scholarly journals Neurosurgical implications of neurofibromatosis Type I in children

2006 ◽  
Vol 20 (6) ◽  
pp. 1-6 ◽  
Author(s):  
Merdas Al-Otibi ◽  
James T. Rutka
Keyword(s):  
Peripheral Nerves ◽  
Neurofibromatosis Type ◽  
Chromosome 17 ◽  
Low Grade ◽  
Type I ◽  
Chiari Malformation Type I ◽  
Orthopedic Surgeons ◽  
Real Risk ◽  
The Brain

Neurofibromatosis Type 1 (NF1) is one of the most common inherited diseases in humans. It is caused by a mutation in the NF1 gene on chromosome 17, and is associated with numerous central and peripheral nervous system manifestations. Children with NF1 are at high risk of harboring numerous lesions that may require the attention of a neurosurgeon. Some of these include optic nerve gliomas, hydrocephalus, intraspinal tumors, and peripheral nerve tumors. Although most of the neoplasms that affect the brain, spine, and peripheral nerves of children are low-grade lesions, there is a small but real risk that some of these lesions may become high grade over time, requiring other forms of therapy than surgery alone. Other associated disorders that may result from NF1 in childhood include Chiari malformation Type I, scoliosis, and pulsating exophthalmos from the absence of the sphenoid wing. In this review, the major lesions that are found in children with NF1 are reviewed as well as the types of treatment that are offered by neurosurgeons and other members of the treating team. Today, optimum care of the child with NF1 is provided by a multidisciplinary team comprising neurosurgeons, neurologists, ophthalmologists, radiologists, orthopedic surgeons, and plastic surgeons.

scholarly journals Glioblastoma Multiforme in the Posterior Cranial Fossa in a Patient with Neurofibromatosis Type I

2009 ◽  
Vol 2009 ◽  
pp. 1-4 ◽  
Author(s):  
Marike L. D. Broekman ◽  
Roelof Risselada ◽  
JooYeon Engelen-Lee ◽  
Wim G. M. Spliet ◽  
Bon H. Verweij
Keyword(s):  
Neurofibromatosis Type ◽  
Type I ◽  
High Grade ◽  
High Grade Astrocytoma ◽  
Increased Risk ◽  
Pilocytic Astrocytomas ◽  
Benign Nature ◽  
Cranial Fossa ◽  
The Brain

Patients with Neurofibromatosis type 1 (NF1) have an increased risk of developing neoplasms. The most common brain tumors, found in 15%–20% of NF1 patients, are hypothalamic-optic gliomas, followed by brainstem and cerebellar pilocytic astrocytomas. These tumors generally have a benign nature. NF1 patients are predisposed to a 5-fold increased incidence of high-grade astrocytomas, which are usually located in supratentorial regions of the brain. We present an NF1 patient who developed a high-grade astrocytoma in the posterior fossa and discuss possible pathophysiological mechanisms.

scholarly journals CO2 Laser Ablation for the Manifestations of Multiple Cutaneous Neurofibromas in an Adult with Neurofibromatosis Type 1(NF1)

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Nicholas Calvin
Keyword(s):  
Laser Ablation ◽  
Co2 Laser ◽  
Neurofibromatosis Type 1 ◽  
Peripheral Nerves ◽  
Post Partum ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Conventional Surgery ◽  
Co2 Laser Ablation

Introduction: Neurofibromatosis type 1 is a rare genetic disorder that is characterized by the growth of noncancerous neurocutaneous tumors that form near the spinal cord and along the peripheral nerves in the body. Symptoms NF-1 are usually detected in infancy or early childhood. However, in some cases, children and adults without family history may have a spontaneous genetic mutation of unknown cause. There are several modalities to treat NF-1, which include conventional surgery removal and CO2 laser ablation. The review of literature aims to compare the efficacy and outcomes of these two modalities. Case presentation: A 32-year old post-partum Australian woman is presented to the neurosurgery department outpatient clinic. When she was around 20-year old, non-painful multiple noncancerous growth along her spine and peripheral nerves and multiple café-au-lait spots started to appear. The size and numbers of growth and spots are gradually increasing as she aged. The diagnosis of NF-1 was made according to the presence of four of the seven diagnostic criteria of the National Institute of Health Consensus Development Conference. Patient is scheduled to go to NF clinic 2 months after the meeting, in which the patient is planned to undergo a treatment of CO2 laser ablation. Conclusions: Studies have shown that CO2 has outperformed conventional surgery in managing the clinical manifestation of NF-1 in term of effectivity and cosmetic outcomes.  Keywords: neurofibromatosis type I, von Recklinghausen’s disease, adult, post-partum woman, CO2 laser ablation

scholarly journals A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Luiza A. Castro-Jorge ◽  
Carla D. Pretto ◽  
Asa B. Smith ◽  
Oded Foreman ◽  
Kelly E. Carnahan ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Time Course ◽  
Interleukin 1 ◽  
Adenovirus Type ◽  
Mouse Strains ◽  
Complex Nature ◽  
Type I ◽  
Viral Loads ◽  
The Brain

ABSTRACT Interleukin-1β (IL-1β), an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor (Il1r1 −/− mice). Il1r1 −/− mice demonstrated reduced survival, greater disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokine and chemokine levels than control C57BL/6J mice. We also examined infections of mice defective in IL-1β production (Pycard −/− mice) and mice defective in trafficking of Toll-like receptors to the endosome (Unc93b1 −/− mice). Pycard −/− and Unc93b1 −/− mice showed lower survival (similar to Il1r1 −/− mice) than control mice but, unlike Il1r1 −/− mice, did not have increased brain viral loads or BBB disruption. Based on the brain cytokine levels, MAV-1-infected Unc93b1 −/− mice had a very different inflammatory profile from infected Il1r1 −/− and Pycard −/− mice. Histological examination demonstrated pathological findings consistent with encephalitis in control and knockout mice; however, intranuclear viral inclusions were seen only in Il1r1 −/− mice. A time course of infection of control and Il1r1 −/− mice evaluating the kinetics of viral replication and cytokine production revealed differences between the mouse strains primarily at 7 to 8 days after infection, when mice began succumbing to MAV-1 infection. In the absence of IL-1 signaling, we noted an increase in the transcription of type I interferon (IFN)-stimulated genes. Together, these results indicate that IL-1 signaling is important during MAV-1 infection and suggest that, in its absence, increased IFN-β signaling may result in increased neuroinflammation. IMPORTANCE The investigation of encephalitis pathogenesis produced by different viruses is needed to characterize virus and host-specific factors that contribute to disease. MAV-1 produces viral encephalitis in its natural host, providing a good model for studying factors involved in encephalitis development. We investigated the role of IL-1 signaling during MAV-1-induced encephalitis. Unexpectedly, the lack of IL-1 signaling increased the mortality and inflammation in mice infected with MAV-1. Also, there was an increase in the transcription of type I IFN-stimulated genes that correlated with the observed increased mortality and inflammation. The findings highlight the complex nature of encephalitis and suggests that IL-1 has a protective effect for the development of MAV-1-induced encephalitis.

The Association of Chiari Type I Malformation and Neurofibromatosis Type 1

1993 ◽  
Vol 32 (3) ◽  
pp. 189-190 ◽  
Author(s):  
Joseph Dooley ◽  
Daniel Vaughan ◽  
Michael Riding ◽  
Peter Camfield
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Chiari Malformation ◽  
Neurofibromatosis Type ◽  
Foramen Magnum ◽  
Type I ◽  
Chiari Type ◽  
Chiari Type I Malformation ◽  
Chiari Type I ◽  
Chiari Malformations

The association of neurofibromatosis type 1 (NF1) with Chiari malformations of the cerebellum and brain stem has been reported on only two previous occasions.1,2 The pathogenesis of both conditions has remained unclear, although the Chiari type I malformation is most likely due to hypoplasia of the posterior fossa with subsequent extension of the cerebellum through the foramen magnum.3 NF1 is also associated with a variety of cerebral dysplasias.4 We present a patient with both of these dysplastic lesions whose Chiari malformation was asymptomatic.

scholarly journals LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii376-iii376
Author(s):  
Nathan Robison ◽  
Jasmine Pauly ◽  
Jemily Malvar ◽  
Sharon Gardner ◽  
Jeffrey Allen ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Dose Reduction ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Neurofibromatosis Type ◽  
Primary Objective ◽  
Preclinical Model ◽  
Low Grade ◽  
Type I ◽  
Open Label

Abstract BACKGROUND RAS/RAF/MEK/ERK pathway activation is the primary driver for most pediatric low-grade gliomas (LGG). Binimetinib is an orally bioavailable MEK1/2 inhibitor found to have significant central nervous system penetration in a preclinical model. OBJECTIVE The primary objective of this multi-institutional open-label phase II study was to assess preliminary efficacy of binimetinib in progressive pediatric LGG. The study included strata for both neurofibromatosis type I (NF1) and non-NF1 associated tumors, as well as a target validation (surgical) stratum. NF1 and surgical strata remain open to enrollment and will be reported separately. METHODS Children aged 1–18 years with previously treated recurrent or progressive LGG were eligible. The dose of binimetinib was 32 mg/m2/dose twice daily. Partial and minor responses were defined, respectively, as 50% and 25% decrease in maximal two-dimensional measurements. RESULTS Fifty-seven eligible patients without NF1, median age 8 years, were enrolled and began treatment; 26 were female; 28 had documented KIAA1549-BRAF fusion. Eleven patients discontinued drug in the first year due to toxicity, and an additional 27 required dose reduction. The most common drug-attributable grade 3 toxicities included creatine kinase elevation (n=9 patients), rash (n=8), and truncal weakness (n=8). Truncal weakness improved or resolved with dose reduction or cessation. Grade 4 toxicities included creatine kinase elevation (n=2) and transient colitis (n=1). Of 44 patients with preliminary response data available, 22 (50%) showed a minor (n=7) or partial (n=15) response. CONCLUSION Binimetinib is active, with manageable toxicities, in children without NF1 with progressive LGG.

scholarly journals A phase II study of continuous oral mTOR inhibitor everolimus for recurrent, radiographic-progressive neurofibromatosis type 1–associated pediatric low-grade glioma: a Neurofibromatosis Clinical Trials Consortium study

2020 ◽  
Vol 22 (10) ◽  
pp. 1527-1535 ◽  
Author(s):  
Nicole J Ullrich ◽  
Sanjay P Prabhu ◽  
Alyssa T Reddy ◽  
Michael J Fisher ◽  
Roger Packer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Neurofibromatosis Type 1 ◽  
Mtor Inhibitor ◽  
Neurofibromatosis Type ◽  
Mtor Pathway ◽  
Pharmacokinetic Parameters ◽  
Low Grade ◽  
Nerve Sheath Tumor ◽  
Pathway Inhibition

Abstract Background Activation of the mammalian target of rapamycin (mTOR) pathway is observed in neurofibromatosis type 1 (NF1) associated low-grade gliomas (LGGs), but agents that inhibit this pathway, including mTOR inhibitors, have not been studied in this population. We evaluate the efficacy of the orally administered mTOR inhibitor everolimus for radiographically progressive NF1-associated pediatric LGGs. Methods Children with radiologic-progressive, NF1-associated LGG and prior treatment with a carboplatin-containing chemotherapy were prospectively enrolled on this phase II clinical trial to receive daily everolimus. Whole blood was analyzed for everolimus and markers of phosphatidylinositol-3 kinase (PI3K)/mTOR pathway inhibition. Serial MRIs were obtained during treatment. The primary endpoint was progression-free survival at 48 weeks. Results Twenty-three participants (median age, 9.4 y; range, 3.2–21.6 y) were enrolled. All participants were initially evaluable for response; 1 patient was removed from study after development of a malignant peripheral nerve sheath tumor. Fifteen of 22 participants (68%) demonstrated a response, defined as either shrinkage (1 complete response, 2 partial response) or arrest of tumor growth (12 stable disease). Of these, 10/15 remained free of progression (median follow-up, 33 mo). All remaining 22 participants were alive at completion of therapy. Treatment was well tolerated; no patient discontinued therapy due to toxicity. Pharmacokinetic parameters and pre-dose concentrations showed substantial between-subject variability. PI3K/mTOR pathway inhibition markers demonstrating blood mononuclear cell mTOR pathway inactivation was achieved in most participants. Conclusion Individuals with recurrent/progressive NF1-associated LGG demonstrate significant disease stability/shrinkage during treatment with oral everolimus with a well-tolerated toxicity profile. Everolimus is well suited for future consideration as upfront or combination therapy in this patient population.

scholarly journals Spontaneous hemothorax associated with neurofibromatosis type I: A review of the literature

2014 ◽  
Vol 05 (03) ◽  
pp. 269-271 ◽  
Author(s):  
Swaroopa Pulivarthi ◽  
Byron Simmons ◽  
John Shearen ◽  
Murali Krishna Gurram
Keyword(s):  
Surgical Treatment ◽  
Neurofibromatosis Type ◽  
Benign Disease ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Review Of The Literature ◽  
Spontaneous Hemothorax ◽  
Massive Hemothorax ◽  
Fatal Complications

ABSTRACTNeurofibromatosis is generally a benign disease, but has the potential for rare and fatal complications, such as spontaneous hemothorax. We report a case of massive hemothorax due to neurofibroma in a 49-year-old woman with neurofibromatosis type 1. The configuration of the radiological opacity and frank blood withdrawn on thoracentesis should suggest the diagnosis of hemothorax in a patient with neurofibromatosis. Surgical treatment for hemothorax is limited by arterial fragility and the prognosis is relatively poor. Any evidence of aneurysmal disease in the thoracic vessels should be aggressively managed percutaneously by coil embolization to prevent future rupture.

scholarly journals Moyamoya syndrome associated with neurofibromatosis type I in a pediatric patient

2011 ◽  
Vol 129 (2) ◽  
pp. 110-112 ◽  
Author(s):  
Luiz Guilherme Darrigo Júnior ◽  
Elvis Terci Valera ◽  
André de Aboim Machado ◽  
Antonio Carlos dos Santos ◽  
Carlos Alberto Scrideli ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Moyamoya Syndrome ◽  
Radiological Findings ◽  
Convulsive Seizures ◽  
Age Range

CONTEXT: Neurofibromatosis type 1 (NF-1) is the most prevalent autosomal dominant genetic disorder among humans. Moyamoya disease is a cerebral vasculopathy that is only rarely observed in association with NF-1, particularly in the pediatric age range. The present study reports an occurrence of this association in an infant. CASE REPORT: An eight-month-old female presented convulsive seizures with clonic movements. The patient suffered an ischemic stroke with hemiparesis. Magnetic resonance imaging revealed radiological findings compatible with moyamoya disease. The diagnosis of NF-1 was made at the age of 20 months. CONCLUSION: Despite the rarity of this association in childhood, children with focal neurological symptoms and a diagnosis of NF-1 deserve to be investigated for moyamoya syndrome.

scholarly journals Brain tumors in neurofibromatosis type 1

2019 ◽  
Vol 2 (Supplement_1) ◽  
pp. i85-i97
Author(s):  
Amanda De Andrade Costa ◽  
David H Gutmann
Keyword(s):  
Tumor Growth ◽  
Neurofibromatosis Type 1 ◽  
Vision Loss ◽  
Critical Role ◽  
Neurofibromatosis Type ◽  
Therapeutic Drug ◽  
Low Grade ◽  
Increased Risk ◽  
Genetically Engineered Mice

Abstract AbstractAs a cancer predisposition syndrome, individuals with neurofibromatosis type 1 (NF1) are at increased risk for the development of both benign and malignant tumors. One of the most common locations for these cancers is the central nervous system, where low-grade gliomas predominate in children. During early childhood, gliomas affecting the optic pathway are most frequently encountered, whereas gliomas of the brainstem and other locations are observed in slightly older children. In contrast, the majority of gliomas arising in adults with NF1 are malignant cancers, typically glioblastoma, involving the cerebral hemispheres. Our understanding of the pathogenesis of NF1-associated gliomas has been significantly advanced through the use of genetically engineered mice, yielding new targets for therapeutic drug design and evaluation. In addition, Nf1 murine glioma models have served as instructive platforms for defining the cell of origin of these tumors, elucidating the critical role of the tumor microenvironment in determining tumor growth and vision loss, and determining how cancer risk factors (sex, germline NF1 mutation) impact on glioma formation and progression. Moreover, these preclinical models have permitted early phase analysis of promising drugs that reduce tumor growth and attenuate vision loss, as an initial step prior to translation to human clinical trials.

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

2011 ◽  
Vol 8 (4) ◽  
pp. 353-356
Author(s):  
Marianna Shvartsbeyn ◽  
Luigi Bassani ◽  
Irina Mikolaenko ◽  
Jeffrey H. Wisoff
Keyword(s):  
Brain Metastasis ◽  
Neurofibromatosis Type 1 ◽  
Wilms Tumor ◽  
Metastatic Tumor ◽  
Neurofibromatosis Type ◽  
Radiological Features ◽  
First Case ◽  
History Of ◽  
The Brain

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

Sign in / Sign up

Export Citation Format

Share Document