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Neuropediatrics Dec 2023This article obtains an overview of the health status of children and adolescents with neurofibromatosis type 1 (NF1) with a focus on the clinical course of the disease,... (Observational Study)
Observational Study
This article obtains an overview of the health status of children and adolescents with neurofibromatosis type 1 (NF1) with a focus on the clinical course of the disease, neuropsychodiagnostic findings, and their impact on quality of life (QoL). In this observational study, data were collected from 24 children and adolescents with NF1 who were cared for at the University Hospital in Innsbruck, Austria, from 2008 to 2022. Data were collected every 6 to 12 months from routine check-ups, including clinical features and imaging findings. Results of neuropsychodiagnostic tests and the KINDL questionnaire to assess QoL were included. Of 24 patients, 15 underwent a neuropsychological examination. Attention performance was examined in 11 of them. Eight of 11 (72%) showed an attention deficit. Assessment for specific developmental disorders showed visual-spatial difficulties in 12/15 (80%) patients. The KINDL questionnaire values ranged from 58.22 to 97.92 (0 stands for reduced QoL, 100 for very good QoL). Patients with scoliosis had a lower range of QoL (56.33-73.96). No trend in QoL was observed in children and adolescents with plexiform neurofibromas, below-average intelligence or optic gliomas. NF1 patients show very different clinical courses. Regular neuropsychological assessment especially with regard to visual-spatial skills and attention deficits is necessary to offer appropriate support, promote children's development, and thus improve their QoL.
Topics: Humans; Child; Adolescent; Neurofibromatosis 1; Quality of Life; Neurofibroma, Plexiform; Attention Deficit Disorder with Hyperactivity; Surveys and Questionnaires
PubMed: 37321252
DOI: 10.1055/s-0043-1768988 -
Internal Medicine (Tokyo, Japan) Oct 2023Plexiform neurofibromas (PNs) occur in approximately 50% of patients with neurofibromatosis type 1 (NF1). PNs are rare in the abdominal cavity and especially rare in...
Plexiform neurofibromas (PNs) occur in approximately 50% of patients with neurofibromatosis type 1 (NF1). PNs are rare in the abdominal cavity and especially rare in hepatobiliary lesions. A 31-year-old man with NF1 had a tumor extending along the celiac artery, superior mesenteric artery, and intrahepatic portal vein. We diagnosed him with diffuse PN based on liver tumor biopsy findings and the tumor form. Because the tumor had invaded along the intrahepatic portal vein, surgical resection was deemed difficult, and the patient was followed up with imaging studies. The patient remained asymptomatic without tumor growth.
Topics: Male; Humans; Adult; Neurofibroma, Plexiform; Neurofibromatosis 1; Abdomen; Liver Neoplasms
PubMed: 36792186
DOI: 10.2169/internalmedicine.1372-22 -
Clinical Trials (London, England) Feb 2024Individuals with neurofibromatosis 1 may experience changes in their appearance due to physical manifestations of the disorders and/or treatment sequelae. Appearance...
BACKGROUND/AIMS
Individuals with neurofibromatosis 1 may experience changes in their appearance due to physical manifestations of the disorders and/or treatment sequelae. Appearance concerns related to these physical changes can lead to psychological distress and poorer quality of life. While many neurofibromatosis 1 clinical trials focus on assessing changes in tumor volume, evaluating patients' perspectives on corresponding changes in symptoms such as physical appearance can be key secondary outcomes. We aimed to determine whether any existing patient-reported outcome measures are appropriate for evaluating changes in appearance concerns within neurofibromatosis 1 clinical trials.
METHODS
After updating our previously published systematic review process, we used it to identify and rate existing patient-reported outcome measures related to disfigurement and appearance. Using a systematic literature search and initial triage process, we focused on identifying patient-reported outcome measures that could be used to evaluate changes in appearance concerns in plexiform or cutaneous neurofibroma clinical trials in neurofibromatosis 1. Our revised Patient-Reported Outcome Rating and Acceptance Tool for Endpoints then was used to evaluate each published patient-reported outcome measures in five domains, including (1) respondent characteristics, (2) content validity, (3) scoring format and interpretability, (4) psychometric data, and (5) feasibility. The highest-rated patient-reported outcome measures were then re-reviewed in a side-by-side comparison to generate a final consensus recommendation.
RESULTS
Eleven measures assessing appearance concerns were reviewed and rated; no measures were explicitly designed to assess appearance concerns related to neurofibromatosis 1. The FACE-Q Craniofacial Module-Appearance Distress scale was the top-rated measure for potential use in neurofibromatosis 1 clinical trials. Strengths of the measure included that it was rigorously developed, included individuals with neurofibromatosis 1 in the validation sample, was applicable to children and adults, covered item topics deemed important by neurofibromatosis 1 patient representatives, exhibited good psychometric properties, and was feasible for use in neurofibromatosis 1 trials. Limitations included a lack of validation in older adults, no published information regarding sensitivity to change in clinical trials, and limited availability in languages other than English.
CONCLUSION
The Response Evaluation in Neurofibromatosis and Schwannomatosis patient-reported outcome working group currently recommends the FACE-Q Craniofacial Module Appearance Distress scale to evaluate patient-reported changes in appearance concerns in clinical trials for neurofibromatosis 1-related plexiform or cutaneous neurofibromas. Additional research is needed to validate this measure in people with neurofibromatosis 1, including older adults and those with tumors in various body locations, and explore the effects of nontumor manifestations on appearance concerns in people with neurofibromatosis 1 and schwannomatosis.
Topics: Child; Humans; Aged; Neurofibromatosis 1; Neurofibroma, Plexiform; Quality of Life; Neurofibromatoses; Neurilemmoma; Skin Neoplasms
PubMed: 38140900
DOI: 10.1177/17407745231205577 -
The American Journal of Dermatopathology Jun 2024Close relationship between melanocytes and neural cells is accepted to reflect their common derivation from the neural crest and tumors combining both elements. We...
Close relationship between melanocytes and neural cells is accepted to reflect their common derivation from the neural crest and tumors combining both elements. We present a series of 10 patients with giant congenital melanocytic nevi (CMN) in which a secondary proliferation (11 lesions) with schwannian and/or perineuriomatous differentiation developed in the course of the disease. The age of the patients (4 male and 6 female) at the time of surgery and histological assessment varied from 3 months to 57 years. Histopathologically, the following subgroups were delineated: (1) nodular/tumoriform "neurotization" in CMN, (2) diffuse neurofibroma-like proliferation within CMN, (3) plexiform neurofibroma-like proliferation within CMN, and (4) diffuse perineuriomatous (hybrid schwannomatous-perineuriomatous) differentiation in CMN. We review the pertinent literature, including the role of recently identified Schwann cell precursors which are believed to represent the nerve-associated state of neural crest-like cells that persists into later developmental stages.
PubMed: 38842402
DOI: 10.1097/DAD.0000000000002754 -
Neuro-oncology Advances 2024Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in...
BACKGROUND
Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in multiple countries, including the USA (≥ 2 years). Until recently, individuals had to take selumetinib twice daily (BID) in a fasted state. This study evaluated the effect of a low-fat meal on selumetinib PK parameters and gastrointestinal (GI) tolerability in adolescent participants with NF1-PN.
METHODS
Eligible participants aged ≥ 12 to < 18 years took 25 mg/m selumetinib BID with a low-fat meal (T1) for 28 days, followed by a 7-day washout, and then administration in a fasted state (T2) for another 28 days. Primary objectives were to evaluate the effect of a low-fat meal on AUC and GI tolerability after multiple selumetinib doses in T1 versus T2. Key secondary objectives were additional PK parameters and adverse events (AEs).
RESULTS
At primary data cut-off, all 24 participants completed T1, and 23 participants completed T2. There were no significant differences in AUC between T1 and T2. In T1 and T2, 29.2% and 33.3% participants, respectively, reported ≥ 1 GI AE. No GI AEs Grade ≥ 3, or serious AEs, or GI AEs resulting in treatment interruptions, discontinuation, or dose reductions were reported in T1 and T2.
CONCLUSIONS
Dosing selumetinib with a low-fat meal had no clinically relevant impact on selumetinib AUC nor GI tolerability in adolescents with NF1-PN.
TRIAL REGISTRATION CLINICALTRIALSGOV ID
NCT05101148.
PubMed: 38721358
DOI: 10.1093/noajnl/vdae036 -
Indian Dermatology Online Journal 2024
PubMed: 38283024
DOI: 10.4103/idoj.idoj_253_23 -
Orbit (Amsterdam, Netherlands) Feb 2024To present a simplified technique in management of complete ptosis secondary to neurofibromatosis.
PURPOSE
To present a simplified technique in management of complete ptosis secondary to neurofibromatosis.
METHODS
This prospective, non-comparative, clinical interventional study included 13 patients with complete ptosis secondary to histologically proved plexiform neurofibromas. It was conducted at the Orbital Unit of Assiut University Hospital, the referral center of Upper Egypt in the period between June 2013 and October 2021. In all cases, a simplified technique of 5 surgical steps was applied: (A) Division of the involved eyelid surgically into three parts by drawing 2 curvilinear lines, the superior line 11 mm below and parallel to the lower eyebrow hairline and the inferior one 10 mm above the lid margin, (B) Resection (full-thickness) of the large middle part which involves the main pathology and lies between the 2 lines, (C) Preservation of the upper part with identification, dissection and clamping of the levator muscle, (D) Refinement of the lower part by removal of any tissue between the skin and the debulked tarsus and (E) Re-suturing of the upper and lower parts in layers; conjunctiva to conjunctiva, levator to tarsus (after resection of a part that corrects the ptosis) and skin to skin.
RESULTS
Ptosis was completely corrected in 8 cases (61.5%) and residual mild ptosis occurred in 5 patients (38.5%). No exposure keratopathy or tumor growth was reported during the follow-up period of minimum 1 year.
CONCLUSIONS
This simplified technique could be considered as a surgical basis for correction of complete ptosis in neurofibromatosis.
Topics: Humans; Blepharoplasty; Prospective Studies; Blepharoptosis; Eyelids; Neurofibromatoses; Retrospective Studies; Oculomotor Muscles
PubMed: 36789974
DOI: 10.1080/01676830.2023.2175875 -
Pediatric Neurology Dec 2023Neurofibromatosis 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...
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Topics: Child; Female; Humans; Male; Hamartoma; Neurofibroma, Plexiform; Neurofibromatosis 1; Optic Nerve Glioma; Retrospective Studies
PubMed: 37806041
DOI: 10.1016/j.pediatrneurol.2023.08.036 -
Neuro-oncology Advances 2023
PubMed: 37841697
DOI: 10.1093/noajnl/vdad125 -
Journal of Pediatric Psychology Jun 2024Neurofibromatosis type 1 (NF1) is a genetic cancer predisposition syndrome that can impact multiple organ systems and is associated with plexiform neurofibroma tumors,...
OBJECTIVES
Neurofibromatosis type 1 (NF1) is a genetic cancer predisposition syndrome that can impact multiple organ systems and is associated with plexiform neurofibroma tumors, requiring care from birth through adulthood. Adolescents and young adults (AYAs) with NF1 face several barriers to transition from pediatric to adult care. This cross-sectional study aimed to assess transition readiness in this population and to evaluate relationships between specific NF1 symptoms and transition readiness.
METHODS
AYAs (aged 16-24) enrolled in existing studies related to NF1 were eligible. AYAs and their parents completed measures of transition readiness (Transition Readiness Assessment Questionnaire version 4 [TRAQ-4]), and AYAs also completed a transition readiness interview (UNC TRxANSITION).
RESULTS
Thirty-eight AYAs (mean age = 19.95 ± 2.68 years) participated in the study. Average TRAQ scores indicated that AYAs were still learning Self-Management skills (M = 3.37, SD = 1.08) and Self-Advocacy skills (M = 3.98, SD = 0.67). Older AYAs had higher TRAQ scores for Self-Management (r = 0.70, p < .001) and Self-Advocacy (r = 0.41, p = .011) than younger AYAs. Parents and AYAs had similar TRAQ scores. About one third of AYAs (37.8%, n = 14) expressed uncertainty about how NF1 might affect them in the future. The remaining AYAs mostly expressed concerns regarding tumor growth, pain, or cancer.
CONCLUSIONS
In this small study, preliminary findings suggest that AYAs with NF1 express confidence in many areas of transition readiness but continue to require support, particularly with Self-Management skills. Given the gaps in understanding of future health risks, AYAs with NF1 would benefit from early assessment, psychoeducation, and support for transition readiness to adult care.
Topics: Adolescent; Female; Humans; Male; Young Adult; Cross-Sectional Studies; Neurofibroma, Plexiform; Neurofibromatosis 1; Surveys and Questionnaires; Transition to Adult Care
PubMed: 38366576
DOI: 10.1093/jpepsy/jsae006