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Sample records for paciente con neurofibromatosis

  1. Neurofibromatosis

    MedlinePlus

    ... can become cancerous. There are three types of neurofibromatosis: Type 1 (NF1) causes skin changes and deformed bones. It usually starts in childhood. Sometimes the symptoms are present at birth. Type 2 (NF2) causes hearing loss, ringing in the ears, ...

  2. Neurofibromatosis 2

    MedlinePlus

    Neurofibromatosis 2 (NF2) is a genetic disorder in which tumors form on the nerves of the brain and ... Ferner RE. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first ... PMID: 17362838 www.ncbi.nlm.nih.gov/pubmed/17362838 . Sahin ...

  3. Segmental neurofibromatosis.

    PubMed

    Galhotra, Virat; Sheikh, Soheyl; Jindal, Sanjeev; Singla, Anshu

    2014-07-01

    Segmental neurofibromatosis is a rare disorder, characterized by neurofibromas or cafι-au-lait macules limited to one region of the body. Its occurrence on the face is extremely rare and only few cases of segmental neurofibromatosis over the face have been described so far. We present a case of segmental neurofibromatosis involving the buccal mucosa, tongue, cheek, ear, and neck on the right side of the face. PMID:25565748

  4. Neurofibromatosis 2

    MedlinePlus

    NF2; Bilateral acoustic neurofibromatosis; Central bilateral acoustic NF ... NF2 include: Brain and spinal tumors Hearing-related (acoustic) tumors Skin tumors Tests include: Genetic testing Medical ...

  5. Segmental neurofibromatosis.

    PubMed

    Adigun, Chris G; Stein, Jennifer

    2011-01-01

    A 59-year-old man presented for evaluation and excision of non-tender, fleshy nodules that were arranged in a dermatomal distribution from the left side of the chest to the left axilla. A biopsy specimen of a nodule was consistent with a neurofibroma. Owing to the lack of other cutaneous findings, the lack of a family history of neurofibromatosis, and the dermatomal distribution of the neurofibromas, this patient met the criteria for a diagnosis of segmental neurofibromatosis (SNF) according to Riccardi's definition of SNF and classification of neurofibromatosis. Because the patient has no complications of neurofibromatosis 1 no medical treatment is required. PMID:22031651

  6. Segmental neurofibromatosis.

    PubMed

    Toy, Brian

    2003-10-01

    Segmental neurofibromatosis is a rare variant of neurofibromatosis in which skin lesions are confined to a circumscribed body segment. A case of a 72-year-old woman with this condition is presented. Clinical features and genetic evidence are reviewed. PMID:14594599

  7. Segmental neurofibromatosis.

    PubMed

    Sobjanek, Michał; Dobosz-Kawałko, Magdalena; Michajłowski, Igor; Pęksa, Rafał; Nowicki, Roman

    2014-12-01

    Segmental neurofibromatosis or type V neurofibromatosis is a rare genodermatosis characterized by neurofibromas, café-au-lait spots and neurofibromas limited to a circumscribed body region. The disease may be associated with systemic involvement and malignancies. The disorder has not been reported yet in the Polish medical literature. A 63-year-old Caucasian woman presented with a 20-year history of multiple, flesh colored, dome-shaped, soft to firm nodules situated in the right lumbar region. A histopathologic evaluation of three excised tumors revealed neurofibromas. No neurological and ophthalmologic symptoms of neurofibromatosis were diagnosed. PMID:25610358

  8. Segmental neurofibromatosis

    PubMed Central

    Dobosz-Kawałko, Magdalena; Michajłowski, Igor; Pęksa, Rafał; Nowicki, Roman

    2014-01-01

    Segmental neurofibromatosis or type V neurofibromatosis is a rare genodermatosis characterized by neurofibromas, café-au-lait spots and neurofibromas limited to a circumscribed body region. The disease may be associated with systemic involvement and malignancies. The disorder has not been reported yet in the Polish medical literature. A 63-year-old Caucasian woman presented with a 20-year history of multiple, flesh colored, dome-shaped, soft to firm nodules situated in the right lumbar region. A histopathologic evaluation of three excised tumors revealed neurofibromas. No neurological and ophthalmologic symptoms of neurofibromatosis were diagnosed. PMID:25610358

  9. [Segmental neurofibromatosis].

    PubMed

    Zulaica, A; Peteiro, C; Pereiro, M; Pereiro Ferreiros, M; Quintas, C; Toribio, J

    1989-01-01

    Four cases of segmental neurofibromatosis (SNF) are reported. It is a rare entity considered to be a localized variant of neurofibromatosis (NF)-Riccardi's type V. Two cases are male and two female. The lesions are located to the head in a patient and the other three cases in the trunk. No family history nor transmission to progeny were manifested. The rest of the organs are undamaged. PMID:2502696

  10. [Bilateral segmental neurofibromatosis].

    PubMed

    Rose, I; Vakilzadeh, F

    1991-12-01

    Segmental neurofibromatosis is a rare type of neurofibromatosis. We report a case of bilateral manifestation, review the literature on this extremely uncommon variant, and discuss the possible causative mechanisms and the genetic risk of segmental neurofibromatosis. PMID:1765491

  11. Segmental neurofibromatosis and malignancy.

    PubMed

    Dang, Julie D; Cohen, Philip R

    2010-01-01

    Segmental neurofibromatosis is an uncommon variant of neurofibromatosis type I characterized by neurofibromas and/or café-au-lait macules localized to one sector of the body. Although patients with neurofibromatosis type I have an associated increased risk of certain malignancies, malignancy has only occasionally been reported in patients with segmental neurofibromatosis. The published reports of patients with segmental neurofibromatosis who developed malignancy were reviewed and the characteristics of these patients and their cancers were summarized. Ten individuals (6 women and 4 men) with segmental neurofibromatosis and malignancy have been reported. The malignancies include malignant peripheral nerve sheath tumor (3), malignant melanoma (2), breast cancer (1), colon cancer (1), gastric cancer (1), lung cancer (1), and Hodgkin lymphoma (1). The most common malignancies in patients with segmental neurofibromatosis are derived from neural crest cells: malignant peripheral nerve sheath tumor and malignant melanoma. The incidence of malignancy in patients with segmental neurofibromatosis may approach that of patients with neurofibromatosis type I. PMID:21137621

  12. Encefalitis por anticuerpos contra el receptor de NMDA: experiencia con seis pacientes pediátricos. Potencial eficacia del metotrexato

    PubMed Central

    Bravo-Oro, Antonio; Abud-Mendoza, Carlos; Quezada-Corona, Arturo; Dalmau, Josep; Campos-Guevara, Verónica

    2016-01-01

    Introducción La encefalitis por anticuerpos contra el receptor de N-metil-D-aspartato (NMDA) es una entidad cada vez más diagnosticada en edad pediátrica. A diferencia de los adultos, en muchos casos no se asocia a tumores y las manifestaciones iniciales en niños más frecuentes son crisis convulsivas y trastornos del movimiento, mientras que en los adultos predominan las alteraciones psiquiátricas. Casos clínicos Presentamos seis casos pediátricos confirmados con anticuerpos contra la subunidad NR1 del receptor de NMDA en suero y líquido cefalorraquídeo. Cinco de los casos comenzaron con crisis convulsivas como manifestación clínica inicial antes de desarrollar el cuadro clásico de esta entidad. En todos los casos se utilizaron esteroides como primera línea de tratamiento, con los que sólo se observó control de las manifestaciones en uno, por lo que el resto de los pacientes requirió inmunomoduladores de segunda línea. Todos los pacientes recibieron metotrexato como tratamiento inmunomodulador para evitar recaídas y la evolución fue a la mejoría en todos ellos. Conclusiones En nuestra serie de pacientes con encefalitis por anticuerpos contra el receptor de NMDA, ninguno se asoció a tumores. Todos los casos recibieron metotrexato por lo menos durante un año, no observamos eventos adversos clínicos ni por laboratorio, ni hubo secuelas neurológicas ni recaídas durante el tratamiento. Aunque es una serie pequeña y es deseable incrementar el número y tiempo de evolución, consideramos el metotrexato una excelente alternativa como tratamiento inmunomodulador para esta patología. PMID:24150952

  13. Pruebas de BRCA en pacientes jóvenes con cáncer

    Cancer.gov

    Pruebas de mutaciones genéticas fuertemente asociadas con un mayor riesgo de cáncer de seno han aumentado dramáticamente entre mujeres menores de 40 años diagnosticadas con la enfermedad, según un nuevo estudio.

  14. Tensión postraumática relacionada con el cáncer (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos acerca de la tensión postraumática y los síntomas relacionados en los pacientes con cáncer, sobrevivientes del cáncer y miembros de la familia. Se discuten la evaluación y el tratamiento de estos síntomas.

  15. [Eye involvement in neurofibromatosis].

    PubMed

    Baier, M; Pitz, S

    2016-05-01

    Neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2) are characterized by an autosomal dominant pattern of inheritance with irregular penetrance and a broad spectrum of different clinical phenotypes. There are large variations in the age of onset, progression and prognosis. Symptoms are often manifested early in childhood. Characteristics which the two main forms NF1 and NF2 have in common are a positive family history, characteristic skin alterations, such as café au lait macules, axillary or inguinal freckling and neural tumors such as neurofibroma and optic glioma (NF1) as well as (bilateral) vestibular schwannomas (NF2). An interdisciplinary cooperation is necessary for the diagnostics and therapy. PMID:27142037

  16. Mosaic neurofibromatosis type 1.

    PubMed

    Liang, Christine; Schaffer, Julie V

    2008-01-01

    A 24-year-old man presented with numerous lentigines and multiple cafe-au-lait macules on both sides of the face, neck, and trunk as well as on the proximal area of the upper extremities and in the axillae. The pigmented lesions had a Blaschko-linear distribution on the upper trunk and were limited to the left side of the abdomen, with a sharp demarcation at the midline. Multiple, cutaneous neurofibromas were found on the trunk, and ophthalmologic examination showed a Lisch nodule in the left iris. The clinical findings and their widespread but segmental distribution were consistent with a diagnosis of mosaic neurofibromatosis type 1. PMID:18627742

  17. [Neurofibromatosis type 2].

    PubMed

    Pérez-Grau, Marta; Miró, Núria; Prades, José; Vergés, Juan; Lareo, Susana; Roca-Ribas, Francesc

    2010-01-01

    Type 2 neurofibromatosis (NF2) is an invalidating, inherited, dominant, autosomal disease. It is commonly confused with type 1 neurofibromatosis, although the two disorders are different. All subjects who inherit a mutated NF2 gene will develop the disease, which is characterised by the growth of schwannomas, generally affecting the vestibular nerve bilaterally, as well as meningiomas and other benign central nervous system tumours, before their third decade of life. It is currently possible to identify the NF2 mutation in most affected families. Up to about 20% of NF2 patients with no family history, apparently sporadic cases, are actually individuals with mosaicism for this mutation. Much of the morbidity from these tumours results from their treatment, which is primarily surgical. Small vestibular schwannomas can often be completely resected with preservation of both hearing and facial function. In case of large tumours it is possible to place a cochlear or brain stem implant during the schwannoma surgery. Age at diagnosis, the presence of intracranial meningiomas, and whether the patient was treated at a specialty centre or not, have been cited as the strongest prognostic factors. PMID:20138250

  18. Segmental neurofibromatosis [NF type - v].

    PubMed

    Arfan-ul-Bari; Simeen-ber-Rahman

    2003-12-01

    Segmental neurofibromatosis is a rare variant of neurofibromatosis in which skin lesions are confined to a circumscribed body segment. A case of a 39-year-old man with this condition is presented, who was having multiple soft skin tumours over a localized area of back with no associated cafe au lait spots, axillary freckles or lish nodules. Histology confirmed the diagnosis of neurofibroma. PMID:15569561

  19. Neurofibromatosis. Clinical overview.

    PubMed

    Brill, C B

    1989-08-01

    Neurofibromatosis is a relatively common genetic disorder of the peripheral and central nervous systems. Virtually all organ systems can be involved, either directly or through neural or vascular influences. Children and adults may be affected; management may become difficult due to mental retardation, learning and behavior disorders, and seizures. Because the condition is inherited in autosomal-dominant fashion, one may have to deal with family members who also have these medical, neurologic, and psychologic problems. Benign or malignant tumors may be found in the brain, spinal cord, and somatic and autonomic peripheral nerves. Malignant tumors may involve the airway, the gastrointestinal tract, the genitourinary tract, and the blood vessels. Clinicians caring for these patients must be aware of these protean manifestations in addition to problems involving their own areas of expertise. PMID:2502339

  20. Perioperative Management of Neurofibromatosis Type 1

    PubMed Central

    Fox, Charles J.; Tomajian, Samir; Kaye, Aaron J.; Russo, Stephanie; Abadie, Jacqueline Volpi; Kaye, Alan D.

    2012-01-01

    Neurofibromatosis type 1 (neurofibromatosis-1), a relatively common single-gene disorder, is caused by a mutation of the NF1 gene that results in a loss of activity or in a nonfunctional neurofibromin protein. Clinical anesthesiologists may find patients with neurofibromatosis-1 challenging because this condition may affect most organ systems and result in a wide variety of presentations and clinical implications. Current neurofibromatosis-1 research studies include genotype-phenotype correlations, investigation of the pathoetiology behind the different clinical manifestations of neurofibromatosis-1, and the search for treatment options for the different features of the disorder. Neurofibromatosis-1–associated complications of the central nervous, respiratory, cardiovascular, musculoskeletal, and gastrointestinal and genitourinary systems all present various degrees of considerations for anesthesiologists. Additionally, neurofibromatosis-1 has dramatic implications for pregnant women. PMID:22778675

  1. Neurofibromatosis type 2.

    PubMed

    Evans, D G R

    2015-01-01

    Type 2 neurofibromatosis (NF2) is an autosomal dominant disorder caused by mutations in the NF2 tumor suppressor gene NF2 on chromosome 22. Around 1 in 33000 people are born with an NF2 mutation although more than one-third of the 60% of de novo cases are not conceived with the mutation but this develops later in embryogenesis (mosaics). NF2 has a substantial effect on life expectancy and individuals with a constitutional truncating mutation have the worst prognosis. The vast majority of people with NF2 will develop bilateral vestibular schwannomas with many developing schwannomas on other cranial, spinal and peripheral nerves. Cranial and spinal meningiomas and intraspinal low grade indolent ependymomas are the other major tumor features. Cutaneous features can be subtle with only 70% having evidence of intracutaneous plaque-like schwannomas or subcutaneous lesions on peripheral nerves. Café-au-lait patches are more frequent than in the general population but in only around 1% will meet NIH criteria for NF1. PMID:26564072

  2. Un programa innovador busca ayudar a las personas que cuidan a pacientes con cáncer

    Cancer.gov

    Artículo sobre un programa educativo del City of Hope Cancer Center que ofrece a los profesionales de salud la información y las herramientas necesarias para ayudar a los familiares a saber cómo cuidarse a si mismos y a sus seres queridos con cáncer.

  3. Segmental neurofibromatosis: report of 3 cases.

    PubMed

    Mansur, Ayşe Tülin; Göktay, Fatih; Akkaya, Ayşe Deniz; Güneş, Pembegül

    2011-01-01

    Segmental neurofibromatosis (SNF) is an uncommon variant of neurofibromatosis type 1 (NF-1) that is characterized by café au lait spots, freckles, and/or neurofibromas limited to a body segment. In this report we describe 3 adult patients with SNF who presented with only neurofibromas. Although 2 patients had no systemic involvement, the third patient had hypertrophic cardiomyopathy, a cardiologic abnormality that is associated with neurofibromatosis. PMID:21323101

  4. Neurofibromatosis: part 2--clinical management.

    PubMed

    Batista, Pollyanna Barros; Bertollo, Eny Maria Goloni; Costa, Danielle de Souza; Eliam, Lucas; Cunha, Karin Soares Gonçalves; Cunha-Melo, José Renan; Darrigo Junior, Luiz Guilherme; Geller, Mauro; Gianordoli-Nascimento, Ingrid Faria; Madeira, Luciana Gonçalves; Mendes, Hérika Martins; Miranda, Débora Marques de; Mata-Machado, Nikolas Andre; Morato, Eric Grossi; Pavarino, Érika Cristina; Pereira, Luciana Baptista; Rezende, Nilton Alves de; Rodrigues, Luíza de Oliveira; Sette, Jorge Bezerra Cavalcanti

    2015-06-01

    Part 1 of this guideline addressed the differential diagnosis of the neurofibromatoses (NF): neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH). NF shares some features such as the genetic origin of the neural tumors and cutaneous manifestations, and affects nearly 80 thousand Brazilians. Increasing scientific knowledge on NF has allowed better clinical management and reduced rate of complications and morbidity, resulting in higher quality of life for NF patients. Most medical doctors are able to perform NF diagnosis, but the wide range of clinical manifestations and the inability to predict the onset or severity of new features, consequences, or complications make NF management a real clinical challenge, requiring the support of different specialists for proper treatment and genetic counseling, especially in NF2 and SCH. The present text suggests guidelines for the clinical management of NF, with emphasis on NF1. PMID:26083891

  5. Hearing Restoration in Neurofibromatosis Type II Patients

    PubMed Central

    Lee, Jeon Mi; Chang, Jin Woo; Choi, Jae Young

    2016-01-01

    Patients with neurofibromatosis type II will eventually succumb to bilateral deafness. For patients with hearing loss, modern medical science technology can provide efficient hearing restoration through a number of various methods. In this article, several hearing restoration methods for patients with neurofibromatosis type II are introduced. PMID:27189272

  6. Neurofibromatosis, Down's syndrome, and acquired abnormalities

    PubMed Central

    Ali, Syed Yousuf; Manne, Vimala; Manne, Ranjit; Himani, Chennamaneni

    2016-01-01

    We report a patient with Down's syndrome and neurofibromatosis who presented with a keloid, sebaceous cyst and acanthosis nigricans, along with dental and ophthalmological defects. The coexistence of neurofibromatosis type 1 and Down's syndrome which are two unrelated genetic conditions is itself a rarity. PMID:27294059

  7. Neurofibromatosis, Down's syndrome, and acquired abnormalities.

    PubMed

    Ali, Syed Yousuf; Manne, Vimala; Manne, Ranjit; Himani, Chennamaneni

    2016-01-01

    We report a patient with Down's syndrome and neurofibromatosis who presented with a keloid, sebaceous cyst and acanthosis nigricans, along with dental and ophthalmological defects. The coexistence of neurofibromatosis type 1 and Down's syndrome which are two unrelated genetic conditions is itself a rarity. PMID:27294059

  8. Hearing Restoration in Neurofibromatosis Type II Patients.

    PubMed

    Lee, Jeon Mi; Chang, Jin Woo; Choi, Jae Young; Chang, Won Seok; Moon, In Seok

    2016-07-01

    Patients with neurofibromatosis type II will eventually succumb to bilateral deafness. For patients with hearing loss, modern medical science technology can provide efficient hearing restoration through a number of various methods. In this article, several hearing restoration methods for patients with neurofibromatosis type II are introduced. PMID:27189272

  9. Bilateral segmental neurofibromatosis diagnosed during pregnancy.

    PubMed

    Maldonado Cid, P; Sendagorta Cudós, E; Noguera Morel, L; Beato Merino, M J

    2011-01-01

    Bilateral segmental neurofibromatosis is a rare subtype of neurofibromatosis type 1 defined by lesions affecting a single segment of the body and crossing the midline, with no systemic involvement. We present a case diagnosed during pregnancy because of the characteristic increase in size of the lesions during this period. PMID:21635828

  10. Genetics Home Reference: neurofibromatosis type 2

    MedlinePlus

    ... tumors associated with neurofibromatosis type 2 are called vestibular schwannomas or acoustic neuromas. These growths develop along ... any age. The most frequent early symptoms of vestibular schwannomas are hearing loss, ringing in the ears ( ...

  11. Vestibular Schwannoma (Acoustic Neuroma) and Neurofibromatosis

    MedlinePlus

    ... Home » Health Info » Hearing, Ear Infections, and Deafness Vestibular Schwannoma (Acoustic Neuroma) and Neurofibromatosis On this page: ... more information about vestibular schwannomas? What is a vestibular schwannoma (acoustic neuroma)? Inner ear with vestibular schwannoma ( ...

  12. Leprosy with neurofibromatosis--a diagnostic dilemma.

    PubMed

    Grover, Chander; Lohra, Manmohan; Nanda, Soni; Reddy, B S N

    2005-03-01

    The coexistence of leprosy with neurofibromatosis is a rare finding and can pose a diagnostic dilemma. Neurofibromatosis coexisting with borderline tuberculoid leprosy has previously not been reported. We report such a case in a 13-year-old boy where biopsy of clinically uninvolved nerve revealed the presence of acid-fast bacilli. A careful diagnostic workup is needed in such cases to ensure proper treatment. Both disorders affect Schwann cells and their relationship merits further consideration. PMID:15881040

  13. Multiple glomus tumors and segmental neurofibromatosis: there are no coincidences.

    PubMed

    Cabral, Rita; Santiago, F; Tellechea, O

    2011-01-01

    Segmental neurofibromatosis is a rare subtype of neurofibromatosis type 1 (NF1). Glomus tumors are uncommon benign tumors. The authors report the association between these two rare conditions, not yet reported. PMID:21426870

  14. A rare case of segmental neurofibromatosis involving the sciatic nerve.

    PubMed

    Trocchia, Aron; Reyes, Alma; Wilson, Jon; Les, Kimberly

    2010-05-01

    Segmental neurofibromatosis (NF-5) is an extremely rare variant of neurofibromatosis involving a single extremity without pathologic features beyond the midline. A case of segmental neurofibromatosis involving the sciatic nerve and its branches is presented with a detailed description of the patient's preoperative findings plus postoperative course through 1-year follow-up. Clinical, histologic, and genetic findings are given along with a brief review of the literature on segmental neurofibromatosis. Last, treatment options and postoperative care recommendations are provided. PMID:20567746

  15. Segmental neurofibromatosis: a rare variant of a common genodermatosis.

    PubMed

    Morais, P; Ferreira, O; Bettencourt, H; Azevedo, F

    2010-10-01

    Segmental neurofibromatosis is a rare disorder characterized by features of neurofibromatosis type 1 circumscribed to a particular body segment. This entity is considered to be the result of a somatic mosaicism and is still under-diagnosed. We report a case of segmental neurofibromatosis and give a brief and up-to-date overview of the disease. PMID:20976418

  16. Neurofibromatosis

    MedlinePlus

    ... Conditions Most Common Searches Adult Strabismus Amblyopia Cataract Conjunctivitis Corneal Abrasions Dilating Eye Drops Lazy eye (defined) ... Loading... Most Common Searches Adult Strabismus Amblyopia Cataract Conjunctivitis Corneal Abrasions Dilating Eye Drops Lazy eye (defined) ...

  17. Neurofibromatosis

    MedlinePlus

    ... transmitting sound sensations to the brain; and the vestibular branch helps people maintain their balance. The characteristic tumors of NF2 are called vestibular schwannomas because of their location and the types ...

  18. Neurofibromatosis

    MedlinePlus

    ... is characterized by slow-growing tumors on the vestibular branch of the right and left eighth cranial nerves, which are called vestibular schwannomas or acoustic neuromas.. The tumors press on ...

  19. Neurofibromatosis

    MedlinePlus

    ... Treatment can help control symptoms. Depending on the type of disease and how serious it is, treatment may include surgery to remove tumors, radiation therapy, and medicines. NIH: National Institute of Neurological Disorders and Stroke

  20. Neurofibromatosis

    MedlinePlus

    ... The spots tend to increase in size and number during the first 10 years of life. Nodule(s) on the skin may develop at any age [See figure 1]. • Eye findings: The ... the iris may increase in number over time. These spots are called Lisch nodules ...

  1. Segmental neurofibromatosis: a report of 3 cases.

    PubMed

    Gabhane, Sushma Kashinath; Kotwal, Mrunmayi Nishikant; Bobhate, Sudhakar K

    2010-01-01

    Neurofibromatosis is a genetic disorder of neural crest-derived cells that primarily affect growth of neural tissues. It is broadly divided into three categories: (a) von Recklinghausen's neurofibromatosis or NF-1, (b) bilateral acoustic neuroma (NF-2), and (c) all other neurofibromatoses, including alternate or atypical forms of the disease. The patients with generalized form of NF1 are characterized by multiple café-au-lait spots and neurofibromas and diagnosed easily. But when an individual has small number of lesions in a limited region of the body it could be neglected by the patient or not be recognized by the clinicians as a segmental form of neurofibromatosis. We describe three cases of segmental neurofibromatosis (SNF). These cases have been classified as segmental NF according to Riccardi's definition of SNF and classification of neurofibromatosis. Segmental form of NF may evolve into a complete form over time. Also, this disorder may be transmitted to the offspring's of these individuals. Hence genetic counseling of these individuals must include these facts. PMID:20418991

  2. Personal de enfermería asume diversas funciones con expansión de programas de gestión para pacientes

    Cancer.gov

    Artículo sobre los profesionales de enfermería oncológica que ayudan a los pacientes durante todas las etapas de la atención oncológica, desde los exámenes de detección y el diagnóstico, hasta el tratamiento y la supervivencia.

  3. Neurofibromatosis type 1 and pregnancy.

    PubMed

    Dugoff, L; Sujansky, E

    1996-12-01

    Neurofibromatosis Type 1 (NF-1) is an autosomal dominant condition which has markedly variable clinical expression, with manifestations ranging from mild cutaneous lesions to severe orthopedic complications and functional impairment. The current obstetrical literature indicates that women with NF-1 have increased complications associated with pregnancy. However, the majority of publications are case reports involving no more than 11 patients each, and are likely biased toward reporting on cases in which complications occurred. This study presents data on pregnancy outcome in 105 women with NF-1. The data were obtained from questionnaires completed by the study participants, and by review of their pregnancy and peripartum medical records. The 105 women had a total of 247 pregnancies, resulting in 182 live births, 44 first trimester spontaneous abortions, 21 elective terminations, and 2 ectopic pregnancies. There were two sets of twins. The cesarean section rate in our series (36%) was greater than the general population rate (9.1-23.5%). In 7 of these patients, the cesarean section was required because of maternal NF-1 complications. The study did not show the previously reported increased incidence of preeclampsia, preterm delivery, intrauterine growth restriction, pregnancy-induced hypertension, stillbirth, spontaneous abortion, or perinatal mortality. Sixty-four (60%) of the one hundred five women reported growth of new neurofibromas during pregnancy and fifty-five (52%) noted enlargement of existing neurofibromas. Nineteen women observed no changes in the size of their neurofibromas and no growth of new neurofibromas during pregnancy. PMID:8957502

  4. The Pathoetiology of Neurofibromatosis 1

    PubMed Central

    Jouhilahti, Eeva-Mari; Peltonen, Sirkku; Heape, Anthony M.; Peltonen, Juha

    2011-01-01

    Although a mutation in the NF1 gene is the only factor required to initiate the neurocutaneous-skeletal neurofibromatosis 1 (NF1) syndrome, the pathoetiology of the multiple manifestations of this disease in different organ systems seems increasingly complex. The wide spectrum of different clinical phenotypes and their development, severity, and prognosis seem to result from the cross talk between numerous cell types, cell signaling networks, and cell–extracellular matrix interactions. The bi-allelic inactivation of the NF1 gene through a “second hit” seems to be of crucial importance to the development of certain manifestations, such as neurofibromas, café-au-lait macules, and glomus tumors. In each case, the second hit involves only one cell type, which is subsequently clonally expanded in a discrete lesion. Neurofibromas, which are emphasized in this review, and cutaneous neurofibromas in particular, are known to contain a subpopulation of NF1-diploinsufficient Schwann cells and a variety of NF1-haploinsufficient cell types. A recent study identified a multipotent precursor cell population with an NF1+/− genotype that resides in human cutaneous neurofibromas and that has been suggested to play a role in their pathogenesis. PMID:21457932

  5. [Bilateral segmental neurofibromatosis simulating epidermal nevus].

    PubMed

    Gambichler, T; Küster, W; Wolter, M; Rapp, S; Altmeyer, P; Hoffmann, K

    2000-11-01

    Neurofibromatosis is a neuroectodermal systemic disease. A rare variant of this condition is bilateral segmental neurofibromatosis. A 29-year-old man presented with bilateral papillomatous plaques in the lumbar dermatomes. Clinically, the lesions were very similar to an epidermal nevus but histologic examination revealed superficial neurofibromas. Family history, ophthalmologic and neurologic investigations were unremarkable. The unusual morphologic presentation of bilateral segmental neurofibromas in this case points to the wide clinical spectrum of the disease and the significance of histologic examination in systematic nevoid lesions. PMID:11116852

  6. Genetics Home Reference: neurofibromatosis type 1

    MedlinePlus

    ... of neurofibromatosis type 1. Semin Pediatr Neurol. 2006 Mar;13(1):8-20. Review. Citation on PubMed ... PubMed Rose VM. Neurocutaneous syndromes. Mo Med. 2004 Mar-Apr;101(2):112-6. Review. Citation on ...

  7. Impact of neurofibromatosis type 1 on school performance.

    PubMed

    Krab, Lianne C; Aarsen, Femke K; de Goede-Bolder, Arja; Catsman-Berrevoets, Coriene E; Arts, Willem F; Moll, Henriette A; Elgersma, Ype

    2008-09-01

    School functioning of 86 Dutch neurofibromatosis type 1 children (7-17 years) using teacher questionnaires was analyzed to determine the impact of neurofibromatosis type 1 on school performance. In all, 75% of the neurofibromatosis type 1 children performed more than 1 standard deviation below grade peers in at least one of the domains of spelling, mathematics, technical reading or comprehensive reading. Furthermore, neurofibromatosis type 1 children had a 4-fold increased risk for attending special education and a 6-fold increased risk for receiving remedial teaching for learning, behavior, speech, or motor problems. Children without apparent learning disabilities still frequently displayed neuropsychological deficits. Only 10% of the children did not show any school-functioning problems. Finally, it was found that the clinical severity of neurofibromatosis type 1 correlated with the cognitive deficits. Taken together, it was shown that neurofibromatosis type 1 has profound impact on school performance. Awareness of these problems may facilitate timely recognition and appropriate support. PMID:18827266

  8. Segmental neurofibromatosis and cancer: report of triple malignancy in a woman with mosaic Neurofibromatosis 1 and review of neoplasms in segmental neurofibromatosis.

    PubMed

    Cohen, Philip R

    2016-01-01

    BackgroundSegmental neurofibromatosis, referred to as mosaic neurofibromatosis 1, patients present with neurofibromas or café au lait macules or both in a unilateral segment of the body.PurposeA woman with segmental neurofibromatosis and triple cancer (renal cell carcinoma, mixed thyroid carcinoma, and lentigo maligna) is described and cancers observed in patients with segmental neurofibromatosis are reviewed.MethodsPubMed was used to search the following terms, separately and in combination: cancer, malignancy, mosaic, neoplasm, neurofibroma, neurofibromatosis, segment, segmental, tumor.ResultsMalignancy (13 cancers) has been observed in 11 segmental neurofibromatosis patients; one patient had three different cancers. The most common neoplasms were of neural crest origin {malignant peripheral nerve sheath tumor (3 patients) and melanoma (3 patients)] and gastrointestinal tract origin [colon (1 patient) and gastric (1 patient)]. Breast cancer, Hodgkin lymphoma, lung cancer, kidney cancer, and thyroid cancer each occurred in one patient.ConclusionsSimilar to patients with von Recklinghausen neurofibromatosis 1, individuals with segmental neurofibromatosis also have a genodermatosis-associated increased risk of developing cancer. PMID:27617721

  9. Segmental neurofibromatosis associated with renal angiomyolipomas.

    PubMed

    Nguyen, Kim-Tan; Chiu, Melvin

    2008-07-01

    Segmental neurofibromatosis (SN) is a rare disorder characterized by neurofibromas or neurofibromas with café-au-lait spots limited to one region of the body without crossing the midline. Renal angiomyolipomas (AMLs) are rare benign neoplasms usually found in association with tuberous sclerosis (TS). Similar to neurofibromatosis (NF), TS has a high spontaneous mutation rate and a family history often is absent. Although both are autosomal dominant diseases with neural involvement, there are few reports in the literature demonstrating a link between the 2 disorders. We report a case of SN associated with renal AMLs. To our knowledge, there has been only 1 prior report of renal AML associated with NF type 1 (NF1), and there have been no prior reports of SN associated with AML. PMID:18712027

  10. Neurofibromatosis: chronological history and current issues*

    PubMed Central

    Antônio, João Roberto; Goloni-Bertollo, Eny Maria; Trídico, Lívia Arroyo

    2013-01-01

    Neurofibromatosis, which was first described in 1882 by Von Recklinghausen, is a genetic disease characterized by a neuroectodermal abnormality and by clinical manifestations of systemic and progressive involvement which mainly affect the skin, nervous system, bones, eyes and possibly other organs. The disease may manifest in several ways and it can vary from individual to individual. Given the wealth of information about neurofibromatosis, we attempted to present this information in different ways. In the first part of this work, we present a chronological history, which describes the evolution of the disease since the early publications about the disorder until the conclusion of this work, focusing on relevant aspects which can be used by those wishing to investigate this disease. In the second part, we present an update on the various aspects that constitute this disease. PMID:23793209

  11. Mouse Models of Neurofibromatosis 1 and 21

    PubMed Central

    Gutmann, David H; Giovannini, Marco

    2002-01-01

    Abstract The neurofibromatoses represent two of the most common inherited tumor predisposition syndromes affecting the nervous system. Individuals with neurofibromatosis 1 (NF1) are prone to the development of astrocytomas and peripheral nerve sheath tumors whereas those affected with neurofibromatosis 2 (NF2) develop schwannomas and meningiomas. The development of traditional homozygous knockout mice has provided insights into the roles of the NF1 and NF2 genes during development and in differentiation, but has been less instructive regarding the contribution of NF1 and NF2 dysfunction to the pathogenesis of specific benign and malignant tumors. Recent progress employing novel mouse targeting strategies has begun to illuminate the roles of the NF1 and NF2 gene products in the molecular pathogenesis of NF-associated tumors. PMID:12082543

  12. Optimizing biologically targeted clinical trials for neurofibromatosis

    PubMed Central

    Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J

    2014-01-01

    Introduction The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2. Areas covered Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution. Expert opinion The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy. PMID:23425047

  13. A Neuropsychological Perspective on Attention Problems in Neurofibromatosis Type 1

    ERIC Educational Resources Information Center

    Templer, Alexandra K.; Titus, Jeffrey B.; Gutmann, David H.

    2013-01-01

    Cognitive problems are common in children with neurofibromatosis type 1 and they can often complicate treatment. The current literature review examines cognitive functioning in neurofibromatosis type 1, with a specific focus on executive functioning. This includes exploration of how deficits in executive functioning are expressed in children with…

  14. Segmental neurofibromatosis of the hand and upper extremity: a case report.

    PubMed

    Ilyas, Asif M; Nourissat, Geoffroy; Jupiter, Jesse B

    2007-12-01

    A case of segmental neurofibromatosis of the upper extremity is presented. Multiple neurofibromas involving different peripheral nerves limited to a single body part or limb is a rare form of neurofibromatosis. The clinical, genetic, and histologic findings of segmental neurofibromatosis are described. The criteria for segmental neurofibromatosis are reviewed, and the differentiation of neurofibromatosis types 1 and 2 and schwannomatosis is also briefly reviewed. PMID:18070641

  15. Association between atypical parathyroid adenoma and neurofibromatosis.

    PubMed

    Favere, Aline Mesquita Ferreira de; Tsukumo, Daniela Miti; Matos, Patrícia Sabino de; Santos, Sérgio Luiz Marques dos; Lalli, Cristina Alba

    2015-10-01

    Primary hyperparathyroidism is a disease characterized by excessive production of parathyroid hormone (PTH), which is due to a parathyroid adenoma in 85% of cases. An atypical parathyroid adenoma, with some histopathological features of parathyroid carcinoma, may be found in some of the cases, although it may not fulfill all the criteria for this diagnosis. Neurofibromatosis type 1 (NF1) is an autosomal dominant systemic disease that may be associated with hyperparathyroidism. We report here the rare combination of a patient with NF1 and clinical manifestations of hyperparathyroidism due to an atypical parathyroid adenoma. PMID:26421674

  16. AUTOIMMUNE HYPOTHYROIDISM IN PATIENT WITH NEUROFIBROMATOSIS-1.

    PubMed

    Faraz, Ahmed; Nafees, Taha; Ahmed, Syed Arsalan; Rizvi, Shahraiz Shah

    2015-01-01

    A 53 year old woman, diagnosed with Neurofibromatosis I with multiple neurfibromas over trunk, upper limb & lower limb, she had café au lait spots on her abdomen skin. She was admitted to the tertiary care setup with the complains of cold intolerance, numbness in the limbs, high blood pressure & constipation, patient also had complain of weight gain, lab revealed high TSH, low Free thyroid hormones & positive anti thyroglobulin antibodies. Case was diagnosed with autoimmune hypothyroidism. This is the first case reported with such association of these two diseases. PMID:27004358

  17. CT of sarcomatous degeneration in neurofibromatosis

    SciTech Connect

    Coleman, B.G.; Arger, P.H.; Dalinka, M.K.; Obringer, A.C.; Raney, B.R.; Meadows, A.T.

    1983-02-01

    Neurofibromatosis is a relatively common disorder that often involves many organ systems. One of the least understood aspects of this malady is a well documented potential for sarcomatous degeneration of neurofibromas. The inability to identify patients at risk and the lack of noninvasive screening methods for symptomatic patients often leads to late diagnosis. In six of seven subsequently proven neurofibrosarcomas, CT demonstrated low-density areas that histopathologically appeared to be due to necrosis, hemorrhage, and/or cystic degeneration. The density differences within these sarcomas were enhanced by the intravenous adminstration of iodinated contrast agents.

  18. Mosaic Neurofibromatosis Type 1: A Systematic Review.

    PubMed

    García-Romero, Maria Teresa; Parkin, Patricia; Lara-Corrales, Irene

    2016-01-01

    Confusion is widespread regarding segmental or mosaic neurofibromatosis type 1 (MNF1). Physicians should use the same terms and be aware of its comorbidities and risks. The objective of the current study was to identify and synthesize data for cases of MNF1 published from 1977 to 2012 to better understand its significance and associations. After a literature search in PubMed, we reviewed all available relevant articles and abstracted and synthetized the relevant clinical data about manifestations, associated findings, family history and genetic testing. We identified 111 articles reporting 320 individuals. Most had pigmentary changes or neurofibromas only. Individuals with pigmentary changes alone were identified at a younger age. Seventy-six percent had localized MNF1 restricted to one segment; the remainder had generalized MNF1. Of 157 case reports, 29% had complications associated with NF1. In one large case series, 6.5% had offspring with complete NF1. The terms "segmental" and "type V" neurofibromatosis should be abandoned, and the correct term, mosaic NF1 (MNF1), should be used. All individuals with suspected MNF1 should have a complete physical examination, genetic testing of blood and skin, counseling, and health surveillance. PMID:26338194

  19. Ullrich-Turner syndrome and neurofibromatosis-1

    SciTech Connect

    Schorry, E.K.; Lovell, A.M.; Saal, H.M.; Milatovich, A.

    1996-12-30

    There is a well-known association between neurofibromatosis-1 (NF1) and Noonan syndrome-like manifestations, including short stature, short broad neck, and hypertelorism. These anomalies are thought to be due to variable expression of the NF1 gene. We report on two girls with NF1 who were found to have the Ullrich-Turner syndrome. Case 1, a 12-year-old white girl, was followed in a Neurofibromatosis Clinic because of multiple cafe-au-lait spots and a family history of NF1 in her mother and sister. On examination, she had short stature, hypertelorism, and short neck with low posterior hairline. Karyotype was 86% 46,XY/14% 45,X. Case 2, the first child of a woman with NF1, presented at birth with lymphedema of hands and feet and a short broad neck. Karyotype was 45,X. At age 23 months she was short, had epicanthic folds, hypertelorism, narrow palate, right simian crease, 19 cafe-au-lait spots, and axillary freckling. We conclude that chromosome studies should be performed in girls with NF1 who have short stature and Noonan- or Ullrich-Turner-like findings. Dilemmas raised by the dual diagnoses of NF1 and Ullrich-Turner syndrome include potential risks of growth hormone therapy and estrogen replacement therapy. 14 refs., 2 figs.

  20. Breast lesions in generalized neurofibromatosis: breast cancer and cystosarcoma phylloides.

    PubMed

    el-Zawahry, M D; Farid, M; Abd el-Latif, A; Horeia, H; el-Gindy, M; Twakal, G

    1989-01-01

    This report describes three cases from one surgical unit of the Mansoura Teaching Hospital of Cairo, Egypt, with generalized neurofibromatosis and associated breast lesions. Two patients had carcinoma of the breast and the third had cystosarcoma phylloides. PMID:2560398

  1. A case of late-onset segmental neurofibromatosis.

    PubMed

    McLimore, Heather; McCaughey, Cort; Vanness, Erin

    2014-04-01

    Segmental neurofibromatosis (NF5) is a rare variant of neurofibromatosis. To our knowledge, there have been few reports of cases presenting later in life. The recognition of NF5 is important, as there have been reports of paraneoplastic manifestations and transmission to offspring. Here we present the case of a patient who presented with NF5 first appearing in her mid-50s. This case illustrates the subtle nature of NF5, which often leads to misdiagnosis. PMID:24908902

  2. Pheochromocytoma and Neurofibromatosis Type 1 in a Patient with Hypertension

    PubMed Central

    Petrovska, Julijana; Kitanovska, Biljana Gerasimovska; Bogdanovska, Stevka; Kuzmanoska, Svetlana Pavleska

    2015-01-01

    BACKGROUND: Neurofibromatosis type 1 is an autosomal dominant condition that has a variety of clinical manifestations. Essential or secondary hypertension may be associated with neurofibromatosis. A rare finding is hypertension due to pheochromocytoma in patient with neurofibromatosis type 1. CASE REPORT: We present a case with a 7-year medical history of hypertension which was poorly controlled and with wide variations of blood pressure before the examination. Investigations did not reveal a secondary cause of hypertension. After the physical examination and establishing the diagnosis of neurofibromatosis, as well as the history of symptomes suggestive of catecholamine discharge, diagnostic procedures for pheochromocytoma were undertaken. Abdominal CT and MRI have proven the presence of a right adrenal tumor mass which was suspected to be a pheochromocytoma. Patient was preoperatively treated for two weeks with alpha and beta blokers and right adrenalectomy was performed. Perioperatively and on a longer term, blood pressure remained well controlled with less antihypertensive therapy. Diagnosis and management of pheochromocytoma in neurofibromatosis involves a dermatologist, endocrinologist, nephrologist and an urologist and requires a well-coordinated multidisciplinary approach. CONCLUSIONS: Pheochromocytoma, although a rare condition in patients with neurofibromatosis, may be a cause for uncontrolled hypertension, as well as other cardiovascular complications and the clinician should do all available clinical investigations to confirm it or exclude it on time. PMID:27275314

  3. Neurofibromatosis Type 1: Modeling CNS Dysfunction

    PubMed Central

    Gutmann, David H.; Parada, Luis F.; Silva, Alcino J.; Ratner, Nancy

    2012-01-01

    Neurofibromatosis type 1 (NF1) is the most common monogenic disorder in which individuals manifest central nervous system (CNS) abnormalities. Affected individuals develop glial neoplasms (optic gliomas, malignant astrocytomas) and neuronal dysfunction (learning disabilities, attention deficits). Nf1 genetically-engineered mouse models have revealed the molecular and cellular underpinnings of gliomagenesis, attention deficit, and learning problems with relevance to basic neurobiology. Using NF1 as a model system, these studies have revealed critical roles for the NF1 gene in non-neoplastic cells in the tumor microenvironment, the importance of brain region heterogeneity, novel mechanisms of glial growth regulation, the neurochemical bases for attention deficit and learning abnormalities, and new insights into neural stem cell function. Here we review recent studies, presented at a symposium at the 2012 Society for Neuroscience annual meeting, that highlight unexpected cell biology insights into RAS and cyclic AMP pathway effects on neural progenitor signaling, neuronal function, and oligodendrocyte lineage differentiation. PMID:23055477

  4. A unique case of hereditary bilateral segmental neurofibromatosis on the face.

    PubMed

    Jankovic, Irena; Kovacevic, Predrag; Visnjic, Milan; Jankovic, Dimitrije; Velickovic, Milena

    2012-01-01

    Segmental neurofibromatosis is a rare clinical finding generally with no family history and facial involvement. There are four subtypes of segmental neurofibromatosis: true segmental, localized cases with deep involvement, hereditary segmental and bilateral segmental neurofibromatosis. Here we report three patients from the same family (father, son and granddaughter) with segmental bilateral neurofibromatosis on the face. This form has not been noticed in the literature. PMID:23197210

  5. A unique case of hereditary bilateral segmental neurofibromatosis on the face*

    PubMed Central

    Jankovic, Irena; Kovacevic, Predrag; Visnjic, Milan; Jankovic, Dimitrije; Velickovic, Milena

    2012-01-01

    Segmental neurofibromatosis is a rare clinical finding generally with no family history and facial involvement. There are four subtypes of segmental neurofibromatosis: true segmental, localized cases with deep involvement, hereditary segmental and bilateral segmental neurofibromatosis. Here we report three patients from the same family (father, son and granddaughter) with segmental bilateral neurofibromatosis on the face. This form hasn't noticed in the literature. PMID:23197210

  6. Familiares a cargo de pacientes de cáncer (PDQ®)—Versión para pacientes

    Cancer.gov

    Sumario informativo revisado por expertos acerca de los desafíos que enfrentan los familiares a cargo de los pacientes con cáncer. Este resumen se centra en las funciones típicas y las inquietudes de las personas a cargo del paciente y en las intervenciones útiles para esas personas.

  7. NEUROFIBROMATOSIS-RELATED TUMORS: EMERGING BIOLOGY AND THERAPIES

    PubMed Central

    Karajannis, Matthias A.; Ferner, Rosalie E.

    2015-01-01

    Purpose of review Over the past decade, substantial insight into the biological function of the tumor suppressors neurofibromin (NF1) and Merlin (NF2) has been gained. The purpose of this review is to highlight some of the major advances in the biology of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) as they relate to the development of novel therapies for these disorders. Recent findings The development of increasingly sophisticated preclinical models over the recent years has provided the platform from which to rationally develop molecular targeted therapies for both NF1 and NF2 related tumors, such as within the Department of Defense-sponsored Neurofibromatosis Clinical Trials Consortium (NFCTC). Summary Clinical trials with molecular targeted therapies have become a reality for NF patients, and hold substantial promise for improving the morbidity and mortality of individuals affected with these disorders. PMID:25490687

  8. Spontaneous Hemothorax in Neurofibromatosis Treated with Percutaneous Embolization

    SciTech Connect

    Arai, Kazunori; Sanada, Junichiro Kurozumi, Akiko; Watanabe, Toshio; Matsui, Osamu

    2007-06-15

    We evaluated the effectiveness of transcatheter arterial coil embolization therapy for the treatment of spontaneous hemothorax followed by aneurysm rupture in neurofibromatosis patients. Three patients were treated for massive hemothorax caused by arterial lesions associated with neurofibromatosis. Bleeding episodes were secondary to ascending cervical artery aneurysm and dissection of vertebral artery in 1 patient, and intercostal artery aneurysm with or without arteriovenous fistula in 2 patients. Patients were treated by transarterial coil embolization combined with chest drainage. In 1 patient, the ruptured ascending cervical artery aneurysm was well embolized but, shortly after the embolization, fatal hemorrhage induced by dissection of the vertebral artery occurred and the patient died. In the other 2 patients, the ruptured intercostal artery aneurysm was well embolized and they were successfully treated and discharged. Transcatheter arterial coil embolization therapy is an effective method for the treatment of spontaneous hemothorax followed by aneurysm rupture in neurofibromatosis patients.

  9. Neurofibromatosis type 2 patient presenting with medulloblastoma

    PubMed Central

    Kalimullah, Jan; Sohail, Abdul Malik Amir Humza; Shahjehan, Rai Dilawar; Siddique, Sabeehuddin; Bari, Muhammad Ehsan

    2015-01-01

    Background: Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a frequency of 1 in 25,000 live births and a penetrance of almost 100% by the sixth decade of life. The main tumors occurring in NF2 patients are bilateral vestibular schwannomas, other peripheral, cranial and spinal nerve schwannomas, intracranial and intraspinal meningiomas, ependymomas, and gliomas. Case Description: We report the case of a 6-year-old boy who presented with a 1-month history of nausea and recurrent vomiting. Physical examination was positive for ataxic gait and left-sided facial nerve palsy. Family history was positive for NF2 in the patient's father and paternal uncle. Magnetic resonance imaging brain revealed a solid enhancing lesion arising from the right cerebellar cortex, which was effacing the fourth ventricles and causing hydrocephalus. Craniotomy and excision of the lesion were performed. Histopathology report confirmed the diagnosis to be desmoplastic medulloblastoma. Based on the patients’ subsequent history and family history, he was diagnosed to be a case of NF2. Conclusion: This is the first case of medulloblastoma occurring in a patient with NF2 and raises the possibility of an association between medulloblastoma and NF2. PMID:26539318

  10. Neurofibromatosis type 1 and malignancy in childhood.

    PubMed

    Varan, A; Şen, H; Aydın, B; Yalçın, B; Kutluk, T; Akyüz, C

    2016-03-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary neurocutaneous syndrome characterized by multi-system involvement and an increased incidence of both benign and malignant tumors. In this study, we evaluated the clinical presentation and prognosis of NF1 and malignancy. Between 1975 and 2013, 26 (5%) of the 473 patients with NF1 at our center developed non-neurofibroma neoplasms. The patient files of 26 subjects with tumors, other than optic glioma, were analyzed retrospectively to evaluate clinical features and treatment results. The age at diagnosis of NF1 ranged from 3 months to 16 years (median 5.5 years). The age range at tumor diagnosis was 1.5-33 years (median 8 years) in these 26 patients. The tumor histological subtypes included the following: 12 soft-tissue tumors (6 malignant peripheral nerve sheath tumors (MPNST), 5 rhabdomyosarcomas (RMS) and 1 malignant fibrous histiocytoma), 11 brain tumors (6 low-grade gliomas, 3 high-grade gliomas, and 2 medulloblastoma), 2 neuroblastomas and 1 non-Hodgkin's lymphoma. Twelve of 26 patients were alive at the time of the study. Although benign brain tumors with NF1 are more common, high-grade brain tumors also occur. Thus, careful and regular follow-up is crucial for early detection of malignancy in NF1 patients. PMID:26073032

  11. Mutational analysis of patients with neurofibromatosis 2

    SciTech Connect

    MacCollin, M.; Ramesh, V.; Pulaski, K.; Trofatter, J.A.; Short, M.P.; Bove, C.; Jacoby, L.B.; Louis, D.N.; Rubio, M.P.; Eldridge, R.

    1994-08-01

    Neurofibromatosis 2 (NF2) is a genetic disorder characterized by the development of multiple nervous-system tumors in young adulthood. The NF2 gene has recently been isolated and found to encode a new member, merlin, of the protein 4.1 family of cytoskeleton-associated proteins. To define the molecular basis of NF2 in affected individuals, the authors have used SSCP analysis to scan the exons of the NF2 gene from 33 unrelated patients with NF2. Twenty unique SSCP variants were seen in 21 patients; 10 of these individuals were known to be the only affected person in their kindred, while 7 had at least one other known affected relative. In all cases in which family members were available, the SSCP variant segregated with the disease; comparison of sporadic cases with their parents confirmed the de novo variants. DNA sequence analysis revealed that 19 of the 20 variants observed are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal RNA splicing. A single patient carried a 3-bp deletion removing a phenylalanine residue. The authors conclude that the majority of NF2 patients carry an inactivating mutation of the NF2 gene and that neutral polymorphism in the gene is rare. 18 refs., 3 figs., 2 tabs.

  12. Epilepsy surgery in Neurofibromatosis Type 1.

    PubMed

    Barba, Carmen; Jacques, Thomas; Kahane, Philippe; Polster, Tilman; Isnard, Jean; Leijten, Frans S S; Ozkara, Cigdem; Tassi, Laura; Giordano, Flavio; Castagna, Maura; John, Alison; Oz, Buge; Salon, Caroline; Streichenberger, Nathalie; Cross, Judith Helen; Guerrini, Renzo

    2013-08-01

    Epilepsy is relatively uncommon in patients with Neurofibromatosis Type 1 (NF1) and seizures are usually well controlled with antiepileptic treatment. However, pharmacoresistance has been reported in patients with NF1 and MRI evidence of malformations of cortical development or glioneuronal tumours. Available information on epilepsy surgery in NF1 is limited to a few patients with gliomas and glioneuronal tumours who underwent lesionectomies. We conducted a survey amongst 25 European epilepsy surgery centres to collect patients with NF1 who had undergone surgery for drug-resistant seizures and identified 12 patients from eight centres. MRI abnormalities were present in all patients but one. They were unilateral temporal in eight, bilateral temporal in one and multilobar or hemispheric in two. Seizures originated from the temporal lobe in ten patients, from the temporo-parieto-occipital region in one, and were bitemporal in one. One year after surgery eight patients were seizure free, one had worthwhile improvement and the remaining three had experienced no benefit. Postoperative outcome, available at 2 years in ten patients and at 5 years in three, remained stable in all but one whose seizures reappeared. Histology revealed dysembryoplastic neuroepithelial tumour (DNET) in five patients, hippocampal sclerosis in four, mixed pathology in one and polymicrogyria in one. No histological abnormality was observed in the remaining patient. Epilepsy surgery can be performed effectively in patients with NF1 provided a single and well-delimited epileptogenic zone is recognized. The high prevalence of DNETs in this series might suggest a non-fortuitous association with NF1. PMID:23597854

  13. Autism Spectrum Disorder Profile in Neurofibromatosis Type I

    ERIC Educational Resources Information Center

    Garg, Shruti; Plasschaert, Ellen; Descheemaeker, Mie-Jef; Huson, Susan; Borghgraef, Martine; Vogels, Annick; Evans, D. Gareth; Legius, Eric; Green, Jonathan

    2015-01-01

    Neurofibromatosis Type 1 (NF1) is a common autosomal dominant single-gene disorder, in which the co-occurrence of autism spectrum disorder (ASD) has attracted considerable research interest recently with prevalence estimates of 21-40%. However, detailed characterization of the ASD behavioral phenotype in NF1 is still lacking. This study…

  14. Articulation in Schoolchildren and Adults with Neurofibromatosis Type 1

    ERIC Educational Resources Information Center

    Cosyns, Marjan; Mortier, Geert; Janssens, Sandra; Bogaert, Famke; D'Hondt, Stephanie; Van Borsel, John

    2012-01-01

    Several authors mentioned the occurrence of articulation problems in the neurofibromatosis type 1 (NF1) population. However, few studies have undertaken a detailed analysis of the articulation skills of NF1 patients, especially in schoolchildren and adults. Therefore, the aim of the present study was to examine in depth the articulation skills of…

  15. Neurofibromatosis-1 with bilateral partial radial artery stenosis

    PubMed Central

    Sangolli, Prabhakar M.

    2012-01-01

    Not much attention is paid to vascular complications in neurofibromatosis-1 (NF-1) though they are well known to occur. A case of vascular NF-1 with bilateral partial radial artery stenosis resulting in digital gangrene involving fingers of both hands is being reported here. Various vascular abnormalities in NF-1 as complications resulting from them and their management is briefly highlighted. PMID:23130265

  16. Speech Disorders in Neurofibromatosis Type 1: A Sample Survey

    ERIC Educational Resources Information Center

    Cosyns, Marjan; Vandeweghe, Lies; Mortier, Geert; Janssens, Sandra; Van Borsel, John

    2010-01-01

    Background: Neurofibromatosis type 1 (NF1) is an autosomal-dominant neurocutaneous disorder with an estimated prevalence of two to three cases per 10 000 population. While the physical characteristics have been well documented, speech disorders have not been fully characterized in NF1 patients. Aims: This study serves as a pilot to identify key…

  17. Generalized metabolic bone disease in Neurofibromatosis type I

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1), but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical, and pathological level the bone involvement ...

  18. Early Grade Repetition and Inattention Associated with Neurofibromatosis Type 1

    ERIC Educational Resources Information Center

    Coude, Francois X.; Mignot, Claire; Lyonnet, Stanislas; Munnich, Arnold

    2007-01-01

    Objective: The authors analyze the occurrence of grade repetition and inattention in children diagnosed with neurofibromatosis type 1 (NF1). Method: The participant group consisted of 310 patients with NF1 and a control group of 242 individuals. The number of grade repetitions for each participant during his or her time in elementary, middle, and…

  19. Targeted therapy for hereditary cancer syndromes: neurofibromatosis type 1, neurofibromatosis type 2, and Gorlin syndrome.

    PubMed

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Hereditary cancer syndromes are well known in the oncology community, typically affecting children, adolescents, and young adults and thereby resulting in great cumulative morbidity and mortality. These syndromes often lag behind their de novo counterparts in the development of approved novel treatment options due to their rarity in the general population. Recent work has allowed the identification of molecular aberrations and associated targeted therapies that may effectively treat these conditions. In this review, we seek to characterize some of the involved aberrations and associated targeted therapies for several germline malignancies, including neurofibromatosis types 1 and 2, and Gorlin syndrome. Though patients with hereditary cancer syndromes may be too rare to effectively include in large clinical trials, by understanding the pathophysiology of these diseases, clinicians can attain insights into the use of targeted therapies in their own practice when treating affected individuals. PMID:25549703

  20. Characterization of naturally occurring cutaneous neurofibromatosis in Holstein cattle. A disorder resembling neurofibromatosis type 1 in humans.

    PubMed Central

    Sartin, E. A.; Doran, S. E.; Riddell, M. G.; Herrera, G. A.; Tennyson, G. S.; D'Andrea, G.; Whitley, R. D.; Collins, F. S.

    1994-01-01

    Neurofibromatosis in cattle is typically a noncutaneous disease. A small group of cows in a Holstein dairy herd developed cutaneous neurofibromatosis. This unique condition was investigated and compared with neurofibromatosis type 1 (NF1) in humans. All cutaneous lesions but one were consistent with neurofibromas in noncutaneous sites in cattle and neurofibromas in patients with NF1. One bovine lesion was classified as a neurofibrosarcoma. Immunohistochemistry and electron microscopy supported Schwannian differentiation in benign and malignant lesions. Linkage analysis with a polymorphism in the bovine NF1 gene confirmed that two affected animals from the same sire inherited the same paternal NF1 allele. Bovine cutaneous neurofibromatosis is a naturally occurring disease in this group of animals, characterized by skin tumors morphologically identical to those of NF1. An informative polymorphism at the NF1 locus of two animals and their sire suggests this disorder may be caused by hereditary mutations at the bovine NF1 locus. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:7977647

  1. Type 1 neurofibromatosis and pulmonary hypertension: a report of two cases and a review

    PubMed Central

    Malviya, Amit; Mishra, Sundeep; Kothari, Shyam S

    2012-01-01

    Pulmonary hypertension in type 1 neurofibromatosis is not well known and was previously attributed to diffuse fibrosing alveolitis and parenchymal tumours. More recently, cases of severe pulmonary hypertension due to pulmonary vasculopathy have been described. Involvement of vascular beds, both large and medium calibre vessels, but not pulmonary vasculature, in type 1 neurofibromatosis is well known. The authors describe two such cases and briefly review the literature. Pulmonary arterial hypertension in neurofibromatosis warrants further studies. PMID:27326022

  2. A segmental neurofibromatosis case with eruptive seborrheic keratoses.

    PubMed

    Takci, Zennure; Simsek, Gulcin Guler; Tekin, Ozlem

    2012-09-01

    Segmental neurofibromatosis (SNF) is a rare variant of neurofibromatosis (NF) type 1 characterized by a restricted distribution of cafe-au-lait macules, and/or neurofibromas, and rarely freckling to a single dermatomal segment. Patients with NF type 1 have an associated increased risk for benign or malignant tumours. The prevalence of typical NF type 1 complications including malignancies in SNF is much lower than the generalized form. Seborrheic keratosis is one of the more common benign epidermal tumour which can be a paraneoplastic syndrome when it arises with an eruptive appearance. To our knowledge in the literature no case of SNF associated with eruptive seborrheic keratoses has been defined. We report the case of a man, aged 51, who had SNF and abruptly developed eruptive seborrheic keratoses. PMID:23139984

  3. Pediatric schwannomatosis, a rare but distinct form of neurofibromatosis.

    PubMed

    Thomas, Anna K; Egelhoff, John C; Curran, John G; Thomas, Bobby

    2016-03-01

    Schwannomatosis is the third major form of neurofibromatosis, distinct from neurofibromatosis type 2 (NF2) and type 1 (NF1). This condition is rare with a variable phenotypic presentation and complex molecular and genetic findings. In this case, a previously healthy teenager was found to have multiple spinal lesions and an enhancing right parotid mass on MRI. On extensive further work-up, this patient met the existing clinical criteria for schwannomatosis. This case report aims to review the clinical features and current diagnostic criteria for schwannomatosis and compare it to NF1 and NF2. Special emphasis will be placed on imaging features that should prompt the radiologist to suggest this rare diagnosis. PMID:26546566

  4. Coexistence of Ankylosing Spondylitis and Neurofibromatosis Type 1

    PubMed Central

    Gundogdu, Baris; Yolbas, Servet; Yildirim, Ahmet; Gonen, Murat

    2016-01-01

    Ankylosing spondylitis (AS) is a systemic disease primarily characterized by the inflammation of sacroiliac joints and axial skeleton. Neurofibromatosis type 1 (NF1) is a multisystem genetic disease which is characterized by cutaneous findings, most importantly café-au-lait spots and axillary freckling, by skeletal dysplasia, and by the growth of both benign and malignant nervous system neoplasms, most notably benign neurofibromas. In this case report, we present a 43-year-old male with AS and NF1. PMID:27597922

  5. Coexistence of Ankylosing Spondylitis and Neurofibromatosis Type 1.

    PubMed

    Gundogdu, Baris; Yolbas, Servet; Yildirim, Ahmet; Gonen, Murat; Koca, Suleyman Serdar

    2016-01-01

    Ankylosing spondylitis (AS) is a systemic disease primarily characterized by the inflammation of sacroiliac joints and axial skeleton. Neurofibromatosis type 1 (NF1) is a multisystem genetic disease which is characterized by cutaneous findings, most importantly café-au-lait spots and axillary freckling, by skeletal dysplasia, and by the growth of both benign and malignant nervous system neoplasms, most notably benign neurofibromas. In this case report, we present a 43-year-old male with AS and NF1. PMID:27597922

  6. Diffusion Tensor Imaging of Neurofibromatosis Bright Objects in Children with Neurofibromatosis Type 1

    PubMed Central

    Ertan, Gulhan; Zan, Elcin; Yousem, David M; Ceritoglu, Can; Tekes, Aylin; Poretti, Andrea; Huisman, Thierry A.G.M.

    2014-01-01

    Summary Neurofibromatosis bright objects (NBOs) are poorly understood. This article aimed to investigate: 1) differences in fractional anisotropy (FA) between NBOs based in gray matter (GM) and white matter (WM), and 2) the relationship between NBOs and the affected white matter tracts. Fourteen NF1 patients were included in this study. Apparent diffusion coefficient (ADC), FA, radial diffusivity (RD) and eigenvalues were used to compare NBOs and matching contralateral normal-appearing sites (NAS). Diffusion tensor imaging scalars were also compared with age-matched healthy controls. Fiber tractography was performed to assess NBO-induced changes in WM trajectories. ADC values were higher for GM and WM NBOs than for NAS and controls. FA values were lower in GM and WM NBOs compared with controls. In all regions, eigenvalues were higher in NBOs than in NAS and controls. Only three out of 18 NOBs appeared to disrupt WM tracts. ADC, λ2 and RD values of WM NBOs were higher in symptomatic compared to asymptomatic patients. Increased ADC, RD and eigenvalues and decreased FA values in NBOs can be explained by myelin and axonal damage. Increased ADC values and RD in WM NBOs correlated with the presence of symptoms. Tract integrity predominated in our study. PMID:25260209

  7. Identification of Growth Hormone Receptor in Plexiform Neurofibromas of Patients with Neurofibromatosis Type 1

    PubMed Central

    Cunha, Karin Soares Gonçalves; Barboza, Eliane Porto; da Fonseca, Eliene Carvalho

    2008-01-01

    OBJECTIVE The aim of this study was to investigate the presence of growth hormone receptor in plexiform neurofibromas of neurofibromatosis type 1 patients. INTRODUCTION The development of multiple neurofibromas is one of the major features of neurofibromatosis type 1. Since neurofibromas commonly grow during periods of hormonal change, especially during puberty and pregnancy, it has been suggested that hormones may influence neurofibromatosis type 1 neurofibromas. A recent study showed that the majority of localized neurofibromas from neurofibromatosis type 1 patients have growth hormone receptor. METHODS Growth hormone receptor expression was investigated in 5 plexiform neurofibromas using immunohistochemistry. RESULTS Four of the 5 plexiform neurofibromas were immunopositive for growth hormone receptor. CONCLUSION This study suggests that growth hormone may influence the development of plexiform neurofibromas in patients with neurofibromatosis type 1. PMID:18297205

  8. Giant plexiform neurofibroma and suboccipital meningocele manifesting as segmental neurofibromatosis.

    PubMed

    Kurimoto, Masanori; Mizumaki, Yasushi; Fukuda, Osamu; Hayashi, Nakamasa; Kuwayama, Naoya; Endo, Shunro

    2008-06-01

    A 34-year-old woman presented with segmental neurofibromatosis manifesting as a soft lump with a large café-au-lait macule on her occipital region and neck. Magnetic resonance imaging showed a thick skin tumor in the occipital region and posterior neck, and a suboccipital meningocele which seemed to have no association with her symptoms. Biopsy lead to a histological diagnosis of giant plexiform neurofibroma. During biopsy, massive local bleeding occurred and hemostasis was achieved by electrocautery and meticulous suture ligation. The postoperative course was uneventful and observation was continued for both the giant plexiform neurofibroma and the meningocele. PMID:18574335

  9. Chronic renal failure and macrogenitalia associated with genitourinary neurofibromatosis.

    PubMed

    Dündar, Bumin Nuri; Oktem, Faruk; Armağan, Abdullah; Dündar, Nihal Olgaç; Bircan, Sema; Yesildag, Ahmet

    2010-02-01

    Neurofibromatosis (NF) is a genetic disorder of the nervous system that primarily affects the development and growth of neural cell tissues. This disorder is characterized by the development of various tumors, including neurofibromas, neuroniomas, malignant and benign peripheral nerve sheath tumors, and meningiomas. Accompanying skin changes and bone deformities are also common in NF. However, genitourinary involvement in NF is a rare condition, and penile enlargement has been reported only in a few males with plexiform NF. We report a 6-year-old boy with chronic renal failure associated with plexiform neurofibromas of the bladder and prostatic urethra which led to urinary obstruction and macrogenitalia due to genitourinary NF. PMID:19826840

  10. Ulcerative colitis and neurofibromatosis type 1 with bilateral psoas muscle neurofibromas: a case report

    PubMed Central

    Tavakkoli, Hamid; Asadi, Mehrnaz; Mahzouni, Parvin; Foroozmehr, Abdolali

    2009-01-01

    The most common gastrointestinal involvement in neurofibromatosis is due to tumoral lesions which may present with gastrointestinal bleeding or obstruction. We report a case of concurrent ulcerative colitis and neurofibromatosis. A 39 year-old woman, known case of neurofibromatosis, was admitted to our department with complaint of chronic bloody diarrhea. After thorough clinical examination and paraclinical assessments, including colonoscopy and biopsy, ulcerative colitis was confirmed as the cause of gastrointestinal bleeding. Another rare finding in this patient was bilateral neurofibroma in psoas muscle that was detected on abdominal spiral Computer Tomography scan. PMID:21772893

  11. Pseudoangiomatous stromal hyperplasia with giant cells in the female breast. No association with neurofibromatosis?

    PubMed

    Zámecník, M; Dubac, V

    2011-04-01

    A simultaneous finding of pseudoangiomatous stromal hyperplasia (PASH) and stromal multinucleated giant cells (MGC) in mammary tissue was previously observed in patients with type-1 neurofibromatosis, indicating that it can represent a morphologic marker for this syndrome. Here, we present PASH with MGC occurring in the left breast of a 39-years-old woman who does not have neurofibromatosis. This case, along with two additional ones reported previously, indicates that PASH with MGC in the female breast may not be associated with neurofibromatosis. PMID:21598761

  12. Patient and physician attitudes regarding clinical trials in neurofibromatosis 1.

    PubMed

    McQueen, Mary; MacCollin, Mia; Gusella, James; Plotkin, Scott R

    2008-12-01

    Neurofibromatosis 1 (NF1) is a multisystem genetic disorder that primarily affects the skin (freckling and café-au-lait macules), nervous system (neurofibromas, optic gliomas, and learning disabilities), and skeletal system (pseudoarthroses). The interest in pharmacological intervention for patients with NF1 has grown in recent years. However, little is known about the attitudes and priorities of patients, families, and physicians regarding participation in clinical trials. We surveyed 74 adult patients or parents of patients with NF1 and 69 care providers participating in a neurofibromatosis clinic to assess their willingness to participate in clinical trials and their opinions about which conditions they thought were most important to treat. Both patients and care providers are willing to participate in clinical trials for NF1 and both groups rate malignant peripheral nerve sheath tumors as the most urgent for new treatments. There are concordant views among patients and physicians concerning clinical trials for NF1, and patients do not dismiss participation in placebo-controlled trials. Neuroscience nurses are poised to facilitate the research process from conception through implementation as they take the viewpoints of our study populations into consideration. PMID:19170300

  13. Segmental neurofibromatosis presenting with congenital excessive skin folds.

    PubMed

    Helfand, Alexander M; Nouriel, Ariella; Zisquit, Jonah; Barzilai, Aviv; Greenberger, Shoshana

    2015-04-01

    Segmental neurofibromatosis (SNF) is a rare type of neurofibromatosis (NF-1) resulting from post-zygotic somatic mutations in the neurofibromin gene that leads to mosaicism. Reported manifestations of SNF include neurofibromas, freckling, or café-au-lait spots limited to a single body region or limb. We present a 5-month-old male referred to our clinic for evaluation of congenital excessive skin folds on the back. A mildly erythematous, poorly demarcated soft plaque was noted, consisting of excessive skin folds. A cluster of light brown hyperpigmented macules was seen overlying the plaque. A punch biopsy of the plaque confirmed a diagnosis of neurofibroma. Further investigation ruled out other manifestations of NF-1. The early onset of our patient's neurofibroma and its gross appearance with redundant skin folds are all unusual features. To our knowledge, congenital excessive skin folds found in a single tumor have not been previously described in the literature as a manifestation of SNF. Clinicians should be educated about the possibility of congenital localized skin folds in association with SNF in order to identify the disease in infancy and monitor any changes in neurofibroma pathology. PMID:26114065

  14. Segmental neurofibromatosis presenting with congenital excessive skin folds

    PubMed Central

    Helfand, Alexander M.; Nouriel, Ariella; Zisquit, Jonah; Barzilai, Aviv; Greenberger, Shoshana

    2015-01-01

    Segmental neurofibromatosis (SNF) is a rare type of neurofibromatosis (NF-1) resulting from post-zygotic somatic mutations in the neurofibromin gene that leads to mosaicism. Reported manifestations of SNF include neurofibromas, freckling, or café-au-lait spots limited to a single body region or limb. We present a 5-month-old male referred to our clinic for evaluation of congenital excessive skin folds on the back. A mildly erythematous, poorly demarcated soft plaque was noted, consisting of excessive skin folds. A cluster of light brown hyperpigmented macules was seen overlying the plaque. A punch biopsy of the plaque confirmed a diagnosis of neurofibroma. Further investigation ruled out other manifestations of NF-1. The early onset of our patient’s neurofibroma and its gross appearance with redundant skin folds are all unusual features. To our knowledge, congenital excessive skin folds found in a single tumor have not been previously described in the literature as a manifestation of SNF. Clinicians should be educated about the possibility of congenital localized skin folds in association with SNF in order to identify the disease in infancy and monitor any changes in neurofibroma pathology. PMID:26114065

  15. NF2/Merlin in hereditary neurofibromatosis 2 versus cancer: biologic mechanisms and clinical associations

    PubMed Central

    Schroeder, Rebecca Dunbar; Angelo, Laura S.; Kurzrock, Razelle

    2014-01-01

    Inactivating germline mutations in the tumor suppressor gene NF2 cause the hereditary syndrome neurofibromatosis 2, which is characterized by the development of neoplasms of the nervous system, most notably bilateral vestibular schwannoma. Somatic NF2 mutations have also been reported in a variety of cancers, but interestingly these mutations do not cause the same tumors that are common in hereditary neurofibromatosis 2, even though the same gene is involved and there is overlap in the site of mutations. This review highlights cancers in which somatic NF2 mutations have been found, the cell signaling pathways involving NF2/merlin, current clinical trials treating neurofibromatosis 2 patients, and preclinical findings that promise to lead to new targeted therapies for both cancers harboring NF2 mutations and neurofibromatosis 2 patients. PMID:24393766

  16. Quality of life among adult patients with neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis: a systematic review of the literature.

    PubMed

    Vranceanu, Ana-Maria; Merker, Vanessa L; Park, Elyse; Plotkin, Scott R

    2013-09-01

    The aim of this study was to review the literature on quality of life among adult patients with neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis, and to identify the specific aspects of quality of life that were studied and reported in this population. We also set out to report predictors of quality of life. Published research reports were included if they described quality of life in this population and met methodological quality according to a list of predefined criteria. Eight studies (7 in NF1, 1 in NF2, 0 in schwannomatosis), conducted between 2001 and 2013, met inclusion criteria. The methodological quality of the eight studies was mostly high according to ratings by predefined criteria. Most studies reported that patients with NF experience decreased quality of life when compared to the general population. Visibility and disease severity were strong predictors of skin-specific quality of life in NF1 patients. However, the majority of findings regarding predictors of quality of life were weak or inconclusive. Given the decreased quality of life in NF patients, it is important to examine more comprehensively the psychosocial factors in this population, especially in patients with NF2 and schwannomatosis. Mind body interventions that address these domains may provide comprehensive and efficacious long term treatment. PMID:23817811

  17. Incidental (malignancy) and coincidental (idiopathic polydactylous longitudinal erythronychia) conditions in patients with segmental neurofibromatosis.

    PubMed

    Cohen, Philip R

    2013-04-01

    Segmental neurofibromatosis (SNF) is an uncommon presentation of neurofibromatosis type 1 (NF-1). Although patients with SNF are at a lower risk for developing NF-l-associated complications, the estimated occurrence of related malignancies may be approaching the frequency observed in patients with NF-1. Idiopathic polydactylous longitudinal erythronychia also may be associated with SNF, though the frequency of this association remains to be determined. PMID:23763076

  18. Criptococosis cutánea primaria en paciente inmunocompetente.

    PubMed

    Osorio, Igor Vázquez; García-Rodiño, Sara; Rodríguez-Rodríguez, Marta; Labandeira, Javier; Suárez-Peñaranda, José Manuel; Sánchez-Aguilar, MDolores; Vázquez-Veiga, Hugo

    2016-01-01

    La criptococosis cutánea es una micosis propia de pacientes inmunodeprimidos, sobre todo aquellos con infección por el virusde la inmunodeficiencia humana (VIH). Sin embargo, existen casos infrecuentes de criptococosis cutánea en pacientes inmunocompetentes, que suelen simular otras dermatosis, lo que retrasa su diagnóstico y tratamiento. Presentamos el caso de un varón pluripatológico de 79 años, con úlceras dolorosas en dorso de mano derecha que no respondían a tratamientos tópicos. A través del estudio histopatológico y micológico se alcanzó el diagnóstico de criptococosis cutánea primaria, lográndose la remisión de las lesiones tras 6 meses de tratamiento con fluconazol. PMID:27617525

  19. Annual review of children with neurofibromatosis type 1.

    PubMed

    Dunning-Davies, B M; Parker, Apj

    2016-04-01

    We aim to provide a concise, evidence-based framework to assist secondary level, community and acute paediatricians during a 20-60 min annual review of children with neurofibromatosis type 1. This review does not cover all aspects of the disorder. We recognise the importance of an overview of the pathogenesis, molecular genetic testing, clinical manifestations and management; we shall cover some of this briefly, but this is not our focus here. We focus instead on the following areas: (A) what questions should be asked during annual review, (B) what should be included in a focused examination, (C) when to request further investigations and (D) when should a referral be made to tertiary specialists and other members of the multidisciplinary team. Ongoing debates regarding screening remain in certain areas, particularly regarding imaging and ophthalmology follow-up; here we summarise the differing opinions and make a recommendation based on the currently available evidence. PMID:26486853

  20. Gastrointestinal stromal tumor with KIT mutation in neurofibromatosis type 1.

    PubMed

    Namgung, Hwan

    2011-10-01

    Multiple jejunalgastrointestinal stromal tumors (GISTs) were found in a 52-year-old woman with a history of neurofibromatosis type 1. These tumors were composed of interlacing fascicles of uniform spindle cells with eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for CD117, CD34 and negative for S-100, smooth muscle actin. Molecular analysis for activating mutations of KIT and PDGFRA was performed in two tumors. Contrary to sporadic GISTs, the NF1-associated GISTs are characterized by rare mutations of KIT or PDGFRA. But, one missense point mutation (Trp557Gly) was identified in KIT exon 11 of the extramural portion of the largest tumor in this case. The intramural portion of the largest tumor and the other tumor had wild type KIT and PDGFRA. PMID:22111084

  1. Autism spectrum disorder profile in neurofibromatosis type I.

    PubMed

    Garg, Shruti; Plasschaert, Ellen; Descheemaeker, Mie-Jef; Huson, Susan; Borghgraef, Martine; Vogels, Annick; Evans, D Gareth; Legius, Eric; Green, Jonathan

    2015-06-01

    Neurofibromatosis Type 1 (NF1) is a common autosomal dominant single-gene disorder, in which the co-occurrence of autism spectrum disorder (ASD) has attracted considerable research interest recently with prevalence estimates of 21-40%. However, detailed characterization of the ASD behavioral phenotype in NF1 is still lacking. This study characterized the phenotypic profile of ASD symptomatology presenting in 4-16 year old children with NF1 (n = 36) using evidence from parent-rated Social Responsiveness Scale and researcher autism diagnostic observation Scale-2. Compared to IQ-matched reference groups of children with autism and ASD, the NF1 profile shows overall similarity but improved eye contact, less repetitive behaviors and better language skills. PMID:25475362

  2. Lower fasting blood glucose in neurofibromatosis type 1

    PubMed Central

    Martins, Aline Stangherlin; Jansen, Ann Kristine; Rodrigues, Luiz Oswaldo Carneiro; Matos, Camila Maria; Souza, Marcio Leandro Ribeiro; de Souza, Juliana Ferreira; Diniz, Maria de Fátima Haueisen Sander; Barreto, Sandhi Maria; Diniz, Leonardo Mauricio; de Rezende, Nilton Alves; Riccardi, Vincent Michael

    2015-01-01

    Studies indicate a lower occurrence of diabetes mellitus (DM) in patients with neurofibromatosis type 1 (NF1). Fasting blood glucose (FBG) level is the main criterion used to diagnose DM and glucose intolerance. Therefore, this study compared FBG level between adults with NF1 and non-NF1 controls. We selected clinical records of 57 out of 701 individuals attending the Neurofibromatosis Outpatient Reference Center of the Clinics Hospital of the Federal University of Minas Gerais in Brazil. The selected patients with NF1 were matched to non-NF1 controls selected from the Brazilian Longitudinal Study of Adult Health according to sex, age (range, 35–74 years) and BMI at a ratio of 1:3. In both groups, individuals with DM were excluded. Median FBG level in the NF1 group (86 mg/dl (range, 56–127 mg/dl)) was lower than that in the non-NF1 control group (102 mg/dl (range, 85–146 mg/dl)) (P<0.001). Prevalence of FBG level ≥100 mg/dl in the NF1 group (16%) was lower than that in the non-NF1 control group (63%) (P<0.05). The chance of a high FBG level was 89% lower in the NF1 group (odds ratio, 0.112; 95% CI, 0.067–0.188) (P<0.05). In conclusion, adults with NF1 showed a lower FBG level and a lower prevalence of high FBG level compared with non-NF1 controls. PMID:26631381

  3. [Neurofibromatosis type 1 and associated clinical abnormalities in 27 children].

    PubMed

    Syrbe, S; Eberle, K; Strenge, S; Bernhard, M K; Herbertz, S; Bierbach, U; Hirsch, W; Froster, U G; Kiess, W; Merkenschlager, A

    2007-01-01

    Neurofibromatosis type 1 is the most common of the phakomatoses and the clinical follow-up is an interdisciplinary challenge. The data of 27 patients with NF1 were systematically reviewed and compared to data from the literature. All of our patients had clinical signs of NF1. Besides the classic criteria café-au-lait spots (100%), freckling (48,1%), positive family history (44,1%), neurofibromas (40,7%), Lisch nodules (22,2%) and optic pathway tumors (22,2%) there were developmental delay (40,7%), macrocephaly (33,3%), strabism (29,6%), scoliosis (18,5%), epilepsy (14,8%), pubertal anomalies (14,8%), short stature (11,1%) and tics. Morphologically, CNS hamartomas (55,5%), astrocytomas (22,2%) and one pheochromocytoma became apparent. Special findings consist of one aneurysm of internal carotic arteria, juvenile xanthogranulomas, a case of pulmonary stenosis and an intracardial tumor. Four new mutations in the NF1 gene were found. Regular screening of optic glioma with MRI had no clinical significance. In contrast to other authors, one of our patients with optic glioma showed clinical progress after twelve years of age. The detection of astrocytomas led only to therapeutic consequences, when clinical signs or symptoms occurred. As with other authors, we found no potential for CNS hamartoma to proliferate. In three cases with pubertal anomalies we found CNS gliomas, which indicates the need for MRI. The expense of screening, apart from clinical surveillance, seems inadequate in relation to clinical relevance and costs. We describe four new mutations in the NF1 gene; there have been no specific genotype-phenotype correlations. Neurofibromatosis type 1 and associated clinical abnormalities in 27 children. PMID:18183640

  4. Bilateral internal auditory canal gangliogliomas mimicking neurofibromatosis Type II

    PubMed Central

    Hooten, Kristopher G.; Oliveria, Seth F.; Sadrameli, Saeed S.; Gandhi, Shashank; Yachnis, Anthony T.; Lewis, Stephen B.

    2016-01-01

    Background: Gangliogliomas are rare low grade, typically well-differentiated, tumors that are composed of mature ganglion cells and neoplastic glial cells. These tumors can appear at virtually any location along the neuroaxis but classically occur in the temporal lobe of young patients. In a small number of cases, gangliogliomas have presented as masses in the brainstem or involving cranial nerves. With the exception of vestibular schwannomas, bilateral tumors in the region of the internal auditory canal (IAC) or cerebellopontine angle (CPA) are exceedingly rare. Case Description: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. Description: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. Conclusion: This is the first reported case of bilateral IAC/CPA gangliogliomas. When evaluating bilateral IAC/CPA lesions with unusual imaging characteristics, ganglioglioma should be included in the differential diagnosis. PMID:27127704

  5. Lower fasting blood glucose in neurofibromatosis type 1.

    PubMed

    Martins, Aline Stangherlin; Jansen, Ann Kristine; Rodrigues, Luiz Oswaldo Carneiro; Matos, Camila Maria; Souza, Marcio Leandro Ribeiro; de Souza, Juliana Ferreira; Diniz, Maria de Fátima Haueisen Sander; Barreto, Sandhi Maria; Diniz, Leonardo Mauricio; de Rezende, Nilton Alves; Riccardi, Vincent Michael

    2016-01-01

    Studies indicate a lower occurrence of diabetes mellitus (DM) in patients with neurofibromatosis type 1 (NF1). Fasting blood glucose (FBG) level is the main criterion used to diagnose DM and glucose intolerance. Therefore, this study compared FBG level between adults with NF1 and non-NF1 controls. We selected clinical records of 57 out of 701 individuals attending the Neurofibromatosis Outpatient Reference Center of the Clinics Hospital of the Federal University of Minas Gerais in Brazil. The selected patients with NF1 were matched to non-NF1 controls selected from the Brazilian Longitudinal Study of Adult Health according to sex, age (range, 35-74 years) and BMI at a ratio of 1:3. In both groups, individuals with DM were excluded. Median FBG level in the NF1 group (86 mg/dl (range, 56-127 mg/dl)) was lower than that in the non-NF1 control group (102 mg/dl (range, 85-146 mg/dl)) (P<0.001). Prevalence of FBG level ≥100 mg/dl in the NF1 group (16%) was lower than that in the non-NF1 control group (63%) (P<0.05). The chance of a high FBG level was 89% lower in the NF1 group (odds ratio, 0.112; 95% CI, 0.067-0.188) (P<0.05). In conclusion, adults with NF1 showed a lower FBG level and a lower prevalence of high FBG level compared with non-NF1 controls. PMID:26631381

  6. Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1.

    PubMed

    Lin, A E; Birch, P H; Korf, B R; Tenconi, R; Niimura, M; Poyhonen, M; Armfield Uhas, K; Sigorini, M; Virdis, R; Romano, C; Bonioli, E; Wolkenstein, P; Pivnick, E K; Lawrence, M; Friedman, J M

    2000-11-13

    Although it is well recognized that a peripheral vasculopathy may occur in patients with neurofibromatosis 1 (NF1), it is unclear whether cardiovascular abnormalities are more common. We reviewed the frequency of cardiovascular abnormalities, in particular, cardiovascular malformations (CVMs), among 2322 patients with definite NF1 in the National Neurofibromatosis Foundation International Database from 1991-98. Cardiovascular malformations were reported in 54/2322 (2.3%) of the NF1 patients, only 4 of whom had Watson syndrome or NF1-Noonan syndrome. There was a predominance of Class II "flow" defects [Clark, 1995: Moss and Adams' Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. p 60-70] (43/54, 80%) among the NF1 patients with CVMs. Pulmonic stenosis, that was present in 25 NF1 patients, and aortic coarctation, that occurred in 5, constitute much larger proportions of all CVMs than expected. Of interest was the paucity of Class I conotruncal defects (2 patients with tetralogy of Fallot), and the absence of atrioventricular canal, anomalous pulmonary venous return, complex single ventricle and laterality defects. Besides the 54 patients with CVMs, there were 27 patients with other cardiac abnormalities (16 with murmur, 5 with mitral valve prolapse, 1 with intracardiac tumor, and 5 with electrocardiogram abnormalities). No patient in this study had hypertrophic cardiomyopathy. There were 16 patients who had a peripheral vascular abnormality without an intracardiac CVM, plus an additional 4 patients among those with a CVM who also had a peripheral vascular abnormality. PMID:11078559

  7. Giant café-au-lait macule in neurofibromatosis 1: a type 2 segmental manifestation of neurofibromatosis 1?

    PubMed

    Yang, Chao-Chun; Happle, Rudolf; Chao, Sheau-Chiou; Yu-Yun Lee, Julia; Chen, WenChieh

    2008-03-01

    Type 2 segmental manifestation of autosomal dominant dermatoses refers to pronounced segmental lesions superimposed on the ordinary nonsegmental phenotype, indicating loss of heterozygosity occurring at an early stage of embryogenesis. We describe a 20-year-old Taiwanese woman with typical lesions of neurofibromatosis type 1 (NF1) in the form of characteristic café-au-lait spots, neurofibromas, axillary freckling and Lisch nodules. In addition, a giant garment-like or "bathing-trunk" café-au-lait macule involved the lower half of the trunk, the buttocks, and parts of the thighs, being superimposed on the ordinary smaller spots of NF1. This large café-au-lait macule may be best explained as an example of type 2 segmental NF1. A novel mutation (3009delG) in exon 23 was also identified in this patient, which has not yet been described in sporadic and familial NF1. PMID:18280349

  8. Combinación de radioterapia con quimioterapia mejora la supervivencia con raro cáncer cerebral

    Cancer.gov

    Los resultados de dos estudios clínicos de seguimiento a largo plazo confirman que ciertos pacientes viven substancialmente más si se les trata con una combinación de quimioterapia y radioterapia en comparación con radioterapia solamente.

  9. Math Learning Disability and Math LD Subtypes: Evidence from Studies of Turner Syndrome, Fragile X Syndrome, and Neurofibromatosis Type 1.

    ERIC Educational Resources Information Center

    Mazzocco, Michele M. M.

    2001-01-01

    This study examined whether indicators of math learning disability were observed in 35 5- and 6-year-olds with either neurofibromatosis, Turner Syndrome, or fragile X syndrome and compared to controls. Findings indicate that girls with fragile X or Turner syndrome but not neurofibromatosis are significantly more likely to have specific math…

  10. Ipsilateral Sphenoid Wing Dysplasia, Orbital Plexiform Neurofibroma and Fronto-Parietal Dermal Cylindroma in a Patient with Segmental Neurofibromatosis.

    PubMed

    Friedrich, Reinhard E; Hagel, Christian; Mautner, Victor-Felix

    2015-12-01

    Neurofibromatosis type 1 (NF1) is an autosomal-dominant inherited disease affecting various parts of the body. Penetrance is almost complete but the phenotype varies considerably. Recently, mosaicism in NF1 has come into the focus of scientific interest. This report refers to a patient with orbitotemporal-confined neurofibromatosis who developed a rare skin tumor in the region. PMID:26637901

  11. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1

    PubMed Central

    Ferner, Rosalie E; Huson, Susan M; Thomas, Nick; Moss, Celia; Willshaw, Harry; Evans, D Gareth; Upadhyaya, Meena; Towers, Richard; Gleeson, Michael; Steiger, Christine; Kirby, Amanda

    2007-01-01

    Neurofibromatosis 1 (NF1) is a common neurocutaneous condition with an autosomal dominant pattern of inheritance. The complications are diverse and disease expression varies, even within families. Progress in molecular biology and neuroimaging and the development of mouse models have helped to elucidate the aetiology of NF1 and its clinical manifestations. Furthermore, these advances have raised the prospect of therapeutic intervention for this complex and distressing disease. Members of the United Kingdom Neurofibromatosis Association Clinical Advisory Board collaborated to produce a consensus statement on the current guidelines for diagnosis and management of NF1. The proposals are based on published clinical studies and on the pooled knowledge of experts in neurofibromatosis with experience of providing multidisciplinary clinical and molecular services for NF1 patients. The consensus statement discusses the diagnostic criteria, major differential diagnoses, clinical manifestations and the present strategies for monitoring and management of NF1 complications. PMID:17105749

  12. Neurofibromatosis Type 1: Transcatheter Arterial Embolization for Ruptured Occipital Arterial Aneurysms

    SciTech Connect

    Kanematsu, Masayuki; Kato, Hiroki; Kondo, Hiroshi; Goshima, Satoshi; Tsuge, Yusuke; Kojima, Toshiaki; Watanabe, Haruo

    2011-02-15

    Two cases of ruptured aneurysms in the posterior cervical regions associated with type-1 neurofibromatosis treated by transcatheter embolization are reported. Patients presented with acute onset of swelling and pain in the affected areas. Emergently performed contrast-enhanced CT demonstrated aneurysms and large hematomas widespread in the posterior cervical regions. Angiography revealed aneurysms and extravasations of the occipital artery. Patients were successfully treated by percutaneous transcatheter arterial microcoil embolization. Transcatheter arterial embolization therapy was found to be an effective method for treating aneurysmal rupture in the posterior cervical regions occurring in association with type-1 neurofibromatosis. A literature review revealed that rupture of an occipital arterial aneurysm, in the setting of neurofibromatosis type 1, has not been reported previously.

  13. VATS resection of an oesophageal leiomyoma in a patient with neurofibromatosis Recklinghausen.

    PubMed

    Schmid, R A; Schöb, O M; Klotz, H P; Vogt, P; Weder, W

    1997-10-01

    A series of reports in the literature suggest an association of neurofibromatosis Recklinghausen with intestinal tumors as carcinoids, leiomyomas and leiomyosarcomas. We present a case of a 23-year-old man with severe cutaneous manifestation of neurofibromatosis. Dysphagia was the main symptom. CT scan suggested the diagnosis of an oesophageal leiomyoma. The oesophageal muscle layers were split and the tumor was enucleated by video assisted thoracoscopic surgery (VATS). The postoperative course was uneventful. The patient was drinking liquids from day 1 and was eating a normal diet from day 3 postoperatively. He was dismissed from the hospital on the 4th postoperative day. We conclude that in patients with neurofibromatosis and oesophageal symptoms an intestinal manifestation of the disease in the oesophagus has to be considered and that VATS resection of intramural and extrinsic oesophageal leiomyomas is the treatment of choice. PMID:9370414

  14. Management of Giant Facial Neurofibroma With Intratumoral Hematoma in Neurofibromatosis Type 1 Patient.

    PubMed

    Tak, Min Sung; Cho, Seong Eun; Kang, Sang Gue; Kim, Chul Han; Lee, Yong Seok

    2016-09-01

    Type-1 neurofibromatosis, a common autosomal dominant disease, is also known as von Recklinghausen disease. Surgical procedures to treat this condition are challenging because of the brittleness of the surrounding blood vessels and soft tissues that bring the risk of causing fatal bleeding. With improvements in neurovascular embolization procedures, some literatures have been published about the application of preoperative embolization for neurofibromatosis. This case report describes a 60-year-old female with Type-1 neurofibromatosis, who presented giant facial neurofibromas with intratumoral hemorrhage on both cheeks. This patient demonstrates that these huge and challenging lesions can be successfully treated with preoperative embolization and surgical treatment. We also discuss the timing of surgical treatment with such lesions. PMID:27603687

  15. Phenotypic variability in monozygotic twins with neurofibromatosis 2.

    PubMed

    Baser, M E; Ragge, N K; Riccardi, V M; Janus, T; Gantz, B; Pulst, S M

    1996-09-01

    Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervous system tumors, and early onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability. The evaluation included gadolinium-enhanced high-resolution magnetic resonance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatellite markers. Each MZ pair was concordant for general phenotypic subtype (mild or severe) and often for the affected organ systems. However, the MZ pairs were discordant for some features of disease presentation or progression. For example, all three pairs were discordant for presence or type of associated cranial tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at least partly due to stochastic processes, such as the loss of the second NF2 allele or alleles of other genes. PMID:8870923

  16. Immune markers in the RASopathy neurofibromatosis type 1.

    PubMed

    Torres, Karen C L; Lima, Giselle; Simões E Silva, Ana C; Lubambo, Isabela; Rodrigues, Luiz O; Rodrigues, Luiza; Silveira, Kátia D; Vieira, Érica L M; Romano-Silva, Marco A; Miranda, Débora M

    2016-06-15

    Neurofibromatosis type 1 (NF1) is a genetic disorder with an early mortality determined mostly by malignancy. Little is known about the immunosurveillance factors in NF1 patients. In this study we evaluated inflammatory markers and their cellular sources in NF1 patients to try understanding the relation of immune factors and the tumorigenesis that characterizes the disease. Using flow cytometry and ELISA, we assayed cytokines, co-stimulatory molecules, the functional state of circulating blood cells and cytokine plasma levels in a case-control transversal study. The frequency of CD4+ T cells seems reduced. In addition, a shift towards an anti-inflammatory profile was observed in cells expressing cytokines, except for a small subpopulation of CD8+ T cells that displayed an increased frequency of cells expressing the pro-inflammatory cytokine Tumor necrosis factor (TNF-α), while plasma soluble levels of Transforming growth factor-beta (TGF-β) and interleukin-6 (IL-6) were increased in NF1 patients. Knowledge of the regulation of NF1 and the role of TGF-beta signaling pathway in malignant peripheral nerve sheath tumor pathogenesis might shed light on molecular carcinogenesis mechanisms and lead to putative interventions both in prevention and treatment of malignant tumors. PMID:27235357

  17. Phenotypic variability in monozygotic twins with neurofibromatosis 2

    SciTech Connect

    Baser, M.E.; Ragge, N.K.; Riccardi, V.M.

    1996-09-06

    Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervous system tumors, and early onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability. The evaluation included gadolinium-enhanced high-resolution magnetic resonance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatellite markers. Each MZ pair was concordant for general phenotypic subtype (mild or severe) and often for the affected organ systems. However, the MZ pairs were discordant for some features of disease presentation or progression. For example, all three pairs were discordant for presence or type of associated cranial tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at least partly due to stochastic processes, such as the loss of the second NF2 allele or alleles of other genes. 42 refs., 1 tab.

  18. Deficient motor timing in children with neurofibromatosis type 1.

    PubMed

    Debrabant, Julie; Plasschaert, Ellen; Caeyenberghs, Karen; Vingerhoets, Guy; Legius, Eric; Janssens, Sandra; Van Waelvelde, Hilde

    2014-11-01

    Neurofibromatosis type 1 (NF1) is one of the most common single-gene disorders affecting fine and visual-motor skills. This case-control study investigated motor timing as a possible related performance deficit in children with NF1. A visual-motor reaction time (VRT) test was administered in 20 NF1 children (mean age 9 years 7 months) and 20 age- and gender-matched typically developing (TD) children. Copying and tracing performance were evaluated using the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI). Children with NF1 responded with an increased reaction time (RT) to temporally predictive stimuli compared to TD children, whereas RT at unpredictive stimuli did not differ between groups. Motor timing indexed by the RT decrease at predictive stimuli significantly associated with the Beery VMI copy and tracing outcomes. Deficient motor timing as an actual symptom may add to further research on the pathogenesis of NF1-associated motor impairment and the development of more effective treatment. PMID:25145806

  19. Young adults' experience of living with neurofibromatosis type 1.

    PubMed

    Hummelvoll, Grete; Antonsen, Kjell Magnus

    2013-04-01

    Neurofibromatosis Type 1 (NF1) may have many psychosocial consequences for affected adults. More knowledge is needed about the experience of psychosocial aspects in different stages of adulthood. This qualitative study aims to describe the experiences and concerns of persons living with NF1 in the early stages of adulthood. In semi-structured interviews, Norwegian adults with NF1 (n = 15) between 18 and 37 years of age described their experiences and concerns. Interview transcripts were analysed in a both concept and data driven way. Severity of NF1 was assessed from interview data. Our data indicate that many informants have more friends than in childhood, including friends with NF1. An important topic is whether or not to inform others about the NF1 diagnosis . Low self-confidence is common, often related to early school failure and bullying or to visible neurofibromas. The unpredictable development of NF1 causes much concern. The experience of NF1's impact seems less associated with the assessed severity than with social network, relation to the labour market, and psychological factors. PMID:22815101

  20. Unroofed coronary sinus in a patient with neurofibromatosis type 1

    PubMed Central

    Bender, Luciano Pereira; Meyer, Maria Rita F.; Rosa, Rafael Fabiano M.; Rosa, Rosana Cardoso M.; Trevisan, Patrícia; Zen, Paulo Ricardo G.

    2013-01-01

    OBJECTIVE: To report the uncommon association between neurofibromatosis type 1 (NF1) and unroofed coronary sinus. CASE DESCRIPTION: Girl with four years and six months old who was hospitalized for heart surgery. The cardiac problem was discovered at four months of life. On physical examination, the patient presented several café-au-lait spots in the trunk and the limbs and freckling of the axillary and groin regions. Her father had similar skin findings, suggesting the NF1 diagnosis. The cardiac evaluation by echocardiography disclosed an atrial septal defect of unroofed coronary sinus type. This cardiac finding was confirmed at surgery. The procedure consisted of the atrial septal defect repair with autologous pericardium. COMMENTS: NF1 is a common autosomal dominant disorder caused by mutations in the NF1 gene. Among the NF1 findings, congenital heart defects are considered unusual. In the literature review, there was no association between NF1 and unroofed coronary sinus, which is a rare cardiac malformation, characterized by a communication between the coronary sinus and the left atrium, resultant from the partial or total absence of the coronary sinus roof. It represents less than 1% of atrial septal defect cases. More reports are important to determine if this association is real or merely casual, since NF1 is a common condition. PMID:24473962

  1. [Social representations of patients and relatives regarding Type 1 Neurofibromatosis].

    PubMed

    Cerello, Alessandra Craig; Gianordoli-Nascimento, Ingrid Faria; Moreira, Alline Hellen; Rocha, Virgínia Silva; Ribeiro, Luciana de Moura; de Rezende, Nilton Alves

    2013-08-01

    Type 1 Neurofibromatosis (NF1) is a disease with diverse manifestations. Few studies have addressed the psychological aspects associated with it from the perspective of those who have NF1 or their relatives. In this study 46 subjects were interviewed, 28 people with NF1 (Group P) and 18 relatives (Group F) seeking to identify the understanding of the day-to-day reality experienced by these two groups and possible distinctions between them, based on the social representations of each group. Data analysis was conducted using Classic Content Analysis. The respondents' answers were organized into categories and subcategories based on their meanings. The results revealed that the quantitative distribution of the categories had similar frequencies for both groups. However, important qualitative differences were observed in terms of the meanings of the answers. Difficulty in obtaining information about NF1 along with few references about social support networks by people with the disease or their family members contributed to the identification of a veil of social invisibility around NF1. These aspects highlight the need for greater investment in research and intervention related to NF1 in order to expand the social coping conditions for those afflicted with the disease. PMID:23896918

  2. Optic Nerve Tortuosity in Individuals with Neurofibromatosis Type 1

    PubMed Central

    Ji, Joyce; Shimony, Joshua; Gao, Feng; McKinstry, Robert C.; Gutmann, David H.

    2014-01-01

    Background Optic nerve tortuosity is often reported in children with neurofibromatosis type 1 (NF1). We describe quantitative and subjective criteria to determine the degree of optic nerve tortuosity in individuals with NF1. Objective To employ quantitative and subjective criteria to assess optic nerve tortuosity in individuals with NF1. Materials and methods A retrospective study over a period of 8 years was performed on children with NF1, with and without optic pathway glioma, compared to children without NF1. A tortuosity index was computed for the optic nerve in each subject using a high resolution 3D T1-weighted magnetization-prepared rapid gradient echo sequence, which was averaged and compared across groups. Results The tortuosity index for subjects with NF1, regardless of an optic pathway glioma, was greater than those without NF1. There was no difference in the tortuosity index between NF1 subjects with optic pathway glioma and NF1 subjects without optic pathway glioma. There was also no correlation between subjective measures of tortuosity and the quantitative scoring (tortuosity index), or between the degree of tortuosity and subject age or gender. Conclusion Individuals with NF1 have increased optic nerve tortuosity relative to unaffected individuals. Quantitative tortuosity index is a superior measure to subjective assessment in the evaluation of optic nerve tortuosity in children with NF1. PMID:23636538

  3. Neurological complications of neurofibromatosis type 1 in adulthood.

    PubMed

    Créange, A; Zeller, J; Rostaing-Rigattieri, S; Brugières, P; Degos, J D; Revuz, J; Wolkenstein, P

    1999-03-01

    Neurofibromatosis type 1 (NF1) is a genetic disease with a wide range of neurological manifestations. To examine these, and to evaluate neurological morbidity in adulthood of patients with NF1, we studied a hospital-based series of 158 patients that included 138 adult patients aged >18 years and 20 children. NF1 evaluation included a multidisciplinary clinical and a clinically oriented radiological investigation. Neurological events occurring during childhood (in both children and adults of the series) and adulthood were recorded. One or several neurological manifestations have been observed in 55% of patients (adults and children) (n = 87). These included: headache (28 patients); hydrocephalus (7); epilepsy (5); lacunar stroke (1); white matter disease (1); intraspinal neurofibroma (3); facial palsy (1); radiculopathy (5); and polyneuropathy (2). Tumours included: optic pathway tumours (20); meningioma (2); cerebral glioma (3); and malignant peripheral nerve sheath tumours (6). Life-threatening complications were observed in five adults and included four malignant peripheral nerve sheath tumours and one meningioma. Pain was the leading symptom in 11 adults and was related to malignant peripheral nerve sheath tumours, complications of intraspinal neurofibromas, subcutaneous neurofibromas and peripheral nerve neurofibromas. NF1 in adults was not associated with other disabling or life-threatening neurological complications. Symptomatic optic pathway tumours, cerebral gliomas, symptomatic aqueductal stenosis and spinal compression due to intraspinal NF were observed exclusively during childhood. In this series, the predominant neurological features of adults with NF1 were chronic pain and malignant peripheral nerve sheath tumours. PMID:10094256

  4. Social functioning in adults with neurofibromatosis type 1.

    PubMed

    Pride, Natalie A; Crawford, Hilda; Payne, Jonathan M; North, Kathryn N

    2013-10-01

    Neurofibromatosis type 1 (NF1) is a common single-gene disorder characterised by a diverse range of cutaneous, neurological and neoplastic manifestations. It is well recognised that children with NF1 have poor peer interactions and are at risk for deficits in social skills. Few studies, however, have examined social functioning in adults with NF1. We aimed to determine whether adults with NF1 are at greater risk for impairment in social skills and to identify potential risk factors for social skills deficits. We evaluated social skills in 62 adults with NF1 and 39 controls using self-report and observer-report measures of social behaviour. We demonstrate that adults with NF1 exhibit significantly less prosocial behaviour than controls. This deficit was associated with social processing abilities and was more evident in males. The frequency of antisocial behaviour was comparable between the two groups, however was significantly associated with behavioural regulation in the NF1 group. These findings suggest that poor social skills in individuals with NF1 are due to deficits in prosocial behaviour, rather than an increase in antisocial behaviour. This will aid the design of interventions aimed at improving social skills in individuals with NF1. PMID:23911645

  5. Dystrophic Spinal Deformities in a Neurofibromatosis Type 1 Murine Model

    PubMed Central

    Yang, Dalong; Yang, Hao; Chen, Shi; Wu, Xiaohua; Li, Xiaohong; Yang, Xianlin; Mohammad, Khalid S.; Guise, Theresa A.; Bergner, Amanda L.; Stevenson, David A.; Yang, Feng-Chun

    2015-01-01

    Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/−;PeriCre and Nf1flox/−;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/−;PeriCre and Nf1flox/−;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36–60% of Nf1flox/−;PeriCre and Nf1flox/−;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population. PMID:25786243

  6. Dystrophic spinal deformities in a neurofibromatosis type 1 murine model.

    PubMed

    Rhodes, Steven D; Zhang, Wei; Yang, Dalong; Yang, Hao; Chen, Shi; Wu, Xiaohua; Li, Xiaohong; Yang, Xianlin; Mohammad, Khalid S; Guise, Theresa A; Bergner, Amanda L; Stevenson, David A; Yang, Feng-Chun

    2015-01-01

    Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population. PMID:25786243

  7. Nevus anemicus: a distinctive cutaneous finding in neurofibromatosis type 1.

    PubMed

    Hernández-Martín, Angela; García-Martínez, Francisco Javier; Duat, Anna; López-Martín, Inmaculada; Noguera-Morel, Lucero; Torrelo, Antonio

    2015-01-01

    Nevus anemicus (NA) is a cutaneous anomaly characterized by pale, well-defined patches with limited vascularization after rubbing. They are largely known to be associated with neurofibromatosis 1 (NF1) and have received little attention in the literature until recently. We sought to characterize the prevalence and clinical features of patients with NA and NF1. We conducted an observational prospective study of 99 children with NF1 at the Hospital Niño Jesús, Madrid, Spain, from January 1, 2012, through July 31, 2013, and reviewed three other series of patients with NF1 and NA recently reported. The prevalence of NA in children with NF1 ranged from 8.8% to 51%, being much more prevalent at younger ages. Prospective studies yielded a higher prevalence than retrospective studies. NA was located most commonly on the trunk, particularly on the anterior chest wall, and was often multiple. Patients with segmental NF1 or isolated café au lait spots rarely had NA, and NA was absent in other genodermatoses. The collection of data was not homogeneous in all studies. NA has a high prevalence in individuals with NF1 patients but seems to be absent in connection with other genodermatoses, therefore its presence can assist in the diagnosis of suspected cases of NF1. The subtle clinical appearance of NA makes its detection difficult, and physicians involved in the care of children with NF1 must be aware of its possible presence and significance. PMID:25690591

  8. Somatic mosaicism in a patient with neurofibromatosis type 1.

    PubMed Central

    Colman, S. D.; Rasmussen, S. A.; Ho, V. T.; Abernathy, C. R.; Wallace, M. R.

    1996-01-01

    Using loss of heterozygosity analysis, a method designed to detect moderate to large gene deletions, we have identified a new-mutation neurofibromatosis type 1 (NF1) patient who is somatically mosaic for a large maternally derived deletion in the NF1 gene region. The deletion extends at least from exon 4 near the 5' end of the gene to intron 39 near the 3' end. The gene-coding region is, therefore, mostly or entirely deleted, encompassing a loss of > or = 100 kb. We hypothesize that the deletion occurred at a relatively early developmental timepoint, since signs of NF1 in this patient are not confined to a specific body region, as seen in "segmental" NF, and since both mesodermally and ectodermally derived cells are affected. This report provides the first molecular evidence of somatic mosaicism in NF1 and, taken together with a recent report of germ-line mosaicism in NF1, adds credence to the concept that mosaicism plays an important role in phenotypic and genetic aspects of NF1 and may even be a relatively common phenomenon. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8644707

  9. Activity and participation in children with neurofibromatosis type 1.

    PubMed

    Johnson, Barbara A; Sheng, Xiaoming; Perry, Amber S; Stevenson, David A

    2014-10-24

    We describe activity and participation in children and youth with neurofibromatosis type 1 (NF1), and compared an intervention and control group after a strengthening program using the Pediatric Outcomes Data Collection Instrument (PODCI) and the Children's Assessment of Participation and Enjoyment (CAPE). Questionnaires were filled out by parents at baseline, 12-weeks, and 1-year. The intervention group performed a strengthening program twice a week for ten weeks, followed by a 9-month independent program. Thirty-six participants (18 control, 18 intervention) between the ages of 5- and 18-years (mean 10.6 years, SD 4.6 years) were enrolled, and 34 completed the 1-year assessment. There were significant differences between formal and informal participation (p<0.0001) in baseline CAPE scores for the entire cohort. At 12 weeks, PODCI upper extremity function improved in intervention and decreased in controls (p=0.040), while happiness declined in intervention and increased in control (p=0.003). There were no significant differences between control and intervention groups in any of the CAPE or PODCI change scores from baseline to 1-year. Upper extremity function, sport and physical function, comfort/pain and happiness PODCI scores were lower than normative values. The NF1 cohort had low participation in formal active physical and skill-based activities. The companionship and location dimensions suggest participation occurs with family and other relatives in the home or a relative's home and reflects a pattern of social isolation from peers. PMID:25462482

  10. Neurocognitive profiles of learning disabled children with neurofibromatosis type 1

    PubMed Central

    Orraca-Castillo, Miladys; Estévez-Pérez, Nancy; Reigosa-Crespo, Vivian

    2014-01-01

    Neurofibromatosis 1 (NF1) is a genetic condition generally associated with intellectual deficiency and learning disabilities. Although there have been groundbreaking advances in the understanding of the molecular, cellular, and neural systems underlying learning deficits associated to NF1 in animal models, much remains to be learned about the spectrum of neurocognitive phenotype associated with the NF1 clinical syndrome. In the present study, 32 children with NF1 ranging from 7 to 14 years were evaluated with neurocognitive tests dedicated to assess basic capacities which are involved in reading and mathematical achievement. Deficits in lexical and phonological strategies and poor number facts retrieval were found underlying reading and arithmetic disorders, respectively. Additionally, efficiencies in lexical/phonological strategies and mental arithmetic were significant predictors of individual differences in reading attainment and math. However, deficits in core numeric capacities were not found in the sample, suggesting that it is not responsible for calculation dysfluency. The estimated prevalence of Developmental Dyscalculia was 18.8%, and the male:female ratio was 5:1. On the other hand, the prevalence of Developmental Dyslexia was almost 3 times as high (50%), and no gender differences were found (male: female ratio = 1:1). This study offers new evidence to the neurocognitive phenotype of NF1 contributing to an in depth understanding of this condition, but also to possible treatments for the cognitive deficits associated with NF1. PMID:24936179

  11. Runx1 contributes to neurofibromatosis type 1 neurofibroma formation

    PubMed Central

    Li, H; Zhao, X; Yan, X; Jessen, WJ; Kim, M-O; Dombi, E; Liu, PP; Huang, G; Wu, J

    2015-01-01

    Neurofibromatosis type 1 (NF1) patients are predisposed to neurofibromas but the driver(s) that contribute to neurofibroma formation are not fully understood. By cross comparison of microarray gene lists on human neurofibroma-initiating cells and developed neurofibroma Schwann cells (SCs) we identified RUNX1 overexpression in human neurofibroma initiation cells, suggesting RUNX1 might relate to neurofibroma formation. Immunostaining confirmed RUNX1 protein overexpression in human plexiform neurofibromas. Runx1 overexpression was confirmed in mouse Schwann cell progenitors (SCPs) and mouse neurofibromas at the messenger RNA and protein levels. Genetic inhibition of Runx1 expression by small hairpin RNA or pharmacological inhibition of Runx1 function by a Runx1/Cbfβ interaction inhibitor, Ro5-3335, decreased mouse neurofibroma sphere number in vitro. Targeted genetic deletion of Runx1 in SCs and SCPs delayed mouse neurofibroma formation in vivo. Mechanistically, loss of Nf1 increased embryonic day 12.5 Runx1+/Blbp+ progenitors that enable tumor formation. These results suggest that Runx1 has an important role in Nf1 neurofibroma initiation, and inhibition of RUNX1 function might provide a novel potential therapeutic treatment strategy for neurofibroma patients. PMID:26073082

  12. Complex Vertebral Arteriovenous Fistula and Ruptured Aneurysm in Neurofibromatosis

    PubMed Central

    Roth, Tori C.; Manness, Wayne K; Hershey, Beverly L.; Yazdi, Joseph

    2000-01-01

    The objective and importance of this study was to describe the challenges encountered with treating a high-flow vertebral arteriovenous fistula (AVF) and ruptured aneurysm in a patient with life-threatening hemorrhage. A 36-year-old female with Neurofibromatosis type 1 (NF1) presented 2 weeks after uneventful cesarean section with a rapidly expanding pulsatile neck mass. Angiography demonstrated a complex left vertebral AVF and multiple associated vertebral artery aneurysms. Emergent endovascular coil embolization was performed using a retrograde and antegrade approach to occlude the fistulas and trap the ruptured aneurysm, successfully treating the acute hemorrhage. Subsequent definitive therapy was accomplished utilizing a combined neurointerventional and neurosurgical strategy of direct-puncture acrylic embolization and ligation of the vertebral artery. Recent advances in neurointerventional technology allow novel approaches in the primary and/or preoperative treatment of complex vascular lesions such as those seen in NF1. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5p40-b PMID:17171099

  13. Cognitive and psychosocial phenotype of young children with neurofibromatosis-1.

    PubMed

    Klein-Tasman, Bonita P; Janke, Kelly M; Luo, Wen; Casnar, Christy L; Hunter, Scott J; Tonsgard, James; Trapane, Pamela; van der Fluit, Faye; Kais, Lorri A

    2014-01-01

    Children with neurofibromatosis-1 (NF1), a neurodevelopmental disorder resulting from a mutation of the NF1 gene (17q11.2), often have difficulties with learning and attention, but there is little research in the early childhood years. In this study, the cognitive and psychosocial functioning of 40 young children with NF1 (ages 3 through 6) was examined and compared both to normative data and to a contrast group comprised of unaffected siblings and community members matched for age and socio-economic status (n = 37). Children with NF1 showed significantly weaker cognitive abilities across all domains and for the vast majority of subtests. Consistent with research in older children, a variety of patterns of intra-individual strength and weakness were present for young children with NF1. Few significant group differences in psychosocial functioning were observed, but the children with NF1 showed significantly greater functional communication problems than did the unaffected group. Overall, the results indicate that in participant groups matched for age and socioeconomic status, cognitive vulnerabilities are evident for close to half of young children with NF1, with some relations to psychosocial functioning, particularly functional communication, attention problems and social skills. PMID:24229851

  14. Neurocognitive profiles of learning disabled children with neurofibromatosis type 1.

    PubMed

    Orraca-Castillo, Miladys; Estévez-Pérez, Nancy; Reigosa-Crespo, Vivian

    2014-01-01

    Neurofibromatosis 1 (NF1) is a genetic condition generally associated with intellectual deficiency and learning disabilities. Although there have been groundbreaking advances in the understanding of the molecular, cellular, and neural systems underlying learning deficits associated to NF1 in animal models, much remains to be learned about the spectrum of neurocognitive phenotype associated with the NF1 clinical syndrome. In the present study, 32 children with NF1 ranging from 7 to 14 years were evaluated with neurocognitive tests dedicated to assess basic capacities which are involved in reading and mathematical achievement. Deficits in lexical and phonological strategies and poor number facts retrieval were found underlying reading and arithmetic disorders, respectively. Additionally, efficiencies in lexical/phonological strategies and mental arithmetic were significant predictors of individual differences in reading attainment and math. However, deficits in core numeric capacities were not found in the sample, suggesting that it is not responsible for calculation dysfluency. The estimated prevalence of Developmental Dyscalculia was 18.8%, and the male:female ratio was 5:1. On the other hand, the prevalence of Developmental Dyslexia was almost 3 times as high (50%), and no gender differences were found (male: female ratio = 1:1). This study offers new evidence to the neurocognitive phenotype of NF1 contributing to an in depth understanding of this condition, but also to possible treatments for the cognitive deficits associated with NF1. PMID:24936179

  15. Cognitive profile of children with neurofibromatosis and reading disabilities.

    PubMed

    Cutting, Laurie E; Levine, Terry M

    2010-01-01

    A large percentage of children with Neurofibromatosis Type 1(NF-1) have learning disabilities, often in the realm of reading. Previous studies have indicated that children with NF-1 show a neuropsychological profile similar to idiopathic reading disabilities (IRD); however, studies typically have not subdivided children with NF-1 into those who do and do not have RD (NF+RD and NFnoRD, respectively). The current study examined the cognitive profile of children with NF-1 with and without RD and compared them to children with IRD as well as to typically developing readers (Controls). Findings showed that children with NF+RD performed similarly to children with IRD on phonological, rapid naming, and reading comprehension measures; however, children with NF+RD displayed pronounced visual-spatial deficits as compared to IRD and Control groups. In addition, when comparing the NF-1 groups to each other as well as to the control and IRD groups, the current study reported that there were no oral language differences; lack of findings in the realm of oral language was attributed to the fact that groups were equated on IQ. Overall, findings suggest that a more refined classification of children with NF-1 may be helpful for tailoring academic interventions. PMID:20521183

  16. Malignant Triton Tumors in Sisters with Clinical Neurofibromatosis Type 1

    PubMed Central

    Alina, Basnet; Sebastian, Jofre A.; Gerardo, Capo

    2015-01-01

    Malignant triton tumors (MTTs) are rare and aggressive sarcomas categorized as a subgroup of malignant peripheral nerve sheath tumors (MPNSTs). MTTs arise from Schwann cells of peripheral nerves or existing neurofibromas and have elements of rhabdomyoblastic differentiation. We report the occurrence of MTTs in two sisters. The first patient is a 36-year-old female who presented with left sided chest wall swelling. She also had clinical features consistent with neurofibromatosis type 1 (NF-1). Debulking of the mass showed high-grade malignant peripheral nerve sheath tumor with skeletal muscle differentiation (MTT). The patient was treated with ifosfamide and adriamycin along with radiation. Four years after treatment, she still has no evidence of disease recurrence. Her sister subsequently presented to us at the age of 42 with left sided lateral chest wall pain. Imaging showed a multicompartmental retroperitoneal cystic mass with left psoas involvement. The tumor was resected and, similarly to her sister, it showed high-grade malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (MTT). The patient was started on chemotherapy and radiation as described above. PMID:26114002

  17. Neurofibromatosis type 1 presenting with plexiform neurofibromas in two patients: MRI features.

    PubMed

    Halefoglu, Ahmet Mesrur

    2012-01-01

    Neurofibromatosis type 1 (NF1), also known as peripheral neurofibromatosis or von Recklinghausen's disease, is one of the most common genetic disorders. It is inherited in an autosomal dominant pattern. Multiple cutaneous neurofibromas are hallmark lesions of NF1. Localized and plexiform neurofibromas of the paraspinal and sacral region are the most common abdominal neoplasms in NF1. Herein, we report two patients with a known history of NF1 presenting with multiple, extensive localized and plexiform neurofibromas. We describe the important distinguishing features of these tumors as seen on magnetic resonance imaging (MRI), including very bright signal intensity and target sign on T2 weighted images. PMID:23049566

  18. Somatostatinoma of the first jejunal loop in a patient with neurofibromatosis von Recklinghausen and bilateral pheochromocytoma.

    PubMed

    Constantinoiu, Silviu; Constantin, Adrian; Predescu, Dragos; Iosif, Cristina; Hoara, Petre; Achim, Florin; Surugiu, Paul; Bacanu, Florin; Cociu, Luminita

    2012-09-01

    Somatostatinoma is a rare neuroendocrine tumor which especially develops in the pancreas. There are few communicated cases about extra-pancreatic localization, having as a particularity the absence of somatostatin hypersecretion syndrome and frequent association with von Recklinghausen neurofibromatosis. We present the case of a 42-year old patient with Von Recklinghausen neurofibromatosis admitted in our clinic with a chronic upper digestive obstruction syndrome. The presence of a first jejunal loop somatostatinoma was an intraoperative surprising diagnosis that imposed jejunal resection and association of complementary specific treatment. Despite the therapeutic correct management, the status of the patient deteriorated very fast, confirming the aggressiveness of this neoplasia. PMID:22819908

  19. [Somatostatin-producing endocrine pancreatic tumor in Recklinghausen's neurofibromatosis. Case report and literature review].

    PubMed

    Saurenmann, P; Binswanger, R; Maurer, R; Stamm, B; Hegglin, J

    1987-07-25

    Somatostatin-producing tumors of the pancreas were first described in 1977. In 1983 a syndrome involving multiple endocrine neoplasias (MEN) was named type III A. This syndrome consists of carcinoid of the duodenum, often producing somatostatin, and von Recklinghausen's disease (neurofibromatosis) or pheochromocytoma. The case is reported of a 62-year-old man with familial neurofibromatosis and a tumor of the head of the pancreas spreading into pars II of the duodenum. After Whipple's duodenopancreatectomy the patient exhibited no further symptoms. Immunohistochemistry served to prove the production of somatostatin and small amounts of calcitonin in the tumor. PMID:2890200

  20. Acute cardiomyopathy and multiorgan failure in a patient with pheochromocytoma and neurofibromatosis type 1.

    PubMed

    Ahmed, Rezwan; Darrat, Yousef; Hamoudeh, Eyad; Elhamdani, Mehair Omar; Yaqub, Abid

    2014-02-01

    Pheochromocytomas are catecholamine secreting tumours of the adrenal gland, discovered in 0.1% of patients with hypertension. Our case highlights an atypical presentation of pheochromocytoma in a patient with Neurofibromatosis type 1 who developed cardiogenic shock with multi-organ failure. The patient demonstrated reversible dilated cardiomyopathy during her hospital stay, and her blood pressure fluctuated widely. Discovery of right adrenal mass followed by biochemical testing facilitated the diagnosis. Judicious medical management led to an uneventful surgical removal of the tumour followed by marked stabilization of her blood pressure. We discuss the characteristics of pheochromocytoma associated with Neurofibromatosis type 1 via reversible cardiac dysfunction. PMID:24640818

  1. Sirolimus for progressive neurofibromatosis type 1–associated plexiform neurofibromas: a Neurofibromatosis Clinical Trials Consortium phase II study

    PubMed Central

    Weiss, Brian; Widemann, Brigitte C.; Wolters, Pamela; Dombi, Eva; Vinks, Alexander; Cantor, Alan; Perentesis, John; Schorry, Elizabeth; Ullrich, Nicole; Gutmann, David H.; Tonsgard, James; Viskochil, David; Korf, Bruce; Packer, Roger J.; Fisher, Michael J.

    2015-01-01

    Background Plexiform neurofibromas (PNs) are benign peripheral nerve sheath tumors that arise in one-third of individuals with neurofibromatosis type 1 (NF1). They may cause significant disfigurement, compression of vital structures, neurologic dysfunction, and/or pain. Currently, the only effective management strategy is surgical resection. Converging evidence has demonstrated that the NF1 tumor suppressor protein, neurofibromin, negatively regulates activity in the mammalian Target of Rapamycin pathway. Methods We employed a 2-strata clinical trial design. Stratum 1 included subjects with inoperable, NF1-associated progressive PN and sought to determine whether sirolimus safely and tolerably increases time to progression (TTP). Volumetric MRI analysis conducted at regular intervals was used to determine TTP relative to baseline imaging. Results The estimated median TTP of subjects receiving sirolimus was 15.4 months (95% CI: 14.3–23.7 mo), which was significantly longer than 11.9 months (P < .001), the median TTP of the placebo arm of a previous PN clinical trial with similar eligibility criteria. Conclusions This study demonstrated that sirolimus prolongs TTP by almost 4 months in patients with NF1-associated progressive PN. Although the improvement in TTP is modest, given the lack of significant or frequent toxicity and the availability of few other treatment options, the use of sirolimus to slow the growth of progressive PN could be considered in select patients. PMID:25314964

  2. Familiares a cargo de pacientes de cáncer: funciones y desafíos (PDQ®)—Versión para profesionales de salud

    Cancer.gov

    Sumario informativo revisado por expertos acerca de los desafíos que enfrentan los familiares a cargo de los pacientes con cáncer. Este resumen se centra en las funciones típicas y las inquietudes de las personas a cargo del paciente y en las intervenciones útiles para esas personas.

  3. PCR-based polymorphisms in neurofibromatosis type 1 (NFI)

    SciTech Connect

    Lai, P.S.; Chee, S.; Low, P.S.

    1994-09-01

    Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders in humans with an incidence of 1 in 3,000. The NF1 gene is located on chromosome 17q 11.2 and encodes an ubiquitously expressed transcript of about 13kb. Direct mutation detection is difficult in this disorder due to the large gene size, high mutation rate and variety of mutations. We have studied the allele frequencies of seven PCR-based polymorphisms. Six of the probes used flank the NF1 gene, namely p11.3C4.2/Msp I (proximal), pEW206/Msp I (distal), p2.f9.8/Rsa I (distal), pEW207/Bgl II (distal), pEW207/Hind III (distal) and pHHH202/Rsa I (proximal). An intragenic RFLP, pEvi 2B-B/Eco R1 polymorphism in intron 27, was also analyzed by PCR. Allele frequencies for 48 normal unrelated individuals were obtained as follows: A1 = 0.40, A2 = 0.6 (p11.3C4.2/Msp I), A1 = 0.44, A2 = 0.56 (pEW206/Msp I), A1 = 0.17, A2 = 0.83 (p2.F9.8/Rsa I), A1 = 0.64, A2 = 0.36 (pEW207/Bgl I), A1 = 0.45, A2 = 0.55 (pEvi 2B-B/Eco RI). Heterozygosity rates of the alleles ranged from 20.8% to 51.7%. Using a combination of these markers, seven local families with NF1 were studied. Normal Mendelian segregation of alleles was observed in these families and no recombination was detected so far. These PCR-based markers were found to be useful for linkage analysis in our families.

  4. Pediatric neurofibromatosis 1 and parental stress: a multicenter study

    PubMed Central

    Esposito, Maria; Marotta, Rosa; Roccella, Michele; Gallai, Beatrice; Parisi, Lucia; Lavano, Serena Marianna; Carotenuto, Marco

    2014-01-01

    Background Neurofibromatosis 1 (NF1) is a complex and multifaceted neurocutaneous syndrome with many and varied comorbidities. The literature about the prevalence and degree of maternal stress and the impact of NF1 in the parent–child interaction is still scant. The aim of this study was to evaluate the prevalence of maternal stress in a large pediatric sample of individuals affected by NF1. Methods Thirty-seven children (19 boys, 18 girls) of mean age 7.86±2.94 (range 5–11) years affected by typical NF1 and a control group comprising 405 typically developing children (207 boys, 198 girls; mean age 8.54±2.47 years) were included in this study. To assess parental stress, the mothers of all individuals (NF1 and comparisons) filled out the Parenting Stress Index-Short Form test. Results The two study groups were comparable for age (P=0.116), gender (P=0.886), and body mass index adjusted for age (P=0.305). Mothers of children affected by NF1 reported higher mean Parenting Stress Index-Short Form scores on the Parental Distress domain (P<0.001), Difficult Child domain (P<0.001), and Total Stress domain than the mothers of typically developing children (controls) (P<0.001). No significant differences between the two groups were found for the Parent-Child Dysfunctional Interaction domain (P=0.566) or Defensive Responding domain scores (P=0.160). Conclusion NF1 is considered a multisystemic and complex disease, with many still unrecognized features in pediatric patients and in their families. In this light, our findings about the higher levels of maternal stress highlight the importance of considering the environmental aspects of NF1 management in developmental age. PMID:24489471

  5. Alterations in White Matter Microstructure in Neurofibromatosis-1

    PubMed Central

    Karlsgodt, Katherine H.; Rosser, Tena; Lutkenhoff, Evan S.; Cannon, Tyrone D.; Silva, Alcino; Bearden, Carrie E.

    2012-01-01

    Neurofibromatosis (NF1) represents the most common single gene cause of learning disabilities. NF1 patients have impairments in frontal lobe based cognitive functions such as attention, working memory, and inhibition. Due to its well–characterized genetic etiology, investigations of NF1 may shed light on neural mechanisms underlying such difficulties in the general population or other patient groups. Prior neuroimaging findings indicate global brain volume increases, consistent with neural over-proliferation. However, little is known about alterations in white matter microstructure in NF1. We performed diffusion tensor imaging (DTI) analyses using tract-based spatial statistics (TBSS) in 14 young adult NF1 patients and 12 healthy controls. We also examined brain volumetric measures in the same subjects. Consistent with prior studies, we found significantly increased overall gray and white matter volume in NF1 patients. Relative to healthy controls, NF1 patients showed widespread reductions in white matter integrity across the entire brain as reflected by decreased fractional anisotropy (FA) and significantly increased absolute diffusion (ADC). When radial and axial diffusion were examined we found pronounced differences in radial diffusion in NF1 patients, indicative of either decreased myelination or increased space between axons. Secondary analyses revealed that FA and radial diffusion effects were of greatest magnitude in the frontal lobe. Such alterations of white matter tracts connecting frontal regions could contribute to the observed cognitive deficits. Furthermore, although the cellular basis of these white matter microstructural alterations remains to be determined, our findings of disproportionately increased radial diffusion against a background of increased white matter volume suggest the novel hypothesis that one potential alteration contributing to increased cortical white matter in NF1 may be looser packing of axons, with or without myelination

  6. Clinical features of 58 Japanese patients with mosaic neurofibromatosis 1.

    PubMed

    Tanito, Katsumi; Ota, Arihito; Kamide, Ryoichi; Nakagawa, Hidemi; Niimura, Michihito

    2014-08-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutation in the NF1 tumor-suppressor gene, and may sometimes manifest in a mosaic form. "Segmental NF1" is generally assumed to be the result of somatic mosaicism for a NF1 mutation, and patients with mosaic NF1 have typical features of NF1 limited to specific body segments. The clinical features of 58 patients (42 females and 16 males; aged 1-69 years; mean age, 23.4 years) with mosaic NF1 seen at the Jikei University Hospital during 2004-2007 and at the Jikei University Daisan Hospital during 2007-2011, were retrospectively studied. Somatic or gonosomal mosaicism was not investigated. Patients were classified into four groups: (i) pigmentary changes (café-au-lait spots and freckling) only (n = 32); (ii) neurofibromas only (n = 5); (iii) neurofibromas and pigmentary changes (n = 13); and (iv) solitary plexiform neurofibromas (n = 8). The area of involvement was variable. The majority of patients were asymptomatic, except patients with plexiform neurofibromas who presented most commonly with pain or tenderness. Lisch nodules were rarely seen. Only four of our 58 patients (6.9%) had specific NF1 complications, including language delay (n = 1) and bone deformity (n = 3). Two patients were ascertained through their children with generalized NF1. Patients with mosaic NF1 are at low risk of developing disease-associated complications, except patients with plexiform neurofibromas. However, they need to be aware of the small risk of having a child with generalized NF1. PMID:25041723

  7. Surgical treatment of early onset scoliosis in neurofibromatosis.

    PubMed

    Greggi, Tiziana; Martikos, Konstantinos

    2012-01-01

    Case series report of twenty-three patients, aged between 4 and 11 years, were surgically treated at the Authors' Spine Surgery Division in the past 15 years. Mean follow-up is 5 years (range, 18 months to 15 years). Mean age at the time of surgical procedure was 9.1 years (range, 4 years to 11 years). Average scoliosis was 48° (range, 38° to 82°) and skeletal maturity according to Risser sign was 0 in all of the patients. Patients were divided into 2 Groups according to the surgical procedure adopted. Posterior only instrumentation was performed in 16 patients that presented with a thoracic kyphosis lower than 50° (Group A), in the remaining 7 patients showing thoracic kyphosis exceeding 50°, combined anterior and posterior instrumented arthrodesis was performed (Group B). One patient, belonging to Group A, was instrumented with growing rod without fusion. Average correction of scoliosis was 60%, overall complication rate 24% and major 7%. Crankshaft phenomenon was observed in 21% (Group A): in these cases, anterior arthrodesis was performed after a mean 15-month from first surgical procedure. Fusion failure was observed in 1 (Group B) patient who underwent revision of posterior instrumentation. Clinical and radiographic evaluation at F-up showed good outcome in terms of deformity progression and quality of life. Early and aggressive surgery is the most effective management for dystrophic curves in neurofibromatosis has been proven to be. Our experience confirms the need for spinal stabilization even in pediatric age in rapidly progressive spinal deformities. PMID:22744522

  8. Alterations in white matter microstructure in neurofibromatosis-1.

    PubMed

    Karlsgodt, Katherine H; Rosser, Tena; Lutkenhoff, Evan S; Cannon, Tyrone D; Silva, Alcino; Bearden, Carrie E

    2012-01-01

    Neurofibromatosis (NF1) represents the most common single gene cause of learning disabilities. NF1 patients have impairments in frontal lobe based cognitive functions such as attention, working memory, and inhibition. Due to its well-characterized genetic etiology, investigations of NF1 may shed light on neural mechanisms underlying such difficulties in the general population or other patient groups. Prior neuroimaging findings indicate global brain volume increases, consistent with neural over-proliferation. However, little is known about alterations in white matter microstructure in NF1. We performed diffusion tensor imaging (DTI) analyses using tract-based spatial statistics (TBSS) in 14 young adult NF1 patients and 12 healthy controls. We also examined brain volumetric measures in the same subjects. Consistent with prior studies, we found significantly increased overall gray and white matter volume in NF1 patients. Relative to healthy controls, NF1 patients showed widespread reductions in white matter integrity across the entire brain as reflected by decreased fractional anisotropy (FA) and significantly increased absolute diffusion (ADC). When radial and axial diffusion were examined we found pronounced differences in radial diffusion in NF1 patients, indicative of either decreased myelination or increased space between axons. Secondary analyses revealed that FA and radial diffusion effects were of greatest magnitude in the frontal lobe. Such alterations of white matter tracts connecting frontal regions could contribute to the observed cognitive deficits. Furthermore, although the cellular basis of these white matter microstructural alterations remains to be determined, our findings of disproportionately increased radial diffusion against a background of increased white matter volume suggest the novel hypothesis that one potential alteration contributing to increased cortical white matter in NF1 may be looser packing of axons, with or without myelination

  9. Potential Influences on Mathematical Difficulties in Children and Adolescents with Neurofibromatosis, Type 1

    ERIC Educational Resources Information Center

    Moore, Bartlett D.

    2009-01-01

    Neurofibromatosis, type 1 (NF-1) is a common genetic disorder affecting 1 in 3,500-4,000 individuals in the world. Mutations of the NF-1 gene produce a myriad of physical, medical, and psychological manifestations. Although there is a very high degree of variability in the manifestations between individuals with NF-1, the majority of children and…

  10. Ultrasound-Guided Popliteal Nerve Block in a Patient with Malignant Degeneration of Neurofibromatosis 1

    PubMed Central

    Desai, Arjun; Carvalho, Brendan; Hansen, Jenna; Hill, Jonay

    2012-01-01

    A 41-year-old female patient with neurofibromatosis 1 presented with new neurologic deficits secondary to malignant degeneration of a tibial lesion. Ultrasound mapping of the popliteal nerve revealed changes consistent with an intraneural neurofibroma. Successful popliteal nerve blockade was achieved under ultrasound guidance. PMID:22649742

  11. Pulsatile enophthalmos, severe esotropia, kinked optic nerve and visual loss in neurofibromatosis type-1

    PubMed Central

    Sachdeva, Virender; Haque, Nazmul; Pathengay, Avinash; Kekunnaya, Ramesh

    2015-01-01

    Neurofibromatosis Type I if associated with aplasia of greater wing of sphenoid may be associated with a pulsatile exophthalmos. However, very rarely it may be associated with a pulsatile enophthalmos. This clinical image describes a rare presentation with pulsatile enophthalmos, esotropia and kinking of the optic nerve due to neurofibomatosis type I. PMID:26903735

  12. Pulsatile enophthalmos, severe esotropia, kinked optic nerve and visual loss in neurofibromatosis type-1.

    PubMed

    Sachdeva, Virender; Haque, Nazmul; Pathengay, Avinash; Kekunnaya, Ramesh

    2015-01-01

    Neurofibromatosis Type I if associated with aplasia of greater wing of sphenoid may be associated with a pulsatile exophthalmos. However, very rarely it may be associated with a pulsatile enophthalmos. This clinical image describes a rare presentation with pulsatile enophthalmos, esotropia and kinking of the optic nerve due to neurofibomatosis type I. PMID:26903735

  13. Detection of Cerebral Vasculopathy by Transcranial Doppler in Children With Neurofibromatosis Type 1.

    PubMed

    Paschoal, Joelma Karin Sagica Fernandes; Paschoal, Fernando Mendes; de Lima, Fernanda Teresa; Pinho, Ricardo Silva; Vilanova, Luiz Celso Pereira; Bor-Seng-Shu, Edson; Masruha, Marcelo Rodrigues

    2016-03-01

    Neurofibromatosis type 1 is characterized by nerve sheath neurofibromas associated with a number of additional clinical features, including cerebrovascular disease. The aim of this study was to use transcranial Doppler as a screening method for identifying cerebral vasculopathy in children with neurofibromatosis type 1. Forty children with neurofibromatosis type 1, aged 5 to 18 years old, were examined by transcranial Doppler. Patients presenting with hemodynamic features of arterial stenosis/occlusion on transcranial Doppler underwent magnetic resonance angiography to confirm the findings. Magnetic resonance angiography was performed on 4 children who exhibited a transcranial Doppler hemodynamic pattern indicative of cerebral vasculopathy. Among these cases, 2 presented internal carotid artery stenosis/occlusion, 1 had bilateral middle cerebral artery stenosis, and 1 presented a normal magnetic resonance angiography result. Transcranial Doppler can be used routinely in the investigation of cerebrovascular disease in neurofibromatosis type 1 patients, where magnetic resonance angiography can be subsequently applied to confirm the diagnosis, further contributing to the prevention of cerebrovascular events. PMID:26184486

  14. Familial bilateral combined hamartoma of retina and retinal pigment epithelium associated with neurofibromatosis 1.

    PubMed

    Yassin, Sanaa A; Al-Tamimi, Elham R

    2012-04-01

    We report a family of three siblings followed between 2005 and 2011 with bilateral combined hamartoma of the retina and retinal pigment epithelium, with the age of diagnosis ranging from 7 to 13 years. The main reason for consultation was reduction of vision and squint. The diagnosis was determined based on the clinical findings on fundus examination: increased pigmentation at the macula with slightly elevated, gray-white macular lesion, tortuosity of perimacular blood vessels and glial epiretinal membrane. The elder brother was found to have left posterior subcapsular cataract. He was also confirmed to have neurofibromatosis type 1, the youngest sister fit in the diagnostic criteria for neurofibromatosis type 1, while the middle sister was presumed to have neurofibromatosis type 1. Follow-up showed stability of the retinal lesion in the three cases, with the progression to develop right posterior subcapsular cataract in the elder sister. This report is aimed to demonstrate that the occurrence of bilateral combined hamartoma of the retina and retinal pigment epithelium could raise the possibility of associated neurofibromatosis. PMID:23960997

  15. A rare case of segmental neurofibromatosis with multiple blue-red pseudoatrophic plaques.

    PubMed

    Diociaiuti, Andrea; Guidi, Beatrice; Surrenti, Tiziana; Boldrini, Renata; Callea, Francesco; El Hachem, May

    2014-09-01

    We report the case of a 5-year-old girl who presented with 2 blue-red atrophic plaques on the left leg as well as subcutaneous nodules that were present since infancy. Although the clinical criteria of neurofibromatosis (NF) were absent, microscopic examination revealed features of a blue-red neurofibroma. PMID:25279476

  16. Neurofibromatosis Type 1 Associated with Hashimoto's Thyroiditis: Coincidence or Possible Link

    PubMed Central

    Nabi, Junaid

    2013-01-01

    Introduction. Hashimoto's thyroiditis is a common form of chronic autoimmune thyroid disease (AITD) and often coexists with other autoimmune diseases, but Hashimoto's thyroiditis associated with an autosomal dominant neurofibromatosis type 1 is exceedingly rare. Case Presentation. A 30-year-old Bengali woman presented to the OPD with complaints of aching pain and tingling sensation in her hands and feet. Physical examination revealed dysmorphic facies, nodular swelling in the neck, cafe-au-lait spots, and neurofibromas covering the entire surface of her body. Her thyroid hormones were within normal limits. Thyroid ultrasound revealed a cystic area in the left lobe of the gland, and ultrasound-guided fine needle aspiration cytology revealed lymphocytic infiltration of the gland, suggesting Hashimoto's thyroiditis. High levels of autoimmune antibodies such as antithyroglobulin and antimicrosomal antibodies confirmed the diagnosis. Conclusion. When encountered with a patient of Neurofibromatosis type 1, a physician should be careful about the possibility of a concomitant autoimmune disease. Clinical presentation of neurofibromatosis and Noonan syndrome often overlaps and recent studies have implicated a mutation in NF1 gene in the etiology of NFNS. More extensive reports and further investigations of such patients having combination of neurofibromatosis type 1 and autoimmune thyroiditis will certainly provide better understanding of this link in the near future. PMID:23691379

  17. Does Attention-Deficit-Hyperactivity Disorder Exacerbate Executive Dysfunction in Children with Neurofibromatosis Type 1?

    ERIC Educational Resources Information Center

    Payne, Jonathan M.; Arnold, Shelley S.; Pride, Natalie A.; North, Kathryn N.

    2012-01-01

    Aim: Although approximately 40% of children with neurofibromatosis type 1 (NF1) meet diagnostic criteria for attention-deficit-hyperactivity disorder (ADHD), the impact of ADHD on the executive functioning of children with NF1 is not understood. We investigated whether spatial working memory and response inhibition are impaired in children with…

  18. Ruptured Aneurysm of Intercostal Arteriovenous Malformation Associated With Neurofibromatosis Type 1: A Case Report

    SciTech Connect

    Kim, Hyung Jun; Seon, Hyun Ju Choi, Song; Jang, Nam Kyu

    2011-02-15

    Intercostal arteriovenous malformations (AVM) are rare, with most being secondary to trauma or iatrogenic therapeutic procedures. Only one case of presumably congenital AVM has been reported. Here we report the first case of a ruptured aneurysm of intercostal AVM associated with neurofibromatosis type 1 in a 32-year-old woman who experienced hypovolemic shock caused by massive hemothorax.

  19. Comunicación en la atención del cáncer (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de la información revisada por expertos acerca de la comunicación con el paciente de cáncer y sus familiares, que incluye los aspectos distintivos de la comunicación con pacientes de cáncer, los factores que afectan la comunicación y la capacitación en aptitudes para la comunicación.

  20. Coexistence of Neurofibromatosis Type-1 and MTHFR C677T Gene Mutation in a Young Stroke Patient: A Case Report

    PubMed Central

    Yilmaz, Halim; Erkin, Gulten; Gumus, Haluk; Nalbant, Lutfiye

    2013-01-01

    In neurofibromatosis type-1 (NF1), cerebrovascular disorders are rarely encountered although vasculopathy is a well-known complication. Several mutations seen in methylenetetrahydrofolate reductase (MTHFR) give rise to the formation of hyperhomocysteinemia and homocystinuria, a considerable risk factor for cardiovascular and cerebrovascular disorders, by leading to enzymatic inactivation. In the paper, a 31-year-old young stroke female patient with the coexistence of neurofibromatosis and MTHFR C677T gene mutation was presented. PMID:23533858

  1. Complicaciones orales de la quimioterapia y la radioterapia (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos acerca de las complicaciones orales, como la mucositis y la disfunción de la glándula salival, que se presentan en pacientes de cáncer tratados con quimioterapia y radioterapia dirigida a la cabeza y el cuello.

  2. Congenital giant plexiform neurofibroma with occipital calvarial dysplasia in association with meningoencephalocele in neurofibromatosis Type 1 and segmental neurofibromatosis: report of 2 cases.

    PubMed

    Dadlani, Ravi; Sadanand, Venkatraman; Ghosal, Nandita; Hegde, Alangar S

    2013-11-01

    Giant plexiform neurofibroma (GPNF) of the scalp is an extremely rare lesion reported in association with neurofibromatosis. Occipital location of GPNF is even more infrequent, especially in association with occipital dysplasia (OD). The authors report 2 pediatric cases of GPNF associated with OD. The first case had an associated meningoencephalocele, and the second had large vascular channels within the lesion and the dominant ipsilateral transverse sinus lying in the center of the calvarial defect. The authors present these 2 unusual cases with a review of literature and discuss the radiological findings, theories of etiopathogenesis of the OD, and management dilemmas. PMID:24032991

  3. Control del dolor: Apoyo para las personas con cáncer

    Cancer.gov

    Contiene información sobre las medicinas contra el dolor para pacientes con cáncer, los planes para controlarlo, cómo hablar con su equipo de atención médica sobre el dolor que usted siente y qué hacer para controlar los efectos físicos y emocionales del

  4. Growth Hormone Deficiency in a Child with Neurofibromatosis-Noonan Syndrome.

    PubMed

    Vurallı, Doğuş; Gönç, Nazlı; Vidaud, Dominique; Özön, Alev; Alikaşifoğlu, Ayfer; Kandemir, Nurgün

    2016-03-01

    Neurofibromatosis-Noonan syndrome (NFNS) is a distinct entity which shows the features of both NF1 (neurofibromatosis 1) and Noonan syndrome (NS). While growth hormone deficiency (GHD) has been relatively frequently identified in NF1 and NS patients, there is limited experience in NFNS cases. The literature includes only one case report of a NFNS patient having GHD and that report primarily focuses on the dermatological lesions that accompany the syndrome and not on growth hormone (GH) treatment. Here, we present a 13-year-old girl who had clinical features of NFNS with a mutation in the NF1 gene. The case is the first NFNS patient reported in the literature who was diagnosed to have GHD and who received GH treatment until reaching final height. The findings in this patient show that short stature is a feature of NFNS and can be caused by GHD. Patients with NFNS who show poor growth should be evaluated for GHD. PMID:26758488

  5. Growth Hormone Deficiency in a Child with Neurofibromatosis-Noonan Syndrome

    PubMed Central

    Vurallı, Doğuş; Gönç, Nazlı; Vidaud, Dominique; Özön, Alev; Alikaşifoğlu, Ayfer; Kandemir, Nurgün

    2016-01-01

    Neurofibromatosis-Noonan syndrome (NFNS) is a distinct entity which shows the features of both NF1 (neurofibromatosis 1) and Noonan syndrome (NS). While growth hormone deficiency (GHD) has been relatively frequently identified in NF1 and NS patients, there is limited experience in NFNS cases. The literature includes only one case report of a NFNS patient having GHD and that report primarily focuses on the dermatological lesions that accompany the syndrome and not on growth hormone (GH) treatment. Here, we present a 13-year-old girl who had clinical features of NFNS with a mutation in the NF1 gene. The case is the first NFNS patient reported in the literature who was diagnosed to have GHD and who received GH treatment until reaching final height. The findings in this patient show that short stature is a feature of NFNS and can be caused by GHD. Patients with NFNS who show poor growth should be evaluated for GHD. PMID:26758488

  6. Malignant Peripheral Nerve Sheath Tumor in Neurofibromatosis Type I : Unusual Presentation of Intraabdominal or Intrathoracic Mass

    PubMed Central

    Kim, Jong Gwang; Sung, Woo Jin; Kim, Dong Hwan; Kim, Young Hwan; Lee, Kyu Bo

    2005-01-01

    A malignant peripheral nerve sheath tumor (MPNST) is an extremely rare soft tissue tumor in the general population. On the other hand, there is a higher incidence of MPNST in patients with neurofibromatosis type I (von Recklinghausen's disease). The common sites are the extremities, trunk, head and neck. However, an intraabdominal or intrathoracic manifestation is uncommon. This paper reports two patients, a 31 year-old woman with multiple neurofibromatosis presenting as an intraabdominal malignant peripheral nerve sheath tumor, and a 33 year-old woman with an intrathoracic malignant peripheral nerve sheath tumor. The patients were treated with chemotherapy followed by radiotherapy. However, one patient died as a result of disease progression 21 months after the diagnosis and the other patient is currently being treated with radiotherapy. PMID:15906964

  7. An Unusual Case of Multiple Intraoral Manifestations of Neurofibromatosis Type 1: Case Report with Literature Review

    PubMed Central

    M, Sheejith; Joseph, Benny; Sheejith, Bhavya

    2014-01-01

    The various oral manifestations of neurofibromatosis in dentulous patients have been documented in literature. Although most of the previous documents have discussed on common findings like a prominent lingual papillae, or solitary overgrowth of gingival soft tissue, this article focuses on a relatively rare occurrence of multiple nodular manifestations of Neurofibromatosis–1 on an edentulous alveolar ridge, tongue, palate and lips of an elderly female patient. PMID:25654048

  8. Aggressive Behaviour of Metastatic Melanoma in a Patient with Neurofibromatosis Type 1

    PubMed Central

    Foley, Robert W.; Maweni, Robert M.; Fabre, Aurelie; Healy, David G.

    2015-01-01

    Malignant melanoma is a common skin neoplasm bearing poor prognosis when presenting with metastases. Rarely melanoma metastases present without an identifiable primary cutaneous lesion despite exhaustive workup. We describe the case of a solitary lung metastasis in a patient with neurofibromatosis type 1 without an identifiable primary tumour. The rapid progression of this malignant neoplasm that led to the patient's death within 1 year is described. PMID:25893129

  9. [Treatment research progress on the treatment of neurofibromatosis type 2-associated vestibular schwannoma].

    PubMed

    Zhao, Yingchao; Yang, Qin; Jiang, Yao

    2015-05-01

    Neurofibromatosis type 2 (NF2) is a dominantly inherited genetic condition. Bilateral vestibular schwannoma, which are benign tumors, composed of neoplastic Schwann cells that arise from the eighth cranial nerve, are the hallmark of NF2. Standard approaches for treatment of growing vestibular schwannoma include observation, surgical removal and radiation therapy. Molecular targeted therapies also present great prosperity in recent years. In this review, we summarize the latest progresses on the treatment of NF2-associated vestibular schwannoma. PMID:26596021

  10. Translaminar screw fixation of a kyphosis of the cervical and thoracic spine in neurofibromatosis.

    PubMed

    Gardner, A; Millner, P; Liddington, M; Towns, G

    2009-09-01

    The spinal manifestations of neurofibromatosis include cervicothoracic kyphosis, in which scalloping of the vertebral body and erosion of the pedicles may render conventional techniques of fixation impossible. We describe a case of cervicothoracic kyphosis managed operatively with a vascularised fibular graft anteriorly across the apex of the kyphus, followed by a long posterior construct using translaminar screws, which allow segmental fixation in vertebral bodies where placement of the pedicle screws was impracticable. PMID:19721057

  11. Cilioretinal Artery Territory Infarction Associated With Papilledema in a Patient With Neurofibromatosis Type 2.

    PubMed

    Mahroo, Omar A; Mohamed, Moin D; Graham, Elizabeth M; Mann, Samantha S; Plant, Gordon T; Afridi, Shazia K; Hammond, Christopher J

    2016-03-01

    Cilioretinal artery territory infarction can occur in isolation or in association with other vascular compromise of the retinal circulation. Our patient, an 18-year-old woman with neurofibromatosis type 2, developed a cilioretinal artery territory infarction in the setting of papilledema. Our case, together with one previous report, suggests that cilioretinal artery territory infarction in the context of papilledema, although rare, is a real entity. PMID:26295608

  12. Multicentric neurofibromatosis with rectal prolapse in a California sea lion (Zalophus californianus).

    PubMed

    Rush, Elizabeth M; Ogburn, Anna L; Garner, Michael M

    2012-03-01

    An approximately 31-yr-old California sea lion (Zalophus californianus) with a history of chronic visual impairment and corneal disease presented with slow onset, progressive neurologic deficits. Treatment for rear flipper paresis was not effective and the animal was euthanatized. Histopathologic findings included hepatocellular and biliary neoplasia, ocular amyloidosis, adrenal adenoma and pheochromocytoma, and spinal cord changes consistent with multicentric neurofibromatosis. This is the first documentation of these conditions in a California sea lion. PMID:22448517

  13. Aromatase excess syndrome presenting with prepubertal gynecomastia in an Egyptian child with type 1 neurofibromatosis

    PubMed Central

    Metwalley, Kotb Abbass; Farghaly, Hekma Saad

    2013-01-01

    A romatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by prepubertal gynecomastia, it responds well to medical treatment. In the absence of prompt suspicion, it can expose the patient to the risk of unnecessary surgical intervention. Up to our best knowledge, the association between AEXS and neurofibromatosis type 1 (NF1) was not reported before. Here, we describe a AEXS presenting with prepubertal gynecomastia in an Egyptian child with NF1 that improved with aromatase inhibitors. PMID:24497716

  14. Prevention and control of neurofibromatosis: memorandum from a joint WHO/NNFF meeting.

    PubMed Central

    1992-01-01

    Neurofibromatosis (NF) is a serious, common, genetically determined neurological disorder; with a prevalence of about 1:4000 births it affects both sexes and all races and ethnic groups. The two major forms are referred to as NF1 and NF2, as suggested in 1987 by a National Institutes of Health Consensus Development Conference on Neurofibromatosis. In NF1, the disease phenotype is more variable and complex than in NF2. Complications can occur in any of the body systems in tissues of ectodermal, mesodermal and neural tube origin; there is marked variation of disease phenotype even within families. The NF2 gene, in contrast, only seems to be expressed in tissues of ectodermal origin and its expression is more uniform both within and between families. The recent discovery and isolation of the gene responsible for the NF1 mutation has practical applications in the field of molecular genetics which could modify the approaches for diagnosis, treatment and prevention of NF. This Memorandum summarizes the discussions and recommendations of the participants at a joint WHO/National Neurofibromatosis Foundation (NNFF) meeting, held in Jacksonville, Florida, USA, on 27-28 January 1991. PMID:1600579

  15. Neurofibromatosis type 1 in two siblings due to maternal germline mosaicism.

    PubMed

    Trevisson, E; Forzan, M; Salviati, L; Clementi, M

    2014-04-01

    Neurofibromatosis type 1 (NF1) is caused by loss of function mutations of the NF1 gene, which are de novo in 50% of cases. Although this gene shows one of the highest mutation rates in the human genome, germline mosaicism is very rare in this condition. We describe the molecular analysis of a family in which neurofibromatosis type 1 occurred in two out of four siblings born to unaffected parents. Molecular analysis of the NF1 gene identified in both patients the same splicing mutation c.1392+1G>A, which was absent in parental lymphocytes. Microsatellite analysis showed that the two affected siblings shared the same maternal allele, however a specific PCR-RFLP assay excluded the presence of the NF1 splicing mutation in multiple maternal tissues. Our molecular and clinical findings are consistent with a germline mosaicism for the NF1 splicing mutation. This is the first case of maternal germline mosaicism for a NF1 mutation characterized so far at the molecular level. Our data confirm that germline mosaicism is rare in neurofibromatosis 1, but it has important implications for genetic counseling. PMID:23621909

  16. What’s New in Neurofibromatosis? Proceedings From The 2009 NF Conference: New Frontiers

    PubMed Central

    Kissil, Joseph; Blakeley, Jaishri; Ferner, Rosalie; Huson, Susan; Kalamarides, Michel; Mautner, Victor-Felix; McCormick, Frank; Morrison, Helen; Packer, Roger; Ramesh, Vijaya; Ratner, Nancy; Rauen, Katherine A.; Stevenson, David; Hunter-Schaedle, Kim; North, Kathryn

    2009-01-01

    The NF Conference is the largest annual gathering of researchers and clinicians focused on neurofibromatosis and has been convened by the Children’s Tumor Foundation for over 20 years. The 2009 NF Conference was held in Portland, Oregon from June 13th – June 16th, 2009 and co-chaired by Kathryn North from the University of Sydney and The Children’s Hospital at Westmead, Sydney, Australia; and Joseph Kissil from the Wistar Institute, Philadelphia. The Conference included 80 platform presentations in 9 sessions over 4 days; over 100 abstracts presented as posters; and three Keynote presentations. To date, there have been tremendous advances in basic research in the pathogenesis of neurofibromatosis, and more recently in progress toward identifying effective drug therapies and the commencement of neurofibromatosis clinical trials. The NF Conference attendees have significantly increased (doubling from 140 in 2005 to 280 attending in 2009) with a significant increase in attendance of physicians and clinical researchers. Correspondingly the NF Conference scope has expanded to include translational research, clinical trials and clinical management issues while retaining a core of basic research. These themes are reflected in the highlights from the 2009 NF Conference presented here. PMID:20082461

  17. Planificación Neuroquirúrgica con Software Osirix

    PubMed Central

    Jaimovich, Sebastián Gastón; Guevara, Martin; Pampin, Sergio; Jaimovich, Roberto; Gardella, Javier Luis

    2014-01-01

    Introducción: La individualidad anatómica es clave para reducir el trauma quirúrgico y obtener un mejor resultado. Actualmente, el avance en las neuroimágenes ha permitido objetivar esa individualidad anatómica, permitiendo planificar la intervención quirúrgica. Con este objetivo, presentamos nuestra experiencia con el software Osirix. Descripción de la técnica: Se presentan 3 casos ejemplificadores de 40 realizados. Caso 1: Paciente con meningioma de la convexidad parasagital izquierda en área premotora; Caso 2: Paciente con macroadenoma hipofisario, operada previamente por vía transeptoesfenoidal en otra institución con una resección parcial; Caso 3: Paciente con lesiones en pedúnculo cerebeloso medio bilateral. Se realizó la planificación prequirúrgica con el software OsiriX, fusionando y reconstruyendo en 3D las imágenes de TC e IRM, para analizar relaciones anatómicas, medir distancias, coordenadas y trayectorias, entre otras funciones. Discusión: El software OsiriX de acceso libre y gratuito permite al cirujano, mediante la fusión y reconstrucción en 3D de imágenes, analizar la anatomía individual del paciente y planificar de forma rápida, simple, segura y económica cirugías de alta complejidad. En el Caso 1 se pudo analizar las relaciones del tumor con las estructuras adyacentes para minimizar el abordaje. En el Caso 2 permitió comprender la anatomía post-operatoria previa del paciente, para determinar la trayectoria del abordaje transnasal endoscópico y la necesidad de ampliar su exposición, logrando la resección tumoral completa. En el Caso 3 permitió obtener las coordenadas estereotáxicas y trayectoria de una lesión sin representación tomográfica. Conclusión: En casos de no contar con costosos sistemas de neuronavegación o estereotáxia el software OsiriX es una alternativa a la hora de planificar la cirugía, con el objetivo de disminuir el trauma y la morbilidad operatoria. PMID:25165617

  18. Spontaneous Rupture of the Hepatic Artery in a Patient with Type 1 Neurofibromatosis Treated by Embolization: A Case Report

    SciTech Connect

    Rao, V. Day, C.P.; Manimaran, N.; Hurlow, R.A.; Orme, R.

    2007-02-15

    We report the case of a 48-year-old man with neurofibromatosis presenting with sudden-onset abdominal pain, profound hypotension, and a drop in hemoglobin. CT scan demonstrated a massive hematoma within the right lobe of the liver with rupture into the peritoneal cavity. Angiography demonstrated diffuse abnormalities of the hepatic circulation with fusifom, ectatic, and stenotic segments. Acute extravasation from a peripheral branch of the right hepatic artery was identified and successfully embolized with subsequent hemodynamic stabilization of the patient. To the best of our knowledge this is the first case report of this kind in a patient with type I neurofibromatosis.

  19. Glomus-like bodies within a neurofibroma: a novel neoplasm arising in neurofibromatosis type 1 or a coincidence?

    PubMed

    Thareja, Sumeet; Honigbaum, Alexis; Jukic, Drazen

    2015-04-01

    Neurofibromatosis type 1 is a relatively common genetic disorder with variable phenotypes. Tumors with features of both glomus tumors and neurofibromas are exceedingly rare in literature. Herein, we report a not yet described neoplasm with features of both a glomangioma/glomus tumor and a neurofibroma arising in a patient with segmental neurofibromatosis. Our case report supports the theory of a common lineage/ancestor cell between neurofibromas and glomus tumors and adds it to the spectrum of neoplasms that may arise in the setting of Von Recklinghausen's disease. PMID:25384450

  20. Adaptación al cáncer: ansiedad y sufrimiento (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos acerca de las difíciles respuestas emocionales que se presentan en muchos de los pacientes con cáncer. Este sumario se enfoca en asuntos de la adaptación normal, alteración psicosocial y trastornos de adaptación.

  1. Desmoplastic melanoma of the eyelid and conjunctival melanoma in neurofibromatosis type 1: a clinical pathological correlation.

    PubMed

    Rubinstein, Tal J; Plesec, Thomas P; Singh, Arun D

    2015-01-01

    A 56-year-old woman with neurofibromatosis type 1 (NF1) presented with a left upper eyelid amelanotic nodule with adjacent eyelid margin hyperpigmentation. Physical examination additionally revealed primary acquired melanosis (PAM) on the palpebral conjunctiva of the same eyelid. Full thickness eyelid excision and conjunctival map biopsy identified desmoplastic melanoma of the eyelid in addition to invasive conjunctival melanoma and conjunctival melanoma in situ. Sentinel lymph node biopsy was negative for metastasis. She was treated with surgical excision for the eyelid melanoma and topical mitomycin C for the conjunctival melanoma. We discuss the rare entity of desmoplastic melanoma of the eyelid and its possible association with NF1. PMID:25233828

  2. 'Moya' than meets the eye: neurofibromatosis type 1 associated with Moyamoya syndrome.

    PubMed

    Tan, R M; Chng, S M; Seow, W T; Wong, J; Lim, C C

    2008-04-01

    Moyamoya syndrome (MMS) is an uncommon association of neurofibromatosis type 1 (NF1). We describe a seven-year-old chinese girl with NF1 and unilateral MMS with multiple hyperintensities on T2-weighted magnetic resonance (MR) images. The ischaemic lesions in the ipsilateral white matter were hypointense on fluid attenuated inversion recovery (FLAIR) MR images, in contrast to the hyperintense "unidentified bright objects" (UBOs) of NF1. Neuroradiologists should be aware of associated MMS in NF1 patients, and distinguish the effects of ischaemia from UBOs, especially on FLAIR MR imaging. PMID:18418511

  3. Brain Herniation in Neurofibromatosis with Dysplasia of Occipital Bone and Posterior Skull Base

    PubMed Central

    Rangarajan, Vithal; Mahore, Amit; Patil, Manoj; Sathe, Prashant; Kaswa, Amol; Gore, Sandeep; Dharurkar, Pralhad; Kawale, Juhi

    2015-01-01

    A 22-year-old female, a known case of neurofibromatosis 1 (NF1), presented with a congenital swelling in the left occipital region. She had developed recent onset dysphagia and localized occipital headache. Neuroradiology revealed a left occipital meningoencephalocele and a left parapharyngeal meningocele. This was associated with ventriculomegaly. She was advised on cranioplasty along with duraplasty which she denied. She agreed to a lumbar-peritoneal shunt. She described a dramatic improvement in her symptoms following the lumbar-peritoneal shunt. Occipital dysplasias, though uncommon, have been reported in the literature. We review this case and its management and discuss relevant literature on occipital dysplasias in NF1. PMID:26600957

  4. Glomus Tumor of the Thenar Eminence in Neurofibromatosis Type 1: Case Report and Literature Review

    PubMed Central

    Scaravilli, Gabriele; Rossi, Roberto; Artiaco, Stefano; Merolla, Giovanni

    2015-01-01

    Neurofibromatosis type 1 (NF1) is a disease characterized by increased tumorigenesis susceptibility, caused by mutations of the oncosuppressor gene NF1. The glomus tumor (GT) is a rare, very painful mesenchymal neoplasm, arising from the glomus body. In recent years, it has been highlighted the association between NF1 and GT. We report a case of a man aged 65 years, suffering from NF1, with intense pain at the thenar eminence of the right hand, successfully treated with the excision of the mass. PMID:25674553

  5. COMT Val158Met Polymorphism Is Associated with Verbal Working Memory in Neurofibromatosis Type 1

    PubMed Central

    Costa, Danielle de Souza; de Paula, Jonas J.; Alvim-Soares, Antonio M.; Pereira, Patrícia A.; Malloy-Diniz, Leandro F.; Rodrigues, Luiz O. C.; Romano-Silva, Marco A.; de Miranda, Débora M.

    2016-01-01

    Neurofibromatosis type I (NF1) is a neurogenetic disease marked by multiple cognitive and learning problems. Genetic variants may account for phenotypic variance in NF1. Here, we investigated the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and working memory and arithmetic performance in 50 NF1 individuals. A significant association of the COMT polymorphism was observed only with verbal working memory, as measured by the backward digit-span task with an advantageous performance for Met/Met carriers. To study how genetic modifiers influence NF1 cognitive performance might be of importance to decrease the unpredictability of the cognitive profile among NF1 patients. PMID:27458360

  6. Tratamiento Quirúrgico de los Meningiomas del Foramen Óptico, Técnicay Resultados de una Serie de 18 Pacientes

    PubMed Central

    Goldschmidt, Ezequiel; Ajler, Pablo; Campero, Álvaro; Landriel, Federico; Sposito, Maximiliano; Carrizo, Antonio

    2014-01-01

    Introducción: los meningiomas del foramen óptico producen un rápido deterioro de la función visual aún cuando su tamaño es pequeño, por eso su diagnóstico y manejo difiere del resto de los meningiomas clinoideos. El propósito de este estudio es presentar la técnica y los resultados de nuestro manejo quirúrgico de meningiomas foraminales (MF). Pacientes y Métodos: se llevó a cabo una revisión de las historias clínicas de 47 pacientes con meningiomas primarios intraorbitarios. Se realizaron 52 cirugías en los pacientes con MF. Se empleó una craneotomía fronto-orbitaria, seguida de una descompresión extradural del canal óptico, resección del componente intraorbitario y exploración intradural del nervio óptico. Resultados: de los 12 pacientes con MF que presentaban la visión conservada, la agudeza visual fue preservada en 7 casos, mejoró en 2, y empeoró en 3. En 18 pacientes, el principal síntoma fue exoftalmos y en 35 pacientes ceguera unilateral. Ocurrieron 6 recurrencias, 2 a 10 años después de la resección quirúrgica. Cinco de ellos fueron reoperados. Se indicó radioterapia después de la recurrencia en 3 pacientes. Conclusión: el manejo de los MF continúa siendo controvertido y frecuentemente se propone un tratamiento conservador. Basados en nuestros hallazgos de frecuente extensión intracraneal, proponemos realizar una resección total o subtotal del tumor, preservando el nervio óptico en pacientes con visión prequirúrgica conservada. PMID:25165616

  7. Using a Virtual Classroom Environment to Describe the Attention Deficits Profile of Children with Neurofibromatosis Type 1

    ERIC Educational Resources Information Center

    Gilboa, Yafit; Rosenblum, Sara; Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Rizzo, Albert; Josman, Naomi

    2011-01-01

    The objectives of this study were to describe the nature of the attention deficits in children with Neurofibromatosis type 1 (NF1) in comparison with typically developing (TD) children, using the Virtual Classroom (VC), and to assess the utility of this instrument for detecting attention deficits. Twenty-nine NF1 children and 25 age-and…

  8. Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.

    PubMed

    Blakeley, Jaishri O; Plotkin, Scott R

    2016-05-01

    Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. PMID:26851632

  9. Enhanced response to the induction of sister chromatid exchange by gamma radiation in neurofibromatosis

    SciTech Connect

    Hafez, M.; Abd el-Nabi, S.M.; el-Wehedi, G.; Al-Tonbary, Y.

    1986-05-15

    The study included 8 unrelated patients with neurofibromatosis, and 10 unrelated normal and healthy persons as controls. Whole blood samples were divided into plastic T flasks and exposed at room temperature to gamma rays. The radiation dose was 36 rad/minute, and the doses delivered were 0, 75, 150 and 300 rad. The lymphocytes were cultured in (RPMI) 1640 tissue culture medium and autologous serum (20%). Phytohemagglutinin and bromodeoxyuridine (Brdu) (10 microM) were added at initiation of culture and harvesting was done 64 to 68 hours after culture initiation. Slides were coded, differential staining was done, and sister chromatid exchanges (SCEs) and aberrations (gaps, breaks, dicentrics, fragments and minutes) were counted. In the controls no significant increase in frequency of SCE has been found (P greater than 0.5). In the patients, the frequencies significantly increased with the increase of dose of irradiation (P less than 0.001). Furthermore, after irradiation, the incidence of gaps, breaks, and dicentrics were significantly increased in patients compared with controls. Moreover, the incidence increased with the increase in the dose of radiation. The results are discussed with a conclusion that the results add to the indication of a genetic predisposition to develop cancer in neurofibromatosis patients.

  10. Neurofibromatosis Type 1: A Novel NF1 Mutation Associated with Mitochondrial Complex I Deficiency

    PubMed Central

    Isidoro, Lara; Rocha, Dalila

    2014-01-01

    Background. Neurofibromatosis type 1 is a multisystemic, progressive disease, with an estimated incidence of 1/3500-2500. Mitochondrial diseases are generally multisystemic and may be present at any age, and the global prevalence is 1/8500. The diagnosis of these disorders is complex because of its clinical and genetic heterogeneity. Case Report. We present a rare case of the association of these two different genetic diseases, in which a heterozygous missense mutation in the NF1 gene was identified which had not yet been described (p.M1149 V). Additionally, the patient is suspected of carrying an unspecified mutation causing respiratory chain complex I deficiency. Clinical presentation included hypotonia, global development delay, reduced growth rate, progressive microcephaly, and numerous café-au-lait spots. Discussion. To the best of our knowledge this is the first report of complex I deficiency in a patient with neurofibromatosis type 1. It is very important to maintain a high index of suspicion for the diagnosis of mitochondrial disorders. In this patient, both the laboratory screening and muscle histology were normal and only the biochemical study of muscle allowed us to confirm the diagnosis. PMID:24711935

  11. Neurocognitive outcomes in neurofibromatosis clinical trials: Recommendations for the domain of attention.

    PubMed

    Walsh, Karin S; Janusz, Jennifer; Wolters, Pamela L; Martin, Staci; Klein-Tasman, Bonita P; Toledo-Tamula, Mary Anne; Thompson, Heather L; Payne, Jonathan M; Hardy, Kristina K; de Blank, Peter; Semerjian, Claire; Gray, Laura Schaffner; Solomon, Sondra E; Ullrich, Nicole

    2016-08-16

    Neurofibromatosis type 1 (NF1) is associated with neurocognitive deficits that can impact everyday functioning of children, adolescents, and adults with this disease. However, there is little agreement regarding measures to use as cognitive endpoints in clinical trials. This article describes the work of the Neurocognitive Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. The goal of this committee is to identify standardized and specific cognitive assessment tools for use in NF clinical trials. The committee first identified cognitive domains relevant to NF1 and prioritized attention as the first domain of focus given prior and current trends in NF1 cognitive clinical trials. Performance measures and behavioral rating questionnaires of attention were reviewed by the group using established criteria to assess patient characteristics, psychometric properties, and feasibility. The highest rated tests underwent side-by-side comparison. The Digit Span subtest from the Wechsler scales was given the highest ratings of the performance measures due to its good psychometrics, feasibility, utility across a wide age range, and extensive use in previous research. The Conners scales achieved the highest ratings of the behavioral questionnaires for similar reasons. Future articles will focus on other cognitive domains, with the ultimate goal of achieving agreement for cognitive endpoints that can be used across NF clinical trials. PMID:27527646

  12. A Case of Malignant Peripheral Sheath Tumor Arising from Neurofibromatosis Type 1

    PubMed Central

    Kang, Min Ju; Kang, Hoon; Kim, Hyung Ok

    2008-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a term encompassing tumors previously diagnosed as malignant schwannoma, malignant neurilemmoma, neurogenic sarcoma, and neurofibrosarcoma The occurrence rate of MPNST in neurofibromatosis type 1 patients is known to be about 4.6%. Tumors occurring in this particular group have a worse prognosis in that they occur at an earlier age, are more centrally located, tend to be of a larger size and show more metastases and recurrences. We present a typical case of MPNST in a 36-year-old man with NF type 1, which occurred on the left buttock. A PET-CT showed findings of possible inguinal lymph node metastasis and a lymph node biopsy confirmed the diagnosis. The patient was treated with wide surgical resection and is undergoing adjuvant radiation therapy. PMID:27303156

  13. A Pilot Study for Evaluation of Hypotonia in Children with Neurofibromatosis Type 1

    PubMed Central

    Soucy, Elizabeth A.; Wessel, Lauren E.; Gao, Feng; Albers, Anne C.; Gutmann, David H.; Dunn, Courtney M.

    2016-01-01

    There are currently no objective criteria to evaluate pediatric hypotonia. The purpose of this pilot study was to identify diagnostic criteria for assessing hypotonia in children with Neurofibromatosis type 1 (NF1). Fifty-five subjects between the ages of 1 and 7 years with a diagnosis of NF1 were evaluated. A physical therapist recorded a subjective tone assessment and objective tone metrics, including ankle dorsiflexion, knee extension, hip abduction, triceps fat percentage, grip strength and head lag during a pull-to-sit test. Multivariate logistic regression analysis showed the presence of head lag paired with increased hip range of motion was a significant predictor of hypotonia. The presence of head lag on a pull-to-sit test paired with increased hip range of motion is an accurate predictor of hypotonia in children with NF1. These objective measures should be prospectively evaluated in other pediatric populations for their ability to predict hypotonia. PMID:24789516

  14. A rare case of a spontaneous neck hematoma in a patient with type 1 neurofibromatosis.

    PubMed

    Dova, Stamatia; Ktenidis, Kyriakos; Karkos, Petros; Blioskas, Sarantis; Psillas, Georgios; Iliadis, Alexandros; Markou, Konstantinos

    2016-10-01

    Neurofibromatosis type 1 (NF-1) is a genetic disorder that affects one in 3000 individuals. Although NF-1 notably involves nerves and connective tissue, vascular involvement in large series is estimated to range from 0.4% to 6.4%. Jugular vein involvement in these patients is rare. Spontaneous neck hematomas and hemorrhages are also unusual. We present a case of a NF-1 patient with a spontaneous neck hematoma with possible leakage from the left internal jugular vein, presenting as a lateral neck mass. The fragility of the vein wall and the surrounding tissue led patient to a severe intraoperative bleeding. Pathological examination revealed degenerated neurofibroma which was in contact with or infiltrated the vein wall. ENT and other clinicians should be aware of this potentially fatal entity considering that it may present as a lateral neck mass. PMID:27061148

  15. fdg-pet in two cases of neurofibromatosis type 1 and atypical malignancies

    PubMed Central

    de Blank, P.; Cole, K.; Kersun, L.; Green, A.; Wilkes, J.J.; Belasco, J.; Bagatell, R.; Bailey, L.C.; Fisher, M.J.

    2014-01-01

    Patients with neurofibromatosis type 1 (nf1) are at increased risk for both benign and malignant tumours, and distinguishing the malignant potential of an individual tumour is a common clinical problem in these patients. Here, we review two cases of uncommon malignancies (Hodgkin lymphoma and mediastinal germ-cell tumour) in patients with nf1. Although 18F-fluorodeoxyglucose positron-emission tomography (fdg-pet) has been used to differentiate benign neurofibromas from malignant peripheral nerve sheath tumours, fdg-pet characteristics for more rare tumours have been poorly described in children with nf1. Here, we report the role of pet imaging in clinical decision-making in each case. In nf1, fdg-pet might be useful in the clinical management of unusual tumour presentations and might help to provide information about the malignant potential of uncommon tumours. PMID:24764718

  16. Neurofibromatosis-related phaeochromocytoma: two cases with large tumours and elevated plasma methoxytyramine

    PubMed Central

    Reda, Elham

    2015-01-01

    Summary We present two cases of adrenal phaeochromocytoma in patients with a previous diagnosis of neurofibromatosis type 1 (NF1). One had an adrenergic phenotype. The other had a more noradrenergic phenotype. Both had large primary tumours, which increases the likelihood of malignancy. Both also had elevated plasma-free methoxytyramine, which has been linked with malignancy even in non-SDHB phaeochromocytomas. Learning points Phaeochromocytoma can have varied clinical presentations.Methoxytyramine can be useful in the biochemical work-up of both SDHB-positive and SDHB-negative phaeochromocytoma.The utility of methoxytyramine as a marker of malignancy in NF1-related phaeochromocytoma is unclear, and cases with elevated titres warrant longer follow-up. PMID:26273474

  17. Focal segmental glomerulosclerosis in association with neurofibromatosis type 1: a case report and proposed molecular pathways.

    PubMed

    Afshinnia, Farsad; Vega-Warner, Virginia; Killen, Paul

    2013-04-01

    A 42-year-old Caucasian female with history of neurofibromatosis type 1 presented with nephrotic range proteinuria and focal segmental glomerulosclerosis (FSGS). On final dose of lisinopril 20 mg/day, protein-creatinine ratio declined to 0.33 within 10 months. We propose the hypothesis that development of FSGS in NF1 may be mediated by activation of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways secondary to up-regulation of ras proteins due to deficient neurofibromin. Since mTOR signaling pathway is partially mediated through angiotensin-II activation, angiotensin-converting enzyme (ACE) inhibition may serve as an effective initial treatment beyond anti-proteinuric properties of ACE-inhibitors. PMID:23805377

  18. [Dopamine-secreting pheochromocytoma with neurofibromatosis type 1 : a case report].

    PubMed

    Nakazawa, Shigeaki; Kishikawa, Hidefumi; Akiyama, Kotaro; Yamanaka, Kazuaki; Hirai, Toshiaki; Nishimura, Kenji; Ichikawa, Yasuji

    2012-10-01

    Pheochromocytoma occurs in 0.1-5.7% of patients with neurofibromatosis type 1 (NF1), while dopamine-secreting pheochromocytoma is rare. We report here a rare case of dopamine-secreting pheochromocytoma in a patient with NF1. A 46-year-old woman with NF1 was referred to our hospital with epigastralgia. The patient had no history of hypertension. Abdominal sonography incidentally revealed a left adrenal tumor, while abdominal computed tomography and magnetic resonance imaging findings showed a left adrenal tumor, sized 63×58 mm. Laboratory evaluations revealed exclusively elevated urine dopamine levels in addition to elevated serum adrenaline and noradrenaline levels. Laparoscopic left adrenalectomy was performed and the dopamine levels and other cathecolamine levels returned to normal postoperatively. PMID:23235276

  19. Unilateral gynecomastia and pseudoangiomatous stromal hyperplasia in neurofibromatosis: case report and review of the literature.

    PubMed

    Kimura, Satoshi; Tanimoto, Akihide; Shimajiri, Shohei; Sasaguri, Takakazu; Yamada, Sohsuke; Wang, Ke-Yong; Guo, Xin; Sasaguri, Yasuyuki

    2012-05-15

    In this article, we describe unilateral gynecomastia and pseudoangiomatous stromal hyperplasia (PASH) in a case of type-1 neurofibromatosis (NF-1). It is important to distinguish PASH from fibroadenoma clinically, and from true blood capillaries and angiosarcoma histologically. In the present case, giant multinucleated cells lined the pseudovascular spaces, which was markedly different from that of conventional breast PASH. The origin of PASH has been reported to be either the fibroblast or the myofibroblast phenotype and may be affected by endocrine signaling because many cases have been reported in premenopausal women, and cases are often estrogen (ER) and progesterone receptor (PR) positive. However, previous reports have identified PASH in NF-1 in juvenile males only, and the cases were negative for α-SMA, ER and PR. The cause and prognosis of PASH in NF-1 may be distinguished from that of conventional PASH, and mast cells, histiocytes and CD54 may play roles. PMID:22520406

  20. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor

    PubMed Central

    Ratner, Nancy; Miller, Shyra J.

    2016-01-01

    Neurofibromatosis type 1 (NF1) is a common genetic disorder that predisposes affected individuals to tumours. The NF1 gene encodes a RAS GTPase-activating protein called neurofibromin and is one of several genes that (when mutant) affect RAS–MAPK signalling, causing related diseases collectively known as RASopathies. Several RASopathies, beyond NF1, are cancer predisposition syndromes. Somatic NF1 mutations also occur in 5–10% of human sporadic cancers and may contribute to resistance to therapy. To highlight areas for investigation in RASopathies and sporadic tumours with NF1 mutations, we summarize current knowledge of NF1 disease, the NF1 gene and neurofibromin, neurofibromin signalling pathways and recent developments in NF1 therapeutics. PMID:25877329

  1. Leiomyoma of the bladder in a patient with von Recklinghausen’s neurofibromatosis

    PubMed Central

    Däuth, T L; Conradie, M; Chetty, R

    2003-01-01

    Leiomyomas are an uncommon manifestation of neurofibromatosis type 1 (NF-1) and occur most often in the gastrointestinal tract. Here, they have a proclivity for the proximal small bowel and tend to be multiple. Urinary tract involvement by NF-1 is usually in the form of neurofibromas, and leiomyomas are exceptionally rare. This report describes a case of solitary leiomyoma occurring in a 49 year old woman with NF-1. The patient had symptoms related to a lower urinary tract infection and on examination was found to have a distended bladder. Imaging of the bladder showed a mass involving the posterior wall, neck, and trigone causing bilateral hydronephrosis. The mass was excised with part of the bladder. Microscopic examination revealed typical features of a leiomyoma and there was strong immunoreactivity for desmin and smooth muscle actin. Leiomyoma must be considered in the differential diagnosis of spindle cell neoplasms in patients with NF-1. PMID:12944559

  2. Jóvenes con cáncer y supervivientes participan en estudio de oncofertilidad

    Cancer.gov

    Artículo sobre los esfuerzos que se realizan para conectar con pacientes jóvenes y lograr su participación en estudios clínicos para evaluar y remediar la esterilidad causada por el cáncer y su tratamiento.

  3. Loss of neurofibromatosis type 1 (NF1) gene expression in pheochromocytomas from patients without NF1

    SciTech Connect

    Geist, R.T.; Gutmann, D.H.; Moley, J.F.

    1994-09-01

    The neurofibromatosis type 1 (NF1) gene encodes a tumor suppressor protein, termed neurofibromin. Loss of NF1 gene expression has been reported in Schwann cell tumors (neurofibrosarcomas) from patients with NF1 as well as malignant and neuroblastomas from patients without NF1. Previously, we demonstrated the lack of neurofibromin expression in six pheochromocytomas from patients with NF1, suggesting that neurofibromin loss is associated with the progression to neoplasia in pheochromocytomas in these patients. The lack of NF1 gene expression in NF1 patient pheochromocytomas supports the notion that neurofibromin might be an essential regulator of cell growth in these cells. To determine whether NF1 gene expression is similarly altered in pheochromocytomas from patients without NF1, twenty pheochromocytomas were examined for the presence of NF1 RNA by reverse-transcribed PCR (RT-PCR). Lack of NF1 gene expression was documented in four of these twenty tumors (20%) which corresponds to previously reported numbers for malignant melanomas and neuroblastomas in non-NF1 patients. Of these twenty pheochromocytomas, one of four sporadic tumors, one of ten tumors from patients with MEN2A, one of four tumors from patients with MEN2B, and one of two tumors from patients with von Hippel-Lindau syndrome demonstrated loss of NF1 gene expression. In all cases, the quality and quantity of tumor RNA was determined by RT-PCR amplification using primers which amplify cyclophilin RNA. We previously demonstrated that these tumors do not harbor activating mutations of the N-ras, K-ras or H-ras proto-oncogenes. These results suggest that loss of NF1 gene expression is frequently associated with the progression to neoplasia in tumors derived from adrenal medullary tissue in patients without clinical manifestations of neurofibromatosis and supports the notion that neurofibromin is a tumor suppressor gene product involved in the pathogenesis of a wide variety of tumor types.

  4. Lack of NF1 gene expression in a sporadic schwannoma from a patient without neurofibromatosis

    SciTech Connect

    Norton, K.K.; Dowton, B.; Silow-Santiago, I.

    1994-09-01

    The neurofibromatosis type 1 (NF1) gene encodes a tumor suppressor protein, neurofibromin, which is expressed at high levels in Schwann cells and other adult tissues. Loss of NF1 gene expression has been reported in Schwann cell tumors (neurofibrosarcomas) from patients with NF1 and its loss is associated with increased proliferation of these cells. We examined one spinal schwannoma from a patient without clinical features of neurofibromatosis type 1 or 2. The tumor was a typical schwannoma confirmed by standard neuropathologic criteria and expressed S100 by immunocytochemistry. NF1 gene expression in this tumor was examined by in situ hybridization using an NF1-specific riboprobe, Northern blot analysis and reverse-transcribed (RT) PCR. Little or no expression of NF1 RNA could be detected using these methods whereas abundant expression of S100, cyclophilin and beta-action RNA was found in the tumor. Fibroblast and Schwann cells were then individually cultured from this schwannoma and the RNA extracted for Northern blot and RT-PCR analysis. In these cultured Schwann cells both from early and late passages, abundant expression of NF1 RNA could be detected. It is unlikely that our culture technique preferentially expanded {open_quotes}normal{close_quotes} Schwann cells, since NF1 acts as a tumor suppressor gene and its presence would not confer any growth advantage over the tumor-derived, neurofibromin-negative Schwann cells which presumably have an increased proliferation rate. Similarly, the conditions used to expand these Schwann cells do not result in increased NF1 gene expression as shown in previous studies. These results suggest that, in some tumors, expression of the NF1 gene can be downregulated by factors produced within the tumor and that this type of tumor suppressor gene downregulation may represent another mechanism other than mutation for turning off the expression of these growth-suppressing genes and allowing for cell proliferation in tumors.

  5. Incidental parenchymal magnetic resonance imaging findings in the brains of patients with neurofibromatosis type 2☆

    PubMed Central

    Vargas, Wendy S.; Heier, Linda A.; Rodriguez, Fausto; Bergner, Amanda; Yohay, Kaleb

    2014-01-01

    Purpose Whereas T2 hyperintensities known as NF-associated bright spots are well described in patients with neurofibromatosis type I (NF-1), there is a paucity of data on incidental findings in patients with neurofibromatosis type II (NF-2). We aim to characterize unexplained imaging findings in the brains of patients with NF-2. Materials and methods This study is retrospective, HIPAA-compliant and approved by the institutional review board. 34 patients with NF-2 underwent brain magnetic resonance imaging (MRI) between January 2000 and December 2012. T2 and T1-weighted imaging characteristics, diffusion weighted imaging (DWI) characteristics, and enhancement patterns were analyzed by visual inspection. Clinical information at time of imaging was available for all patients. Neuropathologic data was available for one patient. Results We found unexplained T2 hyperintensities present on initial imaging in 23/34 patients (67%). Of the 23 patients with unexplained MRI findings, 15 (65%) had wedge-shaped T2 hyperintensities in the subcortical white matter extending to the cortex suggestive of a cortical dysplasia. 3 additional cases (17%) had a lesion within the cerebellum suggestive of a neuronal migration anomaly. In one patient where the MRI was suggestive of focal cortical dysplasia, histopathologic analysis revealed dysplastic glial foci without other alterations of cortical architecture or other cytologic abnormalities. Conclusion Unexplained T2 hyperintensities occur frequently in patients with NF-2. While they may not be the NF-2 equivalent of NF-associated bright spots seen in NF-1, some of these T2 hyperintensities in patients with NF-2 may represent underlying disorders of neuronal migration. Further studies are needed to validate our findings. PMID:24501699

  6. NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome.

    PubMed

    De Luca, Alessandro; Bottillo, Irene; Sarkozy, Anna; Carta, Claudio; Neri, Cinzia; Bellacchio, Emanuele; Schirinzi, Annalisa; Conti, Emanuela; Zampino, Giuseppe; Battaglia, Agatino; Majore, Silvia; Rinaldi, Maria M; Carella, Massimo; Marino, Bruno; Pizzuti, Antonio; Digilio, Maria Cristina; Tartaglia, Marco; Dallapiccola, Bruno

    2005-12-01

    Neurofibromatosis type 1 (NF1) demonstrates phenotypic overlap with Noonan syndrome (NS) in some patients, which results in the so-called neurofibromatosis-Noonan syndrome (NFNS). From a genetic point of view, NFNS is a poorly understood condition, and controversy remains as to whether it represents a variable manifestation of either NF1 or NS or is a distinct clinical entity. To answer this question, we screened a cohort with clinically well-characterized NFNS for mutations in the entire coding sequence of the NF1 and PTPN11 genes. Heterozygous NF1 defects were identified in 16 of the 17 unrelated subjects included in the study, which provides evidence that mutations in NF1 represent the major molecular event underlying this condition. Lesions included nonsense mutations, out-of-frame deletions, missense changes, small inframe deletions, and one large multiexon deletion. Remarkably, a high prevalence of inframe defects affecting exons 24 and 25, which encode a portion of the GAP-related domain of the protein, was observed. On the other hand, no defect in PTPN11 was observed, and no lesion affecting exons 11-27 of the NF1 gene was identified in 100 PTPN11 mutation-negative subjects with NS, which provides further evidence that NFNS and NS are genetically distinct disorders. These results support the view that NFNS represents a variant of NF1 and is caused by mutations of the NF1 gene, some of which have been demonstrated to cause classic NF1 in other individuals. PMID:16380919

  7. Evaluation of tibial osteopathy occurrence in neurofibromatosis type 1 Italian patients.

    PubMed

    Morcaldi, Guido; Clementi, Maurizio; Lama, Giuliana; Gabrielli, Orazio; Vannelli, Silvia; Virdis, Raffaele; Vivarelli, Rossella; Boero, Silvio; Bonioli, Eugenio

    2013-05-01

    Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disorder characterized by high penetrance, widely variable expressivity and occurrence of specific skeletal changes such as tibial osteopathy (TO). We collected data on patients referred to the Italian Neurofibromatosis Study Group in order to compare clinical features between 49 NF1 patients with TO, and 98 age-matched NF1 patients without TO, and to determine whether the presence of TO is associated with a different risk of developing the typical NF1 complications. We assessed both groups for: age at diagnosis of NF1, gender distribution, family history, gender inheritance, presence of scoliosis, sphenoid wing osteopathy, other skeletal abnormalities, macrocrania, hydrocephalus, plexiform neurofibromas, tumors, optic pathway gliomas, T2H (high-signal intensity areas on T2 weighted brain MRI), epilepsy, headache, mental retardation, cardiovascular malformations, and Noonan phenotype. Patients of both groups were subdivided by gender and re-evaluated for these items. Statistical comparison was carried out between the two groups of patients for each feature. We collected data on type of treatment and on the clinical conditions of NF1-TO patients after follow-up. Patient's age at NF1 diagnosis was significantly younger in NF1-TO subjects compared with NF1 subjects without TO, and the incidence of T2H was significantly reduced in NF1-TO males compared with NF1 males without TO. The presence of TO does not imply that there is an increased risk of developing typical complications of NF1 (e.g., optic pathway glioma, plexiform neurofibroma, etc.), however, it does allow us to make an earlier diagnosis of NF1. PMID:23463485

  8. The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features.

    PubMed

    Ruggieri, M; Polizzi, A; Spalice, A; Salpietro, V; Caltabiano, R; D'Orazi, V; Pavone, P; Pirrone, C; Magro, G; Platania, N; Cavallaro, S; Muglia, M; Nicita, F

    2015-05-01

    Spinal neurofibromatosis (SNF) is a related form of neurofibromatosis 1 (NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4-74 years]: 9 SNF families (21/49), 1 mixed SNF/NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non-SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots (MNFSR): 4 mixed SNF/MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café-au-lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio (OR) = 6.16; confidence interval (CI) = 3.14-13.11], which were more frequent in SNF vs MNFSR (p = 0.0271). PMID:25211147

  9. Screening for somatic mutations of the neurofibromatosis genes in nervous system and other solid tumors

    SciTech Connect

    Rangaratnam, S.; Narod, S.; Ruttledge, M.

    1994-09-01

    Von Recklinghausen neurofibromatosis (NF1) and neurofibromatosis type 2 (NF2) are autosomal dominant inherited disorders which predispose carriers to various benign and malignant tumors. Both genes are thought to act as tumor suppressors with inactivation of both alleles resulting in abnormal cell growth. By inference from other hereditary cancer syndromes, it has been hypothesized that somatic mutation at the NF1 and NF2 loci is involved in the development of sporadic tumors of the types found with increased prevalence in these disorders. In addition to other malignancies, individuals with NF1 are at increased risk to develop astrocytomas and rhabdomyosarcomas. We have therefore screened 40 astrocytomas for LOH using three NF1-derived cDNA probes, and have found no abnormalities. Single-strand conformation polymorphism (SSCP) analysis of exons of the NF1 GAP-related domain has also failed to show any variants in a total of 70 astrocytomas and 14 rhabdomyosarcomas (7 each of embryonal and alveolar types). LOH of chromosome 22 markers is known to occur in meningioma, malignant melanoma, breast cancer, and ependymoma. SSCP of all 17 exons of the NF2 gene in 27 melanoma cell lines, 42 breast cancers, and 27 pendymomas revealed no alterations. In a screen of 151 menigiomas, 26 new variants have been found, bringing our total to 50 variants in this sample. These represent inactivating mutations (frameshift, splice-site, and nonsense), determined by direct sequencing. Since the majority of these changes occur in tumors previously shown to have LOH at chromosome 22 markers flanking NF2, our results support a tumor sequence role for this gene in meningiomas. In addition, given that 40% of our tumors do not show LOH over this region, we propose that other genes are involved in the development of this latter subset of meningiomas.

  10. Coexistence of multiple rare spinal abnormalities in type 1 neurofibromatosis: a case report and literature review

    PubMed Central

    Zhao, Chun-Ming; Zhang, Wen-Jie; Huang, Ai-Bing; Chen, Qian; He, Yuan-Long; Zhang, Wei; Yang, Hui-Lin

    2015-01-01

    Orthopaedic involvement is the most common clinical presentation of Neurofibromatosis type 1 (NF-1) patients with the spinal abnormalities more frequently affected. In the spinal deformities of NF-1 patients, despite the scoliosis is the most frequent finding, several distinctive radiographic features, such as dural ectasia, defective pedicles, and spondylolisthesis, are relatively less common. Here, we reported a 16-year-old boy diagnosed with NF-1 who presented with dural ectasia, defective pedicles, and spondylolisthesis concomitantly, described the surgical treatment and provided a literature review. The boy complained of low back and leg pain for two months. On clinical examination, the patient showed multiple café au lait spots on his back and no neurological deficit. He had a family history of neurofibromatosis as his father suffering from NF-1. Imaging results demonstrated mild scoliosis, posterior scalloping of the lumber spine, L5 spondylolisthesis on plain radiographs, and marked dural ectasia of L3-L5 on MRI. Furthermore, the CT scan showed presence of thin pedicles at L3, bilateral symmetrical pedicle clefts at L4, and pars interarticularis fractures at L5. The patient received a long level posterior fusion from L1 to S1 with pedicle screws. Iliac crest autogenous graft mixed with artificial bone were used to achieve solid arthrodesis. At nine-month follow-up, the patient was asymptomatic and able to live a normal life. Our observation demonstrated that familiarity with those distinctive features in NF-1 patients could be contributed to making an early diagnosis and optimizing treatment. PMID:26770321

  11. Añadir quimioterapia después de la radioterapia mejora la supervivencia de adultos con un tipo de tu

    Cancer.gov

    Adultos con gliomas de grado bajo, una forma de tumor cerebral, que recibieron tratamiento con quimioterapia después de la radioterapia vivieron más tiempo que pacientes que recibieron solo radioterapia, según los resultados de seguimiento a largo plazo d

  12. Brain metastasis of Wilms tumor with diffuse anaplasia and complex cytogenetic phenotype in a child with neurofibromatosis Type 1.

    PubMed

    Shvartsbeyn, Marianna; Bassani, Luigi; Mikolaenko, Irina; Wisoff, Jeffrey H

    2011-10-01

    The authors report the first case of a Wilms tumor (WT) with diffuse anaplasia metastatic to the brain in a 13-year-old girl with a history of neurofibromatosis Type 1. At presentation, the metastatic tumor had radiological features that suggested a meningioma. Histologically it was characterized by striking anaplasia and features similar to the patient's previously resected WT with diffuse anaplasia. PMID:21961578

  13. Primary malignant peripheral nerve sheath tumor of the lung in a young child without neurofibromatosis type 1.

    PubMed

    Muwakkit, Samar A; Rodriguez-Galindo, Carlos; El Samra, Ahmad I; Khoury, Ruby; Akel, Samir R; Mroueh, Salman; Razzouk, Bassem; Abboud, Miguel R

    2006-10-15

    Malignant peripheral nerve sheath tumors (MPNST) are uncommon in children and almost half of the cases occur in patients with neurofibromatosis 1 (NF1). We report a child with a primary MPNST of the lung without NF1. MPNST of the lung has similar clinical and radiologic characteristics as pleuropulmonary blastoma. We suggest to include MPNST of the lung in the differential diagnosis of intrapulmonary masses in children. PMID:16544294

  14. Association between Neurofibromatosis Type 1 and Breast Cancer: A Report of Two Cases with a Review of the Literature

    PubMed Central

    Seo, Yoon Nae; Park, Young Mi

    2015-01-01

    Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and is associated with various benign and malignant tumors, including breast cancer. However, an increased risk of breast cancer in NF1 patients has not been widely recognized or accepted. Here, we report two cases of breast cancer in NF1 patients and review the literature on the association between NF1 and breast cancer. PMID:26604930

  15. Ependimoma myxopapilar sacro gigante con osteolisis

    PubMed Central

    Ajler, Pablo; Landriel, Federico; Goldschmidt, Ezequiel; Campero, Álvaro; Yampolsky, Claudio

    2014-01-01

    Objetivo: la presentación de un caso de una paciente con un ependimoma sacro con extensa infiltración y destrucción ósea local. Descripción del caso: una mujer de 53 años acudió a la consulta por dolor lumbosacro y alteraciones sensitivas perineales y esfinterianas. La imágenes por Resonancia Magnética (IRM) y la Tomografía Axial Computada (TAC) mostraron una lesión expansiva gigante a nivel S2-S4 con extensa osteólisis e invasión de tejidos adyacentes. Se realizó una exéresis tumoral completa con mejoría del estatus funcional. La anatomía patológica informó ependimoma mixopapilar. Discusión: la extensión de la resección quirúrgica es el mejor predictor de buen pronóstico. El tratamiento radiante se reserva como opción adyuvante para las resecciones incompletas y recidiva tumoral. La quimioterapia sólo debería utilizarse en casos en que la cirugía y la radioterapia estén contraindicadas. Conclusión: Los ependimomas mixopapilares sacros con destrucción ósea y presentación intra y extradural son muy infrecuentes y deben ser tenidos en cuenta entre los diagnósticos diferenciales preoperatorios. Su resección total, siempre que sea posible, es la mejor alternativa terapéutica. PMID:25165615

  16. The relaxation response resiliency program (3RP) in patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis: results from a pilot study.

    PubMed

    Vranceanu, Ana-Maria; Merker, Vanessa L; Plotkin, Scott R; Park, Elyse R

    2014-10-01

    NF1, NF2, and Schwannomatosis are incurable tumor suppressor syndromes associated with poor quality of life. The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of an NF adapted, 8-week group mind body skills based intervention, the relaxation response resiliency program (3RP) aimed at improving resiliency and increasing satisfaction with life. Patients seen at MGH's Neurofibromatosis Clinic were offered participation if they described difficulties coping to a treating physician. Participants completed measures of life satisfaction, resiliency, stress, mood, lifestyle, pain, post-traumatic growth and mindfulness at baseline and after completing the 3RP program. The intervention had relative feasible enrollment rate (48% rate, 32 out of 67 of patients signing the informed consent form). However, out of the 32 patients who signed the informed consent, only 20 started the study (62.5%) and only 16 completed it (50%), suggesting problems with feasibility. The main reason cited for non-participation was burden of travel to the clinic. The intervention was highly acceptable, as evidenced by an 80% completion rate (16/20). Paired t tests showed significant improvement in resiliency, satisfaction with life, depression, stress, anxiety, mindfulness and post traumatic growth, with effect sizes ranging from 0.73-1.33. There was a trend for significance for improvement in somatization and sleepiness (p = 0.06), with effect sizes of 0.54-0.92 respectively. Statistically nonsignificant improvement was observed in all other measures, with effect sizes small to medium. In sum, the 3RP was found to be relatively feasible, highly acceptable and preliminary efficacious in decreasing symptom burden in this population, supporting the need of a randomized controlled trial. PMID:25022450

  17. RELACIÓN MÉDICO PACIENTE: DERECHOS DEL ADULTO MAYOR

    PubMed Central

    Barrantes-Monge, Melba; Rodríguez, Eduardo; Lama, Alexis

    2009-01-01

    Existen prejuicios en relación con la vejez, incluso entre los profesionales que se dedican a la gerontología. Uno común y peligroso es considerar que los viejos son todos enfermos o discapacitados. La relación médico-paciente es la piedra angular de la práctica y ética médicas. Para alcanzar el respeto por los adultos mayores es necesaria una medicina prudente, basada en una práctica en la cual la reflexión ética y clínica pueda contribuir. Esto último es posible si se hacen valer los derechos del adulto mayor, en particular como paciente para la toma de decisiones. PMID:20379380

  18. Neurofibromatosis-1

    MedlinePlus

    ... Blindness Convulsions Freckles in the underarm or groin Large, soft tumors called plexiform neurofibromas, which may have a dark color and may spread under the surface of the skin Pain (from affected nerves) Small, ...

  19. Neurofibromatosis-1

    MedlinePlus

    ... family who have the same NF1 gene change. "Coffee-with-milk" ( cafe-au-lait ) spots are the ... Call your health care provider if: You notice coffee-with-milk colored spots on your child's skin ...

  20. Neurofibromatosis Specialists

    MedlinePlus

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  1. Mortality associated with neurofibromatosis type 1: A study based on Italian death certificates (1995-2006)

    PubMed Central

    2011-01-01

    Background Persons affected by neurofibromatosis type 1 (NF1) have a decreased survival, yet information on NF1-associated mortality is limited. Methods/Aim The National Mortality Database and individual Multiple-Causes-of-Death records were used to estimate NF1-associated mortality in Italy in the period 1995-2006, to compare the distribution of age at death (as a proxy of survival) to that of the general population and to evaluate the relation between NF1 and other medical conditions by determining whether the distribution of underlying causes of NF1-associated deaths differs from that of general population. Results Of the nearly 6.75 million deaths in the study period, 632 had a diagnosis of NF1, yet for nearly three-fourths of them the underlying cause was not coded as neurofibromatosis. The age distribution showed that NF1-associated deaths also occurred among the elderly, though mortality in early ages was high. The mean age for NF1-associated death was approximately 20 years lower than that for the general population. The gender differential may suggest that women are affected by more severe NF1-related complications, or they may simply reflect a greater tendency for NF1 to be reported on the death certificates of young women. Regarding the relation with other medical conditions, we found an excess, as the underlying cause of death, for malignant neoplasm of connective and other soft tissue and brain, but not for other sites. We also found an excess for obstructive chronic bronchitis and musculoskeletal system diseases among elderly persons. Conclusion This is the first nationally representative population-based study on NF1-associated mortality in Italy. It stresses the importance of the Multiple-Causes-of-Death Database in providing a more complete picture of mortality for conditions that are frequently not recorded as the underlying cause of death, or to study complex chronic diseases or diseases that have no specific International Classification of

  2. Problems with the use of breast conservation therapy for breast cancer in a patient with neurofibromatosis type 1: a case report.

    PubMed

    Hasson, Danielle M; Khera, Samira Y; Meade, Tammi L; Dupont, Elisabeth L; Greenberg, Harvey M; Diaz, Nils M; Romilly, A Pat; Cox, Charles E

    2008-01-01

    Patients with neurofibromatosis type I and breast cancer represent a subset of people who may be considered at high risk for secondary cancers after conventional whole breast radiation therapy and breast conservation surgery. A case of a 49-year-old woman with neurofibromatosis type I is presented. She was diagnosed with a 1.1-cm right breast infiltrating ductal carcinoma. Clinical, diagnostic imaging, and pathologic features are discussed. Her initial treatment plan of breast conserving therapy was thwarted when her sentinel node biopsy was positive for micrometastatic disease in 1/14 lymph nodes. She elected to have a bilateral simple mastectomy. This case addresses the rare dilemma of offering breast conservation therapy as a viable option for patients with neurofibromatosis type I. Current data on radiation-induced secondary cancers such as sarcoma after treatment for breast and other cancers are reviewed. PMID:18248558

  3. Resting state functional MRI reveals abnormal network connectivity in neurofibromatosis 1.

    PubMed

    Tomson, Steffie N; Schreiner, Matthew J; Narayan, Manjari; Rosser, Tena; Enrique, Nicole; Silva, Alcino J; Allen, Genevera I; Bookheimer, Susan Y; Bearden, Carrie E

    2015-11-01

    Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits, and autism spectrum disorders. As a single-gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity magnetic resonance imaging (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted. PMID:26304096

  4. Neurofibromatosis: an update of ophthalmic characteristics and applications of optical coherence tomography

    PubMed Central

    Abdolrahimzadeh, Barmak; Piraino, Domenica Carmen; Albanese, Giorgio; Cruciani, Filippo; Rahimi, Siavash

    2016-01-01

    Neurofibromatosis (NF) is a multisystem disorder and tumor predisposition syndrome caused by genetic mutation on chromosome 17-17q11.2 in NF type 1 (NF1), and on chromosome 22-22q12.2 in NF type 2. The disorder is characterized by considerable heterogeneity of clinical expression. NF1 is the form with the most characteristic ocular manifestations. Lisch nodules of the iris are among the well-known diagnostic criteria for the disease. Glaucoma and associated globe enlargement have been described in a significant proportion of patients with NF1 and orbital–facial involvement. Optic nerve glioma may cause strabismus and proptosis, and palpebral neurofibroma may reach considerable size and occasionally show malignant transformation. Near infrared reflectance has greatly contributed to enhancing our knowledge on choroidal alterations in NF1. Indeed, some authors have proposed to include these among the diagnostic criteria. Optical coherence tomography has given new insight on retinal alterations and is a noninvasive tool in the management of optic nerve gliomas in children. Ocular manifestations in NF type 2 can range from early-onset cataracts in up to 80% of cases to optic nerve hamartomas and combined pigment epithelial and retinal hamartomas. PMID:27257370

  5. Bone Mineral Density in Children and Adolescents with Neurofibromatosis Type 1

    PubMed Central

    Stevenson, David A.; Moyer-Mileur, Laurie J.; Murray, Mary; Slater, Hillarie; Sheng, Xiaoming; Carey, John C.; Dube, Bukhosi; Viskochil, David H.

    2007-01-01

    Objective To assess if children and adolescents with neurofibromatosis type 1 (NF1) have decreased bone mineral density (BMD). Study design Bone densitometry of the whole body, hip and lumbar spine was utilized in a case:control design (84 individuals with NF1: 293 healthy individuals without NF1). Subjects were 5–18 years of age. Individuals with NF1 were compared to controls using an analysis-of-covariance with a fixed set of covariates (age, weight, height, Tanner stage, and sex). Results Individuals with NF1 had decreased areal bone mineral density (aBMD) of the hip (p<0.0001), femoral neck (p<0.0001), lumbar spine (p=0.0025), and whole body subtotal (p<0.0001). When individuals with NF1 were separated into groups with and without a skeletal abnormality, the NF1 individuals without a skeletal abnormality still had statistically significant decreases compared to controls (p<0.0001 for whole body subtotal aBMD) albeit less pronounced than those with osseous abnormalities. Conclusions These data suggest that individuals with NF1 have a unique generalized skeletal dysplasia, predisposing them to localized osseous defects. Dual energy x-ray absorptiometry may prove useful to identify individuals with NF1 who are at risk for clinical osseous complications, and monitoring therapeutic trials. PMID:17188620

  6. Nevus Anemicus As an Additional Diagnostic Marker of Neurofibromatosis Type 1 in Childhood.

    PubMed

    Vaassen, Pia; Rosenbaum, Thorsten

    2016-06-01

    Diagnosis of neurofibromatosis type 1 (NF1) can be established when at least two out of seven defined clinical findings are present. However, a definite clinical diagnosis may be challenging, especially in young children. Therefore, we tried to identify additional clinical signs suggestive of NF1. We observed that nevi anemici (NA) occur with increased frequency in NF1 patients. To establish NA as an additional diagnostic criterion for NF1 we evaluated their exact frequency in children potentially affected by NF1. During a 6-month period we examined 100 NF1 patients and documented patients' age and sex as well as presence, location, and characteristic features of NA. We were able to show that NA are present in 28% of NF1 patients, which is well above the 5% prevalence of NA in the general population. It is not known why NA appear with increased frequency in NF1. We hypothesize that an imbalance between α- and β-adrenergic receptors, resulting in increased α-adrenergic vasoconstriction might be the underlying cause of NF1-associated NA. Based on our own observations and previously published studies, we propose that NA in children with suspected NF1 might facilitate definite diagnosis and improve clinical management. PMID:27019377

  7. Multiple Gastric Gastrointestinal Stromal Tumors in a Patient with Neurofibromatosis Type 1.

    PubMed

    Tomatsu, Makoto; Isogaki, Jun; Watanabe, Takahiro; Yajima, Kiyoshige; Okumura, Takuya; Yamashita, Kimihiro; Suzuki, Kenji; Kawabe, Akihiro; Komiyama, Akira; Hirota, Seiichi

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are relatively common in neurofibromatosis type 1 (NF 1) patients. Approximately 90% of GISTs associated with NF 1 are located in the small intestine, while sporadic GISTs are most commonly located in the stomach. Here we report an extremely rare case of an NF 1 patient with multiple gastric GITs (90 or more) but without multiple small intestinal tumors. A 63-year-old female patient who had a history of NF 1 underwent surgery for a gastric neuroendocrine tumor and gastric submucosal tumor (SMT). During the operation, multiple small nodules were identified on the serosal surface of the upper stomach. SMT and multiple nodules on the serosal surface were diagnosed as GISTs consisting of spindle cells positive for KIT, CD34, and DOG-1. Both GIST and the normal gastric mucosa showed no mutations not only in the c-kit gene (exons 8, 9, 11, 13, and 17) but also in the PDGFRA gene (exons 12, 14, and 18). This patient is being followed up without the administration of a tyrosine kinase inhibitor. PMID:27375917

  8. Imaging considerations of central nervous system manifestations in pediatric patients with neurofibromatosis type 1.

    PubMed

    Menor, F; Martí-Bonmatí, L; Mulas, F; Cortina, H; Olagüe, R

    1991-01-01

    CT and MRI were used in a prospective study of the central nervous system (CNS) manifestations in 41 consecutive children with neurofibromatosis type 1 (NF-1). Gadolinium-DTPA was used in 15 patients. MRI was more effective than CT in delimiting the extension of the optic pathway glioma and in evaluating associated cerebral malformations. MRI visualized lesions generally undetected by CT, in the form of iso- or hyperintense foci with respect to the cerebral cortex in T2-weighted sequences. Well-delimited lesions of high signal intensity were observed in the globus pallidus (22 cases), the internal capsule (6 cases), corpus callosum (2 cases), anterior commissure (1 case) and semioval center (2 cases). Poorly defined hyper- or isointense areas were also observed affecting the cerebellar white matter (21 cases) and brain stem (17 cases). None of these lesions showed Gadolinium-DTPA enhancement, and were of no clinical significance. MRI has displaced CT in the initial diagnosis of patients with NF-1. Periodic annual MRI controls are only justified in patients with MRI changes to evaluate the progression or stabilization of the lesions. PMID:1749666

  9. Depression among adults with neurofibromatosis type 1: prevalence and impact on quality of life.

    PubMed

    Cohen, J S; Levy, H P; Sloan, J; Dariotis, J; Biesecker, B B

    2015-11-01

    Neurofibromatosis type 1 (NF1) carries a significant psychosocial burden for affected individuals. The objective of this study was to measure the prevalence of depressive symptoms among a large sample of adults with NF1 and to quantify the impact of depressive symptoms on quality of life (QoL). This cross-sectional study used an Internet-based questionnaire to collect data from 498 adults who self-reported as having NF1. Using the Center for Epidemiologic Studies Depression (CESD) scale, 55% of all participants (61% of females and 43% of males) scored above 16, indicating a high likelihood of clinical depression. In a multivariate regression model controlling for demographics and potential confounders, depressive symptoms accounted for 32% of the variance in QoL as measured by the Quality of Life Index. This study is the largest to date and found the highest prevalence of depression compared to prior studies. Our data provide more compelling evidence that individuals with NF1 are at increased risk for psychiatric morbidity and suggest that this population should be routinely screened for depression. Because depression was found to be strongly associated with QoL and accounted for nearly one-third of the variance in QoL, it is likely that effectively treating depression may significantly enhance QoL for individuals with NF1. PMID:25534182

  10. An analysis of variation in expression of neurofibromatosis (NF) type I (NFI): Evidence for modifying genes

    SciTech Connect

    Easton, D.F.; Ponder, B.A.J. ); Huson, S.M. ); Ponder, M.A. )

    1993-08-01

    Neurofibromatosis (NF) type 1 (NF1) is notable for its variable expression. To determine whether variation in expression has an inherited component, the authors examined 175 individuals in 48 NF families, including six MZ twin pairs. Three quantitative traits were scored - number of cafe-au-lait patches, number of cutaneous neurofibromas, and head circumference; and five binary traits were scored - the presence or absence of plexiform neurofibromas, optic gliomas, scoliosis, epilepsy, and referral for remedial education. For cafe-au-lait patches and neurofibromas, correlation was highest between MZ twins, less high between first-degree relatives, and lower still between more distant relatives. The high correlation between distant relatives suggests that the type of mutation at the NF1 locus itself plays only a minor role. All of the five binary traits, with the exception of plexiformneurofibromas, also showed significant familial clustering. The familial effects for these traits were consistent with polygenic effects, but there were insufficient data to rule out other models, including a significant effect of different NF1 mutations. There was no evidence of any association between the different traits in affected individuals. The authors conclude that the phenotypic expression of NF1 is to a large extent determined by the genotype at other [open quotes]modifying[close quotes] loci and that these modifying genes are trait specific. 22 refs., 8 tabs.

  11. Consensus Recommendations for Current Treatments and Accelerating Clinical Trials for Patients with Neurofibromatosis Type 2

    PubMed Central

    Blakeley, Jaishri O; Evans, D. Gareth; Adler, John; Brackmann, Derald; Chen, Ruihong; Ferner, Rosalie E.; Hanemann, C. Oliver; Harris, Gordon; Huson, Susan M.; Jacob, Abraham; Kalamarides, Michel; Karajannis, Matthias A.; Korf, Bruce R.; Mautner, Victor-Felix; McClatchey, Andrea I.; Miao, Harry; Plotkin, Scott R.; Slattery, William; Stemmer-Rachamimov, Anat O.; Welling, D. Bradley; Wen, Patrick Y.; Widemann, Brigitte; Hunter-Schaedle, Kim; Giovannini, Marco

    2011-01-01

    Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome characterized by bilateral vestibular schwannomas (VS) which often result in deafness despite aggressive management. Meningiomas, ependymomas and other cranial nerve and peripheral schwannomas are also commonly found in NF2 and collectively lead to major neurologic morbidity and mortality. Traditionally, the overall survival rate in patients with NF2 is estimated to be 38% at 20 years from diagnosis. Hence, there is a desperate need for new, effective therapies. Recent progress in understanding the molecular basis of NF2 related tumors has aided in the identification of potential therapeutic targets and emerging clinical therapies. In June 2010, representatives of the international NF2 research and clinical community convened under the leadership of Drs. D. Gareth Evans (University of Manchester) and Marco Giovannini (House Research Institute) to review the state of NF2 treatment and clinical trials. This manuscript summarizes the expert opinions about current treatments for NF2 associated tumors and recommendations for advancing therapies emerging from that meeting. The development of effective therapies for NF2 associated tumors has the potential for significant clinical advancement not only for patients with NF2 but for thousands of neuro-oncology patients afflicted with these tumors. PMID:22140088

  12. Clinical presentations of 23 half-siblings from a mosaic neurofibromatosis type 1 sperm donor.

    PubMed

    Ejerskov, C; Farholt, S; Skovby, F; Vestergaard, E M; Haagerup, A

    2016-03-01

    The Danish sperm donor number 7042 has fathered several offspring with neurofibromatosis type 1 (NF1) worldwide. NF1 is caused by loss-of-function mutations in the NF1 gene and more than 1000 NF1 mutations are identified. Analysis of the donor sperm demonstrated gonosomal mosaicism with an intragenic deletion involving exons 15-29 in the NF1 gene. At the two Danish reference centres for NF1 patients, we evaluated 23 half-siblings from the donor. Nine were diagnosed with NF1. The severity grade of NF1 progressed from minimal to mild/moderate within 3 years of follow-up. The NF1 phenotype shows great variability in intra- and inter-family expressivity and to date only two NF1 genotype-phenotype correlations have been established. This rare possibility of a long-term follow-up of a cohort of half-siblings with NF1 makes further studies including phenotypic variability and search for modifier genes possible. To achieve this goal, we have initiated The International Donor 7042 NF1 Offspring Registry. Research facilitated via this registry may reveal important new knowledge of clinical characteristics and prognostics for the specific NF1 genotype and thereby contribute to future individualised targeted clinical follow-up and treatment. PMID:25872886

  13. Tumors displaying hybrid schwannoma and neurofibroma features in patients with neurofibromatosis type 2.

    PubMed

    Montgomery, Blake K; Alimchandani, Meghna; Mehta, Gautam U; Dewan, Ramita; Nesvick, Cody L; Miettinen, Markku; Heiss, John D; Asthagiri, Ashok R; Quezado, Martha; Germanwala, Anand V

    2016-01-01

    Although schwannoma and neurofibroma tumors are generally reported as distinct pathologic diagnoses, sporadic schwannoma/neurofibroma hybrid nerve sheath tumors have been reported in the general population with components of both entities. We report the clinicopathological features of these hybrid nerve sheath tumors in patients with neurofibromatosis type 2 (NF2). A retrospective review of nerve sheath tumor surgical specimens from patients with NF2 enrolled at the National Institutes of Health was performed. Those specimens reported to have schwannoma-like and neurofibromalike features were selected for further characterization by morphology, immunohistochemical panel (CD34, S100, neurofilament triplet protein (immunostain) (NFTP), epithelial membrane antigen (EMA)), and confirmation as hybrid tumors. Of 43 total NF2 patients undergoing resection of nerve sheath tumors, 11 specimens from 11 (26%) patients were found to be benign nerve sheath tumors exhibiting hybrid features of both neurofibroma and schwannoma. Immunohistochemical studies showed the schwannoma component to be S100+, CD 34- while the neurofibroma component was CD34+, variable S100+. Our experience emphasizes the importance of including this distinct tumor subtype, the schwannoma/neurofibroma hybrid tumor, in the differential diagnosis of nerve sheath tumors in NF2 patients and suggests that the relationship between neurofibroma and schwannoma tumors is closer than previously suspected.. PMID:26709712

  14. Neuropsychological evaluation and parental assessment of behavioral and motor difficulties in children with neurofibromatosis type 1.

    PubMed

    Coutinho, V; Kemlin, I; Dorison, N; Billette de Villemeur, T; Rodriguez, D; Dellatolas, G

    2016-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystem disorder, with large inter and intrafamilial clinical variability and uncertain prognosis. In children with NF1 cognitive disorders, learning difficulties and behavioral problems are common. The present study aims to establish the neuropsychological and behavioral profiles of 78 patients with NF1, aged between 5 and 18 years, and to examine the relationship between these profiles and the transmission of NF1 (sporadic vs. familial), clinical manifestations, and environmental factors. We used several questionnaires completed by parents and neuropsychological tests. The results confirmed specific neuropsychological disabilities in children with NF1, especially involving visuospatial and fine motor skills, learning difficulties and behavioral problems. Cognitive difficulties were significantly more frequent in patients with familial than in those with sporadic NF1. All parental questionnaires were correlated with each other, but parental reports were not associated with FSIQ, SES, school status, and clinical manifestations of the disease. Neuropsychological tests were poorly related to parental reports of cognitive and behavioral difficulties. PMID:26625207

  15. Retrolabyrinthine approach for cochlear nerve preservation in neurofibromatosis type 2 and simultaneous cochlear implantation

    PubMed Central

    Bento, Ricardo Ferreira; Monteiro, Tatiana Alves; Bittencourt, Aline Gomes; Goffi-Gomez, Maria Valeria Schmidt; de Brito, Rubens

    2013-01-01

    Summary Introduction: Few cases of cochlear implantation (CI) in neurofibromatosis type 2 (NF2) patients had been reported in the literature. The approaches described were translabyrinthine, retrosigmoid or middle cranial fossa. Objectives: To describe a case of a NF2- deafened-patient who underwent to vestibular schwannoma resection via RLA with cochlear nerve preservation and CI through the round window, at the same surgical time. Resumed Report: A 36-year-old woman with severe bilateral hearing loss due to NF2 was submitted to vestibular schwannoma resection and simultaneous CI. Functional assessment of cochlear nerve was performed by electrical promontory stimulation. Complete tumor removal was accomplishment via RLA with anatomic and functional cochlear and facial nerve preservation. Cochlear electrode array was partially inserted via round window. Sound field hearing threshold improvement was achieved. Mean tonal threshold was 46.2 dB HL. The patient could only detect environmental sounds and human voice but cannot discriminate vowels, words nor do sentences at 2 years of follow-up. Conclusion: Cochlear implantation is a feasible auditory restoration option in NF2 when cochlear anatomic and functional nerve preservation is achieved. The RLA is adequate for this purpose and features as an option for hearing preservation in NF2 patients. PMID:25992034

  16. Fatal Retroperitoneal Bleeding Caused by Neurofibromatosis: A Case Report and Review of the Literature

    PubMed Central

    Moerbeek, Patrick R.; van Buijtenen, Jesse M.; van den Heuvel, Baukje; Hoksbergen, Arjan W. J.

    2015-01-01

    A young female was brought into the emergency department with pulseless electrical activity (PEA) after local resection of neurofibromateous lesions. Chest ultrasonography was normal. Abdominal ultrasonography was not performed. After successful resuscitation a total body CT-scan was performed to rule out potential bleeding sources. However, haemodynamic instability reoccurred and the scan had to be aborted at the thoracoabdominal level. No thoracic abnormalities were found. Resuscitation was reinitiated and abdominal ultrasonography was performed, showing a large amount of abdominal fluid. A progressive fall in haemoglobin was noted. Emergency laparotomy was performed, revealing a large retroperitoneal haematoma. Despite ligation and packing, bleeding continued. Postoperative angiography showed active bleeding from a branch of the left internal iliac artery, which could be successfully coiled. Unfortunately, the patient died five days later due to irreversible brain damage. Revision of an MRI scan made one year earlier showed a 10 cm large retroperitoneal neurofibromatous lesion exactly at the location of the current bleeding. This case shows that patients with neurofibromatosis might develop spontaneous life-threatening bleeding from retroperitoneal located lesions. Furthermore, it points out the necessity of focused assessment with ultrasonography of the abdomen in all patients with PEA of unknown origin. PMID:25688270

  17. Soft tissue perineurioma and other unusual tumors in a patient with neurofibromatosis type 1

    PubMed Central

    Schaefer, Inga-Marie; Ströbel, Philipp; Thiha, Aung; Sohns, Jan Martin; Mühlfeld, Christian; Küffer, Stefan; Felmerer, Gunther; Stepniewski, Adam; Pauli, Silke; Agaimy, Abbas

    2013-01-01

    Perineurioma is a rare benign peripheral nerve sheath tumor featuring perineurial differentiation. Perineurioma occurs sporadically with only one reported case in the setting of neurofibromatosis type 1 (NF-1). We present a 6.7-cm soft tissue perineurioma of the lower leg in a 51-year-old man with proven NF-1. The tumor displayed whorled and fascicular pattern with infiltrative margins and expressed EMA, GLUT-1, claudin-1, and CD34. Electron microscopy confirmed diagnosis. Furthermore, lipomatosis, cutaneous angiomatous nodules, vasculopathy, and iliac spine lesion consistent with non-ossifying fibroma were observed. Tumor DNA revealed no NF2 mutations or chromosomal aberrations but a germline NF1-deletion (c.449_502delTGTT) was detected in his blood sample. His brother displayed neurofibromas, duodenal ganglioneuroma and colonic juvenile polyp, and his mother a neurofibroma, cutaneous squamous cell carcinoma, and jejunal gastrointestinal stromal tumor (GIST); both were affected by NF-1. In conclusion, perineurioma may rarely be NF-1 related and should be included in the spectrum of neoplasms occurring in this disorder. PMID:24294391

  18. Neurofibromatosis type 1-associated tumours: Their somatic mutational spectrum and pathogenesis

    PubMed Central

    2011-01-01

    Somatic gene mutations constitute key events in the malignant transformation of human cells. Somatic mutation can either actively speed up the growth of tumour cells or relax the growth constraints normally imposed upon them, thereby conferring a selective (proliferative) advantage at the cellular level. Neurofibromatosis type-1 (NF1) affects 1/3,000-4,000 individuals worldwide and is caused by the inactivation of the NF1 tumour suppressor gene, which encodes the protein neurofibromin. Consistent with Knudson's two-hit hypothesis, NF1 patients harbouring a heterozygous germline NF1 mutation develop neurofibromas upon somatic mutation of the second, wild-type, NF1 allele. While the identification of somatic mutations in NF1 patients has always been problematic on account of the extensive cellular heterogeneity manifested by neurofibromas, the classification of NF1 somatic mutations is a prerequisite for understanding the complex molecular mechanisms underlying NF1 tumorigenesis. Here, the known somatic mutational spectrum for the NF1 gene in a range of NF1-associated neoplasms --including peripheral nerve sheath tumours (neurofibromas), malignant peripheral nerve sheath tumours, gastrointestinal stromal tumours, gastric carcinoid, juvenile myelomonocytic leukaemia, glomus tumours, astrocytomas and phaeochromocytomas -- have been collated and analysed. PMID:22155606

  19. Aberrant Myeloid Differentiation Contributes to the Development of Osteoporosis in Neurofibromatosis Type 1.

    PubMed

    Rhodes, Steven D; Yang, Feng-Chun

    2016-02-01

    Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a common autosomal dominant genetic disorder affecting approximately 1 in 3000 individuals worldwide. NF1 results from heritable or spontaneous mutations of the NF1 tumor suppressor gene. NF1 encodes the protein neurofibromin, which functions to negatively regulate Ras-activity. Approximately 50 % of NF1 patients develop osteopenia or osteoporosis, resulting in significantly increased rates of long-bone fracture and morbidity. While defective osteoblast bone anabolism has been implicated as a central factor in the pathogenesis of NF1 associated skeletal deficits, recent data suggest that NF1 (Nf1) haploinsufficiency within the hematopoietic compartment, particularly in osteoclasts and myeloid progenitors, plays a pivotal role in engendering NF1 osseous manifestations. In this chapter, we review the latest data from clinical studies and murine models delineating a critical role for hematopoietic compartment, myeloid progenitors of NF1 (Nf1) haploinsufficient and their progeny-osteoclasts, in the pathogenesis of NF1 associated osteopenia/osteoporosis and discuss putative targets for future therapeutics. PMID:26932441

  20. Constitutional and mosaic large NF1 gene deletions in neurofibromatosis type 1.

    PubMed Central

    Rasmussen, S A; Colman, S D; Ho, V T; Abernathy, C R; Arn, P H; Weiss, L; Schwartz, C; Saul, R A; Wallace, M R

    1998-01-01

    A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene deletions by comparing patient and parent genotypes at 10 intragenic polymorphic loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases), five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion. These five patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features, in contrast to previous reports of large NF1 deletions. All five deletions were de novo and occurred on the maternal chromosome. However, two patients showed partial LOH, consistent with somatic mosaicism for the deletion, suggesting that mosaicism may be more frequent in NF1 than previously recognised (and may have bearing on clinical severity). We suggest that large NF1 deletions (1) are not always associated with unusual clinical features, (2) tend to occur more frequently on maternal alleles, and (3) are an important mechanism for constitutional and somatic mutations in NF1 patients. Images PMID:9643287

  1. Asfotase-α improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1

    PubMed Central

    de la Croix Ndong, Jean; Makowski, Alexander James; Uppuganti, Sasidhar; Vignaux, Guillaume; Ono, Koichiro; Perrien, Daniel S.; Joubert, Simon; Baglio, Serena R.; Granchi, Donatella; Stevenson, David A.; Rios, Jonathan J.; Nyman, Jeffry S.; Elefteriou, Florent

    2014-01-01

    Mineralization of the skeleton depends on the balance between levels of pyrophosphate (PPi), an inhibitor of hydroxyapatite formation, and phosphate generated from PPi breakdown by alkaline phosphatase (ALP). We report here that ablation of Nf1, encoding the RAS/GTPase–activating protein neurofibromin, in bone–forming cells leads to supraphysiologic PPi accumulation, caused by a chronic ERK–dependent increase in genes promoting PPi synthesis and extracellular transport, namely Enpp1 and Ank. It also prevents BMP2–induced osteoprogenitor differentiation and, consequently, expression of ALP and PPi breakdown, further contributing to PPi accumulation. The short stature, impaired bone mineralization and strength in mice lacking Nf1 in osteochondroprogenitors or osteoblasts could be corrected by enzyme therapy aimed at reducing PPi concentration. These results establish neurofibromin as an essential regulator of bone mineralization, suggest that altered PPi homeostasis contributes to the skeletal dysplasiae associated with neurofibromatosis type-1 (NF1), and that some of the NF1 skeletal conditions might be preventable pharmacologically. PMID:24997609

  2. A case of persistent foot pain in a neurofibromatosis type I patient.

    PubMed

    Stavrinides, Vasilis; Nasra, Salim

    2012-01-01

    Introduction. This is the case of a young male patient who presented to his family physician with atypical left foot pain, which was extremely resistant to analgesia and caused significant disability. Despite extensive investigations, the cause of his pain was not identified until 18 months after his initial symptoms, when the official diagnosis of malignant peripheral nerve sheath tumour (MPNST) was made. Detailed review of the patient's past history established the diagnosis of type I neurofibromatosis (NF-1), previously undetected. Discussion. NF-1 is an autosomal dominant genetic disorder caused by loss of function mutations of the NF1 gene in chromosome 17. Patients with this condition are at increased risk for developing MPNSTs which, however, are treatable only in early stages. Conclusion. Although monitoring NF-1 patients for the development of MPNSTs is common practice, the index of clinical suspicion in patients without an established NF-1 diagnosis is low. Any atypical pain in young adults should raise the possibility of this malignancy, and this case illustrates the fact that MPNSTs can be the first manifestation of NF-1 in patients previously undiagnosed with the disease. PMID:22312371

  3. Concurrent Ulcerative Colitis and Neurofibromatosis Type 1: The Question of a Common Pathway.

    PubMed

    Adams, William; Mitchell, Lisa; Candelaria-Santiago, Roberto; Hefner, Jody; Gramling, Joseph

    2016-02-01

    Patients with neurofibromatosis type 1 (NF1) are prone to the development of gastrointestinal stromal tumors, which may present clinically with hematochezia, obstruction, or abdominal pain. These symptoms are also commonly associated with the presentation of ulcerative colitis (UC). Within the past 5 years, there have been 2 reports of concurrent NF1 and UC and a common pathophysiologic pathway involving mast cells has been postulated. We present the case of a 15-year-old boy with a known history of NF1 who presented with 3 months of hematochezia and loose stools. A colonoscopy revealed pancolitis and histology demonstrating acute cryptitis, focal crypt abscesses, and architectural distortion consistent with UC. Due to the paucity of reported cases, the findings of both diseases in the same individual could reasonably be discounted as coincidence. However, in light of increasing reports of concurrent NF1 and UC, advances in characterizing the microenvironment within neurofibromas, and recent findings regarding potential shared genetic susceptibility, it is increasingly possible that the proposed common pathway is accurate. Our case adds to the literature and underscores the need for further investigation. PMID:26823541

  4. Multiple Gastric Gastrointestinal Stromal Tumors in a Patient with Neurofibromatosis Type 1

    PubMed Central

    Isogaki, Jun; Yajima, Kiyoshige; Yamashita, Kimihiro; Suzuki, Kenji; Hirota, Seiichi

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are relatively common in neurofibromatosis type 1 (NF 1) patients. Approximately 90% of GISTs associated with NF 1 are located in the small intestine, while sporadic GISTs are most commonly located in the stomach. Here we report an extremely rare case of an NF 1 patient with multiple gastric GITs (90 or more) but without multiple small intestinal tumors. A 63-year-old female patient who had a history of NF 1 underwent surgery for a gastric neuroendocrine tumor and gastric submucosal tumor (SMT). During the operation, multiple small nodules were identified on the serosal surface of the upper stomach. SMT and multiple nodules on the serosal surface were diagnosed as GISTs consisting of spindle cells positive for KIT, CD34, and DOG-1. Both GIST and the normal gastric mucosa showed no mutations not only in the c-kit gene (exons 8, 9, 11, 13, and 17) but also in the PDGFRA gene (exons 12, 14, and 18). This patient is being followed up without the administration of a tyrosine kinase inhibitor. PMID:27375917

  5. Neurofibromatosis 1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like symptoms.

    PubMed

    Waheed, Waqar; Nathan, Muriel H; Allen, Gilman B; Borden, Neil M; Babi, M Ali; Tandan, Rup

    2015-01-01

    A 37-year-old man with a known history of neurofibromatosis 1 (NF1) presented within 2 days of diarrhoeal illness followed by encephalopathy, facial twitching, hypoglycaemia, hypotension, tachycardia and low-grade fever. Examination showed multiple café-au-lait spots and neurofibromas over the trunk, arms and legs and receptive aphasia with right homonymous hemianopia, which resolved. Workup for cardiac, inflammatory and infectious aetiologies was unrevealing. A brain MRI showed gyral swelling with increased T2 fluid-attenuated inversion recovery signal and diffusion restriction in the left cerebral cortex. Neuroendocrine findings suggested panhypopituitarism with centrally derived adrenal insufficiency. Supportive treatment, hormone supplementation, antibiotics, antivirals and levetiracetam yielded clinical improvement. A follow-up brain MRI showed focal left parieto-occipital atrophy with findings of cortical laminar necrosis. In conclusion, we describe a case of NF1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like findings, hitherto unreported manifestations of NF1. Prompt recognition and treatment of these associated conditions can prevent devastating complications. PMID:26531733

  6. Progress of hearing loss in neurofibromatosis type 2: implications for future management.

    PubMed

    Kontorinis, Georgios; Nichani, Jaya; Freeman, Simon R; Rutherford, Scott A; Mills, Samantha; King, Andrew T; Mawman, Deborah; Huson, Sue; O'Driscoll, Martin; Gareth Evans, D; Lloyd, Simon K W

    2015-11-01

    The objective of this study was to describe changes in hearing over time in patients with neurofibromatosis type 2 (NF2) treated conservatively. A retrospective case review was conducted in a tertiary referral centre. Pure tone audiometry, speech discrimination scores, serviceable hearing (American Academy of Otolaryngology class A or B) and measurement of vestibular schwannoma (VS) size on magnetic resonance imaging were evaluated in 56 patients (89 ears) with NF2 with at least one conservatively managed VS. Over a mean follow-up period of 7 years (range 0.8-21 years) pure tone average thresholds increased gradually with a mean annual rate of 1.3 dB for the right ear (p = 0.0003) and 2 dB for the left ear (p = 0.0009). Speech discrimination scores dropped with an average annual rate of 1.3 and 0.34% in the right and left ear, respectively. Patients maintained serviceable hearing for an average of 7.6 years (range 2.7-19.3 years). The average annual VS growth was 0.4 mm without any correlation with hearing loss. There was a correlation between patients' age and pure tone threshold increase (p < 0.05 for both ears). In this selected population of patients with NF2, hearing threshold increases were very slow. In NF2 patients with indolently behaving tumours, serviceable hearing can be maintained for a significant length of time, making conservative management an attractive option. PMID:25294053

  7. Detection of Spontaneous Schwannomas by MRI in a Transgenic Murine Model of Neurofibromatosis Type 21

    PubMed Central

    Messerli, SM; Tang, Y; Giovannini, M; Bronsonx, R; Weissleder, R; Breakefield, XO

    2002-01-01

    Abstract Spontaneous schwannomas were detected by magnetic resonance imaging (MRI) in a transgenic murine model of neurofibromatosis type 2 (NF2) expressing a dominant mutant form of merlin under the Schwann cell-specific P0 promoter. Approximately 85% of the investigated mice showed putative tumors by 24 months of age. Specifically, 21% of the mice showed tumors in the intercostal muscles, 14% in the limb muscles, 7% in the spinal cord and spinal ganglia, 7% in the external ear, 14% in the muscle of the abdominal region, and 7% in the intestine; 66% of the female mice had uterine tumors. Multiple tumors were detected by MRI in 21% of mice. The tumors were isointense with muscle by T1-weighted MRI, showed strong enhancement following administration of gadolinium-DTPA, and were markedly hyperintense by T2-weighted MRI, all hallmarks of the clinical manifestation. Hematoxylin and eosin staining and immunohistochemistry indicated that the tumors consisted of schwannomas and Schwann cell hyperplasias. The lesions stained positively for S-100 protein and a marker antigen for the mutated transgenic NF2 protein, confirming that the imaged tumors and areas of hyperplasia were of Schwann cell origin and expressed the mutated NF2 protein. Tumors were highly infectable with a recombinant herpes simplex virus type 1 vector, hrR3, which contains the reporter gene, lacZ. The ability to develop schwannoma growth with a noninvasive imaging technique will allow assessment of therapeutic interventions. PMID:12407444

  8. Is there a relationship between executive functions and academic success in children with neurofibromatosis type 1?

    PubMed

    Gilboa, Yafit; Rosenblum, Sara; Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Josman, Naomi

    2014-01-01

    The present study aimed to compare the executive function (EF) of children with neurofibromatosis type 1 (NF1) to those of typically developing children and to investigate whether those abilities could predict the child's academic success in terms of academic skills and enablers. Twenty-nine children with NF1 and 27 age-and-gender-matched controls (aged 8-16 years) were examined with two tests to measure EF in an ecologically valid manner: the Behavioural Assessment of the Dysexecutive Syndrome in Children (BADS-C) and the parent questionnaire for the Behavior Rating Inventory of Executive Function (BRIEF). In order to evaluate academic success we used the Academic Competence Evaluation Scales (ACES). The performance of the NF1 group was significantly lower on the Water and Key search subtest of the BADS-C and on four scales of the BRIEF: initiate; working memory; plan/organise and organisation of materials. Significant correlations and predictive models via regression analysis were generated for: BADS-C, BRIEF and ACES scores. Based on these findings, children with NF1 have executive dysfunction that partially accounts for their difficulties in academic achievements. PMID:24875728

  9. Giant elephantiasis neuromatosa in the setting of neurofibromatosis type 1: A case report

    PubMed Central

    PONTI, GIOVANNI; PELLACANI, GIOVANNI; MARTORANA, DAVIDE; MANDEL, VICTOR DESMOND; LOSCHI, PIETRO; POLLIO, ANNAMARIA; PECCHI, ANNARITA; DEALIS, CRISTINA; SEIDENARI, STEFANIA; TOMASI, ALDO

    2016-01-01

    Elephantiasis neuromatosa (EN) can arise from a plexiform neurofibroma of the superficial and deep nerves developing from a hyperproliferation of the perineural connective tissue infiltrating adjacent fat and muscles. To date, the clinical association between EN and neurofibromatosis type 1 (NF1) has been poorly defined, particularly with regard to the role of lymphatic alterations and the consequent lymphedema. The present study reports the clinical and biomolecular features of EN in a NF1 patient with the clear clinical diagnostic criteria of multiple cafè-au-lait macules, neurofibromas, EN, a positive family history and a novel NF1 germline c.1541_1542del mutation. Lymphoscintigraphy (LS) highlighted marked dermal backflow in the affected limb, hypertrophy of the ipsilateral inguinal and external iliac lymph nodes, and a bilateral lower limb lymph flow delay. These data support the hypothesis that an extensive hyperproliferative process involving perineural connective, limb soft tissues, bones and the lymphatic system can be responsible for EN in NF1 patients, on the basis of adipocyte metaplasia triggered by lymphostasis and lymphedema, and bone overgrowth and gigantism caused by chronic hyperemia. LS and magnetic resonance imaging can be efficacious tools in the diagnosis and clinical characterization of the early onset of the disease. PMID:27284375

  10. Linkage disequilibrium in the neurofibromatosis 1 (NF1) region: implications for gene mapping.

    PubMed Central

    Jorde, L B; Watkins, W S; Viskochil, D; O'Connell, P; Ward, K

    1993-01-01

    To test the usefulness of linkage disequilibrium for gene mapping, we compared physical distances and linkage disequilibrium among eight RFLPs in the neurofibromatosis 1 (NF1) region. Seven of the polymorphisms span most of the NF1 gene, while the remaining polymorphism lies approximately 70 kb 3' to a stop codon in exon 49. By using Centre d'Etude du Polymorphisme Humain (CEPH) kindreds, 91-110 unrelated parents were genotyped. A high degree of disequilibrium is maintained among the seven intragenic polymorphisms (r > .82, P < 10(-7)), even though they are separated by as much as 340 kb. The 3' polymorphism is only 68 kb distal to the next polymorphism, but disequilibrium between the 3' polymorphism and all others is comparatively low (magnitude of 4 < .33, P values .27-.001). This result was replicated in three sets of unrelated kindreds: the Utah CEPH families, the non-Utah CEPH families, and an independent set of NF1 families. Trigenic, quadrigenic, three-locus, and four-locus disequilibrium measures were also estimated. There was little evidence of higher-order linkage disequilibrium. As expected for a disease with multiple mutations, no disequilibrium was observed between the disease gene and any of the RFLPs. The observed pattern of high disequilibrium within the gene and a loss of disequilibrium 3' to the stop codon could have implications for gene mapping studies. These are discussed, and guidelines for linkage disequilibrium studies are suggested. PMID:8105688

  11. Malignant Peripheral Nerve Sheath Tumors in Children with Neurofibromatosis Type 1

    PubMed Central

    Pourtsidis, Apostolos; Baka, Margarita; Bouhoutsou, Despina; Varvoutsi, Maria; Synodinou, Maria; Giamarelou, Panagiota; Kosmidis, Helen

    2014-01-01

    Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in children and account for approximately 5–10% of all soft tissue sarcomas in adults. MPNSTs may occur independently but individuals with neurofibromatosis type 1 (NF1) have a significantly increased risk. Our aim is to present patients with MPNST treated in our department. Cases and Results. In this report we present 4 cases of MPNSTs (3 females: 13, 12, and 13 years old and 1 male: 10 years old) arising in patients with NF1. All of them presented with an enlarging mass and pain at diagnosis. Tumor was located in the buttock, the spinal cord, the trunk, and the left leg proximal to the heel. Wide excision of the tumor and radiotherapy were applied to all and adjuvant chemotherapy was given to three of them after the disease was progressed. All four died 32, 18, 10, and 22 months after diagnosis with progressive disease locally and pulmonary metastases in two of them. Conclusions. In conclusion, MPNSTs arising in patients with NF1 are high grade sarcomas with short survival. Individuals with NF1 should be followed closely in order to identify early the development of MPNSTs. Aggressive surgery and complete excision significantly improves disease-free survival. The usefulness of radiation therapy in MPNSTs is not determined although all patients will receive radiation therapy at some stage of the disease. The role of chemotherapy is unclear. PMID:25317349

  12. Malignant peripheral nerve sheath tumors in children with neurofibromatosis type 1.

    PubMed

    Pourtsidis, Apostolos; Doganis, Dimitrios; Baka, Margarita; Bouhoutsou, Despina; Varvoutsi, Maria; Synodinou, Maria; Giamarelou, Panagiota; Kosmidis, Helen

    2014-01-01

    Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in children and account for approximately 5-10% of all soft tissue sarcomas in adults. MPNSTs may occur independently but individuals with neurofibromatosis type 1 (NF1) have a significantly increased risk. Our aim is to present patients with MPNST treated in our department. Cases and Results. In this report we present 4 cases of MPNSTs (3 females: 13, 12, and 13 years old and 1 male: 10 years old) arising in patients with NF1. All of them presented with an enlarging mass and pain at diagnosis. Tumor was located in the buttock, the spinal cord, the trunk, and the left leg proximal to the heel. Wide excision of the tumor and radiotherapy were applied to all and adjuvant chemotherapy was given to three of them after the disease was progressed. All four died 32, 18, 10, and 22 months after diagnosis with progressive disease locally and pulmonary metastases in two of them. Conclusions. In conclusion, MPNSTs arising in patients with NF1 are high grade sarcomas with short survival. Individuals with NF1 should be followed closely in order to identify early the development of MPNSTs. Aggressive surgery and complete excision significantly improves disease-free survival. The usefulness of radiation therapy in MPNSTs is not determined although all patients will receive radiation therapy at some stage of the disease. The role of chemotherapy is unclear. PMID:25317349

  13. Neurofibromatosis type 1 and attention deficit hyperactivity disorder: a case study and literature review

    PubMed Central

    Miguel, Carmen Sílvia; Chaim-Avancini, Tiffany M; Silva, Maria Aparecida; Louzã, Mario Rodrigues

    2015-01-01

    Background The cognitive profile of children with neurofibromatosis type 1 (NF1) and attention deficit hyperactivity disorder (ADHD) has been well characterized, but few studies have evaluated the cognitive abilities of adults with NF1 and ADHD. Objectives We investigated 1) the cognitive profile of an adult patient with NF1 and inattention problems, 2) changes in his cognition after 14 months of follow-up, and 3) whether the patient exhibited comorbid NF1 and ADHD or secondary ADHD-like symptoms. Methods We administered neuropsychological tests of executive function, attention, verbal and visual memory, visuospatial function, and language during two evaluations separated by 14 months. Results We found no changes in sustained attention, language, or verbal memory. Visual memory, verbal learning, selective attention inhibitory control, and problem solving declined over time, whereas visual search, psychomotor speed, visuospatial function, and mental flexibility improved. Conclusion Our patient exhibited a cognitive profile characteristic of both NF1 and ADHD, leading to the hypothesis that the patient had comorbid ADHD instead of secondary ADHD-like symptoms. More studies are necessary to characterize the cognition of patients with NF1 and ADHD. PMID:25848279

  14. Spinal cord ependymoma associated with neurofibromatosis 1 : case report and review of the literature.

    PubMed

    Cheng, Hongwei; Shan, Ming; Feng, Chunguo; Wang, Xiaojie

    2014-01-01

    Patients with neurofibromatosis 1 (NF1) are predisposed to develop central nervous system tumors, due to the loss of neurofibromin, an inactivator of proto-oncogene Ras. However, to our knowledge, only three cases of ependymomas with NF1 have been reported in the literature. The authors present a case of NF1 patient with a spinal cord ependymoma. She was referred for about half a year history of increasing numbness that progressed from her fingers to her entire body above the bellybutton. Magnetic resonance imaging revealed a relative-demarcated, heterogeneously enhanced mass lesion accompanied by perifocal edema in C5-7 level, a left-sided T11 spinous process heterogeneously enhanced mass in soft tissue, intervertebral disk hernia in L2-5 level, and widespread punctum enhancing lesion in her scalp and in T11-L5 level. The patient underwent C5-7 laminectomies and total excision of the tumor under operative microscope, and intraoperative ultrasonography and physiological monitoring were used during the surgery. Histopathologically, her tumor was found to be a ependymoma without malignant features (grade II in the World Health Organization classification). Therefore, no adjuvant therapy was applied. Following the operation, the patient showed an uneventful clinical recovery with no evidence of tumor recurrence after one year of follow-up. PMID:24570818

  15. Families dealing with the uncertainty of genetic disorders: the case of Neurofibromatosis Type 1.

    PubMed

    Carrieri, Daniele; Farrimond, Hannah; Kelly, Susan; Turnpenny, Peter

    2016-06-01

    Some scholars contend that genetic medicine is transforming the experience of illness and the social category of the family - bringing future risks into the present, and potentially strengthening familial biological bonds in light of these shared genetic risks. However, research has shown that genetic information is interpreted and acted upon through a rich repertoire of adaptable social, cultural and familial factors which pre-exist and interact with biomedical knowledge. This paper reports research into families living with Neurofibromatosis Type 1 (NF1), a highly uncertain condition the manifestation of which can vary considerably also within the same family and, for this reason, has been defined as a 'condition without parameters'. These characteristics make NF1 a particularly informative condition for the examination of family dynamics around genetic information. The study and the methodology are based on the exploration of family networks and allow us to investigate the interrelation of individual and familial constructions of the uncertainty of NF1. This also allows both theoretical and policy claims to be made about the danger of reductionist thinking about the transformative potential of genetic technologies. PMID:26864895

  16. Underlying mechanisms of writing difficulties among children with neurofibromatosis type 1.

    PubMed

    Gilboa, Yafit; Josman, Naomi; Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Rosenblum, Sara

    2014-06-01

    Writing is a complex activity in which lower-level perceptual-motor processes and higher-level cognitive processes continuously interact. Preliminary evidence suggests that writing difficulties are common to children with Neurofibromatosis type 1 (NF1). The aim of this study was to compare the performance of children with and without NF1 in lower (visual perception, motor coordination and visual-motor integration) and higher processes (verbal and performance intelligence, visual spatial organization and visual memory) required for intact writing; and to identify the components that predict the written product's spatial arrangement and content among children with NF1. Thirty children with NF1 (ages 8-16) and 30 typically developing children matched by gender and age were tested, using standardized assessments. Children with NF1 had a significantly inferior performance in comparison to control children, on all tests that measured lower and higher level processes. The cognitive planning skill was found as a predictor of the written product's spatial arrangement. The verbal intelligence predicted the written content level. Results suggest that high level processes underlie the poor quality of writing product in children with NF1. Treatment approaches for children with NF1 must include detailed assessments of cognitive planning and language skills. PMID:24691356

  17. Nutritional, muscular and metabolic characteristics in patients with neurofibromatosis type 1.

    PubMed

    Koga, Monji; Yoshida, Yuichi; Imafuku, Shinichi

    2016-07-01

    Neurofibromatosis type 1 (NF1) has many reported clinical characteristics. We previously found that NF1 patients (especially men) had lower body mass index (BMI) than controls, but the reason has not been elucidated. To address this issue, a retrospectively case-control study was conducted. Anthropometric and serum chemistry data that potentially relate to BMI were collected from medical records of NF1 patients and their age- and sex-matched controls. Enrollment of 98 adult patients who underwent skin surgery with NF1 (41 men, 57 women) and 173 without NF1 (74 men, 99 women) were investigated. The median BMI in male NF1 patients was significantly lower than that of the controls. Triglycerides in male NF1 patients were significantly lower than male controls, creatine kinase and lactate dehydrogenase in NF1 patients were also lower than controls, aspartate aminotransferase and alanine aminotransferase showed a lower tendency in NF1 patients, but were significantly lower in female patients. With correlation analysis, lactate dehydrogenase was moderately correlated with BMI in male NF1 patients. Creatine kinase and creatinine showed no statistical correlation with BMI in either group. Triglycerides and alanine aminotransferase showed a positive correlation with BMI in both male and female controls, but not in NF1 patients. In conclusion, only lactate dehydrogenase was moderately correlated with BMI in male NF1 patients, although results of some nutritional and metabolic parameters suggest a specific metabolism in NF1. PMID:26705255

  18. Neurofibromatosis type 1 associated low grade gliomas: A comparison with sporadic low grade gliomas.

    PubMed

    Helfferich, Jelte; Nijmeijer, Ronald; Brouwer, Oebele F; Boon, Maartje; Fock, Annemarie; Hoving, Eelco W; Meijer, Lisethe; den Dunnen, Wilfred F A; de Bont, Eveline S J M

    2016-08-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, associated with a variable clinical phenotype including café-au-lait spots, intertriginous freckling, Lisch nodules, neurofibromas, optic pathway gliomas and distinctive bony lesions. NF1 is caused by a mutation in the NF1 gene, which codes for neurofibromin, a large protein involved in the MAPK- and the mTOR-pathway through RAS-RAF signalling. NF1 is a known tumour predisposition syndrome, associated with different tumours of the nervous system including low grade gliomas (LGGs) in the paediatric population. The focus of this review is on grade I pilocytic astrocytomas (PAs), the most commonly observed histologic subtype of low grade gliomas in NF1. Clinically, these PAs have a better prognosis and show different localisation patterns than their sporadic counterparts, which are most commonly associated with a KIAA1549:BRAF fusion. In this review, possible mechanisms of tumourigenesis in LGGs with and without NF1 will be discussed, including the contribution of different signalling pathways and tumour microenvironment. Furthermore we will discuss how increased understanding of tumourigenesis may lead to new potential targets for treatment. PMID:27263935

  19. De novo development of gliomas in a child with neurofibromatosis type 1, fragile X and previously normal brain magnetic resonance imaging

    PubMed Central

    Zafar, Rabia; Hsiao, Esther Y.; Botteron, Kelly N.; McKinstry, Robert C.; Gutmann, David H.

    2016-01-01

    Fifteen to 20% of children with neurofibromatosis type 1 develop low-grade glial neoplasms. However, since neuroimaging is not routinely obtained until a child is clinically symptomatic, little is known about presymptomatic radiographic characteristics of gliomas in this at-risk population. Herein, we describe a child with neurofibromatosis type 1 who initially had normal brain imaging before the development of multifocal gliomas. Comparison of these serial images demonstrated that brain tumors can arise de novo in children with this cancer predisposition syndrome, further underscoring the limited prognostic value of normal baseline magnetic resonance imaging. PMID:26973730

  20. Mechanical Ptosis in Neurofibromatosis Type 1 Heralding the Diagnosis of Right Sided Cervical Vagus Nerve Neurofibroma: A Rare Case Report

    PubMed Central

    Parija, Sucheta; Panda, Bijnya; Pujahari, Susanta; Jena, Satyaswarup

    2016-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder. In NF1, involvement of vagus nerve can occur in the form of neurofibroma. A few cases of neurofibroma of thoracic vagus nerve have been reported while neurofibroma of cervical vagus nerve with NF1 is quite rare. A 19-year-old male came with complaints of decreased vision of both eyes and right sided drooping of eyelid since childhood. He was diagnosed as having NF1 with neurofibroma of right cervical vagus nerve. PMID:27504321

  1. Cochlear Implantation in Patients with Neurofibromatosis Type 2 and Patients with Vestibular Schwannoma in the Only Hearing Ear

    PubMed Central

    Celis-Aguilar, Erika; Lassaletta, Luis; Gavilán, Javier

    2012-01-01

    Cochlear implants are a new surgical option in the hearing rehabilitation of patients with neurofibromatosis type 2 (NF2) and patients with vestibular schwannoma (VS) in the only hearing ear. Auditory brainstem implant (ABI) has been the standard surgical treatment for these patients. We performed a literature review of patients with NF2 and patients with VS in the only hearing ear. Cochlear implantation (CI) provided some auditory benefit in all patients. Preservation of cochlear nerve integrity is crucial after VS resection. Results ranged from environmental sound awareness to excellent benefit with telephone use. Promontory stimulation is recommended although not crucial. MRI can be performed safely in cochlear implanted patients. PMID:22518152

  2. Carpal tunnel syndrome due to a plexiform neurofibroma of the median nerve in a neurofibromatosis type 1 patient: clinical approach.

    PubMed

    Freitas, Daniel; Aido, Ricardo; Sousa, Marco; Costa, Luís; Oliveira, Vânia; Cardoso, Pedro

    2013-01-01

    The authors report the case of a 56-year-old male patient with neurofibromatosis type 1 (NF1) diagnosed during adolescence and with an insidious clinical evolution, characterised by an exuberant cutaneous involvement, referred to the orthopaedics outpatient clinic presenting with carpal tunnel syndrome secondary to a plexiform neurofibroma of the median nerve. A comprehensive clinical approach is discussed, considering the natural history of the disease and its potential complications, as well as the lack of consensus regarding standard therapeutic options for the compressive peripheral neuropathies in the NF1 disease. PMID:23853185

  3. Mechanical Ptosis in Neurofibromatosis Type 1 Heralding the Diagnosis of Right Sided Cervical Vagus Nerve Neurofibroma: A Rare Case Report.

    PubMed

    Mallick, Jyotiranjan; Parija, Sucheta; Panda, Bijnya; Pujahari, Susanta; Jena, Satyaswarup

    2016-06-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder. In NF1, involvement of vagus nerve can occur in the form of neurofibroma. A few cases of neurofibroma of thoracic vagus nerve have been reported while neurofibroma of cervical vagus nerve with NF1 is quite rare. A 19-year-old male came with complaints of decreased vision of both eyes and right sided drooping of eyelid since childhood. He was diagnosed as having NF1 with neurofibroma of right cervical vagus nerve. PMID:27504321

  4. Functional Connectivity Changes and Executive and Social Problems in Neurofibromatosis Type I

    PubMed Central

    Huijbregts, Stephan C.J.; Veer, Ilya Milos; Swaab, Hanna S.; Van Buchem, Mark A.; Schmidt, Reinhold; Rombouts, Serge A.

    2015-01-01

    Abstract Neurofibromatosis type 1 (NF1) has regularly been associated with cognitive, social, and behavioral problems. The fact that many different cognitive and behavioral impairments have been observed in NF1 suggests that networks of brain regions are involved rather than specific brain regions. Here, we examined whether functional connectivity was different in NF1 and, if so, whether associations were present with cognitive, social, and behavioral outcomes. Fourteen NF1 patients (8 male, age: M=12.49, SD=2.65) and 30 healthy controls (HC; 23 male, age: M=12.30, SD=2.94; p=0.835) were included. Functional connectivity was assessed using functional resting-state scanning. We analyzed brain regions that have been associated with cognitive and social functions: the bilateral ventral anterior cingulate cortex (vACC), the bilateral amygdala, the bilateral orbitofrontal cortex (OFC), and the posterior cingulate cortex (PCC). For NF1 patients, connection strengths between brain regions showing HC-NF1 differences were correlated with parent reports of cognitive, social, and behavioral functioning. Compared to HC, patients showed differences in functional connectivity between the left vACC and the frontal cortex, insula, and subcortical areas (caudate, putamen), between the left amygdala and the frontal cortex, insula, supramarginal gyrus, and PCC/precuneus, and between the left OFC and frontal and subcortical areas (caudate, pallidum). In patients, indications were found for associations between increased frontofrontal and temporofrontal functional connectivity with cognitive, social, and behavioral deficits (r-range=0.536–0.851). NF1 patients showed differences in functional connectivity between areas associated with cognitive and social functioning when compared to controls. This, plus the fact that connectivity strengths in these networks were associated with worse cognitive, social, and behavioral outcomes, suggests a neuropathological basis for the widespread

  5. Abnormal relationship between GABA, neurophysiology and impulsive behavior in neurofibromatosis type 1

    PubMed Central

    Ribeiro, Maria J.; Violante, Inês R.; Bernardino, Inês; Edden, Richard A.E.; Castelo-Branco, Miguel

    2016-01-01

    Neurofibromatosis type 1 (NF1) is a neurodevelopmental disorder characterized by a broad spectrum of cognitive deficits. In particular, executive dysfunction is recognized as a core deficit of NF1, including impairments in executive attention and inhibitory control. Yet, the neural mechanisms behind these important deficits are still unknown. Here, we studied inhibitory control in a visual go/no-go task in children and adolescents with NF1 and age- and gender-matched controls (n = 16 per group). We applied a multimodal approach using high-density electroencephalography (EEG), to study the evoked brain responses, and magnetic resonance spectroscopy (MRS) to measure the levels of GABA and glutamate + glutamine in the medial frontal cortex, a brain region that plays a pivotal role in inhibitory control, and also in a control region, the occipital cortex. Finally, we run correlation analyses to identify the relationship between inhibitory control, levels of neurotransmitters, and EEG markers of neural function. Individuals with NF1 showed impaired impulse control and reduced EEG correlates of early visual processing (parieto-occipital P1) and inhibitory control (frontal P3). MRS data revealed a reduction in medial frontal GABA+/tCr (total Creatine) levels in the NF1 group, in parallel with the already reported reduced occipital GABA levels. In contrast, glutamate + glutamine/tCr levels were normal, suggesting the existence of abnormal inhibition/excitation balance in this disorder. Notably, medial frontal but not occipital GABA levels correlated with general intellectual abilities (IQ) in NF1, and inhibitory control in both groups. Surprisingly, the relationship between inhibitory control and medial frontal GABA was reversed in NF1: higher GABA was associated with a faster response style whereas in controls it was related to a cautious strategy. Abnormal GABAergic physiology appears, thus, as an important factor underlying impaired cognition in NF1, in a level and

  6. Peripheral Attentional Targets under Covert Attention Lead to Paradoxically Enhanced Alpha Desynchronization in Neurofibromatosis Type 1

    PubMed Central

    Silva, Gilberto; Ribeiro, Maria J.; Costa, Gabriel N.; Violante, Inês; Ramos, Fabiana; Saraiva, Jorge; Castelo-Branco, Miguel

    2016-01-01

    The limited capacity of the human brain to process the full extent of visual information reaching the visual cortex requires the recruitment of mechanisms of information selection through attention. Neurofibromatosis type-1 (NF1) is a neurodevelopmental disease often exhibiting attentional deficits and learning disabilities, and is considered to model similar impairments common in other neurodevelopmental disorders such as autism. In a previous study, we found that patients with NF1 are more prone to miss targets under overt attention conditions. This finding was interpreted as a result of increased occipito-parietal alpha oscillations. In the present study, we used electroencephalography (EEG) to study alpha power modulations and the performance of patients with NF1 in a covert attention task. Covert attention was required in order to perceive changes (target offset) of a peripherally presented stimulus. Interestingly, alpha oscillations were found to undergo greater desynchronization under this task in the NF1 group compared with control subjects. A similar pattern of desynchronization was found for beta frequencies while no changes in gamma oscillations could be identified. These results are consistent with the notion that different attentional states and task demands generate different patterns of abnormal modulation of alpha oscillatory processes in NF1. Under covert attention conditions and while target offset was reported with relatively high accuracy (over 90% correct responses), excessive desynchronization was found. These findings suggest an abnormal modulation of oscillatory activity and attentional processes in NF1. Given the known role of alpha in modulating attention, we suggest that alpha patterns can show both abnormal increases and decreases that are task and performance dependent, in a way that enhanced alpha desynchronization may reflect a compensatory mechanism to keep performance at normal levels. These results suggest that dysregulation of

  7. Quality of life among children and adolescents with neurofibromatosis 1: a systematic review of the literature.

    PubMed

    Vranceanu, Ana-Maria; Merker, Vanessa L; Park, Elyse R; Plotkin, Scott R

    2015-04-01

    The aim of this research is to identify, within a systematic review, aspects of quality of life (QoL) that are adversely affected in children and adolescents with neurofibromatosis (NF), and to report predictors of quality of life in this population. Published reports of original research were included if they described QoL in children and/or adolescents with NF, and met methodological quality according to a list of predefined criteria. Seven studies conducted between 2006 and 2013 met inclusion criteria. All seven studies examined patients with NF1 and reported that these patients have lower general QoL compared to population norms. Parents' proxy ratings of QoL were generally lower than children's self-report ratings. By parent proxy, familial NF1 was a strong protective factor for QoL, while the opposite was found by child report. By parent proxy, male sex was significantly associated with lower scores on the parental time impact of QoL. Skin-related QoL was only slightly altered in this population, vision-specific QoL was impacted only in patients with vision loss. The majority of findings regarding predictors of QoL in children with NF1 were weak, due to a lack of studies, heterogeneity of samples, and heterogeneity of measurements/predictors assessed. Future studies should examine more comprehensively the psychosocial factors affecting the NF population, especially in young patients with NF2 and schwannomatosis, who have been neglected in prior research. The use of consistent QoL measures is preferred to allow better comparison among studies and conditions. Interventions, including comprehensive mind-body treatments, are warranted to address impaired QoL in children and adolescents with NF1. PMID:25663248

  8. Evidence of polyclonality in neurofibromatosis type 2–associated multilobulated vestibular schwannomas

    PubMed Central

    Dewan, Ramita; Pemov, Alex; Kim, H. Jeffrey; Morgan, Keaton L.; Vasquez, Raul A.; Chittiboina, Prashant; Wang, Xiang; Chandrasekharappa, Settara C.; Ray-Chaudhury, Abhik; Butman, John A.; Stewart, Douglas R.; Asthagiri, Ashok R.

    2015-01-01

    Background Neurofibromatosis type 2 (NF2) is a tumor syndrome that results from mutation of the NF2 tumor suppressor gene. The hallmark of NF2 is the presence of bilateral vestibular schwannoma (VS). Though NF2-associated and sporadic VS share identical histopathologic findings and cytogenetic alterations, NF2-associated VS often appears multilobulated, is less responsive to radiosurgery, and has worse surgical outcomes. Temporal bone autopsy specimens and MRI of the inner ear performed on NF2 patients suggest that multiple discrete tumors may be present within the labyrinth and cerebellopontine angle. Methods Treatment-naïve ears in patients enrolled in a prospective NF2 natural history study (NIH#08-N-0044) were included for MRI analysis. T2-weighted and postcontrast T1-weighted MRIs were evaluated for the presence of multiple discrete tumors or a multilobulated mass. Peripheral blood (germline) and regional samples of tumor tissue were procured from consecutive patients enrolled in this study undergoing resection of a multilobulated VS (MVS). Histopathologic evaluation and genetic analysis (single nucleotide polymorphism array analysis, NF2 sequencing) were performed on each specimen. Results Over half of NF2 ears harbored either an MVS (60/139 ears) or multiple discrete masses (19/139 ears). For 4 successive MVSs, genetic analysis revealed an admixture of cell populations, each with its own somatic NF2 mutation or deletion. Conclusions These findings suggest that the majority of NF2-associated VSs are polyclonal, such that the tumor mass represents a collision of multiple, distinct tumor clones. This explains the characteristic lobulated gross appearance of NF2-associated VS, and may also explain the substantially different treatment outcomes compared with sporadic VS. PMID:25452392

  9. Puberty and Plexiform Neurofibroma Tumor Growth in Patients with Neurofibromatosis Type I

    PubMed Central

    Dagalakis, Urania; Lodish, Maya; Dombi, Eva; Sinaii, Ninet; Sabo, Jessica; Baldwin, Andrea; Steinberg, Seth M.; Stratakis, Constantine A.; Widemann, Brigitte C.

    2013-01-01

    Objective To assess the relationship between pubertal progression and change in PN burden over time in pediatric and young adult patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN). Study design Analyses accounted for sex, age, race, and chemotherapy. Forty-one patients with NF1 (15 female, 26 male) were studied at the National Cancer Institute (NCI). Tanner stage, testosterone, progesterone, estradiol, insulin-like growth factor −1, luteinizing hormone, and follicle stimulating hormone were assessed. Tumor volume was measured using Magnetic Resonance Imaging and lesion detection software developed at NIH. Patients were divided into two groups based upon whether they were actively progressing through puberty (n=16) or peri pubertal (n=25), and were followed for an average of 20 months. Tumor growth rates in the puberty and peri pubertal group were analyzed for a subset of patients. Results There was no statistically significant difference in tumor burden change over time (cc/kg/month) between the pubertal and peri pubertal group (−0.16 ± 0.34 vs. 0.03 ± 1.8, p=0.31), and in the PN growth rates pre and during puberty (p=0.90). Change in tumor volume/patient weight/time did not correlate with testosterone change/time in males or estradiol change/time in females. Conclusion These findings support that hormonal changes of puberty do not accelerate PN growth. Additional long-term follow up of patients is necessary to further characterize the interaction between puberty and tumor growth. PMID:24321536

  10. Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2.

    PubMed

    Hochart, Audrey; Gaillard, Vianney; Baroncini, Marc; André, Nicolas; Vannier, Jean-Pierre; Vinchon, Matthieu; Dubrulle, Frederique; Lejeune, Jean-Paul; Vincent, Christophe; Nève, Véronique; Sudour Bonnange, Héléne; Bonne, Nicolas Xavier; Leblond, Pierre

    2015-09-01

    Vestibular schwannoma (VS) growth in neurofibromatosis type 2 (NF2) can be responsible for brainstem compression and hearing loss. Surgical removal remains the standard therapy despite potential morbidity. Previous studies suggested that the inhibition of the VEGF-pathway with bevacizumab could result in hearing improvement, reduction of the tumor volume or both in adults. We retrospectively describe the French experience of bevacizumab treatment delivered for progressive VS in pediatric NF2 patients. Patients received Bevacizumab 5 or 10 mg/kg every 2 weeks according to the physician's choice. Follow-up included clinical assessment, audiometry and volumetric MRI every 3-6 months. Seven patients harboring 11 VS were included. The median age at inclusion was 15 years (11.4-18.8), and the median treatment duration was 11.3 months (3.2-55.6). At baseline, the median tumor volume was 1.2 cm(3) (0.52-13.5) and the median word recognition score was 90 % (0-100). We observed one major response, two minor responses and a decrease in the rate of tumor growth for the 4 other patients. The median annual growth rate before treatment was significantly higher than after 1 year of treatment (138 vs. 36 %, n = 5, p = 0.043). We noted one hearing improvement over the course of 1 year under treatment (hearing response rate was 14 %). Overall, the treatment was well tolerated. Our study supports that bevacizumab is an attractive therapeutic option for pediatric NF2 patients with growing VS. Thorough multidisciplinary evaluation is necessary to identify the best candidates prior to treatment. It is likely that a better functional outcome would be expected if targeted therapies were discussed early in the management of the disease. PMID:26022982

  11. Diagnostic value of multiple café-au-lait macules for neurofibromatosis 1 in Chinese children.

    PubMed

    Yao, Ruen; Wang, Lili; Yu, Yongguo; Wang, Jian; Shen, Yiping

    2016-05-01

    Neurofibromatosis 1 (NF1) is a common autosomal dominant condition caused by mutations in the NF1 gene. The appearance of multiple café-au-lait macules is an early sign of the condition, which often alert physicians to follow up and further examine the patient for the possibility of NF1. In order to determine the predictive value of multiple café-au-lait macules at early age for NF1 in Chinese patients, we recruited 19 children who shared the common sign of multiple café-au-lait macules from a general pediatric clinic in Shanghai. All the patients were clinically evaluated following the National Institutes of Health criteria for NF1 and molecular tested for sequence variants and copy number changes. Nine children met the clinical diagnostic criteria of NF1, and molecular tests confirmed all nine patients with pathogenic variants including two genomic deletions, two novel frame-shift variants, four novel nonsense and a splicing variants. In addition, four children who did not meet the diagnostic criteria were also found to carry pathogenic NF1 variants. Overall, 68.4% (13/19) of children with café-au-lait macules and various other clinical presentations were molecularly confirmed with NF1. This study demonstrated that the majority of Chinese children with multiple café-au-lait macules who came to seek for medical attention had NF1. Molecular testing is necessary to be used as an adjunct and sometimes as the main tool for confirming and diagnosing children of NF1 at early age. PMID:26458495

  12. Retrosigmoid Craniotomy for Auditory Brainstem Implantation in Adult Patients with Neurofibromatosis Type 2.

    PubMed

    Puram, Sidharth V; Herrmann, Barbara; Barker, Fred G; Lee, Daniel J

    2015-12-01

    Objective To report our technique and experience using a retrosigmoid craniotomy approach for auditory brainstem implantation (ABI) placement in adult neurofibromatosis type 2 (NF2) patients. Design Retrospective case series. Setting Single-center study, Boston, Massachusetts, United States. Participants All NF2 patients who underwent evaluation at Massachusetts Eye and Ear Infirmary and surgery at Massachusetts General Hospital from 2009 to 2013 were reviewed. Six cases of retrosigmoid craniotomy for ABI surgery in five adult NF2 patients were identified. The clinical history, operative course, and outcomes in these patients were reviewed. Main Outcome Measures Postoperative complications and audiological outcomes. Results Indications for ABI surgery were profound hearing loss associated with growth or treatment of bilateral vestibular schwannomas. In all cases, a retrosigmoid craniotomy was performed for tumor resection and ABI placement without complication. Electrode placement was confirmed intraoperatively using electrical-evoked auditory brainstem responses. The ABI was activated in the awake patient 4 to 6 weeks postoperatively. Audiological testing was used to evaluate sound detection and speech perception with the ABI. There were no cases of cerebrospinal fluid leak. Conclusion Retrosigmoid craniotomy is a safe and effective means to provide access to the cochlear nucleus for ABI placement following tumor resection in the adult NF2 patient. Preliminary data indicate that this approach has few complications while offering benefits for hearing. The retrosigmoid craniotomy should be considered a reasonable alternative to the traditional translabyrinthine approach for placement of the ABI in deaf patients who are not candidates for the cochlear implant. PMID:27054058

  13. Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease.

    PubMed Central

    Ruttledge, M. H.; Andermann, A. A.; Phelan, C. M.; Claudio, J. O.; Han, F. Y.; Chretien, N.; Rangaratnam, S.; MacCollin, M.; Short, P.; Parry, D.; Michels, V.; Riccardi, V. M.; Weksberg, R.; Kitamura, K.; Bradburn, J. M.; Hall, B. D.; Propping, P.; Rouleau, G. A.

    1996-01-01

    The gene predisposing to neurofibromatosis type 2 (NF2) on human chromosome 22 has revealed a wide variety of different mutations in NF2 individuals. These patients display a marked variability in clinical presentation, ranging from very severe disease with numerous tumors at a young age to a relatively mild condition much later in life. To investigate whether this phenotypic heterogeneity is determined by the type of mutation in NF2, we have collected clinical information on 111 NF2 cases from 73 different families on whom we have performed mutation screening in this gene. Sixty-seven individuals (56.2%) from 41 of these kindreds revealed 36 different putative disease-causing mutations. These include 26 proposed protein-truncating alterations (frameshift deletions/insertions and nonsense mutations), 6 splice-site mutations, 2 missense mutations, 1 base substitution in the 3' UTR of the NF2 cDNA, and a single 3-bp in-frame insertion. Seventeen of these mutations are novel, whereas the remaining 19 have been described previously in other NF2 individuals or sporadic tumors. When individuals harboring protein-truncating mutations are compared with cases with single codon alterations, a significant correlation (P < .001) with clinical outcome is observed. Twenty-four of 28 patients with mutations that cause premature truncation of the NF2 protein, schwannomin, present with severe phenotypes. In contrast, all 16 cases from three families with mutations that affect only a single amino acid have mild NF2. These data provide conclusive evidence that a phenotype/genotype correlation exists for certain NF2 mutations. PMID:8755919

  14. Lovastatin regulates brain spontaneous low-frequency brain activity in neurofibromatosis type 1.

    PubMed

    Chabernaud, Camille; Mennes, Maarten; Kardel, Peter G; Gaillard, William D; Kalbfleisch, M Layne; Vanmeter, John W; Packer, Roger J; Milham, Michael P; Castellanos, Francisco X; Acosta, Maria T

    2012-04-25

    In the neurofibromatosis type 1 (NF1) mouse model, lovastatin, used clinically for hypercholesterolemia, improves cognitive dysfunction. While such impairment has been studied in NF1, the neural substrates remain unclear. The aim of this imaging add-on to a Phase 1 open-label trial was to examine the effect of lovastatin on Default Network (DN) resting state functional connectivity (RSFC). Seven children with NF1 (aged 11.9 ± 2.2; 1 female) were treated with lovastatin once daily for 12 weeks. A 7-min 3-T echo-planar-imaging scan was collected one day before beginning treatment (off-drug) and the last day of treatment (on-drug) while performing a flanker task. After regressing-out task-associated variance, we used the residual time series as "continuous resting-state data" for RSFC analyses using 11 DN regions of interest. For qualitative comparisons, we included a group of 19 typically developing children (TDC) collected elsewhere. In the on-drug condition, lovastatin increased long-range positive RSFC within DN core regions (i.e., anterior medial prefrontal cortex and posterior cingulate cortex, PCC). In addition, lovastatin produced less diffuse local RSFC in the dorsomedial prefrontal cortex and PCC. The pattern of RSFC observed in the NF1 participants when on-drug closely resembled the RSFC patterns exhibited by the TDC. Lovastatin administration in this open trial regulated anterior-posterior long-range and local RSFC within the DN. These preliminary results are consistent with a role for lovastatin in normalization of developmental processes and with apparent benefits in a mouse NF1 model. PMID:22433254

  15. Psychological disturbance and sleep disorders in children with neurofibromatosis type 1.

    PubMed

    Johnson, Hilary; Wiggs, Luci; Stores, Gregory; Huson, Susan M

    2005-04-01

    The objective of this study was to explore the behaviour, including sleep patterns, of children with neurofibromatosis type 1 (NF1). For this purpose we designed a cross-sectional descriptive survey conducted by postal enquiry with telephone follow-up. Simonds and Parraga's sleep questionnaire and the Strength and Difficulties Questionnaire were used to screen sleep patterns and behaviours respectively. Information was obtained for 64 children (39 male, mean age 10 y 7 mo, SD 4 y 1 mo, range 3 to 18 y; 57% response rate). There were increased numbers of children with NF1 achieving scores in the borderline and abnormal range for ratings of peer problems (p < 0.001), hyperactivity (p < 0.001), emotional symptoms (p < 0.001), and conduct disorder (p < 0.05). Total difficulties score was also high (p < 0.001) in the NF1 group. Only one group of sleep problems, parasomnias (in particular sleepwalking and sleep terrors), had a higher occurrence (p < or = 0.05) in the NF1 group than in the general population. Within the NF1 group, conduct problems (p < or = 0.05), hyperactivity (p < or = 0.01), emotional problems (p < or = 0.01), and the total difficulties score (p < or = 0.01) were all significantly higher in children with frequent sleep disturbance. We conclude that NF1 is associated with sleep and behavioural problems in a high proportion of children. Psychiatric conditions, e.g. attention-deficit-hyperactivity disorder, may be underdiagnosed on a large scale in children with NF1, and the use of simple screening tools in clinical settings may prove beneficial. PMID:15832546

  16. Neurofibromatosis type 1 associated with pheochromocytoma and gastrointestinal stromal tumors: A case report and literature review

    PubMed Central

    PAN, DONGFENG; LIANG, PEIFENG; XIAO, HONGYAN

    2016-01-01

    Neurofibromatosis type 1 (NF1) is a genetic disorder associated with neurofibromin 1 (NF1) gene mutation, which generates an increased risk of variety of tumor types. The current study reports a case involving NF1, pheochromocytoma (PHEO) and gastrointestinal stromal tumors (GIST). A 56-year-old man presented with abdominal pain and polypnea. Clinical investigation revealed multiple diffuse soft-tissue lesions throughout his body, and pigmented macules on the skin. Imaging analyses revealed thoracic scoliosis, multiple subcutaneous nodules in the abdomen and trunk, and a 7.0×7.7×8.9-cm oval-shaped, cystic mass in the left upper abdominal cavity. Immunohistochemical staining indicated that S-100 protein and synaptophysin were highly expressed in adrenal gland neoplasm, whilst CD117 and CD34 were highly expressed in small intestine tumors. The overall clinical and pathological finding suggested a diagnosis of NF1, giant PHEO and small intestinal stromal tumor. In addition, a literature review was conducted to identify the specific clinical features of patients with this condition. Only 11 similar cases have been reported worldwide. In the present study, paroxysmal hypertension occurred in the majority of patients, and GISTs tended to be located in the small intestine. In addition, the present study demonstrated that many of the patients had a poor prognosis. Therefore, the present study indicates that NF1-PHEO-GIST is a special type tumor with varied clinical symptoms, which may be associated with an increased risk for poor prognosis; however, more studies are required to confirm this. PMID:27347193

  17. Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1

    PubMed Central

    2013-01-01

    Background Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders causing learning disabilities by mutations in the neurofibromin gene, an important inhibitor of the RAS pathway. In a mouse model of NF1, a loss of function mutation of the neurofibromin gene resulted in increased gamma aminobutyric acid (GABA)-mediated inhibition which led to decreased synaptic plasticity and deficits in attentional performance. Most importantly, these defictis were normalized by lovastatin. This placebo-controlled, double blind, randomized study aimed to investigate synaptic plasticity and cognition in humans with NF1 and tried to answer the question whether potential deficits may be rescued by lovastatin. Methods In NF1 patients (n = 11; 19–44 years) and healthy controls (HC; n = 11; 19–31 years) paired pulse transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (paired pulse) and synaptic plasticity (paired associative stimulation). On behavioural level the Test of Attentional Performance (TAP) was used. To study the effect of 200 mg lovastatin for 4 days on all these parameters, a placebo-controlled, double blind, randomized trial was performed. Results In patients with NF1, lovastatin revealed significant decrease of intracortical inhibition, significant increase of synaptic plasticity as well as significant increase of phasic alertness. Compared to HC, patients with NF1 exposed increased intracortical inhibition, impaired synaptic plasticity and deficits in phasic alertness. Conclusions This study demonstrates, for the first time, a link between a pathological RAS pathway activity, intracortical inhibition and impaired synaptic plasticity and its rescue by lovastatin in humans. Our findings revealed mechanisms of attention disorders in humans with NF1 and support the idea of a potential clinical benefit of lovastatin as a therapeutic option. PMID:24088225

  18. Associations between allergic conditions and pediatric brain tumors in Neurofibromatosis type 1.

    PubMed

    Porcelli, Bree; Zoellner, Nancy L; Abadin, Salmafatima S; Gutmann, David H; Johnson, Kimberly J

    2016-04-01

    Individuals with Neurofibromatosis type 1 (NF1) are at increased risk for pediatric brain tumors (PBTs), especially optic gliomas; however, factors influencing their development are largely unknown. Extensive research suggests that allergic conditions protect against brain tumors, particularly gliomas in individuals without NF1. In this large cross-sectional study, we employed two different data sources to evaluate evidence for the hypothesis that allergic conditions (allergies, asthma, and eczema) may protect against PBT development in individuals with NF1. We used self- and parent/legal guardian reported questionnaire data from participants in the NF1 Patient Registry Initiative (NPRI, n = 1660) born from 1933 to 2014 to ascertain allergic condition and PBT diagnosis histories. Medical records (MRs) of 629 NF1 patients at a large medical center born from 1930 to 2012 were also reviewed for PBT and allergic condition diagnoses to evaluate additional evidence for our hypothesis. We used logistic regression to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between allergic condition diagnoses and PBTs. Both data sources provided limited to no support for a protective effect of allergies or eczema on PBT development. Non-significant inverse associations between asthma and PBTs were observed (NPRI: OR = 0.80, 95 % CI 0.55-1.17; MR: OR = 0.71, 95 % CI 0.40-1.28) with stronger associations for optic gliomas specifically. Additionally, a significant inverse association was observed in an NPRI subgroup analysis where the reported asthma diagnosis age was younger than the reported PBT diagnosis age (OR = 0.57; 95 % CI 0.36-0.89). Our study supports the hypothesis that asthma protects against PBT development in NF1. PMID:26666764

  19. Surgical correction of severe cervical kyphosis in patients with neurofibromatosis Type 1.

    PubMed

    Kawabata, Soya; Watanabe, Kota; Hosogane, Naobumi; Ishii, Ken; Nakamura, Masaya; Toyama, Yoshiaki; Matsumoto, Morio

    2013-03-01

    Severe cervical kyphosis requiring surgical treatment is rare in patients with neurofibromatosis Type 1 (NF1). When it occurs, however, dystrophic changes in the vertebrae make surgical correction and fusion of the deformity extremely difficult. The authors report on 3 cases of severe cervical kyphosis associated with NF1 that were successfully treated with combined anterior and posterior correction and fusion. All patients underwent halo-gravity traction for approximately 1 month prior to surgery to correct the deformity gradually. Posterior correction and fusion were performed with segmental spinal instrumentation consisting of lateral mass screws, lamina screws, pedicle screws, and polyethylene tape for sublaminar wiring. Anterior spinal fusion was performed using a fibula strut to induce solid bone fusion. All patients used a halo vest for postoperative external fixation. Preoperative CT scans showed dystrophic cervical spine changes, and MR images demonstrated extensive neurofibromas outside the cervical spine in all 3 patients. The preoperative kyphotic angles were as follows: Case 1, 140°; Case 2, 81°; and Case 3, 72°; after halo-gravity traction, the kyphosis angles improved to 50°, 55°, and 51°, respectively; and after surgery, they were 50°, 15°, and 27°, respectively. Solid bone union was observed in all patients at the latest follow-up. All three patients experienced postoperative complications consisting of superficial infection, severe pneumonia, and partial dislocation of the distal fibula graft after removing the halo vest, in one patient each. Although dystrophic cervical vertebral changes in these patients with NF1 complicated the correction of severe cervical kyphosis, the use of preoperative halo-gravity traction, a combination of spinal instrumentations, an anterior strut bone graft, and postoperative halo-vest fixation made it possible to correct the kyphosis, maintain the correction, and achieve solid bone fusion. PMID:23289507

  20. NF1 Exon 22 Analysis of Individuals with the Clinical Diagnosis of Neurofibromatosis Type 1

    PubMed Central

    Muram-Zborovski, Talia M.; Vaughn, Cecily P.; Viskochil, David H.; Hanson, Heather; Mao, Rong; Stevenson, David A.

    2010-01-01

    Café-au-lait macules are frequently seen in Ras-MAPK pathway disorders and are a cardinal feature of neurofibromatosis type 1 (NF1). Most NF1 individuals develop age-related tumorigenic manifestations (e.g. neurofibromas), although individuals with a specific 3-bp deletion in exon 22 of NF1 (c.2970_2972delAAT) have an attenuated phenotype with primarily pigmentary manifestations. Previous reports identify this deletion c.2970_2972delAAT in exon 17 of NF1 using NF Consortium nomenclature. For this report, we elected to use standard NCBI nomenclature, which places this identical deletion within exon 22. SPRED1 causes Legius syndrome, which clinically overlaps with this attenuated NF1 phenotype. In an unselected cohort of 150 individuals who fulfilled NIH clinical diagnostic criteria from an NF Clinic and did not have SPRED1 mutations, we sequenced NF1 exon 22 in order to identify children and adolescents with multiple café-au-lait spots who could be projected to have lower likelihood to develop tumors. Two individuals with NF1 exon 22 mutations were identified: an 11-year-old boy with the c.2970_2972delAAT in-frame deletion and a 4-year-old boy with c.2866dupA. The father of the second patient had an attenuated form of NF1 and showed 24% germline mosaicism of the c.2866dupA mutation in whole blood. These individuals emphasize the need for mutation analysis in some individuals with the clinical diagnosis of NF1 who lack the tumorigenic or classic skeletal abnormalities of NF1. Specifically, with the identification of Legius syndrome, the need to recognize the attenuated phenotype of NF1 mosaicism and confirmation by mutation analysis is increasingly important for appropriate medical management and family counseling. PMID:20602485

  1. The generalized bone phenotype in children with neurofibromatosis 1: a sibling matched case-control study.

    PubMed

    Armstrong, Linlea; Jett, Kimberly; Birch, Patricia; Kendler, David L; McKay, Heather; Tsang, Erica; Stevenson, David A; Hanley, David A; Egeli, Deetria; Burrows, Melonie; Friedman, J M

    2013-07-01

    People with neurofibromatosis 1 (NF1) have low bone mineralization, but the natural history and pathogenesis are poorly understood. We performed a sibling-matched case-control study of bone mineral status, morphology, and metabolism. Eighteen children with NF1 without focal bony lesions were compared to unaffected siblings and local population controls. Bone mineral content at the lumbar spine and proximal femur (dual energy X-ray absorptiometry (DXA)) was lower in children with NF1; this difference persisted after adjusting for height and weight. Peripheral quantitative computed tomography (pQCT) of the distal tibia showed that trabecular density was more severely compromised than cortical. Peripheral QCT-derived estimates of bone strength and resistance to bending and stress were poorer among children with NF1 although there was no difference in fracture frequencies. There were no differences in the size or shape of bones after adjusting for height. Differences in markers of bone turnover between cases and controls were in the directions predicted by animal studies, but did not reach statistical significance. Average serum calcium concentration was higher (although within the normal range) in children with NF1; serum 25-OH vitamin D, and PTH levels did not differ significantly between cases and controls. Children with NF1 were less mature (assessed by pubertal stage) than unaffected siblings or population controls. Children with NF1 have a generalized difference of bone metabolism that predominantly affects trabecular bone. Effects of decreased neurofibromin on bone turnover, calcium homeostasis, and pubertal development may contribute to the differences in bone mineral content observed among people with NF1. PMID:23713011

  2. Parental age and Neurofibromatosis Type 1: a report from the NF1 Patient Registry Initiative.

    PubMed

    Liu, Qian; Zoellner, Nancy; Gutmann, David H; Johnson, Kimberly J

    2015-06-01

    One of the potential etiologies for non-familial Neurofibromatosis Type 1 (NF1) is increasing parental age. We sought to evaluate recent evidence for parental age effects in NF1 in a large study. Individuals with NF1 and a comparison group from the U.S. general population born between 1994 and 2012 were ascertained from the NF1 Patient Registry Initiative (NPRI) and the National Center for Vital Statistics, respectively. Multiple linear regression analysis was employed to identify differences between familial NF1, non-familial NF1, and U.S. population subjects in the mean parental ages at the time of the birth of offspring in each group. In addition, we also evaluated the effect of parental age on NF1 offspring with and without a pediatric brain tumor history. A total of 313 subjects from the NPRI (including 99 brain tumor cases) matched by birth year at a 1:3 ratio to U.S. general population births (n = 939) were included. Compared to the U.S. general population and familial NF1 cases, the mean paternal age for non-familial NF1 cases was 4.34 years (95% CI 3.23-5.46, p ≤ 0.0001) and 3.39 years (95% CI 1.57-5.20, p ≤ 0.0001) older, respectively, after adjusting for birth year. A similar pattern was observed for maternal age. There were no statistically significant differences in the mean maternal or paternal ages between NF1 offspring with and without a pediatric brain tumor. In conclusion, these data support a parental age effect for non-familial NF1 cases, but not for pediatric brain tumors in NF1. PMID:25523354

  3. Cerebellar pleomorphic xanthoastrocytoma in a patient with neurofibromatosis type 1: a case report and literature review.

    PubMed

    Takei, Hidehiro; Rouah, Emilie; Bhattacharjee, Meenakshi B

    2015-01-01

    Pleomorphic xanthoastrocytoma (PXA) is an uncommon tumor of young adults that typically occurs supratentorially. It is generally considered to be a low-grade, circumscribed tumor that when treated by surgical resection has a relatively favorable outcome. Cases of cerebellar PXA are rare, and those associated with neurofibromatosis type 1 (NF1) are even less common, with only 2 cases reported to date. We present herein a third case of PXA-NF1 with unusual features. A 33-year-old woman presented with a history of headache. Her medical and family history was significant for NF1. Brain MRI revealed a 3.4 cm ill-defined lesion with a gyriform enhancing pattern in the left cerebellum, superficially mimicking Lhermitte-Duclos disease. The patient underwent a gross total resection of the lesion and had an unremarkable postoperative course. While the lesion had histological features typical of "pure" PXA (WHO grade II) it had an unusual growth pattern with thickening of the superficial cerebellar folia and predominant leptomeningeal involvement. No BRAF, IDH-1, or IDH-2 mutation was identified. Three months after surgery, local recurrence was detected, and the patient was treated with radiation therapy. One year after the first surgery, she underwent surgical resection of the recurrent/residual tumor. Histologically, the recurrent tumor showed very similar features to the initially resected tumor, with no anaplastic features. Most cerebellar PXAs have an indolent clinical behavior as do most cerebral PXAs. Whether co-existence of NF1 was a factor in altering the clinical course and biologic behavior of this patient's tumor is currently unknown. PMID:26261671

  4. Clinical characteristics and long-term outcomes of moyamoya syndrome associated with neurofibromatosis type 1.

    PubMed

    Han, Cong; Yang, Wei-Zhong; Zhang, Hong-Tao; Ye, Ting; Duan, Lian

    2015-02-01

    Moyamoya syndrome (MMS) associated with neurofibromatosis type 1 (NF1) has rarely been reported anywhere in the world, particularly in Asia. Because of the rarity of this disorder, its natural history, clinical symptoms, management, and follow-up findings remain unclear. The objective of this study was to evaluate the clinical presentation, neurological imaging, and long-term outcomes of patients with this disease by reviewing Chinese patients with MMS associated with NF1. A retrospective review was conducted from the moyamoya disease (MMD) and MMS patient database of our hospital. Six patients who were diagnosed with MMS associated with NF1 between January 2003 and October 2013 were identified. The clinical symptoms were transient ischemic attack (TIA, three patients), headache (one patient), intracerebral hemorrhage (one patient), and cerebral infarction (one patient). The mean age of diagnosis for NF1 and MMS was 2.7 ± 2.1 years (range, 1-6 years) and 11.4 ± 8.3 years (range, 3.5-23 years), respectively. Five of six patients (nine hemispheres) underwent revascularization surgery, and their clinical symptoms were stable during a 46.3 ± 36.1 month (range, 18-108 month) follow-up. One non-surgical patient had a new infarct that resulted in visual field deficits during follow-up. Three patients had radiographic follow-up, and the postoperative angiograms showed successful revascularizations in the operated hemispheres. To conclude, the clinical and radiographic features for MMS-NF1 are similar to those of typical MMD. Routine vascular screening for NF1 patients is necessary for the early identification of MMS and other cerebral arteriopathies. Revascularization surgery may prevent the progression of clinical symptoms and reduce the risk of subsequent strokes. PMID:25443089

  5. Neurofibromatosis 1-related osteopenia often progresses to osteoporosis in 12 years.

    PubMed

    Heervä, Eetu; Leinonen, Pekka; Kuorilehto, Tommi; Peltonen, Sirkku; Pöyhönen, Minna; Väänänen, Kalervo; Peltonen, Juha

    2013-01-01

    The current study is based on our earlier investigation carried out in 1999, where bone mineral density (BMD) of 35 neurofibromatosis type 1 (NF1) patients was measured and osteoporosis was shown to be common in NF1. The findings have been confirmed by a number of later publications. The purpose of the current longitudinal study was to assess the bone health of these 35 NF1 patients 12 years after the initial study. A total of 28 patients were reached, and BMD of 19 patients was subsequently remeasured. Fracture history of 28/35 NF1 patients who were reached was verified from the medical records. Six NF1 patients had osteoporosis in 1999, and three of them had an osteoporotic fracture between 1999 and 2011, showing an increased fracture risk compared to NF1 patients without osteoporosis. BMD of 19 patients was remeasured in 2011, and four patients who had osteopenia in 1999 had osteoporosis in 2011. The decrease in BMD was not explained by changes in smoking habits, physical activity, sunlight exposure, body mass index, or laboratory parameters, even though secondary hyperparathyroidism was common. Osteoporosis was found in 2011 in patients aged 37 years or older, both men and women. The results showed that NF1-related osteopenia often progresses to osteoporosis since BMD decreases with aging even in young patients. Even though our sample size was 19 patients, we recommend follow-up of NF1 patients with osteopenia and consideration of prophylactic measures to prevent osteoporosis and associated fracture risk. PMID:23108390

  6. Clinical Experience With Radiation Therapy in the Management of Neurofibromatosis-Associated Central Nervous System Tumors

    SciTech Connect

    Wentworth, Stacy; Pinn, Melva; Bourland, J. Daniel; Guzman, Allan F. de; Ekstrand, Kenneth; Ellis, Thomas L.; Glazier, Steven S.; McMullen, Kevin P.; Munley, Michael; Stieber, Volker W.; Tatter, Stephen B.; Shaw, Edward G.

    2009-01-01

    Purpose: Patients with neurofibromatosis (NF) develop tumors of the central nervous system (CNS). Radiation therapy (RT) is used to treat these lesions. To better define the efficacy of RT in these patients, we reviewed our 20-year experience. Methods and Materials: Eighteen patients with NF with CNS tumors were treated from 1986 to 2007. Median follow-up was 48 months. Progression was defined as growth or recurrence of an irradiated tumor on serial imaging. Progression-free survival (PFS) was measured from the date of RT completion to the date of last follow-up imaging study. Actuarial rates of overall survival (OS) and PFS were calculated according to the Kaplan-Meier method. Results: Eighty-two tumors in 18 patients were irradiated, with an average of five tumors/patient. Median age at treatment was 25 years (range, 4.3-64 years). Tumor types included acoustic neuroma (16%), ependymoma (6%), low-grade glioma (11%), meningioma (60%), and schwanomma/neurofibroma (7%). The most common indication for treatment was growth on serial imaging. Most patients (67%) received stereotactic radiosurgery (median dose, 1,200 cGy; range, 1,000-2,400 cGy). The OS rate at 5 years was 94%. Five-year PFS rates were 75% (acoustic neuroma), 100% (ependymoma), 75% (low-grade glioma), 86% (meningioma), and 100% (schwanomma/neurofibroma). Thirteen acoustic neuromas had a local control rate of 94% with a 50% hearing preservation rate. Conclusions: RT provided local control, OS, and PFS rates similar to or better than published data for tumors in non-NF patients. Radiation therapy should be considered in NF patients with imaging progression of CNS tumors.

  7. Unusual Case of Angle Closure Glaucoma in a Patient with Neurofibromatosis Type 1

    PubMed Central

    Mantelli, Flavio; Abdolrahimzadeh, Solmaz; Mannino, Giuseppe; Lambiase, Alessandro

    2014-01-01

    We report the case of a 29-year-old female patient who presented with an acute onset of anisocoria, blurred vision, nausea and severe left-sided headache. There was no history of trauma, drug abuse, or instillation of topical mydriatic compounds. The ocular history was negative for similar events. On presentation, her visual acuity was 0.2 in the left and 1.0 in the right eye with a +2.5 dpt sph. correction. Slit-lamp examination demonstrated a shallow anterior chamber as well as the presence of iris nodules in both eyes. These nodules were identified as Lisch nodules as the patient referred to the previous diagnosis as being neurofibromatosis type 1. A third nerve palsy was considered, but a brain MRI showed normal results. Her ocular motility was normal, but the left pupil was mydriatic and poorly reacting to light, with an associated raised intraocular pressure (IOP) of 38 mm Hg. An examination of the fellow eye was normal, with the IOP measuring 18 mm Hg. Gonioscopy of the right eye showed a narrow angle. On further anamnestic investigation, the patient revealed that the pain and the blurred vision begun in the morning while she was helping her mother in the garden. Finally, after showing the patient a picture of Datura flowers, which she recognized immediately, we made the unusual diagnosis of angle closure glaucoma by Datura, a well-known toxic plant with mydriatic properties. The patient was successfully treated with systemic acetazolamide and topical pilocarpine. PMID:25762928

  8. Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients

    PubMed Central

    Zimerman, Máximo; Wessel, Maximilian J.; Timmermann, Jan E.; Granström, Sofia; Gerloff, Christian; Mautner, Victor F.; Hummel, Friedhelm C.

    2015-01-01

    Background Cognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition? Methods We used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls. Findings NF1 patients experienced substantial decline in motor skill acquisition (F = 9.2, p = 0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T = 2.8, p = 0.014), especially evident after the early acquisition phase. Interpretations Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as

  9. Auditory rehabilitation of patients with neurofibromatosis Type 2 by using cochlear implants

    PubMed Central

    Roehm, Pamela C.; St. Clair, Jon Mallen; Jethanamest, Daniel; Golfinos, John G.; Shapiro, William; Waltzman, Susan; Roland, J. Thomas

    2013-01-01

    Object The aim of this study was to determine whether patients with neurofibromatosis Type 2 (NF2) who have intact ipsilateral cochlear nerves can have open-set speech discrimination following cochlear implantation. Methods Records of 7 patients with documented NF2 were reviewed to determine speech discrimination outcomes following cochlear implantation. Outcomes were measured using consonant-nucleus-consonant words and phonemes; Hearing in Noise Test sentences in quiet; and City University of New York sentences in quiet and in noise. Results Preoperatively, none of the patients had open-set speech discrimination. Five of the 7 patients had previously undergone excision of ipsilateral vestibular schwannoma (VS). One of the patients who received a cochlear implant had received radiation therapy for ipsilateral VS, and another was undergoing observation for a small ipsilateral VS. Following cochlear implantation, 4 of 7 patients with NF2 had open-set speech discrimination following cochlear implantation during extended follow-up (15–120 months). Two of the 3 patients without open-set speech understanding had a prolonged period between ipsilateral VS resection and cochlear implantation (120 and 132 months), and had cochlear ossification at the time of implantation. The other patient without open-set speech understanding had good contralateral hearing at the time of cochlear implantation. Despite these findings, 6 of the 7 patients were daily users of their cochlear implants, and the seventh is an occasional user, indicating that all of the patients subjectively gained some benefit from their implants. Conclusions Cochlear implantation can provide long-term auditory rehabilitation, with open-set speech discrimination for patients with NF2 who have intact ipsilateral cochlear nerves. Factors that can affect implant performance include the following: 1) a prolonged time between VS resection and implantation; and 2) cochlear ossification. PMID:21761973

  10. Effector T cell subclasses associate with tumor burden in neurofibromatosis type 1 patients.

    PubMed

    Farschtschi, Said; Park, Su-Jin; Sawitzki, Birgit; Oh, Su-Jun; Kluwe, Lan; Mautner, Victor F; Kurtz, Andreas

    2016-09-01

    Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome caused by mutations of the NF1 gene and resulting dysregulation of the Ras-pathway. In addition to peripheral nerve tumors, affected tissues include the musculoskeletal and cardiovascular system. The immune system has recently been suggested as a possible modulator NF1-related phenotypes. Therefore, we determined the immune phenotype in NF1 patients and investigated its relationship with the phenotypic severity of NF1-related tumor manifestations. We quantified global leukocytes and lymphocyte subpopulations of peripheral blood from 37 NF1 patients and 21 healthy controls by flow cytometry. To associate immune phenotype with tumor phenotype, all NF1 patients underwent whole-body magnetic resonance imaging and total internal tumor volume was calculated. The immunophenotypes were compared among four NF1 groups with different total internal tumor burdens and between NF1 patients and non-NF1 subjects. We found that NF1 patients show a generalized lymphopenia. Closer analysis revealed that the CD8(+)/CD27(-) and CD8(+)/CD57(+) effector T cell fractions strongly increase in NF1 patients with low tumor load and decrease to levels below control in patients with high tumor load. Moreover, increased production of IL2, IFN-γ and TNF-α was found in T cells of NF1 patients upon phorbol-12-myristate acetate (PMA) stimulation compared to healthy controls. The data indicate that decreasing CD8(+)/CD57(+) and CD27(-) T cell fractions correspond to increasing tumor load in NF1 patients, potentially making these populations useful marker for internal tumor burden. PMID:27448806

  11. Long-term visual outcomes of optic pathway gliomas in pediatric patients without neurofibromatosis type 1.

    PubMed

    Wan, Michael J; Ullrich, Nicole J; Manley, Peter E; Kieran, Mark W; Goumnerova, Liliana C; Heidary, Gena

    2016-08-01

    Sporadic optic pathway gliomas (OPGs) have been reported to cause more vision loss than OPGs associated with neurofibromatosis type-1, but long-term visual outcome data are limited. The purpose of this study was to report the visual outcomes of a cohort of pediatric patients with sporadic OPGs. This was a retrospective, cohort study at a tertiary care pediatric hospital and cancer institute. The study included all patients with sporadic OPGs evaluated from 1990 to 2014. The primary outcome was visual acuity at final follow-up. Secondary outcomes were risk factors for a poor visual outcome and the rate of progression. There were 59 pediatric patients included in the study. Median age at presentation was 2.5 years old and median follow-up was 5.2 years. In the worse eye at final follow-up, 16 patients (27 %) were 20/30 or better, 9 patients (15 %) were between 20/40 and 20/80, and 34 patients (58 %) were 20/100 or worse. In the better eye at final follow-up, 33 patients (56 %) were 20/30 or better, 11 patients (19 %) were between 20/40 and 20/80, and 15 patients (25 %) were 20/100 or worse. Risk factors for a poor visual outcome included younger age at presentation, optic nerve pallor, and tumor extent. Of the 54 patients (92 %) who received treatment, 40 (74 %) experienced disease progression during or after treatment. A majority of pediatric patients with sporadic OPGs had significant long-term visual impairment. In spite of treatment, tumor progression is common. Serial ophthalmic examinations with quantitative vision measurements are essential in the management of sporadic OPGs. PMID:27311725

  12. Prevalence of Autism Spectrum Disorder symptoms in children with neurofibromatosis type 1.

    PubMed

    Plasschaert, Ellen; Descheemaeker, Mie-Jef; Van Eylen, Lien; Noens, Ilse; Steyaert, Jean; Legius, Eric

    2015-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition. While considerable work has focused on cognitive functioning, several research groups also observed difficulties in social functioning as a prominent feature of NF1. These problems and the possible link between NF1 and Autism Spectrum Disorder (ASD) have become increasingly important in recent NF1 literature. The aim of the current study was to assess ASD characteristics in a hospital-based NF1 pediatric population (n = 82) using the standardized Children Social Behavior Questionnaire (CSBQ) and Social Responsiveness Scale (SRS) to account for the prevalence, severity, and nature of social problems. In a parallel study, comprehensive ASD assessment was performed in a subgroup of NF1 children with a strong suspicion of ASD (n = 31). Results indicate that NF1 children have more social problems than typical controls, more frequently reported above 8 years. The SRS shows that 63% is at risk of ASD symptoms. According to item analyses, most problems were observed on items measuring orientation in, understanding of and being tuned onto a social situation (CSBQ) and social cognition and communication (SRS). In the parallel study, 27 NF1 children were diagnosed with ASD. These children have a distinct phenotype compared to a heterogeneous ASD group, with pronounced social-communicative impairments and fewer restrictive/repetitive behaviors. This study provides a better understanding of social problems in NF1 and the phenotypical overlap with ASD symptomatology. Despite their willingness to engage with others, NF1 children with or without ASD encounter various difficulties in their social-communicative life. PMID:25388972

  13. Deletions spanning the neurofibromatosis 1 gene: identification and phenotype of five patients.

    PubMed Central

    Kayes, L. M.; Burke, W.; Riccardi, V. M.; Bennett, R.; Ehrlich, P.; Rubenstein, A.; Stephens, K.

    1994-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by marked variation in clinical severity. To investigate the contribution to variability by genes either contiguous to or contained within the NF1 gene, we screened six NF1 patients with mild facial dysmorphology, mental retardation, and/or learning disabilities, for DNA rearrangement of the NF1 region. Five of the six patients had NF1 gene deletions on the basis of quantitative densitometry, locus hemizygosity, and analysis of somatic cell hybrid lines. Analyses of hybrid lines carrying each of the patient's chromosomes 17, with 15 regional DNA markers, demonstrated that each of the five patients carried a deletion > 700 kb in size. Minimally, each of the deletions involved the entire 350-kb NF1 gene; the three genes--EVI2A, EVI2B, and OMG--that are contained within an NF1 intron; and considerable flanking DNA. For four of the patients, the deletions mapped to the same interval; the deletion in the fifth patient was larger, extending farther in both directions. The remaining NF1 allele presumably produced functional neurofibromin; no gene rearrangements were detected, and RNA-PCR demonstrated that it was transcribed. These data provide compelling evidence that the NF1 disorder results from haploid insufficiency of neurofibromin. Of the three documented de novo deletion cases, two involved the paternal NF1 allele and one the maternal allele. The parental origin of the single remaining expressed NF1 allele had no dramatic effect on patient phenotype. The deletion patients exhibited a variable number of physical anomalies that were not correlated with the extent of their deletion. All five patients with deletions were remarkable for exhibiting a large number of neurofibromas for their age, suggesting that deletion of an unknown gene in the NF1 region may affect tumor initiation or development. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8116612

  14. Multidimensional Ultrasound and Computed Tomography Imaging Support in Bleeding Plexiform Neurofibromatosis of the Scalp: A Case Report and Literature Review

    PubMed Central

    Wortsman, Ximena; Lobos, Nelson; De la Parra, Rodrigo; Carreno, Laura

    2015-01-01

    Active bleeding in plexiform neurofibromatosis can be a life-threatening complication in neurofibromatosis type 1 (NF1). The prompt imaging support of 2D-3D ultrasound (US) and computed tomography (CT) during the active hemorrhage phase of cutaneous neurofibromas has not been previously reported. We report a case with NF1 who experienced a sudden swelling in the parieto-temporal region that corresponded to a massive and active hemorrhage within a plexiform neurofibroma. The US and CT imaging characteristics of this bleeding tumor are shown. Active hemorrhage in a plexiform neurofibroma of the scalp appeared in US as a heterogeneous hypodermal mass. CT demonstrated a fully hyperdense soft tissue mass. These characteristics differ from the non-complicated or old hemorrhagic imaging appearances of scalp plexiform neurofibromas and encourage prompt surgical treatment. This case report demonstrates the usefulness of imaging support in the early diagnosis of this hemorrhagic complication of NF1 in the scalp and also stimulates multispecialty management. PMID:26288436

  15. The Use of Next-Generation Sequencing in Molecular Diagnosis of Neurofibromatosis Type 1: A Validation Study

    PubMed Central

    Maruoka, Ryo; Takenouchi, Toshiki; Torii, Chiharu; Shimizu, Atsushi; Misu, Kumiko; Higasa, Koichiro; Matsuda, Fumihiko; Ota, Arihito; Tanito, Katsumi; Kuramochi, Akira; Arima, Yoshimi; Otsuka, Fujio; Yoshida, Yuichi; Moriyama, Keiji; Niimura, Michihito; Saya, Hideyuki

    2014-01-01

    Aims: We assessed the validity of a next-generation sequencing protocol using in-solution hybridization-based enrichment to identify NF1 mutations for the diagnosis of 86 patients with a prototypic genetic syndrome, neurofibromatosis type 1. In addition, other causative genes for classic genetic syndromes were set as the target genes for coverage analysis. Results: The protocol identified 30 nonsense, 19 frameshift, and 8 splice-site mutations, together with 10 nucleotide substitutions that were previously reported to be pathogenic. In the remaining 19 samples, 10 had single-exon or multiple-exon deletions detected by a multiplex ligation-dependent probe amplification method and 3 had missense mutations that were not observed in the normal Japanese SNP database and were predicted to be pathogenic. Coverage analysis of the genes other than the NF1 gene included on the same diagnostic panel indicated that the mean coverage was 115-fold, a sufficient depth for mutation detection. Conclusions: The overall mutation detection rate using the currently reported method in 86 patients who met the clinical diagnostic criteria was 92.1% (70/76) when 10 patients with large deletions were excluded. The results validate the clinical utility of this next-generation sequencing-based method for the diagnosis of neurofibromatosis type 1. Comparable detection rates can be expected for other genetic syndromes, based on the results of the coverage analysis. PMID:25325900

  16. Association of segmental neurofibromatosis 1 and oculo-auriculo-vertebral spectrum in a 24-year-old female.

    PubMed

    Castori, Marco; Majore, Silvia; Romanelli, Francesco; Didona, Biagio; Grammatico, Paola; Zambruno, Giovanna

    2008-01-01

    Segmental neurofibromatosis 1 (SNF1) is a rare genodermatosis caused by somatic mutations in the NF1 gene. It consists of localized characteristic pigmentary lesions (i.e. café-au-lait spots and freckling) and/or neurofibromas intermingled with areas of unaffected skin, often configuring specific mosaic patterns. Oculo-auriculo-vertebral spectrum (OAVS) is a developmental field defect primarily affecting the 1st and 2nd branchial arch derivatives. This condition recognizes a wide range of environmental and genetic causes, including postzygotic mutations. We report on a 24-year-old female presenting with a constellation of features fitting both with SNF1 and OAVS. Neurofibromatosis 1 pigmentary lesions are confined to the left arm and adjacent trunk skin surface with sharp midline demarcation. OAVS characteristic craniofacial anomalies, including neurosensorial hearing loss, hemimandibular and tongue underdevelopment, are homolateral to the SNF1 features. Additional findings, such as prearicular tags and multiple costo-vertebral segmentation defects, mainly involving the cervical and upper thoracic metameres, support the diagnosis of OAVS. To our knowledge, this is the first published patient who presents with an association of SNF1 and OAVS. The spatial relationship between craniofacial and skin pigmentary anomalies has prompted us to speculate about the possible underlying pathogenetic mechanism (s). PMID:18086584

  17. Bilateral and Symmetrical Anteromedial Bowing of the Lower Limbs in a Patient with Neurofibromatosis Type-I

    PubMed Central

    Klaushofer, Klaus; Grill, Franz; Ganger, Rudolf

    2015-01-01

    An 8-year-old girl was referred to our department because of generalized bowing of long bones (radii, ulnae, and femora) and significant bilateral and symmetrical posteromedial bowing of the tibiae and fibulae. The femora were laterally bowed whereas the tibiae and fibulae showed posteromedial bowing between the middle and distal thirds of the tibia with posterior cortical thickening effectively causing the development of bilateral congenital anterolateral bowing of the tibiae and fibulae. We referred to closing-wedge osteotomy of the left tibia along with fibular osteotomy in order to realign the deformity. Due to the delayed appearance of skin stigmata in her early life, the diagnosis of neurofibromatosis was ruled out. At the age of 9 years, café-au-lait spots and axillary freckling were apparent. Genetic tests confirmed von Recklinghausen disease (neurofibromatosis type-I (NF1)) (gene has been localised to 17q22). Interestingly, bilateral and symmetrical anteromedial bowing of the tibiae and fibulae has not been described in patients with NF-I. PMID:25815222

  18. Biome depletion in conjunction with evolutionary mismatches could play a role in the etiology of neurofibromatosis 1.

    PubMed

    Beales, Donna L

    2015-04-01

    Neurofibromatosis 1 (NF1) arises de novo in a striking 30-50% of cases, pointing toward an environmental etiology, though none has been clearly identified. The Biome Depletion Theory posits that the absence of mutualistic and commensal organisms within the human body coupled with modern lifestyle alterations may have profoundly deleterious effects, inclusive of immunologic derangement that is thought to result in allergy, atopy, and numerous autoimmune diseases. Biome depletion has been implicated as a factor in the etiology of both multiple sclerosis and autism spectrum disorders; biome reconstitution, i.e. replenishment of the biome with certain keynote species, is being used in the treatment of these and other autoimmune states. Neurofibromatosis 1 has been associated with allergy, various autoimmune states, multiple sclerosis, and autism. Recent research has posited that NF1, multiple sclerosis and autism may all arise from disturbances in the neural crest during gestation. This paper hypothesizes that there is indirect evidence that a highly inflammatory uterine state may precipitate epigenetic changes in vulnerable NF-related genes in the course of fetal development. The etiology of NF1 may lie in the absence of immunomodulation by commensal and mutualistic species once ubiquitously present in the environment, as well as through adoption of a modern lifestyle that contributes to chronic inflammation. Replenishment of helminths and other missing organisms to the human biome prior to conception as well as addressing nutritional status, psychological stress, and environmental exposures may prevent the development of NF1. PMID:25665856

  19. Neurofibromatosis Type 1 and the “Elephant Man's” Disease: The Confusion Persists: An Ethnographic Study

    PubMed Central

    Legendre, Claire-Marie; Charpentier-Côté, Catherine; Drouin, Régen; Bouffard, Chantal

    2011-01-01

    Background During informal interviews in the course of an ethnographic study on intergenerational dialogue between individuals with neurofibromatosis and their parents, many members of Canadian neurofibromatosis associations stated they continue to be told the condition that afflicts them or their children is the “elephant man's” disease. Today, even though well established clinical criteria make it possible to diagnose and differentiate the two diseases, the confusion between NF1 and the disease of Joseph Merrick, the “elephant man”, persists in both media representations and those of physicians. The objective of this article is to document the persistence of this confusion, to identify the factors that contribute to it, and to identify its impact on the well being of individuals with NF1. Methodology Preliminary stages of an ethnographic study. Principal Findings Our findings show that some reference sources, past medical training, and print and online news media have all contributed to the persistence of the association between NF1 and the disease of Joseph Merrick, the “elephant man”. Our observations suggest that this misconception can have negative medical, social, and psychological impacts on patients and their families and thus increase the burden of the disease. Conclusions Changes of attitude regarding medical teaching and the media could lead to definitively clearing up the confusion. PMID:21347399

  20. Gynecomastia in type-1 neurofibromatosis with features of pseudoangiomatous stromal hyperplasia with giant cells. Report of two cases.

    PubMed

    Damiani, S; Eusebi, V

    2001-05-01

    We describe the histological finding in two cases of gynecomastia in patients with von Recklinghausen's disease. The histological and immunohistochemical features of the two cases were reviewed and compared with those of five cases of gynecomastia in men without clinical evidence of neurofibromatosis. In both patients bearing von Recklinghausen's disease, the breast stroma showed features consistent with pseudoangiomatous stromal hyperplasia (PASH). It was characterised by anastomosing empty spaces lined by spindle and multinucleated giant cells which were positive with CD34 and anti-vimentin antisera and negative with anti-FVIII and CD31 antisera. In two of five of the control cases without neurofibromatosis, the mammary stroma showed focal areas with features of PASH, but no multinucleated giant cells were present in any case. PASH with giant cells should be recognised as a feature of gynecomastia in von Recklinghausen's disease. The presence of multinucleated giant cells is very unusual and, although more cases have to be studied, these cells seem to be a feature of PASH occurring in patients with von Recklinghausen's disease. PMID:11407482

  1. Diagnosis, Management, and New Therapeutic Options in Childhood Neurofibromatosis Type 2 and Related Forms.

    PubMed

    Ruggieri, Martino; Praticò, Andrea Domenico; Evans, Dafydd Gareth

    2015-12-01

    Neurofibromatosis type 2 (NF2; MIM # 101000) is an autosomal dominant disorder characterized by the development of vestibular schwannomas (VSs); schwannomas of other cranial, spinal, and cutaneous nerves; cranial and spinal meningiomas or other central nervous system tumors (eg, ependymomas and astrocytomas) or both. Additional features include eye (eg, early onset cataracts, optic nerve sheath meningiomas, retinal or pigment epithelial hamartomas or both, and epithelial retinal membranes) and skin abnormalities (eg, flat dermal [NF2 plaques] or spherical subcutaneous nodular schwannomas or both, and few, atypical café-au-lait spots). Clinically, children with NF2 fall into 2 main groups: (1) congenital NF2 with bilateral VSs detected as early as the first days to months of life, which can be stable or asymptomatic for 1-2 decades and suddenly progress; and (2) severe prepubertal (Wishart type) NF2 with multiple (and rapidly progressive) central nervous system tumors other-than-VS, which usually presents first, years before VSs, both associated with more marked skin and eye involvement (vs the classical mild adult [Gardner type] NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature). Individuals manifesting unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localized to a part of the peripheral nervous system have mosaic or segmental NF2; individuals developing multiple nonVS, nonintradermal cranial, spinal, and peripheral schwannomas (histologically proven) have schwannomatosis (SWNTS). NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin proteins; mosaic or segmental NF2 is because of mosaic phenomena for the NF2 gene, whereas SWNTS is caused by germline and possibly mosaic mutations either in the SMARCB1 gene (SWNTS1; MIM # 162091) or the LZTR1 gene (SWNTS2; MIM # 615670), both falling

  2. Bone mineral metabolism in patients with neurofibromatosis type 1 (von Recklingausen disease).

    PubMed

    Petramala, Luigi; Giustini, Sandra; Zinnamosca, Laura; Marinelli, Cristiano; Colangelo, Luciano; Cilenti, Giuseppina; Formicuccia, Maria Chiara; D'Erasmo, Emilio; Calvieri, Stefano; Letizia, Claudio

    2012-05-01

    The neurofibromatosis type 1 (NF1) is characterized by specific cutaneous features (neurofibromas, "café-au-lait" spots of the skin) and alterations of several tissue (nervous, vascular) and bone deformities, such as scoliosis, congenital pseudoarthrosis and bone dysplasia of tibia. Moreover, several studies have shown systemic involvement of bone tissue in NF1 patients, leading to reduced bone mass. The aim of our study was to evaluate some bone mineral metabolism parameters before and after calcium and vitamin D supplementation in NF1 patients. We evaluated in 70 NF1 consecutive patients the mineral metabolism and bone mineral density compared with 40 normal subjects. We showed bone alterations in 35% of patients and the increase of bone formation markers, such as bone isoenzyme of alkaline phosphatase (41.2 ± 15.5 vs. 25.6 ± 8.7 UI; P < 0.05, respectively) and osteocalcin (18.1 ± 5.6 vs. 7.6 ± 1.9 ng/ml; P < 0.05) and reduction of circulating levels of (25OH)-vitamin D (21.8 ± 12.3 ng/ml) with an high percentage of hypovitaminosys D (>60%). Moreover, we revealed a significant reduction of bone mass density at spine (L1-L4) (0.935 ± 0.13 vs. 1.110 ± 0.17 g/cm(2); P < 0.001) and femoral neck side (0.765 ± 0.09 vs. 0.839 ± 0.12 g/cm(2); P < 0.02), with high prevalence of osteopenia (44%) and osteoporosis (18%). After 12 months of calcium (1,200 mg/die) and cholecalciferol (800 UI/die) supplementation, we found a significant increase of (25) OH-vitamin D level (21.8 ± 12.3 vs. 35 ± 13 ng/ml; P < 0.01), without changes in bone mass density. In conclusion, NF1 patients may present a mineral bone involvement, with vitamin D deficiency; calcium and vitamin D supplementation is necessary to restore these bone mineral metabolic alterations. PMID:22120694

  3. Multifocal Head and Neck Neurofibromas with Osseous Abnormalities and Muscular Hypoplasia in a Child with Neurofibromatosis: Type I.

    PubMed

    Rath, Rachna; Kaur, Sheetal; Baig, Shadab Ali; Pati, Punyashlok; Sahoo, Sonalisa

    2016-01-01

    Neurofibromatosis type 1 (NF1) is a clinically and genetically distinct disease involving both neuroectodermal and mesenchymal derivatives. Orofacial manifestations in NF1 have been documented before but occurrence of multifocal intraosseous (IO) and extraosseous (EO) neurofibromas is rare. The present case highlights the importance of imaging findings in the diagnosis and management of multifocal jaw, infratemporal, and parotid neurofibromas with muscular hypoplasia in an eight-year-old girl with NF1. Apart from orthopantomograms (OPG), three-dimensional computed tomography (3D CT) and cross-sectional reformations were valuable in delineating the extent of the lytic lesion and identifying additional bony deformities of the mandible. Magnetic resonance imaging (MRI) helped to identify the solid nature of the lesion and true extent of the soft tissue mass. PMID:27382495

  4. Preservation of auditory and vestibular function after surgical removal of bilateral vestibular schwannomas in a patient with neurofibromatosis type 2

    NASA Technical Reports Server (NTRS)

    Black, F. O.; Brackmann, D. E.; Hitselberger, W. E.; Purdy, J.

    1995-01-01

    The outcome of acoustic neuroma (vestibular schwannoma) surgery continues to improve rapidly. Advances can be attributed to several fields, but the most important contributions have arisen from the identification of the genes responsible for the dominant inheritance of neurofibromatosis types 1 (NF1) and 2 (NF2) and the development of magnetic resonance imaging with gadolinium enhancement for the early anatomic confirmation of the pathognomonic, bilateral vestibular schwannomas in NF2. These advances enable early diagnosis and treatment when the tumors are small in virtually all subjects at risk for NF2. The authors suggest that advising young NF2 patients to wait until complications develop, especially hearing loss, before diagnosing and operating for bilateral eighth nerve schwannomas may not always be in the best interest of the patient. To the authors' knowledge, this is the first reported case of preservation of both auditory and vestibular function in a patient after bilateral vestibular schwannoma excision.

  5. Multifocal Head and Neck Neurofibromas with Osseous Abnormalities and Muscular Hypoplasia in a Child with Neurofibromatosis: Type I

    PubMed Central

    Kaur, Sheetal; Baig, Shadab Ali; Pati, Punyashlok; Sahoo, Sonalisa

    2016-01-01

    Neurofibromatosis type 1 (NF1) is a clinically and genetically distinct disease involving both neuroectodermal and mesenchymal derivatives. Orofacial manifestations in NF1 have been documented before but occurrence of multifocal intraosseous (IO) and extraosseous (EO) neurofibromas is rare. The present case highlights the importance of imaging findings in the diagnosis and management of multifocal jaw, infratemporal, and parotid neurofibromas with muscular hypoplasia in an eight-year-old girl with NF1. Apart from orthopantomograms (OPG), three-dimensional computed tomography (3D CT) and cross-sectional reformations were valuable in delineating the extent of the lytic lesion and identifying additional bony deformities of the mandible. Magnetic resonance imaging (MRI) helped to identify the solid nature of the lesion and true extent of the soft tissue mass. PMID:27382495

  6. Intracranial malignant triton tumor in a patient with neurofibromatosis type 1: case report and review of the literature.

    PubMed

    Smith, Ross E; Kebriaei, Meysam A; Gard, Andrew P; McComb, Rodney D; Bridge, Julia A; Lennarson, Peter J

    2014-04-01

    We report the fourth case of an intracranial malignant triton tumor not associated with a cranial nerve in a 26-year-old male with a clinical history of neurofibromatosis type 1. The patient was found unresponsive and displayed confusion, lethargy, hyperreflexia, and dysconjugate eye movements upon arrival at the emergency room. MRI revealed a large bifrontal mass. Biopsy demonstrated a high-grade spindle cell tumor with focal areas of rhabdomyoblasts that stained positive for desmin, myogenin, and muscle-specific actin. Electron microscopy showed skeletal muscle differentiation. Based on the clinical history of NF1 and the pathologic results, a diagnosis of malignant triton tumor was made. The differential diagnosis, immunohistochemistry, molecular genetics, and treatment of malignant triton tumor are reviewed. PMID:23633163

  7. Seizure, spinal schwannoma, peripheral neuropathy and pulmonary stenosis - A rare combination in a patient of Neurofibromatosis 1.

    PubMed

    Ray, Avas Chandra; Karjyi, Nabendu; Roy, Achintya Narayan; Dutta, Arup Kumar; Biswas, Atanu

    2012-01-01

    Neurofibromatosis 1 (NF1) is the most common neurocutaneous syndrome. It is estimated to occur in approximately 1 out of every 3300 infants. The manifestations of this condition are diverse and can arise from almost any system in the body. The neurofibroma is the hallmark lesion of NF1 that develops from peripheral nerves. Here, we are reporting an 18-year-old girl with NF1. Clinical diagnosis was made according to the diagnostic criteria established by the National Institutes of Health Consensus Development Conference in 1987. She presented with quadriparesis due to dumbbell-shaped spinal schwannoma in the cervical region. She had history of recurrent seizures in the past, with poor scholastic performance. There were clinical and electrophysiological features of peripheral neuropathy and clinical and echocardiographical features of pulmonary stenosis. These are uncommon features of NF 1. The presence of all these features in a single patient makes it a unique case. PMID:22412275

  8. Endovascular Internal Trapping of Ruptured Occipital Artery Pseudoaneurysm Associated with Occipital-Internal Jugular Vein Fistula in Neurofibromatosis Type 1.

    PubMed

    Imahori, Taichiro; Fujita, Atsushi; Hosoda, Kohkichi; Kohmura, Eiji

    2016-05-01

    Spontaneous cervical extradural pseudoaneurysms or arteriovenous fistulas (AVFs) are rare vascular diseases. We report a case of ruptured occipital artery (OA) pseudoaneurysm associated with occipital-internal jugular vein (IJV) fistula in neurofibromatosis type 1. Endovascular internal trapping via the OA was attempted; however, the distal entry of the OA could not be accessed because of the high shunt flow and tortuosity of the OA. The distal part of the OA was obliterated with coil via a transvenous approach through the IJV and pseudoaneurysm. The proximal entry of the OA was obliterated with coil and glue under proximal flow control with a balloon, and the fistula was successfully obliterated without placement of coils in the pseudoaneurysm. When ordinary internal trapping via a transarterial approach is not possible, the transvenous approach should be considered as an alternative for AVF associated with an aneurysmal component. PMID:26971039

  9. Combined presence of multiple gastrointestinal stromal tumors along with duodenal submucosal somatostatinoma in a patient with neurofibromatosis type 1.

    PubMed

    Kumar, Tarun; Gupta, Brijnandan; Das, Prasenjit; Jain, Deepali; Jain, Hemant Ashok; Madhusudhan, Kumble S; Dash, Nihar Ranjan; Gupta, Siddhartha Datta

    2016-01-01

    Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, with increased risk of developing benign and malignant tumors of the gastrointestinal tract (GIT). However, the synchronous presence of multiple GIT stromal tumors and duodenal submucosal somatostatinoma, like in this 50-year-old female NF-1 patient, is very rare. She presented with hematemesis, malena, along with multiple neurofibromas all over the body. Thorough radiological and peroperative work-up revealed multiple ulcerated submucosal and serosal nodules in the proximal small intestine. Histological work-up revealed diagnosis of a duodenal submucosal somatostatinoma with multifocal serosal gastrointestinal stromal tumors. This case is being reported to highlight the rare coincidence of multiple GIT tumors in an NF-1 patient. PMID:27510677

  10. Solitary Encapsulated Neurofibroma Not Associated with Neurofibromatosis-1 Affecting Tongue in a 73-Year-Old Female.

    PubMed

    Mahmud, Sk Abdul; Shah, Neha; Chattaraj, Moumita; Gayen, Swagata

    2016-01-01

    Neurofibromas are benign tumors of nerve cell origin arising due to proliferation of Schwann cells and fibroblasts. They are usually asymptomatic and hence remain undiagnosed. They are commonly found on the skin and intraorally tongue is the most common site for their occurrence. Here, we present a unique case of solitary encapsulated neurofibroma in the oral cavity without any clinical manifestations or family history of Neurofibromatosis type 1 in a 73-year-old female patient who presented with a painless swelling on the tongue. The histopathologic findings closely mimicked benign fibrous histiocytoma. In our case, definitive diagnosis of neurofibroma was made based on clinical findings, family history, and histopathological and immunohistochemical evaluation. Through this case report we want to emphasize the role of biopsy and immunohistochemistry in arriving at a confirmatory diagnosis. The patient was treated by surgical excision and showed no signs of recurrence over a follow-up period of 12 months. PMID:27525129

  11. Charcot-Marie-Tooth syndrome and neurofibromatosis type 1 with multiple neurofibromas of the entire spinal nerve roots

    PubMed Central

    Onu, David O; Hunn, Andrew W; Peters-Willke, Jens

    2013-01-01

    The coexistence of polyneuropathy which has the definite clinical and electromyographical findings consistent with Charcot-Marie-Tooth (CMT) syndrome and neurofibromatosis type 1 (NF1) has infrequently been reported. We describe a patient with both CMT and NF1, who had multiple neurofibromas involving the entire spinal neural axis. In addition, he had multiple neurofibromas distributed within the ileopsoas and gluteus muscles and subcutaneous tissues. These lesions were detected readily by MRI and the patient underwent successful surgical resection of the largest tumours compressing bilateral C2 nerve roots. To our knowledge, this is the first reported case of CMT syndrome coexisting with NF1 in which multiple neurofibromas involved the entire spinal nerve roots. We discuss the diagnostic and therapeutic challenges, emphasising the role of MRI and electrophysiology in such cases and provide a literature review. PMID:23853192

  12. Charcot-Marie-Tooth syndrome and neurofibromatosis type 1 with multiple neurofibromas of the entire spinal nerve roots.

    PubMed

    Onu, David O; Hunn, Andrew W; Peters-Willke, Jens

    2013-01-01

    The coexistence of polyneuropathy which has the definite clinical and electromyographical findings consistent with Charcot-Marie-Tooth (CMT) syndrome and neurofibromatosis type 1 (NF1) has infrequently been reported. We describe a patient with both CMT and NF1, who had multiple neurofibromas involving the entire spinal neural axis. In addition, he had multiple neurofibromas distributed within the ileopsoas and gluteus muscles and subcutaneous tissues. These lesions were detected readily by MRI and the patient underwent successful surgical resection of the largest tumours compressing bilateral C2 nerve roots. To our knowledge, this is the first reported case of CMT syndrome coexisting with NF1 in which multiple neurofibromas involved the entire spinal nerve roots. We discuss the diagnostic and therapeutic challenges, emphasising the role of MRI and electrophysiology in such cases and provide a literature review. PMID:23853192

  13. Solitary Encapsulated Neurofibroma Not Associated with Neurofibromatosis-1 Affecting Tongue in a 73-Year-Old Female

    PubMed Central

    Mahmud, Sk. Abdul; Chattaraj, Moumita; Gayen, Swagata

    2016-01-01

    Neurofibromas are benign tumors of nerve cell origin arising due to proliferation of Schwann cells and fibroblasts. They are usually asymptomatic and hence remain undiagnosed. They are commonly found on the skin and intraorally tongue is the most common site for their occurrence. Here, we present a unique case of solitary encapsulated neurofibroma in the oral cavity without any clinical manifestations or family history of Neurofibromatosis type 1 in a 73-year-old female patient who presented with a painless swelling on the tongue. The histopathologic findings closely mimicked benign fibrous histiocytoma. In our case, definitive diagnosis of neurofibroma was made based on clinical findings, family history, and histopathological and immunohistochemical evaluation. Through this case report we want to emphasize the role of biopsy and immunohistochemistry in arriving at a confirmatory diagnosis. The patient was treated by surgical excision and showed no signs of recurrence over a follow-up period of 12 months. PMID:27525129

  14. Relationship between whole-body tumor burden, clinical phenotype, and quality of life in patients with neurofibromatosis.

    PubMed

    Merker, Vanessa L; Bredella, Miriam A; Cai, Wenli; Kassarjian, Ara; Harris, Gordon J; Muzikansky, Alona; Nguyen, Rosa; Mautner, Victor F; Plotkin, Scott R

    2014-06-01

    Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis share a predisposition to develop multiple nerve sheath tumors. Previous studies have demonstrated that patients with NF1 and NF2 have reduced quality of life (QOL), but no studies have examined the relationship between whole-body tumor burden and QOL in these patients. We administered a QOL questionnaire (the SF-36) and a visual analog pain scale (VAS) to a previously described cohort of adult neurofibromatosis patients undergoing whole-body MRI. One-sample t-tests were used to compare norm-based SF-36 scores to weighted population means. Spearman correlation coefficients and multiple linear regression analyses controlling for demographic and disease-specific clinical variable were used to relate whole-body tumor volume to QOL scales. Two hundred forty-five patients (142 NF1, 53 NF2, 50 schwannomatosis) completed the study. Subjects showed deficits in selected subscales of the SF-36 compared to adjusted general population means. In bivariate analysis, increased tumor volume was significantly associated with pain in schwannomatosis patients, as measured by the SF-36 bodily pain subscale (rho = -0.287, P = 0.04) and VAS (rho = 0.34, P = 0.02). Regression models for NF2 patients showed a positive relationship between tumor burden and increased pain, as measured by the SF-36 (P = 0.008). Patients with NF1, NF2, and schwannomatosis suffer from reduced QOL, although only pain shows a clear relationship to patient's overall tumor burden. These findings suggest that internal tumor volume is not a primary contributor to QOL and emphasize the need for comprehensive treatment approaches that go beyond tumor-focused therapies such as surgery by including psychosocial interventions. PMID:24664633

  15. Aumento de la supervivencia en hombres con cáncer de próstata metastásico que reciben quimioterapia

    Cancer.gov

    Los hombres con cáncer de próstata metastásico sensible a las hormonas que recibieron el fármaco quimioterapéutico docetaxel al inicio de la terapia hormonal convencional vivieron más tiempo que los pacientes que recibieron solo terapia hormonal, de acuer

  16. Tensión postraumática relacionada con el cáncer (PDQ®)—Versión para profesionales de salud

    Cancer.gov

    Resumen de información revisada por expertos acerca de la tensión postraumática y síntomas relacionados en los pacientes con cáncer, sobrevivientes del cáncer y miembros de la familia. Se discuten la evaluación y tratamiento de estos síntomas.

  17. Can the diagnosis of NF1 be excluded clinically? A lack of pigmentary findings in families with spinal neurofibromatosis demonstrates a limitation of clinical diagnosis

    PubMed Central

    Burkitt Wright, Emma MM; Sach, Emma; Sharif, Saba; Quarrell, Oliver; Carroll, Thomas; Whitehouse, Richard W; Upadhyaya, Meena; Huson, Susan M; Evans, D Gareth R

    2013-01-01

    Background Consensus clinical diagnostic criteria for neurofibromatosis type I (NF1) include café-au-lait macules and skinfold freckling. The former are frequently the earliest manifestation of NF1, and as such are of particular significance when assessing young children at risk of the condition. A phenotype of predominantly spinal neurofibromatosis has been identified in a small minority of families with NF1, often in association with a relative or absolute lack of cutaneous manifestations. An association with splicing and missense mutations has previously been reported for spinal neurofibromatosis, but on the basis of molecular results in only a few families. Method Patients with spinal NF1 were identified through the Manchester nationally commissioned service for complex NF1. Results Five families with spinal NF1 were identified, with a broad spectrum of NF1 mutations, providing further evidence that this phenotype may arise in association with any genre of mutation in this gene. Pigmentary manifestations were absent or very mild in affected individuals. Several further affected individuals, some with extensive spinal root tumours, were ascertained when additional family members were assessed. Conclusions Clinical NF1 consensus criteria cannot be used to exclude the diagnosis of spinal NF1, especially in childhood. This emphasises the importance of molecular confirmation in individuals and families with atypical presentations of NF1. PMID:23812910

  18. Nam Con Son Basin

    SciTech Connect

    Tin, N.T.; Ty, N.D.; Hung, L.T.

    1994-07-01

    The Nam Con Son basin is the largest oil and gas bearing basin in Vietnam, and has a number of producing fields. The history of studies in the basin can be divided into four periods: Pre-1975, 1976-1980, 1981-1989, and 1990-present. A number of oil companies have carried out geological and geophysical studies and conducted drilling activities in the basin. These include ONGC, Enterprise Oil, BP, Shell, Petro-Canada, IPL, Lasmo, etc. Pre-Tertiary formations comprise quartz diorites, granodiorites, and metamorphic rocks of Mesozoic age. Cenozoic rocks include those of the Cau Formation (Oligocene and older), Dua Formation (lower Miocene), Thong-Mang Cau Formation (middle Miocene), Nam Con Son Formation (upper Miocene) and Bien Dong Formation (Pliocene-Quaternary). The basement is composed of pre-Cenozoic formations. Three fault systems are evident in the basin: north-south fault system, northeast-southwest fault system, and east-west fault system. Four tectonic zones can also be distinguished: western differentiated zone, northern differentiated zone, Dua-Natuna high zone, and eastern trough zone.

  19. Leucemia—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento de la leucemia, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados con este tipo de cáncer.

  20. Linfoma—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del linfoma, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados con este tipo de cáncer.

  1. Neuroblastoma—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento y los exámenes de detección del neuroblastoma, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  2. Brain and behaviour phenotyping of a mouse model of neurofibromatosis type-1: an MRI/DTI study on social cognition.

    PubMed

    Petrella, L I; Cai, Y; Sereno, J V; Gonçalves, S I; Silva, A J; Castelo-Branco, M

    2016-09-01

    Neurofibromatosis type-1 (NF1) is a common neurogenetic disorder and an important cause of intellectual disability. Brain-behaviour associations can be examined in vivo using morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to study brain structure. Here, we studied structural and behavioural phenotypes in heterozygous Nf1 mice (Nf1(+/-) ) using T2-weighted imaging MRI and DTI, with a focus on social recognition deficits. We found that Nf1(+/-) mice have larger volumes than wild-type (WT) mice in regions of interest involved in social cognition, the prefrontal cortex (PFC) and the caudate-putamen (CPu). Higher diffusivity was found across a distributed network of cortical and subcortical brain regions, within and beyond these regions. Significant differences were observed for the social recognition test. Most importantly, significant structure-function correlations were identified concerning social recognition performance and PFC volumes in Nf1(+/-) mice. Analyses of spatial learning corroborated the previously known deficits in the mutant mice, as corroborated by platform crossings, training quadrant time and average proximity measures. Moreover, linear discriminant analysis of spatial performance identified 2 separate sub-groups in Nf1(+/-) mice. A significant correlation between quadrant time and CPu volumes was found specifically for the sub-group of Nf1(+/-) mice with lower spatial learning performance, suggesting additional evidence for reorganization of this region. We found strong evidence that social and spatial cognition deficits can be associated with PFC/CPu structural changes and reorganization in NF1. PMID:27283753

  3. YAP Mediates Tumorigenesis in Neurofibromatosis Type 2 by Promoting Cell Survival and Proliferation through a COX-2-EGFR Signaling Axis.

    PubMed

    Guerrant, William; Kota, Smitha; Troutman, Scott; Mandati, Vinay; Fallahi, Mohammad; Stemmer-Rachamimov, Anat; Kissil, Joseph L

    2016-06-15

    The Hippo-YAP pathway has emerged as a major driver of tumorigenesis in many human cancers. YAP is a transcriptional coactivator and while details of YAP regulation are quickly emerging, it remains unknown what downstream targets are critical for the oncogenic functions of YAP. To determine the mechanisms involved and to identify disease-relevant targets, we examined the role of YAP in neurofibromatosis type 2 (NF2) using cell and animal models. We found that YAP function is required for NF2-null Schwann cell survival, proliferation, and tumor growth in vivo Moreover, YAP promotes transcription of several targets including PTGS2, which codes for COX-2, a key enzyme in prostaglandin biosynthesis, and AREG, which codes for the EGFR ligand, amphiregulin. Both AREG and prostaglandin E2 converge to activate signaling through EGFR. Importantly, treatment with the COX-2 inhibitor celecoxib significantly inhibited the growth of NF2-null Schwann cells and tumor growth in a mouse model of NF2. Cancer Res; 76(12); 3507-19. ©2016 AACR. PMID:27216189

  4. Sudden death due to rupture of the right internal carotid artery in neurofibromatosis type 1: A case report.

    PubMed

    Liang, Yue; Tong, Fang; Zhang, Lin; Li, Wenhe; Zhou, Yiwu

    2016-07-01

    Vascular involvement is a well-recognized manifestation of neurofibromatosis type 1 (NF1) which has the potential to be fatal when disrupted. We here present a case of sudden death due to the fatal arterial rupture resulted from infiltration of the neurofibromas. A 42-year-old man who suffered from NF1 presented a 1-h history of sudden onset of pain in his right cervical region. His condition worsened and became unconscious on his way to the emergency room. Despite resuscitation efforts, he died 30min later without regaining consciousness. Autopsy examination showed that a neurofibroma located around the right internal carotid artery, confirmed immunohistochemically with S-100, vimentin and CD34. Furthermore, proliferation of spindle cells positive for S-100 was seen in the wall of right internal carotid artery, which was disrupted and resulted in a hemorrhage. These findings suggest that the artery was disrupted by neurofibromas in the vascular wall, which led to fragility of the vessel. On the basis of these findings, we concluded that the cause of death was asphyxia resulting from airway obstruction compressed by the hematoma due to the arterial rupture. As the locality of the neurofibroma and hemorrhage were closed to the carotid baroreflex, we considered another possible mechanism of his sudden death, which could be cardiac inhibition induced by vagal stimulation. We hope this case will increase recognition of NF-1 vasculopathy when encountering any sudden death in NF1 patients. PMID:27497331

  5. A refined genetic map of the region of chromosome 17 surrounding the von recklinghausen neurofibromatosis (NF1) gene

    PubMed Central

    Diehl, Scott R.; Boehnke, Michael; Erickson, Robert P.; Ploughman, Lynn M.; Seiler, Kathleen A.; Lieberman, Janice L.; Clarke, H. Bush; Bruce, Melissa A.; Schorry, Elizabeth K.; Pericak-Vance, Margaret; O'Connell, Peter; Collins, Francis S.

    1989-01-01

    The von Recklinghausen neurofibromatosis (NF1) gene has been mapped to the pericentromeric region of chromosome 17. We conducted linkage analyses of NF1 by using 10 polymorphic DNA markers from this chromosomal region. We ascertained 20 American Caucasian NF1 families (163 individuals, 98 NF1 affected) in Michigan and Ohio and also studied a large family ascertained primarily in North Carolina. The following markers were used in this study: HHH202, TH17.19, D17Z1, ERBA1, EW203, EW206, EW207, EW301, CRI-L581, and CRI-L946. NF1 did not recombine with either TH17.19 or HHH202 in any of the informative meioses surveyed (maximum lod scores of 17.04 and 7.21, respectively, at a recombination fraction of .00), indicating that these markers map very close to the NF1 gene. We also report evidence of three instances of recombination between NF1 and the centromeric marker D17Z1 (maximum lod score of 13.43 at a recombination fraction of .04), as well as two crossovers between pairs of marker loci. We find no evidence of locus heterogeneity, and our results support the localization of the NF1 gene to proximal chromosome 17q. PMID:2491779

  6. Perfusion single photon emission computed tomography in a mouse model of neurofibromatosis type 1: towards a biomarker of neurologic deficits.

    PubMed

    Apostolova, Ivayla; Niedzielska, Dagmara; Derlin, Thorsten; Koziolek, Eva J; Amthauer, Holger; Salmen, Benedikt; Pahnke, Jens; Brenner, Winfried; Mautner, Victor F; Buchert, Ralph

    2015-08-01

    Neurofibromatosis type 1 (NF1) is a single-gene disorder affecting neurologic function in humans. The NF1+/- mouse model with germline mutation of the NF1 gene presents with deficits in learning, attention, and motor coordination, very similar to NF1 patients. The present study performed brain perfusion single-photon emission computed tomography (SPECT) in NF1+/- mice to identify possible perfusion differences as surrogate marker for altered cerebral activity in NF1. Cerebral perfusion was measured with hexamethyl-propyleneamine oxime (HMPAO) SPECT in NF1+/- mice and their wild-type littermates longitudinally at juvenile age and at young adulthood. Histology and immunohistochemistry were performed to test for structural changes. There was increased HMPAO uptake in NF1 mice in the amygdala at juvenile age, which reduced to normal levels at young adulthood. There was no genotype effect on thalamic HMPAO uptake, which was confirmed by ex vivo measurements of F-18-fluorodeoxyglucose uptake in the thalamus. Morphologic analyses showed no major structural abnormalities. However, there was some evidence of increased density of microglial somata in the amygdala of NF1-deficient mice. In conclusion, there is evidence of increased perfusion and increased density of microglia in juvenile NF1 mice specifically in the amygdala, both of which might be associated with altered synaptic plasticity and, therefore, with cognitive deficits in NF1. PMID:25785829

  7. Mosaic type-1 NF1 microdeletions as a cause of both generalized and segmental neurofibromatosis type-1 (NF1).

    PubMed

    Messiaen, Ludwine; Vogt, Julia; Bengesser, Kathrin; Fu, Chuanhua; Mikhail, Fady; Serra, Eduard; Garcia-Linares, Carles; Cooper, David N; Lazaro, Conxi; Kehrer-Sawatzki, Hildegard

    2011-02-01

    Mosaicism is an important feature of type-1 neurofibromatosis (NF1) on account of its impact upon both clinical manifestations and transmission risk. Using FISH and MLPA to screen 3500 NF1 patients, we identified 146 individuals harboring gross NF1 deletions, 14 of whom (9.6%) displayed somatic mosaicism. The high rate of mosaicism in patients with NF1 deletions supports the postulated idea of a direct relationship between the high new mutation rate in this cancer predisposition syndrome and the frequency of mosaicism. Seven of the 14 mosaic NF1 deletions were type-2, whereas four were putatively type-1, and three were atypical. Two of the four probable type-1 deletions were confirmed as such by breakpoint-spanning PCR or SNP analysis. Both deletions were associated with a generalized manifestation of NF1. Independently, we identified a third patient with a mosaic type-1 NF1 deletion who exhibited segmental NF1. Together, these three cases constitute the first proven mosaic type-1 deletions so far reported. In two of these three mosaic type-1 deletions, the breakpoints were located within PRS1 and PRS2, previously identified as hotspots for nonallelic homologous recombination (NAHR) during meiosis. Hence, NAHR within PRS1 and PRS2 is not confined to meiosis but may also occur during postzygotic mitotic cell cycles. PMID:21280148

  8. Molecular Characterization of NF1 and Neurofibromatosis Type 1 Genotype-Phenotype Correlations in a Chinese Population

    PubMed Central

    Zhang, Jia; Tong, Hanxing; Fu, Xi’an; Zhang, Yong; Liu, Jiangbo; Cheng, Ruhong; Liang, Jianying; Peng, Jie; Sun, Zhonghui; Liu, Hong; Zhang, Furen; Lu, Weiqi; Li, Ming; Yao, Zhirong

    2015-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease that is primarily characterized by multiple café au-lait spots (CALs) and skin neurofibromas, which are attributed to defects in the tumor suppressor NF1. Because of the age-dependent presentation of NF1, it is often difficult to make an early clinical diagnosis. Moreover, identifying genetic alterations in NF1 patients represents a complex challenge. Currently, there are no effective detective methods, and no comprehensive NF1 mutation data are available for mainland China. We screened 109 Chinese patients from 100 families with NF1-like phenotypes (e.g., CALs, neurofibromas, etc.) using Sanger sequencing, multiplex ligation-dependent probe amplification and cDNA sequencing. NF1 mutations were identified in 97 individuals, among which 34 intragenic mutations have not previously been reported. Our exhaustive mutational analysis detected mutations in 89% (89/100) of the NF1-like probands and 93% (70/75) of subjects fulfilling the National Institutes of Health (NIH) criteria. Our findings indicate that individuals who exclusively present with multiple CALs exhibit a high possibility (76%) of having NF1 and show a significantly lower mutation rate (p = 0.042) compared with subjects who fulfill the NIH criteria, providing clinicians with the information that subjects only with multiple CALs harbor a considerable possibility (24%) of being attributed to other comparable diseases. PMID:26056819

  9. RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth.

    PubMed

    Solga, Anne C; Pong, Winnie W; Kim, Keun-Young; Cimino, Patrick J; Toonen, Joseph A; Walker, Jason; Wylie, Todd; Magrini, Vincent; Griffith, Malachi; Griffith, Obi L; Ly, Amy; Ellisman, Mark H; Mardis, Elaine R; Gutmann, David H

    2015-10-01

    Solid cancers develop within a supportive microenvironment that promotes tumor formation and growth through the elaboration of mitogens and chemokines. Within these tumors, monocytes (macrophages and microglia) represent rich sources of these stromal factors. Leveraging a genetically engineered mouse model of neurofibromatosis type 1 (NF1) low-grade brain tumor (optic glioma), we have previously demonstrated that microglia are essential for glioma formation and maintenance. To identify potential tumor-associated microglial factors that support glioma growth (gliomagens), we initiated a comprehensive large-scale discovery effort using optimized RNA-sequencing methods focused specifically on glioma-associated microglia. Candidate microglial gliomagens were prioritized to identify potential secreted or membrane-bound proteins, which were next validated by quantitative real-time polymerase chain reaction as well as by RNA fluorescence in situ hybridization following minocycline-mediated microglial inactivation in vivo. Using these selection criteria, chemokine (C-C motif) ligand 5 (Ccl5) was identified as a chemokine highly expressed in genetically engineered Nf1 mouse optic gliomas relative to nonneoplastic optic nerves. As a candidate gliomagen, recombinant Ccl5 increased Nf1-deficient optic nerve astrocyte growth in vitro. Importantly, consistent with its critical role in maintaining tumor growth, treatment with Ccl5 neutralizing antibodies reduced Nf1 mouse optic glioma growth and improved retinal dysfunction in vivo. Collectively, these findings establish Ccl5 as an important microglial growth factor for low-grade glioma maintenance relevant to the development of future stroma-targeted brain tumor therapies. PMID:26585233

  10. An intraosseous malignant peripheral nerve sheath tumor of the lumbar spine without neurofibromatosis: Case report and review of the literature.

    PubMed

    Suzuki, Kayo; Yasuda, Taketoshi; Hori, Takeshi; Watanabe, Kenta; Kanamori, Masahiko; Kimura, Tomoatsu

    2014-06-01

    A malignant peripheral nerve sheath tumor (MPNST) is defined as any malignant tumor that develops or differentiates from cells in the peripheral nerve sheath. This tumor is commonly associated with neurofibromatosis type 1 (NF1) and previous radiotherapy treatment. Primary intraosseous MPNSTs are extremely rare and a case of the lumbar spine in a patient without NF1 is reported in the present study, with a review of the intraosseous MPNST literature. A 45-year-old female presented with a 1-month history of severe lower back pain and pain radiating to the left leg. A total en bloc spondylectomy of L4 was performed. The postoperative histopathological diagnosis was MPNST with deletion of NF1, confirmed by dual-color fluorescence in situ hybridization (FISH) analysis. The tumor recurred 1 month following the surgery. Although adjuvant chemotherapy was administered, the patient succumbed due to intramedullary dissemination and carcinomatous meningitis 8 months following the initial consultation. NF1 deletion by FISH analysis may be particularly useful in distinguishing MPNST from other high-grade malignancies with overlapping morphological features. PMID:24932270

  11. Café-au-lait macules and intertriginous freckling in piebaldism: clinical overlap with neurofibromatosis type 1 and Legius syndrome.

    PubMed

    Stevens, Cathy A; Chiang, Pei-Wen; Messiaen, Ludwine M

    2012-05-01

    Piebaldism is an autosomal dominant disorder characterized by congenital hypopigmented patches of skin and hair and has been found to be associated with mutations in the KIT or SLUG genes. Café-au-lait macules (CALM) may occasionally be seen in piebaldism. There are four reports describing six patients who were said to have both piebaldism and neurofibromatosis type 1 (NF1) due to the presence of multiple CALM and intertriginous freckling, but none of these patients had undergone comprehensive NF1 mutation analysis. We describe a large family with piebaldism in which two members meet diagnostic criteria for NF1 based on the presence of >5 CALM and intertriginous freckling. Interestingly, only these two family members are of mixed race, which could be of importance. A novel complex mutation in the KIT gene was identified in several family members affected with piebaldism; the proband meeting diagnostic criteria for NF1 also underwent comprehensive NF1 and SPRED1 testing with no mutations detected. These findings suggest that piebaldism may occasionally include CALM and intertriginous freckling, which may create diagnostic confusion especially in the absence of a family history of piebaldism. However, careful clinical evaluation and molecular testing if necessary should distinguish these two disorders. PMID:22438235

  12. Rare case of optic pathway glioma with extensive intra-ocular involvement in a child with neurofibromatosis type 1.

    PubMed

    Gupta, Vasudha; Sabri, Kourosh; Whelan, Kaitlyn F; Viscardi, Virginia

    2015-01-01

    We present a case of a 3-year-old girl with a positive family history of neurofibromatosis type-1 (NF1) presented with best corrected visual acuity of 20/40 in the right eye and <20/400 in the left eye. External ocular examination revealed left eye proptosis of 3 mm, grade II left relative afferent pupillary defect and full range of ocular motility with no strabismus. Slit lamp examination revealed iris lisch nodules bilaterally. Dilated fundus examination of the right eye was normal. Left eye disclosed a large mass extending from the optic nerve head, with associated subretinal fluid. There was neovascularization at the optic disc as well as a superior retinal hemorrhage. Computed tomography of brain/orbits showed an enlarged left optic nerve with a large mass at the optic nerve head, with no evidence of calcification. In addition, a large left optic pathway glioma (OPG), multiple hamartomas within the brain and a smaller low-grade right OPG was also reported. The remarkable feature of our case is the rare intraocular optic nerve involvement of the OPG. Early and regular ophthalmological assessment of all NF1 suspect/confirmed cases is of paramount importance in order to detect OPG early, resulting in timely intervention and salvage of vision. PMID:25624686

  13. [Molecular diagnosis as a strategy for differential diagnosis and at early ages of neurofibromatosis type 1 (NF1)].

    PubMed

    Gómez, Martha; Batista, Oriana

    2015-10-01

    Neurofibromatosis type 1 (NF1), is a haploinsufficient and multisystemic disease, caused by inherited or sporadic mutations in the NF1 gene. Its incidence is one in 2,500 to 3,000 individuals, it has an autosomal dominant pattern of inheritance, high clinical variability, complete penetrance and age-dependent complications. Neurofibromin is the product of the NF1 gene and is believed to act as a tumor suppressor since the loss of its function has been associated with benign and malignant tumors in neural crest-derived tissues. Only two correlations between clinical phenotype and mutant alleles in the NF1 gene have been observed. The established criteria for disease diagnosis are very efficient in adults and children older than 3 years of age, but not for children under this age. Mutational analysis is therefore recommended to confirm the disease in young children with a negative family history. A pathogenic mutation in the NF1 should be added to the list of diagnostic criteria. Mutational analysis is also recommended for differential diagnosis and for prenatal or pre-implantation genetic diagnosis, taking into consideration the family history and the type of method to be applied. Molecular studies of this disease using different complimentary molecular techniques and bioinformatics tools have characterized NF1 gene mutations at both the DNA and mRNA levels, increasing the mutational spectrum. Consequently, about 1,289 defects have been reported to date, mainly nonsense/missense mutations, deletions and splice site defects. PMID:26633276

  14. Water-clear cell parathyroid adenoma causing primary hyperparathyroidism in a patient with neurofibromatosis type 1: report of a case.

    PubMed

    Kodama, Hitomi; Iihara, Masatoshi; Okamoto, Takahiro; Obara, Takao

    2007-01-01

    Water-clear cell parathyroid adenoma is an exceedingly rare tumor, composed exclusively of tumor cells with abundant foamy cytoplasm. A combination of hyperparathyroidism and neurofibromatosis type 1 (NF1) is also a rare phenomenon. We report an 18-year-old woman with primary hyperparathyroidism caused by water-clear cell parathyroid adenoma in association with NF1. She had renal stones, hypercalcemia, and an elevated plasma level of intact parathyroid hormone. Physical examination revealed a palpable tumor in the right neck, and café-au-lait spots distributed over her entire body. An ultrasound examination showed an isoechoic mass in the right thyroid lobe. Thallium-technetium subtraction scintigraphy showed high thallium accumulation in the right thyroid lobe area. A surgical exploration revealed the palpable mass to be a parathyroid tumor. The pathological features were consistent with water-clear parathyroid adenoma. This is the first reported case of water-clear cell parathyroid adenoma associated with NF1. PMID:17879040

  15. Pseudoangiomatous stromal hyperplasia with multinucleated stromal giant cells is neither exceptional in gynecomastia nor characteristic of neurofibromatosis type 1.

    PubMed

    Pižem, Jože; Velikonja, Mojca; Matjašič, Alenka; Jerše, Maja; Glavač, Damjan

    2015-04-01

    Six cases of gynecomastia with pseudoangiomatous stromal hyperplasia (PASH) and multinucleated stromal giant cells (MSGC) associated with neurofibromatosis type 1 (NF1) have been reported, and finding MSGC within PASH in gynecomastia has been suggested as being a characteristic of NF1. The frequency of PASH with MSGC in gynecomastia and its specificity for NF1 have not, however, been systematically studied. A total of 337 gynecomastia specimens from 215 patients, aged from 8 to 78 years (median, 22 years) were reevaluated for the presence of PASH with MSGC. Breast tissue samples of 25 patients were analyzed for the presence of an NF1 gene mutation using next generation sequencing. Rare MSGC, usually in the background of PASH, were noted at least unilaterally in 27 (13 %) patients; and prominent MSGC, always in the background of PASH, were noted in 8 (4 %) patients. The NF1 gene was mutated in only 1 (an 8-year-old boy with known NF1 and prominent MSGC) of the 25 tested patients, including 6 patients with prominent MSGC and 19 patients with rare MSGC. MSGC, usually in the background of PASH, are not characteristic of NF1. PMID:25586494

  16. The cyclic AMP pathway is a sex-specific modifier of glioma risk in type I neurofibromatosis patients.

    PubMed

    Warrington, Nicole M; Sun, Tao; Luo, Jingqin; McKinstry, Robert C; Parkin, Patricia C; Ganzhorn, Sara; Spoljaric, Debra; Albers, Anne C; Merkelson, Amanda; Stewart, Douglas R; Stevenson, David A; Viskochil, David; Druley, Todd E; Forys, Jason T; Reilly, Karlyne M; Fisher, Michael J; Tabori, Uri; Allen, Jeffrey C; Schiffman, Joshua D; Gutmann, David H; Rubin, Joshua B

    2015-01-01

    Identifying modifiers of glioma risk in patients with type I neurofibromatosis (NF1) could help support personalized tumor surveillance, advance understanding of gliomagenesis, and potentially identify novel therapeutic targets. Here, we report genetic polymorphisms in the human adenylate cyclase gene adenylate cyclase 8 (ADCY8) that correlate with glioma risk in NF1 in a sex-specific manner, elevating risk in females while reducing risk in males. This finding extends earlier evidence of a role for cAMP in gliomagenesis based on results in a genetically engineered mouse model (Nf1 GEM). Thus, sexually dimorphic cAMP signaling might render males and females differentially sensitive to variation in cAMP levels. Using male and female Nf1 GEM, we found significant sex differences exist in cAMP regulation and in the growth-promoting effects of cAMP suppression. Overall, our results establish a sex-specific role for cAMP regulation in human gliomagenesis, specifically identifying ADCY8 as a modifier of glioma risk in NF1. PMID:25381154

  17. Capturing the wide variety of impaired fracture healing phenotypes in Neurofibromatosis Type 1 with eight key factors: a computational study

    PubMed Central

    Carlier, A.; Brems, H.; Ashbourn, J. M. A.; Nica, I.; Legius, E.; Geris, L.

    2016-01-01

    Congenital pseudarthrosis of the tibia (CPT) is a rare disease which normally presents itself during early childhood by anterolateral bowing of the tibia and spontaneous tibial fractures. Although the exact etiology of CPT is highly debated, 40–80% of CPT patients are carriers of a mutation in the Neurofibromatosis Type 1 (NF1) gene, which can potentially result in an altered phenotype of the skeletal cells and impaired bone healing. In this study we use a computational model of bone regeneration to examine the effect of the Nf1 mutation on bone fracture healing by altering the parameter values of eight key factors which describe the aberrant cellular behaviour of Nf1 haploinsufficient and Nf1 bi-allelically inactivated cells. We show that the computational model is able to predict the formation of a hamartoma as well as a wide variety of CPT phenotypes through different combinations of altered parameter values. A sensitivity analysis by “Design of Experiments” identified the impaired endochondral ossification process and increased infiltration of fibroblastic cells as key contributors to the degree of severity of CPT. Hence, the computational model results have added credibility to the experimental hypothesis of a genetic cause (i.e. Nf1 mutation) for CPT. PMID:26822862

  18. Surgical Management of Intracanal Rib Head Dislocation in Neurofibromatosis Type 1 Dystrophic Kyphoscoliosis: Report of Two Cases and Literature Review

    PubMed Central

    Bounakis, Nikolaos; Garrido-Stratenwerth, Enrique

    2016-01-01

    There is still no consensus on the management of severe intracanal RH dislocation in neurofibromatosis type 1 dystrophic kyphoscoliosis. This study notes the early cord function impairment signs, reports a serious complication in a susceptible cord, identifies possible mechanisms of injury, and discusses the management of intracanal RH dislocation presented in the literature. First report is as follows: a 12-year-old female with cord compromise and preoperative neurology that underwent thoracotomy and anterior release. The RH was left in situ following a rib excision. During the posterior stage of the procedure she presented with complete loss of all IOM traces prior to any correction manoeuvres. The neurology recovered 72 h postop and the final correction and instrumented fusion were uneventfully completed 15 days postop. Second report is as follows: a 10-year-old male, whose only neurology was a provoked shock-like sensation to the lower limbs following direct pressure on the rib cage. He underwent an uneventful posterior RH excision and instrumented correction and posterior spinal fusion. In conclusion, any possible cord dysfunction sign should be sought during examination. Decompression of the spinal cord by resecting the impinging bony part, even in the absence of neurological symptoms, is advised before any attempt to release or correct the deformity. PMID:27446620

  19. Abnormal late visual responses and alpha oscillations in neurofibromatosis type 1: a link to visual and attention deficits

    PubMed Central

    2014-01-01

    Background Neurofibromatosis type 1 (NF1) affects several areas of cognitive function including visual processing and attention. We investigated the neural mechanisms underlying the visual deficits of children and adolescents with NF1 by studying visual evoked potentials (VEPs) and brain oscillations during visual stimulation and rest periods. Methods Electroencephalogram/event-related potential (EEG/ERP) responses were measured during visual processing (NF1 n = 17; controls n = 19) and idle periods with eyes closed and eyes open (NF1 n = 12; controls n = 14). Visual stimulation was chosen to bias activation of the three detection mechanisms: achromatic, red-green and blue-yellow. Results We found significant differences between the groups for late chromatic VEPs and a specific enhancement in the amplitude of the parieto-occipital alpha amplitude both during visual stimulation and idle periods. Alpha modulation and the negative influence of alpha oscillations in visual performance were found in both groups. Conclusions Our findings suggest abnormal later stages of visual processing and enhanced amplitude of alpha oscillations supporting the existence of deficits in basic sensory processing in NF1. Given the link between alpha oscillations, visual perception and attention, these results indicate a neural mechanism that might underlie the visual sensitivity deficits and increased lapses of attention observed in individuals with NF1. PMID:24559228

  20. Fused teeth, macrodontia and increased caries are characteristic features of neurofibromatosis type 1 patients with NF1 gene microdeletion

    PubMed Central

    Kobayashi, Ryosuke; Matsune, Kensuke; Ohashi, Hirofumi

    2012-01-01

    Neurofibromatosis type 1 (NF1) is the most common genetic condition caused by NF1 gene alteration. A 1.5 Mb submicroscopic deletion encompassing the entire NF1 gene, is known to be responsible for approximately 5% of NF1 cases. Patients with NF1 deletion, compared to those with NF1 mutation tend to exhibit more severe phenotypes. To know the possible differences in oral/dental features between NF1 deletion and NF1 mutation patients, we examined four patients with NF1 deletion and three with NF1 mutation to compare their oral manifestations. Fused teeth in the mandibular anterior region were found only in the patients with deletion (2/4). Macrodontia was noted in all four patients with an NF1 deletion. Although macrodontia was also found in one patient with a mutation, it was relatively mild compared to the deletion patients. Dental caries were observed in both NF1 deletion (4/4) and mutation (2/3) patients. However, patients with NF1 deletions showed more apparently severe caries (average number of dental caries 12.8) than those with NF1 mutation (average number 5.5). Other features also noted in patients with both deletions and mutations were high-arched palate, hypodontia and malocclusion. Our study might suggest that fused teeth, macrodontia and increased dental caries are distinctive manifestations of NF1 deletion. Providing comprehensive dental care from early infancy would be very important to prevent dental caries especially in patients with NF1 deletion.

  1. Detection of a neurofibromatosis type I (NF1) homologous sequence by PCR: implications for the diagnosis and screening of genetic diseases.

    PubMed

    Gasparini, P; Grifa, A; Origone, P; Coviello, D; Antonacci, R; Rocchi, M

    1993-10-01

    The neurofibromatosis type I (NF1) gene was extensively screened for mutations using single strand conformation polymorphism (SSCP) technology. During the analysis of the NF1 GAP-related domain, electrophoretically abnormal fragments were detected. Direct sequencing of these fragments allowed us to identify the presence of a NF1 highly homologous sequence (NF1HHS). A detailed analysis of a hybrid panel located this sequence on chromosome 15q24-->qter. An accurate search through several data banks demonstrated that this sequence is a new NF1 homologue. This report shows how it is possible to find homologous sequences at random, and subsequently to make wrong interpretations. PMID:8264676

  2. Giant malignant peripheral nerve sheath tumor with cauda equina syndrome and subarachnoid hemorrhage: Complications in a case of type 1 neurofibromatosis.

    PubMed

    Patil, Tushar B; Singh, Maneesh Kumar; Lalla, Rakesh

    2015-01-01

    Type 1 neurofibromatosis (NF1), which mainly involves ectodermal tissue arising from the neural crest, can increase the risk of developing malignant peripheral nerve sheath tumors (MPNSTs), soft tissue sarcomas and subarachnoid hemorrhage. We describe a patient with neurofibromatosis type 1 who developed soft tissue sarcoma, MPNST, and subarachnoid hemorrhage. A 22-year-old male reported right focal seizures consequence to severe headache. He had a weakness in both legs, could walk only with the support of a stick for the last 3 months and suffered from constipation and intermittent urinary retention for the past 1 week. The patient had a history of swelling in the back of left thigh for which surgical resection was done 6 months back. Cutaneous examination revealed multiple nodules of varying sizes all over the body, along with many café-au-lait spots and Lisch nodule in iris. Patient had weakness in bilateral hip abduction, extension, knee flexion, extension and ankle dorsiflexion and plantiflexion. Bilateral ankle reflexes were absent while other deep tendon reflexes were sub-optimal. A noncontrast computed tomography brain indicated subarachnoid hemorrhage in left perisylvian region. Ultrasound of left thigh showed a hypoechoic solid lesion in the posterior aspect of left thigh in muscle plane. Histopathology of the lesion following resection showed features suggestive of a low-grade pleomorphic rhabdomyosarcoma. Histology of cutaneous nodules was consistent with neurofibroma. Magnetic resonance imaging of the lumbosacral spine demonstrated a tumor arising from cauda equina. Histopathological examination of the tumor suggested high-grade MPNST. Unfortunately, the patient's MPNST was inoperable, and he received palliative radiotherapy for local control of the disease. The care of a patient with neurofibromatosis requires a comprehensive multisystem evaluation. MPNST occurs in 8-13% patients with neurofibromatosis. Early diagnosis and surgical resection are key

  3. Unilateral gynaecomastia in a 16-month-old boy with neurofibromatosis type 1 – case report and brief review of the literature

    PubMed Central

    Friedrich, Reinhard E.; Hagel, Christian; Mautner, Victor-Felix

    2015-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that shows high penetrance with a wide variability in the phenotype. Prepubertal enlargement of the breast in male subjects affected by this condition is well known, but rarely reported. The present case report describes diagnosis and therapy of unilateral gynaecomastia in a toddler showing integumental stigmata of NF1. Furthermore, the report provides a brief review of the literature concerning this finding in NF1. According to this review, the present case appears to be one of the youngest NF1-affected males affected by gynaecomastia that has been reported. PMID:26668786

  4. The more you look, the more you find: challenging results on FDG-PET CT in a patient with neurofibromatosis type I

    PubMed Central

    2014-01-01

    Background FDG-PET/CT is part of the standard diagnostic management of a patients with a large variety of common and less common malignant tumors, based on the increased glucose metabolism within tumors. Case presentation A hybrid fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) was performed in a neurofibromatosis patient to rule out relapse of malignant peripheral nerve sheet tumor. The scan revealed non-malignant neurofibromas, a testis seminoma and hypermetabolic syphilitic granulomata. Conclusion This case stresses the need to rule out infectious diseases when atypical hypermetabolic lesions are present. PMID:24885974

  5. Mice with missense and nonsense NF1 mutations display divergent phenotypes compared with human neurofibromatosis type I

    PubMed Central

    Li, Kairong; Turner, Ashley N.; Chen, Min; Brosius, Stephanie N.; Schoeb, Trenton R.; Messiaen, Ludwine M.; Bedwell, David M.; Zinn, Kurt R.; Anastasaki, Corina; Gutmann, David H.; Korf, Bruce R.

    2016-01-01

    ABSTRACT Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by the occurrence of nerve sheath tumors and considerable clinical heterogeneity. Some translational studies have been limited by the lack of animal models available for assessing patient-specific mutations. In order to test therapeutic approaches that might restore function to the mutated gene or gene product, we developed mice harboring NF1 patient-specific mutations including a nonsense mutation (c.2041C>T; p.Arg681*) and a missense mutation (c.2542G>C; p.Gly848Arg). The latter is associated with the development of multiple plexiform neurofibromas along spinal nerve roots. We demonstrate that the human nonsense NF1Arg681* and missense NF1Gly848Arg mutations have different effects on neurofibromin expression in the mouse and each recapitulates unique aspects of the NF1 phenotype, depending upon the genetic context when assessed in the homozygous state or when paired with a conditional knockout allele. Whereas the missense Nf1Gly848Arg mutation fails to produce an overt phenotype in the mouse, animals homozygous for the nonsense Nf1Arg681* mutation are not viable. Mice with one Nf1Arg681* allele in combination with a conditional floxed Nf1 allele and the DhhCre transgene (Nf14F/Arg681*; DhhCre) display disorganized nonmyelinating axons and neurofibromas along the spinal column, which leads to compression of the spinal cord and paralysis. This model will be valuable for preclinical testing of novel nonsense suppression therapies using drugs to target in-frame point mutations that create premature termination codons in individuals with NF1. PMID:27482814

  6. Low-dose bevacizumab induces radiographic regression of vestibular schwannomas in neurofibromatosis type 2: A case report and literature review

    PubMed Central

    LIU, PENGFEI; YAO, QINGYU; LI, NA; LIU, YONGLIANG; WANG, YUGUO; LI, MENG; LI, ZEFU; LI, JIANMIN; LI, GANG

    2016-01-01

    The current case study aimed to explore the efficacy of a low-dose bevacizumab regimen in inhibiting tumor growth and minimizing adverse effects. A 55-year-old man with neurofibromatosis type 2 (NF2) suffered bilateral vestibular schwannomas (VS) measuring 5.25 and 2.54 cm3 on the left and right, respectively. His capacity for bilateral language recognition was impaired. However, the patient refused microsurgical tumor resection and gamma knife therapy. Low-dose bevacizumab regimen (3.3–2.2 mg/kg every 2–4 weeks) was administered by intravenous injection for ~1.5 years to inhibit tumor growth and avoid further deterioration of hearing. Compared with baseline measurements prior to treatment, the bilateral VS regressed to 3.59 cm3 (68%) and 2.08 cm3 (82%) on the left and right, respectively. No hearing improvement was detected; however, the patient subjectively experienced a significant hearing improvement as his ability to communicate with people and distinguish voices was restored. No adverse effects were observed. Bevacizumab provides an alternative treatment option for those who refuse surgical intervention. Given the adverse effects commonly induced by bevacizumab, the use of a low-dose regimen would appear to be promising with regard to tumor regression and hearing preservation for patients with VS in NF2. However, the minimum dose required to sustain a response to bevacizumab in NF2 patients remains unknown. Finding the minimum effective dose sufficient to sustain hearing and/or volumetric response for individual patients is required. PMID:27123050

  7. Association between moyamoya syndrome and the RNF213 c.14576G>A variant in patients with neurofibromatosis Type 1.

    PubMed

    Phi, Ji Hoon; Choi, Jung Won; Seong, Moon-Woo; Kim, Tackeun; Moon, Youn Joo; Lee, Joongyub; Koh, Eun Jung; Ryu, Seul Ki; Kang, Tae Hee; Bang, Jae Seung; Oh, Chang Wan; Park, Sung Sup; Lee, Ji Yeoun; Wang, Kyu-Chang; Kim, Seung-Ki

    2016-06-01

    OBJECTIVE In a minority of patients with neurofibromatosis Type 1 (NF-1), cerebral vasculopathy reminiscent of moyamoya disease develops. This phenomenon is called moyamoya syndrome (MMS), but there are no known risk factors for the prediction of MMS in NF-1 patients. Polymorphism of the RNF213 gene has exhibited strong associations with familial and sporadic moyamoya disease and other cerebral vasculopathies. The aim of this study is to find whether the RNF213 c.14576G>A variant is associated with MMS development in the NF-1 population or not. METHODS The MMS group included 16 NF-1 patients with documented MMS. The control group consisted of 97 NF-1 patients without MMS. Genomic DNA samples were obtained from the saliva or blood of both groups, and the presence of the RNF213 c.14576G>A variant was assessed by Sanger sequencing. RESULTS In the MMS group, 3 patients had the RNF213 c.14576G>A variant (18.7%), whereas no patients with this genetic variation were observed in the control group (0%). There was a meaningful association between the RNF213 c.14576G>A variant and MMS development (p = 0.0024). The crude odds ratio was calculated as 50.57 (95% CI 1.57-1624.41). All 3 patients with MMS and the c.14576G>A variant were diagnosed with MMS at an early age and had bilateral involvement. CONCLUSIONS The RNF213 c.14576G>A variant is more common in NF-1 patients who develop MMS than in NF-1 patients without MMS. This variant might be a susceptibility gene for the NF-1-moyamoya connection. PMID:26849809

  8. Abnormal Brain Activation in Neurofibromatosis Type 1: A Link between Visual Processing and the Default Mode Network

    PubMed Central

    Violante, Inês R.; Ribeiro, Maria J.; Cunha, Gil; Bernardino, Inês; Duarte, João V.; Ramos, Fabiana; Saraiva, Jorge; Silva, Eduardo; Castelo-Branco, Miguel

    2012-01-01

    Neurofibromatosis type 1 (NF1) is one of the most common single gene disorders affecting the human nervous system with a high incidence of cognitive deficits, particularly visuospatial. Nevertheless, neurophysiological alterations in low-level visual processing that could be relevant to explain the cognitive phenotype are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to study early cortical visual pathways in children and adults with NF1. We employed two distinct stimulus types differing in contrast and spatial and temporal frequencies to evoke relatively different activation of the magnocellular (M) and parvocellular (P) pathways. Hemodynamic responses were investigated in retinotopically-defined regions V1, V2 and V3 and then over the acquired cortical volume. Relative to matched control subjects, patients with NF1 showed deficient activation of the low-level visual cortex to both stimulus types. Importantly, this finding was observed for children and adults with NF1, indicating that low-level visual processing deficits do not ameliorate with age. Moreover, only during M-biased stimulation patients with NF1 failed to deactivate or even activated anterior and posterior midline regions of the default mode network. The observation that the magnocellular visual pathway is impaired in NF1 in early visual processing and is specifically associated with a deficient deactivation of the default mode network may provide a neural explanation for high-order cognitive deficits present in NF1, particularly visuospatial and attentional. A link between magnocellular and default mode network processing may generalize to neuropsychiatric disorders where such deficits have been separately identified. PMID:22723888

  9. Mice with missense and nonsense NF1 mutations display divergent phenotypes compared with human neurofibromatosis type I.

    PubMed

    Li, Kairong; Turner, Ashley N; Chen, Min; Brosius, Stephanie N; Schoeb, Trenton R; Messiaen, Ludwine M; Bedwell, David M; Zinn, Kurt R; Anastasaki, Corina; Gutmann, David H; Korf, Bruce R; Kesterson, Robert A

    2016-07-01

    Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by the occurrence of nerve sheath tumors and considerable clinical heterogeneity. Some translational studies have been limited by the lack of animal models available for assessing patient-specific mutations. In order to test therapeutic approaches that might restore function to the mutated gene or gene product, we developed mice harboring NF1 patient-specific mutations including a nonsense mutation (c.2041C>T; p.Arg681*) and a missense mutation (c.2542G>C; p.Gly848Arg). The latter is associated with the development of multiple plexiform neurofibromas along spinal nerve roots. We demonstrate that the human nonsense NF1(Arg681*) and missense NF1(Gly848Arg) mutations have different effects on neurofibromin expression in the mouse and each recapitulates unique aspects of the NF1 phenotype, depending upon the genetic context when assessed in the homozygous state or when paired with a conditional knockout allele. Whereas the missense Nf1(Gly848Arg) mutation fails to produce an overt phenotype in the mouse, animals homozygous for the nonsense Nf1(Arg681*) mutation are not viable. Mice with one Nf1(Arg681*) allele in combination with a conditional floxed Nf1 allele and the DhhCre transgene (Nf1(4F/Arg681*); DhhCre) display disorganized nonmyelinating axons and neurofibromas along the spinal column, which leads to compression of the spinal cord and paralysis. This model will be valuable for preclinical testing of novel nonsense suppression therapies using drugs to target in-frame point mutations that create premature termination codons in individuals with NF1. PMID:27482814

  10. Type 1 neurofibromatosis: selective expression of extracellular matrix genes by Schwann cells, perineurial cells, and fibroblasts in mixed cultures.

    PubMed Central

    Jaakkola, S; Peltonen, J; Riccardi, V; Chu, M L; Uitto, J

    1989-01-01

    Cutaneous neurofibromas, characteristic lesions of neurofibromatosis 1, are composed of an abundant extracellular matrix and nerve connective tissue-derived cell types: Schwann cells, perineurial cells, and fibroblasts. In this study, the extracellular matrix gene expression by these cells was examined under culture conditions that allowed them to be metabolically active and readily identifiable by morphologic and immunocytochemical criteria. Northern hybridizations demonstrated expression of genes for type I, III, IV, and VI collagens, as well as for fibronectin, laminin, and elastin. In situ hybridizations revealed that all three cell types expressed pro alpha 1 (I), pro alpha 2 (VI), and laminin B1 chain genes. However, fibroblasts did not contain [35S]cDNA-mRNA hybrids specific for type IV collagen, whereas both Schwann cells and perineurial cells expressed these genes. Perineurial cells and fibroblasts readily expressed the fibronectin gene whereas Schwann cells were essentially devoid of the corresponding mRNA. Perineurial cells also expressed the gene for laminin A chain. The results indicate that the extracellular matrix gene expression profiles of Schwann cells, perineurial cells, and fibroblasts are distinct: all three cell types are capable of expressing some of the genes for extracellular matrix components, such as type I and VI collagens, whereas Schwann cells and perineurial cells may have the primary role in synthesizing basement membrane zone components, type IV collagen and laminin. These observations potentially relate to the mechanisms of growth and development of human neurofibromas. The results attest to the applicability of the methodology utilized here to study other human tumors with mixed cell populations. Images PMID:2500456

  11. Neurofibromatosis type 1 and Chiari type 1 malformation: A case report and literature review of a rare association

    PubMed Central

    Pozetti, Marianne; Belsuzarri, Telmo Augusto Barba; Belsuzarri, Natalia C. B.; Seixas, Naira B.; Araujo, João F. M.

    2016-01-01

    Background: The association between neurofibromatosis type 1 (NF-I) and Chiari I malformation (CMI) is rare, and not many studies are reported in the literature. Performing magnetic resonance imaging (MRI) in patients with NF-1 is essential because several cases of Chiari type I are completely asymptomatic. We emphasize the need for inclusion of Chiari I as diagnosis in association with NF-1. Case Description: The patient was a 51-year-old black man who presented with complaints of pain and decreased motion and sensibility of his hands, wrists, and forearms, along with progressive dysarthria. Even though the computed tomography (CT) scan of the skull did not show changes, the MRI showed hydro/syringomyelia in the cervical spine area. Midline suboccipital craniectomy with total laminectomy of c1 and partial laminectomy of c2 was performed; tonsillectomy was also performed for cistern expansion because of intense thickening and obliteration of the obex by the cerebellar tonsils. Following treatment, the patient showed remission of symptoms. Conclusion: NF-1 in association with CMI is rare, and early diagnosis and surgical treatment are essential to slow down the myelopathy; although they prevent neurological damages, patients with NF-1 must remain under doctor's attention in case of association with CMI. Our literature review showed that symptoms can vary and include headache, gait disturbance, and sensory/motor diminution, until asymptomatic patients. Moreover, the incidence of NF-1 is considerably higher in CMI patients in comparison to the global incidence (8.6–11.8% and 0.775%, respectively). The surgical technique must be evaluated case by case according to the degree of cerebrospinal fluid obstruction. PMID:27500008

  12. Hyperactive transforming growth factor-β1 signaling potentiates skeletal defects in a neurofibromatosis type 1 mouse model.

    PubMed

    Rhodes, Steven D; Wu, Xiaohua; He, Yongzheng; Chen, Shi; Yang, Hao; Staser, Karl W; Wang, Jiapeng; Zhang, Ping; Jiang, Chang; Yokota, Hiroki; Dong, Ruizhi; Peng, Xianghong; Yang, Xianlin; Murthy, Sreemala; Azhar, Mohamad; Mohammad, Khalid S; Xu, Mingjiang; Guise, Theresa A; Yang, Feng-Chun

    2013-12-01

    Dysregulated transforming growth factor beta (TGF-β) signaling is associated with a spectrum of osseous defects as seen in Loeys-Dietz syndrome, Marfan syndrome, and Camurati-Engelmann disease. Intriguingly, neurofibromatosis type 1 (NF1) patients exhibit many of these characteristic skeletal features, including kyphoscoliosis, osteoporosis, tibial dysplasia, and pseudarthrosis; however, the molecular mechanisms mediating these phenotypes remain unclear. Here, we provide genetic and pharmacologic evidence that hyperactive TGF-β1 signaling pivotally underpins osseous defects in Nf1(flox/-) ;Col2.3Cre mice, a model which closely recapitulates the skeletal abnormalities found in the human disease. Compared to controls, we show that serum TGF-β1 levels are fivefold to sixfold increased both in Nf1(flox/-) ;Col2.3Cre mice and in a cohort of NF1 patients. Nf1-deficient osteoblasts, the principal source of TGF-β1 in bone, overexpress TGF-β1 in a gene dosage-dependent fashion. Moreover, Nf1-deficient osteoblasts and osteoclasts are hyperresponsive to TGF-β1 stimulation, potentiating osteoclast bone resorptive activity while inhibiting osteoblast differentiation. These cellular phenotypes are further accompanied by p21-Ras-dependent hyperactivation of the canonical TGF-β1-Smad pathway. Reexpression of the human, full-length neurofibromin guanosine triphosphatase (GTPase)-activating protein (GAP)-related domain (NF1 GRD) in primary Nf1-deficient osteoblast progenitors, attenuated TGF-β1 expression levels and reduced Smad phosphorylation in response to TGF-β1 stimulation. As an in vivo proof of principle, we demonstrate that administration of the TGF-β receptor 1 (TβRI) kinase inhibitor, SD-208, can rescue bone mass deficits and prevent tibial fracture nonunion in Nf1(flox/-) ;Col2.3Cre mice. In sum, these data demonstrate a pivotal role for hyperactive TGF-β1 signaling in the pathogenesis of NF1-associated osteoporosis and pseudarthrosis, thus implicating the TGF

  13. Diagnostic Accuracy of PET/CT-Guided Percutaneous Biopsies for Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1 Patients

    PubMed Central

    Brahmi, Mehdi; Combemale, Patrick

    2015-01-01

    Background Malignant peripheral nerve sheath tumors (MPNST) are one of the most frequent causes of death in patients with neurofibromatosis type 1 (NF1). Early detection is crucial because complete surgical resection is the only curative treatment. It has been previously reported that an 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) image with a T/L (Tumor/Liver) SUVmax ratio > 1.5 provides a high negative predictive value; however, it is not specific enough to make a NF1-related MPNST diagnosis. A formal proof of malignant transformation from a histological analysis is necessary before surgical excision because the procedure can cause mutilation. The objective of the present work was to investigate the effectiveness of and complications associated with PET/CT-guided percutaneous biopsies for an NF1-related MPNST diagnosis. Methods PET/CT-guided percutaneous biopsy procedures performed on 26 NF1 patients with a clinical suspicion of MPNST and a suspect lesion from a PET/CT scan (T/L SUVmax ratio > 1.5) were retrospectively evaluated. The localization of the suspected malignant site was determined using PET/CT. A stereotactic (ultrasonic and CT control) core biopsy technique was used with a local anesthesia. Results The first PET/CT-guided percutaneous biopsies enabled a pathological diagnosis for all of the patients (no "inconclusive " results were obtained), and no secondary procedures were needed. Among the 26 patients, the histopathological results from the biopsy were malignant in 17 cases and benign (BPNST with atypical cells) in nine cases. No complications from the diagnostic procedure were observed. A surgical resection was performed in 18 patients (seven benign and 11 malignant biopsies), removing the fine needle biopsy scar. In addition, six locally advanced/metastatic MPNST were treated with chemo/radiotherapy, and two BPNST had no progression after a follow-up of 14 and 39 months, respectively. The PET

  14. Posterior Spinal Reconstruction with Pedicle Screws, Multiple Iliac Screws and Wisconsin Spinal Wires in a Patient with Neurofibromatosis Scoliosis: A Case Report.

    PubMed

    Kim, Woong-Beom; Park, Young-Seop; Park, Jong-Hwa; Hyun, Seung-Jae

    2015-09-01

    A 54-year-old female with neurofibromatosis type 1 presented with progressing truncal shift owing to spinal deformity. On plain radiograph, the Cobb angle was 54 degree in coronal plane. Radiological examinations showed severe dystrophic change with dysplastic pedicles, bony scalloping, neural foraminal widening from dural ectasia. The patient underwent deformity correction and reconstruction surgery from the T9 to the pelvis using multiple iliac screws and Wisconsin interspinous segmental instrumentation by wiring due to maximize fixation points. The postoperative course was uneventful. One-year follow-up radiographs showed a successful curve correction with solid fusion. We report a case of pedicle dysplasia and dystrophic change treated by posterior segmental spinal instrumentation and fusion with help of multiple iliac screws and modified Wisconsin interspinous segmental wiring. PMID:26512279

  15. Posterior Spinal Reconstruction with Pedicle Screws, Multiple Iliac Screws and Wisconsin Spinal Wires in a Patient with Neurofibromatosis Scoliosis: A Case Report

    PubMed Central

    Kim, Woong-Beom; Park, Young-Seop; Park, Jong-Hwa

    2015-01-01

    A 54-year-old female with neurofibromatosis type 1 presented with progressing truncal shift owing to spinal deformity. On plain radiograph, the Cobb angle was 54 degree in coronal plane. Radiological examinations showed severe dystrophic change with dysplastic pedicles, bony scalloping, neural foraminal widening from dural ectasia. The patient underwent deformity correction and reconstruction surgery from the T9 to the pelvis using multiple iliac screws and Wisconsin interspinous segmental instrumentation by wiring due to maximize fixation points. The postoperative course was uneventful. One-year follow-up radiographs showed a successful curve correction with solid fusion. We report a case of pedicle dysplasia and dystrophic change treated by posterior segmental spinal instrumentation and fusion with help of multiple iliac screws and modified Wisconsin interspinous segmental wiring. PMID:26512279

  16. An Update on Neurofibromatosis Type 1: Not Just Café-au-Lait Spots, Freckling, and Neurofibromas. An Update. Part I. Dermatological Clinical Criteria Diagnostic of the Disease.

    PubMed

    Hernández-Martín, A; Duat-Rodríguez, A

    2016-01-01

    Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome and probably the one best known to dermatologists, who are generally the first physicians to suspect its diagnosis. Although the genetic locus of NF1 was identified on chromosome 17 in 1987, diagnosis of the disease is still mainly based on clinical observations and the diagnostic criteria of the National Institute of Health, dating from 1988. Cutaneous manifestations are particularly important because café-au-lait spots, freckling on flexural areas, and cutaneous neurofibromas comprise 3 of the 7 clinical diagnostic criteria. However, café-au-lait spots and freckling can also be present in other diseases. These manifestations are therefore not pathognomonic and are insufficient for definitive diagnosis in the early years of life. NF1 is a multisystemic disease associated with a predisposition to cancer. A multidisciplinary follow-up is necessary and dermatologists play an important role. PMID:26979265

  17. Transplacental induction of peripheral nervous tumor in the Syrian golden hamster by N-nitroso-N-ethylurea. A new animal model for von Recklinghausen's neurofibromatosis.

    PubMed Central

    Nakamura, T.; Hara, M.; Kasuga, T.

    1989-01-01

    Multiple peripheral nervous tumors were induced in 45 of 60 (75.0%) Syrian golden hamsters by transplacental administration of N-ethyl-N-nitro-sourea. Moreover, melanomas, pheochromocytomas, and Wilms' tumors developed in six (10.0%), three (5.0%), and 13 (21.7%) animals, respectively. The histologic, immunohistochemical, and electron microscopic findings of the peripheral nervous tumors were similar to those of human neurofibroma, and their growth pattern and distribution resembled those of human von Recklinghausen's neurofibromatosis (VRNF). The occurrence of melanoma, pheochromocytoma, and proliferative foci of melanin-containing cells in neurofibroma suggests that the targets of ENU in hamsters are the neural crest-derived cells. With its high incidence of Wilms' tumor, the hamster with ENU-induced tumors is considered to be a good animal model for human neurocristopathy, including VRNF. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2551169

  18. Aspergilosis cervical con diseminación al sistema nervioso central. Presentación de un caso y revisión de bibliografía

    PubMed Central

    Vergara, Guillermo Enrique; Roura, Natalia; del Castillo, Marcelo; Mora, Andrea; Alcorta, Santiago Condomi; Mormandi, Rubén; Cervio, Andrés; Salvat, Jorge

    2015-01-01

    Introducción: la Aspergilosis Invasiva (AI) del Sistema Nervioso Central (SNC) es infrecuente y ocurre generalmente en pacientes inmunocomprometidos. Puede presentarse con cuadros de meningitis, aneurismas micóticos, infartos o abscesos. Es una infección con pronóstico reservado y puede afectar el SNC de forma primaria o secundaria a partir de un foco que se disemina por vía hematógena. Presentamos el caso de un paciente con AI con invasión primaria a nivel óseo y diseminación posterior al cerebro. Caso clínico: Paciente masculino de 25 años con diagnóstico de leucemia linfática aguda en tratamiento quimioterápico que presentó neumonitis por metotrexate por lo que inicia tratamiento con corticoides. Posteriormente agregó cervicalgia y con el diagnóstico de osteomielitis cervical se realiza punción bajo tomografía computada (TC) sin aislarse gérmenes. Se colocó Halo Vest e inició tratamiento antibiótico empírico. Posteriormente presentó afasia de expresión secundaria a lesión frontal izquierda. Se realizó evacuación de absceso cerebral aislando A. fumigatus. El tratamiento antibiótico específico posterior permitió una buena respuesta clínica y radiológica. Conclusión: La presencia de lesiones en el SNC de pacientes inmunocomprometidos debe incluir a las micosis como diagnóstico diferencial. La evacuación quirúrgica permite llegar rápidamente al diagnóstico mejorando la respuesta posterior al tratamiento antibiótico. Para evaluar la respuesta terapéutica y posibles recaídas se debe realizar un seguimiento periódico clínico radiológico. Palabras clave: Aspergilosis cerebral; Aspergilosis cervical; Aspergilosis invasiva; Voriconazol. PMID:26600985

  19. Learning about Neurofibromatosis

    MedlinePlus

    ... to as bilateral acoustic NF, central NF or vestibular NF, occurs less frequently- 1 in 40,000 ... on the eighth cranial nerves and on the vestibular nerves. These tumors often cause pressure on the ...

  20. Neurofibromatosis (For Parents)

    MedlinePlus

    ... A person with NF2 almost always has bilateral vestibular schwannomas, which are non-cancerous tumors affecting the ... NF2, they don’t develop tumors on the vestibular nerves of the ear and lose their hearing. ...

  1. Synthetic slings: pros and cons.

    PubMed

    Staskin, David R; Plzak, Louis

    2002-10-01

    Historically, the choice of sling material for the treatment of urinary incontinence has been based on the surgeon's preference and experience. In general, pelvic surgeons have not differentiated artificial graft materials by their inherent qualities or for biocompatibility in the female pelvis and vaginal wall. The introduction of new artificial graft materials and new methods of implantation for the correction of genuine stress incontinence has generated renewed interest in the "pros and cons" associated with nonabsorbable material use. In this review, we discuss and differentiate sling materials and techniques. We consider some of the physical and biologic qualities of artificial graft materials, present theories and practices associated with the successful use of permanent grafts, and discuss the natural evolution of artificial graft slings to the current use of the tension-free vaginal tape and Suprapubic Arc Sling System (American Medical Systems, Minneapolis, MN). PMID:12354353

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

    PubMed

    Wang, Tiantian; de Kok, Laura; Willemsen, Rob; Elgersma, Ype; Borst, J Gerard G

    2015-01-01

    Defects in the rat sarcoma viral oncogene homolog (Ras)/extracellular-signal-regulated kinase and the phosphatidylinositol 3-kinase-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 complex (TSC), Fragile X syndrome (FXS), Neurofibromatosis type 1 (NF1), and Costello syndrome. 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 WT 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. PMID:26190969

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

    PubMed Central

    Wang, Tiantian; de Kok, Laura; Willemsen, Rob; Elgersma, Ype; Borst, J. Gerard G.

    2015-01-01

    Defects in the rat sarcoma viral oncogene homolog (Ras)/extracellular-signal-regulated kinase and the phosphatidylinositol 3-kinase-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 complex (TSC), Fragile X syndrome (FXS), Neurofibromatosis type 1 (NF1), and Costello syndrome. 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 WT 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. PMID:26190969

  4. Ewing-like sarcoma with CIC-DUX4 gene fusion in a patient with neurofibromatosis type 1. A hitherto unreported association.

    PubMed

    Tardío, Juan C; Machado, Isidro; Navarro, Lara; Idrovo, Franklin; Sanz-Ortega, Julián; Pellín, Antonio; Llombart-Bosch, Antonio

    2015-11-01

    Sarcoma with CIC-DUX4 gene fusion is emerging as the most prevalent subset of Ewing-like undifferentiated small round cell sarcomas with around 50 cases published. We report hereby the case of a 40-year-old male who presented a CIC-DUX4 sarcoma in deep soft tissues in his thigh. He had been diagnosed with neurofibromatosis type 1 at age 19 and over the years underwent resection of multiple neural neoplasms, including two malignant peripheral nerve sheath tumors with classical spindle-cell histopathology. The CIC-DUX4 sarcoma was treated with surgical resection, radiation and chemotherapy, but lung and brain metastases developed and the patient died from the disease 14 months after diagnosis. This is the first case of sarcoma with CIC-DUX4 gene fusion reported in a patient with NF1. Whether this association is coincidental or CIC-DUX4 sarcomas could be related to NF1 remains to be clarified. Study of alternative molecular alterations in EWSR1-negative undifferentiated small round cell sarcomas is clinically relevant, since CIC-DUX4 sarcomas seem to be a very aggressive subset with poor response to the presently used therapeutic regimens. PMID:26386605

  5. Mitotic recombination and compound-heterozygous mutations are predominant NF1-inactivating mechanisms in children with juvenile myelomonocytic leukemia and neurofibromatosis type 1.

    PubMed

    Steinemann, Doris; Arning, Larissa; Praulich, Inka; Stuhrmann, Manfred; Hasle, Henrik; Stary, Jan; Schlegelberger, Brigitte; Niemeyer, Charlotte M; Flotho, Christian

    2010-02-01

    Children with neurofibromatosis type 1 (NF-1), being constitutionally deficient for one allele of the NF1 gene, are at greatly increased risk of juvenile myelomonocytic leukemia (JMML). NF1 is a negative regulator of RAS pathway activity, which has a central role in JMML. To further clarify the role of biallelic NF1 gene inactivation in the pathogenesis of JMML, we investigated the somatic NF1 lesion in 10 samples from children with JMML/NF-1. We report that two-thirds of somatic events involved loss of heterozygosity (LOH) at the NF1 locus, predominantly caused by segmental uniparental disomy of large parts of chromosome arm 17q. One-third of leukemias showed compound-heterozygous NF1-inactivating mutations. A minority of cases exhibited somatic interstitial deletions. The findings reinforce the emerging role of somatic mitotic recombination as a leukemogenic mechanism. In addition, they support the concept that biallelic NF1 inactivation in hematopoietic progenitor cells is required for transformation to JMML in children with NF-1. PMID:20015894

  6. Neurofibromatosis type 1 molecular diagnosis: what can NGS do for you when you have a large gene with loss of function mutations?

    PubMed Central

    Pasmant, Eric; Parfait, Béatrice; Luscan, Armelle; Goussard, Philippe; Briand-Suleau, Audrey; Laurendeau, Ingrid; Fouveaut, Corinne; Leroy, Chrystel; Montadert, Annelore; Wolkenstein, Pierre; Vidaud, Michel; Vidaud, Dominique

    2015-01-01

    Molecular diagnosis of neurofibromatosis type 1 (NF1) is challenging owing to the large size of the tumour suppressor gene NF1, and the lack of mutation hotspots. A somatic alteration of the wild-type NF1 allele is observed in NF1-associated tumours. Genetic heterogeneity in NF1 was confirmed in patients with SPRED1 mutations. Here, we present a targeted next-generation sequencing (NGS) of NF1 and SPRED1 using a multiplex PCR approach (230 amplicons of ∼150 bp) on a PGM sequencer. The chip capacity allowed mixing 48 bar-coded samples in a 4-day workflow. We validated the NGS approach by retrospectively testing 30 NF1-mutated samples, and then prospectively analysed 279 patients in routine diagnosis. On average, 98.5% of all targeted bases were covered by at least 20X and 96% by at least 100X. An NF1 or SPRED1 alteration was found in 246/279 (88%) and 10/279 (4%) patients, respectively. Genotyping throughput was increased over 10 times, as compared with Sanger, with ∼90€ for consumables per sample. Interestingly, our targeted NGS approach also provided quantitative information based on sequencing depth allowing identification of multiexons deletion or duplication. We then addressed the NF1 somatic mutation detection sensitivity in mosaic NF1 patients and tumours. PMID:25074460

  7. Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1.

    PubMed

    McPherson, John Richard; Ong, Choon-Kiat; Ng, Cedric Chuan-Young; Rajasegaran, Vikneswari; Heng, Hong-Lee; Yu, Willie Shun-Shing; Tan, Benita Kiat-Tee; Madhukumar, Preetha; Teo, Melissa Ching-Ching; Ngeow, Joanne; Thike, Aye-Aye; Rozen, Steven George; Tan, Puay-Hoon; Lee, Ann Siew-Gek; Teh, Bin-Tean; Yap, Yoon-Sim

    2015-12-01

    Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by the development of multiple neurofibromas, cafe-au-lait spots, and Lisch nodules. Individuals with NF1 are at increased risk of developing various tumors, such as malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, leukemia, glioma, rhabdomyosarcoma, and breast cancer. Here, we describe the exome sequencing of breast cancer, MPNST, and neurofibroma from a patient with NF1. We identified a germline mutation in the NF1 gene which resulted in conversion of leucine to proline at amino acid position 847. In addition, we showed independent somatic NF1 mutations in all the three tumors (frameshift insertion in breast cancer (p.A985fs), missense mutation in MPNST (p.G23R), and inframe deletion in dermal neurofibroma (p.L1876del-Inf)), indicating that a second hit in NF1 resulting in the loss of function could be important for tumor formation. Each tumor had a distinct genomic profile with mutually exclusive mutations in different genes. Copy number analysis revealed multiple copy number alterations in the breast cancer and the MPNST, but not the benign neurofibroma. Germline loss of chromosome 6q22.33, which harbors two potential tumor suppressor genes, PTPRK and LAMA2, was also identified; this may increase tumor predisposition further. In the background of NF1 syndrome, although second-hit NF1 mutation is critical in tumorigenesis, different additional mutations are required to drive the formation of different tumors. PMID:26432421

  8. Induction of apoptosis in Neurofibromatosis Type 1 malignant peripheral nerve sheath tumor cell lines by a combination of novel farnesyl transferase inhibitors and lovastatin

    PubMed Central

    Wojtkowiak, Jonathan W.; Fouad, Farid; LaLonde, Daniel T.; Kleinman, Miriam D.; Gibbs, Richard A.; Reiners, John J.; Borch, Richard F.; Mattingly, Raymond R.

    2013-01-01

    Neurofibromatosis Type 1 (NF1) is a genetic disorder that is driven by the loss of neurofibromin (Nf) protein function. Nf contains a Ras GTPase activating domain (Ras-GAP), which directly regulates Ras signaling. Numerous clinical manifestations are associated with the loss of Nf and increased Ras activity. Ras proteins must be prenylated in order to traffic and functionally localize with target membranes. Hence, Ras is a potential therapeutic target for treating NF1. We have tested the efficacy of two novel farnesyl transferase inhibitors (FTI), 1 and 2, alone or in combination with lovastatin, on two NF1 malignant peripheral nerve sheath tumor (MPSNT) cell lines, NF90-8 and ST88-14. Single treatments of 1, 2, or lovastatin had no effect on MPNST cell proliferation. However, low micromolar combinations of 1 or 2 with lovastatin (FTI/lovastatin) reduced Ras prenylation in both MPNST cell lines. Further, this FTI/lovastatin combination treatment reduced cell proliferation and induced an apoptotic response as shown by morphological analysis, pro-caspase-3/-7 activation, loss of mitochondrial membrane potential, and accumulation of cells with sub G1 DNA content. Little to no detectable toxicity was observed in normal rat Schwann cells following FTI/lovastatin combination treatment. These data support the hypothesis that combination FTI plus lovastatin therapy may be a potential treatment for NF1 MPNSTs. PMID:18367665

  9. RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth1

    PubMed Central

    Solga, Anne C.; Pong, Winnie W.; Kim, Keun-Young; Cimino, Patrick J.; Toonen, Joseph A.; Walker, Jason; Wylie, Todd; Magrini, Vincent; Griffith, Malachi; Griffith, Obi L.; Ly, Amy; Ellisman, Mark H.; Mardis, Elaine R.; Gutmann, David H.

    2015-01-01

    Solid cancers develop within a supportive microenvironment that promotes tumor formation and growth through the elaboration of mitogens and chemokines. Within these tumors, monocytes (macrophages and microglia) represent rich sources of these stromal factors. Leveraging a genetically engineered mouse model of neurofibromatosis type 1 (NF1) low-grade brain tumor (optic glioma), we have previously demonstrated that microglia are essential for glioma formation and maintenance. To identify potential tumor-associated microglial factors that support glioma growth (gliomagens), we initiated a comprehensive large-scale discovery effort using optimized RNA-sequencing methods focused specifically on glioma-associated microglia. Candidate microglial gliomagens were prioritized to identify potential secreted or membrane-bound proteins, which were next validated by quantitative real-time polymerase chain reaction as well as by RNA fluorescence in situ hybridization following minocycline-mediated microglial inactivation in vivo. Using these selection criteria, chemokine (C-C motif) ligand 5 (Ccl5) was identified as a chemokine highly expressed in genetically engineered Nf1 mouse optic gliomas relative to nonneoplastic optic nerves. As a candidate gliomagen, recombinant Ccl5 increased Nf1-deficient optic nerve astrocyte growth in vitro. Importantly, consistent with its critical role in maintaining tumor growth, treatment with Ccl5 neutralizing antibodies reduced Nf1 mouse optic glioma growth and improved retinal dysfunction in vivo. Collectively, these findings establish Ccl5 as an important microglial growth factor for low-grade glioma maintenance relevant to the development of future stroma-targeted brain tumor therapies. PMID:26585233

  10. NF1 frameshift mutation (c.6520_6523delGAGA) association with nervous system tumors and bone abnormalities in a Chinese patient with neurofibromatosis type 1.

    PubMed

    Su, S Y; Zhou, X; Pang, X M; Chen, C Y; Li, S H; Liu, J L

    2016-01-01

    Neurofibromatosis type 1, also known as NF1 or von Recklinghausen's disease, is a common neurocutaneous syndrome that presents with multiple café-au-lait patches, skinfold freckling, dermatofibromas, neurofibromas, and Lisch nodules. The mutations of the gene NF1, encoding the protein neurofibromin, have been identified as the cause of this disease. Here, we report a clinical and molecular study of a Chinese patient with multiple café-au-lait skin freckles, dermatofibroma, central and peripheral nervous system tumors, and bone abnormalities attributed to NF1. The patient showed >6 café-au-lait spots on the body and multiple dermatofibromas. A brain glioma and multiple nerve sheath tumors inside and outside the vertebral canal were identified by magnetic resonance imaging, which also showed multiple intercostal nerve schwannomas and hydrocephalies above the cerebellar tentorium. Talipes equinus was also apparent. A mutation analysis of the NF1 gene revealed a novel frameshift mutation in exon 43, consisting of a heterozygous deletion of four nucleotides (GAGA) between positions 6520 and 6523. No NF1 mutations were detected in the patient's parents or younger brother. These results extend the list of known mutations in this gene. The absence of the NF1 mutation in the healthy family members suggests that it is responsible for the NF1 phenotype. To our knowledge, this frameshift mutation represents a novel NF1 case, and may be associated with nervous system tumors and bone abnormalities. PMID:27173220

  11. Sarcoma de tejido blando—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del sarcoma de tejido blando, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados con este tipo de cáncer.

  12. Tumores cerebrales—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento de los tumores cerebrales, así como referencias a estudios clínicos, estadísticas y otros temas relacionados con estos tipos de cáncer.

  13. Mesotelioma maligno—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento y las causas del mesotelioma maligno, así como referencias a estudios clínicos y otros temas relacionados con este tipo de cáncer.

  14. A cytogenetic deletion, del(17)(q11.22q21.1), in a patient with sporadic neurofibromatosis type 1 (NF1) associated with dysmorphism and developmental delay.

    PubMed Central

    Upadhyaya, M; Roberts, S H; Maynard, J; Sorour, E; Thompson, P W; Vaughan, M; Wilkie, A O; Hughes, H E

    1996-01-01

    We report the first visible cytogenetic deletion involving the NF1 gene in a patient with sporadic neurofibromatosis, dysmorphic features, and marked developmental delay. The combined evidence of molecular and cytogenetic techniques based on dosage reduction, hemizygosity for microsatellite markers, high resolution G banding, and FISH analysis, predicts this deletion to be approximately 7 Mb in size. Our findings highlight the importance of conducting a detailed cytogenetic and FISH analysis in patients with NF1 who have additional dysmorphic features or particularly severe learning difficulties. Images PMID:8929953

  15. Etapa final de la vida (PDQ®)—Versión para pacientes

    Cancer.gov

    Sumario informativo revisado por expertos sobre el tratamiento y la atención del paciente de cáncer desde los últimos días hasta las últimas horas de vida; esto incluye los síntomas comunes, los dilemas éticos que pueden surgir y la función que desempeña el oncólogo en proveer cuidados al paciente y su familia durante este período.

  16. Pain interference in youth with neurofibromatosis type 1 and plexiform neurofibromas and relation to disease severity, social-emotional functioning, and quality of life.

    PubMed

    Wolters, Pamela L; Burns, Katherine M; Martin, Staci; Baldwin, Andrea; Dombi, Eva; Toledo-Tamula, Mary Anne; Dudley, William N; Gillespie, Andrea; Widemann, Brigitte C

    2015-09-01

    The physical manifestations of neurofibromatosis type 1 (NF1) can cause chronic pain. This study investigated the impact of pain in youth with NF1 and plexiform neurofibromas (PNs) and its relationship to disease factors, social-emotional functioning, and quality of life (QOL) within a biopsychosocial framework. Caregivers of 59 children and adolescents with NF1 and PNs (6-18 years), and 41 of these youth (10-18 years), completed questionnaires assessing social-emotional functioning and QOL, including an item on pain interference. Measures of disease severity included total PN volume by percent body weight and number of disease complications. Both caregiver (73%) and self-report (59%) ratings indicated that pain interferes with the child's daily functioning despite 33% taking pain medication. Based on caregivers' behavior ratings, more symptoms of anxiety and larger tumor volumes predicted greater pain interference, while greater pain interference, worse depressive symptoms, and more disease complications predicted poorer QOL. As rated by adolescents, more symptoms of anxiety predicted greater pain interference, while greater pain interference and social stress predicted poorer QOL. Further, social-emotional problems mediate the relationship between pain interference and QOL. Thus, pain interferes with daily functioning in the majority of youth with NF1 and PNs even when using pain medication. The impact of pain interference, disease severity, and particularly social-emotional problems on QOL highlights the interaction between physical and psychological states in NF1. Future research and treatment of pain in this population should utilize a biopsychosocial approach and involve multidisciplinary therapies including psychological interventions that target social-emotional functioning. PMID:25976979

  17. Nerve Sheath Tumors in Neurofibromatosis Type 1: Assessment of Whole-Body Metabolic Tumor Burden Using F-18-FDG PET/CT

    PubMed Central

    Salamon, Johannes; Papp, László; Tóth, Zoltán; Laqmani, Azien; Apostolova, Ivayla; Adam, Gerhard; Mautner, Victor F.; Derlin, Thorsten

    2015-01-01

    Purpose To determine the metabolically active whole-body tumor volume (WB-MTV) on F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) in individuals with neurofibromatosis type 1 (NF1) using a three-dimensional (3D) segmentation and computerized volumetry technique, and to compare PET WB-MTV between patients with benign and malignant peripheral nerve sheath tumors (PNSTs). Patients and Methods Thirty-six NF1 patients (18 patients with malignant PNSTs and 18 age- and sex-matched controls with benign PNSTs) were examined by F-18-FDG PET/CT. WB-MTV, whole-body total lesion glycolysis (WB-TLG) and a set of semi-quantitative imaging-based parameters were analyzed both on a per-patient and a per-lesion basis. Results On a per-lesion basis, malignant PNSTs demonstrated both a significantly higher MTV and TLG than benign PNSTs (p < 0.0001). On a per-patient basis, WB-MTV and WB-TLG were significantly higher in patients with malignant PNSTs compared to patients with benign PNSTs (p < 0.001). ROC analysis showed that MTV and TLG could be used to differentiate between benign and malignant tumors. Conclusions WB-MTV and WB-TLG may identify malignant change and may have the potential to provide a basis for investigating molecular biomarkers that correlate with metabolically active disease manifestations. Further evaluation will determine the potential clinical impact of these PET-based parameters in NF1. PMID:26625155

  18. An autopsy case of superficial siderosis of the central nervous system accompanied by anterior sacral polycystic meningocele in neurofibromatosis type 1.

    PubMed

    Matsumoto, Arifumi; Suzuki, Hiroyoshi; Tobita, Muneshige; Hisanaga, Kinya

    2016-07-28

    A 74-year-old female patient, who was diagnosed with neurofibromatosis type 1 (NF1) at the age of 40, was admitted with complaints of flickering vision and gait disturbance for the last 2 years. On admission, neurological examination revealed mild bilateral hearing loss and ataxia in the limb and trunk. Laboratory tests revealed anti-hepatitis C virus (HCV) antibody positivity and elevated HCV RNA by real-time polymerase chain reaction. The cerebrospinal fluid examination revealed a slightly yellowish appearance with elevated total protein levels. Gradient echo T2*-weighted brain magnetic resonance imaging (MRI) demonstrated a rim of hypointense lesions surrounding the surface of the cerebellum, brainstem, frontal and temporal lobes, and thalamus, which was considered as hemosiderin depositions. From these MRI findings, she was diagnosed as having superficial siderosis of the central nervous system. Cerebral angiography revealed an aneurysm-like dilatation at the bifurcation of the right internal carotid-posterior communicating artery. (99m)Tc-ethyl cysteinate dimer single-photon emission computed tomography revealed hypoperfusion in the bilateral frontal and temporal lobes. Pelvic plain X-ray, pelvic computed tomography, and lumbosacral MRI revealed a sacral defect and an anterior sacral polycystic meningocele communicating with the spinal subarachnoid space. The patient's symptoms gradually worsened, and she died of septic shock because of pyelonephritis at the age of 77. An autopsy was performed; on pathological examination, we did not observe any findings associated with rupture of the aneurysm-like dilatation in the bifurcation of the right internal carotid-posterior communicating artery and cerebral amyloid angiopathy. Because duropathies-a new neurological disease concept-have been implicated as a cause of bleeding in the superficial siderosis, the anterior sacral polycystic meningocele, a type of duropathies, was presumed to be the most probable bleeding

  19. The course of cognitive-behavioral development in children with the FMR1 mutation, Williams-Beuren syndrome, and neurofibromatosis type 1: The effect of gender.

    PubMed

    Fisch, Gene S; Carpenter, Nancy; Howard-Peebles, Patricia N; Holden, Jeanette J A; Tarleton, Jack; Simensen, Richard

    2010-06-01

    The course of cognitive-behavioral development in children with intellectual disabilities produced by genetic disorders has only recently begun to be examined systematically. Unfortunately, these studies are few in number. Previously, we examined cognitive-behavioral development in children with the fragile X (FMR1) mutation and found longitudinal decreases in both IQ and adaptive behavior (DQ) scores in most males and females with the full mutation. In this study, we examine longitudinal changes in IQ and DQ in children with neurofibromatosis type 1 (NF1) and Williams-Beuren Syndrome (WBS) by examining differences in composite IQ and DQ scores between the first test (T1) and retest (T2), and compare their developmental trajectory to children with the FMR1 mutation. Sixty-five children with the FMR1 mutation, or NF1, or WBS, ages 4-16 years, were retested two years after initial testing with the Stanford-Binet 4th Edition (SBFE) and the Vineland Adaptive Behavior Scale (VABS). In addition to significant longitudinal declines in IQ and DQ noted previously in children with the FMR1 mutation, we found significant decreases in IQ in males compared to females in the remainder of our sample. We also observed statistically significant decreases in DQ scores among children the FMR1 mutation, as noted previously, but not among children with NF1 or WBS. Moreover, significant declines were found only among males with the FMR1 mutation. Unlike declines in IQ scores, decreases in DQ were not significantly different between males and females. PMID:20503326

  20. Neurofibromatosis 2 (NF2) controls the invasiveness of glioblastoma through YAP-dependent expression of CYR61/CCN1 and miR-296-3p.

    PubMed

    Lee, Hong; Hwang, Su Jin; Kim, Hye Ree; Shin, Chang Hoon; Choi, Kyung Hee; Joung, Je-Gun; Kim, Hyeon Ho

    2016-04-01

    Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor derived from non-neuronal glial cells. Neurofibromatosis 2 (NF2) protein, also termed as merlin, is a well-known tumor suppressor; however, the molecular mechanism underlying this effect has not yet been fully defined. To investigate the role of NF2 in the invasiveness of GBM, we used two GBM cell lines: NF2-expressing T98G cells and NF2-deficient A172 cells. Knockdown of NF2 increased the invasiveness of T98G cells, whereas NF2-overexpressing A172 cells showed decreased invasive activity. Moreover, re-expression of NF2 reversed the high invasiveness of NF2-silenced T98G cells, indicating that NF2 negatively regulates GBM invasiveness. We further found that the NF2-mediated regulation of invasiveness was dependent on YAP and TEAD2 expression levels. NF2 also controlled the expression of YAP targets, including cysteine-rich angiogenic inducer 61 (CYR61/CCN1), by regulating the nuclear localization of YAP. Silencing of CYR61/CCN1 blocked the increased invasiveness of T98G cells, suggesting that CYR61/CCN1 is required for NF2-mediated invasiveness. Through microRNA microarray analysis, we found that NF2 negatively regulates the expression of miR-296-3p. Overexpression of miR-296-3p suppressed the expression of STAT5A, induced the phosphorylation of STAT3 by downregulating SOCS2, and increased the invasiveness of T98G cells. Taken together, we demonstrate that NF2 negatively controls the invasiveness of GBM through YAP-dependent induction of CYR61/CCN1 and miR-296-3p. PMID:26923924

  1. Intracerebral malignant peripheral nerve sheath tumor in a child with neurofibromatosis Type 1 and middle cerebral artery aneurysm treated with endovascular coil embolization.

    PubMed

    Ellis, Michael J; Cheshier, Samuel; Sharma, Sunjay; Armstrong, Derek; Hawkins, Cynthia; Bouffet, Eric; Rutka, James T; Taylor, Michael D

    2011-10-01

    Among the neoplastic conditions that affect patients with neurofibromatosis Type 1 (NF1) are malignant peripheral nerve sheath tumors (MPNSTs), which typically arise from peripheral nerves of the limbs, trunk, and lumbar and brachial plexuses. Ionizing radiation is an established risk factor for MPNST development, especially in susceptible patients such as those with NF1. Patients with NF1 are also at risk for intracranial aneurysms, which are increasingly being successfully managed with endovascular therapies. The authors describe the case of a 9-year-old, previously healthy girl who presented in extremis with a right frontal intracerebral hemorrhage resulting from a ruptured right middle cerebral artery (MCA) trifurcation aneurysm. Following urgent decompressive craniectomy, the patient underwent endovascular coil embolization of the MCA aneurysm without complication. Given her mother's history of NF1, the child underwent genetic testing, which disclosed signs positive for NF1. The patient recovered well, but follow-up MR imaging and MR angiography performed at 14 months demonstrated a large frontotemporal mass encasing the right MCA trifurcation. The patient underwent frontotemporal craniotomy and subtotal resection of the mass, which was histologically found to be an intracranial MPNST. The patient received chemotherapy and focal radiation therapy and remains alive at 6 months postresection. To the authors' knowledge, this represents the only known case of intracranial neoplasm arising in the region of an intracranial aneurysm repaired by endovascular coil embolization. While patients with NF1 represent a population with genetic susceptibility to radiation-induced tumors, the pathogenesis of intracerebral MPNSTs remains poorly understood. PMID:21961539

  2. Acceptance and commitment therapy in youth with neurofibromatosis type 1 (NF1) and chronic pain and their parents: A pilot study of feasibility and preliminary efficacy.

    PubMed

    Martin, Staci; Wolters, Pamela L; Toledo-Tamula, Mary Anne; Schmitt, Shawn Nelson; Baldwin, Andrea; Starosta, Amy; Gillespie, Andrea; Widemann, Brigitte

    2016-06-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder affecting about 1 in 3,500 individuals. Chronic pain is commonly reported among individuals with NF1 and plexiform neurofibroma tumors (PNs). Acceptance and Commitment Therapy (ACT), an empirically supported method for addressing chronic pain, helps individuals re-focus on valued relationships and activities. This pilot study investigated the feasibility and preliminary efficacy of a brief ACT workshop in the NF1 population. Eligible participants included adolescents and young adults (AYA; 12-21 years) with NF1 and chronic pain that interfered with daily functioning and their parents. Patients and parents completed baseline measures of pain interference, pain intensity, functional disability, pain acceptance, depression, and anxiety. Then, AYA and parents participated separately in a 2-day small-group ACT workshop. A telephone booster session occurred 1 month post-intervention. Three-month post-treatment measures were completed by mail. Ten adolescents (4 males; M age = 16.9 years) and seven parents provided baseline and 3-month data. Mean satisfaction with the study was moderate to high (3.9 for patients and 4.6 for parents on a 1-5 scales). Patients and parents reported significant declines in patients' pain interference at 3 months post-treatment. Patient-reported pain intensity significantly declined from baseline to 3 months. Parents reported marginally greater acceptance of their child's pain. No changes emerged in functional ability or mood. Preliminary findings suggest that a brief ACT group intervention is feasible and may help AYA with NF1 and PNs cope with their chronic pain, although larger randomized studies are needed to confirm treatment efficacy. © 2016 Wiley Periodicals, Inc. PMID:27021207

  3. La salud en personas con discapacidad intelectual en España: estudio europeo POMONA-II

    PubMed Central

    Martínez-Leal, Rafael; Salvador-Carulla, Luis; Gutiérrez-Colosía, Mencía Ruiz; Nadal, Margarida; Novell-Alsina, Ramón; Martorell, Almudena; González-Gordón, Rodrigo G.; Mérida-Gutiérrez, M. Reyes; Ángel, Silvia; Milagrosa-Tejonero, Luisa; Rodríguez, Alicia; García-Gutiérrez, Juan C.; Pérez-Vicente, Amado; García-Ibáñez, José; Aguilera-Inés, Francisco

    2011-01-01

    Introducción Estudios internacionales demuestran que existe un patrón diferenciado de salud y una disparidad en la atención sanitaria entre personas con discapacidad intelectual (DI) y población general. Objetivo Obtener datos sobre el estado de salud de las personas con DI y compararlos con datos de población general. Pacientes y métodos Se utilizó el conjunto de indicadores de salud P15 en una muestra de 111 sujetos con DI. Los datos de salud encontrados se compararon según el tipo de residencia de los sujetos y se utilizó la Encuesta Nacional de Salud 2006 para comparar estos datos con los de la población general. Resultados La muestra con DI presentó 25 veces más casos de epilepsia y el doble de obesidad. Un 20% presentó dolor bucal, y existió una alta presencia de problemas sensoriales, de movilidad y psicosis. Sin embargo, encontramos una baja presencia de patologías como la diabetes, la hipertensión, la osteoartritis y la osteoporosis. También presentaron una menor participación en programas de prevención y promoción de la salud, un mayor número de ingresos hospitalarios y un uso menor de los servicios de urgencia. Conclusiones El patrón de salud de las personas con DI difiere del de la población general, y éstas realizan un uso distinto de los servicios sanitarios. Es importante el desarrollo de programas de promoción de salud y de formación profesional específicamente diseñados para la atención de personas con DI, así como la implementación de encuestas de salud que incluyan datos sobre esta población. PMID:21948011

  4. Galaxias australes con núcleo doble

    NASA Astrophysics Data System (ADS)

    Gimeno, G.; Díaz, R.; Carranza, G.

    Se estudia una muestra de galaxias australes con núcleo doble a partir de una búsqueda extensiva en la literatura. Se analizan las características morfológicas, fotométricas y espectroscópicas de la muestra. Para algunas galaxias se han realizado observaciones con el espectrógrafo multifunción (EMF) de la Estación Astrofísica de Bosque Alegre a partir de las cuales se determinaron parámetros cinemáticos.

  5. High-grade spondyloretrolisthesis in a 12-year-old girl with neurofibromatosis type 1: a case report and literature review.

    PubMed

    Martín-Fuentes, Ana María; Pretell-Mazzini, Juan; Curto de la Mano, Angel; Viña-Fernández, Rafael

    2013-03-01

    Neurofibromatosis (NF) type 1 is characterized by several skin, endocrine, central nervous system and musculoskeletal manifestations, spine deformities being the most common, affecting up to 64% of patients. Thoracic kyphoscoliosis is the most common deformity observed; however, high-grade spondylolisthesis and dural defects such as dural ectasia can also be found. The aim of this study is to describe a case of high-grade spondyloretrolisthesis in an NF-1 patient, associated with dural ectasia and extensive lumbar laminectomies, and to discuss our management and review the current literature on this controversial topic. A 12-year-old girl with NF-1 who had undergone extensive lumbar laminectomies in an outside facility presented to our emergency department complaining of back pain and lower limbs upper motor neuron symptoms. Image studies showed a high-grade lumbar spondyloretrolisthesis associated with dural ectasia. The first step of treatment was spine immobilization using a Boston brace. An anterior approach was used, and an L2 corporectomy was performed, using a Moss type cage between L1 and L3 with an instrumented arthrodesis and autologous bone graft for stabilization purposes. The second step planned was a posterior approach for arthrodesis and instrumentation, but after an extensive discussion with the parents and the patient, the parents did not agree to the procedure planned for the patient. A brace was used for 1 year while rehabilitation was performed. At the 1-year follow-up, there was a 70° kyphosis at the thoracolumbar junction but it was clinically stable, with an acceptable sagittal balance. Dural ectasia is not a common finding in children with NF-1; however, it should be identified as its presence may predispose to spine instability and as a consequence the development of a high-grade spondyloretrolisthesis. Even though a few cases have been reported, we believe that it is important to consider the option of a double approach to achieve a

  6. Multidetector CT with 3-dimensional volume rendering in the evaluation of the spine in patients with Neurofibromatosis type 1: a retrospective review in 73 patients

    PubMed Central

    2014-01-01

    Introduction Neurofibromatosis type 1 (NF-1) may involve the spine as various abnormalities including bony dysplasia, scoliosis, and nerve sheath tumors. Surgery may be performed for stabilization of the spine. We have seen an increase in requests for multidetector CT (MDCT) imaging with the (three-dimensional) 3D-volume rendered (VR) images in patients evaluated at our institution. We, therefore, investigated how MDCT could be best utilized in this patient population. Methods Seventy-three patients with NF-1 were identified in whom MDCT imaging was performed for diagnostic, pre-operative, or post-operative evaluation of spinal abnormalities. True axial source images and two dimensional (2D) orthogonal reconstructed MDCT images, as well as the VR images, were compared with plain radiographs and MRI. In addition, the MDCT study was compared to the VR images. These studies were reviewed to compare assessment of A) bony abnormalities such as remodeling from dural ectasia, dysplasia, and fusion, B) abnormal spinal curvature, C) nerve sheath tumors, and D) surgical instrumentation. Results When compared to plain radiographs, the MDCT and VR images were rated as helpful for evaluating the abnormalities of the spine in 19 of 24 patients for a total of 30 findings. This included the following categories A) (n = 6), B) (n = 5), C) (n = 7), and D) (n = 12). Compared to MR, the MDCT and VR study was helpful in evaluating the findings of NF-1 in 24 of 36 patients for a total of 40 findings. This included the following categories A) (n = 12), B) (n = 10), C) (n = 3), and D) (n = 15). When the VR images were compared to the orthogonal MDCT, the VR images was rated as helpful in 41 of 73 patients for a total of 60 findings, including the following categories: A) (n = 11), B) (n = 24), C) (n = 0), and D) (n = 25). Conclusion MDCT has distinct advantages over plain radiographs and MR imaging, and the VR images over MDCT in the

  7. Characterization of spinal findings in children and adults with neurofibromatosis type 1 enrolled in a natural history study using magnetic resonance imaging.

    PubMed

    Nguyen, Rosa; Dombi, Eva; Akshintala, Srivandana; Baldwin, Andrea; Widemann, Brigitte C

    2015-01-01

    To characterize spinal abnormalities in patients with neurofibromatosis type 1 (NF1) using magnetic resonance imaging (MRI). NF1 patients with at least one spine MRI were selected from participants prospectively enrolled in the National Cancer Institute NF1 Natural History Study. Data were analyzed retrospectively. Ninety-seven patients (38 females, median age 14.2 years, standard deviation [SD] 7.6) had baseline imaging of the spine, and 26 patients (27 %) had one follow-up spine MRI (follow up time 2.5 years, SD 1.1, range 0.7-4.7). Seventy-eight patients (80 %) had spinal neurofibromas, with rising frequency from 70 % in patients younger than 10 years to 80 % in patients aged 10-18 years to 89 % in individuals older than 18 years of age. At baseline, 33/97 patients (34 %) had MRI changes consistent with spinal cord compression that was most prevalent at the cervical (43 %) and lumbar spine region (40 %). Seven of nine patients with progression of their spinal neurofibromas developed cord compression. Paraspinal plexiform neurofibromas (PNs) were present in 77/97 patients (79 %), of which 68 patients (88 %) had concomitant spinal neurofibromas. Spinal curvature abnormality was present in 50/97 patients (51 %, 20 females, median age 14.6 years, SD 7.6). Patients with paraspinal PNs had six-fold higher odds of developing spinal curvature abnormalities compared to patients without PN (OR = 5.9, 95 % CI 1.81 to 19.44, p = 0.0033). A total of 58/97 patients (60 %, median age 16.1 years, SD 7.8, range 4.8-48.2 years) presented with neurologic abnormalities that progressed in 12/26 patients (46 %). Substantial spinal neurofibroma and paraspinal PN burden was observed in our study population, which represents a selective group of patients with specifically more severe tumor involvement than the general NF1 population. Occurrence and progression of spinal neurofibromas on repeat evaluations highlight the need for longitudinal clinical monitoring in patients with known

  8. Metabolic Tumour Burden Measured by 18F-FDG PET/CT Predicts Malignant Transformation in Patients with Neurofibromatosis Type-1

    PubMed Central

    Van Der Gucht, Axel; Zehou, Ouidad; Djelbani-Ahmed, Soraya; Valeyrie-Allanore, Laurence; Ortonne, Nicolas; Brugières, Pierre; Wolkenstein, Pierre; Luciani, Alain; Rahmouni, Alain; Sbidian, Emilie; Itti, Emmanuel

    2016-01-01

    Background To investigate the diagnostic and prognostic performances of 18F-FDG PET/CT measures of metabolic tumour burden in patients with neurofibromatosis type-1 (NF1), suspect of malignant transformation. Methods This retrospective study included 49 patients (15–60 years old, 30 women) with a diagnosis of NF1, followed in our Reference Centre for Rare Neuromuscular Diseases, who presented clinical signs of tumour progression (pain, neurological deficit, tumour growth). Quantitative metabolic parameters were measured on 149 tumoral targets, using semi-automatic software and the best cut off values to predict transformation was assessed by Receiver Operating Characteristics (ROC) analysis. Prognostic value of PET/CT metabolic parameters was assessed by Kaplan-Meier estimates of overall survival. Results Lesions were histologically documented in 40 patients: a sarcomatous transformation was found in 16, a dysplastic neurofibroma (NF) in 7, and a benign NF in 17; in the remaining 9 patients, a minimal follow-up of 12 mo (median 59 mo) confirmed the absence of transformation. The optimal cut off values for detection of malignant transformation were, in decreasing order of area under the ROC curves, a tumour-to-liver (T/L) ratio >2.5, SUVmax > 4.5, total lesion glycolysis (TLG) > 377, total metabolic tumour volume (TMTV) > 88 cm3, and heterogeneity index (HIsuv) > 1.69. The best prognostic marker was the TLG: the 4-y estimates of survival were 97% [95% CI, 90% - 100%] in patients with TLG ≤ 377 vs. 27% [95% CI, 5% - 49%] in patients with TLG > 377 (P < 0.0001; χ2 27.85; hazard ratio 13.27 [95% CI, 3.72–47.35]). T/L ratio, SUVmax and TMTV demonstrated slightly lower performance to predict survival, with χ2 ranging 14.41–19.12. The HIsuv index was not predictive of survival. Conclusion Our study demonstrates that TLG and TMTV, as PET/CT measures of metabolic tumour burden, may be used clinically to identify sarcomatous transformation in patients with NF1 and

  9. InterCon Travel Health: Case B

    ERIC Educational Resources Information Center

    Truman, Gregory E.; Pachamanova, Dessislava A.; Goldstein, Michael A.

    2010-01-01

    InterCon provides services to health insurers of foreign tourists who travel to the United States and Canada. Management wants to implement a new information system that will deal with several operational problems, but it is having difficulty securing the capital resources to fund the system's development. After an initial failure, the chief…

  10. conF and conJ contribute to conidia germination and stress response in the filamentous fungus Aspergillus nidulans.

    PubMed

    Suzuki, Satoshi; Sarikaya Bayram, Özlem; Bayram, Özgür; Braus, Gerhard H

    2013-07-01

    Light induces various responses in fungi including formation of asexual and sexual reproductive structures. The formation of conidia in the filamentous fungus Aspergillus nidulans is regulated by red and blue light receptors. Expression of conidia associated con genes, which are widely spread in the fungal kingdom, increases upon exposure to light. We have characterized the light-inducible conF and conJ genes of A. nidulans which are homologs of con-6 and con-10 of Neurospora crassa. con genes are expressed during conidia formation in asexual development. Five minutes light exposure are sufficient to induce conF or conJ expression in vegetative mycelia. Similar to N. crassa there were no significant phenotypes of single con mutations. A double conF and conJ deletion resulted in significantly increased cellular amounts of glycerol or erythritol. This leads to a delayed germination phenotype combined with increased resistance against desiccation. These defects were rescued by complementation of the double mutant strain with either conF or conJ. This suggests that fungal con genes exhibit redundant functions in controlling conidia germination and adjusting cellular levels of substances which protect conidia against dryness. PMID:23644150

  11. Somatic cell nuclear transfer: pros and cons.

    PubMed

    Sumer, Huseyin; Liu, Jun; Tat, Pollyanna; Heffernan, Corey; Jones, Karen L; Verma, Paul J

    2009-01-01

    Even though the technique of mammalian SCNT is just over a decade old it has already resulted in numerous significant advances. Despite the recent advances in the reprogramming field, SCNT remains the bench-mark for the generation of both genetically unmodified autologous pluripotent stem cells for transplantation and for the production of cloned animals. In this review we will discuss the pros and cons of SCNT, drawing comparisons with other reprogramming methods. PMID:20232594

  12. Anticuerpos derivados de pacientes se dirigen a células tumorales

    Cancer.gov

    Artículo del blog Temas y relatos de un anticuerpo derivado de pacientes que destruye células tumorales en estirpes celulares de varios tipos de cáncer e hizo lento el crecimiento en modelos murinos de cáncer de cerebro y pulmón sin signo de efectos.

  13. Capacitación del personal y de los pacientes en torno a los cuidados terminales

    Cancer.gov

    Artículo sobre programas innovadores de base científica para ayudar a médicos y pacientes a hablar sobre la transición de un tratamiento activo para el cáncer a los cuidados en la etapa final de la vida.

  14. Actitudes Éticas de los estudiantes y egresados en carrera de medicina con metodologías activas

    PubMed Central

    Novaes, Maria Rita Carvalho Garbi; Novaes, Luiz Carlos Garcez; Guilhem, Dirce; Stepke, Fernando Lolas; Silveira, Carla Cristina Costa; Komatsu, Ricardo Shoiti; Trindade, Eliane Mendonça Vilar; Guiotti, Murilo Galvão

    2010-01-01

    El presente estudio tiene por objeto desarrollar un diagnostico de la inserción integrada de la ética en la carrera de medicina brasileña con una metodología de aprendizaje basada en problemas y describir las percepciones de actitudes éticas de los estudiantes y egresados. El diseño metodológico es un estudio de caso, descriptivo y documental, con abordaje cualitativo y cuantitativo. La muestra de esta investigación ha sido constituida por 120 estudiantes y 40 egresados de dos promociones del Curso de Medicina de la ESCS. Este proyecto fue aprobado por el Comité de Ética en Investigación - SES/DF. Los estudiantes y egresados de la ESCS demostraron un buen manejo en el abordaje de los conflictos éticos y respeto a los pacientes. Sin embargo, el análisis de sensibilidad ética mostró una fragilidad en las percepciones y aptitudes inapropiadas de los estudiantes de la carrera de medicina, identificada básicamente en los años iniciales, que necesitan más discusiones sistematizadas sobre los aspectos éticos y bioéticos integrados a las actividades prácticas para estimular y fortalecer la reflexión ética de los estudiantes. PMID:20981242

  15. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall...

  16. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  17. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  18. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  19. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  20. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  1. Energy Star program benefits Con Edison

    SciTech Connect

    1995-05-01

    Impressed with savings in energy costs achieved after upgrading the lighting and air conditioning systems at its Manhattan headquarters, Home Box Office (HBO) wanted to do more, James Flock, vice president for computer and office systems, contacted Con Edison Co. of New York in March 1991 to determine what the company could do to save money by reducing energy consumed by personal computers. Arthur Kressner, Con Edison Research and Development manager contacted industry organizations and manufacturers for advice, but was told only to shut off computers at night and on weekends. Kressner arranged a series of meetings with IBM and the Electric Power Research Institute (EPRI) to discuss the issue, then approached the U.S. Environmental Protection Agency (EPA), which was designing a program to promote the introduction and use of energy-efficient office equipment. In 1992, the EPA announced the Energy Star program for PCs, enabling manufacturers to display the Energy Star logo on machines meeting program criteria, including the ability to enter a sleep mode in which neither the computer nor monitor consume more than 30 W or electricity. Industry experts estimate national energy consumption by office equipment could double by the year 2000, but Energy Star equipment is expected to improve efficiency and help maintain electric loads.

  2. Cervical disc arthroplasty: Pros and cons

    PubMed Central

    Moatz, Bradley; Tortolani, P. Justin

    2012-01-01

    Background: Cervical disc arthroplasty has emerged as a promising potential alternative to anterior cervical discectomy and fusion (ACDF) in appropriately selected patients. Despite a history of excellent outcomes after ACDF, the question as to whether a fusion leads to adjacent segment degeneration remains unanswered. Numerous US investigational device exemption trials comparing cervical arthroplasty to fusion have been conducted to answer this question. Methods: This study reviews the current research regarding cervical athroplasty, and emphasizes both the pros and cons of arthroplasty as compared with ACDF. Results: Early clinical outcomes show that cervical arthroplasty is as effective as the standard ACDF. However, this new technology is also associated with an expanding list of novel complications. Conclusion: Although there is no definitive evidence that cervical disc replacement reduces the incidence of adjacent segment degeneration, it does show other advantages; for example, faster return to work, and reduced need for postoperative bracing. PMID:22905327

  3. Oral Ketamine in the Palliative Care Setting: A Review of the Literature and Case Report of a Patient With Neurofibromatosis Type 1 and Glomus Tumor-Associated Complex Regional Pain Syndrome

    PubMed Central

    Soto, Eliezer; Stewart, Douglas R.; Mannes, Andrew J.; Ruppert, Sarah L.; Baker, Karen; Zlott, Daniel; Handel, Daniel; Berger, Ann M.

    2014-01-01

    Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be effective not only for its anesthetic properties but also for the analgesic and opiate-sparing effects. However, data on efficacy and safety of oral ketamine for the treatment of neuropathic or cancer pain syndromes is limited with most of the evidence based on small clinical trials and anecdotal experiences. In this review, we will analyze the clinical data on oral ketamine in the palliative care setting. After an extensive search using five major databases, a total of 19 relevant articles were included. No official clinical guidelines for the use of oral ketamine in this patient population were found. Studies on oral ketamine for cancer and neuropathic pain have shown mixed results which could be partially due to significant differences in hepatic metabolism. In addition, we will include a case report of a 38-year-old female with neurofibromatosis type 1 (NF1) with history of chronic, severe pain in her fingertips secondary to multiple glomus tumors which evolved into CRPS resistant to multiple therapies but responsive to oral ketamine. Based on our experience with oral ketamine, this drug should be administered after an intravenous trial to monitor response and side effects in patients with an adequate functional status. However, patients in the palliative care and hospice setting, especially the one at the end of their lives, may also benefit from oral ketamine even if an intravenous trial is not feasible. PMID:21803784

  4. Oral ketamine in the palliative care setting: a review of the literature and case report of a patient with neurofibromatosis type 1 and glomus tumor-associated complex regional pain syndrome.

    PubMed

    Soto, Eliezer; Stewart, Douglas R; Mannes, Andrew J; Ruppert, Sarah L; Baker, Karen; Zlott, Daniel; Handel, Daniel; Berger, Ann M

    2012-06-01

    Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be effective not only for its anesthetic properties but also for the analgesic and opiate-sparing effects. However, data on efficacy and safety of oral ketamine for the treatment of neuropathic or cancer pain syndromes is limited with most of the evidence based on small clinical trials and anecdotal experiences. In this review, we will analyze the clinical data on oral ketamine in the palliative care setting. After an extensive search using five major databases, a total of 19 relevant articles were included. No official clinical guidelines for the use of oral ketamine in this patient population were found. Studies on oral ketamine for cancer and neuropathic pain have shown mixed results which could be partially due to significant differences in hepatic metabolism. In addition, we will include a case report of a 38-year-old female with neurofibromatosis type 1 (NF1) with history of chronic, severe pain in her fingertips secondary to multiple glomus tumors which evolved into CRPS resistant to multiple therapies but responsive to oral ketamine. Based on our experience with oral ketamine, this drug should be administered after an intravenous trial to monitor response and side effects in patients with an adequate functional status. However, patients in the palliative care and hospice setting, especially the one at the end of their lives, may also benefit from oral ketamine even if an intravenous trial is not feasible. PMID:21803784

  5. A novel neurofibromin (NF1) interaction with the leucine-rich pentatricopeptide repeat motif-containing protein links neurofibromatosis type 1 and the French Canadian variant of Leigh's syndrome in a common molecular complex.

    PubMed

    Arun, Vedant; Wiley, Joseph C; Kaur, Harpreet; Kaplan, David R; Guha, Abhijit

    2013-04-01

    Loss-of-function mutations and deletions in the neurofibromin tumor suppressor gene (NF1) cause neurofibromatosis type 1 (NF-1), the most common inherited syndrome of the nervous system in humans, with a birth incidence of 1:3,000. The most visible features of NF-1 are the neoplastic manifestations caused by the loss of Ras-GTPase-activating protein (Ras-GAP) activity mediated through the GAP-related domain (GRD) of neurofibromin (NF1), the protein encoded by NF1. However, the syndrome is also characterized by cognitive dysfunction and a number of developmental abnormalities. The molecular etiology of many of these nonneoplastic phenotypes remains unknown. Here we show that the tubulin-binding domain (TBD) of NF1 is a binding partner of the leucine-rich pentatricopeptide repeat motif-containing (LRPPRC) protein. These two proteins complex with Kinesin 5B, hnRNP A2, Staufen1, and Myelin Basic Protein (MBP) mRNA, likely in RNA granules. This interaction is of interest in that it links NF-1 with Leigh's syndrome, French Canadian variant (LSFC), an autosomal recessive neurodegenerative disorder that arises from mutations in the LRPPRC gene. Our findings provide clues to how loss or mutation of NF1 and LRPPRC may contribute to the manifestations of NF-1 and LSFC. PMID:23361976

  6. An Update on Neurofibromatosis Type 1: Not Just Café-au-Lait Spots and Freckling. Part II. Other Skin Manifestations Characteristic of NF1. NF1 and Cancer.

    PubMed

    Hernández-Martín, A; Duat-Rodríguez, A

    2016-01-01

    Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome and probably the one best known to dermatologists. Although the genetic locus of NF1 was identified on chromosome 17 in 1987, diagnosis of the disease is still based primarily on clinical observations. The 7 diagnostic criteria of the National Institutes of Health, which were established in 1988, include 3 skin manifestations (café-au-lait spots, freckling on flexural areas, and cutaneous neurofibromas). The age at which these diagnostic lesions appear is variable: onset can be late in some patients while others never develop certain symptoms. Definitive diagnosis may therefore be delayed by years. Although the appearance of the characteristic café-au-lait spots and freckling in the early years of childhood are very suggestive of the disease, these signs are not pathognomonic and, in isolation, do not constitute sufficient evidence to establish a definitive diagnosis. Thus, other diagnoses should be considered in patients whose only symptoms are café-au-lait spots and freckling. By contrast, the presence of multiple cutaneous neurofibromas or at least 1 plexiform neurofibroma is a very specific indication of NF1. Identification of the different types of neurofibroma allows us to confirm the diagnosis and initiate appropriate management. PMID:26956402

  7. RoboCon: A general purpose telerobotic control center

    SciTech Connect

    Draper, J.V.; Noakes, M.W.; Schempf, H.; Blair, L.M.

    1997-02-01

    This report describes human factors issues involved in the design of RoboCon, a multi-purpose control center for use in US Department of Energy remote handling applications. RoboCon is intended to be a flexible, modular control center capable of supporting a wide variety of robotic devices.

  8. Breath Analysis Science at PittCon 2012, Orlando, Florida

    EPA Science Inventory

    Breath analysis science was featured in three organized sessions at this year’s Pittsburgh Conference and Exposition, or ‘PittCon 2012’ (http://www.pittcon.org/). As described in previous meeting reports, PittCon is one of the largest international conferences for analytical chem...

  9. Trazando la materia oscura con cúmulos globulares

    NASA Astrophysics Data System (ADS)

    Forte, J. C.

    Se describe la estrategia adoptada para mapear la distribución de materia oscura y bariónica en galaxias elípticas cuyos cúmulos globulares están siendo observados con los telescopios VLT y Gemini. Se ejemplifican los resultados con los datos obtenidos en el cúmulo de Fornax.

  10. ProCon - PROteomics CONversion tool.

    PubMed

    Mayer, Gerhard; Stephan, Christian; Meyer, Helmut E; Kohl, Michael; Marcus, Katrin; Eisenacher, Martin

    2015-11-01

    With the growing amount of experimental data produced in proteomics experiments and the requirements/recommendations of journals in the proteomics field to publicly make available data described in papers, a need for long-term storage of proteomics data in public repositories arises. For such an upload one needs proteomics data in a standardized format. Therefore, it is desirable, that the proprietary vendor's software will integrate in the future such an export functionality using the standard formats for proteomics results defined by the HUPO-PSI group. Currently not all search engines and analysis tools support these standard formats. In the meantime there is a need to provide user-friendly free-to-use conversion tools that can convert the data into such standard formats in order to support wet-lab scientists in creating proteomics data files ready for upload into the public repositories. ProCon is such a conversion tool written in Java for conversion of proteomics identification data into standard formats mzIdentML and Pride XML. It allows the conversion of Sequest™/Comet .out files, of search results from the popular and often used ProteomeDiscoverer® 1.x (x=versions 1.1 to1.4) software and search results stored in the LIMS systems ProteinScape® 1.3 and 2.1 into mzIdentML and PRIDE XML. This article is part of a Special Issue entitled: Computational Proteomics. PMID:26182917

  11. Pro/con a precessional geodynamo

    NASA Astrophysics Data System (ADS)

    Vanyo, J.

    2003-04-01

    The modest amount of research that exists on the ability, or lack of ability, of mantle precession to power a geodynamo developed mostly during the last half of the 1900s. Papers by Roberts and Stewartson (1965) and by Busse (1968) studied precession generally without a pro/con conclusion. Malkus in the late 1960s attempted to advance a positive role for precession through experiments and analysis. His experiments have survived criticism, but his analyses were discounted, especially by Rochester, Jacobs, Smylie, and Chong (1975) and by Loper (1975). Rochester, et al. critiqued existing analyses of precession, including those of Malkus, but did not reach a strong position either pro or con a precessional geodynamo. Loper argued emphatically that precession was not capable of powering the geodynamo. Explicit analyses that either critique or support Loper’s arguments have yet to appear in the literature. During the 1970s, Vanyo and associates studied energy dissipation during precession of satellite liquid fuels and its effect on satellite attitude stability. Engineers and scientists in every country that has launched satellites completed similar research. Some is published in the aerospace literature, more is available in company and government reports. Beginning in 1981, Vanyo and associates applied this knowledge to the very similar problem of energy dissipation and flow patterns in precessing mechanical models scaled geometrically and dynamically to the Earth’s liquid core. Energy experiments indicate massive amounts of mechanical energy are dissipated at the CMB, and flow experiments show complex motions within the boundary layer and axial flows with helicity throughout the interior. Analysis of Earth core precession also advanced, especially in several papers by Kerswell and by Tilgner in the late 1990s. Detail numerical models have yet to appear. Although progress in understanding the role of precession in Earth core motions has advanced, there remains a

  12. 53. SECONDARY CONNING STATION AFT LOOKING FORWARD ON CENTERLINE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    53. SECONDARY CONNING STATION - AFT LOOKING FORWARD ON CENTERLINE SHOWING ENGINE ORDER TELEGRAPH, HELM, RADAR, GYRO REPEATERS, PORTHOLE WITH BATTLE PORTS CLOSED. - U.S.S. HORNET, Puget Sound Naval Shipyard, Sinclair Inlet, Bremerton, Kitsap County, WA

  13. 52. SECONDARY CONNING STATION FORWARD LOOKING AFT ON CENTERLINE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. SECONDARY CONNING STATION - FORWARD LOOKING AFT ON CENTERLINE SHOWING ENGINE ORDER TELEGRAPH, HELM, RADAR, GYRO REPEATERS, PORTHOLE WITH BATTLE PORTS CLOSED. - U.S.S. HORNET, Puget Sound Naval Shipyard, Sinclair Inlet, Bremerton, Kitsap County, WA

  14. View forward of interior of conning tower and steering station; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View forward of interior of conning tower and steering station; helmsman or observer viewed action through narrow opening at top of photo. (p57) - USS Olympia, Penn's Landing, 211 South Columbus Boulevard, Philadelphia, Philadelphia County, PA

  15. [Cement augmentation of pedicle screws : Pros and cons].

    PubMed

    Schnake, K J; Blattert, T R; Liljenqvist, U

    2016-09-01

    Cement augmentation of pedicle screws biomechanically increases screw purchase in the bone. However, clinical complications may occur. The pros and cons of the technique are discussed from different clinical perspectives. PMID:27514827

  16. Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1.

    PubMed

    Hirata, Yasuko; Brems, Hilde; Suzuki, Mayu; Kanamori, Mitsuhiro; Okada, Masahiro; Morita, Rimpei; Llano-Rivas, Isabel; Ose, Toyoyuki; Messiaen, Ludwine; Legius, Eric; Yoshimura, Akihiko

    2016-02-12

    Constitutional heterozygous loss-of-function mutations in the SPRED1 gene cause a phenotype known as Legius syndrome, which consists of symptoms of multiple café-au-lait macules, axillary freckling, learning disabilities, and macrocephaly. Legius syndrome resembles a mild neurofibromatosis type 1 (NF1) phenotype. It has been demonstrated that SPRED1 functions as a negative regulator of the Ras-ERK pathway and interacts with neurofibromin, the NF1 gene product. However, the molecular details of this interaction and the effects of the mutations identified in Legius syndrome and NF1 on this interaction have not yet been investigated. In this study, using a yeast two-hybrid system and an immunoprecipitation assay in HEK293 cells, we found that the SPRED1 EVH1 domain interacts with the N-terminal 16 amino acids and the C-terminal 20 amino acids of the GTPase-activating protein (GAP)-related domain (GRD) of neurofibromin, which form two crossing α-helix coils outside the GAP domain. These regions have been shown to be dispensable for GAP activity and are not present in p120(GAP). Several mutations in these N- and C-terminal regions of the GRD in NF1 patients and pathogenic missense mutations in the EVH1 domain of SPRED1 in Legius syndrome reduced the binding affinity between the EVH1 domain and the GRD. EVH1 domain mutations with reduced binding to the GRD also disrupted the ERK suppression activity of SPRED1. These data clearly demonstrate that SPRED1 inhibits the Ras-ERK pathway by recruiting neurofibromin to Ras through the EVH1-GRD interaction, and this study also provides molecular basis for the pathogenic mutations of NF1 and Legius syndrome. PMID:26635368

  17. [I costi farmacologici della terapia di conversione con farmaci biologici nel carcinoma del colon-retto con metastasi epatiche].

    PubMed

    Giuliani, Jacopo; Bonetti, Andrea

    2016-08-01

    Riassunto. Lo scopo di questo studio è quello di valutare i costi dei farmaci (con particolare riferimento alle terapie con farmaci biologici) utilizzati nella terapia di conversione in una popolazione non selezionata di pazienti affetti da carcinoma del colon-retto in stadio avanzato, al fine di ottenere una resezione epatica R0. In questa rassegna sono stati selezionati i report completi e gli aggiornamenti di tutti gli studi clinici randomizzati (di fase II e fase III) che confrontassero almeno 2 regimi di terapia con farmaci biologici in prima linea in pazienti affetti da carcinoma del colon-retto in stadio avanzato di malattia. I costi dei farmaci sono stati ricavati dalla nostra Farmacia Ospedaliera e sono espressi in euro (€). Il nostro studio inizia con la valutazione di 683 abstract. 48 tria sono stati considerati adeguati per una successiva analisi. Una valutazione più approfondita ha portato all'esclusione di 37 trial, lasciando alla valutazione finale 11 studi clinici randomizzati (3 trial di fase II, per un totale di 522 pazienti, e 8 studi di fase III, per un totale di 7191 pazienti). I costi dei farmaci utilizzati nella terapia di conversione aumentano con la sostituzione del 5-fluorouracile con la capecitabina e, in misura maggiore, con l'introduzione degli agenti biologici. In questo lavoro sono presentati due punti chiave. Primo, i costi degli agenti farmacologici utilizzati nei regimi di prima linea a base di agenti biologici più comunemente utilizzati nel trattamento del carcinoma del colon-retto in stadio avanzato sono molto variabili. Secondo, i dati di efficacia dei regimi pubblicati, in termini di tassi di resezione, dipendono dalla selezione dei pazienti, dalle caratteristiche del tumore e dal tipo di schema di terapia. PMID:27571559

  18. Paramagnetic-to-Ferromagnetic Transition in Con Under Pressure

    NASA Astrophysics Data System (ADS)

    Kasinathan, Deepa; Pickett, Warren

    2004-03-01

    Motivated by reports of synthesis of zincblende (ZB) structure CrAs in thin film form, strong interest has developed in understanding transition metal pnictides and their tendencies toward magnetic order.Literature on the experimental analysis of the structure of CoN is varied, with reports of both magnetically ordered NaCl structure CoN and non-magnetic ZB CoN. We present results of first principles analysis of electronic structure, magnetism and Murnaghan equation of state for both structures. The non-magnetic ZB structure, stable at ambient pressure transforms to a collapsed ferromagnetic NaCl phase at 10GPa (ΔV = -15%). These results will be compared to data and similarities/differences with other transition metal nitrides will be discussed.

  19. Cáncer de la corteza suprarrenal—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del carcinoma de corteza suprarrenal, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  20. Cáncer de tiroides—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de tiroides, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  1. Cáncer de páncreas—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de páncreas, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  2. Cáncer de vagina—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de vagina, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  3. Cáncer de vulva—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de vulva, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  4. Cáncer de riñón—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de riñón, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados con este tipo de cáncer.

  5. Cáncer de piel (incluye el melanoma)—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento, la prevención, las causas, los exámenes de detección y los estudios clínicos del cáncer de piel, así como referencias a otros temas relacionados con este tipo de cáncer.

  6. Cannabis y canabinoides (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos sobre el uso del Cannabis y canabinoides para el tratamiento de los efectos secundarios relacionados con el tratamiento del cáncer como la náusea y el vómito.

  7. Cáncer de intestino delgado—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de intestino delgado, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  8. Cáncer de pene—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de pene, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  9. Cáncer de paratiroides—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de paratiroides, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  10. Cáncer de testículo—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento, las causas y los exámenes de detección del cáncer de testículo, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  11. Cáncer de vesícula biliar—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de vesícula biliar, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  12. El dolor y el cáncer (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos acerca del dolor como una complicación a causa del cáncer o su tratamiento. Se discuten enfoques sobre el manejo y tratamiento del dolor relacionado con el cáncer.

  13. Cáncer de piel—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento, la prevención, las causas, los exámenes de detección y los estudios clínicos del cáncer de piel, así como referencias a otros temas relacionados con este tipo de cáncer.

  14. Cáncer de hueso—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del cáncer de hueso (óseo), así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer.

  15. Inclusion: The Pros and Cons--A Critical Review

    ERIC Educational Resources Information Center

    Savich, Carl

    2008-01-01

    The purpose of this paper was to review, analyze, and critique the pros and cons, the advantages and disadvantages, of inclusion. The methodology consisted in analyzing and comparing research findings on the benefits and costs of inclusion. Federal legislation and regulations on inclusion were examined, analyzed, and discussed. The results showed…

  16. The Academic Con-Men. Advice to Young College Professors.

    ERIC Educational Resources Information Center

    Kerins, Francis J.

    1979-01-01

    The academic con-man is defined as one who, despite a lack of striking originality or tremendous learning, becomes extraordinary, well-known, and revered in the world of higher education. Advice is offered to young college professors on how they can achieve such status. (Article originally published in 1961.) (AF)

  17. Detail of conning tower atop the submarine. Note the wire ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of conning tower atop the submarine. Note the wire rope wrapped around the base of the tower, which may have been used in an attempt to pull the submarine offshore. - Sub Marine Explorer, Located along the beach of Isla San Telmo, Pearl Islands, Isla San Telmo, Former Panama Canal Zone, CZ

  18. Teaching after Retirement: The Pros and the Cons

    ERIC Educational Resources Information Center

    Sommer, Robert

    2014-01-01

    Having enjoyed teaching during my active career, I continued to teach summer school following retirement. Self-observed sensory and cognitive impairments, although not mentioned by students in their evaluations, induced me to consider the pros and cons of continuing to teach. My hope is that this list of benefits and problems will be of assistance…

  19. LunGradCon: The Lunar Graduate Conference

    NASA Astrophysics Data System (ADS)

    Dove, A.; Poppe, A.; Neish, C.; Fagan, A.; Fuqua, H.; Kramer, G. Y.; Horanyi, M.

    2011-12-01

    Members of the Colorado Center for Lunar Dust and Atmospheric Studies (CCLDAS) initiated the Lunar Graduate Conference (LunGradCon), modeled after the highly successful Astrobiology Graduate Conference (AbGradCon). The purpose of this conference is to enhance the professional development of graduate students and early postdoctoral researchers by providing an opportunity to present and discuss scientific research in an environment of their peers. For the first two years, LunGradCon has been held as a one-day conference in conjunction with the NASA Lunar Science Institue's (NLSI) Lunar Science Forum at the NASA Ames Research Center. Activities include an invited overview talk on each of the NASA Lunar Science Institute's three main research areas (OF the Moon, ON the Moon, and FROM the Moon), submitted oral presentations from graduate students and postdoctoral researchers, and networking opportunities with established member of the lunar science community and the NLSI. In each of the first two years of LunGradCon, there have been 20-25 attendees, with about 15 of those presenting submitted talks. Each speaker received feedback forms from the other participants in order to improve on their presentation techniques. Participants also provided feedback on the conference as a whole in order to evaluate the content and provide suggestions for improvement in following years. Overall, the feedback has been extremely positive. This talk will summarize the achievements of past LunGradCons and plans for expansion of the conference to ensure a long-term positive impact on the early careers of future lunar, planetary and space science researchers.

  20. Cáncer de esófago—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento, la prevención y los exámenes de detección del cáncer de esófago, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados con este tipo de cáncer.

  1. Síndromes cardiopulmonares (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos acerca de las afecciones comunes que producen síntomas en el pecho. Los síndromes cardiopulmonares que se exponen en este sumario son la disnea relacionada con el cáncer, la efusión pleural maligna, la efusión pericárdica y el síndrome de la vena cava superior.

  2. Cáncer de vejiga—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento, las causas y los exámenes de detección del cáncer de vejiga, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados con este tipo de cáncer.

  3. Runtime Verification for Generic Classes with ConGu 2

    NASA Astrophysics Data System (ADS)

    Crispim, Pedro; Lopes, Antónia; Vasconcelos, Vasco T.

    Even though generics became quite popular in mainstream object-oriented (OO) languages, approaches for checking at runtime the conformance of such programs against formal specifications still lack appropriate support. In order to overcome this limitation within ConGu, a tool-based approach we have been developing to support runtime conformance checking of Java programs against algebraic specifications, we recently proposed a notion of refinement mapping that allows to define correspondences between parametric specifications and generic classes. Based on such mappings, we also put forward a notion of conformance between the two concepts. In this paper we present how the new notion of conformance is supported by version 2 of the ConGu tool.

  4. ConStrains identifies microbial strains in metagenomic datasets

    PubMed Central

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-01-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived data sets provides insights into microbial community dynamics. PMID:26344404

  5. ConStrains identifies microbial strains in metagenomic datasets.

    PubMed

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-10-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived datasets provides insights into microbial community dynamics. PMID:26344404

  6. Images in clinical medicine: Segmental neurofibromatosis.

    PubMed

    Ma, Dong-Lai; Hu, Jin

    2015-03-01

    A 4-year-old girl presented for evaluation of cutaneous nodules that had been present on the left side of her trunk since birth. Physical examination revealed numerous soft, nontender papules and nodules across the left upper abdomen and wrapping around to the back. PMID:25738672

  7. Topical Oxygen for Chronic Wounds: A PRO/CON Debate

    PubMed Central

    Mutluoglu, Mesut; Cakkalkurt, Aslican; Uzun, Gunalp; Aktas, Samil

    2014-01-01

    The role of oxygen in wound healing is universally accepted and does not require any further evidence; however the controversy as to whether oxygen delivery systems have the potential to improve wound healing remains to be concluded. Topical oxygen treatment (TOT) involves the delivery of 100% oxygen for a mean of 90 min, once a day at an atmospheric pressure slightly above 1 atm abs. The use of TOT gained increasing interest recently. The current manuscript will summarize the pros and cons of TOT in the view of the available literature. PMID:26199891

  8. Apoyo a Estudios Geodinamicos con GPS en Guatemala

    NASA Astrophysics Data System (ADS)

    Robles, V. R.

    2013-05-01

    El Instituto Geografico Nacional de Guatemala implemento 17 estaciones GNSS en el año 2009, como un proyecto de credito mixto de donacion de equipamiento del Gobierno de Suiza, el cual, este equipamiento de estaciones CORS GNSS es un sistema de recepción y transmisión de datos crudos GPS RInex que utiliza la tecnologia Spider Web de Leica, asi mismo este sistema esta sirviendo para el espablecimiento de un marco geodesico nacional de coordenadas geodesicas oficiales, el cual se calculan u obtienen las velocidades en tiempos temporales programados de las 17 Estaciones CORS. La infraestructura del marco geodesico de Guatemala esta sirviendo de base para las aplicaciones de estudios geodinamicos como el monitoreo de del desplazamiento de las placas tectonicas por medio de un estudio que se inicio en el año de 1999, llamado medicion con GPS el sistema de Fallas de los rios Polochic Motagua de Guatemala, tambien para un estudio que se implemento para deformación de corteza terrestre local en un Volcan Activo de Guatemala llamado Pacaya. Para el estudio de medicion con GPS en el sistema de falla de los Rios del polochic Motagua se implementaron 16 puntos para medir con GPS de dos frecuencias en el año de 1999, el cual, tres puntos son estaciones geodesicas CORS IGS llamados GUAT, ELEN y HUEH, despues en el año de 2003 se hizo otra medicion en un total de 20 puntos, que permitió calcular las velocidades de desplazamieinto de los puntos en mención, usando como referencia el modelo NUVEL 1A de DeMets de la placa de Norteamerica. Este estudio fue en cooperación internacional por la universidad de Nice de Francia y el IGNde Francia. Para el estudio del monitoreo con GPS del volcan activo de Guatemala, se implementaron cuatro puntos al rededor del volcan, el cual, se realizan cuatro mediciones al año, que permiten determinar axialmente la distancias entre los puntos, y rebisar estadisticamente cual es el comportamiento de las distancias en funcion del tiempo, si

  9. RoboCon: Operator interface for robotic applications

    SciTech Connect

    Schempf, H.; Warwick, J.; Fung, M.; Chemel, B.; Blackwell, M.

    1996-12-31

    Carnegie Mellon U. and ORNL`s Robotics and Process Systems Division are developing a state-of-the-art robot operator control station (RoboCon) with standardized hardware and software control interfaces to be adaptable to a variety of remote and robotic equipment currently funded by DOE`s Office of Science & Technology Robotics Technology Development Program. The human operation and telerobotic and supervisory control of sophisticated and remote and robotic systems is a complex, tiring, and non-intuitive activity. Since decontamination & decommissioning, selective equipment removal, mixed waste operations, and in-tank cleanup are going to be a major future activity in DOE environmental restoration and waste management cleanup agenda, it seems necessary to utilize an operator control station and interface which maximizes operator comfort and productivity.

  10. [Modern tribology in total hip arthroplasty: pros and cons].

    PubMed

    Gómez-García, F

    2014-01-01

    The wear products and adverse reactions that occur on bearing surfaces represent one of the greatest challenges in prosthetic replacements, as the latter experience increasing demands due to the large number of young and older adult patients that have a long life expectancy and remarkable activity. The purpose of this review is to analyze the pros and cons of the new advances in the bearing components of the articular surfaces of current total hip arthroplasties. We also discuss the strategies used historically, their problems, results and the surgeon's role in prescribing the tribologic couple that best fits each patient's needs. We conclude with practical recommendations for the prescription and management of the latest articular couples for total hip arthroplasty. PMID:26021098

  11. Molecular classification of myeloproliferative neoplasms-pros and cons.

    PubMed

    Qureshi, Moosa; Harrison, Claire

    2013-12-01

    Dameshek first postulated a common myeloproliferative heritage for the myeloproliferative disorders, now termed neoplasms. This prescient observation was validated by the description of a common mutation in exon 14 of JAK2 for patients with essential thrombocythemia, polycythemia vera and primary myelofibrosis. In recent years, our knowledge of the molecular abnormalities underpinning these disorders has expanded significantly. At the same time, we have continued to use a classification based largely upon the first clinical descriptions of these entities, which sometimes proves problematic in differentiating between these conditions and normal reactive processes, myelodysplasia and between the myeloproliferative neoplasm entities themselves. Here, we discuss the pros and cons of a molecular classification and its potential utility in diagnosis, prognosis, and therapeutics. PMID:24091831

  12. Caffe con Troll: Shallow Ideas to Speed Up Deep Learning

    PubMed Central

    Hadjis, Stefan; Abuzaid, Firas; Zhang, Ce; Ré, Christopher

    2016-01-01

    We present Caffe con Troll (CcT), a fully compatible end-to-end version of the popular framework Caffe with rebuilt internals. We built CcT to examine the performance characteristics of training and deploying general-purpose convolutional neural networks across different hardware architectures. We find that, by employing standard batching optimizations for CPU training, we achieve a 4.5× throughput improvement over Caffe on popular networks like CaffeNet. Moreover, with these improvements, the end-to-end training time for CNNs is directly proportional to the FLOPS delivered by the CPU, which enables us to efficiently train hybrid CPU-GPU systems for CNNs. PMID:27314106

  13. Gradient Optimization for Analytic conTrols - GOAT

    NASA Astrophysics Data System (ADS)

    Assémat, Elie; Machnes, Shai; Tannor, David; Wilhelm-Mauch, Frank

    Quantum optimal control becomes a necessary step in a number of studies in the quantum realm. Recent experimental advances showed that superconducting qubits can be controlled with an impressive accuracy. However, most of the standard optimal control algorithms are not designed to manage such high accuracy. To tackle this issue, a novel quantum optimal control algorithm have been introduced: the Gradient Optimization for Analytic conTrols (GOAT). It avoids the piecewise constant approximation of the control pulse used by standard algorithms. This allows an efficient implementation of very high accuracy optimization. It also includes a novel method to compute the gradient that provides many advantages, e.g. the absence of backpropagation or the natural route to optimize the robustness of the control pulses. This talk will present the GOAT algorithm and a few applications to transmons systems.

  14. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J. ); Do Van Luu; Lee, E.K.; Hong, S.S. )

    1996-01-01

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  15. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J.; Do Van Luu; Lee, E.K.; Hong, S.S.

    1996-12-31

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  16. [Treatment of type 2 diabetes mellitus in patients with chronic kidney disease. Grupo de Trabajo para el Documento de Consenso sobre el tratamiento de la diabetes tipo 2 en el paciente con enfermedad renal crónica].

    PubMed

    Gómez-Huelgas, Ricardo; Martínez-Castelao, Alberto; Artola, Sara; Górriz, José Luis; Menéndez, Edelmiro

    2014-01-21

    Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are highly prevalent chronic diseases, which represent an important public health problem and require a multidisciplinary management. T2DM is the main cause of CKD and it also causes a significant comorbidity with regard to non-diabetic nephropathy. Patients with diabetes and kidney disease represent a special risk group as they have higher morbi-mortality as well as higher risk of hypoglycemia than diabetic individuals with a normal kidney function. Treatment of T2DM in patients with CKD is controversial because of the scarcity of available evidence. The current consensus report aims to ease the appropriate selection and dosage of antidiabetic treatments as well as the establishment of safety objectives of glycemic control in patients with CKD. PMID:24268912

  17. Planificar la transición a la etapa final de la vida (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos sobre la preparación necesaria por parte de los proveedores de atención de la salud, los pacientes y sus familias para la transición a la atención del cáncer avanzado en la etapa final de la vida.

  18. Opciones de cirugía para mujeres con CDIS o con cáncer de seno- página de publicaciones

    Cancer.gov

    Contiene información sobre los tipos de cirugía de seno, como la operación para conservar el seno y la mastectomía, y ayuda a las mujeres diagnosticadas con CDIS o con cáncer de seno a decidir cuál cirugía es la más conveniente para ellas.

  19. Investigation on the conA binding properties of Klebsiella pneumoniae.

    PubMed

    Anuar, A S S; Tay, S T

    2014-12-01

    Klebsiella pneumoniae is a healthcare-associated bacterial pathogen which causes severe diseases in immunocompromised individuals. Concanavalin A (conA), a lectin which recognizes proteins with mannose or glucose residues, has been reported to agglutinate K. pneumoniae and hence, is postulated to have therapeutical potential for K. pneumoniae-induced liver infection. This study investigated the conA binding properties of a large collection of clinical isolates of K. pneumoniae. ConA agglutination reaction was demonstrated by 94 (51.4%) of 183 K. pneumoniae isolates using a microtiter plate assay. The conA agglutination reactions were inhibited in the presence of 2.5 mg/ml D-mannose and 2.5 mg/ml glucose, and following pretreatment of the bacterial suspension with protease and heating at 80ºC. Majority of the positive isolates originated from respiratory specimens. Isolation of conA-binding proteins from K. pneumoniae ATCC 700603 strain was performed using conA affinity column and the conA binding property of the eluted proteins was confirmed by western blotting analysis using conA-HRP conjugates. Proteins with molecular weights ranging from 35 to 60 kDa were eluted from the conA affinity column, of which four were identified as outer membrane protein precursor A (37 kDa), outer membrane protein precursor C (40 kDa), enolase (45 kDa) and chaperonin (60 kDa) using mass spectrometry analysis. Several conA binding proteins (including 45 and 60 kDa) were found to be immunogenic when reacted with rabbit anti-Klebsiella antibody. The function and interplay of the conA binding proteins in bacterium-host cell relationship merits further investigation. PMID:25776607

  20. Caring for Alzheimer's Patients. Supplement to Caregivers' Practical Help to Assist Those Who Care for Patients with Dementia Related Diseases = El Cuidado de los Pacientes de Alzheimer. Suplemento de Ayuda Practica para las Personas Encargadas para Ayudar a los que Cuidan a Pacientes que Sufren de Enfermedades Relacionadas con la Demencia.

    ERIC Educational Resources Information Center

    New York State Office for the Aging, Albany.

    This manual is intended for caregivers of homebound patients with Alzheimer's disease and others who are mentally impaired. It deals with the nature of Alzheimer's, the decline in a patient's abilities, information about available services, and legal and financial issues. The manual provides guidance and suggestions to lessen the daily stress…

  1. ConSearch: An Electronic Document Research and Retrieval Utility for Windows from Management Information Technologies.

    ERIC Educational Resources Information Center

    Combs, Joseph, Jr.

    1995-01-01

    Reviews ConSearch 3.0, a product that provides flexible searching of electronic files, allowing the location of related meanings as well as exact matches. ConSearch 3.0 differs from other file retrieval approaches by relating words in search phrases of questions to the "meaning" of the words, which are stored in a "conceptual database," or lexicon…

  2. Gestational surrogacy: could be a way to be a way to reproduction? Pros and cons.

    PubMed

    Clementina, Peris

    2011-06-01

    The aim of this article was to address pros and cons of gestational surrogacy, the social and psychological issues involved in surrogate motherhood triads. Pros and cons of surrogacy, the possible insurgence of a hematologic disease in the fetus, hemolytic disease of the newborn, naturally acquired microchimerism in surrogacy cases, ethical, medical, psychologic, legal and religious issues of a problem are discussed. PMID:21778533

  3. Meeting Report: Breath Biomarkers Networking Sessions at PittCon 2010, Orlando, Florida

    EPA Science Inventory

    The Pittsburgh Conference and Exposition, or "PittCon" (www.pittcon.org/), is one of the largest international conferences for analytical chemistry and instrumentation typically attracting about 25,000 attendees and 1,000 commercial exhibitors. PittCon began in 1950 as a small sp...

  4. Pros, Cons, and Alternatives to Weight Based Cost Estimating

    NASA Technical Reports Server (NTRS)

    Joyner, Claude R.; Lauriem, Jonathan R.; Levack, Daniel H.; Zapata, Edgar

    2011-01-01

    Many cost estimating tools use weight as a major parameter in projecting the cost. This is often combined with modifying factors such as complexity, technical maturity of design, environment of operation, etc. to increase the fidelity of the estimate. For a set of conceptual designs, all meeting the same requirements, increased weight can be a major driver in increased cost. However, once a design is fixed, increased weight generally decreases cost, while decreased weight generally increases cost - and the relationship is not linear. Alternative approaches to estimating cost without using weight (except perhaps for materials costs) have been attempted to try to produce a tool usable throughout the design process - from concept studies through development. This paper will address the pros and cons of using weight based models for cost estimating, using liquid rocket engines as the example. It will then examine approaches that minimize the impct of weight based cost estimating. The Rocket Engine- Cost Model (RECM) is an attribute based model developed internally by Pratt & Whitney Rocketdyne for NASA. RECM will be presented primarily to show a successful method to use design and programmatic parameters instead of weight to estimate both design and development costs and production costs. An operations model developed by KSC, the Launch and Landing Effects Ground Operations model (LLEGO), will also be discussed.

  5. Pros and Cons of Medical Management of Ulcerative Colitis

    PubMed Central

    Navaneethan, Udayakumar; Shen, Bo

    2010-01-01

    Ulcerative colitis (UC) is a chronic inflammatory disease characterized by diffuse mucosal inflammation limited to the colon and rectum. Although a complete medical cure may not be possible, UC can be treated with medications that induce and maintain remission. The medical management of this disease continues to evolve with a goal to avoid colectomy and ultimately alter the natural history of UC. Emergence of antitumor necrosis factor-α (TNF-α) agents has expanded the medical armamentarium. 5-Aminosalicylates continue to be used in mild to moderate UC and corticosteroids are mainly used for induction of remission with immunomodulators (6-mercaptopurine/azathiopurine/methotrexate) being applied as steroid-sparing agents for maintenance therapy. Infliximab has been approved by the U.S. Food and Drug Administration and used in the treatment of moderate to severe UC; nevertheless, its use may be associated with significant adverse effects and have a negative impact on the postoperative course should the patients undergo restorative proctocolectomy. In addition, there is always a concern about patients' compliance to medical therapy, cost of medications, and risk for UC-associated dysplasia. The authors discuss the pros and cons of medications used in the treatment of UC. PMID:22131893

  6. Cuidados médicos de apoyo en niños (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos acerca de la peculiaridad de los asuntos que surgen durante y después del tratamiento en los niños con cáncer, y como sobrevivientes adultos de cáncer.

  7. Surgical animal models of neuropathic pain: Pros and Cons.

    PubMed

    Challa, Siva Reddy

    2015-03-01

    One of the biggest challenges for discovering more efficacious drugs for the control of neuropathic pain has been the diversity of chronic pain states in humans. It is now acceptable that different mechanisms contribute to normal physiologic pain, pain arising from tissue damage and pain arising from injury to the nervous system. To study pain transmission, spot novel pain targets and characterize the potential analgesic profile of new chemical entities, numerous experimental animal pain models have been developed that attempt to simulate the many human pain conditions. Among the neuropathic pain models, surgical models have paramount importance in the induction of pain states. Many surgical animal models exist, like the chronic constriction injury (CCI) to the sciatic nerve, partial sciatic nerve ligation (pSNL), spinal nerve ligation (SNL), spared nerve injury (SNI), brachial plexus avulsion (BPA), sciatic nerve transaction (SNT) and sciatic nerve trisection. Most of these models induce responses similar to those found in causalgia, a syndrome of sustained burning pain often seen in the distal extremity after partial peripheral nerve injury in humans. Researchers most commonly use these surgical models in both rats and mice during drug discovery to screen new chemical entities for efficacy in the area of neuropathic pain. However, there is scant literature that provides a comparative discussion of all these surgical models. Each surgical model has its own benefits and limitations. It is very difficult for a researcher to choose a suitable surgical animal model to suit their experimental set-up. Therefore, particular attention has been given in this review to comparatively provide the pros and cons of each model of surgically induced neuropathic pain. PMID:24831263

  8. Cáncer de hígado y de conducto biliar—Versión para pacientes

    Cancer.gov

    Información del NCI sobre el tratamiento, la prevención y los exámenes de detección del cáncer de hígado y de conducto biliar, así como referencias a estudios clínicos, investigación y otros temas relacionados con este tipo de cáncer

  9. Determination of composition in stoichiometric Co-N ultrathin films by nitrogen plasma sputtering

    NASA Astrophysics Data System (ADS)

    Su, C. W.; Huang, M. S.; Chang, Y. C.; Tsai, T. H.; Lee, Y. H.; Lee, J. C.

    2009-02-01

    This work utilizes low-energy sputtering to incorporate the generated nitrogen plasma into an epitaxial 1.4nm Co film on the surface of a ZnO(002) substrate. In this method, ultrathin Co-N amorphous films were formed. Interestingly, Co is key to the formation of Co-N films. Without the deposition of Co on the ZnO(002), nitride films cannot be formed. Observations of the surface composition of the Co-N films after the firing of a N+ ion beam onto it demonstrated that the surface concentration of Co reduced at the same rate as the reduction in the concentration of N upon successive sputtering. Theoretical calculations based on the Auger peak-to-peak amplitudes established that the composition of the amorphous Co-N thin films may be Co3N2.

  10. The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM)

    Cancer.gov

    The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM) was formed to promote international, multidisciplinary collaborations to advance our understanding of the etiology and outcomes of kidney cancer.

  11. CONspiracies to crush competition. Hospitals using CON laws to thwart rival's projects.

    PubMed

    Burda, D

    1991-07-01

    In their eagerness to protect their market share and check advances by rivals, hospitals are trying to use state certificate-of-need laws to their advantage. Some hospitals are clinging to CON laws, which require state approval of new construction and renovation, because they protect them from competitors who threaten their market. A look into CON wars in five states uncovers some competitive tactics. PMID:10111448

  12. SLUDGE PARTICLE SEPAPATION EFFICIENCIES DURING SETTLER TANK RETRIEVAL INTO SCS-CON-230

    SciTech Connect

    DEARING JI; EPSTEIN M; PLYS MG

    2009-07-16

    The purpose of this document is to release, into the Hanford Document Control System, FA1/0991, Sludge Particle Separation Efficiencies for the Rectangular SCS-CON-230 Container, by M. Epstein and M. G. Plys, Fauske & Associates, LLC, June 2009. The Sludge Treatment Project (STP) will retrieve sludge from the 105-K West Integrated Water Treatment System (IWTS) Settler Tanks and transfer it to container SCS-CON-230 using the Settler Tank Retrieval System (STRS). The sludge will enter the container through two distributors. The container will have a filtration system that is designed to minimize the overflow of sludge fines from the container to the basin. FAI/09-91 was performed to quantify the effect of the STRS on sludge distribution inside of and overflow out of SCS-CON-230. Selected results of the analysis and a system description are discussed. The principal result of the analysis is that the STRS filtration system reduces the overflow of sludge from SCS-CON-230 to the basin by roughly a factor of 10. Some turbidity can be expected in the center bay where the container is located. The exact amount of overflow and subsequent turbidity is dependent on the density of the sludge (which will vary with location in the Settler Tanks) and the thermal gradient between the SCS-CON-230 and the basin. Attachment A presents the full analytical results. These results are applicable specifically to SCS-CON-230 and the STRS filtration system's expected operating duty cycles.

  13. Evaluation of the ACT*DE*CON{sup SM} process for treating gunite tank sludge

    SciTech Connect

    Spencer, B.B.; Chase, C.W.; Egan, B.Z.

    1996-05-01

    A test was conducted to evaluate this process for selectively removing actinides from Gunite tank sludge. Mixed waste sludge from Gunite tank W-6 was subjected to the ACT*DE*CON selective leaching process. (Nearly all the TRU content was attributed to Pu.) The sludge sample was first washed with 0.01M NaOH to remove excess sodium and nitrate in the interstitial liquid supernatant. The washed wet solids were treated with the ACT*DE*CON solvent (aqueous carbonate solution containing a chelating agent and an oxidant), using a ratio of 20 ml solvent per gram wet solids. Sludge and solvent were separated by centrifugation, and the ACT*DE*CON treatment was repeated twice. Analyses showed that 71% of the solids in the sludge were dissolved while 80% of the TRU-waste components dissolved. Low separation of the TRU-waste components from other components of the sludge mixture is indicated. Almost all the U and Ca were removed from the sludge. For sludges where most of the TRU content is Pu, the ACT*DE*CON process as tested is not effective in rendering the sludge a non-TRU waste. It is recommended that ACT*DE*CON be optimized for this specific application and that other processes using different chelating and oxidizing agents be tested. Also, the ACT*DE*CON process should be tested on TRU mixed waste in which most of the TRU elements are not Pu.

  14. Virulence, Speciation and Antibiotic Susceptibility of Ocular Coagualase Negative Staphylococci (CoNS)

    PubMed Central

    Priya, Ravindran; Mythili, Arumugam; Singh, Yendremban Randhir Babu; Sreekumar, Haridas; Manikandan, Palanisamy; Panneerselvam, Kanesan

    2014-01-01

    Background: Coagulase negative Staphylococci (CoNS) are common inhabitants of human skin and mucous membranes. With the emergence of these organisms as prominent pathogens in patients with ocular infections, investigation has intensified in an effort to identify important virulence factors and to inform new approaches to treatment and prevention. Aim: To isolate CoNS from ocular specimens; to study the possible virulence factors; speciation of coagulase negative staphylococci (CoNS) which were isolated from ocular complications; antibiotic susceptibility testing of ocular CoNS. Materials and Methods: The specimens were collected from the target patients who attended the Microbiology Laboratory of a tertiary care eye hospital in Coimbatore, Tamilnadu state, India. The isolates were subjected to tube and slide coagulase tests for the identification of CoNS. All the isolates were subjected to screening for lipase and protease activities. Screening for other virulence factors viz., slime production on Congo red agar medium and haemagglutination assay with use of 96-well microtitre plates. These isolates were identified upto species level by performing biochemical tests such as phosphatase test, arginine test, maltose and trehalose fermentation tests and novobiocin sensitivity test. The isolates were subjected to antibiotic susceptibility studies, based on the revised standards of Clinical and Laboratory Standards Institutes (CLSI). Results: During the one year of study, among the total 260 individuals who were screened, 100 isolates of CoNS were obtained. Lipolytic activity was seen in all the isolates, whereas 38 isolates showed a positive result for protease. A total of 63 isolates showed slime production. Of 100 isolates, 30 isolates were analyzed for haemagglutination, where 4 isolates showed the capacity to agglutinate the erythrocytes. The results of the biochemical analysis revealed that of the 100 isolates of CoNS, 43% were Staphylococcus epidermidis. The other

  15. conSSert: Consensus SVM Model for Accurate Prediction of Ordered Secondary Structure.

    PubMed

    Kieslich, Chris A; Smadbeck, James; Khoury, George A; Floudas, Christodoulos A

    2016-03-28

    Accurate prediction of protein secondary structure remains a crucial step in most approaches to the protein-folding problem, yet the prediction of ordered secondary structure, specifically beta-strands, remains a challenge. We developed a consensus secondary structure prediction method, conSSert, which is based on support vector machines (SVM) and provides exceptional accuracy for the prediction of beta-strands with QE accuracy of over 0.82 and a Q2-EH of 0.86. conSSert uses as input probabilities for the three types of secondary structure (helix, strand, and coil) that are predicted by four top performing methods: PSSpred, PSIPRED, SPINE-X, and RAPTOR. conSSert was trained/tested using 4261 protein chains from PDBSelect25, and 8632 chains from PISCES. Further validation was performed using targets from CASP9, CASP10, and CASP11. Our data suggest that poor performance in strand prediction is likely a result of training bias and not solely due to the nonlocal nature of beta-sheet contacts. conSSert is freely available for noncommercial use as a webservice: http://ares.tamu.edu/conSSert/ . PMID:26928531

  16. ConA-based glucose sensing using the long-lifetime azadioxatriangulenium fluorophore

    NASA Astrophysics Data System (ADS)

    Cummins, Brian; Simpson, Jonathan; Gryczynski, Zygmunt; Sørensen, Thomas Just; Laursen, Bo W.; Graham, Duncan; Birch, David; Coté, Gerard

    2014-02-01

    Fluorescent glucose sensing technologies have been identified as possible alternatives to current continuous glucose monitoring approaches. We have recently introduced a new, smart fluorescent ligand to overcome the traditional problems of ConA-based glucose sensors. For this assay to be translated into a continuous glucose monitoring device where both components are free in solution, the molecular weight of the smart fluorescent ligand must be increased. We have identified ovalbumin as a naturally-occurring glycoprotein that could serve as the core-component of a 2nd generation smart fluorescent ligand. It has a single asparagine residue that is capable of displaying an N-linked glycan and a similar isoelectric point to ConA. Thus, binding between ConA and ovalbumin can potentially be monovalent and sugar specific. This work is the preliminary implementation of fluorescently-labeled ovalbumin in the ConA-based assay. We conjugate the red-emitting, long-lifetime azadioxatriangulenium (ADOTA+) dye to ovalbumin, as ADOTA have many advantageous properties to track the equilibrium binding of the assay. The ADOTA-labeled ovalbumin is paired with Alexa Fluor 647-labeled ConA to create a Förster Resonance Energy Transfer (FRET) assay that is glucose dependent. The assay responds across the physiologically relevant glucose range (0-500 mg/dL) with increasing intensity from the ADOTA-ovalbumin, showing that the strategy may allow for the translation of the smart fluorescent ligand concept into a continuous glucose monitoring device.

  17. ConSole: using modularity of Contact maps to locate Solenoid domains in protein structures

    PubMed Central

    2014-01-01

    Background Periodic proteins, characterized by the presence of multiple repeats of short motifs, form an interesting and seldom-studied group. Due to often extreme divergence in sequence, detection and analysis of such motifs is performed more reliably on the structural level. Yet, few algorithms have been developed for the detection and analysis of structures of periodic proteins. Results ConSole recognizes modularity in protein contact maps, allowing for precise identification of repeats in solenoid protein structures, an important subgroup of periodic proteins. Tests on benchmarks show that ConSole has higher recognition accuracy as compared to Raphael, the only other publicly available solenoid structure detection tool. As a next step of ConSole analysis, we show how detection of solenoid repeats in structures can be used to improve sequence recognition of these motifs and to detect subtle irregularities of repeat lengths in three solenoid protein families. Conclusions The ConSole algorithm provides a fast and accurate tool to recognize solenoid protein structures as a whole and to identify individual solenoid repeat units from a structure. ConSole is available as a web-based, interactive server and is available for download at http://console.sanfordburnham.org. PMID:24766872

  18. Structural basis of ConM binding with resveratrol, an anti-inflammatory and antioxidant polyphenol.

    PubMed

    Rocha, Bruno A M; Teixeira, Claudener S; Silva-Filho, José C; Nóbrega, Raphael B; Alencar, Daniel B; Nascimento, Kyria S; Freire, Valder N; Gottfried, Carmem J S; Nagano, Celso S; Sampaio, Alexandre H; Saker-Sampaio, Silvana; Cavada, Benildo S; Delatorre, Plínio

    2015-01-01

    Resveratrol can also inhibit the activation of proinflammatory mediators and cytokines at the early gene expression stage. It is well known that lectins are sugar-binding proteins that act as both pro- and anti-inflammatory molecules. Thus, the objective of this work was to verify the binding of a polyphenol compound with a lectin of Canavalia maritima (ConM) based on their ability to inhibit pro-inflammatory processes. To accomplish this, ConM was purified and crystallized, and resveratrol was soaked at 5mM for 2h of incubation. The crystal belongs to the monoclinic space group C2, the final refinement resulted in an Rfactor of 16.0% and an Rfree of 25.5%. Resveratrol binds in the rigid β-sheet through H-bonds and hydrophobic interaction with amino acids that compose the fifth and sixth β-strands of the rigid β-sheet of ConM. The ConM and resveratrol inhibited DPPH oxidation, showing synergic activity with the most effective ratio of 2:3 and carbohydrate binding site is not directly related to antioxidant activity. It is the interaction between ConM and resveratrol that indicates the synergism of these two molecules in acting as free radicals scavengers and in reducing the inflammatory process through the inhibition of many pro-inflammatory events. PMID:25192853

  19. Orbit and spin resolved magnetic properties of size selected [ConRh]⁺ and [ConAu]⁺ nanoalloy clusters.

    PubMed

    Dieleman, Dennis; Tombers, Matthias; Peters, Lars; Meyer, Jennifer; Peredkov, Sergey; Jalink, Jeroen; Neeb, Matthias; Eberhardt, Wolfgang; Rasing, Theo; Niedner-Schatteburg, Gereon; Kirilyuk, Andrei

    2015-11-14

    Bi-metallic nanoalloys of mixed 3d-4d or 3d-5d elements are promising candidates for technological applications. The large magnetic moment of the 3d materials in combination with a high spin-orbit coupling of the 4d or 5d materials give rise to a material with a large magnetic moment and a strong magnetic anisotropy, making them ideally suitable in for example magnetic storage devices. Especially for clusters, which already have a higher magnetic moment compared to the bulk, these alloys can profit from the cooperative role of alloying and size reduction in order to obtain magnetically stable materials with a large magnetic moment. Here, the influence of doping of small cobalt clusters on the spin and orbital magnetic moment has been studied for the cations [Co(8-14)Au](+) and [Co(10-14)Rh](+). Compared to the undoped pure cobalt [Co(N)](+) clusters we find a significant increase in the spin moment for specific Co(N-1)Au(+) clusters and a very strong increase in the orbital moment for some Co(N-1)Rh(+) clusters, with more than doubling for Co12Rh(+). This result shows that substitutional doping of a 3d metal with even just one atom of a 4d or 5d metal can lead to dramatic changes in both spin and orbital moment, opening up the route to novel applications. PMID:26104269

  20. Pros and cons of quitting, self-efficacy, and the stages of change in smoking cessation.

    PubMed

    Dijkstra, A; de Vries, H; Bakker, M

    1996-08-01

    In The Netherlands, 34% of the population smoke, and 70% of these smokers are not planning to quit. The lower percentages in the U.S. population seem to reflect a difference in smoking culture. This study analyzes the pros and cons of quitting and self-efficacy expectation in the 5 stages of change in the Dutch population. The results are compared with the pattern of the pros and cons of smoking and self-efficacy expectations found in U.S. samples. The data show the hypothesized pattern: In the first 2 stages, the expected positive outcomes of quitting discriminated better between the stages than self-efficacy, whereas for later stages, self-efficacy was the better discriminator. This study shows that the stage typology is applicable to the Dutch population and that the pattern of the pros, cons, and self-efficacy is very similar to the pattern found in the U.S. populations. PMID:8803366

  1. C-ON Bond Homolysis of Alkoxyamines, Part 11: Activation of the Nitroxyl Fragment.

    PubMed

    Audran, Gérard; Brémond, Paul; Marque, Sylvain R A; Yamasaki, Toshihide

    2016-03-01

    A few years ago, Bagryanskaya and colleagues (J. Org. Chem. 2011) showed that protonation of the nitroxyl fragment deactivated the alkoxyamine C-ON bond. Conversely, our group showed that protonation (Chem. Commun. 2011), as well as other chemical reactions such as oxidation or amine quaternization (Org. Lett. 2012), of the pyridyl moiety carried by the alkyl fragment was suitable to activate the homolysis of the C-ON bond. To pursue our goal of applying alkoxyamines as theranostic agents (Org. Biomol. Chem. 2014 and Mol. Pharmaceutics 2014) by activation of the C-ON bond homolysis, we turned our interest to the chemical activation of the nitroxyl fragment by oxidation/reduction of selected functions. Conversion of a hydroxyl group located close to the nitroxyl moiety successively into aldehyde, then acid, and eventually into ester, led to a successive decrease in kd. PMID:26878593

  2. ConTour: Data-Driven Exploration of Multi-Relational Datasets for Drug Discovery

    PubMed Central

    Partl, Christian; Lex, Alexander; Streit, Marc; Strobelt, Hendrik; Wassermann, Anne-Mai; Pfister, Hanspeter; Schmalstieg, Dieter

    2016-01-01

    Large scale data analysis is nowadays a crucial part of drug discovery. Biologists and chemists need to quickly explore and evaluate potentially effective yet safe compounds based on many datasets that are in relationship with each other. However, there is a lack of tools that support them in these processes. To remedy this, we developed ConTour, an interactive visual analytics technique that enables the exploration of these complex, multi-relational datasets. At its core ConTour lists all items of each dataset in a column. Relationships between the columns are revealed through interaction: selecting one or multiple items in one column highlights and re-sorts the items in other columns. Filters based on relationships enable drilling down into the large data space. To identify interesting items in the first place, ConTour employs advanced sorting strategies, including strategies based on connectivity strength and uniqueness, as well as sorting based on item attributes. ConTour also introduces interactive nesting of columns, a powerful method to show the related items of a child column for each item in the parent column. Within the columns, ConTour shows rich attribute data about the items as well as information about the connection strengths to other datasets. Finally, ConTour provides a number of detail views, which can show items from multiple datasets and their associated data at the same time. We demonstrate the utility of our system in case studies conducted with a team of chemical biologists, who investigate the effects of chemical compounds on cells and need to understand the underlying mechanisms. PMID:26356902

  3. Experiences using INGRES in a large battlefield simulation (ConMod)

    SciTech Connect

    Rodgers, S.D.

    1989-11-01

    This paper describes the experiences of using INGRES in a large battlefield simulation. The paper includes a project overview, a section on INGRES components, and conclusions. The project overview describes the ConMod project and its objectives. This section also discusses our needs for the project with respect to a data storage system. The section on INGRES components briefly describes what the components are, how we used them in the ConMod project, and their advantages and disadvantages. The last section concludes with some general comments about INGRES and its appropriateness for particular projects. 3 refs.

  4. Obstáculos a la adherencia y retención en los sistemas de salud público y privado según pacientes y personal de salud

    PubMed Central

    Arístegui, Inés; Dorigo, Analía; Bofill, Lina; Bordatto, Alejandra; Lucas, Mar; Cabanillas, Graciela Fernández; Sued, Omar; Cahn, Pedro; Cassetti, Isabel; Weiss, Stephen; Jones., Deborah

    2016-01-01

    Resumen Introducción el Programa Nacional de Sida garantiza el acceso universal a los antirretrovirales, aun así las personas que reciben medicamentos a través del sistema público no logran obtener una carga viral indetectable en la misma proporción que los pacientes del sistema privado. Este estudio cualitativo tiene como objeto identificar los factores asociados a la adherencia y retención en la cascada de atención de VIH de los sistemas de salud público y privado de Buenos Aires, según las percepciones de pacientes y del personal de salud. Métodos se registraron datos cualitativos de 12 entrevistas semi-estructuradas a informantes clave y 4 grupos focales de pacientes y personal de salud tanto del sistema público como privado. Se codificaron y analizaron temas predeterminados sobre adherencia, utilizando el software QRS Nvivo9® de análisis de datos cualitativos. Resultados pacientes y personal de salud de ambos sistemas coinciden en la importancia del estigma asociado al VIH, la relación médicopaciente, la comunicación entre ambos y la división de responsabilidades en relación al tratamiento como aspectos fundamentales para la adherencia y retención en la cascada de atención. Se observan diferencias entre los sistemas en la forma en que algunos de estos aspectos actúan. Las barreras estructurales se presentan como principales obstáculos del sistema público. Discusión se resalta la necesidad de intervenciones focalizadas en la díada médico-paciente que considere las particularidades de cada sistema de atención para facilitar el compromiso del paciente en la adherencia. PMID:26878024

  5. 40 CFR 227.27 - Limiting permissible con-cen-tra-tion (LPC).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Limiting permissible con-cen-tra-tion (LPC). 227.27 Section 227.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Definitions § 227.27 Limiting...

  6. The Con Edison Emergency Child Care Plan for Management Employees: Summary Plan Description.

    ERIC Educational Resources Information Center

    Consolidated Edison Co., Brooklyn, NY.

    This summary plan description offers guidelines for participation in a pilot program that provides short-term emergency care for children of Con Edison managers who are under 13 years old. The plan offers professional, in-home child care that can be used when usual arrangements have collapsed. The summary plan description addresses the following…

  7. Algunas mujeres con cáncer de seno pueden abstenerse de quimioterapia

    Cancer.gov

    Resumen de resultados del estudio TAILORx indica que mujeres con cáncer de seno receptor de hormonas en estadio inicial tienen un riesgo bajo de recurrencia según una prueba de expresión de 21 genes.

  8. CHILES Con Pol: An ultra-deep JVLA survey probing galaxy evolution and cosmic magnetism

    NASA Astrophysics Data System (ADS)

    Hales, Christopher A.; Momjian, Emmanuel; van Gorkom, Jacqueline; Rupen, Michael P.; Greiner, Maksim; Ensslin, Torsten A.; Bonzini, Margherita; Padovani, Paolo; Harrison, Ian; Brown, Michael L.; Gim, Hansung; Yun, Min S.; Maddox, Natasha; Stewart, Adam; Fender, Rob P.; Tremou, Evangelia; Chomiuk, Laura; Peters, Charee; Wilcots, Eric M.; Lazio, Joseph

    2015-08-01

    We are undertaking a 1000 hour campaign with the Karl G. Jansky VLA to survey 0.2 square degrees of the COSMOS field in full polarization continuum at 1.4 GHz. Our observations are part of a joint program with the spectral line COSMOS HI Large Extragalactic Survey (CHILES). When complete, we expect our CHILES Continuum Polarization (CHILES Con Pol) survey to reach an SKA-era sensitivity of 500 nJy per 4 arcsecond resolving beam, the deepest view of the radio sky yet. CHILES Con Pol will open new and fertile parameter space, with sensitivity to star formation rates of 10 Msun per year out to an unprecedented redshift of z=2, and ultra-luminous infrared galaxies and sub-millimeter galaxies out to redshifts of z=8 and beyond. This rich resource will extend the utility of radio band studies beyond the usual radio quasar and radio galaxy populations, opening sensitivity to the starforming and radio-quiet AGN populations that form the bulk of extragalactic sources detected in the optical, X-ray, and infrared bands. In this talk I will outline the key science of CHILES Con Pol, including galaxy evolution and novel measurements of intergalactic magnetic fields. I will present initial results from the first 180 hours of the survey and describe our forthcoming Data Release 1. I invite the astronomical community to consider unique science that can be pursued with CHILES Con Pol radio data.

  9. 40 CFR 227.27 - Limiting permissible con-cen-tra-tion (LPC).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Limiting permissible con-cen-tra-tion (LPC). 227.27 Section 227.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Definitions § 227.27 Limiting...

  10. 40 CFR 227.27 - Limiting permissible con-cen-tra-tion (LPC).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Limiting permissible con-cen-tra-tion (LPC). 227.27 Section 227.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Definitions § 227.27 Limiting...

  11. Asociación de XMRV con enfermedades humanas se debe a contaminación

    Cancer.gov

    Nuevas investigaciones muestran que una asociación, mencionada en numerosos estudios, entre el retrovirus conocido como XMRV y el cáncer de próstata así como el síndrome de fatiga crónica, se debe a contaminación de laboratorio con un virus que se originó en ratones.

  12. A National Look at Postmodernism's Pros and Cons in Educational Leadership

    ERIC Educational Resources Information Center

    Townsell, Rhodena

    2007-01-01

    The purpose of this article is to take a look at the pros and cons of postmodernism. It is imperative for administrators to closely examine educational theories and practices prior to instituting changes. The ability to read and digest challenging material keeps one informed and prepared to lead effectively. This paper will list the pros and cons…

  13. 40 CFR 227.27 - Limiting permissible con-cen-tra-tion (LPC).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Limiting permissible con-cen-tra-tion (LPC). 227.27 Section 227.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Definitions § 227.27 Limiting...

  14. A Qualitative Approach to Upward Evaluation of Leadership Performance: Pros and Cons

    ERIC Educational Resources Information Center

    Turrentine, Cathryn G.; Lener, Edward F.; Young, Michelle L.; Kok, Victoria T.

    2004-01-01

    This article describes a qualitative upward evaluation of the leadership performance of library managers. Follow-up studies were conducted, focusing on the advantages and disadvantages of the qualitative approach to upward appraisal. The authors discuss pros and cons to guide others who might use this methodology for upward appraisals in the…

  15. Non Invasive Biomedical Analysis - Breath Networking Session at PittCon 2011, Atlanta, Georgia

    EPA Science Inventory

    This was the second year that our breath colleagues organized a networking session at the Pittsburgh Conference and Exposition or ''PittCon'' (http://www.pincon.org/).This time it was called "Non-invasive Biomedical Analysis" to broaden the scope a bit, but the primary focus rema...

  16. 40 CFR 227.27 - Limiting permissible con-cen-tra-tion (LPC).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Limiting permissible con-cen-tra-tion (LPC). 227.27 Section 227.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE EVALUATION OF PERMIT APPLICATIONS FOR OCEAN DUMPING OF MATERIALS Definitions § 227.27 Limiting...

  17. Pros and Cons of Teaching Reading to Four- and Five-Year-Olds.

    ERIC Educational Resources Information Center

    Ollila, Lloyd O.

    There are many pros and cons to the recent trend of early reading. The opponents fear that too much emphasis on early reading may lead to a less rounded development of the child; they agree on providing the child with richer and more varied experiences to insure reading readiness. The advocates believe that today's children have already had more…

  18. Mandated Mental Health Insurance: A Complex Case of Pros and Cons. Human Resources Series.

    ERIC Educational Resources Information Center

    Paterson, Andrea

    1986-01-01

    The pros and cons of state laws mandating mental health insurance are discussed in this report. The history of a 1985 Supreme Court case which held that states could mandate mental health benefits introduces the report. In an overview of the issue, the long-standing argument between the insurance industry and the mental health establishment is…

  19. Impact of the ConRed program on different cyberbulling roles.

    PubMed

    Del Rey, Rosario; Casas, José A; Ortega, Rosario

    2016-01-01

    This article presents results from an evaluation of the ConRed cyberbullying intervention program. The program's impacts were separately determined for the different roles within cyberbullying that students can take, i.e., cyber-victims, cyber-bullies, cyber-bully/victims, and bystanders. The ConRed program is a theory-driven program designed to prevent cyberbullying and improve cyberbullying coping skills. It involves students, teachers, and families. During a 3-month period, external experts conducted eight training sessions with students, two with teachers and one with families. ConRed was evaluated through a quasi-experimental design, in which students from three secondary schools were separated into experimental and control groups. The sample comprised 875 students, aged between 11 and 19 years. More students (n = 586) were allocated to the experimental groups at the specific insistence of the management of all schools; the remainder (n = 289) formed the control. Repeated measures MANOVA showed that cyber victims, cyber aggressors and cyberbully/victims reduced their involvement in cyberbullying. Moreover, cyber-victims and bystanders adjusted their perceptions about their control of personal information on the Internet, and cyber aggressors and bystanders reduced their Internet dependence. The ConRed program had stronger effects on male participants, especially in heightening their affective empathy. PMID:26351131

  20. A Manual for Merger. A Guide to Examine the Feasibility & Implications of Merger: The Pros & Cons.

    ERIC Educational Resources Information Center

    Bridgman, John N., Jr., Ed.

    Written for boards of education, school administrators, and others who wish to explore the possibilities of merger within their own counties, this manual examines the pros and cons through the experiences of those who have implemented school district mergers in recent years in North Carolina. Guidelines are provided for implementing mergers…