MedWorm: Neurofibromatosis

The importance of advanced parental age in the origin of neurofibromatosis type 1

American Journal of Medical Genetics Part A — Thu, 02 Feb 2012 05:00:00 +0100

AbstractVon Recklinghausen neurofibromatosis (NF1) is an autosomal dominant disorder with a prevalence about 1/3,000 (1/2,000–1/5,000 in various population‐based studies). About 30–50% of cases are sporadic, resulting from a new mutation. NF1 is fully penetrant by mid‐childhood, stigmata, and medical problems (neurological, dermatological, endocrine, ophthalmological, oncological) are highly variable. Advanced paternal age (APA) has been known to increase the risk of new germline mutations that contribute to the presence of a variety of genetic diseases in the human population. The trend in developed countries has been toward higher parental age due to various reasons. In a cross‐sectional study, in two university hospital centers, data on parental age of 103 children (41 female)...

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Internal tumor burden in neurofibromatosis Type I patients with large NF1 deletions

Genes, Chromosomes and Cancer — Wed, 01 Feb 2012 05:00:00 +0100

AbstractNeurofibromatosis Type 1 (NF1) is a frequent tumor suppressor gene disorder characterized by multiple benign tumors and high risk of malignancy. Internal tumor burden is a major disease‐associated manifestation and can be most adequately assessed by magnetic resonance imaging of the whole body. Approximately 5% of NF1 patients have constitutional large NF1‐deletions that are generally associated with more severe clinical manifestations. Here, we investigated whether these deletion patients also have more and/or larger internal tumors by assessing internal tumors and their total volume (exclusive of cutaneous and subcutaneous) in 38 NF1 deletion patients (including eight mosaic cases) and 114 age‐ and gender‐matched NF1 patients without deletions. The incidence of internal t...

Spontaneous modifications of contrast enhancement in childhood non-cerebellar pilocytic astrocytomas

Neuroradiology — Fri, 27 Jan 2012 17:51:59 +0100

Conclusion In our experience, n-C PA may show variable CE over time in the absence of tumor/residual tumor dimension change. We recommend that CE fluctuations alone cannot be considered an indicator of tumor progression/regression. Content Type Journal ArticleCategory Paediatric NeuroradiologyPages 1-7DOI 10.1007/s00234-012-1010-3Authors Simona Gaudino, Department of Bioimaging and Radiological Sciences, Catholic University, Pol. A. Gemelli, L.go A. Gemelli 8, 000168 Rome, ItalyFrancesca Romana Quaglio, Department of Bioimaging and Radiological Sciences, Catholic University, Pol. A. Gemelli, L.go A. Gemelli 8, 000168 Rome, ItalyChiara Schiarelli, Department of Bioimaging and Radiological Sciences, Catholic University, Pol. A. Gemelli, L.go A. Gemelli 8, 000168 Rome, ...

Peripheral muscle weakness in RASopathies

Muscle and Nerve — Wed, 25 Jan 2012 05:00:00 +0100

The objective was to evaluate handgrip strength in the RASopathies.Methods:Individuals with RASopathies [e.g. Noonan syndrome, Costello syndrome, cardio‐facio‐cutaneous (CFC) syndrome, and neurofibromatosis type 1 (NF1)] and healthy controls were evaluated. Two methods of handgrip strength were tested: GRIP‐D Takei Hand Grip Dynamometer and the Martin vigorimeter. A general linear model was fitted to compare average strength among the groups, controlling for confounders such as age, gender, height, and weight.Results:Takei dynamometer: handgrip strength was decreased in each of the syndromes compared to controls. Decreased handgrip strength compared to sibling controls was also seen with the Martin vigorimeter (p<0.0001).Discussion:Handgrip strength is decreased in the RASopathies...

Abnormal Achromatic and Chromatic Contrast Sensitivity in Neurofibromatosis Type 1 [Eye Movements, Strabismus, Amblyopia, and Neuro-Ophthalmology]

Investigative Ophthalmology — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions. These findings showed that contrast sensitivity is impaired in patients with NF1, associating for the first time abnormal low-level vision to the cognitive profile of this disorder. (Source: Investigative Ophthalmology)

Multiple, Unilateral Lisch Nodules in the Absence of Other Manifestations of Neurofibromatosis Type 1

Advances in Pharmacological Sciences — Mon, 23 Jan 2012 18:36:31 +0100

Lisch nodules associated with Neurofibromatosis Type 1 (NF1) are usually multiple and bilateral in nature. Here, we report a 21-year-old healthy, Caucasian female who was diagnosed with multiple, unilateral Lisch nodules during routine eye examination. A thorough history and physical examination revealed no other signs of NF1. We diagnosed the rare occurrence of numerous, unilateral Lisch nodules in the absence of additional features of NF1 in our patient and provide a discussion concerning the differential diagnosis of Lisch nodules as well as the potential genetic explanation of this finding. (Source: Advances in Pharmacological Sciences)

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A Case of Persistent Foot Pain in a Neurofibromatosis Type I Patient

Diagnostic and Therapeutic Endoscopy — Wed, 18 Jan 2012 12:06:54 +0100

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. (Source: Diagnostic and Therapeutic Endoscopy)

Multiple central nervous system hyperintensities in a child with neurofibromatosis type 1

Revista Paulista de Pediatria — Wed, 18 Jan 2012 06:37:28 +0100

OBJETIVO:Relatar o caso de uma criança com neurofibromatose do tipo 1, apresentando o achado ocasional de múltiplas hiperintensidades e de lesão hamartomatosa pré-quiasmática no sistema nervoso central. DESCRIÇÃO DO CASO: Menino de tez escura de quatro anos, cujo pai apresentava manchas café-com-leite e história de cirurgia de tumor de ouvido. A criança evoluiu com um adequado desenvolvimento neuropsicomotor, sem crises convulsivas ou déficit de aprendizagem. Ao exame físico, possuía múltiplas manchas café-com-leite e efélides. A avaliação pela ressonância nuclear magnética de encéfalo evidenciou múltiplas imagens nodulares hiperintensas em T2 e Flair, com isossinal em T1, localizadas na substância branca dos hemisférios cerebrais, cerebelo e tronco cerebral. Aprese...

Auditory brainstem implant outcomes and MAP parameters: Report of experiences in adults and children

International Journal of Pediatric Otorhinolaryngology — Tue, 17 Jan 2012 21:16:09 +0100

Conclusion: We observed that ABI may be a good option for offering some hearing attention to both adults and children. In children, the results might not be enough to ensure oral language development. Programming the speech processor in children demands higher care to the audiologist. (Source: International Journal of Pediatric Otorhinolaryngology)

Temozolomide for Pediatric High-Grade Gliomas

Current Neurology and Neuroscience Reports — Tue, 17 Jan 2012 07:06:32 +0100

Content Type Journal ArticleCategory Clinical Trial ReportPages 1-3DOI 10.1007/s11910-012-0250-2Authors Roger J. Packer, Center for Neuroscience and Behavioral Medicine, Children’s National Medical Center, Gilbert Neurofibromatosis Institute, Brain Tumor Institute, 111 Michigan Avenue, NW, Washington, DC 20010, USA Journal Current Neurology and Neuroscience ReportsOnline ISSN 1534-6293Print ISSN 1528-4042 (Source: Current Neurology and Neuroscience Reports)

Mitotic recombination of chromosome arm 17q as a cause of loss of heterozygosity of NF1 in neurofibromatosis type 1‐associated glomus tumors

Genes, Chromosomes and Cancer — Tue, 17 Jan 2012 05:00:00 +0100

AbstractNeurofibromatosis type 1 (NF1) is a common, autosomal dominant, tumor‐predisposition syndrome that arises secondary to mutations in NF1. Glomus tumors are painful benign tumors that originate from the glomus body in the fingers and toes due to biallelic inactivation of NF1. We karyotyped cultures from four previously reported and one new glomus tumor and hybridized tumor (and matching germline) DNA on Illumina HumanOmni1‐Quad SNP arrays (∼1 × 106 SNPs). Two tumors displayed evidence of copy‐neutral loss of heterozygosity of chromosome arm 17q not observed in the germline sample, consistent with a mitotic recombination event. One of these two tumors, NF1‐G12, featured extreme polyploidy (near‐tetraploidy, near‐hexaploidy, or near‐septaploidy) across all chromosomes....

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Sciatica from a Foraminal Lumbar Root Schwannoma: Case Report and Review of Literature

Journal of Biomedicine and Biotechnology — Sun, 15 Jan 2012 16:11:39 +0100

Sciatica is commonly caused by lumbar prolapsed intervertebral disc (PID) and other spinal lesions. Uncommon causes like nerve root schwannoma are rarely considered in the differential diagnosis of sciatica. Spinal schwannomas occur both sporadically and in association with neurofibromatosis type 1 (NF1; von Recklinghausen's disease). This case report describes lumbar foraminal schwannoma as an unusual cause of radiculopathy, presenting clinically as a lumbar disc prolapse. The diagnosis was confirmed on MRI scan. Patient had complete symptomatic recovery following surgical enucleation of the tumour mass from the L5 nerve root. This case report is of particular interest as it highlights the diagnostic confusion, which is bound to arise, because the clinical presentation closely mimics a lu...

Lack of Neurofibromatosis Type 2 Gene Promoter Methylation in Sporadic Vestibular Schwannomas

ORL — Thu, 12 Jan 2012 23:00:00 +0100

ORL 2012;74:33–37 (DOI:10.1159/000334968) (Source: ORL)

Neoplasms Associated with Germline and Somatic NF1 Gene Mutations.

The Oncologist — Thu, 12 Jan 2012 05:00:00 +0100

Conclusions. The lack of well-defined screening tests for early detection and the nonspecific clinical presentation contributes to a poorer outcome in malignancies associated with NF1. Small study group size, mixed patient population, and a lack of uniformity in reporting research results make comparison of treatment outcome for this group difficult. An International Consensus Meeting to address and recommend best practices for screening, diagnosis, management, and follow-up of malignancies associated with NF1 is needed. PMID: 22240541 [PubMed - as supplied by publisher] (Source: The Oncologist)

Neurofibromatosis type 1 with dural ectasia

The Journal of Dermatology — Tue, 10 Jan 2012 05:00:00 +0100

(Source: The Journal of Dermatology)

An histologically atypical NF-type 1 patient with a new pathogenic mutation

Neurological Sciences — Thu, 05 Jan 2012 17:06:27 +0100

Abstract Here we describe a case of Neurofibromatosis type 1 (NF1) associated with an atypical histiocytic lesion and a new pathogenic mutation. The genetic analysis revealed an heterozygous mutation in the 5′ splice site of intron 32, 6,084 + 1G → T. Histopathological findings are compatible with juvenile xanthogranuloma. The new, not already described, splicing mutation, is possibly partly responsible of the association between NF1 and the histiocitic lesion. Content Type Journal ArticleCategory Letter to the EditorPages 1-3DOI 10.1007/s10072-011-0897-5Authors Giovanni Bianco, Dipartimento di Neuroscienze, Sezione Neurologia e Neurofisiologia Clinica, Azienda Ospedaliera-Universitaria Senese, Policlinico Le Scotte, Viale Bracci, 53100 Siena, I...

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Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes

Acta Neuropathologica — Fri, 30 Dec 2011 16:42:01 +0100

Abstract Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, p...

Screening for mutation site on the type I neurofibromatosis gene in a family

Child's Nervous System — Fri, 30 Dec 2011 07:09:24 +0100

Conclusions The synonymous mutations in the NF1 gene occur in exons 7, 38, 50, and 56. The CAG homozygous mutations may occur in exon 19, and the C/TAG heterozygous mutations may occur in the others. This mutation may be responsible for NF1 in patients in this family and may warrant extensive research on the NF1 gene. Content Type Journal ArticleCategory Original PaperPages 1-7DOI 10.1007/s00381-011-1653-0Authors Ming Lv, Department of Orthopedics, Central Hospital of Zibo City, Zibo, 255000 ChinaWenhua Zhao, Department of Oncology, Qianfoshan Hospital of Shandong Province, Jinan, 250014 ChinaLin Yan, The No.148 Hospital of People’s Liberation Army, Zibo, 255300 ChinaLiang Chen, Department of Orthopedics, Shandong Provincial Hospital, Jinan, 250021 ChinaKai Cui, K...

Pleomorphic xanthoastrocytoma in two siblings with neurofibromatosis Type 1 (NF-1).

Clinical Neuropathology — Mon, 26 Dec 2011 11:30:12 +0100

Authors: Neal MT, Ellis TL, Stanton CA PMID: 22192706 [PubMed - in process] (Source: Clinical Neuropathology)

Orbitofacial neurofibromatosis: clinical characteristics and treatment outcome

Eye — Fri, 23 Dec 2011 08:00:00 +0100

Authors: I A Chaudhry, J Morales, F A Shamsi, W Al-Rashed, E Elzaridi, Y O Arat, C Jacquemin, D T Oystreck & T M Bosley (Source: Eye)

What Causes a Black Colored Tongue?

PediatricEducation.org — Mon, 19 Dec 2011 00:29:33 +0100

Discussion Although dental caries, strep throat and oral candidiasis are some of the most common oral pathology. The tongue itself can be a source of potential pathology. Geographic tongue, oral candidiasis, and lingual ulcerations are common problems. Most discolorations of the tongue are because of food, drink or medications that are ingested and are self-limited. However discoloration can be a sign of more significant problems. Hairy tongue, often colored black, is a relatively uncommon problem in the US but has a higher incidence reported in Turkey and Iran. It is more common in adults than children but has been reported in a child 2 months of age. It is also called lingua villosa nigra and is a benign condition caused by keratin accumulation usually in the setting of poor oral hygiene...

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Unusual cardiac presentation in neurofibromatosis type 1

European Journal of Echocardiography — Wed, 14 Dec 2011 05:00:00 +0100

(Source: European Journal of Echocardiography)

Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms

Acta Neuropathologica — Sat, 10 Dec 2011 16:55:02 +0100

Abstract Neurofibromas, schwannomas and malignant peripheral nerve sheath tumors (MPNSTs) all arise from the Schwann cell lineage. Despite their common origin, these tumor types have distinct pathologies and clinical behaviors; a growing body of evidence indicates that they also arise via distinct pathogenic mechanisms. Identification of the genes that are mutated in genetic diseases characterized by the development of either neurofibromas and MPNSTs [neurofibromatosis type 1 (NF1)] or schwannomas [neurofibromatosis type 2 (NF2), schwannomatosis and Carney complex type 1] has greatly advanced our understanding of these mechanisms. The development of genetically engineered mice with ablation of NF1, NF2, SMARCB1/INI1 or PRKAR1A has confirmed the key role these genes play in ...

Letter: Misdiagnosis of "neurofibromatosis" in patients with piebaldism.

Dermatol Online J — Wed, 07 Dec 2011 17:30:03 +0100

Letter: Misdiagnosis of "neurofibromatosis" in patients with piebaldism. Dermatol Online J. 2011;17(11):13 Authors: Spritz R Abstract Miminal diagnostic criteria for the diagnosis of neurofibromatosis 1 (NF1) includes six or more café-au-lait macules plus axillary freckling. However, a recent report by Duarte et al claims co-occurrence of piebaldism and NF1 using this minimal criteria. We assert that this is not an accurate conclusion because both of these pigmentary findings occur frequently in typical cases of piebaldism. PMID: 22136869 [PubMed - in process] (Source: Dermatol Online J)

Whole-body MRI in neurofibromatosis: incidental findings and prevalence of scoliosis

Skeletal Radiology — Tue, 06 Dec 2011 17:04:00 +0100

Conclusions Incidental findings in the neurofibromatoses frequently involve the skeleton. Given the relatively high incidence of unsuspected osteonecrosis and stress fractures, close attention to the skeleton on WBMRI is advised. In addition, knowledge of common incidental findings can help clinicians prepare patients who undergo WBMRI for potential unexpected findings. Content Type Journal ArticleCategory Scientific ArticlePages 1-7DOI 10.1007/s00256-011-1333-xAuthors Jacob L. Jaremko, Musculoskeletal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Yawkey 6E, 55 Fruit Street, Boston, MA 02114, USAPeter J. MacMahon, Musculoskeletal Imaging and Intervention, Department of Radiology, Massachusetts General H...

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Histopathological analysis of a 15 year user of an auditory brainstem implant (ABI)

The Laryngoscope — Tue, 06 Dec 2011 05:00:00 +0100

AbstractAuditory brainstem implants (ABIs) can provide highly beneficial hearing sensations to individuals deafened by bilateral vestibular schwannomas (neurofibromatosis type 2). Relatively little is known about the status of stimulated neurons after long‐term ABI use. Direct examination of the cochlear nuclear complex (CN) of one 5‐year ABI user indicated no deleterious effect. Recently, we examined the brainstem of a patient who used his ABI daily for 15 years with excellent performance. There was good preservation of CN cell size, morphology and packing density—a very favorable sign considering that a number of infants are now receiving ABIs. Laryngoscope, 2011. (Source: The Laryngoscope)

Histopathological analysis of a 15‐year user of an auditory brainstem implant

The Laryngoscope — Tue, 06 Dec 2011 05:00:00 +0100

AbstractAuditory brainstem implants (ABIs) can provide highly beneficial hearing sensations to individuals deafened by bilateral vestibular schwannomas (neurofibromatosis type 2). Relatively little is known about the status of stimulated neurons after long‐term ABI use. Direct examination of the cochlear nuclear complex (CN) of one 5‐year ABI user indicated no deleterious effect. Recently, we examined the brainstem of a patient who used his ABI daily for 15 years with excellent performance. There was good preservation of CN cell size, morphology, and packing density, a very favorable sign considering that a number of infants are now receiving ABIs. (Source: The Laryngoscope)

[Unusual clinical manifestations of type 1 neurofibromatosis].

Orvosi Hetilap — Sun, 04 Dec 2011 05:00:00 +0100

Authors: Komlósi K, Polgár N, Hadzsiev K, Ottóffy G, Illés T, Dóczi T, Melegh B Abstract Type 1 neurofibromatosis is an autosomal dominant hamartosis caused by mutations of the neurofibromin-1 gene. The classic features of the clinical phenotype include the presence of café-au-lait spots, neurofibromas, axillary and inguinal freckling, Lisch-nodules and deformities of the skeletal system, as well as the risk of developing multiple tumors, especially in the central nervous system. However, it is known from the literature that the phenotypic variability can pose a huge diagnostic difficulty. Aims: Our institute performs molecular genetic testing of the neurofibromin-1 gene since 2008; during this period several unusual phenotypic variants were found. Results, conclusion: The re...

Consensus recommendations for current treatments and accelerating clinical trials for patients with neurofibromatosis type 2

American Journal of Medical Genetics Part A — Fri, 02 Dec 2011 05:00:00 +0100

AbstractNeurofibromatosis 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 co...

Hyaluronan in intra‐operative edema of NF1‐associated neurofibromas

Neuropathology — Thu, 01 Dec 2011 05:00:00 +0100

The tumor suppressor disorder neurofibromatosis type 1 (NF1) is associated with development of multiple neurofibromas which may grow intraneurally as plexiform neurofibromas (PNF) or intracutaneously (CNF). Upon surgery neurofibromas may show prominent swelling hindering skin‐edge approximation. To assess whether the water binding glycosaminoglycan hyaluronan is involved in intra‐operative swelling, 51 neurofibromas from 33 NF1‐patients were investigated. Hyaluronan was histologically demonstrated and was quantified by ELISA. Molecular weight of hyaluronan was determined by gel filtration. Further, hyaluronan content was measured in cultivated Schwann cells and fibroblasts. Clinically, 67% of PNF were associated with moderate or severe intra‐operative swelling, whereas only 36% of ...

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Discovery of asymptomatic moyamoya arteriopathy in pediatric syndromic populations: radiographic and clinical progression.

Neurosurgical Focus — Thu, 01 Dec 2011 05:00:00 +0100

Conclusions Radiographic progression occurred in the majority of asymptomatic patients and generally heralded subsequent clinical symptoms. These data demonstrate that moyamoya is a progressive disorder, even in asymptomatic populations, and support the rationale of early surgical intervention to minimize morbidity from stroke. PMID: 22133171 [PubMed - in process] (Source: Neurosurgical Focus)

Congenital absence of the superior oblique tendon in Noonan-neurofibromatosis syndrome

Journal of AAPOS — Thu, 01 Dec 2011 05:00:00 +0100

A 5-year-old girl with Noonan-neurofibromatosis syndrome was diagnosed with bilateral superior oblique palsy. At surgery, the right superior oblique tendon was absent, and further exploration revealed abnormal tissue inserting into Tenon's capsule. Orbital imaging was not performed. Congenital absence of the superior oblique tendon was diagnosed. Although Noonan syndrome is known to have many ocular manifestations, absence of the superior oblique tendon has not been previously reported. (Source: Journal of AAPOS)

Articulation in schoolchildren and adults with neurofibromatosis type 1.

Journal of Communication Disorders — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Cosyns M, Mortier G, Janssens S, Bogaert F, D'Hondt S, Van Borsel J Abstract 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 NF1 schoolchildren and adults, both phonetically and phonologically. Speech samples were collected from 43 Flemish NF1 patients (14 children and 29 adults), ranging in age between 7 and 53 years, using a standardized speech test in which all Flemish single speech sounds and most clusters occur in all their permissible syllable positions. Analyses concentr...

Merlin-Deficient Human Tumors Show Loss of Contact Inhibition and Activation of Wnt/β-Catenin Signaling Linked to the PDGFR/Src and Rac/PAK Pathways.

Neoplasia — Thu, 01 Dec 2011 05:00:00 +0100

In this study, we show that proliferative Wnt/β-catenin signaling is elevated as active β-catenin (dephosphorylated at serine 37 and threoine 41) localizes to the nucleus and the Wnt targets genes c-myc and cyclin D1 are upregulated in confluent human schwannoma cells. We demonstrate that Rac effector p21-activated kinase 2 (PAK2) is essential for the activation of Wnt/β-catenin signaling because depletion of PAK2 suppressed active β-catenin, c-myc, and cyclin D1. Most importantly, the link between the loss of the AJ complex and the increased proliferation in human schwannoma cells is connected by Src and platelet-derived growth factor receptor-induced tyrosine 654 phosphorylation on β-catenin and associated with degradation of N-cadherin. We also demonstrate that active merlin mainta...

Parapharyngeal ganglioneuroma with neurofibromatosis: an unusual presentation.

The Annals of Otology, Rhinology, and Laryngology — Thu, 01 Dec 2011 05:00:00 +0100

CONCLUSIONS: Our case illustrates the importance of vigilant preoperative precautions in the management of neurogenic tumors, particularly ganglioneuromas. These usually nonfunctional tumors can result in sudden intraoperative and postoperative hypertensive crises even in the absence of any preoperative autonomic symptoms. PMID: 22279947 [PubMed - in process] (Source: The Annals of Otology, Rhinology, and Laryngology)

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Alternative splicing of the neurofibromatosis type I pre-mRNA.

Bioscience Reports — Tue, 29 Nov 2011 00:00:13 +0100

Authors: Barron VA, Lou H Abstract NF1 (neurofibromatosis type I) is a common genetic disease that affects one in 3500 individuals. The disease is completely penetrant but shows variable phenotypic expression in patients. NF1 is a large gene, and its pre-mRNA undergoes alternative splicing. The NF1 protein, neurofibromin, is involved in diverse signalling cascades. One of the best characterized functions of NF1 is its function as a Ras-GAP (GTPase-activating protein). NF1 exon 23a is an alternative exon that lies within the GAP-related domain of neurofibromin. This exon is predominantly included in most tissues, and it is skipped in CNS (central nervous system) neurons. The isoform in which exon 23a is skipped has 10 times higher Ras-GAP activity than the isoform in which exon 23...

Ultrastructural synaptic changes associated with neurofibromatosis type 1: A quantitative analysis of hippocampal region CA1 in a Nf1+/− Mouse Model

Synapse — Mon, 28 Nov 2011 13:57:24 +0100

AbstractNeurofibromatosis type 1 (NF1) is one of the most frequently diagnosed autosomal dominant inherited disorders resulting in neurological dysfunction, including an assortment of learning disabilities and cognitive deficits. To elucidate the neural mechanisms underlying the disorder, we employed a mouse model (Nf1+/−) to conduct a quantitative analysis of ultrastructural changes associated with the NF1 disorder. Using both serial light and electron microscopy, we examined reconstructions of the CA1 region of the hippocampus, which is known to play a central role in many of the dysfunctions associated with NF1. In general, the morphology of synapses in both the Nf1+/− and wild‐type groups of animals were similar. No differences were observed in synapse per neuron density, pre‐ ...

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

Archives of Dermatological Research — Sat, 26 Nov 2011 16:48:45 +0100

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. Content Type Journal ArticleCategory Short CommunicationPages 1-7DOI 10.1007/s00403-011-1191-3Authors Luigi Petramala, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, ItalySandra Giustini, Department of Dermatology, University ‘‘Sapienza’’, Rome, ItalyLaura Zinnamosca, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, ItalyCristiano Marinelli, Department of Interna...

Early surgical results of auditory brainstem implantation in nontumor patients

The Laryngoscope — Fri, 25 Nov 2011 08:40:05 +0100

Conclusions:Based on our experience, ideal nontumor candidates for ABI include congenitally deaf children who experienced failure after cochlear implantation owing to cochlear nerve deficiency and postlingually deaf adults with severe cochlear ossification. Laryngoscope, 121:2610–;2618, 2011 (Source: The Laryngoscope)

A safe method for excision of a giant neurofibroma on both buttocks using a loop-shaped suture

European Journal of Plastic Surgery — Fri, 25 Nov 2011 06:44:34 +0100

Abstract Neurofibromatosis(NF) is an autosomal dominant systemic disease. Up to 50% of patients with NF are reported to have concomitant vascular abnormalities. In the resection of a larger NF, the risk of uncontrolled hemorrhage is much higher due to the difficulty of hemostasis of large vessels within the tumor. We ligated the base of the giant NF with a simple loop-shaped ligation before removal of the giant NF in both buttocks, following this, we could successfully reduce the amount of hemorrhage during the operation. A 46-year-old female patient presented with giant masses of both gluteal areas, which had been growing slowly for the last 10 years. Each mass was about 35 × 25 cm in size. After designing the elliptical resection margin, we tightened the t...

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Neurofibromatosis type 1 and cerebellar T2‐hyperintensities: the relationship to cognitive functioning

Developmental Medicine and Child Neurology — Thu, 24 Nov 2011 11:30:04 +0100

(Source: Developmental Medicine and Child Neurology)

Neurofibromatosis

New England Journal of Medicine — Wed, 23 Nov 2011 22:00:11 +0100

New England Journal of Medicine, Volume 365, Issue 21, Page 2020, November 2011. (Source: New England Journal of Medicine)

Valosin-containing protein and neurofibromin interact to regulate dendritic spine density

Journal of Clinical Investigation — Wed, 23 Nov 2011 07:09:35 +0100

Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD) is an autosomal dominant disorder characterized by progressive myopathy that is often accompanied by bone weakening and/or frontotemporal dementia. Although it is known to be caused by mutations in the gene encoding valosin-containing protein (VCP), the underlying disease mechanism remains elusive. Like IBMPFD, neurofibromatosis type 1 (NF1) is an autosomal dominant disorder. Neurofibromin, the protein encoded by the NF1 gene, has been shown to regulate synaptogenesis. Here, we show that neurofibromin and VCP interact and work together to control the density of dendritic spines. Certain mutations identified in IBMPFD and NF1 patients reduced the interaction between VCP and neurofibromin and impaired spi...

Another VCP interactor: NF is enough

Journal of Clinical Investigation — Wed, 23 Nov 2011 07:09:35 +0100

Inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD) is a multisystem degenerative disorder caused by mutations in the valosin-containing protein (VCP) gene. How missense mutations in this abundant, ubiquitously expressed, multifunctional protein lead to the degeneration of disparate tissues is unclear. VCP participates in diverse cellular functions by associating with an expanding collection of substrates and cofactors that dictate its functionality. In this issue of the JCI, Wang and colleagues have further expanded the VCP interactome by identifying neurofibromin-1 (NF1) as a novel VCP interactor in the CNS. IBMPFD-associated mutations disrupt binding of VCP to NF1, resulting in reduced synaptogenesis. Thus, aberrant interactions between VCP and NF...

Exploring the somatic NF1 mutational spectrum associated with NF1 cutaneous neurofibromas

European Journal of Human Genetics — Wed, 23 Nov 2011 05:00:00 +0100

Authors: Laura Thomas, Gill Spurlock, Claire Eudall, Nick S Thomas, Matthew Mort, Stephen E Hamby, Nadia Chuzhanova, Hilde Brems, Eric Legius, David N Cooper & Meena Upadhyaya (Source: European Journal of Human Genetics)

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SAG/RBX2/ROC2 E3 Ubiquitin Ligase Is Essential for Vascular and Neural Development by Targeting NF1 for Degradation.

Developmental Cell — Tue, 22 Nov 2011 05:00:00 +0100

We report a critical role for SAG in controlling vascular and neural development by modulating RAS activity via promoting degradation of neurofibromatosis type 1 (NF1). Mice mutant for Sag died at embryonic day 11.5-12.5 with severe abnormalities in vascular and nervous system. Sag inactivation caused Nf1 accumulation and Ras inhibition, which blocks embryonic stem (ES) cells from undergoing endothelial differentiation and inhibits angiogenesis and proliferation in teratomas. Simultaneous Nf1 deletion fully rescues the differentiation defects in Sag(-/-) ES cells and partially rescues vascular and neural defects in Sag(-/-) embryos, suggesting that the effects of Sag deletion may not be solely explained by Nf1 misregulation. Collectively, our study identifies NF1 as a physiological subst...

Vestibular schwannomas occur in schwannomatosis and should not be considered an exclusion criterion for clinical diagnosis

American Journal of Medical Genetics Part A — Mon, 21 Nov 2011 05:00:00 +0100

AbstractSchwannomatosis is a recently delineated inherited condition that has clinical overlap with neurofibromatosis type 2 (NF2). Diagnostic criteria have been developed to distinguish schwannomatosis from NF2, but the existence of mosaic NF2, which may closely mimic schwannomatosis, makes even these criteria problematic. In particular, it is not clear why there is a relative sparing of the cranial nerves from schwannomas in schwannomatosis. We have identified two individuals with schwannomatosis and a unilateral vestibular schwannoma (VS), where a diagnosis of NF2 has been excluded. A third case with an identified SMARCB1 mutation was reported by two radiologists to have a VS, but this was later confirmed as a jugular schwannoma. These cases question whether the current exclusion of a V...

Hyperactivation of mTOR critically regulates abnormal osteoclastogenesis in neurofibromatosis type 1

Journal of Orthopaedic Research — Thu, 17 Nov 2011 07:41:30 +0100

AbstractIndividuals with nerofibromatosis Type 1 (NF1) frequently suffer a spectrum of bone pathologies, such as abnormal skeletal development (scoliosis, congenital bowing, and congenital pseudoarthroses, etc), lower bone mineral density with increased fracture risk. These skeletal problems may result, in part, from abnormal osteoclastogenesis. Enhanced RAS/PI3K activity has been reported to contribute to abnormal osteoclastogenesis in Nf1 heterozygous (Nf1+/−) mice. However, the specific downstream pathways linked to NF1 abnormal osteoclastogenesis have not been defined. Our aim was to determine whether mammalian target of rapamycin (mTOR) was a key effector responsible for abnormal osteoclastogenesis in NF1. Primary osteoclast‐like cells (OCLs) were cultured from Nf1 wild‐type (Nf...

Neurofibromatosis 2011: a report of the Children’s Tumor Foundation Annual Meeting

Acta Neuropathologica — Tue, 15 Nov 2011 06:47:18 +0100

Abstract The 2011 annual meeting of the Children’s Tumor Foundation, the annual gathering of the neurofibromatosis (NF) research and clinical communities, was attended by 330 participants who discussed integration of new signaling pathways into NF research, the appreciation for NF mutations in sporadic cancers, and an expanding pre-clinical and clinical agenda. NF1, NF2, and schwannomatosis collectively affect approximately 100,000 persons in US, and result from mutations in different genes. Benign tumors of NF1 (neurofibroma and optic pathway glioma) and NF2 (schwannoma, ependymoma, and meningioma) and schwannomatosis (schwannoma) can cause significant morbidity, and there are no proven drug treatments for any form of NF. Each disorder is associated with additional mani...

Role of Noncoding RNA ANRIL in Genesis of Plexiform Neurofibromas in Neurofibromatosis Type 1

JNCI — Tue, 15 Nov 2011 05:00:00 +0100

Conclusion Identification of ANRIL as a modifier gene in NF1 may offer clues to the molecular pathogenesis of PNFs, particularly neurofibroma formation, and emphasizes the unanticipated role of large noncoding RNA in activation of critical regulators of tumor development. (Source: JNCI)

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Metanephric Stromal Tumor Arising in a Patient With Neurofibromatosis Type 1 Syndrome

International Journal of Surgical Pathology — Tue, 15 Nov 2011 05:00:00 +0100

Metanephric stromal tumor (MST) is a recently recognized benign renal stromal tumor. MST is thought to be part of a spectrum of benign metanephric renal lesions, which also includes the epithelial lesion metanephric adenoma and the mixed stromal–epithelial lesion metanephric adenofibroma. Metanephric lesions may represent hyperdifferentiated counterparts to Wilms’ tumor (WT). MST characteristically shows renovascular angiodysplasia and juxtaglomerular (JG) cell hyperplasia. This is remarkably similar to the renal pathology described in neurofibromatosis-1 (NF-1) syndrome, a condition which is also associated with WT. Here, we report the first case of MST arising in a patient with NF-1. The patient presented with hypertension, and the MST was associated with florid angiodysplasi...

Unidentified bright objects in neurofibromatosis type 1: Conventional MRI in the follow-up and correlation of microstructural lesions on diffusion tensor images.

European Journal of Paediatric Neurology — Mon, 14 Nov 2011 05:00:00 +0100

CONCLUSIONS: MRI allows for adequate monitoring of the temporal and spatial distribution of UBOs in patients with NF1. DTI confirmed changes in FA despite the disappearance or reduction of UBOs, thereby confirming the hypothesis that microstructural damage occurs in specific brain regions of NF1 patients. PMID: 22088602 [PubMed - as supplied by publisher] (Source: European Journal of Paediatric Neurology)

Fracture through the apex of a delta tibia (minor tibial duplication) following minor injury

Pediatric Radiology — Tue, 08 Nov 2011 19:14:01 +0100

We describe a child with this deformity, who during a 4-year period sustained two separate fractures following relatively minor trauma. In both circumstances, the injury healed well with no evidence of pseudarthrosis formation. Content Type Journal ArticleCategory Case ReportPages 1-5DOI 10.1007/s00247-011-2243-8Authors Premal Amrishkumar Patel, Paediatric Radiology Department, Southampton University Hospitals NHS Trust, Mailpoint 53, C Level, Centre Block, Tremona Road, Southampton, SO16 6YD Hampshire, UKJoseph Jacoby, Paediatric Radiology Department, Southampton University Hospitals NHS Trust, Mailpoint 53, C Level, Centre Block, Tremona Road, Southampton, SO16 6YD Hampshire, UKJoanna Fairhurst, Paediatric Radiology Department, Southampton University Hospitals NHS Trust, Mailpoi...

Objective assessment of nasality in flemish adults with neurofibromatosis type 1

American Journal of Medical Genetics Part A — Thu, 03 Nov 2011 04:00:00 +0100

AbstractWhen characterizing the speech of a patient with neurofibromatosis type 1 (NF1), hypernasality is often mentioned. As few studies applied technically assisted evaluations of nasality in NF1 patients, the aim of the present study was to document the nasal resonance of adults with NF1 using nasometry. The nasometric data obtained from the NF1 patients were compared with the nasalance scores of a healthy control group and with normative data. The final study group consisted of 24 adult NF1 patients and 16 controls, all living in the East Flemish part of Belgium. Nasalance scores were obtained while the participants sustained three vowels (/a:/, /i./, and /u./) and one consonant (/m/) and read three standard nasalance passages. Despite the inter‐ and intra‐subject variability, we o...

Segmental neurofibromatosis.

Dermatol Online J — Wed, 02 Nov 2011 03:40:04 +0100

Authors: Adigun CG, Stein J Abstract 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 [PubMed - in process] (Source: Dermatol Online J)

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Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type‐3 NF1 deletions

Human Mutation — Tue, 01 Nov 2011 04:00:00 +0100

AbstractNonallelic homologous recombination (NAHR) is the major mechanism underlying recurrent genomic rearrangements, including the large deletions at 17q11.2 that cause neurofibromatosis type 1 (NF1). Here we identify a novel NAHR hotspot, responsible for type‐3 NF1 deletions which span 1.0‐Mb. Breakpoint clustering within this 1‐kb hotspot, termed PRS3, was noted in 10 of 11 known type‐3 NF1 deletions. PRS3 is located within the LRRC37B pseudogene of the NF1‐REPb and NF1‐REPc low‐copy repeats. In contrast to other previously characterized NAHR hotspots, PRS3 has not developed on a pre‐existing allelic homologous recombination hotspot. Furthermore, the variation pattern of PRS3 and its flanking regions are unusual since only NF1‐REPc (and not NF1‐REPb) is characterize...

Long-term survival of a patient with a neurofibromatosis Type 1 associated retroperitoneal malignant triton tumor after multi-modality treatment.

Clinical Neuropathology — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Koutsopoulos AV, Mantadakis E, Katzilakis N, Lagoudaki ED, de Bree E, Stiakaki E, Kalmanti M PMID: 22011741 [PubMed - in process] (Source: Clinical Neuropathology)

Juvenile xanthogranuloma: Challenges in complicated cases.

The Australasian Journal of Dermatology — Tue, 01 Nov 2011 04:00:00 +0100

We present challenging cases of JXG from Sydney Children's Hospital, collected over 10 years - two with multisystem involvement and concomitant urticaria, one associated with neurofibromatosis, and one case of giant JXG with an initial histopathological challenge. Although JXG has been reported with urticaria pigmentosa, in two of our cases persistent urticaria, in association with JXG is discussed. PMID: 22070704 [PubMed - in process] (Source: The Australasian Journal of Dermatology)

The systems biology of neurofibromatosis type 1 - Critical roles for microRNA.

Experimental Neurology — Mon, 31 Oct 2011 04:00:00 +0100

Authors: Lee MJ, Cho JH, Galas DJ, Wang K Abstract Neurofibromatosis type 1 (NF1) is one of the most common inherited neurological disorders with a wide range of clinical manifestations. The causative gene for NF1 encodes a multi-domain protein, neurofibromin, which interacts with RAS through its RAS-GAP domain. Dysfunction of neurofibromin results in abnormal RAS activation in the cells which has been thought to be the main process in the initiation and progression of NF1. Based on this hypothesis, inhibitors for various RAS mediated signaling pathways are in different stages of clinical trials to treat NF1 or NF1-associated symptoms. While the molecular genetics of NF1 has made significant progress in recent years, the underlying etiology and progression of NF1 are yet to be full...

Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri

Neurogenetics — Fri, 28 Oct 2011 17:24:31 +0100

Abstract Schwannomatosis is a rare hereditary cancer syndrome in which patients develop multiple non-vestibular schwannomas. The chromatin remodelling gene SMARCB1 (also known as INI1, hSNF5, and BAF47) has been identified as a schwannomatosis predisposing gene, being involved in a subset of sporadic and familial cases. Recent studies have shown that SMARCB1 may also be involved in the development of multiple meningiomas. Previously, we demonstrated that the SMARCB1 exon 2 missense mutation c.143 C > T segregates with the presence of meningiomas in five members of a large family with multiple meningiomas and schwannomas. We extended our genetic analyses by screening 44 additional at-risk family members and identified 13 new carriers. Eleven of these were subjecte...

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Diffuse Lung Disease in Neurofibromatosis

Lung — Fri, 28 Oct 2011 17:17:32 +0100

We report on the clinical, functional and HRCT findings in a patient with neurofibromatosis-associated diffuse lung disease and provide a short literature review. Content Type Journal ArticlePages 1-2DOI 10.1007/s00408-011-9339-7Authors Rocco Trisolini, Thoracic Endoscopy and Pulmonology Unit, Maggiore Hospital, Largo Nigrisoli 2, 40133 Bologna, ItalyVanina Livi, Pulmonary Division, City Hospital, Rimini, ItalyLuigi Lazzari Agli, Pulmonary Division, City Hospital, Rimini, ItalyMarco Patelli, Thoracic Endoscopy and Pulmonology Unit, Maggiore Hospital, Largo Nigrisoli 2, 40133 Bologna, Italy Journal LungOnline ISSN 1432-1750Print ISSN 0341-2040 (Source: Lung)

Diffusion tensor MR imaging in neurofibromatosis type 1: expanding the knowledge of microstructural brain abnormalities

Pediatric Radiology — Fri, 28 Oct 2011 05:48:47 +0100

Conclusions Diffusion tensor MR imaging confirms the influence of UBOs in the decrease of FA values in this series of patients with NF1. Additionally, this technique allows the characterization of microstructural abnormalities even in some brain regions that appear normal in conventional MR sequences. Content Type Journal ArticleCategory Original ArticlePages 1-6DOI 10.1007/s00247-011-2274-1Authors José R. L. Ferraz-Filho, Radiology Department, Medical School in São José do Rio Preto (FAMERP), 5544 Brigadeiro Faria Lima, São Paulo, Brazil 15090-000Antônio J. da Rocha, Radiology Department, School Medical Sciences of the Santa Casa de São Paulo, São Paulo, BrazilMarcos P. Muniz, Radiology Department, Medical School in São José do Rio Preto (FAMERP), 5544 Bri...

Low‐grade gliomas as neurodevelopmental disorders: Insights from mouse models of neurofibromatosis‐1

Neuropathology and Applied Neurobiology — Fri, 28 Oct 2011 04:00:00 +0100

AbstractOver the past few years, the traditional view of brain tumorigenesis has been revolutionized by advances in genomic medicine, molecular biology, stem cell biology, and genetically‐engineered small‐animal modeling. We now appreciate that pediatric brain tumors arise following specific genetic mutations in specialized groups of progenitor cells in concert with permissive changes in the local tumor microenvironment. This interplay between preneoplastic/neoplastic cells and non‐neoplastic stromal cells is nicely illustrated by the Neurofibromatosis type 1 (NF1) inherited cancer syndrome, in which affected children develop low‐grade astrocytic gliomas. In this review, we will use NF1 as a model system to highlight the critical role of growth control pathways, non‐neoplastic ce...

Ganglioglioma of the Thoracolumbar Spinal Cord in a Patient with Neurofibromatosis Type 1: A Case Report and Literature Review

Pediatric Neurosurgery — Wed, 26 Oct 2011 23:00:00 +0100

Pediatr Neurosurg (DOI:10.1159/000331569) (Source: Pediatric Neurosurgery)

[Rare tumors of the lateral ventricle. Review of the literature.]

Neuro-Chirurgie — Mon, 24 Oct 2011 04:00:00 +0100

Authors: Peltier J, Capel C, Nicot B, Baroncini M, Fichten A, Toussaint P, Desenclos C, Lefranc M, Le Gars D, Lejeune JP Abstract Metastases of lateral ventricle (LV) are attached to choroidal plexus. Primary source is cancer of kidney. Two thirds of patients are male. Oligodendrogliomas occur in young females. Signs of increased intracranial pressure are a constant feature. These tumors are found in anterior portion of the LV with severe enhancement and clumped calcifications. Treatment is surgical. Cavernomas have a preponderance of rapid growth with a bleeding revelation. Seizures are rare. Rebleeding is frequent and justifies a surgical treatment. Schwannomas are a rare entity in which the majority of patients are very young. MRI shows calcifications, cystic components and a st...

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Cerebral pleomorphic xanthoastrocytoma associated with NF1: an updated review with a rare atypical case from Africa

Neurosurgical Review — Fri, 21 Oct 2011 15:59:25 +0100

We present a 10-year-old Nigerian boy with NF1 who was found to harbor a thalamic-lateral ventricular solid mass lesion whose histologic and immunohistochemical findings were in keeping with PXA. We also carried out an updated review of the PXA-NF1 literature and found only eight previous reports of this clinical disease association. These reports have been limited to only certain regions of the world, with none yet reported from Africa, South America, Australia, and Eastern Europe. As far as we know, this might be the first such report from Africa. The case we present, in addition, demonstrated some other unique clinical, radiological, and histopathologic characteristics which have been highlighted in this review. Content Type Journal ArticleCategory ReviewPages 1-7DOI 10.1007/s...

Valuing Gene Testing in Children with Possible Neurofibromatosis 1.

Clinical Genetics — Thu, 20 Oct 2011 04:00:00 +0100

We examined the economic value of offering genetic testing to children with possible neurofibromatosis 1 (NF1) in British Columbia. Diagnosis of NF1 is usually made based on diagnostic clinical criteria, but molecular diagnostic testing, currently offered on a case-by-case basis in B.C., now reliably diagnoses NF1 in 95% of cases. Children who present with some clinical features but whose findings are insufficient to meet the diagnostic criteria are labeled as having "possible NF1." Current guidelines call for these children to be followed as they have NF1, leading to annual ophthalmologic exams and screening for complications; thus, there are increased costs to the health care system. We created a model to account for these costs to the health care system, comparing the current protocol w...

Ritalin's Affects On Attention Revealed By Brain Scans

Health News from Medical News Today — Mon, 17 Oct 2011 07:00:00 +0100

Scientists have developed a way to evaluate new treatments for some forms of attention deficit disorder. Working in mice, researchers at Washington University School of Medicine in St. Louis showed that they can use brain scans to quickly test whether drugs increase levels of a brain chemical known as dopamine. In a study published last year, the same group found that raising dopamine levels in mice alleviates attention deficits caused by neurofibromatosis type 1 (NF1), a condition that affects more than 100,000 people in the United States... (Source: Health News from Medical News Today)

[Juvenile xanthogranulomas associated with neurofibromatosis type 1.]

Anales de Pediatria — Mon, 17 Oct 2011 04:00:00 +0100

Authors: Godoy Gijón E, Yuste Chaves M, Sáez Martín LC PMID: 22015054 [PubMed - as supplied by publisher] (Source: Anales de Pediatria)

Aurora and PP1 Regulate KIBRA Phosphorylation [Signal Transduction]

Journal of Biological Chemistry — Fri, 14 Oct 2011 04:00:00 +0100

Recent genetic studies in Drosophila identified Kibra as a novel regulator of the Hippo pathway, which controls tissue growth and tumorigenesis by inhibiting cell proliferation and promoting apoptosis. The cellular function and regulation of human KIBRA remain largely unclear. Here, we show that KIBRA is a phosphoprotein and that phosphorylation of KIBRA is regulated in a cell cycle-dependent manner with the highest level of phosphorylated KIBRA detected in mitosis. We further demonstrate that the mitotic kinases Aurora-A and -B phosphorylate KIBRA both in vitro and in vivo. We identified the highly conserved Ser539 as the primary phosphorylation site for Aurora kinases. Moreover, we found that wild-type, but not catalytically inactive, protein phosphatase 1 (PP1) associates with KIBRA. PP...

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JNK inhibitors increase osteogenesis in Nf1-deficient cells

Bone — Fri, 14 Oct 2011 04:00:00 +0100

In this study we examine the effects of an anthrapyrazolone inhibitor of JNK (SP600125) on inducible osteoprogenitors as well as Nf1-deficient and Nf1-null primary osteoblasts.C2C12 cells, which are highly responsive to rhBMP-2, were examined with exogenous rhBMP-2 and a range of SP600125 doses. Based on the expression of early and late bone markers and matrix mineralization, 10μM SP600125 was found to be pro-osteogenic whether delivered concurrent with or following 2days of rhBMP-2 treatment. Aberrant JNK activity was identified in Nf1-deficient osteoprogenitors (increased rhBMP-2 induced phospho-c-Jun) and in Nf1-null mature osteoblasts (increased total c-Jun). Next, SP600125 was used to treat these cells and was found to facilitate osteogenesis in Nf1-deficient osteoprogenitors, and in...

Pulmonary Complications of Dermatological Disorders

Paediatric Respiratory Reviews — Wed, 12 Oct 2011 04:00:00 +0100

Systemic diseases often manifest with cutaneous findings. Many paediatric conditions with prominent skin findings also have significant pulmonary manifestations. These conditions include inherited multisystem genetic disorders such as yellow-nail syndrome, neurofibromatosis Type 1 (NF1), tuberous sclerosis complex (TSC), hereditary haemorrhagic telangiectasia (HHT), Klippel-Trénaunay-Weber (KTW) syndrome, cutis laxa, Ehlers-Danlos syndrome (EDS), and dyskeratosis congenita and reactive processes such as mastocytosis. This review discusses the common presentations and pulmonary manifestations of these disorders. (Source: Paediatric Respiratory Reviews)

Malignant Peripheral Nerve Sheath Tumor with Fibroblastic Differentiation in a Patient with Neurofibromatosis Type 1: Imprint Cytological Findings

Karger Publishers — Fri, 07 Oct 2011 23:00:00 +0100

Acta Cytologica 2011;55:467–472 (DOI:10.1159/000330676) (Source: Karger Publishers)

Ciliary body cysts in neurofibromatosis: A new coexistence?

Graefe's Archive for Clinical and Experimental Ophthalmology — Thu, 06 Oct 2011 05:49:17 +0100

Conclusion The coexistence of ciliary body cysts and NF1, and the effect of these cysts in the eye should be enlightened with further studies. Content Type Journal ArticleCategory NeurophthalmologyPages 1-5DOI 10.1007/s00417-011-1830-6Authors Sinan Emre, Department of Ophthalmology, Faculty of Medicine, Celal Bayar University, Manisa, TurkeyMelis Palamar, Department of Ophthalmology, Faculty of Medicine, Ege University, Izmir, TurkeyM. Oğuz Ulusoy, Department of Ophthalmology, Faculty of Medicine, Celal Bayar University, Manisa, TurkeyGülsüm Gençoğlan, Department of Dermatology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey Journal Graefe's Archive for Clinical and Experimental OphthalmologyOnline ISSN 1435-702XPrint ISSN 0721-832X (Source: ...

Choroidal Abnormalities Detected by Near-Infrared Reflectance Imaging as a New Diagnostic Criterion for Neurofibromatosis 1

Ophthalmology — Mon, 03 Oct 2011 04:00:00 +0100

Conclusions: Choroidal abnormalities appearing as bright patchy nodules detected by NIR imaging frequently occurred in NF1 patients. The present study shows that NIR examination to detect choroidal involvement should be considered as a new diagnostic criterion for NF1. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. (Source: Ophthalmology)

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[Titulo en ingles.]

Neurocirugia — Sat, 01 Oct 2011 04:00:00 +0100

CONCLUSION. Ganglioneuroma and disk herniation association constitute an excepcional disorder. Its treatment implies surgery resection. PMID: 22031162 [PubMed - as supplied by publisher] (Source: Neurocirugia)

Report of a case of malignant peripheral nerve sheath tumor of the neck with an early local recurrence.

Ear, Nose and Throat Journal — Sat, 01 Oct 2011 04:00:00 +0100

We present a case of MPNST of the neck that arose in a 17-year-old girl, who was also found to have a parapharyngeal neurofibroma. The cervical mass was excised (intraoperative complications precluded removal of the parapharyngeal mass) and radiotherapy was administered, but the patient experienced a recurrence within 2 months. Another surgery was performed, and this time both tumors were removed. At 1 year of follow-up, the patient was without disease, but in postoperative year 2, she died from complications of a cervical recurrence and mediastinal metastasis. PMID: 22033963 [PubMed - in process] (Source: Ear, Nose and Throat Journal)

Radical ways to save skin

Telegraph Health — Fri, 30 Sep 2011 16:21:25 +0100

Enormous advances in techniques to conserve, reconstruct and regrow skin have been made in the last decade, enabling people dreadfully disfigured by accidents or the dice of genetics to live near-normal lives. (Source: Telegraph Health)

How does a 'sonic scalpel' work?

Telegraph Health — Fri, 30 Sep 2011 16:20:36 +0100

Ultrasound emitted by the harmonic scalpel causes friction in a very limited area, heating up the flesh to about 100C, which both cuts it and seals blood vessels at the same time. (Source: Telegraph Health)

'Sonic scalpel' will help rid man of head-to-toe tumours

Telegraph Health — Fri, 30 Sep 2011 13:23:42 +0100

A surgeon is to use a "sonic scalpel" to help rid a man covered from head to toe in tumours of his affliction, the first time the device has been used for such a purpose. (Source: Telegraph Health)

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Gamma Knife surgery for nonvestibular schwannomas: radiological and clinical outcomes.

Journal of Neurosurgery — Fri, 30 Sep 2011 04:00:00 +0100

Conclusions Gamma Knife surgery is a reasonably effective treatment option for patients with nonvestibular schwannomas. Patients require careful follow-up for tumor progression and signs of neurological deterioration. PMID: 21962159 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

Learning Disabilities In Patients With Neurofibromatosis May Be Treated With Common Cholesterol Drug

Health News from Medical News Today — Thu, 29 Sep 2011 08:00:00 +0100

Researchers at Children's National Medical Center have found that a cholesterol-lowering statin drug appears to be safe in children with neurofibromatosis type 1 (NF1) and may improve learning disabilities, including verbal and nonverbal memory. This is the first time that the drug lovastatin has been studied in children with NF1. The study, led by Maria T. Acosta, MD, a pediatric neurologist and researcher at Children's National and clinical director and cognitive director of the Gilbert Family Neurofibromatosis Institute, appears in the October 2011 issue of /iPediatric Neurology... (Source: Health News from Medical News Today)

Surgical treatment of giant plexiform neurofibroma associated with pectus excavatum

Journal of Cardiothoracic Surgery — Wed, 28 Sep 2011 04:00:00 +0100

Plexiform neurofibromas are benign tumours originating from subcutaneous or visceral peripheral nerves, which are usually associated with neurofibromatosis type 1. They are almost always congenital lesions and often cause the surrounding soft tissue and bone to grow aberrantly. We treated a 12-year-old boy who presented with asymmetric pectus excavaum and an anterior chest wall plexiform neurofibroma. The pectus excavaum was corrected by modified Nuss procedure, followed by simultaneous resection of the giant mass. The patient is doing well at the 4 years follow-up visit. (Source: Journal of Cardiothoracic Surgery)

Common cholesterol drug safe, may improve learning disabilities in patients with neurofibromatosis

EurekAlert! - Social and Behavioral Science — Tue, 27 Sep 2011 04:00:00 +0100

(Children's National Medical Center) Researchers at Children's National Medical Center have found that a cholesterol-lowering statin drug appears to be safe in children with neurofibromatosis type 1 (NF1) and may improve learning disabilities, including verbal and nonverbal memory. (Source: EurekAlert! - Social and Behavioral Science)

Pelvic neurofibroma arising from prostate in a case of neurofibromatosis-1

Indian Journal of Urology — Mon, 26 Sep 2011 04:00:00 +0100

We describe a case of pelvic plexiform neurofibroma in a case of NF-1. (Source: Indian Journal of Urology)

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Malignant peripheral nerve sheath tumour presenting as a pneumothorax.

The British Journal of Radiology — Mon, 26 Sep 2011 00:39:26 +0100

We present a unique case of a systemically well 34-year-old male who presented with clinical evidence of a right-sided pneumothorax. The chest radiograph identified the right-sided pneumothorax and revealed an apical pleural mass that was confirmed by intravenous contrast-enhanced CT of the thorax. The patient was referred for video-assisted thorascopic surgical pleurodesis and biopsy of the lesion. Histopathology analyses confirmed the diagnosis of malignant peripheral nerve sheath tumour. To the best of our knowledge, no such case reports have been published in the literature. A diagnosis of malignant peripheral nerve sheath tumour should be considered as one of the rarer possibilities in patients presenting with pneumothoraces in association with apical pleural lesions. PMID: 219339...

Spinal meningioma in childhood: clinical features and treatment

Child's Nervous System — Sat, 24 Sep 2011 15:45:07 +0100

Conclusions Spinal meningioma is an uncommon pediatric neoplasm and has a poor prognosis. It has a male predominance and is inclined to be associated with NF-2, and those that are associated with higher pathologic subtypes and NF-2 have more unfavorable outcome. Every effort should be made to achieve total removal which may decrease the incidence of recurrence. Content Type Journal ArticleCategory Original PaperPages 1-8DOI 10.1007/s00381-011-1570-2Authors Xiao-Qiang Wang, Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040 ChinaXian-Wei Zeng, Department of Neurosurgery, Affiliated Hospital, Weifang Medical University, Shandong, 261053 ChinaBi-Yun Zhang, Department of Radiology, Huashan Hospital, Fudan University, Shanghai, 200040 ChinaY...

Medical management of neurofibromatosis

Paediatrics and Child Health — Thu, 22 Sep 2011 18:42:34 +0100

Abstract: The neurofibromatoses consist of at least three autosomal dominantly inherited disorders, neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis. For many years these conditions were inextricably linked as part of generalized neurofibromatosis (von Recklinghausen disease). Since 1987 with the separate localization of NF1 to chromosome 17q and NF2 (bilateral vestibular schwannoma) to 22q it has been possible to formally separate them. More recently the SMARCB1 gene on 22q has been confirmed as causing a subset of schwannomatosis. The last 20 years has seen a considerable improvement in our knowledge of the clinical and molecular features of these conditions. Both NF1 and NF2 provide the clinician with often complex management decisions. Childhood presen...

PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1 mice.

Experimental Neurology — Thu, 22 Sep 2011 04:00:00 +0100

Authors: Brown JA, Xu J, Diggs-Andrews KA, Wozniak DF, Mach RH, Gutmann DH Abstract Attention system abnormalities represent a significant barrier to scholastic achievement in children with neurofibromatosis-1 (NF1). Using a novel mouse model of NF1-associated attention deficit (ADD), we demonstrate a presynaptic defect in striatal dopaminergic homeostasis and leverage this finding to apply [(11)C]-raclopride positron-emission tomography (PET) in the intact animal. While methylphenidate and l-Deprenyl correct both striatal dopamine levels on PET imaging and defective attention system function in Nf1 mutant mice, pharmacologic agents that target de-regulated cyclic AMP and RAS signaling in these mice do not. These studies establish a robust preclinical model to evaluate promising ag...

Rasopathies: Developmental Disorders That Predispose to Cancer and Skin Manifestations.

Actas Dermo-Sifiliograficas — Wed, 21 Sep 2011 04:00:00 +0100

Authors: Hernández-Martín A, Torrelo A Abstract Proteins belonging to the RAS/mitogen activated protein kinase (MAPK) pathway play key roles in cell proliferation, differentiation, survival, and death. For more than 30years now we have known that 30% of human cancers carry somatic mutations in genes encoding proteins from this pathway. Whereas somatic mutations have a high malignant potential, germline mutations are linked to developmental abnormalities that are often poorly clinically differentiated, although each is dependent upon the specific gene affected. Thus, all patients share varying degrees of mental retardation or learning difficulties, heart disease, facial dysmorphism, skin anomalies, and, in some cases, predisposition to cancer. These syndromes, known as rasopathies...

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Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner [Medical Sciences]

Proceedings of the National Academy of Sciences — Tue, 20 Sep 2011 04:00:00 +0100

In this report, we use a combination of genetic silencing in vitro and conditional mouse transgenesis approaches in vivo to demonstrate that neurofibromin regulates astrocyte cell growth and glioma formation in a TSC/Rheb-independent fashion. First, we show that Nf1 or Pten inactivation, but not Tsc1 loss or Rheb overexpression, increases astrocyte cell growth in vitro. Second, Nf1-deficient increased mTOR signaling and astrocyte hyperproliferation is unaffected by Rheb shRNA silencing. Third, conditional Tsc1 inactivation or Rheb overexpression in glial progenitors of Nf1+/− mice does not lead to glioma formation. Collectively, these findings establish TSC/Rheb-independent mechanisms for mTOR-dependent glial cell growth control and gliomagenesis relevant to the design of therapies for i...

Plexiform neurofibromas in NF1

The Journal of Pediatrics — Mon, 19 Sep 2011 08:50:26 +0100

Children with neurofibromatosis type 1 (NF1) are at risk for a wide variety of clinical problems, some cosmetic and some potentially life-threatening. Of the latter, plexiform neurofibromas (PNs) are among the most serious. Especially when deep, they can cause problems from local pressure and may undergo malignant transformation. (Source: The Journal of Pediatrics)

The co-occurrence of neurofibromatosis type I and nail-patella syndrome in a 5-generation pedigree

Journal of the American Academy of Dermatology — Sun, 18 Sep 2011 01:35:52 +0100

We describe a 5-generation family with 8 members who manifested the clinical features of neurofibromatosis type I (NF1) and nail-patella syndrome (NPS). NF1 and NPS are both autosomal dominant genodermatoses with cutaneous and orthopedic abnormalities (). Gene mutations associated with NF1 and NPS (LMX1B) have been localized to chromosomes 17q11.2 and 9q34.1, respectively. (Source: Journal of the American Academy of Dermatology)

The Receptor Tyrosine Kinase Alk Controls Neurofibromin Functions in Drosophila Growth and Learning

PLoS Genetics — Thu, 15 Sep 2011 04:00:00 +0100

We report two unexpected roles for the Drosophila ortholog dAlk, in body size determination and associative learning. Remarkably, reducing neuronal dAlk activity increased body size and enhanced associative learning, suggesting that its activation is inhibitory in both processes. Consistently, dAlk activation reduced body size and caused learning deficits resembling phenotypes of null mutations in dNf1, the Ras GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis type 1 (NF1) disease gene. We show that dAlk and dNf1 co-localize extensively and interact functionally in the nervous system. Importantly, genetic or pharmacological inhibition of dAlk rescued the reduced body size, adult learning deficits, and Extracellular-Regulated-Kinase (ERK) overactivation dNf1 mut...

Recurrent abdominal complaints caused by a cecal neurofibroma: A case report.

World Journal of Gastroenterology : WJG — Wed, 14 Sep 2011 04:00:00 +0100

We report a case of a patient presenting with dysphagia, weight loss, intermittent abdominal pain and constipation caused by a single cecal neurofibroma obstructing the ileocecal valve. Also gastrointestinal involvement of the lower tract should be considered in patients with NF1 presenting with abdominal complaints. PMID: 22025885 [PubMed - in process] (Source: World Journal of Gastroenterology : WJG)

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Lovastatin as Treatment for Neurocognitive Deficits in Neurofibromatosis Type 1: Phase I Study

Pediatric Neurology — Tue, 13 Sep 2011 03:39:28 +0100

We report on a phase I study examining the safety and tolerability of lovastatin in children with neurofibromatosis type 1. Twenty-four children with neurofibromatosis type 1 underwent a dose-escalation protocol for 3 months to identify the maximum tolerated dose and potential toxicity. Minimal side effects were evident, and no child experienced dose-limiting toxicity. Cognitive evaluations were completed before and after treatment, and the results suggested improvement in areas of verbal and nonverbal memory. Additional analyses, using reliable change indices, indicated improvements exceeding those of test-retest or practice effects in some participants. These observations may be analogous to the improvements observed in a neurofibromatosis type 1 murine model treated with lovastatin, alt...

[Management of plexiform neurofibroma isolated in childhood: About four observations.]

Annales de Chirurgie Plastique et Esthetique — Mon, 12 Sep 2011 04:00:00 +0100

We report four cases of isolated plexiform neurofibromas found in children from topographies and we discuss the pretherapeutic assessment, the surgical management and the long-term follow-up. PMID: 21917371 [PubMed - as supplied by publisher] (Source: Annales de Chirurgie Plastique et Esthetique)

Neurocutaneous syndrome: A prospective study

Indian Journal of Dermatology — Sat, 10 Sep 2011 04:00:00 +0100

Conclusion: As NCS is not an uncommon disease in children, it is always necessary to find out the subtle neurological signs, whenever we observe any case with cutaneous markers suggestive of NCS. In addition, it is a must to do a detailed dermatological examination in a child with central nervous system involvement, in the pediatric population. However, the neurological course cannot be predicted from skin lesions. (Source: Indian Journal of Dermatology)

Chronic myeloid leukemia in an adult ghanaian with sporadic neurofibromatosis 1

Indian Journal of Dermatology — Sat, 10 Sep 2011 04:00:00 +0100

We present an adult Ghanaian with NF1, who subsequently developed CML. Relevance of the case report is discussed. (Source: Indian Journal of Dermatology)

Multiple Cutaneous Plexiform Schwannomas as Initial Presentation of Neurofibromatosis 2 in a 9‐Year‐Old

Pediatric Dermatology — Fri, 09 Sep 2011 04:00:00 +0100

We report here a 9‐year‐old girl who presented with multiple pigmented, slightly tender plaques on her scalp, face, and back that were revealed by histopathology to be plexiform schwannomas. We suspected NF2 and sent the patient’s blood for genetic testing, which confirmed our diagnosis. (Source: Pediatric Dermatology)

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Lower extremity strength and hopping and jumping ground reaction forces in children with neurofibromatosis type 1.

Human Movement Science — Wed, 07 Sep 2011 04:00:00 +0100

Authors: Johnson BA, Macwilliams B, Carey JC, Viskochil DH, D'Astous JL, Stevenson DA Abstract The purpose of this study was to (1) extend the research findings of decreased muscular force production in grip strength to the lower extremity strength of children with NF1 and (2) to determine if there was a relationship between isometric strength and functional activities in children with NF1. Force production was assessed using a hand held dynamometer (HHD) and a functional task (hopping and jumping) on a force plate. Data from twenty-six children with NF1 were compared to data from 48 typically developing children of similar sex, weight and height. Children with NF1 demonstrated statistically significant lower force production with HHD (p<0.01) during hip extension, but similar f...

Rapidly Growing Ulcer in a Patient With Neurofibromatosis Type I.

Actas Dermo-Sifiliograficas — Mon, 05 Sep 2011 04:00:00 +0100

Authors: Toledo-Alberola F, Guijarro-Llorca J PMID: 21899828 [PubMed - as supplied by publisher] (Source: Actas Dermo-Sifiliograficas)

Intraoral plexiform neurofibroma involving the maxilla - pathognomonic of neurofibromatosis type I

Journal of Pediatric Neurosciences — Thu, 01 Sep 2011 23:00:00 +0100

We present a case of intraosseous plexiform neurofibroma of the maxilla in a 2-year old female, which is rare, along with the oral manifestations and clinicopathological characteristics. Because NF-I is one of the most common genetic disorders and oral manifestations are common, knowledge of the variability of presentation in children is necessary for prompt diagnosis. (Source: Journal of Pediatric Neurosciences)

Reconstruction of a Severe Facial Defect by Allotransplantation in Neurofibromatosis Type 1: A Case Report

Transplantation Proceedings — Thu, 01 Sep 2011 04:00:00 +0100

Conclusion: We have reported a case of successful provisional transplantation of a human facial allograft onto the thigh as an alternative technique in human face transplantation. PHT was a reliable alternative procedure to obtain the facial allograft from a cadaveric donor. (Source: Transplantation Proceedings)

Coincidence of GIST and pancreatic endocrine neoplasm in neurofibromatosis

Asia-Pacific Journal of Clinical Oncology — Tue, 30 Aug 2011 12:41:49 +0100

AbstractCarcinoids of the ampulla of Vater are infrequent tumors of which a quarter of cases have been detected in patients with type I neurofibromatosis. This hereditary disease is also associated with gastrointestinal stromal tumors (GIST). However, the coincidence of these three entities together have only been formerly detected in five cases. A 53 year‐old female patient, diagnosed with type I neurofibromatosis, with a malignant carcinoid of ampulla of Vater and multiple gastrointestinal stromal tumors in the duodenum and jejunum, was treated with total pancreatectomy and the excision of her intestinal tumors. Five‐years on, a follow‐up showed the patient to be well, and free from tumor recurrence. The coexistence of an ampullary carcinoid tumor, GIST and neurofibramatosis is ver...

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Merlin/NF2 Functions Upstream of the Nuclear E3 Ubiquitin Ligase CRL4DCAF1 to Suppress Oncogenic Gene Expression.

Science Signaling — Mon, 29 Aug 2011 23:00:00 +0100

Authors: Cooper J, Li W, You L, Schiavon G, Pepe-Caprio A, Zhou L, Ishii R, Giovannini M, Hanemann CO, Long SB, Erdjument-Bromage H, Zhou P, Tempst P, Giancotti FG Abstract Integrin-mediated activation of PAK (p21-activated kinase) causes phosphorylation and inactivation of the FERM (4.1, ezrin, radixin, moesin) domain-containing protein Merlin, which is encoded by the NF2 (neurofibromatosis type 2) tumor suppressor gene. Conversely, cadherin engagement inactivates PAK, thus leading to accumulation of unphosphorylated Merlin. Current models imply that Merlin inhibits cell proliferation by inhibiting mitogenic signaling at or near the plasma membrane. We have recently shown that the unphosphorylated, growth-inhibiting form of Merlin accumulates in the nucleus and binds to the E3 ubi...

Peripheral Nerve Involvement in a Neurofibromatosis Type 2 Patient With Plexiform Neurofibroma of the Cauda Equina: A Sonographic Vignette

Archives of Physical Medicine and Rehabilitation — Mon, 29 Aug 2011 21:23:25 +0100

We report a 20-year-old man with cauda equina syndrome and neurofibromatosis type 2. We discuss the role of sonographic and electromyographic evaluations in the management of our patient and suggest the use of sonographic imaging for visualization of peripheral nerve pathologic states, especially when involvement is widespread. (Source: Archives of Physical Medicine and Rehabilitation)

An Unusual Cause of Abdominal Distension in a 4-Year-Old Boy

Gastroenterology — Mon, 29 Aug 2011 04:00:00 +0100

Question: A 4-year-old boy had Café-au-lait spots on his trunk and extremities since birth. His mother and mother's grandfather had type I neurofibromatosis (NF1). Persistent, abdominal distension and passage of mucoid stools as well as poor appetite bothered him since birth. Rectal manometry showed high anal and rectal pressure at the age of 3. Rectal suction biopsy revealed increased activity of acetylcholinesterase, hypertrophy of nerve bundles, and presence of ganglion cells. Because abdominal ultrasonography disclosed a retroperitoneal mass, abdominal computed tomography (CT) and magnetic resonance imaging (MRI) were performed when he was 3 years of age. Abdominal CT after use of contrast medium revealed an ill-marginated, hypodense mass lesion encasing the celiac trunk and hepatic h...

Cerebral vasospasm after auditory brainstem implantation in a patient with hyperostosis cranialis interna

Clinical Neurology and Neurosurgery — Fri, 26 Aug 2011 04:00:00 +0100

Auditory brainstem implantation (ABI) is indicated in case of bilateral neural deafness. The majority of the patients suffers from bilateral vestibular schwannomas related to neurofibromatosis type 2 . Common other indications for ABI are bilateral severe ossification of the cochlea due to otosclerosis, cochlear obliteration due to meningitis, cochlear aplasia and traumatic cochlear nerve avulsion . ABI can also be considered in case of bilateral vestibulocochlear neuropathy in patients with craniofacial hyperostotic disorders, such as Camurati-Engelmann disease, sclerosteosis, osteopetrosis and craniometaphyseal dysplasia. Hyperostosis Cranialis Interna (HCI) is such a hyperostotic hereditary disease characterised by endosteal hyperostosis and osteosclerosis of the cranium and the skull b...

Retinal Nerve Fiber Layer Thickness in Children With Optic Pathway Gliomas

American Journal of Ophthalmology — Wed, 24 Aug 2011 19:43:59 +0100

We read with great interest the article by Avery and associates published in the March 2011 issue of the journal. Their well-done prospective optical coherence tomography (OCT) study demonstrated that a decrease in retinal nerve fiber layer (RNFL) thickness was associated with decreased visual acuity in children with optic pathway gliomas (OPGs). We would like to draw your attention to our pilot study on the same subject, published in the December 2010 issue of the Journal of the American Association for Pediatric Ophthalmology and Strabismus (J AAPOS) and accompanied by an editorial. Our research was also presented at the annual AAPOS meeting in April 2010. The goal of our study was to examine the utility of OCT in the evaluation of neurofibromatosis type 1 (NF-1) subjects with and withou...

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Tumorigenesis: The origins of glioma

Nature Reviews Cancer — Tue, 23 Aug 2011 23:00:00 +0100

Nature Reviews Cancer 11, 627 (2011). doi:10.1038/nrc3129 Author: Gemma K. Alderton Liu and colleagues identify oligodendrocyte precursor cells as the cell of origin for glioma that is caused by inactivating mutations in neurofibromatosis 1 (Nf1) and Trp53. (Source: Nature Reviews Cancer)

Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors

Genes, Chromosomes and Cancer — Tue, 23 Aug 2011 23:00:00 +0100

In this study, we classified the atypical neurofibromas in the spectrum of NF1‐associated PNSTs by analyzing 65 tumor samples from 48 NF1 patients. We compared tumor‐specific chromosomal copy number alterations between benign neurofibromas, atypical neurofibromas, and MPNSTs (low‐, intermediate‐, and high‐grade) by karyotyping and microarray‐based comparative genome hybridization (aCGH). In 15 benign neurofibromas (4 subcutaneous and 11 plexiform), no copy number alterations were found, except a single event in a plexiform neurofibroma. One highly significant recurrent aberration (15/16) was identified in the atypical neurofibromas, namely a deletion with a minimal overlapping region (MOR) in chromosome band 9p21.3, including CDKN2A and CDKN2B. Copy number loss of the CDKN2A/B ...

Malignant Peripheral Nerve Sheath Tumors (MPNST): The Mayo Clinic Experience

Annals of Surgical Oncology — Tue, 23 Aug 2011 05:56:05 +0100

Conclusions High tumor grade and tumor size ≥5 cm predict adverse DSS for MPNST. In the context of a multidisciplinary treatment regimen, local recurrence and survival outcomes at 5 and 10 years were better than previously reported for MPNST. Content Type Journal ArticleCategory Bone and Soft Tissue SarcomasPages 1-8DOI 10.1245/s10434-011-1978-7Authors Chee-Chee H. Stucky, Department of General Surgery, Mayo Clinic Arizona, Phoenix, AZ, USAKevin N. Johnson, Department of General Surgery, Mayo Clinic Arizona, Phoenix, AZ, USARichard J. Gray, Department of General Surgery, Mayo Clinic Arizona, Phoenix, AZ, USABarbara A. Pockaj, Department of General Surgery, Mayo Clinic Arizona, Phoenix, AZ, USAIdris T. Ocal, Department of Pathology, Mayo Clinic Arizona, Ph...

Total resection of giant plexiform neurofibroma of the entire back in one stage by autologous tumor skin graft

Journal of Plastic, Reconstructive and Aesthetic Surgery — Mon, 22 Aug 2011 04:00:00 +0100

The patient was a thirteen-year-old girl who had many smooth brown freckling spots of various sizes (the diameter of the seven spots exceeded 15 mm) scattered on her body. There was a lesion on her back that had slowly grown over time and quickly in the past three years. The histological examination in a local hospital confirmed the diagnosis of neurofibromatosis type I without malignant transformation. The patient had no history of seizures or learning disabilities. The size of the large neurofibroma on the back extended into the midaxillary line and measured 42 × 48 × 5 cm3 [fig1 left]. An MRI showed a diffuse neurofibroma with associated dysplastic blood vessels exhibiting irregular areas of tunica media and sinusoidal-like vascular channels (pseudo-hemangioma) [ middle]. An angi...

What Causes Pediatric Stroke?

PediatricEducation.org — Mon, 22 Aug 2011 00:55:33 +0100

Discussion Stroke is “…the sudden occlusion or rupture of cerebral arteries or veins resulting in focal cerebral damage and clinical neurological deficits that persist for longer than 24 hours. Stroke can be ischemic, hemorrhagic or both.” Pediatric stroke, especially in a seemingly well child, is uncommon, but not as uncommon as often presumed. Outside the perinatal time period, the rate is 2-13 events /100,000 children/year or about the same rate as pediatric brain tumors. It unfortunately is also common cause of morbidity (75% of survivors have neurological deficits) and death (one of the 10 most common causes). Pediatric stroke presentations includes dystonia, emesis, fever, headache, hemiparesis, irritability, lethargy, and seizures. Adult stroke is often due to arte...

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Magnetic resonance diffusion tensor imaging (MRDTI) of the optic nerve and optic radiations at 3T in children with neurofibromatosis type I (NF-1)

Pediatric Radiology — Sat, 20 Aug 2011 15:50:58 +0100

Conclusion MRDTI can evaluate the optic pathways in children with NF-I. Statistically significant abnormalities were detected in the diffusion tensor metrics of the optic nerves and radiations in children with NF-I compared to age-matched controls. Content Type Journal ArticleCategory Original ArticlePages 1-7DOI 10.1007/s00247-011-2216-yAuthors Christopher G. Filippi, Department of Radiology, University of Vermont School of Medicine-FAHC, 111 Colchester Ave, Burlington, VT 05401, USAAaron Bos, University of Vermont School of Medicine, Burlington, VT, USAJoshua P. Nickerson, Department of Radiology, University of Vermont School of Medicine-FAHC, 111 Colchester Ave, Burlington, VT 05401, USAMichael B. Salmela, Department of Radiology, University of Minnesota School of...

Multiple isolated cutaneous plexiform schwannomas

Indian Journal of Dermatology, Venereology and Leprology — Fri, 19 Aug 2011 23:00:00 +0100

Enas A. S. Attia, Marwa Yassin, Mohamed A Lasheen, Samar Abdalla Salem, Naziha H KhafagyIndian Journal of Dermatology, Venereology, and Leprology 2011 77(5):594-596Plexiform schwannoma is a rare neurogenic tumor, arising from skin and subcutaneous tissue. The presence of multiple schwannomas suggests a possible association with neurofibromatosis type 2 (NF2). A 50-year old male patient presented with multiple papulo-nodular cutaneous lesions on both arms and forearms. Histopathological examination revealed a dermal multinodular pattern of well-circumscribed masses of closely packed cells, with peripheral myxoid tissue, well-encapsulated in a thin collagenous capsule. S-100 immunohistochemical staining was diffusely and strongly positive. Neuron-specific enolase was positive, confirming a n...

Therapeutics for Childhood Neurofibromatosis Type 1 and Type 2

Current Treatment Options in Neurology — Thu, 18 Aug 2011 06:02:54 +0100

Opinion statement Neurofibromatosis type 1 (NF1) and type 2 (NF2) are genetically and medically distinct neurocutaneous disorders that are both associated with tumors affecting the central and peripheral nervous systems. NF1 has a frequency of 1 in 3,000, compared with 1 in 30,000 for NF2. Careful surveillance is important for both conditions, to allow early identification and treatment of complications. The most common and important problems in NF1 are cognitive impairment, optic pathway gliomas, plexiform neurofibromas, and orthopaedic issues. Early intervention and tailored educational programs are indicated for learning difficulties. Attention deficit hyperactivity disorder may be amenable to treatment with stimulant medication. A clinical trial is under way to evaluate...

A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans

PLoS Genetics — Wed, 17 Aug 2011 23:00:00 +0100

by Chip Stewart, Deniz Kural, Michael P. Strömberg, Jerilyn A. Walker, Miriam K. Konkel, Adrian M. Stütz, Alexander E. Urban, Fabian Grubert, Hugo Y. K. Lam, Wan-Ping Lee, Michele Busby, Amit R. Indap, Erik Garrison, Chad Huff, Jinchuan Xing, Michael P. Snyder, Lynn B. Jorde, Mark A. Batzer, Jan O. Korbel, Gabor T. Marth, 1000 Genomes Project As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,...

Simultaneously occurring tumours within the same cerebello-pontine angle: refining literature definitions and proposal for classification

Acta Neurochirurgica — Tue, 16 Aug 2011 06:16:50 +0100

We report on an unusual case of a patient, not affected by neurofibromatosis, harbouring two radiologically spatially contiguous tumours within the same cerebello-pontine angle. Pathological findings were consistent with the diagnosis of two spatially distinct primary tumours, namely a meningioma and a schwannoma. We proposed a classification of tumours occurring at the same location consistent with the different spatial arrangement and histological nature of these conditions. The correct classification of these nosological entities will allow further more accurate evaluations of these cases in order to clarify the pathogenesis, prognosis and best treatment of each one. Content Type Journal ArticleCategory Case ReportPages 1-5DOI 10.1007/s00701-011-1126-yAuthors Paolo Frassanit...

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CT Evaluation of Vocal Cord Paralysis due to Thoracic Diseases: A 10-Year Retrospective Study.

Yonsei Medical Journal — Mon, 15 Aug 2011 14:49:34 +0100

Conclusion: CT is helpful for the early detection of primary malignancy or progression of malignancy between follow-ups. Moreover, it can reveal various non-malignant causes of VCP. PMID: 21786449 [PubMed - in process] (Source: Yonsei Medical Journal)

Clinical sensitivity and specificity of multiple T2-hyperintensities on brain magnetic resonance imaging in diagnosis of neurofibromatosis type 1 in children: diagnostic accuracy study.

Croatian Medical Journal — Sun, 14 Aug 2011 23:00:00 +0100

Conclusion. This study strongly suggests the inclusion of T2-hyperintensities on brain MRI on the list of diagnostic criteria for NF1, especially in children of early age, when the clinical penetration of the NF1 gene has not yet been completely finished. PMID: 21853543 [PubMed - in process] (Source: Croatian Medical Journal)

Subcutaneous tumor seeding after biopsy in gliomatosis cerebri

Journal of Neuro-Oncology — Fri, 12 Aug 2011 06:18:36 +0100

Abstract We observed a patient with subcutaneous seeding from gliomatosis cerebri with a low-grade histopathology. A 33-year-old woman with neurofibromatosis type 1 presented with progressive headache, diplopia, dysphagia, and a rightward instability. On neurological examination dysarthria, gait ataxia, and left-sided central facial and hypoglossal palsies were determined. MRI of the brain demonstrated diffuse, infiltrative non-enhancing lesions in the pons, both cerebellar hemispheres, the parahippocampal gyrus, and the thalamus. A stereotactic biopsy demonstrated an astrocytoma WHO grade 2. These characteristics confirmed gliomatosis cerebri. Three months later, the patient presented with hydrocephalus and a subcutaneous swelling directly underneath the surgical scar. Th...

Adhesion molecule L1 is down-regulated in malignant peripheral nerve sheath tumors versus benign neurofibromatosis type 1–associated tumors

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics — Fri, 12 Aug 2011 04:00:00 +0100

Type 1 neurofibromatosis (NF-1), also known as von Recklinghausen disease, is caused by a disorder of a single gene on chromosome 17 that usually restrains cell division. A sequence that is frequently associated with NF-1 is tumor progression from neurofibromas to malignant peripheral nerve sheath tumors (MPNSTs). The aim of this study was to determine the expression of the neural L1 cell adhesion molecule in dermal-diffuse neurofibromas, plexiform neurofibromas, and MPNSTs of NF-1. We retrospectively analyzed surgically resected primary tumors, including 20 dermal neurofibromas, 23 plexiform neurofibromas, and 17 MPNSTs, by immunohistochemistry in paraffin sections of NF-1 tumors with the use of the L1-specific monoclonal antibody UJ127, which does not cross-react with other members of th...

Management of large vestibular schwannoma. Part I. Planned subtotal resection followed by Gamma Knife surgery: radiological and clinical aspects.

Journal of Neurosurgery — Thu, 11 Aug 2011 23:00:00 +0100

Conclusions Considering the good tumor growth control and facial nerve function preservation as well as the possibility of preserving serviceable hearing and the low number of complications, subtotal resection followed by GKS can be the treatment option of choice for large VSs. PMID: 21838510 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

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Management of large vestibular schwannoma. Part II. Primary Gamma Knife surgery: radiological and clinical aspects.

Journal of Neurosurgery — Thu, 11 Aug 2011 23:00:00 +0100

Conclusions Primary GKS for large VSs leads to acceptable radiological growth rates and clinical control rates, with the chance of hearing preservation. Although a higher incidence of clinical control failure and postradiosurgical morbidity is noted, as compared with that for smaller VSs, primary radiosurgery is suitable for a selected group of patients. The absence of symptomatology due to mass effect on the brainstem or cerebellum is essential, as are close clinical and radiological follow-ups, because there is little reserve for growth or swelling. PMID: 21838503 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

Genetically engineered mouse models shed new light on the pathogenesis of neurofibromatosis type I-related neoplasms of the peripheral nervous system.

Brain Research Bulletin — Tue, 09 Aug 2011 23:00:00 +0100

Authors: Brossier NM, Carroll SL Abstract Neurofibromatosis type 1 (NF1), the most common genetic disorder affecting the human nervous system, is characterized by the development of multiple benign Schwann cell tumors in skin and large peripheral nerves. These neoplasms, which are termed dermal and plexiform neurofibromas respectively, have distinct clinical courses; of particular note, plexiform, but not dermal, neurofibromas often undergo malignant progression to form malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy occurring in NF1 patients. In recent years, a number of genetically engineered mouse models have been created to investigate the molecular mechanisms driving the pathogenesis of these tumors. These models have been designed to address key ...

Macrocephaly in neurofibromatosis type 1: a sign post for optic pathway gliomas?

Child's Nervous System — Sun, 07 Aug 2011 05:48:25 +0100

Conclusion Macrocephaly significantly correlates with the incidence of optic pathway gliomas in children with neurofibromatosis type 1. We therefore hypothesise that in otherwise asymptomatic patients, macrocephaly is an additional indicator for performing MRI to detect optic pathway gliomas. Content Type Journal ArticlePages 1-5DOI 10.1007/s00381-011-1554-2Authors Christina Schindera, Paediatric Neurology, University Children’s Hospital, Inselspital, 3010 Bern, SwitzerlandKevin Wingeier, Paediatric Neurology, University Children’s Hospital, Inselspital, 3010 Bern, SwitzerlandBarbara Goeggel Simonetti, Paediatric Neurology, University Children’s Hospital, Inselspital, 3010 Bern, SwitzerlandMiriam Diepold, Paediatric Haematology and Oncology, University Childre...

The Molecular Genetics of Cystic Fibrosis: The Work of Francis Collins [Classics]

Journal of Biological Chemistry — Thu, 04 Aug 2011 23:00:00 +0100

When Francis Collins enrolled at Yale University to earn a doctorate in physical chemistry, he considered the field of biology to be “chaotic and unpredictable.” However, a biochemistry course unexpectedly sparked his interest and led him to develop the positional cloning technique that he subsequently used to identify the disease-causing mutations for cystic fibrosis, neurofibromatosis, and Huntington disease. The JBC Classic reprinted here follows up on some of Collins' initial cystic fibrosis research, investigating the regulation of the cystic fibrosis transmembrane conductance regulator. (Source: Journal of Biological Chemistry)

Spinal Reconstruction with Pedicle Screw-Based Instrumentation and rhBMP-2 in Patients with Neurofibromatosis and Severe Dural Ectasia and Spinal Deformity: Report of Two Cases and a Review of the Literature.

The Journal of Bone and Joint Surgery. American volume — Wed, 03 Aug 2011 04:00:00 +0100

Authors: Cho SK, Stoker GE, Bridwell KH PMID: 21915529 [PubMed - in process] (Source: The Journal of Bone and Joint Surgery. American volume)

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Malignant peripheral nerve sheath tumor of the vagus nerve in a teenager with the neurofibromatosis 1 gene mutation: a case report

Journal of Pediatric Surgery — Sun, 31 Jul 2011 23:00:00 +0100

Abstract: Malignant peripheral nerve sheath tumors account for approximately 5% to 10% of all soft tissue sarcomas in which 25% to 50% are diagnosed in patients with neurofibromatosis 1 (NF1). Tumors are often located in the proximal portion of the upper and lower extremities and trunk, whereas cervical vagus nerve localizations are extremely rare, and the English literature is limited to isolated case reports. Malignant peripheral nerve sheath tumors usually affect adults. However, earlier presentation is described in patients with the NF1 mutation. The authors describe a very rare case of malignant peripheral nerve sheath tumor of the vagus nerve in a teenage patient with NF1 focusing on surgical management of this uncommon pathology and its histopathologic features to underline the impo...

Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate.

The Journal of Bone and Joint Surgery. British volume — Sat, 30 Jul 2011 10:45:25 +0100

Authors: Schindeler A, Birke O, Yu NY, Morse A, Ruys A, Baldock PA, Little DG Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1(+/-)) mice and control mice. Fractures were open and featured periosteal...

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.

The American Journal of Hospice and Palliative Care — Thu, 28 Jul 2011 23:00:00 +0100

Authors: Soto E, Stewart DR, Mannes AJ, Ruppert SL, Baker K, Zlott D, Handel D, Berger AM 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 o...

Mammographic Signs of Systemic Disease [Breast Imaging]

Radiographics recent issues — Sun, 17 Jul 2011 23:00:00 +0100

Although mammography is primarily used for the detection of breast cancer, it can occasionally reveal breast abnormalities related to extramammary disease. Cardiovascular diseases such as congestive heart failure and central venous obstruction may manifest as venous engorgement and breast edema at mammography. Pathologic arterial calcifications seen at mammography can indicate an underlying risk factor for accelerated atherosclerosis such as chronic renal failure. Connective tissue diseases including rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis-polymyositis, and systemic scleroderma typically manifest with bilateral axillary lymphadenopathy, and stromal calcifications are also seen in the latter three disease processes. Some diseases such as neurofibromatosis type 1 ...

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

Journal of Neurosurgery — Thu, 14 Jul 2011 23:00:00 +0100

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 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

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Intrathoracic vagal nerve schwannoma preoperative diagnosis is correct because of clinical and characteristic ct findings —A case report and review of the literature—

General Thoracic and Cardiovascular Surgery — Wed, 13 Jul 2011 06:11:26 +0100

Abstract A 60-year-old man was operated with the clinical diagnosis of intrathoracic vagal nerve schwannoma because of characteristic CT findings and no symptom of neurofibromatosis. Thoracoscopic surgery was performed and it was confirmed pathologically. Intrathoracic vagal nerve tumor is rare, so preoperative diagnosis seems to be difficult. We review the intrathoracic vagal nerve tumors reported in Japan (52 cases of schwannoma and 9 cases of neurofibroma), and analyzed the tumor location, furthermore, the relationship of neurofibromatosis and schwannoma and neurofibroma on vagal nerve tumor. Content Type Journal ArticlePages 312-317DOI 10.1007/BF03217748Authors Ichizo Suemitsu, Department of Radiology, Mitoyo General Hospital, Kagawa, JapanHiroya Maeda, Department...

At-Risk Phenotype of Neurofibromatose-1 Patients: A Multicentre Case-Control Study

BioMed Central — Tue, 12 Jul 2011 23:00:00 +0100

Conclusion: The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs.Registration details: ORPHA86301 (Source: BioMed Central)

Reason for optimism after facial surgery for neurofibromatosis

L.A. Times - Health — Mon, 11 Jul 2011 23:00:00 +0100

The surgery was the first -- and most extensive -- of what may be three procedures for an Ohio patient who has the genetic disorder, which causes benign tumors to grow on the ends of nerves. (Source: L.A. Times - Health)

Concurrent spinal nerve root schwannoma and meningioma mimicking single‐component schwannoma

Neuropathology — Mon, 11 Jul 2011 23:00:00 +0100

We present a first case of concurrent tumors consisting of schwannoma and meningioma arising at the same spinal level in a patient without neurofibromatosis. A 49‐year‐old man without clinical evidence of neurofibromatosis presented with a 5‐month history of right neck pain. MRI demonstrated an extradural tumor involving the right‐sided C2 nerve root with a small intradural component. T1‐ and T2‐weighted and contrast‐enhanced MRI could not differentiate the intradural tumor as different from the extradural tumor. Total removal of the tumors was performed. No contiguity of the extradural tumor with the intradural tumor was seen. The intradural tumor attached strongly to the dura mater around the C2 nerve root exits. Intraoperative pathological diagnosis confirmed the extradura...

Ruptured Left Subclavian Artery Aneurysm in a 41-Year-Old Woman with Neurofibromatosis Type 1

European Journal of Vascular and Endovascular Surgery — Mon, 11 Jul 2011 04:00:00 +0100

Introduction: Intrinsic lesions of the arterial wall are important manifestations of Neurofibromatosis type 1. Report: A 41-year-old woman with Neurofibromatosis type 1, suffering sudden onset of upper back as well as left shoulder and upper chest pain is addressed to our hospital. The contrast-enhanced thoracic computed tomogram demonstrated a huge hematoma due to ruptured left subclavian artery aneurysm treated with endovascular therapy. (Source: European Journal of Vascular and Endovascular Surgery)

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Hearing preservation after low dose linac radiosurgery for acoustic neuroma depends on initial hearing and time

Radiotherapy and Oncology — Mon, 11 Jul 2011 04:00:00 +0100

Abstract: Purpose: To assess long term outcomes and factors determining hearing preservation after low dose linac stereotactic radiosurgery (SRS) for acoustic neuroma (AN) at the Royal Adelaide Hospital using prospectively collected data.Material and methods: Between 1994 and 2010, 102 patients had SRS for AN. Five patients had neurofibromatosis type 2, six sporadic cases had relapsed after surgery, and the remaining 91 sporadic cases had primary SRS. Dose was 12 or 14Gy. Sustained changes ⩾2mm in any diameter were deemed significant, and useful hearing was defined as inter-aural pure tone average (PTA)⩽50dB. Possible prognostic factors for hearing retention were tested by dividing the patients at pre-specified cutpoints: age (60years), maximum tumour diameter (20mm), initial PTA (20dB...

Hyperactivation of mTOR critically regulates abnormal osteoclastogensis in neurofibromatosis type 1

Journal of Orthopaedic Research — Sun, 10 Jul 2011 23:00:00 +0100

Ruptured Left Subclavian Artery Aneurysm in a 41-Year-Old Woman with Neurofibromatosis Type 1

EJVES Extra — Sun, 10 Jul 2011 23:00:00 +0100

Discussion: A ruptured left subclavian artery is an uncommon but life threatening manifestation in Neurofibromatosis type 1. (Source: EJVES Extra)

Nodular enhancement within the internal auditory canal following retrosigmoid vestibular schwannoma resection: a unique radiological pattern.

Journal of Neurosurgery — Thu, 07 Jul 2011 23:00:00 +0100

Conclusions In contrast to previous publications that have reported a high rate of recurrence in cases involving nodular enhancement within the original tumor bed, postoperative enhancement in the IAC lateral to the original tumor margin appears to carry much less risk for tumor recurrence. These findings may be helpful when counseling patients on the recommended frequency of postoperative follow-up imaging. PMID: 21740115 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

Traumatic upper limb weakness in a man with type 1 neurofibromatosis

Journal of Neurology, Neurosurgery and Psychiatry — Wed, 06 Jul 2011 23:00:00 +0100

A 37-year-old right-handed man presented with left arm weakness 4 months after a shoulder trauma, which was caused by somebody landing on him while swimming. There was initial left upper limb numbness and neck pain radiating to the left back with subsequent weakness of shoulder movement. He had type 1 neurofibromatosis (NF-1) with skin manifestations but no known neurological complication. On examination, power of shoulder abduction, flexion and extension and elbow flexion on the left was 2 (Medical Research Council grade), shoulder elevation was 4+ and there was moderate scapular winging. Power of all other muscle groups was 5. Left biceps and triceps reflexes were decreased. Sensation was normal as was the rest of the neurological examination. Nerve conduction studies showed abnorma...

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Hearing preservation after low dose linac radiosurgery for acoustic neuroma depends on initial hearing and time.

Wed, 06 Jul 2011 23:00:00 +0100

CONCLUSIONS: Tumour control was excellent (99/102=97% freedom from surgical salvage). Hearing preservation was strongly dependent on initial PTA, but there was a steady fall-off in hearing out to at least 10years. PMID: 21741718 [PubMed - as supplied by publisher] (Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology)

Absence of exon 17 c.2970-2872delAAT mutation in Turkish NF1 patients with mild phenotype

Child's Nervous System — Wed, 06 Jul 2011 05:56:01 +0100

Abstract Introduction Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by café-au-lait spots, neurofibromas, skinfold freckles, Lisch nodules, bone deformities, learning disabilities, and predisposition to neoplasms. It is caused by various mutations of the NF1 gene. Recently a 3-bp in-frame deletion in exon 17, c.2970-2972 delAAT mutation, has been associated with a milder phenotype of NF1 manifesting with pigmentary skin changes only. Materials and methods We therefore analyzed 35 NF1 patients without neurofibromas, learning problems, or bone lesions (19 familial, 16 sporadic, age 7–44 years) for exon 17 mutations by DNA sequencing. Results We did not find the c.2970-2972 delAAT mutation in this...

Biomarker MIA Shows Presence Of Neurofibromas

Health News from Medical News Today — Tue, 05 Jul 2011 08:00:00 +0100

Neurofibromatosis (NF1) is a genetic condition which affects one in every 3,000 people. The severity of symptoms can range from benign 'cafÃ© au lait' patches on the skin, through small tumors under the skin and deep plexiform neurofibromas, to malignant tumors of the nerve sheath. New research published in BioMed Central's open access journal BMC Medicine shows that a simple blood test for the protein melanoma-inhibitory activity (MIA) could be used to indicate the presence of neurofibromas even if they cannot be seen... (Source: Health News from Medical News Today)

MIA is a potential biomarker for tumor load in neurofibromatosis type 1

BMC Medicine — Sun, 03 Jul 2011 23:00:00 +0100

Conclusions: MIA is a potential serum biomarker of tumor load in NF1 patients which could be useful in following the disease course and monitoring efficacy of therapies. (Source: BMC Medicine)