Optic Glioma Research Articles

Primary Tumours of The Optic Disc and The Optic Disc Sheath

Primary optic nerve and optic nerve sheath tumors constitute approximately 8% of intraorbital tumors and although most of them are benign, they are manifested by findings that significantly affect visual function such as vision loss, visual field defect and proptosis. Tumors originating from the optic nerve trunk are mostly benign optic nerve glioma, but rarer tumors such as ganglioglioma, medulloepithelioma, hemangioblastoma, melanocytoma and high-grade glioblastomas such as malignant optic nerve glioma can also be detected. Tumors originating from the optic nerve sheath usually have optic nerve sheath meningioma (ONSM), of those with intraorbital and intracanalicular origin are classified as primary and intracranial ONSMs are classified as secondary tumors. Optic glioma, ONSM, and hemangioblastomas can be seen sporadically or as a component of Type 1 and Type 2 Neurofibromatosis (NF) and Von Hippel-Lindau (VHL) syndromes, respectively. Treatment with systemic chemotherapy, surgical resection and radiotherapy methods should be considered when progressive vision loss, visual field defect and cosmetically intolerable proptosis develop in optic nerve and nerve sheath tumors, which can have a quiet course for years in terms of visual function. While systemic chemotherapy is accepted as the main treatment method in optic gliomas, more successful results are obtained with specialized treatment methods such as stereotactic fractionated radiotherapy in ONSMs.

SAT613 A Novel NF1 Mutation As The Underlying Cause Of Dysmorphic Features And Acromegaly In An Atypical Case Of Neurofibromatosis Type 1

Abstract Disclosure: O. Alsagheir: None. L.A. Alobaid: None. M. Alswailem: None. H. Al-Hindi: None. A.S. Alzahrani: None. Introduction: Neurofibromatosis type 1 is an autosomal dominant disease with an estimated incidence of about 1:2000 cases. It is caused by genetic alterations in the gene NF1 encoding the tumor suppressor gene, neurofibromin. Patients with neurofibromatosis 1 are at an increased risk of a number of benign and malignant tumors including optic nerve gliomas, CNS tumors, malignant peripheral nerve sheath tumors, pheochromocytomas and many others. However, pituitary adenomas have been rarely described in neurofibromatosis type 1 and NF1 mutations have been found rarely in patients without manifestations of neurofibromatosis. In this report, we describe a patient with acromegaly who had some dysmorphic features but no clear skin or other manifestations of neurofibromatosis. He was found to have a deletion mutation in NF1 suggesting that his dysmorphic features and acromegaly are atypical manifestations of a previously undiagnosed neurofibromatosis type 1. Case Description: A 26-year-old-man presented at 18 years of age for evaluation of possible ventricular septal defect, which was ruled out by echocardiography, but he was found to have a subaortic membrane with moderate aortic regurgitation. He was also noticed to have coarse facial and body features which raised the possibility of acromegaly. He didn’t notice any facial changes, change in the size of hands and feet, headache or visual disturbances. In the family history, he reported that a number of his siblings are tall with large body habitus; none of them was evaluated or known to have medical illness. Physical examination: height 184 cm, weight 87 Kg, BMI 25, and BP 117/77 mmHg. He has frontal bossing, large supraorbital ridges, macrognathia, and hoarse deep voice but no skin tags, café au let spots, skin fibromas or freckling. Eye examination was unremarkable. Investigations: IGF-1 415 ng/ml (188-400), random GH 1.09 ng.ml (0.1-1.2). An oral glucose tolerance test showed baseline GH 0.99 increased to 8.05 ng/ml. An MRI of the pituitary gland showed a lobulated sellar and suprasellar heterogeneously enhancing pituitary adenoma. A Gallium 68 PET-CT scan showed an intense focus of uptake at the same location. Whole exome sequencing revealed a heterozygous NF1 mutation (NM_001128147.3: c.1782_*2del). This variant is likely pathogenic according to ACMG criteria. Conclusion: This case illustrates the value of whole exome sequencing for genetic testing in diagnosing atypical dysmorphia and other conditions when the diagnosis is not clear on clinical evaluation or conventional investigations. It also describes a rare association of acromegaly with neurofibromatosis. Presentation: Saturday, June 17, 2023

Regos nervo glioma

Optic nerve glioma (ONG) is usually a low-grade tumor of the optic nerve. ONG can affect not only the optic nerve, but also the optic nerve chiasma and optic nerve tract. ONG can be classified as associated with neurofibromatosis type 1 (NF1) or sporadic ONG. Sporadic gliomas are more commonly diagnosed in adults, have an aggressive course, and are known to have a poor outcome. The disease can be asymptomatic. ONG often causes visual disturbances such as reduced visual acuity, visual field defects, and impaired color vision; due to the tumor mass effect, proptosis, strabismus, and diplopia are possible. As the disease progresses, various neurological symptoms can appear, including headache, hemiplegia, and endocrine disorders such as early maturation, growth hormone hypersecretion, or deficiency. A presumed diagnosis is based on clinical presentation and neuroimaging findings. Meanwhile, biopsy should be avoided due to the high probability of optic nerve damage. Treatment is individual for each patient, but remains controversial to this day. Thus, in this article, we review the prevalence, clinic, diagnostic and treatment options of ONG.

Evaluation of Neurofibromatosis Type 1 Associated Optic Pathway Gliomas

Background/Aims: Optic pathway gliomas (OPGs) are low-grade gliomas histologically represented by pilocytic astrocytoma (PA) in 90% of cases, can develop from any part of the visual pathways such as optic nerve, chiasm, optic tract, or optic radiations which frequently involve the hypothalamus. OPGs account for 3–5% of childhood central nervous system (CNS) tumors and about 2% of pediatric glial lesions. OPGs are believed to be the most prevalent intracranial tumor in patients with neurofibromatosis type 1 (NF-1) and can occur in 15–20% of NF-1 cases. The aim of this study is to evaluate the clinical features and treatment response in patients diagnosed with optic glioma and NF-1.
 Methods: All cases diagnosed with OPG and received treatment in the Pediatric Oncology Department, between January 2015 to January 2021 were retrospectively evaluated. Inclusion criteria include children and adolescents with OPG aged between 0 and 18 years. The medical records (gender, age, tumor entity, tumor location) of patients, as well as their treatment history and magnetic resonance imaging (MRI) scans, were examined. The diagnosis of OPG was made clinically and radiologically by the tumor board. The recommendations of the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group were used in the diagnosis and evaluation of treatment response. Patients received intravenous chemotherapy with SIOP LGG 2004 (vincristine- carboplatin) with or without bevacizumab (10 mg/kg, started every 2 weeks), therapy or vinblastine (3 mg/m2, weekly). 
 Results: This study included 27 cases during the study period from January 2015 to January 2021. In this study there were 14 male (51.8 %) and 13 female (48.1 %) patients. The median age was 4.8 (range: 0.5–14.9) years. Biopsy was performed in three patients and the diagnosis was low-grade glioma (pilocytic astrocytoma) for all of them. Chemotherapy was administered to 22 cases in total. Twelve patients received vincristine-carboplatine, 5 patients received vincristine-carboplatin with bevacizumab and 5 patients received vinorelbine. Radiological response was evaluated in all 22 patients at 3 months MRI. No patient had a radiological complete respons, 11 patients (50%) had partial response, 2 patients (9%) presented with a progressive disease, showing an increase in measurements of 35% and 9 patients(40.9%) had stable disease at the 3-month evaluation.
 Conclusions: Systemic and visual problems play a significant role in the selection of treatment for pediatric patients with optic gliomas. An essential treatment option for improving symptoms and reducing tumor size is systemic chemotherapy. A crucial therapy option for enhancing vision is bevacizumab for the patients with NF-associated OPG.

Evaluation of Molecular and Clinical Findings in Children With Neurofibromatosis Type 1: Identification of 15 Novel Variants

BackgroundNeurofibromatosis 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. MethodsThe 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. ResultsA 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. ConclusionsThis 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.

Assessment of Ecotropic Viral Integration Site 2B (EVI2B) Gene in Juvenile Myelomonocytic Leukemia and Neurofibromatosis Type 1 NF1 Tumors.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that affects the development and growth of various tissues. NF1 is a major risk factor for the development of malignancies, particularly malignant peripheral nerve sheath tumors, optic gliomas, and leukemia. NF1 encodes a neurofibromin. Three genes, EVI2A, EVI2B, and OMGP, are embedded within intron 27b of NF1. However, the function of these genes remains unclear. EVI2A and EVI2B encode for putative transmembrane proteins. Mouse homologs are associated with viral insertions involved in leukemia in mice. Mouse Evi2b has been identified as a direct target gene of C/EBPα, a transcription factor critical for myeloid differentiation. Also possible is that these genes are related to the leukemia observed in patients with NF1. These genes might act as modifiers of NF1 phenotypic variations. Therefore, we investigated the EVI2B gene in leukemia and NF1 tumors. We analyzed DNA from 10, 20, and 3 patients with NF1, leukemia, and NF1-leukemia, respectively, and six NF1 tumor tissues. DNA sequencing analysis was used to identify the viral integration sequence, and the protein amounts and EVI2B gene expression were analyzed by flow cytometry and quantitative real-time PCR techniques. The EVI2B gene expression was increased in cutaneous neurofibroma compared with the control both at the level of protein and mRNA. However, its expression in plexiform neurofibroma was decreased significantly at protein level and increased at mRNA level compare to control. Moreover, integration of 455 bases near the 3' end of the exon was detected. When this integrated sequence was blasted into the NCBI retroviral genome database, an 87% match with the HIV-1 virus envelope gene was obtained. These preliminary results show that EVI2B might be important in NF1 tumorigenesis and leukemia.

RETINAL DIALYSIS AND ASSOCIATED RHEGMATOGENOUS RETINAL DETACHMENT IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 1: A CASE SERIES.

Although ophthalmic manifestations of neurofibromatosis Type 1 (NF1), including iris Lisch nodules and optic gliomas, have been well described, retinal involvement in these patients has yet to be established. Characterizing the relationship between NF1 and the retina is necessary to optimize outcomes for these patients. Independent chart review of NF1 patients was conducted. Chart review yielded four patients, with a history of NF1, with subsequent retinal dialysis and rhegmatogenous retinal detachment. These four patients presented to our institution with a rhegmatogenous retinal detachment secondary to a retinal dialysis with no history of trauma. These patients also demonstrated hyperreflective choroidal abnormalities on near-infrared reflectance imaging and optical coherence tomography. Seeing that patients diagnosed with NF1 are susceptible to various ocular manifestations and pathological abnormalities, routine ophthalmic examinations are essential in maintaining their ocular health and minimizing morbidity.

Neurofibromatosis Type 1-Associated Optic Pathway Gliomas: Current Challenges and Future Prospects.

Optic pathway glioma (OPG) occurs in as many as one-fifth of individuals with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Generally considered low-grade and slow growing, many children with NF1-OPGs remain asymptomatic. However, due to their location within the optic pathway, ~20-30% of those harboring NF1-OPGs will experience symptoms, including progressive vision loss, proptosis, diplopia, and precocious puberty. While treatment with conventional chemotherapy is largely effective at attenuating tumor growth, it is not clear whether there is much long-term recovery of visual function. Additionally, because these tumors predominantly affect young children, there are unique challenges to NF1-OPG diagnosis, monitoring, and longitudinal management. Over the past two decades, the employment of authenticated genetically engineered Nf1-OPG mouse models have provided key insights into the function of the NF1 protein, neurofibromin, as well as the molecular and cellular pathways that contribute to optic gliomagenesis. Findings from these studies have resulted in the identification of new molecular targets whose inhibition blocks murine Nf1-OPG growth in preclinical studies. Some of these promising compounds have now entered into early clinical trials. Future research focused on defining the determinants that underlie optic glioma initiation, expansion, and tumor-induced optic nerve injury will pave the way to personalized risk assessment strategies, improved tumor monitoring, and optimized treatment plans for children with NF1-OPG.

Neurofibromatosis type 1, from gene mutation to clinical presentation

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with a prevalence of about1/3000. The clinical diagnosis of NF1 is based on the presence of two or more of the followingcriteria: six or more café au lait spots, >2 neurofibromas of any type, freckling in the axillary oringuinal region, optic glioma, a distinctive osseous lesion such as sphenoid dysplasia or thinning oflong bone cortex with or without pseudoarthrosis, and a first degree relative with NF1.We report A 7-year-old male with multiple café au lait spots diagnosed with Neurofibromatosisin Kigali-Rwanda by using next-generation sequencing and copy number variation analysis, thepatient presented with painless nodular skin lesions that first developed 4 years earlier. Skinnodules initially appeared on the anterior chest wall and progressed to the posterior chest wallextending to the axilla region. His medical history and that of his family were unremarkable. To ourknowledge, this is the first case to be diagnosed using this technology; The disease has numerouscomplications. The mutation rate for NF1-gene is high; 50% of all cases of NF1 are from newmutations. The gene protein product - neurofibromin plays an important role in tumor genesis asa tumor-suppressor gene.Combining both clinical findings and molecular genetic evaluation to identify disease-causingmutations is paramount in confirming the diagnosis. Patient care is best done in a multidisciplinarysetting approach for proper patient satisfaction and better prediction of future prognosis.

Is neurofibromatosis type 1 diagnosed in every patient who presents with café au lait macules? A single-center experience

Objective: Neurofibromatosis type 1 (NF1) is the most common hereditary neurocutaneous syndrome. The most crucial morbidity of
 NF1 is tumors that may develop. Cases with café-au-lait macules (CALMs) which is the first clinical finding of NF1, due to the anxiety
 of its associated morbidity, are referred to the pediatric oncology clinic. In this study, we aimed to examine the characteristics of the
 patients who applied to our outpatient clinic with CALMs.
 Patients and Methods: The data of 157 pediatric patients who applied to our institution with the diagnosis of CALMs between June
 2010 and November 2020 were analyzed retrospectively.
 Results: There were 157 pediatric cases referred to us for CALMs. According to the National Institutes of Health (NIH) diagnostic
 criteria, 109 (69.4%) cases were diagnosed with NF1. The diagnosis of 22 cases with NF1 were supported by genetic examination.
 Optic glioma was detected in 39 (24.8%) cases. In 15 (38.4%) of cases with optic glioma, visual functions were also affected. Second
 diagnostic criterion did not develop during the follow-up period, except for macules, in 48 cases (30.5%).
 Conclusion: In cases with multiple CALMs, the probability of NF1 diagnosis is high, and close and regular follow-up is of great
 importance in catching the development of the second clinical criterion and minimizing its morbidity.

Ophthalmic Manifestation in Neurofibromatosis Type 2

Neurofibromatosis type 2 (NF2) is a genetically determined tumor-predisposing syndrome. Ocular manifestations include cataracts, epiretinal membranes, retinal hamartomas, optic disk gliomas, and optic nerve sheath meningiomas. Moreover, optic disk edema, optical atrophy, motility disorders, pupil and lid dysfunction, and neurotrophic keratitis can be observed as indirect signs. An observational study was conducted with the aim to collect clinical data and describe the most frequent NF2 ocular manifestations. Fourteen patients affected by NF2, according to the Manchester criteria, were enrolled. All patients underwent complete ophthalmologic and orthoptic evaluation and a spectral domain optical coherence tomography. Ocular manifestations were present in all patients. The slit lamp evaluation of the anterior segment highlighted cataracts in five patients, keratitis in two patients, corneal leukoma in two patients, and corneal pannus in one patient. Fundus oculi and OCT evaluation identified epiretinal membranes in four patients, vitreoretinal tufts in three patients, optic nerve edema in one patient, and retinal hamartoma in one patient. Moreover, the orthoptic evaluation identified different types of ocular motility disorders in seven patients. This is a descriptive study of a rare disease with poor previous literature. Clinical data are shown, emphasizing the role of NF2-specific ophthalmological and orthoptic findings to help establish an early diagnosis.

Clinical and imaging characteristics of optic nerve tumors as the differencial diagnosis of optic neuritis

Objective: To investigate the clinical and imaging features of optic nerve tumors that require differential diagnosis from optic neuritis. Methods: A retrospective case series study was conducted. Clinical data of patients diagnosed with optic nerve tumors from January 2017 to December 2021 at the Second Affiliated Hospital of Zhejiang University School of Medicine were collected. A total of 29 patients (39 eyes) with clinical and magnetic resonance imaging (MRI) findings similar to optic neuritis or optic neuropathy were included. There were 15 cases of optic nerve sheath meningioma (ONSM) (17 eyes), 4 cases of optic nerve glioma (ONG) (5 eyes), and 10 cases of infiltrative optic nerve lesions (ION) (17 eyes). All patients underwent best-corrected visual acuity (BCVA), anterior and posterior segment examinations, visual field examination, and orbital or cranial MRI examination. Patient data were observed and analyzed, treatment and follow-up information were recorded, and clinical and imaging features were summarized and compared with those of optic neuritis or optic neuropathy. Results: Among the 29 patients with optic nerve tumors, 10 were male and 19 were female, with an average age of (43.3±13.8) years and a range of 11 to 72 years. The follow-up time was 6.8 (2.0, 11.0) months, with a range of 1 to 33 months. Sixteen patients (21 eyes) with optic nerve tumors were initially misdiagnosed as having acute optic neuritis and showed poor response to steroid treatment. Of these, 9 cases (11 eyes) were ONSM, 4 cases (6 eyes) were ION, and 3 cases (4 eyes) were ONG. The diagnostic delay time was 7.1 (1.5, 12.0) months, with a range of 1 to 24 months. The main clinical symptoms of all affected eyes were acute vision loss in 23 eyes, slow vision loss in 5 eyes, transient blackouts in 4 eyes, and no obvious visual symptoms in 7 eyes. The median BCVA of all affected eyes was 0.1, ranging from light perception to 1.0. Fundus examination results showed optic disc edema in 34 eyes and normal optic disc in 5 eyes among the 39 eyes with optic nerve tumors. A total of 27 patients (33 eyes) completed visual field examinations, which revealed an enlarged physiological blind spot in 11 eyes, a concentric or tubular visual field contraction in 8 eyes, a diffuse decrease in light sensitivity in 7 eyes, an arcuate scotoma in 4 eyes, and a normal visual field in 3 eyes. All affected eyes completed orbital or cranial MRI examinations, which showed mild optic nerve thickening in 22 eyes, significant thickening in 6 eyes with distortion, and no significant thickening in 6 eyes. Contrast-enhanced T1-weighted imaging (T1WI) MRI showed optic nerve parenchymal thickening in 5 eyes, all of which were ONG, and 2 of them had optic nerve parenchymal enhancement. Optic nerve sheath thickening and enhancement without optic nerve parenchymal thickening or enhancement were observed in 28 eyes, including 17 eyes of ION and 11 eyes of ONSM. There were 6 eyes with no obvious optic nerve thickening, which were all ONSM, showing mild or significant thickening and enhancement of the optic nerve sheath without optic nerve parenchymal thickening or enhancement. Conclusions: Optic nerve tumors can present with ophthalmic clinical features similar to optic neuritis, such as optic disc edema, and demonstrate MRI findings that resemble those of optic neuritis. Therefore, differentiation between the two is crucial, based on differences in their natural course and response to steroid therapy.

Strabismus and Exophthalmos in Children: Think of Optic Nerve Glioma

Introduction: Optic nerve gliomas are rare tumors that are mainly observed in children. Exophthalmos and strabismus are the main signs of the disease. Neuroimaging and in particular magnetic resonance imaging is of great help in the diagnosis and follow-up of these tumors. The therapeutic management of these gliomas involves different means: surgical removal, chemotherapy, radiotherapy or abstention under surveillance. The indications must be discussed on a case-by-case basis. We report in this work a case of optic nerve glioma revealed by a strabismus and a unilateral exophthalmos. Case Report: This is a 3-year-old girl from a non-consanguineous marriage, with no specific pathological ATCD, who presented with divergent strabismus with left exophthalmos evolving for 3 months. The ophthalmologic examination noted a constant wide-angle divergent strabismus on the left eye with moderate exophthalmos on the same side. Corrected visual acuity was reduced to near finger count on the left and 5/10 on the right. Somatic examination found café au lait spots on the back and trunk. Cerebral CT showed a bilateral thickening of the optic nerves, fusiform and regular, more marked on the left, isodense to spontaneous contrast, homogeneously enhancing after injection of PDC. On the left, it is responsible for a downward refoulement of the eyeball with grade 1 exophthalmos. An MRI was ordered revealing a regular well-limited fusiform thickening of the optic nerves in T1 isosignal, intermediate in T2 and FLAIR, in diffusion hypersignal without ADC restriction, intensely and finely heterogeneous enhancing after injection of contrast medium. This thickening is responsible for a grade I left exophthalmos, with widening of the optic canals posteriorly and filling of the intraconical fat evoking a glioma appearance. The child was referred to neurosurgery for management. Conclusion: The diagnosis of optic nerve glioma in children is rare, with atypical presentations both in terms .........

Saga of primary myxoid liposarcoma of the orbit

A 24-year-old female presented with proptosis and limitation of eye movements and was investigated radiologically with a tentative diagnosis of lymphangioma. Initial biopsy was considered to be in favor of optic glioma on histopathology, but immunohistochemistry was negative for Glial fibrillary acidic protein (GFAP). A year later, the patient reported back with worsening proptosis. She underwent exenteration of left eye for a posterior mass encasing the optic nerve. The final diagnosis of myxoid liposarcoma was rendered on excision biopsy. The difficulties experienced in establishing diagnosis are shared in this case report.

In childhood, a different electrode placement improves the recording of pattern reversal visual evoked potentials.

In childhood, a different electrode placement improves the recording of pattern reversal visual evoked potentials.

Advances in Targeted Therapy for Neurofibromatosis Type 2 (NF2)-Associated Vestibular Schwannomas.

Neurofibromatosis 2 (NF2) is an autosomal-dominant genetic disorder characterized by bilateral vestibular schwannomas (VS), meningiomas, ependymomas, spinal and peripheral schwannomas, optic gliomas, and juvenile cataracts. Ongoing studies provide new insight into the role of the NF2 gene and merlin in VS tumorigenesis. As NF2 tumor biology becomes increasingly understood, therapeutics targeting specific molecular pathways have been developed and evaluated in preclinical and clinical studies. NF2-associated VS are a source of significant morbidity with current treatments including surgery, radiation, and observation. Currently, there are no FDA-approved medical therapies for VS, and the development of selective therapeutics is a high priority. This manuscript reviews NF2 tumor biology and current therapeutics undergoing investigation for treatment of patients with VS.

Could primary hyperparathyroidism develop in cases with neurofibromatosis type-1-associated pheochromocytoma: Two cases with pheochromocytoma gene panel analysis

Abstract Introduction Neurofibromatosis type-1 (NF-1) is an autosomal dominant genetic disorder. It is associated with the development of café-au-lait macules, axillary and/or inguinal frecklings, Lisch nodules, hypertension, osteoporosis, skeletal abnormalities, as well as benign and malignant tumors, such as optic gliomas, peripheral nerve sheet tumors, and rarely, pheochromocytomas. However, primary hyperparathyroidism is rarely documented in patients with bilateral pheochromocytomas associated with NF-1 and is typically linked to MEN-2 A syndrome. Here we present two cases of NF-1-associated bilateral pheochromocytomas who developed primary hyperparathyroidism during follow-up. Clinical case In 2010, diagnostic ultrasonography performed for abdominal pain in a 60-year-old female patient revealed an adrenal mass. Multiple neurofibromas, axillary freckling, café-au-lait macules, and lisch nodules were found on physical examination (Figure 1A, B, C, and D). A diagnosis of pheochromocytoma was confirmed by high urine metanephrines and a hyperintense, 35 x40 mm mass on T2 weighted MRI sequences. The patient underwent right adrenalectomy. One year later, a diagnosis of primary hyperparathyroidism was made based on the high serum levels of calcium and intact PTH, and low serum phosphorus levels (Table-1). Radiotracer uptake was seen on a parathyroid MIBI scan in the thyroid's right inferior area. During follow-up, a 50×51 mm mass, hyperintense on T2 weighted MRI sequences was discovered on the left adrenal gland (figure 1-E). A diagnosis of pheochromocytoma was confirmed by detecting high plasma metanephrine and normetanephrine levels. The patient underwent left adrenalectomy 5 years following the initial diagnosis. Clinical case A 64-year-old female patient was admitted due to recently developed hypercalcemia. She had previously undergone two successive adrenalectomies, 4 years apart in 1999 and 2003, and was confirmed to have bilateral pheochromocytomas by histopathological analysis. Multiple neurofibromas, axillary freckling, café-au-lait macules, and Lisch nodules were found on physical examination. A diagnosis of primary hyperparathyroidism was made by detecting high serum calcium, intact parathormone, and low serum phosphorus levels. The patient underwent a right parathyroidectomy in 2012. In both cases, a panel analysis of pheochromocytoma gene mutations was carried out. In cases 1 and 2, a heterozygous nonsense mutation (17q11.2, C.2023G>T (P.G675*) and a non-frameshift deletion (17q11.2 c.5036) in the NF-1 gene were respectively found. Both instances tested negative for genetic alterations for RET, FH, MAX, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM-127, and VHL. Conclusion The development of primary hyperparathyroidism in these two cases of pheochromocytomas associated with genetically confirmed NF-1 raises the possibility that primary hyperparathyroidism may develop in patients with NF-1-associated pheochromocytoma.

A RARE CASE OF OPTIC PATHWAY GLIOMA PRESENTING WITH LIMB WEAKNESS

Optic pathway gliomas(OPG) are low-grade neoplasms arising from the pre-cortical optic pathways. OPG can involve the optic nerve,optic chiasm,optic tracts,optic radiations,or the hypothalamus.Most commonly affecting children,they present usually with headache and vision related complaints .In this,we describe the a rare case of optic glioma presenting with limb weakness and role of MRI in it's diagnosis

Spontaneous regression of tumor in a girl with optic pathway glioma with diencephalic syndrome.

Spontaneous regression of tumor in a girl with optic pathway glioma with diencephalic syndrome.

Ocular gamut of neurofibromatosis type 1

Background: Neurofibromatosis type 1 (NF1) is a multi-system autosomal dominant disorder affecting 1 in 3000 individuals. The diagnostic criteria of NF1 includes ocular manifestations. Objective: To study the ophthalmic manifestations of neurofibromatosis type 1 and evaluate complications, if any. Methodology: A total of 30 eyes of 15 neurofibromatosis cases presenting to the ophthalmology outpatient department (OPD) underwent a detailed ocular examination, and clinical manifestations in each case were analyzed. Results: Lisch nodules were the most common presentation. Twenty-eight eyes of 14 patients had bilateral and one had unilateral presentation. Six eyes of three patients had ectropion uveae, one eye had plexiform neurofibroma, and one eye had pulsatile proptosis with absence of lesser wing of sphenoid. Other manifestations seen were optic nerve glioma, secondary optic atrophy, closed angles with raised intraocular pressure (IOP), medullated nerve fiber and retinal pigment epithelium (RPE) atrophic changes. Conclusion: This case series represents a spectrum of ocular manifestations of NF1 and highlights the importance of ocular examination and regular follow-up in these patients.