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Neurofibromatosis is normally a benign (non-cancerous) condition. NF is a range of genetic disorders which cause tumours to grow along various types of nerves and can also affect the bones and skin. The majority of cases are von Recklinghausen's Disease (NF type 1) often characterised by cafe-au-lait spots on the skin. Neurofibromatosis 2 (NF2) is much rarer, this is characterised by multiple tumours on the nerves of the brain and spine, and can affect hearing.

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Latest Research Publications

Information Patients and the Public (7 links)

Information for Health Professionals / Researchers (6 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Kim JY, Lee MY, Lee YC, Shin HY
Neurofibromatosis type 1 with tarsal conjunctiva thickening: A case report.
Medicine (Baltimore). 2019; 98(31):e16699 [PubMed] Related Publications
RATIONALE: We report a rare case of neurofibroma in the form of tarsal conjunctival thickening of the eyelid in patients with neurofibromatosis type 1 (NF1), common ocular complications of which are Lisch nodules, choroidal nodules, and optic nerve glioma.
PATIENT CONCERNS: A 46-year-old female patient was diagnosed with neurofibroma after biopsy and removal of 2 lumbar level intradural masses 15 years ago. She was being monitored without recurrence. When the patient visited our hospital, multiple iris Lisch nodules were found in both her eyes with ill-defined, diffuse thickening in the upper eyelid tarsal conjunctiva of the right eye.
DIAGNOSIS: Neurofibroma was diagnosed by incisional biopsy and immunohistochemistry of the tarsal conjunctiva.
INTERVENTIONS: The patient of the present case did not undergo any additional surgical treatment because tarsal conjunctiva thickening caused little functional problem.
OUTCOMES: The patient has only been regularly examined for changes in size of neurofibroma, and there was no change in size over a 12-month period.
LESSONS: Neurofibroma should be considered as a differential diagnosis if a patient diagnosed with NF1 shows tarsal conjunctiva thickening.

Kumar SSS, Palaniandavan S, Bhargavi MV, et al.
Neurofibromatosis Type 1 Associated with Hashimoto's Thyroiditis.
J Assoc Physicians India. 2018; 66(8):91-92 [PubMed] Related Publications
Hashimoto's thyroiditis is a common form of chronic autoimmune thyroid disease (AITD) and it often coexists with other autoimmune diseases, but Hashimoto's thyroiditis associated with an autosomal dominant neurofibromatosis type 1 is exceedingly rare. A 30-year-old woman presented with complaints of headache for 1 year on and off. Physical examination revealed nodular swelling in the neck, cafe-au-lait spots, and neurofibromas covering the entire surface of her body. Her thyroid hormones were within normal limits. Thyroid ultrasound revealed mild altered heterogeneous echo texture, multiple nodules of varying sizes, with hyper vascularity and ultrasound-guided fine needle aspiration cytology revealed lymphocytic infiltration of the gland, suggesting Hashimoto's thyroiditis. High levels of autoimmune antibodies such as antithyroglobulin and antimicrosomal antibodies confirmed the diagnosis. When encountering a patient with Neurofibromatosis type 1, the possibility of associated autoimmune diseases should be considered. So further studies of such patients having combination of neurofibromatosis type 1 and autoimmune thyroiditis will certainly provide better understanding of this link in the near future.

Bata BM, Hodge DO, Mohney BG
Neurofibromatosis Type 1: A Population-Based Study.
J Pediatr Ophthalmol Strabismus. 2019; 56(4):243-247 [PubMed] Related Publications
PURPOSE: To report the incidence, demographics, and clinical manifestations of neurofibromatosis type 1 among a population-based cohort of patients.
METHODS: The medical records of all patients diagnosed as having neurofibromatosis type 1 while residing in Olmsted County, Minnesota, from January 1, 1980, through December 31, 2009, were retrospectively reviewed.
RESULTS: Fifty patients were diagnosed as having neurofibromatosis type 1 during the 30-year period, yielding an incidence of 1.2 per 100,000 individuals. The mean age at diagnosis was 11.7 years (95% confidence interval [CI]: 0.2 to 47) and 26 (52%) were males. Twenty-eight patients were new mutations, yielding a de novo mutation rate of 56%. During a mean follow-up of 9.8 years (range: 3 weeks to 32 years), café-au-lait macules were diagnosed in 49 individuals (98%), neurofibromas in 26 (52%), and skeletal anomalies in 14 (28%). Three (5.9%) individuals were diagnosed as having glioma of the central nervous system (95% CI: 1.2 to 9.7%) at a mean age of 13 years (range: 5 to 26 years), including 1 patient with optic nerve glioma diagnosed at the age of 26 years. Only 1 (2%) patient was diagnosed as having malignant nerve sheath tumor.
CONCLUSIONS: Although the prevalence and de novo mutation rate of neurofibromatosis type 1 in this population-based study were similar to prior reports, the occurrence of optic nerve gliomas was much lower. [J Pediatr Ophthalmol Strabismus. 2019;56(4):243-247.].

Sanagoo A, Jouybari L, Koohi F, Sayehmiri F
Evaluation of QoL in neurofibromatosis patients: a systematic review and meta-analysis study.
BMC Neurol. 2019; 19(1):123 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The neurofibromatoses (NF) are a group of genetic disorders that interfere negatively with the quality of life (QoL) and influence physical, emotional and social statuses. Studying the effects of neurofibromatoses on various aspects of QoL seems important to implement beneficial strategies in increasing the QoL of NF patients. The aim of this study was to review the literature on quality of life in patients with NF and quantitatively evaluate the effects of Neurofibromatosis on various aspects of quality of life by synthesizing available studies.
METHODS: This article is written according to the PRISMA checklist. Different databases including PubMed, Scopus, Google scholar and Web of Science were searched to identify studies that examined QoL of patients with neurofibromatosis. The relevant data obtained from these papers were analyzed by a random-effects model. The heterogeneity of studies was calculated using the I
RESULTS: Twelve studies were selected as eligible for this research and were included in the final analysis. The number of participants in the study was 7314 individuals containing 910 NF patients (642 NF1 and 268 NF2) and 6404 healthy subjects. The mean scores of sub-scales of QoL were significantly lower in NF patients compared with control except for the scale of cohesion. Family and NF patients had lower quality of life in all aspects of QoL than controls. Also, this meta-analysis shows that NF negatively effects on physical function, bodily pain, mental health, social function and general health. Subgroup analysis showed that NF had negative effects on all sub-scales of QoL if the study was conducted in adults and used a SF-36 questionnaire.
CONCLUSION: This meta-analysis suggests that NF is a broad spectrum disease, affecting physical function, bodily pain, mental health, social function and general health.

Antonopoulos D, Tsilioni I, Balatsos NAA, et al.
The mast cell - neurofibromatosis connection.
J Biol Regul Homeost Agents. 2019 May-Jun,; 33(3):657-659 [PubMed] Related Publications
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting 1/3000 individuals worldwide. It results from germline mutations of the neurofibromin gene and it is fully penetrant by the age of 5. Neurofibromin is a 2818 amino acid protein that is produced in many cell types, but its levels are especially high in the nervous system.

Waisberg V, Rodrigues LOC, Nehemy MB, et al.
Ocular alterations, molecular findings, and three novel pathological mutations in a series of NF2 patients.
Graefes Arch Clin Exp Ophthalmol. 2019; 257(7):1453-1458 [PubMed] Related Publications
PURPOSE: To evaluate ophthalmological and molecular findings in eight patients with a clinical diagnosis of neurofibromatosis type 2 (NF2). New pathological mutations are described and variability in the ophthalmic phenotype and NF2 allelic heterogeneity are discussed.
METHODS: Eye examination was performed in eight NF2 patients, and it included the measurement of the visual acuity, biomicroscopy, dilated fundus examination, color fundus photography, infrared photography, and spectral domain optical coherence tomography (SD-OCT). Molecular analysis was performed with whole-exome sequencing using DNA derived from peripheral blood mononuclear cells from each individual.
RESULTS: Ophthalmological features were present in all patients, ranging from subtle retinal alterations identified only using SD-OCT to severe ocular damage present at birth. Six mutations were observed: two patients with stop codon mutation as shown on table 1 and result section, three patients with frameshift mutation as shown on table 1 and result section. Three novel mutations were found among them.
CONCLUSIONS: It is a descriptive study of a rare disease, with poor previous literature. Clinical and genetic data are shown, reviving the need to further studies to clarify the genotype-phenotype correlations in NF2.

Takeshima Y, Kaku Y, Nishi T, et al.
Multiple Cerebral Aneurysms Associated With Neurofibromatosis Type 1.
J Stroke Cerebrovasc Dis. 2019; 28(7):e83-e91 [PubMed] Related Publications
Neurofibromatosis type 1 (NF1) is a rare disease with an incidence of approximately one in every 3000 births. NF1 is mainly recognized as a tumor suppressor. Vasculopathy in NF1 is well described in the literature, but the association between NF1 and cerebral aneurysm has not been determined. We report a case of a 67-year-old female with NF1 accompanied by 8 cerebral aneurysms. Two of the patient's unruptured aneurysms, the large distal anterior cerebral artery (ACA) aneurysm and anterior communicating artery aneurysm, were initially treated with microsurgical clipping. The peripheral ACA aneurysm gradually increased in size and ruptured after 5 years. Coil embolization was performed for the ruptured aneurysm. Four of the 5 remaining unruptured aneurysms were treated surgically. The patient is currently well, without neurological deficit, and coil embolization is scheduled for the last remaining aneurysm. NF1 is a probable risk factor for multiple cerebral aneurysms due to vessel wall vulnerability. Therapeutic indications for patients with NF1 who show multiple cerebral aneurysms include strict follow-up and aggressive treatment to avoid subarachnoid hemorrhage.

Drucker NA, Blaibel MF, Nagaraju S, et al.
Renal Autotransplant and Celiac Artery Bypass for Aneurysmal Degeneration Related to Neurofibromatosis Type 1.
Vasc Endovascular Surg. 2019; 53(6):497-500 [PubMed] Related Publications
We present a case of an 18-year-old female with neurofibromatosis type 1 who presented with abdominal pain and weight loss secondary to chronic mesenteric ischemia due to celiac axis occlusion and was subsequently found to have multiple visceral artery aneurysms. Of clinical significance, 2 aneurysms of the right renal artery were noted at the hilum, with the larger one having a diameter of 2.4 cm. After initial endovascular treatment with stenting of a concurrent pancreaticoduodenal artery pseudoaneurysm, staged aorto-hepatic bypass and right nephrectomy with renal autotransplantation after back table resection of the aneurysmal segments were successfully completed.

Kinoshita H, Miyakoshi N, Kobayashi T, et al.
A case report of revision occipital-cervical fusion after atlanto-axial instrumentation failure for neurofibromatosis type I.
BMC Surg. 2019; 19(1):44 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Neurofibromatosis type 1 is an autosomal dominant genetic disease with characteristic café-au-lait spots, neurofibroma, and dystrophic changes in the bones. However, complications involving atlanto-axial dislocation are rare.
CASE PRESENTATION: We report a case of neurofibromatosis with atlanto-axial dislocation. The chief complaints were numbness of the upper limb and gait disturbance. We performed short fusion using the Brooks method. However, recurrence of the dislocation was found after 5 months recovery, and the patient underwent posterior fusion from the occipital bone to C4. Thereafter, she had a good postoperative course.
CONCLUSIONS: Neurofibromatosis patients often exhibit a low bone mineral density because of dystrophic changes, and are prone to fragile bones. In the present case, the use of long fusion at the first surgery may have helped to form a strong fusion of fragile bone.

Jia F, Cui X, Wang G, et al.
Spontaneous rotational dislocation of the lumbar spine in type 1 neurofibromatosis: A case report and literature review.
Medicine (Baltimore). 2019; 98(16):e15258 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Scoliosis is the most common form of dystrophic spinal deformities in type 1 neurofibromatosis, whereas a spontaneous rotational dislocation of the lumbar spine is a rare entity. Former researchers had advocated the use of circumferential fusion performed through combined anterior-posterior approaches as the mode of treatment of this situation, but we managed to achieve a solid circumferential fusion equally using posterior approach alone.
PATIENT CONCERNS: A 51-year-old lady presented with severe back pain and no history of trauma, fever, or loss of weight. On examination, she showed several café-au-lait spots on her body and no neurologic deficit.
DIAGNOSES: The imageology revealed a rotational dislocation of the L2 to L3. The diagnosis of neurofibroma was confirmed by biopsy.
INTERVENTIONS: The patient underwent posterior reduction, combined intervertebral-posterolateral fusion, and internal fixation with screws and rods.
OUTCOMES: The patient was satisfied with the back pain relief after surgery and able to live a normal life at follow-up. The imageology showed a good correction of the deformity with a solid bony fusion.
LESSONS: Special attention must be paid to patients who have neurofibromatosis and unexplained back pain for early diagnosis. Early circumferential fusion to reconstruct a stable spine is the key to treatment. Given the result of this case, the prognosis is promising following posterior surgery alone.

Algın Dİ, Tezer FI, Oguz KK, et al.
Pharmacoresistant seizures in neurofibromatosis type 1 related to hippocampal sclerosis: Three case presentation and review.
J Clin Neurosci. 2019; 64:14-17 [PubMed] Related Publications
Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited disorder, with an estimated prevalence of 1 in 3000-4000 people. Seizures occur 4-7% of individuals with NF1, mostly due to associated brain tumors or cortical malformations. Hippocampal sclerosis (HS) in the patients with NF1 has been reported very rarely and only 15 patients were found in review of English literature. We presented here 3 additional patients with NF1 and intractable seizures due to hippocampal sclerosis; in whom one of them underwent epilepsy surgery and he is seizure free for 5 years after right temporal lobectomy.

Friedrich RE, Scheuer HT
Non-odontogenic Intraosseous Radiolucent Lesions of the Mandibular Body Are Rare Findings on Panoramic Views of Patients With Neurofibromatosis Type 1.
Anticancer Res. 2019; 39(4):1971-1985 [PubMed] Related Publications
BACKGROUND/AIM: The purpose of the study was to investigate whether non-odontogenic intraosseous translucent lesions of mandibular body are depicted on radiographs of patients with neurofibromatosis type 1 (NF1).
MATERIALS AND METHODS: The panoramic radiographs of 179 NF1 patients were analysed for translucent lesions of the mandibular body that were of intraosseous, non-odontogenic origin. The results were compared to findings obtained in panoramic radiographs of age- and sex-matched controls.
RESULTS: Only three patients showed intraosseous translucent lesions. These were always unilocular findings. There were no statistically significant differences between the groups (p=0.248).
CONCLUSION: Intraosseous neurofibroma of the jaw is a very rare finding in NF1 patients compared to oral neurofibromas. Accurate and exact diagnosis should be made in the case of such findings because malignant tumours in the jaw area can arise in rare cases in NF1 patients. Plain radiology findings cannot clearly indicate the type and biology of the lesion.

Zhang L, Sun F, Li H, et al.
Neurofibromatosis type I with malignant peripheral nerve sheath tumors in the upper arm: A case report.
Medicine (Baltimore). 2019; 98(13):e15017 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Malignant peripheral nerve sheath tumor occurring in the context of neurofibromatosis type I (NF1) is relatively rare. Herein, we report a case of NF1 with malignant peripheral nerve sheath tumor in the upper arm.
PATIENT CONCERNS: A 24-year-old man presented with a mass in the medial part of the left upper arm that had been present for more than 20 years. In the previous 1 year prior to admission, the mass had grown significantly. Physical examination showed cafe-au-lait spots of variable sizes throughout the body and multiple masses in the medial part of the left upper arm. Three months later after the resection of the masses, the patient was readmitted to our department due to tumor recurrence. Two months after the extended resection, in situ recurrence of the tumor was noted again. Four months after the operation and the administration of radiotherapy, a mass was found in the outside of the left upper arm.
DIAGNOSIS: Immunohistochemical staining showed the masses were positivity for vimentin, CD34, and S100; the tumor cells were negative for PGP9.5, CD57, EMA, and SMA. The Ki-67 labeling index was approximately 40%. A diagnosis of malignant peripheral nerve sheath tumor was made.
INTERVENTIONS: Surgical resection was performed for both the primary tumors and the 2 subsequent recurrence tumors. The patient underwent radiotherapy with 60 Gy in 30 fractions after the third operation. Four months after the administration of radiotherapy, the patient underwent tumorectomy of a mass in the outside of the left upper arm.
OUTCOMES: During the 4-month follow-up after the fourth operation, the patient's condition was stable.
LESSONS: Malignant peripheral nerve sheath tumor in NF1 is an exceedingly rare entity that poses a great diagnostic challenge. High-frequency ultrasound can support the diagnosis.

Carbone M, Vittoria F, Del Sal A
Treatment of early-onset scoliosis with growing rods in patients with neurofibromatosis-1.
J Pediatr Orthop B. 2019; 28(3):278-287 [PubMed] Related Publications
This study aimed at verifying the efficacy of growing rod treatment in patients affected by neurofibromatosis with early-onset scoliosis. The authors present a retrospective case study of seven children treated between 2001 and 2017. Mean age at initial surgery was 7.2 years. Mean Cobb angle was 82.7°. Lengthening was performed once a year. Mean Cobb angle at last follow-up was 50.1°. Mean spinal growth was 13.6 mm/year, with regular gain during lengthening procedures. Mean follow-up period was 7 years after the first surgery. Three patients underwent final fusion. Complications were one proximal junctional kyphosis, nine rod breakages, and one hook dislocation.

Trevisson E, Morbidoni V, Forzan M, et al.
The Arg1038Gly missense variant in the NF1 gene causes a mild phenotype without neurofibromas.
Mol Genet Genomic Med. 2019; 7(5):e616 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by inactivating mutations of the NF1 gene. The wide allelic heterogeneity of this condition, with more than 3,000 pathogenic variants reported so far, is paralleled by its high clinical variability, which is observed even within the same family. The definition of genotype-phenotype correlations has been hampered by the complexity of the NF1 gene and, although a few exceptions have been recognized, the clinical course remains unpredictable in most patients.
METHODS: Sequencing of NF1 in patients with cafè-au-lait spots identified the c.3112A>G variant. RNA analysis and a minigene assay were employed to investigate splicing.
RESULTS: Here we report a novel genotype-phenotype correlation in NF1: the identification of the missense variant NM_000267.3:c.3112A>G p.(Arg1038Gly) in seven individuals from two unrelated families with a mild phenotype. All the patients manifest cafè-au-lait spots without neurofibromas or other NF1-associated complications, and Noonan syndrome features in most cases. The missense variant was not previously reported in available databases, segregates with the phenotype and involves a highly conserved residue. Both a minigene assay and patient's RNA analysis excluded an effect on splicing.
CONCLUSION: Our data support the correlation of the p.Arg1038Gly missense substitution with the cutaneous phenotype without neurofibromas or other complications. This finding may have relevant implications for patients and genetic counseling, but also to get insights into the function of neurofibromin.

Sampson J, Thompson HL, Parilo DMW
Caring for children with neurofibromatosis type 1.
Nursing. 2019; 49(4):30-36 [PubMed] Related Publications
This article discusses the variable physical manifestations of neurofibromatosis type 1 among children in terms of presentation, disease severity, and prognosis, and addresses appropriate nursing interventions and patient teaching.

Moramarco A, Lambiase A, Mallone F, et al.
A characteristic type of retinal microvascular abnormalities in a patient with Neurofibromatosis type 1.
Clin Ter. 2019 Jan-Feb; 170(1):e4-e9 [PubMed] Related Publications
This study aims to describe a typical retinal microvascular abnormality in patients with neurofibromatosis type 1 (NF-1). A 64-year-old man with diagnosis of NF-1 was evaluated by complete ophthalmological examination, including fluorescein angiography and spectral Domain OCT in Near-Infrared (NIR-OCT) modality. Slit lamp exam showed the presence of more than 10 Lisch nodules for each eye. Ophthalmic examinations and NIR-OCT scans showed the presence of retinal tortuous vessels ending in a 'puff of smoke' arrangement. The clinical significance as diagnostic and prognostic factor of this novel type of retinal microvascular abnormality in NF-1 should be further investigated.

Margraf RL, VanSant-Webb C, Mao R, et al.
NF1 Somatic Mutation in Dystrophic Scoliosis.
J Mol Neurosci. 2019; 68(1):11-18 [PubMed] Related Publications
Scoliosis is a common manifestation of neurofibromatosis type 1, causing significant morbidity. The etiology of dystrophic scoliosis in neurofibromatosis type 1 is not fully understood and therapies are lacking. Somatic mutations in NF1 have been shown in tibial pseudarthrosis providing rationale for similar processes in neurofibromatosis type 1-associated dystrophic scoliosis. Spinal samples from surgical procedures with matched peripheral blood of two individuals with neurofibromatosis type 1 and dystrophic scoliosis were obtained and DNA extracted. Next generation sequencing of various spinal sections as well as the germline/blood sample were performed using a RASopathy gene panel (includes the NF1 gene). Variants were compared between the spinal tissue samples and the germline data. In addition, the next generation sequencing allele frequency data were used to detect somatic loss of heterozygosity. All samples had a detected potentially inactivating NF1 germline mutation. Both individuals demonstrated an allelic imbalance inclusive of NF1 in the next generation sequencing data. In addition, for the same two individuals, there was an increase in the % variant reads for the germline mutation in some of the surgical spinal samples corresponding to the allelic imbalance. Contra analysis did not show any deletion in Chromosome 17 next generation sequencing data. Microarray analysis verified somatic copy neutral loss of heterozygosity for these two individuals for the majority of the chromosome 17 q-arm, inclusive of the NF1 gene. These results suggest that the cause of dystrophic scoliosis is multifactorial and that a somatic NF1 mutation contributes to the etiology.

Bulgheroni S, Taddei M, Saletti V, et al.
Visuoperceptual Impairment in Children with NF1: From Early Visual Processing to Procedural Strategies.
Behav Neurol. 2019; 2019:7146168 [PubMed] Free Access to Full Article Related Publications
Visual-spatial impairment has long been considered a hallmark feature of neurofibromatosis type 1 (NF1). No study investigating the cognitive and neuropsychological profile of NF1 used the Rey Complex Figure Test (RCFT) task as the primary measure of visual-perceptual abilities taking into consideration all functions involved including the strategic processing style. We compared 18 children with NF1, 17 siblings (S), and 18 typically developing children (TD) at intelligence scale and RCFT copy, recall, and recognition trials; we also evaluated the copy strategy as a measure of a visual-processing style. Children with NF1 had normal total IQ, with cognitive weaknesses in the perceptual organization and working memory in line with the existing literature. At the RCFT copy, immediate and delay recall scores are significantly lower in NF1 than S and TD, while recognition is in the normal range in all groups. Copy style was poor and less efficient in children with NF1 and correlated to copy and recall ability, but the effect of the group in the RCFT copy and recall remained significantly controlling for strategic approach. The present study confirms visuospatial impairment in children with NF1, due to a deficit in perceptual analysis of shape and their spatial features, in visuomotor integration efficiency and strategies, in recall memory, while recognition memory is preserved. A more configural/holistic style may facilitate both the visual-perceptual and visuomotor ability and the recall process. Visuoperceptual impairment in NF1 seems to be a unified process from early visual processing to higher order functions (planning, strategy, and executive functioning).

Mehlan J, Schüttauf F, Salamon JM, et al.
Manifestations and Treatment of Adult-onset Symptomatic Optic Pathway Glioma in Neurofibromatosis Type 1.
Anticancer Res. 2019; 39(2):827-831 [PubMed] Related Publications
This report describes the diagnosis and treatment of a 27-year-old patient with neurofibromatosis 1 (NF1) and late progression of a pre-existing optic pathway glioma (OPG) that caused significant reduction in vision. OPG is one of the diagnostic criteria for establishing the diagnosis of NF1. Most common findings of NF1 are café-au-lait spots, axillary and inguinal freckling of the skin, iris hamartoma (Lisch nodules), and tumors of the central nervous system and peripheral nerves. We successfully applied a modified International Society of Paediatric Oncology chemotherapy regimen for low-grade glioma in children with carboplatin dose adjustment according to the area under the plasma drug concentration-time curve calculation. During and after the chemotherapy, a clear improvement of the visual capacity was achieved. Age-adapted chemotherapy for symptomatic adult-onset OPG in patients with NF1 should be considered in individual cases.

Shen Z, Wang N, Shi W, et al.
Atypical teratoid rhabdoid tumor mimicking type II neurofibromatosis: A case report.
Medicine (Baltimore). 2019; 98(5):e14308 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Brain magnetic resonance imaging (MRI) images of atypical teratoid rhabdoid tumor (ATRT) often present heterogeneous signals of various cells without remarkable features of the disease. We describe a unique case of atypical brain MRI images presenting as an type II neurofibromatosis and explore some diagnostic hints.
PATIENT CONCERNS: A 1-year-and-7-month-old boy admitted to our department with a 7-day history of drowsiness and 2-day history of emesis, and his presenting complaint was repeated vomit. On physical examination, he had drowsiness, positive sun set sign, slow light reflection, high muscular tension of limbs and 55 cm head circumference. MRI presented masses of bilateral auditory nerve distribution area, the fourth ventricle and right frontal lobe, obstructive hydrocephalus, and amplified cisterna magna. Particularly, dumbbell shape tumor in left cerebellopontine angle area and the fourth ventricle showed iso- or hypo-intensity on T1-weighted image and mix-intensity on T2-weighted image with irregular frontier, obvious mutual high and low signal on T2-weighted image, and growing along cerebrospinal fluid pathway.
DIAGNOSIS: The diagnosis of type II neurofibromatosis (NF-II) was considered pre-operatively. After surgery, postoperative histopathology confirmed the diagnosis of ATRT.
INTERVENTIONS: After ventriculo-peritoneal (VP) shunt, no evidence of tumor was inspected in cerebrospinal fluid, and enhancement MRI showed heterogeneous contrast signal on dumbbell shape tumor. We executed an incomplete microsurgery for dumbbell shape lesion in left auditory nerve distribution area and the fourth ventricle for differential diagnosis and facilitating further treatment.
OUTCOMES: The patient did not recover well postoperatively and suffered from severe pulmonary infection. Refusing further intervention in view of poor prognosis of ATRT, the patient was transferred to another hospital for rehabilitation care. The patient died from progressive tumor and respiratory failure after 2 months.
LESSONS: The diagnosis of ATRT can be challenging, in our case due to the disturbance of bilateral auditory nerve distribution area tumors. Under MRI, Irregular frontier, obvious mutual high and low signal on T2-weighted image, growing along cerebrospinal fluid pathway, and heterogeneous contrast enhancement should lead the clinician to strongly consider ATRT.

Kundu R, Gupta S, Kaushik R, et al.
Isolated giant ileal neurofibroma sans neurofibromatosis.
Indian J Cancer. 2018 Jul-Sep; 55(3):301-303 [PubMed] Related Publications
Neurofibromas are benign neoplasms that are usually seen in hereditary disorders such as von Recklinghausen's disease [neurofibromatosis type 1 (NF1)]. The occurrence of isolated ileal neurofibroma in patients without the classic manifestations of NF1 or multiple endocrine neoplasia (MEN) syndromes is an extremely rare entity . We report one such case of isolated ileal neurofibroma in a 60 year old woman without any other stigmata of NF. It may be the initial manifestation of NF1 or MEN 2b or malignant transformation, all of which necessitate further follow-up of these patients.

Ho CY, Deardorff R, Kralik SF, et al.
Comparison of multi-shot and single shot echo-planar diffusion tensor techniques for the optic pathway in patients with neurofibromatosis type 1.
Neuroradiology. 2019; 61(4):431-441 [PubMed] Related Publications
PURPOSE: Diffusion tensor imaging (DTI) may be helpful in assessing optic pathway integrity as a marker for treatment in neurofibromatosis type 1 (NF1) patients with optic gliomas (OG). However, susceptibility artifacts are common in typical single-shot echo planar imaging (ssDTI). A readout-segmented multi-shot EPI technique (rsDTI) was utilized to minimize susceptibility distortions of the skull base and improve quantitative metrics.
METHODS: Healthy controls, children with NF1 without OG, and NF1 with OG ± visual symptoms were included. All subjects were scanned with both rsDTI and ssDTI sequences sequentially. Diffusion metrics and deterministic fiber tracking were calculated. Tract count, volume, and length were also compared by a two-factor mixed ANOVA.
RESULTS: Five healthy controls, 7 NF1 children without OG, and 12 NF1 children with OG were imaged. Six OG patients had visual symptoms. Four subjects had no detectable optic pathway fibers on ssDTI due to susceptibility, for which rsDTI was able to delineate. Tract count (p < 0.001), tract volume (p < 0.001), and FA (P < 0.001) were significantly higher for rsDTI versus ssDTI for all subjects. MD (p < 0.001) and RD (p < 0.001) were significantly lower for rsDTI vs ssDTI. Finally, MD, AD, and RD had a significantly lower difference in NF1 children with visual symptoms compared to NF1 children without visual symptoms only on ssDTI scans.
CONCLUSION: DTI with readout-segmented multi-shot EPI technique can better visualize the optic pathway and allow more confident measurements of anisotropy in NF1 patients. This is shown by a significant increase in FA, tract count, and volume with rsDTI versus ssDTI.

Funes CJ, Zale EL, Luberto CM, Vranceanu AM
Home practice and quality of life among patients with neurofibromatosis randomized to a mind-body intervention.
Complement Ther Med. 2019; 42:114-118 [PubMed] Related Publications
OBJECTIVES: The purpose of this study was to summarize home practice in patients with neurofibromatosis (NF) randomized to an 8-week group mind-body intervention, the Relaxation Response Resiliency Program for NF (3RP-NF). We further examined the association between home practice and changes in four domains of quality of life (QoL).
METHODS: Data are derived from a single-blind RCT of the 3RP-NF (N = 31) delivered via videoconferencing versus an attention placebo control. 3RP-NF participants submitted weekly home practice logs to the group leader prior to each weekly session, which included information regarding their engagement of relaxation response (RR)-eliciting skills and appreciation skills. Physical, psychological, social and environmental QoL were measured at baseline, post-intervention and at a 6-months follow up.
RESULTS: Participants reported engaging in home practice of RR-eliciting skills on average 28.55 days (SD = 10.79) and appreciation skills on average 24.39 days (SD = 13.48) over the 49-day treatment period. Participants reported an average of 383.42 (SD = 274.38) minutes of RR-eliciting skills home practice and an average of 49.13 (SD = 41.90) appreciations skills home practice. A significant association was observed between frequency of RR-eliciting skills home practice and physical QoL at the 6-month follow-up (r = .383, p = .034).
CONCLUSIONS: Participants with NF are able and willing to practice RR-eliciting skills and appreciation skills outside of treatment sessions. Frequency of RR-eliciting skills home practice may be associated with improvement in physical QoL. Future research should replicate these efforts with larger samples, and attempt to identify additional factors that predict optimal response to mind-body interventions other than home practice.

Linehan A, Harrold E, Pilson K, McCaffrey J
Recurrent vulvar melanoma in a patient with neurofibromatosis and gastrointestinal stromal tumour.
BMJ Case Rep. 2019; 12(1) [PubMed] Related Publications
We report a case of a 51-year-old woman with neurofibromatosis who presented in 2012 with postmenopausal bleeding. Excision biopsy of a pigmented lesion of the labia minora was consistent with an ulcerated vulvar BRAF wild type malignant melanoma (MM). Initial excision was followed by radical vulvectomy and adjuvant interferon. Local recurrence in January 2017 was further resected. Positron emission tomography (PET)-CT in May 2017 identified an FDG avid omental deposit; consistent histologically with MM when resected. Postoperative PET-CT in August 2017 demonstrated local recurrence. In the setting of resected stage IV disease and a third local recurrence, the decision was made to instigate immunotherapy. Vulvar melanoma is rare accounting for 0.2% of all melanoma. Presentation is typically a decade later than cutaneous melanoma with a tendency to late metastases and poorer prognosis. Given their rarity the treatment paradigm is less clearly defined and largely extrapolated from that of cutaneous melanomas.

Guo C, Chen L, Qu Y, Hu X
Novel Three-Dimensional Morphometry to Reassess Orbit Deformities Associated With Orbital-Periorbital Plexiform Neurofibroma.
J Craniofac Surg. 2019 Mar/Apr; 30(2):e147-e151 [PubMed] Related Publications
BACKGROUND: Orbit deformities are usually found in neurofibromatosis type 1 patients, especially those with orbital-periorbital plexiform neurofibroma (OPPN). Unfortunately, current morphometry is complicated and, in some cases, cannot be performed on the deformed orbit due to the destruction of landmarks. Herein, we present a novel 3-dimensional (3D) morphometry for these orbital measurements.
METHODS: We retrospectively reviewed 29 patients with OPPN, and another 29 disseminated cutaneous neurofibroma patients served as controls. All patients had undergone craniofacial computed tomography and 3D reconstruction. New morphometry was used to measure the area of the orbital rim (OR) and superior orbital fissure (SOF).
RESULTS: For the 29 patients with OPPN, the area of the OR at the affected side was 14.18 ± 3.50 cm, while the OR at the nonaffected side was 12.32 ± 1.38 cm. In addition, the area of the SOF at the affected side was 5.37 ± 5.75 cm, while that at the nonaffected side was 1.27 ± 1.03 cm. The OR and SOF at the affected side are more likely to become enlarged compared with those at the nonaffected side. Among the 29 patients with OPPN, the novel morphometry could be performed in 19 cases (65.5%) that cannot be measured by previous morphometry.
CONCLUSION: The novel morphometry is convenient and reproducible, which optimizes its application in pathologic cases, especially those involving deformed orbits.

Thavaraputta S, Graham S, Rivas Mejia AM, Lado-Abeal J
Duodenal somatostatinoma presenting as obstructive jaundice with the coexistence of a gastrointestinal stromal tumour in neurofibromatosis type 1: a case with review of the literature.
BMJ Case Rep. 2019; 12(1) [PubMed] Related Publications
Somatostatinomas are rare neuroendocrine tumours, mostly located in the pancreas or duodenum, with an estimated incidence of 1 in 40 million. Duodenal somatostatinomas (DSs) are usually found in association with neurofibromatosis type 1 (NF1), tuberous sclerosis and Von Hippel-Lindau syndrome. Gastrointestinal stromal tumours (GIST) have also been described in NF1, but the association with somatostatinoma is very uncommon. We report the case of a patient with NF1 who presented with obstructive jaundice due to multiple firm nodules around the ampulla of Vater. A pancreaticoduodenectomy was performed and revealed a 1 cm duodenal/ampullary mass which stained positive for somatostatin, together with a GIST also found on the duodenal wall. Despite its rarity, ampullary somatostatinomas should be considered in the differential diagnosis of biliary tract dilation in patients with NF1.

Chen J, Landegger LD, Sun Y, et al.
A cerebellopontine angle mouse model for the investigation of tumor biology, hearing, and neurological function in NF2-related vestibular schwannoma.
Nat Protoc. 2019; 14(2):541-555 [PubMed] Free Access to Full Article Related Publications
Neurofibromatosis type II (NF2) is a disease that lacks effective therapies. NF2 is characterized by bilateral vestibular schwannomas (VSs) that cause progressive and debilitating hearing loss, leading to social isolation and increased rates of depression. A major limitation in NF2 basic and translational research is the lack of animal models that allow the full spectrum of research into the biology and molecular mechanisms of NF2 tumor progression, as well as the effects on neurological function. In this protocol, we describe how to inject schwannoma cells into the mouse brain cerebellopontine angle (CPA) region. We also describe how to apply state-of-the-art intravital imaging and hearing assessment techniques to study tumor growth and hearing loss. In addition, ataxia, angiogenesis, and tumor-stroma interaction assays can be applied, and the model can be used to test the efficacy of novel therapeutic approaches. By studying the disease from every angle, this model offers the potential to unravel the basic biological underpinnings of NF2 and to develop novel therapeutics to control this devastating disease. Our protocol can be adapted to study other diseases within the CPA, including meningiomas, lipomas, vascular malformations, hemangiomas, epidermoid cysts, cerebellar astrocytomas, and metastatic lesions. The entire surgical procedure takes ~45 min per mouse and allows for subsequent longitudinal imaging, as well as neurological and hearing assessment, for up to 2 months.

Wang Y, Li P, Wang B, et al.
Identification of myeloid-derived suppressor cells that have an immunosuppressive function in NF2 patients.
J Cancer Res Clin Oncol. 2019; 145(2):523-533 [PubMed] Related Publications
PURPOSE: There is no targeted drug therapy for NF2 patients, and surgery or radiosurgery is not always effective. Therefore, the exploration of new therapeutic pathways is urgently needed.
METHODS: We analyzed the expression of cytokines in the serum of NF2 patients and determined the percentage of HLA-DR
RESULTS: NF2 patients are in an immunosuppressed state with elevated IL-10 and TGF-β expression in plasma and the lymphocytes from NF2 patients secrete less IFN-γ and CD3

Su XJ, Li Q, Shen HX
Arteriovenous Fistula Inside Cervical Spinal Canal Associated with Neurofibromatosis Type 1.
World Neurosurg. 2019; 123:283-285 [PubMed] Related Publications
BACKGROUND: Neurofibromatosis type 1 (NF-1) is an autosomal dominant disease caused by mutation on chromosome 17, which affects the skin, vascular system, nervous system, and skeleton system. Arteriovenous fistula (AVF) is one of the recognized complications of NF-1.
CASE DESCRIPTION: We report a case of a 33-year-old woman with NF-1 with cervical spine AVF inside the cervical spinal canal who presented with progressive spinal cord compression which was abnormal. After sufficient preparation, the patient underwent vascular embolization, and then symptoms of spinal cord compression significantly improved.
CONCLUSIONS: This report reminds readers of the possibility of AVF if there is a space-occupying lesion inside the cervical spinal canal and to do computed tomography angiography examination when necessary.

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