[Neurovascular pathology in a patient with neurofibromatosis type 1. Case report]. / Patología neurovascular en el paciente con neurofibromatosis de tipo 1. A propósito de un caso.

INTRODUCTION: Neurovascular involvement in patients with neurofibromatosis type 1 (NF1) presents with a wide spectrum of manifestations. Its frequency is low, albeit probably underestimated. There is currently no known specific treatment, and treatment is based on recommendations with limited evidence. This report describes a case of vascular dysplasia in a patient with NF1. CASE REPORT: A 67-year-old woman with a genetic diagnosis of NF1 and a history of multiple exeresis of neurofibromas in the left cervical region. The patient presented with a painful flare-up and swelling in the region. A cervical magnetic resonance imaging was performed, which showed signs of plexiform neurinoma growth and a lesion suggestive of aneurysm in the left cervical internal carotid artery. A subsequent computed tomographic angiography confirmed the presence of a thrombosed aneurysm with associated critical stenosis, and identified three additional aneurysms in the proximal left vertebral artery. Given the asymptomatic presentation and adequate haemodynamic compensation, the patient was prescribed a conservative treatment and clinicoradiological follow-up. CONCLUSIONS: Neurovascular alterations associated with NF1 are infrequent, and the optimal treatment for them is unknown. Studies to define its true prevalence, determine its pathophysiological substrate and estimate the risk of cerebrovascular complications more precisely are needed. This could provide more robust recommendations for the population of NF1 patients, especially in asymptomatic cases.

TITLE: Patología neurovascular en el paciente con neurofibromatosis de tipo 1. A propósito de un caso.Introducción. La afectación neurovascular en pacientes con neurofibromatosis de tipo 1 (NF1) cursa con un amplio espectro de manifestaciones y su frecuencia es baja, aunque probablemente infraestimada. En la actualidad, su tratamiento específico se desconoce y se basa en recomendaciones con bajo nivel de evidencia. Se describe un caso de displasia vascular en una paciente con NF1. Caso clínico. Mujer de 67 años con diagnóstico genético de NF1 e historia de exéresis múltiple de neurofibromas en la región cervical izquierda. La paciente presentaba un cuadro de reagudización dolorosa y tumefacción en dicha región, por lo que se le realizó una resonancia magnética cervical, que mostró signos de crecimiento de neurinomas plexiformes y una lesión sugestiva de aneurisma en la arteria carótida interna izquierda cervical. Un estudio de angiotomografía computarizada posterior confirmó la presencia de un aneurisma trombosado con estenosis crítica asociada e identificó tres aneurismas adicionales en la arteria vertebral izquierda proximal. Ante la presentación asintomática y la adecuada compensación hemodinámica, se decidió tratamiento conservador y seguimiento clinicorradiológico. Conclusiones. Las alteraciones neurovasculares asociadas a la NF1 son infrecuentes y su tratamiento óptimo se desconoce. Son necesarios estudios que definan con mayor precisión su prevalencia real, su sustrato fisiopatológico y una estimación del riesgo de complicaciones cerebrovasculares. De este modo, se podrían ofrecer recomendaciones más sólidas para la población de pacientes con NF1, especialmente en los casos asintomáticos.

[Hemoperitoneum secondary to a malignant tumor of the sheath of the peripheral nerve in the liver]. / Hemoperitoneo secundario a tumor maligno de la vaina del nervio periférico en hígado.

Malignant peripheral nerve sheath tumors are frequently associated with neurofibromatosis type 1. They are usually located in the extremities or in the axial area. Its visceral location is very rare and its hepatic origin is infrequent. They tend to be aggressive with a poor response to chemotherapy and radiotherapy, so surgical management is the best treatment option. We present the case of a young man with neurofibromatosis type 1, who presented with hemoperitoneum as a complication of a malignant tumor of the peripheral nerve sheath located in the liver.

Giant cell granuloma and neurofibroma in the mandible of a patient with neurofibromatosis type 1: a long-term follow-up case report with radiological and surgical aspects and a review of the literature.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain is frequently performed on patients with neurofibromatosis type 1 (NF1), to detect and follow-up intracranial findings. In addition, NF1-related pathologies can appear in the jaws. This case study investigates if it is advantageous to assess the depicted parts of the jaws in the imaging of NF1 patients with intracranial findings, thereby detecting jaw pathologies in their initial stages. CASE PRESENTATION: We report on the 3-year management with clinical and radiological follow-ups of a central giant cell granuloma and a neurofibroma in the mandible of a patient with NF1 who underwent examinations with brain MRIs. A review of the mandible in the patient's MRIs disclosed lesions with clear differences in progression rates. CONCLUSION: NF1-related jaw pathologies may be detected in the early stages if the depicted parts of the jaws are included in the assessment of the imaging of NF1 patients with intracranial findings. This could impact the treatment of eventual pathologies before lesion progression and further damage to the vicinity.

Reconstruction of congenital pseudarthrosis of the radius with a vascularized tibial periosteal transplant: A case report.

Congenital pseudarthrosis of the forearm poses a considerable challenge because of its rarity. The objective of this report is to introduce a novel surgical technique for its treatment. Here, we document a case of congenital pseudarthrosis of the radius in a 3-year-old boy diagnosed with type-1 neurofibromatosis. The surgical treatment involved the excision of approximately 9 cm of native radial periosteum and a bifocal radius osteotomy, which was supplemented with a vascularized tibial periosteal transplant to facilitate bone healing. Anastomosis between the anterior tibial vessels and radial vessels was performed. No immediate or late postoperative complications were observed. After 3 weeks, a robust callus formation was observed, and during a follow-up examination 3 years and 4 months later, a wide range of active forearm rotation was noted. This report suggests that vascularized periosteal flaps show promise as a viable treatment option for congenital pseudarthrosis of the forearm. They offer an alternative to vascularized fibular grafts or single-bone forearm constructs.

Multimodal Imaging Characteristics and Diagnostic Value of Choroidal Nodules in Patients with Neurofibromatosis Type 1.

Objectives: Yasunari nodules are choroidal lesions observed in patients diagnosed with neurofibromatosis type 1 (NF-1) and characterized by relatively irregular dome-shaped, plaque-like, or patchy boundaries. The present study examines the multimodal imaging characteristics of Yasunari nodules and their value in the diagnosis of NF-1. Materials and Methods: Medical records including optical coherence tomography (OCT), enhanced depth imaging OCT, infrared reflectance (IR) imaging, OCT angiography, and color fundus images of NF-1 patients who were examined at the Department of Ophthalmology in Dokuz Eylül University Faculty of Medicine between January 2022 and December 2023 were retrospectively reviewed for the presence of Yasunari nodules. Results: A total of 54 eyes of 27 patients were included in the study. At least one choroidal nodule was detected on IR imaging in 52 eyes (96.3%). In 31 (72.1%) of the 43 eyes (79.6%) with available high-quality OCT angiography images, choroidal nodules were observed as areas showing a flow deficit in the choriocapillaris layer. Of the total 54 eyes included, Lisch nodules without choroidal nodules were observed in 2 eyes (3.7%). In 16 eyes (29.6%), Lisch nodules were not detected despite the presence of choroidal nodules. Both Lisch nodules and choroidal nodules were detected in the other 36 eyes (66.7%). Conclusion: Yasunari nodules are frequently observed in NF-1 cases and can be easily detected with multimodal imaging techniques, especially IR imaging. The ability to visualize choroidal nodules before the appearance of Lisch nodules demonstrates the importance of Yasunari nodules in the diagnosis of NF-1.

NF1+/ex42del miniswine model the cellular disruptions and behavioral presentations of NF1-associated cognitive and motor impairment.

Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1+/ex42del miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology. The prefrontal lobe, anterior cingulate, and hippocampus from NF1+/ex42del and wild-type miniswine were examined longitudinally, revealing abnormalities in mature oligodendrocytes and astrocytes, and microglial activation over time. Imbalances in GABA: Glutamate ratios and GAD67 expression were observed in the hippocampus and motor cortex, supporting the role of disruption in inhibitory neurotransmission in NF1 cognitive impairment and motor dysfunction. Moreover, NF1+/ex42del miniswine demonstrated slower and shorter steps, indicative of a balance-preserving response commonly observed in NF1 patients, and progressive memory and learning impairments. Collectively, our findings affirm the effectiveness of NF1+/ex42del miniswine as a valuable resource for assessing cognitive and motor impairments associated with NF1, investigating the involvement of specific neural circuits and glia in these processes, and evaluating potential therapeutic interventions.

Inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1: a case report.

BACKGROUND: Inflammatory rhabdomyoblastic tumors are relatively recently recognized soft tissue tumors with a low malignant potential. Here, we present a case of concurrent inflammatory rhabdomyoblastic tumor (IRMT), adrenal pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1 (NF1). To our knowledge, this is the first time that this constellation of tumors has been described in the literature. CASE PRESENTATION: A female patient in her late 20s with known NF1 was diagnosed with an inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a short succession. IRMT was found to harbor a near-haploid genome and displayed a typical immunohistochemical profile as well as a focal aberrant p53 expression pattern. CONCLUSIONS: This case report strengthens the theory that defects in the tumor suppressor NF1 play a central role in the pathogenesis of inflammatory rhabdomyoblastic tumors and that IRMT may be part of the spectrum of neurofibromatosis type 1 related tumors.

Selumetinib for children with neurofibromatosis type 1 and plexiform neurofibromas: A plain language summary of SPRINT.

WHAT IS THIS SUMMARY ABOUT?: This summary describes a publication about a study called SPRINT. The SPRINT study included 50 children with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN) that could not be removed with surgery. PNs are tumors that grow along nerves and can cause various problems for children, such as pain, changes to appearance, and muscle weakness. In SPRINT, the study team wanted to learn whether a medication called selumetinib was able to shrink the PN caused by NF1 (also known as NF1-related PN), and if shrinking PNs helped relieve children of the problems caused by it. To assess how selumetinib might help, children had scans to measure the size of their PN, completed questionnaires, and had a variety of other tests done by their doctor. Their caregivers also completed questionnaires about their child. The children took selumetinib capsules twice a day on an empty stomach. WHAT WERE THE RESULTS?: The results showed that selumetinib was able to shrink the PN for most children (68%). The results also showed that the problems caused by the children's PNs mostly improved while on selumetinib treatment. SPRINT also showed that the side effects of selumetinib were mainly mild and could be managed by doctors. WHAT DO THE RESULTS MEAN?: Before SPRINT, there were not many treatment options for children with NF1 and PN as there were no medications that had been shown to shrink PN, and surgery was not always possible. SPRINT showed that this medication shrinks most PNs and could help children with NF1 and PN. In April 2020, selumetinib was approved by the US Food and Drug Administration (FDA) because of the results of SPRINT. Selumetinib was the first and, as of February 2024, is the only medicine that can be prescribed by doctors to help children with NF1-related PN. Clinical Trial Registration: NCT01362803 (SPRINT) (ClinicalTrials.gov).

An Overview of Optic Pathway Glioma With Neurofibromatosis Type 1: Pathogenesis, Risk Factors, and Therapeutic Strategies.

Optic pathway gliomas (OPGs) are most predominant pilocytic astrocytomas, which are typically diagnosed within the first decade of life. The majority of affected children with OPGs also present with neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome. OPGs in individuals with NF1 primarily affect the optic pathway and lead to visual disturbance. However, it is challenging to assess risk in asymptomatic patients without valid biomarkers. On the other hand, for symptomatic patients, there is still no effective treatment to prevent or recover vision loss. Therefore, this review summarizes current knowledge regarding the pathogenesis of NF1-associated OPGs (NF1-OPGs) from preclinical studies to seek potential prognostic markers and therapeutic targets. First, the loss of the NF1 gene activates 3 distinct Ras effector pathways, including the PI3K/AKT/mTOR pathway, the MEK/ERK pathway, and the cAMP pathway, which mediate glioma tumorigenesis. Meanwhile, non-neoplastic cells from the tumor microenvironment (microglia, T cells, neurons, etc.) also contribute to gliomagenesis via various soluble factors. Subsequently, we investigated potential genetic risk factors, molecularly targeted therapies, and neuroprotective strategies for tumor prevention and vision recovery. Last, potential directions and promising preclinical models of NF1-OPGs are presented for further research. On the whole, NF1-OPGs develop as a result of the interaction between glioma cells and the tumor microenvironment. Developing effective treatments require a better understanding of tumor molecular characteristics, as well as multistage interventions targeting both neoplastic cells and non-neoplastic cells.

MEK-SHP2 inhibition prevents tibial pseudarthrosis caused by NF1 loss in Schwann cells and skeletal stem/progenitor cells.

Congenital pseudarthrosis of the tibia (CPT) is a severe pathology marked by spontaneous bone fractures that fail to heal, leading to fibrous nonunion. Half of patients with CPT are affected by the multisystemic genetic disorder neurofibromatosis type 1 (NF1) caused by mutations in the NF1 tumor suppressor gene, a negative regulator of RAS-mitogen-activated protein kinase (MAPK) signaling pathway. Here, we analyzed patients with CPT and Prss56-Nf1 knockout mice to elucidate the pathogenic mechanisms of CPT-related fibrous nonunion and explored a pharmacological approach to treat CPT. We identified NF1-deficient Schwann cells and skeletal stem/progenitor cells (SSPCs) in pathological periosteum as affected cell types driving fibrosis. Whereas NF1-deficient SSPCs adopted a fibrotic fate, NF1-deficient Schwann cells produced critical paracrine factors including transforming growth factor-ß and induced fibrotic differentiation of wild-type SSPCs. To counteract the elevated RAS-MAPK signaling in both NF1-deficient Schwann cells and SSPCs, we used MAPK kinase (MEK) and Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) inhibitors. Combined MEK-SHP2 inhibition in vivo prevented fibrous nonunion in the Prss56-Nf1 knockout mouse model, providing a promising therapeutic strategy for the treatment of fibrous nonunion in CPT.

Distinct attentional and executive profiles in neurofibromatosis type 1: Is there difference with primary attention deficit-hyperactivity disorder?

PURPOSE: Attentional and executive dysfunctions are the most frequent cognitive disorders in neurofibromatosis type 1 (NF1), with a high prevalence of attention deficit-hyperactivity disorder (ADHD). We (i) compared attentional profiles between NF1 children with and without ADHD and children with primary ADHD criteria and (ii) investigated the possible relationship between attentional disorders and "unidentified bright objects" (UBOs) in NF1. METHODS: This retrospective study included 47 NF1 children, 25 with ADHD criteria (NF1+adhd group), matched for age, sex, and cognitive level with 47 children with primary ADHD (ADHD group). We collected computer task (sustained-attention, visuomotor-decision, inhibition, and cognitive-flexibility tasks) scores normalized for age and sex, and brain magnetic resonance imaging data. RESULTS: (i) Working memory was impaired in all groups. (ii) Omissions (p < 0.002) and response-time variability (p < 0.05) in sustained-attention and visuomotor-decision tasks and errors (p < 0.02) in the cognitive-flexibility task were lower for the NFI+adhd and ADHD groups than for the NF1-no-adhd group. (iii) The NF1+adhd group had slower response times (p ≤ 0.02) for inhibition and visuomotor-decision tasks than the other groups. (iv) We found no relevant association between cognitive performance and UBOs. CONCLUSIONS: NF1 children with ADHD have an attentional and executive functions deficit profile similar to that of children with primary ADHD, but with a slower response-time, increasing learning difficulties. The atypical connectivity of fronto-striatal pathways, poorer dopamine homeostasis, and increased GABA inhibition observed in NF1 renders vulnerable the development of the widely distributed neural networks that support attentional, working-memory, and executive functions.

Free fibula flap to achieve bone union after congenital pseudoarthrosis of the forearm in neurofibromatosis: Technical report based on 3 cases, and literature review.

Congenital pseudarthrosis of the forearm bones (CPFBs) is rare, with only 106 reported cases, and is frequently associated with neurofibromatosis (NF). Approximately 5% of patients with NF develop pseudarthrosis, and 50% of patients with pseudarthrosis have NF. Achieving bone union is difficult in congenital pseudarthrosis. Many methods have been attempted, including casting, internal fixation with or without grafting, and electrical stimulation, but failure is frequent. Free vascularized fibular flaps (FVFs) have been used to bridge long bone defects since 1975 and in tibial pseudarthrosis since 1979. In CPFB, FVF is more successful than other methods in achieving union and is the current treatment of choice. Here, we presented three cases of forearm pseudarthrosis treated with FVF, reviewed the literature on CPFB, and discussed some technical aspects of FVF treatment. Three cases of congenital pseudoarthrosis were treated with free fibula flaps, diagnosed at ages of 7 years (ulna), 15 months (radius), and 9 years (radius and ulna). Two flaps were stabilized with intramedullary wires and latterly, one with compression plates. One persistent nonunion received revision nonvascularized bone grafting and plating. All patients achieved union by 11 months after index surgery. Reconstruction with vascularized fibula is the treatment of choice because it offers the highest published union rates and good functional results. Complete resection of the affected bone and stable fixation, latterly with compression plates are critical to success. Surgery is technically demanding, and complications are common. Secondary surgery may be required, but outcomes are favorable. LEVEL OF EVIDENCE: IV.

The impact of cutaneous neurofibromas on quality of life and mental health in neurofibromatosis type 1.

The skin manifestations of neurofibromatosis 1 significantly reduce health-related quality-of-life. However, data on the utility of existing surveys in capturing neurofibromatosis 1 skin treatment outcomes are lacking. This quantitative study examined the relationship between clinician-rated severity and visibility and patient-rated itch and quality-of-life (QoL) to (1) establish baseline levels of skin- and condition-specific-related QoL, itch, depression and anxiety; (2) identify patient concerns to inform the development and evaluation of skin interventions; and (3) compare the sensitivity of different QoL measures. Validated scales included Skindex-29, Dermatology Life Quality Index (DLQI), Neurofibromatosis 1-adult quality-of-life (NF1-AdQOL) questionnaire, and the Hospital Anxiety and Depression Scale (HADS). We recruited 100 participants (response rate: 95%). Of these, 42% reported itch and 23% had probable clinical anxiety. Our cohort had higher levels of anxiety and total HADS scores compared to a control population. Using multivariate regression analysis, increasing visibility significantly predicted poorer QoL using the Skindex-29, NF1-AdQOL, and DLQI (p < 0.05); and itch significantly predicted worse QoL in Skindex-29 and NF1-AdQOL (p < 0.05). The highest mean scoring questions in Skindex-29 and NF1-AdQOL concerned worry about worsening skin disease and embarrassment. The highest mean scoring questions in DLQI were regarding itch, pain, and embarrassment. Items asking specifically about cutaneous neurofibromas (cNF) scored higher than comparable skin-specific questions (t-test p value <0.05). In summary, this study provides insights into the factors contributing to impaired QoL, anxiety, and mood in NF1 patients with cutaneous neurofibromas. Key factors identified for use in cNF measures include visibility, itch, anxiety, embarrassment, fears of worsening skin disease, and cNF-specific questions.

Guided Growth to Treat Anterolateral Tibial Bowing Associated with Congenital Pseudarthrosis of the Tibia.

BACKGROUND: Anterolateral tibial bowing associated with congenital tibial pseudarthrosis occurs often in patients with neurofibromatosis type 1 and results from the inability of the fractured bone to unite, leading to persistent nonunion, abnormal bone growth, and further bowing of the tibia. Current surgical and nonsurgical approaches demonstrate persistent nonunion or refracture, often resulting in amputation. METHODS: This report describes the management of 3 patients with anterolateral tibial bowing and NF1 who underwent distal tibia-guided growth. RESULTS: The patients had an average age of 1.6 years at initial operation, with a total of 3 to 4 surgeries over an average of 2.1 years. The latest follow-up on all patients is included, at a mean of 5.1 years after the initial operation. All 3 patients experienced substantial functional improvement and improved alignment of the mechanical axis of the tibia. One patient has experienced refracture. CONCLUSIONS: Our study indicates that guided growth can serve as an additional surgical option to improve ALTB and potentially reduce the risk of fracture and pseudarthrosis by restoring normal mechanical alignment. LEVEL OF EVIDENCE: Level-IV, Case Series.

Jaffe-Campanacci syndrome; a case series and review of the literature.

BACKGROUND: Jaffe-Campanacci syndrome is a rare syndrome, characterized by multiple non-ossifying fibromas (NOF) and cafe-au-lait patches. The name was coined in 1982 by Mirra after Jaffe who first described the case in 1958. Although it's suggested there is a relation with Neurofibromatosis type 1, there is still no consensus on whether Jaffe-Campanacci syndrome is a subtype or variant of neurofibromatosis-1(NF-1). CASE PRESENTATION: In this article, we present a case series of 2 patients. The first case is a 13-year-old male with Jaffe-Campanacci syndrome who presented with a distal femur fracture. His father had positive features of both Jaffe-Campanacci syndrome and NF-1, while his sister only had features of NF-1, so we presented both. CONCLUSION: Jaffe-Campanacci has a clear relationship with type 1 neurofibromatosis, which still has to be genetically established. Due to the presence of several large non-ossifying fibromas of the long bones, it is linked to a significant risk of pathological fractures. We concur with previous authors, that an osseous screening program should be performed for all patients with newly diagnosed type 1 neurofibromatosis, to identify non-ossifying fibromas and assess the potential for pathological fracture. Moreover, siblings of patients with NF-1 should be screened for multiple NOFs that may carry a high risk of pathological fractures.

Surgical Treatment Outcomes of Anterior-Only Correction and Reconstruction for Severe Cervical Kyphotic Deformity with Neurofibromatosis-1: A Retrospective Study with a 5-Year Follow-Up.

OBJECTIVES: Currently, anterior-only (AO), posterior-only, and combined anterior-posterior spinal fusions are common strategies for treating cervical kyphosis in patients with neurofibromatosis-1 NF-1. Nevertheless, the choice of surgical strategy remains a topic of controversy. The aim of our study is to evaluate the safety and effectiveness of anterior decompression and spinal reconstruction for the treatment of cervical kyphosis in patients with NF-1. METHODS: Twelve patients with NF-1-associated cervical kyphotic deformity were reviewed retrospectively between January 2010 and April 2020. All patients underwent AO correction and reconstruction. The X-ray was followed up in all these patients to assess the preoperative and postoperative local kyphosis angle (LKA), the global kyphosis angle (GKA), the sagittal vertical axis, and the T1 slope. The visual analog scale score, Japanese Orthopedic Association (JOA) score, and neck disability index (NDI) score were used to evaluate the improvement inclinical symptoms. The results of the difference in improvement from preoperatively to the final follow-up assessment were assessed using a paired t-test or Mann-Whitney U-test. RESULTS: The LKA and GKA decreased from the preoperative average of 64.42 (range, 38-86) and 35.50 (range, 10-81) to an average of 16.83 (range, -2 to 46) and 4.25 (range, -22 to 39) postoperatively, respectively. The average correction rates of the LKA and GKA were 76.11% and 111.97%, respectively. All patients had achieved satisfactory relief of neurological symptoms (p < 0.01). JOA scores were improved from 10.42 (range, 8-16) preoperatively to 15.25 (range, 11-18) at final follow-up (p < 0.01). NDI scores were decreased from an average of 23.25 (range, 16-34) preoperatively to an average of 7.08 (range, 3-15) at the final follow-up (p < 0.01). CONCLUSION: Anterior-only correction and reconstruction is a safe and effective method for correcting cervical kyphosis in NF-1 patients. In fixed cervical kyphosis cases, preoperative skull traction should also be considered.

Identifying Lesions of the Corpus Callosum in Patients With Neurofibromatosis Type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystemic autosomal dominant disorder that includes intracranial lesions such as unidentified bright objects (UBOs)-areas of increased T2 signal on magnetic resonance imaging (MRI)-and tumors known as gliomas. The presence of these lesions in the corpus callosum (CC) has not been previously studied in a large cohort. METHODS: We reviewed medical records of 681 patients (aged three months to 86 years) followed at our institution from 2000 to 2023 with NF1 and one or more brain MRI. Patients with lesions in the CC were identified, and RAPNO/RANO criteria were used to determine changes in size over time, where a change of 25% in the product of perpendicular measurements indicates growth or shrinkage. RESULTS: Forty-seven patients had CC UBOs, most of which were in the splenium (66.0%). Seventeen patients had CC gliomas (10% of those with any glioma), two of whom had two gliomas. Seventeen of 19 gliomas were in the splenium. Over follow-up, eight of 19 remained stable, three shrunk, and eight grew. The mean percentage change in the product of the dimensions was 311.5% (ranging from -46.7% to 2566.6%). Of the eight lesions that grew, one required treatment. CONCLUSIONS: There is a 6.9% and 2.5% prevalence of CC UBOs and gliomas, respectively, in our cohort of patients with NF1. Most lesions are present in the splenium, and although some gliomas demonstrate significant growth, they rarely require treatment. This work is the largest series of CC lesions in NF1 and adds to the growing data to inform appropriate follow-up.

Incidence of Ophthalmological Complications in NF-1 Patients Treated with MEK Inhibitors.

MEK inhibitors (MEKi) represent innovative and promising treatments for managing manifestations of neurofibromatosis type 1 (NF1). To mitigate potential ophthalmic side effects, such as MEKi-associated retinopathy (MEKAR), patients undergoing MEKi therapy routinely receive ophthalmology evaluations. Our study aims to assess the necessity of this regular screening within a predominantly pediatric NF1 population by examining the occurrence of ocular adverse events (OAE). A retrospective study evaluated 45 NF1 patients receiving MEKi. Inclusion criteria included baseline and follow-up examinations following the initiation of MEKi therapy. At each assessment, a comprehensive eye evaluation was performed, comprising a dilated fundus examination, ocular coherence tomography of the macula and nerve fiber layer, and Humphrey visual field testing. Twenty-six patients, with an average age of 13 years (range 2-23 years) and an average follow-up duration of 413 days were included in the analysis. Three different MEKi were used: selumetinib (77%), trametinib (23%), and mirdametinib (4%). None of the patients experienced retinopathy at any point during the study. Some patients had pre-existing optic neuropathies (27%), but no instances of nerve changes occurred after commencing MEKi therapy. Four patients (15%) exhibited symptoms of dry eye, all of which were effectively managed with topical lubrication.

Recurrent spontaneous pneumothorax in an NF1 patient with a novel causative variant: broadening genotype-phenotype correlations.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance, most commonly known to affect the skin and eyes. Although lung involvement in the form of cysts and bullae occurs in up to 20% of adults, the seemingly intuitive association of NF1 and spontaneous pneumothorax is not widely recognised among clinicians. Here, we report the second case of recurring spontaneous pneumothorax in the context of NF1 with a confirmed molecular diagnosis. In both cases, the NF1 variants featured a premature stop codon in the C-terminal protein domain. Interestingly, our patient had mild skin symptoms, suggesting that spontaneous pneumothorax may not be correlated with cutaneous disease severity. More genotype-phenotype correlation studies are needed for NF1 in general and for its link to spontaneous pneumothorax in particular.