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Ophthalmology Jan 2017Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas... (Review)
Review
TOPIC
Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas (PNs) involving the eyelid, orbit, periorbital, and facial structures (orbital-periorbital plexiform neurofibroma [OPPN]) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem.
CLINICAL RELEVANCE
Although NF1 is a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. Although medical and surgical interventions have been reported, there are no agreed-on criteria for when OPPNs require therapy and which treatment produces the best outcome.
METHODS
Because a multidisciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics, and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual or aesthetic sequelae complicates the design of evidence-based studies and feasible clinical trials.
RESULTS
In September 2013, a multidisciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN.
CONCLUSIONS
This consensus statement provides recommendations for ophthalmologic monitoring, outlines treatment indications and forthcoming biologic therapy, and discusses challenges to performing clinical trials in this complicated condition.
Topics: Child; Consensus; Delivery of Health Care, Integrated; Disease Management; Eyelid Neoplasms; Humans; Interdisciplinary Communication; Neurofibroma, Plexiform; Neurofibromatosis 1; Orbital Neoplasms; Practice Guidelines as Topic
PubMed: 27817916
DOI: 10.1016/j.ophtha.2016.09.020 -
Surgical Neurology Feb 2005Plexiform neurofibromas are rarely found in the cauda equina. The most recent report of a plexiform neurofibroma of the cauda equina noted only 2 previously described...
BACKGROUND
Plexiform neurofibromas are rarely found in the cauda equina. The most recent report of a plexiform neurofibroma of the cauda equina noted only 2 previously described cases.
CASE DESCRIPTION
To these we add the current case, as well as 2 additional previously published cases. We report the case of a 44-year-old man with a sudden exacerbation of his long-standing lower-back and bilateral leg pain. An intradural lesion was seen on magnetic resonance imaging and he underwent surgery. Intraoperatively, there were swollen nerve roots and tumor insinuating itself between the roots. A biopsy was performed, and pathology findings were consistent with plexiform neurofibroma.
CONCLUSIONS
Plexiform neurofibroma of the cauda equina is a rare tumor, with variable manifestations. These tumors are not amenable to complete resection. Surgical treatment consists of either partial resection or biopsy, possibly with dural grafting for decompression.
Topics: Adult; Biopsy; Cauda Equina; Humans; Magnetic Resonance Imaging; Male; Neurofibroma, Plexiform; Spinal Cord Neoplasms; Treatment Outcome
PubMed: 15680670
DOI: 10.1016/j.surneu.2004.02.037 -
Ear, Nose, & Throat Journal Jun 2013Neurofibromatosis (NF) is a genetically inherited, autosomal dominant disease, characterized by multiple cafe au lait spots, cutaneous neurofibromas and "Lisch nodules."...
Neurofibromatosis (NF) is a genetically inherited, autosomal dominant disease, characterized by multiple cafe au lait spots, cutaneous neurofibromas and "Lisch nodules." Neurofibromatosis can develop from a neural source at any age. However, neurofibroma of the larynx is extremely rare and is usually manifested by obstructive airway symptoms. We encountered a 5-year-old child presenting with stridor and dyspnea, who had a diagnosis of laryngeal plexiform neurofibroma. The purpose of our report is the consideration of laryngeal NF in the differential diagnosis of dyspnea in infants and children.
Topics: Child, Preschool; Diagnosis, Differential; Dyspnea; Hemangioma; Hoarseness; Humans; Laryngeal Neoplasms; Laryngostenosis; Male; Neurofibroma, Plexiform; Neurofibromatosis 1; Respiratory Sounds; Vocal Cord Paralysis
PubMed: 23780601
DOI: 10.1177/014556131309200619 -
Neurology May 2002Neurofibromatosis type 1 (NF1) is one of the most common neurogenetic diseases affecting adults and children. Neurofibromas are one of the most common of the protean... (Review)
Review
Neurofibromatosis type 1 (NF1) is one of the most common neurogenetic diseases affecting adults and children. Neurofibromas are one of the most common of the protean manifestations of NF1. Plexiform neurofibromas, which will frequently cause cosmetic abnormalities, pain, and neurologic deficits, are composed of "neoplastic" Schwann cells accompanied by other participating cellular and noncellular components. There is increasing evidence that loss of NF1 expression in neoplastic Schwann cells is associated with elevated levels of activated RAS, supporting the notion that the NF1 gene product, neurofibromin, acts as a growth regulator by inhibiting ras growth-promoting activity. In addition, there is increasing evidence that other cooperating events, which may be under cytokine modulation, are important for neurofibroma development and growth. Treatment of plexiform neurofibromas has been empiric, with surgery being the primary option for those with progressive lesions causing a major degree of morbidity. The efficacy of alternative treatment approaches, including the use of antihistamines, maturation agents, and antiangiogenic drugs, has been questionable. More recently, biologic-based therapeutic approaches, using drugs that target the molecular genetic underpinnings of plexiform neurofibromas or cytokines believed important in tumor growth, have been initiated. Evaluation of such trials is hindered by the unpredictable natural history of plexiform neurofibromas and difficulties in determining objective response in tumors that are notoriously large and irregular in shape. Innovative neuroimaging techniques and the incorporation of quality-of-life scales may be helpful in evaluation of therapeutic interventions. The ability to design more rational therapies for NF1-associated neurofibromas is heavily predicated on an improved understanding of the molecular and cellular biology of the cells involved in neurofibroma formation and growth.
Topics: Biological Therapy; Clinical Trials as Topic; Humans; Neurofibroma, Plexiform; Neurofibromatosis 1
PubMed: 12041525
DOI: 10.1212/wnl.58.10.1461 -
Ophthalmic Plastic and Reconstructive...A 4-year-old boy with a known diagnosis of neurofibromatosis 1 (NF1) and a diffusely infiltrative plexiform neurofibroma (PN) of the left orbit was started on...
A 4-year-old boy with a known diagnosis of neurofibromatosis 1 (NF1) and a diffusely infiltrative plexiform neurofibroma (PN) of the left orbit was started on selumetinib treatment for progressively worsening amblyopia. The patient first presented with new-onset left ptosis at 11 months old. He subsequently developed refractory anisometropic amblyopia of the left eye, in addition to clinically significant left proptosis and hypoglobus that interfered with glasses wear for his amblyopia treatment. The plexiform neurofibroma was not amenable to surgical resection and selumetinib treatment was initiated 3 years after the initial diagnosis. The patient showed remarkable clinical and radiographic improvement in tumor burden after treatment. Best corrected visual acuity improved from 20/50 to 20/20- in his amblyopic eye. Relative proptosis of the affected eye also improved from 4mm to 2mm on Hertel measurements, which allowed for consistent glasses wear. Adverse effects from the treatment were limited to an acneiform rash, which resolved following dose reduction according to the FDA dosing guidelines.
Topics: Male; Humans; Child, Preschool; Infant; Amblyopia; Neurofibroma, Plexiform; Neurofibromatosis 1; Exophthalmos
PubMed: 36807287
DOI: 10.1097/IOP.0000000000002330 -
Internal Medicine (Tokyo, Japan) Oct 2023Plexiform neurofibromas (PNs) occur in approximately 50% of patients with neurofibromatosis type 1 (NF1). PNs are rare in the abdominal cavity and especially rare in...
Plexiform neurofibromas (PNs) occur in approximately 50% of patients with neurofibromatosis type 1 (NF1). PNs are rare in the abdominal cavity and especially rare in hepatobiliary lesions. A 31-year-old man with NF1 had a tumor extending along the celiac artery, superior mesenteric artery, and intrahepatic portal vein. We diagnosed him with diffuse PN based on liver tumor biopsy findings and the tumor form. Because the tumor had invaded along the intrahepatic portal vein, surgical resection was deemed difficult, and the patient was followed up with imaging studies. The patient remained asymptomatic without tumor growth.
Topics: Male; Humans; Adult; Neurofibroma, Plexiform; Neurofibromatosis 1; Abdomen; Liver Neoplasms
PubMed: 36792186
DOI: 10.2169/internalmedicine.1372-22 -
Child's Nervous System : ChNS :... Nov 2023Plexiform neurofibromas are the hallmark of neurofibromatosis type 1 (NF1) and significantly contribute to the overall burden of disease. While surgical excision has...
Plexiform neurofibromas are the hallmark of neurofibromatosis type 1 (NF1) and significantly contribute to the overall burden of disease. While surgical excision has long been the only available therapy, the MEK inhibitor (MEKi) selumetinib has been approved as a non-surgical treatment option for these tumors in 2020 (USA) and 2021 (Europe), respectively. However, selumetinib will result in tumor shrinkage only after several months of therapy and might not prevent malignant transformation of a plexiform neurofibroma that occurs with a frequency of 10-15%. Here, we demonstrate that surgical excision might be the therapy of choice in some plexiform neurofibromas despite the availability of MEKi therapy.
Topics: Humans; Neurofibroma, Plexiform; Neurofibroma; Neurofibromatosis 1; Europe
PubMed: 37344677
DOI: 10.1007/s00381-023-06029-5 -
International Journal of Medical... 2023Targeted therapy of Neurofibromatosis type 1 (NF1) related plexiform neurofibroma (pNF) aiming at MEK molecule has not demonstrated a convincing result for complete...
Targeted therapy of Neurofibromatosis type 1 (NF1) related plexiform neurofibroma (pNF) aiming at MEK molecule has not demonstrated a convincing result for complete disease inhibition, probably due to other signal pathways crosstalk. Our previous study revealed an increased nuclear translocation of YAP molecule in NF1 related pNF. Herein, we decided to further investigate the therapeutic relations of YAP interference during the MEK treatment against NF1 related pNF. By means of selumetinib (MEK-inhibitor), RNA-sequencing was firstly performed to identify the changes of signal pathways in pNF Schwann cells, which was probably related to YAP regulation. Nuclear-cytoplasmic fractionation and western blotting were performed to show the intracellular YAP changes under selumetinib treatment. Thirdly, a series of assays were performed including flow cytometry, CCK-8, and colony/sphere formation under dual treatment of selumetinib and verteporfin (YAP-inhibitor). In addition, Chou-Talalay method was adopted to evaluate the synergistic inhibiting effects of such drug combination. Xenograft study was also used to detect the combining effects . RNA-sequencing revealed that selumetinib treatment might be associated with the undesirable activation of Hippo pathway in NF1 related pNF tumor cells, which might reduce its pharmaceutic effects. Next, nuclear-cytoplasmic fractionation and further studies demonstrated that selumetinib could promote the nuclear translocation and transcriptional activation of YAP , which might cause the aforementioned resistance to selumetinib treatment. Additionally, when combined treatments were performed based on verteporfin and selumetinib, synergistic effects were observed on cytotoxicity of NF1 related pNF tumor cells and xenograft models. YAP inhibition can effectively sensitize NF1 related pNF tumor cells to selumetinib. Dual targeting of YAP and MEK might be a promising therapeutic strategy for treating NF1 related pNF.
Topics: Humans; Neurofibroma, Plexiform; Neurofibromatosis 1; Verteporfin; Mitogen-Activated Protein Kinase Kinases
PubMed: 36619222
DOI: 10.7150/ijms.78386 -
International Angiology : a Journal of... Dec 2016The aim of this study was to identify Magnetic Resonance Imaging (MRI) characteristics that reliably distinguish deep plexiform neurofibromas (PNFs) from venous...
BACKGROUND
The aim of this study was to identify Magnetic Resonance Imaging (MRI) characteristics that reliably distinguish deep plexiform neurofibromas (PNFs) from venous malformations (VMs).
METHODS
A database search was conducted for patients that were referred with a vascular anomaly but had a neurofibroma instead. Clinical and imaging features of patients with venous malformations as the most common referral diagnosis were compared to those with PNFs. The imaging features of deep PNFs recorded were: anatomical location, size, morphology, margins, signal intensity and post-contrast enhancement pattern.
RESULTS
Ten patients with PNFs were identified. Five patients had adequate imaging. These five patients were included in our study. There were 3 female and 2 male patients ranging in age from 10 months to 21 years. Deep PNFs were located in the cervicofacial region (N.=3), lower extremity (N.=1) and back/flank region (N.=1). The most common clinical features of all these patients were palpable mass (N.=5) and pain (N.=4). The MRI features that distinguished VMs from deep PNFs were the serpiginous morphology, relatively intermediate T-2 signal intensity and peculiar enhancement pattern without fluid-fluid levels or phleboliths and nerve root involvement. The target sign can be regularly found in PNFs, but may be also present in VMs and other vascular lesions.
CONCLUSIONS
Target signs, a typical sign of PNFs may be absent and can also be found in vascular anomalies, leading to confusion in diagnosis. PNFs can be reliably distinguished from VMs on MRI based on the above mentioned features.
Topics: Child; Databases, Factual; Diagnostic Errors; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Neurofibroma, Plexiform; Predictive Value of Tests; Retrospective Studies; Ultrasonography, Doppler; Vascular Malformations; Vascular Neoplasms; Veins; Young Adult
PubMed: 26868134
DOI: No ID Found -
Current Medical Research and Opinion May 2021Plexiform neurofibroma (PN) is one of the most striking clinical features of neurofibromatosis 1. Growth of PN can occur at any stage of life but mostly in childhood and...
Plexiform neurofibroma (PN) is one of the most striking clinical features of neurofibromatosis 1. Growth of PN can occur at any stage of life but mostly in childhood and during hormonal changes. They arise from multiple nerve fascicles and may transform into malignant peripheral nerve sheath tumors. There was previously no approved medical therapy for tumor shrinkage or regression. Surgery is not always possible due to inaccessible location, involvement of vital tissue, optimal timing, and incomplete removal. Recently, the US Food and Drug Administration approved selumetinib for pediatric patients, 2 years of age and older, with neurofibromatosis type 1 who have symptomatic, inoperable tumor. Neurofibromin, a 2818 amino acid long cytoplasmic protein, is the product of the NF1 gene. It inhibits the activity of Ras GTPase proteins. Lack of functional neurofibromin in patients with NF1 leads to dysregulated Ras and tumorigenesis. RAS MAPK pathway is hyper activated in NF1. Selumetinib is an inhibitor of MEK1 and MEK2 proteins, which play an important role in the MAPK signaling pathway related to tumor growth. Approval was based on one pivotal, single-arm, phase II trial. 70% of participants experienced confirmed partial response of tumor shrinkage, and 68% also had improvement of related complications, and other studies have also shown beneficial responses. The major limitation of this molecule regarding its mechanism of action is the dose-dependent effect of MEK inhibition in growth of neurofibroma. Long-term safety and efficacy studies are to be done in the future to establish selumetininb as a useful medicine.
Topics: Benzimidazoles; Child; Humans; Neurofibroma, Plexiform; Neurofibromatosis 1; Pharmaceutical Preparations; United States
PubMed: 33683166
DOI: 10.1080/03007995.2021.1900089