordingly, we found that loss of either Pten or Tsc1 caused comparable increases in soma size, dendrite length and action potential properties. However, the effects of Pten and Tsc1 loss on synaptic transmission were different. Loss of Pten lead to an increase in both excitatory and inhibitory neurotransmission, while loss of Tsc1 did not affect excitatory neurotransmission and reduced inhibitory transmission by decreasing mIPSC amplitude. Although the loss of Pten or Tsc1 both increased downstream mTORC1 signaling, phosphorylation of Akt was increased in Pten-ko and decreased in Tsc1-ko neurons, potentially accounting for the different effects on synaptic transmission. Despite the different effects at the synaptic level, our data suggest that loss of Pten or Tsc1 may both lead to an increase in the ratio of excitation to inhibition at the network level, an effect that has been proposed to underlie both epilepsy and autism.

Ruthenium (II) complexes of thiosemicarbazone: Synthesis, biosensor applications and evaluation as antimicrobial agents

International Nuclear Information System (INIS)

Yildirim, Hatice; Guler, Emine; Yavuz, Murat; Ozturk, Nurdan; Kose Yaman, Pelin; Subasi, Elif; Sahin, Elif; Timur, Suna

2014-01-01

A conformationally rigid half-sandwich organoruthenium (II) complex [(η 6 -p-cymene)RuClTSC N–S ]Cl, (1) and carbonyl complex [Ru(CO)Cl(PPh 3 ) 2 TSC N–S ] (2) have been synthesized from the reaction of [{(η 6 -p-cymene)RuCl} 2 (μ-Cl) 2 ] and [Ru(H)(Cl)(CO)(PPh 3 ) 3 ] with thiophene-2-carboxaldehyde thiosemicarbazon (TSC) respectively and both novel ruthenium (II) complexes have been characterized by elemental analysis, FT-IR and NMR spectroscopy. The peripheral TSC in the complexes acts as an electrochemical coupling unit providing the ability to carry out electrochemical deposition (ED) and to form an electro-deposited film on a graphite electrode surface. The biosensing applicability of complexes 1 and 2 was investigated by using glucose oxidase (GOx) as a model enzyme. Electrochemical measurements at − 0.9 V versus Ag/AgCl electrode by following the ED Ru(II) reduction/oxidation due to from the enzyme activity, in the presence of glucose substrate. The designed biosensor showed a very good linearity for 0.01–0.5 mM glucose. The in vitro antimicrobial activities of complexes 1 and 2 were also investigated against nine bacterial strains and one fungus by the disc diffusion test method. No activity was observed against the Gram-negative strains and fungus, whereas complex 1 showed moderate antibacterial activities against Gram-positive bacterial strains. - Highlights: • Novel Ru (II) thiosemicarbazone complexes were synthesized and characterized. • Electrochemical depositions were performed. • Rigid half-sandwich Ru (II) complex showed enhanced antibacterial activity

Dysregulation of chromatin remodelling complexes in amyotrophic lateral sclerosis.

Science.gov (United States)

Tibshirani, Michael; Zhao, Beibei; Gentil, Benoit J; Minotti, Sandra; Marques, Christine; Keith, Julia; Rogaeva, Ekaterina; Zinman, Lorne; Rouaux, Caroline; Robertson, Janice; Durham, Heather D

2017-11-01

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with paralysis resulting from dysfunction and loss of motor neurons. A common neuropathological finding is attrition of motor neuron dendrites, which make central connections vital to motor control. The chromatin remodelling complex, neuronal Brahma-related gene 1 (Brg1)-associated factor complex (nBAF), is critical for neuronal differentiation, dendritic extension and synaptic function. We have identified loss of the crucial nBAF subunits Brg1, Brg1-associated factor 53b and calcium responsive transactivator in cultured motor neurons expressing FUS or TAR-DNA Binding Protein 43 (TDP-43) mutants linked to familial ALS. When plasmids encoding wild-type or mutant human FUS or TDP-43 were expressed in motor neurons of dissociated spinal cord cultures prepared from E13 mice, mutant proteins in particular accumulated in the cytoplasm. Immunolabelling of nBAF subunits was reduced in proportion to loss of nuclear FUS or TDP-43 and depletion of Brg1 was associated with nuclear retention of Brg1 mRNA. Dendritic attrition (loss of intermediate and terminal dendritic branches) occurred in motor neurons expressing mutant, but not wild-type, FUS or TDP-43. This attrition was delayed by ectopic over-expression of Brg1 and was reproduced by inhibiting Brg1 activity either through genetic manipulation or treatment with the chemical inhibitor, (E)-1-(2-Hydroxyphenyl)-3-((1R, 4R)-5-(pyridin-2-yl)-2, 5-diazabicyclo[2.2.1]heptan-2-yl)prop-2-en-1-one, demonstrating the importance of Brg1 to maintenance of dendritic architecture. Loss of nBAF subunits was also documented in spinal motor neurons in autopsy tissue from familial amyotrophic sclerosis (chromosome 9 open reading frame 72 with G4C2 nucleotide expansion) and from sporadic cases with no identified mutation, pointing to dysfunction of nBAF chromatin remodelling in multiple forms of ALS. © The Author 2017. Published by Oxford University Press. All rights reserved

Ruthenium (II) complexes of thiosemicarbazone: Synthesis, biosensor applications and evaluation as antimicrobial agents

Energy Technology Data Exchange (ETDEWEB)

Yildirim, Hatice [Dokuz Eylul University, The Graduate School of Natural and Applied Sciences, Department of Chemistry, 35160 Buca, Izmir (Turkey); Guler, Emine [Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir (Turkey); Yavuz, Murat, E-mail: myavuz@dicle.edu.tr [Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir (Turkey); Dicle University, Faculty of Science, Department of Chemistry, 21280 Diyarbakir (Turkey); Ozturk, Nurdan; Kose Yaman, Pelin [Dokuz Eylul University, The Graduate School of Natural and Applied Sciences, Department of Chemistry, 35160 Buca, Izmir (Turkey); Subasi, Elif; Sahin, Elif [Dokuz Eylul University, Faculty of Science, Department of Chemistry, 35160 Buca, Izmir (Turkey); Timur, Suna [Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir (Turkey); Ege University, Institute on Drug Abuse, Toxicology and Pharmaceutical Science (BATI), 35100 Bornova, Izmir (Turkey)

2014-11-01

A conformationally rigid half-sandwich organoruthenium (II) complex [(η{sup 6}-p-cymene)RuClTSC{sup N–S}]Cl, (1) and carbonyl complex [Ru(CO)Cl(PPh{sub 3}){sub 2}TSC{sup N–S}] (2) have been synthesized from the reaction of [{(η"6-p-cymene)RuCl}{sub 2}(μ-Cl){sub 2}] and [Ru(H)(Cl)(CO)(PPh{sub 3}){sub 3}] with thiophene-2-carboxaldehyde thiosemicarbazon (TSC) respectively and both novel ruthenium (II) complexes have been characterized by elemental analysis, FT-IR and NMR spectroscopy. The peripheral TSC in the complexes acts as an electrochemical coupling unit providing the ability to carry out electrochemical deposition (ED) and to form an electro-deposited film on a graphite electrode surface. The biosensing applicability of complexes 1 and 2 was investigated by using glucose oxidase (GOx) as a model enzyme. Electrochemical measurements at − 0.9 V versus Ag/AgCl electrode by following the ED Ru(II) reduction/oxidation due to from the enzyme activity, in the presence of glucose substrate. The designed biosensor showed a very good linearity for 0.01–0.5 mM glucose. The in vitro antimicrobial activities of complexes 1 and 2 were also investigated against nine bacterial strains and one fungus by the disc diffusion test method. No activity was observed against the Gram-negative strains and fungus, whereas complex 1 showed moderate antibacterial activities against Gram-positive bacterial strains. - Highlights: • Novel Ru (II) thiosemicarbazone complexes were synthesized and characterized. • Electrochemical depositions were performed. • Rigid half-sandwich Ru (II) complex showed enhanced antibacterial activity.

A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation

NARCIS (Netherlands)

Dalle Pezze, Piero; Sonntag, Annika G; Thien, Antje; Prentzell, Mirja T; Gödel, Markus; Fischer, Sven; Neumann-Haefelin, Elke; Huber, Tobias B; Baumeister, Ralf; Shanley, Daryl P; Thedieck, Kathrin

2012-01-01

The kinase mammalian target of rapamycin (mTOR) exists in two multiprotein complexes (mTORC1 and mTORC2) and is a central regulator of growth and metabolism. Insulin activation of mTORC1, mediated by phosphoinositide 3-kinase (PI3K), Akt, and the inhibitory tuberous sclerosis complex 1/2

Development of a Novel NMR-based Rheb GTPase Assay and Molecular Characterization of TSC2 GAP Activity

Science.gov (United States)

2010-05-01

GTPase) that belongs to the Ras superfamily and has homologs in yeast, fungi , slime mold, fruit fly, zebra fish, and mammals (1–3). Ge- netic and...characterization of TSC2 disease mutations affecting its GAP activity (months 9-12) While the final aspects of this task are yet to be completed, we have...domain mutants of TSC2 that we examined affected its enzymatic activ- ity. This method can now be applied to study the function and regulation of other

Pediatric Multiple Sclerosis: Genes, Environment, and a Comprehensive Therapeutic Approach.

Science.gov (United States)

Cappa, Ryan; Theroux, Liana; Brenton, J Nicholas

2017-10-01

Pediatric multiple sclerosis is an increasingly recognized and studied disorder that accounts for 3% to 10% of all patients with multiple sclerosis. The risk for pediatric multiple sclerosis is thought to reflect a complex interplay between environmental and genetic risk factors. Environmental exposures, including sunlight (ultraviolet radiation, vitamin D levels), infections (Epstein-Barr virus), passive smoking, and obesity, have been identified as potential risk factors in youth. Genetic predisposition contributes to the risk of multiple sclerosis, and the major histocompatibility complex on chromosome 6 makes the single largest contribution to susceptibility to multiple sclerosis. With the use of large-scale genome-wide association studies, other non-major histocompatibility complex alleles have been identified as independent risk factors for the disease. The bridge between environment and genes likely lies in the study of epigenetic processes, which are environmentally-influenced mechanisms through which gene expression may be modified. This article will review these topics to provide a framework for discussion of a comprehensive approach to counseling and ultimately treating the pediatric patient with multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Linfangioleiomiomatosis pulmonar: Caso clínico

OpenAIRE

Silva O,Rafael; Puelma C,Felipe; Retamal P,Víctor; Rojas SM,Pedro; Cruzat C,Claudio; Reyes G,Cecilia

2009-01-01

Lymphangioleiomyomatosis (LAM) is a rare interstitial lung disease, of unknown etiology, affecting almost exclusively women. Microscopically LAM consists of a diffuse proliferation of smooth muscle cells. LAM can occur without evidence of other diseases (sporadic LAM) or in conjunction with tuberous sclerosis complex (TSC). It presents with progressive breathlessness or with recurrent pneumothorax or chylothorax. We report a 33 year-old woman with a history of recurrent pneumothorax. Computed...

Treatment of Advanced Malignant Uterine Perivascular Epithelioid Cell Tumor with mTOR Inhibitors: Single-institution Experience and Review of the Literature.

Science.gov (United States)

Starbuck, Kristen D; Drake, Richard D; Budd, G Thomas; Rose, Peter G

2016-11-01

Uterine perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors. Many have malignant behavior, and no successful treatment strategy has been established. Identification of mutations in the tuberous sclerosis 1 (TSC1) and TSC2 genes producing constitutive activation of the mammalian target of rapamycin (mTOR) pathway presents an opportunity for targeted therapy. Patients with advanced malignant uterine PEComa treated with mTOR inhibitors were identified and records were retrospectively reviewed for treatment response based on radiographic assessment. Three patients with advanced uterine PEComas underwent debulking surgery followed by mTOR inhibitor therapy; two had a complete response to therapy and disease in one patient progressed. Given the absence of effective therapies for malignant uterine PEComas, targeting the mTOR pathway is a logical strategy to pursue given the known pathobiology involving the Tuberous Sclerosis complex. Treatment of malignant uterine PEComas with mTOR inhibitors was effective in two out of three patients after surgical resection, with durable response. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Development of a TSC-Setup for the Characterization of Electron and Hole Traps in Irradiated Silicon Sensors

CERN Document Server

Stricker, Miriam

2015-01-01

For the characterization of radiation damage in silicon detectors a low-noise TSC-Setup was built to analyze charge trapping in the temperature range between 15 K and 250 K. The setup offers the possibility to perform Thermally Stimulated Current (TSC) and IV measurements and also to anneal samples at temperatures up to 180 ◦C. A first annealing study on a proton irradiated silicon pad sensor was performed. This study focuses mainly on the variation of the trap concentration and the results are compared to literature.

Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

Science.gov (United States)

Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

2014-01-01

The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

Modeling TSC and LAM Using Patient Derived Induced Pluripotent Stem Cells

Science.gov (United States)

2016-10-01

drug screens . We have now made TSC2 deficient human cells using patient induced pluripotent stem cells (iPSCs...Therapeutics.” Canadian Association of Research in Regenerative Medicine (CARRM), Ottawa, ON, CANADA March 7, 2015 • “ Stem cell approaches to model human... Stem cell approaches to model human development and disease.” Australian Regenerative Medicine Institute, Melbourne, Victoria, AUSTRALIA November

TSC1 and TSC2 regulate cilia length and canonical Hedgehog signaling via different mechanisms

DEFF Research Database (Denmark)

Rosengren, Thomas; Larsen, Lasse Jonsgaard; Pedersen, Lotte Bang

2018-01-01

Primary cilia are sensory organelles that coordinate multiple cellular signaling pathways, including Hedgehog (HH), Wingless/Int (WNT) and Transforming Growth Factor-β (TGF-β) signaling. Similarly, primary cilia have been implicated in regulation of mTOR signaling, in which Tuberous Sclerosis Com...

Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options

Directory of Open Access Journals (Sweden)

Wang S

2014-10-01

Full Text Available Shelly Wang,1 Aria Fallah2,3 1Department of Neurosurgery, University of Toronto, Toronto, ON, Canada; 2Department of Neurosurgery, Miami Children’s Hospital, Miami, FL, USA; 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada Abstract: Seizures are clinically significant manifestations associated with 79%–90% of patients with tuberous sclerosis complex. Often occurring within the first year of life in the form of infantile spasms, seizures interfere with neuropsychiatric, social, and cognitive development and carry significant individual and societal consequences. Prompt identification and treatment of seizures is an important focus in the overall management of tuberous sclerosis complex patients. Medical management, either after seizure onset or prophylactically in infants with electroencephalographic abnormalities, is considered first-line therapy. Vigabatrin and adrenocorticotropic hormone have emerged over the past few decades as mainstay pharmacologic modalities. Furthermore, emerging research on mammalian target of rapamycin inhibitors demonstrated promise for the management of seizures and subependymal giant cell astrocytoma. For appropriate surgical candidates with an epileptogenic zone associated with one or more glioneuronal hamartomas, ideally in noneloquent cortex, resective surgery can be considered, which provides a cure in 56% of patients. For medically refractory patients who do not meet criteria for curative surgery, palliative surgical approaches focused on reducing seizure burden, in the form of corpus callosotomy and vagus nerve stimulation, are alternative management options. Lastly, the ketogenic diet, a reemerging therapy based on the anticonvulsant effects of ketone bodies, can be utilized independently or in conjunction with other treatment modalities for the management of difficult-to-treat seizures. Keywords: epilepsy, adrenocorticotropic hormone, vigabatrin, mammalian

Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity is Decreased in Multiple Sclerosis Patients: Effects of β-Interferon Treatment

Directory of Open Access Journals (Sweden)

Iain Hargreaves

2018-02-01

Full Text Available Objectives: Evidence of mitochondrial respiratory chain (MRC dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS. However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment. Methods: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls. Results: MRC Complex IV activity was found to be significantly decreased (p < 0.05 in MS patients (2.1 ± 0.8 k/nmol × 10−3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10−3. Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10−3 was not found to be significantly different from that of the controls. Conclusions: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s of action of β-interferon.

Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis.

Science.gov (United States)

Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D; Parkhitko, Andrey; Morrison, Tasha A; Silverman, Edwin K; Henske, Elizabeth P; Yu, Jane J

2013-07-01

Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)-2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)-2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM.

Faslodex Inhibits Estradiol-Induced Extracellular Matrix Dynamics and Lung Metastasis in a Model of Lymphangioleiomyomatosis

Science.gov (United States)

Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D.; Parkhitko, Andrey; Morrison, Tasha A.; Silverman, Edwin K.; Henske, Elizabeth P.

2013-01-01

Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)–2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)–2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM. PMID:23526212

Renal angiomyolipoma bleeding in a patient with TSC2/PKD1 contiguous gene syndrome after 17 years of renal replacement therapy.

Science.gov (United States)

Furlano, Mónica; Barreiro, Yaima; Martí, Teresa; Facundo, Carme; Ruiz-García, César; DaSilva, Iara; Ayasreh, Nadia; Cabrera-López, Cristina; Ballarín, José; Ars, Elisabet; Torra, Roser

We report the case of a 32-year-old male diagnosed with TSC2/PKD1 contiguous gene syndrome, presenting with tuberous sclerosis (TS) and autosomal dominant polycystic kidney disease simultaneously. He progressed to end-stage renal disease and received a kidney transplant at the age of 12. The native kidneys presented angiomyolipomas (AML), which are common benign tumours in patients with TS. Seventeen years after transplantation, he presented with abdominal pain, anaemia and a retroperitoneal haematoma, the latter caused by renal AML bleeding. Selective embolisation was performed. Our patient could have benefited from the administration of mTOR inhibitors at transplant. This therapy is immunosuppressive and reduces the size of benign tumours in TS as well as the risk of rupture and bleeding. This patient did not receive mTOR inhibitors at the time of the transplant because the relationship between mTOR inhibitors and TS was unknown at that time. This case confirms the persistent risk of renal AML bleeding for both transplanted patients and patients on dialysis. As a result, we would recommend routine check-ups of native kidneys and nephrectomy assessment. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Simulations of ITER disruption and VDE scenarios with TSC and comparison with DINA results

International Nuclear Information System (INIS)

Bandyopadhyay, I.

2008-01-01

Vertical Displacement Events (VDEs) and plasma current disruptions pose one of the major concerns for the lifetime of in-vessel components in ITER, as well as for machine robustness, as large electromagnetic and thermal loads will induced at such events. Hence, accurate modelling of such events is crucial for estimating disruption induced forces. In the past, ITER disruption modelling has been carried out for ITER using the DINA code. However, since predictive simulations of such events depend on a large number of model assumptions, there exists chances of large error bars on the model predictions. As such it is imperative to validate the code results with other models. Towards this objective, we have carried out the VDE and Disruption simulations using the TSC code and the results are compared with the earlier DINA predictions. A detailed electromagnetic model of the ITER vessel, blankets and the first wall components has been created in TSC. In both VDE and disruption cases, the initial plasma is taken as ITER reference scenario 2 end of burn (EOB) specifications with I p = 15 MA, B t = 5 .3 T, e > 8.8 keV, e > = 1.1 x 10 20 m -3 . The plasma current disruption is initiated by dropping the plasma β in 1 msec, so that after the β crash e > = 6 eV, following which the plasma position control is switched off, resulting in a plasma current quench in about 65 msec. On the other hand, in the VDE case, the plasma control is switched off which results in either upward or downward VDE depending on the initial position of the plasma current centroid. In this case the plasma current remains close to 15 MA for a much longer time, about 700 msec in the simulations till the edge safety factor (q) becomes less than 1.5, following which the β is crashed resulting in plasma current quench. Significant differences exist in the DINA and TSC models, for example, even though the plasma current quench rate predicted by the models matches well in till the halo currents start flowing

Challenges in the management of a case of tuberous sclerosis

Directory of Open Access Journals (Sweden)

Anubhav Rathi

2012-01-01

Full Text Available Tuberous sclerosis complex is a multi-system disorder with autosomal dominant inheritance, which can affect the brain, heart, skin, kidneys, lungs, and retina. We hereby report therapeutic challenges faced in a case of an adolescent male suffering from tuberous sclerosis.

Impaired mTOR Macroautophagy and Neurocognitive Deficits in Tuberous Sclerosis Complex

Science.gov (United States)

2017-07-01

LTP) and long term depression (LTD), both of which are well-known electrophysiological surrogates of hippocampus dependent learning and memory. Our...4 4. Impact…………………………...…………………………………… 9 5. Changes/ Problems ...….……………………………………………… 10 6. Products…………………………………….……….….……………. 11 7...Atg7CKO, n=14). Compared to controls, *, pɘ.05; **, pɘ.01, Student t test. A B C Figure 2. Cognitive deficits in 3month old Tsc2+/- mice

The Human Papillomavirus Type 16 E6 Oncoprotein Activates mTORC1 Signaling and Increases Protein Synthesis ▿ †

OpenAIRE

Spangle, Jennifer M.; Münger, Karl

2010-01-01

The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y....

Evaluation of the of antibacterial efficacy of polyvinylpyrrolidone (PVP) and tri-sodium citrate (TSC) silver nanoparticles

Science.gov (United States)

Dey, Arindam; Dasgupta, Abhirup; Kumar, Vijay; Tyagi, Aakriti; Verma, Anita Kamra

2015-09-01

We present silver nanoparticles as the new age broad spectrum antibiotic. Siver nanoparticles exhibit unique physical and chemical properties that make them suitable for understanding their biological potential as antimicrobials. In this study, we explored the antibacterial activity of silver nanoparticles (TSC-AgNPs) and silver nanoparticles doped with polyvinylpyrrolidone (PVP-AgNPs) against Gram-negative and Gram-positive bacteria, Escherichia coli (DH5α) and Staphylococcus aureus, (ATCC 13709). Nucleation and growth kinetics during the synthesis process of AgNPs were precisely controlled using citrate (TSC) and further doped with polyvinylpyrrolidone (PVP). This resulted in the formation of two different sized nanoparticles 34 and 54 nm with PDI of 0.426 and 0.643. The physical characterization was done by nanoparticle tracking analysis and scanning electron microscopy, the results of which are in unison with the digital light scattering data. We found the bactericidal effect for both TSC-AgNPs and PVP-AgNPs to be dose-dependent as determined by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against E. coli and S. aureus. Interestingly, we also observed that AgNPs showed enhanced antimicrobial activity with a MIC of 26.75 and 13.48 µg/ml for E. coli and S. aureus, respectively, while MBC for AgNPs are 53.23 and 26.75 µg/ml for E. coli and S. aureus, respectively. Moreover, AgNPs showed increased DNA degradation as observed confirming its higher efficacy as antibacterial agent than the PVP doped AgNPs.

New management algorithms in multiple sclerosis

DEFF Research Database (Denmark)

Sorensen, Per Soelberg

2014-01-01

complex. The purpose of the review has been to work out new management algorithms for treatment of relapsing-remitting multiple sclerosis including new oral therapies and therapeutic monoclonal antibodies. RECENT FINDINGS: Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis......PURPOSE OF REVIEW: Our current treatment algorithms include only IFN-β and glatiramer as available first-line disease-modifying drugs and natalizumab and fingolimod as second-line therapies. Today, 10 drugs have been approved in Europe and nine in the United States making the choice of therapy more...

Outpatient physiotherapy and complex inpatient rehabilitation in multiple sclerosis patients: are there any differences?

Czech Academy of Sciences Publication Activity Database

Řasová, K.; Bartušková, T.; Rybníčková, M.; Dobrovodská, G.; Marková, M.; Jandová, D.; Zimová, D.; Bučilová, V.; Štětkářová, I.; Špaňhelová, S.; Kovari, M.; Cichy, B.; Krupová, M.; Vlčková, K.; Martinková, Patrícia

2013-01-01

Roč. 19, 11 Suppl. (2013), s. 116-116 ISSN 1352-4585. [Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis /29./. 02.10.2013-05.10.2013, Copenhagen] Grant - others:Univerzita Karlova(CZ) Prvouk P34 Institutional support: RVO:67985807 Keywords : physiotherapy * multiple sclerosis Subject RIV: FH - Neurology

Rehabilitation in multiple sclerosis.

Science.gov (United States)

Kubsik-Gidlewska, Anna M; Klimkiewicz, Paulina; Klimkiewicz, Robert; Janczewska, Katarzyna; Woldańska-Okońska, Marta

2017-07-01

The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The publications on the problem discuss a wide range of methods of physiotherapy that can be used in order to reduce the degree of disability and alleviate the symptoms associated with the disease. The complexity of the disease, the difficulty in determining the appropriate treatment and a wide range of symptoms require a comprehensive approach to the patient, which would include both pharmacology and neurorehabilitation. Rehabilitation, which includes psychotherapy and symptomatic therapy, is regarded nowadays as the best form of treatment for multiple sclerosis. An indepth diagnostic assessment of functional status and prognosis should be carried out before the start of the rehabilitation process. The prognosis should take into account the mental state, the neurological status and the awareness of the patient. The kinesiotherapy program in multiple sclerosis is based on a gradation of physiotherapy which assumes a gradual transition from basic movements to more complex ones till global functions are obtained. The most appropriate form of treatment is functional rehabilitation combined with physical procedures. Recent reports indicate the need for aerobic training to be included in the rehabilitation program. The introduction of physical activities, regardless of the severity of the disease, will reduce the negative effects of akinesia, and thus increase the functional capabilities of all body systems.

The immunogenetics of multiple sclerosis

DEFF Research Database (Denmark)

Svejgaard, A.

2008-01-01

with complex genetic backgrounds. HLA controls immune response genes and HLA associations indicate the involvement of autoimmunity. Multiple sclerosis (MS) was one of the first conditions proven to be HLA associated involving primarily HLA class II factors. We review how HLA studies give fundamental...

Tuberous sclerosis

Directory of Open Access Journals (Sweden)

Krishnan S

1996-01-01

Full Text Available Although tuberous sclerosis has been described with a diagnostic triad, it is not present consistently in all cases. Variety of skin manifestations were reported in tuberous sclerosis. This studay was undertaken to assess the frequency of various skin changes in tuberous sclerosis. Ten consecutive cases of tuberous sclerosis were studied. Angiofibroma was the commonest cutaneous manifestation. Atypical fibroxanthoma, dermatofibroma and neurofibroma were also noticed as interesting associations.

siRNA-mediated Erc gene silencing suppresses tumor growth in Tsc2 mutant renal carcinoma model.

Science.gov (United States)

Imamura, Osamu; Okada, Hiroaki; Takashima, Yuuki; Zhang, Danqing; Kobayashi, Toshiyuki; Hino, Okio

2008-09-18

Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery of siRNAs for stable treatment except short hairpin RNAs (shRNAs). On the other hand, there are many reports of systemic delivery of siRNAs for transient treatment using liposome carriers and others. With regard to shRNAs, a report showed fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Therefore, we decided to use original siRNA microspheres instead of shRNA for stable treatment of disease. In this study, we designed rat-specific siRNA sequences for Erc/mesothelin, which is a tumor-specific gene expressed in the Eker (Tsc2 mutant) rat model of hereditary renal cancer and confirmed the efficacy of gene silencing in vitro. Then, by using siRNA microspheres, we found that the suppression of Erc/mesothelin caused growth inhibition of Tsc2 mutant renal carcinoma cells in tumor implantation experiments in mice.

X-irradiation of thyroid during therapy of patients with multiple sclerosis

International Nuclear Information System (INIS)

Agte, B.S.; Efimova, A.S.; Kalmykova, T.N.; Bajkova, V.P.

1985-01-01

X-radiation of 27 patients with thyroid at acute therapeutically resistant, progradient form of multiple sclerosis has been applied. Indistinct therapeutic effect attributed to depression of auto-aggressive allergic processes in cerebrospinal formations is noted in 20 patients after one or two courses of radiotherapy. The method can be used in complex therapy of progradient forms of multiple sclerosis

Fulltext PDF

Indian Academy of Sciences (India)

approximately two-thirds of TSC cases are either sporadic or new mutations (i.e. with no .... Financial support from the Department of Biotechnology, New Delhi, ... a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell.

Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

Science.gov (United States)

Hernández, Wilfredo; Paz, Juan; Carrasco, Fernando; Spodine, Evgenia; Manzur, Jorge; Sieler, Joachim; Blaurock, Steffen; Beyer, Lothar

2013-01-01

The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to PdII through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (IC50 = 0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50 = 23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.). PMID:24391528

A time-resolved current method and TSC under vacuum conditions of SEM: Trapping and detrapping processes in thermal aged XLPE insulation cables

Science.gov (United States)

Boukezzi, L.; Rondot, S.; Jbara, O.; Boubakeur, A.

2017-03-01

Thermal aging of cross-linked polyethylene (XLPE) can cause serious concerns in the safety operation in high voltage system. To get a more detailed picture on the effect of thermal aging on the trapping and detrapping process of XLPE in the melting temperature range, Thermal Stimulated Current (TSC) have been implemented in a Scanning Electron Microscope (SEM) with a specific arrangement. The XLPE specimens are molded and aged at two temperatures (120 °C and 140 °C) situated close to the melting temperature of the material. The use of SEM allows us to measure both leakage and displacement currents induced in samples under electron irradiation. The first represents the conduction process of XLPE and the second gives information on the trapping of charges in the bulk of the material. TSC associated to the SEM leads to show spectra of XLPE discharge under thermal stimulation using both currents measured after electron irradiation. It was found that leakage current in the charging process may be related to the physical defects resulting in crystallinity variation under thermal aging. However the trapped charge can be affected by the carbonyl groups resulting from the thermo-oxidation degradation and the disorder in the material. It is evidenced from the TSC spectra of unaged XLPE that there is no detrapping charge under heat stimulation. Whereas the presence of peaks in the TSC spectra of thermally aged samples indicates that there is some amount of trapped charge released by heating. The detrapping behavior of aged XLPE is supported by the supposition of the existence of two trap levels: shallow traps and deep traps. Overall, physico-chemical reactions under thermal aging at high temperatures leads to the enhancement of shallow traps density and changes in range of traps depth. These changes induce degradation of electrical properties of XLPE.

Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

Directory of Open Access Journals (Sweden)

Souheil El-Chemaly

2012-09-01

Full Text Available The primary function of the lymphatic system is absorbing and transporting macromolecules and immune cells to the general circulation, thereby regulating fluid, nutrient absorption and immune cell trafficking. Lymphangiogenesis plays an important role in tissue inflammation and tumour cell dissemination. Lymphatic involvement is seen in lymphangioleiomyomatosis (LAM and idiopathic pulmonary fibrosis (IPF. LAM, a disease primarily affecting females, involves the lung (cystic destruction, kidney (angiomyolipoma and axial lymphatics (adenopathy and lymphangioleiomyoma. LAM occurs sporadically or in association with tuberous sclerosis complex (TSC. Cystic lung destruction results from proliferation of LAM cells, which are abnormal smooth muscle-like cells with mutations in the TSC1 or TSC2 gene. Lymphatic abnormalities arise from infiltration of LAM cells into the lymphatic wall, leading to damage or obstruction of lymphatic vessels. Benign appearing LAM cells possess metastatic properties and are found in the blood and other body fluids. IPF is a progressive lung disease resulting from fibroblast proliferation and collagen deposition. Lymphangiogenesis is associated with pulmonary destruction and disease severity. A macrophage subset isolated from IPF bronchoalveolar lavage fluid (BALF express lymphatic endothelial cell markers in vitro, in contrast to the same macrophage subset from normal BALF. Herein, we review lymphatic involvement in LAM and IPF.

Effects of Acupuncture on Gait of Patients with Multiple Sclerosis.

Science.gov (United States)

Criado, Maria Begoña; Santos, Maria João; Machado, Jorge; Gonçalves, Arminda Manuela; Greten, Henry Johannes

2017-11-01

Multiple sclerosis is considered a complex and heterogeneous disease. Approximately 85% of patients with multiple sclerosis indicate impaired gait as one of the major limitations in their daily life. Acupuncture studies found a reduction of spasticity and improvement of fatigue and imbalance in patients with multiple sclerosis, but there is a lack of studies regarding gait. We designed a study of acupuncture treatment, according to the Heidelberg model of Traditional Chinese Medicine (TCM), to investigate if acupuncture can be a useful therapeutic strategy in patients with gait impairment in multiple sclerosis of relapsing-remitting type. The sample consisted of 20 individuals with diagnosis of multiple sclerosis of relapsing-remitting type. Gait impairment was evaluated by the 25-foot walk test. The results showed differences in time to walk 25 feet following true acupuncture. In contrast, there was no difference in time to walk 25 feet following sham acupuncture. When using true acupuncture, 95% of cases showed an improvement in 25-foot walk test, compared with 45% when sham acupuncture was done. Our study protocol provides evidence that acupuncture treatment can be an attractive option for patients with multiple sclerosis, with gait impairment.

Coarctation of the aorta and renal artery stenosis in tuberous sclerosis

Energy Technology Data Exchange (ETDEWEB)

Flynn, P M; Robinson, M B; Stapleton, F B; Roy, S III; Koh, G; Tonkin, I L.D.

1984-07-01

Among neurocutaneous disorders, coarctation of the abdominal aorta and renal artery stenosis have traditionally been associated with neurofibromatosis. We report a 5-year-old girl who was discovered to have bilateral renal artery stenosis, coarctation of the abdominal aorta, renal cysts and typical skin lesions of tuberous clerosis during the evaluation of asymptomatic hypertension. Renal vascular hypertension has not been reported previously in tuberous sclerosis. We conclude that the tuberous sclerosis complex should be expanded to include vascular malformations and the hypertension should not be assumed to be secondary to renal hamartomata or cysts in patients with tuberous sclerosis.

Coarctation of the aorta and renal artery stenosis in tuberous sclerosis

International Nuclear Information System (INIS)

Flynn, P.M.; Robinson, M.B.; Stapleton, F.B.; Roy, S. III; Koh, G.; Tonkin, I.L.D.; Tennessee Univ., Memphis; Tennessee Univ., Memphis; LeBonheur Children's Medical Center, Memphis, TN

1984-01-01

Among neurocutaneous disorders, coarctation of the abdominal aorta and renal artery stenosis have traditionally been associated with neurofibromatosis. We report a 5-year-old girl who was discovered to have bilateral renal artery stenosis, coarctation of the abdominal aorta, renal cysts and typical skin lesions of tuberous clerosis during the evaluation of asymptomatic hypertension. Renal vascular hypertension has not been reported previously in tuberous sclerosis. We conclude that the tuberous sclerosis complex should be expanded to include vascular malformations and the hypertension should not be assumed to be secondary to renal hamartomata or cysts in patients with tuberous sclerosis. (orig.)

Prenatally Diagnosis and Outcome of Fetuses with Cardiac Rhabdomyoma – Single Centre Experience

Science.gov (United States)

Bejiqi, Ramush; Retkoceri, Ragip; Bejiqi, Hana

2017-01-01

BACKGROUND Cardiac rhabdomyoma (CRs) are the most common primary tumour of the heart in infants and children. Usually are multiple and, basing on the location can cause a haemodynamic disturbance, dysrhythmias or heart failure during the fetal and early postnatal period. CRs have a natural history of spontaneous regression and are closely associated with tuberous sclerosis complex (TSC). It has an association with tuberous sclerosis (TS), and in those, the tumour may regress and disappear completely, or remain consistent in size. AIM: We aimed to evaluate the prenatal diagnosis, clinical presentation and outcome of CRs and their association with TSC in a single centre. The median follow-up period was three years (range: 6 months - 5 years). MATERIAL AND METHODS: We reviewed medical records of all fetuses diagnosed prenatally with cardiac rhabdomyoma covering the period January 2010 to December 2016 which had undergone detailed ultrasound evaluation at a single centre with limited technical resources. RESULTS: Twelve fetuses were included in the study; mostly had multiple tumours and a total of 53 tumours were identified in all patients - the maximum was one fetus with16 tumours. All patients were diagnosed prenatally by fetal echocardiography. In two patient’s haemodynamic disturbances during the fetal period was noted and pregnancies have been terminated. After long consultation termination of pregnancy was chosen by the parents in totally 8 cases. In four continuing pregnancies during the first year of live tumours regressed. TSC was diagnosed in all patients during the follow-up. CONCLUSIONS: Cardiac rhabdomyoma are benign from the cardiovascular standpoint in most affected fetuses. An early prenatal diagnosis may help for an adequate planning of perinatal monitoring and treatment with the involvement of a multidisciplinary team. Large tumour size, the number of tumours and localisation may cause hydrops, and they are significantly associated with poor

The essential role of t cells in multiple sclerosis: A reappraisal

Directory of Open Access Journals (Sweden)

Cris S Constantinescu

2014-04-01

Full Text Available Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which destruction of myelin and nerve axons has been shown to be mediated by immune mechanisms. Although the focus of research has been traditionally on T cells as key mediators of the immunopathology, more recent efforts at understanding this complex disorder have been directed increasingly at other cellular and humoral elements of the immune response. This review is a reappraisal of the crucial role of T cells, in particular the CD4+ helper T-cell subset, in multiple sclerosis. Recent evidence is discussed underlining the predominant contribution of T-cell-associated genes to the genome-wide association study results of multiple sclerosis susceptibility, the loss of T-cell quiescence in the conversion from clinically isolated syndrome to clinically definite multiple sclerosis, and the fact that T cells represent the main target of effective immunomodulatory and immunosuppressive treatments in multiple sclerosis.

Therapeutic use of sport climbing for patients with multiple sclerosis

Directory of Open Access Journals (Sweden)

Ana Ožura

2009-05-01

Full Text Available Sport climbing is a form of exercise that requires complex and variable movement. Because of the use of the so-called "top-rope system", this is a safe activity appropriate for individuals with physical disabilities. Therefore, climbing might prove to be an effective form of therapy for patients with multiple sclerosis. Multiple sclerosis is a chronic neurological disease that may include motor and cognitive deficits as well as affective disturbances. The illness is characterized by multifocal areas of brain damage (plaques, as consequence of autoimmune inflammation. Sport climbing might be a potentially useful activity for treating spasticity, improving a person's self image and certain aspects of cognition, such as attention and executive functions, as well as for managing emotional disturbances. All of the above are areas where patients with multiple sclerosis might be in need of assistance. The article also describes the experience of a patient with multiple sclerosis who was enrolled in our climbing program. Future research is needed to evaluate the effect of climbing therapy for patients with multiple sclerosis.

Sclerosis: Implications for Interhemispheric Communication

Directory of Open Access Journals (Sweden)

A. Lunardelli

2014-01-01

Full Text Available We report a case of a 47-year-old woman with 35-year history of multiple sclerosis, who showed alien hand signs, a rare behavioural disorder that involves unilateral goal-directed movements that are contrary to the individual's intention. Alien hand syndrome has been described in multiple sclerosis (MS only occasionally and is generally suggestive of callosal disconnection. The patient presented also with bilateral limb apraxia and left hand agraphia, raising the possibility of cortical dysfunction or disconnection, in addition to corpus callosum and white matter involvement. Her specific pattern of symptoms supports the role of the corpus callosum in interhemispheric communication for complex as well as fine motor activities and may indicate that it can serve as both an inhibitory and excitatory function depending on task demands.

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Science.gov (United States)

Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

2013-01-01

Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

Topical sirolimus for the treatment of angiofibromas in tuberous sclerosis

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Salih Levent Cinar

2017-01-01

Full Text Available Background: The skin is one of the most affected organs in tuberous sclerosis complex and angiofibromas are seen in almost 80% of such patients. These benign tumors impose a great psycho-social burden on patients. Objective: The aim of the study was to evaluate the effectiveness and tolerability of topical sirolimus for facial angiofibromas in patients with tuberous sclerosis complex. Methods: This was a prospective, single-blinded, cross-over study which involved twelve patients. We investigated the effect and safety of topical 0.1% sirolimus, which was obtained by crushing sirolimus tablets and mixing it with petrolatum. The patients were asked to apply the cream to one side of their face, and vaseline to the other side. The effect of topical sirolimus was evaluated using the “facial angiofibroma severity index.” Results: There was a significant improvement in the redness and extension of the tumors on the sides to which the active ingredient was applied. Some side effects such as itching and irritation occurred in three patients, which were treated with topical hydrocortisone cream. Conclusion: Topical sirolimus appears to be a promising, fairly well tolerated treatment for facial angiofibromas in patients with tuberous sclerosis complex. Although its efficacy diminishes with time, repetitive usage is effective.

Monoclonal Antibodies for Relapsing Multiple Sclerosis

DEFF Research Database (Denmark)

Blinkenberg, Morten; Soelberg Sørensen, Per

2017-01-01

Treatment of multiple sclerosis (MS) has improved considerably over the last decade because of new insights into MS pathology and biotechnological advances. This has led to the development of new potent pharmaceutical compounds targeting different processes in the complex autoimmune pathology...... the context of different treatment strategies. Finally, we consider the most important future developments....

Ballistic Simulation Method for Lithium Ion Batteries (BASIMLIB) Using Thick Shell Composites (TSC) in LS-DYNA

Science.gov (United States)

2016-08-04

BAllistic SImulation Method for Lithium Ion Batteries (BASIMLIB) using Thick Shell Composites (TSC) in LS-DYNA Venkatesh Babu, Dr. Matt Castanier, Dr...and behavior of the cells through experimental and modeling at their crash worthiness laboratory • Most of the simulation work on the batteries are...at a single cell level and gap exists to simulate the batteries at their full pack capacity - Firstly, requires an enormous amount of computational

Effect of beta-agonists on LAM progression and treatment.

Science.gov (United States)

Le, Kang; Steagall, Wendy K; Stylianou, Mario; Pacheco-Rodriguez, Gustavo; Darling, Thomas N; Vaughan, Martha; Moss, Joel

2018-01-30

Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2 +/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.

Can multiple sclerosis as a cognitive disorder influence patients? dreams?

OpenAIRE

Moghadasi, Abdorreza Naser; Owji, Mahsa

2013-01-01

Dream should be considered as a kind of cognitive ability that is formed parallel to other cognitive capabilities like language. On the other hand, multiple sclerosis (MS) is a complex disease that can involve different aspects of our cognition. Therefore, MS may influence patients’ dreams. In fact, we do not know what the importance of dream is in MS, but further studies may introduce dream and dreaming as a sign of improvement or progression in MS disease.Multiple sclerosis (MS) is a diseas...

Genomic screening for dissection of a complex disease: The multiple sclerosis phenotype

Energy Technology Data Exchange (ETDEWEB)

Haines, J.L.; Bazyk, A.; Gusella, J.F. [Massachusetts General Hospital, Boston, MA (United States)] [and others

1994-09-01

Application of positional cloning to diseases with a complex etiology is fraught with problems. These include undefined modes of inheritance, heterogeneity, and epistasis. Although microsatellite markers now make genotyping the genome a straightforward task, no single analytical method is available to efficiently and accurately use these data for a complex disease. We have developed a multi-stage genomic screening strategy which uses a combination of non-parametric approaches (Affected Pedigree Member (APM) linkage analysis and robust sib pair analysis (SP)), and the parametric lod score approach (using four different genetic models). To warrant follow-up, a marker must have two or more of: a nominal P value of 0.05 or less on the non-parametric tests, or a lod score greater than 1.0 for any model. Two adjacent markers each fulfilling one criterion are also considered for follow-up. These criteria were determined both by simulation studies and our empirical experience in screening a large number of other disorders. We applied this approach to multiple sclerosis (MS), a complex neurological disorder with a strong but ill-defined genetic component. Analysis of the first 91 markers from our screen of 55 multiplex families found 5 markers which met the SP criteria, 13 markers which met the APM criteria, and 8 markers which met the lod score criteria. Five regions (on chromosomes 2, 4, 7, 14, and 19) met our overall criteria. However, no single method identified all of these regions, suggesting that each method is sensitive to various (unknown) influences. The chromosome 14 results were not supported by follow-up typing and analysis of markers in that region, but the chromosome 19 results remain well supported. Updated screening results will be presented.

Guidance of reactor operators and TSC personnel with the severe accident management guidance under shutdown and low power conditions

International Nuclear Information System (INIS)

Van Haesendonck, M.F.; Prior, R.P.

2000-01-01

The Westinghouse Owners Group Severe Accident Management Guidance (WOG SAMG) was developed between 1991 and 1994. The primary goals for severe accident management that form the basis of the WOG SAMG are to terminate any radioactive releases to the environment; to prevent failure of any containment fission product boundary and to return the plant to a controlled stable condition. The WOG SAMG is primarily a TSC tool for mitigation of low probability core damage events. The philosophy is that control room operators should remain focused on the prevention of core damage, whereas the TSC personnel should concentrate on the mitigation of the severe accident. The symptom based package is built up as a structured process for choosing appropriate actions based on actual plant conditions. No detailed knowledge of severe accident phenomena is required. The scope of the WOG SAMG is limited to severe accidents resulting from initiating events occurring during full power operation. However, a number of studies such as the EdF EPS 1300 Probabilistic Safety Assessment (PSA), the shutdown Probabilistic Risk Assessment (PRA) for Surry, the BERA shutdown PRA for Beznau, the EPRI/ Westinghouse ORAM methodology etc. have shown that the frequency of core damage (a severe accident) during shutdown and low power operation can be of the same order of magnitude as for full power operation. The at-power SAMG is viewed as the resolution of the severe accident issue. Similarly, it is expected that as shutdown PRAs mature, the final resolution of the severe accident issue will lie in SAMG for low power and shutdown operation. Therefore in resolution of this issue, Westinghouse has developed the Shutdown Severe Accident Management Guidance (SSAMG) which gives guidance for both control room and TSC personnel to mitigate a severe accident under shutdown or low power conditions. In the last few years, many LWR plants have been implementing SAMG. In the US, all plants have developed SAMG, and many

Multiple sclerosis

Science.gov (United States)

... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

Everolimus Alleviates Obstructive Hydrocephalus due to Subependymal Giant Cell Astrocytomas.

Science.gov (United States)

Moavero, Romina; Carai, Andrea; Mastronuzzi, Angela; Marciano, Sara; Graziola, Federica; Vigevano, Federico; Curatolo, Paolo

2017-03-01

Subependymal giant cell astrocytomas (SEGAs) are low-grade tumors affecting up to 20% of patients with tuberous sclerosis complex (TSC). Early neurosurgical resection has been the only standard treatment until few years ago when a better understanding of the molecular pathogenesis of TSC led to the use of mammalian target of rapamycin (mTOR) inhibitors. Surgical resection of SEGAs is still considered as the first line treatment in individuals with symptomatic hydrocephalus and intratumoral hemorrhage. We describe four patients with symptomatic or asymptomatic hydrocephalus who were successfully treated with the mTOR inhibitor everolimus. We collected the clinical data of four consecutive patients presenting with symptomatic or asymptomatic hydrocephalus due to a growth of subependymal giant cell atrocytomas and who could not undergo surgery for different reasons. All patients experienced a clinically significant response to everolimus and an early shrinkage of the SEGA with improvement in ventricular dilatation. Everolimus was well tolerated by all individuals. Our clinical series demonstrate a possible expanding indication for mTOR inhibition in TSC, which can be considered in patients with asymptomatic hydrocephalus or even when the symptoms already appeared. It offers a significant therapeutic alternative to individuals that once would have undergone immediate surgery. Everolimus might also allow postponement of a neurosurgical resection, making it elective with an overall lower risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Thermal Scanning Conductometry (TSC) as a General Method for Studying and Controlling the Phase Behavior of Conductive Physical Gels.

Science.gov (United States)

Bielejewski, Michal

2018-01-23

The thermal scanning conductometry protocol is a new approach in studying ionic gels based on low molecular weight gelators. The method is designed to follow the dynamically changing state of the ionogels, and to deliver more information and details about the subtle change of conductive properties with an increase or decrease in the temperature. Moreover, the method allows the performance of long term (i.e. days, weeks) measurements at a constant temperature to investigate the stability and durability of the system and the aging effects. The main advantage of the TSC method over classical conductometry is the ability to perform measurements during the gelation process, which was impossible with the classical method due to temperature stabilization, which usually takes a long time before the individual measurement. It is a well-known fact that to obtain the physical gel phase, the cooling stage must be fast; moreover, depending on the cooling rate, different microstructures can be achieved. The TSC method can be performed with any cooling/heating rate that can be assured by the external temperature system. In our case, we can achieve linear temperature change rates between 0.1 and approximately 10 °C/min. The thermal scanning conductometry is designed to work in cycles, continuously changing between heating and cooling stages. Such an approach allows study of the reproducibility of the thermally reversible gel-sol phase transition. Moreover, it allows the performance of different experimental protocols on the same sample, which can be refreshed to initial state (if necessary) without removal from the measuring cell. Therefore, the measurements can be performed faster, in a more efficient way, and with much higher reproducibility and accuracy. Additionally, the TSC method can be also used as a tool to manufacture the ionogels with targeted properties, like microstructure, with an instant characterization of conductive properties.

[An autopsy case of amyotrophic lateral sclerosis with prominent muscle cramps, fasciculation, and high titer of anti-voltage gated potassium channel (VGKC) complex antibody].

Science.gov (United States)

Sato, Aki; Sakai, Naoko; Shinbo, Junsuke; Hashidate, Hideki; Igarashi, Shuichi; Kakita, Akiyoshi; Yamazaki, Motoyoshi

2014-01-01

The patient was a 55-year-old male who had prominent fasciculation and muscle cramps. Muscle weakness and atrophy of the trunk, respiratory system, and extremities gradually progressed. On the basis of these features, we diagnosed this patient as having amyotrophic lateral sclerosis (ALS), however, the upper motor neuron signs were not significant. Following the detection of the anti-voltage gated potassium channel (VGKC) complex antibody at 907.5 pM (normal VGKC complex antibody in the development of cramp-fasciculation syndrome has been speculated. In this ALS patient, the antibodies might be associated with pathomechanisms underlying the characteristic symptoms.

Association between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis

International Nuclear Information System (INIS)

Medina, Yimy F; Martinez, Jose B; Fernandez, Andres R; Quintana, Gerardo; Restrepo, Jose Felix; Rondon, Federico; Gamarra, Antonio Iglesias

2010-01-01

Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoimmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.

An investigation of multidisciplinary complex health care interventions - steps towards an integrative treatment model in the rehabilitation of People with Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Skovgaard Lasse

2012-04-01

Full Text Available Abstract Background The Danish Multiple Sclerosis Society initiated a large-scale bridge building and integrative treatment project to take place from 2004–2010 at a specialized Multiple Sclerosis (MS hospital. In this project, a team of five conventional health care practitioners and five alternative practitioners was set up to work together in developing and offering individualized treatments to 200 people with MS. The purpose of this paper is to present results from the six year treatment collaboration process regarding the development of an integrative treatment model. Discussion The collaborative work towards an integrative treatment model for people with MS, involved six steps: 1 Working with an initial model 2 Unfolding the different treatment philosophies 3 Discussing the elements of the Intervention-Mechanism-Context-Outcome-scheme (the IMCO-scheme 4 Phrasing the common assumptions for an integrative MS program theory 5 Developing the integrative MS program theory 6 Building the integrative MS treatment model. The model includes important elements of the different treatment philosophies represented in the team and thereby describes a common understanding of the complexity of the courses of treatment. Summary An integrative team of practitioners has developed an integrative model for combined treatments of People with Multiple Sclerosis. The model unites different treatment philosophies and focuses on process-oriented factors and the strengthening of the patients’ resources and competences on a physical, an emotional and a cognitive level.

Deontological aspects of the amyotrophic lateral sclerosis

Directory of Open Access Journals (Sweden)

T. M. Alekseeva

2017-01-01

Full Text Available One of the significant problems in deontology is the degree of awareness of terminally ill patients regarding the diagnosis and prognosis of their disease. This topic is complex and relevant, it touches ethical and psychological, legal and medical aspects. The article discusses the positive and negative aspects of fully informing patients  with amyotrophic lateral sclerosis about the fatal diagnosis. There are 2  clinical cases reflecting different approaches of this complex issue: full awareness and concealment of the diagnosis.

Optical Coherence Tomography-A New Diagnostic Tool to Evaluate Axonal Degeneration in Multiple Sclerosis: A Review

Directory of Open Access Journals (Sweden)

Nilüfer Kale

2010-09-01

Full Text Available Multiple sclerosis is an inflammatory demyelinating disorder of the central nervous system with a wide spectrum of clinical signs and symptoms. Multiple sclerosis lesions have a predilection for the optic nerves, periventricular white matter, brainstem, spinal cord, and cerebellum. The mechanisms responsible for multiple sclerosis are complex and heterogeneous across patients and disease stages. No specific markers exist for the definite diagnosis and prognosis of multiple sclerosis. The afferent visual pathway, which extends from the retina to the primary visual cortex including the optic nerve, is one of the most commonly affected sites in multiple sclerosis (94-99%. Pathology of affected optic nerves exhibits inflammation, demyelination, gliosis, axonal injury, and thinning of the retinal nerve fiber layer (RNFL. The RNFL is composed of unmyelinated axons, and measuring RNFL thickness is a viable method to monitor axonal loss reflecting disease progression. Optical coherence tomography is a noninvasive and reproducible tool in assessing the impact of multiple sclerosis on the thickness of the RNFL. Assessment of the afferent visual pathway using clinical, imaging and electrophysiological methods provides insights into the pathophysiology of multiple sclerosis and may also serve a prognostic role in multiple sclerosis

Temporal lobe sclerosis associated with hippocampal sclerosis in temporal lobe epilepsy: neuropathological features.

Science.gov (United States)

Thom, Maria; Eriksson, Sofia; Martinian, Lillian; Caboclo, Luis O; McEvoy, Andrew W; Duncan, John S; Sisodiya, Sanjay M

2009-08-01

Widespread changes involving neocortical and mesial temporal lobe structures can be present in patients with temporal lobe epilepsy and hippocampal sclerosis. The incidence, pathology, and clinical significance of neocortical temporal lobe sclerosis (TLS) are not well characterized. We identified TLS in 30 of 272 surgically treated cases of hippocampal sclerosis. Temporal lobe sclerosis was defined by variable reduction of neurons from cortical layers II/III and laminar gliosis; it was typically accompanied by additional architectural abnormalities of layer II, that is, abnormal neuronal orientation and aggregation. Quantitative analysis including tessellation methods for the distribution of layer II neurons supported these observations. In 40% of cases, there was a gradient of TLS with more severe involvement toward the temporal pole, possibly signifying involvement of hippocampal projection pathways. There was a history of a febrile seizure as an initial precipitating injury in 73% of patients with TLS compared with 36% without TLS; no other clinical differences between TLS and non-TLS cases were identified. Temporal lobe sclerosis was not evident preoperatively by neuroimaging. No obvious effect of TLS on seizure outcome was noted after temporal lobe resection; 73% became seizure-free at 2-year follow-up. In conclusion, approximately 11% of surgically treated hippocampal sclerosis is accompanied by TLS. Temporal lobe sclerosis is likely an acquired process with accompanying reorganizational dysplasia and an extension of mesial temporal sclerosis rather than a separate pathological entity.

Multiple sclerosis

International Nuclear Information System (INIS)

Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

2008-01-01

Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

Synthesis, structural characterization and cytotoxic activity of two new organoruthenium(II complexes

Directory of Open Access Journals (Sweden)

SANJA GRGURIC-SIPKA

2008-06-01

Full Text Available Two new p-cymene ruthenium(II complexes containing as additional ligands N-methylpiperazine ([(η6-p-cymeneRuCl2(CH3NH(CH24NH]PF6, complex 1 or vitamin K3-thiosemicarbazone ([(η6-p-cymeneRuCl2(K3tsc], complex 2 were synthesized starting from [(η6-p-cymene2RuCl2]2 and the corresponding ligand. The complexes were characterized by elemental analysis, IR, electronic absorption and NMR spectroscopy. The X-ray crystal structure determination of complex 1 revealed “piano-stool” geometry. The differences in the cytotoxic activity of the two complexes are discussed in terms of the ligand present.

Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis

Science.gov (United States)

2016-07-01

tsc1 and tsc2 loss of function mutations in Schizosaccharomyces pombe. Northeast Regional Yeast Meeting, June 16-17, University at Buffalo, The State...AWARD NUMBER: W81XWH-14-1-0169 TITLE: Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of...SUBTITLE Using Genetic Buffering Relationships Identified in Fission 5a. CONTRACT NUMBER W81XWH-14-1-0169 Yeast to Elucidate the Molecular Pathology

Structural and dynamical insights on HLA-DR2 complexes that confer susceptibility to multiple sclerosis in Sardinia: a molecular dynamics simulation study.

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Amit Kumar

Full Text Available Sardinia is a major Island in the Mediterranean with a high incidence of multiple sclerosis, a chronic autoimmune inflammatory disease of the central nervous system. Disease susceptibility in Sardinian population has been associated with five alleles of major histocompatibility complex (MHC class II DRB1 gene. We performed 120 ns of molecular dynamics simulation on one predisposing and one protective alleles, unbound and in complex with the two relevant peptides: Myelin Basic Protein and Epstein Barr Virus derived peptide. In particular we focused on the MHC peptide binding groove dynamics. The predisposing allele was found to form a stable complex with both the peptides, while the protective allele displayed stability only when bound with myelin peptide. The local flexibility of the MHC was probed dividing the binding groove into four compartments covering the well known peptide anchoring pockets. The predisposing allele in the first half cleft exhibits a narrower and more rigid groove conformation in the presence of myelin peptide. The protective allele shows a similar behavior, while in the second half cleft it displays a narrower and more flexible groove conformation in the presence of viral peptide. We further characterized these dynamical differences by evaluating H-bonds, hydrophobic and stacking interaction networks, finding striking similarities with super-type patterns emerging in other autoimmune diseases. The protective allele shows a defined preferential binding to myelin peptide, as confirmed by binding free energy calculations. All together, we believe the presented molecular analysis could help to design experimental assays, supports the molecular mimicry hypothesis and suggests that propensity to multiple sclerosis in Sardinia could be partly linked to distinct peptide-MHC interaction and binding characteristics of the antigen presentation mechanism.

Reassessment of the role of TSC, mTORC1 and microRNAs in amino acids-meditated translational control of TOP mRNAs.

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Ilona Patursky-Polischuk

Full Text Available TOP mRNAs encode components of the translational apparatus, and repression of their translation comprises one mechanism, by which cells encountering amino acid deprivation downregulate the biosynthesis of the protein synthesis machinery. This mode of regulation involves TSC as knockout of TSC1 or TSC2 rescued TOP mRNAs translation in amino acid-starved cells. The involvement of mTOR in translational control of TOP mRNAs is demonstrated by the ability of constitutively active mTOR to relieve the translational repression of TOP mRNA upon amino acid deprivation. Consistently, knockdown of this kinase as well as its inhibition by pharmacological means blocked amino acid-induced translational activation of these mRNAs. The signaling of amino acids to TOP mRNAs involves RagB, as overexpression of active RagB derepressed the translation of these mRNAs in amino acid-starved cells. Nonetheless, knockdown of raptor or rictor failed to suppress translational activation of TOP mRNAs by amino acids, suggesting that mTORC1 or mTORC2 plays a minor, if any, role in this mode of regulation. Finally, miR10a has previously been suggested to positively regulate the translation of TOP mRNAs. However, we show here that titration of this microRNA failed to downregulate the basal translation efficiency of TOP mRNAs. Moreover, Drosha knockdown or Dicer knockout, which carries out the first and second processing steps in microRNAs biosynthesis, respectively, failed to block the translational activation of TOP mRNAs by amino acid or serum stimulation. Evidently, these results are questioning the positive role of microRNAs in this mode of regulation.

Cofortification of ferric pyrophosphate and citric acid/trisodium citrate into extruded rice grains doubles iron bioavailability through in situ generation of soluble ferric pyrophosphate citrate complexes.

Science.gov (United States)

Hackl, Laura; Cercamondi, Colin I; Zeder, Christophe; Wild, Daniela; Adelmann, Horst; Zimmermann, Michael B; Moretti, Diego

2016-05-01

Iron fortification of rice is a promising strategy for improving iron nutrition. However, it is technically challenging because rice is consumed as intact grains, and ferric pyrophosphate (FePP), which is usually used for rice fortification, has low bioavailability. We investigated whether the addition of a citric acid/trisodium citrate (CA/TSC) mixture before extrusion increases iron absorption in humans from FePP-fortified extruded rice grains. We conducted an iron absorption study in iron-sufficient young women (n = 20), in which each participant consumed 4 different meals (4 mg Fe/meal): 1) extruded FePP-fortified rice (No CA/TSC); 2) extruded FePP-fortified rice with CA/TSC added before extrusion (CA/TSC extruded); 3) extruded FePP-fortified rice with CA/TSC solution added after cooking and before consumption (CA/TSC solution); and 4) nonextruded rice fortified with a FeSO4 solution added after cooking and before consumption (reference). Iron absorption was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. In in vitro experiments, we assessed the soluble and dialyzable iron from rice meals in which CA/TSC was added at different preparation stages and from meals with different iron:CA:TSC ratios. Fractional iron absorption was significantly higher from CA/TSC-extruded meals (3.2%) than from No CA/TSC (1.7%) and CA/TSC solution (1.7%; all P solubility and dialyzability were higher in CA/TSC-extruded rice than in rice with No CA/TSC and CA/TSC solution, and solubility increased with higher amounts of added CA and TSC in extruded rice. Iron bioavailability nearly doubled when CA/TSC was extruded with FePP into fortified rice, resulting in iron bioavailability comparable to that of FeSO4 We attribute this effect to an in situ generation of soluble FePP citrate moieties during extrusion and/or cooking because of the close physical proximity of FePP and CA/TSC in the extruded rice matrix. This trial was registered at

Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study.

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John J Bissler

Full Text Available We examined the long-term effects of everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.Following favorable results from the double-blind core phase of EXIST-2 (NCT00790400, patients were allowed to receive open-label everolimus (extension phase. Patients initially randomly assigned to everolimus continued on the same dose; those who were receiving placebo crossed over to everolimus 10 mg/day. Dose modifications were based on tolerability. The primary end point was angiomyolipoma response rate, defined as a ≥50% reduction from baseline in the sum volume of target renal angiomyolipomas in the absence of new target angiomyolipomas, kidney volume increase of >20% from nadir, and angiomyolipoma-related bleeding grade ≥2. The key secondary end point was safety.Of the 112 patients who received ≥1 dose of everolimus, 58% (95% CI, 48.3% to 67.3% achieved angiomyolipoma response. Almost all patients (97% experienced reduction in renal lesion volumes at some point during the study period. Median duration of everolimus exposure was 46.9 months. Sixteen (14.3% patients experienced angiomyolipoma progression at some point in the study. No angiomyolipoma-related bleeding or nephrectomies were reported. One patient on everolimus underwent embolization for worsening right flank pain. Subependymal giant cell astrocytoma lesion response was achieved in 48% of patients and skin lesion response in 68% of patients. The most common adverse events suspected to be treatment-related were stomatitis (42%, hypercholesterolemia (30.4%, acne (25.9%, aphthous stomatitis and nasopharyngitis (each 21.4%. Ten (8.9% patients withdrew because of an adverse event. Renal function remained stable, and the frequency of emergent adverse events generally decreased over time.Everolimus treatment remained safe and effective over approximately 4 years. The overall risk/benefit assessment supports the use

Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

Science.gov (United States)

Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

2017-07-01

The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

CCR5 in Multiple Sclerosis : expression, regulation, and modulation by statins

NARCIS (Netherlands)

Kuipers, Hedwich Fardau

2007-01-01

Activation of microglia, the macrophages of the central nervous system, is a key element in multiple sclerosis (MS) lesion development and is characterized by enhanced expression of both classes of major histocompatibility complex (MHC) molecules. This enhanced expression results from increased

Vascular comorbidities in multiple sclerosis

DEFF Research Database (Denmark)

Thormann, Anja; Magyari, Melinda; Koch-Henriksen, Nils

2016-01-01

To investigate the occurrence of vascular comorbidities before and after the clinical onset of multiple sclerosis. In this combined case-control and cohort study, all Danish born citizens with onset of multiple sclerosis 1980-2005 were identified from the Danish Multiple Sclerosis Registry...... and randomly matched with controls regarding year of birth, gender, and municipality on January 1st in the year of multiple sclerosis (MS) onset (index date). Individual-level information on comorbidities was obtained from several independent nationwide registries and linked to the study population by unique...

Symptomatic management in multiple sclerosis

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Pushkar Shah

2015-01-01

Full Text Available Multiple sclerosis (MS is the commonest cause of disability in young adults. While there is increasing choice and better treatments available for delaying disease progression, there are still, very few, effective symptomatic treatments. For many patients such as those with primary progressive MS (PPMS and those that inevitably become secondary progressive, symptom management is the only treatment available. MS related symptoms are complex, interrelated, and can be interdependent. It requires good understanding of the condition, a holistic multidisciplinary approach, and above all, patient education and empowerment.

Rehabilitation and multiple sclerosis

DEFF Research Database (Denmark)

Dalgas, Ulrik

2011-01-01

In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point......, a paradigm shift is taking place and it is now increasingly acknowledged that exercise therapy is both safe and beneficial. Robot-assisted training is also attracting attention in multiple sclerosis rehabilitation. Several sophisticated commercial robots exist, but so far the number of scientific studies...... promising. This drug has been shown to improve walking ability in some patients with multiple sclerosis, associated with a reduction of patients' self-reported ambulatory disability. Rehabilitation strategies involving these different approaches, or combinations of them, may be of great use in improving...

Fatigue and Multiple Sclerosis

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... to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area Donate Donate ... of MS What Causes MS? Who Gets MS? Multiple Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis ...

Does vagotomy protect against multiple sclerosis?

Science.gov (United States)

Sundbøll, Jens; Horváth-Puhó, Erzsébet; Adelborg, Kasper; Svensson, Elisabeth

2017-07-01

To examine the association between vagotomy and multiple sclerosis. We conducted a matched cohort study of all patients who underwent truncal or super-selective vagotomy and a comparison cohort, by linking Danish population-based medical registries (1977-1995). Hazard ratios (HRs) for multiple sclerosis, adjusting for potential confounders were computed by means of Cox regression analysis. Median age of multiple sclerosis onset corresponded to late onset multiple sclerosis. No association with multiple sclerosis was observed for truncal vagotomy (0-37 year adjusted HR=0.91, 95% confidence interval [CI]: 0.48-1.74) or super-selective vagotomy (0-37 year adjusted HR=1.28, 95% CI: 0.79-2.09) compared with the general population. We found no association between vagotomy and later risk of late onset multiple sclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Motor neuron disease (amyotrophic lateral sclerosis) arising from longstanding primary lateral sclerosis

NARCIS (Netherlands)

Bruyn, R. P.; Koelman, J. H.; Troost, D.; de Jong, J. M.

1995-01-01

Three men were initially diagnosed as having primary lateral sclerosis (PLS), but eventually developed amyotrophic lateral sclerosis (ALS) after 7.5, 9, and at least 27 years. Non-familial ALS and PLS might be different manifestations of a single disease or constitute completely distinct entities.

Multiple sclerosis and organic solvents

DEFF Research Database (Denmark)

Mortensen, J T; Brønnum-Hansen, Henrik; Rasmussen, K

1998-01-01

We investigated a possible causal relation between exposure to organic solvents in Danish workers (housepainters, typographers/printers, carpenters/cabinetmakers) and onset of multiple sclerosis. Data on men included in the Danish Multiple Sclerosis Register (3,241 men) were linked with data from......, and butchers. Over a follow-up period of 20 years, we observed no increase in the incidence of multiple sclerosis among men presumed to be exposed to organic solvents. It was not possible to obtain data on potential confounders, and the study design has some potential for selection bias. Nevertheless......, the study does not support existing hypotheses regarding an association between occupational exposure to organic solvents and multiple sclerosis....

Antecedents of Coping with the Disease in Patients with Multiple Sclerosis: A Qualitative Content Analysis.

Science.gov (United States)

Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

2017-01-01

Due to many physical and mental disorders that occur in multiple sclerosis patients, identifying the factors affecting coping based on the experiences of patients using qualitative study is essential to improve their quality of life. This study was conducted to explore the antecedents of coping with the disease in patients with multiple sclerosis. This is a qualitative study conducted on 11 patients with multiple sclerosis in 2015 in Tehran, Iran. These patients were selected based on purposive sampling. Data were collected using semi-structured and in-depth interviews and coded. These data were analyzed using the conventional content analysis. The rigor of qualitative data using the criteria proposed by Guba and Lincoln were assessed. Five main categories were revealed: (1) social support, (2) lenience, (3) reliance on faith, (4) knowledge of multiple sclerosis and modeling, and (5) economic and environmental situation. Each category had several distinct sub-categories. The results of this study showed that coping with multiple sclerosis is a complex, multidimensional and contextual concept that is affected by various factors in relation to the context of Iran. The findings of the study can provide the healthcare professionals with deeper recognition and understanding of these antecedents to improve successful coping in Iranian patients suffering from multiple sclerosis.

Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

NARCIS (Netherlands)

Cenit, M.C.; Simeon, C.P.; Vonk, M.C.; Callejas-Rubio, J.L.; Espinosa, G.; Carreira, P.; Blanco, F.J.; Narvaez, J.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Garcia, I.; Garcia-Hernandez, F.J.; Gallego, M.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; Garcia de la Pena, P.; Lopez-Longo, F.J.; Gonzalez-Gay, M.A.; The Spanish Scleroderma, G.; Hesselstrand, R.; Riemekasten, G.; Witte, T.J.M. de; Voskuyl, A.E.; Schuerwegh, A.J.; Madhok, R.; Fonseca, C.; Denton, C.; Nordin, A.; Palm, O.; Laar, J.M. van; Hunzelmann, N.; Distler, J.H.; Kreuter, A.; Herrick, A.; Worthington, J.; Koeleman, B.P.; Radstake, T.R.D.J.; Martin, J.

2012-01-01

OBJECTIVE: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and

Treatment of Cognitive Impairment in Multiple Sclerosis

Science.gov (United States)

Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis.

Science.gov (United States)

Liśkiewicz, Arkadiusz D; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin-Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska-Szypułka, Halina

2016-02-19

Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, Egon; Stenager, E N; Knudsen, Lone

1994-01-01

In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

Interferon Treatment of Multiple Sclerosis

OpenAIRE

Alajbegovic, Azra; Deljo, Dervis; Alajbegovic, Salem; Djelilovic-Vranic, Jasminka; Todorovic, Ljubica; Tiric-Campara, Merita

2012-01-01

Introduction: In the treatment of Multiple Sclerosis (MS) differ: treatment of relapse, treatment slow the progression of the disease (immunomodulators and immunosuppression), and symptomatic treatment. The aim: The aim of this study is to analyze the application of interferon therapy in the treatment of MS-E: Process the disease, patients with multiple sclerosis who have passed the commission for multiple sclerosis at the Neurology Clinic of Clinical Center of Sarajevo University as a refere...

Hippocampal Sclerosis in Older Patients

Science.gov (United States)

Cykowski, Matthew D.; Powell, Suzanne Z.; Schulz, Paul E.; Takei, Hidehiro; Rivera, Andreana L.; Jackson, Robert E.; Roman, Gustavo; Jicha, Gregory A.; Nelson, Peter T.

2018-01-01

Context Autopsy studies of the older population (≥65 years of age), and particularly of the “oldest-old” (≥85 years of age), have identified a significant proportion (~20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. Objective To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). Data Sources Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. Conclusions In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology. PMID:28467211

Treatment of Cognitive Impairment in Multiple Sclerosis

OpenAIRE

Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the co...

A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK.

Science.gov (United States)

Morgan, Sarah; Shatunov, Aleksey; Sproviero, William; Jones, Ashley R; Shoai, Maryam; Hughes, Deborah; Al Khleifat, Ahmad; Malaspina, Andrea; Morrison, Karen E; Shaw, Pamela J; Shaw, Christopher E; Sidle, Katie; Orrell, Richard W; Fratta, Pietro; Hardy, John; Pittman, Alan; Al-Chalabi, Ammar

2017-06-01

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls. About 10% of patients were predicted to carry a pathological expansion of the C9orf72 gene. We found an increased burden of rare variants in patients within the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2. We found 11 patients (1%) carried more than one pathogenic variant (P = 0.001) consistent with an oligogenic basis of amyotrophic lateral sclerosis. These findings show that the genetic architecture of amyotrophic lateral sclerosis is complex and that variation in the regulatory regions of associated genes may be important in disease pathogenesis. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Magnetic resonance imaging abnormalities in multiple sclerosis: A review

International Nuclear Information System (INIS)

Saharian, M. A.; Shakaouri Rad, A.; Motamedi, M.; Pakdaman, H.; Radue, E. W.

2007-01-01

:During the last two decades, magnetic resonance imaging has been widely used In the diagnosis and treatment monitoring of multiple sclerosis. MRI, both conventional and non conventional methods, has transformed all aspects of M S research and clinical practice in recent years. Although advanced imaging methods have added much more to our knowledge about pathogenesis and natural history of the disease but their cost, availability, complexity and lack of validation have limited their use in routine clinical practice. Conventional MR techniques including proton density, T1/T2-Weighted images and fluid- attenuated inversion recovery sequences are now accepted in standard protocols for diagnosis and treatment outcome measures in clinical trials of multiple sclerosis. This review will focus on the type, morphology and evolution of M S lesions regarding conventional MRI and their use for treatment monitoring in daily clinical practice

Multiple Sclerosis After Infectious Mononucleosis

DEFF Research Database (Denmark)

Nielsen, Trine Rasmussen; Rostgaard, Klaus; Nielsen, Nete Munk

2007-01-01

BACKGROUND: Infectious mononucleosis caused by the Epstein-Barr virus has been associated with increased risk of multiple sclerosis. However, little is known about the characteristics of this association. OBJECTIVE: To assess the significance of sex, age at and time since infectious mononucleosis......, and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. DESIGN: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the Danish...... Multiple Sclerosis Registry. SETTING: Statens Serum Institut. PATIENTS: A cohort of 25 234 Danish patients with mononucleosis was followed up for the occurrence of multiple sclerosis beginning on April 1, 1968, or January 1 of the year after the diagnosis of mononucleosis or after a negative Paul...

TSC measurements on proton-irradiated p-type Si-sensors

Energy Technology Data Exchange (ETDEWEB)

Donegani, Elena; Fretwurst, Eckhart; Garutti, Erika; Junkes, Alexandra [University of Hamburg (Germany)

2016-07-01

Thin n{sup +}p Si sensors are potential candidates for coping with neutron equivalent fluences up to 2.10{sup 16} n{sub eq}/cm{sup 2} and an ionizing dose in the order of a few MGy, which are expected e.g. for the HL-LHC upgrade. The aim of the present work is to provide experimental data on radiation-induced defects in order to: firstly, get a deeper understanding of the properties of hadron induced defects, and secondly develop a radiation damage model based on microscopic measurements. Therefore, the outcomes of Thermally Stimulated Current measurements on 200 μm thick Float-Zone (FZ) and Magnetic Czochralski (MCz) diodes will be shown, as a results of irradiation with 23 MeV protons and isothermal annealing. The samples were irradiated in the fluence range (0.3-1).10{sup 14} n{sub eq}/cm{sup 2}, so that the maximal temperature at which the TSC signal is still sharply distinguishable from the dark current is 200 K. In particular, special focus will be given to the defect introduction rate and to the issue of boron removal in p-type silicon. Annealing studies allow to distinguish which defects mainly contribute to the leakage current and which to the space charge, and thus correlate microscopic defects properties with macroscopic sensor properties.

A Case of Morvan Syndrome Mimicking Amyotrophic Lateral Sclerosis With Frontotemporal Dementia.

Science.gov (United States)

Freund, Brin; Maddali, Manoj; Lloyd, Thomas E

2016-06-01

Morvan syndrome is a rare autoimmune/paraneoplastic disorder involving antibodies to the voltage-gated potassium channel complex. It is defined by subacute encephalopathy, neuromuscular hyperexcitability, dysautonomia, and sleep disturbance. It may present a diagnostic dilemma when trying to differentiate from amyotrophic lateral sclerosis with frontotemporal dementia. A 76-year-old man with a history of untreated prostate adenocarcinoma was evaluated for subacute cognitive decline, diffuse muscle cramps, and hyponatremia. MRI demonstrated atrophy most prominent in the frontal and temporal regions. Electromyography (EMG) demonstrated diffuse myokymia/neuromyotonia. Polysomnography lacked REM and N3 sleep. Paraneoplastic panel detected antibodies to voltage-gated potassium channel complex (CASPR2 subtype). It is difficult to differentiate between Morvan syndrome and amyotrophic lateral sclerosis with frontotemporal dementia with examination and neuroimaging alone. There may be a link between Morvan syndrome and prostate adenocarcinoma which could help with screening/diagnosis. The authors found that laboratory and neurophysiological tests are indispensable in diagnosing and treating Morvan syndrome.

Multiple Sclerosis and Vitamin D

Science.gov (United States)

... Editors David C. Spencer, MD Steven Karceski, MD Multiple sclerosis and vitamin D Andrew J. Solomon, MD WHAT ... caused by improper immune responses (autoimmune diseases), including multiple sclerosis (MS). A recent Patient Page in Neurology provided ...

Chromosomal radiosensitivity in patients with multiple sclerosis

International Nuclear Information System (INIS)

Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia; Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria; Groudeva, Violeta; Hadjidekova, Savina; Domínguez, Inmaculada

2013-01-01

Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

Chromosomal radiosensitivity in patients with multiple sclerosis

Energy Technology Data Exchange (ETDEWEB)

Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia [III Neurological Clinic, University Hospital Saint Naum, Sofia (Bulgaria); Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria [Laboratory of Radiation Genetics, NCRRP, Sofia (Bulgaria); Groudeva, Violeta [Department of Diagnostic Imaging, University Hospital St. Ekaterina, Sofia (Bulgaria); Hadjidekova, Savina [Department of Medical Genetics, Medical University, Sofia (Bulgaria); Domínguez, Inmaculada, E-mail: idomin@us.es [Department of Cell Biology, Faculty of Biology, University of Seville, Avda. Reina Mercedes 6, 41012 (Spain)

2013-09-15

Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

Molecular Mechanisms Underlying the Epileptogenesis and Seizure Progression in Tuberous Sclerosis Complex 1 Deficient Mouse Models

Science.gov (United States)

2016-10-01

dysregulation in epileptogenesis in the developing brain? 2) What are the molecular mechanisms downstream of mTOR hyperactivation that trigger epileptogenesis...underlying epilepsy. Hopefully, a knowledge of these mechanisms will aid in a rational development of therapies. KEYWORDS Tuberous Sclerosis, Epilepsy

Impact of genetic risk loci for multiple sclerosis on expression of proximal genes in patients

KAUST Repository

James, Tojo; Lindé n, Magdalena; Morikawa, Hiromasa; Fernandes, Sunjay Jude; Ruhrmann, Sabrina; Huss, Mikael; Brandi, Maya; Piehl, Fredrik; Jagodic, Maja; Tegner, Jesper; Khademi, Mohsen; Olsson, Tomas; Gomez-Cabrero, David; Kockum, Ingrid

2018-01-01

Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as Multiple Sclerosis (MS

[Future challenges in multiple sclerosis].

Science.gov (United States)

Fernández, Óscar

2014-12-01

Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Skin scoring in systemic sclerosis

DEFF Research Database (Denmark)

Zachariae, Hugh; Bjerring, Peter; Halkier-Sørensen, Lars

1994-01-01

Forty-one patients with systemic sclerosis were investigated with a new and simple skin score method measuring the degree of thickening and pliability in seven regions together with area involvement in each region. The highest values were, as expected, found in diffuse cutaneous systemic sclerosis...... (type III SS) and the lowest in limited cutaneous systemic sclerosis (type I SS) with no lesions extending above wrists and ancles. A positive correlation was found to the aminoterminal propeptide of type III procollagen, a serological marker for synthesis of type III collagen. The skin score...

Evaluation of the TSC Dolphin Computer Assisted Instructional System in the Chapter 1 Program of the District of Columbia Public Schools. Final Report 85-9.

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Harris, Carolyn DeMeyer; And Others

Dolphin is a computer-assisted instruction system used to teach and reinforce skills in reading, language arts, and mathematics. An evaluation of this system was conducted to provide information to TSC Division of Houghton Mifflin regarding its effectiveness and possible modifications to the system. The general design of the evaluation was to…

Two-stage clustering (TSC: a pipeline for selecting operational taxonomic units for the high-throughput sequencing of PCR amplicons.

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Xiao-Tao Jiang

Full Text Available Clustering 16S/18S rRNA amplicon sequences into operational taxonomic units (OTUs is a critical step for the bioinformatic analysis of microbial diversity. Here, we report a pipeline for selecting OTUs with a relatively low computational demand and a high degree of accuracy. This pipeline is referred to as two-stage clustering (TSC because it divides tags into two groups according to their abundance and clusters them sequentially. The more abundant group is clustered using a hierarchical algorithm similar to that in ESPRIT, which has a high degree of accuracy but is computationally costly for large datasets. The rarer group, which includes the majority of tags, is then heuristically clustered to improve efficiency. To further improve the computational efficiency and accuracy, two preclustering steps are implemented. To maintain clustering accuracy, all tags are grouped into an OTU depending on their pairwise Needleman-Wunsch distance. This method not only improved the computational efficiency but also mitigated the spurious OTU estimation from 'noise' sequences. In addition, OTUs clustered using TSC showed comparable or improved performance in beta-diversity comparisons compared to existing OTU selection methods. This study suggests that the distribution of sequencing datasets is a useful property for improving the computational efficiency and increasing the clustering accuracy of the high-throughput sequencing of PCR amplicons. The software and user guide are freely available at http://hwzhoulab.smu.edu.cn/paperdata/.

Multiple sclerosis

International Nuclear Information System (INIS)

Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

1986-01-01

Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

Lung commitment in Tuberous Sclerosis

International Nuclear Information System (INIS)

Carrillo B, Jorge A; Araque G, Julio Mario; Camargo P, Carlos B

1992-01-01

Tuberous sclerosis is a rare hereditary anomaly characterized by hamartomas in many parts of the body. Lung involvement is found in only one of 100 cases. In this case report we present a patient with lung involvement in tuberous sclerosis

Demyelination versus remyelination in progressive multiple sclerosis

DEFF Research Database (Denmark)

Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

2010-01-01

The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

Profile modification computations for LHCD experiments on PBX-M using the TSC/LSC model

International Nuclear Information System (INIS)

Kaita, R.; Ignat, D.W.; Jardin, S.C.; Okabayashi, M.; Sun, Y.C.

1996-01-01

The TSC-LSC computational model of the dynamics of lower hybrid current drive has been exercised extensively in comparison with data from a Princeton Beta Experiment-Modification (PBX-M) discharge where the measured q(0) attained values slightly above unity. Several significant, but plausible, assumptions had to be introduced to keep the computation from behaving pathologically over time, producing singular profiles of plasma current density and q. Addition of a heuristic current diffusion estimate, or more exactly, a smoothing of the rf-driven current with a diffusion-like equation, greatly improved the behavior of the computation, and brought theory and measurement into reasonable agreement. The model was then extended to longer pulse lengths and higher powers to investigate performance to be expected in future PBX-M current profile modification experiments. copyright 1996 American Institute of Physics

Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling.

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Aruna D Balgi

Full Text Available BACKGROUND: Mammalian target of rapamycin complex 1 (mTORC1 is a protein kinase that relays nutrient availability signals to control numerous cellular functions including autophagy, a process of cellular self-eating activated by nutrient depletion. Addressing the therapeutic potential of modulating mTORC1 signaling and autophagy in human disease requires active chemicals with pharmacologically desirable properties. METHODOLOGY/PRINCIPAL FINDINGS: Using an automated cell-based assay, we screened a collection of >3,500 chemicals and identified three approved drugs (perhexiline, niclosamide, amiodarone and one pharmacological reagent (rottlerin capable of rapidly increasing autophagosome content. Biochemical assays showed that the four compounds stimulate autophagy and inhibit mTORC1 signaling in cells maintained in nutrient-rich conditions. The compounds did not inhibit mTORC2, which also contains mTOR as a catalytic subunit, suggesting that they do not inhibit mTOR catalytic activity but rather inhibit signaling to mTORC1. mTORC1 inhibition and autophagosome accumulation induced by perhexiline, niclosamide or rottlerin were rapidly reversed upon drug withdrawal whereas amiodarone inhibited mTORC1 essentially irreversibly. TSC2, a negative regulator of mTORC1, was required for inhibition of mTORC1 signaling by rottlerin but not for mTORC1 inhibition by perhexiline, niclosamide and amiodarone. Transient exposure of immortalized mouse embryo fibroblasts to these drugs was not toxic in nutrient-rich conditions but led to rapid cell death by apoptosis in starvation conditions, by a mechanism determined in large part by the tuberous sclerosis complex protein TSC2, an upstream regulator of mTORC1. By contrast, transient exposure to the mTORC1 inhibitor rapamycin caused essentially irreversible mTORC1 inhibition, sustained inhibition of cell growth and no selective cell killing in starvation. CONCLUSION/SIGNIFICANCE: The observation that drugs already

Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

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Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

2004-01-01

Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external

Hippocampal sclerosis in advanced age: clinical and pathological features

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Schmitt, Frederick A.; Lin, Yushun; Abner, Erin L.; Jicha, Gregory A.; Patel, Ela; Thomason, Paula C.; Neltner, Janna H.; Smith, Charles D.; Santacruz, Karen S.; Sonnen, Joshua A.; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Woodard, John L.; Van Eldik, Linda J.; Kryscio, Richard J.

2011-01-01

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer’s disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer’s Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n = 106). For individuals aged ≥95 years at death (n = 179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of ‘definite’ Alzheimer’s disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n = 10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar

Hippocampal sclerosis in advanced age: clinical and pathological features.

Science.gov (United States)

Nelson, Peter T; Schmitt, Frederick A; Lin, Yushun; Abner, Erin L; Jicha, Gregory A; Patel, Ela; Thomason, Paula C; Neltner, Janna H; Smith, Charles D; Santacruz, Karen S; Sonnen, Joshua A; Poon, Leonard W; Gearing, Marla; Green, Robert C; Woodard, John L; Van Eldik, Linda J; Kryscio, Richard J

2011-05-01

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR

PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis.

Directory of Open Access Journals (Sweden)

Kathrin Thedieck

Full Text Available TOR (Target of Rapamycin is a highly conserved protein kinase and a central controller of cell growth. TOR is found in two functionally and structurally distinct multiprotein complexes termed TOR complex 1 (TORC1 and TOR complex 2 (TORC2. In the present study, we developed a two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS based proteomic strategy to identify new mammalian TOR (mTOR binding proteins. We report the identification of Proline-rich Akt substrate (PRAS40 and the hypothetical protein Q6MZQ0/FLJ14213/CAE45978 as new mTOR binding proteins. PRAS40 binds mTORC1 via Raptor, and is an mTOR phosphorylation substrate. PRAS40 inhibits mTORC1 autophosphorylation and mTORC1 kinase activity toward eIF-4E binding protein (4E-BP and PRAS40 itself. HeLa cells in which PRAS40 was knocked down were protected against induction of apoptosis by TNFalpha and cycloheximide. Rapamycin failed to mimic the pro-apoptotic effect of PRAS40, suggesting that PRAS40 mediates apoptosis independently of its inhibitory effect on mTORC1. Q6MZQ0 is structurally similar to proline rich protein 5 (PRR5 and was therefore named PRR5-Like (PRR5L. PRR5L binds specifically to mTORC2, via Rictor and/or SIN1. Unlike other mTORC2 members, PRR5L is not required for mTORC2 integrity or kinase activity, but dissociates from mTORC2 upon knock down of tuberous sclerosis complex 1 (TSC1 and TSC2. Hyperactivation of mTOR by TSC1/2 knock down enhanced apoptosis whereas PRR5L knock down reduced apoptosis. PRR5L knock down reduced apoptosis also in mTORC2 deficient cells. The above suggests that mTORC2-dissociated PRR5L may promote apoptosis when mTOR is hyperactive. Thus, PRAS40 and PRR5L are novel mTOR-associated proteins that control the balance between cell growth and cell death.

The genetics of multiple sclerosis: review of current and emerging candidates

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Muñoz-Culla M

2013-08-01

Full Text Available Maider Muñoz-Culla,1,2 Haritz Irizar,1,2 David Otaegui1,2 1Multiple Sclerosis Unit, Instituto Biodonostia, San Sebastián, Spain; 2Red Española de Esclerosis Múltiple (REEM, Barcelona, Spain Abstract: Multiple sclerosis (MS is a complex disease in which environmental, genetic, and epigenetic factors determine the risk of developing the disease. The human leukocyte antigen region is the strongest susceptibility locus linked to MS, but it does not explain the whole heritability of the disease. To find other non-human leukocyte antigen loci associated with the disease, high-throughput genotyping, sequencing, and gene-expression studies have been performed, producing a valuable quantity of information. An overview of the genomic and expression studies is provided in this review, as well as microRNA-expression studies, highlighting the importance of combining all the layers of information in order to elucidate the causes or pathological mechanisms occurring in the disease. Genetics in MS is a promising field that is presumably going to be very productive in the next decade understanding the cross talk between all the factors contributing to the development of MS. Keywords: multiple sclerosis, genetics, gene expression, microRNA

Multiple Sclerosis: Can It Cause Seizures?

Science.gov (United States)

... multiple sclerosis and epilepsy? Answers from B Mark Keegan, M.D. Epileptic seizures are more common in ... controlled with anti-seizure medication. With B Mark Keegan, M.D. Lund C, et al. Multiple sclerosis ...

Suicide among Danes with multiple sclerosis

DEFF Research Database (Denmark)

Brønnum-Hansen, H; Stenager, E; Nylev Stenager, E

2005-01-01

OBJECTIVE: To compare the suicide risk among Danish citizens with multiple sclerosis with that of the general population, and to evaluate changes over 45 years. METHODS: The study was based on linkage of the Danish Multiple Sclerosis Registry to the Cause of Death Registry. It comprised all 10...... taken their own lives, whereas the expected number of suicides was 54.2 (29.1 men, 25.1 women). Thus the suicide risk among persons with multiple sclerosis was more than twice that of the general population (SMR = 2.12). The increased risk was particularly high during the first year after diagnosis (SMR...... = 3.15). CONCLUSIONS: The risk of suicide in multiple sclerosis was almost twice as high as expected more than 20 years after diagnosis. The excess suicide risk has not declined since 1953....

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

Science.gov (United States)

Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

Comorbidity of Bipolar Disorder and Multiple Sclerosis: A Case Report

Directory of Open Access Journals (Sweden)

Necla Keskin

2013-08-01

Full Text Available Multiple sclerosis is a chronic demyelinating disease of a central nervous system. Neuropsychiatric symptoms are common in multiple sclerosis and bipolar disorder is one of the most common psychiatric disorders that coexist with multiple sclerosis. Manic episodes may be the first presenting symptom of multiple sclerosis as comorbid pathology or as an adverse effect of pharmacotherapies used in multiple sclerosis. The comorbidity of bipolar disorder and multiple sclerosis is well-proven but its etiology is not known and investigated accurately. Recent studies support a common genetic susceptibility. Management of bipolar disorder in multiple sclerosis is based on evidence provided by case reports and treatment should be individualized. In this report, the association between bipolar disorder and multiple sclerosis, epidemiology, ethiology and treatment is discussed through a case had diagnosed as multiple sclerosis and had a manic episode with psychotic features. [Cukurova Med J 2013; 38(4.000: 832-836

Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis.

Science.gov (United States)

Hamid, Kabir Magaji; Mirshafiey, Abbas

2016-02-01

Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear. In this study, the link between proangiogenic factors and multiple sclerosis pathogenesis was examined by conducting a systemic review. Thus we searched the English medical literature via PubMed, ISI web of knowledge, Medline and virtual health library (VHL) databases. In this review, we describe direct and indirect roles of some proangiogenic factors in MS pathogenesis and report the association of these factors with pathological and inflammatory angiogenesis.

Erasmus Syndrome: Silicosis and Systemic Sclerosis.

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Jain, Shubhra; Joshi, Vinod; Rathore, Yogendra S; Khippal, Narendra

2017-01-01

Several occupational hazards, especially exposure to silica, have been implicated as causal factors for the development of scleroderma-like disorders. Compared to other connective tissue disorders, silica-associated systemic sclerosis (SA-SS) is relatively rare. Silica-induced scleroderma is indistinguishable from idiopathic systemic sclerosis. However, the former expresses a high predisposition of pulmonary involvement and anti-Scl-70 antibody. We report the case of a 42-year-old male, stone cutter by occupation, who was diagnosed as simple chronic silicosis and developed systemic sclerosis.

Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy

Science.gov (United States)

2013-01-01

Background Skeletal muscle mass is determined by the balance between protein synthesis and degradation. Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of protein translation and has been implicated in the control of muscle mass. Inactivation of mTORC1 by skeletal muscle-specific deletion of its obligatory component raptor results in smaller muscles and a lethal dystrophy. Moreover, raptor-deficient muscles are less oxidative through changes in the expression PGC-1α, a critical determinant of mitochondrial biogenesis. These results suggest that activation of mTORC1 might be beneficial to skeletal muscle by providing resistance to muscle atrophy and increasing oxidative function. Here, we tested this hypothesis by deletion of the mTORC1 inhibitor tuberous sclerosis complex (TSC) in muscle fibers. Method Skeletal muscles of mice with an acute or a permanent deletion of raptor or TSC1 were examined using histological, biochemical and molecular biological methods. Response of the muscles to changes in mechanical load and nerve input was investigated by ablation of synergistic muscles or by denervation . Results Genetic deletion or knockdown of raptor, causing inactivation of mTORC1, was sufficient to prevent muscle growth and enhance muscle atrophy. Conversely, short-term activation of mTORC1 by knockdown of TSC induced muscle fiber hypertrophy and atrophy-resistance upon denervation, in both fast tibialis anterior (TA) and slow soleus muscles. Surprisingly, however, sustained activation of mTORC1 by genetic deletion of Tsc1 caused muscle atrophy in all but soleus muscles. In contrast, oxidative capacity was increased in all muscles examined. Consistently, TSC1-deficient soleus muscle was atrophy-resistant whereas TA underwent normal atrophy upon denervation. Moreover, upon overloading, plantaris muscle did not display enhanced hypertrophy compared to controls. Biochemical analysis indicated that the atrophy response of muscles was based on the

Multiple Sclerosis: associated cardiometabolic risks and impact of exercise therapy

OpenAIRE

Jacobs, Jasper

2016-01-01

Multiple sclerosis (MS) is characterized by complex heterogeneous symptoms, which often leads to a more sedentary lifestyle. This lifestyle increases the likelihood to develop secondary health problems, like cardiometabolic risk (CMR) profile. However, in other population these secondary health problems can be, partly, reversed by exercise therapy. We hypothesized that MS affects the CMR profile, but the outcome can be reversed following exercise therapy. Persons with MS and matched healthy c...

Laboratory diagnosis of multiple sclerosis

International Nuclear Information System (INIS)

Sand, T.; Stovner, L.J.; Rinck, P.A.; Nilsen, G.; Romslo, I.

1991-01-01

In 26 patients with multiple sclerosis 100% responded abnormally to magnetic resonance imaging of the brain. Lesions in the posterior fossa were observed in 18 patients. The auditory brain stem response was abnormal in 15 patients, and 22 had abnormal immunoglobulins in the cerebrospinal fluid. The correlation between abnormalities of the auditory brain stem response and the magnetic resonance images was greatest in a subgroup where the two investigations were performed within a ten day interval. Results from magnetic resonance imaging, evoked potentials and cerebrospinal fluid investigations were used to reclassify 13 of 15 patients with clinically ''possible'' or ''probable''multiple sclerosis to a higher level using Poser's criteria. Evoked potentials (the auditory brain stem response in particular) correlated best with clinical multiple sclerosis category. The authors recommend that the magnetic resonance imaging is established as a first-hand investigation in evaluation of multiple sclerosis. Evoked potentials and cerebrospinal fluid investigations may prove to be more specific, however, and these investigations should also be performed as a routine. 23 refs., 2 figs., 2 tabs

Exploring change in a group-based psychological intervention for multiple sclerosis patients.

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Borghi, Martina; Bonino, Silvia; Graziano, Federica; Calandri, Emanuela

2018-07-01

The study is focused on a group-based cognitive behavioral intervention aimed at promoting the quality of life and psychological well-being of multiple sclerosis patients. The study investigates how the group intervention promoted change among participants and fostered their adjustment to the illness. The intervention involved six groups of patients (a total of 41 patients) and included four consecutive sessions and a 6-month follow-up. To explore change, verbatim transcripts of the intervention sessions were analyzed using a mixed-methods content analysis with qualitative data combined with descriptive statistics. The categories of resistance and openness to change were used to describe the process of change. Resistance and openness to change coexisted during the intervention. Only in the first session did resistance prevail over openness to change; thereafter, openness to change gradually increased and stabilized over time, and openness to change was then always stronger than resistance. The study builds on previous research on the effectiveness of group-based psychological interventions for multiple sclerosis patients and gives methodological and clinical suggestions to health care professionals working with multiple sclerosis patients. Implications for rehabilitation The study suggests that a group-based cognitive behavioral intervention for multiple sclerosis patients focused on the promotion of identity redefinition, a sense of coherence and self-efficacy in dealing with multiple sclerosis fosters the process of change and may be effective in promoting patients' adjustment to their illness. Health care professionals leading group-based psychological interventions for multiple sclerosis patients should be aware that resistance and openness to change coexist in the process of change. The study suggests that the duration of the intervention is a crucial factor: a minimum of three sessions appears to be necessary for group participants to develop greater openness

Multiple Sclerosis

Science.gov (United States)

Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

Gait Characteristics in Adolescents With Multiple Sclerosis.

Science.gov (United States)

Kalron, Alon; Frid, Lior; Menascu, Shay

2017-03-01

Multiple sclerosis is a progressive autoimmune disease of the central nervous system. A presentation of multiple sclerosis before age18 years has traditionally been thought to be rare. However, during the past decade, more cases have been reported. We examined gait characteristics in 24 adolescents with multiple sclerosis (12 girls, 12 boys). Mean disease duration was 20.4 (S.D. = 24.9) months and mean age was 15.5 (S.D. = 1.1) years. The mean expanded disability status scale score was 1.7 (S.D. = 0.7) indicating minimal disability. Outcomes were compared with gait and the gait variability index value of healthy age-matched adolescents. Adolescents with multiple sclerosis walked slower with a wider base of support compared with age-matched healthy control subjects. Moreover, the gait variability index was lower in the multiple sclerosis group compared with the values in the healthy adolescents: 85.4 (S.D. = 8.1) versus 96.5 (S.D. = 7.4). We present gait parameters of adolescents with multiple sclerosis. From a clinical standpoint, our data could improve management of walking dysfunction in this relatively young population. Copyright © 2016 Elsevier Inc. All rights reserved.

Primary progressive multiple sclerosis in the Polish population

Directory of Open Access Journals (Sweden)

Waldemar Brola

2017-03-01

Full Text Available Objectives: The aim of the study was the epidemiological analysis and evaluation of selected clinical and sociodemographic factors in Polish patients with primary progressive multiple sclerosis. Methods: The study included patients from 7 provinces in central and eastern Poland registered in the Registry of Patients with Multiple Sclerosis on 31 December 2016. The incidence of various forms of the disease was compared, and clinical, demographic and social disparities between relapsing-remitting and primary progressive multiple sclerosis were analysed. Results: Of 3,199 registered patients, 2,188 persons (66.2% had the relapsing-remitting form of multiple sclerosis, 774 (24.2% had the secondary progressive type and 307 (9.6% suffered from primary progressive disease. The first symptoms of primary progressive multiple sclerosis appeared almost 10 years later than in patients with the relapsing-remitting type (39.2 ± 11.4 vs. 29.8 ± 9.8. The period from the first symptoms to diagnosis was more than twice as long in patients with primary progressive multiple sclerosis (5.8 ± 3.4 as in those with relapsing-remitting disease (2.4 ± 1.6. The average degree of disability in the Expanded Disability Status Scale was similar and amounted to 3.2 ± 2.1 for relapsing-remitting and 3.6 ± 2.4 for primary progressive multiple sclerosis. The relapsing-remitting form was observed more often in women (2.4:1, and the primary progressive form appeared with equal frequency in both sexes (1:1. Disease-modifying treatment was received by 34% of patients with relapsing-remitting and in only 1.9% of patients with primary progressive multiple sclerosis. Conclusions: The primary progressive form affects approximately 10% of Polish patients with multiple sclerosis. The first symptoms appear at about 40 years of age with equal frequency in both sexes, and its diagnosis takes more than twice as much time as in the case of relapsing-remitting multiple

Sestrin regulation of TORC1: Is Sestrin a leucine sensor?

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Lee, Jun Hee; Cho, Uhn-Soo; Karin, Michael (Michigan); (UCSD)

2016-06-07

Sestrins are highly conserved, stress-inducible proteins that inhibit target of rapamycin complex 1 (TORC1) signaling. After their transcriptional induction, both vertebrate and invertebrate Sestrins turn on the adenosine monophosphate (AMP)–activated protein kinase (AMPK), which activates the tuberous sclerosis complex (TSC), a key inhibitor of TORC1 activation. However, Sestrin overexpression, on occasion, can result in TORC1 inhibition even in AMPK-deficient cells. This effect has been attributed to Sestrin’s ability to bind the TORC1-regulating GATOR2 protein complex, which was postulated to control trafficking of TORC1 to lysosomes. How the binding of Sestrins to GATOR2 is regulated and how it contributes to TORC1 inhibition are unknown. New findings suggest that the amino acid leucine specifically disrupts the association of Sestrin2 with GATOR2, thus explaining how leucine and related amino acids stimulate TORC1 activity. We discuss whether and how these findings fit what has already been learned about Sestrin-mediated TORC1 inhibition from genetic studies conducted in fruit flies and mammals.

Predicting Falls in People with Multiple Sclerosis: Fall History Is as Accurate as More Complex Measures

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Michelle H. Cameron

2013-01-01

Full Text Available Background. Many people with MS fall, but the best method for identifying those at increased fall risk is not known. Objective. To compare how accurately fall history, questionnaires, and physical tests predict future falls and injurious falls in people with MS. Methods. 52 people with MS were asked if they had fallen in the past 2 months and the past year. Subjects were also assessed with the Activities-specific Balance Confidence, Falls Efficacy Scale-International, and Multiple Sclerosis Walking Scale-12 questionnaires, the Expanded Disability Status Scale, Timed 25-Foot Walk, and computerized dynamic posturography and recorded their falls daily for the following 6 months with calendars. The ability of baseline assessments to predict future falls was compared using receiver operator curves and logistic regression. Results. All tests individually provided similar fall prediction (area under the curve (AUC 0.60–0.75. A fall in the past year was the best predictor of falls (AUC 0.75, sensitivity 0.89, specificity 0.56 or injurious falls (AUC 0.69, sensitivity 0.96, specificity 0.41 in the following 6 months. Conclusion. Simply asking people with MS if they have fallen in the past year predicts future falls and injurious falls as well as more complex, expensive, or time-consuming approaches.

Association between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis; Asociacion de LES y esclerosis multiple: esclerosis lupoide.

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Medina, Yimy F; Martinez, Jose B; Fernandez, Andres R; Quintana, Gerardo; Restrepo, Jose Felix; Rondon, Federico; Gamarra, Antonio Iglesias

2010-07-01

Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoimmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.

The treatment of skin ulcers in patients with systemic sclerosis

OpenAIRE

M. Matucci- Cerinic; F. Braschi; A. Moggi Pignone; L. Amanzi; G. Fiori

2011-01-01

Systemic Sclerosis (Ssc) is a complex disease of the connective tissue, characterized by progressive thickening and fibrosis of the skin and the internal organs and by diffused damage of the microvascular system. The fibrosis ones of the skin associated to the characteristic vascular alterations lead to the genesis of ulcers, more or less extended, often multiple, peripheral localization, chronic course, painful, able to influence patient’s quality of life. Indeed, immunity reactivity, the th...

Multiple sclerosis - etiology and diagnostic potential.

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Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Multiple sclerosis - etiology and diagnostic potential

Directory of Open Access Journals (Sweden)

Joanna Kamińska

2017-06-01

Full Text Available Multiple sclerosis (MS is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS, secondary progressive multiple sclerosis (SPSM, primary progressive multiple sclerosis (PPMS, and progressive-relapsing multiple sclerosis (RPMS. Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald’s diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI, cerebrospinal fluid (CSF analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of differentdiagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Update on the Cytogenetics and Molecular Genetics of Chordoma

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Larizza Lidia

2005-02-01

Full Text Available Abstract Chordoma is a rare mesenchymal tumour of complex biology for which only histologic and immunohistochemical criteria have been defined, but no biomarkers predicting the clinical outcome and response to treatment have yet been recognised. We herein review the interdisciplinary information achieved by epidemiologists, neurosurgeons and basic scientists on chordoma, usually a sporadic tumour, which also includes a small fraction of familial cases. Main focus is on the current knowledge of the genetic alterations which might pinpoint candidate genes and molecular mechanisms shared by sporadic and familiar chordomas. Due to the scarcity of the investigated tumour specimens and the multiple chromosome abnormalities found in tumours with aberrant karyotypes, conventional cytogenetics and Fluorescence In Situ Hybridization failed to detect recurrent chordoma-specific chromosomal rearrangements. Genome-wide approaches such as Comparative Genomic Hybridization (CGH are yet at an initial stage of application and should be implemented using BAC arrays either genome-wide or targeting selected genomic regions, disclosed by Loss of Heterozygosity (LOH studies. An LOH region was shown by a systematic study on a consistent number of chordomas to encompass 1p36, a genomic interval where a candidate gene was suggested to reside. Despite the rarity of multiplex families with chordoma impaired linkage studies, a chordoma locus could be mapped to chromosome 7q33 by positive lod score in three independent families. The role in chordomagenesis of the Tuberous Sclerosis Complex (TSC genes has been proved, but the extent of involvement of TSC1 and TSC2 oncosuppressors in chordoma remains to be assessed. In spite of the scarce knowledge on the genetics and molecular biology of chordoma, recent initiation of clinical trials using molecular-targeted therapy, should validate new molecular targets and predict the efficacy of a given therapy. Comparative genetic and

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis.

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Goris, An; Pauwels, Ine; Gustavsen, Marte W; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D'Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G; Gourraud, Pierre-Antoine; Sawcer, Stephen J; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F

2015-03-01

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10(-16)). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10(-7)). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10(-37)). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10(-22)), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10(-6)). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

Science.gov (United States)

Pauwels, Ine; Gustavsen, Marte W.; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D.; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D’Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A.; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H.; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G.; Gourraud, Pierre-Antoine; Sawcer, Stephen J.; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F.

2015-01-01

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index—the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10−16). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10−7). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10−37). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10−22), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10−6). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such

Progression of regional grey matter atrophy in multiple sclerosis.

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Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-06-01

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple

Progression of regional grey matter atrophy in multiple sclerosis

Science.gov (United States)

Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-01-01

Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse

Emotional Disorders in People with Multiple Sclerosis

Science.gov (United States)

... Evidence-based Guideline for PATIENTS and their FAMILIES EMOTIONAL DISORDERS IN PEOPLE WITH MULTIPLE SCLEROSIS This fact sheet presents the current research on emotional disorders in multiple sclerosis (MS) and summarizes the ...

Hippocampal Sclerosis in Older Patients: Practical Examples and Guidance With a Focus on Cerebral Age-Related TDP-43 With Sclerosis.

Science.gov (United States)

Cykowski, Matthew D; Powell, Suzanne Z; Schulz, Paul E; Takei, Hidehiro; Rivera, Andreana L; Jackson, Robert E; Roman, Gustavo; Jicha, Gregory A; Nelson, Peter T

2017-08-01

- Autopsy studies of the older population (≥65 years of age), and particularly of the "oldest-old" (≥85 years of age), have identified a significant proportion (∼20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. - To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). - Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. - In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology.

Vitamin D Levels Predict Multiple Sclerosis Progression

Science.gov (United States)

... Research Matters NIH Research Matters February 3, 2014 Vitamin D Levels Predict Multiple Sclerosis Progression Among people ... sclerosis (MS), those with higher blood levels of vitamin D had better outcomes during 5 years of ...

Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis

Science.gov (United States)

Zambonin, Jessica L.; Zhao, Chao; Ohno, Nobuhiko; Campbell, Graham R.; Engeham, Sarah; Ziabreva, Iryna; Schwarz, Nadine; Lee, Sok Ee; Frischer, Josa M.; Turnbull, Doug M.; Trapp, Bruce D.; Lassmann, Hans; Franklin, Robin J. M.

2011-01-01

Mitochondrial content within axons increases following demyelination in the central nervous system, presumably as a response to the changes in energy needs of axons imposed by redistribution of sodium channels. Myelin sheaths can be restored in demyelinated axons and remyelination in some multiple sclerosis lesions is extensive, while in others it is incomplete or absent. The effects of remyelination on axonal mitochondrial content in multiple sclerosis, particularly whether remyelination completely reverses the mitochondrial changes that follow demyelination, are currently unknown. In this study, we analysed axonal mitochondria within demyelinated, remyelinated and myelinated axons in post-mortem tissue from patients with multiple sclerosis and controls, as well as in experimental models of demyelination and remyelination, in vivo and in vitro. Immunofluorescent labelling of mitochondria (porin, a voltage-dependent anion channel expressed on all mitochondria) and axons (neurofilament), and ultrastructural imaging showed that in both multiple sclerosis and experimental demyelination, mitochondrial content within remyelinated axons was significantly less than in acutely and chronically demyelinated axons but more numerous than in myelinated axons. The greater mitochondrial content within remyelinated, compared with myelinated, axons was due to an increase in density of porin elements whereas increase in size accounted for the change observed in demyelinated axons. The increase in mitochondrial content in remyelinated axons was associated with an increase in mitochondrial respiratory chain complex IV activity. In vitro studies showed a significant increase in the number of stationary mitochondria in remyelinated compared with myelinated and demyelinated axons. The number of mobile mitochondria in remyelinated axons did not significantly differ from myelinated axons, although significantly greater than in demyelinated axons. Our neuropathological data and findings in

Socket sclerosis--an obstacle for orthodontic space closure?

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Baumgaertel, Sebastian

2009-07-01

Socket sclerosis is a rare reaction to tooth extraction resulting in high-density bone in the center of the alveolar process, where, under normal circumstances, cancellous bone is to be expected. In an adult orthodontic patient, routine extractions of the mandibular first permanent bicuspids were performed, resulting in socket sclerosis and unsuccessful orthodontic space closure. Orthodontic mini-implants were inserted to augment anchorage and aid in space closure. In the presence of socket sclerosis, conventional orthodontic mechanics failed to close the extraction spaces. However, with absolute anchorage in place, space closure occurred at a nearly normal rate. After treatment, no signs of socket sclerosis were discernible on the periapical radiographs. Socket sclerosis can be an obstacle for orthodontic space closure if traditional mechanics are employed. However, mini-implant-reinforced anchorage can lead to successful space closure, resulting in complete resolution of the sclerotic sites.

Nuclear magnetic resonance relaxation in multiple sclerosis

DEFF Research Database (Denmark)

Larsson, H B; Barker, G J; MacKay, A

1998-01-01

OBJECTIVES: The theory of relaxation processes and their measurements are described. An overview is presented of the literature on relaxation time measurements in the normal and the developing brain, in experimental diseases in animals, and in patients with multiple sclerosis. RESULTS...... AND CONCLUSION: Relaxation time measurements provide insight into development of multiple sclerosis plaques, especially the occurrence of oedema, demyelination, and gliosis. There is also evidence that normal appearing white matter in patients with multiple sclerosis is affected. What is now needed are fast...

Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016.

Science.gov (United States)

García Merino, A; Ramón Ara Callizo, J; Fernández Fernández, O; Landete Pascual, L; Moral Torres, E; Rodríguez-Antigüedad Zarrantz, A

2017-03-01

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Increased cortical and deep grey matter sodium concentration is associated with physical and cognitive disability in relapse-onset multiple sclerosis

DEFF Research Database (Denmark)

Brownlee, WJ; Alves Da Mota, Patricia; Prados, Ferran

digit modalities test (SDMT) and tests of verbal and visual memory. Linear regression was used to compare differences in tissue TSC between groups. Multivariable linear regression was used to identify independent associations between TSC and disability with adjustment for age, sex, disease duration......=0.40) and visual memory (β=-0.06, 95%CI -0.11, -.0.02, R2=0.19). Conclusion: Sodium accumulation in cortical and deep grey matter may reflect underlying neurodegeneration that is relevant to the development of long-term disability and cognitive impairment in relapse-onset MS. 23Na-MRI may become a secondary...

Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk

DEFF Research Database (Denmark)

Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J

2018-01-01

Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18...... and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1......,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion...

The management of multiple sclerosis in children: a European view

DEFF Research Database (Denmark)

Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey

2010-01-01

in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce...... in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.......About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity...

Two-locus linkage analysis in multiple sclerosis (MS)

Energy Technology Data Exchange (ETDEWEB)

Tienari, P.J. (National Public Health Institute, Helsinki (Finland) Univ. of Helsinki (Finland)); Terwilliger, J.D.; Ott, J. (Columbia Univ., New York (United States)); Palo, J. (Univ. of Helsinki (Finland)); Peltonen, L. (National Public Health Institute, Helsinki (Finland))

1994-01-15

One of the major challenges in genetic linkage analyses is the study of complex diseases. The authors demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, they have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family member than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested. 41 refs., 6 tabs.

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Knudsen, L; Jensen, K

1991-01-01

In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Jensen, K

1990-01-01

An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Mads S. Bergholt

2017-12-01

Full Text Available Analyzing lipid composition and distribution within the brain is important to study white matter pathologies that present focal demyelination lesions, such as multiple sclerosis. Some lesions can endogenously re-form myelin sheaths. Therapies aim to enhance this repair process in order to reduce neurodegeneration and disability progression in patients. In this context, a lipidomic analysis providing both precise molecular classification and well-defined localization is crucial to detect changes in myelin lipid content. Here we develop a correlated heterospectral lipidomic (HSL approach based on coregistered Raman spectroscopy, desorption electrospray ionization mass spectrometry (DESI-MS, and immunofluorescence imaging. We employ HSL to study the structural and compositional lipid profile of demyelination and remyelination in an induced focal demyelination mouse model and in multiple sclerosis lesions from patients ex vivo. Pixelwise coregistration of Raman spectroscopy and DESI-MS imaging generated a heterospectral map used to interrelate biomolecular structure and composition of myelin. Multivariate regression analysis enabled Raman-based assessment of highly specific lipid subtypes in complex tissue for the first time. This method revealed the temporal dynamics of remyelination and provided the first indication that newly formed myelin has a different lipid composition compared to normal myelin. HSL enables detailed molecular myelin characterization that can substantially improve upon the current understanding of remyelination in multiple sclerosis and provides a strategy to assess remyelination treatments in animal models.

Recurrent myelinoclastic diffuse sclerosis: a case report of a child with Schilder's variant of multiple sclerosis

International Nuclear Information System (INIS)

Fitzgerald, M.J.; Coleman, L.T.

2000-01-01

Myelinoclastic diffuse sclerosis (MDS, Schilder's disease) is a rare CNS demyelinating disorder affecting mainly children and usually presenting as an intracranial mass lesion. We report the first case of recurrent intracranial MDS where the third episode of demyelination involved the cervical spinal cord. This may represent a subset of the disease, which should be considered as Schilder's variant (childhood form) of multiple sclerosis. (orig.)

Reproduction and the risk of multiple sclerosis

DEFF Research Database (Denmark)

Magyari, Melinda; Koch-Henriksen, Nils Iørgen; Pfleger, Claudia Christina

2013-01-01

The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men.......The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men....

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Jensen, K

1988-01-01

Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

Diagnosis and Management of Systemic Sclerosis: A Practical Approach.

Science.gov (United States)

Lee, Jason J; Pope, Janet E

2016-02-01

Systemic sclerosis is a devastating multisystem rheumatologic condition that is characterized by autoimmunity, tissue fibrosis, obliterative vasculopathy and inflammation. Clinical presentation and course of the condition vary greatly, which complicates both diagnosis and corresponding treatment. In this regard, recent advances in disease understanding, both clinically and biochemically, have led to newer classification criteria for systemic sclerosis that are more inclusive than ever before. Still, significant disease modifying therapies do not yet exist for most patients. Therefore, organ-based management strategies are employed and research has been directed within this paradigm focusing on either the most debilitating symptoms, such as Raynaud's phenomenon, digital ulcers and cutaneous sclerosis, or life-threatening organ involvement such as interstitial lung disease and pulmonary arterial hypertension. The current trends in systemic sclerosis diagnosis, evidence-based treatment recommendations and potential future directions in systemic sclerosis treatment are discussed.

Endoplasmic reticulum stress response as a potential therapeutic target in multiple sclerosis

OpenAIRE

Getts, Meghann Teague; Getts, Daniel R.; Kohm, Adam P.; Miller, Stephen D

2008-01-01

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Since current treatments are aimed at nonspecifically down-regulating inflammation and natural mechanisms of repair and remyelination within the CNS are inadequate for recovery of function, MS patients presently only have available treatments that delay symptom progression. The complex nature of this disease means that only multifaceted treatments hold the promise of a cure. Recent studies i...

Registers of multiple sclerosis in Denmark

DEFF Research Database (Denmark)

Koch-Henriksen, N; Magyari, M; Laursen, B

2015-01-01

between a number of different environmental exposures in the past and the subsequent risk of MS. Some of these studies have been able to exonerate suspected risk factors. The other register, the nationwide Danish Multiple Sclerosis Treatment Register, is a follow-up register for all patients who have......There are two nationwide population-based registers for multiple sclerosis (MS) in Denmark. The oldest register is The Danish Multiple Sclerosis Registry (DMSR), which is an epidemiological register for estimation of prevalence and incidence of MS and survival, and for identifying exposures earlier...... received disease-modifying treatments since 1996. It has, in particular, contributed to the knowledge of the role of antibodies against the biological drugs used for the treatment of MS....

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

Science.gov (United States)

Cantarel, Brandi L; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M; Mowry, Ellen M

2015-06-01

Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

Multiple sclerosis research

International Nuclear Information System (INIS)

Battaglia, M.A.

1990-01-01

This volume proceedings contains four contributions which are in INIS scope, dealing with MRI and SPECT in the diagnosis of multiple sclerosis and assessment of disease activity. (H.W.). refs.; figs.; tabs

[Current therapy of multiple sclerosis].

Science.gov (United States)

Antonio García Merino, J

2014-12-01

Since the introduction of interferon beta 1 b for the treatment of multiple sclerosis, there has been a progressive increase in the number of drugs available for this disease. Currently, 11 drugs have been approved in Spain, and their indications depend on specific clinical characteristics. The present article reviews these indications and also discusses other medications without official approval that have also been used in multiple sclerosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Neuraxial anesthesia in patients with multiple sclerosis - a systematic review

Directory of Open Access Journals (Sweden)

Helmar Bornemann-Cimenti

Full Text Available Abstract Background and objectives: Current guidelines for neuraxial analgesia in patients with multiple sclerosis are ambiguous and offer the clinician only a limited basis for decision making. This systematic review examines the number of cases in which multiple sclerosis has been exacerbated after central neuraxial analgesia in order to rationally evaluate the safety of these procedures. Methods: A systematic literature search with the keywords "anesthesia or analgesia" and "epidural, peridural, caudal, spinal, subarachnoid or intrathecal" in combination with "multiple sclerosis" was performed in the databases PubMed and Embase, looking for clinical data on the effect of central neuraxial analgesia on the course of multiple sclerosis. Results and conclusions: Over a period of 65 years, our search resulted in 37 reports with a total of 231 patients. In 10 patients multiple sclerosis was worsened and nine multiple sclerosis or neuromyelitis optica was first diagnosed in a timely context with central neuraxial analgesia. None of the cases showed a clear relation between cause and effect. Current clinical evidence does not support the theory that central neuraxial analgesia negatively affects the course of multiple sclerosis.

Multiple Sclerosis.

Science.gov (United States)

Plummer, Nancy; Michael, Nancy, Ed.

This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Knudsen, L; Jensen, K

1994-01-01

In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

Serum total antioxidant capacity in patients with multiple sclerosis

Directory of Open Access Journals (Sweden)

Almira Hadžović-Džuvo

2011-02-01

Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system (CNS. It is characterized by loss of myelin, the fatty tissue that surrounds and protects nerve fibres allowing them to conduct electrical impulses. Recent data indicate that oxidative stress (OS plays a major role in the pathogenesis of multiple sclerosis (MS. The aim of this study was to estimate level of serum total antioxidative capacity in patients with multiple sclerosis. Our cross-sectional study included 33 patients with MS and 24 age and sex matched control subjects. All our patients had a Poser criteria for definite diagnostic categories of multiple sclerosis. Serum total antioxidant capacity (TAC was measured by quantitative colorimetric determination, using Total antioxidant Capacity-QuantiCromAntioxidant Assay Kit (BioAssay systems, USA; DTAC-100. Mean serum TAC in multiple sclerosis group of patients was 119.2 mM Trolox equivalents and was significantly lower (p<0.001 compared to the control group of subjects (167.1 mM Trolox equivalents. Our results showed that oxidative stress plays an important role in pathogenesis of multiple sclerosis. This finding, also, suggests the importance of antioxidants in diet and therapy of MS patients.

Sit less and move more: perspectives of adults with multiple sclerosis.

Science.gov (United States)

Aminian, Saeideh; Ezeugwu, Victor E; Motl, Robert W; Manns, Patricia J

2017-12-20

Multiple sclerosis is a chronic neurological disease with the highest prevalence in Canada. Replacing sedentary behavior with light activities may be a feasible approach to manage multiple sclerosis symptoms. This study explored the perspectives of adults with multiple sclerosis about sedentary behavior, physical activity and ways to change behavior. Fifteen adults with multiple sclerosis (age 43 ± 13 years; mean ± standard deviation), recruited through the multiple sclerosis Clinic at the University of Alberta, Edmonton, Canada, participated in semi-structured interviews. Interview audios were transcribed verbatim and coded. NVivo software was used to facilitate the inductive process of thematic analysis. Balancing competing priorities between sitting and moving was the primary theme. Participants were aware of the benefits of physical activity to their overall health, and in the management of fatigue and muscle stiffness. Due to fatigue, they often chose sitting to get their energy back. Further, some barriers included perceived fear of losing balance or embarrassment while walking. Activity monitoring, accountability, educational and individualized programs were suggested strategies to motivate more movement. Adults with multiple sclerosis were open to the idea of replacing sitting with light activities. Motivational and educational programs are required to help them to change sedentary behavior to moving more. IMPLICATIONS FOR REHABILITATION One of the most challenging and common difficulties of multiple sclerosis is walking impairment that worsens because of multiple sclerosis progression, and is a common goal in the rehabilitation of people with multiple sclerosis. The deterioration in walking abilities is related to lower levels of physical activity and more sedentary behavior, such that adults with multiple sclerosis spend 8 to 10.5 h per day sitting. Replacing prolonged sedentary behavior with light physical activities, and incorporating education

Demyelination of subcortical nuclei in multiple sclerosis

Science.gov (United States)

Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

2016-02-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

Symptomatic Epstein-Barr virus infection and multiple sclerosis.

OpenAIRE

Martyn, C N; Cruddas, M; Compston, D A

1993-01-01

In a case-control study of 214 patients with multiple sclerosis, recall of infectious mononucleosis in subjects seropositive for Epstein-Barr viral capsid antigen was associated with a relative risk of 2.9 (95% CI 1.1 to 7.2). Those who reported having infectious mononucleosis before the age of 18 years had a relative risk of multiple sclerosis of 7.9 (95% CI 1.7 to 37.9). The pathogenesis of multiple sclerosis may involve an age-dependent host response to Epstein-Barr virus infection.

Neuroendocrine Immunoregulation in Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Nathalie Deckx

2013-01-01

Full Text Available Currently, it is generally accepted that multiple sclerosis (MS is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

Clinical Usefulness of Aripiprazole and Lamotrigine in Schizoaffective Presentation of Tuberous Sclerosis.

Science.gov (United States)

Lee, Seung-Yup; Min, Jung-Ah; Lee, In Goo; Kim, Jung Jin

2016-08-31

Tuberous sclerosis is not as rare as once thought and has high psychiatric comorbidities. However, bipolar or psychotic features associated with tuberous sclerosis have been rarely reported. This report first presents a tuberous sclerosis patient, resembling a schizoaffective disorder of bipolar type. A patient with known tuberous sclerosis displayed mood fluctuation and psychotic features. Her symptoms did not remit along with several psychiatric medications. After hospitalization, the patient responded well with lamotrigine and aripiprazole without exacerbation. As demonstrated in this case, tuberous sclerosis may also encompass bipolar affective or psychotic features. We would like to point out the necessity to consider bipolarity in evaluating and treating tuberous sclerosis.

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

Science.gov (United States)

Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

2017-03-01

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved

Demyelination of subcortical nuclei in multiple sclerosis

International Nuclear Information System (INIS)

Krutenkova, E; Aitmagambetova, G; Khodanovich, M; Yarnykh, V; Bowen, J; Gangadharan, B; Henson, L; Mayadev, A; Repovic, P; Qian, P

2016-01-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus. (paper)

Tomography patterns of lung disease in systemic sclerosis

Energy Technology Data Exchange (ETDEWEB)

Bastos, Andrea de Lima; Correa, Ricardo de Amorim; Ferreira, Gilda Aparecida, E-mail: andrealb@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina

2016-09-15

Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses. (author)

Tomography patterns of lung disease in systemic sclerosis

Directory of Open Access Journals (Sweden)

Andréa de Lima Bastos

Full Text Available Abstract Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed, Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses.

Tomography patterns of lung disease in systemic sclerosis

International Nuclear Information System (INIS)

Bastos, Andrea de Lima; Correa, Ricardo de Amorim; Ferreira, Gilda Aparecida

2016-01-01

Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses. (author)

Unusual renal angiomyolipoma in tuberous sclerosis

International Nuclear Information System (INIS)

Schwartz, A.M.

1980-01-01

A patient with tuberous sclerosis and a normal intravenous urogram 5 years previously presented with a large and palpable upper pole renal mass. Since patients with tuberous sclerosis have small bilateral hamartomas, a Wilms' tumor was suspected. In retrospect, inhomogeneous nephrograms should have alerted the radiologist to the multiplicity of other small lesions. Also, a partially lucent rim should have substantiated that the lesion was not a Wilms' tumor. (orig.) [de

Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease

Science.gov (United States)

Disanto, Giulio; Berlanga, Antonio J.; Handel, Adam E.; Para, Andrea E.; Burrell, Amy M.; Fries, Anastasia; Handunnetthi, Lahiru; De Luca, Gabriele C.; Morahan, Julia M.

2011-01-01

Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. Although the etiology and the pathogenesis of MS has been extensively investigated, no single pathway, reliable biomarker, diagnostic test, or specific treatment have yet been identified for all MS patients. One of the reasons behind this failure is likely to be the wide heterogeneity observed within the MS population. The clinical course of MS is highly variable and includes several subcategories and variants. Moreover, apart from the well-established association with the HLA-class II DRB1*15:01 allele, other genetic variants have been shown to vary significantly across different populations and individuals. Finally both pathological and immunological studies suggest that different pathways may be active in different MS patients. We conclude that these “MS subtypes” should still be considered as part of the same disease but hypothesize that spatiotemporal effects of genetic and environmental agents differentially influence MS course. These considerations are extremely relevant, as outcome prediction and personalised medicine represent the central aim of modern research. PMID:21197462

Comparing Effects of TCR and TSC on MHO Distance Protection Setting in 400 kV Algerian Transmission Line

Directory of Open Access Journals (Sweden)

Mohamed ZELLAGUI

2012-11-01

Full Text Available This paper presents a study on the performances of distance relays setting in 400 kV in Eastern Algerian transmission networks at Sonelgaz Group (Algerian company of Electrical and Gas compensated by shunt Flexible AC Transmission System (FACTS. The facts are used for controlling transmission voltage, power flow, reactive power, and damping of power system oscillations in high power transfer levels. The effects of SVC devices i.e. Thyristor Controlled Reactor (TCR and the Thyristor Switched Capacitors (TSC insertion, on the total impedance of a transmission line protected by MHO distance relay are investigated. The modified setting zones protections for three forward zones (Z1, Z2 and Z3 have been calculated in order to improve the performances of distance relay protection and prevent circuit breaker nuisance tripping.

Evaluation of thermal sprayed metallic coatings for use on the structures at Launch Complex 39

Science.gov (United States)

Welch, Peter J.

1990-01-01

The current status of the evaluation program is presented. The objective was to evaluate the applicability of Thermal Sprayed Coatings (TSC) to protect the structures in the high temperature acid environment produced by exhaust of the Solid Rocket Boosters during the launches of the Shuttle Transportation System. Only the relatively low cost aluminum TSC which provides some cathodic protection for steel appears to be a practical candidate for further investigation.

Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis.

Science.gov (United States)

Paquin, M-Ê; El Mendili, M M; Gros, C; Dupont, S M; Cohen-Adad, J; Pradat, P-F

2018-01-01

There is an emerging need for biomarkers to better categorize clinical phenotypes and predict progression in amyotrophic lateral sclerosis. This study aimed to quantify cervical spinal gray matter atrophy in amyotrophic lateral sclerosis and investigate its association with clinical disability at baseline and after 1 year. Twenty-nine patients with amyotrophic lateral sclerosis and 22 healthy controls were scanned with 3T MR imaging. Standard functional scale was recorded at the time of MR imaging and after 1 year. MR imaging data were processed automatically to measure the spinal cord, gray matter, and white matter cross-sectional areas. A statistical analysis assessed the difference in cross-sectional areas between patients with amyotrophic lateral sclerosis and controls, correlations between spinal cord and gray matter atrophy to clinical disability at baseline and at 1 year, and prediction of clinical disability at 1 year. Gray matter atrophy was more sensitive to discriminate patients with amyotrophic lateral sclerosis from controls ( P = .004) compared with spinal cord atrophy ( P = .02). Gray matter and spinal cord cross-sectional areas showed good correlations with clinical scores at baseline ( R = 0.56 for gray matter and R = 0.55 for spinal cord; P amyotrophic lateral sclerosis. © 2018 by American Journal of Neuroradiology.

The Danish Multiple Sclerosis Treatment Register

Directory of Open Access Journals (Sweden)

Magyari M

2016-10-01

Full Text Available Melinda Magyari,1,3 Nils Koch-Henriksen,1,2 Per Soelberg Sørensen3 1Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, Copenhagen, 2Department of Clinical Epidemiology, Clinical Institute, University of Aarhus, Aarhus, 3Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim of the database: The Danish Multiple Sclerosis Treatment Register (DMSTR serves as a clinical quality register, enabling the health authorities to monitor the quality of the disease-modifying treatment, and it is an important data source for epidemiological research. Study population: The DMSTR includes all patients with multiple sclerosis who had been treated with disease-modifying drugs since 1996. At present, more than 8,400 patients have been registered in this database. Data are continuously entered online into a central database from all sites in Denmark at start and at regular visits. Main variables: Include age, sex, onset year and year of the diagnosis, basic clinical information, and information about treatment, side effects, and relapses. Descriptive data: Notification is done at treatment start, and thereafter at every scheduled clinical visit 3 months after treatment start, and thereafter every 6 months. The longitudinally collected information about the disease activity and side effects made it possible to investigate the clinical efficacy and adverse events of different disease-modifying therapies. Conclusion: The database contributed to a certain harmonization of treatment procedures in Denmark and will continue to be a major factor in terms of quality in clinical praxis, research and monitoring of adverse events, and plays an important role in research. Keywords: multiple sclerosis, epidemiology, immunomodulatory treatment, neutralizing antibodies, observational studies, registry research, disease modifying therapy

Risks of multiple sclerosis in relatives of patients in Flanders, Belgium

NARCIS (Netherlands)

Carton, H; Vlietinck, R; Debruyne, J; DeKeyser, J; DHooghe, MB; Loos, R; Medaer, R; Truyen, L; Yee, IML; Sadovnick, AD

Objectives - To calculate age adjusted risks for multiple sclerosis in relatives of Flemish patients with multiple sclerosis. Methods - Lifetime risks were calculated using the maximum likelihood approach. Results - Vital information was obtained on 674 probands with multiple sclerosis in Flanders

Retinal layer segmentation in multiple sclerosis

DEFF Research Database (Denmark)

Petzold, Axel; Balcer, Laura J; Calabresi, Peter A

2017-01-01

BACKGROUND: Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal...... layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT. METHODS: In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people...... with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified...

Selected methods of rehabilitation in systemic sclerosis

Directory of Open Access Journals (Sweden)

Agnieszka Gerkowicz

2017-09-01

Full Text Available Systemic sclerosis is a chronic connective tissue disease characterized by microvascular abnormalities, immune disturbances and progressive fibrosis of the skin and internal organs. Skin involvement may result in contractures, leading to marked loss of hand mobility, adversely affecting the performance of daily activities and decreasing the quality of life. Face involvement not only causes functional loss, but also lowers the self-esteem of patients. Increasing attention has recently been focused on the need to rehabilitate patients with systemic sclerosis in order to prevent the development of joint contractures and loss of mobility. The study presents a review of the current literature on rehabilitation possibilities in patients with systemic sclerosis, with a special focus on physiotherapy methods.

Systematic approach to understanding the pathogenesis of systemic sclerosis.

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Zuo, Xiaoxia; Zhang, Lihua; Luo, Hui; Li, Yisha; Zhu, Honglin

2017-10-01

Systemic sclerosis (SSc) is a complex heterogeneous autoimmune disease. Progressive organ fibrosis is a major contributor to SSc mortality. Despite extensive efforts, the underlying mechanism of SSc remains unclear. Efforts to understand the pathogenesis of SSc have included genomics, epigenetics, transcriptomic, proteomic and metabolomic studies in the last decade. This review focuses on recent studies in SSc research based on multi-omics. The combination of these technologies can help us understand the pathogenesis of SSc. This review aims to provide important information for disease identification, therapeutic targets and potential biomarkers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Adie’s Tonic Pupil in Systemic Sclerosis: A Rare Association

Directory of Open Access Journals (Sweden)

Anusha Venkataraman

2015-01-01

Full Text Available We report a rare association of Adie’s tonic pupil in a patient with systemic sclerosis who was otherwise systemically stable. This paper is an effort to unravel whether the tonic pupil and systemic sclerosis are an association by chance (which may be the case or systemic sclerosis is the source of the tonic pupil.

Multiple sclerosis and other white matter diseases

International Nuclear Information System (INIS)

Zimmerman, R.A.

1991-01-01

The diagnosis of multiple sclerosis (MS) by computerized tomography and nuclear magnetic resonance are shown, including the examination of cerebral spinal fluid. Lymphocytic, foamy histiocytic perivascular cuffing, degenerated oligodendrocytes, and microglia proliferation with relative axonal sparing are presented. In the latter stage of the chronic MS plaque there is sclerosis with microcystic formation with complete demyelination and organization. (author)

Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

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Mackenzie, Catherine; Green, Jan

2009-01-01

Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

The natural history of primary progressive multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus; Kingwell, Elaine; Rieckmann, Peter; Tremlett, Helen

2009-01-01

Background: Primary progressive multiple sclerosis (PPMS) carries the worst prognosis of the multiple sclerosis (MS) subtypes and is currently untreatable. A previous analysis of the British Columbia MS database challenged the view that disability progression is rapid in PPMS, but identified few

Examining the Factor Structure and Psychometric Properties of the Quality of Life Scale among People with Multiple Sclerosis

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Fitzgerald, Shawn M.; Li, Jian; Rumrill, Phillip D., Jr.; Bishop, Malachy; Merchant, William R.

2015-01-01

Rehabilitation counseling researchers seeking to more fully understand the phenomenon of psychosocial adaptation to disability are devoting increased attention to the impact of disability on quality of life (QOL). This impact has been of particular interest among multiple sclerosis (MS) researchers. The complex etiology, unpredictable nature, and…

The Practice of Sport in Multiple Sclerosis: Update.

Science.gov (United States)

Donze, Cecile; Massot, Caroline; Hautecoeur, Patrick; Cattoir-Vue, Helene; Guyot, Marc-Alexandre

The practice of sport by multiple sclerosis patients has long been controversial. Recent studies, however, show that both sport and physical activity are essential for these patients. Indeed, they help to cope with the effects of multiple sclerosis, such as fatigue, reduced endurance, loss of muscle mass, and reduction of muscle strength. The beneficial effects of physical activity on these patients have been underlined in several studies, whereas those of practicing sport have been the subject of fewer evaluations and assessments. The aim of this update is to report on the effects of sport on multiple sclerosis patients. The benefits of sport have been demonstrated in several studies. It helps multiple sclerosis patients to increase their balance, resistance to fatigue, mobility and quality of life. Several biases in these studies do not enable us to recommend the practice of some of these sports on a routine basis.

Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis.

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Panas, M; Karadima, G; Kalfakis, N; Psarrou, O; Floroskoufi, P; Kladi, A; Petersen, M B; Vassilopoulos, D

2000-12-01

The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n = 72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis.

Brain magnetic resonance imaging findings in patients with systemic sclerosis.

Science.gov (United States)

Mohamed, Reem H A; Nassef, Amr A

2010-02-01

Systemic sclerosis is a multisystem disease where functional and structural abnormalities of small blood vessels prevail. Recently, transient ischemic attacks, ischemic stroke, and hemorrhages have been reported as primary consequence of vascular central nervous system affection in systemic sclerosis. Magnetic resonance imaging (MRI) is considered to be the most sensitive diagnostic technique for detecting symptomatic and asymptomatic lesions in the brain in cases of multifocal diseases. Evaluate brain changes in patients with systemic sclerosis using MRI. Thirty female patients with systemic sclerosis aged 27-61 years, with disease duration of 1-9 years and with no history of other systemic disease or cerebrovascular accidents, were enrolled. An age-matched female control group of 30 clinically normal subjects, underwent brain MR examination. Central nervous system involvement in the form of white matter hyperintense foci of variable sizes were found in significantly abundant forms in systemic sclerosis patients on MR evaluation than in the age-related control group, signifying a form of central nervous system vasculopathy. Such foci showed no definite correlation with disease duration, yet they showed significant correlation to severity of peripheral vascular disease, headaches, fainting attacks and depression in the group under study. Asymptomatic as well as symptomatic central nervous system ischemic vasculopathy is not uncommon in systemic sclerosis patients and MRI is considered a sensitive noninvasive screening tool for early detection of CNS involvement in patients with systemic sclerosis.

[Effects of nutritional status on the multiple sclerosis disease: systematic review].

Science.gov (United States)

Ródenas Esteve, Irene; Wanden-Berghe, Carmina; Sanz-Valero, Javier

2018-01-19

To review the available scientific literature about the effects of nutritional status on the multiple sclerosis disease. A systematic review of the scientific literature in the Medline (PubMed), Scopus, Cochrane Library and Web of Science databases through November 2016. Search equation: ("Multiple Sclerosis"[Mesh] OR "Multiple Sclerosis"[Title/Abstract] OR "Disseminated Sclerosis"[Title/Abstract] OR "Multiple Sclerosis Acute Fulminating"[Title/Abstract]) AND ("Nutritional Status"[Mesh] OR "Nutritional Status"[Title/Abstract] OR "Nutrition Status"[Title/Abstract]). The quality of the selected articles was discussed using the STROBE questionnaire. The search was completed through experts inquiry and additional review of the bibliographic references included in the selected papers. The concordance between authors (Kappa index) had to be higher than 80% for inclusion in this review. Of the 160 references recovered, after applying inclusion and exclusion criteria, 29 articles were selected for review. Concordance between evaluators was 100.00%. The most studies established vitamin D levels. Others focused their research on finding out which nutrient deficits might be related to the multiple sclerosis development. Vitamin D may influence multiple sclerosis improvement. Sunlight and physical activity would be important factors, with nutritional status, in the course of this disease. It is necessary to produce new specific works that will delve into the subject to find out more about the relationship between nutritional status and multiple sclerosis.

Atypical findings on computed tomography in tuberous sclerosis

International Nuclear Information System (INIS)

Glass, R.B.J.; Mendelsohn, D.B.; Hertzanu, Y.

1984-01-01

In 3 patients with tuberous sclerosis computed tomography showed numerous low-density areas suggestive of brain demyelination. In addition, solitary small subependymal calcifications were noted. These features in an infant or child with unexplained seizures should alert one to the diagnosis of tuberous sclerosis

38 CFR 3.318 - Presumptive service connection for amyotrophic lateral sclerosis.

Science.gov (United States)

2010-07-01

... connection for amyotrophic lateral sclerosis. 3.318 Section 3.318 Pensions, Bonuses, and Veterans' Relief... sclerosis. (a) Except as provided in paragraph (b) of this section, the development of amyotrophic lateral... under this section: (1) If there is affirmative evidence that amyotrophic lateral sclerosis was not...

Evolving concepts in the treatment of relapsing multiple sclerosis

DEFF Research Database (Denmark)

Comi, Giancarlo; Radaelli, Marta; Soelberg Sørensen, Per

2017-01-01

In the past 20 years the treatment scenario of multiple sclerosis has radically changed. The increasing availability of effective disease-modifying therapies has shifted the aim of therapeutic interventions from a reduction in relapses and disability accrual, to the absence of any sign of clinical...... or MRI activity. The choice for therapy is increasingly complex and should be driven by an appropriate knowledge of the mechanisms of action of the different drugs and of their risk-benefit profile. Because the relapsing phase of the disease is characterised by inflammation, treatment should be started...... as early as possible and aim to re-establish the normal complex interactions in the immune system. Before starting a treatment, neurologists should carefully consider the state of the disease, its prognostic factors and comorbidities, the patient's response to previous treatments, and whether the patient...

SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis.

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Orlacchio, Antonio; Babalini, Carla; Borreca, Antonella; Patrono, Clarice; Massa, Roberto; Basaran, Sarenur; Munhoz, Renato P; Rogaeva, Ekaterina A; St George-Hyslop, Peter H; Bernardi, Giorgio; Kawarai, Toshitaka

2010-02-01

The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria. The exclusion criterion was a diagnosis of hereditary spastic paraplegia with thin corpus callosum in line with an established protocol. Additional pathological and genetic evaluations were also performed. Surprisingly, 12 sequence alterations in the spatacsin gene (one of which is novel, IVS30 + 1 G > A) were identified in 10 unrelated pedigrees with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival. The countries of origin of these families were Italy, Brazil, Canada, Japan and Turkey. The variants seemed to be pathogenic since they co-segregated with the disease in all pedigrees, were absent in controls and were associated with amyotrophic lateral sclerosis neuropathology in one member of one of these families for whom central nervous system tissue was available. Our study indicates that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized, including autosomal recessive juvenile amyotrophic lateral sclerosis.

Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis.

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Iparraguirre, Leire; Muñoz-Culla, Maider; Prada-Luengo, Iñigo; Castillo-Triviño, Tamara; Olascoaga, Javier; Otaegui, David

2017-09-15

Multiple sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g. microRNAs). Indeed, some of these have been suggested as biomarkers for multiple sclerosis even though few biomarkers have reached the clinical practice. Recently, a novel family of non-coding RNAs, circular RNAs, has emerged as a new player in the complex network of gene-expression regulation. MicroRNA regulation function through a 'sponge system' and a RNA splicing regulation function have been proposed for the circular RNAs. This regulating role together with their high stability in biofluids makes them seemingly good candidates as biomarkers. Given the dysregulation of both protein-coding and non-coding transcriptome that have been reported in multiple sclerosis patients, we hypothesised that circular RNA expression may also be altered. Therefore, we carried out expression profiling of 13.617 circular RNAs in peripheral blood leucocytes from multiple sclerosis patients and healthy controls finding 406 differentially expressed (P-value  1.5) and demonstrate after validation that, circ_0005402 and circ_0035560 are underexpressed in multiple sclerosis patients and could be used as biomarkers of the disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Metaphyseal sclerosis in patients with chronic renal failure

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Young, W.; Sevcik, M.; Tallroth, K. (Michigan Univ., Ann Arbor (USA). Dept. of Radiology)

1991-04-01

We reviewed radiographs of the hand and wrists of 33 patients with immature skeletons and chronic renal disease. Various radiographic manifestations of renal osteodystrophy were seen, including osteopenia in 23 patients (70%), subperiosteal resorption in 20 (61%), distal tuft resorption in 14 (42%), sclerosis of vertebral bodies in 2 (6%), and soft-tissue calcification in 1 (3%). We also noted that 13 patients (39%) exhibited metaphyseal sclerosis adjacent to the growth plates. Five of these 13 showed persistent sclerosis years after the growth plates had fused. None of the patients showed other radiographic changes of rickets, and there was no correlation between the serum calcium, phosphorus, or aluminum levels and the presence of metaphyseal sclerosis. Neiter was there any association with the underlying cause of renal failure, method of treatment, presence of a transplant, or type of dialysis. We view this finding as another manifestation of renal osteodystrophy. The importance of distinguishing it from other sclerotic lesions is discussed. (orig.).

Metaphyseal sclerosis in patients with chronic renal failure

International Nuclear Information System (INIS)

Young, W.; Sevcik, M.; Tallroth, K.

1991-01-01

We reviewed radiographs of the hand and wrists of 33 patients with immature skeletons and chronic renal disease. Various radiographic manifestations of renal osteodystrophy were seen, including osteopenia in 23 patients (70%), subperiosteal resorption in 20 (61%), distal tuft resorption in 14 (42%), sclerosis of vertebral bodies in 2 (6%), and soft-tissue calcification in 1 (3%). We also noted that 13 patients (39%) exhibited metaphyseal sclerosis adjacent to the growth plates. Five of these 13 showed persistent sclerosis years after the growth plates had fused. None of the patients showed other radiographic changes of rickets, and there was no correlation between the serum calcium, phosphorus, or aluminum levels and the presence of metaphyseal sclerosis. Neiter was there any association with the underlying cause of renal failure, method of treatment, presence of a transplant, or type of dialysis. We view this finding as another manifestation of renal osteodystrophy. The importance of distinguishing it from other sclerotic lesions is discussed. (orig.)

The risk of fracture in incident multiple sclerosis patients

DEFF Research Database (Denmark)

Bazelier, Marloes T; Bentzen, Joan; Vestergaard, Peter

2012-01-01

Patients with multiple sclerosis (MS) may be at increased risk of fractures owing to osteoporosis and falling.......Patients with multiple sclerosis (MS) may be at increased risk of fractures owing to osteoporosis and falling....

Characteristics and correlates of coping with multiple sclerosis: a systematic review.

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Keramat Kar, Maryam; Whitehead, Lisa; Smith, Catherine M

2017-10-10

The purpose of this systematic review was to examine coping strategies that people with multiple sclerosis use, and to identify factors that influence their coping pattern. This systematic review followed the Joanna Briggs Institute guidelines for synthesizing descriptive quantitative research. The following databases were searched from the inception of databases until December 2016: Ovid (Medline, Embase, CINAHL, and PsycINFO), Science Direct, Web of Science, and Scopus. Manual search was also conducted from the reference lists of retrieved articles. Findings related to the patterns of coping with multiple sclerosis and factors influencing coping with multiple sclerosis were extracted and synthesized. The search of the database yielded 455 articles. After excluding duplicates (n = 341) and studies that did not meet the inclusion criteria (n = 27), 71 studies were included in the full-text review. Following the full-text, a further 21 studies were excluded. Quality appraisal of 50 studies was completed, and 38 studies were included in the review. Synthesis of findings indicated that people with multiple sclerosis use emotional and avoidance coping strategies more than other types of coping, particularly in the early stages of the disease. In comparison to the general population, people with multiple sclerosis were less likely to use active coping strategies and used more avoidance and emotional coping strategies. The pattern of coping with multiple sclerosis was associated with individual, clinical and psychological factors including gender, educational level, clinical course, mood and mental status, attitude, personality traits, and religious beliefs. The findings of this review suggest that considering individual or disease-related factors could help healthcare professionals in identifying those less likely to adapt to multiple sclerosis. This information could also be used to provide client-centered rehabilitation for people living with multiple

The risk of multiple sclerosis in bereaved parents

DEFF Research Database (Denmark)

Li, J; Johansen, C; Brønnum-Hansen, Henrik

2004-01-01

Previous studies have suggested that psychological stress may play a role in the risk of multiple sclerosis (MS), but the evidence is very limited.......Previous studies have suggested that psychological stress may play a role in the risk of multiple sclerosis (MS), but the evidence is very limited....

Incidence of multiple sclerosis in Denmark 1948-1982

DEFF Research Database (Denmark)

Koch-Henriksen, Nils; Brønnum-Hansen, Henrik; Hyllested, K

1992-01-01

The incidence rates of multiple sclerosis (MS) in Denmark were estimated as a result of a continuous nationwide epidemiological survey since 1948 by the Danish Multiple Sclerosis Registry (DMSR). Among cases notified to the DMSR, 6,478 met the diagnostic criteria and had onset of MS from 1948...

A proposal of criteria for the classification of systemic sclerosis.

Science.gov (United States)

Nadashkevich, Oleg; Davis, Paul; Fritzler, Marvin J

2004-11-01

Sensitive and specific criteria for the classification of systemic sclerosis are required by clinicians and investigators to achieve higher quality clinical studies and approaches to therapy. A clinical study of systemic sclerosis patients in Europe and Canada led to a set of criteria that achieve high sensitivity and specificity. Both clinical and laboratory investigations of patients with systemic sclerosis, related conditions and diseases with clinical features that can be mistaken as part of the systemic sclerosis spectrum were undertaken. Laboratory investigations included the detection of autoantibodies to centromere proteins, Scl-70 (topoisomerase I), and fibrillarin (U3-RNP). Based on the investigation of 269 systemic sclerosis patients and 720 patients presenting with related and confounding conditions, the following set of criteria for the classification of systemic sclerosis was proposed: 1) autoantibodies to: centromere proteins, Scl-70 (topo I), fibrillarin; 2) bibasilar pulmonary fibrosis; 3) contractures of the digital joints or prayer sign; 4) dermal thickening proximal to the wrists; 5) calcinosis cutis; 6) Raynaud's phenomenon; 7) esophageal distal hypomotility or reflux-esophagitis; 8) sclerodactyly or non-pitting digital edema; 9) teleangiectasias. The classification of definite SSc requires at least three of the above criteria. Criteria for the classification of systemic sclerosis have been proposed. Preliminary testing has defined the sensitivity and specificity of these criteria as high as 99% and 100%, respectively. Testing and validation of the proposed criteria by other clinical centers is required.

Multiple Sclerosis, Personal Stories | NIH MedlinePlus the Magazine

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... of this page please turn Javascript on. Feature: Multiple Sclerosis Personal Stories: Nicole Lemelle, Iris Young, Michael Anthony, ... something quite different for a person living with multiple sclerosis, such as his girlfriend's brother, Chuy. The more ...

Trigeminal root entry zone involvement in neuromyelitis optica and multiple sclerosis.

Science.gov (United States)

Sugiyama, Atsuhiko; Mori, Masahiro; Masuda, Hiroki; Uchida, Tomohiko; Muto, Mayumi; Uzawa, Akiyuki; Ito, Shoichi; Kuwabara, Satoshi

2015-08-15

Trigeminal root entry zone abnormality on brain magnetic resonance imaging has been frequently reported in multiple sclerosis patients, but it has not been investigated in neuromyelitis optica patients. Brain magnetic resonance imaging of 128 consecutive multiple sclerosis patients and 46 neuromyelitis optica patients was evaluated. Trigeminal root entry zone abnormality was present in 11 (8.6%) of the multiple sclerosis patients and two (4.3%) of the neuromyelitis optica patients. The pontine trigeminal root entry zone may be involved in both multiple sclerosis and neuromyelitis optica. Copyright © 2015 Elsevier B.V. All rights reserved.

MR spectroscopy of cervical spinal cord in patients with multiple sclerosis

International Nuclear Information System (INIS)

Kendi, Ayse Tuba Karaguelle; Kendi, Mustafa; Tan, Funda Uysal; Tellioglu, Serdar; Huvaj, Sinef

2004-01-01

MR spectroscopy (MRS) of the brain in patients with multiple sclerosis has been well studied. However, in vivo MRS of the spinal cord in patients with MR spectroscopy has not been reported to our knowledge. We performed MRS of normal-appearing cervical spinal cords in multiple sclerosis patients and in healthy controls. N-acetyl aspartate was shown to be reduced within the cervical spinal cord of multiple sclerosis patients when compared with healthy controls. This finding supports axonal loss and damage within even normal-appearing spinal cords of multiple sclerosis patients. (orig.)

Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis.

Science.gov (United States)

Calvo-Barreiro, Laura; Eixarch, Herena; Montalban, Xavier; Espejo, Carmen

2018-02-01

The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Increasing occurrence of multiple sclerosis in women correlates to hygiene level

Directory of Open Access Journals (Sweden)

Wojciech Cendrowski

2014-12-01

Full Text Available Introduction: The increasing incidence of multiple sclerosis, particularly among women in Europe and North America, has a multifactorial aetiology. Method: The aim of the current study was to ascertain the relation between the hygiene level and occurrence of multiple sclerosis in women in Poland. The study was based on a large cohort of 14,200 multiple sclerosis individuals (male – 6,106, female – 8,094 who died in the years 1981–2010 in Poland. The female to male ratio (the F:M ratio in the multiple sclerosis group was calculated using the number of deaths per year. The rate of late mortality in infants (LMI per 1,000 live births yearly was used as a marker of the hygiene level. A correlation analysis was carried out between the rate of LMI and the F:M ratio in the multiple sclerosis cohort in the years 1981–2010. Demographic data were obtained from the Central Statistical Office in Warsaw. Results: The F:M ratio in the multiple sclerosis group evidently increased (range 1.08–1.79 in the years 1981–2010, showing increasing occurrence of multiple sclerosis in women (p < 0.0001. A significant, strong and inverse correlation was found between the marker of the hygiene level (LMI rate and the F:M ratio in the multiple sclerosis group over three decades: linear correlation coefficient by Pearson: r = –0.693, p < 0.0001. By contrast with this result, no correlation was established between the hygiene level marker and proportion of women to men in the general population on account of extremely low variance of the F:M ratio (0.000025. Conclusion: The improvement of the hygiene level showed association with the increasing occurrence of multiple sclerosis in women in the years 1981–2010. The higher the hygiene level was, the greater the occurrence of female multiple sclerosis in Poland.

Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

Science.gov (United States)

Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

2016-04-01

Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic

Cultivating the Multiple Sclerosis Workforce of the Future.

Science.gov (United States)

DeLuca, Gabriele C; Buckle, Guy; Cortese, Irene; Graves, Jennifer S; Halper, June; Newsome, Scott D; Sicotte, Nancy; Ford, Corey C

2017-01-01

Multiple sclerosis (MS) is a complex neurologic disorder that affects people with ever-changing needs. The MS health-care field has entered an era of exponential knowledge growth in which better understanding of the immunologic dysregulation of the disease has translated into an expanding array of treatment options. It is estimated that, if it has not already, within the next decade the demands of a growing MS patient population will outstrip the number of professionals dedicated to the management of this chronic, lifelong disease. Therefore, there is a pressing need to attract and retain clinicians in this dynamic field. In response to this need, the Foundation of the Consortium of Multiple Sclerosis Centers organized a 2-day colloquium, a Mentorship Forum, on January 23-24, 2015, bringing together talented internal medicine and neurology trainees from across North America with an interest in MS and neuroimmunology. This article highlights the rationale for the MS Mentorship Forum, its structure and content, and its outcomes. We believe that the stage has been set to interest young, promising clinicians in learning more about MS and to encourage them to consider a career in this field. In so doing, we hope to contribute to the development of the next generation of MS experts to make a palpable difference in the lives of those affected by MS.

Non-invasive examination of multiple sclerosis patients

International Nuclear Information System (INIS)

Weerd, A.W. de.

1981-01-01

Multiple sclerosis is characterized by a wide range of symptoms and, in many cases, by a highly erratic course. As a result diagnosis is often a problem. Two non-invasive examinations, Computer Tomography (CT scan) and the Evoked Response test (ER), are the subjects of this study which, according to available literature, both can play a role in the establishment of the diagnosis of multiple sclerosis. Clinical trials have been performed and both methods demonstrated abnormalities of the central nervous system which were not suspected on clinical grounds; as a result both methods of examination can contribute to the early establishment of the diagnosis of multiple sclerosis. In addition the diagnosis can be determined with greater certainty when the findings of the CT-scan and the evoked response test are taken into consideration. (Auth.)

Spinal-cord swelling in acute multiple sclerosis

International Nuclear Information System (INIS)

Kikuchi, Seiji; Tashiro, Kunio; Naganuma, Mutsuo; Hida, Kazutoshi; Iwasaki, Yoshinobu; Abe, Hiroshi; Miyasaka, Kazuo

1986-01-01

Despite the frequent involvement of the spinal cord by multiple sclerosis, reports concerning neuroradiological findings regarding these lesions have been limited; most of them have demonstrated a normal or small spinal cord. Two cases of acute paraparesis showed evidence of spinal-cord swelling on myelography and CT myelography, initially suggesting the diagnosis of an intramedullary tumor. Spinal-cord swelling was demonstrated more clearly on CT myelography than on conventional myelography. The diagnosis of multiple sclerosis was made with the aid of the CSF findings, the clinical course, and the contracting-cord sign. The ''contracting-cord sign'' means the diminution of the spinal-cord diameter in the chronic stage. Since acute multiple sclerosis may produce spinal-cord swelling simulating a tumor, careful investigations are necessary to avoid unwarranted surgical interventions. (author)

76 FR 78823 - Schedule for Rating Disabilities; Evaluation of Amyotrophic Lateral Sclerosis

Science.gov (United States)

2011-12-20

...; Evaluation of Amyotrophic Lateral Sclerosis AGENCY: Department of Veterans Affairs. ACTION: Final rule... revising the disability evaluation criterion provided for amyotrophic lateral sclerosis (ALS) to provide an...) a proposed rule that would revise the evaluation criterion for amyotrophic lateral sclerosis (ALS...

Vision and vision-related outcome measures in multiple sclerosis

Science.gov (United States)

Balcer, Laura J.; Miller, David H.; Reingold, Stephen C.

2015-01-01

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis. PMID:25433914

Balo's concentric sclerosis; value of magnetic resonance imaging in diagnosis

International Nuclear Information System (INIS)

Singh, S.; Kuruvilla, A.; Korah, I.P.; Alexander, M.

1999-01-01

We report two cases of Balo's concentric sclerosis that demonstrate the typical magnetic resonance imaging (MRI) findings of concentric rings of demyelination involving the superficial and deep white matter and sparing the cortex. In both cases biopsy was not performed as MRI findings and multi-mode evoked potential studies were consistent with demyelinating illness. The theories regarding the pathogenesis of this peculiar appearance are briefly reviewed. Balo's concentric sclerosis is a very rare type of demyelinating disease characterized pathologically by large alternating lamellae of demyelinated and myelinated white matter arranged in a concentric pattern. This progressive disease is more often found in young male adults and is more common in the Philippines. Balo's concentric sclerosis is considered an unusual variant of multiple sclerosis (MS); however, some authors believe it to be a different entity. Although the pathogenesis of the concentric sclerosis is debated, the cause of demyelination is generally presumed to be the same as that of multiple sclerosis. There is striking resemblance between the magnetic resonance (MR) appearance and the histopathological features of MS. Not all cases may show a typical MR appearance. Prior to MR imaging, most of them were diagnosed at post-mortem. To our knowledge, few cases have been diagnosed by MR imaging in life. Copyright (1999) Blackwell Science Pty Ltd

Acute form of multiple sclerosis in a child simulation encephalitis

International Nuclear Information System (INIS)

Niagolova, S.; Karapasheva, V.; Nikolova, M.

2007-01-01

Multiple sclerosis (MS) is considered the most common demyelinating process involving the CNS. Although usually considered an adult disease multiple sclerosis can begin to manifest during childhood. The clinical presentation of the disease in early childhood can range from paraesthesias to dramatic presentations, suggesting diffuse encephalopathy with cerebral oedema, meningismus and impaired consciousness. Multiple sclerosis is usually characterized by a typical relapsing-remitting clinical course. But there are acute, clinically fulminant forms with atypical. neurologic symptoms and death in months. MRI has become increasingly relevant in the diagnosis of multiple sclerosis in the past years. Yet, the specificity is limited. Atypical forms of MS and other diseases of CNS may show similar patterns on MRI. We report a case of 7 years old boy with clinically fulminant Marburg type of multiple sclerosis that ended with death in two months. The patient was a diagnostic problem despite the certain degree of clinical and radiological suspicion. The postmortem diagnosis is based on pathomorphologic changes (gross pathologic and microscopic features) in CNS.The present case is of clinical, radiological and pathomorphologic interest because of its early onset in childhood, unusual clinical course and acute progression. Awareness of the MRI features of multiple sclerosis and MS-variants (subtypes) may help in such atypical presentations in childhood. (authors)

Multiple sclerosis: current immunological aspects

Directory of Open Access Journals (Sweden)

Carlos Cuevas-García

2017-02-01

Full Text Available Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed on its origin: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration. In this review, the immune reaction main components and neurodegeneration present in multiple sclerosis are analyzed, as well as the inflammatory cascade associated with demyelination. Available treatments’ main purpose is to modulate aspects related to the adaptive immune response (B and T cells. The therapeutic challenge will be antigen-specific immune-tolerance induction, for example, with the use of tolerance protocols with peptides or DNA or nanoparticles vaccines. Future therapies should aim to control innate components (microglia, macrophages, astrocytes and to promote remyelination. To optimize the treatment, a combined therapeutic approach targeting the control of inflammatory and neurodegenerative components of the disease and monitoring of biomarkers will be necessary.

Multiple sclerosis pathogenesis: missing pieces of an old puzzle.

Science.gov (United States)

Rahmanzadeh, Reza; Brück, Wolfgang; Minagar, Alireza; Sahraian, Mohammad Ali

2018-06-08

Traditionally, multiple sclerosis (MS) was considered to be a CD4 T cell-mediated CNS autoimmunity, compatible with experimental autoimmune encephalitis model, which can be characterized by focal lesions in the white matter. However, studies of recent decades revealed several missing pieces of MS puzzle and showed that MS pathogenesis is more complex than the traditional view and may include the following: a primary degenerative process (e.g. oligodendroglial pathology), generalized abnormality of normal-appearing brain tissue, pronounced gray matter pathology, involvement of innate immunity, and CD8 T cells and B cells. Here, we review these findings and discuss their implications in MS pathogenesis.

Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis

DEFF Research Database (Denmark)

Dalbjerg, Sara Maria; Tsakiri, Anna; Fredriksen, Jette Lautrup

2016-01-01

Background Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis...... associated with Interferon-beta treatment. Case presentation We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved...... Interferon-beta-1-alpha therapy in patients with multiple sclerosis....

Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm.

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Giovannoni, Gavin

2018-06-01

The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely. A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function. The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.

[Multiple sclerosis, loss of functionality and gender].

Science.gov (United States)

Bravo-González, Félix; Álvarez-Roldán, Arturo

2017-12-01

To identify the type of support and assistance that patients with multiple sclerosis need in order to cope with the loss of functionality, and to show how gender affects the perception of these needs. Interpretative-phenomenological qualitative study. Granada (Spain). Year: 2014. Intentional sample: 30 patients and 20 family caregivers. Data were gathered from 26 interviews and 4 focus groups. The data were coded and analysed with the NVivo programme. The multiple sclerosis patients and family caregivers had different perceptions of the loss of capacity to undertake activities of daily living. Being able to self care was considered the last vestige of autonomy. The women with multiple sclerosis tried to take on the responsibility of housework, but the male caregivers became gradually involved in these tasks. Gender roles were redefined with respect to housekeeping. The multiple sclerosis patients showed a need for emotional support. Some of the men had abandoned the stereotype of the strong male as a result of the decline in their health. Adaptations in the home took place without planning them in advance. The use of mobility devices started on an occasional basis. A fear of stigma was an obstacle for regular use of assistive technology. Health care for people with multiple sclerosis should include family caregivers. Gender influences the perception that caregivers and patients have of the assistance they require to maximise their quality of life. This flags up several intervention areas for the follow-up and long-term care of these patients by the healthcare system. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Imaging features of encapsulating peritoneal sclerosis in continuous ambulatory peritoneal dialysis patients.

LENUS (Irish Health Repository)

Ti, Joanna P

2010-07-01

OBJECTIVE: The purpose of this article is to present the spectrum of radiologic findings of encapsulating peritoneal sclerosis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). CONCLUSION: Although a rare diagnosis, encapsulating peritoneal sclerosis in patients undergoing CAPD has a high morbidity and mortality. Diagnosis is often delayed because clinical features are insidious and nonspecific. Radiologic imaging may be helpful in the early diagnosis of encapsulating peritoneal sclerosis and in facilitating timely intervention for CAPD patients with encapsulating peritoneal sclerosis.

The prevalence of median neuropathy at wrist in systemic sclerosis patients at Srinagarind Hospital

Directory of Open Access Journals (Sweden)

Thanaporn Nimitbancha

2015-01-01

Full Text Available Objectives: To determine the prevalence and factor related with median neuropathy at wrist (MNW in systemic sclerosis patients. Study Design: Cross-sectional study. Setting: Srinagarind Hospital, Khon Kaen, Thailand. Participants: Systemic sclerosis patients who attended the Scleroderma Clinic, Srinagarind Hospital. Materials and Methods: Seventyfive systemic sclerosis patients were prospectively evaluated by questionnaire, physical examination, and electrodiagnostic study. The questionnaire consisted of the symptoms, duration, and type of systemic sclerosis. The physical examination revealed skin score of systemic sclerosis, pinprick sensation of median nerve distribution of both hands, and weakness of both abductor pollicis brevis muscles. The provocative test which were Tinel′s sign and Phalen′s maneuver were also examined. Moreover, electrodiagnostic study of the bilateral median and ulnar nerves was conducted. Results: The prevalence of MNW in systemic sclerosis patients was 44% - percentage of mild, moderate, and severe were 28%, 9.3%, and 6.7%, respectively. The prevalence of asymptomatic MNW was 88%. There were no association between the presence of MNW and related factors of systemic sclerosis. Conclusions: MNW is one of the most common entrapment neuropathies in systemic sclerosis patients. Systemic sclerosis patients should be screened for early signs of MNW.

Lung volume recruitment in multiple sclerosis.

Directory of Open Access Journals (Sweden)

Nadim Srour

Full Text Available INTRODUCTION: Pulmonary function abnormalities have been described in multiple sclerosis including reductions in forced vital capacity (FVC and cough but the time course of this impairment is unknown. Peak cough flow (PCF is an important parameter for patients with respiratory muscle weakness and a reduced PCF has a direct impact on airway clearance and may therefore increase the risk of respiratory tract infections. Lung volume recruitment is a technique that improves PCF by inflating the lungs to their maximal insufflation capacity. OBJECTIVES: Our goals were to describe the rate of decline of pulmonary function and PCF in patients with multiple sclerosis and describe the use of lung volume recruitment in this population. METHODS: We reviewed all patients with multiple sclerosis referred to a respiratory neuromuscular rehabilitation clinic from February 1999 until December 2010. Lung volume recruitment was attempted in patients with FVC <80% predicted. Regular twice daily lung volume recruitment was prescribed if it resulted in a significant improvement in the laboratory. RESULTS: There were 79 patients included, 35 of whom were seen more than once. A baseline FVC <80% predicted was present in 82% of patients and 80% of patients had a PCF insufficient for airway clearance. There was a significant decline in FVC (122.6 mL/y, 95% CI 54.9-190.3 and PCF (192 mL/s/y, 95% 72-311 over a median follow-up time of 13.4 months. Lung volume recruitment was associated with a slower decline in FVC (p<0.0001 and PCF (p = 0.042. CONCLUSION: Pulmonary function and cough decline significantly over time in selected patients with multiple sclerosis and lung volume recruitment is associated with a slower rate of decline in lung function and peak cough flow. Given design limitations, additional studies are needed to assess the role of lung volume recruitment in patients with multiple sclerosis.

Pharmacological management of spasticity in multiple sclerosis

DEFF Research Database (Denmark)

Otero-Romero, Susana; Sastre-Garriga, Jaume; Comi, Giancarlo

2016-01-01

Background and objectives: Treatment of spasticity poses a major challenge given the complex clinical presentation and variable efficacy and safety profiles of available drugs. We present a systematic review of the pharmacological treatment of spasticity in multiple sclerosis (MS) patients. Methods...... improvement is seen with the previous drugs. Nabiximols has a positive effect when used as add-on therapy in patients with poor response and/or tolerance to first-line oral treatments. Despite limited evidence, intrathecal baclofen and intrathecal phenol show a positive effect in severe spasticity...... and suboptimal response to oral drugs. Conclusion: The available studies on spasticity treatment offer some insight to guide clinical practice but are of variable methodological quality. Large, well-designed trials are needed to confirm the effectiveness of antispasticity agents and to produce evidence...

Epidemiological and biochemical aspects of progression in multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus Werner

2008-01-01

Patients with a progressive form of multiple sclerosis have the worst prognosis. They can expect that their symptoms will steadily worsen, and there is currently no treatment that has a proven effect on progressive multiple sclerosis. The underlying pathophysiology of the progressive forms of

Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) - Feasibility testing, pilot randomised controlled trial and mixed methods process evaluation.

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Rahn, A C; Köpke, S; Backhus, I; Kasper, J; Anger, K; Untiedt, B; Alegiani, A; Kleiter, I; Mühlhauser, I; Heesen, C

2018-02-01

Treatment decision-making is complex for people with multiple sclerosis. Profound information on available options is virtually not possible in regular neurologist encounters. The "nurse decision coach model" was developed to redistribute health professionals' tasks in supporting immunotreatment decision-making following the principles of informed shared decision-making. To test the feasibility of a decision coaching programme and recruitment strategies to inform the main trial. Feasibility testing and parallel pilot randomised controlled trial, accompanied by a mixed methods process evaluation. Two German multiple sclerosis university centres. People with suspected or relapsing-remitting multiple sclerosis facing immunotreatment decisions on first line drugs were recruited. Randomisation to the intervention (n = 38) or control group (n = 35) was performed on a daily basis. Quantitative and qualitative process data were collected from people with multiple sclerosis, nurses and physicians. We report on the development and piloting of the decision coaching programme. It comprises a training course for multiple sclerosis nurses and the coaching intervention. The intervention consists of up to three structured nurse-led decision coaching sessions, access to an evidence-based online information platform (DECIMS-Wiki) and a final physician consultation. After feasibility testing, a pilot randomised controlled trial was performed. People with multiple sclerosis were randomised to the intervention or control group. The latter had also access to the DECIMS-Wiki, but received otherwise care as usual. Nurses were not blinded to group assignment, while people with multiple sclerosis and physicians were. The primary outcome was 'informed choice' after six months including the sub-dimensions' risk knowledge (after 14 days), attitude concerning immunotreatment (after physician consultation), and treatment uptake (after six months). Quantitative process evaluation data

ECTRIMS/ACTRIMS 2017: Closing in on neurorepair in progressive multiple sclerosis.

Science.gov (United States)

Kremer, David; Küry, Patrick; Hartung, Hans-Peter

2018-04-01

While there is now a multitude of potent medications for relapsing-remitting multiple sclerosis (RRMS), effective therapies targeting neurodegeneration in progressive multiple sclerosis types are still lacking. Stimulation of neurorepair in this disease remains a pathogenetically defined treatment goal. However, therapeutic progress is slowed by the still inadequate tool set to capture "regeneration/repair" in MS and to define appropriate outcomes in clinical trials. In this review, we discuss studies investigating promising regenerative agents for progressive MS which were recently presented during the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)/Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017 meeting in Paris.

What's new in multiple sclerosis spasticity research? Poster session highlights.

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Linker, Ralf

2017-11-01

Each year at the Multiple Sclerosis Experts Summit, relevant research in the field of multiple sclerosis spasticity is featured in poster sessions. The main studies presented at this year's meeting are summarized herein.

Different Sex-Based Responses of Gut Microbiota During the Development of Hepatocellular Carcinoma in Liver-Specific Tsc1-Knockout Mice.

Science.gov (United States)

Huang, Rong; Li, Ting; Ni, Jiajia; Bai, Xiaochun; Gao, Yi; Li, Yang; Zhang, Peng; Gong, Yan

2018-01-01

Gut microbial dysbiosis is correlated with the development of hepatocellular carcinoma (HCC). Therefore, analyzing the changing patterns in gut microbiota during HCC development, especially before HCC occurrence, is essential for the diagnosis and prevention of HCC based on gut microbial composition. However, these changing patterns in HCC are poorly understood, especially considering the sex differences in HCC incidence and mortality. Here, with an aim to determine the relationship between gut microbiota and HCC development in both sexes, and to screen potential microbial biomarkers for HCC diagnosis, we studied the changing patterns in the gut microbiota from mice of both sexes with liver-specific knockout of Tsc1 ( LTsc1KO ) that spontaneously developed HCC by 9-10 months of age and compared them to the patterns observed in their wide-type Tsc1 fl/fl cohorts using high-throughput sequencing. Using the LTsc1KO model, we were able to successfully exclude the continuing influence of diet on the gut microbiota. Based on gut microbial composition, the female LTsc1KO mice exhibited gut microbial disorder earlier than male LTsc1KO mice during the development of HCC. Our findings also indicated that the decrease in the relative abundance of anaerobic bacteria and the increase in the relative abundance of facultative anaerobic bacteria can be used as risk indexes of female HCC, but would be invalid for male HCC. Most of the changes in the gut bacteria were different between female and male LTsc1KO mice. In particular, the increased abundances of Allobaculum , Erysipelotrichaceae, Neisseriaceae, Sutterella , Burkholderiales, and Prevotella species have potential for use as risk indicators of female HCC, and the increased abundances of Paraprevotella, Paraprevotellaceae, and Prevotella can probably be applied as risk indicators of male HCC. These relationships between the gut microbiota and HCC discovered in the present study may serve as a platform for the identification

Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study.

Science.gov (United States)

Al-Chalabi, Ammar; Calvo, Andrea; Chio, Adriano; Colville, Shuna; Ellis, Cathy M; Hardiman, Orla; Heverin, Mark; Howard, Robin S; Huisman, Mark H B; Keren, Noa; Leigh, P Nigel; Mazzini, Letizia; Mora, Gabriele; Orrell, Richard W; Rooney, James; Scott, Kirsten M; Scotton, William J; Seelen, Meinie; Shaw, Christopher E; Sidle, Katie S; Swingler, Robert; Tsuda, Miho; Veldink, Jan H; Visser, Anne E; van den Berg, Leonard H; Pearce, Neil

2014-11-01

Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995-2012), the Netherlands (2006-12), Italy (1995-2004), Scotland (1989-98), and England (2002-09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register. We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r(2)=0·95, Ireland r(2)=0·99, Italy r(2)=0·95, the Netherlands r(2)=0·99, and Scotland r(2)=0·97; overall r(2)=0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5-5·0), with similar estimates for men (4·6, 4·3-4·9) and women (5·0, 4·5-5·5). A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues. UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the

Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

Science.gov (United States)

Navas, Carlos; Torres-Duque, Carlos A; Munoz-Ceron, Joe; Álvarez, Carlos; García, Juan R; Zarco, Luis; Vélez, Lázaro A; Awad, Carlos; Castro, Carlos Alberto

2018-01-01

Multiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis. The purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis. A panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed. Tuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease. Latent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

[Current description of multiple sclerosis].

Science.gov (United States)

Río, Jordi; Montalbán, Xavier

2014-12-01

Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Parent-of-origin effect in multiple sclerosis: observations from interracial matings.

Science.gov (United States)

Ramagopalan, S V; Yee, I M; Dyment, D A; Orton, S-M; Marrie, R A; Sadovnick, A D; Ebers, G C

2009-08-25

Multiple sclerosis (MS) is a complex neurologic disease with a striking geographical distribution. In Canada, prevalence is high in Caucasians of Northern European ancestry and uncommon in North American Aboriginals, many of whom now have Caucasian admixture. The population-based Canadian Collaborative Project on the Genetic Susceptibility to MS provided the characteristics of 58 individuals with 1 Caucasian and 1 North American Aboriginal parent from a database of 30,000 MS index cases. We found that MS index cases with a Caucasian mother and a North American Aboriginal father had a higher sib recurrence risk and greater F:M sex ratio (p = 0.043) than patients with a North American Aboriginal mother and Caucasian father. Maternal parent-of-origin effects in multiple sclerosis disease etiology previously seen in studies of half-siblings and avuncular pairs are also seen in Caucasian-North American Aboriginal admixture matings and warrant further investigation. A differential influence of maternal risk transmission on the sex ratio of affected offspring is implied. The method of analysis used may have broader implications for detection of parent-of-origin effects in admixture cohorts.

Positron emission tomography neuroimaging in amyotrophic lateral sclerosis: what is new?

International Nuclear Information System (INIS)

Quartuccio, N.; Van Weehaeghe, D.; Van Laere, K.; Cistaro, A.; Jonsson, C.; Pagani, M.

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a neuro degenerative disease involving upper and lower motor neurons, extra-motor neurons, microglia and astrocytes. The neuro degenerative process results in progressive muscle paralysis and even in cognitive impairment. Within the complex diagnostic work-up, positron emission tomography (PET) represents a valuable imaging tool in the assessment of patients with ALS. PET, by means of different radiotracers (i.e. 18 F-fluorodeoxyglucose, 6-[ 18 F]fluoro-L-dopa, [ 11 C]flumazenil) can assess the status of the wide range of brain regions and neural circuits, which can be affected by ALS. Furthermore, experimental radio compounds have been developed for the evaluation of white matter, which plays a role in the progression of the disease. Here we present a comprehensive review including in different sections the most relevant PET studies: studies investigating ALS and ALS-mimicking conditions (especially primary lateral sclerosis and other neuro degenerative diseases), articles selecting specific subsets of patients (with bulbar or spinal onset), studies investigating patients with familial type of ALS, studies evaluating the role of the white matter in ALS and papers evaluating the diagnostic sensitivity of PET in ALS patients

Magnetic resonance in multiple sclerosis

International Nuclear Information System (INIS)

Scotti, G.; Caputo, D.; Cazzullo, C.L.

1986-01-01

Magnetic Resonance Imaging was performed in more than 200 patients with clinical suspicion or knowledge of Multiple Sclerosis. One hundred and forty-seven (60 males and 87 females) had MR evidence of multiple sclerosis lesions. The MR signal of demyelinating plaques characteristically has prolonged T1 and T2 relaxation times and the T2-weighted spin-echo sequences are generally superior to the T1-weighted images because the lesions are better visualized as areas of increased signal intensity. MR is also able to detect plaques in the brainstem, cerebellum and within the cervical spinal cord. MR appears to be an important, non-invasive method for the diagnosis of Multiple Sclerosis and has proven to be diagnostically superior to CT, evoked potentials (EP) and CSF examination. In a selected group of 30 patients, with the whole battery of the relevant MS studies, MR was positive in 100%, CT in 33,3%, EP in 56% and CSF examination in 60%. In patients clinically presenting only with signs of spinal cord involvement or optic neuritis or when the clinical presentation is uncertain MR has proven to be a very useful diagnostic tool for diagnosis of MS by demonstrating unsuspected lesions in the cerebral hemispheres. (orig.)

Multiple Sclerosis: Hope Through Research | NIH MedlinePlus the Magazine

Science.gov (United States)

... of this page please turn Javascript on. Feature: Multiple Sclerosis Hope Through Research Past Issues / Spring 2012 Table ... that television journalist Neil Cavuto was diagnosed with multiple sclerosis (MS) more than 15 years ago. And that ...

Amyloid PET in pseudotumoral multiple sclerosis.

Science.gov (United States)

Matías-Guiu, Jordi A; Cabrera-Martín, María Nieves; Cortés-Martínez, Ana; Pytel, Vanesa; Moreno-Ramos, Teresa; Oreja-Guevara, Celia; Carreras, José Luis; Matías-Guiu, Jorge

2017-07-01

Pseudotumoral multiple sclerosis is a rare form of demyelinating disease of the central nervous system. Positron emission tomography (PET) using amyloid-tracers has also been suggested as a marker of damage in white matter lesions in multiple sclerosis due to the nonspecific uptake of these tracers in white matter. We present the case of a 59 year-old woman with a pathological-confirmed pseudotumoral multiple sclerosis, who was studied with the amyloid tracer 18 F-florbetaben. The patient had developed word-finding difficulties and right hemianopia twelve years ago. In that time, MRI showed a lesion on the left hemisphere with an infiltrating aspect in frontotemporal lobes. Brain biopsy showed demyelinating areas and inflammation. During the following years, two new clinical relapses occurred. 18 F-florbetaben PET showed lower uptake in the white matter lesion visualized in the CT and MRI images. Decreased tracer uptake was also observed in a larger area of the left hemisphere beyond the lesions observed on MRI or CT. White matter lesion volume on FLAIR was 44.2mL, and tracer uptake change between damaged white matter and normal appearing white matter was - 40.5%. Standardized uptake value was inferior in the pseudotumoral lesion than in the other white matter lesions. We report the findings of amyloid PET in a patient with pseudotumoral multiple sclerosis. This case provides further evidence on the role of amyloid PET in the assessment of white matter and demyelinating diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis

International Nuclear Information System (INIS)

Biggins, J.A.; Taylor, A.; Caspary, E.A.

1978-01-01

Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

Science.gov (United States)

Casanova, Bonaventura; Jarque, Isidro; Gascón, Francisco; Hernández-Boluda, Juan Carlos; Pérez-Miralles, Francisco; de la Rubia, Javier; Alcalá, Carmen; Sanz, Jaime; Mallada, Javier; Cervelló, Angeles; Navarré, Arantxa; Carcelén-Gadea, María; Boscá, Isabel; Gil-Perotin, Sara; Solano, Carlos; Sanz, Miguel Angel; Coret, Francisco

2017-07-01

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

Multiple sclerosis: general features and pharmacologic approach

International Nuclear Information System (INIS)

Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio

2009-01-01

Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)

Chemokine receptor CCR5 in interferon-treated multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, F; Kristiansen, T B; Wittenhagen, P

2007-01-01

To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

Synaptic pathology in the cerebellar dentate nucleus in chronic multiple sclerosis.

Science.gov (United States)

Albert, Monika; Barrantes-Freer, Alonso; Lohrberg, Melanie; Antel, Jack P; Prineas, John W; Palkovits, Miklós; Wolff, Joachim R; Brück, Wolfgang; Stadelmann, Christine

2017-11-01

In multiple sclerosis, cerebellar symptoms are associated with clinical impairment and an increased likelihood of progressive course. Cortical atrophy and synaptic dysfunction play a prominent role in cerebellar pathology and although the dentate nucleus is a predilection site for lesion development, structural synaptic changes in this region remain largely unexplored. Moreover, the mechanisms leading to synaptic dysfunction have not yet been investigated at an ultrastructural level in multiple sclerosis. Here, we report on synaptic changes of dentate nuclei in post-mortem cerebella of 16 multiple sclerosis patients and eight controls at the histological level as well as an electron microscopy evaluation of afferent synapses of the cerebellar dentate and pontine nuclei of one multiple sclerosis patient and one control. We found a significant reduction of afferent dentate synapses in multiple sclerosis, irrespective of the presence of demyelination, and a close relationship between glial processes and dentate synapses. Ultrastructurally, we show autophagosomes containing degradation products of synaptic vesicles within dendrites, residual bodies within intact-appearing axons and free postsynaptic densities opposed to astrocytic appendages. Our study demonstrates loss of dentate afferent synapses and provides, for the first time, ultrastructural evidence pointing towards neuron-autonomous and neuroglia-mediated mechanisms of synaptic degradation in chronic multiple sclerosis. © 2016 International Society of Neuropathology.

New approaches in the management of multiple sclerosis

Directory of Open Access Journals (Sweden)

Laurie J Barten

2010-11-01

Full Text Available Laurie J Barten1, Douglas R Allington1, Kendra A Procacci2, Michael P Rivey11The University of Montana and Community Medical Center, Missoula, MT, USA; 2The University of Montana School of Pharmacy, Missoula, MT, USAAbstract: Multiple sclerosis (MS is a central nervous system chronic inflammatory disease that is characterized by an extensive and complex immune response. Scientific advances have occurred in immunology, pathophysiology, and diagnostic and clinical assessment tools, and recent discovery of unique therapeutic targets has spurred numerous Phase II and Phase III clinical trials. Reductions in MS relapse rates and improvements in T2 or gadolinium-enhancing lesion burdens have been reported from Phase III trials that include fingolimod, alemtuzumab, cladribine, and rituximab. Promising Phase II trial data exist for teriflunomide, daclizumab, laquinimod, and fumarate. The optimism created by these favorable findings must be tempered with evaluation of the adverse effect profile produced by these new agents. Given the discovery of progressive multifocal leukoencephalopathy with the use of natalizumab, ongoing vigilance for rare and life-threatening reactions due to new agents should be paramount. Patients with MS often experience difficulty with ambulation, spasticity, and cognition. Recent clinical trial data from two Phase III dalfampridine-SR trials indicate certain patients receive benefits in ambulation. This article provides an overview of data from clinical trials of newer agents of potential benefit in MS.Keywords: multiple sclerosis, Phase II trials, Phase III trials, progressive multifocal leukoencephalopathy, monoclonal antibody

Cavernous angioma associated with ipsilateral hippocampal sclerosis

International Nuclear Information System (INIS)

Okujava, M.; Ebner, A.; Schmitt, J.; Woermann, F.G.

2002-01-01

We report two cases with extratemporal cavernous angioma (CA) and coexisting ipsilateral hippocampal sclerosis. Classically dual pathology is defined as the association of hippocampal sclerosis with an extrahippocampal lesion. Subtle changes in hippocampus might be overlooked in the presence of an unequivocal extrahippocampal abnormality. Seizure outcome after epilepsy surgery in cases with dual pathology is less favourable if only one of the lesions is removed. Dual pathology must always be considered in diagnostic imaging of patients with intractable epilepsy and CA. (orig.)

Cavernous angioma associated with ipsilateral hippocampal sclerosis

Energy Technology Data Exchange (ETDEWEB)

Okujava, M [Institute of Radiology and Interventional Diagnostics, Tbilisi (Georgia); Ebner, A; Schmitt, J; Woermann, F G [Bethel Epilepsy Centre, Mara Hospital, Bielefeld (Germany)

2002-07-01

We report two cases with extratemporal cavernous angioma (CA) and coexisting ipsilateral hippocampal sclerosis. Classically dual pathology is defined as the association of hippocampal sclerosis with an extrahippocampal lesion. Subtle changes in hippocampus might be overlooked in the presence of an unequivocal extrahippocampal abnormality. Seizure outcome after epilepsy surgery in cases with dual pathology is less favourable if only one of the lesions is removed. Dual pathology must always be considered in diagnostic imaging of patients with intractable epilepsy and CA. (orig.)

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

Science.gov (United States)

Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

2015-01-01

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

Science.gov (United States)

2015-10-01

AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

Hippocampal sclerosis in children younger than 2 years

Energy Technology Data Exchange (ETDEWEB)

Kadom, Nadja [Children' s National Medical Center, Department of Diagnostic Imaging and Radiology, Washington, DC (United States); Tsuchida, Tammy; Gaillard, William D. [Children' s National Medical Center, Department of Neurology, Washington, DC (United States)

2011-10-15

Hippocampal sclerosis (HS) is rarely considered as a diagnosis in children younger than 2 years. To describe imaging features in conjunction with clinical information in patients with hippocampal sclerosis who are younger than 2 years. We retrospectively reviewed MR brain imaging and clinical information in five children in whom the diagnosis of HS was made both clinically and by MRI prior to 2 years of age. Imaging features establishing the diagnosis of hippocampal sclerosis were bright T2 signal and volume loss, while the internal architecture of the hippocampal formation was preserved in almost all children. Clinically, all children had an infectious trigger. It is necessary for radiologists to consider HS in children with certain clinical features to plan an MRI protocol that is appropriate for detection of hippocampal pathology. (orig.)

Hippocampal sclerosis in children younger than 2 years

International Nuclear Information System (INIS)

Kadom, Nadja; Tsuchida, Tammy; Gaillard, William D.

2011-01-01

Hippocampal sclerosis (HS) is rarely considered as a diagnosis in children younger than 2 years. To describe imaging features in conjunction with clinical information in patients with hippocampal sclerosis who are younger than 2 years. We retrospectively reviewed MR brain imaging and clinical information in five children in whom the diagnosis of HS was made both clinically and by MRI prior to 2 years of age. Imaging features establishing the diagnosis of hippocampal sclerosis were bright T2 signal and volume loss, while the internal architecture of the hippocampal formation was preserved in almost all children. Clinically, all children had an infectious trigger. It is necessary for radiologists to consider HS in children with certain clinical features to plan an MRI protocol that is appropriate for detection of hippocampal pathology. (orig.)

Chronic progressive multiple sclerosis

International Nuclear Information System (INIS)

Buffoli, A.; Micheletti, E.; Capra, R.; Mattioli, F.; Marciano', N.

1991-01-01

A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Istituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable

Abundance of Stress, Anxiety and Depression in Multiple Sclerosis Patients

Directory of Open Access Journals (Sweden)

A. Dehghan

2013-05-01

Conclusion: The findings of this research revealed high stress, anxiety and depression in Multiple Sclerosis Patients that can jeopardize their health. Hence the providing appropriate education for coping and adapting with the symptoms in Multiple Sclerosis Patients seems to be necessary.

The Cyanobacteria Derived Toxin Beta-N-Methylamino-L-Alanine and Amyotrophic Lateral Sclerosis

Directory of Open Access Journals (Sweden)

Elijah W. Stommel

2010-12-01

Full Text Available There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis. The non-protein amino acid beta-N-methylamino-L-alanine (BMAA was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer’s disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin.

Current concepts in multiple sclerosis

International Nuclear Information System (INIS)

Wiethoelter, Horst; Dichgans, Johannes

1991-01-01

This volume contains 9 articles dealing with the use of nuclear magnetic resonance imaging and positron emitted tomography in the diagnosis and staging of multiple sclerosis. (H.W.). refs.; figs.; tabs

Intraspinal Stem Cell Transplantation for Amyotrophic Lateral Sclerosis

Science.gov (United States)

Chen, Kevin S.; Sakowski, Stacey A.; Feldman, Eva L.

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder in which the loss of upper and lower motor neurons produces progressive weakness and eventually death. In the decades since the approval of riluzole, the only FDA approved medication to moderately slow progression of ALS, no new therapeutics have arisen to alter the course of the disease. This is partly due to our incomplete understanding of the complex pathogenesis of motor neuron degeneration. Stem cells have emerged as an attractive option in treating ALS since they come armed with equally complex cellular machinery and may modulate the local microenvironment in many ways to rescue diseased motor neurons. While various stem cell types are being evaluated in preclinical and early clinical applications, here we review the preclinical strategies and advances supporting the recent clinical translation of neural progenitor cell therapy for ALS. Specifically, we focus on the use of spinal cord neural progenitor cells and the pipeline starting from preclinical studies to the designs of the Phase I and IIa clinical trials involving direct intraspinal transplantation in humans. PMID:26696091

Association of autoimmune hepatitis and multiple sclerosis: a coincidence?

Directory of Open Access Journals (Sweden)

Marta Sofia Mendes Oliveira

2015-09-01

Full Text Available Autoimmune hepatitis is a chronic liver inflammation resulting from deregulation of immune tolerance mechanisms. Multiple sclerosis is also an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. Here we present a case of an 18 year old female with multiple sclerosis was treated with glatiramer acetate and with interferon beta 1a at our hospital. Seven months after initiating treatment, liver dysfunction occurred. Clinical and laboratory findings were suggestive of drug-induced hepatitis, which led to discontinuation of treatment with interferon. Facing a new episode of acute hepatitis one year later, she was subjected to a liver biopsy, and the analysis of autoantibodies was positive for smooth muscle antibodies. Given the diagnosis of autoimmune hepatitis she started therapy with prednisolone and azathioprine, with good clinical and analytical response. Besides, the demyelinating lesions of multiple sclerosis became lower. In conclusion, there are only a few cases that describe the association of autoimmune hepatitis with multiple sclerosis, and there is a chance both diseases have the same autoimmune inflammatory origin.

The enigma of multiple sclerosis: inflammation and neurodegeneration cause heterogeneous dysfunction and damage

DEFF Research Database (Denmark)

Owens, Trevor

2003-01-01

progression correlate with axonal damage, and that brain atrophy resulting from axonal loss is a feature of early multiple sclerosis, and is not restricted to the secondary progressive forms of the disease. Inflammatory mediators (CD8 T cells and antibodies) are implicated in axonal damage, and treatment...... cells for oligodendrocytes. SUMMARY: Oligodendrocyte precursors are abundant in multiple sclerosis lesions, but fail to remyelinate. Oligodendrocyte growth and regeneration are probably compromised by the action of growth inhibitory signals and lack of growth stimuli. Inflammatory cells and mediators......PURPOSE OF REVIEW: The demyelinating disease multiple sclerosis has an autoimmune inflammatory component, which has dominated the description of multiple sclerosis. A degenerative component to multiple sclerosis was always apparent, but was underappreciated until recently. Recent work has brought...

Investigation of vertebral ''end plate sclerosis''

International Nuclear Information System (INIS)

Lee, S.W.; Mathie, A.G.; Jackson, J.E.; Hughes, S.P.F.

2001-01-01

To evaluate the association between vertebral ''end plate sclerosis'' and neck pain. A retrospective study was carried out of lateral cervical spine radiographs with a Picture Archive and Communication System (PACS). Two hundred patients' files were randomly assessed, comprising four equal groups, A to D. The mean ages of the patients were 62±7.4 years, 61±7.5 years, 40±5.6 years and 23±5.6 years respectively. In group A, all patients had symptoms of neck pain and a radiographic diagnosis of ''end plate sclerosis'' of the cervical spine. In groups B to D, asymptomatic patients were recruited and their age groups were 50-69, 30-49 and 10-29 years respectively. Using the PACS, the radiographic density and the sagittal diameter, thickness and area of the end plates at the C5 level were measured. Results and conclusions: No significant differences were found in the radiographic density of the end plates either between the symptomatic and asymptomatic groups (groups A and B), or between different age groups (groups B, C and D). A significant increase in end plate area and thickness was found, however, in both group B (P<0.005) and group C (P<0.01) in comparison with group D. This indicates that the extent of end plate sclerosis increases with age. Our results suggest that the radiographic density of cervical vertebral end plates correlates neither with neck pain nor with increasing age. The radiological sign of ''end plate sclerosis'' may be over-reported, further limiting its value in the assessment of patients with cervical spondylosis. (orig.)

Self care programs and multiple sclerosis: physical therapeutics treatment - literature review.

Science.gov (United States)

Demaille-Wlodyka, S; Donze, C; Givron, P; Gallien, P

2011-03-01

To clarify the therapeutic education program impact with multiple sclerosis patients, literature review. Highlight contents and efficacy. A non-systematic review on Medline, PubMed and Cochrane library databases from 1966 to 2010 using the following keywords: "multiple sclerosis", "self-care", "self-management" and specific symptoms keywords. Clinical trials and randomized clinical trials, as well as literature reviews published in English, French and German will be analyzed. Counseling is a part of the non-pharmacological management of chronic illnesses such as multiple sclerosis. Symptoms' diversity and the different clinical forms limit standardized programs of self-care management, applicable to patients. In the literature review, counseling programs have often low metrology. A behavior change with patients and medical staff could exist. To empower the patient, to reduce symptoms' impact and to improve treatment access are the aims of educational therapy. Therapeutic education program for multiple sclerosis patients could progress with their standardization and assessment, for each sign. To promote the educational therapy of multiple sclerosis patients, a specific training for medical staff, as specific financing are necessary. 2011 Elsevier Masson SAS. All rights reserved.

Cross-diagnostic validity of the SF-36 physical functioning scale in patients with stroke, multiple sclerosis and amyotrophic lateral sclerosis: a study using Rasch analysis

NARCIS (Netherlands)

Dallmeijer, Annet J.; de Groot, Vincent; Roorda, Leo D.; Schepers, Vera P. M.; Lindeman, Eline; van den Berg, Leonard H.; Beelen, Anita; Dekker, Joost

2007-01-01

The aim of this study was to investigate unidimensionality and differential item functioning of the SF-36 physical functioning scale (PF10) in patients with various neurological disorders. Patients: Patients post-stroke (n = 198), with multiple sclerosis (n = 151) and amyotrophic lateral sclerosis

Differential Vocational Rehabilitation Service Patterns Related to the Job Retention and Job-Seeking Needs of Individuals with Multiple Sclerosis

Science.gov (United States)

Tansey, Timothy N.; Strauser, David; Frain, Michael P.; Bishop, Malachy; Chiu, Chung-Yi; Kaya, Cahit; Chan, Fong

2015-01-01

The experience of living with multiple sclerosis (MS) can have a profound effect on employment. The impact of MS is a complex interaction of personal, medical, functional, financial, and psychosocial variables that ultimately results in up to 80% of persons with MS leaving their jobs within 10 years of their diagnosis. The aim of this study was to…

Balo`s concentric sclerosis; value of magnetic resonance imaging in diagnosis

Energy Technology Data Exchange (ETDEWEB)

Singh, S.; Kuruvilla, A.; Korah, I.P. [Christian Medical College and Hospital, Vellore, Tamilnadu, (India). Department of Radiodiagnosis; Alexander, M. [Christian Medical College and Hospital, Vellore, Tamilnadu, (India). Department of Neurosciences

1999-08-01

We report two cases of Balo`s concentric sclerosis that demonstrate the typical magnetic resonance imaging (MRI) findings of concentric rings of demyelination involving the superficial and deep white matter and sparing the cortex. In both cases biopsy was not performed as MRI findings and multi-mode evoked potential studies were consistent with demyelinating illness. The theories regarding the pathogenesis of this peculiar appearance are briefly reviewed. Balo`s concentric sclerosis is a very rare type of demyelinating disease characterized pathologically by large alternating lamellae of demyelinated and myelinated white matter arranged in a concentric pattern. This progressive disease is more often found in young male adults and is more common in the Philippines. Balo`s concentric sclerosis is considered an unusual variant of multiple sclerosis (MS); however, some authors believe it to be a different entity. Although the pathogenesis of the concentric sclerosis is debated, the cause of demyelination is generally presumed to be the same as that of multiple sclerosis. There is striking resemblance between the magnetic resonance (MR) appearance and the histopathological features of MS. Not all cases may show a typical MR appearance. Prior to MR imaging, most of them were diagnosed at post-mortem. To our knowledge, few cases have been diagnosed by MR imaging in life. Copyright (1999) Blackwell Science Pty Ltd 15 refs., 2 figs.

Magnetic resonance imaging in the diagnostics of multiple sclerosis

International Nuclear Information System (INIS)

Larsen, J.P.; Tjoerstad, K.; Kaass, B.; Oedegaard, H.

1987-01-01

Multiple sclerosis is an important and frequent neurological disease and the diagnosis might be difficult. The clinical criteria of multiple sclerosis and the role of laboratory examinations in the diagnosis of the disease are discussed. In particular the help offered by the magnetic resonance imaging method is the subject of this paper. Three patients are reported and discussed

Clustering of multiple sclerosis in Galion, Ohio, 1982-1985

Energy Technology Data Exchange (ETDEWEB)

Ingalls, T.H. (Boston Univ. School of Medicine, MA (USA))

1989-09-01

Epidemiologic evidence indicates that the outbreak of 30-40 cases of multiple sclerosis and other demyelinating syndromes in Galion, Ohio, USA, during 1982-1985 was related to an excess concentration of heavy-metal wastes, especially of cadmium and chromium in sewage and river water. Both multiple sclerosis and myasthenia gravis were diagnosed by board-certified neurologists.

The management of multiple sclerosis in children: a European view

DEFF Research Database (Denmark)

Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey

2010-01-01

About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity i...

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

Science.gov (United States)

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0

Fingolimod hydrochloride for the treatment of relapsing remitting multiple sclerosis.

Science.gov (United States)

Thomas, Katja; Proschmann, Undine; Ziemssen, Tjalf

2017-10-01

Fingolimod was the first oral and the first in class disease modifying treatment in multiple sclerosis that acts as sphingosine-1-phospathe receptor agonist. Since approval in 2010 there is a growing experience with fingolimod use in clinical practice, but also next-generation sphingosin-1-receptor agonists in ongoing clinical trials. Growing evidence demonstrates additional effects beyond impact on lymphocyte circulation, highlighting further promising targets in multiple sclerosis therapy. Areas covered: Here we present a systematic review using PubMed database searching and expert opinion on fingolimod use in clinical practice. Long-term data of initial clinical trials and post-marketing evaluations including long-term efficacy, safety, tolerability and management especially within growing disease modifying treatment options and pre-treatment constellation in multiple sclerosis patients are critically discussed. Furthermore novel findings in mechanism of actions and prospective on additional use in progressive forms in multiple sclerosis are presented. Expert opinion: There is an extensive long-term experience on fingolimod use in clinical practice demonstrating the favorable benefit-risk of this drug. Using a defined risk management approach experienced MS clinicians should apply fingolimod after critical choice of patients and review of clinical aspects. Further studies are essential to discuss additional benefit in progressive forms in multiple sclerosis.

Effect of 12-Week Pilates Trainning on EDSS in Women Suffering fromMultiple Sclerosis

OpenAIRE

Z Shanazari; SM Marandi; S Samie

2013-01-01

Abstract Background & aim: Multiple sclerosis is a debilitating disease that strikes the immune system. Multiple sclerosis is a chronic disease which debilitates the nervous system. The study was evaluated the effects of Pilates exercise on women with physical disabilities suffering from multiple sclerosis for 12 weeks .The aim of this study was to investigating the effects of Pilates trainning on EDSS of women suffering from Multiple Sclerosis (MS) for 12 weeks. Methods: In the pres...

Seizures in multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus; Uyttenboogaart, Maarten; Polman, Susan; De Keyser, Jacques

Seizures have long been recognized to be part of the disease spectrum of multiple sclerosis (MS). While they occur in only a minority of patients with MS, epileptic seizures can have serious consequences. The treatment of MS can be epileptogenic, and antiepileptic treatment can conversely worsen the

Vaccines and multiple sclerosis

DEFF Research Database (Denmark)

Mailand, Mia Topsøe; Frederiksen, Jette Lautrup

2017-01-01

on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles–mumps–rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse...

[Effect of preventive treatment on cognitive performance in patients with multiple sclerosis].

Science.gov (United States)

Shorobura, Maria S

2018-01-01

Introduction: cognitive, emotional and psychopathological changes play a significant role in the clinical picture of multiple sclerosis and influence the effectiveness of drug therapy, working capacity, quality of life, and the process of rehabilitation of patients with multiple sclerosis. The aim: investigate the changes in cognitive function in patients with multiple sclerosis, such as information processing speed and working memory of patients before and after treatment with immunomodulating drug. Materials and methods:33 patients examined reliably diagnosed with multiple sclerosis who were treated with preventive examinations and treatment from 2012 to 2016. For all patients with multiple sclerosis had clinical-neurological examination (neurological status using the EDSS scale) and the cognitive status was evaluated using the PASAT auditory test. Patient screening was performed before, during and after the therapy. Statistical analysis of the results was performed in the system Statistica 8.0. We used Student's t-test (t), Mann-Whitney test (Z). Person evaluated the correlation coefficients and Spearman (r, R), Wilcoxon criterion (T), Chi-square (X²). Results: The age of patients with multiple sclerosis affects the growth and EDSS scale score decrease PASAT to treatment. Duration of illness affects the EDSS scale score and performance PASAT. Indicators PASAT not significantly decreased throughout the treatment. Conclusions: glatiramer acetate has a positive effect on cognitive function, information processing speed and working memory patients with multiple sclerosis, which is one of the important components of the therapeutic effect of this drug.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

Science.gov (United States)

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin

Suicide and multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E N; Stenager, Egon; Koch-Henriksen, N

1992-01-01

In a nationwide investigation the risk of death by suicide for patients with multiple sclerosis (MS) was assessed using records kept at the Danish Multiple Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death. The investigation covers all MS patients registered with DSMR...... with an onset of the disease within the period 1953-85, or for whom MS was diagnosed in the same period. Fifty three of the 5525 cases in the onset cohort group committed suicide. Using the figures from the population death statistics by adjustment to number of subjects, duration of observation, sex, age......, and calendar year at the start of observation, the expected number of suicides was calculated to be nearly 29. The cumulative lifetime risk of suicide from onset of MS, using an actuarial method of calculation, was 1.95%. The standard mortality ratio (SMR) of suicide in MS was 1.83. It was highest for males...

Reproductive History and Risk of Multiple Sclerosis

DEFF Research Database (Denmark)

Nielsen, N. M.; Jorgensen, K. T.; Stenager, E.

2011-01-01

Background: It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting. Methods: Using national databases, we established a cohort comprising 4.4 million...... Danish men and women born between 1935 and 1989 and alive in 1968 or later. We obtained information about their live-born children, pregnancy losses, pregnancy complications, and infertility diagnoses. MS cases in the cohort were identified through 2004 in the Danish Register of Multiple Sclerosis...

Increased rate of treatment with antidepressants in patients with multiple sclerosis

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Harhoff, Mette; Andersen, Per Kragh

2008-01-01

The prevalence of depression and anxiety is increased in patients with multiple sclerosis, but it has not been investigated whether these conditions are treated in clinical practice. The objective of this study was to investigate whether the rate of treatment with antidepressants is increased...... in patients with multiple sclerosis compared with patients with other chronic illnesses and compared with the general population. By linkage of nationwide case registers, all patients were identified, who had received a main diagnosis of multiple sclerosis or osteoarthritis at first admission or during...... outpatient contact in the period 1995-2000 in Denmark. Rates of subsequent purchase of antidepressants for these patients were calculated. In total, 417 patients with a main diagnosis of multiple sclerosis and 12 127 patients with a main diagnosis of osteoarthritis, at first discharge from hospital...

How multiple sclerosis is related to animal illness, stress and diabetes

Energy Technology Data Exchange (ETDEWEB)

Warren, S.A.; Warren, K.G.; Greenhill, S.; Paterson, M.

1982-02-15

At the University of Alberta's multiple sclerosis research clinic 100 patients with multiple sclerosis were matched to control patients for age, sex, race and zone of residence before the age of 15 years. Case and control subjects were interviewed and information was collected by questionnaire on factors that might play a role in the development of multiple sclerosis. The only factors found to be significantly associated with the development of this disorder were a history of leisure time spent in physical activities before the onset of symptoms, exposure to animal illness -- specifically canine distemper -- and a history of severe or prolonged emotional stress. The study also confirmed a familial predisposition to multiple sclerosis and suggested a relation between the disorder and a personal or family history of diabetes mellitus.

Multiple sclerosis in magnetic resonance

International Nuclear Information System (INIS)

Bekiesinska-Figatowska, M.; Walecki, J.; Stelmasiak, Z.

1994-01-01

The authors analyzed MR examination of 277 patients with multiple sclerosis. White matter hyperintesities in brain were found in 270 of them, in spinal cord in 32. The most frequently they were found in periventricular white matter, in subcortical localization and in the corpus callosum. MR examination allows the estimate the activity of the disease on the basis of the presence of edema around the plaques and their contrast enhancement with Gd-DTPA. About one third of all cases were accompanied by cortical brain atrophy (the most often seen in the frontal lobes), subcortical brain atrophy was less frequent. In about two third of all cases the corpus callosum atrophy was found. MR examination is a highly sensitive method of multiple sclerosis diagnosis, of the assessment of its activity and progression. (author)

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

Science.gov (United States)

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk: A Danish Nationwide Cohort Study.

Science.gov (United States)

Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J; Dreyer, Lene; Gislason, Gunnar; Ahlehoff, Ole

2018-03-13

Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion, systemic sclerosis is a significant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease.

Gastric antral vascular ectasia--a cause of refractory anaemia in systemic sclerosis.

LENUS (Irish Health Repository)

Busteed, S

2012-02-03

Recurrent gastrointestinal haemorrhage is an uncommon manifestation of systemic sclerosis. We report a case of gastrointestinal bleeding due to gastric antral vascular ectasia (GAVE) in a patient with systemic sclerosis. Failure to recognise the condition as a cause of gastrointestinal bleeding may delay the instigation of appropriate treatment. GAVE should be considered in the differential diagnosis of anaemia in patients with autoimmune conditions such as systemic sclerosis and primary biliary cirrhosis.

Tuberous sclerosis: Improvement of diagnosis by CT and MRI

International Nuclear Information System (INIS)

Dewes, W.; Henkes, H.; Richter, J.; Kretschmer, A.; Benz, P.; Brill, G.

1992-01-01

Ten children and a 22-y old women with tuberous sclerosis were studied. All children were epileptic but only 8 had skin lesions (white spots, adenoma sebaceum), 4 had rhabdomyoma of the heart and 4 children had strocytoma of the retina; only in 4 children was the entire triad of tuberous sclerosis seen. The young woman with a hemorrhage of an angiolipoma of the kidney had no other symptoms of tuberous sclerosis. All patients had pathologic CT and MRT findings; 4 different types of lesion were seen in MRT. In order to elucidate humangenetic aspects and to demonstrate the underlying disease all children with epileptic disorders and also all patients without the full triad of symptoms should be examined by MRT. (orig.) [de

Pediatric multiple sclerosis: current perspectives on health behaviors

Directory of Open Access Journals (Sweden)

Sikes EM

2018-03-01

Full Text Available Elizabeth Morghen Sikes,1 Robert W Motl,1 Jayne M Ness2 1Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Pediatric Neurology, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: Pediatric-onset multiple sclerosis (POMS accounts for ~5% of all multiple sclerosis cases, and has a prevalence of ~10,000 children in the USA. POMS is associated with a higher relapse rate, and results in irreversible disability on average 10 years earlier than adult-onset multiple sclerosis. Other manifestations of POMS include mental and physical fatigue, cognitive impairment, and depression. We believe that the health behaviors of physical activity, diet, and sleep may have potential benefits in POMS, and present a scoping review of the existing literature. Methods: We identified papers by searching three electronic databases (PubMed, GoogleScholar, and CINAHL. Search terms included: pediatric multiple sclerosis OR pediatric onset multiple sclerosis OR POMS AND health behavior OR physical activity OR sleep OR diet OR nutrition OR obesity. Papers were included in this review if they were published in English, referenced nutrition, diet, obesity, sleep, exercise, or physical activity, and included pediatric-onset multiple sclerosis as a primary population. Results: Twenty papers were identified via the literature search that addressed health-promoting behaviors in POMS, and 11, 8, and 3 papers focused on diet, activity, and sleep, respectively. Health-promoting behaviors were associated with markers of disease burden in POMS. Physical activity participation was associated with reduced relapse rate, disease burden, and sleep/rest fatigue symptoms. Nutritional factors, particularly vitamin D intake, may be associated with relapse rate. Obesity has been associated with increased risk of developing POMS. POMS is associated with better sleep hygiene, and this may benefit fatigue and quality of life

Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

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Metzger, Aude; Le Bars, Emmanuelle; Deverdun, Jeremy; Molino, François; Maréchal, Bénédicte; Picot, Marie-Christine; Ayrignac, Xavier; Carra, Clarisse; Bauchet, Luc; Krainik, Alexandre; Labauge, Pierre; Menjot de Champfleur, Nicolas

2018-03-01

The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R 2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

Potassium channel abnormalities are consistent with early axon degeneration of motor axons in the G127X SOD1 mouse model of amyotrophic lateral sclerosis

DEFF Research Database (Denmark)

Maglemose, Rikke; Hedegaard, Anne; Lehnhoff, Janna

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, which selectively affects upper and lower motoneurones. The underlying pathophysiology of the disease is complex but electrophysiological studies of peripheral nerves in ALS patients as well as human autopsy studies indicate...

Physical activity and exercise priorities in community dwelling people with multiple sclerosis: a Delphi study.

Science.gov (United States)

Stennett, Andrea; De Souza, Lorraine; Norris, Meriel

2018-07-01

Exercise and physical activity have been found to be beneficial in managing disabilities caused by multiple sclerosis. Despite the known benefits, many people with multiple sclerosis are inactive. This study aimed to identify the prioritised exercise and physical activity practices of people with multiple sclerosis living in the community and the reasons why they are engaged in these activities. A four Round Delphi questionnaire scoped and determined consensus of priorities for the top 10 exercise and physical activities and the reasons why people with multiple sclerosis (n = 101) are engaged in these activities. Data were analysed using content analysis, descriptive statistics, and non-parametric tests. The top 10 exercise and physical activity practices and the top 10 reasons why people with multiple sclerosis (n = 70) engaged in these activities were identified and prioritised. Consensus was achieved for the exercise and physical activities (W = 0.744, p multiple sclerosis engaged in exercise and physical activity were diverse. These self-selected activities and reasons highlighted that people with multiple sclerosis might conceptualise exercise and physical activity in ways that may not be fully appreciated or understood by health professionals. Considerations of the views of people with multiple sclerosis may be essential if the goal of increasing physical activity in this population is to be achieved. Implications for Rehabilitation Health professionals should work collaboratively with people with multiple sclerosis to understand how they prioritise activities, the underlying reasons for their prioritisations and embed these into rehabilitation programmes. Health professionals should utilise activities prioritised by people with multiple sclerosis in the community as a way to support, promote, and sustain exercise and physical activity in this population. Rehabilitation interventions should include both the activities people with multiple

MR in the diagnosis and monitoring of multiple sclerosis: An overview

International Nuclear Information System (INIS)

Rovira, Alex; Leon, Adelaida

2008-01-01

Multiple sclerosis is a chronic, persistent inflammatory-demyelinating disease of the central nervous system that typically presents as an acute clinically isolated syndrome attributable to a monofocal or multifocal demyelinating lesion, which usually affects the optic nerve, spinal cord, or brainstem and cerebellum. Although the diagnosis of multiple sclerosis is still based on clinical findings, magnetic resonance imaging is now integrated in the overall diagnostic scheme of the disease because of its unique sensitivity to demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Conventional magnetic resonance imaging techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences are highly sensitive in detecting multiple sclerosis plaques and provide a quantitative assessment of inflammatory activity and lesion load. However, there is a persisting mismatch between clinical and magnetic resonance imaging efficacy of approved treatments, which underlies the fact that this technique does not suffice to explain the entire spectrum of the disease process. In recent years, great effort has been dedicated to overcoming these limitations by using non-conventional magnetic resonance-derived metrics that can selectively measure the more destructive aspects of multiple sclerosis pathology and monitor the reparative mechanisms. These metrics, which include unenhanced T1-weighted imaging, measures of central nervous system atrophy, magnetization transfer imaging, proton magnetic resonance spectroscopy, diffusion-weighted imaging, and functional magnetic resonance imaging, provide a better approximation of the pathological substrate of the multiple sclerosis plaques, have increased our understanding of the pathogenesis of the disease, and have proven useful for studying the natural history of multiple sclerosis and monitoring the effects of new treatments. Therefore, magnetic resonance imaging not only plays an

MR in the diagnosis and monitoring of multiple sclerosis: An overview

Energy Technology Data Exchange (ETDEWEB)

Rovira, Alex [Magnetic Resonance Unit (I.D.I.), Department of Radiology, Hospital Universitari Vall d' Hebron, Barcelona (Spain)], E-mail: alex.rovira@idi-cat.org; Leon, Adelaida [Magnetic Resonance Unit (I.D.I.), Department of Radiology, Hospital Universitari Vall d' Hebron, Barcelona (Spain)

2008-09-15

Multiple sclerosis is a chronic, persistent inflammatory-demyelinating disease of the central nervous system that typically presents as an acute clinically isolated syndrome attributable to a monofocal or multifocal demyelinating lesion, which usually affects the optic nerve, spinal cord, or brainstem and cerebellum. Although the diagnosis of multiple sclerosis is still based on clinical findings, magnetic resonance imaging is now integrated in the overall diagnostic scheme of the disease because of its unique sensitivity to demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Conventional magnetic resonance imaging techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences are highly sensitive in detecting multiple sclerosis plaques and provide a quantitative assessment of inflammatory activity and lesion load. However, there is a persisting mismatch between clinical and magnetic resonance imaging efficacy of approved treatments, which underlies the fact that this technique does not suffice to explain the entire spectrum of the disease process. In recent years, great effort has been dedicated to overcoming these limitations by using non-conventional magnetic resonance-derived metrics that can selectively measure the more destructive aspects of multiple sclerosis pathology and monitor the reparative mechanisms. These metrics, which include unenhanced T1-weighted imaging, measures of central nervous system atrophy, magnetization transfer imaging, proton magnetic resonance spectroscopy, diffusion-weighted imaging, and functional magnetic resonance imaging, provide a better approximation of the pathological substrate of the multiple sclerosis plaques, have increased our understanding of the pathogenesis of the disease, and have proven useful for studying the natural history of multiple sclerosis and monitoring the effects of new treatments. Therefore, magnetic resonance imaging not only plays an

Multiple sclerosis: Pregnancy and women's health issues.

Science.gov (United States)

Mendibe Bilbao, M; Boyero Durán, S; Bárcena Llona, J; Rodriguez-Antigüedad, A

2016-08-18

The course of multiple sclerosis (MS) is influenced by sex, pregnancy and hormonal factors. To analyse the influence of the above factors in order to clarify the aetiopathogenic mechanisms involved in the disease. We conducted a comprehensive review of scientific publications in the PubMed database using a keyword search for 'multiple sclerosis', 'MS', 'EAE', 'pregnancy', 'hormonal factors', 'treatment', and related terms. We reviewed the advances presented at the meeting held by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in March 2013 in London, as well as recommendations by international experts. We provide recommendations for counselling and treating women with MS prior to and during pregnancy and after delivery. Current findings on the effects of treatment on the mother, fetus, and newborn are also presented. We issue recommendations for future research in order to address knowledge gaps and clarify any inconsistencies in currently available data. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Cell-based therapeutic strategies for multiple sclerosis.

Science.gov (United States)

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

Science.gov (United States)

Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

2010-11-01

Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

Neural correlates of alerting and orienting impairment in multiple sclerosis patients.

Science.gov (United States)

Vázquez-Marrufo, Manuel; Galvao-Carmona, Alejandro; González-Rosa, Javier J; Hidalgo-Muñoz, Antonio R; Borges, Mónica; Ruiz-Peña, Juan Luis; Izquierdo, Guillermo

2014-01-01

A considerable percentage of multiple sclerosis patients have attentional impairment, but understanding its neurophysiological basis remains a challenge. The Attention Network Test allows 3 attentional networks to be studied. Previous behavioural studies using this test have shown that the alerting network is impaired in multiple sclerosis. The aim of this study was to identify neurophysiological indexes of the attention impairment in relapsing-remitting multiple sclerosis patients using this test. After general slowing had been removed in patients group to isolate the effects of each condition, some behavioral differences between them were obtained. About Contingent Negative Variation, a statistically significant decrement were found in the amplitude for Central and Spatial Cue Conditions for patient group (pmultiple sclerosis. P1 and N1 delayed latencies are evidence of the demyelination process that causes impairment in the first steps of the visual sensory processing. Lastly, P3 amplitude shows a general decrease for the pathological group probably indexing a more central impairment. These results suggest that the Attention Network Test give evidence of multiple levels of attention impairment, which could help in the assessment and treatment of relapsing-remitting multiple sclerosis patients.

Increased cortical and deep grey matter sodium concentration is associated with physical and cognitive disability in relapse-onset multiple sclerosis

DEFF Research Database (Denmark)

Brownlee, WJ; Alves Da Mota, Patricia; Prados, Ferran

digit modalities test (SDMT) and tests of verbal and visual memory. Linear regression was used to compare differences in tissue TSC between groups. Multivariable linear regression was used to identify independent associations between TSC and disability with adjustment for age, sex, disease duration......=0.40) and visual memory (β=-0.06, 95%CI -0.11, -.0.02, R2=0.19). Conclusion: Sodium accumulation in cortical and deep grey matter may reflect underlying neurodegeneration that is relevant to the development of long-term disability and cognitive impairment in relapse-onset MS. 23Na-MRI may become a secondary......-appearing white matter (NAWM), T1-isointense and T1-hypointense lesions was calculated. Physical disability was assessed using the Expanded Disability Status Scale (EDSS), timed 25-foot walk test (TWT) and 9-hole peg test (9HPT). Cognition was assessed using the paced auditory serial addition test (PASAT), symbol...

Tuberous sclerosis: diffusion MRI findings in the brain

International Nuclear Information System (INIS)

Sener, R.N.

2002-01-01

Diffusion MRI has mainly been used for detection of acute ischemia, and for distinction of cytotoxic and vasogenic edema. We applied diffusion MRI in patients with tuberous sclerosis in order to evaluate diffusion imaging characteristics of parenchymal changes. Five children with known tuberous sclerosis were included in this study. The MRI examinations were performed on a 1.5-T MR unit. Diffusion MRI was obtained using the echo-planar imaging sequence. Apparent diffusion coefficient (ADC) values from the abnormal brain parenchyma were calculated directly from automatically generated ADC maps. Seven normal children were available for comparison. In this control group the mean ADC value of the normal white matter was 0.84±0.12 x 10 -3 mm 2 /s. In tuberous sclerosis patients the mean ADC value of the white matter hamartomas (n=20) was apparently high (1.52±0.24 x 10 -3 mm 2 /s) compared with that of normal white matter. The ADC value of calcified hamartomas was ''zero''. The ADC value within a giant cell tumor was 0.89 x 10 -3 mm 2 /s, similar to that of normal cerebral white matter. The ADC maps were superior to b=1000 s/mm 2 (true diffusion) images with respect to lesion evaluation, and they provided mathematical information on tissue integrity. With respect to detection of the exact numbers and sizes of the parenchymal hamartomas fluid-attenuated inversion recovery images were superior to ADC maps. It is believed that diffusion MRI can be useful in evaluation of various parenchymal changes associated with tuberous sclerosis. Further studies on tuberous sclerosis, and on various brain lesions, would provide increasing data on this relatively new MRI sequence. (orig.)

Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

Science.gov (United States)

Katz Sand, Ilana B.; Honce, Justin M.; Lublin, Fred D.

2015-01-01

Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient’s ‘multiple sclerosis-like’ phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. PMID:25636970

Inhibition of bovine viral diarrhea virus RNA synthesis by thiosemicarbazone derived from 5,6-dimethoxy-1-indanone.

Science.gov (United States)

Castro, Eliana F; Fabian, Lucas E; Caputto, María E; Gagey, Dolores; Finkielsztein, Liliana M; Moltrasio, Graciela Y; Moglioni, Albertina G; Campos, Rodolfo H; Cavallaro, Lucía V

2011-06-01

In the present work, we described the activity of the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone (TSC), which we previously characterized as a new compound that inhibits bovine viral diarrhea virus (BVDV) infection. We showed that TSC acts at a point of time that coincides with the onset of viral RNA synthesis and that it inhibits the activity of BVDV replication complexes (RCs). Moreover, we have selected five BVDV mutants that turned out to be highly resistant to TSC but still susceptible to ribavirin (RBV). Four of these resistant mutants carried an N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). The remaining mutant showed an A392E mutation within the same protein. Some of these mutants replicated slower than the wild-type (wt) virus in the absence of TSC, whereas others showed a partial reversion to the wt phenotype over several passages in the absence of the compound. The docking of TSC in the crystal structure of the BVDV RdRp revealed a close contact between the indane ring of the compound and several residues within the fingers domain of the enzyme, some hydrophobic contacts, and hydrogen bonds with the thiosemicarbazone group. Finally, in the mutated RdRp from resistant BVDV, these interactions with TSC could not be achieved. Interestingly, TSC inhibited BVDV replication in cell culture synergistically with RBV. In conclusion, TSC emerges as a new nonnucleoside inhibitor of BVDV RdRp that is synergistic with RBV, a feature that turns it into a potential compound to be evaluated against hepatitis C virus (HCV).

Use of Sugammadex in a Patient with Amyotrophic Lateral Sclerosis

Science.gov (United States)

Kelsaka, Ebru; Karakaya, Deniz; Zengin, Eyüp Cağatayn

2013-01-01

Objective To report on general anesthesia management in amyotrophic lateral sclerosis. Case Presentation and Intervention A 47-year-old man presented with fracture of the humerus. The patient was diagnosed with amyotrophic lateral sclerosis. General anesthesia was induced with propofol, rocuronium and remifentanil. After uneventful surgical repair, TOF (train-of-four) ratio reached >0.90 at the end of operation. However, muscle strength and tidal volume were inadequate. After sugammadex 2 mg kg−1 i.v. was given, the patient was extubated 120 s later. Conclusion This case highlights that rocuronium and sugammadex can be used safely in patients with amyotrophic lateral sclerosis undergoing surgery with general anesthesia. PMID:23075763