Neurofibromatosis Type 1 Patients Research Articles

Analysis of the current Covid-19 infection and vaccination status in patients with neurofibromatosis type 1

BackgroundTo investigate the common symptoms after Covid-19 infection, characteristics of adverse events after vaccination, changes in clinical manifestations related to Neurofibromatosis type 1 (NF1), as well as the current vaccination status and factors related to vaccine hesitation among NF1 patients, in order to provide a basis for scientific protection and vaccine acceptance in NF1 individuals in the new phase of pandemic management. MethodsFrom December 29, 2022, to January 10, 2023, we conducted a self-assessment questionnaire survey among diagnosed NF1 patients. General data were provided including sex, age, main clinical presentations, and current treatment. This study mainly focused on the infection and vaccination status of Covid-19 among these patients with NF1. The data were statistically analyzed using SPSS26.0 software. ResultsOf the 250 questionnaires distributed, 226 were valid. Among the 164 patients (72.6%) with Covid-19 infection, the most common infection symptoms and incidence of patients were not significantly different from those in the normal population (P>0.05), but the incidence of symptoms such as nasal congestion, headache, myalgia, sore throat, abdominal pain, diarrhea, and eye discomfort was higher than that in the normal population (P<0.05), and no severe infection was observed; 186 patients (82.3%) had completed the Covid-19 vaccination, and more than half of those who were not vaccinated had no plans for vaccination. Among the vaccinated patients, there was no significant difference in the incidence of adverse events, such as fever, pain, redness, and swelling at the injection site after vaccination, compared to the normal population (P>0.05), but the incidence of fatigue and headache was higher in NF1 patients (P<0.001). Most patients with NF1 believe that there is no significant progressive change in NF1-related clinical manifestations after Covid-19 infection and vaccination. ConclusionCurrently, some NF1 patients appear to be worried about the evolution of their disease after Covid-19 infection in the face of large fluctuations in the pandemic situation, and some patients hesitate to receive the vaccine due to their special disease condition. Thus, clinical trials should be conducted to develop a refined pandemic response and vaccination program for this special group.

Breast Cancer Screening Utilization and Outcomes in Women With Neurofibromatosis Type 1

IntroductionWomen with neurofibromatosis type 1 (NF1) have up to a 5-fold increased risk for breast cancer before age 50 and a 3.5-fold increased risk of breast cancer overall. The purpose of our study was to assess breast cancer screening utilization and outcomes in this population. Patients and MethodsThis IRB approved HIPAA compliant study retrospectively assessed consecutive NF1 patients (January 2012-December 2021) with recorded clinical visits and/or breast imaging. Patient demographics, risk factors, and screening mammogram and breast magnetic resonance imaging (MRI) outcomes were recorded. Descriptive statistics were obtained and standard breast screening measures were calculated. ResultsOne hundred and eleven women (median age 43, range 30-82) were eligible for screening based on current NCCN guidelines. A total of 86% (95/111) of all patients and 80% (24/30) of patients under age 40 had at least 1 mammogram. In contrast, 28% (31/111) of all patients and 33% (25/76) of patients ages 30 to 50 had at least 1 screening MRI. Of 368 screening mammograms performed, 38 of 368 (10%) resulted in the recall, and 22 of 368 (6%) resulted in a biopsy. Of 48 screening MRIs performed, 19 of 48 (40%) short-term follow-ups and 12 of 48 (25%) biopsies were recommended. All 6 screen-detected cancers in our cohort were detected initially on screening mammograms. ConclusionResults confirm the utility and performance of screening mammography in the NF1 population. The low utilization of MRI in our cohort limits the evaluation of outcomes via this modality and suggests there may be an education or interest gap among referrers and patients regarding supplemental screening recommendations.

Vitamin D and Bone Metabolism in Adult Patients with Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a genetic multisystemic autosomal dominant disorder determining reduced life expectancy due to higher risk of developing benign and malignant tumors. Low levels of vitamin D and reduced bone mineral density (BMD) have been reported in young patients with NF1. However, correlation between vitamin D and NF1 phenotype needs to be elucidated. Aim of this study was to assess vitamin D levels and bone metabolism in NF1 patients, analyzing potential correlations with clinical phenotype. A cross-sectional study was carried out in a monocentric series of NF1 patients, evaluating genotype, clinical phenotype, BMD, biochemical evaluation with focus on serum 25OH-vitamin D, parathyroid hormone (PTH), calcium and phosphate levels. Correlations between clinical manifestations, neurofibromas, and vitamin D status have been studied in comparison with healthy controls. 31 NF1 adult patients were matched for sex, age and body mass index with 31 healthy controls. A significantly difference in vitamin D level emerged in NF1 patients compared to controls. Interestingly low vitamin D levels correlated with a more aggressive phenotype and with a bigger size of neurofibromas. These data underline that vitamin D deficiency/insufficiency may play a role in clinical severity of neurofibromas in patients with NF1, suggesting the need to check bone status and replace vitamin D in these patients.

Neuropsychiatric Manifestations, Reduced Self-Esteem and Poor Quality of Life in Children and Adolescents with Neurofibromatosis Type 1 (NF1): The Impact of Symptom Visibility and Bullying Behavior.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition, associated with neurocutaneous manifestations and neuropsychiatric manifestations. The present study explored the prevalence of bullying/cyberbullying behaviors and victimization behaviors in a cohort of children and adolescents with NF1. Possible gender differences and predictors of psychological symptoms, quality of life (QoL), and self-esteem were also examined. Thirty-eight school-aged participants with NF1 completed a psychological evaluation designed to assess anxiety and depression symptomatology, QoL, self-esteem, and the prevalence and extent of bullying/cyberbullying and victimization behaviors. We found that our participants frequently reported victimization behaviors rather than bullying/cyberbullying ones. Moreover, participants complained of depressive and anxiety symptomatology together with reduced self-esteem, and low psychosocial quality of life, with females reporting more severe performances than males. Furthermore, we found that reduced self-esteem was associated with more visibility of the NF1 symptoms, and victimization behaviors were found to mediate the relationship between anxiety and psychosocial QoL. Our findings indicated the presence of a maladaptive loop in children and adolescents with NF1 patients characterized by psychological symptoms, unfavorable self-perception, low self-esteem, and psychosocial difficulties that might be worsened by experiencing victimization behaviors. These results suggest the need to use a multidisciplinary approach in the diagnosis and treatment of NF1.

Identification of therapeutic sensitivities in a spheroid drug combination screen of Neurofibromatosis Type I associated High Grade Gliomas.

Neurofibromatosis Type 1 (NF1) patients develop an array of benign and malignant tumors, of which Malignant Peripheral Nerve Sheath Tumors (MPNST) and High Grade Gliomas (HGG) have a dismal prognosis. About 15-20% of individuals with NF1 develop brain tumors and one third of these occur outside of the optic pathway. These non-optic pathway gliomas are more likely to progress to malignancy, especially in adults. Despite their low frequency, high grade gliomas have a disproportional effect on the morbidity of NF1 patients. In vitro drug combination screens have not been performed on NF1-associated HGG, hindering our ability to develop informed clinical trials. Here we present the first in vitro drug combination screen (21 compounds alone or in combination with MEK or PI3K inhibitors) on the only human NF1 patient derived HGG cell line available and on three mouse glioma cell lines derived from the NF1-P53 genetically engineered mouse model, which sporadically develop HGG. These mouse glioma cell lines were never exposed to serum, grow as spheres and express markers that are consistent with an Oligodendrocyte Precursor Cell (OPC) lineage origin. Importantly, even though the true cell of origin for HGG remains elusive, they are thought to arise from the OPC lineage. We evaluated drug sensitivities of the three murine glioma cell lines in a 3D spheroid growth assay, which more accurately reflects drug sensitivities in vivo. Excitingly, we identified six compounds targeting HDACs, BRD4, CHEK1, BMI-1, CDK1/2/5/9, and the proteasome that potently induced cell death in our NF1-associated HGG. Moreover, several of these inhibitors work synergistically with either MEK or PI3K inhibitors. This study forms the basis for further pre-clinical evaluation of promising targets, with an eventual hope to translate these to the clinic.

Neurofibromatosis Type 1 (NF1): Addressing the Transition from Pediatric to Adult Care.

Health care transition, or HCT, is the process of adolescents and young adults moving from a child/family-centered model of health care to an adult/patient-centered model of health care. Healthcare providers have an essential role in this process which can be especially challenging for individuals with medical or special healthcare needs. Neurofibromatosis type 1 (NF1) is a complex multisystem disorder requiring lifelong medical surveillance, education, and psychosocial support. This review highlights the transition needs of NF1 patients and provides resources for both clinicians and families to facilitate HCT in this population. The authors propose a framework for the development of an effective NF1 transition program by using the Six Core Elements model of the Got Transition program, reviewing existing literature, and incorporating author experiences in the care and transition of NF1 patients.

Relative size of fungiform papillae in patients with neurofibromatosis Type 1

ObjectiveTo explore possible manifestations of neurofibromatosis on the tongue, especially, enlarged papillae fungiformes. According to the literature, enlarged fungiform papillae of the tongue are a very common oral finding in patients with Neurofibromatosis Type 1 (NF1). Materials and MethodsFirstly, photos of 18 NF1 patients’ tongues, taken at different times were compared to rule of possible fluctuating papillae size. Secondly, 60 photos of 60 patients with NF1 were age/sex matched, blinded and compared to 60 photos of 60 healthy patients. Three independent medical doctors rated the photos in regard of the fungiform papillae as smaller/same/larger at two different times. The inter- and intraindividual results were compared.Thirdly, fungiform papillae of 11 NF1 patients were quantitatively measured using the Denver protocol. ResultsThe fungiform papillae showed a stable size. The comparison of the healthy individuals to the NF1 patients suggests that the larger papillae are significantly more frequent in NF1 patients than in age- and gender-matched non-NF1 individuals. The agreement between two ratings of each of the 3 raters at different time points was two moderate and one substantial, the agreement among raters was only fair, since the Fleiss’ Kappa value of all 6 ratings was 0.38. ConclusionAlthough this study confirms that the evaluation of the size of the fungiform papillae by visual inspection only is very subjective, the fungiform papillae in NF1 patients do seem to be enlarged at a statistically significant level. Nonetheless the statistical difference is not distinctive enough to establish this as a diagnostic tool in diagnosing NF1. Clinical RelevanceFacilitating the diagnosis of NF1 is an important factor in finding the correct treatment for these patients. A clinical inspection of the tongue is a simple and non-invasive procedure. This paper addresses the question if an inspection of the tongue, especially the fungiform papillae is a reliable indicator for the diagnosis of NF1.

Neurofibromatosis Type 1-Associated Plexiform Neurofibromas of the Face and Adjacent Head Regions: Topography of Lesions and Surgical Treatment Data of 179 Patients

IntroductionFacial plexiform neurofibromas (FPNF) are rare tumors frequently diagnosed in patients with neurofibromatosis type 1 (NF1), a tumor predisposition syndrome. FPNF often grows invasively and destructively, which may complicate surgical treatment. Data on the frequency, location, and surgical procedures of patients with NF1-associated FPNF are scarce. This study provides treatment data from a nationally networked reference center for the treatment of NF1 patients.Material and MethodsThe localization and treatment data of 179 NF1 patients with FPNF were analyzed. Photographically documented tumors of the study area, further determined by imaging, were manually transferred to a facial scheme and digitized. The digitized registrations of the facial extensions of the tumors of each patient were overlaid in a single image (Photoshop™), so that the file of the facial scheme contained the sum of the tumor localization. Finally, the frequency of tumor localization was indicated with a color code. The frequency of tumor extension-related coded colors was applied to outline the lesions' topography on schematic face drawings (heat map).ResultsThe distribution of the tumors showed no side preference. The need for the treatment of patients with orbital/periorbital manifestations became evident in the graphic representations. Tumors do not respect anatomical units. However, the classification of the face according to dermatomes, especially the trigeminal nerve, offers indications of tumor spread and guides treatment planning. The mean number of surgical measures per patient was 2.21 (median: 1). Extensive swelling, hematoma, and delayed wound healing were all common postoperative complications.ConclusionThe color-coded, schematic overview of the frequency distribution of cutaneous tumor spread in NF1 patients with FPNF illustrates the importance of orbital/periorbital and cheek tumor manifestations in patients' treatment needs. The imaging procedure is suitable for controlling natural tumor growth in the same way as the documentation of the post-surgical course. Repeated interventions in the region are included in surgical planning of the progressing tumor disease.

The evaluation of anterior thalamic radiation with diffusion tensor imaging in children with neurofibromatosis type-1

To determine whether there is a difference in the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the anterior thalamic radiation (ATR), which are involved in the inhibitory control mechanism, in Neurofibromatosis type-1 (NF1) patients with or without Neurofibromatosis bright objects (NBOs), in comparison to the healthy control group. Thirty children diagnosed with NF1 and 17 age-matched children were included in the study. 30 children with NF1 had a mean age of 10.47±5.43, compared to 11.35±5.43 of the control group. NF1 patients were divided into two groups as those with and without NBOs. The comparison was made by measuring ADC and FA values of ATR in patients with NF1 and a healthy control group. There was a significant difference in terms of ADC and FA values of ATR between the patients with NF1 and the control group. While a significant decrease was seen in FA values of ATR, ADC values were increased. There was a significant difference in ATR ADC and FA values between NF1 patients with and without NBOs and the healthy control group. On the other hand, no major difference was displayed between NF1 patients with NBOs and without NBOs in terms of ATR ADC and FA values. The results of increased ADC and decreased FA values may denote the demyelination process in ATR. We speculate that the onset of microstructural damage in the ATR may result in executive function impairment, particularly in the inhibitory control mechanism.

Mandibular symmetry on posterior-anterior cephalograms of neurofibromatosis type 1 patients with facial plexiform neurofibroma.

Neurofibromatosis type 1 (NF1) is an is an autosomal dominant heritable tumor predisposition syndrome.. Peripheral nerve sheath tumors (PNST) are a hallmark of NF1. Plexiform neurofibromas (PNF) are neoplasms that are characteristic of NF1, often causing disfiguring effects (e.g., on the face), and are considered precancerous lesions. Previous studies have shown that facial PNF (FPNF) have an impact on the shape of facial bones. This study examines deviations of mandibular symmetry from cephalometric reference planes considering the topography of FPNF. The posterior-anterior (PA) cephalograms of 168 patients with NF1 were examined. We compared three groups: patients with FPNF (n=74), with disseminated cutaneous neurofibroma (DNF (n=94)), and control subjects without NF1 (n=23). The PNF group was subtyped with respect to facial PNST type and location. Typical mandibular cephalometric reference points were determined (condyle, antegonion, and menton). The skeletal measurement points of the mandible in FPNF patients often differ significantly from those of the DNF group. It has been proven that typical asymmetries of the median-sagittal measurement points are indicators of PNF. Differences within the trigeminal tumor spread patterns are indicated in the measured values. A local tumor effect (PNF) on the relation of the measurement points to the reference planes is made plausible by the study results. The investigations prove that tumor type (FPNF) and the number of FPNF affected branches of the trigeminal nerve may correlate with significant deviations of mandible from symmetry on PA projections. The presented study shows that characteristic patterns of mandibular deformity can be measured on standardized radiographs in NF1 patients with FPNF. Mandibular deformities imaged on standardized radiographs may be initial indicators of a previously unrecognized NF1. Tumor-associated alterations of the mandible should be considered in the classification systems of pathognomonic, diagnostically pioneering osseous findings in NF1. The radiological findings provide clues for planning mandibular osteotomies in NF1 patients, especially for assessing facial regions typically highly vascularized by tumor spread. Furthermore, the radiological findings are an indication of a tumor potentially invading and destroying adjacent masticatory and mimic muscle, findings that may have an influence on surgical measures (function, aesthetics, and wound healing).

Sphenoid dysplasia in patients with neurofibromatosis type 1: Clinical features and imaging findings including cerebrospinal fluid alterations.

Neurofibromatosis Type 1 (NF-1) is a genetic disorder that occurs in 1:2500-3000 live births and may involve multiple organs. An uncommon but well-known phenomena is sphenoid dysplasia, which appears in 3-11% of the patients, and may result in significant lowering of the orbit. Understanding the cause and development of this process might predict its course and its treatment. The records of 29 patients with PNF in the head and neck region were searched for location of the PNF and type of surgery. Photographs were studied for facial disturbances, including vertical dystopia, hypertelorism, ptosis, exophthalmos and enophthalmos. MR and CT scans were studied for the presence of PNF, aspect of the sphenoid bone, alteration in the CSF circulation, and other tumour involvement. Fourteen of 29 patients with PNF in the head and neck presented with sphenoid dysplasia. All 14 patients had their PNF located in the periorbital region. Increased locoregional CSF collections were seen in almost all of these patients. Besides glioma of the optical nerve or hamartomas in the cerebrum and cerebellum, there were no other tumours found. Surgical treatment varies from simple excision to excessive debulking of the PNF, reconstruction of the orbit and even enucleation. Although sphenoid dysplasia is uncommon in NF-1 patients, early recognition is important to prevent facial disfigurement and vision loss. Clinicians should be aware that abnormalities in the periorbital region and especially vertical dystopia might be the first sign of sphenoid dysplasia. Performing a CT or black-bone MR scan would be the next step to confirm or exclude sphenoid dysplasia and abnormal CSF dynamics.

Withdrawal of bevacizumab is associated with rebound growth of vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis patients.

Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS). In patients with VS associated with NF2, vascular endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option. The aim of this study is to retrospectively evaluate NF2 patient responses to bevacizumab on VS growth and symptom progression. This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Out of 76 patients with NF2 evaluated between 2020 and 2022, we identified 19 that received treatment with bevacizumab. Thirteen of these patients discontinued bevacizumab after median treatment duration of 12.2 months. The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March, 2023. Fifteen patients had evaluable brain MRI data, which demonstrated partial responses in 5 patients, stable disease in 8, and progression in 2. Within 6 months of bevacizumab discontinuation, 5 patients had rebound growth of their VS greater than 20% from their previous tumor volume, while 3 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. Our single-institution experience confirms prior studies that bevacizumab can control progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.

Safety and Efficacy of Mek Inhibitors in the Treatment of Plexiform Neurofibromas: A Retrospective Study.

Plexiform neurofibromas (PN) represent the main cause of morbidity in patients affected by Neurofibromatosis Type 1 (NF1). Until recently, surgery has been the main treatment option in these patients, but it is burdened with a low efficacy rate and a high incidence of side effects as well as recurrence. In recent years, MEK inhibitors (MEKi) such as selumetinib and trametinib have shown great promise. We retrospectively describe a single center cohort of NF1 patients affected by PN1 and treated with MEKi since 2019 to 2021. Patients recruited in the study were affected by PN that were not eligible to complete surgical excision, symptomatic or with major cosmetic deformation or functional neurological deficits. Most patients experienced improvement in clinical symptoms and quality of life, with reduction or stabilization of lesions. However, no complete response was achieved. The most common adverse effects involved the skin, affecting every patient. Importantly, no life-threatening adverse effects occurred. In our experience, MEKi treatment has been shown to be both safe and effective in improving symptomatology and quality of life.

A Nationwide Study Characterizing the Risk and Outcome Profiles of Multilevel Fusion Procedures in Neuromuscular Scoliosis Patients with Neurofibromatosis Type 1

Spine abnormalities are a common manifestation of Neurofibromatosis Type 1 (NF1); however, the outcomes of surgical treatment for NF1-associated spinal deformity are not well explored. The purpose of this study was to investigate the outcome and risk profiles of multilevel fusion surgery for NF1 patients. The National Inpatient Sample was queried for NF1 and non-NF1 patient populations with neuromuscular scoliosis who underwent multilevel fusion surgery involving eight or more vertebral levels between 2004 and 2017. Multivariate regression modeling was used to explore the relationship between perioperative variables and pertinent outcomes. Of the 55,485 patients with scoliosis, 533 patients (0.96%) had NF1. Patients with NF1 were more likely to have comorbid solid tumors (P < 0.0001), clinical depression (P < 0.0001), peripheral vascular disease (P < 0.0001), and hypertension (P < 0.001). Following surgery, NF1 patients had a higher incidence of hydrocephalus (0.6% vs. 1.9% P= 0.002), seizures (4.9% vs. 5.7% P= 0.006), and accidental vessel laceration (0.3% vs.1.9% P= 0.011). Although there were no differences in overall complication rates or in-hospital mortality, multivariate regression revealed NF1 patients had an increased probability of pulmonary (OR 0.5, 95%CI 0.3-0.8, P= 0.004) complications. There were no significant differences in utilization, including nonhome discharge or extended hospitalization; however, patients with NF1 had higher total hospital charges (mean -$18739, SE 3384, P < 0.0001). These findings indicate that NF1 is associated with certain complications following multilevel fusion surgery but does not appear to be associated with differences in quality or cost outcomes. These results provide some guidance to surgeons and other healthcare professionals in their perioperative decision making by raising awareness about risk factors for NF1 patients undergoing multilevel fusion surgery. We intend for this study to set the national baseline for complications after multilevel fusion in the NF1 population.

PATH-07. MULTIPLATFORM MOLECULAR ANALYSES REFINE CLASSIFICATION AND PROGNOSTICATION OF GLIOMAS ARISING IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 1

Abstract BACKGROUND Gliomas arising in patients with neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade (LG) or high-grade (HG), and follow an indolent or aggressive clinical course. Comprehensive profiling of genetic alterations beyond NF1 and epigenetic classification of these tumors remain limited. METHODS Next-generation sequencing and DNA methylation profiling was performed on gliomas from 47 NF1 patients and correlated with clinicopathologic features, treatment, and outcomes. RESULTS 30 tumors demonstrated biallelic inactivation of NF1 without additional oncogenic alterations (“molecular LG subgroup”, median age 14 yrs). The remaining 17 tumors harbored additional oncogenic alterations beyond NF1 (“molecular HG subgroup”, median age 28), most frequently CDKN2A homozygous deletion (n=13), ATRX mutation (n=8), PIK3CA or PIK3R1 mutation (n=4), and TP53 mutation (n=3). Survival analysis showed significant differences in time to progression (137 vs 11 mos, p&amp;lt; 0.0001) and median survival time (undefined vs 37 mos, p &amp;gt; 0.0001) for molecular LG versus HG subgroups. DNA methylation profiles of the molecular LG subgroup resolved into a new epigenetic cluster closest to but divergent from the three existing reference classes of sporadic pilocytic astrocytoma. DNA methylation profiles of the molecular HG subgroup demonstrated most tumors epigenetically align with either HGAP or various subclasses of IDH-wildtype GBM. CONCLUSION NF1-associated gliomas stratify into two molecular subgroups. The “molecular LG subgroup” occurs primarily during childhood, harbors biallelic NF1 inactivation only, follows a more indolent clinical course, and has a unique epigenetic signature for which we propose the terminology “pilocytic astrocytoma, arising in the setting of NF1”. The “molecular HG subgroup” occurs primarily during adulthood, harbors additional oncogenic alterations including CDKN2A homozygous deletion and ATRX mutation, follows a more aggressive clinical course, and is epigenetically diverse. These findings highlight recurrently altered pathways in NF1-associated gliomas and help inform targeted therapeutic strategies for this patient population.

Abnormal peripheral blood cell counts in neurofibromatosis type 1

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant disease characterized by neurofibromas with infiltration of mast cells. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR) and basophil-to-lymphocyte ratio (BLR) are examined as markers for various diseases. However, these parameters have not yet been assessed for NF1. This study therefore examined these parameters in NF1 patients. We recruited 153 NF patients (78 males, 75 females) and 51 control patients (31 males, 20 females). Complete blood counts were performed, then NLR, LMR, PLR and BLR were calculated. Neutrophil count was significantly higher in male NF1 patients than in male controls. Lymphocyte count was significantly lower in NF1 patients than in controls for both sexes. Monocyte count was significantly higher in male NF1 patients than in male controls. Basophil count was significantly higher in male NF1 patients than in male controls. NLR, PLR and BLR were significantly higher in NF1 patients than in controls for both sexes. LMR was significantly lower in NF1 patients than in controls for both sexes. NF1 shows high NLR, PLR and BLR and low lymphocyte count and LMR.

Role of nerves in neurofibromatosis type 1-related nervous system tumors.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that affects nearly 1 in 3000 infants. Neurofibromin inactivation and NF1 gene mutations are involved in various aspects of neuronal function regulation, including neuronal development induction, electrophysiological activity elevation, growth factor expression, and neurotransmitter release. NF1 patients often exhibit a predisposition to tumor development, especially in the nervous system, resulting in the frequent occurrence of peripheral nerve sheath tumors and gliomas. Recent evidence suggests that nerves play a role in the development of multiple tumor types, prompting researchers to investigate the nerve as a vital component in and regulator of the initiation and progression of NF1-related nervous system tumors. In this review, we summarize existing evidence about the specific effects of NF1 mutation on neurons and emerging research on the role of nerves in neurological tumor development, promising a new set of selective and targeted therapies for NF1-related tumors.

Spontaneous Pneumothorax: A Rare Complication of Neurofibromatosis Type 1 Associated Diffuse Lung Disease

The visually striking neurocutaneous findings of neurofibromatosis type 1 (NF1) are well recognized and have been well documented throughout scientific literature. While not uncommon, the pulmonary manifestations of NF1 are unknown to many physicians. Complications of NF1 associated diffuse lung disease (NF-DLD) include pulmonary hypertension, pulmonary artery stenosis, subpleural cysts, and spontaneous pneumothorax. We present a case of a 34-year-old male with NF-DLD found incidentally in adolescence with previous apical bleb repair, presenting nearly twenty years later with spontaneous pneumothorax. In NF1 patients with pulmonary complaints, NF-DLD should be assessed with computed tomography (CT) and physicians should be familiar with associated complications.

Precocious and accelerated puberty in children with neurofibromatosis type 1: results from a close follow-up of a cohort of 45 patients.

Central precocious puberty (CPP) in neurofibromatosis type 1 (NF1) occurs mainly in association with optic pathway glioma (OPG), but it can also develop in the absence of OPG. The aim of this study was to analyze the prevalence of puberty disorders in children with NF1 and its association with OPG and its location. A retrospective study of 45 children with NF1 (68.9% boys) followed at our center between 2008 and 2020 was conducted. A cerebral MRI scan was performed in all children. We analyzed auxological, laboratory, and imaging data of children with CPP or accelerated puberty (AP). Treatments used for CPP/AP and their effect on height were also evaluated. The prevalence of puberty disorders in our cohort was 17.8% (male to female ratio of 7:1). CPP and AP were diagnosed in 8/45 (17.8%) NF1 children. Among children with puberty disorders, 5/8 (62.5%) had an OPG with chiasm involvement, 1/8 (12.5%) had an isolated optic nerve tumor, and 2/8 (25%) did not have any evidence of OPG on MRI. Fisher's exact test showed an association between CPP/AP and chiasm OPG (p = 0.025). Treatment with triptorrelin was initiated in 5/8 children, of whom four attained final predicted height. Our study confirms the higher prevalence of CPP/AP in NF1 patients, as well as an association between chiasm OPG and puberty disorders. However, CPP/AP also occurred in the absence of OPG with an incidence of 9.1%. Comprehensive evaluation of every child with NF1 regardless of the presence of OPG is therefore essential.

S3481 Small Bowel Obstruction Caused by Neurofibromatosis

Introduction: We report an unusual case of acute small bowel obstruction in a woman with Neurofibromatosis type 1 (NF1) caused by numerous gastrointestinal neurofibromas. NF1 is an autosomal dominant genetic disorder that is classically characterized by the development of cutaneous neurofibromas, but less commonly, it is associated with a variety of gastrointestinal tumors including plexiform neurofibromas, mucosal ganglioneuromas, and gastrointestinal stromal tumors [1]. Up to 25% of patients with NF1 are reported to have a gastrointestinal tumor of some kind, but it is estimated that only 5% develop gastrointestinal symptoms including bleeding, abdominal pain, abdominal distention, constipation, and very rarely small bowel obstruction (SBO) [2]. Case Description/Methods: Patient is a 26-year-old female with a past medical history significant for poorly controlled Crohn’s disease who presented due to abdominal pain and hematochezia. Physical exam was notable for pain in the right upper quadrant. CT abdomen and pelvis with contrast showed high-grade small bowel obstruction with tethering of small bowel centrally concerning for active Crohn’s disease. Colorectal surgery was consulted and performed laparotomy with ileocecectomy and end ileostomy formation. The terminal ileum and cecum were sent to pathology for further analysis. The pathology report showed “wall thickening with extensive neural hyperplasia (ganglioneuromatosis) and plexiform neurofibromas. The features seen in the resection favor intestinal neurofibromatous proliferations with secondary chronic mucosal changes. There is no transmural inflammation, granulomas or other features typically seen in Crohn's disease.” (Figure) Discussion: This patient was initially thought to have SBO due to Crohn’s disease flare, but pathology report showed that the underlying cause was secondary to plexiform neurofibromas. A systematic review of the literature shows that this is a rare finding as only 25 cases were identified from 1972 to 2013 of NF1 patients who underwent laparotomy for SBO [2]. SBO is a rare but possible manifestation of NF1.Figure 1.: CT Abdomen / Pelvis showing high grade small bowel obstruction.