Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model.

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

A life-threatening, massive subcutaneous hematoma caused by trauma in a patient with neurofibromatosis type 1: a case report and literature review.

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that can give rise to the formation of vascular lesions in affected individuals. These lesions, whether occurring spontaneously or as a result of trauma, have the potential to cause severe and even fatal hemorrhage. Case description: We presented a case demonstrating the most extensive hematoma ever documented in a patient with NF1, resulting from a minor trauma. He experienced hemodynamic instability due to severe anemia. Arteriography revealed a rupture in the intercostal artery, which was successfully treated through interventional embolization to stop the hemorrhage. Additionally, we implemented a refined surgical approach, beginning with suturing, followed by the meticulous resection of necrotic and aberrant tissues, thereby markedly diminishing bleeding. Conclusion: Minor trauma may cause severe bleeding in patients with NF1, which can be life-threatening. Timely diagnosis of NF1 and effective hemostatic techniques are key to successful treatment.

The profile of epilepsy and its characteristics in children with neurocutaneous syndromes.

Objectives: The profile of seizures in neurocutaneous syndromes is variable. We aimed to define the characteristics of epilepsy in children with neurocutaneous syndromes. Materials and Methods: Cross-sectional study over 18 months at a tertiary care pediatric hospital, including children with neurocutaneous syndromes aged between 1 and 15 years, using the 2017-International League Against Epilepsy classification. Results: In 119 children with neurocutaneous syndromes, 94 (79%) had epilepsy. In eight children with neurofibromatosis one with epilepsy, 5 (62.5%) had generalized motor tonic-clonic seizures, 1 (12.5%) had generalized motor epileptic spasms, 1 (12.5%) had generalized motor automatism, and 1 (12.5%) had a focal seizure. In 69 children with tuberous sclerosis complex with epilepsy, 30 (43.5%) had generalized motor epileptic spasms, 23 (33.3%) had focal seizures, and nine (13.0%) had generalized motor tonic-clonic seizures. In 14 children with Sturge-Weber syndrome with epilepsy, 13 (92.8%) had focal seizures, and 1 (7.2%) had generalized motor tonic seizures. Statistically significant associations were found between epilepsy and intellectual disability (P = 0.02) and behavioral problems (P = 0.00). Conclusion: Profiling seizures in children with neurocutaneous syndromes are paramount in devising target-specific treatments as the epileptogenesis in each syndrome differs in the molecular pathways leading to the hyperexcitability state. Further multicentric studies are required to unravel better insights into the epilepsy profile of neurocutaneous syndromes.

Obstructive Hydrocephalus Due to Aggressive Posterior Fossa Tumor Exhibiting Histological Characteristics of Pilocytic Astrocytoma in Two Adult Neurofibromatosis Type 1 (NF1) Cases.

Neurofibromatosis type 1 (NF1) is an autosomal dominant syndrome caused by germline alteration of the NF1gene. Among various NF1-related manifestations, obstructive hydrocephalus especially in adult NF1 cases is less frequently found. We report two adult NF1 cases exhibiting obstructive hydrocephalus due to an aggressive posterior fossa tumor exhibiting pathological characteristics of pilocytic astrocytoma as NF1-related manifestations. In these two cases, we performed endoscopic third ventriculostomy (ETV) and tumor biopsy as an initial treatment. The initial pathological diagnosis of the tumor is conventional pilocytic astrocytoma. After biopsy both cases revealed rapid tumor growth, therefore, we performed tumor removal, chemotherapy, and radiation therapy during an aggressive clinical course. However, both cases revealed dismal prognosis due to the progression of the tumor in spite of successful management of hydrocephalus by an initial ETV. DNA methylation analysis revealed that the tumor of one case matched high-grade astrocytoma with piloid features (HGAP). Most central nervous system tumors developed in NF1 are less aggressive such as pilocytic astrocytoma; however, recently a few studies revealed that HGAP, which has been a newly introduced malignant tumor in the World Health Organization Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS 5), rarely develops in NF1 cases. These findings suggested that HGAP might be one of the important causes of obstructive hydrocephalus in adult NF1 cases.

Neurofibromatosis type 1 with huge intrathoracic meningoceles misdiagnosed as pleural effusion: A case report and literature review.

BACKGROUND: Neurofibromatosis type 1 is a genetic disease that affects multiple organs and systems, leading to various clinical manifestations. In Neurofibromatosis type 1, rare intrathoracic meningoceles often occur alongside bone dysplasia. These meningoceles contain cerebrospinal fluid and can be mistakenly diagnosed as 'pleural effusion'. CASE PRESENTATION: In this case report, we mistakenly identified 'cerebrospinal fluid' as 'pleural effusion' and proceeded with drainage. This error posed significant risks to the patient and holds valuable implications for the future diagnosis and treatment of similar patients. CONCLUSIONS: In patients with Neurofibromatosis type 1 complicated by spinal deformity, there is a high incidence of intrathoracic meningoceles. Treatment strategies may differ based on the specific features of the lesions, and collaboration among multiple disciplines can significantly improve patient outcomes.

DRI Triton SS-OCT applied to detect choroidal nodules in paediatric patients affected by NF1.

Purpose: To examine whether image processing of non-mydriatic DRI Triton SS-OCT (Topcon Corporation, Tokyo, Japan) using the red free filter could assess the presence of choroidal nodules and thus include their detection as a diagnostic criterion in neurofibromatosis type 1 (NF1). Material and methods: We included 417 eyes from 210 patients, 377 - from 190 patients diagnosed with NF1 according to the criteria established by the National Institutes of Health Consensus Development Conference (NIH) and 40 from 20 healthy patients as a control group. The mean age was 9.4 years (range 2 years-18 years). All patients had their visual acuity measured by a test according to age, were examined for the presence of lisch nodules and an Optical Coherence Tomography (OCT) of the macular area was performed. All the OCT images were analysed to check if visible nodules could be identified. Results: Ages 14 (95% CI=(9.7,18.3)) and 12 years (95% CI=(9.1,14)) are the cut-off points that best separate those with choroidal nodules with Triton OCT and lisch with slit lamp, respectively, from those without. lisch nodules were detected in 50% of cases of NF1 patients. The presence of choroidal nodules did not present a statistically significant correlation with the occurrence of optic pathway glioma (p = 0.96) nor with the patient's visual worsening (p = 0.072). A statistically significant correlation was observed between the presence of choroidal nodules and the presence of lisch nodules (p < 0.05). Conclusion: The Topcon Triton OCT red free tool would not be a good tool to detect choroidal nodules in patients with NF1 because of its low sensitivity. If the presence of choroidal nodules were to be included in the diagnostic criteria for NF1, it would be convenient to use a device with red and infrared radiations.

Drosophila Contributions towards Understanding Neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a multisymptomatic disorder with highly variable presentations, which include short stature, susceptibility to formation of the characteristic benign tumors known as neurofibromas, intense freckling and skin discoloration, and cognitive deficits, which characterize most children with the condition. Attention deficits and Autism Spectrum manifestations augment the compromised learning presented by most patients, leading to behavioral problems and school failure, while fragmented sleep contributes to chronic fatigue and poor quality of life. Neurofibromin (Nf1) is present ubiquitously during human development and postnatally in most neuronal, oligodendrocyte, and Schwann cells. Evidence largely from animal models including Drosophila suggests that the symptomatic variability may reflect distinct cell-type-specific functions of the protein, which emerge upon its loss, or mutations affecting the different functional domains of the protein. This review summarizes the contributions of Drosophila in modeling multiple NF1 manifestations, addressing hypotheses regarding the cell-type-specific functions of the protein and exploring the molecular pathways affected upon loss of the highly conserved fly homolog dNf1. Collectively, work in this model not only has efficiently and expediently modelled multiple aspects of the condition and increased understanding of its behavioral manifestations, but also has led to pharmaceutical strategies towards their amelioration.

Histologic correlates of "Choroidal abnormalities" in Neurofibromatosis type 1 (NF1).

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder characterized by proliferation of cells from neural crest origin. The most common manifestations are cutaneous, neurologic, skeletal and ocular. The distinction of NF1 from other syndromes with multiple café-au-lait macules may be difficult in the pediatric age group, and ocular findings, especially Lisch nodules (i.e., melanocytic hamartomas on the irides), are a useful, early diagnostic tool. In recent years, novel ocular manifestations descriptively referred to as "choroidal abnormalities", choroidal "hyperpigmented spots" and "retinal vascular abnormalities" have been recognized in NF1. Choroidal abnormalities (CA) appear as bright patchy nodules that can be best detected with near-infrared ocular coherence tomography imaging (NIR-OCT). Because of their high specificity and sensitivity for NF1, CA have been added as an ocular diagnostic criterion of NF1 as an alternative to Lisch nodules. Although CA are important ocular diagnostic criteria for NF1, the histologic correlates are controversial. We present the postmortem ocular pathology findings of an NF1 patient for whom clinical notes and ocular imaging were available. Findings in this patient included choroidal hyperpigmented spots on funduscopy and retinal vascular abnormalities, both of which have been reported to be closely associated with CA. Histologic examination of the eyes showed multiple clusters of melanocytes of varying sizes in the choroid. Pathologic review of 12 additional postmortem eyes from 6 NF1 patients showed multiple, bilateral choroidal melanocytic aggregates in all eyes. These findings suggest that the CA seen on NIR-OCT and the hyperpigmented spots seen clinically in NF1 patients are manifestations of multifocal choroidal melanocytic clusters, consistent with choroidal melanocytic hamartomas. Lisch nodules, often multiple, were present in all eyes with morphology that differed from the choroidal hamartomas. As such, although CA and Lisch nodules are melanocytic hamartomas, there are clear phenotypical differences in their morphologies.

Functional and Radiological Outcomes of All-Posterior Surgical Correction of Dystrophic Curves in Patients with Neurofibromatosis Type 1.

STUDY DESIGN: A retrospective cohort study. PURPOSE: To determine outcomes following all-posterior surgery using computed tomography navigation, hybrid stabilization, and multiple anchor point techniques in patients with neurofibromatosis type 1 (NF-1) and dystrophic scoliosis. OVERVIEW OF LITERATURE: Previous studies favored antero-posterior fusion as the most reliable method; however, approaching the spine anteriorly was fraught with significant complications. With the advent of computer assisted navigation and multiple anchor point method, posterior only approach is reporting successful outcomes. METHODS: This study included patients who underwent all-posterior surgical deformity correction for dystrophic NF-1 curves. Coronal and sagittal Cobbs angles, apical rotation, and the presence of dystrophic features were evaluated before surgery. Postoperatively, sagittal, coronal, and axial correction, implant position, and implant densities were evaluated. The decline in curve correction and implant-related complications were evaluated at follow-up. Clinical outcomes were evaluated using the Scoliosis Research Society-22 revised index. RESULTS: This study involved 50 patients with a mean age of 13.6 years and a mean follow-up duration of 5.52 years. With a mean coronal flexibility of 18.7%, the mean apical vertebral rotation (AVR), preoperative coronal Cobb angle, and sagittal kyphosis were 27.4°, 64.01°, and 47.70°, respectively. The postoperative mean coronal Cobb angle was 30.17° (p <0.05), and the sagittal kyphosis angle was 25.4° (p <0.05). The average AVR correction rate was 41.3%. The correction remained significant at the final mean follow-up, with a coronal Cobb angle of 34.14° and sagittal kyphosis of 25.02° (p <0.05). The average implant density was 1.41, with 46% of patients having a high implant density (HID). The HID had a markedly higher mean curve correction (29.30° vs. 38.05°, p <0.05) and a lower mean loss of correction (5.7° vs. 3.8°, p <0.05). CONCLUSIONS: Utilizing computer-assisted navigation, hybrid instrumentation, and multiple anchor point technique and attaining high implant densities, this study demonstrates successful outcomes following posterior-only surgical correction of dystrophic scoliosis in patients with NF-1.

Ressecção do tumor e colocação de enxerto de pele parcial no couro cabeludo em um paciente com neurofibromatose tipo 1 / Tumor resection and partial skin graft placement on the scalp in a patient with Neurofibromatosis type 1

A neurofibromatose tipo 1 (NF1) é um distúrbio neurocutâneo hereditário no qual se formam tumores no sistema nervoso (neurofibromas). Os neurofibromas são os tumores benignos mais comuns na NF1. O tipo, o tamanho, o número e a localização dos neurofibromas devem ser considerados para a escolha do tratamento. Apresentamos um caso de NF1, no qual foi realizada uma ampla ressecção do couro cabeludo devido à presença de múltiplos neurofibromas. Associado a isso, a reconstrução foi realizada com retalhos de avanço mais autoenxerto de pele parcial, com resultados favoráveis e boa cobertura das áreas onde os tumores foram removidos.

Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder in which tumors form in the nervous system (neurofibromas). Neurofibromas are the most common benign tumors in NF1. The type, size, number, and location of the neurofibromas should be considered for the choice of treatment. We present a case of NF1, in which a wide scalp resection was performed due to the presence of multiple neurofibromas. Associated with this, reconstruction was performed with advancement flaps plus partial skin autograft with favorable results and good coverage of the areas where the tumors were removed.

Impact of neurofibromatosis type 1 on quality of life using the Skindex-29 questionnaire quality of life in NF1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common RASopathies predisposing affected patients to melanic lesions and benign tumors. NF1 is associated with considerable esthetic and functional burden negatively affecting the patient's quality of life (QoL). This study aims to assess the clinical features of NF1 patients and evaluate their impact on QoL. We identified NF1 patients from a public health database of a region in Spain. All patients underwent clinical and ophthalmological evaluation for NF1 features. We measured QoL using the Spanish version of the Skindex-29. RESULTS: Forty patients fulfilled the NF1 National Institute of Health criteria when we recruited patients. The median age was 42.00 years (IQR 26.5 -53.75). The median total Skindex-29 score was 12.3 (IQR 5.9-22.4); (emotion: 15.0, IQR 5.0-37.5; symptoms 8.9, IQR 0.0-17.9 and functioning 8.3; IQR 0.5-18.3). Women and NF1 patients with lower educational levels were associated with poorer QoL scores. We identified itching and sleep troubles to influence NF1 patients' QoL negatively. CONCLUSION: NF1 considerably influences the psychological well-being of NF1 patients. We observed that female and low-educated patients scored higher on the emotional dimension of the Skindex-29 and could, therefore, be more at risk of depression. We also pointed out some "minor symptoms" that negatively impact NF1 patients' QoL such, as itching and sleep troubles which doctors could treat if sought by doctors.

Highly Active Relapsing-Remitting Multiple Sclerosis with Neurofibromatosis Type 1: Radiological Aspects and Therapeutic Challenges - Case Report.

Introduction: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease which can rarely co-exist with neurofibromatosis 1 (NF1), a neurocutaneous inherited disorder that predisposes to oncogenesis. Patients who suffer from both conditions can be challenging cases for clinicians, as clinical symptoms and radiological findings may overlap, while MS immune-modifying treatments could further increase the risk of oncogenesis. Case Presentation: In this study, we describe the case of a 27-year-old woman who presented with signs and symptoms of optic neuritis and was then diagnosed with both MS and NF1. As the patient continued to experience MS relapses despite initial interferon-beta treatment, she was subsequently switched to natalizumab and responded well. Conclusion: This case illustrates how MRI lesion differentiation with the co-existence of MS and NF1 can be difficult due to overlaps in lesion characteristics, while treatment decisions can be challenging mainly due to scarce data on the oncogenic risk of MS immunomodulary therapies. Therefore, clinicians need to balance out the risk of malignancy development with the risk of progressive neurological disability when treating such patients.

Whole-Body Positron Emission Tomography with 18F-Fluorodeoxyglucose/Magnetic Resonance Imaging as a Screening Tool for the Detection of Malignant Transformation in Individuals with Neurofibromatosis Type 1.

Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in patients with neurofibromatosis type 1. They can result from premalignant neurofibromas, including neurofibromas with atypia and atypical neurofibromatous neoplasms of uncertain biologic potential. Some phenotypic characteristics have been described as associated with their development. The aim of this study was to outline our use of whole-body positron emission tomography with 18F-fluorodeoxyglucose/magnetic resonance imaging in adults with neurofibromatosis type 1, especially in the screening of asymptomatic individuals with a higher risk of developing an MPNST, and to study its impact on neurofibroma classification (malignant vs premalignant) and MPNST staging over time. Individuals with neurofibromatosis type 1 who underwent a positron emission tomography with 18F-fluorodeoxyglucose/magnetic resonance imaging between 2017 and 2021 were included, analyzing separately the screened population. Maximum standard uptake value and diffusion-weighted imaging were assessed. Biopsy/surgery confirmed the diagnosis. In all, 345 positron emission tomography with 18F-fluorodeoxyglucose/magnetic resonance imaging were performed in 241 patients, including 149 asymptomatic (62%) but at-risk patients. Eight MPNSTs in 8 screened individuals (5%), 6 neurofibromas with atypia in 4 individuals (3%), and 29 atypical neurofibromatous neoplasms of uncertain biologic potential in 23 individuals (15%) were diagnosed. Over time, the proportion of grade 3 MPNST and the malignant/premalignant ratio in screened individuals significantly decreased (P = .03 and P < .001, respectively). This study emphasizes the diagnostic and screening performances of whole-body positron emission tomography with 18F-fluorodeoxyglucose/magnetic resonance imaging in adults with neurofibromatosis type 1.

Tibial Dysplasia in Neurofibromatosis-1: A Rare Case Report and Review of Literature.

Background: Neurofibromatosis-1 (NF-1) is a neurocutaneous disorder, primarily affecting the skin and nervous system. Concomitant multi-system involvement is also seen. Orthopedic manifestations of NF-1 are one area that is understudied and underreported, highlighting the importance of this case report. Case Report: A 16-year-old male presented with painless swelling on the posteromedial aspect of the lower right tibia, which was confirmed to be a dysplastic mass on biopsy. Physical examination also revealed cafe au lait macules and axillary freckling, leading to a diagnosis of NF-1. Discussion: Bony lesions in NF-1 patients mainly include the spine and tibia. Congenital tibial dysplasia is commonly associated with NF-1 and may progress to pseudoarthrosis if early management is not started. Treatment modalities include excision, bracing, and fixation. Conclusion: Further research is required to have a more comprehensive view of NF-1 and orthopedics, to diagnose and manage such bony complications.

Patient characteristics, treatment patterns, healthcare resource utilization, and costs among patients diagnosed with neurofibromatosis type 1 with and without plexiform neurofibromas in Japan.

OBJECTIVES: The objectives of this study were to retrospectively investigate the patient characteristics, treatment patterns, healthcare resource utilization (HCRU), and healthcare costs related to management of neurofibromatosis type 1 (NF1) in Japan. METHODS: Cohorts of NF1 patients with or without plexiform neurofibromas (PN) were identified from the Medical Data Vision database in 2008-2019. Baseline characteristics, NF1 medications, HCRU, and associated costs were assessed using descriptive statistics. All-cause HCRU and costs following the first confirmed NF1 diagnosis date were analyzed per patient per year (PPPY) in Japanese Yen (JPY) and United States Dollar (USD). RESULTS: A total of 4394 NF1 patients without PN and 370 NF1 patients with PN were identified. The mean age was 35.0 and 36.9 years, respectively. The proportion of patients with PN treated with medications was higher than that in patients without PN (except for antirheumatic/immunologic agents). Analgesics/non-steroidal anti-inflammatory drugs were the most frequently prescribed NF1 medications (44.3% and 56.0% in patients without and with PN, respectively), followed by inpatient prescriptions of opioids/opioid-like agents (17.8% and 27.6%, respectively). Inpatient admissions accounted for the highest costs in both cohorts with the average cost PPPY being JPY 2,133,277 (USD 19,861) for patients without PN and JPY 1,052,868 (USD 9802) for patients with PN. CONCLUSIONS: NF1 is treated primarily with supportive care with analgesics/non-steroidal anti-inflammatory drugs being the most frequently prescribed NF1 medications in Japan. Findings underscored the unmet need and substantial economic burden among patients with NF1 and highlighted the need for new treatment options for patients with this disease.

Giant gluteal and vesical plexiform neurofibromas in a patient with neurofibromatosis type 1: a case report.

BACKGROUND: Neurofibromatosis type 1 is a neurocutaneous genetic disorder caused by mutations in the NF1 gene, resulting in the formation of benign tumors called neurofibromas. The most common type of tumor seen in patients with neurofibromatosis type 1 is the slow-growing and benign neurofibroma, with a subtype called plexiform neurofibroma being particularly common and causing pain, functional impairment, and cosmetic disfigurement. CASE PRESENTATION: We report the case of a 20-year-old North African female patient with a history of neurofibromatosis type 1 who presented with a growing mass in her right gluteal region, which was later diagnosed as a giant cutaneous neurofibroma. Imaging studies revealed infiltration in several regions, including the urinary bladder wall, resulting in significant bilateral hydronephrosis. The patient is currently being monitored, and no excisional procedures are planned. CONCLUSIONS: Neurofibromatosis type 1 can cause a variety of clinical symptoms, including the development of large plexiform neurofibromas. It is important to closely monitor patients with neurofibromatosis type 1 for the early detection of neurofibromas. Early detection and prompt surgical intervention are essential for preventing complications.

Qualidade de vida de portadores de neurofibromatose tipo 1: um protocolo de revisão de escopo / Quality of life of type 1 neurofibromatosis patients: a scoping review protocol

OBJETIVO: Mapear conceitos, achados e limitações acerca da qualidade de vida de crianças, adolescentes e adultos jovens portadores de neurofibromatose tipo 1. MÉTODO: Trata-se de um protocolo de revisão de escopo baseado nas diretrizes do Joanna Briggs Institute (JBI). A busca de dados será realizada nas plataformas PubMed/MEDLINE, EMBASE, Web of Science, Lilacs, CINAHL, Open Grey e Google Scholar. Os manuscritos encontrados serão organizados através da ferramenta Rayyan para identificação e exclusão de duplicatas. Na sequência, os artigos e demais materiais seguirão na mesma ferramenta para triagem e seleção de estudos elegíveis por dois pesquisadores independentes, sendo esse processo todo descrito em um fluxograma adaptado do Checklist PRISMA-ScR. Os dados extraídos dos manuscritos elegíveis serão apresentados em tabelas, quadros e fluxogramas, conforme pertinente. Os dados serão discutidos e inter-relacionados, com a finalidade de identificar potencialidades e limitações acerca do tema de pesquisa.

OBJECTIVE: To map concepts, findings, and limitations related to quality of life in children, adolescents, and young adults with neurofibromatosis type 1. METHOD: This is a scoping review protocol based on Joanna Briggs Institute (JBI) guidelines. Data searches will be conducted on PubMed/MEDLINE, EMBASE, Web of Science, Lilacs, CINAHL, Open Grey, and Google Scholar. The retrieved manuscripts will be organized using the Rayyan tool for duplicate identification and removal. Subsequently, the articles and other materials will be processed in the same tool for screening and selecting eligible studies by two independent researchers, and this entire process will be described in a flowchart adapted from the PRISMA-ScR checklist. As appropriate, data extracted from eligible manuscripts will be presented in tables, figures, and flowcharts. The data will be discussed and correlated to identify potential strengths and limitations related to the research topic.

A simplified technique for correction of complete ptosis secondary to palpebral neurofibromatosis.

PURPOSE: To present a simplified technique in management of complete ptosis secondary to neurofibromatosis. METHODS: This prospective, non-comparative, clinical interventional study included 13 patients with complete ptosis secondary to histologically proved plexiform neurofibromas. It was conducted at the Orbital Unit of Assiut University Hospital, the referral center of Upper Egypt in the period between June 2013 and October 2021. In all cases, a simplified technique of 5 surgical steps was applied: (A) Division of the involved eyelid surgically into three parts by drawing 2 curvilinear lines, the superior line 11 mm below and parallel to the lower eyebrow hairline and the inferior one 10 mm above the lid margin, (B) Resection (full-thickness) of the large middle part which involves the main pathology and lies between the 2 lines, (C) Preservation of the upper part with identification, dissection and clamping of the levator muscle, (D) Refinement of the lower part by removal of any tissue between the skin and the debulked tarsus and (E) Re-suturing of the upper and lower parts in layers; conjunctiva to conjunctiva, levator to tarsus (after resection of a part that corrects the ptosis) and skin to skin. RESULTS: Ptosis was completely corrected in 8 cases (61.5%) and residual mild ptosis occurred in 5 patients (38.5%). No exposure keratopathy or tumor growth was reported during the follow-up period of minimum 1 year. CONCLUSIONS: This simplified technique could be considered as a surgical basis for correction of complete ptosis in neurofibromatosis.