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Hearing loss has not been thoroughly investigated as a comorbidity in larger cohorts with neurofibromatosis type 1 (NF1). Available audiometric data were reviewed from patients with NF1 seen at a tertiary pediatric hospital to assess prevalence and risk factors for hearing loss. 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. 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. [ABSTRACT FROM AUTHOR]

Approximately 40% of pheochromocytoma and paraganglioma (PPGL) cases are familial, typically presenting earlier with more complex symptoms. This paper synthesizes literature and guidelines to inform on clinical characteristics and perioperative care for PPGL. Pheochromocytoma in von Hippel-Lindau (VHL) disease exhibits heightened secretion activity without significant perioperative hemodynamic changes. Tumors in multiple endocrine neoplasia type 2 (MEN2) have a stronger endocrine function, which may induce hemodynamic fluctuations during surgery. Therefore, pheochromocytoma screening is essential at all stages of MEN2. Neurofibromatosis type 1 (NF1) often presents multisystem lesions and can result in difficult airway. Pheochromocytoma should be evaluated when NF1 patients present hypertension. Pheochromocytoma and paraganglioma type 5 may present multiple lesions of pheochromocytoma or paraganglioma. In summary, hereditary PPGLs may present with severe lesions in other systems, beyond tumor function. A multi-disciplinary team (MDT) approach is often invaluable in perioperative management. [ABSTRACT FROM AUTHOR]

Sleep disturbances are often found in people with monogenic intellectual disability syndromes (MIDS), representing an interesting target for investigation as these disturbances are likely to contribute to other behavioral phenotypes. Animal models recapitulate many features of MIDS, including sleep and circadian phenotypes, which allows dissection of the mechanisms that lead to sleep disruption. Recent studies suggest links between sleep/circadian rhythm disruptions and metabolic deficits, which are supported by animal models of MIDS. A mechanistic understanding of these links could suggest noninvasive treatments, including dietary interventions, for MIDS. Beneficial effects of current therapies that improve behavior, including sleep, in MIDS may be mediated in part by metabolic mechanisms. Intellectual disability is defined as limitations in cognitive and adaptive behavior that often arise during development. Disordered sleep is common in intellectual disability and, given the importance of sleep for cognitive function, it may contribute to other behavioral phenotypes. Animal models of intellectual disability, in particular of monogenic intellectual disability syndromes (MIDS), recapitulate many disease phenotypes and have been invaluable for linking some of these phenotypes to specific molecular pathways. An emerging feature of MIDS, in both animal models and humans, is the prevalence of metabolic abnormalities, which could be relevant for behavior. Focusing on specific MIDS that have been molecularly characterized, we review sleep, circadian, and metabolic phenotypes in animal models and humans and propose that altered metabolic state contributes to the abnormal sleep/circadian phenotypes in MIDS. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. (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. 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. • NF1 children show working-memory impairment as primary ADHD children • NF1+adhd and primary ADHD children show similar attentional and executive profiles • NF1+adhd children differ from primary ADHD by being slower on visuomotor tests • Unidentified bright objects in NF1 do not correlate with cognitive performance [ABSTRACT FROM AUTHOR]

The treatment of symptomatic pseudarthrosis via posterior-only approaches in the setting of neurofibromatosis 1 (NF1) is challenging due to dural ectasias, resulting in erosion of the posterior elements. The purpose of this report is to illustrate a minimally invasive method for performing anterior thoracic fusion for pseudarthrosis in a patient with NF1-associated scoliosis and dysplastic posterior elements. To the best of our knowledge, this is the first documented case of using video-assisted thoracoscopic lateral interbody fusion to treat pseudarthrosis for NF1-associated spinal deformity. The patient underwent video-assisted thoracoscopic anterior spinal fusion via a direct lateral interbody approach with interbody cage placement at T10-T11 and T11-T12, followed by revision of his posterior spinal fusion and instrumentation. The patient had an uneventful postoperative course. At 6 months of follow-up, the patient had complete resolution of his preoperative symptoms and had returned to full-time work with no complaints. At 3 years postoperatively, the patient reported being satisfied with the operation and had continued to work full-time without restrictions. To the best of our knowledge, this is the first report of pseudarthrosis in the setting of NF1-associated scoliosis treated via minimally invasive anterior thoracic fusion facilitated by video-assisted thoracoscopic surgery. This is a powerful technique that allows for safe access for anterior thoracic fusion in the setting of dysplastic posterior anatomy and poor posterior bone stock. [ABSTRACT FROM AUTHOR]

To compare the diagnostic test of integrated 2-[18F]-fluoro-2-deoxy- d- glucose positron-emission tomography/computed tomography (FDG PET/CT) with that of magnetic resonance imaging (MRI) for the differentiation of malignant peripheral nerve sheath tumours (MPNSTs) in neurofibromatosis type 1 (NF1) patients. A systematic search was performed in PubMed and EMBASE (last updated in 30 November 2022). Studies investigating the performance of FDG PET/CT and MRI for differentiation of MPNSTs were eligible for inclusion. Only studies reporting a direct comparison between these imaging methods were considered to establish precise summary estimates in the same setting of patients. The pooled estimate of sensitivity of FDG PET/CT was 0.99 and a pooled specificity of 0.53. The pooled estimate of sensitivity of MRI was 0.85 and a pooled specificity of 0.85. Analysis of the available studies indicated that FDG PET/CT and MRI had similar diagnostic performances for differentiation of MPNSTs in patients with NF1; however, either technique can be a complement to the other rather than being used singly. • F-18 FDG PET/CT and MRI were compared for differentiation of MPNSTs. • Both techniques showed similar accuracies for differentiation of MPNSTs. • Each modality can be a complement to other rather than being used singly. [ABSTRACT FROM AUTHOR]

For unilateral Dodge Class Ⅰ optic pathway glioma (OPG-uDCⅠ) without neurofibromatosis type 1, unilateral isolated optic nerve gliomas before the optic chiasm have been confirmed to possibly cause visual deterioration and poor prognosis. For this type of highly selective localized tumor, we explored surgery as the only treatment method. This article retrospectively analyzed and summarized the clinical data of this case series, with the aim of exploring the main technical details and clinical prognosis. Included were patients with OPG-uDCⅠ without neurofibromatosis type 1 and experiencing vision loss on the affected side. The fronto-orbital approach was used, which was mainly divided into 3 parts: intraorbital, optic canal, and intracranial. All patients underwent prechiasmatic resection without any adjuvant treatments. The follow-up period was 3 months after surgery, and magnetic resonance imaging and contralateral visual acuity were reviewed annually after surgery. All OPG-uDCⅠ cases were completely removed without any adjuvant treatments, and there was no recurrence during the follow-up period. Pathological results showed that, except for 1 adult patient with pilomyxoid astrocytoma (World Health Organization grade Ⅱ), the others all had pilocytic astrocytoma (World Health Organization grade Ⅰ). Five patients experienced transient ptosis, and all recovered 3 months after surgery. For OPG-uDCⅠ without neurofibromatosis type 1, radical prechiasmatic resection of the tumor is possible, without the need for postoperative radiotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disease and is caused by mutations in the NF1 gene. The most common clinical features of NF1 are pigmentary abnormalities such as café-au-lait spots and inguinal or axillary freckling, cutaneous and plexiform neurofibromas, hamartomas of the iris, optic gliomas, and bone lesions. The aim of this retrospective study was to define the clinical and molecular characteristics of a pediatric sample of NF1, as well as the mutational spectrum and genotype-phenotype correlation. The study included 40 children with clinically suspected NF1. The patients were screened for NF1 mutations by DNA-based sequencing. In addition, all the patients were studied by multiplex ligation-dependent probe amplification (MLPA) to identify any duplications or deletions in NF1. The demographic, clinical, and genetic features of the children were characterized. A total of 40 children with NF1 were included. Of those, 28 were female and 12 were male. The mean age was 8.91 years. An NF1 variant was discovered in 28 of 40 patients (70%). Among these mutations, intronic mutations were the most frequently detected mutations; 15 of these variants had not been previously reported. Only one patient had a whole NF1 gene deletion. This study expands the spectrum of mutations in the NF1 gene. This study also showed that genetic screening using both next-generation sequencing and MLPA had a positive effect on diagnosis and genetic counseling in patients with suspected NF1. [ABSTRACT FROM AUTHOR]

Neurofibromas are frequently present in the skin, but are uncommon in the oral and maxillofacial region. There are three histological variants of neurofibroma: localized, diffuse, and plexiform. The plexiform histological variant of neurofibroma is the least common and is a rare occurrence in the oral cavity. Furthermore, plexiform neurofibroma is usually pathognomonic of neurofibromatosis type 1. A case of solitary plexiform neurofibroma of the tongue with no evidence of neurofibromatosis in a 50-year-old female Chinese patient is reported here. The lesion presented as a single, large, well-circumscribed rounded mass in the left hemi-tongue. The tumour was completely excised. No recurrence was observed at the 6-month follow-up. [ABSTRACT FROM AUTHOR]

Intrascrotal neurofibromas are extensive tumors that grow from peripheral nerves within the scrotum and are exceedingly rare among the benign extratesticular tumors. Though the risk is low, potential for malignancy and patient discomfort make diagnosis and surgical evaluation imperative. Pediatric neurofibromas are typically only associated with neurofibromatosis type 1. However, herein, we describe a rare case of a benign, intrascrotal plexiform neurofibroma in a 10-year-old male who lacks any stigmata associated with this genetic disorder. Diagnostic and surgical challenges as well as histopathological findings are discussed. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF-1) is an autosomal dominant condition characterized by café-au-lait spots, neurofibromas, and multisystem involvement, including vasculopathy that may lead to ischemic or hemorrhagic events. Cases of vascular occlusions involving the retinal or ophthalmic circulation have also been described. The majority of cases with reported outcomes describe poor visual acuity following resolution. We report a case of retinal and ophthalmic artery occlusion resulting in ocular ischemic syndrome in a patient with NF1 who had remarkable improvement in retinal perfusion and visual acuity following high-dose corticosteroid treatment. [ABSTRACT FROM AUTHOR]

This study aims to (1) investigate health-related quality of life (HRQoL) in children with Neurofibromatosis Type 1 (NF1) using the Pediatric Quality of Life inventory (PedsQL) and the Child Health Questionnaire (CHQ); and (2) compare the psychometric properties and content of these questionnaires in NF1 patients. PedsQL and CHQ proxy-reports were administered to parents/caregivers of 160 patients with NF1 aged 5–12 years. HRQoL scores were compared with Dutch population norms using independent t-tests. Psychometric properties (feasibility and reliability) were assessed by floor/ceiling effects and Cronbach's alpha coefficient. A principal component analysis (PCA) with varimax rotation was performed to identify the data's internal structure. By content mapping, we identified unique constructs of each questionnaire. Proxy-reported HRQoL was significantly lower on all PedsQL subscales for children aged 5–7 years, and on 4/6 subscales for children aged 8–12 years compared to norms. Significantly lower HRQoL was reported on 6/14 CHQ subscales (children 5–7 years) and 9/14 subscales (children 8–12 years). The PedsQL showed slightly better feasibility and reliability. The PCA identified two components, representing psychosocial and physical aspects of HRQoL, explaining 63% of total variance. Both questionnaires showed relevant loadings on both components. The CHQ subscales concerning parents and family were considered unique contributions. Proxy-reported HRQoL of children with NF1 is significantly lower compared to norms on multiple domains. Both questionnaires adequately measure HRQoL in children with NF1. However, the PedsQL has slightly better psychometric properties, while the CHQ covers a unique dimension of HRQoL associated with disease impact on parents and family. • PedsQL and CHQ scores were compared to population norms. • Proxy-reported Quality of Life of children with Neurofibromatosis Type 1 is reduced. • Principal component analysis: questionnaires adequately measure Quality of Life. • CHQ covers a unique dimension of Quality of Life: disease impact on family. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a genetic neurocutaneous disorder commonly associated with motor and cognitive symptoms that greatly impact quality of life. Transcranial magnetic stimulation (TMS) can quantify motor cortex physiology, reflecting the basis for impaired motor function as well as, possibly, clues for mechanisms of effective treatment. We hypothesized that children with NF1 have impaired motor function and altered motor cortex physiology compared to typically developing (TD) control children and children with attention-deficit/hyperactivity disorder (ADHD). Children aged 8-17 years with NF1 (n = 21) were compared to children aged 8-12 years with ADHD (n = 59) and TD controls (n = 88). Motor development was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS) scale. The balance of inhibition and excitation in motor cortex was assessed using the TMS measures short-interval cortical inhibition (SICI) and intracortical facilitation (ICF). Measures were compared by diagnosis and tested using bivariate correlations and regression for association with clinical characteristics. In NF1, ADHD severity scores were intermediate between the ADHD and TD cohorts, but total PANESS scores were markedly elevated (worse) compared to both (P < 0.001). Motor cortex ICF (excitatory) was significantly lower in NF1 than in TD and ADHD (P < 0.001), but SICI (inhibitory) did not differ. However, in NF1, better PANESS scores correlated with lower SICI ratios (more inhibition; ρ = 0.62, P = 0.003) and lower ICF ratios (less excitation; ρ = 0.38, P = 0.06). TMS-evoked SICI and ICF may reflect processes underlying abnormal motor function in children with NF1. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome that affects multiple organ systems resulting in widespread symptoms, including cognitive deficits. In addition to the criteria required for an NF1 diagnosis, approximately 70% of children with NF1 present with Unidentified Bright Objects (UBOs) or Focal Areas of Signal Intensity, which are hyperintense bright spots seen on T2-weighted magnetic resonance images and seen more prominently on FLAIR magnetic resonance images (Sabol et al., 2011). Current findings relating the presence/absence, quantities, sizes, and locations of these bright spots to cognitive abilities are mixed. To contribute to and hopefully disentangle some of these mixed findings, we explored potential relationships between metrics related to UBOs and cognitive abilities in a sample of 28 children and adolescents with NF1 (M=12.52 years; SD=3.18 years; 16 male). We used the Lesion Segmentation Tool (LST) to automatically detect and segment the UBOs. The LST was able to qualitatively and quantitatively reliably detect UBOs in images of children with NF1. Using these automatically detected and segmented lesions, we found that while controlling for age, biological sex, perceptual IQ, study, and scanner, "total UBO volume", defined as the sum of all the voxels representing all of the UBOs for each participant, helped explain differences in word reading, phonological awareness, and visuospatial skills. These findings contribute to the emerging NF1 literature and help parse the specific deficits that children with NF1 have, to then help improve the efficacy of reading interventions for children with NF1. • Children with Neurofibromatosis type 1 often present with Unidentified Bright Objects (UBOs). • The Lesion Segmentation Tool can be used to segment UBOs. • In previous literature, findings linking UBOs to cognition are inconsistent. • UBO volume relates to word reading, phonological awareness, visuospatial, and language skills. [ABSTRACT FROM AUTHOR]

Neurofibromatosis (NF) is an inherited neuroectodermal abnormality that primarily affects the growth of neural tissues, and Riccardi classified it into eight types. Segmental neurofibromatosis, which is a rare form of neurofibromatosis, is classified as type 5. We report a case for very unusual presentation of segmental NF with unilateral lisch nodules and uncommon sites involving the scalp. Moreover, we could find only one case report of segmental NF with lisch nodules in the literature and could not find any case report involving the scalp. [ABSTRACT FROM AUTHOR]

Since 1990's, the cognitive profile of children with a neurofibromatosis type 1 (NF1) has been refined by many different studies. Children with NF1 may exhibit a variety of cognitive dysfunctions. Memory difficulties have been reported, but the results are contradictory and, compared to other cognitive functions, memory has been less evaluated. The aim of this study was to investigate the memory profile in NF1 with a particular population, children with NF1 without attention deficit hyperactivity disorder (ADHD). Eighteen children with NF1 without ADHD and eighteen typically developing aged from 8 to 12.6 years were compared in terms of both their verbal and visual working memory, anterograde memory, and procedural perceptual-motor memory. We also assessed semantic and autobiographical memory. Our results indicate the existence of memory difficulties in children with NF1 without ADHD in verbal working and anterograde memory but not in terms of the visual domain. They also experienced difficulties recalling personal memories but these were improved by cueing. However, semantic memory and procedural perceptual-motor memory was preserved. These results highlight a difference between memory systems in children with NF1 without ADHD and the importance to assess the different memory systems, the nature of information and the processes in long-term memory in NF1 population. However, our results raise questions about the possible links between these difficulties and the executive functions. The specifics of memory profile in children with NF1 must be taken into consideration in these children's clinical follow-up, in order to understand their learning difficulties and to make adaptations to their care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Trigeminal schwannoma is an uncommon tumor in pediatric patients. Several surgical approaches have been described in the literature. The case of an 11-year-old boy with a giant dumbbell-shaped trigeminal schwannoma removed through a 2-stage approach was presented with an intraoperative video. Using PubMed and Scopus, the literature on trigeminal schwannoma in pediatric patients was searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search strategy yielded 312 titles, of which 13 were included in the review. Cases of trigeminal schwannoma were described, with a highly variable clinical presentation and anatomical arrangement in cranial fossae. Two-stage approaches were reported, although most studies described single-stage approaches. Common postoperative outcomes were a range of disturbances of cranial nerve V. The surgical approach varies based on the tumor conformation. However, a 2-stage pterional subtemporal and semisitting retrosigmoid approach is a safe, practical, and effective strategy for the removal of dumbbell-shaped trigeminal schwannoma in a pediatric patient. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate functional and aesthetic outcomes in patients undergoing deep-plane facelifts for the management of extensive hemifacial tumors. The retrospective study included patients who had been diagnosed with benign tumors with extensive hemifacial involvement. All patients underwent tumor debulking via a dual-plane facelift approach, assisted by an ICG camera to visualize the facial nerve structures. To manage the laxity of the skin envelope, the deep-plane face-lift was performed by suspending the superficial musculoaponeurotic layer, followed by suture fixation to the parotid-masseteric fascia. Clinical outcomes, including complications, House–Brackmann grading for facial paralysis, and tumor recurrence rate were investigated. Quantitative facial nerve examination was carried out using FACE-gram software (Massachusetts Eye and Ear Infirmary, Boston, USA) to measure mouth corner movement at rest and when smiling. Using preoperative and 1-year postoperative 3D photographs, facial symmetry was assessed using comparisons of facial volume and the root-mean-square deviation (RMSD) value to represent the height difference between each hemiface. In total, 25 patients who met the inclusion criteria were recruited to the study. Regarding the types of tumor, 13 of the 25 patients were diagnosed with vascular lesions and the other 12 with neurofibromatosis plexiform. Following surgery, two patients showed temporary palsy of the buccal branches — grade II on the House–Brackmann scale — but neural functioning was eventually restored during the follow-up period. During resting, the mouth corner excursion ratio was significantly improved, from 1.11 ± 0.19 preoperatively to 1.02 ± 0.08 postoperatively (p = 0.022). The facial volume ratio was significantly improved in the lower face, from 1.57 ± 0.66 preoperatively to 1.19 ± 0.18 postoperatively (p = 0.008). The RMSD was significantly decreased, from 4.56 ± 2.35 mm preoperatively to 2.08 ± 0.99 mm postoperatively (p < 0.001), representing a decrease in facial asymmetry. Within the limitations of the study, it seems that the ICG camera-assisted deep-plane facelift technique allows preservation of facial nerve functioning and enhances facial symmetry when managing extensive hemifacial tumors. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a phenotypically heterogenous multisystem cancer predisposition syndrome manifesting in childhood and adolescents. Central nervous system (CNS) manifestations include structural, neurodevelopmental, and neoplastic disease. We aimed to (1) characterize the spectrum of CNS manifestations of NF1 in a paediatric population, (2) explore radiological features in the CNS by image analyses, and (3) correlate genotype with phenotypic expression for those with a genetic diagnosis. We performed a database search in the hospital information system covering the period between January 2017 and December 2020. We evaluated the phenotype by retrospective chart review and imaging analysis. 59 patients were diagnosed with NF1 [median age 10.6 years (range, 1.1–22.6); 31 female] at last follow-up, pathogenic NF1 variants were identified in 26/29. 49/59 patients presented with neurological manifestations including 28 with structural and neurodevelopmental findings, 16 with neurodevelopmental, and 5 with structural findings only. Focal areas of signal intensity (FASI) were identified in 29/39, cerebrovascular anomalies in 4/39. Neurodevelopmental delay was reported in 27/59 patients, learning difficulties in 19/59. Optic pathway gliomas (OPG) were diagnosed in 18/59 patients, 13/59 had low-grade gliomas outside the visual pathways. 12 patients received chemotherapy. Beside the established NF1 microdeletion, neither genotype nor FASI were associated with the neurological phenotype. NF1 was associated with a spectrum of CNS manifestations in at least 83.0% of patients. Regular neuropsychological assessment complementing frequent clinical and ophthalmologic testing for OPG is necessary in the care of each child with NF1. • Neurological manifestations were present in 83.0% of children/adolescents with NF1. • Cerebrovascular anomalies were identified in 6.8% of patients, 3.4% sustained a stroke. • Optic pathway and other low-grade gliomas were diagnosed in 30.5% and 22.0% patients. • Neither genotype nor FASI were associated with the neurological phenotype. • Regular neuropsychological and ophthalmological assessments are indicated. [ABSTRACT FROM AUTHOR]

A retrospective observational study. To introduce a novel hybrid technique using segmentation correction (SC) and to compare it with traditional correction (TC) in treating dystrophic scoliosis secondary to neurofibromatosis type 1 (NF1-S) lacking pedicles in the apical area. We reviewed the NF1-S cases lacking pedicles diagnosed in our hospital between January 2015 and December 2019. Patients were divided into the SC and TC groups and were followed up for at least 2 years. The degree of deformities, correction rate, and vertebral rotatory subluxation (RS) were assessed before the operation, post-traction, post operation, and during follow-up visits. A total of 27 patients were included in the SC group and 21 in the TC group. There was no significant difference in the 2 groups before the surgery regarding age, height, weight, degree of deformities, and spinal flexibility. The correction rate of patients in the SC group was higher (57.7% ± 17.3% vs. 40.9% ± 19.0%, P = 0.002) than in the TC group. During the 2-year follow-up, the loss of Cobb angles of the SC group in both coronal and sagittal planes were lower than those of the TC group (coronal plane, 1.2° ± 1.1° vs. 2.0° ± 1.4°, P = 0.039; sagittal plane, 0.9° ± 0.5° vs. 1.7° ± 1.0°, P = 0.002). The SC technique showed better deformity correction than TC, suggesting that SC may be an alternative method for treating NF1-S patients lacking pedicles in the apical area. [ABSTRACT FROM AUTHOR]

High cervical intradural extramedullary tumors are uncommon. Their relationship to surrounding neural structures and vertebral arteries makes surgical excision challenging. No previous studies have compared high cervical to subaxial cervical intradural extramedullary spinal tumors to elucidate their unique characteristics and surgical outcomes. We performed a retrospective study in which patients who underwent excision of a cervical intradural extramedullary tumor were divided into a high cervical group and a subaxial cervical group. Variables included sex, age, Charlson Comorbidity Index, volume, laterality, preoperative weakness, use of neuromonitoring and drains, instrumented fusion, complications, length of stay, histology, discharge location, recurrence, and duration of follow-up. Variables were compared between the 2 groups. Limb power and Nurick classification were charted preoperatively, at discharge, and at 6 months to plot their recovery trajectory. Eighty-four patients with a total of 90 tumors were enrolled, including 40 patients in the high cervical group and 44 patients in the subaxial spine group. More patients with neurofibromas (P = 0.011) and bilateral tumors (P = 0.044) were in the high cervical group. A greater prevalence of neurofibromatosis type 1 was significant for bilateral high cervical tumors (P = 0.033). More patients in the subaxial group had instrumented fusion (P = 0.045). More patients in the high cervical group had improvement in limb power (P = 0.025) and Nurick classification (P = 0.0001) postoperatively before discharge. By 6 months, both groups had similar recovery. No mortality was attributable to surgery in either group. High cervical intradural extramedullary spine tumors have more bilateral tumors associated with neurofibromatosis type 1. Despite the challenging anatomy, surgical resection is safe with good outcomes in this group. [ABSTRACT FROM AUTHOR]

Spinal lesions are a known manifestation of neurofibromatosis type 1 (NF1). The aim of this retrospective review was to analyze and report the prevalence of spinal lesions on imaging in a large NF1 center. The data were collected from a period of 62 months from a cohort of 514 patients. Data were collected from multidisciplinary team meeting reports that included radiologic reports of each patient investigating 20 distinct variables. The prevalence of each of these lesions was calculated, and any statistically significant associations were investigated using the χ2 test. Four-hundred forty-seven patients had classic NF1, and 67 patients had spinal NF1. Many of the patients had spinal abnormalities; 25.7% of these patients were found to have dural ectasia, whereas 44.9% of patients had a spinal deformity. A statistically significant association between dural ectasia and spinal neurofibromatosis was established (P < 0.05). An additional statically significant association was established between dural ectasia and spinal deformity (P < 0.00001). The patients with spinal nerve root tumors were identified, and it was found that 49.8% of patients possessed these tumors, whereas 56.3% of these tumors were intraspinal tumors. The most common region affected was the cervical spine, and the most common spinal level was C2. This high prevalence of spinal tumours in mobile areas of the spine is possibly the result of a combination of genetic predisposition and repeated microtraumas resulting in tumor formation. This is the largest reported study of spinal lesions in NF1 based on imaging and offers insights into the etiology and relationships between lesions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome caused by pathogenic variants in NF1 , which negatively regulates the RAS pathway. Knowledge of the genotype-phenotype correlation in this disease is an important tool for prognostic evaluation and early detection of malignant peripheral nerve sheath tumors (MPNST), present in approximately 10% of these patients. We present the case of a teenager with a left jaw MPNST and a previously unreported germline pathogenic variant on NF1. An 11-year-old female with a NF1 clinical diagnosis was referred to our hospital with a MPNST in an advanced state. A previously unreported NF1 pathogenic variant was obtained (GRCh37: NM_182493.2 c.3299C>G, p.Ser1100*). Despite great efforts from the surgical and medical teams, the tumor progression couldn't be halted, resulting in the patient's death. As MPNSTs are refractory to current treatment regimens, early diagnosis, and development of new therapies, such as MEK inhibitors, is necessary for reducing morbidity and mortality within NF1 patients. This increases the importance of a more widespread genetic testing strategy. The report of a novel NF1 pathogenic variant in a patient with maternally inherited neurofibromatosis type 1 and a MPNST increases the knowledge of the genotype-phenotype correlation in the disease. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the traditional 2-rod correction technique with the sectional correction technique in terms of radiographic results and clinical outcomes for patients with dystrophic scoliosis caused by neurofibromatosis type 1 (NF1). From May 2015 to April 2018, 53 patients with dystrophic scoliosis caused by NF1 underwent 1-stage posterior corrective surgery. Patients were separated into 2 groups based on technique: the sectional correction technique (SC group) and the traditional 2-rod technique (TT group). Before surgery and at the final follow-up, the demographic information, radiographic parameters, and clinical outcomes were compared between the groups using independent-sample t tests. The SC group consisted of 24 patients, while the TT group consisted of 29 patients. Patients in the SC group showed a higher coronal balance distance after the operation (8.3 ± 8.2 mm vs. 16.2 ± 8.8 mm, P = 0.002) and at the final follow-up (9.5 ± 9.3 mm vs. 19.3 ± 10.1 mm, P < 0.0001). At the last follow-up, the loss of correction in the SC group was 2.2 ± 0.9 and 2.1 ± 0.7 in the coronal and sagittal planes, respectively, and these values were significantly lower than those in the TT group (5.3 ± 1.6 in the coronal plane and 4.5 ± 1.9 in the sagittal plane, both P < 0.05). The SC group had better improvement based on appearance and satisfaction score at the final follow-up. The sectional correction technique using a concave domino connector can restore coronal imbalance and reduce the risk of implant failure. [ABSTRACT FROM AUTHOR]

Optic pathway and hypothalamic gliomas (OPHGs) are challenging to surgically remove owing to their anatomical relationship. We previously reported on surgical treatment outcomes over a 10-year time frame. The purpose of this study was to update the OPHG clinical outcomes for cases in which chemotherapy has become the primary treatment option. The role of surgery was also revisited. Patients with a diagnosis of OPHG who underwent treatment at Seoul National University Children's Hospital from February 1999 to July 2019 were included. A multidisciplinary approach was used to determine the patients' treatment plans. Chemotherapy was the first-line treatment for all patients. When symptoms of hydrocephalus existed, debulking surgery was performed to reopen the flow of cerebrospinal fluid. The study included 47 patients with OPHGs. The mean age was 6.9 years. Neurofibromatosis 1 was diagnosed in 3 patients. The extent of removal was none or biopsy in 13 (28%) cases, partial resection in 23 (49%) cases, and subtotal to gross total resection in 11 (23%) cases. In 32 (68%) patients, chemotherapy was first-line treatment. Ascites after ventriculoperitoneal shunt occurred in 3 cases, and 2 cases were successfully managed with debulking surgery. Treatment outcomes showed a 5-year overall survival rate of 97.7% and a 5-year progression-free survival rate of 47.7%. OPHG management using less invasive operations and chemotherapy as first-line treatment is feasible. Debulking surgery in patients with OPHGs may be considered in cases with cerebrospinal fluid pathway obstruction, progression despite chemotherapy or radiation, and refractory shunt-related ascites. [ABSTRACT FROM AUTHOR]

• Studying VEP plasticity might be a novel neurophysiological outcome measure associated with cognitive disability in NF1. • The NF1 group had a non-potentiated response to VEP induction. • The control group revealed a potentiated VEP response during continuous visual stimulation without delay. The inability to properly process visual information has been frequently associated with neurofibromatosis type 1 (NF1). Based on animal studies, the cause of cognitive disabilities in NF1 is hypothesized to arise from decreased synaptic plasticity. Visual cortical plasticity in humans can be investigated by studying visual evoked potentials (VEPs) in response to visual stimulation. VEP plasticity was assessed by measuring the increase of the peak amplitudes C1, P1, and N1 induced by 10-min modulation of checkerboard reversals in 22 adult NF1 patients and 30 controls. VEP signals were recorded pre-modulation, during modulation, and at 2, 7, 12, 17, 22, 27 min post-modulation. The P1 amplitude increased significantly comparing post-modulation to pre-modulation in the control group. This potentiation was not observed in the NF1 group. Visual cortical plasticity could be measured using VEPs in response to visual stimulation in the control group. Individuals with NF1 may have reduced visual cortical plasticity, as indicated by their non-potentiated response to VEP induction. These findings should be interpreted with caution due to high inter-subject variability. The present study contributes to an improved assessment of the feasibility for using neurophysiological outcome measures in intervention studies of cognitive deficits among patients with NF1. [ABSTRACT FROM AUTHOR]

Patient engagement is increasingly recognized as a valuable, essential aspect of Neurofibromatosis research given the unique experiences and morbidities associated with the diagnosis. Engaging patients and families can enhance the relevance, methodology, and feasibility of clinical trials. A REDCap survey ascertaining information on NF-related morbidities, priorities, and interests in cognitive and social-emotional research, and willingness to participate in research was dispensed to 4,565 individuals consented to the Children's Tumor Foundation (CTF) Registry with NF1. This included children and adults with NF1 and parents/caregivers of children with NF1. 525 individuals fully completed the survey: 295 parents/caregivers (M age child = 10.12, range = 3–24), 194 adults with NF1 (M age = 45.73, range = 19–81), and 36 children with NF1 (M age = 12.61, range = 10–17). Less than 10% of respondents have participated in cognitive research, while 42.4–49.5% indicated having sought opportunities for cognitive research. Most (79.4–82.4%) respondents reported that cognitive research is very/extremely important, with learning/academics and emotional functioning were priorities. Willingness to participate in research aligned with areas of importance. Analysis highlights that most survey respondents believe cognitive and social-emotional research is very important, but a relatively small number have participated. This finding may highlight poor dissemination of information of research opportunities to the broader NF community and limitations to access based on geography or other factors. Respondents indicate that learning/academic problems and emotional challenges to be research priorities. Continuing to engage patients and families with NF is expected to enhance the value and engagement in cognitive research. [ABSTRACT FROM AUTHOR]

Introduction: The neurofibromatoses comprise three different genetic conditions causing considerable morbidity and mortality: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). This review summarizes recent and ongoing clinical trials involving patients with neurofibromatoses to better understand the current state of clinical trial research centered around these conditions and inform areas of need.Methods: A search was conducted using the Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases. Inclusion and exclusion criteria were designed to identify clinical trials focused on patients with NF1, NF2, or SWN completed in or after 2010 and in process as of December 31, 2021. Information was collected using standardized guidelines.Results: A total of 134 clinical trials were included, with 75 (56%) completed and 59 (44%) in process. For completed trials, 74% (n = 56) involved patients with NF1, and of those based on specific tumors (n = 26, 46%), the majority focused on plexiform neurofibromas (PNs) (n = 12, 46%). For ongoing trials, 79% (n = 47) involve patients with NF1, and of those based on specific tumors (n = 29, 61%), the majority are focused on PNs (n = 13, 45%).Conclusion: Both recent and ongoing clinical trials have primarily focused on patients with NF1 and the treatment of PNs. This research has led to the first FDA-approved drug for NF1-PN and has changed management of these tumors, allowing for systemic therapy rather than reliance on only a surgical modality. Trials evaluating comorbid psychiatric conditions and quality of life among patients with any of the neurofibromatoses appear less common. These areas may warrant focus in future studies to improve clinical management. [ABSTRACT FROM AUTHOR]

Background: Moyamoya syndrome (MMS) is a progressive cerebral arteriopathy with increased incidence in children with neurofibromatosis type 1 (NF1). Despite the potential for significant neurological morbidity including stroke, little is known about the natural history, and no guidelines exist for screening and management of NF1-associated MMS.Methods: We identified 152 literature cases of children aged ≤18 years with NF1-associated MMS. A meta-analysis was performed evaluating clinical and neuroimaging findings and patient outcomes. Data from 19 patients with NF1-associated MMS from our center treated from January 1995 to July 2020 were abstracted via chart review and similarly analyzed for clinical and neuroimaging features.Results: Meta-analysis of literature cases showed a median age of MMS diagnosis of 6 years (interquartile range 3 to 10.8 years). Optic pathway gliomas were more common in patients with MMS (42%) compared with historical prevalence. Stroke or transient ischemic attack (TIA) was present at diagnosis in 46%. TIA and stroke were more common in patients with bilateral versus unilateral MMS (62% vs 34%, P = 0.001) and in children aged <4 years versus those aged ≥4 years (61% vs 40%, P = 0.02). Compared with the literature cases, our cohort was more frequently asymptomatic (42% vs 25%) and less likely to present with TIA or stroke (32% vs 46%) at diagnosis.Conclusions: These data suggest there is an aggressive form of MMS in children with NF1 <4 years of age. Therefore, early screening should be considered to facilitate early detection and treatment of cerebral arteriopathy. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF-1) is the most common neurocutaneous syndrome with an autosomal dominant inheritance. However, half of the cases are de novo mutations. Involvement of bone, skin (cafe au lait macules), as well as ocular and tumoral formations is also associated with NF-1. Here, we present our case series of patients with bone deformities. The medical files of patients with NF-1 who were followed up by the same doctor in the pediatric neurology outpatient clinic over 2 years were retrospectively analyzed. Overall, 19 girls and 13 boys were diagnosed with NF-1. Of these 32 patients, 12 (nine girls, three boys) were found to have bone pathologies. The average age was of these patients with bone pathology was 7.5 and 9.5 years. Scoliosis, bowing, short stature, and long bone cysts were found in descending order of frequency. Severe adhesions in the hands and feet as well as phalangeal hypoplasia were noted in one patient. NF-1 requires a multidisciplinary approach. Routine follow-up is very important as it is known that deformities that affect different systems may appear or increase with age. Severe hand and foot anomalies seen in one of our patients did not seem to be associated with NF-1. [ABSTRACT FROM AUTHOR]

As the most common malignant tumor, gliomas remain a poor prognosis while chemotherapy resistance is a medical problem for the treatment of glioma. Considering the correlation between drug resistance and ferroptosis, this study aims to explore the mechanism of chemotherapy resistance in glioma from the perspective of epigenetics. Because of the low expression of long non-coding RNA (lncRNA) ATXN8 opposite strand (ATXN8OS) in glioma cell lines, the role of ATXN8OS was explored by the detection on ferrous iron (Fe2+)/lipid reactive oxygen species (ROS), function experiments and assays performed with xenograft model, proving that ATXN8OS inhibited temozolomide (TMZ)-resistance of glioma. After subcellular fractionation and FISH assays revealed that ATXN8OS was mainly located in cytoplasm, we determined the RNA binding protein (RBP) of ATXN8OS as adenosine deaminase acting on RNA (ADAR) via RNA binding protein immunoprecipitation (RIP), RNA pull down and western blot assays. Furthermore, we verified that ATXN8OS stabilized glutaminase 2 (GLS2) mRNA by recruiting ADAR and GLS2 restrained TMZ-resistance of glioma both in vitro and in vivo. Rescue experiments indicated that ATXN8OS modulated TMZ-resistance of glioma through GLS2. In conclusion, ATXN8OS mediated ferroptosis and regulated the TMZ-resistance of glioma via ADAR/GLS2 pathway. [Display omitted] • ATXN8OS is firstly verified to regulate ferroptosis and TMZ-resistance of glioma. • It is a novel finding that ATXN8OS stabilizes GLS2 mRNA via recruiting ADAR. • ATXN8OS mediates ferroptosis and TMZ-resistance of glioma via ADAR/GLS2 pathway. [ABSTRACT FROM AUTHOR]

An 8-month-old girl referred from her pediatrician with a diagnosis of neurofibromatosis type 1 (NF1) presented with an enlarged cloudy cornea of the left eye and a swollen left side of the face. Her left eye had intraocular pressure (IOP) of 21 mm Hg, corneal diameter of 16 mm, ectropion uvea, cup:disk ratio of 0.9, axial length of 28.06 mm, and S-shaped upper lid deformity. Uneventful combined trabeculotomy-trabeculectomy with mitomycin C was performed. On postoperative day 1, there was a new total hyphema that persisted for 2 weeks. An anterior chamber washout was performed, revealing the source of bleeding to be a persistent tunica vasculosa lentis along the zonules of the lens. Viscotamponade was performed, and the corneal wounds were closed, with the ocular tension slightly elevated. Bleeding did not recur for the following 5 months, and IOP was controlled until final follow-up. [ABSTRACT FROM AUTHOR]

Our study aimed to report the normative values for optic nerve diameter in different age groups in MR imaging (MRI) in the pediatric population and to find a cut-off value for diagnosis in different age groups to be used for the diagnosis of optic glioma in patients with Neurofibromatosis 1(NF1). Orbital MRI obtained from 2011 to 2021 for children with and without NF1 were reviewed. Patients were divided into three groups: NF1 with glioma (group 1, n = 38), NF1 without glioma (group 2, n = 57), and healthy controls (group 3, n = 295). Two radiologists assessed diameter and tortuosity using validated criteria. The optic nerve measurements were obtained by two radiologists in two plans (axial and coronal sections) at five locations; retroocular, midsegment, and prechiasmatic segment on axial plane and retroocular segment and chiasmatic on coronal plane. Optic nerves were divided into 4 age groups: 0–2 years, 2–6 years, 6–12 years, and 12–18 years. It was observed that optic nerve diameters increased with age in healthy individuals. In subjects in groups 1 and 2, the mean diameter of the optic nerve was significantly greater at all locations compared with control individuals. Tortuosity scores were significantly associated in NF1 subjects with optic glioma than in NF1 subjects without optic glioma. We present the normative values obtained by measuring optic nerve diameters in pediatric populations (0–18 years) on MRI of our center. A rapid increase in optic nerve diameter was observed in the first 6 years of life, followed by a slower increase. Quantitative reference values for optic nerve diameter will benefit the development of objective diagnostic criteria for optic nerve gliomas (ONGs) secondary to NF1. • Some asymptomatic cases of optic glioma can also be detected while scanning for NF-1. • Risk assessment is difficult in asymptomatic patients with NF-1, due to the lack of valid biomarkers for optic glioma. • Quantitative reference values for optic nerve may contribute to objective diagnostic criteria for optic gliomas. [ABSTRACT FROM AUTHOR]

Today's estimates indicate that nearly 50% of children with Neurofibromatosis type 1 (NF1) suffer from reading disabilities, with a high impact on their academic achievement. In addition to the well-documented importance of phonological skills in reading acquisition and neurodevelopmental disorders, visual-attention processes also appear as important factors in learning to read. The present study aimed at assessing the role of visual-processing dysfunction in the high prevalence of reading disabilities in NF1 children and providing a useful tool for clinician in the early detection of reading impairment in this neurogenetic disorder. Forty-two children with NF1 and 42 typically developing children (TD) participated in the study. All were right-handed and did not present intellectual disability or attention deficit hyperactivity disorder. Visual-attention processes were assessed with the Developmental Eye Movement (DEM) test, together with the NF1 children's reading level. NF1 children with and without reading disabilities were then compared. The results showed that visual-processing deficits were highly present among the NF1 children included in our study. Furthermore, poor readers with NF1 presented an increased risk of visual-processing deficits compared to peers. This finding supports the role of visual-processing deficits in the reading difficulties encountered in nearly half of children with NF1. Finally, in NF1 children without intellectual or attention disability, visual-processing deficits emerge as one of the clinical markers of reading disabilities. The study holds important clinical implications both for the identification, by providing a useful screening tool, and the management of reading disabilities in NF1 children. • Visual-processing deficits are highly present among NF1 children without ADHD. • Poor readers appeared to be at increased risk for visual deficits. • Visual-processing deficits emerge as a clinical marker of reading impairment in our NF1 sample. • Visual processes assessment should become systematic to improve schooling in NF1. • The DEM-test is a useful tool in the clinical management of the NF1 without ADHD. [ABSTRACT FROM AUTHOR]

To provide a comprehensive characterization of verbal learning and memory (VLM) abilities in youth with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) and to evaluate disease severity as a predictor of VLM functioning over time. As part of a longitudinal natural history study, youth with NF1 and PNs were administered repeat neuropsychological assessments, including measures of VLM and ratings of NF1 disease severity completed by a medical professional. This sub-study analyzed data from 89 patients (M age baseline = 13.1, SD = 4.3 years, range 6–24 years) who had completed tests of VLM abilities and verbal attention at either baseline and/or 36 months. VLM scores across the sample fell predominantly within the average range of functioning at both time points. However, relative to peers with mild NF1 disease severity, youth with moderate/severe NF1 disease showed lower functioning across multiple VLM domains at 36 months, even after controlling for the effects of verbal attention. Exclusive use of overall domain scores does not fully characterize VLM functioning in youth with NF1 and PNs. Additionally, children and adolescents with more severe NF1 disease should be monitored more closely for verbal memory challenges and targeted for interventions. • VLM appears to be relatively intact in youth with NF1. • Overall memory scores may not fully represent VLM in youth with NF1. • Youth with moderate/severe NF1 disease have lower VLM functioning over time. [ABSTRACT FROM AUTHOR]

A 16-year-old male presented with solitary occipital plexiform neurofibroma, which had grown slowly over several years to reach giant size, thereby mimicking a "double head." There were no features of neurofibromatosis type 1. Total excision of the neurofibroma was done by infiltrating adrenaline circumferentially around the tumor before scalp incision. The feeding arteries were identified in the dense connective tissue above the aponeurosis and ligated or cauterized. Dissection was then carried out in the loose areolar tissue preserving the periosteal layer. There was no evidence of malignant transformation on histopathology, and 5-year follow-up showed no tumor recurrence. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a common neurologic complication of neurofibromatosis type 1 (NF-1) in childhood. A great number of learning disabilities appear in 30%−65% of children with NF-1. The aim of the study is to compare intelligence quotient (IQ) scores between children with NF-1 and comparable control groups. A literature review was conducted using the following databases: Cochrane, PubMed, Wiley, Microsoft Academic, and Google Scholar. We identified 180 papers. The pertinence of any study to the inclusion criteria was determined by assessing the title, key words, and abstracts. Data were extracted using multiple variables that were formulated incongruent with the study aim and then further analyzed. Eleven articles met our criteria, with the highest level of evidence of 3c. A total of 483 NF1 and 443 control participants were included in this meta-analysis. The average and standard deviation of the age was 9.15 ± 3.15 years with an age range of 3.3−18 including 488 male and 438 female. The pooled estimate of the mean difference in all 3 parameters used full-scale IQ, verbal IQ, and performance IQ. Statistically, there was a significantly lower IQ in the NF-1 group compared with the control group with a 95% CI and (P < 0.00001). The current meta-analysis illustrated a significant intellectual deficit in children with NF-1 compared with their typically developed peers who were matched by age. Performance IQ was significantly impaired compared with verbal IQ in NF-1 children. The current findings may guide experts to tailor individualized educational programs for children with NF-1. [ABSTRACT FROM AUTHOR]

In patients with neurofibromatosis type 1 (NF1), it is important to accurately determine when plexiform neurofibroma (pNF) transforms to a malignant peripheral nerve sheath tumor (MPNST). The purpose of this study is to investigate the usefulness of diffusion-weighted imaging (DWI) in differentiating pNF and MPNST in NF1 patients. Among the NF1 patients who were referred to our hospital between 1985 and 2015, 10 cases of MPNST and 19 cases of pNF were included. We evaluated features of standard magnetic resonance imaging according to the differentiation criteria of malignancy from benignancy as previously reported, apparent diffusion coefficient (ADC) value based on the DWI and the correlation between ADC value and benignancy/malignancy. ROC analysis was performed to determine the appropriate cutoff value of ADC. There were significant differences between MPNST and pNF in the size of the tumor (P = 0.009), peripheral enhancement pattern (P = 0.002), perilesional edema-like zone (P = 0.0008), and intratumoral cystic change (P = 0.02). The mean and minimum values of ADC were significantly lower in MPNST than those in pNF (P = 0.03 and P = 0.003, respectively). When we set a cutoff value of mean ADC as 1.85 × 10–3 mm2/s, the sensitivity and specificity were 80% and 74%, respectively. The area under the curve value improved by adding the Wasa score to the mean ADC evaluation. ADC values determined by DWI are useful in differentiating MPNST from pNF and adding ADC evaluation to standard MRI evaluation improved the diagnostic accuracy. [ABSTRACT FROM AUTHOR]

A 2-month-old girl presented with malignant arterial hypertension revealing bilateral renal artery stenosis secondary to neurofibromatosis type 1 (NF1). Life-supporting care was initiated immediately. High-dose peripheral vasodilator therapy induced life-threatening toxicity; vascular surgery was therefore performed. Technical difficulties due to the young age and low body weight of the patient resulted in fatal bleeding. Renovascular disease is an important cause of pediatric hypertension. NF1-associated renovascular hypertension in young pediatric patients is rare, and its highly specialized management is best delivered via a multidisciplinary approach. The long-term prognosis remains poor. [ABSTRACT FROM AUTHOR]

• In a selected group of Neurofibromatosis type 1 gene carriers, procedural learning performance was intact. • No abnormalities were seen in short interval intracortical inhibition of the motor cortex in rest and movement. • According to phenotype severity the population of gene carriers most likely comprises different subgroups. Neurofibromatosis type 1 (NF1) 1 NF1 Neurofibromatosis type 1 1 is known to cause learning deficits in affected individuals. There has been evidence linking altered gamma-aminobutyric acid (GABA) 2 GABA Gamma-aminobutyric acid 2 mediated inhibition to learning impairments in rodent models and humans with NF1. Still, evidence on the role of GABA in learning deficits associated with NF1 is inconclusive. We examined procedural learning and motor cortex excitability through intracortical facilitation and short interval intracortical inhibition and its activity dependent modulation while performing a procedural sequence learning task in 16 asymptomatic NF1 gene carriers. We aimed to analyze potential brain-behavior correlations in a carefully selected sample of gene carriers in order to minimize confounding factors. Gene carriers did not differ from healthy controls when learning the task with their non-dominant hand over three days of training. Electrophysiological data did not reveal alterations in patients' inhibitory function of the motor cortex. In contrast with previous publications reporting various cognitive deficits in clinically asymptomatic individuals with NF1, here asymptomatic gene carriers did not show major neuropsychological or behavioral abnormalities. Our results support the concept that gene carriers may not always be impaired by the condition and the population of individuals with NF1 most likely comprises different subgroups according to patients' phenotype severity. [ABSTRACT FROM AUTHOR]

The impact of the Neurofibromatosis type 1 (NF1) on cognition have been subject to much clinical investigation, but environmental modifiers of disease expression have not yet been systematically investigated. The aim of this paper is to determine the role of demographic and environmental factors such as age, sex, socioeconomic status, parental NF1 status and neurological complications on the cognitive, behavioural and academic outcomes in NF1. Participants included 206 children aged 4–18 years seen within the Manchester clinical research NF1 service. Multiple linear regression models were used to study the effect of the hypothesized predictor variables on cognitive, behavioural and academic outcomes. Relative to population norms, 80% of the NF1 sample demonstrated significantly lower scores in at least one cognitive, behavioural or academic domains. Family history of NF1 and lower SES were independently associated with poorer cognitive, behavioural and academic outcomes. Neurological problems such as epilepsy and hydrocephalus were associated with lower IQ and academic skills. Cognitive and behavioural phenotypes emerge commonly via a complex interplay between genes and environmental factors, and this is true also of a monogenic condition such as NF1. Early interventions and remedial education may be targeted to risk groups such those with familial NF1, families with lower SES and those with associated neurological comorbidities. • Higher SES is associated with higher IQ, lower levels of ADHD symptomatology and better social communication abilities. • Having a parent with NF1 is associated with lower IQ even when controlling for SES. • Environmental factors are important determinants of the cognitive/behavioural phenotype in NF1. [ABSTRACT FROM AUTHOR]

Background: Given the expanding evidence of clinico-radiological differences between moyamoya disease (MMD) and moyamoya syndrome (MMS), we compared the clinical and radiographic features of childhood MMD and MMS to identify predictors of ischemic event recurrence.Methods: We reviewed a pediatric moyamoya cohort followed between 2003 and 2019. Clinical and radiographic characteristics at diagnosis and follow-up were abstracted. Comparisons between MMD and MMS as well as between MMD and two MMS subgroups (neurofibromatosis [MMS-NF1] and sickle cell disease [MMS-SCD]) were performed.Results: A total of 111 patients were identified. Patients with MMD presented commonly with transient ischemic attacks (TIAs) (35 % MMD versus 13% MMS-NF1 versus 9.5% MMS-SCD; P = 0.047). Symptomatic stroke presentation (MMD 37% versus MMS-NF1 4% versus 33%; P = 0.0147) and bilateral disease at diagnosis (MMD 73% versus MMS-NF1 22 % versus MMS-SCD 67%; P = 0.0002) were uncommon in MMS-NF1. TIA recurrence was common in MMD (hazard ratio 2.86; P = 0.001). The ivy sign was absent on neuroimaging in a majority of patients with MMS-SCD (MMD 67% versus MMS-NF1 52% versus MMS-SCD 9.5%; P = 0.0002). Predictors of poor motor outcome included early age at diagnosis (odds ratio [OR] 8.45; P = 0.0014), symptomatic stroke presentation (OR 6.6; P = 0.019), and advanced Suzuki stage (OR 3.59; P = 0.019).Conclusions: Moyamoya exhibits different phenotypes based on underlying etiologies. Frequent TIAs is a common phenotype of MMD and symptomatic stroke presentation a common feature of MMD and MMS-SCD, whereas unilateral disease and low infarct burden are common in MMS-NF1. In addition, absence of ivy sign is a common phenotype in MMS-SCD. [ABSTRACT FROM AUTHOR]

Background: Multiple non-ossifying fibromas (MNOF) could be presented with other extraskeletal anomalies (syndromic) or not (non-syndromic). In this study, we aimed to compare characteristic features and local recurrence between symptomatic syndromic and non-syndromic MNOFs.Methods: Thirty-five patients with symptomatic MNOF were included in this study, comprised of 30 patients without the café-au-lait spot (non-syndromic) and five with café-au-lait spots plus other signs of neurofibromatosis type 1 (syndromic). Characteristic features of the patients and lesions were compared between syndromic and non-syndromic MNOFs. The lesions were treated with curettage and bone graft. The rate of local recurrences was also compared between the two groups of syndromic and non-syndromic MNOF.Results: Study population included 19 (54.3%) males and 16 (45.7%) females with the mean age of 7.63 ± 3.1 years (range 4-11). The mean follow-up of the patients was 65.6 ± 38.2 months (range 24-96). The lesion was bilateral in 13.3% of non-syndromic MNOFs and 80% of syndromic MNOFs. This difference was statistically significant (p = 0.01). After curettage and bone grafting, the lesion recurred in 6.7%of non-syndromic MNOFs and 60% of the syndromic MNOF. This difference was statistically significant, as well (p = 0.01). No other significant difference was found between syndromic and non-syndromic MNOFs.Conclusions: The syndromic form of MNOF is much less prevalent and is associated with a higher rate of recurrence after surgical removal. Therefore, a more rigorous removal of the MNOF lesions might be necessary when presented in a syndromic context. [ABSTRACT FROM AUTHOR]