Optic Pathway Gliomas Research Articles

Clinical and radiological features of orbito-temporal neurofibromatosis

Neurofibromatosis- 1 (NF- 1) is an autosomal dominant condition belonging to the well-known group of neurocutaneous syndromes. It affects 1 in 3500 persons. It is caused by a mutation in the neurofibromin gene localized to chromosome 17q11.2. which codes for a protein involved in the normal cell cycle regulation. Therefore NF-1 gene mutations predispose the individual to various benign and malignant tumors. The diagnosis of NF-1 remains largely clinical, given its characteristic lesions. Here we describe one such case with hallmark lesions of NF-1. A 12-year-old boy presented with a slow-growing and progressive right upper lid mass causing severe drooping, vision impairment and facial disfiguration. On detailed ophthalmic examination he was found to have severe ptosis, Lisch nodules and keratoconus. A systemic examination revealed café au lait spots and axillary freckling. Radiological imaging showed sphenoid wing dysplasia, encephalocele and optic pathway glioma. The patient was taken up for debulking surgery and a referral to the neurosurgery department was sent. He has been on follow up for last 12 months. This case first presented to an ophthalmology clinic and thus, as an ophthalmologist, keeping in mind the associated intraorbital and intracranial pathology can be life-saving. A multidisciplinary approach is needed in the management of such severe cases of NF-1.

Torkildsen shunt as an option for hydrocephalus associated with optic pathway glioma

Hydrocephalus caused by optic pathway glioma (OPG) is most often treated with a ventriculoperitoneal shunt (VPS), but this treatment may present complications such as ascites. Hence, ventriculocisternal shunt is an option worth considering. This article reports a case in which it was decided to place a ventriculocisternal or Torkildsen shunt in a patient with hydrocephalus caused by OPG. Case Report: A 12-year-old girl, amaurotic, with a VPS due to hydrocephalus caused by an OPG, reported to the emergency room with abdominal distension and pain and difficulty in walking. Computed tomography of the abdomen was performed, and a large amount of fluid was evidenced in the peritoneal cavity (ascites). Liver and kidney functions were normal. In the surgical procedure, the distal extremity of the ventriculoperitoneal catheter was exposed, and 3 L of ascites fluid of cerebrospinal origin was drained. After 10 days of antibiotic therapy, a ventriculocisternal or Torkildsen shunt was placed. After 4 years of follow-up, the patient has no complaints. Discussion: Arne Torkildsen was the first to perform a ventriculocisternal shunt in 1937; it is indicated in cases of hydrocephalus with obstruction of the aqueduct or third ventricle. In OPG, increased protein levels in CSF and the use of platinum-based chemotherapy agents would explain the development of ascites after VPS placement. In these cases of hydrocephalus with third ventricle tumor infiltrating the hypothalamus, the ventriculocisternal shunt can be used as an option in specific cases.

Neurofibromatosis Type 1 in Children: A Single-Center Experience.

Objective:Neurofibromatosis (NF) is the most common autosomal dominantly inherited neurocutaneous syndrome. The characteristic features of NF type 1 (NF-1) are café au lait spots, axillary and inguinal freckling, peripheral neurofibromas, optic pathway glioma, and Lisch nodules. The present study aimed to analyze the clinical features of children with NF-1.Materials and Methods:In this study, the children with NF-1 diagnosed and followed-up in our center between 2000 and 2020 were retrospectively evaluated. Demographic and clinical features of patients were defined.Results:The study group consisted of 52 patients. Of those, 25 were boys and 27 were girls. The children’s median age at diagnosis was 5.9 years (1-15.8). Café au lait (CAL) spots and axillary/inguinal freckling were observed in 50 and 24 patients, respectively. Neurofibroma was present in 22 cases. Ten of the cohort had optic gliomas, and 39 of them had cranial hamartomas. Orthopedic complications such as scoliosis, tibial pseudoarthrosis, and osteoporosis were observed in 13 patients. Eleven children had neurocognitive disorders.Conclusions:Early diagnosis is important in neurofibromatosis to prevent the complications of the disease. Also, neurological development and secondary malignancy follow-up should be done carefully in this group of patients.

Postoperative hydrocephalus is a high-risk lethal factor for patients with low-grade optic pathway glioma

Objectives To explore the prognostic factors of patients with low-grade optic pathway glioma (OPG) and the optimal treatment to reduce the incidence of postoperative hydrocephalus. Patients and methods This single-center study retrospectively analyzed data from 66 patients with OPGs who underwent surgery. The patients were followed, and overall survival (OS) and progression-free survival (PFS) were determined. The effects of different treatments on the hydrocephalus of patients were compared. Results Postoperative hydrocephalus was identified as a factor to increase the risk of mortality by 1.99-fold (p = .028). And, 5-year survival rate was significantly lower among patients with postoperative hydrocephalus (p = .027). The main factors leading to preoperative hydrocephalus in patients are large tumor volume and invasion into the third ventricle. Gross total resections (GTR) could reduce the risk of long-term hydrocephalus (p = .046). Age younger than 4 years (p = .046) and tumor invasion range/classification (p = .029) are the main factors to reduce the five-year survival rate. Postoperative radiotherapy (RT) and chemotherapy (CT) had no significant effects on OS. Extraventricular drainage (EVD) was not associated with perioperative infection (p = .798 > .05) and bleeding (p = .09 > .05). Compared with 2 stage surgery (external ventricular drainage or ventriculoperitoneal shunt (VPS) was first placed, followed by tumor resection), 1 stage surgery (direct resection of tumor) had no complication increase. Conclusions Postoperative hydrocephalus is mostly obstructive hydrocephalus, and it is an important factor that reduces the OS of patients with low-grade OPGs. Surgery to remove the tumor to the greatest extent improves cerebrospinal fluid circulation is effective at reducing the incidence postoperative hydrocephalus. For patients whose ventricles are still dilated after surgery, in addition to considering poor ventricular compliance, they need to be aware of the persistence and progression of hydrocephalus.

A rare association of phakomatosis

Simultaneous occurrence of neurofibromatosis and tuberous sclerosis is very rare. A 55-year-old hypertensive man was referred for ophthalmic evaluation. On examination, Lisch nodules were seen over the iris in both the eyes with fundus showing bilateral temporal pallor. Magnetic resonance imaging (MRI) brain was done to rule out optic pathway gliomas. MRI brain was negative for gliomas but showed subependymal nodules in the ventricles, a feature of Tuberous sclerosis. A screening computed tomography (CT) abdomen showed multiple angiomyolipoma in the kidney, which confirmed the diagnosis. It is important to be aware of this rare co-existence so that a devastating consequence can be prevented.

Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1.

BackgroundNeurofibromatosis 1 (NF1; OMIM# 162200) is a common autosomal dominant genetic disease [incidence: ~1:3500]. In 95% of cases, clinical diagnosis of the disease is based on the presence of at least two of the seven National Institute of Health diagnostic criteria. The molecular pathology underlying this disorder entails mutation in the NF1 gene. The aim of this study was to investigate clinical and molecular characteristics of a cohort of Egyptian NF1 patients.MethodThis study included 35 clinically diagnosed NF1 patients descending from 25 unrelated families. Patients had ≥2 NIH diagnostic criteria. Examination of NF1 gene was done through direct cDNA sequencing of multiple overlapping fragments. This was supplemented by NF1 multiple ligation dependent probe amplification (MLPA) analysis of leucocytic DNA.ResultsThe clinical presentations encompassed, café‐au‐lait spots in 100% of probands, freckling (52%), neurofibromas (20%), Lisch nodules of the iris (12%), optic pathway glioma (8%), typical skeletal disorders (20%), and positive family history (32%).Mutations could be detected in 24 families (96%). Eight mutations (33%) were novel.ConclusionThis study illustrates the underlying molecular pathology among Egyptian NF1 patients for the first time. It also reports on 8 novel mutation expanding pathogenic mutational spectra in the NF1 gene.

LGG-14. PRESENTATION CHARACTERISTICS AND TREATMENT OUTCOMES FOR PEDIATRIC OPTIC PATHWAY GLIOMAS IN QATAR

ObjectivesTo review the presentation characteristics and treatment outcomes for pediatric optic pathway gliomas (OPG) in Qatar. MethodsRetrospective review of data for children with OPG from January 2009 to February 2021. Presenting features, diagnostic imaging and indications for treatment were reviewed. Progression free survival (PFS) and overall survival(OS) were computed using standard statistical methods. Medical notes were also reviewed for visual outcomes. ResultsNineteen patients were diagnosed with OPG during the study period. There were 10 (52%) females. Median age was 29 months (range 6–186) months. Eleven (57%) tumors were related to neurofibromatosis Type 1 (NF-1). Nine (47%) of OPG were located in optic nerves, 5 (26%) were chiasmatic/suprasellar, while the remaining 5(26%) involved a combination of structures. Seven(36%) children presented with oculo-visual symptoms. Another 7 were diagnosed on screening imaging for NF-1. Seven(36%) children had debulking surgery/biopsy, while the remaining patients were diagnosed on neuro-imaging alone. Thirteen (68%) patients were treated with chemotherapy and 2 received additional radiotherapy. Indications for non-surgical treatment included visual impairment (46%) and large/progressive tumor (54%). Carboplatin based regimes were used as first line chemotherapy for 76 % of patients. Five (38%) patients required more than one lines of treatment. OS and PFS at 36 months were 100% and 48%. Baseline visual assessment showed 5 children each (26%) had unilateral and bilateral visual impairment, while 9 (48%) had normal vision. Of the 6 children receiving chemotherapy for visual impairment, 2 (33%) showed improvement. Of the 7 children treated for large/progressive tumors, 3 (42%) showed partial response, 2(28%) had progressive disease and 1 had stable disease after the first line therapy. ConclusionsOur results are in-keeping with international data for optic pathway gliomas. Early referral and diagnosis may improve visual outcomes for this group of tumors.

Comparison of two surgical methods for the treatment of optic pathway gliomas in the intraorbital segment: an analysis of long-term clinical follow-up, which evaluates the surgical outcomes.

BackgroundThis study analyzes two kinds of surgical methods for the treatment of optic pathway gliomas (OPGs) in the intraorbital segment, as well as the surgical outcomes of OPGs.MethodsThe clinical data of 86 patients with OPGs treated in our center was analyzed retrospectively, and the clinical symptoms, treatment methods, and follow-up results were recorded.ResultsFor OPGs in the intraorbital segment, the optic nerve sheath incision was performed to remove a tumor while retaining the optic nerve sheath in Group 1 (n=36). The optic nerve sheath and the tumor were simultaneously removed without retaining the optic nerve sheath in group 2 (n=50). The effects of the design of the surgical methods on the post-surgical outcome are: One patient (1/36, 2.8%) had recurrence in Group 1 and one patient (1/50, 2.0%) had recurrence in group 2. The differences in the surgical outcomes of the two groups regarding exophthalmos, conjunctiva swelling, eye movement disorder, and ptosis were found to be statistically significant (P<0.05). Compared with group 2, the surgical outcomes in the postoperative phase of Group 1 were more satisfactory.ConclusionsThe two surgical methods do not increase the recurrence rate of tumors. The resection of OPGs through an optic nerve sheath incision was found to be an ideal surgical method for reducing complications in the postoperative phase and for providing better surgical outcomes.

EPCT-16. LENALIDOMIDE ACTIVITY IN PILOCYTIC ASTROCYTOMA AND OPTIC PATHWAY GLIOMAS: REPORT ON CHILDREN’S ONCOLOGY GROUP ACNS1022

Children with low-grade glioma have excellent survival rates but often suffer from the morbidity of treatment, particularly from cytotoxic chemotherapies. Targeted agents appear to have some activity but the long-term effects of inhibiting normal developmental pathways are unknown. Lenalidomide is an oral immunomodulatory agent with additional properties including anti-angiogenesis. Phase I studies indicated greater tolerability of this agent compared to adults, and a potential dose-response effect. We performed a Phase 2 trial of lenalidomide in children with pilocytic astrocytoma and optic pathway gliomas who failed initial therapy. The primary objective was to determine the objective response rate of children randomized to Regimen A low-dose (20 mg/m2 /dose) or Regimen B high-dose (115 mg/m2 /dose) lenalidomide, each administering lenalidomide daily x 21 days of each 28-day course. Secondary objectives included estimation of event-free survival (EFS) in this population and correlation of plasma lenalidomide concentration with toxicity and outcome. Results74 eligible patients were enrolled (n=37 to each arm). The pre-defined activity level of interest was achieved for both arms. Objective responses were observed in both arms, with 4 partial responses in each. A total of n=18 patients completed 26 courses of therapy (Arm A, n=12, Arm B, n=6) The median number of courses on each arm was 14 (range 2–26) for Arm A and 11 for Arm B (range 1- 26). Of the 74 eligible patients who received study drug, 30 required a dose reduction for toxicity (Arm A, n=6, Arm B, n=24) and 16 discontinued treatment on protocol due to toxicity (Arm A, n=2, Arm B, n=14). ConclusionLenalidomide demonstrates a sufficient level of activity in children with low-grade glioma to warrant further exploration in Phase 3 studies. Low-dose (20 mg/m2) lenalidomide appears to have better tolerability.

LGG-10. AN UNUSUAL PRESENTATION OF BILATERAL OPTIC NERVE GLIOMA IN CROUZON SYNDROME

Optic pathway gliomas (OPGs) are low grade gliomas intrinsic to the visual pathway, frequently associated with Neurofibromatosis Type 1 (NF-1). Bilateral OPGs without chiasmatic involvement are almost pathognomonic for NF-1. We report an unusual case of bilateral optic nerve glioma without chiasmatic involvement in a 17-month old male patient with craniosynostosis and Crouzon Syndrome, an autosomal dominant disorder caused by activating FGFR2 mutations associated with craniosynostosis and optic atrophy. The patient’s c.1032 G>A pathogenic variant in FGFR2 is a variant known to affect splicing and results in a protein that lacks part of an important domain involved in ligand binding. Although FGFR1 mutations have been implicated in low-grade glioma through MAPK activation, FGFR2 mutations have not yet been described in OPGs, although they have been described in epileptogenic low-grade gliomas and mixed neuronal-glial tumors. Our patient presented with worsening vision in the setting of known Crouzon Syndrome. An eye examination revealed bilateral primary optic atrophy. Brain and orbital MRIs demonstrated fusiform dilation and STIR hyperintensity of the intraorbital segments of the optic nerves bilaterally with normal pre-chiasmatic optic segments. There were no other radiographic or physical stigmata suggestive of NF-1. Next generation sequencing and copy number analysis from peripheral blood were negative for variants in NF1. RNA based studies for NF1 aberrations are pending. Although follow up MRI scans demonstrated stable size of his OPGs, the risk of further visual deficit was considered significant due to his pre-existing optic atrophy and poor baseline visual acuity. Therefore, he was started on vincristine and carboplatin chemotherapy according to A9952, and induction therapy has been well tolerated. To our knowledge, this is the first patient with Crouzon Syndrome who has developed bilateral optic pathway gliomas. Orbital MRIs should be considered for these patients with worsening visual acuity not explained by other causes.

RARE-03 CENTRAL NERVOUS SYSTEM TUMORS IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1, A COHORT FROM A NATIONAL PEDIATRIC ONCOLOGY CENTER

Approximately 15% of the children with Neurofibromatosis type 1 (NF1) develop a central nervous system (CNS) tumor, predominantly optic pathway glioma. However, other brain tumor types are also frequent, resulting in a heterogenous population regarding tumor type, symptoms and treatment. Even though many tumors are indolent, clinical deterioration or radiological progression requires surveillance and treatment. Pediatric oncology care in the Netherlands has been centralized into the Princess Máxima Center since June 2018, providing care for the majority of Dutch NF1 CNS tumor patients. This retrospective cohort study describes the course of disease in NF1 patients with a CNS tumor diagnosed between 2005–2020, based on data from patient files. The population consisted of 95 patients (48 males), median age at diagnosis 4.3 (range 0.8–17.2) and 12.6 (range 2.9–19.9) years at follow up, 27% familiar NF1, mostly nonsense or frameshift mutations. Neurological and/or visual symptoms were present in 64 (67.4%) patients. 63.6% of the tumors was in the optic pathway, 9.1% in the cerebellum. Biopsy in 19/95 revealed 1 ependymoma and 18 low grade glioma, with rarely additional molecular changes besides NF1. Kaplan Meier median PFS was 24 months (range 3–174.5, n=65) in symptomatic presenting patients, 34 months (range 5–165, n=20) in asymptomatic patients with abnormal ophthalmological and/or neurological exam and 67.3 months (range 7–130, n=10) in asymptomatic patients without abnormalities at exam. Treatment was indicated in 53 (55.8%), predominantly chemotherapy (n=49), with substantial toxicity. Carboplatin allergy was seen in 29/44 (65.9%) patients, peripheral neuropathy in 21/46 (45.7%) patients receiving vincristine, and 5/10 patients receiving irinotecan and bevacizumab ended treatment early due to toxicity. In conclusion: analysis of our extensive cohort of NF1 patients with a CNS tumor indicates the relevance of regular screening of NF1 patients without complaints and critical surveillance and systematical documentation of treatment toxicity.

NF1 mutation drives neuronalactivity-dependent initiation of optic glioma.

Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with theneurofibromatosis1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood3,4, raising the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis1 tumour suppressor gene (Nf1)5 to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome.

Predictive Modeling for Clinical Features Associated With Neurofibromatosis Type 1.

ObjectiveTo perform a longitudinal analysis of clinical features associated with neurofibromatosis type 1 (NF1) based on demographic and clinical characteristics and to apply a machine learning strategy to determine feasibility of developing exploratory predictive models of optic pathway glioma (OPG) and attention-deficit/hyperactivity disorder (ADHD) in a pediatric NF1 cohort.MethodsUsing NF1 as a model system, we perform retrospective data analyses using a manually curated NF1 clinical registry and electronic health record (EHR) information and develop machine learning models. Data for 798 individuals were available, with 578 comprising the pediatric cohort used for analysis.ResultsMales and females were evenly represented in the cohort. White children were more likely to develop OPG (odds ratio [OR]: 2.11, 95% confidence interval [CI]: 1.11–4.00, p = 0.02) relative to their non-White peers. Median age at diagnosis of OPG was 6.5 years (1.7–17.0), irrespective of sex. Males were more likely than females to have a diagnosis of ADHD (OR: 1.90, 95% CI: 1.33–2.70, p < 0.001), and earlier diagnosis in males relative to females was observed. The gradient boosting classification model predicted diagnosis of ADHD with an area under the receiver operator characteristic (AUROC) of 0.74 and predicted diagnosis of OPG with an AUROC of 0.82.ConclusionsUsing readily available clinical and EHR data, we successfully recapitulated several important and clinically relevant patterns in NF1 semiology specifically based on demographic and clinical characteristics. Naive machine learning techniques can be potentially used to develop and validate predictive phenotype complexes applicable to risk stratification and disease management in NF1.

Molecular Characterization of Medulloblastoma in a Patient with Neurofibromatosis Type 1: Case Report and Literature Review

Brain tumors are the most common solid neoplasms of childhood. They are frequently reported in children with Neurofibromatosis type 1 (NF1). The most frequent central nervous system malignancies described in NF1 are optic pathway gliomas and brainstem gliomas. Medulloblastoma (MB) in NF1 patients is extremely rare, and to our knowledge, only 10 cases without molecular characterization are described in the literature to date. We report the case of a 14-year-old girl with NF1 that came to our attention for an incidental finding of a lesion arising from cerebellar vermis. The mass was completely resected, revealing a localized classic medulloblastoma (MB), subgroup 4. She was treated as a standard-risk MB with a dose-adapted personalized protocol. The treatment proved to be effective, with minor toxicity. Brain and spine MRI one year after diagnosis confirmed the complete remission of the disease. To our knowledge, this is the only case of MB reported in a patient with NF1 with molecular characterization by the methylation profile. The association between NF1 and MB, although uncommon, may not be an accidental occurrence.

Correlation Between Ophthalmologic and Neuroradiologic Findings in Type 1 Neurofibromatosis.

Neurofibromatosis Type 1 (NF-1) is a genetic disease affecting the eye, and ocular findings such as Lisch nodules (LN) or optic pathway gliomas (OPGs) are a part of its diagnostic criteria. Recent imaging technologies such as infrared (IR) imaging and optical coherence tomography (OCT) have highlighted the visualization of choroidal focal abnormalities in these patients, even in the absence of other ocular lesions. This study aimed to establish a morphological multimodal evaluation of choroidal findings in patients with NF-1, correlating them with central nervous system (CNS) findings. This retrospective study included 44 eyes from 22 patients with NF-1. Central 30° IR imaging was obtained, and the number and total area of detectable lesions were calculated. Both macular and optic disc scanning with OCT were performed, with and without the enhanced depth imaging technique, to assess the presence of choroidal focal hyperreflective lesions. Central macular thickness, ganglion cell layer, and outer nuclear layer thickness were assessed, as well as subfoveal choroidal thickness. The peripapillary retinal nerve fiber layer (RNFL) thickness was also assessed. Patients' magnetic resonance images (MRI) were reviewed and categorized by a neuroradiology specialist, determining the presence of OPGs and CNS hamartomas. Correlations between the ophthalmological and neuroradiological findings were established. Patients' mean age was 16.4 ± 7.3 years and 59.1% were women. On the MRI, 86.4% of the patients had CNS hamartomas, and 34.1% of the eyes had OPGs. LN were described in 29.5% of the eyes, whereas a total of 63.4% of the eyes presented the characteristic hyperreflective lesions in IR imaging, all of them matching the underlying choroidal lesions. A mean of 2.9 ± 3.3 lesions per eye and a median total lesion area of 1.52 mm2 were found. The presence of OPGs was correlated with a greater number (P = 0.004) and a larger area (P = 0.006) of IR lesions. For a cut-off of 3.5 lesions per eye, the sensitivity and specificity for the presence of OPGs were 75% and 80%, respectively. For a total lesion area of 2.77 mm2, the sensitivity and specificity for the presence of OPGs were 69.2% and 93.1%, respectively. Eyes with OPGs presented a significant reduction in the temporal RNFL (P = 0.018) thickness, as well as a reduction in subfoveal choroid thickness (P = 0.04). No relations were found between CNS hamartomas and ophthalmological findings. This study suggests that focal choroidal abnormalities are correlated with the presence of CNS lesions as OPGs in patients with NF-1, and it might be a surrogate for the need for CNS imaging in these patients.

Early radiotherapy preserves vision in sporadic optic pathway glioma.

Sporadic optic pathway/hypothalamic gliomas represent a unique entity within pediatric low-grade glioma. Despite favorable survival, location makes treatment difficult and local progression debilitating. This study is a longitudinal assessment of visual acuity (VA) among children treated within the last 2 decades. Clinical characteristics were abstracted for patients treated from 2000 to 2018 at Texas Children's Cancer Center in Houston. Ophthalmologic data taken at 3- to 6-month intervals were examined with age-appropriate VA metrics converted to the LogMAR (logarithm of the minimum angle of resolution) scale. Kaplan-Meier blindness-free survival (BFS) curves, calculated as time-to-bilateral functional blindness (LogMAR ≥0.8 in both eyes), were calculated for patients receiving early radiation therapy (RT; upfront or as first-line salvage treatment) or chemotherapy (CT) and evaluated using the log-rank test. Thirty-eight patients with a median follow-up of 8.5 years (range, 2-17 years) were identified. Median age at diagnosis was 3 years (interquartile range, <1-6 years). Early RT was administered in 11 patients (29%). Twenty-seven patients (71%) were treated primarily with CT, initiated at a median age of 3.5 years (range, <1-11 years). Eight patients in the CT group did eventually require RT secondary to VA loss and following multiple lines of CT. Median age at RT for all patients was 11 years (range, 3-17 years). BFS rates were 81% at 5 years and 60% at 8 years for CT and 100% at 5 and 8 years for early RT (P = .017). In a contemporary cohort, early RT, defined as initial or first-line salvage therapy, was found to have superior BFS for appropriately selected patients with sporadic optic pathway/hypothalamic gliomas. Children with low-grade brain tumors of the optic pathway generally have excellent long-term survival; however, given the location of these tumors, there can commonly be threatened vision if the tumor grows. Although radiation is generally deferred in children on the basis of legitimate concerns regarding the effects on the developing brain, it may represent a vision-preserving therapy for well-selected older patients.

PEDIATRIC OPTIC PATHWAY GLIOMA: DIENCEPHALIC SYNDROME

Diencephalic cachexia (DC ) is a metabolic disorder characterized by a decrease in body weight. DC usually occurs in the presence of glioma brain tumors extended into the optic pathway. These tumors are very aggressive and have poor prognosis.Objective: to analyze the clinical course of optic pathway gliomas (OPG s) in patients with and without DC .Material and Methods. The study included 264 patients aged 0 to 18 years with an initial diagnosis of OPG s registered in the N.N. Burdenko National Medical Research Center of neurosurgery from 01/01/2003 to 12/31/2015. Patients were divided into two groups: without DC (204 people) and with DC (60 children). Results: neurofibromatosis type I (NFI) was much more common in children without DC , and pilomyxoid histology was much more prevalent in children with DC . Five-year overall survival (OS ) and event-free survival EFS were significantly lower in children with DC than in children without DC (82 ± 5 % and 96 ± 1 %, respectively versus 37 ± 7 % and 62 ± 3 %, respectively). It was found that in the DC group, the OS and EFS rates were significantly lower in girls, in children without NFI, in children without histological verification and in children with pilocytic astrocytomas. It was also found that in the DC group, OS rates were significantly lower in children under 1 year, and EFS rates were significantly lower in children aged more than 12 months. The number of patients without events were significantly higher in the group without DC (p=0.001). The number of deaths in the postoperative period was significantly higher in children with DC (p&lt;0.001). Diabetes insipidus and hyponatremia were significantly more common in patients with diencephalic cachexia, and vision improvement after treatment was significantly more likely to occur in patients without DC .Conclusion. OPG s in patients with DC have a more aggressive clinical course, which requires more careful treatment and observation.

Neurosurgical experience of managing optic pathway gliomas

BackgroundOptic pathway gliomas (OPGs), also known as visual pathway gliomas, are debilitating tumors that account for 3–5% of all pediatric brain tumors. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of these tumors results in visual loss and blindness, endocrine and hypothalamic dysfunction, hydrocephalus, and premature death. Their involvement of the visual pathways and proximity to other eloquent brain structures typically precludes complete resection or optimal radiation dosing without incurring significant neurological injury. There are various surgical interventions that can be performed in relation to these lesions including biopsy, cerebrospinal fluid diversion, and partial or radical resection, but their role is a source of debate. This study catalogues our surgical experience and patient outcomes in order to support decision-making in this challenging pathology.MethodsA retrospective review of all cases of OPGs treated in a single center from July 1990 to July 2020. Data was collected on patient demographics, radiographic findings, pathology, and management including surgical interventions. Outcome data included survival, visual function, endocrine, and hypothalamic dysfunction.ResultsOne hundred twenty-one patients with OPG were identified, and 50 of these patients underwent a total of 104 surgical procedures. These included biopsy (31), subtotal or gross total resection (20 operations in 17 patients), cyst drainage (17), Ommaya reservoir insertion (9), or cerebrospinal fluid diversion (27). During the study period, there was 6% overall mortality, 18% hypothalamic dysfunction, 20% endocrine dysfunction, and 42% had some cognitive dysfunction. At diagnosis 75% of patients had good or moderate visual function in at least one eye, and overall, this improved to 83% at the end of the study period. In comparison the worst eye had good or moderate visual function in 56%, and this reduced to 53%. Baseline and final visual function were poorer in patients who had a surgical resection, but improvements in vision were still found—particularly in the best eye.Discussion/conclusionOPG are debilitating childhood tumor that have lifelong consequences in terms of visual function and endocrinopathies/hypothalamic dysfunction; this can result in substantial patient morbidity. Decisions regarding management and the role of surgery in this condition are challenging and include cerebrospinal fluid diversion, biopsy, and in highly select cases cystic decompression or surgical resection. In this paper, we review our own experience, outcomes, and surgical philosophy.

Endoscopic Management of Intra Ventricular Tumours

Objective: Neuroendoscopic removal of intraventricular tumors is difficult and time consuming because of the lack of an effective decompression system that can be used through the working channel of the endoscope. The authors report on the utilization of an endoscopic ultrasonic aspirator in the resection of intraventricular tumors. Methods: Seventeen pediatric patients (14 male, 3 female), ages 1-15 years old, underwent surgery via a purely endoscopic approach using a Gaab rigid endoscope and endoscopic ultrasonic aspirator. Ten patients presented with an intraventricular tumor, three with paraventricular, and 4 with suprasellar lesions. Histology analysis showed 6/17 glial tumors, 3/17 with subependymal giant cell astrocytomas (associated with tuberous sclerosis), two cases presented with intraventricular metastases from high-grade tumors (medulloblastoma, atypical teratoid rhabdoid tumor), 4/17 with suprasellar tumors (2 craniopharyngiomas and 2 optic pathway gliomas), and two with pineal region tumors (1 immature teratoma, 1 PNET). In all patients, the endoscopic trajectory and ventricular access were guided by electromagnetic neuronavigation. Fifteen patients underwent surgery via a precoronal bur hole while supine. In 1 case, surgery was performed through a frontal anterior bur hole and one patient underwent surgery via a posterior parietal approach to the trigone while in a lateral position. The endoscopic technique consisted of visualization of the tumor, ventricular washing to dilate the ventricles and to control bleeding, obtaining a tumor specimen with biopsy forceps, and ultrasonic aspiration of the tumor. Bleeding was controlled with irrigation, monopolar coagulation, and a thulium laser. Results/Discussion: In 9 cases, the resection was total or near total (more than 90% of lesion removed). In 8 cases, the resection was partial or biopsy. Histological evaluation of the collected material (withdrawn using biopsy forceps and aspirated with an ultrasonic aspirator) was diagnostic in all cases. The duration of surgery ranged from 30 to 120 minutes. One case was complicated by subdural hygroma requiring a subduro-peritoneal shunt implant. The dry field technique was used in cases with persistence of bleeding. Conclusion: Patients harboring intraventricular tumors are in most cases ideal candidates for endoscopy biopsy/resection. In this series, endoscopic ultrasonic aspiration proved to be a safe and reliable method for achieving extensive decompression or complete removal in the management of intra- and/or paraventricular lesions in pediatric patients.

Vision Outcomes for Pediatric Patients With Optic Pathway Gliomas Associated With Neurofibromatosis Type I: A Systematic Review of the Clinical Evidence.

Children with neurofibromatosis type I (NF1) have a higher predisposition for low-grade astrocytomas of the optic pathway, commonly referred to as optic pathway gliomas (OPGs). OPGs can result in visual deterioration. Treatment outcomes in OPG-NF1 management are often reported around tumor stabilization. We sought to compare vision outcomes associated with different OPG treatment strategies to inform about this important functional metric. A meta-analysis exploring the different modalities to treat children with OPG-NF1 was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using multiple databases. Of the 113 articles identified in the search, 23 full text articles, representing 564 patients, were included for review. These articles included retrospective, prospective, and randomized controlled studies on observation (n=9), chemotherapy (n=19), radiation therapy (n=6), and surgery (n=7). Of the patients undergoing observation, 87% (60/69) demonstrated stable acuity. In the chemotherapy studies, 27.3% (72/264) demonstrated improved acuity/visual field and/or visual-evoked potential amplitudes, 39.4% (104/264) stable acuity, and 33.3% (88/264) deterioration. Both the radiation and surgical treatments reported worsening acuity at 90.9% (10/11) and 73.3% (11/15), respectively. Causal associations are not known. Indications for and timing of treatment choice warrant larger scale study to provide further understanding.