Direct comparison of the diagnostic accuracy of 2-[18F]-fluoro-2-deoxy-d-glucose PET/CT and MRI for the differentiation of malignant peripheral nerve sheath tumour in neurofibromatosis type I: a meta-analysis.

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Comparing 3D imaging devices for the measurement of cutaneous neurofibromas in patients with Neurofibromatosis Type 1.

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.

Pathogenesis and treatment of a giant occipital bone defect with meningoencephalocele in an NF1 child: case report and review of the literature.

Autosomal dominantly inherited neurofibromatosis type I (NF1) is a systemic disorder caused by a mutation of a gene on chromosome 17q11.2 and characterized by multiple café-au-lait spots, lentiginous macules, Lisch nodules of the iris, and tumors of the nervous system. Bony manifestations such as scoliosis, dysplasia of the greater sphenoidal wing, tibial pseudoarthrosis, short stature, and macrocephaly have been reported in approximately 50% of patients. However, calvarial bone defects are rare. After screening 324 articles, 23 cases (12 adult and 11 pediatric patients) of occipital bone defects in NF1 patients were selected. All patients had a single/multiple bone defect over the lambdoid suture. Adjacent benign plexiform neurofibromas were observed in 14 patients (60.8%, 7 adults and 7 children); one adult patient was diagnosed with neurofibrosarcoma. Meningoencephalocele over the occipital defect was noted in 8 cases (34.78%, all adults). Cranioplasty was performed in only 17.39% of patients. Histologic examination was performed in 7 of the 15 patients with associated neurofibromas/neurofibrosarcomas. Biopsy of the bone margins surrounding the defect was performed in only one case. Pathologic examination of the herniated parieto-occipital or cerebellar tissue was not performed in any of the patients studied. We report the case of a 9-year-old girl with NF1 and a significant occipital bone defect and performed a systematic review of the relevant literature to highlight the challenges in treating this condition and to investigate the underlying mechanisms contributing to bone defects or dysplasia in NF1.

Association of plexiform and diffuse neurofibromas with malignant peripheral nerve sheath tumor in NF I patients: a whole-body MRI assessment.

OBJECTIVE: The aim of this study is to evaluate neurofibromatosis type 1 (NF1) patients with whole-body MRI (WBMRI) to investigate the frequency of plexiform neurofibromas (pNFs), diffuse neurofibromas (dNFs), and malignant peripheral nerve sheath tumors (MPNSTs). MATERIALS AND METHODS: In this retrospective cross-sectional study, between the years 2015 and 2023, 83 consecutive patients with known NF1 underwent a total of 110 WBMRI screenings for MPNST using a standardized institutional protocol. The lesions are categorized as discrete lesions, pNFs, dNFs, and MPNSTs. Histopathology served as the reference standard for all MPNSTs. RESULTS: Among the 83 patients analyzed, 53 (64%) were women and 30 were men (36%) of ages 36.94±14.43 years (range, 15-66 years). Of the 83 patients, 33 have a positive family history of NF1 and positive genetic studies. Seven of 83 (8%) have only dNF, 20/83 (24%) have pNF, 28/83 (34%) have both dNF and pNF, and 28/83 (34%) have neither. Of the 83 patients, eight (9.6%) were diagnosed with nine total MPNSTs. Age range for patients with MPNSTs at time of diagnosis was 22-51, with an average age of 33.4 years. Only one MPNST (11%) developed from underlying pNF 4 years after WBMRI along the right bronchial tree. Three of eight (37.5%) patients with MPNST died within 5 years of pathologic diagnosis. CONCLUSION: This study suggests the absence of a predisposition for development of MPNST from pNFs and dNFs in the setting of NF1. As such, these lesions may not need special surveillance compared to discrete peripheral nerve sheath tumors.

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

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

The impact of changes in gadolinium-enhancement on disease progression in children with neurofibromatosis type 1-associated optic pathway glioma: a retrospective analysis.

PURPOSE: There has been limited investigation of imaging features associated with visual acuity (VA) decline and initiation of treatment for patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). METHODS: To evaluate the association of increased gadolinium enhancement with decline in VA, initiation of chemotherapy, and tumor growth, we performed a retrospective cohort study of children diagnosed with NF1-OPG between January 2006 to June 2016. Two cohorts were defined: a new diagnosis and a longitudinal cohort. Outcomes were examined at 1 and 2 years from initial diagnosis, and 1 and 2 years from initial increase in enhancement in the longitudinal cohort. RESULTS: Eighty patients were eligible; all 80 contributed to the new diagnosis cohort and 73 to the longitudinal cohort. Fifty-six patients (70%) demonstrated enhancing NF1-OPG at diagnosis. 39% of patients in the new diagnosis cohort and 45% of those in the longitudinal cohort developed increased enhancement during the study period. There was no significant association between increases in enhancement and VA decline in the newly diagnosed or longitudinal cohorts, as well as with initiation of treatment in the longitudinal cohort. Although there was an association of enhancement increase with treatment in the new diagnosis cohort, this association was not maintained when stratified by concurrent change in tumor size. CONCLUSION: Increased gadolinium-enhancement independent of a concurrent increase in tumor size on MRI should not be used as a marker of NF1-OPG progression and does not appear to be associated with visual decline or initiation of chemotherapy.

Diagnosis of neonatal neurofibromatosis type 1: a case report and review of the literature.

BACKGROUND: Neurofibromatosis Type 1 (NF1) is a rare genetic disorder characterized with the development of multiple benign tumors on the nerves and skin. CASE PRESENTATION: This report described a neonatal case with a large mass observed on the left side of the maxillofacial and cervical region at birth. Meantime, multiple cafe-au-lait macules (CALMs) were seen on the trunk and both lower extremities. CONCLUSIONS: In this case, the clinical features of the rare NF1 neonate are discussed along with its ultrasound findings.

Neurofibromatosis type1, type 2, tuberous sclerosis and Von Hippel-Lindau disease.

Neurocutaneous syndromes (also known as phakomatoses) are heterogenous group of disorders that involve derivatives of the neuroectoderm. Each disease has diagnostic and pathognomonic criteria, once identified, thorough clinical examination to the patient and the family members should be done. Magnetic resonance imaging (MRI) is used to study the pathognomonic findings withing the CNS (Evans et al. in Am J Med Genet A 152A:327-332, 2010). This chapter includes the 4 most common syndromes faced by neurosurgeons and neurologists; neurofibromatosis types 1 and 2, tuberous sclerosis and Von Hippel-Lindau disease. Each syndrome has specific genetic anomaly that involves a tumor suppressor gene and the loss of inhibition of specific pathways. The result is a spectrum of cutaneous manifestations and neoplasms.

MRI-guided laser interstitial thermal therapy for deep-seated gliomas in children with neurofibromatosis type 1: report of two cases.

PURPOSE: Nearly a quarter of neurofibromatosis type 1 (NF 1)- associated diencephalic low-grade tumors are refractory to chemotherapy. Addition of alternative treatment options with laser interstitial thermal therapy will have a positive impact on the outcome of these patients. METHODS: We report on two illustrated cases of pediatric NF1- associated, chemoresistant, WHO grade 1 pilocytic astrocytomas treated with laser interstitial thermal therapy (LITT). RESULTS: Both tumors responded favorably to LITT. CONCLUSION: LITT should be considered as a treatment option for chemoresistant deep-seated NF1-associated low-grade gliomas.

Clinical and Sonographic Classification of Neurofibromas in Children with Neurofibromatosis Type 1 - A Cluster Analysis.

PURPOSE: High-frequency ultrasound allows the accurate identification of neurofibromas in neurofibromatosis type 1 (NF1). This study aimed to analyze the ultrasound features of neurofibromas in children with NF1, to establish a classification based on the clinical and sonographic patterns of the different types of neurofibromas, and to evaluate the interobserver correlation coefficient (κ) of this classification. MATERIALS AND METHODS: In this prospective, single referral center observational study, clinical and ultrasound findings of neurofibromas in children diagnosed with NF 1 were analyzed. To identify the ultrasound patterns, a cluster analysis allowing the inclusion of both clinical and ultrasound data was designed. The κ coefficient was calculated using 9 external evaluators. RESULTS: 265 ultrasound scans were performed on a total of 242 neurofibromas from 108 children diagnosed with NF1. Cluster analysis allowed the identification of 9 patterns (Snedecor's F, P < 0.001) classified as "classic" cutaneous neurofibroma, blue-red neurofibroma, pseudoatrophic neurofibroma, nodular subcutaneous neurofibroma, diffuse subcutaneous neurofibroma, congenital cutaneous neurofibroma, congenital plexiform neurofibroma, congenital diffuse and plexiform neurofibroma, and subfascial neurofibroma. The κ coefficient of the interobserver ratings was 0.82. CONCLUSION: Patterns identified in the cluster analysis allow neurofibromas to be classified with a very high interobserver correlation.

Insights into Novel Choroidal and Retinal Clinical Signs in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a rare inherited neurocutaneous disorder with a major impact on the skin, nervous system and eyes. The ocular diagnostic hallmarks of this disease include iris Lisch nodules, ocular and eyelid neurofibromas, eyelid café-au-lait spots and optic pathway gliomas (OPGs). In the last years, new manifestations have been identified in the ocular district in NF1 including choroidal abnormalities (CAs), hyperpigmented spots (HSs) and retinal vascular abnormalities (RVAs). Recent advances in multi-modality imaging in ophthalmology have allowed for the improved characterization of these clinical signs. Accordingly, CAs, easily detectable as bright patchy nodules on near-infrared imaging, have recently been added to the revised diagnostic criteria for NF1 due to their high specificity and sensitivity. Furthermore, subclinical alterations of the visual pathways, regardless of the presence of OPGs, have been recently described in NF1, with a primary role of neurofibromin in the myelination process. In this paper, we reviewed the latest progress in the understanding of choroidal and retinal abnormalities in NF1 patients. The clinical significance of the recently revised diagnostic criteria for NF1 is discussed along with new updates in molecular diagnosis. New insights into NF1-related neuro-ophthalmic manifestations are also provided based on electrophysiological and optical coherence tomography (OCT) studies.

Diagnostic value of 18F-FDG PET-CT in detecting malignant peripheral nerve sheath tumors among adult and pediatric neurofibromatosis type 1 patients.

PURPOSE: Detecting malignant peripheral nerve sheath tumors (MPNSTs) remains difficult. 18F-FDG PET-CT has been shown helpful, but ideal threshold values of semi-quantitative markers remain unclear, partially because of variation among scanners. Using EU-certified scanners diagnostic accuracy of ideal and commonly used 18F-FDG PET-CT thresholds were investigated and differences between adult and pediatric lesions were evaluated. METHODS: A retrospective cohort study was performed including patients from two hospitals with a clinical or radiological suspicion of MPNST between 2013 and 2019. Several markers were studied for ideal threshold values and differences among adults and children. A diagnostic algorithm was subsequently developed. RESULTS: Sixty patients were included (10 MPNSTs). Ideal threshold values were 5.8 for SUVmax (sensitivity 0.70, specificity 0.92), 5.0 for SUVpeak (sensitivity 0.70, specificity 0.97), 1.7 for TLmax (sensitivity 0.90, specificity 0.86), and 2.3 for TLmean (sensitivity 0.90, specificity 0.79). The standard TLmean threshold value of 2.0 yielded a sensitivity of 0.90 and specificity of 0.74, while the standard SUVmax threshold value of 3.5 yielded a sensitivity of 0.80 and specificity of 0.63. SUVmax and adjusted SUV for lean body mass (SUL) were lower in children, but tumor-to-liver ratios were similar in adult and pediatric lesions. Using TLmean > 2.0 or TLmean < 2.0 and SUVmax > 3.5, a sensitivity and specificity of 1.00 and 0.63 can be achieved. CONCLUSION: 18F-FDG PET-CT offers adequate accuracy to detect MPNSTs. SUV values in pediatric MPNSTs may be lower, but tumor-to-liver ratios are not. By combining TLmean and SUVmax values, a 100% sensitivity can be achieved with acceptable specificity.

Tumor load rather than contrast enhancement is associated with the visual function of children and adolescents with optic pathway glioma - a retrospective Magnetic Resonance Imaging study.

INTRODUCTION: Optic pathway gliomas are often asymptomatic tumors occurring in children with neurofibromatosis type 1 (NF1 + OPG) or sporadically (spOPG). Treatment is usually prompted by visual loss and/or tumor progression on MRI. The aim of this study was to investigate the relationship between visual acuity (VA), tumor growth, and contrast enhancement to provide more distinct indications for the administration of gadolinium-based contrast agents. METHODS: Tumor load was retrospectively measured and enhancement semi-quantitatively scored on 298 MRIs of 35 patients (63% NF1 + OPG). Spearman rank correlation between tumor load and enhancement was calculated and a linear mixed model used to examine the influence of tumor load and enhancement on corresponding VA tests (LogMAR). RESULTS: The optic nerve width in NF1 + OPGs was strongly associated with VA (regression coefficient 0.75; confidence interval 0.61-0.88), but weakly with enhancement (0.06; -0.04-0.15). In spOPGs, tumor volume and optic nerve width were more relevant (0.31; -0.19-0.81 and 0.39; 0.05-0.73) than enhancement (0.09; -0.09-0.27). CONCLUSIONS: Tumor load measures may be more relevant for the surveillance of optic pathway gliomas than enhancement, given that VA is the relevant outcome parameter. Regular contrast administration should therefore be questioned in these patients.

Neurofibromatosis from Head to Toe: What the Radiologist Needs to Know.

Neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) are autosomal dominant inherited neurocutaneous disorders or phakomatoses secondary to mutations in the NF1 and NF2 tumor suppressor genes, respectively. Although they share a common name, NF1 and NF2 are distinct disorders with a wide range of multisystem manifestations that include benign and malignant tumors. Imaging plays an essential role in diagnosis, surveillance, and management of individuals with NF1 and NF2. Therefore, it is crucial for radiologists to be familiar with the imaging features of NF1 and NF2 to allow prompt diagnosis and appropriate management. Key manifestations of NF1 include café-au-lait macules, axillary or inguinal freckling, neurofibromas or plexiform neurofibromas, optic pathway gliomas, Lisch nodules, and osseous lesions such as sphenoid dysplasia, all of which are considered diagnostic features of NF1. Other manifestations include focal areas of signal intensity in the brain, low-grade gliomas, interstitial lung disease, various abdominopelvic neoplasms, scoliosis, and vascular dysplasia. The various NF1-associated abdominopelvic neoplasms can be categorized by their cellular origin: neurogenic neoplasms, interstitial cells of Cajal neoplasms, neuroendocrine neoplasms, and embryonal neoplasms. Malignant peripheral nerve sheath tumors and intracranial tumors are the leading contributors to mortality in NF1. Classic manifestations of NF2 include schwannomas, meningiomas, and ependymomas. However, NF2 may have shared cutaneous manifestations with NF1. Lifelong multidisciplinary management is critical for patients with either disease. The authors highlight the genetics and molecular pathogenesis, clinical and pathologic features, imaging manifestations, and multidisciplinary management and surveillance of NF1 and NF2. Online supplemental material is available for this article. ©RSNA, 2022.

Treatment of Plexiform Neurofibromas with MEK Inhibitors: First Results with a New Therapeutic Option.

Neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PN) are peripheral nerve sheath tumors that can significantly affect the quality of life. Until recently, surgery was the only treatment for these tumors. However, in most cases, surgery cannot achieve complete tumor removal and carries a high risk of postoperative deficits. Therefore, the recent approval of the MEK inhibitor selumetinib for the treatment of NF1-associated PN provides a long-awaited novel therapeutic option. Here, we report our experience with MEK inhibitor treatment in 12 pediatric NF1 patients with inoperable symptomatic PN. Eight patients received trametinib (median therapy duration 12.13 months and range 4-29 months), and four patients received selumetinib (median therapy duration 6.25 months and range 4-11 months). Volumetric magnetic resonance imaging (MRI) after 6 months of treatment was available for seven trametinib patients (median tumor volume reduction of 26.5% and range 11.3-55.7%) and two selumetinib patients (21.3% tumor volume reduction in one patient and +3% tumor volume change in the other one). All patients reported clinical benefits such as improved range of motion or reduced disfigurement. Therapy-related adverse events occurred in 58.3% of patients and mainly consisted of skin toxicity, paronychia, and gastrointestinal symptoms. Two patients discontinued trametinib treatment after 14 and 29 months when severe skin toxicity occurred and no further reduction of tumor size was observed. In one patient, discontinuation of therapy resulted in a 27.2% tumor volume increase as demonstrated on volumetric MRI 6 months later. Our data show that MEK inhibition is a novel therapeutic approach for inoperable PN with promising results and a manageable safety profile.

The Utility of Early Brain MRI for Patients with Neurofibromatosis Type 1 and Optic Pathway Glioma: A Long-Term Follow-Up in a Tertiary Referral Hospital.

Screening studies have shown detection of optic pathway gliomas (OPGs) in 8 to 31% of children with neurofibromatosis type 1 (NF1). Many of those affected show prolonged indolent phases, but others develop vision disturbances even before diagnosis and treatment. We assessed the clinical presentation at diagnosis, location, natural progression, and risk factors for impaired vision of OPG. The clinical database of the NF1 multidisciplinary clinic of Schneider Children's Medical Center of Israel was reviewed for all patients diagnosed and followed with NF1 during 2007 to 2019. OPG was diagnosed by hyperintensity and thickening along the optic pathway on T2-weighted brain magnetic resonance imaging (MRI), with or without contrast enhancement. Of 257 children with NF1 who underwent MRI, 57 (22%) were diagnosed with OPG; 31 (54%) were females. Twenty-five (44%) had familial NF1. Fifteen (26%) who exhibited tumor progression and worsening in ophthalmic examinations required treatment. Post-chiasmatic glioma was a predictive factor for treatment (p < 0.05), whereas MRI done later and female gender were not significant. Four patients who eventually needed therapy had normal ophthalmic examinations at least 1 year prior to their first MRI. For 6 (40%) of the patients treated, vision continued to worsen. Our findings demonstrate that normal ophthalmic examinations do not always exclude OPG in children with NF1. Early brain MRI before age 36 months may detect OPG, lead to better follow-up and early treatment, and help improve vision outcome.

Scoliosis in Neurofibromatosis Type 1 on Whole-Body Magnetic Resonance Imaging: Frequency and Association With Intraspinal and Paraspinal Tumors.

OBJECTIVES: Scoliosis is a common orthopedic problem in patients with neurofibromatosis 1 (NF1). Spinal deformities are found in 77% of all NF1 cases, with no widely accepted etiology. This study aimed to evaluate the frequency and types of scoliosis in NF1 patients using whole-body magnetic resonance imaging and to assess the association of intraspinal and paraspinal tumors with the imaging findings of scoliosis. METHODS: A total of 122 NF1 patients with whole-body magnetic resonance imaging were found from the electronic medical records. Ninety-seven cases that met the inclusion criteria were identified. All patients underwent 3-T magnetic resonance imaging with automated software fusion of the 3 sets of short TI inversion recovery and 3-dimensional T1-weighted coronal images. Frequency and location of scoliosis and intraspinal and paraspinal tumors were recorded. Patients with severe dystrophic-type scoliosis were separately identified, and Cobb angles were measured for all such cases. Association analysis was performed. A P value less than 0.05 was considered statistically significant. RESULTS: Ninety-seven patients with NF1 were evaluated. Two had prior spinal surgery and were excluded. The final sample of 95 patients included 33 (35%) men and 62 (65%) women with a mean ± SD body mass index of 25.82 (4.96) kg/m2. Of the 95 patients, 43 (45.3%) had scoliosis, 13 of 43 (30.2%) of which were severely angled. Of the 95 patients, 25 (26.3%) had locoregional tumor presence. Intraclass correlation for Cobb angles measured 0.99 (confidence interval, 0.98-1.0). Fisher exact test determined no association between scoliosis and presence of either paraspinal or intraspinal tumors (P = 0.485). There was also no association between the tumors and severe dystrophic scoliosis (P = 1.0). CONCLUSIONS: This study found no association between the presence of locoregional spinal tumors and scoliosis in NF1 patients. This work adds to the body of knowledge of scoliosis in NF1 patients and infers that presence of scoliosis should not mandate immediate search for locoregional spinal tumors.

Deletion of the whole NF1 gene in a three-generation family with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder characterized by café-au-lait macules (CALMs), skinfold freckling, Lisch nodules, and neurofibromas. It is associated with heterozygous mutations in the neurofibromatosis type 1 (NF1) gene. Whole NF1 deletion has been described in some cases, but most cases are sporadic, and familial forms are extremely rare. To date, only two-generation familial forms have been described. OBJECTIVE: To describe a whole NF1 gene deletion in a three-generation family with neurofibromatosis type 1. METHODS: Physical examinations, laboratory tests, structural neuroimaging studies, whole-exome sequencing, and multiplex ligation-dependent probe amplification analysis were carried out. RESULTS: All the affected individuals within this three-generation family, including the 14-year-old female proband, her 40-year-old father, and 63-year-old grandmother, exhibited such typical manifestations of NF1 as CALMs and cutaneous neurofibromas, CALMs increased in size with age. The affected subjects had more localized hyperpigmentation and CALMs within the lesion areas, mainly in the chest, abdomen, waist, and back. In addition, learning disorder was observed in the proband, and brain MRI revealed abnormal high signal lesions in the brainstem. All the affected subjects had normal birth history and had no significant past medical history. Whole-exome sequencing and subsequent multiplex ligation-dependent probe amplification analysis identified deletion of the whole NF1 gene, co-segregating with the NF1 phenotype in an autosomal dominant pattern. CONCLUSIONS: Our findings are the first to identify whole NF1 deletion in a three-generation family with autosomal dominant NF1 and broaden the understanding of the genetic spectrum of NF1-associated NF1.

A rare MRI finding of NF-1: perineural arachnoidal gliomatosis.

Optic pathway gliomas are the most common central nervous system neoplasms in patients with neurofibromatosis type 1. Perineural arachnoidal gliomatosis is a rare and distinctive growth pattern of optic nerve glioma, in which the tumor infiltrates through the pia mater and pre-dominantly involves the subarachnoid space around the optic nerve. Here, we report an 8-year-old girl with perineural arachnoidal gliomatosis associated with neurofibromatosis type 1.

Hippocampal sclerosis and epilepsy surgery in neurofibromatosis type 1: case report of a 3-year-old child explored by SEEG and review of the literature.

PURPOSE: Epilepsy associated with neurofibromatosis type 1 (NF1) is infrequent and usually controlled with anti-epileptic drugs. However, in some drug-resistant patients a presurgical evaluation should be considered. Hippocampal sclerosis (HS) is one of the rare causes of epilepsy in neurofibromatosis type 1, which can lead to surgery. METHODS: We present a three-year-old child with refractory epilepsy associated with several structural brain abnormalities but normal hippocampi on brain MRI and a heterozygous variant in the NF1 gene (c.2542G > A). A complete presurgical evaluation was performed including stereo-electroencephalography (SEEG). RESULTS: Usual seizures were recorded, and the seizure onset zone was delineated in the anterior hippocampus. Pathological examination performed after a tailored mesio-temporal resection confirmed hippocampal sclerosis, and the child achieved seizure freedom with 2 years of follow-up. CONCLUSION: This rare pediatric case illustrates that NF1 may be associated with early-onset refractory epilepsy secondary to MRI-negative HS, supporting the major role of SEEG in the presurgical evaluation of patients with extended cortical malformations.