Treatment Of Optic Pathway Gliomas Research Articles

Case report: use of conium maculatum as an aid to lower limb pain and paresia in type 1 neurofibromatosis in treatment of optic pathway glioma

Neurofibromatosis type 1 is one of the most common autosomal dominant disorders, presenting a higher risk of developing plexiform tumors and neurofibromas, whose conventional treatment, based on surgical, chemotherapy or radiotherapy procedures, still has limitations. Comorbidities such as neuralgic, muscular or paretic and paralytic pain may occur depending on the tumor situation or the plexiform neurofibroma. Given the difficult approach to these patients, and with the aim of expanding research and homeopathic knowledge about these cases, we present a case of pain associated with lumbosacral plexiform neurofibroma during oncological treatment for Glioma of the Optic Pathways, without surgical indication, but with difficult pain. control, even when using analgesics and antidepressants. Chemotherapy oncological treatment, due to crises and maintenance of pain, had been postponed. As an aid in controlling the symptoms, considering the ascending paretic pain syndrome of the left lower limb, the homeopathic medicine Conium maculatum was used as a complementary aid to the therapy. The patient's symptoms improved and she was able to continue with the chemotherapy treatment indicated, with a progressive reduction in the use of analgesics until they were discontinued.

Inoperable Optic Pathway Glioma: A Seven-Year-Old Male with >35 Years Overall Survival Following Treatment with Antineoplastons

Optic pathway glioma (OPG) is a low-grade tumor developing along the pre-cortical optic pathways and can involve the optic nerve, optic chiasm, optic tracts, and hypothalamus. Objective: A male child with newly diagnosed and unresectable OPG is presented to 1) review the earliest use of Antineoplastons A10 and AS2-1 for the treatment of brain tumors and 2) demonstrate the efficacy of Antineoplastons in the treatment of OPG. On April 18, 1988, a seven-year-old male child presented to the Burzynski Clinic (BC) with headaches. Based on prior, non-enhanced MRIs and biopsy, an unresectable suprasellar OPG was diagnosed. Antineoplaston therapy was started on a “proof of principle” basis. Tumor response was measured by magnetic resonance imaging (MRI) scans of the brain. Results: A brain MRI, performed on May 31, 1989, demonstrated an enhancing suprasellar nodule measuring 4.37 cm2. On August 24, 1990, brain MRI demonstrated a 0.96 cm2 enhancing nodule, indicating the achievement of a partial response (PR). Following higher dose intravenous (IV) and oral Antineoplastons, brain MRI performed on January 24, 1997, demonstrated a residual 0.4 cm2 enhancing nodule, indicating an enduring PR. All Antineoplaston therapy was discontinued on August 21, 2000. At last follow-up, > 35 years since the start of Antineoplaston therapy, the patient was healthy and showed no evidence of tumor progression. “Proof of principle” Antineoplaston therapy utilized in a seven-year-old male with unresectable OPG produced an objective response (OR) and prolonged overall survival. Antineoplaston therapy is an attractive therapeutic option for children with OPG.

The role of visual electrodiagnostics in management of children with neurofibromatosis type 1.

To evaluate the role of visual electrodiagnostic testing in children with neurofibromatosis type 1 (NF1) despite improved accessibility to magnetic resonance imaging (MRI). The records from 39 children (78 eyes, 15 boys, 24 girls, average age at last visit of 11.5 ± 4.3years, average follow-up time of 7.8 ± 3.9years) with genetically confirmed NF1 were retrospectively analysed. They all underwent a thorough ophthalmological investigation, including age-appropriate visual acuity testing, anterior segment evaluation for Lisch nodules and a dilated fundus examination. If children were cooperative enough, colour vision was tested using the Hardy-Rand-Rittler test, visual fields were evaluated with Goldmann perimetry. All performed MRI of the brain and orbits as part of the standard of care protocol. Visual electrodiagnostics included electroretinography (ERG) and visual evoked potentials (VEP) using a standard protocol in older children, whereas with less cooperative children a modified protocol according to the Great Ormond Street Hospital (GOSH protocol) was used. The average visual acuity was 0.8 ± 0.3, colour vision was abnormal in 6%, perimetry in 8%, Lisch nodules were present in 62%, and the optic disc was pale in 66% of all eyes. Plexiform neurofibroma of the eyelid/orbit was present in 4%. Optic pathway glioma (OPG) was detected with MRI in 22 (57%) and in 6/22 treatment was indicated. Other intracranial NF1-related lesions were documented in 70% of children. VEP were abnormal in 16/39 of all children with NF1 (41%) comprising 14/22 (65%) of children with confirmed OPG and 2/17 (12%) of children without OPG. All full-field and pattern ERG responses were within normal limits. All individual VEP results are described and three cases from this cohort of children are presented in detail to illustrate the importance of VEP testing. In Case 1, VEP abnormality suggested subsequent MRI of the brain under general anaesthesia, which was otherwise contraindicated according to normal clinical findings and his young age. In Cases 2 and 3, VEP provided more precise functional information during the follow-up of OPG, while other psychophysical tests remained unchanged. Electrodiagnostics has multifactorial role and importance in children with NF1, either when visual pathway function is impaired in young children, even before MRI under general anaesthesia and other psychophysical tests can be performed, as well as for a more precise monitoring of the visual pathway function before potential treatment of OPG, or after it, to evaluate its success.

Endoscopic ultrasonic aspiration as alternative to more invasive surgery in initial management of optic pathway gliomas in children.

Optic pathway gliomas (OPGs) presenting with acute hydrocephalus represent a true neurosurgical and neurooncological challenge. Two main strategies are currently used: microsurgical removal of the tumor, restoring CSF pathways, and endoscopic biopsy associated with ventriculo-peritoneal shunt implantation. Since the availability of an ultrasonic aspirator handpiece, that can be used inside the working channel of a neuroendoscope, a different less invasive surgical strategy can be used. Four pediatric patients were treated by endoscopic ultrasonic aspiration, in order to remove the upper pole of the tumor, obtaining tissue for diagnosis and restoring CSF pathways as initial treatment of OPG invading the third ventricle and causing hydrocephalus due to simultaneous blockage of both Monro foramina and of the Sylvian aqueduct. Surgical technique is described. Pre-operative and post-operative volumes were calculated on magnetic resonance imaging. In all cases, the surgical procedure was uneventful, the biopsy was diagnostic, and CSF pathways were restored. The amount of tumor removed ranged between 31 and 76%. All patients underwent oncological treatment of their tumors. One patient received V-P shunt only 1year after endoscopic decompression due to tumor progression. Our preliminary results show that the use of endoscopic cavitron aspirator is safe and effective to obtain CSF flow restoration and tumor biopsy (for histological and molecular purposes), avoiding CSF shunt implant in the acute phase and offering the chance to obtain a consistent tumor debulking in a minimally invasive fashion. Neuroendoscopic approach together with modern target therapy offers the opportunity to avoid or delay major surgery.

Impact of systemic anticancertherapy in pediatric optic pathway glioma on visual function: A systematic review.

Pediatric optic pathway glioma (OPG) can seriously decrease visual function in the case of progression. Systemic anticancer therapy (SAT) is considered the treatment of first choice for unresectable OPG. New SAT modalities for the treatment of progressive OPG have been introduced in the last decade, including VEGF and MAPK pathway inhibition. This systematic review evaluated the effect of SAT on change in visual acuity and visual field in OPG. A systematic review was performed on SAT for OPG (January 1990 to August 2020). MEDLINE and EMBASE (Ovid) were searched for studies reporting on change in visual acuity and visual field after treatment with SAT for OPG. Overall, 11 series, including 358 patients, fulfilled the eligibility criteria. After follow-up of median 3.7 years (range: cessation of SAT- 8.2 years), improvement in binocular VA was found in 0-45% of studies, stability in 18-77% and a decrease in 0-82%. Two studies reported on change in visual field (improvement in 19% and 71% of patients), although either the change was not defined or the testing strategy was lacking. Considerable heterogeneity was present among the included studies, such as variety in the combinations of SAT administered, status of neurofibromatosis type 1, definition regarding change in visual acuity, 1- or 2-eye analysis, diversity in anatomic location, and extent of follow-up, all of which made meta-analysis inappropriate. This systematic review suggests that the impact of SAT in OPG on visual function is still unclear. The wide ranges reported on the efficacy of SAT and the observed heterogeneity highlight the need for prospective studies with uniform definitions of outcome parameters.

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.

Central and peripheral steady-state visual evoked potentials in children with optic pathway gliomas.

Treatment of optic pathway gliomas is prompted by neuroradiological evidence of tumor growth, usually associated with progressive visual loss. Despite therapy, approximately 40% will show visual deterioration. Treatment outcome is largely based on the preservation of vision. However, current visual function assessment is often unreliable in children with optic pathway gliomas who have limited collaboration. Thus, there is a need for new clinical tools to evaluate visual functions in these children. The aim of the study was to assess the value of steady-state visual evoked potentials as a tool to assess function in the central and peripheral visual fields of children with optic pathway gliomas. Ten patients with optic pathway gliomas and 33 healthy controls (ages 3 to 18years) were tested using steady-state visual evoked potentials. The dartboard stimulus consisted of one central circle alternating at 16reversals/s and one peripheral hoop alternating at 14.4reversals/s, separated by a hoop of gray space. It was presented monocularly at 30% and 96% contrasts. Results indicated that central signal-to-noise ratios were significantly lower in children with optic pathway gliomas compared to controls. However, no significant group difference was detected in the peripheral visual field. Steady-state visual evoked potentials could eventually be implemented in the clinical assessment and follow-up of central visual field deficits in uncooperative or nonverbal children but seem to have limited usefulness for evaluation of peripheral visual field deficits. Additional studies are needed to identify testing parameters for full visual field assessment.

Long-term visual acuity in patients with optic pathway glioma treated during childhood with up-front BB-SFOP chemotherapy-Analysis of a French pediatric historical cohort.

BackgroundVisual outcome is one of the main issues in the treatment of optic pathway glioma in childhood. Although the prognostic factors of low vision have been discussed extensively, no reliable indicators for visual loss exist. Therefore, we aimed to define initial and evolving factors associated with long-term vision loss.MethodsWe conducted a multicenter historical cohort study of children treated in France with up-front BB-SFOP chemotherapy between 1990 and 2004. Visual acuity performed at the long-term follow-up visit or within 6 months prior was analyzed. Logistic regression analysis was used to estimate the effects of clinical and radiological factors on long-term visual outcome.FindingsOf the 180 patients in the cohort, long-term visual acuity data were available for 132 (73.3%) patients (median follow-up: 14.2 years; range: 6.1–25.6). At the last follow-up, 61/132 patients (46.2%) had impaired vision, and 35 of these patients (57.3%) were partially sighted or blind. Multivariate analysis showed that factors associated with a worse prognosis for long-term visual acuity were an age at diagnosis of < 1 year (OR 3.5 [95% CI: 1.1–11.2], p = 0.04), tumor extent (OR 4.7 [95% CI: 1.2–19.9], p = 0.03), intracranial hypertension requiring one or more surgical procedures (OR 5.6 [95% CI: 1.8–18.4], p = 0.003), and the need for additional treatment after initial BB-SFOP chemotherapy (OR 3.5 [95% CI: 1.1–11.9], p = 0.04). NF1 status did not appear as a prognostic factor, but in non-NF1 patients, a decrease in tumor volume with contrast enhancement after BB-SFOP chemotherapy was directly associated with a better visual prognosis (OR 0.8 [95% CI: 0.8–0.9], p = 0.04).InterpretationOur study confirms that a large proportion of children with optic pathway glioma have poor long-term outcomes of visual acuity. These data suggest new prognostic factors for visual acuity, but these results need to be confirmed further by large- and international-scale studies.

Advanced Magnetic Resonance Imaging in Optic Pathway Gliomas

Optic pathway gliomas (OPGs) are low-grade neoplasm of the precortical visual pathway commonly associated with neurofibromatosis type 1. Although these tumors rarely threaten life, up to half of affected children will undergo visual acuity loss that cannot be corrected with refractive lenses. Given the variability in clinical course and the importance of visual function in the treatment of OPG, advanced magnetic resonance (MR) techniques that help identify early vision loss or predict future dysfunction would be important in the management of OPG. In this article, we review the clinical features and management of OPGs and discuss recent advances in MR imaging (MRI) applicable to OPGs, including MR spectroscopy, diffusion-weighted imaging, diffusion tensor imaging, MR perfusion imaging, and MR fingerprinting. If these techniques can be used to help inform clinical decision making, MRI may provide a fast and noninvasive method to help guide clinical practice.

Treatment of neuro-ophthalmic and orbitofacial manifestations of neurofibromatosis type 1

Optic pathway gliomas (OPGs) and orbitofacial plexiform neurofibromas are two of the more common ophthalmic manifestations of neurofibromatosis type 1. This article reviews recent advances in the treatment of these challenging lesions. Recent advances in the treatment of OPGs include chemotherapeutic, radiation-based, and surgical interventions. Chemotherapy continues to be the mainstay of treatment of these lesions, but the effects on visual outcome are variable. Fractionated radiotherapy and gamma knife treatment have been studied as an alternative to conventional radiotherapy and have demonstrated fewer vision and life-threatening side-effects. Surgical resection can be undertaken through multiple approaches depending upon the extent of the lesion. The management of the orbitofacial neurofibroma is primarily surgical, and the systematic surgical approach to these lesions is discussed. OPGs and orbitofacial neurofibromas are clinically diverse. Although the advances in the treatment of both are promising, recent studies demonstrate the great variety in treatment approaches and suggest a need for standardized outcome metrics for research that can ultimately contribute to guidelines for treatment.

Longitudinal Measures of Visual Function, Tumor Volume, and Prediction of Visual Outcomes after Treatment of Optic Pathway Gliomas

To examine longitudinal changes in visual acuity, tumor volume, and visual evoked potentials (VEP) before and after treatment in children with optic pathway gliomas. Retrospective cohort study. Twenty-one patients (0.7-9 years of age). Patients initially were treated either by chemotherapy (n = 18) or radiotherapy (n = 3). Patients were followed up with serial magnetic resonance imaging, age-corrected visual acuity measurements in logarithm of the minimum angle of resolution (logMAR) units, and pattern VEP. Longitudinal visual outcome data were obtained on average for 9 years (range, 4-16 years). Tumor volumes before and after treatment were estimated in 15 patients. Multivariate regression was used to predict visual outcomes. Visual acuity, relative tumor volumes, and VEP. Before treatment, 81% of patients had reduced visual acuity and 81% had optic nerve pallor, whereas all had a reduced VEP in 1 or both eyes. After initial treatment, tumor volume decreased in 53%, stabilized in 27%, and progressively increased in 20%. Treatment arrested the rapid decline in visual acuity loss and stabilized visual acuity for 4 to 5 years. The rate of visual acuity decline was not correlated with tumor shrinkage. Sixty-two percent of patients required additional treatment with either chemotherapy or radiation because of tumor growth or progressive loss of visual function. Visual acuity at last examination was stable or improved in 33% of patients, but on average declined 0.4 logMAR units. Visual acuity was 20/200 or better in 1 eye of 62% of patients. The rate of visual acuity decline was predicted weakly by tumor volume at presentation (R(2) = 0.19; P<0.009). Visual acuity at last examination was predicted best by visual acuity and tumor volume at presentation (R(2) = 0.66; P<0.001). Systemic chemotherapy arrested the decline in visual acuity and stabilized vision on average for 5 years. At presentation, VEPs were a more sensitive indicator of optic pathway damage than visual acuity or optic nerve appearance. Although tumor reduction or stabilization was achieved in 80% of patients, pre-existing visual damage, indexed by objective measures of tumor volume and visual function, limited visual outcomes. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Optic pathway gliomas in neurofibromatosis‐1: Controversies and recommendations

Optic pathway glioma (OPG), seen in 15% to 20% of individuals with neurofibromatosis type 1 (NF1), account for significant morbidity in young children with NF1. Overwhelmingly a tumor of children younger than 7 years, OPG may present in individuals with NF1 at any age. Although many OPG may remain indolent and never cause signs or symptoms, others lead to vision loss, proptosis, or precocious puberty. Because the natural history and treatment of NF1-associated OPG is different from that of sporadic OPG in individuals without NF1, a task force composed of basic scientists and clinical researchers was assembled in 1997 to propose a set of guidelines for the diagnosis and management of NF1-associated OPG. This new review highlights advances in our understanding of the pathophysiology and clinical behavior of these tumors made over the last 10 years. Controversies in both the diagnosis and management of these tumors are examined. Finally, specific evidence-based recommendations are proposed for clinicians caring for children with NF1.

Assessment of Progression and Treatment Response of Optic Pathway Glioma with Positron Emission Tomography using α-[11C]Methyl-l-Tryptophan

To report the utility of positron emission tomography (PET) with alpha-[(11)C]methyl-L-tryptophan (AMT) for monitoring progression and response to treatment of an isolated optic pathway glioma (OPG) in a 16-year-old girl. Positron emission tomography scanning of the brain was performed 20 minutes after intravenous administration of AMT. The AMT-PET images were reconstructed and examined for tumor uptake of the tracer in correlation with coregistered magnetic resonance images. The PET scan demonstrated increased uptake of AMT by OPG in a clinically symptomatic child whose magnetic resonance imaging (MRI) was inconclusive for morphological changes of the tumor. The tracer uptake was dramatically decreased on the images obtained after chemotherapy. Subsequently, AMT-PET revealed a new tumor lesion of increased AMT uptake when the patient developed vision problems and MRI showed no significant interval morphological changes. Significant vision improvement was observed after external beam radiotherapy for the newly identified tumor lesion. Positron emission tomography with alpha-[(11)C]methyl-L-tryptophan may be useful for monitoring progression and response to treatment of OPGs, which needs to be further investigated in a prospective study of more patients, including those with neurofibromatosis.

Optic gliomas of the anterior visual pathway

To review advances in the diagnosis and management of optic-pathway gliomas made within the past 5 years. Important papers regarding optic-pathway gliomas have been published recently in the following areas: neuroimaging, natural history and how the presence of neurofibromatosis type 1 affects it, unusual presentations, visual prognosis, and treatment with fractionated stereotactic radiotherapy. The diagnosis and treatment of optic-pathway gliomas has been aided greatly by a greater understanding of the natural history of these tumors and their prognosis related to the presence of neurofibromatosis type 1. Advances in magnetic resonance imaging are helping to delineate tumor extent. Newer radiation techniques that spare surrounding tissues are being used to treat optic-pathway gliomas, but chemotherapy has become the first-line treatment modality.

DNA topoisomerase IIα expression in optic pathway gliomas of childhood

DNA topoisomerase IIα (Topo IIα) is linked to tumour cell growth and chemoresistance. We examined immunohistochemically Topo IIα expression levels in a series of 36 consecutive paediatric optic pathway glioma (OPG) patients. Topo IIα labelling index (LI) ranged from 0.0 to 11.6 and was significantly associated with patient age, with higher levels of Topo IIα in children ⩽3 years (P=0.031). Topo IIα expression did not correlate with patient survival. Topo IIα LI was not significantly increased in specimens of repeat surgery. Topo IIα LI closely correlated with MIB-1 LI (R=0.781, P<0.001). We conclude that Topo IIα expression correlates with tumour cell proliferation in paediatric OPGs. Assessment of cell proliferation, however, does not assist in refining prognostic predictions. Enhanced Topo IIα expression in children ⩽3.0 years suggests that Topo IIα-interfering anticancer compounds for adjuvant treatment of OPGs may be of particular benefit to young children.

A practice pathway for the management of gliomas of the anterior visual pathway: an update and an evidence-based approach

Purpose: To propose a practice pathway based upon the available medical literature for the management of optic pathway gliomas. Methods: A computerized Medline search of the English language literature on optic pathway gliomas from 1966 to 1998 was made. A practice pathway for the management of these tumors was developed based upon the available evidence. Results: The results of the practice pathway are summarized in an easy-to-follow, user-friendly treatment algorithm. Conclusion: The treatment of optic pathway gliomas is controversial. The use of an evidence-based practice pathway may assist the clinician in the management of these difficult cases.