RESUMEN
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that is caused by a mutation in the NF1 gene, which is located on chromosome 17q11.2, which encodes for a protein known as "Neurofibromin", which acts as an inhibitor of oncogene RAS. This gene mutation causes tumours to grow on nerves which results in other systemic abnormalities such as skin changes, bone and eye abnormalities, hormonal imbalances, and diversity in achievement of puberty with neurologic complications. NF1 has a wide variety of associations in context with puberty. It is important to determine the cause of precocious and delayed puberty in order to establish an early treatment plan, to lead a successful prognosis, and decrease complications. The case reports of two patients presenting with dichotomous pubertal variation in association with NF1 are presented.
Asunto(s)
Neurofibromatosis 1 , Humanos , Neurofibromatosis 1/genética , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/diagnóstico , Masculino , Adolescente , Femenino , Niño , Pubertad Precoz/etiología , Pubertad Precoz/diagnóstico , Pubertad Tardía/etiología , Pubertad Tardía/diagnóstico , PubertadRESUMEN
BACKGROUND: Cutaneous neurofibromas (cNFs) are a major cause of disfigurement in patients with Neurofibromatosis Type 1 (NF1). However, clinical trials investigating cNF treatments lack standardised outcome measures to objectively evaluate changes in cNF size and appearance. 3D imaging has been proposed as an objective standardised outcome measure however various systems exist with different features that affect useability in clinical settings. The aim of this study was to compare the accuracy, precision, feasibility, reliability and accessibility of three imaging systems. MATERIALS AND METHODS: We compared the Vectra-H1, LifeViz-Micro and Cherry-Imaging systems. A total of 58 cNFs from 13 participants with NF1 were selected for imaging and analysis. The primary endpoint was accuracy as measured by comparison of measurements between imaging systems. Secondary endpoints included reliability between two operators, precision as measured with the average coefficient of variation, feasibility as determined by time to capture and analyse an image and accessibility as determined by cost. RESULTS: There was no significant difference in accuracy between the three devices for length or surface area measurements (p > 0.05), and reliability and precision were similar. Volume measurements demonstrated the most variability compared to other measurements; LifeViz-Micro demonstrated the least measurement variability for surface area and image capture and analysis were fastest with LifeViz-Micro. LifeViz-Micro was better for imaging smaller number of cNFs (1-3), Vectra-H1 better for larger areas and Cherry for uneven surfaces. CONCLUSIONS: All systems demonstrated excellent reliability but possess distinct advantages and limitations. Surface area is the most consistent and reliable parameter for measuring cNF size in clinical trials.
Asunto(s)
Imagenología Tridimensional , Neurofibromatosis 1 , Neoplasias Cutáneas , Humanos , Neurofibromatosis 1/diagnóstico por imagen , Neurofibromatosis 1/patología , Neurofibromatosis 1/complicaciones , Reproducibilidad de los Resultados , Imagenología Tridimensional/métodos , Femenino , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Masculino , Adulto , Neurofibroma/diagnóstico por imagen , Neurofibroma/patología , Adulto Joven , Diseño de Equipo , Adolescente , Sensibilidad y Especificidad , Estudios de Factibilidad , Persona de Mediana Edad , Análisis de Falla de Equipo , Dermoscopía/métodos , Dermoscopía/instrumentaciónRESUMEN
Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, is caused by mutations in the NF1 gene, which encodes the GTPase-activating protein neurofibromin. The pathogenesis of the tumor progression of benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. Here, we found that interferon-induced transmembrane protein 1 (IFITM1) was downregulated in MPNST tissues compared to those in PN tissues from patients with NF1. Overexpression of IFITM1 in NF1-associated MPNST cells resulted in a significant decrease in Ras activation (GTP-Ras) and downstream extracellular regulatory kinase 1/2 (ERK1/2) phosphorylation, whereas downregulation of IFITM1 via treatment with small interfering RNA in normal Schwann cells had the opposite result, indicating that expression levels of IFITM1 are closely associated with tumor progression in NF1. Treatment of MPNST cells with interferon-gamma (IFN-γ) significantly augmented the expression of IFITM1, thereby leading to a decrease in Ras and ERK1/2 activation. Despite the small number of patient samples, these findings may potentially provide a new target for chemotherapy in patients with NF1-associated MPNSTs. In xenograft mice injected with MPNST cells, IFN-γ treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-γ is a good candidate for the therapeutic treatment of MPNSTs in NF1.
Asunto(s)
Antígenos de Diferenciación , Neoplasias de la Vaina del Nervio , Neurofibromatosis 1 , Humanos , Animales , Neurofibromatosis 1/metabolismo , Neurofibromatosis 1/genética , Neurofibromatosis 1/patología , Neurofibromatosis 1/complicaciones , Ratones , Neoplasias de la Vaina del Nervio/metabolismo , Neoplasias de la Vaina del Nervio/genética , Neoplasias de la Vaina del Nervio/patología , Línea Celular Tumoral , Antígenos de Diferenciación/metabolismo , Antígenos de Diferenciación/genética , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Masculino , Interferón gamma/metabolismo , Sistema de Señalización de MAP Quinasas , Proteínas ras/metabolismo , Proteínas ras/genética , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , AdultoRESUMEN
Neurofibromatosis type 1 (OMIM 162200) affects ~ 1 in 3,000 individuals worldwide and is one of the most common monogenetic neurogenetic disorders that impacts brain function. The disorder affects various organ systems, including the central nervous system, resulting in a spectrum of clinical manifestations. Significant progress has been made in understanding the disorder's pathophysiology, yet gaps persist in understanding how the complex signaling and systemic interactions affect the disorder. Two features of the disorder are alterations in neuronal function and metabolism, and emerging evidence suggests a potential relationship between them. This review summarizes neurofibromatosis type 1 features and recent research findings on disease mechanisms, with an emphasis on neuronal and metabolic features.
Asunto(s)
Neurofibromatosis 1 , Neuronas , Neurofibromatosis 1/metabolismo , Neurofibromatosis 1/fisiopatología , Neurofibromatosis 1/complicaciones , Humanos , Neuronas/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatología , AnimalesRESUMEN
Trametinib, an MEK inhibitor, may offer a new therapeutic option for patients with NF1-related GIST.
Asunto(s)
Tumores del Estroma Gastrointestinal , Neurofibromatosis 1 , Piridonas , Pirimidinonas , Humanos , Piridonas/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Pirimidinonas/uso terapéutico , Neurofibromatosis 1/tratamiento farmacológico , Neurofibromatosis 1/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Hearing loss has not been thoroughly investigated as a comorbidity in larger cohorts with neurofibromatosis type 1 (NF1). METHODS: Available audiometric data were reviewed from patients with NF1 seen at a tertiary pediatric hospital to assess prevalence and risk factors for hearing loss. RESULTS: Of 1172 patients with NF1 seen between 2010 and 2022, 90 had available audiometric data and 48 of 90 patients (53%) had one or more audiogram revealing hearing loss. Those not referred to audiology were presumed to have normal hearing, resulting in a conservative hearing loss estimate of 4% for children and young adults with NF1. Of 90 patients with audiograms, 29 (32%) had conductive loss (CHL), 15 (17%) had sensorineural loss (SNHL), and 3 (3%) had mixed hearing loss. Hearing loss type was undetermined for one patient. For children with CHL, six had permanent CHL secondary to plexiform neurofibroma, 19 CHL were transient due to active middle ear dysfunction, and four CHL cases were indeterminate in etiology. For three children with SNHL or mixed hearing loss, etiology included history of ototoxic chemotherapy and/or family history of SNHL. In the 16 patients with SNHL or mixed hearing loss with more than one audiogram over time, progressive hearing decline was noted in eight of 16, and 26 of 178 hearing thresholds (15%) progressed. CONCLUSIONS: Our findings suggest that audiometric evaluations should be considered for at least a subset of children with NF1, given the higher-than-expected rate of hearing loss in patients with NF1 compared with the general population.
Asunto(s)
Pérdida Auditiva , Hospitales Pediátricos , Neurofibromatosis 1 , Humanos , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/epidemiología , Niño , Masculino , Femenino , Adolescente , Incidencia , Pérdida Auditiva/epidemiología , Pérdida Auditiva/etiología , Preescolar , Adulto Joven , Centros de Atención Terciaria , Atención Terciaria de Salud , Adulto , Audiometría , Estudios Retrospectivos , Comorbilidad , LactanteRESUMEN
Individuals with the genetic disorder neurofibromatosis type 1 (NF1) are typically diagnosed in a medical hospital setting strongly relying on the presence of well-defined physical symptoms such as neurofibromas or pigmentary spots (known as café-au-lait spots). In mental health care settings, however, aside from a few highly specialized centres, the diagnosis and treatment of individuals with NF1 receives little attention, while the need for psychological treatment is increasingly identified, both in clinical practice and in the scientific literature. Occasional referrals of individuals with NF1 to the mental health services are often only targeted at psychological assessment. Subsequent treatment, however, is usually lacking. We describe two individuals with NF1 for whom by means of specialized clinical neuropsychological assessment, participation in a tailored dialectical behavior therapy (DBT) skills training was indicated. We exposit how they were able to develop their skills and how they themselves and their significant others experienced the treatment.
Asunto(s)
Neurofibromatosis 1 , Humanos , Neurofibromatosis 1/terapia , Neurofibromatosis 1/psicología , Neurofibromatosis 1/complicaciones , Regulación Emocional , Adulto , Femenino , Resultado del Tratamiento , Masculino , Terapia ConductistaRESUMEN
BACKGROUNDS: Iris nodules are frequently noted as clinical manifestations of neurofibromatosis type 1 but the other intraocular manifestations are rare. The purpose of this study is to present a patient with a phthisic eye who underwent enucleation for a cosmetic reason after 15-year follow-up and also to review 14 patients with enucleation described in the literature. CASE PRESENTATION: A 17-year-old man with neurofibromatosis type 1 from infancy underwent the enucleation of phthisic left eye and also had the resection of eyelid subcutaneous mass lesions on the left side for a cosmetic reason. He had undergone four-time preceding surgeries for eyelid and orbital mass reduction on the left side in childhood and had developed total retinal detachment 10 years previously. Pathologically, the enucleated eye showed massive retinal gliosis positive for both S-100 and glial fibrillary acidic protein (GFAP) in the area with involvement of the detached retinal neuronal layer, together with a more fibrotic lesion along the choroid which were, in contrast, negative for both S-100 and GFAP. The choroid, ciliary body, and iris did not show apparent neurofibroma while episcleral neurofibroma was present. LITERATURE REVIEW: In review of enucleated eyes of 14 patients in the literature, buphthalmic eyes with early-onset glaucoma on the unilateral side was clinically diagnosed in 9 patients who frequently showed varying extent of hemifacial neurofibromatosis which involved the eyelid and orbit on the same side. Pathologically, neurofibromas in varying extent were found in the choroid of 12 patients. One patient showed choroidal malignant melanoma on the left side and fusiform enlargement of the optic nerve on the right side suspected of optic nerve glioma. The phthisic eye in another patient showed massive retinal gliosis similar to the present patient. CONCLUSIONS: In summary of the 15 patients with neurofibromatosis type 1, including the present patient, buphthalmic or phthisic eyes with no vision were enucleated for cosmetic reasons and showed choroidal neurofibroma in most patients and massive retinal gliosis in two patients including the present patient.
Asunto(s)
Enucleación del Ojo , Neurofibromatosis 1 , Humanos , Masculino , Adolescente , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/diagnóstico , Neurofibromatosis 1/patología , Estudios de SeguimientoRESUMEN
The neurofibromatosis type 1 (NF1) RASopathy is associated with persistent fibrotic nonunions (pseudarthrosis) in human and mouse skeletal tissue. Here, we performed spatial transcriptomics to define the molecular signatures occurring during normal endochondral healing following fracture in mice. Within the control fracture callus, we observed spatially restricted activation of morphogenetic pathways, such as TGF-ß, WNT, and BMP. To investigate the molecular mechanisms contributing to Nf1-deficient delayed fracture healing, we performed spatial transcriptomic analysis on a Postn-cre;Nf1fl/- (Nf1Postn) fracture callus. Transcriptional analyses, subsequently confirmed through phospho-SMAD1/5/8 immunohistochemistry, demonstrated a lack of BMP pathway induction in Nf1Postn mice. To gain further insight into the human condition, we performed spatial transcriptomic analysis of fracture pseudarthrosis tissue from a patient with NF1. Analyses detected increased MAPK signaling at the fibrocartilaginous-osseus junction. Similar to that in the Nf1Postn fracture, BMP pathway activation was absent within the pseudarthrosis tissue. Our results demonstrate the feasibility of delineating the molecular and tissue-specific heterogeneity inherent in complex regenerative processes, such as fracture healing, and reconstructing phase transitions representing endochondral bone formation in vivo. Furthermore, our results provide in situ molecular evidence of impaired BMP signaling underlying NF1 pseudarthrosis, potentially informing the clinical relevance of off-label BMP2 as a therapeutic intervention.
Asunto(s)
Proteínas Morfogenéticas Óseas , Curación de Fractura , Neurofibromatosis 1 , Seudoartrosis , Transducción de Señal , Transcriptoma , Animales , Seudoartrosis/metabolismo , Seudoartrosis/genética , Ratones , Humanos , Proteínas Morfogenéticas Óseas/metabolismo , Proteínas Morfogenéticas Óseas/genética , Neurofibromatosis 1/genética , Neurofibromatosis 1/metabolismo , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/patología , Curación de Fractura/genética , Fracturas Óseas/metabolismo , Fracturas Óseas/genética , Modelos Animales de Enfermedad , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Perfilación de la Expresión GénicaRESUMEN
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.
Asunto(s)
Hemoperitoneo , Neoplasias Hepáticas , Neoplasias de la Vaina del Nervio , Humanos , Masculino , Hemoperitoneo/etiología , Neoplasias de la Vaina del Nervio/complicaciones , Neoplasias de la Vaina del Nervio/diagnóstico , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/secundario , Adulto , Neurofibromatosis 1/complicacionesRESUMEN
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.
Asunto(s)
Neurofibromatosis 1 , Humanos , Neurofibromatosis 1/complicaciones , Femenino , Anciano , Arteria Carótida Interna/diagnóstico por imagen , Imagen por Resonancia Magnética , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/complicaciones , Aneurisma/diagnóstico por imagen , Aneurisma/etiología , Aneurisma/complicacionesRESUMEN
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.
Asunto(s)
Granuloma de Células Gigantes , Imagen por Resonancia Magnética , Neoplasias Mandibulares , Neurofibroma , Neurofibromatosis 1 , Humanos , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/diagnóstico por imagen , Neurofibromatosis 1/patología , Granuloma de Células Gigantes/diagnóstico por imagen , Granuloma de Células Gigantes/patología , Neoplasias Mandibulares/diagnóstico por imagen , Neoplasias Mandibulares/patología , Neoplasias Mandibulares/cirugía , Neurofibroma/diagnóstico por imagen , Neurofibroma/patología , Neurofibroma/cirugía , Estudios de Seguimiento , Enfermedades Mandibulares/diagnóstico por imagen , Enfermedades Mandibulares/patología , Enfermedades Mandibulares/cirugía , Femenino , MasculinoRESUMEN
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.
Asunto(s)
Neurofibromatosis 1 , Seudoartrosis , Tibia , Humanos , Seudoartrosis/congénito , Seudoartrosis/cirugía , Neurofibromatosis 1/complicaciones , Tibia/cirugía , Tibia/anomalías , Masculino , Femenino , Lactante , Estudios de Seguimiento , Preescolar , Fracturas de la Tibia/cirugía , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Ratones Noqueados , Neurofibromina 1 , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Seudoartrosis , Células de Schwann , Animales , Femenino , Humanos , Masculino , Ratones , Diferenciación Celular/efectos de los fármacos , Fibrosis , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Neurofibromatosis 1/patología , Neurofibromatosis 1/metabolismo , Neurofibromatosis 1/complicaciones , Neurofibromina 1/metabolismo , Neurofibromina 1/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/antagonistas & inhibidores , Seudoartrosis/patología , Seudoartrosis/metabolismo , Seudoartrosis/congénito , Células de Schwann/metabolismo , Células de Schwann/efectos de los fármacos , Células de Schwann/patología , Células Madre/metabolismo , Células Madre/efectos de los fármacos , Tibia/patologíaRESUMEN
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.
Asunto(s)
Peroné , Colgajos Tisulares Libres , Seudoartrosis , Humanos , Seudoartrosis/cirugía , Seudoartrosis/congénito , Seudoartrosis/etiología , Peroné/trasplante , Niño , Colgajos Tisulares Libres/trasplante , Masculino , Femenino , Trasplante Óseo/métodos , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/cirugía , Lactante , Radio (Anatomía)/cirugía , Radio (Anatomía)/trasplante , Radio (Anatomía)/anomalías , Antebrazo/cirugía , Cúbito/cirugíaRESUMEN
Background: To investigate whether there is a difference in mean diffusivity (MD) and fractional anisotropy (FA) values in the auditory pathways of neurofibromatosis type 1 patients with and without focal areas of abnormal signal intensity (FASI) compared to healthy controls by using diffusion tensor imaging (DTI). Methods: Patients were classified as group 1 with focal areas of abnormal signal intensity in the brainstem, group 2 without focal areas of abnormal signal intensity, and healthy control group 3 according to the MRI findings. Mean diffusivity and fractional anisotropy values of lateral lemniscus, inferior colliculus, corpus geniculatum mediale, Heschl gyrus, and brainstem were compared between groups. The correlation between mean diffusivity and fractional anisotropy values of auditory pathways and age was investigated. Results: There was a significant difference between group 1 and group 2 in terms of mean diffusivity and fractional anisotropy values at lateral lemniscus, inferior colliculus, corpus geniculatum mediale, and Heschl gyrus. Increased mean diffusivity and decreased fractional anisotropy values at brainstem were found in group 1. There was a significant difference between group 1 and group 3 in terms of mean diffusivity values at all auditory pathways. Fractional anisotropy values obtained from lateral lemniscus, inferior colliculus, and Heschl gyrus decreased in group 1 compared with group 3. There was a negative correlation between mean diffusivity values and positive correlation between fractional anisotropy values at lateral lemniscus, inferior colliculus, Heschl gyrus, and age. Conclusions: Our diffusion tensor imaging findings show that the neuronal integrity of the auditory pathways is affected in neurofibromatosis type 1 patients with brainstem focal areas of abnormal signal intensity. We think that the disappearance of brainstem focal areas of abnormal signal intensity associated with myelin repair and the regression of diffusion tensor imaging changes in the auditory pathways occur simultaneously with advancing age in patients with neurofibromatosis type 1.
Asunto(s)
Vías Auditivas , Tronco Encefálico , Imagen de Difusión Tensora , Neurofibromatosis 1 , Humanos , Neurofibromatosis 1/diagnóstico por imagen , Neurofibromatosis 1/complicaciones , Masculino , Femenino , Niño , Imagen de Difusión Tensora/métodos , Vías Auditivas/diagnóstico por imagen , Vías Auditivas/patología , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/patología , Anisotropía , Adolescente , PreescolarRESUMEN
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.
Asunto(s)
Angiografía con Fluoresceína , Imagen Multimodal , Neurofibromatosis 1 , Tomografía de Coherencia Óptica , Humanos , Neurofibromatosis 1/diagnóstico , Neurofibromatosis 1/complicaciones , Femenino , Masculino , Tomografía de Coherencia Óptica/métodos , Estudios Retrospectivos , Adulto , Angiografía con Fluoresceína/métodos , Adolescente , Persona de Mediana Edad , Adulto Joven , Niño , Coroides/patología , Coroides/diagnóstico por imagen , Enfermedades de la Coroides/diagnóstico , Fondo de OjoRESUMEN
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.