Aggressive Low-Grade Optic Nerve Glioma in Adults

Abstract

Primary optic nerve gliomas are most commonly benign pilocytic astrocytomas (World Health Organization [WHO] Grade I) occurring in childhood and following an indolent course. Malignant optic gliomas occur in adulthood and follow an extremely aggressive course, with rapid infiltration of the chiasm, blindness, and death typically within months. A third category of optic glioma, occurring in adulthood, histopathologically benign (WHO Grade I–II) but following an aggressive course, has been rarely reported. The authors describe clinical and histopathologic features of clinically aggressive but histopathologically benign optic nerve gliomas of adulthood. Retrospective review of cases of biopsy-proven optic nerve glioma in the neuro-ophthalmology division of the Jules Stein Eye Institute from 1990 to 2011 was carried out. Cases following an aggressive course were selected for review of clinical, neuroradiologic, and histopathologic features. Three cases were selected for detailed study. Ages ranged from 31 to 45 years. All were initially diagnosed with optic nerve inflammation or benign neoplasm based on clinical and neuroradiologic features, but all suffered neuroradiologic extension and rapid deterioration of vision in the affected eye to no light perception over 3–8 weeks. Optic nerve biopsies were undertaken for the suspicion of malignancy. Features ranged from WHO Grade I (pilocytic astrocytoma, ganglioglioma) in two cases, to WHO Grade II in one case (diffuse astrocytoma, histopathologically benign, but associated with aggressive features such as high p53 [13–21%] and Ki-67 [40%]). The diffuse astrocytoma case subsequently developed extensive intracranial extension suspicious for malignant transformation. These findings indicate that benign optic nerve glioma in adults may be initially misdiagnosed as inflammation, be clinically aggressive, and require excision to prevent further intracranial involvement.     

Chemotherapy for Optic Nerve Glioma in A Child with Neurofibromatosis Type-1

The majority of optic pathway tumors associated with Neurofibromatosis type-1 (NF-1) are benign, slow-growing lesions: however, rapidly growing tumors, which cause proptosis and visual loss, can sometimes occur. Optimal management of these tumors is still unclear. We report the case of a 12-year-old male, affected by NF-1 who was found to have a rapidly growing right optic nerve glioma, treated with carboplatin and vincristine. During chemotherapy, optic disc swelling rapidly disappeared; the orbital tumor decreased in size, with magnetic resonance imaging (MRI) evidence of tumor shrinkage. There was a progressive improvement in visual acuity and Visually Evoked Potential (VEP) amplitudes. Children with NF-1 associated optic pathway tumors should not receive chemotherapy unless there is documented progressive disease. Nevertheless, in contrast with previous studies, this case demonstrates that chemotherapy can be a safe and effective treatment for NF-1-associated optic nerve glioma, and should not be reserved only for patients with optic chiasm or tract involvement.     

Optic Nerve Biopsy via a Medial Transconjunctival Orbitotomy Approach in the Diagnosis of Optic Nerve and Sheath Tumors

Purpose:?To evaluate the role of optic nerve biopsy in the diagnosis and management of optic nerve and sheath tumors.

Methods:?Seven patients with progressive optic nerve and sheath tumors for whom treatment was deemed necessary were included in this study. Optic nerve biopsy via a medial transconjunctival orbitotomy approach was performed in all patients

Results:?There were no complications related to the surgical procedure. Histopathological examination revealed that five patients had juvenile pilocytic astrocytoma (JPA) and two patients had optic nerve sheath meningioma (ONSM). All patients received external beam radiotherapy (EBRT).

Conclusions:?Many other benign and malignant optic nerve and sheath tumors have imaging features similar to those seen in JPA and ONSM. Therefore, it is important to establish histopathologic diagnosis before embarking on treatment. Furthermore, tissue diagnosis is required prior to EBRT in many institutions because of concerns about medicolegal liability. Optic nerve biopsy via a transconjunctival orbitotomy procedure in seven patients yielded histopathologic confirmation of the existing pathology and was not associated with any complications in this series.     

Protective Role of Limitrin in Experimental Autoimmune Optic Neuritis

PurposeThis study investigated the role of limitrin in the pathogenesis of demyelinating optic neuritis using an experimental autoimmune optic neuritis (EAON) model.MethodsEAON was induced in mice via subcutaneous injection with myelin oligodendrocyte glycoprotein peptide. Limitrin protein and mRNA expression were examined in the optic nerve before and after EAON induction. Proinflammatory cytokine expression profiles and degree of glial activation were compared between wild-type (WT) and limitrin knockout mice by real-time PCR and histologic analysis, respectively, after EAON induction. Plasma limitrin levels in patients with optic neuritis and healthy controls were measured by ELISA.ResultsLimitrin expression, observed in astrocytes in the optic nerve of WT mice, was lower in EAON-induced than in naïve WT mice. A comparative analysis of WT and limitrin knockout mice revealed that limitrin deficiency induced more severe neuroinflammation and glial hyperactivation in the optic nerve after EAON induction. Limitrin-deficient astrocytes were more chemotactically responsive to neuroinflammatory stimulation than WT astrocytes. Patients with optic neuritis demonstrated higher plasma limitrin levels than healthy controls (P = 0.0001), which was negatively correlated with visual acuity at the nadir of the optic neuritis attack (r = 0.46, P = 0.036).ConclusionsLimitrin deficiency induced severe neuroinflammation and reactive gliosis in the optic nerve after EAON induction. Our results imply that astrocyte-derived limitrin may protect against neuroinflammation by decreasing immune cell infiltration into the optic nerve. The plasma limitrin level may reflect the extent of blood–brain barrier disruption and provide a valuable biomarker reflecting the severity of optic neuritis.     

Optic Nerve Enhancement and Restricted Diffusion in Postoperative Visual Loss

Postoperative visual loss is rare and most often due to posterior ischemic optic neuropathy. We describe optic nerve MR imaging of a 37-year-old man with postoperative visual loss due to posterior ischemic optic neuropathy after complicated aortic aneurysm surgery. MR demonstrated restricted diffusion and focal enhancement of both optic nerves. Combined restricted diffusion and focal enhancement is a unique MR imaging feature with postoperative vision loss.     

神经生长因子治疗非动脉炎性前部缺血性视神经病变的临床效果

目的：观察神经生长因子（NGF）治疗非动脉炎性前部缺血性视神经病变（NA-AION）的临床疗效。 方法：前瞻性随机对照研究。选择2016年7月至2019年6月涟水县人民医院眼科收治的NA-AION患 者58例（58眼）,根据随机数字表法分为对照组和观察组,对照组29例（29眼）予以糖皮质激素+活血 通络颗粒+复方樟柳碱治疗,观察组29例（29眼）在对照组基础上加NGF治疗。比较2组治疗的总有 效率、治疗前后最佳矫正视力（BCVA）、30°范围视野检查平均缺损（MD）、视盘视网膜神经纤维层 （RNFL）厚度。数据采用Fisher精确检验、t检验及非参数检验。结果：治疗后,观察组总有效率明 显高于对照组（P=0.04）,观察组BCVA小数视力0.1以上所占百分比明显高于对照组（P<0.001）,但 观察组的MD和RNFL厚度均明显低于对照组（t=2.59,P=0.01;t=4.86,P<0.001）。2组治疗后均无明 显不良反应。结论：加用NGF治疗NA-AION可获得更好的疗效,能提高患者视力,改善视野,降低 RNFL厚度。     

Effects of Nerve Growth Factor in the Treatment of Non-Arteritic Anterior Ischemic Optic Neuropathy

Objective: To observe the effects of nerve growth factor (NGF) in the treatment of non-arteritic anterior ischemic optic neuropathy (NA-AION). Methods: This was a prospective, randomized, controlled study. Fifty-eight NA-AION patients (58 eyes) admitted to Lianshui County People's Hospital from July 2016 to June 2019 were selected, and then were divided into a control group and an observation group based on the random numerical table method. The control group (29 patients with 29 eyes) were given glucocorticoid hormones, Huoxue Tongluo granules and an anisodine compound. While the observation group (29 patients with 29 eyes), were treated with NGF in addition to the treatment plan previously described. The total effective rate, best corrected visual acuity (BCVA), the 30-degree visual-field examination mean deviation (MD) and the disc retinal nerve fiber layer (RNFL) thickness of the two groups were compared. Data were analyzed by the Fisher's exact test, a t test and a non-parametric test. Results: After treatment, the total effective rate for the observation group was significantly higher than that for the control group (P=0.04),the percentage of BCVA above 0.1 in the observation group was significantly higher than that in the control group (P<0.001), and both the MD and RNFL thickness in the observation group were significantly lower than those in the control group (t=2.59, P=0.01; t=4.86, P<0.001). There were no obvious adverse reactions for either group after treatment. Conclusions: The treatment of NA-AION with NGF can obtain a better effective rate, improve the patient's vision, improve the visual field and reduce RNFL thickness.     

Novel NR2F1 variant identified by whole-exome sequencing in a patient with Bosch–Boonstra–Schaaf optic atrophy syndrome

Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is an extremely rare autosomal dominant disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, hearing loss, and optic nerve atrophy. This syndrome is caused by loss-of-function variants in the nuclear receptor subfamily 2 group F member 1 (NR2F1) gene. To date, approximately 80 patients have been reported with BBSOAS. Here, we describe a 3-year-old infant with delayed development, intellectual disability, strabismus, nystagmus, and optic atrophy with well-characterized features associated with BBSOAS. Whole-exome sequencing revealed a novel heterozygous missense mutation ({"type":"entrez-nucleotide","attrs":{"text":"NM_005654.6","term_id":"1519315434","term_text":"NM_005654.6"}}NM_005654.6:c.437G>A, p.Cys146Tyr) in the NR2F1 gene. This missense variant is predicted to be deleterious by the protein prediction tools (SIFT, PolyPhen-2, and MutationTaster). To the best of our knowledge, this is the first patient with BBSOAS reported from Turkey.