Neurofibromatosis type 1 (NF1) is an autosomal dominant neoplastic disease caused by mutations in the NF1 gene and one of the most challenging diseases to treat. Patients have a characteristic phenotype with neurofibromas as the main features in different forms, including numerous cutaneous neurofibromas, plexiform neurofibromas involving the primary nerves, or malignant peripheral nerve sheath tumors with a very short survival period after malignant transformation. NF1 patients also suffer from multi-system involvement, with a high rate of deformity and disability, making complete surgical resection more difficult. Currently, there is no consensus on the diagnosis and treatment of NF1 in China, and different disciplines have different understandings of NF1. Multidisciplinary systematic evaluations and cooperative treatments are the keys to improve the treatment, quality of life, and prognosis of NF1 patients. In 2020, the Department of Plastic Surgery of the Ninth People’s Hospital of Shanghai Jiaotong University School of Medicine led the establishment of the first multi-center collaboration group for NF1 in China. Furthermore, the group had worked with renowned experts from the various departments including surgical oncology, medical oncology, dermatology, reproductive medicine, et al. in China to formulate the “Expert consensus on diagnosis and management of neurofibromatosis type 1 (2021 edition)”, aiming to promote standardized and homogeneous treatment covering the whole life cycle of NF1 patients and improve the treatment level and outcome of NF1 patients in China.
ObjectiveTo summarize the treatment strategies and clinical experiences of 5 cases of giant plexiform neurofibromas (PNF) involving the head, face, and neck. MethodsBetween April 2021 and May 2023, 5 patients with giant PNFs involving the head, face, and neck were treated, including 1 male and 4 females, aged 6-54 years (mean, 22.4 years). All tumors showed progressive enlargement, involving multiple regions such as the maxillofacial area, ear, and neck, significantly impacting facial appearance. Among them, 3 cases involved tumor infiltration into deep tissues, affecting development, while 4 cases were accompanied by hearing loss. Imaging studies revealed that all 5 tumors predominantly exhibited an invasive growth pattern, in which 2 and 1 also presenting superficial and displacing pattern, respectively. The surgical procedure followed a step-by-step precision treatment strategy based on aesthetic units, rather than simply aiming for maximal tumor resection in a single operation. Routine preoperative embolization of the tumor-feeding vessels was performed to reduce bleeding risk, followed by tumor resection combined with reconstructive surgery. Results All 5 patients underwent 1-3 preoperative embolization procedures, with no intraoperative hemorrhagic complications reported. Four patients required intraoperative blood transfusion. A total of 10 surgical procedures were performed across the 5 patients. One patient experienced early postoperative flap margin necrosis due to ligation for hemostasis; however, the incisions in the remaining patients healed without complications. All patients were followed up for a period ranging from 6 to 36 months, with a mean follow-up duration of 21.6 months. No significant tumor recurrence was observed during the follow-up period. Conclusion For patients with giant PNF involving the head, face, and neck, precision treatment strategy can effectively control surgical risks and improve the standard of aesthetic reconstruction. This approach enhances overall treatment outcomes by minimizing complications and optimizing functional and cosmetic results.
Objective To summarize the latest developments in neurosurgical treatments for neurofibromatosis type 1 (NF1) and explore therapeutic strategies to provide comprehensive treatment guidelines for clinicians. Methods The recent domestic and international literature and clinical cases in the field of NF1 were reviewed. The main types of neurological complications associated with NF1 and their treatments were thorough summarized and the future research directions in neurosurgery was analyzed. Results NF1 frequently results in complex and diverse lesions in the central and peripheral nervous systems, particularly low-grade gliomas in the brain and spinal canal and paraspinal neurofibromas. Treatment decisions should be made by a multidisciplinary team. Symptomatic plexiform neurofibromas and tumors with malignant imaging evidence require neurosurgical intervention. The goals of surgery include reducing tumor size, alleviating pain, and improving appearance. Postoperative functional rehabilitation exercises, long-term multidisciplinary follow-up, and psychosocial interventions are crucial for improving the quality of life for patients. Advanced imaging guidance systems and artificial intelligence technologies can help increase tumor resection rates and reduce recurrence. Conclusion Neurosurgical intervention is the primary treatment for symptomatic plexiform neurofibromas and malignant peripheral nerve sheath tumors when medical treatment is ineffective and the lesions progress rapidly. Preoperative multidisciplinary assessment, intraoperative electrophysiological monitoring, and advanced surgical assistance devices significantly enhance surgical efficacy and safety. Future research should continue to explore new surgical techniques and improve postoperative management strategies to achieve more precise and personalized treatment for NF1 patients.
ObjectiveTo evaluate the effectiveness of Cross-Union surgery for the treatment of pseudarthrosis of the tibia (PT) with neurofibromatosis type 1 (NF1). MethodsThe clinical data of 8 children of PT with NF1 who met the selection criteria between January 2018 and December 2023 was retrospectively analyzed. There were 5 boys and 3 girls, and the operative age ranged from 1.8 to 13.3 years with a median age of 3.5 years. According to Paley classification, there were 2 cases of type 2a, 2 cases of type 3, 2 cases of type 4a, and 2 cases of type 4c. There were 5 cases of first operation and 3 cases of re-fracture after previous operation. Six cases had leg length discrepancy before operation, and 2 of them had shortening over 2.0 cm. Except for 1 case of ankle fusion, the other 7 cases had ankle valgus. Preoperative coronal/sagittal angulation was recorded. Postoperative pseudarthrosis healing and refracture were observed. Leg length discrepancy and tibiotalar angle were measured and recorded before operation and at last follow-up. Inan imaging evaluation criteria was used to evaluate the imaging effect. ResultsAll patients were followed up 12-37 months (mean, 23.5 months). One pseudarthrosis failed to heal at 12 months after operation and healed at 3 months after reoperation, while the other pseudarthrosis healed with a healing rate of 87.5% and a healing time of 4-8 months (mean, 5.3 months). No refracture occurred during the follow-up. At last follow-up, there were 2 new cases with leg length discrepancy, which were 0.7 cm and 1.3 cm, respectively. In 2 cases with the leg length discrepancy more than 2.0 cm before operation, the improvement was from 4.1 cm and 12.6 cm to 2.1 cm and 9.0 cm, respectively. There was no significant difference in leg length discrepancy between pre- and post-operation in 8 cases (P>0.05). At last follow-up, 6 patients still had ankle valgus, and there was no significant difference in the tibiotalar angle between pre- and post-operation (P>0.05); the tibial coronal/sagittal angulation significantly improved when compared with that before operation (P<0.05). According to Inan imaging evaluation criteria, 1 case was good, 6 cases were fair, and 1 case was poor. Conclusion Cross-Union surgery is an effective method for the treatment of PT with NF1 in children, can achieve good bone healing results with a low risk of re-fracture. The surgery may not have significant effects on leg length discrepancy and ankle valgus, and further treatment may be required.
Objective To explore the clinical features, surgical treatment, and effectiveness of neurofibromas associated with neurofibromatosis type 1 (NF1). Methods A clinical data of 41 patients with NF1 admitted between December 2018 and April 2024 was retrospectively analyzed. There were 15 males and 26 females, with an average age of 27.5 years (range, 5-61 years). Only one type of neurofibroma existed in 3 patients and the rest of the patients had more than two types of neurofibromas. Fourteen patients had total resection of multiple cutaneous neurofibromas (CNF). Eighteen patients of diffuse neurofibromas underwent total, near-total, or subtotal resection. Among the 13 patients of localized nodular neurofibromas, 9 of benign tumors underwent total sub-capsular resection and 4 of malignant peripheral nerve sheath tumor (MPNST) underwent maginal resection, and only 1 underwent postoperative radiotherapy and chemotherapy. Among the 15 patients of plexiform neurofibromas (PNF), 5 patients underwent both superficial and deep PNF resection, 2 underwent the superficial PNF resection, and 8 underwent the large nodular lesions in the deep PNF resection. There were 8 MPNST, of which 7 cases underwent total sub-capsular resection and large tumor capsule resection under neurophysiological monitoring, and 1 case with the tumor located on the top of the head underwent wide resection and skin grafting. One patient underwent proton knife therapy after surgery, 2 patients did not receive radiotherapy, and the remaining patients received conventional radiotherapy. Results All patients were followed up after surgery, and the follow-up time was 3-66 months, with an average of 25.0 months. Patients with CNF recovered satisfactorily after surgery, and there was no recurrence during follow-up. Patients with diffuse neurofibromas relieved preoperative symptoms after surgery. Three patients with diffuse neurofibromas located in the head and face recurred during follow-up. The patients with benign localized nodular neurofibromas recovered well after surgery, and only 1 patient had transient regional neuralgia after surgery. Among the patients with MPNST, 2 patients died of recurrence and lung metastasis, while the remaining 2 patients had no recurrence and metastasis during follow-up. All preoperative symptoms disappeared in patients with benign PNF, and no tumor recurrence was observed during follow-up. Two patients with PNF located in the brachial plexus had difficulty in shoulder abduction after surgery, 1 patient with PNF located in vagus developed hoarseness after surgery. Among the 8 patients with MPNST in PNF, 1 died of lung metastases and 1 died of systemic failure. The remaining 6 patients were in stable condition during follow-up, and no tumor recurrence or metastasis was observed. Conclusion According to the clinical features of neurofibromas in patients with NF1, choosing appropriate surgical approaches can obtain good effectiveness. Because of the difficulty of completely resection, diffuse neurofibromas, especially those located in the head and face, are prone to recurrence after surgery. MPNST has the worst prognosis, high incidence of recurrence/metastasis, and short survival period. Total resection combined with radiotherapy can decrease local recurrence.
Objective To summarize application effect and clinical experience of multimodal intraoperative neurophysiological monitoring (IONM) technology in the surgery of neurofibromatosis type 1 (NF1) related peripheral nerve tumors. Methods A retrospective study was conducted on NF1 patients, who admitted between January 2019 and December 2023 and treated with peripheral nerve tumor resection surgery assisted by multimodal IONM technology. There were 49 males and 45 females. The age ranged from 5 to 78 years, with an average of 33.7 years. Tumor morphological classification included 71 cases of nodular type, 13 cases of diffuse type, and 10 cases of mixed type. Target tumors were distributed in craniofacial region (47 cases), neck (11 cases), trunk (12 cases), and limbs (24 cases). Preoperatively, 44 cases had no obvious neurological symptoms, while the remaining patients had neurological symptoms, including 15 cases of visual impairment, 5 cases of hearing impairment, 16 cases of somatic movement disorders, and 31 cases of somatic sensory disorders, of which 7 cases had more than one symptom. IONM plans were selected based on the relevant nerves and adjacent important structures of the target tumor, including visual evoked potential (17 cases), somatosensory evoked potential (44 cases), motor evoked potential (88 cases), and electromyogram (94 cases).Results All surgeries were successfully completed. Ninety-three patients underwent total/near total resection and 1 patient underwent palliative resection. Pathological examination showed 80 cases of neurofibroma and 14 cases of malignant peripheral nerve sheath tumors. Complications included 2 cases of hematoma and 3 cases of incision infection. All patients were followed up 3-61 months (median, 15 months). During follow-up, no significant changes in neurological symptoms or tumor recurrence were found. Among the patients with preoperative visual impairment, there were 14 cases with no improvement in symptoms and 1 with improvement after surgery. Among the patients with somatic movement disorders, there were 11 cases with no improvement in symptoms, 3 cases with improvement, 2 cases with aggravation, 4 newly onset cases, and 1 case with significant impact on daily life after surgery. Among the patients with somatic sensory disorders, there were 17 cases with no improvement in symptoms, 14 cases with improvement, and 13 newly onset cases. The patients with hearing impairment showed improvement after surgery. Conclusion The clinical manifestations of NF1 related peripheral nerve tumors are complex. Multimodal IONM technology can provide real-time detection of nerve provocation and damage. Surgical treatment with multimodal IONM technology is safe and can reduce complications.
ObjectiveTo summarize the terms and definitions related to neurofibromatosis type 1 (NF1) with a view to standardizing and unifying the existing terminology system. Methods To review the research literature related to NF1 at home and abroad, and to summarize the expressions of the disease and related terms. Results There are still some limitations in the current knowledge of NF1, especially in the expression of the terminology, and there are discrepancies in the description and naming of NF1-related features in different medical literatures and clinical guides. There are differences in the description and naming of NF1-related features in different medical literature and clinical guidelines. Through a systematic review of the literature, this paper provides a detailed compendium and summary of the terms and definitions of NF1-related clinical manifestations, pathological features, and genetic types, and further standardizes and unifies existing diagnostic criteria and terminology systems. ConclusionThe terms and definitions of NF1-related clinical manifestations are summarized to enhance the knowledge of clinicians and researchers related to NF1.
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease caused by the mutations in the NF1 gene, with an incidence of approximately 1/3 000. Affecting multiple organs and systems throughout the body, NF1 caused a wide variety of clinical symptoms. A comprehensive multidisciplinary diagnostic and treatment model is needed to meet the diverse needs of NF1 patients and improve their quality of life. In recent years, the emergence of targeted therapies has further benefited NF1 patients, and the number of clinical consultations has increased dramatically. However, due to the rarity of the disease itself and insufficient attention previously, the standardized, systematic, and precise diagnosis and treatment model of NF1 still needs to be further improved. In this paper, we reviewed the current status of comprehensive diagnosis and treatment of NF1 in China, combine with our long-term experiences in diagnosis and treatment of this disease. Meanwhile, we propose future directions and several suggestions for the comprehensive diagnosis and treatment model for Chinese NF1 patients.
Objective To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. Methods The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized. Results NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety. ConclusionGene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease caused by mutations in the NF1 gene. The disease is characterized by neurofibromatosis, which simultaneously affects multiple systems such as nerves, skin, and bone, and has complex clinical manifestations. Since the National Institutes of Health (NIH) established diagnostic criteria in 1988, the diagnosis and treatment of NF1 have progressed significantly. However, due to the complexity of the disease and the lack of effective treatments, the diagnosis and treatment of NF1 still face many challenges. Strengthening multidisciplinary collaboration, improving and popularizing disease diagnosis and treatment strategies, and developing more effective drugs and treatment methods are the keys to further improve the treatment level of NF1 diseases.